Fatty acid nitroalkenes ameliorate glucose intolerance and pulmonary hypertension in high-fat diet-induced obesity

Aims Obesity is a risk factor for diabetes and cardiovascular diseases, with the incidence of these disorders becoming epidemic. Pathogenic responses to obesity have been ascribed to adipose tissue (AT) dysfunction that promotes bioactive mediator secretion from visceral AT and the initiation of pro-inflammatory events that induce oxidative stress and tissue dysfunction. Current understanding supports that suppressing pro-inflammatory and oxidative events promotes improved metabolic and cardiovascular function. In this regard, electrophilic nitro-fatty acids display pleiotropic anti-inflammatory signalling actions. Methods and results It was hypothesized that high-fat diet (HFD)-induced inflammatory and metabolic responses, manifested by loss of glucose tolerance and vascular dysfunction, would be attenuated by systemic administration of nitrooctadecenoic acid (OA-NO2). Male C57BL/6j mice subjected to a HFD for 20 weeks displayed increased adiposity, fasting glucose, and insulin levels, which led to glucose intolerance and pulmonary hypertension, characterized by increased right ventricular (RV) end-systolic pressure (RVESP) and pulmonary vascular resistance (PVR). This was associated with increased lung xanthine oxidoreductase (XO) activity, macrophage infiltration, and enhanced expression of pro-inflammatory cytokines. Left ventricular (LV) end-diastolic pressure remained unaltered, indicating that the HFD produces pulmonary vascular remodelling, rather than LV dysfunction and pulmonary venous hypertension. Administration of OA-NO2 for the final 6.5 weeks of HFD improved glucose tolerance and significantly attenuated HFD-induced RVESP, PVR, RV hypertrophy, lung XO activity, oxidative stress, and pro-inflammatory pulmonary cytokine levels. Conclusions These observations support that the pleiotropic signalling actions of electrophilic fatty acids represent a therapeutic strategy for limiting the complex pathogenic responses instigated by obesity.Fil: Kelley, Eric E.. University of Pittsburgh; Estados UnidosFil: Baust, Jeff. University of Pittsburgh; Estados UnidosFil: Bonacci, Gustavo Roberto. University of Pittsburgh; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Golin Bisello, Franca. University of Pittsburgh; Estados UnidosFil: Devlin, Jason E.. University of Pittsburgh; Estados UnidosFil: Croix, Claudette M. St.. University of Pittsburgh; Estados UnidosFil: Watkins, Simon C.. University of Pittsburgh; Estados UnidosFil: Gor, Sonia. University of Pittsburgh; Estados UnidosFil: Cantu Medellin, Nadiezhda. University of Pittsburgh; Estados UnidosFil: Weidert, Eric R.. University of Pittsburgh; Estados UnidosFil: Frisbee,Jefferson C.. University of Virginia; Estados UnidosFil: Gladwin, Mark T.. University of Pittsburgh; Estados UnidosFil: Champion, Hunter C.. University of Pittsburgh; Estados UnidosFil: Freeman, Bruce A.. University of Pittsburgh; Estados UnidosFil: Khoo, Nicholas K.H.. University of Pittsburgh; Estados Unido

Recurrent deletions of ULK4 in schizophrenia : a gene crucial for neuritogenesis and neuronal motility

Peer reviewedPublisher PD

Literacy for Empowerment and Social Change

While it may be true that the electronic age has devalued literacy, what seems more serious is the way in which certain groups have been so devalued that they are inhibited in their acquisition of literacy skills. Many poor and minority students are prevented from developing their cognitive and manipulative skills beyond a minimal level. Perhaps what needs changing is not the level of skills in literacy or functional competence butthe level of hope and expectation among bypassed people in our society. Action research might be designed to focus on competencies presently existing and valued and, at the same time, on the changes that occur when groups develop new hope for themselves and a more dynamic vision of the options available to them

Letter from Alexander St. Clair Hunter to James B. Finley

Hunter was charged by circuit rider Burroughs Westlake (Mad River Circuit) with falsehood, a charge that he adamantly denies. Following his conviction, he decided that he would appeal the decision. He asks Presiding Elder James B. Finley (Lebanon District) for his help. Abstract Number - 64https://digitalcommons.owu.edu/finley-letters/1062/thumbnail.jp

Control of cortex development by ULK4, a rare risk gene for mental disorders including schizophrenia

