Relations of civil liberties and women's health satisfaction around the globe: the explanatory power of autonomy

Research on how sociopolitical factors differentially affect the health and well-being of individuals is nascent and mechanisms responsible have not yet been identified. This work examined how the civil liberties afforded across 79 countries differentially affect the health satisfaction of men and women and tested one potential reason for this link: autonomy satisfaction, the experience of being choiceful, and free to express oneself. Women reported lower health satisfaction in countries that were lower in civil liberties, a relation mediated by autonomy. Implications for women and other marginalized groups most affected by a society’s restrictive policies and norms are discussed

Receptor-associated protein blocks internalization and cytotoxicity of myeloma light chain in cultured human proximal tubular cells.

BACKGROUND: Free light chains (LCs) are among the many ligands that bind to cubilin/megalin for endocytosis via the clathrin-dependent endosomal/lysosomal pathway. Receptor associated protein (RAP), is a 39 kDA high-affinity, chaperone-like ligand for megalin that assists in the proper folding and functioning of megalin/cubilin. Although RAP is known to inhibit ligand binding to megalin/cubilin, its effect on LC endocytosis has not been shown directly. METHODS AND PRINCIPAL FINDINGS: We investigated whether RAP can block the endocytosis of LC in cultured human proximal tubule cells and whether this can prevent LC cytotoxicity. Immunofluorescence microscopy and flow cytometry showed that fluorescently labeled LC endocytosis was markedly inhibited in HK-2 cells pretreated with human RAP. The effect of RAP was dose-dependent, and was predominantly on endocytosis as it had no effect on the small acid-washable fraction of LC bound to cell membrane. RAP significantly inhibited LC induced cytokine production and phosphorylation of ERK1/2 and p38 MAPK. Prolonged exposure to LC for 48 h resulted in epithelial-to-mesenchymal transformation in HK-2 cells as evidenced by marked reduction in the expression of the epithelial cell marker E-cadherin, and increased the expression of the mesenchymal marker α-SMA, which was also prevented by RAP in the endocytosis medium. CONCLUSIONS: RAP inhibited LC endocytosis by ∼88% and ameliorated LC-induced cytokine responses and EMT in human PTCs. The results not only provide additional evidence that LCs endocytosis occurs via the megalin/cubilin endocytic receptor system, but also show that blocking LC endocytosis by RAP can protect proximal tubule cells from LC cytotoxicity

Deformation patterns in the Van region (Eastern Turkey) and their significance for the tectonic framework

The area of investigation is located on the south-eastern shore of Lake Van in Eastern Turkey where a destructive earthquake took place on 23rd October. 2011 (Mw =7.1). Following the earthquake, different source mechanisms, deformations, and types of faulting have been suggested by different scientists. In this research, Edremit district and vicinities located on the southern side of Van have been investigated to understand the deformation pattern in a travertine (400 ka) formation on the surface, and its structural and stratigraphic relationships with the main faults under the surface by using two-dimensional (2D) Electrical Resistivity Tomography (ERT) profiles. The results were used to document the deformation pattern of rocks with the Miocene and the Holocene (400 ka travertine) in ages. By means of the investigations, deformation patterns implying the tectonic regimes during the Oligocene-Miocene-Pliocene, and Quaternary time have been determined. According to detailed field work, the local principal stress direction has been defined as approximately N35 degrees W. This is also supported by the joint set and slip-plane data. Moreover, Oligocene-Miocene units provide a similar principal stress direction. Our data suggest that the southern part of the Elmalik fault is characteristic of reverse faults rather than of the normal fault system that has been previously reported. In addition, the Gurpinar fault controlling the deformation patterns of the region is a reverse fault with dextral component

Endocytosis of FITC-κLC in cultured human proximal tubule epithelial cells (a representative field with two cells is shown).

<p>HK-2 cells were grown on a glass chamber in 8-well culture slide for 2 days and then observed by fluorescence microscopy. <b>A.</b> FITC without LC in control cells counterstained with DAPI for 30 min. <b>B:</b> after FITC-LC (25 µg/ml) uptake by HK-2 cells grown on slide chamber for 45 min at 37°C after acid wash to strip membrane bound fluorescence and counterstained with DAPI shows distribution of FITC-LC in the cytosol (green fluorescence). <b>C:</b> Pretreatment with 1 uM receptor-associated protein (RAP) markedly inhibits FITC-LC fluorescence in HK-2 cells.</p

Effect of receptor-associated protein (RAP) on the expression of E-cadherin and α-SMA in myeloma light chain exposed human renal proximal tubule epithelial cells.

<p>RAP, 1 µM, prevented LC induced decrease in the epithelial cell marker E-cadherin (<b>A</b>), and reduced the increased expression of myofibroblast marker α-SMA (<b>B</b>), demonstrating that RAP protected cells from LC-induced EMT (representative blot from 3 experiments). Quantitative densitometric measurement of the effect of RAP pre-treatment followed by κ-LC in HK2 cells on the production of E-cadherin (<b>C</b>) and α-SMA (<b>D</b>) proteins. **p<0.01 compared to κ-LC alone.</p

Effect RAP on myeloma light chain (LC)- stimulated cytokine production.

<p>Cells were pre-incubated for 1-h with or without 1 µM RAP and then exposed to 25 µM myeloma LC for a further 4-h. Interleukins 6 and 8 were then assayed in the cell supernatants. LC-stimulated the production of both IL-6 and IL-8, and both were significantly inhibited by the presence of RAP, 1 µM, in cell culture medium (p<0.05). Bars represent the mean ± SE for each group (n = 3, *p<0.05 vs LC, **p<0.01 vs LC, one-way ANOVA).</p