Salmonella enterica serovar Typhimurium promotes apoptosis in activated neutrophils

Apoptosis is an extremely important and highly regulated function in neutrophils. As the most abundant, but shortest-lived white blood cells, they must initiate this process in the absence of pathogens and selectively release their potent cytotoxic components when pathogens are present. Many pathogens are able to modulate this process in neutrophils, either for the host\u27s benefit or for their own. Previous work has shown that transmigration across a T84 intestinal epithelial crypt cell monolayer increases the ability of neutrophils to bind and kill Salmonella enterica serovar Typhimurium (S. Typhimurium). The goal of this work was to see how S. Typhimurium affects the cell death rate of human PMN. S. Typhimurium had little to no effect on inactivated neutrophils. When neutrophils were activated, either chemically through phorbol 12-myristate 13-acetate (PMA) or physiologically through transmigration, however, their normal apoptosis rate was delayed (p\u3c0.0001). When S. Typhimurium was present at a ratio of ten bacteria to one neutrophil, apoptosis was significantly increased in these activated neutrophils more prominently when anaerobically grown (p=0.0027) compared to aerobically grown (p=.012). Caspase-3 (p=0 .0129), but not -8 or -9, was associated with bacterial induced apoptosis in these studies. We conclude that S. Typhimurium modulates the rate of apoptosis in neutrophils, but only once these host cells have become activated. Our results provide further insights into the early events involved in Salmonella infections

Beyond The Three-Category Model: An Exploration Of Sexual Orientation In Women Aged 18 And Older

This qualitative study increases our understanding of sexual orientation in women aged 18 and older whose experiences do not fit within the three-category (heterosexual, bisexual, homosexual) model of sexual orientation. Through in-depth interviewing, this study explored the thoughts, feelings, and experiences of five women who described their sexual orientation as \u27unlabeled\u27, \u27mostly heterosexual\u27, and/or reported experiencing sexual fluidity. The results suggest that gender is not always the determining factor in an individual\u27s experience of attraction and that the three-category model is an oversimplification of the complexity inherent in sexual orientation. The lived experience of the women in this study calls for the development of a more inclusive model of sexual orientation. Findings in this and other studies expanding on our awareness of sexual fluidity can be used to improve sexuality education in schools, to train counselors and psychologists effectively to understand and validate the experiences of clients, to promote healthy conversation about sexuality as an aspect of identity, and to reduce the stigma surrounding same-sex attraction in the United States

Why genes evolve faster on secondary chromosomes in bacteria

In bacterial genomes composed of more than one chromosome, one replicon is typically larger, harbors more essential genes than the others, and is considered primary. The greater variability of secondary chromosomes among related taxa has led to the theory that they serve as an accessory genome for specific niches or conditions. By this rationale, purifying selection should be weaker on genes on secondary chromosomes because of their reduced necessity or usage. To test this hypothesis we selected bacterial genomes composed of multiple chromosomes from two genera, Burkholderia and Vibrio, and quantified the evolutionary rates (dN and dS) of all orthologs within each genus. Both evolutionary rate parameters were faster among orthologs found on secondary chromosomes than those on the primary chromosome. Further, in every bacterial genome with multiple chromosomes that we studied, genes on secondary chromosomes exhibited significantly weaker codon usage bias than those on primary chromosomes. Faster evolution and reduced codon bias could in turn result from global effects of chromosome position, as genes on secondary chromosomes experience reduced dosage and expression due to their delayed replication, or selection on specific gene attributes. These alternatives were evaluated using orthologs common to genomes with multiple chromosomes and genomes with single chromosomes. Analysis of these ortholog sets suggested that inherently fast-evolving genes tend to be sorted to secondary chromosomes when they arise; however, prolonged evolution on a secondary chromosome further accelerated substitution rates. In summary, secondary chromosomes in bacteria are evolutionary test beds where genes are weakly preserved and evolve more rapidly, likely because they are used less frequently

