Mechanism of Action of Secreted Newt Anterior Gradient Protein

Anterior gradient (AG) proteins have a thioredoxin fold and are targeted to the secretory pathway where they may act in the ER, as well as after secretion into the extracellular space. A newt member of the family (nAG) was previously identified as interacting with the GPI-anchored salamander-specific three-finger protein called Prod1. Expression of nAG has been implicated in the nerve dependence of limb regeneration in salamanders, and nAG acted as a growth factor for cultured newt limb blastemal (progenitor) cells, but the mechanism of action was not understood. Here we show that addition of a peptide antibody to Prod1 specifically inhibit the proliferation of blastema cells, suggesting that Prod1 acts as a cell surface receptor for secreted nAG, leading to S phase entry. Mutation of the single cysteine residue in the canonical active site of nAG to alanine or serine leads to protein degradation, but addition of residues at the C terminus stabilises the secreted protein. The mutation of the cysteine residue led to no detectable activity on S phase entry in cultured newt limb blastemal cells. In addition, our phylogenetic analyses have identified a new Caudata AG protein called AG4. A comparison of the AG proteins in a cell culture assay indicates that nAG secretion is significantly higher than AGR2 or AG4, suggesting that this property may vary in different members of the family

Left Displacement of the Abomasum in 4 Beef Calves

Citation: Oman, R. E., Streeter, R. N., Reppert, E. J., & Chako, C. Z. (2016). Left Displacement of the Abomasum in 4 Beef Calves. Journal of Veterinary Internal Medicine, 30(4), 1376-1380. doi:10.1111/jvim.14353BackgroundLittle is known about the occurrence rate, underlying etiology or treatment of left displacement of the abomasum in beef calves. ObjectiveDescribe the clinical presentation, diagnosis and treatment of left displacement of the abomasum in 4 beef calves. AnimalsFour client-owned beef breed calves with left displaced abomasum (LDA). MethodsRetrospective case series. Hospital medical records were reviewed to identify all beef breed cattle under the age of 6 months diagnosed with LDA. ResultsFour beef calves were treated for left displacement of the abomasum. All four had a history of decreased appetite and left-sided abdominal distention. Two had recently been treated for necrotic laryngitis and one was being treated for clostridial abomasitis. Ultrasonography confirmed the abomasum to be displaced between the rumen and the left body wall in all calves. The calves were initially treated by rolling to correct the abomasal displacement. The abomasum redisplaced in 3 of 4 calves within 1 hour to 6 days; 1 calf developed a mesenteric volvulus. A right paramedian abomasopexy was performed in all cases. Three of 4 calves grew well and remained in the herd 6-18 months later; 1 calf was euthanized because of complications associated with necrotic laryngitis. Conclusions and clinical importanceLeft displacement of the abomasum should be considered as a differential diagnosis for beef calves with abdominal distention. Concurrent necrotic laryngitis can increase the risk of abomasal displacement in beef calves. Treatment should include surgical correction as rolling is not curative and might be associated with mesenteric volvulus

Exploring diurnal variation using piecewise linear splines:an example using blood pressure

Background: There are many examples of physiological processes that follow a circadian cycle and researchers are interested in alternative methods to illustrate and quantify this diurnal variation. Circadian blood pressure (BP) deserves additional attention given uncertainty relating to the prognostic significance of BP variability in relation to cardiovascular disease. However, the majority of studies exploring variability in ambulatory blood pressure monitoring (ABPM) collapse the data into single readings ignoring the temporal nature of the data. Advanced statistical techniques are required to explore complete variation over 24 h. Methods: We use piecewise linear splines in a mixed-effects model with a constraint to ensure periodicity as a novel application for modelling daily blood pressure. Data from the Mitchelstown Study, a cross-sectional study of Irish adults aged 47–73 years (n = 2047) was utilized. A subsample (1207) underwent 24-h ABPM. We compared patterns between those with and without evidence of subclinical target organ damage (microalbuminuria). Results: We were able to quantify the steepest rise and fall in SBP, which occurred just after waking (2.23 mmHg/30 min) and immediately after falling asleep (−1.93 mmHg/30 min) respectively. The variation about an individual’s trajectory over 24 h was 12.3 mmHg (standard deviation). On average those with microalbuminuria were found to have significantly higher SBP (7.6 mmHg, 95% CI 5.0–10.1) after adjustment for age, sex and BMI. Including an interaction term between each linear spline and microalbuminuria did not improve model fit. Conclusion: We have introduced a practical method for the analysis of ABPM where we can determine the rate of increase or decrease for different periods of the day. This may be particularly useful in examining chronotherapy effects of antihypertensive medication. It offers new measures of short-term BP variability as we can quantify the variation about an individual’s trajectory but also allows examination of the variation in slopes between individuals (random-effects)

ResearchGate versus Google Scholar: Which finds more early citations?

