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  • 1995-1999  (20,973)
  • 1985-1989  (20,057)
  • 1810-1819
  • Polymer and Materials Science  (31,432)
  • Biochemistry and Biotechnology  (8,389)
  • Genetics  (1,213)
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  • 1
    Electronic Resource
    Electronic Resource
    Mitochondrial DNA mutation at np 3243 in a family with maternally inherited diabetes mellitus (1999)
    Springer
    Acta diabetologica 36 (1999), S. 163-167 
    Details
    ISSN: 1432-5233
    Keywords: Key words Mitochondrial DNA ; Genetics ; Maternally inherited diabetes mellitus ; Deafness ; np 3243 mutation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mitochondrial DNA (mtDNA) gene defects may play a role in the development of maternally inherited diabetes mellitus and deafness (MIDD). A family from Southern Italy who showed maternal transmission of type 2 diabetes mellitus with three individuals affected is described. A 10.4 kb deletion and mutations at nucleotide positions (np) 3243, 7445 and 11778 in the mtDNA of six relatives were sought. The mitochondrial np 3243 mutation of the tRNA Leu (UUR) gene was identified in a boy affected by optic atrophy and mental retardation, as well as in his diabetic mother. No other mutations or deletions were found. Our study points out the variable phenotypic expression of the np 3243 mtDNA mutation. This may suggest the presence of other mitochondrial or nuclear mutations required to modulate the phenotype. A clinical and metabolic follow-up of all family members was necessary to understand the role of the np 3243 mutation, especially in one child affected by optic atrophy and mental retardation. Further studies will be aimed at investigating the prevalence of mutations and deletions of mtDNA in type 2 diabetes mellitus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s005920050161
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  • 2
    Electronic Resource
    Electronic Resource
    AC/GT and AG/CT microsatellite repeats in peach [Prunus persica (L) Batsch]: isolation, characterisation and cross-species amplification in Prunus (1999)
    Springer
    Theoretical and applied genetics 99 (1999), S. 65-72 
    Details
    ISSN: 1432-2242
    Keywords: Key words Simple sequence repeat (SSR) ; Microsatellites ; Molecular markers ; Genetics ; Fingerprinting
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  We report the sequences of 17 primer pairs of microsatellite loci, which we have cloned and sequenced from two genomic libraries of peach [Prunus persica (L) Batsch] ‘Redhaven’, enriched for AC/GT and AG/CT repeats respectively. For ten of these microsatellite loci we were able to demonstrate Mendelian inheritance in a segregating back-cross population; the remainder did not segregate. The polymorphism of the microsatellites was evaluated in a panel of ten peach genotypes, including true-to-type peaches, nectarines and one canning-peach. Fifteen microsatellites (88%) were polymorphic showing 2–4 alleles each. The mean heterozygosity, averaged over all loci, was 0.32 and significantly higher than that reported in the literature for isozymes and molecular markers, such as RFLPs and RAPDs. We have also assayed the cross-species transportability and found that ten microsatellite (59%) gave apparently correct amplification in all Prunus species surveyed, namely P. domestica (European plum), P. salicina (Japanese plum), P. armeniaca (apricot), P. dulcis (almond), P. persica var. vulgaris (peach), P. persica var. laevis (nectarine), P. avium (sweet cherry) and P. cerasus (sour cherry), with three of them also being amplified in Malus (apple). The remaining microsatellites gave less-extensive amplification. Because of their appreciable polymorphism and wide cross-species transportability, most of these new markers can be integrated into the linkage maps which are currently being constructed in peach, as well as in other stone fruit crops, such as almond, apricot, cherry and plum.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001220051209
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  • 3
    Electronic Resource
    Electronic Resource
    Pathologie der Rhabdo- myosarkome des Kindes- und Adoleszentenalters Ein Bericht des Kindertumorregisters bei der Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH) (1999)
    Springer
    Der Pathologe 20 (1999), S. 87-97 
    Details
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Rhadomyosarkom ; Klassifizierung ; Immunhistochemie ; Genetik ; Prognose ; Key words Rhabdomyosarcoma ; Classification ; Immunohistochemistry ; Genetics ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Rhabdomyosarcoma (RMS) is the most important and a very heterogeneous group of malignant soft tissue tumors of childhood and adolescence.The two major subtypes (embryonal and alveolar) share a common myogenic differentiation, but seem to be histogenetically not related. The so-called ’International Classification of Rhabdomyosarcoma’ includes, besides the two major subtypes, the botryoid and leiomyomatous subtypes of embryonal RMS which are associated with a better prognosis and are treated less aggressively according to current protocols. In addition, the solid variant of alveolar RMS is included in the alveolar group of RMS. The identification of the various subtypes is necessary and important because the treatment with the current protocols is also related to histology. Using conventional stains and immunohistochemistry, these subtypes are distinguishable. Genetic analysis can be helpful in the demonstration of t(2;13) or t(1;13) translocations in alveolar RMS. The identification of alveolar RMS with t(1;13) translocation might become important in the future, because this type of translocation seems to be related to a better prognosis as compared to tumors with a t(2;13) translocation.
    Notes: Zusammenfassung Rhabdomyosarkome stellen eine heterogene Gruppe von ganz verschiedenartigen, histogenetisch wohl nicht zusammengehörenden Tumoren dar. Nach der heute verwendeten „Internationalen Klassifikation” der Rhabdomyosarkome werden neben der Unterteilung in embryonalen und alveoläre Rhabdomyossarkome auch Subtypen des embryonalen RMS identifiziert (botryoider und leiomyomatöser Subtyp), die durch eine günstigere Prognose und durch die Notwendigkeit einer weniger aggressive Therapie gekennzeichnet sind. Durch Einsatz von verschiedenen histologischen und immunhistochemischen Färbungen ist die Identifizierung der verschiedenen Typen der RMS heute möglich und auch zwingend notwendig, da die einzelnen Entitäten nach ganz unterschiedlichen Therapieprotokollen behandelt werden. Der Nachweis typischer molekulargenetischer Veränderungen kann in der Unterscheidung insbesondere von embryonalen und alveolären RMS hilfreich sein. In der Regel ist die Abgrenzung zwischen diesen beiden Entitäten auch an konventionell gefärbten Schnittpräparaten möglich. Die Identifizierung von alveolären RMS mit einer t(1;13)-Translokation könnte in Zukunft eine große Bedeutung haben, da diese genetische Veränderung möglicherweise mit einer günstigeren Prognose assoziert sein könnte als die t(2;13)-Translokation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002920050326
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  • 4
    Electronic Resource
    Electronic Resource
    Etiology of the inflammatory bowel diseases (1999)
    Springer
    International journal of colorectal disease 14 (1999), S. 2-9 
    Details
    ISSN: 1432-1262
    Keywords: Key words Inflammatory bowel disease ; Crohn's disease ; Ulcerative colitis ; Epidemiology ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Inflammatory bowel diseases (IBD) are complex disorders. While the exact etiology of these diseases remains unknown, recent progress in the epidemiology and genetics of IBD has clearly demonstrated both environmental and genetic factors to play a role in the development of the disease, and it is expected that some risk factors are common for both Crohn's disease (CD) and ulcerative colitis (UC). The environmental factor(s) are associated with the Western way of life in the second half of the twentieth century. Cigarette smoking is presently the best known environmental factor. However, the effect of tobacco is opposite in CD and UC. A familial history of IBD is the most important risk factor for developing the disease, suggesting a genetic predisposition to IBD. This hypothesis has recently been confirmed by the localization of at least two susceptibility loci on chromosomes 12 and 16. These genes seem to play a role in both CD and UC. They must now to be identified.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003840050175
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  • 5
    Electronic Resource
    Electronic Resource
    Genetik schizophrener Störungen Neuere Konzepte und Befunde (1999)
    Springer
    Der Nervenarzt 70 (1999), S. 955-969 
    Details
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Schizophrenie ; Genetik ; Schizophrenes Spektrum ; Kopplungsuntersuchungen ; Assoziationsuntersuchungen ; Key words Schizophrenia ; Genetics ; Schizophrenia spectrum ; Linkage studies ; Association studies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Schizophrenia is a genetic complex disease as it does not follow monogenic transmission while non-familial environmental factors have a strong additional impact. A heterogenous, continuous phenotype is transmitted in families which can now be more precisely characterized. Genes coding for proteins with presumed pathophysiological relevance are apparently not playing a major causal role. However, in the last three years several (currently seven) candidate regions have been identified in a replicable manner by linkage studies. These regions are likely to host susceptibility genes for schizophrenia, but none of them has been identified up to now. Given these findings, polygenic transmission has now become very likely. The candidate regions are currently being narrowed down by various promising techniques.
    Notes: Zusammenfassung Die Schizophrenie gehört zu den genetisch komplexen Erkrankungen, die keinem monogenen Erbgang folgen und bei denen auch nichtfamiliäre Umgebungsfaktoren eine wichtige Rolle spielen. Dabei wird intrafamiliär ein heterogener, quantitativ variierender Phänotyp übertragen, der zunehmend genauer charakterisiert werden kann. Keines der bekannten Gene mit vermuteter pathophysiologischer Relevanz spielt nach den bisherigen Erkenntnissen eine substantielle Rolle. In den vergangenen drei Jahren ist es aber erstmals durch Kopplungsuntersuchungen gelungen, mehrere replizierbare Kandidatenregionen (derzeit sieben) auf dem Genom zu identifizieren, in denen vermutlich Suszeptibilitätsgene für Schizophrenie liegen. Keines dieser Gene wurde jedoch bislang identifiziert. Mit diesen Befunden ist eine polygene Übertragung der Schizophrenie sehr wahrscheinlich geworden. Verschiedene Techniken zur Eingrenzung der Kandidatenregionen werden derzeit erfolgreich angewandt.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001150050524
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  • 6
    Electronic Resource
    Electronic Resource
    A mutation at codon 279 (N279K) in exon 10 of the Tau gene causes a tauopathy with dementia and supranuclear palsy (1999)
    Springer
    Acta neuropathologica 98 (1999), S. 62-77 
    Details
    ISSN: 1432-0533
    Keywords: Key words Frontotemporal dementia ; Genetics ; Progressive supranuclear palsy ; Tauopathy ; Exon ; amplifcation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recently intronic and exonic mutations in the Tau gene have been found to be associated with familial neurodegenerative syndromes characterized not only by a predominantly frontotemporal dementia but also by the presence of neurological signs consistent with the dysfunction of multiple subcortical neuronal circuitries. Among families, the symptomatology appears to vary in quality and severity in relation to the specific Tau gene mutation and often may include parkinsonism, supranuclear palsies, and/or myoclonus, in addition to dementia. We carried out molecular genetic and neuropathological studies on two patients from a French family presenting, early in their fifth decade, a cognitive impairment and supranuclear palsy followed by an akinetic rigid syndrome and dementia. The proband died severely demented 7 years after the onset of the symptoms; currently, his brother is still alive although his disease is progressing. In both patients, we found a Tau gene mutation in exon 10 at codon 279, resulting in an asparagine to lysine substitution (N279K). Neuropathologically, widespread neuronal and glial tau accumulation in the cortex, basal ganglia, brain stem nuclei as well as in the white matter were the hallmark of the disease. These deposits were shown by immunohistochemistry and immunoelectron microscopy, using a battery of antibodies to phosphorylation-dependent and phosphorylation-independent epitopes present in multiple tau regions. In the neocortex, tau-immunopositive glial cells were more numerous than immunopositive neurons; the deeper cortical layers as well as the white matter adjacent to the cortex contained the largest amount of immunolabeled glial cells. In contrast, some brain stem nuclei contained more neurons with tau deposits than immunolabeled glial cells. The correlation of clinical, neuropathological and molecular genetic findings emphasize the phenotypic heterogeneitiy of diseases caused by Tau gene mutations. Furthermore, to test the effect of the N279K mutation and compare it with the effect of the P301L exon 10 mutation on alternative splicing of Tau exon 10, we used an exon amplification assay. Our results suggest that the N279K mutation affects splicing similar to the intronic mutations, allowing exon 10 to be incorporated more frequently in the Tau transcript.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010051052
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  • 7
    Electronic Resource
    Electronic Resource
    Analysis of potential phosphorylation sites in human T cell leukemia virus type 1 Tax (1999)
    Springer
    Journal of biomedical science 6 (1999), S. 206-212 
    Details
    ISSN: 1423-0127
    Keywords: Tax ; HTLV-1 ; Trans-activation ; Phosphorylation ; Mutagenesis ; Transcription ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The human T cell leukemia virus type 1 (HTLV-1) Tax is a phosphoprotein, however, the contribution of phosphorylation to Tax activity is unknown. Previous studies have shown that phosphorylation of Tax occurs on serine residue(s), within one tryptic fragment, in response to 4β-phorbol-12β-myristate-13α-acetate, in both mouse and human cells. Studies were conducted in multiple cell lines to identify the specific phosphorylated serines as a prelude to functional analysis. The phosphorylation pattern of Tax was found to be different in 293T and COS-7 cells in comparison with MT-4 and Px-1 cells. However, one tryptic fragment remained consistent in comigration analyses among all cell lines. Using selected Tax serine mutants a tryptic fragment containing a serine at residue 113 believed to be the site of phosphorylation of Tax did not comigrate with the common phosphorylated tryptic fragment. Analysis of selected Tax mutants for ability totrans-activate the cytomegalovirus promoter demonstrated mutation of serine 77 to alanine reducedtrans-activation by 90% compared to wild-type Tax. However, examination of the phosphorylation pattern of the serine 77 mutant demonstrated that it is not the site of phosphorylation. These studies demonstrate the importance of using relevant cell lines to characterize the role of phosphorylation in protein function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02255904
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  • 8
    Electronic Resource
    Electronic Resource
    Controlling septation in fission yeast: finding the middle, and timing it right (1999)
    Springer
    Current genetics 35 (1999), S. 571-584 
    Details
    ISSN: 1432-0983
    Keywords: Key words Cytokinesis ; Kinase ; Mitosis ; Schizosaccharomyces pombe ; Cell division ; Phosphatase ; Mutant ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The fission yeast Schizosaccharomyces pombe provides a simple eukaryotic model for the study of cytokinesis. S. pombe cells are rod-shaped, grow mainly by elongation at their tips, and divide by binary fission after forming a centrally placed division septum. Analysis of mutants has begun to shed light upon how septum formation and cytokinesis are regulated both spatially and temporally. Some of the proteins involved in these events have been functionally conserved throughout eukaryotic evolution, suggesting that aspects of this control will be common to all eukaryotic cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002940050455
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  • 9
    Electronic Resource
    Electronic Resource
    Clinical relevance of monosomy 22q11.2 in children with pulmonary atresia and ventricular septal defect (1999)
    Springer
    European journal of pediatrics 158 (1999), S. 302-307 
    Details
    ISSN: 1432-1076
    Keywords: Key words Congenital heart disease ; Pulmonary atresia and ventricular septal defect ; Genetics ; Monosomy 22q11.2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of our study was to describe the prevalence and the clinical spectrum of monosomy 22q11.2 in a population of patients with pulmonary atresia and ventricular septal defect. We examined all 44 patients with this conotruncal cardiac malformation who presented to our institution from January 1994 until December 1997. The type of collateral lung perfusion was recorded including anomalies of the pulmonary arteries as well as facial and immunological abnormalities. Molecular-cytogenetic testing for a 22q11.2 microdeletion was performed using the probes D22S75 and cHKAD26. Statistical differences were evaluated with the Fisher's Exact Test. Monosomy 22q11.2 was present in ten children (23%) with major aortopulmonary collateral arteries (group 1). The remaining 13 children (29%) with major aortopulmonary collateral arteries (group 2) and all 21 children (48%) with ductus arteriosus (group 3) were negative for this microdeletion. All children in group 1 had facial anomalies, six had mild immunological abnormalities including decreased CD 4+ or CD 8+ cells. Anomalies of the pulmonary vascular bed were significantly more frequent in children of group 1 (9/10) than in children of group 2 (4/13) or group 3 (0/21). Due to these pulmonary vascular anomalies, corrective surgery had been accomplished in fewer children with monosomy 22q11.2 (none in group 1) as compared to 7/13 children in group 2 and 14/21 children in group 3. Conclusion In children with pulmonary atresia and ventricular septal defect, monosomy 22q11.2 is preferentially associated with major aortopulmonary collateral arteries. Due to the higher incidence of pulmonary arterial abnormalities, successful surgical repair will require a different therapeutic approach in most patients with this microdeletion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004310051077
