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An AIDS information center.

Because busy members of the health care team are confronted with a plethora of articles and information on AIDS, the Health Sciences Library at the University of Alabama has developed a current awareness information center on AIDS. The materials in the center can be easily accessed by patrons. Books and audiovisuals are included in the center; however, the primary emphasis is on accessing articles in journals to which the library subscribes and the journals which have granted blanket photocopy permission. The planning and organization of the center are described.

Acquired Immunodeficiency Syndrome↗

Selling the silver: country house libraries and the history of science.

Country houses have long acted as scholarly research centres, and the contents and organization of their libraries reveal how knowledge was created and transmitted through scientific networks: they provide material evidence of intellectual and social cultures. Manuscripts are particularly appreciated in this regard because they are unique, but individual books also differ and copies of the same book are not always identical -- they might be annotated by authors and readers, and the printed text can vary as well -- so they also carry invaluable historical information. When libraries are broken up, access to the past is permanently blocked.

Biological Science Disciplines↗

Insights into TOR function and rapamycin response: chemical genomic profiling by using a high-density cell array method.

With the advent of complete genome sequences, large-scale functional analyses are generating new excitement in biology and medicine. To facilitate genomewide functional analyses, we developed a high-density cell array with quantitative and automated readout of cell fitness. Able to print at > x 10 higher density on a standard microtiter plate area than currently possible, our cell array allows single-plate screening of the complete set of Saccharomyces cerevisiae gene-deletion library and significantly reduces the amount of small molecules and other materials needed for the study. We used this method to map the relation between genes and cell fitness in response to rapamycin, a medically important natural product that targets the eukaryotic kinase Tor. We discuss the implications for pharmacogenomics and the uncharted complexity in genotype-dependent drug response in molecularly targeted therapies. Our analysis leads to several basic findings, including a class of gene deletions that confer better fitness in the presence of rapamycin. This result provides insights into possible therapeutic uses of rapamycin/CCI-779 in the treatment of neurodegenerative diseases (including Alzheimer's, Parkinson's, and Huntington's diseases), and cautions the possible existence of similar rapamycin-enhanceable mutations in cancer. It is well established in yeast that although TOR2 has a unique rapamycin-insensitive function, TOR1 and TOR2 are interchangeable in the rapamycin-sensitive functions. We show that even the rapamycin-sensitive functions are distinct between TOR1 and TOR2 and map the functional difference to a approximately 120-aa region at the N termini of the proteins. Finally, we discuss using cell-based genomic pattern recognition in designing electronic or optical biosensors.

Cell Cycle Proteins↗

Identification of potential vaccine and drug target candidates by expressed sequence tag analysis and immunoscreening of Onchocerca volvulus larval cDNA libraries.

The search for appropriate vaccine candidates and drug targets against onchocerciasis has so far been confronted with several limitations due to the unavailability of biological material, appropriate molecular resources, and knowledge of the parasite biology. To identify targets for vaccine or chemotherapy development we have undertaken two approaches. First, cDNA expression libraries were constructed from life cycle stages that are critical for establishment of Onchocerca volvulus infection, the third-stage larvae (L3) and the molting L3. A gene discovery effort was then initiated by random expressed sequence tag analysis of 5,506 cDNA clones. Cluster analyses showed that many of the transcripts were up-regulated and/or stage specific in either one or both of the cDNA libraries when compared to the microfilariae, L2, and both adult stages of the parasite. Homology searches against the GenBank database facilitated the identification of several genes of interest, such as proteinases, proteinase inhibitors, antioxidant or detoxification enzymes, and neurotransmitter receptors, as well as structural and housekeeping genes. Other O. volvulus genes showed homology only to predicted genes from the free-living nematode Caenorhabditis elegans or were entirely novel. Some of the novel proteins contain potential secretory leaders. Secondly, by immunoscreening the molting L3 cDNA library with a pool of human sera from putatively immune individuals, we identified six novel immunogenic proteins that otherwise would not have been identified as potential vaccinogens using the gene discovery effort. This study lays a solid foundation for a better understanding of the biology of O. volvulus as well as for the identification of novel targets for filaricidal agents and/or vaccines against onchocerciasis based on immunological and rational hypothesis-driven research.

Animals↗

Ethics and the GMC core curriculum: a survey of resources in UK medical schools.

