Creep Behavior of an Oxide/Oxide Composite with Monazite Coating at Elevated Temperatures

This study focuses on experimental investigation of stress-rupture behavior (creep response) of an oxide/oxide composite in a cross-ply (0/90) lay-up at elevated temperature. The test material, Nextel 610/monazite/alumina composite, employs monazite, an oxidation-resistant interfacial coating designed to improve performance at elevated temperatures. The experimental program included monotonic tensile tests to failure and creep-rupture tests at elevated temperatures. Tensile tests served to establish an ultimate tensile strength (UTS) for the material. The ensuing creep-rupture tests involved stress levels at varying percentages of the UTS. Stress-rupture curves at 900 and 1100 degrees C were established. A family of creep curves for various constant stress levels at 900 and 1100 degrees C was produced. Composite microstructure, as well as damage and failure mechanisms were also investigated

Dislocation and degradation from the ER are regulated by cytosolic stress

Akey step in ER-associated degradation (ERAD) is dislocation of the substrate protein from the ER into the cytosol to gain access to the proteasome. Very little is known about how this process is regulated, especially in the case of polytopic proteins. Using pulse-chase analysis combined with subcellular fractionation, we show that connexins, the four transmembrane structural components of gap junctions, can be chased in an intact form from the ER membrane into the cytosol of proteasome inhibitor–treated cells. Dislocation of endogenously expressed connexin from the ER was reduced 50–80% when the cytosolic heat shock response was induced by mild oxidative or thermal stress, but not by treatments that instead upregulate the ER unfolded protein response. Cytosolic but not ER stresses slowed the normally rapid degradation of connexins, and led to a striking increase in gap junction formation and function in otherwise assembly-inefficient cell types. These treatments also inhibited the dislocation and turnover of a connexin-unrelated ERAD substrate, unassembled major histocompatibility complex class I heavy chain. Our findings demonstrate that dislocation is negatively regulated by physiologically relevant, nonlethal stress. They also reveal a previously unrecognized relationship between cytosolic stress and intercellular communication

Intracellular Transport, Assembly, and Degradation of Wild-Type and Disease-linked Mutant Gap Junction Proteins

More than 130 different mutations in the gap junction integral plasma membrane protein connexin32 (Cx32) have been linked to the human peripheral neuropathy X-linked Charcot–Marie–Tooth disease (CMTX). How these various mutants are processed by the cell and the mechanism(s) by which they cause CMTX are unknown. To address these issues, we have studied the intracellular transport, assembly, and degradation of three CMTX-linked Cx32 mutants stably expressed in PC12 cells. Each mutant had a distinct fate: E208K Cx32 appeared to be retained in the endoplasmic reticulum (ER), whereas both the E186K and R142W mutants were transported to perinuclear compartments from which they trafficked either to lysosomes (R142W Cx32) or back to the ER (E186K Cx32). Despite these differences, each mutant was soluble in nonionic detergent but unable to assemble into homomeric connexons. Degradation of both mutant and wild-type connexins was rapid (t1/2 \u3c 3 h) and took place at least in part in the ER by a process sensitive to proteasome inhibitors. The mutants studied are therefore unlikely to cause disease by accumulating in degradation-resistant aggregates but instead are efficiently cleared from the cell by quality control processes that prevent abnormal connexin molecules from traversing the secretory pathway

Phytochemistry Predicts Habitat Selection by an Avian Herbivore at Multiple Spatial Scales

