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Biomedical subjects

James Smith

Publications and source records attributed to James Smith.

At least 37 records · Page 2Linked to original sources
PubMed2005

Developing a scholarship community.

PURPOSE: To report the results of a multidisciplinary, interinstitutional writing support group established to facilitate faculty scholarly productivity. ORGANIZING CONCEPT: The road to scholarship can be filled with many obstacles, among them time constraints, teaching and meeting demands, student needs, office interruptions, and lack of colleagueship. The problems associated with lack of colleagueship, in particular, can be compounded for faculty who work in isolated contexts with few, if any, senior faculty to serve as mentors. METHODS OF DEVELOPMENT: The Western Writers Coercion Group evolved over a 2-year period from a small group of nursing faculty at a single institution to include, by its second year, 21 faculty from five western university campuses and three academic disciplines. The group met biweekly via teleconference with the objectives of defining and accomplishing realistic individual scholarship goals and providing a forum for the critical exchange of ideas. RESULTS: The ongoing support and mentoring of the group led to significant writing outcomes in the form of manuscripts submitted for publication, abstracts submitted for conference presentation, grant proposals developed, and collegial relationships formed. DISCUSSION: Although the benefits of group participation varied somewhat for faculty at different points in the career trajectory, they seemed to accrue at all levels of development. Group members underscored the many less quantifiable advantages of group participation: exposure to broader professional perspectives, the formation of key professional relationships, the enrichment of multidisciplinary input, and individualized assistance with time management, goal setting, and actual drafts. CONCLUSIONS: The structure and experience of this group, which continues to meet regularly, might be a model to guide other groups of scholars who face geographic isolation and who struggle with balancing time and work and finding motivation for the process of writing.

Attitude of Health Personnel↗
PubMed2004

Mutagenic insertion and chromosome engineering resource (MICER).

Embryonic stem cell technology revolutionized biology by providing a means to assess mammalian gene function in vivo. Although it is now routine to generate mice from embryonic stem cells, one of the principal methods used to create mutations, gene targeting, is a cumbersome process. Here we describe the indexing of 93,960 ready-made insertional targeting vectors from two libraries. 5,925 of these vectors can be used directly to inactivate genes with an average targeting efficiency of 28%. Combinations of vectors from the two libraries can be used to disrupt both alleles of a gene or engineer larger genomic changes such as deletions, duplications, translocations or inversions. These indexed vectors constitute a public resource (Mutagenic Insertion and Chromosome Engineering Resource; MICER) for high-throughput, targeted manipulation of the mouse genome.

Animals↗
PubMed2004

An overview of Ensembl.

Ensembl (http://www.ensembl.org/) is a bioinformatics project to organize biological information around the sequences of large genomes. It is a comprehensive source of stable automatic annotation of individual genomes, and of the synteny and orthology relationships between them. It is also a framework for integration of any biological data that can be mapped onto features derived from the genomic sequence. Ensembl is available as an interactive Web site, a set of flat files, and as a complete, portable open source software system for handling genomes. All data are provided without restriction, and code is freely available. Ensembl's aims are to continue to "widen" this biological integration to include other model organisms relevant to understanding human biology as they become available; to "deepen" this integration to provide an ever more seamless linkage between equivalent components in different species; and to provide further classification of functional elements in the genome that have been previously elusive.

Computational Biology↗
PubMed2004

Optimization of a multi-gene HIV-1 recombinant subtype CRF02_AG DNA vaccine for expression of multiple immunogenic forms.

We developed an AIDS vaccine for Western and West-Central Africa based on a DNA plasmid vector expressing HIV-1 recombinant subtype CRF02_AG gag, pol, and env genes. To optimize the production of noninfectious HIV-like particles (VLPs) and potentially improve the effectiveness of the vaccine, we generated four potential vaccine constructs: the parental (IC2) and three modifications (IC25, IC48, and IC90) containing mutations within the HIV protease. While the parental construct IC2 expressed aggregates of Gag proteins, the IC25 construct resulted in the production of immature VLPs (the core comprises unprocessed Pr(55Gag)). The remaining two constructs (IC48 and IC90) produced mature VLPs (the core comprises processed capsid p24) in addition to immature VLPs and aggregates of Gag proteins. VLPs incorporated significant levels of mature gp120 envelope glycoprotein. Importantly, the mature VLPs were fusion competent and entered coreceptor-specific target cells. The production of multiple antigenic forms, including fusion-competent VLPs, by candidate DNA vaccine constructs may provide immunologic advantages for induction of protective cellular and humoral responses against HIV-1 proteins.