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  • 10
    Electronic Resource
    Electronic Resource
    Linkage analysis of candidate myelin genes in familial multiple sclerosis (1999)
    Springer
    Neurogenetics 2 (1999), S. 155-162 
    Details
    ISSN: 1364-6753
    Keywords: Key words Multiple sclerosis ; Genetics ; Myelin basic protein ; Myelin oligodendrocyte glycoprotein ; Proteolipid protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: ABSTRACT Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system. A complex genetic etiology is thought to underlie susceptibility to this disease. The present study was designed to analyze whether differences in genes that encode myelin proteins influence susceptibility to MS. We performed linkage analysis of MS to markers in chromosomal regions that include the genes encoding myelin basic protein (MBP), proteolipid protein (PLP), myelin-associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMGP), and myelin oligodendrocyte glycoprotein (MOG) in a well-characterized population of 65 multiplex MS families consisting of 399 total individuals, 169 affected with MS and 102 affected sibpairs. Physical mapping data permitted placement of MAG and PLP genes on the Genethon genetic map; all other genes were mapped on the Genethon genetic map by linkage analysis. For each gene, at least one marker within the gene and/or two tightly linked flanking markers were analyzed. Marker data analysis employed a combination of genetic trait model-dependent (parametric) and model-independent linkage methods. Results indicate that MAG, MBP, OMGP, and PLP genes do not have a significant genetic effect on susceptibility to MS in this population. As MOG resides within the MHC, a potential role of the MOG gene could not be excluded.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s100480050076
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  • 11
    Electronic Resource
    Electronic Resource
    Management of mantle cell lymphoma (1999)
    Springer
    Annals of hematology 78 (1999), S. 485-494 
    Details
    ISSN: 1432-0584
    Keywords: Key words Mantle cell lymphoma ; Classification ; Pathology ; Prognosis ; Immunology ; Genetics ; Antineoplastic agents ; Combined ; Therapeutic use ; Radiotherapy ; Hematopoietic stem cell transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002770050545
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  • 12
    Electronic Resource
    Electronic Resource
    Why is acute leukemia more common in males? A possible sex-determined risk linked to the ABO blood group genes (1999)
    Springer
    Annals of hematology 78 (1999), S. 233-236 
    Details
    ISSN: 1432-0584
    Keywords: Key words Acute leukemia ; Genetics ; Sex ; ABO Blood group
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Acute leukemia is more common in males at almost every age, and this fact remains unexplained. A study was carried out in northeast peninsular Malaysia, where the population is predominantly Malay, to examine whether there was a difference in ABO blood group distribution between males and females with acute leukemia (AL). The ABO blood groups of 109 male and 79 female patients with AL (98 ALL, 90 AML) were compared with those of 1019 controls. In the control population, 39.7% were group O. Among males with AL, 39.4% were group O, whereas among females with AL, the proportion was 24.1% (p=0.03). The same trend to a lower proportion of group O among females was seen if the group was divided into adult/pediatric or lymphoblastic/myeloblastic groups, though these differences were not statistically significant. If these findings can be confirmed, they suggest the presence of a "sex-responsive" gene near to the ABO gene locus on chromosome 9, which relatively protects group O women against AL, at least in our population. The existence of such a gene might also partly explain why acute leukemia, and possibly other childhood cancers, are more common in males.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002770050507
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  • 13
    Electronic Resource
    Electronic Resource
    The neurofibromatoses. An overview (1999)
    Springer
    Italian journal of neurological sciences 20 (1999), S. 89-108 
    Details
    ISSN: 1126-5442
    Keywords: Key words Neurofibromatosis ; Nf1 ; Nf2 ; Mosaic/segmental neurofibromatosis ; Variants ; Classification ; Neurological manifestations ; Genetics ; Childhood ; Adulthood
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The last two decades have seen clinical and molecular delineation of the different forms of neurofibromatosis. Differentiation of these forms is not just an academic exercise: their natural history, management and genetic counselling are quite different. Of the numerical classifications of neurofibromatosis proposed in the past, only neurofibromatosis type 1 (Nf1) and neurofibromatosis type 2 (Nf2) are now well delineated clinically and have been shown to be distinct at the molecular level. For both forms of neurofibromatosis, patients with clinical generalised disease have been demonstrated to be mosaic at the molecular level, and features of segmental or mosaic Nf1 and Nf2 have been delineated. Other reported forms of neurofibromatosis are rarer; they include Watson syndrome, hereditary spinal neurofibromatosis, familial intestinal neurofibromatosis, autosomal dominant café-au-lait spots alone, autosomal dominant neurofibromas alone, and schwannomatosis, the latter believed to be a variant of Nf2. Further delineation is neeeded for individuals having overlapping features of Noonan's syndrome and neurofibromatosis (the so-called Noonan/neurofibromatosis syndrome) and the syndrome of “multiple naevi, multiple schwannomas and multiple vaginal leiomyomas”. In this article we review the forms of neurofibromatosis which we believe are true clinical entities. Particular attention is given to the neurological manifestations of neurofibromatosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s100720050017
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  • 14
    Electronic Resource
    Electronic Resource
    Insulin resistance and impaired insulin secretion due to phosphofructo-1-kinase-deficiency in humans (1999)
    Springer
    Journal of molecular medicine 77 (1999), S. 96-103 
    Details
    ISSN: 1432-1440
    Keywords: Key words Diabetes ; Genetics ; Phosphofructokinase ; Glycogenosis ; NIDDM ; PFK
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The etiology of non-insulin-dependent diabetes mellitus (NIDDM) is usually explained as a combination of peripheral insulin resistance and impaired beta-cell function. Phosphofructo-1-kinase (PFK1) is a rate limiting enzyme in glycolysis, and its muscle subtype (PFK1-M) deficiency leads to an autosomal recessively inherited disorder known as glycogenosis type VII or Tarui’s disease. It was evaluated whether PFK1-M deficiency leads to NIDDM in humans. A core family of four was evaluated for PFK1-M deficiency by DNA- and enzyme-activity-analyses. All members underwent oral and intravenous glucose tolerance test (oGTT/ivgtt), as well as an insulin sensitivity test (IST) using octreotide. Results: Father (46 years, BMI 22.4 kg/m2) and older son (19 years, BMI 17.8 kg/m5) showed homozygous PFK1-M deficiency, while mother (47 years, BMI 28.4 kg/m5) and younger son (13 years, BMI 16.5 kg/m5) were shown to be heterozygously PFK1-M-deficient on enzyme activity levels. DNA analysis revealed an exon 5-missense-mutation at one allele of all four members, and an exon 22-frameshift-mutation at the other allele of the two homozygously affected individuals. By oGTT the father showed impaired glucose tolerance, and the mother clinical diabetes. By ivGTT both parents and the older son had a decreased first phase insulin secretion, and a diminished glucose disappearance rate. The IST showed marked insulin resistance in both parents and the older son, and moderate resistance in the younger son, previously not described. Conclusion: PFK1-M-deficiency leads to a metabolic state typical for early NIDDM in homozygously affected humans, especially concerning insulin resistance and loss of first phase beta-cell insulin secretion, and may contribute to the manifestation of NIDDM in a subgroup of patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001090050311
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  • 15
    Electronic Resource
    Electronic Resource
    Polymorphisms in the glutamate transporter gene EAAT2 in European ALS patients (1999)
    Springer
    Journal of neurology 246 (1999), S. 1140-1144 
    Details
    ISSN: 1432-1459
    Keywords: Key words Amyotrophic lateral sclerosis ; Genetics ; Glutamate transporter gene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Amyotrophic lateral sclerosis (ALS) is a progressive neurological disorder characterised by degeneration of upper and lower motor neurons. Whilst the primary pathogenic trigger is unknown in most cases, evidence is mounting to implicate a role for glutamate-mediated neurotoxicity in the disorder. Recent studies have shown reduced levels of the mainly astroglial glutamate transporter EAAT2 in ALS motor cortex and spinal cord and multiple abnormal EAAT2 mRNA species in ALS brain tissue. One cause of the low EAAT2 levels may be that point mutations in the EAAT2 gene, EAAT2, result in an abnormal unstable protein. To test this hypothesis we analysed EAAT2 in 128 sporadic and 23 familial European ALS cases. No variants within the coding sequence of EAAT2 to affect the protein sequence nor in the consensus splice sites of the flanking intronic sequences were found in any cases, similar to findings in other reports. Frequent polymorphisms within the flanking intronic sequences of both exons 2 and 4 were seen but at similar frequencies in controls. Mechanisms other than mutations within the coding region of EAAT2 must therefore be responsible for the low levels of EAAT2 seen in most cases of ALS.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004150050532
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  • 16
    Electronic Resource
    Electronic Resource
    Early diagnosis and the clinical genetics of Alzheimer’s disease (1999)
    Springer
    Journal of neurology 246 (1999), S. 69-72 
    Details
    ISSN: 1432-1459
    Keywords: Key words Alzheimer’s disease ; Genetics ; Genetic counseling ; Predictive testing ; Diagnosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Alzheimer’s disease (AD) has a significant genetic background manifested as autosomal dominant inheritance in some early-onset families and as familial risk in late-onset cases. Three genes responsible for early-onset autosomal dominant AD have been identified, and one gene, apolipoprotein E, has been confirmed as a susceptibility gene for late-onset forms of the disorder. These findings raise the possibility of genetic testing, either for early diagnosis or prediction. For early-onset autosomal dominant AD genetic testing will have a limited but useful role in confirming diagnosis in established cases and in predictive counselling for relatives; a situation analogous to that for Huntington’s disease. For late-onset AD significant problems remain to be overcome before the advances in molecular genetics have a direct clinical application
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004150050310
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  • 17
    Electronic Resource
    Electronic Resource
    Self-incompatibility in passion fruit: evidence of two locus genetic control (1999)
    Springer
    Theoretical and applied genetics 98 (1999), S. 564-568 
    Details
    ISSN: 1432-2242
    Keywords: Key words Passiflora ; Self-incompatibility ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  The self-incompatibility in yellow passion fruit was previously described as homomorphic sporophytic with monofactorial inheritance. Five progenies were obtained by bud-selfing. The plants of these progenies were selfed, reciprocally crossed within each progeny and crossed with known incompatible phenotypes to identify their phenotypic group. Fruit set was evaluated at the 7th day after pollination. Two progenies consisted of two self-incompatible groups, the other three formed three suck groups. The groups were identified as S1, S2, S3, S4, S5 and S6. The results provide evidence that the self-incompatibility of passion fruit is controlled by two loci, the S-gene and another, whose expression needs to be investigated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001220051105
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  • 18
    Electronic Resource
    Electronic Resource
    A stylar ribonuclease assay to detect self-compatible seedlings in almond progenies (1999)
    Springer
    Theoretical and applied genetics 99 (1999), S. 800-810 
    Details
    ISSN: 1432-2242
    Keywords: Key words Almond ; Compatibility ; Genetics ; Prunus dulcis ; Ribonucleases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  Six almond progenies, each the product of a cross between a self-compatible and a self-incompatible parent, were analysed for stylar ribonucleases. Proteins were extracted and separated using non-equilibrium pH gradient electrofocusing (NEPHGE), and the gels were stained for ribonuclease activity. Most seedlings showed either two principal bands, interpreted as corresponding to two incompatibility alleles, or a single band. The seedlings were also bagged in the field at flowering time to determine fruit set after selfing, and some were also examined for the growth of pollen-tubes in selfed styles using UV fluorescence microscopy. With very few exceptions, those seedlings showing single-banded zymograms were found to be self-compatible according to field and microscope studies, and those with two bands were found to be self-incompatible. We conclude that the allele for self-compatibility in almond does not code for ribonuclease activity and that the ribonuclease isoenzyme assay is a convenient technique for predicting self-compatibility in segregating progenies. A novel band in two derivatives of ’Ferrastar’ was ascribed to a new incompatibility allele, S 10 .
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001220051299
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  • 19
    Electronic Resource
    Electronic Resource
    Craniosynostosis: from a clinical description to an understanding of bone formation of the skull (1999)
    Springer
    Child's nervous system 15 (1999), S. 676-680 
    Details
    ISSN: 1433-0350
    Keywords: Key words Craniosynostosis ; Genetics ; FGFR ; Msx2 ; Development ; Skull
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The genetic studies of syndromic craniosynostoses lead to the characterisation of genes that regulate the correct development of the bones of the skull. From these studies, it appears that FGF/FGFR signalling has a crucial role in this problem. Numerous mutations affecting the genes coding for FGFR1, 2 or 3 are responsible for these syndromes. It is interesting to note that some identical mutations produced various different phenotypes, suggesting that other genes modulate the phenotypic expressivity. The other involved genes in these syndromes code for such proteins as Msx2 or Twist that interact in the cellular pathways responsible for FGF action. From these genetic studies, it is now important to establish the role of these proteins during the development of the skull. Msx2 plays a repressive role in osteogenesis, whereas FGFRs act as promoting proteins. In the near future, it will be very important to improve our understanding of these phenomena in order to test specific treatments to prevent the development of such syndromes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003810050457
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  • 20
    Electronic Resource
    Electronic Resource
    Division of labor in a dynamic environment: response by honeybees (Apis mellifera) to graded changes in colony pollen stores (1999)
    Springer
    Behavioral ecology and sociobiology 46 (1999), S. 171-179 
    Details
    ISSN: 1432-0762
    Keywords: Key words Honeybee ; Apis mellifera ; Division of labor ; Genetics ; Pollen foraging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  A fundamental requirement of task regulation in social groups is that it must allow colony flexibility. We tested assumptions of three task regulation models for how honeybee colonies respond to graded changes in need for a specific task, pollen foraging. We gradually changed colony pollen stores and measured behavioral and genotypic changes in the foraging population. Colonies did not respond in a graded manner, but in six of seven cases showed a stepwise change in foraging activity as pollen storage levels moved beyond a set point. Changes in colony performance resulted from changes in recruitment of new foragers to pollen collection, rather than from changes in individual foraging effort. Where we were able to track genotypic variation, increases in pollen foraging were accompanied by a corresponding increase in the genotypic diversity of pollen foragers. Our data support previous findings that genotypic variation plays an important role in task regulation. However, the stepwise change in colony behavior suggests that colony foraging flexibility is best explained by an integrated model incorporating genotypic variation in task choice, but in which colony response is amplified by social interactions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002650050607
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  • 21
    Electronic Resource
    Electronic Resource
    Erbliche Ursachen und Risikofaktoren der Alzheimer-Krankheit (1999)
    Springer
    Der Nervenarzt 70 (1999), S. 195-205 
    Details
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Alzheimer-Krankheit ; Genetik ; Risikofaktoren ; Genetische Beratung ; Key words Alzheimer’s disease ; Genetics ; Risk factors ; Genetic counseling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary A multifactorial etiology underlies the majority of cases of Alzheimer’s disease (AD). Both ill-defined environmental and genetic factors contribute to the development of the disease. Allele ɛ4 of ApoE is a genetic risk factor. Its presence increases the risk of developing AD. However, presence of e4 is neither necessary nor sufficient for the disease to arise. Apart from the common multifactorial forms of the disease, there are rare variants which are inherited as Mendelian traits. To date three genes are known that can be mutated in these rare forms of AD. Of these, mutations in the gene presenilin 1 on chromosome 14 are most frequent. In addition, mutations in the gene presenilin 2 on chromosome 1 and in the amyloid precursor protein gene (APP on chromosome 21) occur in autosomal dominant AD. This article reviews our present knowledge of the genetics of AD and discusses its relevance for patients with AD and their relatives.
