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Abstract Ring‐necked pheasant (Phasianus colchicus) demographic response is sensitive to chick survival and nest success. The establishment and management of grasslands within agricultural landscapes, often through cropland conversion programs (e.g., Conservation Reserve Program [CRP]), have positive impacts on survival and nest success. Newly established CRP and early successional habitat can provide vegetative structure selected by pheasant chicks. Ideal brood habitat provides an abundance of arthropods, an open understory promoting efficient chick movement, and a protective canopy cover. However, the natural succession of grasslands changes desired vegetative structure and challenges managers with providing adequate habitat for pheasant chicks. We investigated the efficacy of different methods of CRP management, including haying, burning, herbicide application, interseeding, and grazing, to provide adequate brood rearing habitat in cool‐ and warm‐season grasslands. We assessed chick body mass change using human‐imprinted ring‐necked pheasant chicks and investigated changes in vegetation composition and structure in relation to various habitat treatments in north‐central and north‐eastern South Dakota during mid‐June and mid‐July of 2013, 2014, and 2015. Generally, treatments that incorporated interseeding, herbicide application, or their combination had the greatest chick mass gain, reduced litter cover and depth, and increased bare ground and forb cover. Effective management for brood habitat may require more aggressive techniques than simple haying or prescribed fire techniques.

Abstract High-quality global isotopic databases provide Earth scientists with robust means for developing and testing a variety of geological hypotheses. Database design establishes the range of questions that can be addressed, and validation techniques can enhance data quality. Here, six validated global isotopic databases provide extensive records of analyses from U-Pb in detrital zircon, Lu-Hf in zircon, Sm-Nd from whole rocks, and δ18O in zircon. The U-Pb detrital zircon records are segregated into three independently sampled databases. Independent samples are critical for testing the replicability of results, a key requisite for gaining confidence in the validity of a hypothesis. An advantage of our updated databases is that a hypothesis developed from one of the global detrital zircon databases can be immediately tested with the other two independent detrital zircon databases to assess the replicability of results. The independent εHf(t) and εNd(t) values provide similar means of testing for replicable results. This contribution discusses database design, data limitations, and validation techniques used to ensure the data are optimal for subsequent geological investigations.

Through many decades of preclinical research, great progress has been achieved in understanding the complex nature of spinal cord injury (SCI). Preclinical research efforts have guided and shaped clinical trials, which are growing in number by the year. Currently, 1,149 clinical trials focused on improving outcomes after SCI are registered in the U.S. National Library of Medicine at ClinicalTrials.gov. We conducted a systematic analysis of these SCI clinical trials, using publicly accessible data downloaded from ClinicalTrials.gov. After extracting all available data for these trials, we categorized each trial according to the types of interventions being tested and the types of outcomes assessed. We then evaluated clinical trial characteristics, both globally and by year, in order to understand the areas of growth and change over time. With regard to clinical trial attributes, we found that most trials have low enrollment, only test single interventions, and have limited numbers of primary outcomes. Some gaps in reporting are apparent; for instance, over 75% of clinical trials with “Completed” status do not have results posted, and the Phase of some trials is incorrectly classified as “Not applicable” despite testing a drug or biological compound. When analyzing trials based on types of interventions assessed, we identified the largest representation in trials testing rehab/training/exercise, neuromodulation, and behavioral modifications. Most highly represented primary outcomes include motor function of the upper and lower extremities, safety, and pain. The most highly represented secondary outcomes include quality of life and pain. Over the past 15 years, we identified increased representation of neuromodulation and rehabilitation trials, and decreased representation of drug trials. Overall, the number of new clinical trials initiated each year continues to grow, signifying a hopeful future for the clinical treatment of SCI. Together, our work provides a comprehensive glimpse into the past, present, and future of SCI clinical trials, and suggests areas for improvement in clinical trial reporting.

