Library

feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 11
    Electronic Resource
    Electronic Resource
    Oxford, UK : Munksgaard International Publishers
    Immunological reviews 188 (2002), S. 0 
    ISSN: 1600-065X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary: Progress in human tumor immunology has recently been accelerated by new assays for antigen-specific cytotoxic T lymphocytes (CTLs). We have used tetrameric MHC class I complexes (tetramers) to study melanoma-specific CTLs both in vivo and in vitro, and have utilized the results to optimize vaccination strategies for patients. Tetramers have provided some of the best evidence to date that CTL responses against melanoma antigens arise spontaneously in patients. However, CTL responses to common (nonmutated) melanoma epitopes are generally weak or localized, and occur mostly in advanced metastatic disease, hence justifying early immunotherapeutic approaches. These observations led us to design a polyvalent vaccine construct for early administration to melanoma patients at high risk of progression. To compare possible vaccination protocols, we encoded this construct in several different vectors, and developed novel tetramers to track responses to the human melanoma epitopes in transgenic mice. Priming and boosting with the same poly-epitope construct encoded in heterologous vectors led to the expansion of CTLs with a single dominant specificity. Separating the antigens for independent presentation by antigen-presenting cells reversed the effect of immunodominance and induced a powerful polyvalent CTL response. These results provide important pointers for future vaccination trials, and tetramers will form an important tool in the immunomonitoring of these clinical studies.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 12
    ISSN: 1527-3458
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The development of selective ligands targeting neuronal nicotinic acetylcholine receptors to alleviate symptoms associated with neurodegenerative diseases presents the advantage of affecting multiple deficits that are the hallmarks of these pathologies. TC-1734 is an orally active novel neuronal nicotinic agonist with high selectivity for neuronal nicotinic receptors. Microdialysis studies indicate that TC-1734 enhances the release of acetylcholine from the cortex. TC-1734, by either acute or repeated administration, exhibits memory enhancing properties in rats and mice and is neuroprotective following excitotoxic insult in fetal rat brain in cultures and against alterations of synaptic transmission induced by deprivation of glucose and oxygen in hippocampal slices. At submaximal doses, TC-1734 produced additive cognitive effects when used in combination with tacrine or donepezil. Unlike (-)-nicotine, behavioral sensitization does not develop following repeated administration of TC-1734. Its pharmacokinetic (PK) profile (half-life of 2 h) contrasts with the long lasting improvement in working memory (18 h) demonstrating that cognitive improvement extends beyond the lifetime of the compound. The very low acute toxicity of TC-1734 and its receptor activity profile provides additional mechanistic basis for its suggested potential as a clinical candidate. TC-1734 was very well tolerated in acute and chronic oral toxicity studies in mice, rats and dogs. Phase I clinical trials demonstrated TC-1734's favorable pharmacokinetic and safety profile by acute oral administration at doses ranging from 2 to 320 mg.The bioavailability, pharmacological, pharmacokinetic, and safety profile of TC-1734 provides an example of a safe, potent and efficacious neuronal nicotinic modulator that holds promise for the management of the hallmark symptomatologies observed in dementia.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 13
    ISSN: 1365-3091
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Geosciences
    Notes: Abstract The north-east Australian margin is the largest modern example of a tropical mixed siliciclastic/carbonate depositional system, with an outer shelf hosting the Great Barrier Reef (GBR) and an inner shelf dominated by fluvially sourced siliciclastic sediment wedges. The long-term interplay between these sediment components and sea level is recorded in the Queensland Trough, a 1–2 km deep N–S elongate basin situated between the GBR platform and the Queensland Plateau. In this paper, 154 samples from 45 surface grabs and six well-dated piston cores were analysed for total carbonate content, carbonate mineralogy and Sr concentration to establish spatial and temporal patterns of carbonate accumulation in the Queensland Trough over the last 300 kyr. Surface carbonate contents are lowest on the inner-shelf (〈5%) and in the trough axis (〈60%) because of siliciclastic dilution. Carbonate on the shelf is mostly Sr-rich aragonite and high-Mg calcite (HMC), whereas that in the basin is mostly low-Mg calcite. Once normalized to remove the effects of siliciclastic dilution, surface Sr-rich aragonite and HMC abundances decrease linearly to background levels ≈ 100 km seaward of the shelf edge. Core samples show that, over time, normalized aragonite and Sr abundances are greatest during periods of shelf flooding and lowest when sea level drops below the shelf edge. This is consistent with changes in the production of coral and calcareous algae, and the shedding of their debris from the shelf. Interestingly, normalized HMC concentrations on the slope peak during periods of major transgression, perhaps because of maximum off-shelf transport from inter-reef areas or intermediate water dissolution. After accounting for siliciclastic dilution, there are strong similarities in both spatial and temporal patterns of carbonate minerals between slopes and basins of the north-east Australian margin and those of pure carbonate margins such as the Bahamas. A limited set of basic processes, including the formation and breakdown of carbonate on the shelf, the transport of carbonate off the shelf and eustatic sea level, probably controls carbonate accumulation in slope and basin settings of tropical environments, irrespective of proximal siliciclastic sediment sources.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 14
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Molecular microbiology 48 (2003), S. 0 
