Miracle-dz/UniFAR-FTUs huggingface dataset:
Dispersion of endoplasmic reticulum-associated compartments by 4-phenyl butyric acid in yeast cells.

In yeast Saccharomyces cerevisiae cells, some aberrant multimembrane-spanning proteins are not transported to the cell surface but form and are accumulated in endoplasmic reticulum (ER)-derived subcompartments, known as the ER-associated compartments (ERACs), which are observed as puncta under fluorescence microscopy. Here we show that a mutant of the cell surface protein Pma1, Pma1-2308, was accumulated in the ERACs, as well as the heterologously expressed mammalian cystic fibrosis transmembrane conductance regulator (CFTR), in yeast cells. Pma1-2308 and CFTR were located on the same ERACs. We also note that treatment of cells with 4-phenyl butyric acid (4-PBA) compromised the ERAC formation by Pma1-2308 and CFTR, suggesting that 4-PBA exerts a chaperone-like function in yeast cells. Intriguingly, unlike ER stress induced by the canonical ER stressor tunicamycin, ER stress that was induced by Pma1-2308 was aggravated by 4-PBA. We assume that this observation demonstrates a beneficial aspect of ERACs, and thus propose that the ERACs are formed through aggregation of aberrant transmembrane proteins and work as the accumulation sites of multiple ERAC-forming proteins for their sequestration. Key words: protein aggregation, organelle, unfolded protein response, ER stress, 4-PBA.
HOTAIR regulates lipopolysaccharide‐induced inflammatory response in hepatocytes

It has been widely accepted that long‐noncoding RNA (lncRNA) HOX transcript antisense intergenic RNA (HOTAIR) emerges as a crucial mediator in inflammation. Here, we first detected HOTAIR in lipopolysaccharide (LPS)‐treated normal human liver cell line (L02) and hepatocellular carcinoma cell lines (C3A, HepG2, and SMMC‐7721). Further, we explored the biological function of HOTAIR in LPS‐induced hepatocytes (L02 and C3A) lesions and investigated the molecular mechanisms. Besides, we focused on inflammatory signaling crosstalk. The inflammatory insults were assayed by cell counting kit‐8 (CCK‐8), cell cycle and apoptosis analysis kit, and immunoblotting assay. HOTAIR level was examined by reverse‐transcription polymerase chain reaction. To determine the effect of HOTAIR silence or overexpression in inflammation, we applied quantitative reverse‐transcription polymerase chain reaction, immunoblotting assay, and enzyme‐linked immuno sorbent assay. Regulator inhibitors of Janus kinase/signal transducer and activator of transcription (JAK2/STAT3; AG490) and nuclear factor κB (NF‐κB; BAY‐11–7082) were applied to treat cells. Our results suggested that LPS induced the overexpression of HOTAIR in L02, C3A, HepG2, and SMMC‐7721 cells. LPS repressed viability, induced apoptosis, and facilitated the expression of interleukin (IL)‐1β, IL‐6, and tumor necrosis factor (TNF)‐α in L02 and C3A cells. IL‐1β, IL‐6, and TNF‐α were upregulated by HOTAIR overexpression while downregulated by HOTAIR knockdown in LPS‐treated cells. We further observed that HOTAIR overexpression accelerated LPS‐induced phosphorylation whereas HOTAIR silence blocked this progress. Inhibition of JAK/STAT and NF‐κB contributed to the suppression of cytokines which was evoked by LPS. Collectively, our findings indicated that HOTAIR exerted a crucial role in cytokines expression by activating JAK/STAT and NF‐κB.
A TFAP2C Gene Signature Is Predictive of Outcome in HER2-Positive Breast Cancer

The AP-2γ transcription factor, encoded by the TFAP2C gene, regulates the expression of estrogen receptor-alpha (ERα) and other genes associated with hormone response in luminal breast cancer. Little is known about the role of AP-2γ in other breast cancer subtypes. A subset of HER2+ breast cancers with amplification of the TFAP2C gene locus becomes addicted to AP-2γ. Herein, we sought to define AP-2γ gene targets in HER2+ breast cancer and identify genes accounting for physiologic effects of growth and invasiveness regulated by AP-2γ. Comparing HER2+ cell lines that demonstrated differential response to growth and invasiveness with knockdown of TFAP2C, we identified a set of 68 differentially expressed target genes. CDH5 and CDKN1A were among the genes differentially regulated by AP-2γ and that contributed to growth and invasiveness. Pathway analysis implicated the MAPK13/p38δ and retinoic acid regulatory nodes, which were confirmed to display divergent responses in different HER2+ cancer lines. To confirm the clinical relevance of the genes identified, the AP-2γ gene signature was found to be highly predictive of outcome in patients with HER2+ breast cancer. We conclude that AP-2γ regulates a set of genes in HER2+ breast cancer that drive cancer growth and invasiveness. The AP-2γ gene signature predicts outcome of patients with HER2+ breast cancer and pathway analysis predicts that subsets of patients will respond to drugs that target the MAPK or retinoic acid pathways. Implications: A set of genes regulated by AP-2γ in HER2+ breast cancer that drive proliferation and invasion were identified and provided a gene signature that is predictive of outcome in HER2+ breast cancer.
Comparison of the Effects of the Alcalase-Hydrolysates of Caseinate, and of Fish and Bovine Gelatins on the Acidification and Textural Features of Set-Style Skimmed Yogurt-Type Products

