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  • Electronic Resource  (1,672)
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  • 2000-2004  (29)
  • 1995-1999  (1,643)
  • 2000  (29)
  • 1995  (1,643)
  • Biochemistry and Biotechnology  (1,318)
  • Genetics  (356)
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  • Electronic Resource  (1,672)
  • Loose Leaf
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  • 2000-2004  (29)
  • 1995-1999  (1,643)
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  • 1
    Electronic Resource
    Electronic Resource
    A study of Italian families with cluster headache (2000)
    Springer
    The journal of headache and pain 1 (2000), S. S165 
    Details
    ISSN: 1129-2377
    Keywords: Key words Cluster headache ; Familial occurrence ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A Danish genetic study showed increased risk of cluster headache (CH) among relatives of CH patients. We studied the families of 191 CH patients (118 males, 73 females; mean age 45.9 years) attending the Milan Headache Center. Information on 3589 relatives was collected by direct interview of the probands (n = 118) or by mailed questionnaire (n = 73). The diagnostic criteria of the IHS were used. A positive family history was found in 19% (37 of 191) of the families. A total of 32 first-degree (32 of 1036, 3.1%) and 15 second-degree (15 of 2553, 0.6%) relatives were affected. The relative risk of CH was 26.89 (95% CI, 17.57–36.21) in the first-degree relatives and 4.35 (95% CI, 2.13–5.21) in second-degree relatives. This study shows increased familial risk of cluster headache in an Italian population and confirms that cluster headache is, in some families, and inherited disorder.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s101940070012
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  • 2
    Electronic Resource
    Electronic Resource
    Molecular genetics and migraine (2000)
    Springer
    The journal of headache and pain 1 (2000), S. S135 
    Details
    ISSN: 1129-2377
    Keywords: Key words Migraine ; Headache ; Genetics ; Serotonin ; Dopamine ; Mitochondria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Migraine carries a significant hereditary determination. Familial hemiplegic migraine (FHM) has been recently linked to mutations in the CACNA1A gene on chromosome 19. CACNA1A codes for a subunit of a neural calcium channel. Other linkage loci on chromosome 1q21-23 and 1q31 have been reported. Several linkage and association studies have been performed to determine the role of the CACNA1A gene, and of other candidate genes implicated in the metabolism of serotonin and dopamine, in the more common types of migraine. Co-morbidity of migraine with vascular events has been analysed versus genetic prothrombotic factors and mitochondrial DNA, and genes involved in the inflammatory cascade have been explored. Though no definite conclusions have emerged from these studies as yet, molecular genetics of migraine can be expected to unravel the complex aetiologies of these fascinating diseases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s101940070007
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  • 3
    Electronic Resource
    Electronic Resource
    Molecular variation within the dopamine receptor DRD2 gene in migraine (2000)
    Springer
    The journal of headache and pain 1 (2000), S. S147 
    Details
    ISSN: 1129-2377
    Keywords: Key words Dopamine ; Migraine ; Genetics ; DRD2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Molecular genetics offers a novel approach to the understanding and management of migraine since the disorder is known to have a strong genetic component. In recent studies, polymorphisms in the genes for dopamine receptors have been evaluated. Both positive and negative association studies have been reported. In particular, these data suggest that activation of the DRD2 receptor plays a modifying role in the pathophysiology of migraine. As a result, existing data provide a molecular rationale for the documented efficacy of dopamine D2 receptor antagonists in the treatment of migraine. Therefore, at the present time, molecular genetic data provide support for the hypothesis that susceptibility to migraine may be modified, in part, by variations in dopamine DRD2 receptor function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s101940070009
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  • 4
    Electronic Resource
    Electronic Resource
    Genetic factors in migraine and chronic tension-type headache (2000)
    Springer
    The journal of headache and pain 1 (2000), S. S157 
    Details
    ISSN: 1129-2377
    Keywords: Key words Migraine ; Chronic tension type headache ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Pathophysiological studies have dominated migraine research for several years. However, these studies are difficult to interpret because it is difficult to decide whether the observed phenomena are primary or secondary to the migraine attack. For that reason it is important that future migraine research focus on studies that concern migrain etiology. Migraine is a paroxysmal disorder. It is most likely and ion-channel disorder like familial hemiplegic migraine. The present paper focuses on genetic factors in migraine and chronic tension-type headache.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s101940070011
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  • 5
    Electronic Resource
    Electronic Resource
    Central nervous system hemangioblastomas, endolymphatic sac tumors, and von Hippel-Lindau disease (2000)
    Springer
    Neurosurgical review 23 (2000), S. 1-22 
    Details
    ISSN: 1437-2320
    Keywords: Key words Von Hippel-Lindau disease ; Hemangioblastoma ; Endolymphatic sac tumor ; Angiogenesis ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Von Hippel-Lindau disease (VHL) is a hereditary cancer syndrome caused by germline mutations of the VHL tumor suppressor gene. Major progress has been made in the last decade in both clinical and fundamental aspects of VHL. The VHL gene product, pVHL, has major and multiple functions: pVHL regulates not only first angiogenesis but also extracellular matrix formation and the cell cycle. A molecular diagnosis of VHL is now available, leading to a transformation in clinical management of patients and their families. Diagnosis of VHL has to be suspected in patients with a VHL-related tumor without familial history and especially in case of hemangioblastoma or endolymphatic sac tumors. Such patients should be systematically investigated for clinical and molecular evidence of VHL disease. Treatment of symptomatic hemangioblastomas remains mainly neurosurgical, often in emergency, but stereotactic radiosurgery is emerging as an alternative therapeutic procedure. In the future, antiangiogenic drugs could represent a potential medical treatment of CNS hemangioblastomas in view of their highly vascular structure. Lastly, visceral manifestations of VHL disease are also of critical importance and require early detection for effective treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s101430050024
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  • 6
    Electronic Resource
    Electronic Resource
    Dopamine genes and migraine (2000)
    Springer
    The journal of headache and pain 1 (2000), S. S153 
    Details
    ISSN: 1129-2377
    Keywords: Key words Migraine ; Genetics ; Dopamine ; Hypersensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Migraine is a common chronic disorder with an etiology still mostly unknown. Several neurotransmitters such as dopamine and serotonin are considered to be involved in the pathogenesis of the disease and the study of their systems is crucial in the understanding of migraine. Dopaminergic receptors are variously represented in human CNS and periphery. The hypothesis that a hypersensitivity of the dopaminergic system may have a role in migraine is based on clinical and genetic data. Genetic data are represented by association studies using dopaminergic genes as candidate genes which show that the D2 receptor gene appears to be involved in the pathogenesis of migraine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s101940070010
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  • 7
    Electronic Resource
    Electronic Resource
    HLA and migraine genes (2000)
    Springer
    The journal of headache and pain 1 (2000), S. S141 
    Details
    ISSN: 1129-2377
    Keywords: Key words Migraine ; Genetics ; Human leukocyte antigens ; Heredity ; Susceptibility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Human leukocyte Antigens (HLA) are encoded by genes located on chromosome 6p21. Genes important in migraine are being recognized in two basic ways: association studies and linkage analysis. One of the strongest associations is with the HLA region. Actually, genome scan studies suggest that multiple genes are involved in both migraine without aura (MWoA) and migraine with aura (MWA). However, both MWoA and MWA are disorders in which multiple factors, including environmental and genetic factors, confer disease susceptibility. Linkage analysis is identifying new candidate genes that will help to explain the etiology of migraine. In this review previous studies regarding genetic susceptibility to migraine are analyzed, particularly those related to the HLA region. I discuss evidence that HLA shared-hyplotypes in MWoA-affected pairs in different than that expected, that HLA-DR2 antigen provides additional basis for the proposed genetic heterogeneity between MWoA and MWA, and lastly that TNFB gene studies seem to play an important role in the susceptibility to MWoA. In the past years, major advances hae been made in understanding the genetic foundation of MWoA and MWA. Our reported genome-scan studies support the concept that MWoA/MWA are coinherited with a particular HLA region. However, the examination of candidate genes (Ca2+ channel, vascular, CNS, etc.) in a large migraine population seems to be the correct direction in which we have to move. More MWoA/MWa gene studies are needed to test this developing hypothesis and to further establish the complete genetic scenario of migraine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s101940070008
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  • 8
    Electronic Resource
    Electronic Resource
    Progress in the clinical and molecular genetics of familial parkinsonism (2000)
    Springer
    Neurogenetics 2 (2000), S. 207-218 
    Details
    ISSN: 1364-6753
    Keywords: Key words Parkinson's disease ; Familial Parkinson's disease ; Synuclein ; Parkin ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: ABSTRACT¶Parkinson's disease (PD) is a neurodegenerative disease with clinical features resulting from deficiency of dopamine in the nigrostriatal system. Most PD cases are sporadic and the primary cause of the disease is still unknown. Recently, familial PD and parkinsonism have received much attention because these forms of the disease might provide clues to the genetic risk factors involved in the pathogenesis of idiopathic PD. To date, two causative genes, α-synuclein and the parkin gene, have been identified. α-Synuclein is involved in the pathogenesis of an autosomal dominant form of PD and constitutes a major component of the Lewy body, which is a pathological hallmark of idiopathic PD. In addition, mutations in the parkin gene have been identified as the cause of autosomal recessive juvenile parkinsonism (AR-JP). AR-JP manifests itself as a highly selective degeneration of the substantia nigra and the locus coeruleus, but without Lewy body formation. In addition to these two genes, four chromosomal loci have been linked to other forms of familial PD. Furthermore, there are a number of other pedigrees of familial PD in which linkage to known genetic loci has been excluded. Molecular cloning of these disease genes and elucidation of the function of their gene products will greatly contribute to our understanding of the pathogenesis of idiopathic PD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s100489900083
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  • 9
    Electronic Resource
    Electronic Resource
    Association of TNFA gene polymorphism at position –308 with susceptibility to irritant contact dermatitis (2000)
    Springer
    Immunogenetics 51 (2000), S. 201-205 
    Details
    ISSN: 1432-1211
    Keywords: Key words Skin ; Genetics ; TNFA ; ¶Inflammation ; PCR-RFLP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Mechanisms underlying susceptibility to skin irritants are not clearly understood. Cytokines play a key role in inflammation, and functional polymorphisms in cytokine genes may affect responses to irritants. We investigated the relationship between polymorphism in the tumor necrosis factor (TNF) α-chain gene and responses to irritants. Volunteers (n=221) tested with sodium dodecyl sulfate (SDS) and benzalkonium chloride (BKC) were divided into responders and nonresponders and high and low irritant-threshold groups. DNA was assayed for the TNF-308 polymorphism by a polymerase chain reaction-restriction fragment length polymorphism method. There was a significant increase in the A allele (P=0.030) and AA genotype (P=0.023) in both the SDS low irritant-threshold group and in SDS responders (A allele P=0.022, AA genotype P=0.048). In the BKC low irritant-threshold group, we found a significant increase in the A allele (P=0.002) and AA genotype (P=0.016). Individuals with a low threshold to both irritants demonstrated a significant increase (P=0.002) in the A allele. This is the first description of a nonatopic genetic marker for irritant susceptibility in normal individuals. Genotyping for theTNF-308 polymorphism may thus contribute to screening of individuals deemed at risk of developing irritant contact dermatitis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050032
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  • 10
    Electronic Resource
    Electronic Resource
    Susceptibility to critical illness: reserve, response and therapy (2000)
    Springer
    Intensive care medicine 26 (2000), S. S057 
    Details
    ISSN: 1432-1238
    Keywords: Key words Critical illness ; Intensive care ; Severity of illness ; Scoring systems ; Genetics ; Susceptibility ; Education
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Risk of critical illness is determined both by genetic and environmental influences, particularly those relating to infectious and cardiovascular diseases. Physiologically-based scoring systems cannot measure prior risk because they do not quantify physiological reserve independently of the acute illness. Genetic profiling could be useful for risk assessment. Early detection of critical illness involves identifying physiological ’triggers' for referral; this requires the education of nursing and medical staff in their significance. Analysis of the relationship between risk factors and interventions may need complex modelling techniques. Therapeutic strategies depend on the nature of the underlying problem: the most useful are likely to be those which enhance tissue oxygen delivery and resistance to infection.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001340051120
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  • 11
    Electronic Resource
    Electronic Resource
    Oligohydramnion, renal failure and no pulmonary hypoplasia in glomerulocystic kidney disease (2000)
    Springer
    Pediatric nephrology 14 (2000), S. 319-321 
    Details
    ISSN: 1432-198X
    Keywords: Key words Glomerulocystic kidney disease ; Oligohydramnion ; Renal failure-neonate ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Two newborns with glomerulocystic kidney disease manifesting as late onset oligohydramnion and neonatal anuria, yet without severe respiratory distress, are presented. They had a similar perinatal course and associated clinical manifestations. No associated congenital or inherited malformation syndrome could be defined. Both infants’ parents were first degree cousins and belonged to the same small Bedouin tribe, and neither they nor the infants’ siblings had polycystic kidneys or renal insufficiency, pointing to either a possible genetic etiology or a common external toxic exposure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004670050767
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  • 12
    Electronic Resource
    Electronic Resource
    Bridging the gap between molecular genetics and metabolic medicine: access to genetic information (2000)
    Springer
    European journal of pediatrics 159 (2000), S. S183 
    Details
    ISSN: 1432-1076
    Keywords: Key words Database ; Genetics ; Information services ; Internet ; Mutation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thanks to the World Wide Web, most results of research in genetics are made available in public databases. At the present time there are resources on genetic diseases, genes and their location, mutations of already cloned genes and on laboratories performing the mutation analysis. The main resources on phenotypes are On-line Mendelian Inheritance in Man (OMIM), Pedbase, GeneClinics, London Dysmorphology Database (LDDB) and Orphanet. The main resources on human genes are, in addition to OMIM, the Genome Database, Genatlas and Genecard. There are also two major sequence databases. All of them can be queried using the OMIM number of the disease. Central databases of mutations, as well as locus specific databases have been created. Their list is maintained at the Human Genome Organisation mutation database initiative website. Several initiative have been taken to integrate all these data and help the clinician to find out quickly what he/she needs. The website of the National Center for Biotechnology Information is the best example of such an effort with sections on diseases, a genome guide, and locus links. Several databases of genetic testing resources have been established. GeneTests is an on-line genetics resource that contains a directory of North American laboratories providing testing for heritable disorders. Orphanet is a similar database on French services which is in the process of becoming a European database. Conclusion Even if clinicians do not have as many services at their disposal as the molecular geneticists, various useful databases already exist and should no longer be ignored in practice.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00014399