AIDS Vaccines↗
PubMed2004

Detection of Cryptosporidium oocysts and Giardia cysts in swimming pool filter backwash water concentrates by flocculation and immunomagnetic separation.

The purpose of the present study was to evaluate techniques for detection of Giardia cysts and Cryptosporidium oocysts in swimming pool filter backwash water. Calcium carbonate flocculation was used for water samples concentration of 1 l filter backwash water samples. Immunomagnetic separation (IMS) was used for separation of cysts and oocysts from detrital material. Cysts and oocysts were then detected using direct immunofluorescence. ColorSeed C&G was used as an internal standard. Recoveries were examined at several processing points. Highest recoveries (23% Cryptosporidium, 18% Giardia) were obtained using lower filter backwash volumes, greater IMS volumes, and addition of Tween20 to backwash samples prior to processing. The combination of CaCO3 flocculation, IMS and direct immunofluorescence was found to be an effective tool for the detection and quantification of Giardia spp. and Cryptosporidium spp. in filter backwash water samples.

Animals↗
PubMed2004

The Ensembl Web site: mechanics of a genome browser.

The Ensembl Web site (http://www.ensembl.org/) is the principal user interface to the data of the Ensembl project, and currently serves >500,000 pages (approximately 2.5 million hits) per week, providing access to >80 GB (gigabyte) of data to users in more than 80 countries. Built atop an open-source platform comprising Apache/mod_perl and the MySQL relational database management system, it is modular, extensible, and freely available. It is being actively reused and extended in several different projects, and has been downloaded and installed in companies and academic institutions worldwide. Here, we describe some of the technical features of the site, with particular reference to its dynamic configuration that enables it to handle disparate data from multiple species.

Animals↗
PubMed2004

To prevent, react, and rebuild: health research and the prevention of genocide.

OBJECTIVE: To develop an approach to the primary prevention of genocide, based on established public health-based violence prevention methods derived from a variety of high-risk settings. DATA SOURCES: (1) Peer-reviewed literature in the fields of public health, violence/injury prevention, medicine, economics, sociology, psychology, history, and genocide studies, (2) demographic and health data bases made available by governments and international organizations, (3) reports on recent episodes of genocide published by international and nongovernmental organizations, (4) newspaper and journalistic accounts of recent and past genocides, (5) archival testimonies of genocide victims and perpetrators, and (6) court transcripts of international genocide prosecutions. STUDY DESIGN: The research was conducted as a medical-historical policy analysis synthesizing data within the following framework: (1) Assessment of current violence and injury prevention models for suitability in the prevention of extreme, population-wide violence, (2) analysis of morbidity and mortality data to quantify the impact of genocide on the health of populations, (3) making an inventory of the known societal risk factors for genocidal violence, (4) identification of the theorized, modifiable attitudinal risk factors for genocidal behavior within a population health model, and (5) assessment of existing projects targeting primary violence and injury prevention in high risk jurisdictions, for future adaptation within a structured, public health approach. PRINCIPAL FINDINGS: Mortality rates due to genocidal violence are far in excess of other public health emergencies including malaria and HIV/AIDS. The immediate and long-range health consequences of genocide include the sequelae of infectious diseases, organ system failure, and psychiatric disorders, conferring an increased burden of disease on affected populations for multiple subsequent generations. The impact of genocide on local health economies is catastrophic, and the opportunity costs of diverting scarce global health dollars toward ameliorating genocide related outcomes are substantial. Structural risk factors for genocide within societies include: totalitarian government, exclusionary ideologies, armed conflict, economic hardship, and inaction of bystander nations. Proposed psychological risk factors for genocidal behavior include: moral exclusion, authority orientation, action in self-interest, desensitization, and compartmentalized thinking. Violence and injury prevention models, incorporating what is currently known about the societal and behavioral risk factors for genocide in high-risk populations, may be modified to address the primary prevention of catastrophic violence on a population-wide scale. A number of existent global peace building initiatives may serve as models for the design of future prevention initiatives in high-risk, pre-genocide jurisdictions. CONCLUSIONS: Our analysis suggests that genocide is one of the most pressing threats to the health of populations in the twenty-first century. Recent advances in the public health discipline of violence prevention provide a blueprint for approaches to primary genocide prevention based on epidemiological methods.

Health Services Research↗
PubMed2003

Photosynthetic genes are differentially transcribed during the dehydration-rehydration cycle in the resurrection plant, Xerophyta humilis.