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The smallest cellular genomes are found in obligate symbiotic and pathogenic bacteria living within eukaryotic hosts. In comparison with large genomes of free-living relatives, these reduced genomes are rearranged and have lost most regulatory elements. To test whether reduced bacterial genomes incur reduced regulatory capacities, we used full-genome microarrays to evaluate transcriptional response to environmental stress in Buchnera aphidicola, the obligate endosymbiont of aphids. The 580 genes of the B. aphidicola genome represent a subset of the 4500 genes known from the related organism, Escherichia coli. Although over 20 orthologues of E. coli heat stress (HS) genes are retained by B. aphidicola, only five were differentially expressed after near-lethal heat stress treatments, and only modest shifts were observed. Analyses of upstream regulatory regions revealed loss or degradation of most HS (σ32) promoters. Genomic rearrangements downstream of an intact HS promoter yielded upregulation of a functionally unrelated and an inactivated gene. Reanalyses of comparable experimental array data for E. coli and Bacillus subtilis revealed that genome-wide differential expression was significantly lower in B. aphidicola. Our demonstration of a diminished stress response validates reports of temperature sensitivity in B. aphidicola and suggests that this reduced bacterial genome exhibits transcriptional inflexibility.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 15
    ISSN: 1460-2466
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Media Resources and Communication Sciences, Journalism
    Notes: Early channel reliance research compared different modes of communication to assess relationships among nonverbal and verbal cues. Emerging communication technologies represent a new venue for gaining insights into the same relationships. In this article, the authors advance a principle of interactivity as a framework for decomposing some of those relationships and report an experiment in which physical proximity—whether actors are in the same place (“co-located”) or interacting at a distance (“distributed”)—and the availability of other nonverbal environmental, auditory, and visual information in distributed modes is varied. Results indicate that both proximity and availability of nonverbal cues affect communication processes, social judgments participants make about each other, and task performance. The authors discuss implications about gains and losses due to presence of nonverbal features.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 16
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of fish biology 61 (2002), S. 0 
    ISSN: 1095-8649
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 17
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Nuclear extrachromosomal DNA elements have been identified in several kinetoplastids such as Leishmania and Trypanosoma cruzi, but never in Trypanosoma brucei. They can occur naturally or arise spontaneously as the result of sublethal drug exposure of parasites. In most cases, they are represented as circular elements and are mitotically unstable. In this study we describe the presence of circular DNA in the nucleus of Trypanosoma brucei. This novel type of DNA was termed NR-element (NlaIII repeat element). In contrast to drug-induced episomes in other kinetoplastids, the T. brucei extrachromosomal NR-element is not generated by drug selection. Furthermore, the element is stable during mitosis over many generations. Restriction analysis of tagged NR-element DNA, unusual migration patterns during pulsed field gel electrophoresis (PFGE) and CsCl/ethidium bromide equilibrium centrifugation demonstrates that the NR-element represents circular DNA. Whereas it has been found in all field isolates of the parasites we analysed, it is not detectable in some laboratory strains notably the genome reference strain 927. The DNA sequence of this element is related to a 29 bp repeat present in the subtelomeric region of VSG-bearing chromosomes of T. brucei. It has been suggested that this subtelomeric region is part of a transition zone on chromosomes separating the relatively stable telomeric repeats from the recombinationaly active region downstream of VSG genes. Therefore, we discuss a functional connection between the occurrence of this circular DNA and subtelomeric recombination events in T. brucei.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 18
    Electronic Resource
    Electronic Resource
    Copenhagen : International Union of Crystallography (IUCr)
    Acta crystallographica 57 (2001), S. 506-515 
    ISSN: 1399-0047
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Notes: X-ray crystal structures of three forms of human mitochondrial branched-chain aminotransferase (BCAT) were solved by molecular-replacement methods, using Escherichia coli BCAT as the search model. The enzyme is a homodimer and the polypeptide chain of each monomer has two domains. The small domain is composed of residues 1–175 and the large domain is composed of residues 176–365. The active site is close to the dimer interface. The 4′-aldehyde of the PLP cofactor is covalently linked to the ε-amino group of the active-site lysine, Lys202, via a Schiff-base linkage in two of the structures. In the third structure, the enzyme is irreversibly inactivated by Tris. The overall fold of the dimer in human mitochondrial BCAT is similar to the structure of two bacterial enzymes, E. coli BCAT and D-amino acid aminotransferase (D-AAT). The residues lining the putative substrate-binding pocket of human BCAT and D-AAT are completely rearranged to allow catalysis with substrates of opposite stereochemistry. In the case of human mitochondrial branched-chain aminotransferase, a hydrogen-bond interaction between the guanidinium group of Arg143 in the first monomer with the side-chain hydroxyl of Tyr70 in the second monomer is important in the formation of the substrate-binding pocket.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 19
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] The viruses HIV-1, Epstein–Barr virus (EBV), cytomegalovirus (CMV) and hepatitis C virus (HCV) are characterized by the establishment of lifelong infection in the human host, where their replication is thought to be tightly controlled by virus-specific CD8+ T cells. Here we present detailed ...
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 20
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Here we show that apoptotic cells overexpress vinculin and are ingested by dendritic cells, which subsequently cross-prime vinculin-specific cytotoxic T lymphocytes (CTLs). Successful cross-priming requires that the apoptotic cells provide maturation signals to dendritic cells through ...
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...