A Combined Spectral and Energy Morphology Analysis of Gamma Ray Source HAWC J2031+415 in the Cygnus Constellation

HAWC J2031+415 is a probable pulsar wind nebula (PWN) located in the Cygnus Cocoon region near a complex OB star cluster. First observed by the High-Energy-Gamma-Ray Astronomy (HEGRA) observatory in the TeV energy regime, the source had no apparent counterpart in lower energy ranges. Previous work using 1343 days of data from the High-Altitude Water Cherenkov (HAWC) Gamma-Ray Observatory has determined that three sources are present in the Region of Interest (ROI): HAWC J2031+415, HAWC J2030+409 (also known as the Cocoon), and 3HWC J2020+403 (associated with the Gamma Cygni supernova remnant) \cite{Ian_01, Binita_01}. In this work, I use the newest data set containing 2000 days of data from HAWC to analyze the region. I apply a systematic source searching method to determine the number of sources, their locations, and spectra. Three estimators are used to determine the spectral energy distribution for HAWC J2031+415 and the best fit is found to be a power law with an exponential cut-off. I then isolate HAWC J2031+415 and perform an energy-dependent morphology study of the source. No measurable energy dependence of the morphology was found. Additional data will allow for more detailed studies of the region

FUNCTIONAL EFFECTS OF DIET INDUCED OBESITY ON PERMEABLIZED RAT MUSCLE FIBRES

INTRODUCTION Muscle performance is determined by the metabolic, calcium handling, and sarcomeric characteristics of its constituent fibres. Diet induced obesity (DIO) may influence contractile performance in whole muscle, but little is known about the effects of DIO at the single fibre level. Particularly, how DIO might influence the contractile characteristics of single fibres free from the influence of metabolic or calcium handling properties is not established. There is some limited evidence to suggest that DIO may influence the sarcomeric proteins. For example, troponin T, an important regulatory protein found on the thin filament, exhibits a shift from the fast T3 isoform, to the slow T1 isoform, in mouse soleus muscle following high fat feeding, with no associated change in myosin heavy chain isoform [1]. These results suggest that DIO may cause fast fibres to express slow isoforms of sarcomeric proteins in postural muscles of mixed fibre-type. The purpose of this study was to assess the force-calcium and force-velocity relationships of skinned fast and slow fibres of vastus intermedius, a mixed fibre-type postural muscle [2], in chow-fed rats and a rat model of DIO. It was hypothesized that fast fibres from DIO rats would exhibit characteristics associated with a slower fibre phenotype, including increased calcium sensitivity and lower shortening velocities. METHODS Individually housed male Sprague-Dawley rats, aged 10-12 weeks, were randomized to undergo diet induced obesity (DIO) where they were fed a high fat, high sugar diet (n = 6) or a standard chow diet (n = 6) for 12 weeks. The caloric content of DIO diets was 40% fat and 45% sucrose, compared to chow diets which consisted of 12% fat and 0% sucrose. Both vastus intermedius muscles were collected from each rat. Similar to the mouse soleus, the fibre type distribution of rat vastus intermedius is approximately 50% type I and 50% type IIa fibres [2]. Muscles were chemically skinned in a glycerol-rigor solution for 2 weeks.  Two fast and two slow fibres per animal were then isolated and mounted in a model 802B skinned fibre test system (Aurora Scientific) at 2.4 µm sarcomere length for testing.  Preliminary fibre type assessment was made using a strontium sensitivity test [3].  The force-pCa relationship was assessed from pCa 7.2 to pCa 4.2. The force-velocity relationship was assessed by measuring the shortening velocity during isotonic contractions.  Maximal shortening velocity (Vmax) was assessed by a slack test protocol. Statistical differences were determined using Student’s t-test or a two-way factorial ANOVA and Newman-Keuls post-hoc analysis as appropriate, α = 0.05. RESULTS Dual-energy X-ray absorptiometry scans revealed DIO rats had significantly higher body mass, fat mass, and greater percent body fat than chow fed rats (all p<0.05), while lean mass was not significantly different between groups. DIO did not affect the force per cross-sectional area (CSA) of skinned fibres (Table 1). Fast DIO fibres had significantly lower maximum shortening velocities when compared to fast chow fibres (p<0.05; Table 1). No such differences were observed in slow fibres. Independent of fibre type, DIO fibres had significantly higher calcium sensitivity than chow fibres (p<0.01, Table 1).  While the Hill coefficient of the force pCa relationship was different between fast and slow chow fibres, no differences were seen in DIO fibres (p<0.05; Table 1).DISCUSSION AND CONCLUSIONS Consistent with a fast to slow phenotype transition, Vmax was lower in fast DIO fibres. However, DIO influenced the force-calcium relationship of both fast and slow fibres. Therefore, adaptations are not limited to fast fibres, but rather influence contractility on a larger scale. Whether this influence is global or localized to postural muscles remains to be determined. The specific isoforms of contractile proteins expressed in single fibres should be assessed following DIO

