Miracle-dz/UniFAR-FTUs huggingface dataset:
Excitatory cholinergic responses in mouse colon intramuscular interstitial cells of Cajal are due to enhanced Ca2+ release via M3 receptor activation

Colonic intramuscular interstitial cells of Cajal (ICC‐IM) are associated with cholinergic varicosities, suggesting a role in mediating excitatory neurotransmission. Ca2+ release in ICC‐IM activates Ano1, a Ca2+‐activated Cl− conductance, causing tissue depolarization and increased smooth muscle excitability. We employed Ca2+ imaging of colonic ICC‐IM in situ, using mice expressing GCaMP6f in ICC to evaluate ICC‐IM responses to excitatory neurotransmission. Expression of muscarinic type 2, 3 (M2, M3), and NK1 receptors were enriched in ICC‐IM. NK1 receptor agonists had minimal effects on ICC‐IM, whereas neostigmine and carbachol increased Ca2+ transients. These effects were reversed by DAU 5884 (M3 receptor antagonist) but not AF‐DX 116 (M2 receptor antagonist). Electrical field stimulation (EFS) in the presence of L‐NNA and MRS 2500 enhanced ICC‐IM Ca2+ transients. Responses were blocked by atropine or DAU 5884, but not AF‐DX 116. ICC‐IM responses to EFS were ablated by inhibiting Ca2+ stores with cyclopiazonic acid and reduced by inhibiting Ca2+ influx via Orai channels. Contractions induced by EFS were reduced by an Ano1 channel antagonist, abolished by DAU 5884, and unaffected by AF‐DX 116. Colonic ICC‐IM receive excitatory inputs from cholinergic neurons via M3 receptor activation. Enhancing ICC‐IM Ca2+ release and Ano1 activation contributes to excitatory responses of colonic muscles.
The Albedo of Ryugu: Evidence for a High Organic Abundance, as Inferred from the Hayabusa2 Touchdown Maneuver

The Hayabusa2 mission successfully collected samples from the asteroid Ryugu last year and will return these to Earth in December 2020. It is anticipated that the samples will enable the analysis of terrestrially uncontaminated organic matter and minerals. Such analyses are in turn expected to elucidate the evolution of organic matter through Solar System history, including the origination and processing of biogenically important molecules, which could have been utilized by the first organisms on Earth. In anticipation, studies have made predictions concerning the properties of Ryugu, including its composition. The spectral characteristics of Ryugu, such as albedo, have been employed to relate the asteroid to members of the carbonaceous chondrite group that have been identified on Earth. However, the recent Hayabusa2 touchdown highlights a disparity between the color of surfaces of displaced platy fragments, indicating a brightening trend for the surface exposed to space compared to that facing into the body. Here we present a mass balance calculation with reference to data from the literature, which indicates that Ryugu may contain a significantly higher abundance of organic matter (likely >50%) than the currently most accepted meteorite analogues. A high organic content may result in high levels of extractable organic matter for the second touchdown site, where the spacecraft sampled freshly exposed material. However, high abundances of insoluble aromatic/graphitic rich organic matter may be present in the first touchdown site, which sampled the surface of Ryugu that had been exposed to space. Moreover, we suggest that the potentially high organic abundance and the rubble-pile nature of Ryugu may originate from the capture of rocky debris by a comet nucleus and subsequent water-organic-mineral interactions and sublimation of water ice.
The effect of the AKT1 gene and cannabis use on cognitive performance in healthy subjects