    Notes: Zusammenfassung Der Großteil der Fälle von Alzheimer-Krankheit (AK) hat eine multifaktorielle Ätiologie. Das bedeutet, bisher nicht genauer bekannte Umwelteinflüsse und genetische Faktoren spielen bei der Entwicklung der Krankheit eine wesentliche Rolle. Von seiten der Genetik unterscheidet man bei der AK gegenwärtig genetische Risikofaktroren und Mutationen. Der einzige bisher gesicherte genetische Risikofaktor ist das Allel ɛ4 des Gens für Apolipoprotein E auf Chromosom 19. Dieses Allel erhöht die Wahrscheinlichkeit, an der AK zu erkranken, ist jedoch weder eine notwendige noch eine hinreichende Bedingung. Neben den häufigen Formen mit multifaktorieller Ätiologie kommen seltene Varianten der Krankheit vor, die nach Mendelschen Regeln vererbt werden. Bisher sind 3 Gene bekannt, die bei diesen seltenen, in der Regel früh auftretenden und autosomal dominant vererbten Formen mutiert sein können. Am häufigsten findet sich bei den autosomal-dominanten Fällen eine Mutation im Gen präsenilin 1 auf Chromosom 14, seltener liegen Mutationen im Gen präsenilin 2 auf Chromosom 1 und im Gen des Amyloid- Vorläuferproteins auf Chromosom 21 vor. In diesem Beitrag geben wir eine Übersicht über gegenwärtige Befunde zur Genetik der AK und diskutieren die Bedeutung dieses Wissens für Patienten und deren Verwandte.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001150050423
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  • 22
    Electronic Resource
    Electronic Resource
    Crosses between diabetic BB/OK and wild rats confirm that a third gene is essential for diabetes development (1998)
    Springer
    Acta diabetologica 35 (1998), S. 109-111 
    Details
    ISSN: 1432-5233
    Keywords: Key words BB rat ; Diabetes ; Genetics ; Crossing study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Several crossing studies with diabetic BB rats have shown that in addition to the lymphopenia (Iddm1) and the MHC class II genes of the RT1u haplotype (Iddm2) there are further non-MHC genes essential for diabetes development. Because diabetes-resistant inbred rat strains may be homozygous for one of the diabetogenic non-MHC genes, masking the expression of diabetogenic genes and leading to an underestimation of the number of diabetogenic genes, we crossed wild and diabetic BB/OK rats. The F1 hybrids were backcrossed onto diabetic female (BC1W-F, n=97) and male BB/OK rats (BC1W-M, n=98) transferred to a specified-pathogen-free environment and studied for the frequency and age at onset of diabetes up to an age of 30 weeks. Comparing the results of these BC1 W hybrids with similarly derived hybrids using diabetes-resistant DA rats (BC1DA-F, n=113; BC1DA-M, n=216), the diabetes frequency in total was comparable indicating the action of three recessive genes. The percentage of diabetics in Iddm1 and Iddm2 homozygotes confirmed the existence of the third gene, Iddm3, but there were some sex differences; significantly more male than female BC1W-F and significantly more BC1DA-M than BC1DA-F males were diabetic. Regarding the age at onset, the BC1W-F hybrids manifested not only significantly earlier, but also more uniformly than BC1DA-F and BC1-M hybrids.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s005920050114
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  • 23
    Electronic Resource
    Electronic Resource
    Hepatocyte nuclear factor-1a gene and non-insulin-dependent diabetes mellitus in the Japanese population (1998)
    Springer
    Acta diabetologica 35 (1998), S. 150-153 
    Details
    ISSN: 1432-5233
    Keywords: Key words Non-insulin-dependent diabetes mellitus ; MODY ; Hepatocyte nuclear factor-1α ; Genetics ; Microsatellite polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recently, hepatocyte nuclear factor-1α (HNF-1α, which is encoded by the TCF1 gene) mutations were reported in a subset of patients with maturity onset diabetes of the young (MODY3). We studied the contribution of TCF1 to genetic susceptibility to common non-insulin-dependent diabetes mellitus (type 2) in Japanese subjects by investigating allelic association with type 2 diabetes use of three markers. We also studied the frequency of the G191D mutation, the only mutation of TCF1 reported so far in late-onset type 2 diabetes. A total of 356 subjects were studied. There were no significant differences in allele frequency of the three markers between patients with type 2 diabetes and control subjects. A G191D mutation was not found in the subjects studied, giving a frequency of less than 0.4% in common type 2 diabetes. The lack of association of type 2 diabetes with three markers in and near TCF1 suggests that mutations in TCF1 derived from a limited number of founders are not a major cause of common type 2 diabetes even in the genetically homogeneous Japanese population. The data also indicate that the G191D mutation in TCF1 plays little, if any, role in susceptibility to common type 2 diabetes in the Japanese.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s005920050120
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  • 24
    Electronic Resource
    Electronic Resource
    The effect of genotype on response thresholds to sucrose and foraging behavior of honey bees (Apis mellifera L.) (1998)
    Springer
    Journal of comparative physiology 182 (1998), S. 489-500 
    Details
    ISSN: 1432-1351
    Keywords: Key words Honey bee ; Behavior ; Genetics ; Neurobiology ; Foraging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Honey bee foragers were tested for their proboscis extension response (PER) to water and varying solutions of sucrose. Returning pollen and nectar foragers were collected at the entrance of a colony and were assayed in the laboratory. Pollen foragers had a significantly higher probability of responding to water and to lower concentrations of sucrose. Bees derived from artificially selected high- and low-pollen-hoarding strains were also tested using the proboscis extension assay. Returning foragers were captured and tested for PERs to 30% sucrose. Results demonstrated a genotypic effect on PERs of returning foragers. The PERs of departing high- and low-strain foragers were consistent with those of returning foragers. The PERs were related to nectar and water reward perception of foragers. High strain bees were more likely to return with loads of water and lower concentrations of sucrose than foragers from the low pollen strain. Low-strain bees were more likely to return empty. We identified a previously mapped genomic region that contains a variable quantitative trait locus that appears to influence sucrose response thresholds. These studies demonstrate a gene-brain-behavior pathway that can be altered as a consequence of colony-level selection for quantities of stored food.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003590050196
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  • 25
    Electronic Resource
    Electronic Resource
    Genetics of psoriasis (1998)
    Springer
    Archives of dermatological research 290 (1998), S. 463-476 
    Details
    ISSN: 1432-069X
    Keywords: Key words Psoriasis ; Genetics ; HLA ; Linkage ; Epidemiology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Non-pustular psoriasis consists of two disease subtypes, type I and type II, which demonstrate distinct characteristics. Firstly the disease presents in different decades of life, in type I before the age of 40 years and later in type II. Secondly, contrasting frequencies of HLA alleles are found: type I patients express predominantly HLA-Cw6, -B57, and -DR7, whereas in type II patients HLA-Cw2 is overrepresented. Finally, familial inheritance is found in type I but not in type II psoriasis. The study of concomitant diseases in psoriasis contributes to deciphering the distinct patterns of the disease. Defence against invading microorganisms seems better developed in psoriatics than in controls. This evolutionary benefit may have caused the overall high incidence of psoriasis of 2%. Psoriasis is a multifactorial and heterogenetically inherited disease. The heterogeneity is evident by the diversity of genetically linked markers. The multifactorial component results from the observation of external trigger mechanisms, such as the Koebner phenomenon, stress and the intake of certain drugs. Twin studies have shown that environmental factors contribute to the onset of the disease. In type I psoriasis, special extended haplotypes such as EH57.1 (HLA-Cw6-B57-DRB1*0701-DQA1*0201-DQBl*0303) and EH65.1 (HLA-Cw8-B65-DRB1*0102-DQB1*0501) have been found to be increased. The application of microsatellite techniques has identified distinct positions on several chromosomes at which putative psoriasis genes may be located. Disease susceptibility genes are thought to be present on chromosomes 4q, 6p, 16q, 17q and 20p. Moreover, on chromosome 1q, genes regulating epidermal differentiation have been identified. Linkage to this area has been proposed. Furthermore, psoriasis gene loci on chromosomes 2, 8 and 20 have been suggested.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004030050338
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  • 26
    Electronic Resource
    Electronic Resource
    Recent advances in genetic research on schizophrenia (1998)
    Springer
    Journal of biomedical science 5 (1998), S. 28-30 
    Details
    ISSN: 1423-0127
    Keywords: Genetics ; Schizophrenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Evidence for genetic factors in schizophrenia is reviewed with regard to family, twin and adoption studies, and recent advances in molecular genetic technology are applied to explore possible gene loci susceptible to schizophrenia. Application of neuropsychological and neuroimaging methodologies are also reviewed with an aim to develop criteria for defining phenotypes for genetic studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02253353
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  • 27
    Electronic Resource
    Electronic Resource
    Prediction of febrile seizures in siblings: a practical approach (1998)
    Springer
    European journal of pediatrics 157 (1998), S. 340-344 
    Details
    ISSN: 1432-1076
    Keywords: Key words Febrile seizures ; Genetics ; Family ; Risk factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To quantify the risk of febrile seizures (FS) in relatives of children with FS and to predict the risk of FS in siblings, we calculated cumulative risks of FS in first degree relatives of 129 children with FS. The study was conducted as a prospective follow up study of FS recurrences at the outpatient clinic of the Sophia Children's Hospital in Rotterdam. Thirteen parents and 12 siblings had experienced FS, accounting for a 6-year cumulative risk of 7%. The risk of FS was increased in relatives of children with recurrent FS (12%). The risk of FS in siblings (10%) in our study was more than twice the average risk in a similar population (4%). A positive FS history in a parent, young age at onset in the proband, and recurrences in the proband were selected in a multivariable prediction model. If two or more of these risk factors were present, the risk of West European siblings to develop FS was 46% (hazard ratio 5.4). Conclusion The cumulative risk of FS in siblings of children with FS is increased. The age attained risk of FS can be estimated using a practical model incorporating three readily available risk factors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004310050824
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  • 28
    Electronic Resource
    Electronic Resource
    Paternal age is a risk factor for Alzheimer disease in the absence of a major gene (1998)
    Springer
    Neurogenetics 1 (1998), S. 277-280 
    Details
    ISSN: 1364-6753
    Keywords: Key words Alzheimer disease ; Risk factors ; Parental age ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: ABSTRACT We compared the parental age at birth of patients with Alzheimer disease (AD) with that of cognitively healthy control subjects. Within 206 carefully diagnosed AD patients, two groups were distinguished according to the likelihood of carrying a major gene for AD (MGAD). This likelihood was calculated by applying a Bayesian approach which incorporates data on aggregation of the disease, age at onset, and "censoring" ages within the family. All AD patients were ranked by MGAD probability. According to the sample's quartiles, two subgroups were defined representing the 52 individuals with the lowest and the 52 with the highest MGAD probability. Age at onset of dementia, education, and apolipoprotein E ε  4 allele frequencies were not statistically different between the two groups. Fathers of patients with a low MGAD probability were significantly older (35.7±8.1 years) than fathers of both other groups (high MGAD probability 31.3±6.9 years, P =0.004; controls 32.6±6.8 years, P =0.04, n=50). The differences for mothers were less pronounced and not statistically significant. These findings suggest that increased paternal age is a risk factor for AD in the absence of a major gene, whereas increased maternal age and AD are associated only weakly and independently of genetic disposition.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s100480050041
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  • 29
    Electronic Resource
    Electronic Resource
    Recent progress in the genetics of human epilepsies (1998)
    Springer
    Neurogenetics 1 (1998), S. 153-163 
    Details
    ISSN: 1364-6753
    Keywords: Key words Epilepsy ; Genetics ; Linkage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: ABSTRACT Despite several lines of evidence indicating a strong genetic influence in the etiology of idiopathic epilepsies, progress in the mapping and identification of human epilepsy genes has been limited until recently. In addition to the localisation and/or isolation of several genes causing progressive epilepsies associated with cerebral degeneration, at least seven human genomic regions (6p, 8q, 10q, 15q, 16p, 19q, 20q) are now known to harbour genes implicated in idiopathic epilepsies. In the case of nocturnal frontal lobe epilepsy, mutations in a nicotinic acetylcholine receptor subunit gene have been identified. Systematic studies of rare epileptic disorders inherited as monogenic Mendelian traits, as well as studies on more complex polygenic idiopathic epilepsies, are still needed in order to identify all the epilepsy genes. This will allow better diagnosis and genetic counseling in families of affected individuals, a better understanding of both the pathophysiology of epilepsies and normal brain functioning, and the design of new pharmacological and genetic therapies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s100480050024
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  • 30
    Electronic Resource
    Electronic Resource
    Microsatellite DNA in Actinidia chinensis: isolation, characterisation, and homology in related species (1998)
    Springer
    Theoretical and applied genetics 97 (1998), S. 1269-1278 
    Details
    ISSN: 1432-2242
    Keywords: Key words Simple sequence repeat (SSR) ; Microsatellites ; Molecular markers ; Genetics ; Kiwifruit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  We have isolated and sequenced 263 microsatellite-containing clones from two small insert libraries of Actinidia chinensis enriched for (AC/GT) and (AG/CT) repeats, respectively. Primer pairs were designed for 203 microsatellite loci and successfully amplified from both plasmid and A. chinensis genomic DNA. In this paper we report the sequences of 40 primer pairs for which we have demonstrated Mendelian segregation in the progeny from controlled crosses. The polymorphism of ten microsatellites of each type was evaluated in four diploid and six tetraploid genotypes of A. chinensis. All microsatellites proved to be polymorphic, the number of alleles per locus detected in polyacrylamide sequencing gels ranging from 9 to 17. The high degree of polymorphism in Actinidia renders these markers useful either for mapping in A. chinensis or for fingerprinting cultivars of both domesticated kiwifruit species (A. chinensis and A. deliciosa). While most primer pairs produced single amplification products, about 20% generated banding patterns consistent with the amplification of two different loci. This supports the hypothesis that diploid species of Actinidia (2n=2x=58) are polyploid in origin with a basic chromosome number x=14/15 and that chromosome duplication may have occurred during the evolution of the genus. Finally, we have assayed the cross-species transportability of primer pairs designed from A. chinensis sequences and have found extensive cross-species amplification within the genus Actinidia; 75% of primer pairs gave successful amplification in the eight species assayed (A. arguta, A. rufa, A. polygama, A. chrysantha, A. callosa, A. hemsleyana, A. eriantha, and A. deliciosa), which are representative of the four sections into which the genus is currently split.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001220051019
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  • 31
    Electronic Resource
    Electronic Resource
    Fruit tree genetics at a turning point: the almond example (1998)
    Springer
    Theoretical and applied genetics 96 (1998), S. 588-601 
    Details
    ISSN: 1432-2242
    Keywords: Key words Fruit trees ; Genetics ; Almond ; Prunus amygdalus ; Breeding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  The large size and the long generation time of fruit trees generally reduce the possibilities of obtaining genetic information on the transmission and heritability of useful agronomic traits in these species. However, from breeding work carried out with fruit trees, an important amount of data is now available, although large differences are apparent among the different species. There is not much information known about almond compared to what is available on other Prunus fruit species, but more data have been accumulated on it than on most of the other nut trees, thus making almond special among all the temperate fruit and nut species. Only five qualitative traits have been described in almond, with an additional two also possibly qualitative. Heritabilities have been estimated for an important number of quantitative traits, mainly phenological times and fruit characters. Important information is available on molecular markers, including enzymes, RFLPs, RAPDs and other recently developed markers. Linkages, however, have only been established among molecular markers, allowing accurate genetic maps to be built but not yet enabling agronomical characters to be located in these maps, probably because the latter have not been sufficiently studied. The effectiveness of the application of genetic maps in plant breeding will depend on the accuracy of the study of different agronomic traits and their expression, implying more field work and recognition of this work. Ultimately, any new fruit cultivar has to be grown in the field and has to allow the grower to make a profit.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001220050777
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  • 32
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    Electronic Resource
    Cytological basis for a tetraspory in Cupressus sempervirens L. megagametogenesis and its implications in genetic studies (1998)
    Springer
    Theoretical and applied genetics 96 (1998), S. 776-779 
    Details
    ISSN: 1432-2242
    Keywords: Key words Cupressus sempervirens ; Cytology ; Megasporogenesis ; Megagametogenesis ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  The processes of megasporogenesis and early megagametogenesis were cytologically investigated in Cupressus sempervirens L. in order to elucidate, at the cellular level, the origin of the megagametophyte. After pollination, sporogenous tissue developed in the chalazal region of the nucellus, but only one megaspore mother cell differentiated and divided meiotically without cell-wall formation. This led to the development of a cell with four nuclei which directly functioned as a megaspore. The C. sempervirens megagametophyte is thus tetrasporic, in contrast to the majority of conifers where the megagametophyte is monosporic. The consequenses of this observation are discussed from a genetics point of view.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001220050801
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  • 33
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    Electronic Resource
    Patient regrets after bilateral prophylactic mastectomy (1998)
    Springer
    Annals of surgical oncology 5 (1998), S. 603-606 
    Details
    ISSN: 1534-4681
    Keywords: Breast cancer ; Genetics ; Prophylactic mastectomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The discovery of a cadre of breast cancer susceptibility genes has resulted in an increase in the number of women seeking information about prophylactic breast surgery, but virtually no large-scale prospective databases exist to assist women considering prophylactic mastectomy. Methods: The authors constructed a National Prophylactic Mastectomy Registry comprised of a volunteer population of 817 women from 43 states who have undergone prophylactic mastectomy. Results: In the registry, 370 women had undergone bilateral prophylactic mastectomy. Twenty-one (5%) women expressed regrets about the procedure. The median follow-up was 14.6 years (mean 14.8 years; range 0.2–51 years). Those with regrets were subsetted into those with major (n=10) or minor (n=7) regrets. Regrets were more common in those women with whom discussion about prophylactic mastectomy was initiated by a physician (19/255), compared with patients who initiated the discussion themselves (2/108;P〈.05). Conclusions: The overall satisfaction rate of 95% reported here may be explained by the voluntary nature of this registry. The most important factor that predicts an unfavorable outcome following bilateral prophylactic mastectomy is a physician-initiated discussion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02303829
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  • 34
    Electronic Resource
    Electronic Resource
    Autosomal recessive polycystic kidney disease (1998)
    Springer
    Journal of molecular medicine 76 (1998), S. 303-309 
    Details
    ISSN: 1432-1440
    Keywords: Key words Autosomal recessive polycystic kidney disease ; Linkage study ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Autosomal recessive polycystic kidney disease (ARPKD) is a rare inherited disorder which usually becomes clinically manifest in early childhood, although the spectrum of ARPKD is much more variable than generally known. Presentation of ARPKD at later ages and survival into adulthood have been observed in many cases. The responsible gene has been mapped to chromosome 6p. Thus there is no evidence of genetic heterogeneity. The most important indication for DNA diagnosis is the prenatal diagnosis in families with at least one affected child. The critical region has been narrowed with the use of recombinant families of about 4 cM. Several possible candidate genes have been excluded.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001090050221
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    The possibilities of modeling neural networks in the framework of the thermodynamics of genetically disordered systems (glasses) (1998)
    Springer
    Journal of biological physics 24 (1998), S. 41-58 
    Details
    ISSN: 1573-0689
    Keywords: Neural networks ; Associative memory ; Brain functions ; Disordered systems ; Genetics ; Synergetics ; Self-organization ; Vitreous state
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Abstract Non-spin glasses possess a number of specific features which, in structural and dynamic aspects, are close to conditions necessary for neural networks to function. In a disordered network there exists a plurality of structural parameters and a number of two-level states defined by double-well potentials. Their characteristics are specified by the conditions of glass formation, i.e. by genesis. The thermodynamic description of glass as a self-organizing system (that does not require introducing an interacting potential model) leads to an unambiguous conclusion that its frequency spectrum is predetermined by the structure, which is characterized by zero-point entropy. Glass is a natural system of oscillators which form a disordered network. In this sense, glass conforms to a known model of a disordered neural network formed by interconnected oscillators. If one assumes that in living organisms the structure of a neural network (the brain) is inherited according to a genetic mechanism, the quickness of learning and recognition of patterns, the stability of associative memory and other capabilities have to be inherited genetically. The more ordered a neural network formed by distinguishable neurons, the better its capabilities.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1005071706864
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    Genetic and Shared Environmental Influences on Adolescent BMI: Interactions with Race and Sex (1998)
    Springer
    Behavior genetics 28 (1998), S. 265-278 
    Details
    ISSN: 1573-3297
    Keywords: Genetics ; body mass index ; adolescents ; race ; sex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Psychology
    Notes: Abstract The present study uses a behavioral genetic design to investigate the genetic and environmental influences on variation in adolescent body mass index (BMI) and to determine whether the relative influences of genetic and environmental factors on variation in BMI are similar across racial groups and sexes. Data for the present study come from the National Longitudinal Study on Adolescent Health (Add Health), a large, nationally representative study of adolescent health and health-related behaviors. The Add Health sample contains a subset of sibling pairs that differs in levels of genetic relatedness, making it well suited for behavioral genetics analyses. The present study examines whether genetic and environmental influences on adolescent BMI are the same for males and females and for Black and White adolescents. Results indicate that genetic factors contribute substantially to individual differences in adolescent BMI, explaining between 45 and 85% of the variance in BMI. Furthermore, based on an analysis of opposite-sex sibling pairs, the genes that influence variation in adolescent BMI are similar for males and females. However, the relative importance of genetic and environmental influences on variation in BMI differs for males and females and for Blacks and Whites. Although parameter estimates could be constrained to be equal for Black and White males, they could not be constrained to be equal for Black and White females. Moreover, the best-fitting model for Black females was an ADE model, for White females it was an ACE model, and for males it was an AE model. Thus, shared environmental influences are significant for White female adolescents, but not for Black females or males. Likewise, nonadditive genetic influences are indicated for Black females, but not for White females or males. Implications of these results are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1021619329904
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    Neuronal ceroid lipofuscinoses: a review (1998)
    Springer
    Neurological sciences 19 (1998), S. 271-276 
    Details
    ISSN: 1590-3478
    Keywords: Neuronal ceroid lipofuscinosis ; Clinical features ; Classification ; Diagnosis ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Sommario Le ceroido lipofuscinosi neuronali (NCL) sono tra le encefalopatie progressive più freguenti nell'infanzia ed interessano, seppure più raramente, l'adulto. Clinicamente sono caratterizzate da demenza, deficit visivo, epilessia e disturbi motori. Gli aspetti patologici specifici sono rappresentati da degenerazione neuronale ed accumulo lisosomiale di lipopigmento in differenti tipi cellulari. Il difetto biochimico della malattia non e noto. La classificazione delle NCL, basata su criteri clinici, distingue sei forme classiche ed altre forme atipiche. L'elettrofisiologia e la neuroradiologia sono di importante ausilio diagnostico, ma la diagnosi si fonda sull'identificazione dell'accumulo di lipopigmento the presenta pattern ultrastrutturali specifici. Differenti difetti genetici sono stati dimostrati in diverse forme cliniche, ma il meccanismo patogenetico molecolare rimane ancora da chiarire.
