'Correction:' Serum transforming growth factor beta-1 (TGF-beta-1) levels in diabetic patients are not associated with pre-existent coronary artery disease

<p>Abstract</p> <p>Background</p> <p>The association between TGF-β1 levels and long-term major adverse cardiovascular events (MACE) in patients with coronary artery disease (CAD) is controversial. No study specifically addressed patients with CAD and diabetes mellitus (DM). The association between TGF-β1 levels and long-term major adverse cardiovascular events (MACE) in patients with coronary artery disease (CAD) is controversial. No study specifically addressed patients with CAD and diabetes mellitus (DM).</p> <p>Methods</p> <p>Patients (n = 135, 30–80 years) referred for coronary angiography were submitted to clinical and laboratory evaluation, and the coronary angiograms were evaluated by two operators blinded to clinical characteristics. CAD was defined as the presence of a 70% stenosis in one major coronary artery, and DM was characterized as a fasting glycemia > 126 mg/dl or known diabetics (personal history of diabetes or previous use of anti-hyperglycemic drugs or insulin). Based on these criteria, study patients were classified into four groups: no DM and no CAD (controls, C n = 61), DM without CAD (D n = 23), CAD without DM (C-CAD n = 28), and CAD with DM (D-CAD n = 23). Baseline differences between the 4 groups were evaluated by the χ²test for trend (categorical variables) and by ANOVA (continuous variables, post-hoc Tukey). Patients were then followed-up during two years for the occurrence of MACE (cardiac death, stroke, myocardial infarction or myocardial revascularization). The association of candidate variables with the occurrence of 2-year MACE was assessed by univariate analysis.</p> <p>Results</p> <p>The mean age was 58.2 ± 0.9 years, and 51% were men. Patients with CAD had a higher mean age (p = 0.011) and a higher percentage were male (p = 0.040). There were no significant baseline differences between the 4 groups regarding hypertension, smoking status, blood pressure levels, lipid levels or inflammatory markers. TGF-β1 was similar between patients with or without CAD or DM (35.1 ×/÷ 1.3, 33.6 ×/÷ 1.6, 33.9 ×/÷ 1.4 and 31.8 ×/÷ 1.4 ng/ml in C, D, C-CAD and D-CAD, respectively, p = 0.547). In the 2-year follow-ip, independent predictors of 2-year MACE were age (p = 0.007), C-reactive protein (p = 0.048) and systolic blood pressure (p = 0.008), but not TGF-β1.</p> <p>Conclusion</p> <p>Serum TGF-β1 was not associated with CAD or MACE occurrence in patients with or without DM.</p

TGF-β Is Required for Vascular Barrier Function, Endothelial Survival and Homeostasis of the Adult Microvasculature

Pericyte-endothelial cell (EC) interactions are critical to both vascular development and vessel stability. We have previously shown that TGF-β signaling between EC and mural cells participates in vessel stabilization in vitro. We therefore investigated the role of TGF-β signaling in maintaining microvessel structure and function in the adult mouse retinal microvasculature. TGF-β signaling was inhibited by systemic expression of soluble endoglin (sEng) and inhibition was demonstrated by reduced phospho-smad2 in the adult retina. Blockade of TGF-β signaling led to increased vascular and neural cell apoptosis in the retina, which was associated with decreased retinal function, as measured by electroretinogram (ERG). Perfusion of the inner retinal vasculature was impaired and was accompanied by defective autoregulation and loss of capillary integrity. Fundus angiography and Evans blue permeability assay revealed a breakdown of the blood-retinal-barrier that was characterized by decreased association between the tight junction proteins zo-1 and occludin. Inhibition of TGF-β signaling in cocultures of EC and 10T1/2 cells corroborated the in vivo findings, with impaired EC barrier function, dissociation of EC from 10T1/2 cells, and endothelial cell death, supporting the role of EC-mesenchymal interactions in TGF-β signaling. These results implicate constitutive TGF-β signaling in maintaining the integrity and function of the adult microvasculature and shed light on the potential role of TGF-β signaling in vasoproliferative and vascular degenerative retinal diseases

Using behavior-analytic implicit tests to assess sexual interests among normal and sex-offender populations

