Adherence of Staphylococcus aureus is enhanced by an endogenous secreted protein with broad binding activity

A novel mechanism for enhancement of adherence of Staphylococcus aureus to host components is described. A secreted protein, Eap (extracellular adherence protein), was purified from the supernatant of S. aureus Newman and found to be able to bind to at least seven plasma proteins, e.g., fibronectin, the alpha-chain of fibrinogen, and prothrombin, and to the surface of S. aureus. Eap bound much less to cells of Staphylococcus epidermidis, Streptococcus mutans, or Escherichia coli. The protein can form oligomeric forms and is able to cause agglutination of S. aureus. Binding of S. aureus to fibroblasts and epithelial cells was significantly enhanced by addition of Eap, presumably due to its affinity both for plasma proteins on the cells and for the bacteria.     

Access to Alcohol Outlets,Alcohol Consumption and Mental Health

The objective of this study was to investigate residential exposure to alcohol outlets in relation to alcohol consumption and mental health morbidity (anxiety, stress, and depression). This was a cross-sectional study of 6,837 adults obtained from a population representative sample for the period 2006–2009 in Perth, Western Australia. The number of alcohol outlets was ascertained for a 1600 m service area surrounding the residential address. Zero-inflated negative binomial and logistic regression were used to assess associations with total alcohol consumption, harmful alcohol consumption (7–10 drinks containing 10 g of alcohol for men, 5–6 drinks for women) and medically diagnosed and hospital contacts (for anxiety, stress, and depression), respectively. The rate ratio for the number of days of harmful consumption of alcohol per month and the number of standard drinks of alcohol consumed per drinking day was 1.06 (95% CI: 1.02, 1.11) and 1.01 (95% CI: 1.00, 1.03) for each additional liquor store within a 1600 m service area, respectively. The odds ratio of hospital contact for anxiety, stress, or depression was 1.56 (95% CI: 0.98, 2.49) for those with a liquor store within the service area compared to those without. We observed strong evidence for a small association between residential exposure to liquor stores and harmful consumption of alcohol, and some support for a moderate-sized effect on hospital contacts for anxiety, stress, and depression.     

The human sef-a isoform utilizes different mechanisms to regulate receptor tyrosine kinase signaling pathways and subsequent cell fate

Negative feedback is among the key mechanisms for regulating receptor tyrosine kinase (RTK) signaling. Human Sef, a recently identified inhibitor of RTK signaling, encodes different isoforms, including a membrane spanning (hSef-a) and a cytosolic (hSef-b) isoform. Previously, we reported that hSef-b inhibited fibroblast proliferation and prevented the activation of mitogen-activated protein kinase (MAPK), without affecting protein kinase B/Akt or p38 MAPK. Conflicting results were reported concerning hSef-a inhibition of MAPK activation, and the effect of hSef-a on other RTK-induced signaling pathways is unknown. Here we show that, in fibroblasts, similar to hSef-b, ectopic expression of hSef-a inhibited fibroblast growth factor-induced cell proliferation. Unlike hSef-b, however, the growth arrest was mediated via a MAPK-independent mechanism, and was accompanied by elevated p38 MAPK phosphorylation and inhibition of protein kinase B/Akt. In addition, hSef-a, but not hSef-b, mediated apoptosis in fibroblast growth factor-stimulated cells. Chemical inhibitor of p38 MAPK abrogated the effect of hSef-a on apoptosis. In epithelial cells, ectopic expression of hSef-a inhibited the activation of MAPK, whereas down-regulation of endogenous hSef-a significantly increased MAPK activation and accelerated growth factor-dependent cell proliferation. These results indicate that hSef-a is a multifunctional negative modulator of RTK signaling and clearly demonstrate that hSef-a can inhibit the activation of MAPK, although in a cell type-specific manner. Moreover, the differences between the activities of hSef-a and hSef-b suggest that hSef isoforms can control signal specificity and subsequent cell fate by utilizing different mechanisms to modulate RTK signaling.