THE EFFECTS OF DIET INDUCED OBESITY ON THE FORCE-LENGTH RELATIONSHIP IN RAT SOLEUS

INTRODUCTION Obesity is associated with chronic inflammation, which has been shown to affect the integrity of musculoskeletal tissues [1]. Previous data from our group suggests that obesity can result in intramuscular fat deposition [1]. It is unclear if this structural alteration has functional consequences, as the implications of obesity on muscle mechanics are not well understood. Therefore, the purpose of this study was to quantify the active force produced by soleus muscles of obese and non-obese rats at a range of muscle lengths. As the inclusion of fat into the muscle fibers will leave less room for contractile proteins, we hypothesized that obese rats will produce lower forces normalized to muscle mass at every length than non-obese control rats.   METHODS Fourteen rats were randomly allocated to a 12-week diet: either an obesity-inducing high fat high sucrose diet (DIO, 40% fat, 45% sucrose, n=8) or a standard chow diet (chow, 12% fat 0% sucrose, n=6). Prior to surgery, body composition was evaluated using dual energy X-ray absorptiometry. Custom-made tibial nerve cuffs were surgically attached to the right tibial nerve of each animal. The soleus was exposed, mechanically isolated, and clamped to a force transducer. The muscle was then stretched to a predetermined length and electrically stimulated at 3 times the motor unit threshold (50Hz) and the force output was measured [3]. Force tracings were digitized using WINDAQ® software. Passive, active, and total forces produced by the soleus were normalized to the maximum in vivo length of each animal. Forces were averaged into 5% length intervals within each animal. Students t-tests or a two-way ANOVA were conducted between groups, and a Bonferroni correction was used as needed, α=0.05. RESULTS DIO rats had increased body mass (DIO 816.4 ± 30.1g, chow 645.0 ± 28.3g; p<0.05) and body fat (DIO 39.2 ± 1.3%, chow 21.8 ± 2.1%; p<0.05) compared to chow-fed rats. Soleus mass (DIO: 0.28 ± 0.01 g, chow: 0.26 ± 0.11 g, p=0.32), was similar between the two groups. Absolute peak isometric force was similar between the two groups (DIO: 2.58 ± 0.10 N, chow: 2.18 ± 0.34 N, p=0.23). Active isometric force normalized to soleus mass was significantly higher in DIO group rats at every muscle length (Figure 1, p<0.05). DISCUSSION AND CONCLUSIONS On average, DIO rats produced more active force at a given normalized length and soleus mass than chow rats, a finding that refutes our original hypothesis. Since optimal length occurs at the same relative muscle length for both groups, and since the decline in force from maximum is similar between groups, it appears that fascicle length, and an associated shift in the force-length relationship cannot explain our results. Results of differences in the force-velocity relationship (not shown here) suggest that the DIO rats may have a higher proportion of fast twitch fibres, but the relative force among slow and fast fibres is similar, and thus also should not affect these results. The results suggest that the force per cross-sectional area is higher in muscles from obese compared to lean rats, a finding that defies explanation at this time and needs thorough investigation in the future. Histology and tests looking at fibre and cell level muscle structures may provide more insight

Non-localized postactivation performance enhancement (PAPE) effect in trained athletes: a pilot study

Fifteen trained athletes were assessed for postactivation performance enhancement (PAPE) of squat jumps (SJ) and power push-ups (PPU) following upper body activation, lower body activation, upper and lower body activation, and rest. SJ improved similarly across all four conditions. PPU could not be assessed. Since the protocol of SJ and PPU involved upper and lower body activation and caused PAPE in SJ, future work is required to determine if a non-localized PAPE effect exists.CTS-527: Actividad física y deportiva en el medio acuátic

Genome-wide changes in genetic diversity in a population of Myotis lucifugus affected by white-nose syndrome

Novel pathogens can cause massive declines in populations, and even extirpation of hosts. But disease can also act as a selective pressure on survivors, driving the evolution of resistance or tolerance. Bat white-nose syndrome (WNS) is a rapidly spreading wildlife disease in North America. The fungus causing the disease invades skin tissues of hibernating bats, resulting in disruption of hibernation behavior, premature energy depletion, and subsequent death. We used whole-genome sequencing to investigate changes in allele frequencies within a population of Myotis lucifugus in eastern North America to search for genetic resistance to WNS. Our results show low F-ST values within the population across time, i.e., prior to WNS (Pre-WNS) compared to the population that has survived WNS (Post-WNS). However, when dividing the population with a geographical cut-off between the states of Pennsylvania and New York, a sharp increase in values on scaffold GL429776 is evident in the Post-WNS samples. Genes present in the diverged area are associated with thermoregulation and promotion of brown fat production. Thus, although WNS may not have subjected the entire M. lucifugus population to selective pressure, it may have selected for specific alleles in Pennsylvania through decreased gene flow within the population. However, the persistence of remnant sub-populations in the aftermath of WNS is likely due to multiple factors in bat life history.Peer reviewe