This work was supported by the grants from British Council China (Sino-UK higher Education for PhD studies) to Y.D. and C.D.M., and also from the following funding resources: Tenovus Scotland (G12/05, B.L.), The Carnegie Trust (RG13060-10, B.L.) and National Natural Science Foundation of China (91232724, Y.D.; 31100788, L.Z.; 81200933, N.N.S.; 31528011, B.L. and Y.D.).Peer reviewedPublisher PD

Validation of the SenseWear armband in circuit resistance training with different loads

The use of the SenseWear™ armband (SWA), an objective monitor of physical activity, is a relatively new device used by researchers to measure energy expenditure. These monitors are practical, relatively inexpensive and easy-to-use. The aim of the present study was to assess the validity of SWAs for the measurement of energy expenditure (EE) in circuit resistance training (CRT) at three different intensities in moderately active, healthy subjects. The study subjects (17 females, 12 males) undertook CRT at 30, 50 and 70% of the 15 repetition maximum for each exercise component wearing an SWA as well as an Oxycon Mobile (OM) portable metabolic system (a gold standard method for measuring EE). The EE rose as exercise intensity increased, but was underestimated by the SWAs. For women, Bland-Altman plots showed a bias of 1.13 ± 1.48 METs and 32.1 ± 34.0 kcal in favour of the OM system, while for men values of 2.33 ± 1.82 METs and 75.8 ± 50.8 kcal were recorded

Utilisation of underwater acoustic backscatter systems to characterise nuclear waste suspensions remotely

This paper reports application of ABS (Acoustic Backscatter Systems) to address nuclear waste management within the UK. ABS offers a route towards an online monitoring system to characterise wastes safely and remotely in real-time, during pipeline transportation; resulting in reduced hazard reduction timescales and taxpayer cost savings. Here, an ultrasonic velocimetry profiler (UVP) was used to analyse glass dispersions of varying concentrations, to assess online waste monitoring applicability. Acoustic backscatter profiles were collected to establish attenuation coefficients for two glass sizes (∼40 and 80 µm) with 2 and 4 MHz probes. The 4 MHz probes were the most highly attenuating while transducer active radius had a negligible effect on probe sensitivity with either glass. A calibration procedure was used to measure sediment attenuation coefficients, which were compared to model estimates and experimental literature. For most systems, measured coefficients were close to estimated values, highlighting improved calibration accuracy, due to the mixing tank used. However, values for the smaller glass and 2 MHz probes overestimated model predictions, due to additional viscous attenuation. The measured value for the larger glass with 4 MHz probes was underestimated, this was caused by high attenuation reaching the instrument noise-floor, limiting the region available for analysis

The effect of exercise induced hyperthermia on muscle fibre conduction velocity during sustained isometric contraction

This study investigated the effect of dynamic exercise in a hot environment on muscle fibre conduction velocity (MFCV) of the knee extensors during a sustained isometric contraction. Seven trained male cyclists (mean [±SD], age, and V_ O2max were 35 ± 9.9 and 57.4 ± 6.6 ml kg1 min1) cycled for 50 min at 60% of peak power output in either: (1) 40 C (HOT); or (2) 19 C (NEUTRO); and (3) remained passive in 40 C (PASS). Post-intervention a 100 s maximal sustained isometric contraction (SMC) of the knee extensors was performed. Rectal temperature increased (p < 0.01) for both HOT and NEUTRO with PASS unchanged and with HOT rising higher (p < 0.01) than NEUTRO (38.6 ± 0.4 vs. 37.6 ± 0.4 C). Muscle temperature increased (p < 0.01) for all three conditions with HOT rising the highest (p < 0.01) (40.3 ± 0.5 vs. 38.3 ± 0.3 and 37.6 ± 1.3 C for NEUTRO and PASS, respectively). Lactate showed higher accumulation (p < 0.01) for HOT than NEUTRO (6.9 ± 2.3 vs. 4.2 ± 2.1 mmol l1). During SMC the torque, electromyography root mean squared (RMS) and MFCV all significantly (p < 0.01) declined. Only in HOT did MFCV decline significantly (p < 0.01) less than torque and RMS (9.9 ± 6.2% vs. 37.5 ± 17.8% and 37.6 ± 21.4%, respectively). In conclusion, during exercise induced hyperthermia, reduced motor unit recruitment as opposed to slower conducting properties of the muscle fibre appears to be responsible for the greater reduction in torque output

Writing in Britain and Ireland, c. 400 to c. 800

No abstract available

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente