PTP1B Regulates Leptin Signal Transduction In Vivo

AbstractMice lacking the protein-tyrosine phosphatase PTP1B are hypersensitive to insulin and resistant to obesity. However, the molecular basis for resistance to obesity has been unclear. Here we show that PTP1B regulates leptin signaling. In transfection studies, PTP1B dephosphorylates the leptin receptor-associated kinase, Jak2. PTP1B is expressed in hypothalamic regions harboring leptin-responsive neurons. Compared to wild-type littermates, PTP1B−/− mice have decreased leptin/body fat ratios, leptin hypersensitivity, and enhanced leptin-induced hypothalamic Stat3 tyrosyl phosphorylation. Gold thioglucose treatment, which ablates leptin-responsive hypothalamic neurons, partially overcomes resistance to obesity in PTP1B−/− mice. Our data indicate that PTP1B regulates leptin signaling in vivo, likely by targeting Jak2. PTP1B may be a novel target to treat leptin resistance in obesity

Dynamics of immunological reactivity indices in patients with laryngal papillomatosis at different periods after complex treatment with antivirus qudrivalent vaccine "Gardasil"

The aim of the study is to determine di­sorders of immune homeostasis in patients with laryngeal papillomatosis at different periods after complex treatment with the inclusion of the “Gardasil” quadrivalent vaccine in the adjuvant therapy. Studies of the immunity state were conducted in 26 patients with laryngeal papillomatosis (LP) before, 2-12 and 13-29 months after complex treatment, consisting of surgical removal of papillomas and anti-relapse therapy, including inhalation of Laferobion, taking a vitamin-mineral complex and a course of vaccination with antiviral “Gardasil” quadrivalent vaccine according to which the second and third injections were administered in 2 and 6 months after the first. Significant disorders of cellular and humoral immunity indices in patients with LP were revealed in the form of multidirectional changes in the functional activity of natural killer cells, a decrease in the total number of T lymphocytes, mainly due to CD4 + subpopulation, increase in circulating immune complexes level in blood serum and concentration of secretory IgA in the secretion of the oropharynx. Disbalance in the patient’s cytokine system resulted in increased γ-IFN and TNF-α serum levels, an increase in spontaneous production of interferon and inhibition of stimulated production of λ - and γ-interferon by blood cells in vitro. Complex treatment with the use of the “Gardasil” quadrivalent antiviral vaccine in the postoperative period contributed to the normalization of most immunological reactivity indices that were altered in patients. The results indicate the prospects of using the antiviral vaccine as part of adjuvant antirelapse therapy after surgical treatment of LP patients and indicate the advisability of long-term clinical and immunological monitoring at different periods after vaccination

"Pi of the Sky" - all-sky, real-time search for fast optical transients

An apparatus to search for optical flashes in the sky is described. It has been optimized for gamma ray bursts (GRB) optical counterparts. It consists of 2x16 cameras covering all the sky. The sky is monitored continuously and the data are analysed on-line. It has self-triggering capability and can react to external triggers with negative delay. The prototype with two cameras has been installed at Las Campanas (Chile) and is operational from July 2004. The paper presents general idea and describes the apparatus in detail. Performance of the prototype is briefly reviewed and perspectives for the future are outlined

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Performance and Operation of the CMS Electromagnetic Calorimeter

The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented

First measurements of the performance of the Barrel RPC system in CMS

During the summer 2006, a first integrated test of a part of the CMS experiment was performed at CERN collecting a data sample of several millions of cosmic rays events. A fraction of the Resistive Plate Chambers system was successfully operated. Results on the RPC performance are reported

Regulation of Brown Fat Adipogenesis by Protein Tyrosine Phosphatase 1B

Protein-tyrosine phosphatase 1B (PTP1B) is a physiological regulator of insulin signaling and energy balance, but its role in brown fat adipogenesis requires additional investigation.To precisely determine the role of PTP1B in adipogenesis, we established preadipocyte cell lines from wild type and PTP1B knockout (KO) mice. In addition, we reconstituted KO cells with wild type, substrate-trapping (D/A) and sumoylation-resistant (K/R) PTP1B mutants, then characterized differentiation and signaling in these cells. KO, D/A- and WT-reconstituted cells fully differentiated into mature adipocytes with KO and D/A cells exhibiting a trend for enhanced differentiation. In contrast, K/R cells exhibited marked attenuation in differentiation and lipid accumulation compared with WT cells. Expression of adipogenic markers PPARγ, C/EBPα, C/EBPδ, and PGC1α mirrored the differentiation pattern. In addition, the differentiation deficit in K/R cells could be reversed completely by the PPARγ activator troglitazone. PTP1B deficiency enhanced insulin receptor (IR) and insulin receptor substrate 1 (IRS1) tyrosyl phosphorylation, while K/R cells exhibited attenuated insulin-induced IR and IRS1 phosphorylation and glucose uptake compared with WT cells. In addition, substrate-trapping studies revealed that IRS1 is a substrate for PTP1B in brown adipocytes. Moreover, KO, D/A and K/R cells exhibited elevated AMPK and ACC phosphorylation compared with WT cells.These data indicate that PTP1B is a modulator of brown fat adipogenesis and suggest that adipocyte differentiation requires regulated expression of PTP1B

Resistive Plate Chambers performance with Cosmic Rays in the CMS experiment

The Resistive Plate Chambers are used in the CMS experiment as a dedicated muon trigger both in barrel and endcap system. About 4000 square meter of double gap RPCs have been produced and have been installed in the experiment since more than one year and half. The full barrel system and a fraction of the endcaps have been monitored to study dark current behaviour and system stability, and have been extensively commissioned with Cosmic Rays collected by the full CMS experiment

Unsaturated Fatty Acids Revert Diet-Induced Hypothalamic Inflammation in Obesity

Background: In experimental models, hypothalamic inflammation is an early and determining factor in the installation and progression of obesity. Pharmacological and gene-based approaches have proven efficient in restraining inflammation and correcting the obese phenotypes. However, the role of nutrients in the modulation of hypothalamic inflammation is unknown. Methodology/Principal Findings: Here we show that, in a mouse model of diet-induced obesity, partial substitution of the fatty acid component of the diet by flax seed oil (rich in C18:3) or olive oil (rich in C18:1) corrects hypothalamic inflammation, hypothalamic and whole body insulin resistance, and body adiposity. In addition, upon icv injection in obese rats, both v3 and v9 pure fatty acids reduce spontaneous food intake and body mass gain. These effects are accompanied by the reversal of functional and molecular hypothalamic resistance to leptin/insulin and increased POMC and CART expressions. In addition, both, v3 and v9 fatty acids inhibit the AMPK/ACC pathway and increase CPT1 and SCD1 expression in the hypothalamus. Finally, acute hypothalamic injection of v3 and v9 fatty acids activate signal transduction through the recently identified GPR120 unsaturated fatty acid receptor. Conclusions/Significance: Unsaturated fatty acids can act either as nutrients or directly in the hypothalamus, reverting dietinduced inflammation and reducing body adiposity. These data show that, in addition to pharmacological and geneti

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)