Receptor-type Guanylyl Cyclases Confer Thermosensory Responses in C. elegans.

Thermosensation is critical for optimal regulation of physiology and behavior. C. elegans acclimates to its cultivation temperature (Tc) and exhibits thermosensitive behaviors at temperatures relative to Tc. These behaviors are mediated primarily by the AFD sensory neurons, which are extraordinarily thermosensitive and respond to thermal fluctuations at temperatures above a Tc-determined threshold. Although cGMP signaling is necessary for thermotransduction, the thermosensors in AFD are unknown. We show that AFD-specific receptor guanylyl cyclases (rGCs) are instructive for thermosensation. In addition to being necessary for thermotransduction, ectopic expression of these rGCs confers highly temperature-dependent responses onto diverse cell types. We find that the temperature response threshold is determined by the rGC and cellular context, and that multiple domains contribute to their thermosensory properties. Identification of thermosensory rGCs in C. elegans provides insight into mechanisms of thermosensation and thermal acclimation and suggests that rGCs may represent a new family of molecular thermosensors.This work was funded in part by the NIH (R01 GM081639 and P01 GM103770 – P.S., T32007292 – V.M.H. and P01NS079419 - T.O.).This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.neuron.2016.03.00

Significance of myocardial tenascin-C expression in left ventricular remodelling and long-term outcome in patients with dilated cardiomyopathy

Aim Dilated cardiomyopathy (DCM) has a variety of causes, and no useful approach to predict left ventricular (LV) remodelling and long-term outcome has yet been established. Myocardial tenascin-C (TNC) is known to appear under pathological conditions, possibly to regulate cardiac remodelling. The aim of this study was to clarify the significance of myocardial TNC expression in LV remodelling and the long-term outcome in DCM. Methods and results One hundred and twenty-three consecutive DCM patients who underwent endomyocardial biopsy for initial diagnosis were studied. Expression of TNC in biopsy sections was analysed immunohistochemically to quantify the ratio of the TNC-positive area to the whole myocardial tissue area (TNC area). Clinical parameters associated with TNC area were investigated. The patients were divided into two groups based on receiver operating characteristic analysis of TNC area to predict death: high TNC group with TNC area ≥2.3% (22 patients) and low TNC group with TNC area <2.3% (101 patients). High TNC was associated with diabetes mellitus. Comparing echocardiographic findings between before and 9 months after endomyocardial biopsy, the low TNC group was associated with decreased LV end-diastolic diameter and increased LV ejection fraction, whereas the high TNC group was not. Survival analysis revealed a worse outcome in the high TNC group than in the low TNC group (P < 0.001). Multivariable Cox regression analysis revealed that TNC area was independently associated with poor outcome (HR = 1.347, P = 0.032). Conclusions Increased myocardial TNC expression was associated with worse LV remodeling and long-term outcome in DCM

Modularization as a system life cycle management strategy:Drivers, barriers, mechanisms and impacts

This literature-grounded research contributes to a deeper understanding of modularization as a system life cycle management strategy, by providing a comprehensive view of its key barriers, drivers, possible mechanisms of implementation and impact. This comprehensive view, arranged into a decision-making–driven ontology, enables a decision maker to systematically identify modularization implementation opportunities in different industrial and service domains. The proposed ontology transforms modularization into a fully operationalizable strategy and contributes to a paradigm shift in the understanding of modularization, from a pure design option (i.e. modularity) to a fully strategic choice that, by nature, impacts on many of the system’s life cycle phases and involves a number of stakeholders

Feeding state-dependent regulation of developmental plasticity via CaMKI and neuroendocrine signaling

Information about nutrient availability is assessed via largely unknown mechanisms to drive developmental decisions, including the choice of Caenorhabditis elegans larvae to enter into the reproductive cycle or the dauer stage. In this study, we show that CMK-1 CaMKI regulates the dauer decision as a function of feeding state. CMK-1 acts cell-autonomously in the ASI, and non cell-autonomously in the AWC, sensory neurons to regulate expression of the growth promoting daf-7 TGF-β and daf-28 insulin-like peptide (ILP) genes, respectively. Feeding state regulates dynamic subcellular localization of CMK-1, and CMK-1-dependent expression of anti-dauer ILP genes, in AWC. A food-regulated balance between anti-dauer ILP signals from AWC and pro-dauer signals regulates neuroendocrine signaling and dauer entry; disruption of this balance in cmk-1 mutants drives inappropriate dauer formation under well-fed conditions. These results identify mechanisms by which nutrient information is integrated in a small neuronal network to modulate neuroendocrine signaling and developmental plasticity. © Neal et al.1

Real-time Optical Fiber Sensor For Hydro-alcoholic Solutions

The real-time determination of hydro-alcoholic concentration in alcohol distillation plants is a primordial condition in order to preserve the quality and reduce production losses. Presented research proposes a Fresnel reflectometric optical fiber sensor for the determination of hydro-alcoholic concentration in liquids. The intensity of reflected light and the sample temperature are continuously measured and processed by a fast algorithm. Calibration curves were prepared for a range from 0 to 100% of water in alcohol (ethanol) and adjusted to second order polynomials. According to functional tests, sensor provides maximal error of 1.3 % for concentration values and proportionates practically real-time analysis. © 2009 SPIE.7503Kamm, B., Gruber, P.R., Kamm, M., (2006) Biorefineries - Industrial Processes and Products: Status Quo and Future Directions, 1. , 964 p, Wiley-VCH, Weinheim, GermanyGusken, E., Salgado, R.M., Rossel, C.E.V., Ohishi, T., Suzuki, C.K., Hybrid optical fiber sensor and artificial neural networks system for bioethanol quality control and productivity enhancement (2008) 19th International Conference on Optical Fibre Sensors, , PerthPrasad, P.R., Rao, K.S.R., Bhuvaneswari, K., Praveena, N., Srikanth, Y.V.V., Determination of ethanol in blend petrol by gas chromatography and Fourier transform infrared spectroscopy (2008) Energy Sources, Part A: Recovery, Utilization, and Environmental EffectsYano, T., Aimi, T., Nakano, Y., Tamai, M., Prediction of the concentrations of ethanol and acetic acid in the culture broth of a rice vinegar fermentation using near-infrared spectroscopy (1997) J. Ferm. Bioeng, 84 (5), pp. 461-465Cardona, C.A., Sanches, O.J., Fuel ethanol production: Process design trends and integration opportunities (2007) Bioresource Technology, 98, pp. 2415-2457Kim, C.B., Su, C.B., Measurement of the refractive index of liquids at 1.3 and 1.5 microns using a fibre optic Fresnel ratiometer (2004) Meas. Sci. Technol, 15, pp. 1683-1686Lee, B., Review of present status of optical fiber sensors (2000) Opt. Fiber Technol, 71 (10), pp. 3864-3868Cho, S., Chung, H., Woo, Y.A., Kim, H.J., Determination of water content in ethanol by miniaturized near-infrared (NIR) systems (2005) Bull. Korean. Chem. Soc, 26 (1), pp. 115-118King, D., Lyons, W.B., Flanagan, C., Lewis, E., An optical-fiber sensor for use in water systems utilizing digital signal processing techniques and artificial neural network pattern recognition (2004) IEEE Sens. J, 4 (1), pp. 21-27C.K. Suzuki, E. Gusken, A.C. Mercado, E. Fujiwara, E. Ono, Fiber Optics Sensing System For Liquid Fuels, OMPI Patent, Prot. PCT/BR2008/000231, 2007Meyer, R.D., Eesley, G.L., Optical fiber refractometer (1987) Rev. Sci. Instrum, 58 (11), pp. 2047-2048Scott Jr., T.A., Refractive index of ethanol-water mixtures and density and refractive index of ethanol-water-ethyl ether mixtures (1946) J. Phys. Chem, 50 (5), pp. 406-41

Real-time optical fibre sensor for hydro-alcoholic solutions

Abstract The fast determination of ethanol-water concentration in alcohol distillation plants is a primordial requirement to preserve the quality and reduce production losses. The present research proposes an optical fibre sensor for the measurement of hydro-alcoholic concentration in liquids based on the Fresnel reflection principle. The reflection intensities of ethanol samples with 0-100% of water content were measured at different temperatures for 1310 nm and 1550 nm wavelengths. Calibration curves were prepared by fitting the experimental data and implemented in a computer algorithm. According to the functional tests, the sensor is capable of identifying samples with less than 1% error on concentration and providing practically real-time analysis

Mendelian randomization study of B-type natriuretic peptide and type 2 diabetes: evidence of causal association from population studies

&lt;p&gt;Background: Genetic and epidemiological evidence suggests an inverse association between B-type natriuretic peptide (BNP) levels in blood and risk of type 2 diabetes (T2D), but the prospective association of BNP with T2D is uncertain, and it is unclear whether the association is confounded.&lt;/p&gt; &lt;p&gt;Methods and Findings: We analysed the association between levels of the N-terminal fragment of pro-BNP (NT-pro-BNP) in blood and risk of incident T2D in a prospective case-cohort study and genotyped the variant rs198389 within the BNP locus in three T2D case-control studies. We combined our results with existing data in a meta-analysis of 11 case-control studies. Using a Mendelian randomization approach, we compared the observed association between rs198389 and T2D to that expected from the NT-pro-BNP level to T2D association and the NT-pro-BNP difference per C allele of rs198389. In participants of our case-cohort study who were free of T2D and cardiovascular disease at baseline, we observed a 21% (95% CI 3%-36%) decreased risk of incident T2D per one standard deviation (SD) higher log-transformed NT-pro-BNP levels in analysis adjusted for age, sex, body mass index, systolic blood pressure, smoking, family history of T2D, history of hypertension, and levels of triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The association between rs198389 and T2D observed in case-control studies (odds ratio = 0.94 per C allele, 95% CI 0.91-0.97) was similar to that expected (0.96, 0.93-0.98) based on the pooled estimate for the log-NT-pro-BNP level to T2D association derived from a meta-analysis of our study and published data (hazard ratio = 0.82 per SD, 0.74-0.90) and the difference in NT-pro-BNP levels (0.22 SD, 0.15-0.29) per C allele of rs198389. No significant associations were observed between the rs198389 genotype and potential confounders.&lt;/p&gt; &lt;p&gt;Conclusions: Our results provide evidence for a potential causal role of the BNP system in the aetiology of T2D. Further studies are needed to investigate the mechanisms underlying this association and possibilities for preventive interventions.&lt;/p&gt

The diacylglycerol kinase α/Atypical PKC/β1 integrin pathway in SDF-1α mammary carcinoma invasiveness

Diacylglycerol kinase α (DGKα), by phosphorylating diacylglycerol into phosphatidic acid, provides a key signal driving cell migration and matrix invasion. We previously demonstrated that in epithelial cells activation of DGKα activity promotes cytoskeletal remodeling and matrix invasion by recruiting atypical PKC at ruffling sites and by promoting RCP-mediated recycling of α5β1 integrin to the tip of pseudopods. In here we investigate the signaling pathway by which DGKα mediates SDF-1α-induced matrix invasion of MDA-MB-231 invasive breast carcinoma cells. Indeed we showed that, following SDF-1α stimulation, DGKα is activated and localized at cell protrusion, thus promoting their elongation and mediating SDF-1α induced MMP-9 metalloproteinase secretion and matrix invasion. Phosphatidic acid generated by DGKα promotes localization at cell protrusions of atypical PKCs which play an essential role downstream of DGKα by promoting Rac-mediated protrusion elongation and localized recruitment of β1 integrin and MMP-9. We finally demonstrate that activation of DGKα, atypical PKCs signaling and β1 integrin are all essential for MDA-MB-231 invasiveness. These data indicates the existence of a SDF-1α induced DGKα - atypical PKC - β1 integrin signaling pathway, which is essential for matrix invasion of carcinoma cells

SIRT1 disruption in human fetal hepatocytes leads to increased accumulation of glucose and lipids

There are unprecedented epidemics of obesity, such as type II diabetes and non-alcoholic fatty liver diseases (NAFLD) in developed countries. A concerning percentage of American children are being affected by obesity and NAFLD. Studies have suggested that the maternal environment in utero might play a role in the development of these diseases later in life. In this study, we documented that inhibiting SIRT1 signaling in human fetal hepatocytes rapidly led to an increase in intracellular glucose and lipids levels. More importantly, both de novo lipogenesis and gluconeogenesis related genes were upregulated upon SIRT1 inhibition. The AKT/FOXO1 pathway, a major negative regulator of gluconeogenesis, was decreased in the human fetal hepatocytes inhibited for SIRT1, consistent with the higher level of gluconeogenesis. These results indicate that SIRT1 is an important regulator of lipid and carbohydrate metabolisms within human fetal hepatocytes, acting as an adaptive transcriptional response to environmental changes

Chronic non-transmural infarction has a delayed recovery of function following revascularization

<p>Abstract</p> <p>Background</p> <p>The time course of regional functional recovery following revascularization with regards to the presence or absence of infarction is poorly known. We studied the effect of the presence of chronic non-transmural infarction on the time course of recovery of myocardial perfusion and function after elective revascularization.</p> <p>Methods</p> <p>Eighteen patients (mean age 69, range 52-84, 17 men) prospectively underwent cine magnetic resonance imaging (MRI), delayed contrast enhanced MRI and rest/stress 99m-Tc-tetrofosmin single photon emission computed tomography (SPECT) before, one and six months after elective coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI).</p> <p>Results</p> <p>Dysfunctional myocardial segments (n = 337/864, 39%) were classified according to the presence (n = 164) or absence (n = 173) of infarction. Infarct transmurality in dysfunctional segments was largely non-transmural (transmurality = 31 ± 22%). Quantitative stress perfusion and wall thickening increased at one month in dysfunctional segments without infarction (p < 0.001), with no further improvement at six months. Despite improvements in stress perfusion at one month (p < 0.001), non-transmural infarction displayed a slower and lesser improvement in wall thickening at one (p < 0.05) and six months (p < 0.001).</p> <p>Conclusions</p> <p>Dysfunctional segments without infarction represent repetitively stunned or hibernating myocardium, and these segments improved both perfusion and function within one month after revascularization with no improvement thereafter. Although dysfunctional segments with non-transmural infarction improved in perfusion at one month, functional recovery was mostly seen between one and six months, possibly reflecting a more severe ischemic burden. These findings may be of value in the clinical assessment of regional functional recovery in the time period after revascularization.</p