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  • 13
    Electronic Resource
    Electronic Resource
    Genetic determinants of hyperhomocysteinaemia: the roles of cystathionine β-synthase and 5,10-methylenetetrahydrofolate reductase (2000)
    Springer
    European journal of pediatrics 159 (2000), S. S208 
    Details
    ISSN: 1432-1076
    Keywords: Key words Cardiovascular disease ; Cystathionine β-synthase ; Genetics ; Methylenetetrahydrofolate reductase ; Mild hyperhomocysteinaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Over the last decade mild hyperhomocysteinaemia has widely been recognised as a new risk factor for arteriosclerosis and thrombosis. Main regulating enzymes of homocysteine (Hcy) metabolism are cystathionine β-synthase (CBS), methionine synthase and methylenetetrahydrofolate reductase (MTHFR). Early studies on patients with vascular disease described elevated Hcy concentrations after methionine loading and decreased CBS activity, resembling heterozygotes for CBS deficiency. Therefore, heterozygosity for CBS deficiency was proposed as the main cause of mild hyperhomocysteinaemia. However, more recent enzymatic and molecular genetic studies have demonstrated that heterozygosity for CBS deficiency is not or only a very minor cause of mild hyperhomocysteinaemia in vascular disease. We discovered two common genetic causes of mild hyperhomocysteinaemia, the 677C 〉 T and the 1298A 〉 C mutations in the coding region of MTHFR. The 677C 〉 T mutation causes reduced enzyme activity with thermolabile protein properties, elevated Hcy and low-normal or decreased plasma folate levels. The 1298A 〉 C mutation relates also to decreased enzyme activity, but not to thermolabile protein, and Hcy and folate levels are not influenced. However, compound heterozygosity for these two mutations, i.e. individuals with the 677CT/1298AC genotype, have elevated Hcy and decreased plasma folate levels. Gene-enviroment interactions between 677C 〉 T and folate is demonstrated in individuals with the 677TT genotype. Those with low-normal folate have elevated Hcy, whereas those with high-normal folate have normal Hcy concentrations. The elevated Hcy levels due to these mutations can be normalised by administration of folate, but whether folate reduces the risk of cardiovascular disease remains to be established. Conclusion Heterozygosity for cystathionine β-synthase deficiency is a minor cause of hyperhomocysteinaemia. The current data on mutations in the methylenetetrahydrofolate reductase gene do not tell us whether elevated plasma homocysteine plays a causal role in vascular disease. Low cellular vitamin status may be a possible cause and homocysteine may just be a marker for this situation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00014405
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  • 14
    Electronic Resource
    Electronic Resource
    Aetiology of overweight and obesity in children and adolescents (2000)
    Springer
    European journal of pediatrics 159 (2000), S. S35 
    Details
    ISSN: 1432-1076
    Keywords: Key words Obesity ; Genetics ; Child ; Nutrient balance ; Energy balance ; Environment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The epidemic diffusion of obesity in industrialised countries has promoted research on the aetiopathogenesis of this disorder. The purpose of this review is to focus mainly on the contribution that European research has made to this field. Available evidence suggests that obesity results from multiple interactions between genes and environment. Parents obesity is the most important risk factor for childhood obesity. Twin, adoption, and family studies indicated that inheritance is able to account for 25% to 40% of inter-individual difference in adiposity. Single gene defects leading to obesity have been discovered in animals and, in some cases, confirmed in humans as congenital leptin deficiency or congenital leptin receptor deficiency. However, in most cases, genes involved in weight gain do not directly cause obesity but they increase the susceptibility to fat gain in subjects exposed to a specific environment. Both genetic and environmental factors promote a positive energy balance which cause obesity. The relative inefficiency of self-adapting energy intake to energy requirements is responsible for fat gain in predisposed individuals. The role of the environment in the development of obesity is suggested by the rapid increase of the prevalence of obesity accompanying the rapid changes in the lifestyle of the population in the second half of this century. Early experiences with food, feeding practices and family food choices affect children's nutritional habits. In particular, the parents are responsible for food availability and accessibility in the home and they affect food preferences of their children. Diet composition, in particular fat intake, influences the development of obesity. The high energy density and palatability of fatty foods as well as their less satiating properties promotes food consumption. TV viewing, an inactivity and food intake promoter, was identified as a relevant risk factor for obesity in children. Sedentarity, i.e. a low physical activity level, is accompanied by a low fat oxidation rate in muscle and a low fat oxidation rate is a risk factor of fat gain or fat re-gain after weight loss. Conclusion Further research is needed to identify new risk factors of childhood obesity, both in the genetic and environmental areas, which may help to develop more effective strategies for the prevention and treatment of obesity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00014361
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  • 15
    Electronic Resource
    Electronic Resource
    Genotyping of presenilin-1 polymorphism in amyotrophic lateral sclerosis (2000)
    Springer
    Journal of neurology 247 (2000), S. 940-942 
    Details
    ISSN: 1432-1459
    Keywords: Key words Amyotrophic lateral sclerosis ; Genetics ; Presenilin-1 intron 8 polymorphism ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The mechanisms underlying motor neuron degeneration in amyotrophic lateral sclerosis are not fully understood. Recent studies suggest that apoptosis is involved in the abnormal neural death that occurs in this devastating disease. Presenilin-1, a transmembrane protein, seems to be implicated in apoptosis. To determine whether presenilin-1 intron 8 polymorphism has an influence in the course of amyotrophic lateral sclerosis, we examined this polymorphism genotypes in a large group of patients (n=72) with amyotrophic lateral sclerosis and in a random sample of 213 healthy individuals. The results showed a significant difference in genotype (P 〈 0.04) and allele (P 〈 0.03) distribution between patients and controls. These results suggest a possible intervention of presenilin-1 in the pathogenesis of amyotrophic lateral sclerosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004150070050
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  • 16
    Electronic Resource
    Electronic Resource
    Vascular risk factors in dementia (2000)
    Springer
    Journal of neurology 247 (2000), S. 81-87 
    Details
    ISSN: 1432-1459
    Keywords: Key words Dementia ; Vascular ¶dementia ; Alzheimer’s disease ; Risk factors, stroke ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This review describes differing profiles of vascular risk factors in different types of dementia. Although vascular risk factors are related to various types of strokes, their independent effect on the occurrence of poststroke dementia appears to be small. Various risk factors have been identified for microangiopathy-related cerebral abnormalities, such as white matter changes and lacunae, which are the core lesions for the development of a vascular dementia syndrome without stroke symptoms. Most consistently, arterial hypertension and diabetes mellitus have been found to be associated with such brain abnormalities. Diastolic blood pressure seems to be of particular importance as recent investigations demonstrate that this factor is related to the course of multiple lacunar strokes and the progression of white matter disease. Epidemiological studies report that various vascular risk factors including arterial hypertension, diabetes mellitus, and atrial fibrillation may also be associated with Alzheimer’s disease. There is also evidence of a direct relationship between Alzheimer’s disease and general atherosclerosis. Further investigations are needed to determine whether these associations are due to the weakness of diagnostic criteria, or whether vascular risk factors indeed modulate the clinical expression of primary degenerative dementia. Common susceptibility genes leading to shared risk factors may be one of the reasons for a higher coincidence of Alzheimer’s disease and vascular dementia than can be expected by chance. A modulatory effect of vascular risk factors in the development of primary degenerative dementia may extend treatment options.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004150050021
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  • 17
    Electronic Resource
    Electronic Resource
    The monoamine oxidase B gene GT repeat polymorphism and Parkinson’s disease in a Chinese population (2000)
    Springer
    Journal of neurology 247 (2000), S. 52-55 
    Details
    ISSN: 1432-1459
    Keywords: Key words Parkinson’s disease ; Monoamine oxidase B ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Monoamine oxidase B (MAOB) metabolises dopamine and activates neurotoxins known to induce parkinsonism in humans and primates. Therefore the MAOB gene (MAOB; Xp15.21–4) is a candidate gene for Parkinson’s disease (PD). Longer length dinucleotide repeat sequences in a highly polymorphic GT repeat region of intron 2 of this gene showed an association with PD in an Australian cohort. We repeated this allele-association study in a population of 176 Chinese PD patients ¶(90 men, 86 women) and 203 age-matched controls (99 men, 104 women). Genomic DNA was extracted from venous blood and the polymerase chain reaction was used to amplify the appropriate regions of the MAOB gene. The length of each (GT) repeat sequence was determined by 5% polyacrylamide denaturing gel electrophoresis. There was no significant difference in allele frequencies of the (GT) repeat allelic variation between patients and controls (χ2 = 2.48; df = 5, P 〈 0.75). Therefore the longer length GT repeat alleles are not associated with PD in this Chinese population. Possible reasons for the discrepancy between Chinese and Australian populations include a different interaction between this genetic factor and environmental factors in the two populations and the possibility that the long length GT repeat alleles may represent a marker mutation, genetically linked to another susceptibility allele in whites but not in Chinese. Methodological differences in the ascertainment of cases and controls in this cohort could also explain the observed differences. Further study is required to determine whether the longer length GT repeat alleles are true susceptibility alleles in PD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004150050010
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  • 18
    Electronic Resource
    Electronic Resource
    Progressive supranuclear palsy: earlier age of onset in patients with the τ protein A0/A0 genotype (2000)
    Springer
    Journal of neurology 247 (2000), S. 206-208 
    Details
    ISSN: 1432-1459
    Keywords: Key words Progressive ¶supranuclear palsy ; Genetics ; Clinical characteristics ; Parkinsonism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Genetic studies have detected an association between the presence of the τ gene A0 allele and patients with progressive supranuclear palsy (PSP). This study examined whether patients with this polymorphism exhibit distinct demographic or clinical characteristics. We studied 26 patients who fulfilled clinical criteria for the diagnosis of PSP, 20 who had the A0/A0 genotype and 6 who had other genotypes. A questionnaire on demographic data, past medical history, familial history, and initial symptoms was completed as part of the consultation. A complete neurological examination was performed and PSP symptoms were quantified following Golbe’s PSP disability scale. We found a significant difference in the age at onset of PSP symptoms, which was 65.9 ± 5.3 years in the A0/A0 group and 71.2 ± 5.6 in the non-A0/A0 group (P = 0.016). There were no significant differences in the years from disease onset between the two groups. Symptom severity did not differ significantly in patients with the different A0/A0 genotypes. The detection of significantly lower age at onset with the A0/A0 alleles is consistent with the known association of this genotype as a risk factor for PSP. No significant differences were detected in symptom severity between the two groups of patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004150050564
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  • 19
    Electronic Resource
    Electronic Resource
    Incidence of CSF abnormalities in siblings of multiple sclerosis patients and unrelated controls (2000)
    Springer
    Journal of neurology 247 (2000), S. 616-622 
    Details
    ISSN: 1432-1459
    Keywords: Key words Multiple sclerosis ; Siblings ; Genetics ; Oligoclonal bands ; Measles
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We found that 19% (9/47) of healthy siblings of patients with clinically definite multiple sclerosis had an intrathecal immunological reaction with two or more 2 CSF-enriched oligoclonal bands (OCBs), in contrast to (4%) (2/50) unrelated healthy controls. Furthermore, in this group of nine healthy sibs the measles CSF IgG antibody titers were higher than that of the other sibs and that of controls. There were also differences in the serum titers for measles IgG antibody, which were higher in the group of all healthy sibs than in healthy volunteers, and (as with CSF titers) higher in the subgroup of healthy sibs with two or more 2 CSF-enriched OCBs than the other sibs. Thus a significant proportion of healthy siblings to MS patients have a partially hyperimmune condition similar to that occurring in MS, which in 19% manifested itself as an OCB reaction, in 9% as increased CSF measles IgG antibody titers, and in 21% as increased serum measles IgG antibody titers, these phenomena tending to occur in the same individuals. This condition is characterized by CSF-enriched OCBs with undefined specificity, although some increased antiviral reactivity is found both in the serum and CSF. While it needs further characterization, a genetic trait interacting with common infections is suggested. The recurrence risk of this condition is approximately five times higher than the 3–4% recurrence risk for manifest MS reported for sibs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004150070130
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  • 20
    Electronic Resource
    Electronic Resource
    Perspectives in pediatric neurosurgery (2000)
    Springer
    Child's nervous system 16 (2000), S. 809-820 
    Details
    ISSN: 1433-0350
    Keywords: Keywords Pediatric neurosurgery ; Molecular biology ; Genetics ; Novel therapeutics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The new millennium beckons for novel advances in the diagnosis and treatment of pediatric neurosurgical conditions. Almost every aspect of pediatric neurosurgery has changed over the last decade. Undoubtedly with the application of knowledge in molecular biology to human disease many aspects of neurosurgery, especially neuro-oncology and the field of neuro-developmental anomalies, will change appreciably over the next decade. Overall, the trend in surgery in general and neurosurgery in particular is toward less invasive procedures and possibly non-surgical interventions. This review will briefly cover many of the important areas of pediatric neurosurgery. We will describe the state-of-the-art of our subspecialty and discuss possible future directions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003810000345
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  • 21
    Electronic Resource
    Electronic Resource
    Re-examination of (in)compatibility genotypes of two John Innes self-compatible sweet cherry selections (2000)
    Springer
    Theoretical and applied genetics 101 (2000), S. 234-240 
    Details
    ISSN: 1432-2242
    Keywords: Key words Cherry ; Genetics ; Compatibility ; Incompatibility ; Isoelectric focusing ; Prunus avium ; Ribonuclease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  The (in)compatibility genotypes of two self-compatible sweet cherry selections, JI 2420 and JI 2434, originating from the John Innes Institute were re-examined. The selections and seedlings derived from them were analysed for stylar ribonucleases, which are known to correlate with S alleles, and the outcome of test crosses was recorded. JI 2420, which had been reported previously as S 3 S 4 ", where " indicates loss of pollen activity, was deduced to have the genotype S 4 S 4 ’. For JI 2434, which had been reported previously as S 3 S 4 0 , S 3 S 3 0 or S 3 S 3 ", where 0 indicates loss of pollen and stylar activity, two different clones were identified. One, at East Malling, was deduced to be S 3 "S 4 ; the other, at Ahrensburg, appeared to be S 3 S 3 " or S 3 S 3 0 .
