Regulation of metabolism is complex and involves enzymes and membrane transporters, which form networks to support energy dynamics. Lactate, as a metabolic intermediate from glucose or glycogen ...breakdown, appears to play a major role as additional energetic substrate, which is shuttled between glycolytic and oxidative cells, both under hypoxic and normoxic conditions. Transport of lactate across the cell membrane is mediated by monocarboxylate transporters (MCTs) in cotransport with H
, which is a substrate, a signal and a modulator of metabolic processes. MCTs form a "transport metabolon" with carbonic anhydrases (CAs), which not only provide a rapid equilibrium between CO
, HCO
and H
, but, in addition, enhances lactate transport, as found in
oocytes, employed as heterologous expression system, as well as in astrocytes and cancer cells. Functional interactions between different CA isoforms and MCTs have been found to be isoform-specific, independent of the enzyme's catalytic activity, and they require physical interaction between the proteins. CAs mediate between different states of metabolic acidosis, induced by glycolysis and oxidative phosphorylation, and play a relay function in coupling pH regulation and metabolism. In the brain, metabolic processes in astrocytes appear to be linked to bicarbonate transport and to neuronal activity. Here, we focus on physiological processes of energy dynamics in astrocytes as well as on the transfer of energetic substrates to neurons.
Context . The colliding-wind region in binary systems made up of massive stars allows us to investigate various aspects of shock physics, including particle acceleration. Particle accelerators of ...this kind are mainly identified thanks to their synchrotron radio emission and dubbed particle-accelerating colliding-wind binaries. Aims . Our objective is first to validate the notion that obtaining snapshot high-resolution radio images of massive binaries constitutes a relevant approach to unambiguously identifying particle accelerators. Second, we intend to exploit these images to characterise the synchrotron emission of two specific targets, HD 167971 and HD 168112, which are known particle accelerators. Methods . We traced the radio emission from the two targets at 1.6 GHz with the European Very Long Baseline Interferometry (VLBI) Network, with an angular resolution of a few milli-arcseconds. Results . Our measurements allowed us to obtain images for both targets. For HD 167971, our observation occurs close to apastron, at an orbital phase where the synchrotron emission is at minimum. For HD 168112, we resolved for the very first time the synchrotron emission region. The emission region appears slightly elongated, in agreement with the expectations for a colliding-wind region. In both cases, the measured emission is significantly stronger than the expected thermal emission from the stellar winds, lending strong support to their non-thermal nature. Conclusions . Our study offers a significant contribution to the still poorly addressed question of high angular resolution radio imaging of colliding-wind binaries. We show that snapshot VLBI measurements constitute an efficient approach to investigate these objects, with promising results in terms of the identification of additional particle accelerators, coupled with their applicability in revealing long-period binaries.
Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases, comprising seven categories. Genetic data could potentially be used to help redefine JIA categories and improve the current ...classification system. The human leucocyte antigen (HLA) region is strongly associated with JIA. Fine-mapping of the region was performed to look for similarities and differences in HLA associations between the JIA categories and define correspondences with adult inflammatory arthritides.
Dense genotype data from the HLA region, from the Immunochip array for 5043 JIA cases and 14 390 controls, were used to impute single-nucleotide polymorphisms, HLA classical alleles and amino acids. Bivariate analysis was performed to investigate genetic correlation between the JIA categories. Conditional analysis was used to identify additional effects within the region. Comparison of the findings with those in adult inflammatory arthritic diseases was performed.
We identified category-specific associations and have demonstrated for the first time that rheumatoid factor (RF)-negative polyarticular JIA and oligoarticular JIA are genetically similar in their HLA associations. We also observe that each JIA category potentially has an adult counterpart. The RF-positive polyarthritis association at HLA-DRB1 amino acid at position 13 mirrors the association in adult seropositive rheumatoid arthritis (RA). Interestingly, the combined oligoarthritis and RF-negative polyarthritis dataset shares the same association with adult seronegative RA.
The findings suggest the value of using genetic data in helping to classify the categories of this heterogeneous disease. Mapping JIA categories to adult counterparts could enable shared knowledge of disease pathogenesis and aetiology and facilitate transition from paediatric to adult services.