OBJECTIVES: To study the resources available and resources needed for ethics teaching to medical students in UK medical schools as required by the new GMC core curriculum. DESIGN: A structured questionnaire was piloted and then circulated to deans of medical schools. SETTING: All UK medical schools. RESULTS: Eighteen out of 28 schools completed the questionnaire, the remainder either indicating that their arrangements were "under review" (4) or not responding (6). Among those responding: 1) library resources, including video and information technology were found to be fairly well developed; 2) many schools had a good supply of handouts and sample cases for teaching; 3) most had a written syllabus, and 4) two-thirds examined in the subject. However, many schools indicated that there was an urgent need for: 1) full-time teachers (most ethics teaching is still by part-time and voluntary staff); funding for books and journals, and 3) additional teaching materials (including further case vignettes, handouts and sample exam questions). CONCLUSIONS: There has been a considerable overall improvement in resources for medical ethics teaching since the time of the last national survey (The Pond Report). However, provision varies widely from medical school to medical school. The particular needs identified were for full-time teachers, library resources and teaching materials. Wider use of existing organisations concerned with medical ethics could help to meet these needs.

Curriculum↗

Identification of a ferritin light chain pseudogene near the glycerol kinase locus in Xp21 by cDNA amplification for identification of genomic expressed sequences.

We used cDNA amplification for identification of genomic expressed sequences (CAIGES) to identify genes in the glycerol kinase region of the human X chromosome. During these investigations we identified the sequence for a ferritin light chain (FTL) pseudogene in this portion of Xp21. A human liver cDNA library was amplified by vector primers, labeled, and hybridized to Southern blots of EcoRI-digested human genomic DNA from cosmids isolated from yeast artificial chromosomes in the glycerol kinase region of Xp21. A 3.1-kb restriction fragment hybridized with the cDNA library, was subcloned and sequenced, and a 440-bp intronless sequence was found with strong similarity to the FTL coding sequence. Therefore, the FTL pseudogene that had been mapped previously to Xp22.3-21.2 was localized specifically to the glycerol kinase region. The CAIGES method permits rapid screening of genomic material and will identify genomic sequences with similarities to genes expressed in the cDNA library used to probe the cloned genomic DNA, including pseudogenes.

Base Sequence↗

Medical researchers and clinicians as seekers of information: the Nigeria case study.

Medical researchers and clinicians drawn from a random sample of health professionals in Nigeria were surveyed by means of a questionnaire to determine their sources of information. Sources of information were categorized into library related sources and non-library related sources in the first instance and responses analyzed in order to demonstrate which of the two categories of sources are utilized most by medical researchers or clinicians. A two-factor ANOVA analysis with repeated measures on one factor showed that researchers make significantly more use of library related sources of information than clinicians. A further grouping of source into bibliographic sources and AV materials and their subsequent analysis by use of a chi-square test, showed that clinicians make significantly greater use of AV materials than researchers, while the reverse is the case for bibliographic sources.

Developing Countries↗

Identification of a potent and selective oxytocin antagonist, from screening a fully encoded differential release combinatorial chemical library.

A library of 1,296 1,4-benzodiazepines was prepared on 160 microM Tentagel beads. Compounds are attached to the beads using orthogonally cleavable linkers. The library was first screened as pools of 30 beads where 50% of the material is released and screened. GW405212X, a selective oxytocin antagonist, was identified by picking single beads from active pools.

Animals↗

'One bead two compound libraries' for detecting chemical and biochemical conversions.

When combinatorial chemistry was introduced 13 years ago, the expectations were high for the delivery of results, particularly in the pharmaceutical industry. However, combinatorial chemistry was implemented independently of the application for which the products were going to be used. Resins developed only for efficient solid-phase synthesis were used and products were employed in existing assays developed for traditional solution studies. There was almost no assay or technology development and the use of real combinatorial methods soon had to give way to high-throughput synthesis and traditional screening. However, during recent years more sophisticated resins and assay techniques have been developed that may result in a second and more successful implementation of real integrated combinatorial chemistry. The first in this line of new developments is the 'one bead two compound' assay, in which the resin bead in addition to a combinatorial library member contains a reporter compound that can act as a beacon to monitor the activity of the library member. This powerful concept can be generally applied in all fields of combinatorial chemistry including drug, catalysts and material development.

Catalysis↗

MEDICAL INTERLIBRARY LOAN PATTERNS.

During the academic year 1958/59, a survey was made of interlibrary loan requests originating at Columbia University Medical Library. A high percentage of requests came from a relatively few requesters. However, analysis based on "one-time" and "repeat" categories for the patron and his requests indicated a situation less extreme than "monopoly use by an elite group." Requests were classed by type, age, language, title, etc., and were also correlated with such variables as citation source, requester's academic status and experience, and estimated importance of material. The analysis aims to uncover patterns significant for cooperative planning. Did the repeat and one-time requester show distinctive characteristics and habits? Which materials attracted more repeat requests? Findings generally favored cooperation, at least for a library servicing nonstudent researchers. Unpredictability of researchers' needs was noted. Apart from specific findings, this paper offers methods for statistical analysis of interlibrary loans.

Data Collection↗

Large-scale identification of transcripts expressed in a symbiotic fungus (Termitomyces) during plant biomass degradation.