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001220051474
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  • 22
    Electronic Resource
    Electronic Resource
    Characterisation and analysis of microsatellite loci in a mangrove species, Avicennia marina (Forsk.) Vierh. (Avicenniaceae) (2000)
    Springer
    Theoretical and applied genetics 101 (2000), S. 279-285 
    Details
    ISSN: 1432-2242
    Keywords: Key words Avicennia marina ; Microsatellite ; Mangrove ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  An enriched microsatellite library of the mangrove species Avicennia marina was constructed, in which 85.8% of the clones contained microsatellite sequences. Of the microsatellite repeat sequences isolated, 55.0% were di-nucleotides, 34.2% were tri-nucleotides, 50.0% were perfect, 24.2% were imperfect, and 15.0% were compound. Four different di-nucleotide repeats were isolated with repeat lengths ranging from 5 to 33; ten different tri-nucleotide repeats were isolated with repeat lengths ranging from 3 to 25. The most common di-nucleotide was the AC/TG repeat; the most common tri-nucleotide was the CCG/GGC repeat. Sixteen microsatellite sequences were selected for primer design, and 6 primers were selected to investigate the polymorphism detected among 15 individuals of A. marina from three natural populations in Australia. A total of 40 alleles were detected at 6 microsatellite loci. The number of alleles per microsatellite locus ranged from 5 to 13. On average, 7 alleles were detected per locus. All microsatellite loci showed high levels of gene diversity (heterozygosity), with values ranging from 0.53 to 0.88; the mean value of gene diversity was 0.70. Microsatellite loci were also tested for conservation across Avicennia species. There was a decline in amplification success with increasing divergence between Avicennia species. The results indicate that microsatellites are abundant in the Avicennia genome and can be valuable genetic markers for assessing the effects of deforestation and forest fragmentation in mangrove communities, which is an important issue for mangrove conservation and afforestation schemes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001220051480
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  • 23
    Electronic Resource
    Electronic Resource
    Dopamine D3 receptor variant and tardive dyskinesia (2000)
    Springer
    European archives of psychiatry and clinical neuroscience 250 (2000), S. 31-35 
    Details
    ISSN: 1433-8491
    Keywords: Key words Pharmacogenetics ; Genetics ; Risk factor ; Choreoathetotic movements
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the search for genetic factors contributing to tardive dyskinesia, dopamine receptor genes are considered major candidates. The dopamine D3 receptor is of primary interest as dopamine D3 receptor knock-out mice show locomotor hyperactivation resembling extrapyramidal side-effects of neuroleptic treatment. Furthermore, Steen and colleagues (1997) recently reported an association between tardive dyskinesia and a dopamine D3 receptor gene variant. In the present study we tried to replicate this finding. We investigated 157 patients with schizophrenia or schizoaffective disorder receiving long-term neuroleptic medication who never or persistently displayed tardive dyskinesia. As advanced age is a main risk factor for tardive dyskinesia, we also compared older patients with a long duration of schizophrenia not displaying tardive dyskinesia to younger patients with a shorter duration of the illness displaying tardive dyskinesia. However, we found no evidence that the dopamine D3 receptor gene is likely to confer susceptibility to the development of tardive dyskinesia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00007536
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  • 24
    Electronic Resource
    Electronic Resource
    Dopamine D4 receptor gene polymorphism and personality traits in healthy volunteers (2000)
    Springer
    European archives of psychiatry and clinical neuroscience 250 (2000), S. 203-206 
    Details
    ISSN: 1433-8491
    Keywords: Key words Dopamine receptor D4 ; Genetics ; Personality inventory ; Polymorphism ; Excitement-Seeking
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An association between long alleles of a variable number tandem repeat (VNTR) polymorphism in the dopamine receptor D4 gene and the extraversion related personality traits Excitement and Novelty Seeking has been reported in healthy subjects. In an attempt to replicate the previous findings, 256 healthy Caucasian volunteers were analysed for a potential relationship between the dopamine receptor D4 exon III VNTR polymorphism and Extraversion as assessed by the Revised Neo Personality Inventory (NEO PI-R). The present study did not yield evidence for an association between Extraversion and the dopamine receptor D4 polymorphism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004060070025
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  • 25
    Electronic Resource
    Electronic Resource
    ICAM-1 gene is not associated with multiple sclerosis in sardinian patients (2000)
    Springer
    Journal of neurology 247 (2000), S. 677-680 
    Details
    ISSN: 1432-1459
    Keywords: Key words Multiple sclerosis ; Genetics ; ICAM-1 gene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An increased amount of the intercellular adhesion molecule (ICAM) 1 molecule has been found in the blood of actively relapsing multiple sclerosis (MS) patients, but is unclear whether this enhanced expression is partially causative of the MS process, or whether it is merely an epiphenomenon of the inflammatory-immunological reaction. Using the transmission disequilibrium test (TDT), we studied exon 4 and exon 6 polymorphism of the ICAM-1 gene from 157 families with both parents, one affected and one healthy sib coming from Sardinia, an Italian island having a high incidence and prevalence of MS. TDT did not show variation in the expected 50:50 frequency in transmission in either healthy or affected sibs, using phenotypic or genotypic analysis. Moreover, independence from the predisposing HLA-DRB1-DQA1-DQB1 haplotype was confirmed by TDT analysis performed on the patients stratified according to the presence or absence of the HLA-DRB1, DQA1, DQB1 Sardinian predisposing haplotypes. Our data suggest that the increased expression of the ICAM-1 molecule observed in both blood and periplaque microvessels may be considered a consequence of the inflammatory process rather than the result of a genetic variation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004150070109
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  • 26
    Electronic Resource
    Electronic Resource
    A novel hypersensitive resistance response against potato virus A in cultivar ’Shepody’ (2000)
    Springer
    Theoretical and applied genetics 100 (2000), S. 401-408 
    Details
    ISSN: 1432-2242
    Keywords: Key words Complementary genes ; Extreme virus resistance ; Genetics ; Necrotic tubers ; Restricted virus distribution ; Solanum tuberosum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  The potato cultivar ’Shepody’ is susceptible to a number of potato viruses including potato virus Y (PVY, potyvirus) but was found to possess extreme resistance to another potyvirus, potato virus A (PVA). ’Shepody’ plants were resistant to PVA infection in manual and graft inoculations. PVA replication was not detected in any of the inoculated plants by ELISA, an infectivity assay and RT-PCR. However, ’Shepody’ plants grafted with shoots containing PVA developed a novel symptomology which resembled a virus infection in appearance and in rate of translocation to the entire plant. Efforts to transmit the symptom-inducing agent manually failed. Graft-inoculation to potato virus indicator plants and PVA-susceptible potato plants showed that the symptom inducer was PVA at an extremely low concentration, detected using RT-PCR followed by Southern blot assay. Tubers from grafted but resistant ’Shepody’ plants had necrotic surfaces and internal spots. PVA was detected from necrotic areas but not from the non-necrotic ones. However, plants resulting from necrotic tubers were free from aerial leaf symptoms observed in grafted plants and produced non-necrotic normal tubers. A trace-back of the parental lineage of ’Shepody’ indicated that the resistance had been introgressed from the cultivar ’Bake King’. Analysis of progeny of a cross of resistant ’Shepody’ to the susceptible ’Goldrus’ indicated that this resistance is controlled by two independent dominant complementary genes in contrast to monogenic resistance reported for other potato viruses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001220050053
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  • 27
    Electronic Resource
    Electronic Resource
    A pathophysiological study of neuronal ceroid lipofuscinoses in 17 patients: critical review and methodological proposal (2000)
    Springer
    Neurological sciences 21 (2000), S. S89 
    Details
    ISSN: 1590-3478
    Keywords: Key words Evoked potentials ; Ceroid lipofuscinoses ; Mutation ; Classification ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The importance of visual evoked potential (VEPs) and electroencephalography for diagnosing and distinghishing the infantile (INCL), late-infantile (LINCL) and juvenile (JNCL) forms of neuronal ceroid lipofuscinoses (NCL) is well established. Variant forms with protracted clinical courses and atypical symptoms have been described recently, whose neurophysiological characteristics sometimes overlap those of LINCL and JNCL. It is unclear whether these variant forms are due to phenotypic variability of known genetic defects, or represent new mutations. Twenty-eight NCL patients have been diagnosed at our institute; a proportion of them were investigated genetically. In 17 we performed neurophysiological investigations including VEPs, brainstem auditory (BAEP) and upper limb somatosensory (SEP) evoked potentials. We found typical and diagnostic electrophysiological involvement of the visual system in 8 patients with classic forms of NCL. Furthermore, the distinctive features of the multimodal evoked potentials in most of the six patients with variant NCL suggest that these are distinct genetic entities.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s100720070046
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  • 28
    Electronic Resource
    Electronic Resource
    Cavernous angiomas of the nervous system in Italy: clinical and genetic study (2000)
    Springer
    Neurological sciences 21 (2000), S. 129-134 
    Details
    ISSN: 1590-3478
    Keywords: Key words Nervous system ; Cavernous angiomas ; Genetics ; Onset symptoms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We performed a clinical and genetic study of patients affected by cavernous angiomas (CA) of the nervous system. We examined initial signs and symptoms in sporadic and familial cases. We obtained clinical, neuroimaging and genetic data on 15 Italian patients with CA of the nervous system with positive, doubtful or apparently negative family history. Genetic markers surrounding three different gene regions (7q, 3q and 7p) were analysed. In one small family, genetic linkage was consistent with all chromosome loci. In another family with the unusual association of cerebral and spinal CA, linkage with chromosome 7q and, likely, 7p was excluded, while linkage with locus 3q was possible. Our results indicate that Italian families with CA may show genetic heterogeneity. Non-specific and subtle onset symptoms hide the presence of CA within families. Patients with multiple CA may have silent cerebral lesions confirming the low penetrance of clinical signs in spite of radiological ones.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s100720070087
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  • 29
    Electronic Resource
    Electronic Resource
    Alcohol-sensitive hereditary essential myoclonus with dystonia: a study of 6 Brazilian patients (2000)
    Springer
    Neurological sciences 21 (2000), S. 373-377 
    Details
    ISSN: 1590-3478
    Keywords: Key words Myoclonus-dystonia ; Essential myoclonus ; Dystonia ; Alcohol ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We present the clinical profile of a group of patients with myoclonus and dystonia sensitive to alcohol and address these cases in the context of essential myoclonus. Six patients from 4 families were selected: 4 men and 2 women with myoclonus affecting predominantly the arms. Active movements of these segments elicited the dystonic and myoclonic movements. A marked improvement with alcohol intake was seen. Laboratory findings including EEG, SSEP, and cranial CT and MRI were normal. Surface EMG recording showed bursts with duration of 30–112 ms in 3 patients. One patient showed a triphasic recording pattern (agonist-antagonist-agonist) of ballistic type. Our findings suggest that the myoclonus-dystonia disorder is present in Brazilian patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s100720070053
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  • 30
    Electronic Resource
    Electronic Resource
    Characterization of B-cell lines from SLE patients and their relatives (1995)
    Springer
    Rheumatology international 15 (1995), S. 89-93 
    Details
    ISSN: 1437-160X
    Keywords: SLE Lupus ; BBV transformation ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Epstein-Barr-virus (EBV)-transformed lymphoblastoid B-cell lines were generated from peripheral blood lymphocytes of 55 patients with systemic lupus erythematosus (SLE) and 44 healthy relatives. All donors have previously been extensively characterized with regard to clinical, serologic, and genetic parameters. Here, peripheral blood lymphocytes and lines were characterized for cell surface antigens. Furthermore, autoantibody production and proliferation rate of the cell lines were monitored. A significant difference between patients and relatives was the lower proliferation rate of EBV-transformed cell lines of the SLE patients. All SLE cell lines are available for interested researches and can be obtained from the European Cell Bank, Salisbury, UK.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00302123
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  • 31
    Electronic Resource
    Electronic Resource
    Genetic mapping of adrenergic receptor genes in humans (1995)
    Springer
    Journal of molecular medicine 73 (1995), S. 299-306 
    Details
    ISSN: 1432-1440
    Keywords: Adrenergic receptors ; Human genetics ; Restriction fragment length polymorphism ; Chromosome mapping ; Linkage ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have genetically mapped the genes encoding four human adrenergic receptors (ARs) of subtypes α1C, α2A, α2B, and β1, which are prototypic G protein coupled receptors that mediate the physiological effects of neurotransmitters, hormones, and drugs. We placed these genes onto the Cooperative Human Linkage Center (CHLC) and Genethon framework maps, within confidence intervals with greater than 1000∶1 odds. With multipoint analysis the α1C gene (locus ADRA1C) mapped to the interval between NEFL and D8S283; α2-C4, the gene encoding the α2C AR (locus ADRA2C), mapped to the interval between D4S126 and D4S62; and the α2-C10 (α2A AR)/β1 haplotype (loci ADRA2A/ ADRB1) mapped to the interval between D10S259 and D10S187. A fifth AR gene, β2, yielded significant LOD scores with markers on the long arm of chromosome 5; however, this locus (ADRB2) could not be mapped to any specific interval with odds of greater than 1000∶1. The two AR genes that are completely linked, α2-C10 and β1, were oriented on their shared 225-kb genomic fragment relative to the direction of transcription, with β1 being 5′ to α2-C10. The positioning of these genes on high-density framework maps allows them to be tested as candidates in a spectrum of diseases that might involve AR dysfunction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00231616
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  • 32
    Electronic Resource
    Electronic Resource
    Insertion/deletion polymorphism in the angiotensin-converting enzyme gene associated with macroangiopathy and blood pressure in patients with non-insulin-dependent diabetes mellitus (1995)
    Springer
    Journal of molecular medicine 73 (1995), S. 307-311 
    Details
    ISSN: 1432-1440
    Keywords: Atherosclerosis ; Hypertension ; Type 2 diabetes ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the search for new risk factors for diabetic macroangiopathy the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene was studied in 237 consecutive patients (125 men and 112 women) with non-insulin-dependent diabetes. The female population showed an excess of ischemic electro-cardiographic changes or definite myocardial infarctions in the patients homozygous for the deletion [D/D; odds ratio (OR) 2.8; 95% confidence interval (CI) 1.4–5.3] and in the insertion/deletion heterozygotes (I/D; OR 1.8; CI 1.1–3.1) compared with the patients homozygous for the insertion (I/I). In the total series coronary heart disease, cerebrovascular disease, and claudication were more often observed in the patients with I/D (OR 1.5; CI 1.0–2.2) or the D/D genotype patients (OR 1.7; CI 1.1–2.6) than in those with the genotype I/I. The systolic blood pressure was lower in patients with genotype I/I (138±19 mmHg) than in those with the genotype I/D (149±22 mmHg) or D/D (150±21 mmHg; P〈0.02). The prevalence of hypertension and the median urinary albumin excretion rate also tended to be lowest in the I/I genotype patients. Multiple logistic analysis revealed that in women the angiotensin-converting enzyme D/D genotype is independently associated with coronary heart disease. Our findings suggest that variation at the angiotensin-converting enzyme gene locus is one of the factors involved in the predisposition of diabetic patients to the development of arterial disease and hypertension.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00231617
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  • 33
    Electronic Resource
    Electronic Resource
    Mixed desmoplastic primitive neuroepithelial tumor of infancy: a light microscopic, immunocytochemical, ultrastructural and genetic study (1995)
    Springer
    Acta neuropathologica 89 (1995), S. 99-104 
    Details
    ISSN: 1432-0533
    Keywords: Primitive neuroepithelial tumor ; Desmoplastic small cell tumor ; Brain tumor of infancy Immunocytochemistry ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We describe a case of a desmoplastic brain tumor which was initially resected from the right fronto-temporal region in a 2 year-old boy. This nodular, calcified tumor was vascularized by the internal carotid artery and the middle meningeal artery branches. Grossly, it contained several mucoid cysts. Light microscopy showed cords or nests of small cuboidal cells surrounded by a loose connective tissue and desmoplasic areas containing fibers and spindle cells. The cuboidal cells expressed epithelial, neuronal and neuroendocrine markers. Some foci of spindle cells showed glial differentiation. The tumor recurred 16 months later and displayed some characteristics of the small cell neuroepithelial component, mitoses being conspicuous. Electron microscopy revealed undifferentiated clear cells, some containing neurosecretory granules. Karyotyping demonstrated the following formula: 〈 15 〉 46, t(8;11) (a13; q11). The chromosome 11 breakpoint was different from that described in Ewing's sarcoma. This isolated translocation has not been previously reported to our knowledge. These unusual features lead us to report this case and to discuss its pathogenesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00294266
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  • 34
    Electronic Resource
    Electronic Resource
    Sex segregation ratio and gender expression in the genus Actinidia (1995)
    Springer
    Sexual plant reproduction 8 (1995), S. 129-132 
    Details
    ISSN: 1432-2145
    Keywords: Sex control ; Disomic segregation ; Dioecy Kiwifruit ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The sex segregation ratio was checked in bi-parental families of Actinidia deliciosa (2n=6x=174) obtained by crossing four females (A12, Mo3, Br4, Hw1) with two males (T2, M1) and one fruiting male (M3h, subandroecious) according to a factorial mating design. The M3h fruiting male was also selfed. The sex ratio was checked in maternal families of A. kolomikta (2n=2x) and A. chinensis (2n=2x) as well as in A. deliciosa. Seedlings of both diploid species took 3–4 years to progress beyond juvenility, whereas a noticeable number of seedlings from biparental crosses of A. deliciosa involving A12 and Hw1 as seed parents were still non-flowering after seven growing seasons. Open-pollinated families of both diploid and hexaploid species as well as most families from biparental crosses showed a sex segregation ratio approaching 1∶1. Subandroecious lines with different degrees of ovary and pistil development appeared in proportions of 0–4.2%, depending on the cross, but only 6 of the 2567 male vines checked were capable of setting fruit. No case of self-fertility or apomixis was detected among 1866 bagged female vines. Selfed M3h progenies gave only female and male phenotypes in a ratio of 1 female to 3 males. No off-type vines were found among these progenies. The same disomic sex segregation ratio seems to be operating at different ploidy levels in the genus Actinidia. Since selfed fruiting males produced both female and male individuals, the male sex appears to be the heterogametic one. Such evidence indicates that a monofactorial system based on one or more linked genes or on an X/Y chromosome set must be controlling sex expression. How a monofactorial sex-determining mechanism could operate in polyploids to give a 1∶1 female: male ratio is discussed. Minor modifying gene(s) seem to be responsible for the feminization of males, and their expression appears enhanced by environmental conditions. Masculinizing gene(s) seem to be lacking in female genotypes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00242255