Previous electrophysiological investigations have evaluated movement-related beta (14–28Hz) oscillatory activity in healthy participants. These studies have described an abrupt decrease in beta ...activity that starts before movement onset, and a sharp increase in beta power that peaks after movement termination. These neural responses have been respectively termed the event-related beta desynchronization or pre-movement beta ERD, and the post-movement beta rebound (PMBR). Previous studies have shown that a variety of movement parameters and demographic factors (e.g., age) modulate the amplitude of these oscillatory responses, and in the current study we evaluated whether the amplitudes follow a biological temporal rhythm (e.g., circadian), as it is known that spontaneous beta levels increase from morning to afternoon in some brain areas. To this end, we used magnetoencephalography (MEG) to evaluate oscillatory activity during a right hand finger-tapping task in four participants who were recorded at three different times (09:00, 12:00, 16:00) on three consecutive days (i.e., 36 total MEG sessions). All MEG data were corrected for head motion and examined in the time–frequency domain using beamforming methods. We found a significant linear increase in beta ERD amplitude from 09:00 to 16:00h in the left precentral gyrus, left premotor cortices, left supplementary motor area (SMA), and right precentral and postcentral gyri. In contrast, the amplitude of the PMBR was very steady across the day in all brain regions except the left SMA, which exhibited a linear increase from morning to afternoon. Finally, beta levels during the baseline period also increased from 09:00 to 16:00 in most regions of the cortical sensorimotor network. These data show that both the pre-movement beta ERD and spontaneous beta levels strongly increase from morning to afternoon in the motor cortices, which may indicate that the amplitude of the beta ERD response is determined by the spontaneous beta level during the motor planning period.
•Each participant performed a finger-tapping task during nine MEG recording sessions.•MEG recordings occurred at 09:00, 12:00, and 16:00 on three consecutive days.•MEG data was examined in the time–frequency domain and imaged using a beamformer.•Significant linear increase with time was observed in beta ERD amplitude in sensorimotor areas.•Beta ERD amplitude may be determined by spontaneous beta levels during the baseline.
Implementation theory suggests that first-level leaders, sometimes referred to as middle managers, can increase clinicians' use of evidence-based practice (EBP) in healthcare settings by enacting ...specific leadership behaviors (i.e., proactive, knowledgeable, supportive, perseverant with regard to implementation) that develop an EBP implementation climate within the organization; however, longitudinal and quasi-experimental studies are needed to test this hypothesis.
Using data collected at three waves over a 5-year period from a panel of 30 outpatient children's mental health clinics employing 496 clinicians, we conducted a quasi-experimental difference-in-differences study to test whether within-organization change in implementation leadership predicted within-organization change in EBP implementation climate, and whether change in EBP implementation climate predicted within-organization change in clinicians' use of EBP. At each wave, clinicians reported on their first-level leaders' implementation leadership, their organization's EBP implementation climate, and their use of both EBP and non-EBP psychotherapy techniques for childhood psychiatric disorders. Hypotheses were tested using econometric two-way fixed effects regression models at the organization level which controlled for all stable organizational characteristics, population trends in the outcomes over time, and time-varying covariates.
Organizations that improved from low to high levels of implementation leadership experienced significantly greater increases in their level of EBP implementation climate (d = .92, p = .017) and within-organization increases in implementation leadership accounted for 11% of the variance in improvement in EBP implementation climate beyond all other covariates. In turn, organizations that improved from low to high levels of EBP implementation climate experienced significantly greater increases in their clinicians' average EBP use (d = .55, p = .007) and within-organization improvement in EBP implementation climate accounted for 14% of the variance in increased clinician EBP use. Mediation analyses indicated that improvement in implementation leadership had a significant indirect effect on clinicians' EBP use via improvement in EBP implementation climate (d = .26, 95% CI .02 to .59).
When first-level leaders increase their frequency of implementation leadership behaviors, organizational EBP implementation climate improves, which in turn contributes to increased EBP use by clinicians. Trials are needed to test strategies that target this implementation leadership-EBP implementation climate mechanism.
To standardize the recording of surgical phenotypic information on endometriosis and related sample collections obtained at laparoscopy, allowing large-scale collaborative research into the ...condition.
An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries.
Two workshops were conducted in 2013, bringing together 54 clinical, academic, and industry leaders in endometriosis research and management worldwide.
None.
