Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Analysis of an Essential GSP1/Ran Ortholog Gene, CpRan1, from the Chestnut Blight Fungus Cryphonectria parasitica Using a Heterokaryon

Functional analysis of a GSP1/Ran ortholog, CpRan1, from Cryphonectria parasitica was conducted. Genotype analysis revealed that the putative CpRan1-null mutant was a heterokaryotic transformant harboring two different types of nuclei, one with the wild-type CpRan1 allele and the other with the CpRan1-null mutant allele. The mycelial growth and colony morphology of the heterokaryotic transformant was normal. Microscopic analysis of the resulting conidia (aseptate and monokaryotic asexual spores) demonstrated that although normal germinating spores were observed from conidia harboring a nucleus with the wild-type CpRan1 allele, a number of residual conidia that did not germinate existed. Complementation analysis using protoplasts from the heterokaryon with the wild-type CpRan1 allele confirmed that the CpRan1 gene is essential to C. parasitica. Complementation analysis using the various CpRan1 chimera constructs allowed us to perform a functional analysis of essential amino acids of the CpRan1. Among the four suggested essential amino acids, Lys-97 for ubiquitination was determined to not be an essential residue. Moreover, the CpRan1-null mutant allele was successfully complemented with mouse Ran gene, which suggested that the biological function of Ran gene is evolutionary conserved and that our heterokaryon rescue can be applied for the functional analysis of heterologous genes.
Heart rate during work and heart rate variability during the following night: a day-by-day investigation on the physical activity paradox among blue-collar workers

Objectives: Contrary to leisure-time physical activity, occupational physical activity (OPA) may have harmful health effects, called the physical activity paradox. A proposed mechanism is that OPA can elevate the heart rate (HR) for several hours per day. We aimed to investigate the association between the mean intensity of OPA and HR variability (HRV) indices the following night. Methods: Three cohorts (NOMAD, DPhacto, and Physical Workload and Fitness) involving blue-collar workers from different sectors were merged in this study. HR monitors (Actiheart) recorded 24-hour inter-beat intervals (IBI) for up to four consecutive days. The relative intensity of the mean HR during work was estimated by HR reserve (%HRR), and time-domain indices of HRV were analyzed during the following night. Data were analyzed using a multilevel growth model to test the association between mean %HRR during work and HRV indices at night in a day-by-day analysis adjusted for age, BMI, alcohol consumption, smoking, and occupation. Results: The dataset included a sample of 878 Danish blue-collar workers, with a mean %HRR during work of 31%, and 42% worked at an intensity ≥30%HRR. The multilevel model showed negative within- and between-subject associations between %HRR during work and HRV indices at night. Conclusions: Our results indicate a higher %HRR during work to associate with lower HRV indices the following night and a higher HR, reflecting an imbalanced autonomic cardiac modulation. This finding supports a high mean HR during work to be a potential underlying mechanism for the harmful health effect of OPA.
Running and Swimming Differently Adapt the BDNF/TrkB Pathway to a Slow Molecular Pattern at the NMJ

Physical exercise improves motor control and related cognitive abilities and reinforces neuroprotective mechanisms in the nervous system. As peripheral nerves interact with skeletal muscles at the neuromuscular junction, modifications of this bidirectional communication by physical activity are positive to preserve this synapse as it increases quantal content and resistance to fatigue, acetylcholine receptors expansion, and myocytes’ fast-to-slow functional transition. Here, we provide the intermediate step between physical activity and functional and morphological changes by analyzing the molecular adaptations in the skeletal muscle of the full BDNF/TrkB downstream signaling pathway, directly involved in acetylcholine release and synapse maintenance. After 45 days of training at different intensities, the BDNF/TrkB molecular phenotype of trained muscles from male B6SJLF1/J mice undergo a fast-to-slow transition without affecting motor neuron size. We provide further knowledge to understand how exercise induces muscle molecular adaptations towards a slower phenotype, resistant to prolonged trains of stimulation or activity that can be useful as therapeutic tools.
The ‘Shape-Shifter’ Peptide from the Disulphide Isomerase PmScsC Shows Context-Dependent Conformational Preferences

Multiple crystal structures of the homo-trimeric protein disulphide isomerase PmScsC reveal that the peptide which links the trimerization stalk and catalytic domain can adopt helical, β-strand and loop conformations. This region has been called a ‘shape-shifter’ peptide. Characterisation of this peptide using NMR experiments and MD simulations has shown that it is essentially disordered in solution. Analysis of the PmScsC crystal structures identifies the role of intermolecular contacts, within an assembly of protein molecules, in stabilising the different linker peptide conformations. These context-dependent conformational properties may be important functionally, allowing for the binding and disulphide shuffling of a variety of protein substrates to PmScsC. They also have a relevance for our understanding of protein aggregation and misfolding showing how intermolecular quaternary interactions can lead to β-sheet formation by a sequence that in other contexts adopts a helical structure. This ‘shape-shifting’ peptide region within PmScsC is reminiscent of one-to-many molecular recognition features (MoRFs) found in intrinsically disordered proteins which are able to adopt different conformations when they fold upon binding to their protein partners.
First Report of blaNDM-1 Bearing IncX3 Plasmid in Clinically Isolated ST11 Klebsiella pneumoniae from Pakistan