Why Genes Evolve Faster on Secondary Chromosomes in Bacteria

In bacterial genomes composed of more than one chromosome, one replicon is typically larger, harbors more essential genes than the others, and is considered primary. The greater variability of secondary chromosomes among related taxa has led to the theory that they serve as an accessory genome for specific niches or conditions. By this rationale, purifying selection should be weaker on genes on secondary chromosomes because of their reduced necessity or usage. To test this hypothesis we selected bacterial genomes composed of multiple chromosomes from two genera, Burkholderia and Vibrio, and quantified the evolutionary rates (dN and dS) of all orthologs within each genus. Both evolutionary rate parameters were faster among orthologs found on secondary chromosomes than those on the primary chromosome. Further, in every bacterial genome with multiple chromosomes that we studied, genes on secondary chromosomes exhibited significantly weaker codon usage bias than those on primary chromosomes. Faster evolution and reduced codon bias could in turn result from global effects of chromosome position, as genes on secondary chromosomes experience reduced dosage and expression due to their delayed replication, or selection on specific gene attributes. These alternatives were evaluated using orthologs common to genomes with multiple chromosomes and genomes with single chromosomes. Analysis of these ortholog sets suggested that inherently fast-evolving genes tend to be sorted to secondary chromosomes when they arise; however, prolonged evolution on a secondary chromosome further accelerated substitution rates. In summary, secondary chromosomes in bacteria are evolutionary test beds where genes are weakly preserved and evolve more rapidly, likely because they are used less frequently

Traumatic brain injury as a risk factor for Alzheimer disease. Comparison of two retrospective autopsy cohorts with evaluation of ApoE genotype

BACKGROUND AND PURPOSE: The impact of traumatic brain injury (TBI) on the pathogenesis of Alzheimer disease (AD) is still controversial. The aim of our retrospective autopsy study was to assess the impact of TBE and ApoE allele frequency on the development of AD. MATERIAL AND METHODS: We examined 1. the incidence of AD pathology (Braak stageing, CERAD, NIA-Reagan Institute criteria) in 58 consecutive patients (mean age ± SD 77.0 ± 6.8 years) with residual closed TBI lesions, and 2. the frequency of TBI residuals in 57 age-matched autopsy proven AD cases. In both series, ApoE was evaluated from archival paraffin-embedded brain material. RESULTS: 1. TBE series: 12.1 % showed definite and 10.3% probable AD (mean age 77.6 and 75.2 years), only 2/13 with ApoEε3/4. From 45 (77.6%) non-AD cases (mean age 78.2 years), 3 had ApoEε3/4. The prevalence of 22.4% AD in this small autopsy cohort was significantly higher than 3.3% in a recent large clinical series and 14% in the general population over age 70. 2. In the AD cohort with ApoEε4 allele frequency of 30% similar to other AD series, residuals of closed TBI were seen in 4 brains (7%) (mean age ± SD 78.2 ± 6.4), all lacking the ApoEε4 allele. TBI incidence was slightly lower than 8.5% in the clinical MIRAGE study. CONCLUSIONS: The results of this first retrospective autopsy study of TBI, ApoEε allele frequency, and AD confirm clinical studies suggesting severe TBI to be a risk factor for the development AD higher in subjects lacking ApoEε4 alleles. Further studies in larger autopsy series are needed to elucidate the relationship between TBI, genetic predisposition, and AD

A quantitative meta-analysis of neurocognitive functioning in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is associated with regional alterations in brain structure and function that are hypothesized to contribute to symptoms and cognitive deficits associated with the disorder. We present here the first systematic meta-analysis of neurocognitive outcomes associated with PTSD to examine a broad range of cognitive domains and describe the profile of cognitive deficits, as well as modifying clinical factors and study characteristics. This report is based on data from 60 studies totaling 4,108 participants, including 1,779 with PTSD, 1,446 trauma-exposed comparison participants, and 895 healthy comparison participants without trauma exposure. Effect-size estimates were calculated using a mixed-effects meta-analysis for 9 cognitive domains: attention/working memory, executive functions, verbal learning, verbal memory, visual learning, visual memory, language, speed of information processing, and visuospatial abilities. Analyses revealed significant neurocognitive effects associated with PTSD, although these ranged widely in magnitude, with the largest effect sizes in verbal learning (d = -.62), speed of information processing (d = -.59), attention/working memory (d = -.50), and verbal memory (d =-.46). Effect-size estimates were significantly larger in treatment-seeking than community samples and in studies that did not exclude participants with attention-deficit/hyperactivity disorder, and effect sizes were affected by between-group IQ discrepancies and the gender composition of the PTSD groups. Our findings indicate that consideration of neuropsychological functioning in attention, verbal memory, and speed of information processing may have important implications for the effective clinical management of persons with PTSD. Results are further discussed in the context of cognitive models of PTSD and the limitations of this literature