Nature of fatty acids in high fat diets differentially delineates obesity-linked metabolic syndrome components in male and female C57BL/6J mice

<p>Abstract</p> <p>Background</p> <p>Adverse effects of high-fat diets (HFD) on metabolic homeostasis are linked to adipose tissue dysfunction. The goal of this study was to examine the effect of the HFD nature on adipose tissue activity, metabolic disturbances and glucose homeostasis alterations in male mice compared with female mice.</p> <p>Methods</p> <p>C57BL/6J mice were fed either a chow diet or HFD including vegetal (VD) or animal (AD) fat. Body weight, plasmatic parameters and adipose tissue mRNA expression levels of key genes were evaluated after 20 weeks of HFD feeding.</p> <p>Results</p> <p>HFD-fed mice were significantly heavier than control at the end of the protocol. Greater abdominal visceral fat accumulation was observed in mice fed with AD compared to those fed a chow diet or VD. Correlated with weight gain, leptin levels in systemic circulation were increased in HFD-fed mice in both sexes with a significant higher level in AD group compared to VD group. Circulating adiponectin levels as well as adipose tissue mRNA expression levels were significantly decreased in HFD-fed male mice. Although its plasma levels remained unchanged in females, adiponectin mRNA levels were significantly reduced in adipose tissue of both HFD-fed groups with a more marked decrease in AD group compared to VD group. Only HFD-fed male mice were diabetic with increased fasting glycaemia. On the other hand, insulin levels were only increased in AD-fed group in both sexes associated with increased resistin levels. VD did not induce any apparent metabolic alteration in females despite the increased weight gain. Peroxisome Proliferator-Activated Receptors gamma-2 (PPARγ2) and estrogen receptor alpha (ERα) mRNA expression levels in adipose tissue were decreased up to 70% in HFD-fed mice but were more markedly reduced in male mice as compared with female mice.</p> <p>Conclusions</p> <p>The nature of dietary fat determines the extent of metabolic alterations reflected in adipocytes through modifications in the pattern of adipokines secretion and modulation of key genes mRNA expression. Compared with males, female mice demonstrate higher capacity in controlling glucose homeostasis in response to 20 weeks HFD feeding. Our data suggest gender specific interactions between the diet's fatty acid source, the adipocyte-secreted proteins and metabolic disorders.</p

Direct Association of Protein-tyrosine Phosphatase PTP-PEST with Paxillin

Tyrosine phosphorylation of focal adhesion-associated proteins may be involved in the regulation of the cytoskeleton and in the control of signals for growth and survival. The focal adhesion kinase (FAK) functions in regulating tyrosine phosphorylation of several of these proteins, including paxillin, tensin, and p130(cas). Protein- tyrosine phosphatases, the counterparts of protein-tyrosine kinases, also presumably regulate phosphorylation of these proteins. We have tested the hypothesis that FAK intimately associates with a protein-tyrosine phosphatase. Protein-tyrosine phosphatase activity associated with the recombinant C-terminal domain of FAK in vitro and could be coimmunoprecipitated with both FAK and paxillin from lysates of chicken embryo cells. However, the interaction with FAK appeared to be indirect and mediated via paxillin. The protein-tyrosine phosphatase was subsequently identified as protein-tyrosine phosphatase-PEST, a nonreceptor protein-tyrosine phosphatase. The C-terminal noncatalytic domain of protein-tyrosine phosphatase-PEST directly bound to paxillin in vitro. The association of both a protein-tyrosine kinase and a protein-tyrosine phosphatase with paxillin suggests that paxillin may play a critical role in the regulation of the phosphotyrosine content of proteins in focal adhesions

Responsible Conduct of Research in Research-Creation: Moving into Uncharted Terrain

Responsible conduct of research (RCR) is ubiquitous, and present in most areas of research. One area that has received little attention is Research-Creation (RC): • an emergent eld at the interface of academic research and creative activities • in Quebec, Canada, RC is de ned as “research activities or approaches that foster the creation or interpretation/ performance of literary or artistic works of all types” Researcher-Creators – who are at the same time researchers and practising artists, musicians, or designers – may be faced with very di erent issues or challenges from colleagues in the rest of academia. • How do researcher-creators reconcile their dual obligations to creation and to research? • Are the usual research ethics guidelines (e.g., TCPS2, ICH relevant and how do they apply? • How do the creative/artistic dimensions of research a ect evaluations by grant committees and REBs? To better understand how RCR issues are articulated in the very heterogeneous RC community, we combine here results from a literature review and an international survey on RCR in RC.FRQ Action concerté

