Response of Listeria Monocytogenes to Bile Salts

Listeria monocytogenes is a food-borne pathogen responsible for the disease listeriosis. The infectious process depends upon survival in high bile salt conditions encountered throughout the gastrointestinal tract, including the gallbladder. However, it is not clear how bile salt resistance mechanisms are induced, especially under physiologically relevant conditions. This study sought to determine how L. monocytogenes responds to bile salts under anaerobic conditions. The study found resistance to be strain specific and not dependent upon virulence. Changes in the expressed proteome were analyzed using multidimensional protein identification technology coupled with electrospray ionization tandem mass spectrometry. A general response among virulent and avirulent strains found significant alterations in intensity of cell wall associated proteins, DNA repair proteins, protein folding chaperones and oxidative response proteins. Strain viability was correlated with an initial osmotic stress response followed by strain specific proteins associated with biofilm formation in EGDe and a transmembrane efflux pump in F2365

Beta3 integrin haplotype influences gene regulation and plasma von Willebrand factor activity

The Leu33Pro polymorphism of the gene encoding beta(3) integrin (ITGB3) is associated with acute coronary syndromes and influences platelet aggregation. Three common promoter polymorphisms have also been identified. The aims of this study were to (1) investigate the influence of the ITGB3 -400C/A, -425A/C and -468G/A promoter polymorphisms on reporter gene expression and nuclear protein binding and (2) determine genotype and haplotype associations with platelet alpha(IIb)beta(3) receptor density. Promoter haplotypes were introduced into an ITGB3 promoter-pGL3 construct by site directed mutagenesis and luciferase reporter gene expression analysed in HEL and HMEC-1 cells. Binding of nuclear proteins was assessed by electrophoretic mobility shift assay. The association of ITGB3 haplotype with platelet alpha(IIb)beta(3) receptor density was determined in 223 subjects. Species conserved motifs were identified in the ITGB3 promoter in the vicinity of the three polymorphisms. The GAA, GCC, AAC, AAA and ACC constructs induced approximately 50% increased luciferase expression relative to the GAC construct in both cell types. Haplotype analysis including Leu33Pro indicated five common haplotypes; no associations between ITGB3 haplotypes and receptor density were found. However, the GCC-Pro33 haplotype was associated with significantly higher vWF activity (128.6 [112.1-145.1]%) compared with all other haplotypes (107.1 [101.2-113.0]%, p=0.02). In conclusion, the GCC-Pro33 haplotype was associated with increased vWF activity but not with platelet alpha(IIb)beta(3) receptor density, which may indicate ITGB3 haplotype influences endothelial function

Association between hypertensive disorders of pregnancy and later risk of cardiovascular outcomes

Funder: Homerton College, University of Cambridge (GB)BACKGROUND: Hypertensive disorders of pregnancy are common pregnancy complications that are associated with greater cardiovascular disease risk for mothers. However, risk of cardiovascular disease subtypes associated with gestational hypertension or pre-eclampsia is unclear. The present study aims to compare the risk of cardiovascular disease outcomes for women with and without a history of gestational hypertension and pre-eclampsia using national hospital admissions data. METHODS: This was a retrospective cohort study of national medical records from all national health service hospitals in England. Women who had one or more singleton live births in England between 1997 and 2015 were included in the analysis. Risk of total cardiovascular disease and 19 pre-specified cardiovascular disease subtypes, including stroke, coronary heart disease, cardiomyopathy and peripheral arterial disease was calculated separately for women with a history of gestational hypertension and pre-eclampsia compared to normotensive pregnancies. RESULTS: Amongst 2,359,386 first live births there were 85,277 and 74,542 hospital admissions with a diagnosis of gestational hypertension and pre-eclampsia, respectively. During 18 years (16,309,386 person-years) of follow-up, the number and incidence of total CVD for normotensive women, women with prior gestational hypertension and women with prior pre-eclampsia were: n=8668, 57.1 (95% CI:55.9-58.3) per 100,000 person-years; n=521, 85.8 (78.6-93.5) per 100,000 person-years and n=518, 99.3 (90.9-108.2) per 100,000 person-years, respectively. Adjusted HRs (aHR) for total CVD were: aHR (95% CI) = 1.45 (1.33-1.59) for women with prior gestational hypertension and, aHR=1.62 (1.48-1.78) for women with prior pre-eclampsia. Gestational hypertension was strongly associated with dilated cardiomyopathy, aHR=2.85 (1.67-4.86), and unstable angina, aHR=1.92 (1.33-2.77). Pre-eclampsia was strongly associated with hypertrophic cardiomyopathy, aHR=3.27 (1.49-7.19), and acute myocardial infarction, aHR=2.46 (1.72-3.53). Associations were broadly homogenous across cardiovascular disease subtypes and increased with a greater number of affected pregnancies. CONCLUSIONS: Women with either previous gestational hypertension or pre-eclampsia are at greater risk of a range of cardiovascular outcomes. These women may benefit from clinical risk assessment or early interventions to mitigate their greater risk of various cardiovascular outcomes.Cambridge BHF Centre of Research Excellence (RE/13/6/30180

An evaluation of the family support initiative at Galbraith Elementary School

75 leaves ; 28 cm. --This paper discusses the issues involved in family support, and describes the family room initiative implemented at Galbraith Elementary school in the 1996-97 school year. A series of three focus groups were held with staff, students, and parents involved in the program. Each group discussed five key areas in the project which included how and why people became involved in the program, examples of parental and community interaction, how the project changed parenting skills, what additional community resources were being utilized, and how the program could improve. The findings from this research indicate that parent advocacy, staff ability to communicate with parents, and a sense of place for parents in the school are enhanced by this program

Deficiency of plasminogen activator inhibitor‐2 results in accelerated tumor growth

BackgroundUpregulation of the plasminogen activation system, including urokinase plasminogen activator (uPA), has been observed in many malignancies, suggesting that co‐opting the PA system is a common method by which tumor cells accomplish extracellular matrix proteolysis. PAI‐2, a serine protease inhibitor, produced from the SERPINB2 gene, inhibits circulating and extracellular matrix‐tethered uPA. Decreased SERPINB2 expression has been associated with increased tumor invasiveness and metastasis for several types of cancer. PAI‐2 deficiency has not been reported in humans and PAI‐2‐deficient (SerpinB2−/−) mice exhibit no apparent abnormalities.ObjectivesWe investigated the role of PAI‐2 deficiency on tumor growth and metastasis.MethodsTo explore the long‐term impact of PAI‐2 deficiency, a cohort of SerpinB2−/− mice were aged to >18 months, with spontaneous malignancies observed in 4/9 animals, all of apparently vascular origin. To further investigate the role of PAI‐2 deficiency in malignancy, SerpinB2−/− and wild‐type control mice were injected with either B16 melanoma or Lewis lung carcinoma tumor cells, with markedly accelerated tumor growth observed in SerpinB2−/− mice for both cell lines. To determine the relative contributions of PAI‐2 from hematopoietic or nonhematopoietically derived sources, bone marrow transplants between wild‐type C57BL/6J and SerpinB2−/− mice were performed.Results and ConclusionsOur results suggest that PAI‐2 deficiency increases susceptibility to spontaneous tumorigenesis in the mouse, and demonstrate that SerpinB2 expression derived from a nonhematopoietic compartment is a key host factor in the regulation of tumor growth in both the B16 melanoma and Lewis lung carcinoma models.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163438/2/jth15054_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163438/1/jth15054.pd

Derivation of an analytical expression for the power coupling coefficient for offset launch into multimode fiber

The demand for higher bandwidth in local area networks (LANs) has fuelled considerable research in techniques for mitigating modal dispersion in multimode fiber (MMF).These techniques include selective mode excitation, offset launching, angular multiplexing and electronic dispersion compensation, all of which strive to optimize the channel impulse response of a MMF.To obtain the optimal bandwidth-enhancement results from these techniques, knowledge of the distribution of power coupling coefficients given an arbitrary offset launch in a MMF is important.In this paper, an analytical expression for the power coupling coefficient for an incident Gaussian beam launched with a radial offset into a MMF having an infinite parabolic refractive index profile is derived.This expression is useful in understanding the parameters which may affect the power coupling coefficient and how they may enhance the MMF bandwidth. The power coupling coefficients obtained from the derived analytical expression are compared with numerical results and are in excellent agreement.The analytical expression may be extended to manufactured MMF