Lysosomal-associated Transmembrane Protein 4B (LAPTM4B) Decreases Transforming Growth Factor β1 (TGF-β1) Production in Human Regulatory T Cells

Production of active TGF-β1 is one mechanism by which human regulatory T cells (Tregs) suppress immune responses. This production is regulated by glycoprotein A repetitions predominant (GARP), a transmembrane protein present on stimulated Tregs but not on other T lymphocytes (Th and CTLs). GARP forms disulfide bonds with proTGF-β1, favors its cleavage into latent inactive TGF-β1, induces the secretion and surface presentation of GARP·latent TGF-β1 complexes, and is required for activation of the cytokine in Tregs. We explored whether additional Treg-specific protein(s) associated with GARP·TGF-β1 complexes regulate TGF-β1 production in Tregs. We searched for such proteins by yeast two-hybrid assay, using GARP as a bait to screen a human Treg cDNA library. We identified lysosomal-associated transmembrane protein 4B (LAPTM4B), which interacts with GARP in mammalian cells and is expressed at higher levels in Tregs than in Th cells. LAPTM4B decreases cleavage of proTGF-β1, secretion of soluble latent TGF-β1, and surface presentation of GARP·TGF-β1 complexes by Tregs but does not contribute to TGF-β1 activation. Therefore, LAPTM4B binds to GARP and is a negative regulator of TGF-β1 production in human Tregs. It may play a role in the control of immune responses by decreasing Treg immunosuppression.     

Genome-Wide Association Mapping of Fertility Reduction upon Heat Stress Reveals Developmental Stage-Specific QTLs in Arabidopsis thaliana

For crops that are grown for their fruits or seeds, elevated temperatures that occur during flowering and seed or fruit set have a stronger effect on yield than high temperatures during the vegetative stage. Even short-term exposure to heat can have a large impact on yield. In this study, we used Arabidopsis thaliana to study the effect of short-term heat exposure on flower and seed development. The impact of a single hot day (35°C) was determined in more than 250 natural accessions by measuring the lengths of the siliques along the main inflorescence. Two sensitive developmental stages were identified, one before anthesis, during male and female meiosis, and one after anthesis, during fertilization and early embryo development. In addition, we observed a correlation between flowering time and heat tolerance. Genome-wide association mapping revealed four quantitative trait loci (QTLs) strongly associated with the heat response. These QTLs were developmental stage specific, as different QTLs were detected before and after anthesis. For a number of QTLs, T-DNA insertion knockout lines could validate assigned candidate genes. Our findings show that the regulation of complex traits can be highly dependent on the developmental timing.     

Apparent annual survival of staging ruffs during a period of population decline: insights from sex and site-use related differences

The ruff Philomachus pugnax, a lekking shorebird wintering in Africa and breeding across northern Eurasia, declined severely in its western range. Based on a capture-mark-resighting programme (2004–2011) in the westernmost staging area in Friesland (the Netherlands), we investigated changes in apparent annual survival in relation to age and sex to explore potential causes of decline. We also related temporal variation in apparent survival to environmental factors. We used the Capture-Mark-Recapture multievent statistical framework to overcome biases in survival estimates after testing for hidden heterogeneity of detection. This enabled the estimation of the probability to belong to high or low detectability classes. Apparent survival varied between years but was not related to weather patterns along the flyway, or to flood levels in the Sahel. Over time, a decline in apparent survival is suggested. Due to a short data series and flag loss in the last period this cannot be verified. Nevertheless, the patterns in sex-specific detectability and survival lead to new biological insights. Among highly detectable birds, supposedly most reliant on Friesland, males survived better than females ( = 0.74, range 0.51–0.93; = 0.51, range 0.24–0.81). Among low detectable birds, the pattern is reversed ( = 0.64, range 0.37–0.89; = 0.73, range 0.48–0.93). Probably the staging population contains a mixture of sex-specific migration strategies. A loss of staging females could greatly affect the dynamics of the western ruff population. Further unravelling of these population processes requires geographically extended demographic monitoring and the use of tracking devices.     