Animal habitat selection is a process that functions at multiple, hierarchically structured spatial scales. Thus multi-scale analyses should be the basis for inferences about factors driving the habitat selection process. Vertebrate herbivores forage selectively on the basis of phytochemistry, but few studies have investigated the influence of selective foraging (i.e., fine-scale habitat selection) on habitat selection at larger scales. We tested the hypothesis that phytochemistry is integral to the habitat selection process for vertebrate herbivores. We predicted that habitats selected at three spatial scales would be characterized by higher nutrient concentrations and lower concentrations of plant secondary metabolites (PSMs) than unused habitats. We used the Greater Sage-Grouse (Centrocercus urophasianus), an avian herbivore with a seasonally specialized diet of sagebrush, to test our hypothesis. Sage-Grouse selected a habitat type (black sagebrush, Artemisia nova) with lower PSM concentrations than the alternative (Wyoming big sagebrush, A. tridentata wyomingensis). Within black sagebrush habitat, Sage-Grouse selected patches and individual plants within those patches that were higher in nutrient concentrations and lower in PSM concentrations than those not used. Our results provide the first evidence for multi-scale habitat selection by an avian herbivore on the basis of phytochemistry, and they suggest that phytochemistry may be a fundamental driver of habitat selection for vertebrate herbivores

Premature T cell aging in major depression: A double hit by the state of disease and cytomegalovirus infection

Childhood trauma; Major depressive disorder; T cytotoxic cellTrauma infantil; Trastorn depressiu major; cèl·lula T citotòxicaTrauma infantil; Trastorno depresivo mayor; célula T citotóxicaIntroduction Previous research indicates that premature T cell senescence is a characteristic of major depressive disorder (MDD). However, known senescence inducing factors like cytomegalovirus (CMV) infection or, probably, childhood adversity (CA) have not been taken into consideration so far. Objective Differentiation and senescent characteristics of T cells of MDD patients were investigated in relation to healthy controls (HC), taking the CMV seropositivity and CA into account. Methods 127 MDD and 113 HC of the EU-MOODSTRATIFICATION cohort were analyzed. Fluorescence activated cell sorting (FACS) analysis was performed to determine B, NK, and T cell frequencies. In a second FACS analysis, naïve, effector memory (Tem), central memory (Tcm), effector memory cells re-expressing RA (TEMRA), as well as CD28+ and CD27+ memory populations, were determined of the CD4+ and CD8+ T cell populations in a subsample (N = 35 MDD and N = 36 HC). CMV-antibody state was measured by IgG ELISA and CA by the Childhood Trauma Questionnaire. Results We detected a CMV-antibody positivity in 40% of MDD patients (35% HC, n. s.) with seropositive MDD cases showing a higher total childhood trauma score. Second, a higher inflation of memory CD4+ T helper cells in CMV seronegative patients as compared to seronegative HC and reduced numbers of naïve CD4+ T helper cells in CMV seropositive patients (not in CMV seropositive HC) were found. Third, a higher inflation of memory CD8+ T cytotoxic cells in CMV seropositive cases as compared to CMV seropositive HC, particularly of the TEMRA cells, became apparent. Higher percentages of CD4+ TEMRA and late stage CD27−CD28− TEMRA cells were similar in both HC and MDD with CMV seropositivity. Overall, apportioning of T cell subpopulations did not differ between CA positive vs negative cases. Conclusions MDD patients show several signs of a CMV independent “MDD specific” premature T cell aging, such as a CMV independent increase in CD4+ T memory cells and a latent naïve CD4 T-cell reduction and a latent CD8+ T-cell increase. However, these two latent T cell senescence abnormalities only become evident with CMV infection (double hit).This work was supported by the European Commission: EU 7th Framework program (grant number EU-FP7-CP-IP-2008-222963) and Horizon 2020 (grant number H2020-SC1-2016-2017/H2020-SC1-2017-Two-Stage-RTD) grants were received by HAD, Erasmus Medical Center Rotterdam. The funding source had no role in the study design, the data collection, the analysis and interpretation of data, the manuscript writing, and in the decision to submit the article for publication

Efficacy of Sertraline Plus Placebo or Add-On Celecoxib in Major Depressive Disorder: Macrophage Migration Inhibitory Factor as a Promising Biomarker for Remission After Sertraline-Results From a Randomized Controlled Clinical Trial