Menthol Cigarette Smoking and Obesity in Young Adult Daily Smokers in Hawaii

This study investigates 1) the relationship between menthol cigarette smoking and obesity and 2) the association of body mass index with the nicotine metabolite ratio among menthol and non-menthol daily smokers aged 18–35 (n = 175). A brief survey on smoking and measures of height and weight, carbon monoxide, and saliva samples were collected from participants from May to December 2013 in Honolulu, Hawaii. Multiple regression was used to estimate differences in body mass index among menthol and non-menthol smokers and the association of menthol smoking with obesity. We calculated the log of the nicotine metabolite ratio to examine differences in the nicotine metabolite ratio among normal, overweight, and obese smokers. Sixty-eight percent of smokers used menthol cigarettes. Results showed that 62% of normal, 54% of overweight, and 91% of obese smokers used menthol cigarettes (p = .000). The mean body mass index was significantly higher among menthol compared with non-menthol smokers (29.4 versus 24.5, p = .000). After controlling for gender, marital status, educational attainment, employment status, and race/ethnicity, menthol smokers were more than 3 times as likely as non-menthol smokers to be obese (p = .04). The nicotine metabolite ratio was significantly lower for overweight menthol smokers compared with non-menthol smokers (.16 versus .26, p = .02) in the unadjusted model, but was not significant after adjusting for the covariates. Consistent with prior studies, our data show that menthol smokers are more likely to be obese compared with non-menthol smokers. Future studies are needed to determine how flavored tobacco products influence obesity among smokers

Small Molecule Inhibitors of the Neuropilin-1 Vascular Endothelial Growth Factor A (VEGF-A) Interaction†

We report the molecular design and synthesis of EG00229, 2, the first small molecule ligand for the VEGF-A receptor neuropilin 1 (NRP1) and the structural characterization of NRP1-ligand complexes by NMR spectroscopy and X-ray crystallography. Mutagenesis studies localized VEGF-A binding in the NRP1 b1 domain and a peptide fragment of VEGF-A was shown to bind at the same site by NMR, providing the basis for small molecule design. Compound 2 demonstrated inhibition of VEGF-A binding to NRP1 and attenuated VEGFR2 phosphorylation in endothelial cells. Inhibition of migration of endothelial cells was also observed. The viability of A549 lung carcinoma cells was reduced by 2, and it increased the potency of the cytotoxic agents paclitaxel and 5-fluorouracil when given in combination. These studies provide the basis for design of specific small molecule inhibitors of ligand binding to NRP1

All clinically-relevant blood components transmit prion disease following a single blood transfusion: a sheep model of vCJD

Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. Whilst the epidemic appears to be waning, there is much concern that vCJD infection may be perpetuated in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported and linked to blood collected from pre-clinically affected donors. Using an animal model in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion

Rifaximin Exerts Beneficial Effects Independent of its Ability to Alter Microbiota Composition

Rifaximin has clinical benefits in minimal hepatic encephalopathy (MHE) but the mechanism of action is unclear. The antibiotic-dependent and -independent effects of rifaximin need to be elucidated in the setting of MHE-associated microbiota. To assess the action of rifaximin on intestinal barrier, inflammatory milieu and ammonia generation independent of microbiota using rifaximin

Neuropilin-1 mediates PDGF stimulation of vascular smooth muscle cell migration and signalling via p130Cas

NRP1 (neuropilin-1) is a co-receptor for members of the VEGF (vascular endothelial growth factor) family in endothelial cells, but is increasingly implicated in signalling induced by other growth factors. NRP1 is expressed in VSMCs (vascular smooth muscle cells), but its function and the mechanisms involved are poorly understood. The present study aimed to determine, the role of NRP1 in the migratory response of HCASMCs (human coronary artery smooth muscle cells) to PDGF (platelet-derived growth factor), and to identify the signalling mechanisms involved. NRP1 is highly expressed in HAoSMCs (human aortic smooth muscle cells) and HCASMCs, and modified in VSMCs by CS (chondroitin sulfate)-rich O-linked glycosylation at Ser(612). HCASMC migration induced by PDGF-BB and PDGF-AA was inhibited by NRP1 siRNA (small interfering RNA), and by adenoviral overexpression of an NRP1 mutant lacking the intracellular domain (Ad.NRP1 Delta C). NRP1 co-immunoprecipitated with PDGFR alpha (PDGF receptor alpha), and immunofluorescent staining indicated that NRP1 and PDGFR alpha co-localized in VSMCs. NRP1 siRNA also inhibited PDGF-induced PDGFR alpha activation. NRP1-specific siRNA, Ad.NRP1 Delta C and removal of CS glycans using chondroitinase all inhibited PDGF-BB and -AA stimulation of tyrosine phosphorylation of the adapter protein, p130(Cas) (Cas is Crk-associated substrate), with little effect on other major signalling pathways, and p130(Cas) knockdown inhibited HCASMC migration. Chemotaxis and p130(Cas) phosphorylation induced by PDGF were inhibited by chondroitinase, and, additionally, adenoviral expression of a non-glycosylatable NRP1S612A mutant inhibited chemotaxis, but not p130(Cas) phosphorylation. These results indicate a role for NRP1 and NRP1 glycosylation in mediating PDGF-induced VSMC migration, possibly by acting as a co-receptor for PDGFR alpha and via selective mobilization of a novel p130(Cas) tyrosine phosphorylation pathway