Effects of spinal or general anesthesia on F₂-isoprostanes and isofurans during ischemia/reperfusion of the leg in patients undergoing knee replacement surgery

General and spinal anesthesia are used extensively in orthopedic surgery. However, these methods of anesthesia may result in different amounts of oxygen being delivered to the patient. Ischemia/reperfusion injury after release of the tourniquet initiates free radical-mediated oxidative stress. F₂-isoprostanes are reliable markers of in vivo lipid peroxidation. However, under conditions of high oxygen tension, isofurans are formed. We aimed to compare plasma isofurans and F₂-isoprostanes in spinal versus general anesthesia in patients undergoing knee-replacement surgery in a randomized, blinded study. Thirty-nine patients were randomized to spinal (SA; n = 19) or general anesthesia (GA; n = 20). Blood was collected before anesthesia, and a tourniquet was then applied to the limb during surgery. After release of the tourniquet, blood samples were collected at 30 min, 2 h, and 24 h for measurement of plasma F₂-isoprostanes and isofurans by gas chromatography–mass spectrometry. The two groups were comparable in age and body mass index. Plasma F₂-isoprostanes were significantly lower in the GA patients compared with the SA patients (p = 0.045). In contrast, the GA patients had significantly elevated plasma isofurans (p = 0.032). Increased isofurans during GA compared with SA are likely to reflect increased oxidative stress due to elevated oxygen concentrations during GA. Further studies are required to assess the implications of these findings on perioperative outcomes.     

Sex allocation in haplodiploids is mediated by egg size: evidence in the spider mite Tetranychus urticae Koch

Haplodiploid species display extraordinary sex ratios. However, a differential investment in male and female offspring might also be achieved by a differential provisioning of eggs, as observed in birds and lizards. We investigated this hypothesis in the haplodiploid spider mite Tetranychus urticae, which displays highly female-biased sex ratios. We show that egg size significantly determines not only larval size, juvenile survival and adult size, but also fertilization probability, as in marine invertebrates with external fertilization, so that female (fertilized) eggs are significantly larger than male (unfertilized) eggs. Moreover, females with on average larger eggs before fertilization produce a more female-biased sex ratio afterwards. Egg size thus mediates sex-specific egg provisioning, sex and offspring sex ratio. Finally, sex-specific egg provisioning has another major consequence: male eggs produced by mated mothers are smaller than male eggs produced by virgins, and this size difference persists in adults. Virgin females might thus have a (male) fitness advantage over mated females.     

Role of exopolymeric substances (EPS) in the stability of the biofilm of Thiomonas arsenivorans grown on a porous mineral support

Biochemical methods were selected to evaluate the role of exopolymeric substances in the stability of biofilms used in bioremediation processes. Biofilms of Thiomonas arsenivorans formed on pozzolana were thus treated with pronase (protein target), lectins (Con A or PNA), calcofluor or periodic acid (polysaccharides target), DNase (DNA target), and lipase (triglycerides target). Neither protease nor DNase treatments had any effect on bacterial adhesion. Lectins and calcofluor treatments mainly affected young biofilms. Lipase treatment had a noticeable effect on biofilm stability whatever the biofilm age. Results suggest that it would be an increased resistance of mature biofilms that protects them from external attacks.     

Thermal and hydrodynamic modelling of active catheters for interventional radiology

Interventional radiologists desire to improve their operating tools such as catheters. Active catheters in which the tip is moved using shape memory alloy actuators activated using the Joule effect present a promising approach for easier navigation in the small vessels. However, the increase in temperature caused by this Joule effect must be controlled in order to prevent damage to blood cells and tissues. This paper is devoted to the simulation and experimental validation of a fluid-thermal model of an active catheter prototype. Comparisons between computer-predicted and experimentally measured temperatures are presented for both experiments in air and water at 37°C. Good agreement between the computational and experimental results is found, demonstrating the validity of the developed computer model. These comparisons enable us to highlight some important issues in the modelling process and to determine the optimal current for the activation of the catheter.