Background: There is no established superior treatment for femoral neck impingement cysts, which may be symptomatic and can create a challenge in the arthroscopic treatment of femoroacetabular impingement. Isolated decompression of these cysts may lead to biomechanical compromise and an increased risk of femoral neck fracture similar to that associated with cortical perforation in osteoplasty of cam lesions, given the remaining focal osseous disruption and cortical discontinuity analogous to a burr perforation. Indications: In patients undergoing arthroscopic treatment of femoroacetabular impingement and found to have femoral neck impingement cyst warranting decompression, occlusion of the remaining defect with a biocomposite anchor may improve symptoms related to the impingement cyst as well as reduce the risk of femoral neck fracture. Technique Description: This surgical technique video demonstrates the filling of a femoral neck impingement cyst using a case example of a very active middle-aged woman undergoing arthroscopic treatment of femoroacetabular impingement. During cam osteoplasty in the peripheral compartment phase, the cyst is decompressed using a curette. An appropriately sized bioabsorbable suture anchor is secured into the defect and the sutures removed. The osteoplasty is resumed over the screw to achieve contouring of the femoral neck commensurate with an adequate head-neck offset confirmed by dynamic intraoperative hip examination. Results: Postoperative imaging from this procedure reveals bony in-fill with gradual dissolution of the biocomposite anchor. In our cohort of patients treated with biocomposite anchors concomitant to arthroscopic treatment of femoracetabular impingement with follow-up ranging from 2 to 12 years, there were no self-reported femoral neck fractures. Discussion/Conclusion: We expect that treatment of femoral neck impingement cysts with biocomposite anchors will stimulate bony in-fill of the defect stimulated by the anchor, with a decrease in the risk of femoral neck fracture as compared with an untreated cyst. Further research is needed to strengthen the evidence surrounding comparative treatment of impingement cysts as well as the optimal choice of material in the case of occlusion with a biocomposite anchor.

Molecular mechanisms by which glucose modulates L-type Ca2+ channel activity and vascular reactivity are unclear. Here the authors report a nanocomplex orchestrated by AKAP5 that facilitates local purinergic stimulation of L-type Ca2+ channels and vasoconstriction during diabetic hyperglycemia.

Abstract Objectives Transcatheter aortic valve implantation is a recognized treatment for patients with severe aortic stenosis at all risk groups. However, permanent pacemaker rates remain high for self expandable transcatheter valves and permanent pacemaker implantation has been associated with increased morbidity. In this analysis we aim to evaluate short term clinical outcomes post self expandable transcatheter aortic valve implantation and determine risk factors for permanent pacemaker implantation. Methods 88 patients with severe aortic stenosis with transcatheter aortic valve implantation performed between the year 2016–2018 were retrospectively analyzed. Outcomes of interest included 1- year all cause mortality, 30-day major adverse cardiovascular events, permanent pacemaker and paravalvular leak rates. Survival analysis was performed with Kaplan Meier analysis and risk factors for survival and permanent pacemaker rates were identified with log rank test and regression analysis. Results The mean age of the cohort was 80.3 +/− 6.9 years. The mean STS score was 9.25. The 30 day all-cause mortality was 5.7% and 1-year all cause mortality was 16.7%. 80 patients had transfemoral transcatheter aortic valve implantation, and a majority of the patients (85.2%) were implanted with Corevalve Evolut R device. The device success rate was 88.6%. Multivariate analysis identified concomitant severe coronary artery disease (OR = 18.2 +/− 0.9; P = 0.002), pre transcatheter aortic valve implantation atrial fibrillation (OR = 8.6 +/− 0.91; P = 0.02) and post procedural disabling stroke (OR = 32.6 +/− 1.35; P = 0.01) as risk factors for 1-year mortality. The 30-day pacemaker rate was 17.6%. The presence of right bundle branch block (OR 11.1 +/− 0.86; P = 0.005), non-coronary cusp implantation depth (OR = 1.34 +/− 0.15; P = 0.05) and a non coronary cusp implantation depth / membranous septal length ratio of more than 50% were associated with post procedural pacemaker implantation (OR = 29.9 +/− 1.72; P = 0.05). Among the 15 patients with post procedural pacemaker implantation, 40% were found to be non-pacemaker dependent at 1 year. Conclusion Short term outcomes of transcatheter aortic valve implantation in severe aortic stenosis patients are promising. Pacemaker rates remain high. More studies are needed to evaluate the factors that influence pacemaker rates and dependence to further improve transcatheter aortic valve implantation outcomes.