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  • 35
    Electronic Resource
    Electronic Resource
    Opioid operant self-administration, analgesia, stimulation and respiratory depression inμ-deficient mice (1995)
    Springer
    Psychopharmacology 117 (1995), S. 23-31 
    Details
    ISSN: 1432-2072
    Keywords: Opioid ; Genetics ; Self-administration ; CXBK/ByJ ; Reinforcement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It is commonly thought thatμ-receptors play an important role in the reinforcing effects of opioids. In the present study, inbred strains widely divergent in CNS opiate receptor densities were used to investigate the influence of genetic variation in receptor concentration on opioid-reinforced behavior. In particular, the CXBK/ByJ mice were used as an investigative tool because of their significantly lower number of CNSμ opioid receptors. The behavioral pharmacology of opioids in theμ-deficient CXBK/ByJ mice was compared to other commonly used inbred mouse strains, C57BL/6J and BALB/cJ, and the opiate receptor rich CXBH/ByJ mice. Operant opioid reinforced behavior, opioid-induced locomotor stimulation, analgesia and respiratory depression were investigated in all four inbred strains. To assess the acquisition and maintenance of opioid reinforced behavior, oral self-administration of the potent benzimidazole opioid, etonitazene, was determined using an operant fixed-ratio schedule of reinforcement (FR 8). Acquisition of etonitazene-reinforced behavior was established in all four strains including theμ-deficient CXBK/ByJ mice. However, there were significant genetic differences in the amount of drug intake during the maintenance of opioid-reinforced behavior and extinction behavior following vehicle substitution. For example, drug intake was significantly greater in the BK versus BH mice during the maintenance phase and an extinction burst was seen in the BH but not the BK mice following vehicle substitution. Thus,μ-receptor density may not account for individual variability in the acquisition of opioid-reinforced behavior under these conditions. Sensitivity to etonitazene-induced respiratory depression, stimulation of locomotor activity and analgesia were unrelated to drug intake during self-administration sessions across these four inbred strains. These data indicate that inherited differences in CNSμ-opiate receptor concentrations do not affect acquisition of etonitazene-reinforced behavior.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245094
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  • 36
    Electronic Resource
    Electronic Resource
    Chromosomal mapping of loci influencing sensitivity to cocaine-induced seizures in BXD recombinant inbred strains of mice (1995)
    Springer
    Psychopharmacology 117 (1995), S. 62-66 
    Details
    ISSN: 1432-2072
    Keywords: Cocaine ; Quantitative trait loci ; Seizure ; Recombinant inbred strains ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Among inbred mice, genetic factors mediate differences in sensitivity to the convulsant properties of cocaine; however, the gene(s) underlying cocaine's effects have not been identified. To help elucidate the gene(s) responsible for cocaine seizure susceptibility, we used recombinant inbred-quantitative trait loci (RI-QTL) analyses to identify chromosomal loci associated with cocaine-induced seizures. RI-QTL analyses seek to identify associations between a quantitative measure of a particular phenotype and one or more previously mapped marker genes across a panel of RI strains. This report describes an RI-QTL analysis of cocaine seizure susceptibility among 26 BXD RI strains. These strains showed a skewed, bimodal range of seizure susceptibility which could be the result of one or more modifying genes acting in concert with a major gene to influence cocaine sensitivity. Correlating the percent seizures displayed by each strain following 60 mg/kg cocaine with chromosomal marker data for these strains revealed a number of significant correlations clustered in two regions on chromosomes 12 and 6. This is the first identification of putative chromosomal loci associated with a cocaine-related phenotype and should facilitate identification of the gene(s) underlying cocaine toxicity and other cocaine-related phenotypes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245099
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  • 37
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    Electronic Resource
    Genetic counselling on brittle grounds: recurring osteogenesis imperfecta due to parental mosaicism for a dominant mutation (1995)
    Springer
    European journal of pediatrics 154 (1995), S. 123-129 
    Details
    ISSN: 1432-1076
    Keywords: Key words Osteogenesis imperfecta ; Collagen I ; Mosaicism ; Genetics ; Recurrence risk
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Osteogenesis imperfecta (OI), a dominantly inherited connective tissue disorder, is usually caused by defects in collagen I. There is growing evidence for parental mosaicism that results in affected children born to unaffected parents. This situation poses a difficult task for the geneticist because a mosaic parent may appear clinically healthy while carrying the mutation in a fraction of her or his gonadal cells. To illustrate this problem, we report a Swiss couple whose first child was affected with severe OI. The unexpected recurrence of the disorder in the second child raised the suspicion of a recessive trait or, rather, of parental mosaicism. We identified the responsible collagen mutation in the COL1A2 gene (Gly688Ser in the α2(I)-chain) in both children and demonstrated the father to be a somatic mosaic for this mutation and to have subtle clinical signs such as soft skin and short stature that may be a result of his mosaic state.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004310050261
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  • 38
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    Electronic Resource
    Floating-Harbor syndrome: description of a further patient, review of the literature, and suggestion of autosomal dominant inheritance (1995)
    Springer
    European journal of pediatrics 154 (1995), S. 658-661 
    Details
    ISSN: 1432-1076
    Keywords: Floating-Harbor syndrome ; Growth retardation ; Dysmorphology ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Abstract The Floating-Harbor syndrome is a growth retardation syndrome with delayed bone age, speech development, and typical facial features. The face is triangular with deep-set eyes, long eyelashes, bulbous nose, wide columella, short philtrum, and thin lips. We present an additional patient and review 16 cases from the literature. The possible phenotype in the patient's mother suggests a dominant mode of inheritance for the syndrome. Conclusion The Floating Harbor syndrome is a growth deficiency syndrome characterized by proportionate short stature, characteristic face and delayed speech development. Inheritance is possibly autosomal dominant.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02079072
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  • 39
    Electronic Resource
    Electronic Resource
    Fetal brain disruption sequence in sisters (1995)
    Springer
    European journal of pediatrics 154 (1995), S. 654-657 
    Details
    ISSN: 1432-1076
    Keywords: Fetal development ; Brain diseases ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report two female siblings with the fetal brain disruption sequence. Extensive investigation of both children failed to define a definitive aetiology but clinical and laboratory findings are consistent with a hitherto unknown storage disease. We postulate that the accumulation of a neurotoxic metabolite may be responsible for the disease phenotype observed. This is the first report of recurrence of the fetal brain disruption sequence and supports the existence of a genetic form of this condition. Previous reports have emphasized possible environmental aetiologies. Infants with fetal brain disruption sequence should be investigated exhaustively and, in the absence of definitive evidence of an environmental cause, the possibility of a genetic aetiology should be considered. In some families the recurrence risk may be as high as one in four.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02079071
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  • 40
    Electronic Resource
    Electronic Resource
    Fetal brain disruption sequence in sisters (1995)
    Springer
    European journal of pediatrics 154 (1995), S. 654-657 
    Details
    ISSN: 1432-1076
    Keywords: Key words Fetal development ; Brain diseases ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report two female siblings with the fetal brain disruption sequence. Extensive investigation of both children failed to define a definitive aetiology but clinical and laboratory findings are consistent with a hitherto unknown storage disease. We postulate that the accumulation of a neurotoxic metabolite may be responsible for the disease phenotype observed. This is the first report of recurrence of the fetal brain disruption sequence and supports the existence of a genetic form of this condition. Previous reports have emphasized possible environmental aetiologies. Infants with fetal brain disruption sequence should be investigated exhaustively and, in the absence of definitive evidence of an environmental cause, the possibility of a genetic aetiology should be considered. In some families the recurrence risk may be as high as one in four.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004310050366
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  • 41
    Electronic Resource
    Electronic Resource
    Floating-Harbor syndrome: description of a further patient, review of the literature, and suggestion of autosomal dominant inheritance (1995)
    Springer
    European journal of pediatrics 154 (1995), S. 658-661 
    Details
    ISSN: 1432-1076
    Keywords: Key words Floating-Harbor ; syndrome ; Growth retardation ; Dysmorphology ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The Floating-Harbor syndrome is a growth retardation syndrome with delayed bone age, speech development, and typical facial features. The face is triangular with deep-set eyes, long eyelashes, bulbous nose, wide columella, short philtrum, and thin lips. We present an additional patient and review 16 cases from the literature. The possible phenotype in the patient's mother suggests a dominant mode of inheritance for the syndrome. Conclusion The Floating Harbor syndrome is a growth deficiency syndrome characterized by proportionate short stature, characteristic face and delayed speech development. Inheritance is possibly autosomal dominant.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004310050367
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  • 42
    Electronic Resource
    Electronic Resource
    A genetic study of idiopathic focal dystonias (1995)
    Springer
    Journal of neurology 242 (1995), S. 508-511 
    Details
    ISSN: 1432-1459
    Keywords: Dystonia ; Torticollis ; Blepharospasm ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The inheritance of focal dystonias was investigated in 43 families containing 43 index cases with torticollis (n = 21), blepharospasm (n = 18) and writer's cramp (n = 4). They generated a potential population of 235 first-degree relatives, and 168 out of 179 living first-degree relatives were examined. Ten relatives with dystonia were identified in ten families. Another two parents from two of the same group of ten families were affected according to the family history. The majority of the secondary cases (six patients, five siblings, and one child) were not aware of any dystonia. The tendency for affected relatives to have the same type of dystonia as index patients was observed only for torticollis. Overall, 23% of index patients had relatives with dystonia. Segregation analysis suggested the presence of an autosomal dominant gene or genes with reduced penetrante underlying focal dystonia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00867421
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  • 43
    Electronic Resource
    Electronic Resource
    Genetische Faktoren bei der Entstehung und Progression maligner Melanome (1995)
    Springer
    Der Hautarzt 46 (1995), S. 394-399 
    Details
    ISSN: 1432-1173
    Keywords: Schlüsselwörter Malignes Melanom ; Genetische Instabilität ; Genetik ; Syndrom der dysplastischen Nävi ; Xeroderma pigmentosum ; Key words Malignant melanoma ; Genetic instability ; Genetics ; Dysplastic nevus syndrome ; Xeroderma pigmentosum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Exposure of the skin to ultraviolet irradiation is an important risk factor for the development of malignant melanoma, with UVA possibly playing an important role. Hereditary factors are also relevant. In the dysplastic nevus syndrome a genetic instability has been shown by different methods. In xeroderma pigmentosum the DNA repair defect is thought to be responsible for the high incidence of malignant melanoma. Frequent and non-random changes in certain chromosomes have been demonstrated in melanoma cells. These might contain sequences that control melanoma growth or melanoma suppressor genes. Especially the short arm of chromosome 9 is thought to contain one of these genes. This hypothesis is supported by a genetic linkage analysis in melanoma families and the demonstration of a germ line deletion of the locus 9p21 in a patient with eight primary melanomas. Changes in known tumor suppressor genes and oncogenes have also been reported in melanoma, but no consistent sequence of genetic events is known.
    Notes: Zusammenfassung Die Exposition der Haut mit ultravioletten Strahlen ist ein wichtiger Risikofaktor für die Entwicklung eines malignen Melanoms. Möglicherweise spielt hierbei UVA-A eine besondere Rolle. Daneben sind hereditäre Faktoren von Bedeutung. Während beim Syndrom der dysplastischen Nävi eine genetische Instabilität mit verschiedenen Methoden nachgewiesen wurde, wird bei Xeroderma pigmentosum der DNA-Reparaturdefekt für die hohe Melanominzidenz verantwortlich gemacht. In Melanomzellen sind überzufällig häufig karyotypische Veränderungen in bestimmten Chromosomen gefunden worden. Diese enthalten möglicherweise Melanomwachstumsregulierende Sequenzen oder Melanom-Suppressorgene. Insbesondere der kurze Arm des Chromosoms 9 steht in Verdacht, eines dieser Gene zu enthalten. Diese Hypothese wird auch unterstützt durch eine genetische Kopplungsanalyse an Melanomfamilien und dem Nachweis einer Keimbahndeletion des Lokus 9p21 bei einer Patientin mit 8 primären Melanomen. Veränderungen an bereits bekannten Tumorsuppressorgenen oder Onkogenen sind ebenfalls in Melanomen beschrieben worden, ohne daß jedoch eine konsistente Reihenfolge von genetischen Ereignissen bekannt wäre.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001050050272
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  • 44
    Electronic Resource
    Electronic Resource
    Myotonic dystrophy in a large Sicilian kinship: a case report (1995)
    Springer
    Child's nervous system 11 (1995), S. 453-455 
    Details
    ISSN: 1433-0350
    Keywords: Myotonic ; Dystrophy ; Muscle disease ; Genetics ; Case report
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A large Sicilian kinship in which myotonic dystrophy (DM) affected spanning four generations is presented. The pedigree clearly illustrates the phenomenon of anticipation, and illustrates that this phenomenon is more marked when transmission occurs through an affected female rather than an affected male. The pedigree is interpreted in light of recent genetic advances in DM. Neurosurgeons and neurologists should consider a diagnosis of DM when asked to evaluate a floppy infant with enlarged lateral ventricles, and should be aware of special features regarding its inheritance pattern.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00334964
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  • 45
    Electronic Resource
    Electronic Resource
    Characterization of Japanese families with early-onset type 2 (non-insulin dependent) diabetes mellitus and screening for mutations in the glucokinase and mitochondrial tRNALeu(UUR) genes (1995)
    Springer
    Acta diabetologica 32 (1995), S. 17-22 
    Details
    ISSN: 1432-5233
    Keywords: Maturity-onset diabetes of the young (MODY) ; Genetics ; Diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Genetic linkage studies of families with earlyonset type 2 diabetes have facilitated the identification of diabetes-susceptibility genes. In order to assess the feasibility of using linkage approaches to identify genes responsible for the development of type 2 diabetes in Japanese subjects, we examined our clinical records for multigenerational families suitable for genetic studies. We identified 16 families in which at least one subject was diagnosed with type 2 diabetes before 25 years of age. Seven of these families had a pattern of inheritance consistent with a diagnosis of maturity-onset diabetes of the young (MODY) and nine families showed a complex pattern of inheritance of type 2 diabetes with transmission of diabetes-susceptibility genes from both parents. The glucokinase and mitochondrial tRNALeu(UUR) genes were screened for mutations in at least one affected subject from each family in order to assess the contribution of mutations in these genes to the development of the diabetes. No mutations were found, which suggests that the diabetes in these families resulted from mutations in other genes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00581039
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  • 46
    Electronic Resource
    Electronic Resource
    Domestication via hybridization of the wild tetraploid oats Avena magna and A. murphyi (1995)
    Springer
    Theoretical and applied genetics 91 (1995), S. 639-646 
    Details
    ISSN: 1432-2242
    Keywords: Gene introgression ; Genetics ; Linkage ; Taxonomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The wild tetraploid (2n=28) oat species Avena magna and A. murphyi have been domesticated by having been transferred from the common oat, A sativa (2n=42), the characteristics of non-shedding spikelets glabrous and yellow lemma, and reduced awn formation. Domestication has been achieved by crossing the common oat with either of the tetraploid species and then backcrossing the pentaploid hybrids with pollen of the tetraploid wild parent. Among the BC plants obtained only a few produced some seeds. Fertile tetraploids exhibiting the domesticated syndrome have been selected for in the F2 generation. Although morphologically they were almost indistinguishable from the common oat, they were tetraploids. Wild x domesticated A. magna hybrids were vigorous and fertile. They retained their spikelets at maturity, lemma color and pubescence were intermediate between the parental lines, and awns were formed only on the lower floret of the spikelet. Each of these characteristics segregated in a 3∶1 fashion, indicating single gene control, as in the common oat. These four characteristics formed a linkage group in one F2 family and two linkage groups in the other two families. The usefulness of the domesticated tetraploids for oat research and production has been discussed. Taxonomically, the domesticated tetraploids were ranked as subspecies: A. magna ssp. domestica, and A. murphyi ssp. rigida.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00223291
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  • 47
    Electronic Resource
    Electronic Resource
    Diallel analysis for mineral element absorption in tropical adapted soybeans [Glycine max (L.) Merrill] (1995)
    Springer
    Theoretical and applied genetics 90 (1995), S. 707-713 
    Details
    ISSN: 1432-2242