Fungus-growing termites have a symbiotic relationship with the basidiomycetes of the genus Termitomyces. This symbiotic system is able to degrade dead plant material efficiently. We conducted expressed sequence tag (EST) analysis of a symbiotic Termitomyces fungus degrading plant material in a field nest of the termite Macrotermes gilvus. A subtractive cDNA library was also investigated to facilitate the discovery of genes expressed specifically under the symbiotic conditions. A total of 2,613 ESTs were collected and resulted in 1,582 nonredundant tentative consensus sequences, of which approximately 59% showed significant similarity to known protein sequences. A number of homologous sequences to genes involved in plant cell wall degradation were identified and a majority of them encoded putative pectinolytic enzymes. Real-time quantitative reverse transcriptase polymerase chain reaction analyses confirmed significant upregulation of putative stress response genes under symbiotic conditions. The present ESTs database provides a valuable resource for molecular biological study of plant material degradation in the symbiosis between termites and fungi.

Agaricales↗

Comparison of American medical dictionaries.

Although American medical dictionaries are a valuable part of any medical library collection, the attributes of each of the four major dictionaries are often unknown and the reference material contained in each unused. The medical librarian should be aware of the differences and values of each dictionary and try to have at least one edition of each available to library users in order to maintain an adequate reference collection.

Book Selection↗

Genomic Profiling of Chromatin State Using CUT&Tag.

Alterations in chromatin state, mediated through histone modifications and the incorporation of histone variants, are fundamental to establishing transcriptional networks and cell identity. Recent advances in low-input epigenome profiling methods, such as CUT&Tag and CUT&RUN, have enabled the study of chromatin states from very limited starting materials. In this chapter, we describe procedures for generating CUT&Tag libraries to profile histone modifications and histone variants in early-developing zebrafish embryos.

Animals↗

[Effectiveness of inhaled corticosteroids in chronic obstructive lung disease: systematic review].

BACKGROUND: Inhaled corticosteroids are increasingly being used in patients with chronic obstructive lung disease (COPD), but their effectiveness is disputed. The aim of this study was to define the clinical effectiveness of inhaled corticosteroids in non-asthmatic COPD by a systematic review of the literature. MATERIAL AND METHOD: Literature searches were conducted in Medline, the Cochrane library and the Spanish Medical Index. Only placebo-controlled trials were included. All trials were reviewed by two authors and data were extracted in a pre-defined manner. Meta-analytic techniques were used to estimate global effects when data were comparable. RESULTS: No clinical trials on the role of inhaled corticosteroids during COPD exacerbations were found. Twelve studies on patients under a stable condition were identified and included in the review. Short-term studies showed that inhaled corticosteroids induced a small increase in FEV1 (average: 96 ml after 1-6 months). Longer term studies indicated that after 1-3 years of continued therapy, FEV1 was higher in treated than in control patients, but the difference was small (51 ml, CI 3-98). There were no consistent effects on symptom scores or the frequency of exacerbations. CONCLUSION: The results of this review do not support the systematic use of inhaled corticosteroids in patients with non-asthmatic COPD.

Administration, Inhalation↗

Peptide mimics of a conformationally constrained protective epitopes of respiratory syncytial virus fusion protein.

AIMS: To identify peptides that mimic (mimotopesi conformational and protective epitopes of RSV fusion protein and to assess their efficacy as immunogens and potential vaccines. MATERIAL AND METHODS: An 8-mer solid-phase (TG resin) library was screened with a neutralising and protective RSV fusion protein specific monoclonal antibodies (Mab-19). After selection of positive beads, reactive sequences were identified by microsequencing and 8-mer peptides were synthesised. Improvement of binding was analysed by amino acid replacement using the SPOTs method. RESULTS: Mabs were not able to bind to the free and soluble peptides, nor did these peptides induce anti-RSV specific antibodies. However, several peptides re-synthesised on a TG resin (to produce de-protected 8-mer peptides linked to the resin) or as SPOTs reacted specifically. Therefore it was critical to be able to reproduce this conformation in order to use these mimotopes as immunogens and potential vaccines. Using C-terminal constrained versions of the mimotopes, strong binding of one of the Mabs to the peptides was demonstrated by surface-plasmon resonance. Immunisation of Balb/c mice with these peptide-mimics produced anti-sera that: (1) reacted specifically with RSV; (2) inhibited the binding of the Mab to the virus; (3) neutralised RSV in vitro with high titres (range: 80-640); and (4) reduce significantly the viral load in the lungs of mice challenged with RSV (P < 0.01). CONCLUSIONS: This report demonstrates for the first time that: (1) a protective epitope of the conserved RSV fusion protein can be mimicked by synthetic peptides; and (2) immunisations with these mimotopes induced specific anti-RSV neutralising antibodies and reduced viral load in vivo. These results represent a novel concept for the development of a vaccine against RSV.

Animals↗