Background: Evidence suggests that the AKT1 gene may modulate the degree to which cannabis use induces cognitive alterations in patients with a psychotic disorder. Aim: To examine the interplay between AKT1 and cannabis use in terms of the cognitive performance of the general population. Methods: Our sample consisted of 389 Spanish university students. Sustained attention was measured via the Continuous Performance Test–Identical Pairs, immediate and delayed verbal memory with the Logical Memory subtest of the Wechsler Memory Scale, and working memory with the Wisconsin Card Sorting Test. Lifetime cannabis use frequency was assessed and individuals were classified as cannabis users or non-users. Two single nucleotide polymorphisms of the AKT1 gene were genotyped and, according to previous studies, each subject was defined as a carrier of two, one or no copies of the haplotype (rs2494732(C)–rs1130233(A)). Multiple linear regressions were conducted to test the effect of the genetic variability and cannabis use (and their interaction) on cognitive performance. Results: An effect of the AKT1 haplotype was found on attention scores: individuals with two copies of the haplotype performed better (β=0.18, p<0.001 (adjusted for false discovery rate)), while neither cannabis nor the AKT1–cannabis interaction was associated with attention. No effect of AKT1, cannabis or the AKT1–cannabis interaction was found on verbal memory or working memory. Conclusions: Our study provides additional evidence that AKT1 modulates cognitive performance. However, in our non-clinical sample, the previously reported interaction between cannabis use and the AKT1 gene was not replicated.
An Inertial Measurement Unit Based Method to Estimate Hip and Knee Joint Kinematics in Team Sport Athletes on the Field.

Current athlete monitoring practice in team sports is mainly based on positional data measured by global positioning or local positioning systems. The disadvantage of these measurement systems is that they do not register lower extremity kinematics, which could be a useful measure for identifying injury-risk factors. Rapid development in sensor technology may overcome the limitations of the current measurement systems. With inertial measurement units (IMUs) securely fixed to body segments, sensor fusion algorithms and a biomechanical model, joint kinematics could be estimated. The main purpose of this article is to demonstrate a sensor setup for estimating hip and knee joint kinematics of team sport athletes in the field. Five male subjects (age 22.5 ± 2.1 years; body mass 77.0 ± 3.8 kg; height 184.3 ± 5.2 cm; training experience 15.3 ± 4.8 years) performed a maximal 30-meter linear sprint. Hip and knee joint angles and angular velocities were obtained by five IMUs placed on the pelvis, both thighs and both shanks. Hip angles ranged from 195° (± 8°) extension to 100.5° (± 8°) flexion and knee angles ranged from 168.6° (± 12°) minimal flexion and 62.8° (± 12°) maximal flexion. Furthermore, hip angular velocity ranged between 802.6 °·s-1 (± 192 °·s-1) and -674.9 °·s-1 (± 130 °·s-1). Knee angular velocity ranged between 1155.9 °·s-1 (± 200 °·s-1) and -1208.2 °·s-1 (± 264 °·s-1). The sensor setup has been validated and could provide additional information with regard to athlete monitoring in the field. This may help professionals in a daily sports setting to evaluate their training programs, aiming to reduce injury and optimize performance.
Social support and self-esteem on the association between stressful life events and mental health outcomes among college students

ABSTRACT The purpose of this research is to determine whether social support (informal and formal) and self-esteem can moderate the associations between life stress and mental health among college students. The research questions for the study are as follows: i) Does life stress affect mental health among college students? ii) Do social support (informal and formal) and self-esteem predict this association? iii) What are the characteristics of students predicting life stress, social support and self-esteem? Using a survey design (n = 184), respondents were asked about stressful life events, formal and informal social support, self-esteem, depression, anxiety, and baseline characteristics (age, sexual orientation, post graduate status, family size, income, employment status, participation in activities at school, and previous mental health diagnoses). Regression analysis found that students who experienced more stressful life events reported higher depression and anxiety. Informal social support and self-esteem significantly enhanced positive mental health. However, formal social support was not found to impact students’ mental health. Younger students tend to have lower self-esteem and higher mental health problems. Students who worked part-time and participated in extra curriculum activities used more forma social services. Students who had previous mental health diagnoses had higher mental health problems.
Placental gene editing via trophectoderm-specific Tat-Cre/loxP recombination

ABSTRACT The ways in which placental defects affect embryonic development are largely overlooked because of the lack of a trophoblast-specific approach for conditional gene ablation. To tackle this, we have established a simple, fast and efficient method for trophectodermal Tat-Cre/loxP recombination. We used the natural permeability barrier in mouse blastocysts in combination with off-the-shelf Tat-Cre recombinase to achieve editing of conditional alleles in the trophoblast lineage. This direct approach enables gene function analysis during implantation and placentation in mice, thereby crucially helping to broaden our understanding of human reproduction and development. Summary: Trophoblast-specific Cre/loxP recombination is achieved by using the natural permeability barrier of the blastocyst, restricting Tat-Cre activity to the trophectoderm.
Associations between parent and child physical activity and eating behaviours in a diverse sample: an ecological momentary assessment study