    Keywords: Mineral stress ; Nutrient efficiency ; Aluminium tolerance ; Inheritance ; Genetics ; Breeding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The Brazilian tropical adapted soybeans contains, in addition to superior morphological characters, genetic factors for tolerance to cultivation in acidic, mineral-stressed soils. However, the selection process for these hindrances has been empirical, and information on the genetics of mineral element uptake by the plant is necessary. The objective of this investigation was to identify the mode of inheritance for the absorption of phosphorus, potassium, calcium, magnesium, iron, aluminium, manganese, zinc and copper in a 9 × 9 diallel cross. General combining ability (GCA) was higher than specific combining ability (SCA), with the exception of copper, manganese and zinc, indicating predominantly additive effects. The ratios of GCA/SCA varied between 3.4 (calcium) and 8.5 (magnesium). The regression of covariance (Wr) on variance (Vr) showed that the additive-dominance model explained the genetic differences in this germ plasm. However, the detection of overdominance could be related to possible heterozygosity in the parental varieties for mineral absorption. Broad-sense heritability values were higher than narrow sense heritability values for aluminium, iron, potassium, calcium and magnesium, being in the range of 67.9–86.9% and 42.0–56.6%, respectively. This is an indication that soybeans can be further improved to efficient utilisation of nutrients and to tolerate toxic factors in the soil.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00222137
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  • 48
    Electronic Resource
    Electronic Resource
    Allelic relationships between genes for resistance to tomato spotted wilt tospovirus in Capsicum chinense (1995)
    Springer
    Theoretical and applied genetics 90 (1995), S. 146-149 
    Details
    ISSN: 1432-2242
    Keywords: Capsicum chinense ; Resistance gene ; Genetics ; Pepper ; Tomato spotted wilt virus ; Tospoviruses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Pepper (Capsicum chinense Jacq.) has been reported to be an important reservoir of resistance genes to tomato spotted wilt virus (TSWV). The genes for TSWV resistance present in three C. chinense lines (‘PI 152225’, ‘PI 159236’ and ‘Panca’) were investigated for allelism. All resistant lines were crossed with each other. Parents, F1, backcrosses and F2 populations (including reciprocals) developed from those crosses were mechanically inoculated with a highly virulent TSWV isolate. Susceptible C. annuum cv ‘Magda’ was used to check inoculum virulence. Fifty plants of the F1 hybrids; ‘Magda’ x ‘PI 152225’, ‘Magda’ x ‘PI 159236’, and ‘Magda’ x 'Panca, were also inoculated with the TSWV isolate. The resistance response in all C. chinense sources was associated with a localized, hypersensitive-like reaction that was phenotypically expressed as a prompt formation of large local lesions accompanied by premature leaf abscission. All F1 generations presented a final score of resistant; indicating that the expression of resistance to TSWV is conditioned by a dominant gene regardless of the source. The absence of segregation for resistance to TSWV that was observed in all generations of the crosses between C. chinense lines indicated that either a tightly linked group of genes exists or that the resistance is governed by the same single major gene (probably the already described Tsw gene). Previous reports have indicated that the Tsw gene is not effective against tospovirus members of serogroup II, i.e. tomato chlorotic spot virus (TCSV) and groundnut ring spot virus (GRSV). In the assay described here, all of the C. chinense lines showed, after mechanical inoculation, an identical susceptibility response to the TCSV and GRSV isolates.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00221009
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  • 49
    Electronic Resource
    Electronic Resource
    Identification of genomic regions affecting plant height in sorghum and maize (1995)
    Springer
    Theoretical and applied genetics 90 (1995), S. 380-388 
    Details
    ISSN: 1432-2242
    Keywords: Genetics ; Breeding ; Sorghum bicolor Zea mays
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The objective of this study was to use restriction fragment length polymorphisms (RFLPs) to determine the genetic location and effects of genomic regions controlling plant height in sorghum. F2 plants (152) from the cross CK60 x PI229828 were used. Genomic and cDNA clones (106) identified 111 loci distributed among ten linkage groups covering 1299 cM. Interval mapping identified four regions, each in a separate linkage group. These regions may correspond to loci (dw) previously identified by alleles with qualitative effects. Also, these regions identified in sorghum may be orthologous to those previously reported for plant height in maize. Gene effects and gene action varied among genomic regions. In each region, PI229828 alleles resulted in increased plant height. Each region accounted for 9.2–28.7% of the phenotypic variation. Positive, additive effects ranged from 15 to 32cm. Tallness was dominant or overdominant and conferred by alleles from PI229828 for three quantitative trait loci (QTL). At the fourth QTL, PI229828 contributed to increased plant height, but short stature was partially dominant. One digenic interaction was significant. The presence of a PI229828 allele at one region diminished the effects of the other region. A multiple model indicated that these four regions collectively accounted for 63.4% of the total phenotypic variation. The utility of this information for germplasm conversion through backcross breeding is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00221980
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  • 50
    Electronic Resource
    Electronic Resource
    Industrial mycology and the new genetics (1995)
    Springer
    Journal of industrial microbiology and biotechnology 14 (1995), S. 355-364 
    Details
    ISSN: 1476-5535
    Keywords: Transformation ; Fungi ; Yeast ; Genetics ; Biotechnology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Summary The genetic investigation of fungi has been extended substantially by DNA-mediated transformation, providing a supplement to more conventional genetic approaches based upon sexual and parasexual processes. Initial transformation studies with the yeastSaccharomyces cerevisiae provided the model for transformation systems in other fungi with regard to methodology, vector construction and selection strategies. There are, however, certain differences betweenS. cerevisiae and filamentous fungi with regard to type of genomic insertion and the availability of shuttle vectors. Single-site linked insertions are common in yeast due to the high level of homology required for recombination between vectored and genomic sequences, whereas mycelial fungi often show a high frequency of heterologous and unlinked insertions, often in the form of random and multiple-site integrations. While extrachromosomally-maintained or replicative vectors are readily available for use with yeasts, such vectors have been difficult to construct for use with filamentous fungi. The development of vectors for replicative transformation with these fungi awaits further study. It is proposed that replicative vectors may be inherently less efficient for use with mycelial fungi relative to yeasts, since the mycelium, as an extended and semicontinuous network of cells, may delimit an adequate diffusion of the vector carrying the selectable gene, thus leading to a high frequency of abortive or unstable transformants.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01569951
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  • 51
    Electronic Resource
    Electronic Resource
    Have fishes had their chips? The dilemma of threatened fishes (1995)
    Springer
    Environmental biology of fishes 43 (1995), S. 1-27 
    Details
    ISSN: 1573-5133
    Keywords: Conservation ; Extinction ; Rarity ; Biodiversity ; Breeding guilds ; Endemism ; Speciation ; Habitat degradation ; Environmental management ; Invasive fishes ; Genetics ; Ecology ; Stenotopy ; Captive propagation ; Legislation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Synopsis The conservation status and factors threatening fishes worldwide are reviewed in order to introduce a series of one-page articles on ‘Threatened fishes of the world’, and to encourage the incorporation of information on threatened fishes into international conservation programmes. Information on fish extinction and threat rates are compared with those of other animal groups, and the unique characteristics of fish conservation problems are highlighted. At present 979 species of fishes are listed as threatened in the IUCN Red List and at least 36 species and three subspecies are listed as recently extinct. It is argued that these figures are probably gross underestimates and that they may mislead conservation authorities and resource users about the seriousness of the situation. Freshwater fishes may be the most threatened group of vertebrates after the Amphibia. Urgent action is required to save many narrowly endemic, stenotopic species from extinction, especially in Africa, Asia and South America. The conservation of common species that drive essential ecological processes is also important. Anthropogenic pressures, especially habitat degradation, the introduction of invasive species and pollution, on inland and coastal waters are particularly severe and many major fish communities are threatened with elimination throughout the world. The conservation of marine fishes is complicated by the fact that it is difficult to ascertain their rarity. The importance of the retention of genetic variation is highlighted, and both orthodox and innovative conservation measures are encouraged. Further research on minimum viable populations, genetics, and the factors that cause fishes to become vulnerable to extinction, is urgently required.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00001812
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  • 52
    Electronic Resource
    Electronic Resource
    Adaptive on-line model for aerobic Saccharomyces cerevisiae fermentation (1995)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 48 (1995), S. 631-638 
    Details
    ISSN: 0006-3592
    Keywords: Saccharomyces cerevisiae ; fermentation ; on-line simulation ; state estimation ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: In order to study and control fermentation processes, indirect on-tine measurements and mathematical models can be used. In this article we present a mathematical on-line model for fermentation processes. The model is based on atom and partial mass balances as well as on equations describing the acid-base system. The model is brought into an adaptive form by including transport equations for mass transfer and unstructured expressions for the fermentation kinetics. The state of the process, i.e., the concentrations of biomass, substrate, and products, can be estimated on-line using the balance part of the model completed with measurement equations for the input and output flows of the process. Adaptivity is realized by means of on-line estimation of parameters in the transport and kinetic expressions using recursive regression analysis. These expressions can thus be used in the model as valid equations enabling prediction of the process. This makes model-based automation of the process and testing of the validity of the measurement variables possible. The model and the on-line principles are applied to a 3.5-L laboratory tormentor in which Saccharomyces cerevisiae is cultivated. The experimental results show that the model-based estimation of the state and the predictions of the process correlate closely with high-performance liquid chromatography (HPLC) analyses. © 1995 John Wiley & Sons, Inc.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260480611
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  • 53
    Electronic Resource
    Electronic Resource
    Kinetics of chlorinated ethylene dehalogenation under methanogenic conditions (1995)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 48 (1995), S. 659-666 
    Details
    ISSN: 0006-3592
    Keywords: methanogenic activity ; ethylene ; dechlorination ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Kinetics were determined for methanogenic activity and chlorinated ethylene dehalogenation by a methanol-enriched, anaerobic sediment consortium. The culture reductively dechlorinated perchloroethylene (PCE) to trichloroethylene (TCE), 1,1-dichloroethylene (1,1-DCE), vinylchloride (VC), and ethylene and ethane. The absence : of methanol or the addition of 2-bromoethanesulfonic. acid in the presence of methanol suppressed both methanogenic activity and dechlorination. In contrast, acetate production continued in the presence of 2-bromoethanesulfonic acid. These results suggest that dechlorination was strongly linked to methane formation and not to acetate production. A kinetic model, developed to describe both methanogenesis and dechlorination, successfully predicted experimentally measured concentrations of biomass, methane, substrate, and chlorinated ethylenes. The average maximum specific dehalogenation rates for PCE, TCE, 1,1-DCE, and VC were 0.9 ± 0.6, 0.4 ± 0.1, 12 ± 0.1, and 2.5 ± 1.7 μmol contaminant/ g. DW/day, respectively. This pattern for dechlorination rates is distinctly different than that reported for transition metal cofactors, where rates drop by approximately one order of magnitude as each successive chlorine is removed. The experimental results and kinetic analysis suggest that it will be impractical to targeting methanol consuming methanogenic organisms for in situ ground-water restoration. © 1995 John Wiley & Sons, Inc.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260480614
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  • 54
    Electronic Resource
    Electronic Resource
    Enhancement of antibody production by growth factor addition in perfusion and hollow-fiber culture systems (1995)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 48 (1995), S. 673-680 
    Details
    ISSN: 0006-3592
    Keywords: bovine serum albumin ; growth factor ; hollow-fiber culture ; perfusion culture ; antibody production rate ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The effects of the high-molecular-weight growth factors, transferrin and bovine serum albumin (BSA), on antibody production were analyzed quantitatively in continuous hollow-fiber cultivation over a period of 60 days. Transferrin enhanced cell growth but had no significant effect on the specific antibody production rate, whereas BSA significantly enhanced antibody production. The antibody production rate was increased 4- and 14-fold respectively by feeding BSA at 2 and 5 g L-1 into the EC side of the system (the side connected to the cell-containing outer part of the hollow-fiber unit) compared with the production achieved without BSA. Addition of 5 g L1 BSA into the IC side of the system (the side connected to the inner part of the hollow-fiber unit) resulted in a 2.5-fold increase in the antibody production rate. The effect of BSA was also analyzed using the perfusion culture system with a separation unit. When fresh medium containing either 2 or 5 g L-1 BSA was fed into the reactor, both the specific growth rate and specific death rate increased, while the specific antibody production rate was increased 2- and 25-fold, respectively, by feeding BSA at these two concentrations compared with no addition. Comparing the two systems, the increase in the antibody production rate achieved with the hollow-fiber system was threefold greater than that in the perfusion culture system with the same concentration of BSA feeding. © 1995 John Wiley & Sons, Inc.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260480616
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  • 55
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    Empirical evaluation of the influence of side chains on the conformational entropy of the polypeptide backbone (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 22 (1995), S. 132-140 
    Details
    ISSN: 0887-3585
    Keywords: protein folding ; protein stability ; mutational effects ; φ, ψ distribution ; Ramachandran map ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Changes in amino acid side chains have long been recognized to alterthe range and distribution of φ, ψ angles found in the main chain of polypeptides. Altering the range and distribution of φ, ψ angles also alters the conformational entropy of the flexible denatured state and may thus stabilize or destabilize it relative to the comparatively conformationally rigid native state. A database of 12,320 residues from 61 nonhomologous, high resolution crystal structures was examined to determine the φ, ψ conformational preferences of each of the 20 amino acids. These observed distributions in the native state of proteins are assumed to also reflect the distributions found in the denatured state. The distributionswere used to approximate the energy surface for each residue, allowing the calculation of relative conformational entropies for each residue relative to glycine. In the most extreme case, replacement of glycine by proline, conformational entropy changes will stabilize the native state relative to the denatured state by -0.82 ± 0.08 kcal/mol at 20°C. Surprisingly, alanine is found to be the most ordered residue other than proline. This unexpected result is a result of the high percentage of alanines found in helical conformations. This either indicates that the observed distributions in the native state do not reflect the distributions in the denatured state, or that alanine is much more likely to adopt a helical conformation in the denatured state than residues with longer side chains. Among those residues with φ, ψ angles compatible with helix incorporation the percentage of alanines actually in helices is very similar to other residues. This and the consistent ordering of alanine relative to other residues regardless of secondary structure are evidence that φ, ψ distributions in native states reflect those in the denatured states. © 1995 Wiley-Liss, Inc.
    Additional Material: 1 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340220206
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    Molecular dynamics simulations of rubredoxin from Clostridium pasteurianum: Changes in structure and electrostatic potential duringredox reactions (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 22 (1995), S. 154-167 
    Details
    ISSN: 0887-3585
    Keywords: iron-sulfur proteins ; electron transfer ; oxidation-reduction potentials ; solvent accessibility ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Molecular dynamics simulations of Clostridium pasteurianum rubredoxin in the oxidized and reduced forms have been performed. Good agreement between both forms and crystal data has been obtained (rms deviation of backbone atoms of 1.06 and 1.42 Å, respectively), which was due in part to the use of explicit solvent and counterions. The reduced form exhibits an unexpected structural change: the redox site becomes much more solvent-accessible, so that water enters a channel between the surface and the site, but with little actual structural rearrangement (the rms deviation of backbone atoms between the oxidized and reduced is 0.77 Å). The increase in solvent accessibility is also seen, although to a much lesser extent, between the oxidized and reduced crystal structures of Pyrococcus furiosus rubredoxin, but no high resolution crystal or nuclear magnetic resonance solution data exist for reduced C. pasteurianum rubredoxin. The electrostatic potential at the iron site and fluctuations in the potential, which contribute to both the redox and electron transfer properties, have also been evaluated for both the oxidized and the reduced simulations. These results show that the backbone plays a significant role (62-70 kcall/mol/e) and the polar sidechains contribute relatively little (0-4 kcal/mol/e) to the absolute electrostatic potential at the iron of rubredoxin for both forms. However, both groups contribute significantly to the change in redox state by becoming more polarized and more densely packed around the redox site upon reduction. Furthermore, these results show that the solvent becomes much more polarized in the reduced form than in the oxidized form, even excluding the penetrating water. Finally, the simulation indicates that the contribution of the charged side chains to the electrostatic potential is largely canceled by that of the counterions. © 1995 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340220208
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    Crystallization of UDP-N-acetylglucosamine O-acyltransferase from Escherichia coli (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 22 (1995), S. 191-192 
    Details
    ISSN: 0887-3585
    Keywords: lipopolysaccharide ; lipid A ; endotoxin ; protein structure ; acyltransferase ; X-ray crystallography ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Crystals of UDP-N-acetylglucosamine O-acyltransferase (lpxA) fromEscherichia coli have been obtained from solutions of sodium/potassium phosphate and dimethylsulfoxide. These crystals belong to the cubic space group P213 (a = 99.0 Å), diffract X-raysto approximately 2.5 Å resolution and contain one subunit of the enzyme in the asymmetric unit. © 1995 Wiley-Liss, Inc.