A postsurgical scoring sheet containing general and gynecological patient and procedural information, extent of disease, the location and type of endometriotic lesion, and any other findings was developed during several rounds of review. Comments and any systematic surgical data collection tools used in the reviewers' centers were incorporated.
The development of a standard recommended (SSF) and minimum required (MSF) form to collect data on the surgical phenotype of endometriosis.
SSF and MSF include detailed descriptions of lesions, modes of procedures and sample collection, comorbidities, and potential residual disease at the end of surgery, along with previously published instruments such as the revised American Society for Reproductive Medicine and Endometriosis Fertility Index classification tools for comparison and validation.
This is the first multicenter, international collaboration between academic centers and industry addressing standardization of phenotypic data collection for a specific disease. The Endometriosis Phenome and Biobanking Harmonisation Project SSF and MSF are essential tools to increase our understanding of the pathogenesis of endometriosis by allowing large-scale collaborative research into the condition.
The long-term (over more than one decade) X-ray emission from two massive stellar systems known to be particle accelerators is investigated using XMM–Newton. Their X-ray properties are interpreted ...taking into account recent information about their multiplicity and orbital parameters. The two targets, HD 168112 and HD 167971, appear to be overluminous in X-rays, lending additional support to the idea that a significant contribution of the X-ray emission comes from colliding-wind regions. The variability of the X-ray flux from HD 168112 is interpreted in terms of varying separation expected to follow the 1/D rule for adiabatic shocked winds. For HD 167971, marginal decrease of the X-ray flux in September 2002 could tentatively be explained by a partial wind eclipse in the close pair. No long-term variability could be demonstrated despite the significant difference of separation between 2002 and 2014. This suggests that the colliding-wind region in the wide orbit does not contribute a lot to the total X-ray emission, with a main contribution coming from the radiative shocked winds in the eclipsing pair. The latter result provides evidence that shocks in a colliding-wind region may be efficient particle accelerators even in the absence of bright X-ray emission, suggesting that particle acceleration may operate in a wide range of conditions. Finally, in hierarchical triple O-type systems, thermal X-rays do not necessarily constitute an efficient tracer to detect the wind–wind interaction in the long-period orbit.
Clinicians’ self‐efficacy with regard to delivering evidence‐based interventions (EBIs) to youth is an important target for both improving EBI use in the community and mitigating the risk of ...clinician burnout and turnover. Examining predictors of clinician self‐efficacy to treat trauma‐exposed youth is, therefore, an important step for informing the design of implementation strategies to enhance the mental health workforce's capacity to deliver EBIs in this population. We examined predictors of clinician self‐efficacy in working with trauma‐exposed youth in a sample of practicing mental health clinicians (N = 258, M age = 34.4 years, 85.0% female). Clinicians were recruited and surveyed as part of a larger study examining how clients’ exposure to potentially traumatic events influences clinician decision‐making. Results of regression models indicated that training in any trauma treatment model, being trained via a variety of formats (e.g., in‐person training, online, supervision), and training in a variety of treatment models were all associated with higher perceived self‐efficacy regarding effectively treating trauma‐exposed youth. Of the treatment models and training formats examined, receiving in‐person training, R2 = .10, and training in trauma‐focused cognitive behavioral therapy, R2 = .10, were the strongest predictors of higher self‐efficacy ratings. Clinician discipline, R2 = .04, and clinical practice factors, R2 = .20, were also related to self‐efficacy. Collectively, the R2 indicated a large effect, with the predictors explaining 25.4% of the variance in self‐efficacy ratings. Implications for designing implementation strategies targeting clinician self‐efficacy and future research are discussed.
Adult human height is one of the classical complex human traits. We searched for sequence variants that affect height by scanning the genomes of 25,174 Icelanders, 2,876 Dutch, 1,770 European ...Americans and 1,148 African Americans. We then combined these results with previously published results from the Diabetes Genetics Initiative on 3,024 Scandinavians and tested a selected subset of SNPs in 5,517 Danes. We identified 27 regions of the genome with one or more sequence variants showing significant association with height. The estimated effects per allele of these variants ranged between 0.3 and 0.6 cm and, taken together, they explain around 3.7% of the population variation in height. The genes neighboring the identified loci cluster in biological processes related to skeletal development and mitosis. Association to three previously reported loci are replicated in our analyses, and the strongest association was with SNPs in the ZBTB38 gene.
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