    Notes: Abstract Neuronal ceroid lipofuscinoses (NCLs) are among the most common neurodegenerative diseases in childhood but rarely present in adulthood. The main symptoms are psychomotor deterioration, visual failure, epilepsy and motor disturbances. The NCLs are morphologically characterized by the accumulation of lipopigments within numerous cell types and loss of neurons. Pathogenesis is unknown. The current clinical classification recognizes six classic types of NCL and several atypical forms. Electrophysiological and neuroradiological findings may be of diagnostic significance, but disease recognition rests on the demonstration of a typical ultrastructural pattern. Genetic studies have demonstrated that several different genetic loci are involved in the pathogenesis of NCL, but the molecular mechanisms underlying neuronal death and lipopigment accumulation are not understood.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00713852
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    Characterization of receptors with a new negative image: Use in molecular docking and lead optimization (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 30 (1998), S. 321-336 
    Details
    ISSN: 0887-3585
    Keywords: surface characterization ; DOCK ; structure-based molecular design ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The characterization of receptor binding sites is an important aspect of molecular docking, molecular recognition, and the structure-based design process. This characterization can take several forms: the receptor surface itself can be delineated or described, the space adjacent to the surface can be chemically mapped, or a negative image of the protein binding region can be generated. In this report, we describe a new method of constructing a negative image through generation of a set of spheres. These spheres lie along the receptor surface, and their centers represent possible ligand atom positions. By the method in which they are constructed, these spheres carry a limited amount of energetic and chemical information in addition to their primary geometric information. We test the accuracy of the image by comparing sphere positions to the positions of bound ligand atoms and propose a figure of merit for such tests. Then, we use the spheres to orient ligands in enzyme active sites and show how they can be used to generate low scoring configurations more efficiently than other approaches that search orientation space. In addition, two novel applications of these spheres are described: they are used to help identify structural differences among families of enzymes and to suggest points for ligand modification in analog design. Proteins 30:321-336, 1998. © 1998 Wiley-Liss, Inc.
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    Nitric oxide myoglobin: Crystal structure and analysis of ligand geometry (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 30 (1998), S. 352-356 
    Details
    ISSN: 0887-3585
    Keywords: myoglobin ; nitric oxide ; ligand binding ; X-ray crystallography ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The structure of the ferrous nitric oxide form of native sperm whale myoglobin has been determined by X-ray crystallography to 1.7 Å resolution. The nitric oxide ligand is bent with respect to the heme plane: the Fe-N-O angle is 112°. This angle is smaller than those observed in model compounds and in lupin leghemoglobin. The exact angle appears to be influenced by the strength of the proximal bond and hydrogen bonding interactions between the distal histidine and the bound ligand. Specifically, the Nε atom of histidine64 is located 2.8 Å away from the nitrogen atom of the bound ligand, implying electrostatic stabilization of the FeNO complex. This interpretation is supported by mutagenesis studies. When histidine64 is replaced with apolar amino acids, the rate of nitric oxide dissociation from myoglobin increases tenfold. Proteins 30:352-356, 1998. © 1998 Wiley-Liss, Inc.
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    A general method of domain closure is applied to phosphoglycerate kinase and the result compared with the crystal structure of a closed conformation of the enzyme (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 30 (1998), S. 372-380 
    Details
    ISSN: 0887-3585
    Keywords: protein modeling ; crystal structure ; conformation change ; prediction ; mechanism ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The occurrence of large domain motions associated with the mechanism of action of many proteins is well established. We present a general method of predicting domain closure applicable to proteins containing domains separated by an apparent hinge. The method attempts to allow for natural directional bias within the closing protein by repeatedly applying a weak pulling force over a short distance between pairs of atoms chosen at random in the two domains in question. Appropriate parameters governing the pulling function were determined empirically. The method was applied to the bi-lobal protein PGK and a closed-form activated ternary complex generated for Bacillus stearothermophilus PGK. This model was compared with the recently determined crystal structure of closed-form Trypanosoma brucei PGK. The model predicts the correct hinge regions, although the magnitude of movement at one hinge point was overestimated, and provides a reasonable representation of the closed-form ternary complex. Proteins 30:372-380, 1998. © 1998 Wiley-Liss, Inc.
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    Improved protein free energy calculation by more accurate treatment of nonbonded energy: Application to chymotrypsin inhibitor 2, V57A (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 30 (1998), S. 388-400 
    Details
    ISSN: 0887-3585
    Keywords: molecular dynamics ; free energy perturbation ; thermodynamics integration ; spherical solvent boundary potential ; cell multipole method ; Nosé-Hoover equation ; component analysis ; chymotrypsin inhibitor 2 ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: We developed a software package for improved free energy calculation, in which spherical solvent boundary potential, cell multipole method, and Nosé-Hoover equation are employed. The performance of the developed software package is demonstrated in the case of valine to alanine mutation of the 57th residue in chymotrypsin inhibitor 2. By using this package, we obtained results quantitatively comparable to experimental results. By the free energy component analysis, it is shown that leucine 51, arginine 65, arginine 67, and phenylalanine 69 residues contribute significantly to the total free energy shift, ΔΔG. Among them, contribution from the hydrophilic arginine 67 residue, which is in close contact with the mutation site, is the largest. Structure around the mutation site is largely changed by the mutation. The structure change is caused mainly by two effects, hydrophobic interaction and short-range interaction along the sequence. Effects of Nosé-Hoover algorithm and Kirkwood reaction field are also discussed. Proteins 30:388-400, 1998. © 1998 Wiley-Liss, Inc.
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    Proteolysis as a probe of thermal unfolding of cytochrome C (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 30 (1998), S. 435-441 
    Details
    ISSN: 0887-3585
    Keywords: cytochrome c ; thermal unfolding ; proteolysis ; proteinase K ; thermolysin ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Recent hydrogen exchange experiments on native cytochrome c implicate a sequential unfolding pathway in contrast to a simple two-state process. We have studied the heat-induced unfolding of this protein by using spectroscopic measurements to detect changes in conformation and proteolytic enzyme digestion to identify regions of the protein that are labile. Several spectroscopic profiles were monitored: CD at 222 nm, a measurement of secondary structure change in the protein, the absorbance at 280 nm, involving the local environment of Trp 59, and absorbance at 420 nm, the Soret band of the heme. The apparent Tm values for these probes differ, consistent with an unfolding pathway containing intermediates. The limited digestion by proteinase K is consistent with population of an intermediate state in unfolding. We find a single strong region of cleavage at low temperature with retention of structure in each fragment. Proteins 30:435-441, 1998. © 1998 Wiley-Liss, Inc.
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  • 43
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    Crystallographic and spectroscopic characterization of a molecular hinge: Conformational changes in bothropstoxin I, a dimeric Lys49-phospholipase A2 homologue (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 30 (1998), S. 442-454 
    Details
    ISSN: 0887-3585
    Keywords: venom toxin ; protein-membrane interaction ; X-ray diffraction ; spectroscopy ; quaternary structural change ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Bothropstoxin I (BthTX-I) from the venom of Bothrops jararacussuis a myotoxic phospholipase A2 (PLA2) homologue which, although catalytically inactive due to an Asp49→Lys substitution, disrupts the integrity of lipid membranes by a Ca2+-independent mechanism. The crystal structures of two dimeric forms of BthTX-I which diffract X-rays to resolutions of 3.1 and 2.1 Å have been determined. The monomers in both structures are related by an almost perfect twofold axis of rotation and the dimer interfaces are defined by contacts between the N-terminal α-helical regions and the tips of the β-wings of partner monomers. Significant differences in the relative orientation of the monomers in the two crystal forms results in “open” and “closed” dimer conformations. Spectroscopic investigations of BthTX-I in solution have correlated these conformational differences with changes in the intrinsic fluorescence emission of the single tryptophan residues located at the dimer interface. The possible relevance of this structural transition in the Ca2+-independent membrane damaging activity is discussed. Proteins 30:442-454, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
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    Electronic Resource
    Structure-based design of model proteins (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 31 (1998), S. 10-20 
    Details
    ISSN: 0887-3585
    Keywords: protein design ; lattice model ; protein stability ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A structure-based, sequence-design procedure is proposed in which one considers a set of decoy structures that compete significantly with the target structure in being low energy conformations. The decoy structures are chosen to have strong overlaps in contacts with the putative native state. The procedure allows the design of sequences with large and small stability gaps in a random-bond heteropolymer model in both two and three dimensions by an appropriate assignment of the contact energies to both the native and nonnative contacts. The design procedure is also successfully applied to the two-dimensional HP model. Proteins 31:10-20, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
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    Modelling repressor proteins docking to DNA (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 33 (1998), S. 535-549 
    Details
    ISSN: 0887-3585
    Keywords: docking ; protein-DNA ; prediction ; structure ; base recognition ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The docking of repressor proteins to DNA starting from the unbound protein and model-built DNA coordinates is modeled computationally. The approach was evaluated on eight repressor/DNA complexes that employed different modes for protein/ DNA recognition. The global search is based on a protein-protein docking algorithm that evaluates shape and electrostatic complementarity, which was modified to consider the importance of electrostatic features in DNA-protein recognition. Complexes were then ranked by an empirical score for the observed amino acid /nucleotide pairings (i.e., protein-DNA pair potentials) derived from a database of 20 protein/DNA complexes. A good prediction had at least 65% of the correct contacts modeled. This approach was able to identify a good solution at rank four or better for three out of the eight complexes. Predicted complexes were filtered by a distance constraint based on experimental data defining the DNA footprint. This improved coverage to four out of eight complexes having a good model at rank four or better. The additional use of amino acid mutagenesis and phylogenetic data defining residues on the repressor resulted in between 2 and 27 models that would have to be examined to find a good solution for seven of the eight test systems. This study shows that starting with unbound coordinates one can predict three-dimensional models for protein/DNA complexes that do not involve gross conformational changes on association. Proteins 33:535-549, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
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  • 46
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    Influence of protein structure databases on the predictive power of statistical pair potentials (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 31 (1998), S. 139-149 
    Details
    ISSN: 0887-3585
    Keywords: protein structure ; statistical potentials ; protein structure database ; assessing protein models ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A long standing goal in protein structure studies is the development of reliable energy functions that can be used both to verify protein models derived from experimental constraints as well as for theoretical protein folding and inverse folding computer experiments. In that respect, knowledge-based statistical pair potentials have attracted considerable interests recently mainly because they include the essential features of protein structures as well as solvent effects at a low computing cost. However, the basis on which statistical potentials are derived have been questioned. In this paper, we investigate statistical pair potentials derived from protein three-dimensional structures, addressing in particular questions related to the form of these potentials, as well as to the content of the database from which they are derived. We have shown that statistical pair potentials depend on the size of the proteins included in the database, and that this dependence can be reduced by considering only pairs of residue close in space (i.e., with a cutoff of 8 Å). We have shown also that statistical potentials carry a memory of the quality of the database in terms of the amount and diversity of secondary structure it contains. We find, for example, that potentials derived from a database containing α-proteins will only perform best on α-proteins in fold recognition computer experiments. We believe that this is an overall weakness of these potentials, which must be kept in mind when constructing a database. Proteins 31:139-149, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
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  • 47
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    Crystal structure of the disulfide-stabilized Fv fragment of anticancer antibody B1: Conformational influence of an engineered disulfide bond (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 31 (1998), S. 128-138 
    Details
    ISSN: 0887-3585
    Keywords: antibody ; antitumor ; single chain Fv ; variable domains ; X-ray crystallography ; protein structure ; protein stability ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A recombinant Fv construct of the B1 monoclonal antibody that recognizes the LewisY-related carbohydrate epitope on human carcinoma cells has been prepared. The Fv is composed of the polypeptide chains of the VH and VL domains expressed independently and isolated as inclusion bodies. The Fv is prepared by combining and refolding equimolar amounts of guanidine chloride solubilized inclusion bodies. The Fv is stabilized by an engineered interchain disulfide bridge between residues VL100 and VH44. This construct has a similar binding affinity as that of the single-chain construct (Benhar and Pastan, Clin. Cancer Res. 1:1023-1029, 1995). The B1 disulfide-stabilized Fv (B1dsFv) crystallizes in space group P6122 with the unit cell parameters a = b = 80.1 Å, and c = 138.1 Å. The crystal structure of the B1dsFv has been determined at 2.1-Å resolution using the molecular replacement technique. The final structure has a crystallographic R-value of 0.187 with a root mean square deviation in bond distance of 0.014 Å and in bond angle of 2.74°. Comparisons of the B1dsFv structure with known structures of Fv regions of other immunoglobulin fragments shows closely related secondary and tertiary structures. The antigen combining site of B1dsFv is a deep depression 10-Å wide and 17-Å long with the walls of the depression composed of residues, many of which are tyrosines, from complementarity determining regions L1, L3, H1, H2, and H3. Model building studies indicate that the LewisY tetrasaccharide, Fuc-Gal-Nag-Fuc, can be accommodated in the antigen combining site in a manner consistent with the epitope predicted in earlier biochemical studies (Pastan, Lovelace, Gallo, Rutherford, Magnani, and Willingham, Cancer Res. 51:3781-3787, 1991). Thus, the engineered disulfide bridge appears to cause little, if any, distortion in the Fv structure, making it an effective substitute for the B1 Fab. Proteins 31:128-138, 1998. Published 1998 Wiley-Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America.