The development of implicit tests for measuring biases and behavioral predispositions is a recent development within psychology. While such tests are usually researched within a social-cognitive paradigm, behavioral researchers have also begun to view these tests as potential tests of conditioning histories, including in the sexual domain. The objective of this paper is to illustrate the utility of a behavioral approach to implicit testing and means by which implicit tests can be built to the standards of behavioral psychologists. Research findings illustrating the short history of implicit testing within the experimental analysis of behavior are reviewed. Relevant parallel and overlapping research findings from the field of social cognition and on the Implicit Association Test are also outlined. New preliminary data obtained with both normal and sex offender populations are described in order to illustrate how behavior-analytically conceived implicit tests may have potential as investigative tools for assessing histories of sexual arousal conditioning and derived stimulus associations. It is concluded that popular implicit tests are likely sensitive to conditioned and derived stimulus associations in the history of the test-taker rather than 'unconscious cognitions', per se

Phenotype-dependent apoptosis signalling in mesothelioma cells after selenite exposure

<p>Abstract</p> <p>Background</p> <p>Selenite is a promising anticancer agent which has been shown to induce apoptosis in malignant mesothelioma cells in a phenotype-dependent manner, where cells of the chemoresistant sarcomatoid phenotype are more sensitive.</p> <p>Methods</p> <p>In this paper, we investigate the apoptosis signalling mechanisms in sarcomatoid and epithelioid mesothelioma cells after selenite treatment. Apoptosis was measured with the Annexin-PI assay. The mitochondrial membrane potential, the expression of Bax, Bcl-XL, and the activation of caspase-3 were assayed with flow cytometry and a cytokeratin 18 cleavage assay. Signalling through JNK, p38, p53, and cathepsins B, D, and E was investigated with chemical inhibitors. Furthermore, the expression, nuclear translocation and DNA-binding activity of p53 was investigated using ICC, EMSA and the monitoring of p21 expression as a downstream event. Levels of thioredoxin (Trx) were measured by ELISA.</p> <p>Results</p> <p>In both cell lines, 10 μM selenite caused apoptosis and a marked loss of mitochondrial membrane potential. Bax was up-regulated only in the sarcomatoid cell line, while the epithelioid cell line down-regulated Bcl-XL and showed greater caspase-3 activation. Nuclear translocation of p53 was seen in both cell lines, but very little p21 expression was induced. Chemical inhibition of p53 did not protect the cells from apoptosis. p53 lost its DNA binding ability after selenite treatment and was enriched in an inactive form. Levels of thioredoxin decreased after selenite treatment. Chemical inhibition of MAP kinases and cathepsins showed that p38 and cathepsin B had some mediatory effect while JNK had an anti-apoptotic role.</p> <p>Conclusion</p> <p>We delineate pathways of apoptosis signalling in response to selenite, showing differences between epithelioid and sarcomatoid mesothelioma cells. These differences may partly explain why sarcomatoid cells are more sensitive to selenite.</p

Evolutionary potential and adaptation of Banksia attenuata (Proteaceae) to climate and fire regime in southwestern Australia, a global biodiversity hotspot

Substantial climate changes are evident across Australia, with declining rainfall and rising temperature in conjunction with frequent fires. Considerable species loss and range contractions have been predicted; however, our understanding of how genetic variation may promote adaptation in response to climate change remains uncertain. Here we characterized candidate genes associated with rainfall gradients, temperatures, and fire intervals through environmental association analysis. We found that overall population adaptive genetic variation was significantly affected by shortened fire intervals, whereas declining rainfall and rising temperature did not have a detectable influence. Candidate SNPs associated with rainfall and high temperature were diverse, whereas SNPs associated with specific fire intervals were mainly fixed in one allele. Gene annotation further revealed four genes with functions in stress tolerance, the regulation of stomatal opening and closure, energy use, and morphogenesis with adaptation to climate and fire intervals. B. attenuata may tolerate further changes in rainfall and temperature through evolutionary adaptations based on their adaptive genetic variation. However, the capacity to survive future climate change may be compromised by changes in the fire regime

What Do Unions Do for Economic Performance?

