ALMA Survey of Lupus Class III Stars: Early Planetesimal Belt Formation and Rapid Disk Dispersal

Class III stars are those in star forming regions without large non-photospheric infrared emission, suggesting recent dispersal of their protoplanetary disks. We observed 30 class III stars in the 1-3 Myr Lupus region with ALMA at ∼856μm, resulting in 4 detections that we attribute to circumstellar dust. Inferred dust masses are 0.036 − 0.093M⊕, ∼1 order of magnitude lower than any previous measurements; one disk is resolved with radius ∼80 au. Two class II sources in the field of view were also detected, and 11 other sources, consistent with sub-mm galaxy number counts. Stacking non-detections yields a marginal detection with mean dust mass ∼0.0048M⊕. We searched for gas emission from the CO J=3-2 line, and present its detection to NO Lup inferring a gas mass (4.9 ± 1.1) × 10−5 M⊕ and gas-to-dust ratio 1.0 ± 0.4. Combining our survey with class II sources shows a gap in the disk mass distribution from 0.09 − 2M⊕ for >0.7M⊙ Lupus stars, evidence of rapid dispersal of mm-sized dust from protoplanetary disks. The class III disk mass distribution is consistent with a population model of planetesimal belts that go on to replenish the debris disks seen around main sequence stars. This suggests that planetesimal belt formation does not require long-lived protoplanetary disks, i.e., planetesimals form within ∼2 Myr. While all 4 class III disks are consistent with collisional replenishment, for two the gas and/or mid-IR emission could indicate primordial circumstellar material in the final stages of protoplanetary disk dispersal. Two class III stars without sub-mm detections exhibit hot emission that could arise from ongoing planet formation processes inside ∼1 au

Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid

Caspase-8 is involved in death receptor-mediated apoptosis in type II cells, the proapoptotic programme of which is triggered by truncated Bid. Indeed, caspase-8 and Bid are the known intermediates of this signalling pathway. Cardiolipin has been shown to provide an anchor and an essential activating platform for caspase-8 at the mitochondrial membrane surface. Destabilisation of this platform alters receptor-mediated apoptosis in diseases such as Barth Syndrome, which is characterised by the presence of immature cardiolipin which does not allow caspase-8 binding. We used a simplified in vitro system that mimics contact sites and/or cardiolipin-enriched microdomains at the outer mitochondrial surface in which the platform consisting of caspase-8, Bid and cardiolipin was reconstituted in giant unilamellar vesicles. We analysed these vesicles by flow cytometry and confirm previous results that demonstrate the requirement for intact mature cardiolipin for caspase-8 activation and Bid binding and cleavage. We also used confocal microscopy to visualise the rupture of the vesicles and their revesiculation at smaller sizes due to alteration of the curvature following caspase-8 and Bid binding. Biophysical approaches, including Laurdan fluorescence and rupture/tension measurements, were used to determine the ability of these three components (cardiolipin, caspase-8 and Bid) to fulfil the minimal requirements for the formation and function of the platform at the mitochondrial membrane. Our results shed light on the active functional role of cardiolipin, bridging the gap between death receptors and mitochondria

A systematic review of the literature on the effectiveness of exercise therapy for groin pain in athletes

<p>Abstract</p> <p>Background</p> <p>Athletes competing in sports that require running, changes in direction, repetitive kicking and physical contact are at a relatively higher risk of experiencing episodes of athletic groin pain. To date, there has been no systematic review that aims to inform clinicians about the best available evidence on features of exercise interventions for groin pain in athletes. The primary aim of this systematic review was to evaluate the available evidence on the effectiveness of exercise therapy for groin pain in athletes. The secondary aim of this review was to identify the key features of exercise interventions used in the management of groin pain in an athletic population.</p> <p>Methods</p> <p>MEDLINE, CINAHL, PubMed, SPORTSDiscus, Embase, AMED, Ovid, PEDro, Cochrane Controlled Trials Register and Google Scholar databases were electronically searched. Data relating to research design, sample population, type of sport and exercise intervention was extracted. The methodological evaluation of included studies was conducted by using a modified quantitative critical appraisal tool.</p> <p>Results</p> <p>The search strategy identified 468 studies, 12 of which were potentially relevant. Ultimately five studies were included in this review. Overall the quality of primary research literature was moderate, with only one randomised controlled trial identified. All included studies provided evidence that an exercise intervention may lead to favourable outcomes in terms of return to sport. Four of the five studies reviewed included a strengthening component and most utilised functional, standing positions similar to those required by their sport. No study appropriately reported the intensity of their exercise interventions. Duration of intervention ranged from 3.8 weeks to 16 weeks. All five studies reported the use of one or more co-intervention.</p> <p>Conclusion</p> <p>Best available evidence to date, with its limitations, continues to support common clinical practice of exercise therapy as a key component of rehabilitation for groin pain in athletes. Overall, the available evidence suggests that exercise, particularly strengthening exercise of the hip and abdominal musculature could be an effective intervention for athletes with groin pain. Literature provides foundational evidence that this may need to be in the form of progressive exercises (static to functional) and performed through range. There is currently no clear evidence regarding the most effective intensity and frequency of exercise, because of a lack of reporting in the primary literature.</p