Abstract Objective: This study is a secondary data analysis that examines the association between parent modelling of dietary intake and physical activity and the same child behaviours among different races/ethnicities using innovative, rigorous and objective measures. Design: Ecological momentary assessment surveys were sent to parents to assess whether their child had seen them exercise or consume food. Dietary recall data and accelerometry were used to determine dietary intake and physical activity behaviours of children. Setting: Participants were randomly selected from primary care clinics, serving low-income and racially/ethnically diverse families in Minnesota, USA. Participants: Participants were families with children aged 5–7 years old who lived with parents 50 % of the time and shared at least one meal together. Results: A 10 percentage point higher prevalence in parent modelling of fruit and vegetable intake was associated with 0·12 higher serving intake of those same foods in children. The prevalence of parent modelling of eating energy dense foods (10 % prevalence units) was associated with 0·09 higher serving intake of sugar-sweetened beverages. Furthermore, accelerometry-measured parent sedentary hours was strongly correlated with child sedentary time (0·37 child sedentary hours per parent sedentary hours). An exploratory interaction analysis did not reveal any statistical evidence that these relationships depended on the child’s race/ethnic background. Conclusions: Interventions that increase parent modelling of healthy eating and minimise modelling of energy dense foods may have favourable effects on child dietary quality. Additionally, future research is needed to clarify the associations of parent modelling of physical activity and children’s physical activity levels.
YejM Controls LpxC Levels by Regulating Protease Activity of the FtsH/YciM Complex of Escherichia coli

Lipid homeostasis is critical for proper envelope functions. The level of LpxC, which catalyzes the first committed step of lipopolysaccharide (LPS) synthesis, is controlled by an essential protease complex comprised of FtsH and YciM. Work carried out here suggests YejM, an essential envelope protein, plays a central role in sensing the state of LPS synthesis and controls LpxC levels by regulating the activity of FtsH/YciM. All four essential proteins are attractive targets of therapeutic development. ABSTRACT LpxC is a deacetylase that catalyzes the first committed step of lipid A biosynthesis in Escherichia coli. LpxC competes for a common precursor, R-3-hydroxymyristoyl-UDP-GlcNAc, with FabZ, whose dehydratase activity catalyzes the first committed step of phospholipid biosynthesis. To maintain the optimum flow of the common precursor to these two competing pathways, the LpxC level is controlled by FtsH/YciM-mediated proteolysis. It is not known whether this complex or another protein senses the status of lipid A synthesis to control LpxC proteolysis. The work carried out in this study began with a novel mutation, yejM1163, which causes hypersensitivity to large antibiotics such as vancomycin and erythromycin. Isolates resistant to these antibiotics carried suppressor mutations in the ftsH and yciM genes. Western blot analysis showed a dramatically reduced LpxC level in the yejM1163 background, while the presence of ftsH or yciM suppressor mutations restored LpxC levels to different degrees. Based on these observations, it is proposed that YejM is a sensor of lipid A synthesis and controls LpxC levels by modulating the activity of the FtsH/YciM complex. The truncation of the periplasmic domain in the YejM1163 protein causes unregulated proteolysis of LpxC, thus diverting a greater pool of R-3-hydroxymyristoyl-UDP-GlcNAc toward phospholipid synthesis. This imbalance in lipid synthesis perturbs the outer membrane permeability barrier, causing hypersensitivity toward vancomycin and erythromycin. yejM1163 suppressor mutations in ftsH and yciM lower the proteolytic activity toward LpxC, thus restoring lipid homeostasis and the outer membrane permeability barrier. IMPORTANCE Lipid homeostasis is critical for proper envelope functions. The level of LpxC, which catalyzes the first committed step of lipopolysaccharide (LPS) synthesis, is controlled by an essential protease complex comprised of FtsH and YciM. Work carried out here suggests YejM, an essential envelope protein, plays a central role in sensing the state of LPS synthesis and controls LpxC levels by regulating the activity of FtsH/YciM. All four essential proteins are attractive targets of therapeutic development.
Acute effects of MDMA on trust, cooperative behaviour and empathy: A double-blind, placebo-controlled experiment