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    Interaction of transmembrane helices by a knobs-into-holes packing characteristic of soluble coiled coils (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 31 (1998), S. 150-159 
    Details
    ISSN: 0887-3585
    Keywords: photosynthetic reaction center ; bacteriorhodopsin ; cytochrome C oxidase ; zipper ; packing ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Membrane-embedded protein domains frequently exist as α-helical bundles, as exemplified by photosynthetic reaction centers, bacteriorhodopsin, and cytochrome C oxidase. The sidechain packing between their transmembrane helices was investigated by a nearest-neighbor analysis which identified sets of interfacial residues for each analyzed helix-helix interface. For the left-handed helix-helix pairs, the interfacial residues almost exclusively occupy positions a, d, e, or g within a heptad motif (abcdefg) which is repeated two to three times for each interacting helical surface. The connectivity between the interfacial residues of adjacent helices conforms to the knobs-into-holes type of sidechain packing known from soluble coiled coils. These results demonstrate on a quantitative basis that the geometry of sidechain packing is similar for left-handed helix-helix pairs embedded in membranes and coiled coils of soluble proteins. The transmembrane helix-helix interfaces studied are somewhat less compact and regular as compared to soluble coiled coils and tolerate all hydrophobic amino acid types to similar degrees. The results are discussed with respect to previous experimental findings which demonstrate that specific interactions between transmembrane helices are important for membrane protein folding and/or oligomerization. Proteins 31:150-159, 1998. © 1998 Wiley-Liss, Inc.
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    Protein folding in the landscape perspective: Chevron plots and non-arrhenius kinetics (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 30 (1998), S. 2-33 
    Details
    ISSN: 0887-3585
    Keywords: chevron plot ; energy landscape ; folding funnel ; kinetic trap ; lattice models ; non-Arrhenius behavior ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: We use two simple models and the energy landscape perspective to study protein folding kinetics. A major challenge has been to use the landscape perspective to interpret experimental data, which requires ensemble averaging over the microscopic trajectories usually observed in such models. Here, because of the simplicity of the model, this can be achieved. The kinetics of protein folding falls into two classes: multiple-exponential and two-state (single-exponential) kinetics. Experiments show that two-state relaxation times have “chevron plot” dependences on denaturant and non-Arrhenius dependences on temperature. We find that HP and HP+ models can account for these behaviors. The HP model often gives bumpy landscapes with many kinetic traps and multiple-exponental behavior, whereas the HP+ model gives more smooth funnels and two-state behavior. Multiple-exponential kinetics often involves fast collapse into kinetic traps and slower barrier climbing out of the traps. Two-state kinetics often involves entropic barriers where conformational searching limits the folding speed. Transition states and activation barriers need not define a single conformation; they can involve a broad ensemble of the conformations searched on the way to the native state. We find that unfolding is not always a direct reversal of the folding process. Proteins 30:2-33, 1998. © 1998 Wiley-Liss, Inc.
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  • 50
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    Feature-extraction from endopeptidase cleavage sites in mitochondrial targeting peptides (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 30 (1998), S. 49-60 
    Details
    ISSN: 0887-3585
    Keywords: kohonen network ; mitochondrial processing peptidase (MPP) ; mitochondrial intermediate peptidase (MIP) ; neural network ; protein import ; sequence motif ; mitochondrial targeting ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Cleavage sites in nuclear-encoded mitochondrial protein targeting peptides (mTPs) from mammals, yeast, and plants have been analysed for characteristic physicochemical features using statistical methods, perceptrons, multilayer neural networks, and self-organizing feature maps. Three different sequence motifs were found, revealing loosely defined arginine motifs with Arg in positions -10, -3, and -2. A self-organizing feature map was able to cluster these three types of endopeptidase target sites but did not identify any species-specific characteristics in mTPs. Neural networks were used to define local sequence features around precursor cleavage sites. Proteins 30:49-60, 1998. © 1998 Wiley-Liss, Inc.
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    Don Caspar, TMV, and protein-protein interactions (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 30 (1998), S. 109-112 
    Details
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: No abstract.
    Additional Material: 2 Ill.
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    A hybrid sequence approach to the paracelsus challenge (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 30 (1998), S. 136-143 
    Details
    ISSN: 0887-3585
    Keywords: protein design ; protein structure ; circular dichroism ; trifluoroethanol ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Inspired by the Paracelsus Challenge of Rose and Creamer (Proteins 19:1-3, 1994), we have designed a protein sequence that is 50% identical to an all-helical protein but is intended to fold into a largely β-sheet structure. Rather than attempt a de novo design, our strategy was to construct a hybrid sequence based on a helical “parent” protein (434 Cro) and a “target” protein with the desired fold (the B1 domain of protein G). The hybrid sequence (Crotein-G) is 50% identical to 434 Cro but is also 62% identical to the B1 domain of protein G. We also created a variant of Crotein-G (ZCrotein-G) that contains a potential His3Cys1 zinc binding site. At low protein concentrations and in the presence of 20% 2,2,2-trifluoroethanol (TFE) (v/v), the circular dichroism spectra of the designed proteins are distinct from that of 434 Cro and similar to that of the B1 domain of protein G. However, the proteins fail to denature in a cooperative manner. Furthermore, aggregation occurs at moderate protein concentrations or in the absence of TFE. Addition of zinc to ZCrotein-G does not promote structure formation. In summary, 434 Cro has been altered to something that may resemble the B1 domain of protein G, but the protein does not adopt a native structure. Proteins 30:136-143, 1998. © 1998 Wiley-Liss, Inc.
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    Monte Carlo simulation of denaturation of adsorbed proteins (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 30 (1998), S. 168-176 
    Details
    ISSN: 0887-3585
    Keywords: denaturation kinetics ; irreversible conformational changes ; metastable states ; folding temperature ; lattice model ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Denaturation of model proteinlike molecules at the liquid-solid interface is simulated over a wide temperature range by employing the lattice Monte Carlo technique. Initially, the molecule containing 27 monomers of two types (A and B) is assumed to be adsorbed in the native folded state (a 3 × 3 × 3 cube) so that one of its sides is in contact with the surface. The details of the denaturation kinetics are found to be slightly dependent on the choice of the side, but the main qualitative conclusions hold for all the sides. In particular, the kinetics obey approximately the conventional first-order law at T 〉 Tc (Tc is the collapse temperature for solution). With decreasing temperature, below Tc but above Tf (Tf is the folding temperature for solution), deviations appear from the first-order kinetics. For the most interesting temperatures, that is, below Tf, the denaturation kinetics are shown to be qualitatively different from the conventional ones. In particular, the denaturation process occurs via several intermediate steps due to trapping in metastable states. Mathematically, this means that (i) the transition to the denatured state of a given molecule is nonexponential, and (ii) the denaturation process cannot be described by a single rate constant kr. One should rather introduce a distribution of values of this rate constant (different values of kr correspond to the transitions to the altered state via different metastable states). Proteins 30:168-176, 1998. © 1998 Wiley-Liss, Inc.
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    Monte Carlo simulation of the kinetics of protein adsorption (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 30 (1998), S. 177-182 
    Details
    ISSN: 0887-3585
    Keywords: adsorption ; irreversible conformational changes ; denaturation rate constant ; kinetic control ; diffusion control ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Adsorption of proteins occurs via diffusion toward the interface, actual adsorption, and subsequent irreversible conformational changes resulting in denaturation of the native protein structure. The conventional kinetic models describing these steps are based on the assumption that the denaturation transitions obey the first-order law with a single value of the denaturation rate constant kr. Meanwhile, recent Monte Carlo simulations indicate that, in general, the denaturation process cannot be described by a single rate constant kr. One should rather introduce a distribution of this rate constant (physically, different values of kr correspond to the transitions to the altered state via different metastable states). We have calculated the kinetics of irreversible adsorption of proteins with and without distribution of the denaturation rate constant kr in the limits when protein diffusion in the solution is, respectively, rapid or slow. In both cases, the adsorption kinetics with distribution of kr are found to be close to those with a single-valued rate constant kr provided that the average value of kr in the former case is equal to kr for the latter case. This conclusion holds even for wide distributions of kr. The consequences of this finding for the fitting of global experimental kinetics on the basis of phenomenological equations are briefly discussed. Proteins 30:177-182, 1998. © 1998 Wiley-Liss, Inc.
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    Structural diversity of sequentially identical subsequences of proteins: Identical octapeptides can have different conformations (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 30 (1998), S. 228-231 
    Details
    ISSN: 0887-3585
    Keywords: protein folding ; local vs. non-local interactions ; secondary structure prediction ; fragment matching algorithms ; PDB ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: One of the most important questions in the protein folding problem is whether secondary structures are formed entirely by local interactions. One way to answer this question is to compare identical subsequences of proteins to see if they have identical structures. Such an exercise would also reveal a lower limit on the number of amino acids needed to form unique secondary structures. In this context, we have searched the April 1996 release of the Protein Data Bank for sequentially identical subsequences of proteins and compared their structures. We find that identical octamers can have different conformations. In addition, there are several examples of identical heptamers with different conformations, and the number of identical hexamers with different conformations has increased since the previous PDB releases. These observations imply that secondary structure can be formed entirely by non-local interactions and that an identical match of up to eight amino acids may not imply structural similarity. In addition to the larger context of the protein folding problem, these observations have implications for protein structure prediction methods. Proteins 30:228-231, 1998. © 1998 Wiley-Liss, Inc.
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    Structural modeling of the complex between an acetylcholine receptor-mimicking antibody and its snake toxin antigen (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 30 (1998), S. 249-263 
    Details
    ISSN: 0887-3585
    Keywords: antibody-antigen complex ; snake toxin ; protein docking ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The antibody Mα2-3 neutralizes the functional, acetylcholine receptor binding activity of its antigen, neurotoxin α, and exhibits several other properties in common with the receptor itself. We present here the results of calculations examining the three-dimensional structure of the toxin α:Mα2-3 complex. The antigen structure, determined by nuclear magnetic resonance spectroscopy,1 was docked to models of the variable fragment of the antibody combining site2 by using a method based on surface complementarity and maximization of buried surface area3,4 while taking into account the possibility of conformational change on complexation. Extensive experimental information on the location of the functional epitope was incorporated into the analysis and used to screen candidate geometries of the complex resulting from the modeling. Eight plausible structures that are in accord with the experimental data were derived. Common structural features of the models are discussed, and residues of the antibody-combining site that are expected to play important roles in complexation are identified. In particular, three epitope residues that, according to mutagenesis experiments, make particularly strong contributions to the binding, interact excentrically and do not make contact with the central loops of the combining site, L3 and H3. Proteins 30:249-263, 1998. © 1998 Wiley-Liss, Inc.
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    Tertiary structure prediction of the KIX domain of CBP using Monte Carlo simulations driven by restraints derived from multiple sequence alignments (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 30 (1998), S. 287-294 
    Details
    ISSN: 0887-3585
    Keywords: protein structure prediction ; side chain contact prediction ; lattice protein models ; CREB-binding protein ; KIX domain ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Using a recently developed protein folding algorithm, a prediction of the tertiary structure of the KIX domain of the CREB binding protein is described. The method incorporates predicted secondary and tertiary restraints derived from multiple sequence alignments in a reduced protein model whose conformational space is explored by Monte Carlo dynamics. Secondary structure restraints are provided by the PHD secondary structure prediction algorithm that was modified for the presence of predicted U-turns, i.e., regions where the chain reverses global direction. Tertiary restraints are obtained via a two-step process: First, seed side-chain contacts are identified from a correlated mutation analysis, and then, a threading-based algorithm expands the number of these seed contacts. Blind predictions indicate that the KIX domain is a putative three-helix bundle, although the chirality of the bundle could not be uniquely determined. The expected root-mean-square deviation for the correct chirality of the KIX domain is between 5.0 and 6.2 Å. This is to be compared with the estimate of 12.9 Å that would be expected by a random prediction, using the model of F. Cohen and M. Sternberg (J. Mol. Biol. 138:321-333, 1980). Proteins 30:287-294, 1998. © 1998 Wiley-Liss, Inc.
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    Mass spectrometric identification and microcharacterization of proteins from electrophoretic gels: Strategies and applications (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 33 (1998), S. 74-89 
    Details
    ISSN: 0887-3585
    Keywords: mass spectrometry ; matrix-assisted laser desorption/ionization ; electrospray ; database searching ; gel electrophoresis ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The entire genomic DNA sequences of a number of prokaryotic and eukaryotic species are now available and many more, including the human genome, will be completed in the near future. The state-of-life of a cell at any given time, however, is defined by its protein composition, i.e., its proteome. Gel electrophoresis, mass spectrometry, and bioinformatics will be important tools for protein and proteome analysis in the post-genome era. Protein identification from electrophoretic gels by mass spectrometric peptide mapping or peptide sequencing combined with sequence database searching is established and has been applied to numerous biological systems. We describe current strategies and selected applications in molecular and cell biology. The next challenges are detailed structure/function analyses, which include studying the molecular composition of multiprotein complexes and characterization of secondary modifications of proteins. The advantages and limitations of a number of mass spectrometry-based strategies designed for microcharacterization of low amounts of protein from electrophoretic gels are discussed and illustrated by examples. Proteins Suppl. 2:74-89, 1998. © 1998 Wiley-Liss, Inc.
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    A fusion protein between serum amyloid A and staphylococcal nuclease - synthesis, purification, and structural studies (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 30 (1998), S. 381-387 
    Details
    ISSN: 0887-3585
    Keywords: serum amyloid A ; fluorescence ; circular dichroism ; acute phase ; denaturation ; nuclease ; amyloidosis ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: We developed a recombinant DNA system to overexpress a fusion protein between the small, minimally soluble acute phase serum protein, serum amyloid A (SAA), and the bacterial enzyme staphylococcal nuclease (SN). This fusion protein is very soluble and is immunoreactive to polyclonal anti-SAA antibodies. Tryptophan fluorescence shows smooth denaturation curves for the fusion protein in guanidinium HCl or potassium thiocyanate. Fluorescence also indicates that only a single tryptophan residue (of the four present) is accessible to iodide quenching and, presumably, is exposed on the surface of the fusion protein. Circular dichroism (CD) shows a significant signal indicating α-helix, which can be attributed to the SAA portion of the molecule; these are the first CD spectral data available for SAA. pH titration shows persistence of helix domains for the fusion protein at pH 3.0, in contrast to the denaturation of SN under the same conditions. (The entire fusion protein shows a random coil pattern below pH 3.0.) By exploiting the structural and solubility properties of SN, this fusion protein has provided the first structural data about SAA - the precursor of the amyloid deposits in secondary amyloidosis. This fusion protein should be useful for further physical and physiologic studies of SAA. Proteins 30:381-387, 1998. © 1998 Wiley-Liss, Inc.
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    The PDP: Past, present, and future (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 30 (1998), S. 1-1 
    Details
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: No abstract.
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    Direct observation of an altered quaternary-structure transition in a mutant aspartate transcarbamoylase (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 31 (1998), S. 383-390 
    Details
    ISSN: 0887-3585
    Keywords: time-resolved small-angle X-ray scattering ; allosterism ; domain closure ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Time-resolved small-angle X-ray scattering (TR-SAXS) was used to monitor the structural changes that occur upon the binding of the natural substrates to a mutant version of the allosteric enzyme aspartate transcarbamoylase from Escherichia coli, in which the creation of a critical link stabilizing the R state of the enzyme is hindered. Previously, SAXS experiments at equilibrium showed that the structures of the unligated mutant enzyme and the mutant enzyme saturated with a bisubstrate analog are indistinguishable from the T and R state structures, respectively, of the wild-type enzyme (Tauc et al., Protein Sci. 3:1998-2004, 1994). However, as opposed to the wild-type enzyme, the combination of one substrate, carbamoyl phosphate, and succinate, an analog of aspartate, did not convert the mutant enzyme into the R state. By using TR-SAXS we have been able to study the transient steady-state during catalysis using the natural substrates rather than the nonreactive substrate analogs. The steady-state in the presence of saturating amount of substrates is a mixture of 60% T and 40% R structures, which is further converted entirely to R in the additional presence of ATP. These results provide a structural explanation for the reduced cooperativity observed with the mutant enzyme as well as for the stimulation by ATP at saturating concentrations of substrates. They also illustrate the crucial role played by domain motions and quaternary-structure changes for both the homotropic and heterotropic aspects of allostery. Proteins 31:383-390, 1998. © 1998 Wiley-Liss, Inc.
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    Structural investigation of C4b-binding protein by molecular modeling: Localization of putative binding sites (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 31 (1998), S. 391-405 
    Details
    ISSN: 0887-3585
    Keywords: complement control protein ; protein modeling ; blood coagulation ; C4b-binding protein ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: C4b-binding protein (C4BP) contributes to the regulation of the classical pathway of the complement system and plays an important role in blood coagulation. The main human C4BP isoform is composed of one β-chain and seven α-chains essentially built from three and eight complement control protein (CCP) modules, respectively, followed by a nonrepeat carboxy-terminal region involved in polymerization of the chains. C4BP is known to interact with heparin, C4b, complement factor I, serum amyloid P component, streptococcal Arp and Sir proteins, and factor VIII/VIIIa via its α-chains and with protein S through its β-chain. The principal aim of the present study was to localize regions of C4BP involved in the interaction with C4b, Arp, and heparin. For this purpose, a computer model of the 8 CCP modules of C4BP α-chain was constructed, taking into account data from previous electron microscopy (EM) studies. This structure was investigated in the context of known and/or new experimental data. Analysis of the α-chain model, together with monoclonal antibody studies and heparin binding experiments, suggests that a patch of positively charged residues, at the interface between the first and second CCP modules, plays an important role in the interaction between C4BP and C4b/Arp/Sir/heparin. Putative binding sites, secondary-structure prediction for the central core, and an overall reevaluation of the size of the C4BP molecule are also presented. An understanding of these intermolecular interactions should contribute to the rational design of potential therapeutic agents aiming at interfering specifically some of these protein-protein interactions. Proteins 31:391-405, 1998. © 1998 Wiley-Liss, Inc.