ResearchGate has launched its own citation index by extracting citations from documents uploaded to the site and reporting citation counts on article profile pages. Since authors may upload preprints to ResearchGate, it may use these to provide early impact evidence for new papers. This article assesses the whether the number of citations found for recent articles is comparable to other citation indexes using 2675 recently-published library and information science articles. The results show that in March 2017, ResearchGate found less citations than did Google Scholar but more than both Web of Science and Scopus. This held true for the dataset overall and for the six largest journals in it. ResearchGate correlated most strongly with Google Scholar citations, suggesting that ResearchGate is not predominantly tapping a fundamentally different source of data than Google Scholar. Nevertheless, preprint sharing in ResearchGate is substantial enough for authors to take seriously

The MDM2-p53 pathway is involved in preconditioning-induced neuronal tolerance to ischemia.

Brain preconditioning (PC) refers to a state of transient tolerance against a lethal insult that can be evoked by a prior mild event. It is thought that PC may induce different pathways responsible for neuroprotection, which may involve the attenuation of cell damage pathways, including the apoptotic cell death. In this context, p53 is a stress sensor that accumulates during brain ischemia leading to neuronal death. The murine double minute 2 gene (MDM2), a p53-specific E3 ubiquitin ligase, is the main cellular antagonist of p53, mediating its degradation by the proteasome. Here, we study the role of MDM2-p53 pathway on PC-induced neuroprotection both in cultured neurons (in vitro) and rat brain (in vivo). Our results show that PC increased neuronal MDM2 protein levels, which prevented ischemiainduced p53 stabilization and neuronal death. Indeed, PC attenuated ischemia-induced activation of the p53/PUMA/caspase-3 signaling pathway. Pharmacological inhibition of MDM2-p53 interaction in neurons abrogated PC-induced neuroprotection against ischemia. Finally, the relevance of the MDM2-p53 pathway was confirmed in rat brain using a PC model in vivo. These findings demonstrate the key role of the MDM2-p53 pathway in PC-induced neuroprotection against a subsequent ischemic insult and poses MDM2 as an essential target in ischemic tolerance

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV

The azimuthal anisotropy of charged particles in PbPb collisions at nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS detector at the LHC over an extended transverse momentum (pt) range up to approximately 60 GeV. The data cover both the low-pt region associated with hydrodynamic flow phenomena and the high-pt region where the anisotropies may reflect the path-length dependence of parton energy loss in the created medium. The anisotropy parameter (v2) of the particles is extracted by correlating charged tracks with respect to the event-plane reconstructed by using the energy deposited in forward-angle calorimeters. For the six bins of collision centrality studied, spanning the range of 0-60% most-central events, the observed v2 values are found to first increase with pt, reaching a maximum around pt = 3 GeV, and then to gradually decrease to almost zero, with the decline persisting up to at least pt = 40 GeV over the full centrality range measured.Comment: Replaced with published version. Added journal reference and DO

Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV

How does the built environment affect teenagers (aged 13–14) physical activity and fitness? A cross-sectional analysis of the ACTIVE Project

Built environments have been cited as important facilitators of activity and research using geographic information systems (GIS) has emerged as a novel approach in exploring environmental determinants. The Active Children Through Individual Vouchers Evaluation Project used GIS to conduct a cross-sectional analysis of how teenager's (aged 13-14) environments impacted on their amount of activity and influences fitness. The ACTIVE Project recruited 270 participants aged 13-14 (year 9) from 7 secondary schools in south Wales, UK. Demographic data and objective measures of accelerometery and fitness were collected from each participant between September and December 2016. Objective data was mapped in a GIS alongside datasets relating to activity provision, active travel routes, public transport stops, main roads and natural resources. This study shows that fitness and physical activity are not correlated. Teenagers who had higher levels of activity also had higher levels of sedentary time/inactivity. Teenagers showed higher amounts of moderate-to-vigorous physical activity if their homes were closer to public transport. However, they were also more active if their schools were further away from public transport and natural resources. Teenagers were fitter if schools were closer to natural resources. Sedentary behaviour, fitness and activity do not cluster in the same teenagers. Policymakers/planning committees need to consider this when designing teenage friendly environments. Access to public transport, active travel, green space and activities that teenagers want, and need could make a significant difference to teenage health