Commercial caseinate and two gelatins from bovine and fish skin were hydrolyzed by alcalase, and used at 2 g/kg in skimmed bovine milk that was then fermented with a commercial direct vat set starter, to clarify different effects of these hydrolysates on acidification and textural attributes of set-style yogurt samples. Compared with the fermentation of the yogurt sample without hydrolysate addition, the two gelatin hydrolysates in the yogurt samples endowed lower titratable acidity but higher pH values and thus delayed yogurt fermentation, while the caseinate hydrolysate showed an effect opposite to the two gelatin hydrolysates. The two gelatin hydrolysates induced worse quality attributes for the resultant yogurt samples, including higher syneresis extent, smaller hysteresis loop areas, and lower values in these textural indices like hardness, adhesiveness, apparent viscosity, elastic and viscous moduli. However, the caseinate hydrolysate led to improved quality attributes. Moreover, bovine gelatin hydrolysate always had a greater negative effect than fish gelatin hydrolysate on yogurt acidification and texture. It is concluded that these gelatin hydrolysates could confer the yogurt with intended bio-activities of gelatin hydrolysates but negatively impact yogurt acidification and texture, while the caseinate hydrolysate might be helpful for yogurt processing by shortening fermentation time and improving yogurt texture.
Fabrication of Robust Hydrogen Evolution Reaction Electrocatalyst Using Ag2Se by Vacuum Evaporation

Much research has been done on reliable and low-cost electrocatalysts for hydrogen generation by water splitting. In this study, we synthesized thin films of silver selenide (Ag2Se) using a simple thermal evaporation route and demonstrated their electrocatalytic hydrogen evolution reaction (HER) activity. The Ag2Se catalysts show improved electrochemical surface area and good HER electrocatalytic behavior (367 mV overpotential @ 10 mA·cm−2, exchange current density: ~1.02 × 10−3 mA·cm−2, and Tafel slope: 53 mV·dec−1) in an acidic medium). The reliability was checked in 0.5 M sulfuric acid over 20 h. Our first-principles calculations show the optimal energy of hydrogen adsorption, which is consistent with experimental results. The works could be further extended for finding a new catalyst by associating the selenide, sulfide or telluride-based materials without complex catalyst synthesis procedures.
Point-of-Care Clinical Trials in Sports Medicine Research: Identifying Effective Treatment Interventions Through Comparative Effectiveness Research.

CONTEXT Recently, calls to conduct comparative effectiveness research (CER) in athletic training to better support patient care decisions have been circulated. Traditional research methods (eg, randomized controlled trials [RCTs], observational studies) may be ill-suited for CER. Thus, innovative research methods are needed to support CER efforts. OBJECTIVES To discuss the limitations of traditional research designs in CER studies, describe a novel methodologic approach called the point-of-care clinical trial (POC-CT), and highlight components of the POC-CT (eg, incorporation of an electronic medical record [EMR], Bayesian adaptive feature) that allow investigators to conduct scientifically rigorous studies at the point of care. DESCRIPTION Practical concerns (eg, high costs and limited generalizability of RCTs, the inability to control for bias in observational studies) may stall CER efforts in athletic training. In short, the aim of the POC-CT is to embed a randomized pragmatic trial into routine care; thus, patients are randomized to minimize potential bias, but the study is conducted at the point of care to limit cost and improve the generalizability of the findings. Furthermore, the POC-CT uses an EMR to replace much of the infrastructure associated with a traditional RCT (eg, research team, patient and clinician reminders) and a Bayesian adaptive feature to help limit the number of patients needed for the study. Together, the EMR and Bayesian adaptive feature can improve the overall feasibility of the study and preserve the typical clinical experiences of the patient and clinician. CLINICAL AND RESEARCH ADVANTAGES The POC-CT includes the basic tenets of practice-based research because studies are conducted at the point of care, in real-life settings, and during routine clinical practice. If implemented effectively, the POC-CT can be seamlessly integrated into daily clinical practice, allowing investigators to establish patient-reported evidence that may be quickly applied to patient care decisions. This design appears to be a promising approach for CER investigations and may help establish a "learning health care system" in the sports medicine community.
Identification and characterisation of capidermicin, a novel bacteriocin produced by Staphylococcus capitis