Background: 3,4-Methylenedioxymethamphetamine (MDMA) is being actively researched as an adjunct to psychotherapy. It may be beneficial to trust, empathy and cooperative behaviour due to its acute prosocial effects. Aim: To test (a) the acute effects of MDMA on measures of empathy, trust and cooperative behaviour, and (b) subacute changes in mood three days after MDMA administration. Methods: Twenty-five participants (n=7 female), participated in this double-blind, repeated-measures, placebo-controlled experiment. Participants attended two acute sessions, one week apart. Each acute session was followed by a subacute session three days later. Participants received placebo (100 mg ascorbic acid) during one acute session, and MDMA (100 mg MDMA-HCl) at the other, with order counterbalanced. Participants completed the following tasks assessing prosocial behaviour: a trust investment task, a trustworthy face rating task, an empathic stories task, a public project game, a dictator game and an ultimatum game. Participants reported subjective effects. Blood was taken pre-drug, 2 and 4 hours post-drug, and tested for plasma MDMA levels. Results: MDMA acutely increased self-reported ‘closeness to others’ and ‘euphoria’ and increased plasma concentrations of MDMA. MDMA did not significantly change task-based empathy, trust or cooperative behaviour. Using Bayesian analyses, we found evidence that MDMA and placebo did not differ in their effects on empathy and cooperative behaviour. MDMA did not significantly change subacute mood and this was supported by our Bayesian analyses. Conclusion: Despite augmentation in plasma MDMA levels and subjective drug effects, we found no increase in prosocial behaviour in a laboratory setting.
INDUCTION OF POSTERIOR VITREOUS DETACHMENT IN PEDIATRIC PATIENTS BY RADIAL PERIFOVEAL STRIPPING

Supplemental Digital Content is Available in the Text. This case details a novel technique of posterior vitreous detachment induction during pars plana vitrectomy by radial perifoveal stripping with a flex loop. Background/Purpose: In certain cases, there may be firm adherence of the cortical vitreous to the retinal surface during pars plana vitrectomy. This report aims to present an alternative method of posterior vitreous detachment (PVD) induction at the macula with the use of a flexible loop. Methods: A 5-year-old girl underwent 25-gauge pars plana vitrectomy for optic pit maculopathy. Triamcinolone is used for staining. Posterior vitreous detachment was induced in the perifoveal area with 360° radial peeling. The vitrector was then used to lift and complete the PVD. Results: Posterior vitreous detachment was able to be induced with minimal trauma to the retinal surface. There were no postoperative complications from the procedure. Conclusion: Posterior vitreous detachment induction at the macula using a flexible loop and radial stripping is a safe and reliable alternative to conventional techniques.
Electroacupuncture ameliorates post-traumatic stress disorder in rats via a mechanism involving the BDNF-TrkB signaling pathway.

Post-traumatic stress disorder (PTSD) is a mental health condition triggered by a terrifying event, causing flashbacks, nightmares and severe anxiety. It develops in individuals who have experienced a shocking, scary, or dangerous event. Electroacupuncture is reported to be effective for the treatment of PTSD. The present study was carried out to investigate the protective effect of electroacupuncture in a rat model of PTSD, and the mechanism involved. Specific-pathogen-free male Sprague Dawley rats (n = 30) weighing 180 - 220 g (mean weight = 200 ± 20 g) were randomly assigned to three groups of ten rats each: control group, single-prolonged stress (SPS) group, and treatment group. The treatment group rats received electroacupuncture. Changes in PTSD-like behavior were assessed using locomotor activity, elevated plus-maze (EPM) and fear conditioning tests. The mRNA and protein expressions of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) were determined using real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Co-immunoprecipitation (Co-IP) was used to measure BDNF and TrkB binding interaction, while chromatin immunoprecipitation (ChIP) was used to evaluate the binding between cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) and its target genes. Electroacupuncture significantly increased locomotor activity and exploratory behavior, but significantly reduced general fear and anxiety in SPS rats (p < 0.05). It also significantly upregulated the mRNA and protein expressions of BDNF and TrkB, and increased the binding of BDNF to its receptor TrkB (p < 0.05). Electroacupuncture significantly increased the binding of CREB to BDNF promoter region (p < 0.05). Electroacupuncture ameliorates PTSD in rats via a mechanism involving the BDNF-TrkB signaling pathway.
Multi‐parametric system for risk stratification in mitral regurgitation: A multi‐task Gaussian prediction approach