Brain disorders can create maladaptive attractions, such as in addiction or self-harming. Here the authors use multiple valence modes of the central amygdala to create such attractions, arbitrarily making rats into ‘sucrose addicts' or ‘cocaine addicts', or causing maladaptive attraction to shocks.

Background During adolescence, deselection from sport occurs during team try-outs when month of birth, stage of growth and maturation may influence selection. Aim The purpose of this study was to identify differences in growth and maturity related factors between those selected and deselected in youth sports teams and identify short-term associations with continued participation. Subjects and methods Eight hundred and seventy participants, aged 11–17 years, were recruited from six sports try-outs in Saskatchewan, Canada: baseball, basketball, football, hockey, soccer and volleyball. Two hundred and forty-four of the initial 870 (28%) returned for follow-up at 36 months. Chronological (years from birth), biological (years from age at peak height velocity (APHV)) and relative (month of birth as it relates to the selection band) ages were calculated from measures of date of birth, date of test, height, sitting height and weight. Parental heights were measured or recalled and participant’s adult height predicted. Reference standards were used to calculate z-scores. Sports participation was self-reported at try-outs and at 36-month follow-up. Results There was an over-representation of players across all sports born in the first and second quartiles of the selection bands (p

Athletes regularly face the possibility of failing to meet expectations in training and competition, and it is essential that they are equipped with strategies to facilitate coping after receiving performance feedback. Self-compassion is a potential resource to help athletes manage the various setbacks that arise in sport over and above other psychological resources. The primary purpose of this research was to explore how athletes respond to objective biomechanical feedback given after a performance. Specifically, we investigated if levels of self-compassion, self-esteem, self-criticism, and concern over mistakes were related to one another before and after a series of sprint tests interspersed with biomechanical feedback, and whether self-compassionate athletes achieved a better sprint performance after receiving and implementing biomechanical feedback. Forty-eight athletes (20 female: Mage = 19.8 years, SD = 3.1; 28 male: Mage = 23.6 years, SD = 7.8) completed online measures of self-compassion, self-esteem, self-criticism and concern over mistakes before performing four sets of 40-m sprints. Participants received personalized biomechanical feedback after each sprint that compared their performance to gold standard results. Following all sprints, they then completed measures of self-criticism, and reported emotions, thoughts, and reactions. Self-compassion was positively correlated with self-esteem (r = 0.57, p < 0.01) and negatively related to both self-criticism (r = −0.52, p < 0.01) and concern over mistakes (r = −0.69, p < 0.01). We also found that athletes with higher levels of self-compassion prior to sprint performance experienced less self-critical thoughts following biomechanical feedback and subsequent sprint trials (r = −0.38, p < 0.01). Although the results of this study provide some support for the effectiveness of self-compassion in promoting healthy emotions, thoughts, and reactions in response to sprint performance-based biomechanical feedback, a moderated regression analysis between the first and fourth sprint time variables revealed that self-compassion was not a moderator for change in sprint performance (R2 = 0.64, ΔR2 = 0.10, p > 0.05). These findings suggest that there are likely longer-term benefits of athletes using self-compassion to cope with biomechanical feedback, but that any benefits might be limited in a short series of sprint trials.