Twenty years have passed since Freeman and Medoff's What Do Unions Do? This essay assesses their analysis of how unions in the U.S. private sector affect economic performance - productivity, profitability, investment, and growth. Freeman and Medoff are clearly correct that union productivity effects vary substantially across workplaces. Their conclusion that union effects are on average positive and substantial cannot be sustained, subsequent evidence suggesting an average union productivity effect near zero. Their speculation that productivity effects are larger in more competitive environments appears to hold up, although more evidence is needed. Subsequent literature continues to find unions associated with lower profitability, as noted by Freeman and Medoff. Unions are found to tax returns stemming from market power, but industry concentration is not the source of such returns. Rather, unions capture firm quasi-rents arising from long-lived tangible and intangible capital and from firm-specific advantages. Lower profits and the union tax on asset returns leads to reduced investment and, subsequently, lower employment and productivity growth. There is little evidence that unionization leads to higher rates of business failure. Given the decline in U.S. private sector unionism, I explore avenues through which individual and collective voice might be enhanced, focusing on labor law and workplace governance defaults. Substantial enhancement of voice requires change in the nonunion sector and employer as well as worker initiatives. It is unclear whether labor unions would be revitalized or further marginalized by such an evolution

Examination of alkali-activated material nanostructure during thermal treatment

The key nanostructural changes occurring in a series of alkali-activated materials (AAM) based on blends of slag and fly ash precursors during exposure to temperatures up to 1000 °C are investigated. The main reaction product in each AAM is a crosslinked sodium- and aluminium-substituted calcium silicate hydrate (C-(N)-A-S-H)-type gel. Increased alkali content promotes the formation of an additional sodium aluminosilicate hydrate (N-A-S-(H)) gel reaction product due to the structural limitations on Al substitution within the C-(N)-A-S-H gel. Heating each AAM to 1000 °C results in the crystallisation of the disordered gels and formation of sodalite, nepheline and wollastonite. Increased formation of N-A-S-(H) reduces binder structural water content after thermal treatment and correlates closely with previous observations of improved strength retention and reduced microcracking in these AAM after heating to 1000 °C. This provides new insight into thermally induced changes to gel atomic structure and thermal durability of C-(N)-A-S-H/N-A-S-H gel blends which are fundamental for the development of new fire-resistant construction materials

Using an equity-based framework for evaluating publicly funded health insurance programmes as an instrument of UHC in Chhattisgarh State, India

Universal health coverage (UHC) has provided the impetus for the introduction of publicly funded health insurance (PFHI) schemes in the mixed health systems of India and many other low- and middle-income countries. There is a need for a holistic understanding of the pathways of impact of PFHI schemes, including their role in promoting equity of access. Methods: This paper applies an equity-oriented evaluation framework to assess the impacts of PFHI schemes in Chhattisgarh State by synthesising literature from various sources and highlighting knowledge gaps. Data were collected from an extensive review of publications on PFHI schemes in Chhattisgarh since 2009, including empirical studies from the first author's PhD and grey literature such as programme evaluation reports, media articles and civil society campaign documents. The framework was constructed using concepts and frameworks from the health policy and systems research literature on UHC, access and health system building blocks, and is underpinned by the values of equity, human rights and the right to health

Surviving in isolation: genetic variation, bottlenecks and reproductive strategies in the Canarian endemic Limonium macrophyllum (Plumbaginaceae)

Oceanic archipelagos are typically rich in endemic taxa, because they offer ideal conditions for diversification and speciation in isolation. One of the most remarkable evolutionary radiations on the Canary Islands comprises the 16 species included in Limonium subsection Nobiles, all of which are subject to diverse threats, and legally protected. Since many of them are single-island endemics limited to one or a few populations, there exists a risk that a loss of genetic variation might limit their longterm survival. In this study, we used eight newly developed microsatellite markers to characterize the levels of genetic variation and inbreeding in L. macrophyllum, a species endemic to the North-east of Tenerife that belongs to Limonium subsection Nobiles. We detected generally low levels of genetic variation over all populations (HT = 0.363), and substantial differentiation among populations (FST = 0.188;RST = 0.186) coupled with a negligible degree of inbreeding (F = 0.042). Obligate outcrossing may have maintained L. macrophyllum relatively unaffected by inbreeding despite the species’ limited dispersal ability and the genetic bottlenecks likely caused by a prolonged history of grazing. Although several factors still constitute a risk for the conservation of L. macrophyllum, the lack of inbreeding and the recent positive demographic trends observed in the populations of this species are factors that favour its future persistence

A table for linear and certain other interpolations on spectrograms

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