Trastorno depresivo mayor; Tratamiento antiinflamatorio; CitocinaTrastorn depressiu major; Tractament antiinflamatori; CitocinaMajor depressive disorder; Anti-inflammatory treatment; CytokineIntroduction: Previous research delivers strong indications that inflammatory activation leads to treatment resistance in a subgroup of patients with Major Depressive Disorder (MDD). Thus, tailored interventions are needed. The present study aimed to find potential biomarkers that may enable patients to be stratified according to immune activation. Methods: A phase IIa randomized placebo-controlled trial was performed to assess levels of inflammatory compounds in responders/remitters and non-responders/non-remitters to sertraline plus celecoxib (n = 20) and sertraline plus placebo (n = 23). Levels of macrophage migration inhibitory factor, neopterin, and tumor necrosis factor alpha were determined by enzyme-linked immunosorbent assay; response and remission were measured by reduction of the Montgomery Åsberg Depression Rating Scale score. Results: Both treatment groups showed a significant decline in depression symptoms, but no difference was found between groups. A clear pattern emerged only for macrophage migration inhibitory factor: placebo remitters showed significantly lower baseline levels than non-remitters (a similar trend was seen in responders and non-responders) while celecoxib responders showed a trend for higher baseline levels than non-responders. Conclusion: Small subsample sizes are a notable limitation, wherefore results are preliminary. However, the present study provides novel insights by suggesting macrophage migration inhibitory factor as a promising biomarker for treatment choice.This present work was funded by the EU 7th Framework program (grant number EU-FP7-CP-IP-2008-222963/EU-FP7-PEOPLE-2009-IAPP-MarieCurie-286334) and Horizon 2020 (grant number H2020-SC1-2016-2017/H2020-SC1-2017-Two-Stage-RTD). Further, part of this work was supported by the foundation Immunität und Seele. The funders had no role in the study design, data collection and analysis, or decision to publish

High-rate low-temperature dc pulsed magnetron sputtering of photocatalytic TiO2films: the effect of repetition frequency

The article reports on low-temperature high-rate sputtering of hydrophilic transparent TiO2thin films using dc dual magnetron (DM) sputtering in Ar + O2mixture on unheated glass substrates. The DM was operated in a bipolar asymmetric mode and was equipped with Ti(99.5) targets of 50 mm in diameter. The substrate surface temperature Tsurfmeasured by a thermostrip was less than 180 °C for all experiments. The effect of the repetition frequency frwas investigated in detail. It was found that the increase of frfrom 100 to 350 kHz leads to (a) an improvement of the efficiency of the deposition process that results in a significant increase of the deposition rate aDof sputtered TiO2films and (b) a decrease of peak pulse voltage and sustaining of the magnetron discharge at higher target power densities. It was demonstrated that several hundreds nm thick hydrophilic TiO2films can be sputtered on unheated glass substrates at aD = 80 nm/min, Tsurf < 180 °C when high value of fr = 350 kHz was used. Properties of a thin hydrophilic TiO2film deposited on a polycarbonate substrate are given

Assembly of a polymer lab-on-chip device for impedimetric measurements of D-dimers in whole blood

This paper reports the development and characterisation of an assembly technology for a polymer lab-on-chip. The system consists of a 150 m deep hot embossed microfluidic channel in polycarbonate and Au electrodes fabricated separately by photolithography on polyethylenenaphthalate. The system is designed for impedimetric immunoassay detection in whole blood. Electrode layer and microfluidic substrate are joined by means of a 50 m thick double-sided medical grade adhesive tape, adjusted with an optical alignment system. The bond proved to be liquid tight at room temperature. An alignment accuracy of 34 m (+/- 19 m) evaluated over a set of 23 samples, was achieved. The effect of alignment accuracy of the intermediate adhesive film on whole blood flow properties in the device is studied. Already an alignment error of 70 m increases the flushing out time of whole blood by approximately 20 %