Corticotropin releasing factor (CRF) systems in limbic structures are posited to mediate stress-induced relapse in addiction, traditionally by generating distress states that spur drug consumption as attempts at hedonic self-medication. Yet evidence suggests that activating CRF-expressing neurons in the central amygdala (CeA) or nucleus accumbens (NAc) can magnify incentive motivation in absence of distress, at least for sucrose rewards. However, traditional CRF hypotheses in addiction neuroscience are primarily directed toward drug rewards. The question remains open whether CRF systems can similarly act via incentive motivation mechanisms to promote pursuit of drug rewards, such as cocaine. Here we tested whether optogenetic excitation of CRF-containing neurons in either NAc medial shell, lateral CeA, or dorsolateral BNST of transgenic Crh-Cre+ rats would spur preference and pursuit of a particular laser-paired cocaine reward over an alternative cocaine reward, and whether excitation served as a positively-valenced incentive itself, through laser self-stimulation tests. We report that excitation of CRF-containing neurons in either NAc or CeA recruited mesocorticolimbic circuitry to amplify incentive motivation to pursue the laser-paired cocaine: focusing preference on the laser-paired cocaine reward in a two-choice task, and spurred pursuit as doubled breakpoint in a progressive ratio task. Crucially indicating positive-valence, excitation of CRF neurons in NAc and CeA also was actively sought after by most rats in self-stimulation tasks. Conversely, CRF neuronal activation in BNST was never self-stimulated, but failed to enhance cocaine consumption. Collectively, we find that NAc and CeA CRF-containing neurons can amplify pursuit and consumption of cocaine by positively-valenced incentive mechanisms, without any aversive distress.

Abstract. Promoting intestinal epithelial regeneration remains a major medical challenge. Female patients taking nonsteroidal anti-inflammatory drugs are less likely to have upper gastrointestinal bleeding and ulcers than males. Using a nonsteroidal anti-inflammatory drug-induced intestinal damage mouse model, we verified that female mice recover faster than males following acute intestinal insult. Using ex vivo intestinal organoid cultures, we showed that estrogen is necessary and sufficient in enhancing the female organoid formation from breached isolated crypts via the estrogen receptor β receptor. Thus, estrogen promotes female intestinal epithelial organoid regeneration to lower the incidence of intestinal bleeding and ulceration. Animal studies were approved by University of Utah IACUC under protocol number 16-05012 and 18-02010.

Abstract Background Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer associated with poor survival outcomes in patients with distant metastatic disease (mMCC). In an initial analysis from JAVELIN Merkel 200, a phase 2, prospective, open-label, single-arm trial in mMCC, avelumab—a human anti–programmed death-ligand 1 (PD-L1) monoclonal antibody—showed promising efficacy and a safety profile that was generally manageable and tolerable. Here, we report the efficacy of avelumab after ≥1 year of follow-up in patients with distant mMCC that had progressed following prior chemotherapy for metastatic disease. Patients and methods Patients received avelumab 10 mg/kg by 1-h intravenous infusion every 2 weeks until confirmed disease progression, unacceptable toxicity, or withdrawal. The primary endpoint was best overall response. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results Patients (N = 88) were followed for a minimum of 12 months. The confirmed objective response rate was 33.0% (95% CI, 23.3%-43.8%; complete response: 11.4%). An estimated 74% of responses lasted ≥1 year, and 72.4% of responses were ongoing at data cutoff. Responses were durable, with the median DOR not yet reached (95% CI, 18.0 months-not estimable), and PFS was prolonged; 1-year PFS and OS rates were 30% (95% CI, 21%-41%) and 52% (95% CI, 41%-62%), respectively. Median OS was 12.9 months (95% CI, 7.5-not estimable). Subgroup analyses suggested a higher probability of response in patients receiving fewer prior lines of systemic therapy, with a lower baseline disease burden, and with PD-L1–positive tumors; however, durable responses occurred irrespective of baseline factors, including tumor Merkel cell polyomavirus status. Conclusions With longer follow-up, avelumab continues to show durable responses and promising survival outcomes in patients with distant mMCC whose disease had progressed after chemotherapy. Trial registration Clinicaltrials.gov identifier: NCT02155647.

Background & Aims: Emerging data on the gut microbiome in autism spectrum disorder (ASD) suggest that altered hostâmicrobe interactions may contribute to disease symptoms. Although gut microbial communities in children with ASD are reported to differ from individuals with neurotypical development, it is not known whether these bacteria induce pathogenic neuroimmune signals. Methods: Because commensal clostridia interactions with the intestinal mucosa can regulate disease-associated cytokine and serotonergic pathways in animal models, we evaluated whether microbiome-neuroimmune profiles (from rectal biopsy specimens and blood) differed in ASD children with functional gastrointestinal disorders (ASD-FGID, n = 14) compared with neurotypical (NT) children with FGID (NT-FGID, n = 15) and without abdominal pain (NT, n = 6). Microbial 16S ribosomal DNA community signatures, cytokines, and serotonergic metabolites were quantified and correlated with gastrointestinal symptoms. Results: A significant increase in several mucosa-associated Clostridiales was observed in ASD-FGID, whereas marked decreases in Dorea and Blautia, as well as Sutterella, were evident. Stratification by abdominal pain showed multiple organisms in ASD-FGID that correlated significantly with cytokines (interleukin [IL]6, IL1, IL17A, and interferon-γ). Group comparisons showed that IL6 and tryptophan release by mucosal biopsy specimens was highest in ASD children with abdominal pain, whereas serotonergic metabolites generally were increased in children with FGIDs. Furthermore, proinflammatory cytokines correlated significantly with several Clostridiales previously reported to associate with ASD, as did tryptophan and serotonin. Conclusions: Our findings identify distinctive mucosal microbial signatures in ASD children with FGID that correlate with cytokine and tryptophan homeostasis. Future studies are needed to establish whether these disease-associated Clostridiales species confer early pathogenic signals in children with ASD and FGID. Keywords: Microbiome, MicrobiomeâGutâBrain Axis, Gastrointestinal Disorders, Mucosa, Serotonin

The aim of the study was to determine the effects of exercise training on improving the thoracic perivascular adipose tissue (tPVAT) phenotype (inflammation, oxidative stress, and proteasome function) in metabolic syndrome and its subsequent actions on aortic function. Methods: Lean and obese (model of metabolic syndrome) Zucker rats (n=8/group) underwent 8-weeks of control conditions or treadmill exercise (70% of max speed, 1 h/day, 5 days/week). At the end of the intervention, the tPVAT was removed and conditioned media was made. The cleaned aorta was attached to a force transducer to assess endothelium-dependent and independent dilation in the presence or absence of tPVAT-conditioned media. tPVAT gene expression, inflammatory /oxidative phenotype, and proteasome function were assessed. Results: The main findings were that Ex induced: (1) a beige-like, anti-inflammatory tPVAT phenotype; (2) a greater abundance of •NO in tPVAT; (3) a reduction in tPVAT oxidant production; and (4) an improved tPVAT proteasome function. Regarding aortic function, endothelium-dependent dilation was greater in exercised lean and obese groups vs. controls (p

Soil vapor extraction (SVE) has been used at sites across the Department of Energy complex, including sites where legacy subsurface wastes represent a potential source of groundwater contamination. At Los Alamos National Laboratory (LANL), leakage from waste drums buried at an inactive chemical waste site has created a subsurface vapor plume of volatile organic compounds (VOCs). Soil vapor extraction operation in 2015 and rebound testing through 2017 were successful in reducing the plume’s mass and mitigating VOC migration toward the water table. However, the possibility that waste drums could fail and release VOCs could pose a challenge in the future. To explore the impacts of drum failure, as well as the capabilities of SVE remediation, we simulated hypothetical contaminant release scenarios and subsequent SVE remediation. Three-dimensional subsurface VOC behavior, including advection, diffusion, and plume interactions with topography, were simulated using the porous flow simulator Finite Element Heat and Mass Transfer. Simulations of future site conditions have allowed identification of “sentry” boreholes that can be monitored for early detection in case of drum failure. Sentry boreholes can also be used to set concentration thresholds above which SVE should be initiated. For the LANL site, simulations show that SVE can be started 3 yr following drum failure and remain a viable remediation tool. More broadly, the principles outlined in this work can be used to support remediation planning at other subsurface waste sites. Predictive models of future releases can be analyzed to set concentration threshold values, guide selection of sentry boreholes, and increase operational efficiency.