One hundred human-derived coagulase negative staphylococci (CoNS) were screened for antimicrobial activity using agar-based deferred antagonism assays with a range of indicator bacteria. Based on the findings of the screen and subsequent well assays with cell free supernatants and whole cell extracts, one strain, designated CIT060, was selected for further investigation. It was identified as Staphylococcus capitis and herein we describe the purification and characterisation of the novel bacteriocin that the strain produces. This bacteriocin which we have named capidermicin was extracted from the cell-free supernatant of S. capitis CIT060 and purified to homogeneity using reversed-phase high performance liquid chromatography (RP-HPLC). Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometric (MS) analysis revealed that the capidermicin peptide has a mass of 5,464 Da. Minimal inhibitory concentration (MIC) experiments showed that capidermicin was active in the micro-molar range against all the Gram-positive bacteria that were tested. Antimicrobial activity was retained over a range of pHs (2–11) and temperatures (10–121°C x 15 mins). The draft genome sequence of S. capitis CIT060 was determined and the genes predicted to be involved in the biosynthesis of capidermicin were identified. These genes included the predicted capidermicin precursor gene, and genes that are predicted to encode a membrane transporter, an immunity protein and a transcriptional regulator. Homology searches suggest that capidermicin is a novel member of the family of class II leaderless bacteriocins.
“Every structure we're taught goes out the window”: General practitioners' experiences of providing help for patients with emotional concerns'

Abstract Up to 40% of general practitioners (GP) consultations contain an emotional component. General practitioners (GPs) have to provide care with limited time and resources. This qualitative study aimed to explore how GPs care for patients experiencing emotional concerns within the constraints of busy clinical practice. Seven GPs participated in three focus groups. Groups were recorded, transcribed and analysed thematically. Three themes were identified. (a) Collaboratively negotiated diagnosis: How patients' emotional concerns are understood and managed is the result of a negotiation between patient and GP belief models and the availability of treatments including talking therapy. (b) Doctor as drug: Not only is a continuous relationship between GPs and patients therapeutic in its own right, it is also necessary to effectively diagnose and engage patients in treatment as patients may experience stigma regarding emotional concerns. (c) Personal responsibility and institutional pressure: GPs feel personally responsible for supporting patients through their care journey, however, they face barriers due to lack of time and pressure from guidelines. GPs are forced to prioritise high‐risk patients and experience an emotional toll. In conclusion, guidelines focus on diagnosis and a stepped‐care model, however, this assumes diagnosis is relatively straightforward. GPs and patients have different models of psychological distress. This and the experience of stigma mean that establishing rapport is an important step before the GP and patient negotiate openly and develop a shared understanding of the problem. This takes time and emotional resources to do well. Longer consultations, continuity of care and formal supervision for GPs could enable them to better support patients.
The mouse fetal‐placental arterial connection: A paradigm involving the primitive streak and visceral endoderm with implications for human development

In Placentalia, the fetus depends upon an organized vascular connection with its mother for survival and development. Yet, this connection was, until recently, obscure. Here, we summarize how two unrelated tissues, the primitive streak, or body axis, and extraembryonic visceral endoderm collaborate to create and organize the fetal‐placental arterial connection in the mouse gastrula. The primitive streak reaches into the extraembryonic space, where it marks the site of arterial union and creates a progenitor cell pool. Through contact with the streak, associated visceral endoderm undergoes an epithelial‐to‐mesenchymal transition, contributing extraembryonic mesoderm to the placental arterial vasculature, and to the allantois, or pre‐umbilical tissue. In addition, visceral endoderm bifurcates into the allantois where, with the primitive streak, it organizes the nascent umbilical artery and promotes allantoic elongation to the chorion, the site of fetal‐maternal exchange. Brachyury mediates streak extension and vascular patterning, while Hedgehog is involved in visceral endoderm's conversion to mesoderm. A unique CASPASE‐3‐positive cell separates streak‐ and non‐streak‐associated domains in visceral endoderm. Based on these new insights at the posterior embryonic‐extraembryonic interface, we conclude by asking whether so‐called primordial germ cells are truly antecedents to the germ line that segregate within the allantois, or whether they are placental progenitor cells. Incorporating these new working hypotheses into mutational analyses in which the placentae are affected will aid understanding a spectrum of disorders, including orphan diseases, which often include abnormalities of the umbilical cord, yolk sac, and hindgut, whose developmental relationship to each other has, until now, been poorly understood.
Manual wheelchair’s turning resistance: swivelling resistance parameters of front and rear wheels on different surfaces

