CiteULike: Author Staats

Mast cell activators: a new class of highly effective vaccine adjuvants

James Mclachlan — 2008-05-08T08:03:42-00:00

Nature Medicine, Vol. 14, No. 5. (20 April 2008), pp. 536-541.

Mast cells (MCs) have recently received recognition as prominent effectors in the regulation of immune cell migration to draining lymph nodes and lymphocyte activation. However, their role in the development of humoral immune responses is not clear. Here, we demonstrate that subcutaneous or nasal administration of small-molecule MC activators with vaccine antigens evokes large increases in antigen-specific serum immunoglobulin G (IgG) responses. These responses were MC dependent and correlated with increased dendritic cell and lymphocyte recruitment to draining lymph nodes. Nasal instillation of these formulations also evoked antigen-specific secretory IgA and provided protection against anthrax lethal toxin challenge in vitro and against vaccinia virus infection in vivo. Collectively, these results define the MC as an integral sensory arm of the adaptive immune system. Moreover, they highlight MC activators as a new class of vaccine adjuvants, capable of inducing protective antigen-specific immune responses through needle-free routes of administration.

SNP500Cancer: a public resource for sequence validation, assay development, and frequency analysis for genetic variation in candidate genes.

BR Packer — 2008-07-15T14:21:53-00:00

Nucleic acids research, Vol. 34, No. Database issue. (1 January 2006)

The SNP500Cancer database provides sequence and genotype assay information for candidate SNPs useful in mapping complex diseases, such as cancer. The database is an integral component of the NCI Cancer Genome Anatomy Project (http://cgap.nci.nih.gov). SNP500Cancer reports sequence analysis of anonymized control DNA samples (n = 102 Coriell samples representing four self-described ethnic groups: African/African-American, Caucasian, Hispanic and Pacific Rim). The website is searchable by gene, chromosome, gene ontology pathway, dbSNP ID and SNP500Cancer SNP ID. As of October 2005, the database contains >13 400 SNPs, 9124 of which have been sequenced in the SNP500Cancer population. For each analysed SNP, gene location and >200 bp of surrounding annotated sequence (including nearby SNPs) are provided, with frequency information in total and per subpopulation as well as calculation of Hardy-Weinberg equilibrium for each subpopulation. The website provides the conditions for validated sequencing and genotyping assays, as well as genotype results for the 102 samples, in both viewable and downloadable formats. A subset of sequence validated SNPs with minor allele frequency >5% are entered into a high-throughput pipeline for genotyping analysis to determine concordance for the same 102 samples. In addition, the results of genotype analysis for select validated SNP assays (defined as 100% concordance between sequence analysis and genotype results) are posted for an additional 280 samples drawn from the Human Diversity Panel (HDP). SNP500Cancer provides an invaluable resource for investigators to select SNPs for analysis, design genotyping assays using validated sequence data, choose selected assays already validated on one or more genotyping platforms, and select reference standards for genotyping assays. The SNP500Cancer database is freely accessible via the web page at http://snp500cancer.nci.nih.gov.

Swine and poultry pathogens: the complete genome sequences of two strains of Mycoplasma hyopneumoniae and a strain of Mycoplasma synoviae.

AT Vasconcelos — 2008-04-17T01:57:56-00:00

Journal of bacteriology, Vol. 187, No. 16. (August 2005), pp. 5568-5577.

This work reports the results of analyses of three complete mycoplasma genomes, a pathogenic (7448) and a nonpathogenic (J) strain of the swine pathogen Mycoplasma hyopneumoniae and a strain of the avian pathogen Mycoplasma synoviae; the genome sizes of the three strains were 920,079 bp, 897,405 bp, and 799,476 bp, respectively. These genomes were compared with other sequenced mycoplasma genomes reported in the literature to examine several aspects of mycoplasma evolution. Strain-specific regions, including integrative and conjugal elements, and genome rearrangements and alterations in adhesin sequences were observed in the M. hyopneumoniae strains, and all of these were potentially related to pathogenicity. Genomic comparisons revealed that reduction in genome size implied loss of redundant metabolic pathways, with maintenance of alternative routes in different species. Horizontal gene transfer was consistently observed between M. synoviae and Mycoplasma gallisepticum. Our analyses indicated a likely transfer event of hemagglutinin-coding DNA sequences from M. gallisepticum to M. synoviae.

Management of chronic pain.

MA Ashburn — 2008-06-07T12:39:49-00:00

Lancet, Vol. 353, No. 9167. (29 May 1999), pp. 1865-1869.

Chronic pain is a common condition for which patients seek care from various health-care providers. This type of pain causes much suffering and disability and is frequently mistreated or undertreated. Patients who present for evaluation for chronic pain should undergo a careful assessment before therapy. Patients with chronic pain commonly experience depression, sleep disturbance, fatigue, and decreased overall physical and mental functioning. They frequently require an interdisciplinary model of care to allow care givers to address the multiple components of the patient's pain experience. After a careful evaluation, therapy may include medication, nerve blocks, active physical therapy, behavioural interventions, and assistance with vocational evaluation and training. Less frequently therapy may include placement of implantable devices to alter the pain experience. These patients suffer from a chronic condition and often require long-term care, with frequent reassessment and adjustment of therapy. Although cure is possible, it is also infrequent. Therefore, therapy is provided with the aim of decreasing pain and suffering while improving physical and mental functioning.

Tracking of electron beams with numerically determined space charge forces

J Staats — 2008-06-06T14:33:35-00:00

Particle Accelerator Conference, 1999. Proceedings of the 1999, Vol. 4 (1999), pp. 2740-2742 vol.4.