    Additional Material: 1 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340220212
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    Comparison of the effects of hydrophobicity, amphiphilicity, and α-helicity on the activities of antimicrobial peptides (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 22 (1995), S. 182-186 
    Details
    ISSN: 0887-3585
    Keywords: hydrophobic moment ; peptide-cell ; membrane interactions ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Multiple linear regression was used to quantify the dependence of the antimicrobial activity of 13 peptides upon three calculated or experimentally determined parameters: mean hydrophobicity, mean hydrophobic moment, and α-helix content. Mean hydrophobic moment is a measure of the amphiphilicity of peptides in an α-helical conformation. Antimicrobial activity was quantified as the reciprocal of the measured minimal inhibitory concentration (MIC) against Escherichia coli. One of the peptides was magainin 2, and the remainder were novel peptides designed for this study. The multiple linear regression results revealed that the amphiphilicity of the peptides was the most important factor governing anti-microbial activity compared to mean hydrophobicity orα-helix content. A better regression cf the data was obtained using In(1/MIC + constant) as the dependent variable than with either 1/MIC or In(1/MIC). These results should be useful in designing peptides with higher antimicrobial activity. © 1995 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340220210
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    Exploring the binding preferences/specificity in the active site of human cathepsin E (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 22 (1995), S. 168-181 
    Details
    ISSN: 0887-3585
    Keywords: aspartic proteinase ; enzyme kinetics ; rule-based model ; chromogenic assay ; synthetic substrate ; inhibitor ; molecular modeling ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Aspartic proteinases are produced in the human body by a variety of cells. Some of these proteins, examples of which are pepsin, gastricsin, and renin, are secreted and exert their effects in the extracellular spaces. Cathepsin D and cathepsin E on the other hand are intracellular enzymes. The least characterized of the human aspartic proteinases is cathepsin E. Presented here are results of studies designed to characterize the binding specificities in the active site of human cathepsin E with comparison to othermechanistically similar enzymes. A peptide series based on Lys-Pro-Ala-Lys-Phe*Nph-Arg-Leu was generatedto elucidate the specificity in the individual binding pockets with systematic substitutions in the P5- P2 and P2′-P3′ based on charge, hydrophobicity, and hydrogen bonding. Also, to explore the S2 binding preferences, asecond series of peptides based on Lys-Pro-Ile-Glu-Phe*Nph-Arg-Leu was generated with systematic replacements in the P2 position. Kinetic parameters were determined forboth sets of peptides. The results were correlated to a rule-based structural model of human cathepsin E, constructed on the known three-dimensional structures of several highly homologous aspartic proteinases; porcine pepsin, bovine chymosin, yeast proteinase A, human cathepsin D, andmouse and human renin. Important specificity-determining interactions were found in the S3 (Glu13) and S2 (Thr-222, Gln-287, Leu-289, Ile-300)subsites. © 1995 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340220209
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    Masthead (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 22 (1995) 
    Details
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340220301
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    Crystallization, characterization, and preliminary crystallographic studies of mitochondrial carbamoyl phosphate synthetase I of Rana catesbeiana (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 22 (1995), S. 193-196 
    Details
    ISSN: 0887-3585
    Keywords: urea cycle ; frog ; liver ; carbamyl phosphate synthetase ; X-ray diffraction ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Carbamoyl phosphate synthetase I (ammonia; E C 6.3.4.16) was purified from the liver of Rana catesbeiana (bullfrog). Crystals of the protein have been obtained at 22°C by the hanging drop vapor diffusion technique, with polyethylene glycol as precipitant. Tetragonal crystals of about 0.3 × 0.3 × 0.7 mm diffract at room temperature to at least 3.5 Å using a conventional source and are stable to X-radiation for about 12 h. Therefore, these crystals are suitablefor high resolution studies. The space group is P41212 (or its enantiomorph P43212), with unit cell dimensions a = b = 291.6 Å and c = 189.4 Å. Density packing considerations areconsistent with the presence of 4-6 monomers (Mr of the monomer, 160,000) in the asymmetric unit. Amino-terminal sequence of the enzyme and of a chymotryptic fragment of 73.7 kDa containing the COOH-terminus has been obtained. The extensive sequence identity with rat and human carbamoyl phosphate synthetase I indicates the relevance for mammals of structural data obtained with the frog enzyme. © 1995 Wiley-Liss, Inc.
    Additional Material: 1 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340220213
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    Prediction of the structure of GroES and its interaction with GroEL (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 22 (1995), S. 199-209 
    Details
    ISSN: 0887-3585
    Keywords: chaperonins ; electron microscopy ; FTIR ; molecular modeling ; structure prediction ; contact prediction ; active site prediction ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The three-dimensional structure of the GroES monomer and its interaction with GroEL has been predicted using a combination of prediction tools and experimental data obtained by biophysical [electron microscope (EM), Fourier transform infrared (FTIR), and nuclear magnetic resonance (NMR)] and biochemical techniques. The GroES monomer, according to the prediction, is composed of eight β-strands forming a β-barrel with loose ends. In the model, β-strands 5-8 run along the outer surface of GroES, forming an antiparallel β-sheet with β4 loosely bound to one of the edges. β-strands 1-3 would then be parallel and placed in the interior of the molecule. Loops 1-3 would face the internal cavity of the GroEL-GroES complex, and together with conserved residues in loops 5 and 7, would form the active surface interacting with GroEL. © 1995 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340220302
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    Structural model of the photosynthetic reaction center of Rhodobacter capsulatus (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 22 (1995), S. 226-244 
    Details
    ISSN: 0887-3585
    Keywords: photosynthesis ; protein structure ; homology modeling ; molecular mechanics ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The reaction center (RC) from the photosynthetic bacterium Rhodobacter (Rb.) capsulatus has been the subject of a considerable amount of molecular biological and spectroscopic work aimed at improving our understanding of the primary steps of photosynthesis. However, no three-dimensional structure is available for this protein. We present here a model obtained by combining information from the structure of the highly homologous RC from Rhodopseudomonas (Rps.) viridis with molecular mechanics and simulated annealing calculations. In the Rb. Capsulatus model the orientations of the bacteriochlorophyll monomer and the bacteriopheophytin on the branch inactive in electron transfer differ significantly from those in the RCs of Rps. Viridis and Rb. Sphaeroides. The bacteriopheophytin orientational difference is in good accord with previous linear dichroism measurements. A comparison is made of interactions between the pigments and the protein environment that may be of functional significance in Rps. viridis, Rb. sphaeroides, and Rb. capsulatus. © 1995 Wiley-Liss, Inc.
    Additional Material: 8 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340220304
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    Structural basis for serpin inhibitor activity (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 22 (1995), S. 210-225 
    Details
    ISSN: 0887-3585
    Keywords: serpin-proteinase complex ; mutants ; deamidation ; α-helix-β-sheet conversion ; homology modeling ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The mechanism of formation and the structures of serpin-inhibitor complexes are not completely understood, despite detailed knowledge of the structures of a number of cleaved and uncleaved inhibitor, noninhibitor, and latent serpins. It has been proposed from comparison of inhibitor and noninhibitor serpins in the cleaved and uncleaved forms that insertion of strand s4A into preexisting β-sheet A is a requirement for serpin inhibitor activity. We have investigated the role of this strand in formation of serpin-proteinase complexes and in serpin inhibitor activity through homology modeling of wild type inhibitor, mutant substrate, and latent serpins, and of putative serpin-proteinase complexes. These models explain the high stability of the complexes and provide an understanding of substrate behavior in serpins with point mutations in s4A and of latency in plasmingoen activator inhibitor I. © 1995 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340220303
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    The cytidylyltransferase superfamily: Identification of the nucleotide-binding site and fold prediction (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 22 (1995), S. 259-266 
    Details
    ISSN: 0887-3585
    Keywords: homology search ; phosphodiesterases ; sequence analysis ; structure prediction ; threading ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The crystal structure of glycerol-3-phosphate cytidylyltransferase from B. subtilis (TagD) is about to be solved. Here, we report a testable structure prediction based on the identification by sequence analysis of a superfamily of functionally diverse but structurally similar nucleotide-binding enzymes. We predict that TagD is a member of this family. The most conserved region in this superfamily resembles the ATP-binding HiGH motif of class I aminoacyI-tRNA synthetases. The predicted secondary structure of cytidylyltransferase and its homologues is compatible with the α/β topography of the class I aminoacyl-tRNA synthetases. The hypothesis of similarity of fold is strengthened by sequence-structure alignment and 3D model building using the known structure of tyrosyl tRNA synthetase as template. The proposed 3D model of TagD is plausible both structurally, with a well packed hydrophobic core, and functionally, as the most conserved residues cluster around the putative nucleotide binding site. If correct, the model would imply a very ancient evolutionary link between class I tRNA synthetases and the novel cytidylyltransferase superfamily. © 1995 Wiley-Liss, Inc.
    Additional Material: 3 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340220306
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    Hard α-keratin IF: A structural model lacking a head-to-tail molecular overlap but having hybrid features characteristic of both epidermal keratin and vimentin IF (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 22 (1995), S. 267-272 
    Details
    ISSN: 0887-3585
    Keywords: α-keratin ; intermediate filaments ; epidermal keratin ; vimentin ; keratinopathies ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: In intermediate filaments (IF) both epidermal keratin and vimentin molecules have been shown to have an eight residue head to-tail overlap between the rod domains of similarly directed molecules. In the case of the epidermal keratins this region has also been shown to have particular structural/functional significance since it represents a hot-spot for mutations in the four keratinopathies characterized to date. While there is good evidence that this head-to-tail overlap is present in IF containing Type III, IV, and V chains, as well as in the epidermal keratin IF (Ib/IIb), there are no data currently available for the hard α-keratin IF (Ia/IIa). Using a variety of data derived from X-ray diffraction and crosslinking studies, as well as theoretical modeling, it is now possible to demonstrate that the overlap region is not a feature of hard α-keratin IF. Indeed, it is shown that there is a nine residue gap between consecutive parallel molecules in the IF. An explanation for this observation is presented in terms of compensating disulfide bonds that occur both within the IF, and between the IF and the matrix in which the IF are embedded. © 1995 Wiley-Liss, Inc.
    Additional Material: 2 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340220307
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    The catalytic domain of a bacterial lytic transglycosylase defines a novel class of lysozymes (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 22 (1995), S. 245-258 
    Details
    ISSN: 0887-3585
    Keywords: bacterial muramidase ; peptidoglycan ; structure comparison ; sequence motifs ; structure/function relationships ; evolutionary relationships ; X-ray structure ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The 70-kDa soluble lytic transglycosylase (SLT70) from Escherichia coli is a bacterial exo-muramidase that cleaves the cell wall peptidoglycan, producing 1,6-anhydro-muropeptides. The X-ray structure of SLT70 showed that one of its domains is structurally related to lysozyme, although there is no obvious similarity in amino acid sequence. To relate discrete structural features to differences in reaction mechanism and substrate/product specificity, we compared the threedimensional structure of the catalytic domain of SLT70 with the structures of three typical representatives of the lysozyme superfamily: chicken-type hen egg-white lysozyme, goosetype swan egg-white lysozyme, and phage-type lysozyme from bacteriophage T4. We find a particularly close relationship between the catalytic domain of SLT70 and goose-type lysozyme, with not only a significant similarity in overall structure, but even a weak homology in amino acid sequence. This finding supports the notion that the goose-type lysozyme takes up a central position in the lysozyme superfamily and that it is structurally closest to the lysozyme ancestors. The saccharide-binding groove is the most conserved part in the four structures, but only two residues are absolutely preserved: the “catalytic” glutamic acid and a structurally required glycine. The “catalytic” aspartate is absent in SLT70, a difference that can be related to a different mechanism of cleavage of the β-1,4-glycosidic bond. The unique composition of amino acids at the catalytic site, and the observation of a number of differences in the arrangements of secondary structure elements, define the catalytic domain of SLT70 as a novel class of lysozymes. Its fold is expected to be exemplary for other bacterial and bacteriophage muramidases with lytic transglycosylase activity. © 1995 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340220305
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    Size-independent comparison of protein three-dimensional structures (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 22 (1995), S. 273-283 
    Details
    ISSN: 0887-3585
    Keywords: globular proteins ; protein structure analysis ; optimal rigid body superposition ; three-dimensional structural motif ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Protein structures are routinely compared by their root-mean-square deviation (RMSD) in atomic coordinates after optimal rigid body superposition. What is not so clear is the significance of different RMSD values, particularly above the customary arbitrary cutoff for obvious similarity of 2-3 Å. Our earlier work argued for an intrinsic cutoff for protein similarity that varied with the number of residues in the polypeptide chains being compared. Here we introduce a new measure, ρ, of structural similarity based on RMSD that is independent of the sizes of the molecules involved, or of any other special properties of molecules. When ρ is less than 0.4-0.5, protein structures are visually recognized to be obviously similar, but the mathematically pleasing intrinsic cutoff of ρ〉1.0 corresponds to overall similarity in folding motif at a level not usually recognized until smoothing of the polypeptide chain path makes it striking. When the structures are scaled to unit radius of gyration and equal principle moments of inertia, the comparisons are even more universal, since they are no longer obscured by differences in overall size and ellipticity. With increasing chain length, the distribution of ρ for pairs of random structures is skewed to higher values, but the value for the best 1% of the comparisons rises only slowly with the number of residues. This level is close to an intrinsic cutoff between similar and dissimilar comparisons, namely the maximal scaled ρ possible for the two structures to be more similar to each other than one is to the other's mirror image. The intrinsic cutoff is independent of the number of residues or points being compared. For proteins having fewer than 100 residues, the 1% ρ falls below the intrinsic cutoff, so that for very small proteins, geometrically significant similarity can often occur by chance. We believe these ideas will be helpful in judging success in NMR structure determination and protein folding modeling. © 1995 Wiley-Liss, Inc.
    Additional Material: 9 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340220308
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    Crystallization and preliminary crystallographic analysis of a 2,3-dihydroxybiphenyl dioxygenase from Pseudomonas sp. strain KKS102 having polychlorinated biphenyl (PCB)-degrading activity (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 22 (1995), S. 284-286 
    Details
    ISSN: 0887-3585
    Keywords: PCB degrading enzyme ; dioxygenase ; crystallization ; polychlorinated biphenyl ; selenomethionine ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Crystals have been obtained for a 2,3-dihydroxybiphenyl dioxygenase (conventionally called BphC) from a polychlorinated biphenyl (PCB)-degrader, Pseudomonas sp. strain KKS1O2. The crystals were grown using both ammonium sulfate and MPD as the precipitating agents. The crystals belonged to a tetragonal space group (I422) and diffracted to 2.5 Å. © 1995 Wiley-Liss, Inc.
    Additional Material: 2 Ill.
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  • 70
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    Cloning and expression of the uracil-DNA glycosylase inhibitor (UGI) from bacteriophage PBS-1 and crystallization of a uracil-DNA glycosylase-UGI complex (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 22 (1995), S. 287-289 
    Details
    ISSN: 0887-3585
    Keywords: DNA repair ; PCR ; Bacillus subtilis ; herpes simplex virus ; protein-protein interaction ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The uracil-DNA glycosylase inhibitory protein (UGI) from the bacterio-phage PBS-l has been cloned and overexpressed. The nucleotide sequence is identical to that for the previously described PBS-2 inhibitor. The recombinant PBS-l UGI inhibits the uracil-DNA glycosylase from herpes simplex virus type-l (HSV-l UDGase), and a complex between the HSV-l UDGase and PBS-l UGI has been crystallized. The crystals have unit cell dimensions a = 143.21 Å, c = 40.78 Å and are in a polar hexagonal space group. There is a single complex in the asymmetric unit with a solvent content of 62% by volume and the crystals diffract to 2.5Å on a synchrotron radiation source. © 1995 Wiley-Liss, Inc.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340220310
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    Crystallization and preliminary X-ray crystallographic studies of nonhistone region of macroH2A.1 (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 22 (1995), S. 290-292 
    Details
    ISSN: 0887-3585
    Keywords: macroH2A ; specialized nucleosomes ; fusion protein ; crystallization ; X-ray diffraction ; noncrystal-lographic symmetry ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Histone macroH2A has a novel hybrid structure consisting of a large nonhistone region and a region that closely resembles a full-length histone H2A. One key to understanding macroH2A function is determining the structure and function of its nonhistone region. The nonhistone region of one of the two known macroH2A subtypes was expressed in Escherichia coli and purified using affinity and molecular sieve chromatography. Crystals of the protein suitable for structural studies were grown from polyethylene glycol solutions by vapor equilibration techniques. The crystals belong to the hexagonal space group P64 (or its enantiomorph P62) with unit cell parameters: a = b = 106.2 Å, c = 125.9 Å, α = β = 90°, and γ = 120°. There are four molecules in the asymmetric unit. Self-rotation function studies revealed three twofold noncrystallographic rotation axes related approximately by 222 symmetry. These crystals have 47% solvent content and diffract to 3.8 Å resolution. © 1995 Wiley-Liss, Inc.