We hypothesized that a multi‐parametric approach incorporating medical comorbidity information, electrocardiographic P‐wave indices, echocardiographic assessment, neutrophil‐to‐lymphocyte ratio (NLR) and prognostic nutritional index (PNI) calculated from laboratory data can improve risk stratification in mitral regurgitation (MR).
How does cultural capital keep you thin? Exploring unique aspects of cultural class that link social advantage to lower body mass index

Abstract A widely used indicator for cultural class is strongly related to a lower body mass index (BMI): cultural capital measured as ‘highbrow' taste. This study’s objective was to theorise and measure aspects of cultural class that are more plausibly linked to low BMI, and subsequently explore their relevance. Building on Bourdieusian theory we derive four of those aspects: ‘refinement’ (valuing form and appearance over function and substance), ‘asceticism’ (self‐imposed constraints), ‘diversity’ (appreciation of variety in and of itself) and ‘reflexivity’ (reflexive deliberation and internal dialogue). Using standardised interviews with 597 participants in the Dutch GLOBE study in 2016, we subsequently demonstrate: (i) newly developed survey items can reliably measure four aspects of cultural class: ‘asceticism’, ‘general refinement’, ‘food refinement’ and ‘reflexivity’ (Cronbach’s alphas between 0.67–0.77); (ii) embodied/objectified cultural capital (i.e. ‘highbrow’ taste) was positively associated with general refinement, food refinement and reflexivity, whereas institutionalised cultural capital (i.e. education) was positively associated with asceticism and reflexivity; (iii) asceticism, general refinement, reflexivity, but not food refinement, were associated with a lower BMI; (iv) asceticism, general refinement and reflexivity together accounted for 52% of the association between embodied/objectified cultural capital and BMI, and 38% of the association between institutionalised cultural capital and BMI.
Nrf2/HO-1 mediates the neuroprotective effects of pramipexole by attenuating oxidative damage and mitochondrial perturbation after traumatic brain injury in rats

ABSTRACT Pramipexole (PPX), a D2-like receptor agonist, is generally used in the treatment of Parkinson's disease and restless leg syndrome. Its neuroprotective effects have been shown against various neurological disorders. Recent research work has demonstrated that PPX exerts neuroprotection through mitochondria. However, the neuromodulator-related effects of PPX against traumatic brain injury (TBI) remain unexplored. The present study, therefore, investigated the mechanism of neuroprotection by PPX against oxidative stress, mitochondrial dysfunction and neuronal damage following TBI in rats. We hypothesized that the neuroprotection by PPX in TBI-subjected rats might involve activation of the Nrf2/HO-1 (also known as Nfe2l2/Hmox1) signaling pathway. PPX was injected intraperitoneally (0.25 mg/kg body weight and 1.0 mg/kg body weight) at different time intervals post-TBI. Several neurobehavioral parameters were assessed at 48 h post-TBI, and the brain was isolated for molecular and biochemical analysis. The results demonstrated that PPX treatment significantly improved the behavioral deficits, decreased the lipid peroxidation rate, increased glutathione levels and decreased 4-hydroxynonenal levels in TBI-subjected rats. PPX also increased the activities of glutathione peroxidase and superoxide dismutase enzymes. In addition, PPX treatment inhibited mitochondrial reactive oxygen species production, restored mitochondrial membrane potential and increased ATP levels after a TBI. Further, PPX treatment reduced the Bax/Bcl2 ratio and translocation of Bax to mitochondria and cytochrome-c to the cytosol. Finally, PPX treatment greatly accelerated the translocation of Nrf2 to the nucleus and upregulated HO-1 protein expression. We conclude that the neuroprotective effects of PPX are mediated by activation of the Nrf2/HO-1 signaling pathway following TBI. This article has an associated First Person interview with the first author of the paper. Editor's choice: We administered pramipexole (PPX) to rats after a traumatic brain injury (TBI) and evaluated various parameters, which indicate that the neuroprotective effects of PPX are mediated by activation of the Nrf2/HO-1 signaling pathway following TBI.