Mechanism of copper(II)-induced misfolding of Parkinson's disease protein

α-synuclein (aS) is a natively unfolded pre-synaptic protein found in all Parkinson's disease patients as the major component of fibrillar plaques. Metal ions, and especially Cu(II), have been demonstrated to accelerate aggregation of aS into fibrillar plaques, the precursors to Lewy bodies. In this work, copper binding to aS is investigated by a combination of quantum and molecular mechanics simulations. Starting from the experimentally observed attachment site, several optimized structures of Cu-binding geometries are examined. The most energetically favorable attachment results in significant allosteric changes, making aS more susceptible to misfolding. Indeed, an inverse kinematics investigation of the configuration space uncovers a dynamically stable β-sheet conformation of Cu-aS that serves as a nucleation point for a second β-strand. Based on these findings, we propose an atomistic mechanism of copper-induced misfolding of aS as an initial event in the formation of Lewy bodies and thus in PD pathogenesis

Selenoether oxytocin analogues have analgesic properties in a mouse model of chronic abdominal pain

Poor oral availability and susceptibility to reduction and protease degradation is a major hurdle in peptide drug development. However, drugable receptors in the gut present an attractive niche for peptide therapeutics. Here we demonstrate, in a mouse model of chronic abdominal pain, that oxytocin receptors are significantly upregulated in nociceptors innervating the colon. Correspondingly, we develop chemical strategies to engineer non-reducible and therefore more stable oxytocin analogues. Chemoselective selenide macrocyclization yields stabilized analogues equipotent to native oxytocin. Ultra-high-field nuclear magnetic resonance structural analysis of native oxytocin and the seleno-oxytocin derivatives reveals that oxytocin has a pre-organized structure in solution, in marked contrast to earlier X-ray crystallography studies. Finally, we show that these seleno-oxytocin analogues potently inhibit colonic nociceptors both in vitro and in vivo in mice with chronic visceral hypersensitivity. Our findings have potentially important implications for clinical use of oxytocin analogues and disulphide-rich peptides in general

A perspective on the measurement of time in plant disease epidemiology

The growth and development of plant pathogens and their hosts generally respond strongly to the temperature of their environment. However, most studies of plant pathology record pathogen/host measurements against physical time (e.g. hours or days) rather than thermal time (e.g. degree-days or degree-hours). This confounds the comparison of epidemiological measurements across experiments and limits the value of the scientific literature

A Systematic Review of the Effect of Cognitive Strategies on Strength Performance

Background Researchers have tested the beliefs of sportspeople and sports medicine specialists that cognitive strategies influence strength performance. Few investigators have synthesised the literature. Objectives The specific objectives were to review evidence regarding (a) the cognitive strategy–strength performance relationship; (b) participant skill level as a moderator; and (c) cognitive, motivational, biomechanical/physiological, and emotional mediators. Method Studies were sourced via electronic databases, reference lists of retrieved articles, and manual searches of relevant journals. Studies had to be randomised or counterbalanced experiments with a control group or condition, repeated measures, and a quality control score above 0.5 (out of 1). Cognitive strategies included goal setting, imagery, self-talk, preparatory arousal, and free choice. Dependent variables included maximal strength, local muscular endurance, or muscular power. Results Globally, cognitive strategies were reliability associated with increased strength performance (results ranged from 61 to 65 %). Results were mixed when examining the effects of specific strategies on particular dependent variables, although no intervention had an overall negative influence. Indeterminate relationships emerged regarding hypothesised mediators (except cognitive variables) and participant skill level as a moderator. Conclusions Although cognitive strategies influence strength performance, there are knowledge gaps regarding specific types of strength, especially muscular power. Cognitive variables, such as concentration, show promise as possible mediators

Gating at the Mouth of the Acetylcholine Receptor Channel: Energetic Consequences of Mutations in the αM2-Cap

Gating of nicotinic acetylcholine receptors from a C(losed) to an O(pen) conformation is the initial event in the postsynaptic signaling cascade at the vertebrate nerve-muscle junction. Studies of receptor structure and function show that many residues in this large, five-subunit membrane protein contribute to the energy difference between C and O. Of special interest are amino acids located at the two transmitter binding sites and in the narrow region of the channel, where C↔O gating motions generate a low↔high change in the affinity for agonists and in the ionic conductance, respectively. We have measured the energy changes and relative timing of gating movements for residues that lie between these two locations, in the C-terminus of the pore-lining M2 helix of the α subunit (‘αM2-cap’). This region contains a binding site for non-competitive inhibitors and a charged ring that influences the conductance of the open pore. αM2-cap mutations have large effects on gating but much smaller effects on agonist binding, channel conductance, channel block and desensitization. Three αM2-cap residues (αI260, αP265 and αS268) appear to move at the outset of channel-opening, about at the same time as those at the transmitter binding site. The results suggest that the αM2-cap changes its secondary structure to link gating motions in the extracellular domain with those in the channel that regulate ionic conductance