This review takes a historical perspective on concepts in the psychology of motivation and emotion, and surveys recent developments, debates and applications. Old debates over emotion have recently risen again. For example, are emotions necessarily subjective feelings? Do animals have emotions? I review evidence that emotions exist as core psychological processes, which have objectively detectable features, and which can occur either with subjective feelings or without them. Evidence is offered also that studies of emotion in animals can give new insights into human emotions. Beyond emotion, motivation concepts have changed over decades too, and debates still continue. Motivation was once thought in terms of aversive drives, and reward was thought of in terms of drive reduction. Motivation-as-drive concepts were largely replaced by motivation-as-incentive concepts, yet aversive drive concepts still occasionally surface in reward neuroscience today. Among incentive concepts, incentive salience is a core motivation process, mediated by brain mesocorticolimbic systems (dopamine-related systems) and sometimes called ‘wanting’ (in quotation marks), to distinguish it from cognitive forms of desire (wanting without quotation marks). Incentive salience as ‘wanting’ is separable also from pleasure ‘liking’ for the same reward, which has important implications for several human clinical disorders. Ordinarily, incentive salience adds motivational urgency to cognitive desires, but ‘wanting’ and cognitive desires can dissociate in some conditions. Excessive incentive salience can cause addictions, in which excessive ‘wanting’ can diverge from cognitive desires. Conversely, lack of incentive salience may cause motivational forms of anhedonia in depression or schizophrenia, whereas a negatively-valenced form of ‘fearful salience’ may contribute to paranoia. Finally, negative ‘fear’ and ‘disgust’ have both partial overlap but also important neural differences.

ABSTRACT Population status and habitat use of yellow rails (Coturnicops noveboracensis), Nelson's sparrows (Ammodramus nelsoni), and Le Conte's sparrows (A. leconteii) are poorly known, so standardized surveys of these species are needed to inform conservation planning and management. A protocol for monitoring secretive marsh birds exists; however, these species regularly call at night and may be missed during early morning surveys. We tested the effectiveness of autonomous recording units (hereafter, recording units) to survey these species by analyzing recorded vocalizations using bioacoustics software. We deployed 22 recording units at 54 sites in northern Minnesota and eastern North Dakota, USA, and conducted traditional broadcast surveys during May–June, 2010 and 2011. We compared detection probabilities between recording units and standard monitoring protocols using robust‐design occupancy models. On average, recording units detected 0.59 (SE = 0.11) fewer Le Conte's sparrows, 0.76 (SE = 0.15) fewer Nelson's sparrows, and 1.01 (SE = 0.14) fewer yellow rails per survey than were detected using the standard protocol. Detection probabilities using the standard protocol averaged 0.95 (yellow rail; 95% CI = 0.86–0.98), 0.93 (Le Conte's sparrow; 95% CI = 0.78–0.98), and 0.89 (Nelson's sparrow; 95% CI = 0.56–0.98), but averaged 0.71 (yellow rail; 95% CI = 0.56–0.83), 0.61 (Le Conte's sparrow; 95% CI = 0.42–0.78), and 0.51 (Nelson's sparrow; 95% CI = 0.19–0.82) using recording units. Reduced detection by recording units was likely due to the ability of human listeners to identify birds calling at greater distances. Recording units may be effective for surveying nocturnal secretive marsh birds if investigators correct for differential detectability. Reduced detectability may be outweighed by the increased spatial and temporal coverage feasible with recording units. © 2015 The Wildlife Society.