Comprehensive High-resolution Chemical Spectroscopy of Barnard's Star with SPIRou

Determination of fundamental parameters of stars impacts all fields of astrophysics, from galaxy evolution to constraining the internal structure of exoplanets. This paper presents a detailed spectroscopic analysis of Barnard's star that compares an exceptionally high-quality (signal-to-noise ratio of $>$2500 in the $H$ band), high-resolution NIR spectrum taken with CFHT/SPIRou to PHOENIX-ACES stellar atmosphere models. The observed spectrum shows thousands of lines not identified in the models with a similar large number of lines present in the model but not in the observed data. We also identify several other caveats such as continuum mismatch, unresolved contamination and spectral lines significantly shifted from their expected wavelengths, all of these can be a source of bias for abundance determination. Out of $>10^4$ observed lines in the NIR that could be used for chemical spectroscopy, we identify a short list of a few hundred lines that are reliable. We present a novel method for determining the effective temperature and overall metallicity of slowly-rotating M dwarfs that uses several groups of lines as opposed to bulk spectral fitting methods. With this method, we infer $T_{\rm eff}$ = 3231 $\pm$ 21 K for Barnard's star, consistent with the value of 3238 $\pm$ 11 K inferred from the interferometric method. We also provide abundance measurements of 15 different elements for Barnard's star, including the abundances of four elements (K, O, Y, Th) never reported before for this star. This work emphasizes the need to improve current atmosphere models to fully exploit the NIR domain for chemical spectroscopy analysis.Comment: 24 pages, 18 figures, submitted to Ap

Optimizing Nervous System-Specific Gene Targeting with Cre Driver Lines: Prevalence of Germline Recombination and Influencing Factors.

The Cre-loxP system is invaluable for spatial and temporal control of gene knockout, knockin, and reporter expression in the mouse nervous system. However, we report varying probabilities of unexpected germline recombination in distinct Cre driver lines designed for nervous system-specific recombination. Selective maternal or paternal germline recombination is showcased with sample Cre lines. Collated data reveal germline recombination in over half of 64 commonly used Cre driver lines, in most cases with a parental sex bias related to Cre expression in sperm or oocytes. Slight differences among Cre driver lines utilizing common transcriptional control elements affect germline recombination rates. Specific target loci demonstrated differential recombination; thus, reporters are not reliable proxies for another locus of interest. Similar principles apply to other recombinase systems and other genetically targeted organisms. We hereby draw attention to the prevalence of germline recombination and provide guidelines to inform future research for the neuroscience and broader molecular genetics communities

CO or no CO? Narrowing the CO abundance constraint and recovering the H2O detection in the atmosphere of WASP-127 b using SPIRou

Precise measurements of chemical abundances in planetary atmospheres are necessary to constrain the formation histories of exoplanets. A recent study of WASP-127b, a close-in puffy sub-Saturn orbiting its solar-type host star in 4.2 d, using HST and Spitzer revealed a feature-rich transmission spectrum with strong excess absorption at 4.5 um. However, the limited spectral resolution and coverage of these instruments could not distinguish between CO and/or CO2 absorption causing this signal, with both low and high C/O ratio scenarios being possible. Here we present near-infrared (0.9--2.5 um) transit observations of WASP-127 b using the high-resolution SPIRou spectrograph, with the goal to disentangle CO from CO2 through the 2.3 um CO band. With SPIRou, we detect H2O at a t-test significance of 5.3 sigma and observe a tentative (3 sigma) signal consistent with OH absorption. From a joint SPIRou + HST + Spitzer retrieval analysis, we rule out a CO-rich scenario by placing an upper limit on the CO abundance of log10[CO]<-4.0, and estimate a log10[CO2] of -3.7^(+0.8)_(-0.6), which is the level needed to match the excess absorption seen at 4.5um. We also set abundance constraints on other major C-, O-, and N-bearing molecules, with our results favoring low C/O (0.10^(+0.10)_(-0.06)), disequilibrium chemistry scenarios. We further discuss the implications of our results in the context of planet formation. Additional observations at high and low-resolution will be needed to confirm these results and better our understanding of this unusual world.Comment: 23 pages, 13 figures, Submitted for publication in the Monthly Notice of the Royal Astronomical Societ