One of the desiccation-tolerant mechanisms of the resurrection plant, Xerophyta humilis, is the ability to shut down photosynthesis reversibly. The X. humilis psbR and ChlP genes, encoding the 10 kDa polypeptide of photosystem II (PSII) and a geranylgeranyl reductase, respectively, were isolated in a differential display screen as dehydration-down-regulated and rehydration-up-regulated transcripts. Two other PSII genes, psbA (chloroplast-encoded) and psbP (nuclear-encoded), isolated by degenerate primer PCR, display a similar trend in expression.

Acclimatization↗
PubMed2003

D-amino acid residues in peptides and proteins.

We have investigated the D-amino acid residues present in Protein Data Bank (PDB) entries, categorizing them into "real" D-residues and artifacts. In polypeptide chains of more than 20 residues, only a single instance of a "real" D-residue, other than those deliberately designed or engineered, was found. This example was the result of a slow chemical epimerization process. Another 12 designed D-residues were found in these longer polypeptide chains. Smaller peptides of 20 or fewer residues contained 479 "real" D-residues, the majority in various gramicidin, actinomycin, or cyclosporin structures. We found 148 PDB entries with "real" D-residues and a further 186, in which all apparent D-residues are artifacts. Investigating the (phi, psi) preferences of the "real" D-residues, we found that the region around (-60 degrees, -45 degrees ) was almost completely unoccupied, even though it is not formally disallowed. We link the low propensity to occupy this region with the alpha-helix destabilizing properties of D-residues.

Amino Acids↗
PubMed2003

DNA microarrays for comparative genomic hybridization based on DOP-PCR amplification of BAC and PAC clones.

We have designed DOP-PCR primers specifically for the amplification of large insert clones for use in the construction of DNA microarrays. A bioinformatic approach was used to construct primers that were efficient in the general amplification of human DNA but were poor at amplifying E. coli DNA, a common contaminant of DNA preparations from large insert clones. We chose the three most selective primers for use in printing DNA microarrays. DNA combined from the amplification of large insert clones by use of these three primers and spotted onto glass slides showed more than a sixfold increase in the human to E. coli hybridization ratio when compared to the standard DOP-PCR primer, 6MW. The microarrays reproducibly delineated previously characterized gains and deletions in a cancer cell line and identified a small gain not detected by use of conventional CGH. We also describe a method for the bulk testing of the hybridization characteristics of chromosome-specific clones spotted on microarrays by use of DNA amplified from flow-sorted chromosomes. Finally, we describe a set of clones selected from the publicly available Golden Path of the human genome at 1-Mb intervals and a view in the Ensembl genome browser from which data required for the use of these clones in array CGH and other experiments can be downloaded across the Internet.

Animals↗
PubMed2002

Generation of a consensus sequence from prevalent and incident HIV-1 infections in West Africa to guide AIDS vaccine development.

We considered several key issues regarding the development of a DNA-based human immunodeficiency virus type 1 (HIV-1) vaccine: (1) should the candidate vaccine construct be derived from incident or prevalent HIV-1 strains; and (2) should circulating plasma virus, archived HIV-1 provirus recovered from peripheral blood mononuclear cells, or both be included? To address these questions, we collected circulating HIV-1 strains from infected individuals residing in Abidjan, Côte d'Ivoire. From a panel of 23 strains, 22 were HIV-1 subtype A in gag, 19 of which phylogenetically clustered with the recombinant HIV-1, CRF02-AG strains from West Africa. The mosaic genome of CRF02-AG was confirmed by sequencing the protease gene. A consensus gag p24 protein sequence was generated and 147 of 148 codons were identical to CRF02-AG (IbNG). Regardless of the sequence origin (RNA, provirus, incident, or prevalent), the gag p24 consensus sequences were highly representative of these distinct virologic compartments. These data suggest that the consensus sequence generated from incident and prevalent infections may provide an appropriate sequence for a DNA vaccine and is largely representative of the major circulating viral strain.

Africa, Western↗
PubMed2002

A physical map of the mouse genome.

A physical map of a genome is an essential guide for navigation, allowing the location of any gene or other landmark in the chromosomal DNA. We have constructed a physical map of the mouse genome that contains 296 contigs of overlapping bacterial clones and 16,992 unique markers. The mouse contigs were aligned to the human genome sequence on the basis of 51,486 homology matches, thus enabling use of the conserved synteny (correspondence between chromosome blocks) of the two genomes to accelerate construction of the mouse map. The map provides a framework for assembly of whole-genome shotgun sequence data, and a tile path of clones for generation of the reference sequence. Definition of the human-mouse alignment at this level of resolution enables identification of a mouse clone that corresponds to almost any position in the human genome. The human sequence may be used to facilitate construction of other mammalian genome maps using the same strategy.

Animals↗