Ingested food is received, mixed, and ground into chyme by distinct gastric motility patterns. Diabetes impairs gastric muscle function, but the mechanisms underlying diabetes-induced gastric muscle dysfunction are unknown. Here, we compared the expression and phosphorylation of Ca2+ sensitization and contractile proteins in human gastric muscles from obese nondiabetic and diabetic patients. We also compared the spontaneous phasic contractions and the contractile responses evoked by electrical field stimulation of cholinergic motor neurons. Fundus and antrum muscles were obtained from sleeve gastrectomies and were used in in vitro myobath contractile studies and for capillary electrophoresis and immunodetection of γ-actin, CPI-17, pT38-CPI-17, MYPT1, pT853-MYPT1, pT696-MYPT1, myosin light chain (MYL9), pS19-MYL9, myosin light chain kinase (MYLK), protein phosphatase-1δ (PP1δ), and Rho-associated kinase (ROCK2). In diabetic fundus muscles, MYLK, ROCK2, and PP1δ expression was unchanged; MYPT1 and CPI-17 expression was decreased; and the pT853/MYPT1 and pT38/CPI-17 ratios, but not the pT696/MYPT1 ratio, were increased. Although MYL9 expression was increased, the pS19/MYL9 ratio was unchanged in diabetic fundus muscles. In diabetic antrum muscles, MYLK and MYL9 expression was unchanged, but ROCK2, CPI-17, and PP1δ expression was decreased. The pT38/CPI-17 ratio was unchanged, while the pS19/MYL9, pT853/MYPT1, and pT696/MYPT1 ratios were decreased, consistent with the reduced ROCK2 expression. The frequencies of spontaneous phasic contractions from nondiabetic and diabetic gastric fundus and antrum muscles did not significantly differ from each other, regardless of age, sex, or diabetic status. The fold increases in the contractions of diabetic fundus and antrum muscles in response to increased frequencies of electrical field stimulation were significantly lower compared to nondiabetic fundus and antrum muscles. The altered contractile responses and the protein expression and phosphorylation in gastric muscles of obese patients with diabetes illustrate the importance of understanding how smooth muscle Ca2+ sensitization mechanisms contribute to gastric motility.

Mouse knockouts facilitate the study ofgene functions. Often, multiple abnormal phenotypes are induced when a gene is inactivated. The International Mouse Phenotyping Consortium (IMPC) has generated thousands of mouse knockouts and catalogued their phenotype data. We have acquired metabolomics data from 220 plasma samples from 30 unique mouse gene knockouts and corresponding wildtype mice from the IMPC. To acquire comprehensive metabolomics data, we have used liquid chromatography (LC) combined with mass spectrometry (MS) for detecting polar and lipophilic compounds in an untargeted approach. We have also used targeted methods to measure bile acids, steroids and oxylipins. In addition, we have used gas chromatography GC-TOFMS for measuring primary metabolites. The metabolomics dataset reports 832 unique structurally identified metabolites from 124 chemical classes as determined by ChemRICH software. The GCMS and LCMS raw data files, intermediate and finalized data matrices, R-Scripts, annotation databases, and extracted ion chromatograms are provided in this data descriptor. The dataset can be used for subsequent studies to link genetic variants with molecular mechanisms and phenotypes.

Zircon age peaks at 2100–1650 and 1200–1000 Ma correlate with craton collisions in the growth of supercontinents Nuna and Rodinia, respectively, with a time interval between collisions mostly