A tracking algorithm for the description of electron beams using grid-based space charge fields is compared to a method based on point-to-point calculations. The charged particles' equations of motion are solved with a fifth-order embedded Runge-Kutta method using the concept of macroparticles. The space charge forces are determined in the bunch's restframe with a multigrid-method

The need for psychological restoration as a determinant of environmental preferences

Terry Hartig — 2008-05-06T03:59:19-00:00

Journal of Environmental Psychology, Vol. 26, No. 3. (September 2006), pp. 215-226.

Environmental preferences vary with the environments evaluated and the people who evaluated them. When research has considered the explanatory power of person variables, it has focused on traits or demographic characteristics. Little research has considered how environmental preferences vary with regularly occurring psychological states, such as attentional fatigue. In this experiment, we investigated the need for psychological restoration as a within-individual determinant of the common preference differential between natural and urban environments. We treated preference as an attitude, constituted of beliefs about the likelihood of restoration during a walk in a given environment and the evaluation of restoration given different restoration needs. College students (N=103) completed the procedure just before a morning lecture (less fatigue condition) or immediately after an afternoon lecture, which itself followed the passage of time and other activities over the day (more fatigue condition). In both fatigue conditions, participants reported more favorable attitudes toward a walk in a forest than a walk in a city center, but this difference was larger with the more fatigued. This result apparently owes to the more fatigued participants' more positive evaluation of attentional recovery, and a greater judged likelihood of restoration when walking in the forest.

Genome-wide association study of prostate cancer identifies a second risk locus at 8q24

Meredith Yeager — 2007-04-26T11:42:06-00:00

Nature Genetics, Vol. 39, No. 5. (01 April 2007), pp. 645-649.

Multiple loci identified in a genome-wide association study of prostate cancer

Gilles Thomas — 2008-02-27T13:30:56-00:00

Nature Genetics, Vol. 40, No. 3. (10 February 2008), pp. 310-315.

Positive selection in phytotoxic protein-encoding genes of Botrytis species

Martijn Staats — 2007-02-07T12:34:21-00:00

Fungal Genetics and Biology, Vol. 44, No. 1. (January 2007), pp. 52-63.

Evolutionary patterns of sequence divergence were analyzed in genes from the fungal genus Botrytis (Ascomycota), encoding phytotoxic proteins homologous to a necrosis and ethylene-inducing protein from Fusarium oxysporum. Fragments of two paralogous genes (designated NEP1 and NEP2) were amplified from all known Botrytis species and sequenced. NEP1 sequences of two Botrytis species contain premature stop codons, indicating that they may be non-functional. Both paralogs of all species encode proteins with a remarkably similar predicted secondary structure, however, they contain different types of post-translational modification motifs, which are conserved across the genus. While both NEP genes are, overall, under purifying selection, we identified a number of amino acids under positive selection based on inference using maximum likelihood models. Positively selected amino acids in NEP1 were not under selection in corresponding positions in NEP2. The biological significance of positively selected residues and the role of NEP proteins in pathogenesis remain to be resolved.

Histochemical and genetic analysis of host and non-host interactions of Arabidopsis with three Botrytis species: an important role for cell death control

VAN Baarlen — 2007-01-08T06:05:59-00:00

Molecular Plant Pathology, Vol. 8, No. 1. (January 2007), pp. 41-54.

Immunologic characterization of CD7-deficient mice.

DM Lee — 2006-05-11T13:48:38-00:00

J Immunol, Vol. 160, No. 12. (15 June 1998), pp. 5749-5756.

Human CD7 is an Ig superfamily molecule that is expressed on mature T and NK lymphocytes. Although in vitro studies have suggested a role for CD7 in lymphoid development and function, the exact function of CD7 in vivo has remained elusive. One patient has been reported with SCID syndrome attributed to CD7 deficiency. To study in vivo functions of CD7, we have generated CD7-deficient mice and assessed their lymphoid development and function. CD7-deficient mice were viable, had normal peripheral blood and spleen lymphocyte numbers, and had normal specific Ab responses with Ag-driven Ig isotype switching. Thymocyte numbers were normal in 4-wk-old, 6-mo-old, and 1-yr-old CD7-deficient mice, but in 3-mo-old CD7-deficient mice, total thymocyte numbers were significantly increased by 60% (p < 0.02) compared with normal age-matched +/+ littermates. CD7-deficient splenocytes proliferated normally in response to various mitogens, including PHA, anti-CD3, Con A, and LPS. While NK cell numbers and cytolytic activity to YAC targets were normal, CD7-deficient mice had lower Ag-induced MHC class I-restricted CTL activity against OVA-transfected target cells than did +/+ control mice. Thus, CD7-deficient mice did not have a SCID syndrome, but rather had transient increases in thymocyte numbers at age 3 mo and altered splenocyte Ag-specific CTL effecter cell activity. These data suggest a role for CD7 in regulating intrathymic T cell development and in mediating CTL effecter function.

Cardiolipin polyspecific autoreactivity in two broadly neutralizing HIV-1 antibodies.

BF Haynes — 2005-08-24T14:50:21-00:00

Science, Vol. 308, No. 5730. (24 June 2005), pp. 1906-1908.

The design of a human immunodeficiency virus-1 (HIV-1) immunogen that can induce broadly reactive neutralizing antibodies is a major goal of HIV-1 vaccine development. Although rare human monoclonal antibodies (mAbs) exist that broadly neutralize HIV-1, HIV-1 envelope immunogens do not induce these antibody specificities. Here we demonstrate that the two most broadly reactive HIV-1 envelope gp41 human mAbs, 2F5 and 4E10, are polyspecific autoantibodies reactive with the phospholipid cardiolipin. Thus, current HIV-1 vaccines may not induce these types of antibodies because of autoantigen mimicry of the conserved membrane-proximal epitopes of the virus. These results may have important implications for generating effective neutralizing antibody responses by using HIV-1 vaccines.