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    Species dependence of enzyme-substrate encounter rates for triose phosphate isomerases (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 31 (1998), S. 406-416 
    Details
    ISSN: 0887-3585
    Keywords: electrostatics ; Brownian dynamics ; triose phosphate isomerase ; diffusion-control ; similarity index ; rate enhancement ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Triose phosphate isomerase (TIM) is a diffusion-controlled enzyme whose rate is limited by the diffusional encounter of the negatively charged substrate glyceraldehyde 3-phosphate (GAP) with the homodimeric enzyme's active sites. Translational and orientational steering of GAP toward the active sites by the electrostatic field of chicken muscle TIM has been observed in previous Brownian dynamics (BD) simulations. Here we report simulations of the association of GAP with TIMs from four species with net charges at pH 7 varying from -12e to +12e. Computed second-order rate constants are in good agreement with experimental data. The BD simulations and computation of average Boltzmann factors of substrate-protein interaction energies show that the protein electrostatic potential enhances the rates for all the enzymes. There is much less variation in the computed rates than might be expected on the basis of the net charges. Comparison of the electrostatic potentials by means of similarity indices shows that this is due to conservation of the local electrostatic potentials around the active sites which are the primary determinants of electrostatic steering of the substrate. Proteins 31:406-416, 1998. © 1998 Wiley-Liss, Inc.
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    Functional conformational changes of endo-1,4-xylanase II from Trichoderma reesei: A molecular dynamics study (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 31 (1998), S. 434-444 
    Details
    ISSN: 0887-3585
    Keywords: hinge ; structural change ; xylose ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Recent crystallographic studies have revealed a range of structural changes in the three-dimensional structure of endo-1,4-xylanase (XYNII) from Trichoderma reesei. The observed conformational changes can be described as snapshots of an open-close movement of the active site of XYNII. These structures were further analyzed in this study. In addition, a total of four 1 ns molecular dynamics (MD) simulations were performed representing different states of the enzyme. A comparison of the global and local changes found in the X-ray structures and the MD runs suggested that the simulations reproduced a similar kind of active site opening and closing as predicted by the crystal structures. The open-close movement was characterized by the use of distance difference matrixes and the Hingefind program (Wriggers and Schulten, Proteins 29:1-14, 1997) to be a ‘hinge-bending’ motion involving two large rigidly-moving regions and an extended hinge. This conformational feature is probably inherent to this molecular architecture and probably plays a role in the function of XYNII. Proteins 31:434-444, 1998. © 1998 Wiley-Liss, Inc.
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    Interaction of human SRY protein with DNA: A molecular dynamics study (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 31 (1998), S. 417-433 
    Details
    ISSN: 0887-3585
    Keywords: molecular dynamics ; sex-determining region Y (SRY) protein ; high mobility group (HMG) box ; DNA-binding proteins ; DNA bending ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Molecular dynamics simulations have been conducted to study the interaction of human sex-determining region Y (hSRY) protein with DNA. For this purpose, simulations of the hSRY high mobility group (HMG) domain (hSRY-HMG) with and without its DNA target site, a DNA octamer, and the DNA octamer alone have been carried out, employing the NMR solution structure of hSRY-HMG-DNA complex as a starting model. Analyses of the simulation results demonstrated that the interaction between hSRY and DNA was hydrophobic, just a few hydrogen bonds and only one water molecule as hydrogen-bonding bridge were observed at the protein-DNA interface. These two hydrophobic cores in the hSRY-HMG domain were the physical basis of hSRY-HMG-DNA specific interaction. They not only maintained the stability of the complex, but also primarily caused the DNA deformation. The salt bridges formed between the positive-charged residues of hSRY and phosphate groups of DNA made the phosphate electroneutral, which was advantageous for the deformation of DNA and the formation of a stable complex. We predicted the structure of hSRY-HMG domain in the free state and found that both hSRY and DNA changed their conformations to achieve greater complementarity of geometries and properties during the binding process; that is, the protein increased the angle between its long and short arms to accommodate the DNA, and the DNA became bent severely to adapt to the protein, although the conformational change of DNA was more severe than that of the hSRY-HMG domain. The sequence specificity and the role of residue Met9 are also discussed. Proteins 31:417-433, 1998. © 1998 Wiley-Liss, Inc.
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    Density functional studies on herpes simplex virus type 1 thymidine kinase-substrate interactions: The role of Tyr-172 and Met-128 in thymine fixation (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 31 (1998), S. 453-459 
    Details
    ISSN: 0887-3585
    Keywords: quantum mechanical calculations ; substrate-enzyme interactions ; mutants ; functional role of amino acids ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The enzyme herpes simplex virus type 1 thymidine kinase (HSV1 TK) salvages thymidine into the DNA metabolism of the virus. In the active site, the thymine ring of the nucleoside binds in a pocket, formed by two residues, Tyr-172 and Met-128, in a sandwich-type orientation. To investigate the nature of the thymine-enzyme pocket interactions, we have carried out density functional theory calculations with gradient-corrected exchange-correlation functionals of models of the thymine-HSV1 TK adduct. Our calculations indicate that the role of Met-128 in the substrate fixation is purely steric and hydrophobic, while the substrate-Tyr-172 interaction is essentially electrostatic in nature. These findings are completely consistent with the available catalytic properties of mutants on the 128 position. Proteins 31:453-459, 1998. © 1998 Wiley-Liss, Inc.
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    Electrostatics, allostery, and activity of the yeast chorismate mutase (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 31 (1998), S. 445-452 
    Details
    ISSN: 0887-3585
    Keywords: chorismate mutase ; activity ; allosteric ; electrostatics ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The predicted active site of chorismate mutase of baker's yeast Saccharomyces cerevisiae has been studied by continuum electrostatics, molecular surface/volume calculations, and molecular modeling. Our study shows that despite being subject to an allosteric transition, the enzyme's active-site pocket neither decreased in volume nor deformed significantly in shape between the active R state and the inactive T state. We find that the polar atmosphere in the pocket is responsible for the enzyme's affinity. A single amino acid, Glu23, can adequately account for the atmospheric variation. This residue swings into the active-site pocket from the R state to the T state. In the R state, Glu23 on helix H2 doubly pairs with Arg204 and Lys208 of H11, which is packed against H2. In the T state, a slide occurs between H11 and H2 such that Glu23 can no longer interact with Lys208 and competes with Asp24 for interacting with Arg204. Consequently, Glu23 is found in the T state to couple with Arg157, an active-site residue critical to substrate binding. The tandem sliding of H11 in both monomers profoundly changes the interactions in the dimer interface. The loop between H11 and H12 demonstrates the largest conformational change. Hence, we establish a connection between the allosteric transition and the activity of the enzyme. The conformational change in the transition is suggested to propagate into the active-site pocket via a series of polar interactions that result in polarity reversal in the active-site pocket, which regulates the enzyme's activity. Proteins 31:445-452, 1998. © 1998 Wiley-Liss, Inc.
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    Evidence of new cadmium binding sites in recombinant horse L-chain ferritin by anomalous Fourier difference map calculation (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 31 (1998), S. 477-485 
    Details
    ISSN: 0887-3585
    Keywords: X-ray structure ; L-chain apoferritin ; metal binding sites ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: We refined the structure of the tetragonal form of recombinant horse L-chain apoferritin to 2.0 Å and we compared it with that of the cubic form previously refined to the same resolution. The major differences between the two structures concern the cadmium ions bound to the residues E130 at the threefold axes of the molecule. Taking advantage of the significant anomalous signal (f′′ = 3.6 e-) of cadmium at 1.375 Å, the wavelength used here, we performed anomalous Fourier difference maps with the refined model phases. These maps reveal the positions of anomalous scatterers at different locations in the structure. Among these, some are found near residues that were known previously to bind metal ions, C48, E57, C126, D127, E130, and H132. But new cadmium binding sites are evidenced near residues E53, E56, E57, E60, and H114, which were suggested to be involved in the iron loading process. The quality of the anomalous Fourier difference map increases significantly with noncrystallographic symmetry map averaging. Such maps reveal density peaks that fit the positions of Met and Cys sulfur atoms, which are weak anomalous scatterers (f′′ = 0.44 e-). Proteins 31:477-485, 1998. © 1998 Wiley-Liss, Inc.
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    The biology workbench - A seamless database and analysis environment for the biologist (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 32 (1998), S. 1-2 
    Details
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: No abstract.
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    Calculation of HyHel10-lysozyme binding free energy changes: Effect of ten point mutations (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 33 (1998), S. 39-48 
    Details
    ISSN: 0887-3585
    Keywords: antibody ; antigen ; electrostatics ; binding ; finite difference ; Poisson-Boltzmann ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The change in free energy of binding of hen egg white lysozyme (HEL) to the antibody HyHel-10 arising from ten point mutations in HEL (D101K, D101G, K96M, K97D, K97G, K97G, R21E, R21K, W62Y, and W63Y) was calculated using a combination of the finite difference Poisson-Boltzmann method for the electrostatic contribution, a solvent accessible surface area term for the non-polar contribution, and rotamer counting for the sidechain entropy contribution. Comparison of experimental and calculated results indicate that because of pKa shifts in some of the mutated residues, primarily those involving Aspartate or Glutamate, proton uptake or release occurs in binding. When this effect was incorporated into the binding free energy calculations, the agreement with experiment improved significantly, and resulted in a mean error of about 1.9 kcal/mole. Thus these calculations predict that there should be a significant pH dependence to the change in binding caused by these mutations. The other major contributions to binding energy changes comes from solvation and charge charge interactions, which tend to oppose each other. Smaller contributions come from nonpolar interactions and sidechain entropy changes. The structures of the HyHel-10-HEL complexes with mutant HEL were obtained by modeling, and the effect of the modeled structure on the calculations was also examined. “Knowledge based” modeling and automatic generation of models using molecular mechanics produced comparable results. Proteins 33:39-48, 1998. © 1998 Wiley-Liss, Inc.
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    Crystal structure of a complex formed between proteolytically-generated lactoferrin fragment and proteinase KAtomic coordinates have been deposited with the Protein Data Bank, Brookhaven National Laboratory. (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 33 (1998), S. 30-38 
    Details
    ISSN: 0887-3585
    Keywords: lactoferrin ; proteinase K ; complex, hydrolysis ; structure ; inhibitor ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Lactoferrin is an iron binding glycoprotein with a molecular weight of 80 kDa. The molecule is divided into two lobes representing the N-terminal and C-terminal halves of the polypeptide chain, each containing an iron binding site. The serine proteinases such as trypsin, chymotrypsin, and pepsin hydrolyze lactoferrin into two unequal halves while proteinase K divides this protein into two equal halves. In the first step of hydrolysis by proteinase K, the C- and N-lobes, each having a molecular weight of approximately 40 kDa, are generated. In the next step, the lobes are further hydrolyzed into small molecular weight peptides. The proteinase K isolated from the hydrolyzed product does not show enzymatic activity suggesting that the enzyme is inhibited. Furthermore, the hydrolysis experiments on N-lobe and C-lobe showed that the inhibitory fragment came from the C-lobe. The purified lactoferrin fragment was found to be a decapeptide with an amino acid sequence of H2N-Val-Ala-Gln-Gly-Ala-Ala-Gly-Leu-Ala-COOH. The complex formed between proteinase K and lactoferrin fragment was crystallized by microdialysis. The crystals belonged to the monoclinic space group P21with cell dimensions a = 44.4 Å, b = 38.6 Å, c = 79.2 Å, β = 105.8o and Z = 2. The crystal structure has been determined at 2.4 Å resolution. It has been refined to an R factor of 0.163 for 9044 reflections. The Lf-fragment forms several intermolecular interactions with proteinase K. The Ser-224 Oγ and His-57 Nε2 move away to a distance of 3.68 Å in the complex. In the crystal structure, Gln-3I (I indicates inhibitor i.e., lactoferrin fragment) is involved in a direct intermolecular interaction with a symmetry related proteinase K molecule through a strong hydrogen bond with Asp-254. The mode of intermolecular interactions in the complex conformational features of the enzyme and placement of the fragment with respect to the enzyme resemble with the molecular complex of proteinase K with its natural inhibitor PKI3 from wheat. Proteins 33:30-38, 1998. © 1998 Wiley-Liss, Inc.
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    Dictionary of recurrent domains in protein structures (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 33 (1998), S. 88-96 
    Details
    ISSN: 0887-3585
    Keywords: fold classification ; substructures ; Dali ; protein families ; structural similarity ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The rapid growth in the number of experimentally determined three-dimensional protein structures has sharpened the need for comprehensive and up-to-date surveys of known structures. Classic work on protein structure classification has made it clear that a structural survey is best carried out at the level of domains, i.e., substructures that recur in evolution as functional units in different protein contexts. We present a method for automated domain identification from protein structure atomic coordinates based on quantitative measures of compactness and, as the new element, recurrence. Compactness criteria are used to recursively divide a protein into a series of successively smaller and smaller substructures. Recurrence criteria are used to select an optimal size level of these substructures, so that many of the chosen substructures are common to different proteins at a high level of statistical significance. The joint application of these criteria automatically yields consistent domain definitions between remote homologs, a result difficult to achieve using compactness criteria alone. The method is applied to a representative set of 1,137 sequence-unique protein families covering 6,500 known structures. Clustering of the resulting set of domains (substructures) yields 594 distinct fold classes (types of substructures). The Dali Domain Dictionary (http://www.embl-ebi.ac.uk/dali) not only provides a global structural classification, but also a comprehensive description of families of protein sequences grouped around representative proteins of known structure. The classification will be continuously updated and can serve as a basis for improving our understanding of protein evolution and function and for evolving optimal strategies to complete the map of all natural protein structures. Proteins 33:88-96, 1998. © 1998 Wiley-Liss, Inc.
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    Crystal structures of HLA-A*0201 complexed with antigenic peptides with either the amino- or carboxyl-terminal group substituted by a methyl group (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 33 (1998), S. 97-106 
    Details
    ISSN: 0887-3585
    Keywords: antigenic peptides ; class I MHC molecules ; HLA-A2 complexes ; hydrogen bonds ; protein structure ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The crystal structures of class I major histocompatibility complex (MHC) molecules complexed with antigenic peptides revealed a network of hydrogen bonds between the charged amino- and carboxyl-termini of the peptides and conserved MHC residues at both ends of the peptide binding site. These interactions were shown to contribute substantially to the stability of class I MHC/peptide complexes by thermal denaturation studies using synthetic peptides in which either the amino- or carboxyl-terminal group is substituted by a methyl group. Here we report crystal structures of HLA-A*0201 complexed with these terminally modified synthetic peptides showing that they adopt the same bound conformation as antigenic peptides. A number of variations in peptide conformation were observed for the terminally modified peptides, including in one case, a large conformational difference in four central peptide residues that is apparently caused by the lattice contact. This is reminiscent of the way binding a T-cell receptor changed the conformation of central residues of an MHC-bound peptide. The structures determined identify which conserved hydrogen bonds are eliminated in terminally substituted peptides and suggest an increased energetic importance of the interactions at the peptide termini for MHC-peptide stability. Proteins 33:97-106, 1998. © 1998 Wiley-Liss, Inc.
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    AmbiPack: A systematic algorithm for packing of macromolecular structures with ambiguous distance constraints (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 32 (1998), S. 26-42 
    Details
    ISSN: 0887-3585
    Keywords: intermolecular restraints ; solid-state NMR ; symmetric multimer ; branch and bound ; amyloid ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The determination of structures of multimers presents interesting new challenges. The structure(s) of the individual monomers must be found and the transformations to produce the packing interfaces must be described. A substantial difficulty results from ambiguities in assigning intermolecular distance measurements (from nuclear magnetic resonance, for example) to particular intermolecular interfaces in the structure. Here we present a rapid and efficient method to solve the packing and the assignment problems simultaneously given rigid monomer structures and (potentially ambiguous) intermolecular distance measurements. A promising application of this algorithm is to couple it with a monomer searching protocol such that each monomer structure consistent with intramolecular constraints can be subsequently input to the current algorithm to check whether it is consistent with (potentially ambiguous) intermolecular constraints. The algorithm AmbiPack uses a hierarchical division of the search space and the branch-and-bound algorithm to eliminate infeasible regions of the space. Local search methods are then focused on the remaining space. The algorithm generally runs faster as more constraints are included because more regions of the search space can be eliminated. This is not the case for other methods, for which additional constraints increase the complexity of the search space. The algorithm presented is guaranteed to find all solutions to a predetermined resolution. This resolution can be chosen arbitrarily to produce outputs at various level of detail. Illustrative applications are presented for the P22 tailspike protein (a trimer) and portions of β-amyloid (an ordered aggregate). Proteins 32:26-42, 1998. © 1998 Wiley-Liss, Inc.