BackgroundL-type CaV1.2 channels undergo cooperative gating to regulate cell function, although mechanisms are unclear. This study tests the hypothesis that phosphorylation of the CaV1.2 pore-forming subunit α1C at S1928 mediates vascular CaV1.2 cooperativity during diabetic hyperglycemia.MethodsA multiscale approach including patch-clamp electrophysiology, super-resolution nanoscopy, proximity ligation assay, calcium imaging' pressure myography, and Laser Speckle imaging was implemented to examine CaV1.2 cooperativity, α1C clustering, myogenic tone, and blood flow in human and mouse arterial myocytes/vessels.ResultsCaV1.2 activity and cooperative gating increase in arterial myocytes from patients with type 2 diabetes and type 1 diabetic mice, and in wild-type mouse arterial myocytes after elevating extracellular glucose. These changes were prevented in wild-type cells pre-exposed to a PKA inhibitor or cells from knock-in S1928A but not S1700A mice. In addition, α1C clustering at the surface membrane of wild-type, but not wild-type cells pre-exposed to PKA or P2Y11 inhibitors and S1928A arterial myocytes, was elevated upon hyperglycemia and diabetes. CaV1.2 spatial and gating remodeling correlated with enhanced arterial myocyte Ca2+ influx and contractility and in vivo reduction in arterial diameter and blood flow upon hyperglycemia and diabetes in wild-type but not S1928A cells/mice.ConclusionsThese results suggest that PKA-dependent S1928 phosphorylation promotes the spatial reorganization of vascular α1C into "superclusters" upon hyperglycemia and diabetes. This triggers CaV1.2 activity and cooperativity, directly impacting vascular reactivity. The results may lay the foundation for developing therapeutics to correct CaV1.2 and arterial function during diabetic hyperglycemia.

We retrospectively investigated the association between platelet autoantibody specificity and response to intravenous immunoglobulin G (IVIG) in 17 patients with immune thrombocytopenia (ITP). Platelet-associated antibodies against glycoprotein (GP) IIb/IIIa, GPIb/IX, and GPIa/IIa were detected in 13, 10, and 8 patients, respectively. A response occurred in 7 of 7 patients without anti-GPIb/IX, but in only 3 of 10 patients with anti-GPIb/IX (p

Contribution of brake particle emissions to ambient PM2.5 is increasing. Previous studies focused on determination of brake emission rate from lab testing and so it lacks brake activity of real world conditions. The study aimed to establish a test method to determine brake activity of a heavy-duty vehicle. Brake parameters and vehicle parameters were measured during two chassis cycles and two on-road test tests. Brake activity was quantified with brake pressure signal as the first indicator and vehicle speed as the second indicator. Temperature increase was related to the kinetic loss of the vehicle and cooling and heating of brake pad was repeated during on road test. Resulting brake activity was presented in the form of histogram. Future test should use shorter copper cap for thermocouple to better sense friction surface temperature. It is recommended to measure both activity and emissions during on-road test so that a better relationship can be established between brake activity and brake particle emissions.View the NCST Project Webpage

Hyperserotonemia, or elevated levels of whole blood serotonin (WB5-HT), was the first biomarker linked to autism spectrum disorder (ASD). Despite numerous studies investigating the etiology of hyperserotonemia, results have been inconsistent. Recent findings suggest a relationship between the immune system and hyperserotonemia. The current study investigated whether intestinal 5-HT levels, 5-HT gene expression, or intestinal cell types predict WB5-HT. Participants included thirty-one males aged 3-18 who were classified into one of three groups: ASD and functional GI issues, typically developing with GI issues, and typically developing without GI issues. Samples from a lower endoscopy were analyzed to examine the pathways in predicting WB-5HT. Results demonstrated an association between T-Lymphocytes and WB5-HT.

Encapsulation of pancreatic islets prevents graft revascularization after transplantation, resulting in graft hypoxia and attrition. Hypoxia-resistant islets would be ideal for encapsulation. Tilapia, a tropical teleost fish, have large, anatomically discrete islets that can be easily harvested without expensive, fickle islet isolation procedures and that provide mammalian-like glucose tolerance profiles when transplanted into diabetic recipients. Because tilapia can live in stagnant water, we speculated that tilapia islets might tolerate lower oxygen tensions than mammalian islets. Tilapia and rat islets (n = 30) were placed in paired 60-mm Petri dishes containing 10 mL of deoxygenated CMRL-1066 media and cultured together in sealed chambers gassed with 95% N 2 /5% CO 2 . Islet viability was determined by fluorscein diacetate/ethidium bromide staining at intervals varying from 2.5 h to 7 days; blood gas measurements were obtained on media samples at the end of selected incubation intervals. Rat islets underwent near-total necrosis and fragmentation in