    Additional Material: 2 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340220311
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  • 72
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    Crystallization and preliminary crystallographic data for class I deoxyribose-5-phosphate aldolase from Escherichia coli: An Application of Reverse Screening (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 22 (1995), S. 67-72 
    Details
    ISSN: 0887-3585
    Keywords: aldolase ; protein complex crystallization ; crystallization screening ; X-ray crystallography ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: X-ray quality crystals of class I deoxyribose-5-phosphate aldolase from Escherichia coli have been obtained for the unliganded enzyme and in complex with its substrate, 2-deoxyribose-5-phosphate. The enzyme catalyzes the reversible cleavage of 2-deoxyribose-5-phosphate to acetaldehyde and D-glyceraldehyde-3-phosphate. The unliganded and complex crystals are prismatic long rods and belong to the orthorhombic space group P212121 with cell dimensions a = 183.1 Å, b = 61.4 Å, c = 49.3 Å and a = 179.2 Å, b = 60.5, Å, c = 49.1 Å, respectively. Two molecules in the asymmetric unit are related by a noncrystallo-graphic 2-fold axis. The crystals are stable in the X-ray beam and diffract to at least 2.6 Å. A new method, reverse screening, designed to minimize protein utilization during the screening process was used to determine supersaturation and crystallization conditions. © 1995 Wiley-Liss, Inc.
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    Masthead (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 22 (1995) 
    Details
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340220201
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    Crystallization and preliminary diffraction studies of thioesterase II from rat mammary gland (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 22 (1995), S. 73-75 
    Details
    ISSN: 0887-3585
    Keywords: thioesterase ; crystallization ; X-ray diffraction ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Thioesterase II from rat mammary gland has been crystallized in the presence of decanoic acid by the vapor diffusion method. The crystals belong to the orthorhombic space group P212121, and have cell dimensions, a = 52.7 Å, b = 78.0 Å, and c = 133.6 Å. The asymmetric unit likely consists of two protein monomers based on predictions from its calculated Matthews coefficient. Crystals typically diffract to at least 2.5 Å resolution and are suitable for X-ray crystallographic analysis. © 1995 Wiley-Liss, Inc.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340220111
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    Crystallization and preliminary X-ray diffraction studies of the cartilage link protein from bovine trachea (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 22 (1995), S. 76-78 
    Details
    ISSN: 0887-3585
    Keywords: arthritis ; cartilage ; crystallization ; link protein ; proteoglycan aggregate ; X-ray crystallography ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Cartilage extracellular matrix link protein, having molecular mass of approximately 40 kDa, is a metalloprotein that binds divalent cations and is only soluble in low ionic strength solutions. The link protein was purified from bovine trachea and has been crystallized by a vapor diffusion method using PEG 3350 as precipitant. The crystal symmetry is P1, and the unit cell dimensions are a = 43.55, b = 53.11, c = 60.10 Å, α = 90.44, β = 106.21, γ = 101.51°. The VM of 1.8 Å3/Da is consistent with the presence of two molecules of the link protein in the asymmetric unit. The crystals diffract X-rays from a synchrotron source to 1.7 Å resolution. © 1995 Wiley-Liss, Inc.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340220112
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    Accurate general method for lattice approximation of three-dimensional structure of a chain molecule (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 22 (1995), S. 100-109 
    Details
    ISSN: 0887-3585
    Keywords: protein structure ; RNA structure ; lattice model ; chain connectivity ; self-avoiding ; dynamic programming ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: An algorithm based on dynamic programming gives the lattice models having the minimal RMS deviations from the actual folds of protein (RNA, etc.) chains for a given lattice and a given orientation of the macromolecule relative to the lattice. The algorithm is applicable for 3-D lattices of any kind. The accuracy of the lattice approximation increases when the distance between neighbor chain links is not rigidly fixed. Special repulsive potentials facilitate generation of self-avoiding lattice chains. The results of model building show the efficiency and precisionof this proposed general method when compared with others. © 1995 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340220203
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    Crystallization and preliminary crystallographic study of human CksHs1: A cell cycle regulatory protein (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 21 (1995), S. 70-73 
    Details
    ISSN: 0887-3585
    Keywords: cell cycle protein ; crystallization ; X-ray diffraction ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The cell cycle regulatory protein CksHs1 has been crystallized in a form suitable for X-ray studies. CksHsl crystals were grown in the presence of vanadate, a phos-phatase inhibitor, but were also obtained with phosphate or tungstate as a cofactor. They belong to the hexagonal space group P6122 with unit cell dimensions: a=b=94 Å, c=131.6 Å, and γ =120. The crystals grown in the presence of vanadate diffract X-rays to at least 2.8 Å. Molecular replacement results from the homologous human CksHs2 structure reveal that a dimer forms the crystal habit, giving the unusual Vm value of 4.4 Å3/Da or a solvent content of 72%. © 1995 Wiley-Liss, Inc.
    Additional Material: 2 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340210109
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  • 78
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    Modulation of DNA-binding specificity within the nuclear receptor family by substitutions at a single amino acid position (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 21 (1995), S. 57-67 
    Details
    ISSN: 0887-3585
    Keywords: glucocorticoid receptor ; DNA binding domain ; mutant ; yeast ; transcription factor ; transactivation ; modeling ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Regulation of gene expression involves a large number of transcription factors with unique DNA-binding properties. Many transcription factors belong to families of related proteins that bind to similar but distinct sequences. In this study we have analyzed how amino acid substitutions at a single position in the DNA-binding domain modulate the DNA binding specificity within the nuclear receptor family of transcription factors. All possible amino acids were introduced at the first position in the DNA recognition helix, and the specificities of the mutants were analyzed using response elements containing all combinations of bases at two variable base pair positions. All mutant proteins were functional in DNA binding, and could be divided into classes of mutants with different response element specificities. By combining functional data with analysis of the structural effects of the mutations by molecular modeling, we could identify both prohibitive steric interactions as well as positive interactions, such as hydrogen bonds, that function as important determinants for specificity. Only the residues found naturally in the glucocorticoid and estrogen receptors, glycine and glutamate, produce unique binding specificities. The specificities of the other mutants overlap with each other somewhat but the substitutions clearly have potential to contribute to diversity within the nuclear receptor family. © 1995 Wiley-Liss, Inc.
    Additional Material: 4 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340210107
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    An analysis of side chain interactions and pair correlations within antiparallel β-sheets: The differences between backbone hydrogen-bonded and non-hydrogen-bonded residue pairs (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 22 (1995), S. 119-131 
    Details
    ISSN: 0887-3585
    Keywords: antiparallel β-sheet ; twist ; protein folding ; side chain interactions ; branched amino acids ; cystine-rich proteins ; side chain packing ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Cross-strand pair correlations are calculated for residue pairs in antiparallel β-sheet for two cases: pairs whose backbone atoms are hydrogen bonded together (H-bonded site) and pairs which are not (non-H-bonded site). The statistics show that this distinction is important. When glycine is located on the edge of a sheet, it shows a 3:1 preference for the H-bonded site. Thestrongest observed correlations are for pairs of disulfide-bonded cystines, many of which adopt a close-packed conformation with each cystine in a spiral conformation of opposite chirality to its partner. It is likely that these pairs are a signature for the family of small, cystine-rich proteins. Most other strong positive and negative correlations involve charged and polar residues. It appears that electrostatic compatibility is the strongest factor affecting pair correlation. Significant correlations are observed for β- and γ-branched residues inthe non-H-bonded site. An examination of the structures showsa directionality in side chain packing. There is a correlation between (1) the directionality in the packing interactions of non-H-bonded β- and γ-branched residue pairs, (2) the handedness of the observed enantiomers of chiral β-branched side chains, and (3) the handedness of the twist of β-sheet. These findings have implications for the formation of β-sheets during protein folding and the mechanism by which the sheet becomes twisted. © 1995 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340220205
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  • 80
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    An automated method for dynamic ligand design (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 23 (1995), S. 472-490 
    Details
    ISSN: 0887-3585
    Keywords: drug design ; FKBP ; FK506 ; immunophilin ; MCSS ; DLD ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: An automated method for the dynamic ligand design (DLD) for a binding site of known structure is described. The method can be used for the creation of de novo ligands and for the modification of existing ligands. The binding site is saturated with atoms (sp3 carbon atoms in the present implementation) that form molecules under the influence of a potential function that joins atoms to each other with the correct stereochemistry. The resulting molecules are linked to precomputed functional group minimum energy positions in the binding site. The generalized potential function allows atoms to sample a continuous parameter space that includes the Cartesian coordinates and their occupancy and type, e.g., the method allows change of an sp3 carbon into an sp2 carbon or oxygen. A parameter space formulated in this way can then be sampled and optimized by a variety of methods. In this work, molecules are generated by use of a Monte Carlo simulated annealing algorithm. The DLD method is illustrated by its application to the binding site of FK506 binding protein (FKBP), an immunophilin. De novo ligands are designed and modification of the immunosuppressant drug FK506 are suggested. The results demonstrate that the dynamic ligand design approach can automatically construct ligands which complement both the shape and charge distribution of the binding site. © 1995 Wiley-Liss, Inc.
    Additional Material: 9 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340230403
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    Docking of a human rhinovirus neutralizing antibody onto the viral capsid (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 23 (1995), S. 491-501 
    Details
    ISSN: 0887-3585
    Keywords: antibody structure ; viral neutralization ; human rhinovirus ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The structure of the complex between the Fab fragment of a human rhinovirus serotype 2 (HRV2) neutralizing antibody (8F5) and a cross-reactive synthetic peptide derived from the viral capsid protein VP2 has been recently determined by crystallographic methods.1 The conformation adopted by the peptide was very similar to and could be superimposed onto the corresponding region of the viral protein VP2 of human rhinovirus 1A (HRV1A) whose three-dimensional structure is known.2 The structure of the Fab fragment determined in the complex was docked onto the viral capsid using the superimposition transformation found for the peptide. In the resulting model the Fab protrudes almost radially to about 60 Å from the surface of the virion without any major steric problem. The Fab fragment was then placed on each one of the 60 equivalent epitopes using the T = 1 icosahedral symmetry of the virus. The closest pairs of Fab fragments are related by viral 2-fold axes and run almost parallel to each other without clashing. These axes of symmetry from the viral particle could thus be coincident with the dyad axes of the antibodies. Furthermore, comparison of the three-dimensional structure of the Fab/peptide complex with the structure of the Fab fragment alone3 indicates that the flexibility of the antibody's elbow would facilitate bivalent attachment to the same viral particle. In accordance with the docking results, experimental determination of the stoichiometry of binding yielded a ratio of 30 IgG molecules per virion also suggesting bivalent attachment of antibody 8F5 onto the viral particle. The neutralization of viral infectivity, being neither aggregation (this paper) nor inhibition of receptor binding,4 might be mainly achieved by reducing viral spread from cell to cell and/or inhibition of uncoating. © 1995 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
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    Toward understanding the structure and interactions of microtubules and motor proteins (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 23 (1995), S. 502-509 
    Details
    ISSN: 0887-3585
    Keywords: microtubules ; molecular motors ; electron cryomicroscopy ; decorated microtubules ; microtubule organization ; structure of microtubule/motor domain complexes ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: To obtain an overall three-dimensional picture of the interaction between microtubules and the motor proteins of the kinesin family it will be necessary to take account of both atomic resolution structures obtained by X-ray crystallography and medium resolution reconstructions obtained by electron cryomicroscopy. We examine the problems associated with obtaining the required structural information from electron micrographs of vitreous ice-embedded microtubules decorated with motor domains. We find that the minus-end directed motor, ncd, decorates microtubules with an 80 Å periodicity as for kinesin. Our theoretical analysis and experiments with ncd illustrate the difficulty in determining unambiguously the surface lattice organization by diffraction analysis of micrographs. 3D reconstructions of decorated microtubules are required to accurately locate the motor domains. Helical diffraction theory is not usually applicable because microtubules are cylindrical structures that rarely have complete helical symmetry. We propose using a back-projection method based on the long pitch helices formed by individual protofilaments. Model reconstructions show that this approach is feasible. © 1995 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340230405
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  • 83
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    Binding geometry of α-helices that recognize DNA (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 23 (1995), S. 525-535 
    Details
    ISSN: 0887-3585
    Keywords: DNA-protein interaction ; crystal structure ; transcription factor ; gene regulation ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Many transcription factors have an α-helix that binds to DNA bases in a specific fashion. The DNA-binding geometry of these recognition helices varies substantially. We define a set of parameters to describe the binding geometry of recognition helices and analyze specific stereochemical elements that determine particular geometries. Because the convex surface of the helix must fit into the concave surface of the DNA major groove, the number of degrees of freedom of the recognition helix is reduced from a possible six to a single angle, which we call α. The chemically interacting DNA bases and amino acid residues must lie along a common line and have the same spacing along it. This pairing of base positions with residue positions seems to restrict the binding geometry further to a set of discrete values for α. © 1995 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340230407
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    Crystallographic structure of metal-free concanavalin A at 2.5 Å resolution (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 23 (1995), S. 510-524 
    Details
    ISSN: 0887-3585
    Keywords: lectin ; demetallized ; peptide bond isomerization ; inter-dimer interactions ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The three-dimensional structure of demetallized concanavalin A has been determined at 2.5 Å resolution and refined to a crystallographic R-factor of 18%. The lectin activity of concanavalin A requires the binding of both a transition metal ion, generally Mn2+, and a Ca2+ ion in two neighboring sites in close proximity to the carbohydrate binding site. Large structural differences between the native and the metal-free lectin are observed in the metal-binding region and consequently for the residues involved in the specific binding of saccharides. The demetallization invokes a series of conformational changes in the protein backbone, apparently initiated mainly by the loss of the calcium ion. Most of the Mn2+ ligands retain their position, but the Ca2+ binding site is destroyed. The Ala207-Asp208 peptide bond, in the β-strand neighboring the metal-binding sites, undergoes a cis to trans isomerization. The cis conformation for this bond is a highly conserved feature among the leguminous lectins and is critically maintained by the Ca2+ ion in metal-bound concanavalin A. A further and major change adjacent to the isomerized bond is an expansion of the loop containing the monosaccharide ligand residues Leu99 and Tyr100. The dispersion of the ligand residues for the monosaccharide binding site (Asn14, Agr228, Asp208, Leu99, and Tyr100) in metalfree concanavalin A abolishes the lectin's ability to bind saccharides. Since the quaternary structure of legume lectins is essential to their biological role, the tetramer formation was analyzed. In the crystal (pH 5), the metal-free concanavalin A dimers associate into a tetramer that is similar to the native one, but with a drastically reduced number of inter-dimer interactions. This explains the tetramer dissociation into dimers below pH values of 6.5. © 1995 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340230406
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    Atomic and residue hydrophilicity in the context of folded protein structures (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 23 (1995), S. 536-547 
    Details
    ISSN: 0887-3585
    Keywords: water ; hydrophobicity ; hydration ; X-ray crystallography ; solvation ; ordered solvent ; molecular recognition ; water-protein interactions ; drug and inhibitor design ; protein surface analysis ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Water-protein interactions drive protein folding, stabilize the folded structure, and influence molecular recognition and catalysis. We analyzed the closest protein contacts of 10,837 water molecules in crystallographic structures to define a specific hydrophilicity scale reflecting specific rather than bulk solvent interactions. The tendencies of different atom and residue types to be the nearest protein neighbors of bound water molecules correlated with other hydrophobicity scales, verified the relevance of crystallographically determined water positions, and provided a direct experimental measure of water affinity in the context of the folded protein. This specific hydrophilicity was highly correlated with hydrogen-bonding capacity, and correlated better with experimental than computationally derived measures of partitioning between aqueous and organic phases. Atoms with related chemistry clustered with respect to the number of bound water molecules. Neutral and negatively charged oxygen atoms were the most hydrophilic, followed by positively-charged then neutral nitrogen atoms, followed by carbon and sulfur atoms. Agreement between observed side-chain specific hydrophilicity values and values derived from the atomic hydrophilicity scale showed that hydrophilicity values can be synthesized for different functional groups, such as unusual side or main chains, discontinuous epitopes, and drug molecules. Two methods of atomic hydrophilicity analysis provided a measure of complementarity in the interfaces of trypsin:pancreatic trypsin inhibitor and HIV protease:U-75875 inhibitor complexes. © 1995 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340230408
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    A model for the LexA repressor DNA complex (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 21 (1995), S. 226-236 
    Details
    ISSN: 0887-3585
    Keywords: doeking ; Monte Carlo ; LexA repressor ; DNA binding domain ; protein-DNA interaction ; solution structure ; molecular recognition ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A structural model for the interaction of the LexA repressor DNA binding domain (DBD) with operator DNA is derived by means of Monte Carlo docking. Protein-DNA complexes were generated by docking the LexA repressor DBD NMR solution structure onto both rigid and bent B-DNA structures while giving energy bonuses for contacts in agreement with experimental data. In the resulting complexes, helix III of the LexA repressor DBD is located in the major groove of the DNA and residues Asn-41, Glu-44, and Glu-45 form specific hydrogen bonds with bases of the CTGT DNA sequence. Ser-39, Ala-42, and Asn-41 are involved in a hydrophobic interaction with the methyl group of the first thymine base. Residues in the loop region connecting the two β-sheet strands are involved in nonspecific contacts near the dyad axis of the operator. The contacts observed in the docked complexes cover the entire consensus CTGT half-site DNA operator, thus explaining the specificity of the LexA repressor for such sequences. In addition, a large number of nonspecific interactions between protein and DNA is observed. The agreement between the derived model for the LexA repressor DBD/DNA complex and experimental biochemical results is discussed. © 1995 Wiley-Liss, Inc.