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    Accuracy of side-chain prediction upon near-native protein backbones generated by ab initio folding methods (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 33 (1998), S. 204-217 
    Details
    ISSN: 0887-3585
    Keywords: rotamer libraries ; energy minimization ; self consistent mean-field theory ; torsion space ; modeling ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The ab initio folding problem can be divided into two sequential tasks of approximately equal computational complexity: the generation of native-like backbone folds and the positioning of side chains upon these backbones. The prediction of side-chain conformation in this context is challenging, because at best only the near-native global fold of the protein is known. To test the effect of displacements in the protein backbones on side-chain prediction for folds generated ab initio, sets of near-native backbones (≤ 4 Å Cα RMS error) for four small proteins were generated by two methods. The steric environment surrounding each residue was probed by placing the side chains in the native conformation on each of these decoys, followed by torsion-space optimization to remove steric clashes on a rigid backbone. We observe that on average 40% of the χ1 angles were displaced by 40° or more, effectively setting the limits in accuracy for side-chain modeling under these conditions. Three different algorithms were subsequently used for prediction of side-chain conformation. The average prediction accuracy for the three methods was remarkably similar: 49% to 51% of the χ1 angles were predicted correctly overall (33% to 36% of the χ1+2 angles). Interestingly, when the inter-side-chain interactions were disregarded, the mean accuracy increased. A consensus approach is described, in which side-chain conformations are defined based on the most frequently predicted χ angles for a given method upon each set of near-native backbones. We find that consensus modeling, which de facto includes backbone flexibility, improves side-chain prediction: χ1 accuracy improved to 51-54% (36-42% of χ1+2). Implications of a consensus method for ab initio protein structure prediction are discussed. Proteins 33:204-217, 1998. © 1998 Wiley-Liss, Inc.
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    Molecular dynamics simulations of human carbonic anhydrase II: Insight into experimental results and the role of solvation (1998)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 33 (1998), S. 119-134 
    Details
    ISSN: 0887-3585
    Keywords: molecular modeling ; proton transfer ; enzyme catalysis ; mutations ; molecular mechanics ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: In this paper, the carbonic anhydrase II (CA II) enzyme active site is modeled using ab initio calculations and molecular dynamics simulations to examine a number of important issues for the enzyme function. It is found that the Zn2+ ion is dominantly tetrahedrally coordinated, which agrees with X-ray crystallographic studies. However, a transient five-fold coordination with an extra water molecule is also found. Studies of His64 conformations upon a change in the protonation states of the Zn-bound water and the His64 residue also confirm the results of an X-ray study which suggest that the His64 conformation is quite flexible. However, the degree of water solvation is found to affect this behavior. Water bridge formation between the Zn-bound water and the His64 residue was found to involve a free energy barrier of 2-3 kcal/mol and an average lifetime of several picoseconds, which supports the concept of a proton transfer mechanism through such a bridge. Mutations of various residues around the active site provide further insight into the corresponding experimental results and, in fact, suggest an important role for the solvent water molecules in the CA II catalytic mechanism. Proteins 33:119-134, 1998. © 1998 Wiley-Liss, Inc.
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    Synthesis, homopolymerization, and block copolymerization of N-ethyl-2-ethynyl-pyridinium trifluoromethanesulfonate with styrene and butadiene (1998)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part A: Polymer Chemistry 36 (1998), S. 703-712 
    Details
    ISSN: 0887-624X
    Keywords: synthesis ; homopolymerization ; block copolymerization ; N-ethyl-2-ethyl-pyridinium ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A novel acetylenic monomer 2-N-ethyl pyridinium trifluoromethane sulfonate (2EPyEtTf) was synthesized and polymerized. Diblock copolymers of 2EPyEtTf with styrene and with butadiene were prepared. Initiation of the polymerization by living anionic polystyryl--Li+ and polybutadienyl--Li+ (Scheme 1) resulted in polystyrene-block-poly(N-ethyl-2-ethynylpyridinium trifluoromethanesulfonate) (PS57PA8), and polybutadiene -block-poly(N-ethyl-2-ethynylpyridinium trifluoromethanesulfonate) (PB30PA8). These amphiphilic block molecules contain rigid, conjugated, and strongly hydrophilic polyacetylene chain fragments attached to hydrophobic polystyrene or flexible polybutadiene chain fragments. The structure of these copolymers was studied by FTIR, UV-visible, and NMR spectroscopy. GPC and viscometry were also used to obtain information on the molecular mass and the molecular mass distribution. Thermal behavior was investigated by means of TGA and DSC. Both block copolymers were shown to form stable monolayers at the air-water interface. The positively charged rigid polyacetylene portion of the copolymer is believed to be partially submerged, while the more flexible hydrophobic chains are forced out of the water. Multilayers of PB30PA8 deposited using the Langmuir-Blodgett technique were found to be less uniform than in the case of the previously reported polystyrene-block-poly(2EPyMeTf) (PS12PA4) copolymer (Balogh et al., Macromolecules, 29, 1996). Polycation-polyanion self-assembly deposition was also investigated, using polystyrenesulfonate (PSS) as polyanion. While PS57PA8/PSS layer-by-layer deposition was not uniform, it was found that PB30PA8/PSS gave homogenous and stable films on hydrophilic glass substrates. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 703-712, 1998
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    Kinetics of the photoinitiated inverse microemulsion polymerization of 2-methacryloyl oxyethyl trimethyl ammonium chloride (1998)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part A: Polymer Chemistry 36 (1998), S. 737-748 
    Details
    ISSN: 0887-624X
    Keywords: inverse microemulsion polymerization ; MADQUAT ; nucleation ; photopolymerization ; molecular weights ; flocculants ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The polymerization of inverse microemulsions of 2-methacryloyl oxyethyl trimethyl ammonium chloride stabilized by a blend of nonionic emulsifiers (a sorbitan sesquioleate and a sorbitan monooleate) and initiated by UV light in the presence of Azobis(isobutyronitrile) (AIBN) was investigated. The effect of initiator concentration, light intensity, emulsifier concentration, and dispersed phase weight fraction on the polymerization rate (Rp), number of polymer particles (Np), and polymer molecular weight (Mw) was studied. The application of this process to tubular reactors is discussed. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 737-748, 1998
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    Molecular weight distribution of crosslinked polymers produced in emulsion (1998)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part A: Polymer Chemistry 36 (1998), S. 1127-1156 
    Details
    ISSN: 0887-624X
    Keywords: emulsion polymerization ; crosslinking and long-chain branching ; molecular weight distribution ; compartmentalization ; gel formation ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A kinetic model for evaluating the chain length distribution of a branched polymer produced in emulsion was developed. Chain branching occurring through any intermolecular mechanism is considered, namely, crosslinking, chain transfer to polymer and propagation to terminal double bond. The model accounts for active chain compartmentalization and, when coupled to a model able to describe the evolution of the polymerization system, allows evaluation of the cumulative properties of the produced polymer both in the pregel and postgel phases. The numerical difficulties related to the description of a rather wide polymer chain population and of gel formation are overcome by using the ‘numerical fractionation’ technique. A parametric analysis of both instantaneous and cumulative properties is reported and discussed, with special attention to the role of radical compartmentalization in determining the molecular weight properties of a polymer produced in emulsion. Significant differences with the molecular weights computed using models developed for homogeneous (non compartmentalized) systems have been found. A comparison with the predictions of Flory's statistical theory is also reported in terms of gel point and gel weight fraction. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 1127-1156, 1998
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    Cationic copolymerization of cyclic ketene acetals: The effect of substituents on reactivity (1998)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part A: Polymer Chemistry 36 (1998), S. 861-871 
    Details
    ISSN: 0887-624X
    Keywords: 2-methylene-1,3-dioxane ; 4-methyl-2-methylene-1,3-dioxane ; 4,4,6-trimethyl-2-methylene-1,3-dioxane ; 2-methylene-1,3-dioxolane ; 4-methyl-2-methylene-1,3-dioxolane ; 4,5-dimethyl-2-methylene-1,3-dioxolane ; cationic copolymerization ; reactivity ratio ; relative reactivity ; ring-retained polymerization ; cyclic ketene acetals ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Cationic copolymerizations of 4-methyl-2-methylene-1,3-dioxane, 2 (M1), with 2-methylene-1,3-dioxane, 1 (M2); of 4,4,6-trimethyl-2-methylene-1,3-dioxane, 3 (M1), with 2-methylene-1,3-dioxane, 1 (M2); of 4-methyl-2-methylene-1,3-dioxolane, 5 (M1), with 2-methylene-1,3-dioxolane, 4 (M2); and of 4,5-dimethyl-2-methylene-1,3-dioxolane, 6 (M1), with 2-methylene-1,3-dioxolane, 4 (M2) were conducted. The reactivity ratios for these four types of copolymerizations were r1 = 1.73 and r2 = 0.846; r1 = 2.26 and r2 = 0.310; r1 = 1.28 and r2 = 0.825; r1 = 2.23 and r2 = 0.515, respectively. The relative reactivities of these monomers towards cationic polymerization are: 3 〉 2 〉 1; and 6 〉 5 〉 4. With both five- and six-membered ring cyclic ketene acetals, the reactivity increased with increasing methyl substitution on the ring. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 861-871, 1998
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    Enzymatic activity of trypsin adsorbed on temperature-sensitive composite polymer particles (1998)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part A: Polymer Chemistry 36 (1998), S. 883-888 
    Details
    ISSN: 0887-624X
    Keywords: temperature sensitive ; particle ; emulsion polymerization ; morphology ; adsorption ; enzyme ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Two kinds of temperature-sensitive composite polymer particles were prepared by seeded emulsion copolymerizations of (dimethylamino)ethyl methacrylate and ethylene glycol dimethacrylate with 0.14 μm-sized polystyrene and 0.26 μm-sized poly(methylmethacrylate) seed particles. To evaluate the usefulness as a carrier for biomolecules, the enzymatic activities of trypsin adsorbed on these two composite polymer particles were measured at temperatures above and below each lower critical solution temperature (LCST). In both cases, adsorbed trypsin retained its enzymatic activity during repeated adsorption/desorption measurements. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 883-888, 1998
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    Synthesis of (1→6)-2,5-anhydro-D-glucitol through cyclopolymerization of 3,4-di-O-allyl-1,2 : 5,6-dianhydro-D-mannitol and optical resolution ability of its derivative in HPLC (1998)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part A: Polymer Chemistry 36 (1998), S. 901-909 
    Details
    ISSN: 0887-624X
    Keywords: (1→6)-2,5-anhydro-D-glucitol ; HPLC ; optical resolution ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The cyclopolymerization of 3,4-di-O-allyl-1,2 : 5,6-dianhydro-D-mannitol (1) was carried out using BF3·OEt2 and t-BuOK. The polymer obtained by the polymerization with BF3·OEt2 mainly consisted of (1→6)-bonded 3,4-di-O-allyl-2,5-anhydro-D-glucitol as the five-membered constitutional repeating unit, though it contained a small amount of other cyclic repeating units. On the other hand, during the polymerization using t-BuOK, the stereoregular polymer (1→6)-linked 3,4-di-O-allyl-2,5-anhydro-D-glucitol (2) was synthesized via a regio- and stereoselective mechanism. Cleavage of the allyl ether linkage in polymer 2 occurred to produce the polymer consisting of only 2,5-anhydro-D-glucitol units, i.e., (1→6)-2,5-anhydro-D-glucitol (3). Chromatographic enantioseparation of chloroquine and tröger base has been performed on (3,5-dimethylphenyl)carbamate and 4-methylbenzoate derivatives of 3 as a chiral stationary phase for high-performance liquid chromatography. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 901-909, 1998
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    Model structures of thermoplastic polyesters having regularly alternated aromatic and fluorinated segments (1998)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part A: Polymer Chemistry 36 (1998), S. 939-947 
    Details
    ISSN: 0887-624X
    Keywords: fluorine ; perfluoropolyether ; polyester ; segmented ; thermoplastic ; interfacial synthesis ; thermal transitions ; dynamic-mechanical properties ; chemical resistance ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Linear segmented polyesters containing soft perfluoropolyether (PFPE) and hard aromatic segments are obtained by an interfacial polycondensation reaction of an acyl chloride-ended fluorinated prepolymer with various aromatic diphenols in the presence of phase transfer catalysts (PTC) as accelerators. Experimental conditions for reaching high molecular weights are discussed. The calorimetric analysis (DSC) of all the polyesters synthesized shows a typical biphasic morphology, where a very low Tg (〈 -110°C) corresponding to the segregated PFPE moiety, is always accompanied by another Tg or a higher melting temperature, depending on the nature of the hard phase. Dynamic-mechanical analysis (DMA) has been carried out confirming the DSC results and suggesting diversified mechanical behaviors at the various temperatures in line with the amorphous or semicrystalline nature of the polymer. Chemical resistance was finally tested by dipping in several solvents and chemicals. The new polyesters show high contact angles, a moderate swelling in many organic solvents and excellent stability in aggressive hydrolytic environments. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 939-947, 1998
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    Thermosensitive lactitol-based polyether polyol (LPEP) hydrogels (1998)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part A: Polymer Chemistry 36 (1998), S. 979-984 
    Details
    ISSN: 0887-624X
    Keywords: lactitol ; hydrogel ; polyether polyol ; PEO and PPO linkage ; swelling degree ; thermosensitivity ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A series of new thermosensitive polymer hydrogels were prepared by reacting acylated poly(ethylene glycol) bis(carboxymethyl) ether (PEGBCOCl) with lactitol-based polyether polyols (LPEP). The polyether polyols were generated from propoxylation of lactitol and have molecular weights ranging from 1337 to 4055 g/mol. The hydrogels absorb water up to 1000% of their dry weight and expel free water at temperatures at and above 30°C. The wide ranging swelling behavior and excellent thermosensitivity depend closely on the degree of crosslinking and the propylene oxide lengths in the polyols. Differential scanning calorimetry of the hydrogels showed two endotherms associated with the phase transitions of PO and EO segments in the hydrogel structures. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 979-984, 1998
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    Kinetic and microstructure studies of poly(ethylene-co-p-methylstyrene) copolymers prepared by metallocene catalysts with constrained ligand geometry (1998)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part A: Polymer Chemistry 36 (1998), S. 1017-1029 
    Details
    ISSN: 0887-624X
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: This paper discusses the poly(ethylene-co-p-methylstyrene) copolymers prepared by metallocene catalysts, such as Et(Ind)2ZrCl2 and [C5Me4(SiMe2NtBu)]-TiCl2, with constrained ligand geometry. The copolymerization reaction was examined by comonomer reactivity (reactivity ratio and comonomer conversion versus time), copolymer microstructure (DSC and 13C-NMR analyses) and the comparisons between p-methylstyrene and other styrene-derivatives (styrene, o-methylstyrene and m-methylstyrene). The combined experimental results clearly show that p-methylstyrene performs distinctively better than styrene and its derivatives, due to the cationic coordination mechanism and spatially opened catalytic site in metallocene catalysts with constrained ligand geometry. A broad composition range of random poly(ethylene-co-p-methylstyrene)copolymers were prepared with narrow molecular weight and composition distributions. With the increase of p-methylstyrene concentration, poly(ethylene-co-p-ethylstyrene)copolymer shows systematical decrease of melting point and crystallinity and increase of glass transition temperature. At above 10 mol % of p-methylstyrene, the crystallinity of copolymer almost completely disappears. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 1017-1029, 1998
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    Synthesis and spinning of a thermotropic liquid crystal copolyester containing a semirigid cycloaliphatic spacer (1998)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part A: Polymer Chemistry 36 (1998), S. 1473-1480 
    Details
    ISSN: 0887-624X
    Keywords: thermotropic polymers ; liquid crystalline polymers ; semirigid spacers ; melt spinning ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A thermotropic, liquid crystalline copolyester, based on 2-chlorohydroquinone, 1,4-cyclohexanedimethanol and terephthaloyl chloride, has been synthesized and melt spun. The cyclohexanedimethylene moiety acts as a semirigid spacer, introducing flexibility while preserving the thermotropic nature of the polymer. Melt-spun fibers were observed to have a high degree of molecular alignment owing to the nematic nature of the melt. Both polymer and fiber properties have been characterized. Characterization techniques used to this end include elemental analysis, hot-stage polarized light microscopy, scanning electron microscopy, dilute solution viscometry, Fourier transform infrared spectroscopy, nuclear magnetic resonance, differential scanning calorimetry, and thermogravimetric analysis. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 1473-1480, 1998
    Additional Material: 9 Ill.