Abstract Purpose Daily locomotion with a manual wheelchair includes curvilinear movements. However, little is known about the resisting forces in play during turning manoeuvres where the wheels are generally both rolling and swivelling. This study aimed at quantifying the swivelling resistance parameters of several wheels on different surfaces and to evaluate the effect of the curvature radius on these parameters. Materials and methods A specific test bench was designed allowing the swivelling resistance parameters of a wheel rolling while swivelling to be determined. Seven wheels (3 front and 4 rear wheels), three surfaces (plywood, linoleum and carpet), two loads (25 and 45 kg) and five curvature radii (from 0 to 0.4 m) were tested through a full factorial design experiment. Results Results showed that the wheel type was the most influential factor on swivelling resistance parameters, followed by the surface and the curvature radius. The effect of the load on swivelling resistance parameters was found negligible when compared to the influence of other factors. A predictive model for swivelling resistance parameters of the different wheel/surface combinations was proposed, as a function of the curvature radius. Conclusion This study allowed the swivelling resistance parameters of different wheel/surface combinations to be quantified, as a function of the curvature radius of the wheel trajectory. Combined with data on rolling resistance, these data could now be used to assess energy losses during real life ambulation or to achieve more realistic behaviour in virtual rehabilitation environment. Implications for rehabilitation Swivelling resistances are increased by carpet surfaces compared to tile surfaces. Conversely to rolling resistance, castors wheels are less prone to swivelling resistance than rear wheels The swivelling resistance of a wheel rolling while swivelling is decreased compared to a pure swivelling movement. Combined with data on rolling resistance, these data on swivelling resistance would allow energy loss during daily life activity to be determined or as input data for the control of wheelchair simulator in virtual environment used for rehabilitation.
Effects of a mat Pilates programme on muscular strength and endurance in elderly women

Ageing decreases physical functioning while dependency increases. Arising from these physical limitations is an increasing urge for the use of complementary and alternative medicine such as Pilates. However, whether Pilates should be used as a substitute for conventional modes of exercises, especially in the elderly is debatable. The present study was thus conducted to determine the effects of mat Pilates on muscular strength and endurance in elderly women (aged > 60 years). Fifty sedentary, apparently healthy females aged 60 and older were randomly assigned into a control (CG, n = 25) or an intervention (IG, n = 25) group. The IG took part in an eight-week progressive mat Pilates exercise programme, three times weekly while the CG did not participate in any structured exercises throughout the eight-week period. All subjects underwent pre- and post-test in which muscular strength and muscular endurance were assessed. Results obtained from the present study indicate that eight-weeks of mat Pilates produced significant (p ≤ 0.05) improvements in upper-body muscular strength (19.12 ± 5.13 repetitions (reps) - 27.84 ± 5.68 reps; p = 0.000), lower-body muscular strength (13.24 ± 3.23 reps - 7.52 ± 3.81 reps; p = 0.000) and muscular endurance (24.48 ± 11.62 reps to 44.16 ± 18.97 reps; p = 0.000). It is therefore, concluded that an eight-week mat Pilates exercise programme is sufficient enough to produce significant improvements in muscular strength and muscular endurance in elderly women. Keywords: Aged, alternative medicine, complementary medicine, exercise, muscular performance, power African Journal for Physical, Health Education, Recreation and Dance (AJPHERD) Vol. 18, No. 2 (June) 2012, pp. 299-307
Evaluation of a professional development experience designed to equip school support staff with skills to facilitate youth mental health promotion

Background: Public policy across the world is increasingly focusing on the role of mental health promotion in whole of health strategies. There is a growing evidence-base that mental health promotion, delivered by trained facilitators, is effective in promoting self-awareness and self-care to prevent the damaging effects of ongoing stress in one’s life and to promote early detection of any possible emerging mental health problems. Within Australia, however, few clinicians or school staff are confident or trained in mental health promotion. Aims: This paper reports the results of a two-day training designed for facilitators of a mental health program for secondary-school students. The goal was to develop facilitators’ knowledge and understanding of best practice in youth mental health promotion and to increase their confidence in delivering the program. Design: A mixed methods evaluation assessed the impact that a solution-focused training program had on participating facilitators. Methods: A questionnaire was created and included eight quantitative items and one open ended, qualitative question. Twenty-seven nurses and guidance officers from central Queensland were recruited via convenience sampling and data were analysed using descriptive statistics and thematic analysis. Results: The evaluation revealed that participants’ perception of their ability to facilitate a youth mental health program significantly improved after completing the training. Qualitative data indicated that participants found the professional development experience to be valuable, provide useful and transferable skills, and believed it to be necessary for mental health promotion work. Conclusion: By providing detailed description of the program’s content and processes, other mental health professionals may be inspired to further develop effective learning experiences.