    Additional Material: 4 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340210305
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  • 87
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    Packing constraints of hydrophobic side chains in (α/β)8 barrels (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 21 (1995), S. 256-260 
    Details
    ISSN: 0887-3585
    Keywords: α/β - barrel ; α/β - hyperboloid - 8 ; three-dimensional structure ; local tight packing of hydrophobic groups ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: An analysis of possible tight packing of hydrophobic groups simultaneously at the both surfaces of β-hyperboloid-8 was conducted. This analysis shows that the disposition of amino acid side chains at the real β-structure's surface is unique. If we sign the mean distance between adjacent β-strands as “a,” and the mean distance along β-strand between Cα atoms, whose side chains are directed to one side of the β-sheet, as “b,” the ratio b/a = √2 very precisely. This ratio ensures the most efficient packing of side hydrophobic groups at the outer surface of β-hyperboloid-8, forming, at the same time, the second by efficiency packing at its inner surface. © 1995 Wiley-Liss, Inc.
    Additional Material: 3 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340210308
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    The first solvation shell of magnesium ion in a model protein environment with formate, water, and X-NH3, H2S, imidazole, formaldehyde, and chloride as ligands: An ab initio study (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 21 (1995), S. 244-255 
    Details
    ISSN: 0887-3585
    Keywords: carboxylate ; magnesium ; hydration ; ligand ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The first coordination shell of an Mg(II) ion in a model protein environment is studied. Complexes containing a model carboxylate, an Mg(II) ion, various ligands (NH3, H2S, imidazole, and formaldehyde) and water of hydration about the divalent metal ion were geometry optimized. We find that for complexes with the same coordination number, the unidentate carboxylate-Mg(II) ion is greater than 10 kcal mol-1 more stable than the bidentate orientation. Imidazole was found to be the most stable ligand, followed in order by NH3 formaldehyde, H2O, and H2S. © 1995 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
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  • 89
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    Protein conformational landscapes: Energy minimization and clustering of a long molecular dynamics trajectory (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 23 (1995), S. 97-110 
    Details
    ISSN: 0887-3585
    Keywords: bovine pancreatic trypsin inhibitor ; cluster analysis ; conformational searching ; molecular dynamics ; protein tertiary structure ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Using energy minimization and cluster analysis, we have analyzed a 1020 ps molecular dynamics trajectory of solvated bovine pancreatic trypsin inhibitor. Elucidation of conformational sub states in this way both illustrates the degree of conformational convergence in the simulation and reduces the structural data to a tractable subset. The relative movement of structures upon energy minimization was used to estimate the sizes of features on the protein potential energy surface. The structures were analyzed using their pairwise root-mean-square Cα deviations, which gave a global measure of conformational changes that would not be apparent by monitoring single degrees of freedom. At time scales of 0.1 ps, energy minimization detected sharp transitions between energy minima separated by 0.1 Å rms deviation. Larger conformational clusters containing these smaller minima and separated by 0.25 Å were seen at 1 ps time scales. Both of these small features of the conformational landscape were characterized by movements in loop regions associated with small, correlated backbone dihedral angle shifts. On a nanosecond time scale, the main features of the protein energy landscape were clusters separated by over 0.7 Å rms deviation, with only seven of these sub states visited over the 1 ns trajectory. These substates, discernible both before and after energy minimization, differ mainly in a monotonic pivot of the loop residues 11-18 over the course of the simulation. This loop contains lysine 17, which specifically binds to trypsin in the active site. The trajectory did not return to previously visited clusters, indicating that this trajectory has not been shown to have completely sampled the conformational substates available to it. Because the apparent convergence to a single region of conformation space depends on both the time scale of observation and the size of the conformational features examined, convergence must be operationally defined within the context of the simulation. © 1995 Wiley-Liss, Inc.
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    URL: http://dx.doi.org/10.1002/prot.340230111
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  • 90
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    Crystallization and preliminary X-ray diffraction studies of complexes between an influenza hemagglutinin and fab fragments of two different monoclonal antibodies (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 23 (1995), S. 115-117 
    Details
    ISSN: 0887-3585
    Keywords: antibody-protein complex ; influenza virus hemagglutinin ; protein recognition ; crystallization ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Fab fragments from two different monoclonal antibodies (BH151 and HC45) which bind to the same antigenic region of the influenza hemagglutinin were crystallized as complexes with the hemagglutinin. The complexes crystallize in PEG 600, pH 6.0, and PEG 2000, pH 8.5, respectively. Both crystals belong to space group P321, with very similar unit cell dimensions. © 1995 Wiley-Liss, Inc.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340230113
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  • 91
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    Crystallization and preliminary X-ray investigation of recombinant human interleukin 10 (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 22 (1995), S. 187-190 
    Details
    ISSN: 0887-3585
    Keywords: cytokine ; BCRF1 ; protein structure ; crystal seeding ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Crystals of recombinant human interleukin 10 have been grown from solutions of ammonium sulfate. The crystals are tetragonal, space group P41212 or P43212; the unit cell axes are a = 36.5 Å and c = 221.9 Å. There is the equivalent of one polypeptide chain in the asymmetric unit. The crystals are stable to X-rays and diffract to at least 2.5 Å resolution. © 1995 Wiley-Liss, Inc.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340220211
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  • 92
    Electronic Resource
    Electronic Resource
    Purification, crystallization, and preliminary X-ray diffraction analyses of the bacterial chemotaxis receptor modifying enzymes (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 21 (1995), S. 345-350 
    Details
    ISSN: 0887-3585
    Keywords: methyltransferase ; methylesterase ; protein modification ; S-adenosyl-L-methionine ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Bacterial chemotaxis receptor modifying enzymes from Salmonella typhimurium have been crystallized using microseeding techniques. The crystals of the S-adenosyl-L-methionine-dependent methyl transferase, CheR, belong to the monoclinic space group P21 with cell constants a = 55.1 Å, b = 48.1 Å, c = 63.1 Å, β = 112.3°. The crystals of the catalytic domain of the methylesterase, CheB, belong to the trigonal space group P3221 or P3121 with unit cell dimensions of a = b = 63.4 Å, c = 86.8 Å. Both crystals contain one molecule per asymmetric unit and have calculated Matthews' volumes of 2.4 Å3/Da. © 1995 Wiley-Liss, Inc.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340210407
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  • 93
    Electronic Resource
    Electronic Resource
    Masthead (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 21 (1995) 
    Details
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340210101
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  • 94
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    Predicted secondary and supersecondary structure for the serine-threonine-specific protein phosphatase family (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 21 (1995), S. 1-10 
    Details
    ISSN: 0887-3585
    Keywords: protein structure prediction ; protein phosphatase ; evolution ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A bona fide consensus prediction for the secondary and supersecondary structure of the serine-threonine specific protein phosphatases is presented. The prediction includes assignments of active site segments, an internal helix, and a region of possible 310 helical structure. An experimental structure for a member of this family of proteins should appear shortly, allowing this prediction to be evaluated. © 1995 Wiley-Liss, Inc.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340210102
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  • 95
    Electronic Resource
    Electronic Resource
    Thermodynamic genetics of the folding of the B1 immunoglobulin-binding domain from streptococcal protein G (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 21 (1995), S. 11-21 
    Details
    ISSN: 0887-3585
    Keywords: phage display ; protein stability ; genetic selection ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A method has been developed to select proteins that are thermodynamically destabilized yet still folded and functional. The DNA encoding the B1 IgG-binding domain from Group G Streptococcus (Strp G) has been fused to gene III of bacteriophage M13. The resulting fusion protein is displayed on the surface of the phage thus enabling the phage to bind to IgG molecules. In addition, these phage exhibit a small plaque phenotype that is reversed by mutations that destabilize the Strp G domain. By selecting phage with large plaque morphology that retain their IgG-binding function, it is possible to identify mutants that are folded but destabilized compared with wild-type Strp G. Such mutants can be divided into three general categories: (1) those that disrupt packing of hydrophobic side chains in the protein interior; (2) those that destabilize secondary structure; and (3) those that alter specific hydrogen bonds involving amino acid side chains. A number of the mutants have been physically characterized by circular dichroism and nuclear magnetic resonance and have been shown to have structures similar to wild-type Strp G but stabilities that were decreased by 2-5 kcal/mol. © 1995 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340210103
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  • 96
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    Electronic Resource
    Elusive affinities (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 21 (1995), S. 30-39 
    Details
    ISSN: 0887-3585
    Keywords: protein-protein interaction ; protein-DNA interaction ; microcalorimetry ; heat capacity changes ; entropy ; accessible surface area ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The affinity of two molecules for each other and its temperature dependence are determined by the change in enthalpy, free enthalpy, entropy, and heat capacity upon dissociation. As we know the forces that stabilize-protein-protein or protein-DNA association and the three-dimensional structures of the complex, we can in principle derive values for each one of these parameters. The calculation is done first in gas phase by molecular mechanics, then in solution with the help of hydration parameters calibrated on small molecules. However, estimates of enthalpy and entropy changes in gas phase have excessively large error bars even under the approximation that the components of the complex associate as rigid bodies. No reliable result can be expected at the end. The fit to experimental values derived from binding and calorimetric measurements is poor, except for the dissociation heat capacity. This parameter can be attributed mostly to the hydration step and it correlates with the size of the interface. Many protein-protein complexes have interface areas in the range 1200-2000 Å2 and only small conformation changes, so the rigid body approximation applies. It is less generally valid in protein-DNA complexes, which have interfaces covering 2200-3100 Å2, large dissociation heat capacities, and affect both the conformation and the dynamics of their components. © 1995 Wiley-Liss, Inc.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340210105
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  • 97
    Electronic Resource
    Electronic Resource
    Crystallization and preliminary structural studies of the ncd motor domain (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 21 (1995), S. 68-69 
    Details
    ISSN: 0887-3585
    Keywords: microtubule motors ; X-ray diffraction ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The motor domain of the kinesin homolog ncd has been crystallized in the presence of MgATP by the vapor diffusion method using polyethylene glycol as the precipitant. The crystals belong to the orthorhombic space group I222 with unit cell dimensions a = 127.1 Å, b = 122.3 Å, c = 68.0 Å, and there is one ncd molecule per asymmetric unit. The crystals diffract X-ray to at least 2.3 Å and are appropriate for high-resolution structure determination. © 1995 Wiley-Liss, Inc.
    Additional Material: 1 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340210108
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  • 98
    Electronic Resource
    Electronic Resource
    Molecular dynamics simulations of alcohol dehydrogenase with a four- or five-coordinate catalytic zinc ion (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 21 (1995), S. 40-56 
    Details
    ISSN: 0887-3585
    Keywords: zinc parameterization ; effective force-field ; four-coordination ; five-coordination ; reaction mechanism ; ligand exchange ; bond length constraint ; ligand dynamics ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A detailed parameterization is presented of a zinc ion with one histidine and two cysteinate ligands, together with one or two water, hydroxide, aldehyde, alcohol, or alkoxide ligands. The parameterization is tailored for the active site of alcohol dehydrogenase and is obtained entirely from quantum chemical computations. The force-field reproduces excellently the geometry of quantum chemically optimized zinc complexes as well as the crystallographic geometry of the active site of alcohol dehydrogenase and small organic structures. The parameterization is used in molecular dynamics simulations and molecular mechanical energy minimizations of alcohol dehydrogenase with a four- or five-coordinate catalytic zinc ion. The active-site zinc ion seems to prefer four-coordination over five-coordination by at least 36 kJ/mol. The only stable binding site of a fifth ligand at the active-site zinc ion is opposite to the normal substrate site, in a narrow cavity behind the zinc ion. Only molecules of the size of water or smaller may occupy this site. There are large fluctuations in the geometry of the zinc coordination sphere. A four-coordinate water molecule alternates frequently (every 7 ps) between the substrate site and the fifth binding site and even two five coordinate water molecules may interchange ligation sites without prior dissociation. Ligand exchange at the zinc ion probably proceeds by a dissociative mechanism. The results show that it is essential to allow for bond stretching degrees of freedom in molecular dynamics simulations to get a correct description of the dynamics of the metal coordination sphere; bond length constraints may restrict the accessible part of the phase space and therefore lead to qualitatively erroneous results. © 1995 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340210106
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  • 99
    Electronic Resource
    Electronic Resource
    LINUS: A hierarchic procedure to predict the fold of a protein (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 22 (1995), S. 81-99 
    Details
    ISSN: 0887-3585
    Keywords: protein folding ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: We describe LINUS, a hierarchic procedure to predict the fold of a protein from its amino acid sequence alone. The algorithm, which has been implemented in a computer program, was applied to large, overlapping fragments from a diverse test set of 7 X-ray-elucidated proteins, with encouraging results. For all proteins but one, the overall fragment topology is well predicted, including both secondary and supersecondary structure. The algorithm was also applied to a molecule of unknown conformation, groES, inwhich X-ray structure determination is presently ongoing. LINUS is an acronym for Local Independently Nucleated Units of Structure. The procedure ascends the folding hierarchy in discrete stages, with concomitant accretion of structure at each step. The chain is represented by simplified geometry and folds under the influence of a primitive energy function. The only accurately described energetic quantity in this work is hard sphere repulsion-the principal forceinvolved in organizing protein conformation [Richards, F. M. Ann. Rev. Biophys. Bioeng. 6:151-176, 1977]. Among other applications, the method is a natural tool for use in the human genome initiative. © 1995 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340220202
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  • 100
    Electronic Resource
    Electronic Resource
    Investigation of the folding pathway of the TEM-1 β-lactamase (1995)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 22 (1995), S. 110-118 
    Details
    ISSN: 0887-3585
    Keywords: protein folding ; guanidine hydrochloride denaturation ; molten globule ; folding/unfolding kinetics ; proline isomerization ; slow-folding forms ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The TEM-1 β-lactamase is a globular protein containing 12 proline residues. The folding mechanism of this enzyme was investigated by kinetic and equilibrium experiments with the help of fluorescence spectroscopy and circular dichroism. The equilibrium denaturation of the protein induced by guanidine hydrochloride occurs in two discrete steps, indicating the existence of a thermodynamically stable intermediate state. Thisstate is 5.2 ± 0.4 kcal/mol less stable than the native conformation and 5.7 ± 0.2 kcal/mol more stable than the fully denaturedprotein. This intermediate state exhibits a high content of native secondary structure elements but is devoid of specific tertiary organization; its relation to the “molten globule” is discussed. Refolding kinetic experimentsrevealed the existence of a transient intermediate conformation between thethermodynamically stable intermediate and the native protein. This transient intermediate appears rapidly during the folding reaction. It exhibits a secondary structure content very similar to that of the native protein and has also recovered a significant amount of tertiary organisation. The final refolding step of the TEM-1 β-lactamase, leading to the native enzyme, is dominated by two major slow kinetic phases which probablyreflect a very complex process kinetically limited by proline cis/transisomerization. © 1995 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340220204
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