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  • 87
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    Electronic Resource
    Synthesis and properties of copolymers from 2-hydroxyethyl methacrylate-linked nonsteroidal antiinflammatory agents with methacrylic acid (1998)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part A: Polymer Chemistry 36 (1998), S. 1481-1490 
    Details
    ISSN: 0887-624X
    Keywords: ibuprofen ; ketoprofen ; naproxen ; copolymer reactivity ; thermal stability ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Three nonsteroidal antiinflammatory drugs, 2-(4-isobutylphenyl)-propionic acid (ibuprofen), 2-(3-benzoylphenyl)-propionic acid (ketoprofen), and 2-(6-methoxy-2-naphthyl)-propionic acid (naproxen), were covalently linked with 2-hydroxyethyl methacrylate (HEMA). The drug-linked HEMA (M1) (ibuprofen-linked HEMA abbreviated as HI; ketoprofen-linked HEMA as HK, and naproxen-linked HEMA as HN), were respectively copolymerized with methacrylic acid (M2), MA, to obtain macromolecular prodrugs. The compositions of the copolymers were determined by means of a 1H-NMR spectroscopy and monomer reactivity ratios were estimated using the Kelen-Tüdös linear differential equation. The reactivity ratios are: r1 = 0.101 ± 0.012, r2 = 1.071 ± 0.065 for HI-MA; r1 = 0.344 ± 0.066, r2 = 0.966 ± 0.032 for HN-MA, and r1 = 0.650 ± 0.182, r2 = 1.032 ± 0.106 for HK-MA, respectively. The monomer reactivity toward to MA radical estimated from 1/r2 values is almost same for all three monomers (1/r2 ∼ 1). The glass transition temperatures of three drug-linked homopolymers go hand in hand with the steric hindrance of three drugs, i.e., ketoprofen 〉 naproxen ≫ ibuprofen calculated the minimum energy by computer molecular modeling. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 1481-1490, 1998
    Additional Material: 8 Ill.
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  • 88
    Electronic Resource
    Electronic Resource
    Liquid chromatography of macromolecules at the critical adsorption point. II. Role of column packing: Bare silica gel (1998)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part A: Polymer Chemistry 36 (1998), S. 1363-1371 
    Details
    ISSN: 0887-624X
    Keywords: liquid chromatography ; column packing ; bare silica gel ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Liquid chromatography of macromolecules at the critical adsorption point (LC CAP) presents a potentially very powerful method for molecular characterization of complex polymers. However, LC CAP applicability is limited due to various experimental problems. The pore sizes and surface chemistry of the column packings belong to the most important weak points of the method. The LC CAP behavior of poly(methyl methacrylate)s was investigated using bare silica gels of 6, 12, and 100 nm pore sizes and with various amounts of surface silanols. Tetrahydrofuran as the adsorption suppressing liquid and toluene as the adsorption promoting liquid were mixed to form the “nearly critical” eluents. Both pore size and surface chemistry of silica were found to strongly influence the retentive characteristics of the system in the critical adsorption area. Macromolecules that were large enough to be excluded from the packing pores hardly followed the LC CAP rules: their retention volumes changed irregularly with the polymer molar mass and their recovery dropped sharply. The narrow pore silica gel-packed column governed the elution patterns of the whole column set composed of silica gels with different pore sizes. This makes the conventional LC CAP characterization of common polymers with broader molar mass distribution impractical and even not feasible. A hybrid column system was proposed containing narrow pore nonadsorptive column added in series to the meso- and macroporous LC CAP silica gels. This narrow pore column would allow separation of gas, impurities, and system peaks from the polymer peaks. The possible successive changes of the surface of silica gel, e.g., due to formation of silanols by hydrolysis or due to irreversible adsorption of some admixtures from the sample or eluent may make the LC CAP irrepeatable. Pronounced peak broadening was observed in the critical adsorption area and this effect increased strongly with the polymer molar mass. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 1363-1371, 1998
    Additional Material: 7 Ill.
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  • 89
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    Electronic Resource
    New polymer syntheses. XCVII. Hyperbranched LC-polyesters based on β-(4-hydroxyphenyl)propionic acid and 4-hydroxybenzoic acid (1998)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part A: Polymer Chemistry 36 (1998), S. 1397-1405 
    Details
    ISSN: 0887-624X
    Keywords: hyperbranched polyesters ; nematic phase ; phloritic acid ; vectra ; melt rheology ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Two classes of liquid crystalline hyperbranched copolyesters were prepared by the copolycondensation of silylated 3,5-bis(acetoxy)benzoic acid with mixtures of mesogenic difunctional monomers. The first class of LC-copolyesters was obtained from 1 : 1 mixtures (molar ratio) of silylated β-(4-acetoxyphenyl)propionic acid and silylated 4-acetoxybenzoic acid (poly(HPPA/HBA)). The second class of LC-copolyesters was obtained by additional copolycondensation of silylated 6-acetoxy-2-naphthoic acid. The hyperbranched copolyesters of this ternary system poly(HPPA/HBA/HNA) proved to be less crystalline in contrast to the binary system. In both classes of LC-copolyesters the degree of branching was varied via the feed ratio of 3,5-dihydroxybenzoic acid. A minimum segment length of 6 difunctional monomer units between the branching points is required to establish a nematic phase. However, a greater segment length is needed to obtain a homogeneous LC-phase. The poly(HPPA/HBA) copolyesters were also characterized by melt rheology. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 1397-1405, 1998
    Additional Material: 8 Ill.
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  • 90
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    Electronic Resource
    Polymerization of acrylates by atom transfer radical polymerization. Homopolymerization of 2-hydroxyethyl acrylate (1998)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part A: Polymer Chemistry 36 (1998), S. 1417-1424 
    Details
    ISSN: 0887-624X
    Keywords: 2-hydroxyethyl acrylate ; poly(2-hydroxyethyl acrylate) ; atom transfer radical polymerization (ATRP) ; controlled free radical polymerization ; MALDI-MS ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The application of atom transfer radical polymerization (ATRP) to the homopolymerization of 2-hydroxyethyl acrylate, a functional monomer, is reported. The polymerizations exhibit first-order kinetics, and molecular weights increase linearly with conversion. Polydispersities remain low throughout the polymerization (Mw/Mn ≈ 1.2). Reactions were conducted in bulk and in 1 : 1 (by volume) aqueous solution; the latter demonstrates the resilience of ATRP to protic media. Analysis of poly(2-hydroxyethyl acrylate) by MALDI-MS and 1H-NMR shows Mn,exp to be much closer to Mn,th than those observed by SEC using polystyrene standards. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 1417-1424, 1998
    Additional Material: 4 Ill.
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  • 91
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    Electronic Resource
    Unbridged bivalent lanthanidocenes for isotactic and stereomultiblock polymerization of methyl methacrylate (1998)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part A: Polymer Chemistry 36 (1998), S. 1599-1606 
    Details
    ISSN: 0887-624X
    Keywords: bivalent organolanthanides ; polymerization ; methyl methacrylate ; stereomultiblock polymer ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Bivalent organolanthanides with unbridged substituted indenyl or fluorenyl ligands (1-SiMe3Ind)2YTHF (I), (9-SiMe3Flu)2YTHF (II), were found to efficiently catalyze the stereoregular polymerization of methyl methacrylate. The microstructure of resultant polymers was shown to be dependent of a conformation that the ligands adopt at the polymerization temperature. The formation of isotactic rich PMMAs from complex II was proposed to be associated with the fluctuation of the 9-trimethylsilylfluorenyls around a C2 symmetric twisted-conformation. The formation of the multi(syndioPMMA-block-iso-PMMA) polymers from the mixture of rac- and meso-isomers of I was rationalized on the basis of competing conjugate addition and inversion of the metallocene conformation. Surprisingly, both rac- and meso-isomers of I were found to operate with similar activity and stereospecifity, although the stereospecific operation of the meso-form was not completely understandable. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 1599-1606, 1998
    Additional Material: 1 Ill.
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  • 92
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    Electronic Resource
    Novel hydrogen-transfer polymerization of vinyl monomer derived from p-toluenesulfonyl isocyanate and acrylamide (1998)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part A: Polymer Chemistry 36 (1998), S. 1491-1494 
    Details
    ISSN: 0887-624X
    Keywords: sulfonyl isocyanate ; acrylamide ; hydrogen-transfer polymerization ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: No abstract.
    Additional Material: 1 Ill.
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  • 93
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    Electronic Resource
    p-Nitrophenol permeability and temperature characteristics of an acryloyl-L-proline methyl ester-based porous gel membrane (1998)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part A: Polymer Chemistry 36 (1998), S. 1495-1500 
    Details
    ISSN: 0887-624X
    Keywords: acryloyl-L-proline methyl ester (A-ProOMe) ; methacryloyl-L-proline methyl ester (MA-ProOMe) ; porous gel membranes ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Thermoresponsive porous gel membranes were synthesized by a simultaneously occurring process consisting of radiation-induced polymerization and crosslinking in aqueous solutions at various concentrations of acryloyl-L-proline methyl ester(A-ProOMe) without a crosslinker. Permeation of p-nitrophenol (PNP) through a thermoresponsive porous gel membrane obtained at a monomer concentration of 80% (w/w) drastically reduced around 14°C, the lower critical solution temperature (LCST) of linear poly(A-ProOMe) in water, from 0.60 × 10-3 cm/min at 10°C to no permeation at 18°C, accompanied by changes in both size and shape of pores associated with gel shrinkage. Moreover, it was found that porous gel membranes with a porosity of approximately 60% had a greater PNP permeability constant through porous gel membranes with mutually connected pores obtained at a monomer concentration of 50% (w/w) than individually supported pores obtained at a monomer concentration of 70% (w/w). © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 1495-1500, 1998
    Additional Material: 9 Ill.
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  • 94
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    Electronic Resource
    Polymerization under a magnetic field. VI. Triplet dye-sensitized photopolymerization of acrylamide and methyl methacrylate (1998)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part A: Polymer Chemistry 36 (1998), S. 1509-1513 
    Details
    ISSN: 0887-624X
    Keywords: methylene blue ; dye-sensitized photopolymerization ; magnetic field ; triplet state ; acrylamide ; methyl methacrylate ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Methylene blue sensitized photopolymerization of acrylamide (AM) and methyl methacrylate (MMA) using triethanolamine or the sodium salt of EDTA as a reducing agent has been investigated under the influence of a magnetic field (0-7.3 kG). There was no effect of the magnetic field (MF) on the polymerization of AM and MMA in aqueous medium. However, in the water-methanol mixture (1 : 1) the yield of polymer decreases and the molecular weight increases in both cases under MF. This has been explained on the basis of the triplet mechanism. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 1509-1513, 1998
    Additional Material: 5 Tab.
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  • 95
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    Electronic Resource
    Porous monodisperse poly(divinylbenzene) microspheres by precipitation polymerization (1998)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part A: Polymer Chemistry 36 (1998), S. 1543-1551 
    Details
    ISSN: 0887-624X
    Keywords: polymer microspheres ; monodisperse ; crosslinked ; porosity ; porogen ; precipitation polymerization ; divinylbenzene ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The precipitation polymerization of commercial divinylbenzene in acetonitrile containing up to 40 vol. % toluene or other cosolvents is shown to produce novel porous monodisperse poly(divinylbenzene) microspheres. These microspheres have diameters between 4 and 7 μm, total pore volumes of up to 0.52 cm3/g, and surface areas of up to 800 m2/g. As no surfactant nor stabilizer was used in the preparation of these particles, their surfaces are free of any such residues. The particles were slurry-packed into stainless steel columns for size exclusion chromatography evaluation, and the results show an exclusion limit at molecular weights of 500 g/mol. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 1543-1551, 1998
    Additional Material: 6 Ill.
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  • 96
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    Electronic Resource
    (Diisopropylamido) bis (methylcyclopentadienyl) lanthanides as single-component initiators for polymerization of methyl methacrylate (1998)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part A: Polymer Chemistry 36 (1998), S. 1593-1597 
    Details
    ISSN: 0887-624X
    Keywords: MMA ; polymerization ; (diisopropylamido)bis(methylcyclopentadienyl)lanthanides ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: It was first found that (diisopropylamido)bis(methylcyclopentadienyl)lanthanides (MeC5H4)2LnN(i-Pr)2(THF) (Ln = Yb (1), Er (2), Y (3)) exhibit extremely high catalytic activity in the polymerization of methyl methacrylate. The reactions can be carried out over a quite broad range of polymerization temperatures from -78 to 40°C. The catalytic activity of the complexes increases with an increase of ionic radii of the metal elements, i.e. Y 〉 Er 〉 Yb. The results of GPC (gel permeation chromatography) indicate that the number-average molecular weights (Mn) of polymers obtained exceed 100 × 103 and the molecular weight distribution (Mw/Mn) becomes broad with the increase of temperature. Furthermore highly syndiotactic PMMA (87.7%) can be obtained by lowering the reaction temperature to -78°C. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 1593-1597, 1998
    Additional Material: 1 Ill.
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  • 97
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    Electronic Resource
    Preparation and properties of poly(styrene-co-maleic anhydride)/silica hybrid materials by the in situ sol-gel process (1998)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part A: Polymer Chemistry 36 (1998), S. 1607-1613 
    Details
    ISSN: 0887-624X
    Keywords: sol-gel ; hybrid material ; poly(styrene-co-maleic anhydride) ; tetraethoxysilane ; (3-aminopropyl)triethoxysilane ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Poly(styrene-co-maleic anhydride)/silica hybrid material has been successfully prepared from styrene-maleic anhydride copolymer and tetraethoxysilane (TEOS) in the presence of a coupling agent (3-aminopropyl)triethoxysilane (APTES) by an in situ sol-gel process. It was observed that the gel time of sol-gel solution was dramatically influenced by the amount of APTES. The hybrid material exhibits optical transparency almost as good as both silica gel and the copolymer. The covalent bonds between organic and inorganic phases were introduced by the aminolysis reaction of the amino group with maleic anhydride units of copolymer to form a copolymer bearing trimethoxysilyl groups, which undergo hydrolytic polycondensation with TEOS. The differential scanning calorimetry (DSC) showed that the glass transition temperature of the hybrid materials increases with increasing of SiO2 composition. Photographs of scanning electron microscopy (SEM) and atomic force microscopy (AFM) inferred that the size of the inorganic particles in the hybrid materials was less than 20 nm. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 1607-1613, 1998
    Additional Material: 8 Ill.
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  • 98
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    Electronic Resource
    Influence of plasma treatment on the molar mass of poly(ethylene terephthalate) investigated by different chromatographic and spectroscopic methods (1998)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part A: Polymer Chemistry 36 (1998), S. 1639-1648 
    Details
    ISSN: 0887-624X
    Keywords: poly(ethylene terephthalate) (PET) ; plasma ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The influence of different types of low and atmospheric pressure plasma on poly(ethylene terephthalate) (PET) has been studied in terms of changes in molar mass and molar mass distribution. Apart from a variation of plasma gases (oxygen, helium) different types of plasma (microwave, radio frequency, corona discharge) were used for the plasma surface modification. The changes in molar mass and types of functional end groups of lower molar mass products were investigated by means of matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOFMS), whereas the high-molar mass fraction was analyzed by means of size-exclusion chromatography (SEC). The formation of crosslinked products during exposure to a helium plasma, which emits preponderately energy-rich and intense ultraviolet radiation, was proved by means of thermal field-flow fractionation (ThFFF). This method combined with a multiangle laser light scattering (MALLS) detector allows detection of weakly crosslinked polymers and microgels. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 1639-1648, 1998
    Additional Material: 9 Ill.
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  • 99
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    Electronic Resource
    Synthesis and properties of poly(ether imide)s derived from 2,6-bis(3,4-dicarboxyphenoxy)naphthalene dianhydride and aromatic diamines (1998)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part A: Polymer Chemistry 36 (1998), S. 1657-1665 
    Details
    ISSN: 0887-624X
    Keywords: 2,6-bis(3,4-dicarboxyphenoxy)naphthalene dianhydride ; poly(ether imide)s ; thermal behavior ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A new naphthalene unit-containing bis(ether anhydride), 2,6-bis(3,4-dicarboxyphenoxy)naphthalene dianhydride, was synthesized in three steps starting from the nucleophilic nitrodisplacement reaction of 2,6-dihydroxynaphthalene and 4-nitrophthalonitrile in N,N-dimethylformamide (DMF) solution in the presence of potassium carbonate, followed by alkaline hydrolysis of the intermediate bis(ether dinitrile) and subsequent dehydration of the resulting bis(ether diacid). High-molar-mass aromatic poly(ether imide)s were prepared using a conventional two-step polymerization process from the bis(ether anhydride) and various aromatic diamines. The intermediate poly(ether amic acid)s had inherent viscosities of 0.65-2.03 dL/g. The films of poly(ether imide)s derived from two rigid diamines, i.e. p-phenylenediamine and benzidine, crystallized during the thermal imidization process. The other poly(ether imide)s belonged to amorphous materials and could be fabricated into transparent, flexible, and tough films. These aromatic poly(ether imide) films had yield strengths of 104-131 MPa, tensile strengths of 102-153 MPa, elongation to break of 8-87%, and initial moduli of 1.6-3.2 GPa. The glass transition temperatures (Tg's) of poly(ether imide)s were recorded in the range of 220-277°C depending on the nature of the diamine moiety. All polymers were stable up to 500°C, with 10% weight loss being recorded above 550°C in both air and nitrogen atmospheres. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 1657-1665, 1998
    Additional Material: 2 Ill.
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  • 100
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    Electronic Resource
    A simple method for the anionic polymerization of α-carbonyl acids in water (1998)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part A: Polymer Chemistry 36 (1998), S. 1683-1683 
    Details
    ISSN: 0887-624X
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
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