The New Delhi Metallo-β-lactamase (NDM) is among the most threatening forms of carbapenemases produced by K. pneumoniae, well-known to cause severe worldwide infections. The molecular epidemiology of blaNDM-1-harboring K. pneumoniae is not well elucidated in Pakistan. Herein, we aim to determine the antibiotics-resistance profile, genes type, molecular type, and plasmid analysis of 125 clinically isolated K. pneumoniae strains from urine samples during July 2018 to January 2019 in Pakistan. A total of 34 (27.2%) K. pneumoniae isolates were carbapenemases producers, and 23 (18.4%) harbored the blaNDM-1 gene. The other carbapenemases encoding genes, i.e., blaIMP-1 (7.2%), blaVIM-1 (3.2%), and blaOXA-48 (2.4%) were also detected. The Multi Locus Sequence Typing (MLST) results revealed that all blaNDM-1-harboring isolates were ST11. The other sequence types detected were ST1, ST37, and ST105. The cluster analysis of Xbal Pulsed Field Gel Electrophoresis (PFGE) revealed variation amongst the clusters of the identical sequence type isolates. The blaNDM-1 gene in all of the isolates was located on a 45-kb IncX3 plasmid, successfully transconjugated. For the first time, blaNDM-1-bearing IncX3 plasmids were identified from Pakistan, and this might be a new primary vehicle for disseminating blaNDM-1 in Enterobacteriaceae as it has a high rate of transferability.
Custom-Fitted In- and Around-the-Ear Sensors for Unobtrusive and On-the-Go EEG Acquisitions: Development and Validation

Objectives: This paper aims to validate the performance and physical design of a wearable, unobtrusive ear-centered electroencephalography (EEG) device, dubbed “EARtrodes”, using early and late auditory evoked responses. Results would also offer a proof-of-concept for the device to be used as a concealed brain–computer interface (BCI). Design: The device is composed of a custom-fitted earpiece and an ergonomic behind-the-ear piece with embedded electrodes made of a soft and flexible combination of silicone rubber and carbon fibers. The location of the conductive silicone electrodes inside the ear canal and the optimal geometry of the behind-the-ear piece were obtained through morphological and geometrical analysis of the human ear canal and the region around-the-ear. An entirely conductive generic earpiece was also developed to assess the potential of a universal, more affordable solution. Results: Early latency results illustrate the conductive silicone electrodes’ capability to record quality EEG signals, comparable to those obtained with traditional gold-plated electrodes. Additionally, late latency results demonstrate EARtrodes’ capacity to reliably detect decision-making processes from the ear. Conclusions: EEG results validate the performance of EARtrodes as a circum-aural and intra-aural EEG recording system adapted for a wide range of applications in audiology, neuroscience, clinical research, and as an unobtrusive BCI.
Maneuverability of the Scope and Instruments within Three Different Single-Incision Laparoscopic Ports: An Experimental Pilot Study

Simple Summary Single-port access systems, used to perform endoscopic surgery through a single incision, are currently used in many human and veterinary surgeries. These systems present some technical challenges as they offer limited space for manipulation. No objective study has evaluated the degree of possible movement within different single-port access systems. This study aimed to measure and compare the possible movements of the endoscope and instruments within three single-port access systems: the Covidien SILS-port, Storz Endocone, and glove port. The glove port consists of a surgical glove and an O-ring retractor. A clear acrylic box with artificial skin was used to mimic the abdominal wall and cavity. A motion capture system with 18 cameras was used to trace the possible movements of the endoscope. The volume of the cone-shaped three-dimensional figure described by the scope when circled 360° was used to compare maneuverability across the three systems. The glove port showed higher maneuverability than the two commercially available ports when an endoscope alone, or an endoscope and instrument, was or were inserted. A higher degree of maneuverability is positively associated with easier handling of the endoscope and instruments during surgical procedures. The findings of this study may benefit students and young professionals by helping them to select an easy-to-use single-port access system when beginning single-incision endoscopic surgery. Abstract Single-port access systems (SPASs) are currently used in human and veterinary surgeries. However, they pose technical challenges, such as instrument crowding, intra- and extracorporeal instrument collision, and reduced maneuverability. Studies comparing the maneuverability of the scopes and instruments in different SPASs are lacking. This study aimed to compare the maneuverability of three different SPASs: the Covidien SILS-port, Storz Endocone, and glove port. A clear acrylic box with artificial skin placed at the bottom was used to mimic the abdominal wall and cavity. The three SPASs were placed from below, and a 10-mm endoscope and 5-mm instrument were introduced. A motion analysis system consisting of 18 cameras and motion analysis software were used to track the movement of the endoscope and instrument, to determine the volume of the cone-shaped, three-dimensional figures over which movement was possible, with higher values indicating greater maneuverability. The Mann–Whitney U test was used for the analysis. The maneuverability of the endoscope alone was significantly higher in the glove port system than in the other two SPASs. When inserting an additional instrument, the maneuverability significantly decreased in the SILS-port and Endocone, but not in the glove port. The highest maneuverability overall was found in the glove port.
Comprehensive Stability Study of Vitamin D3 in Aqueous Solutions and Liquid Commercial Products

Vitamin D3 has numerous beneficial effects, such as musculoskeletal, immunomodulatory, and neuroprotective. However, its instability is the main obstacle to formulating quality products. Despite increased attention and growing use, data on vitamin D3 stability is scarce because data from individual studies is inconclusive and mostly qualitative. Therefore, we have systematically investigated the influence of various factors (temperature, light, oxygen, pH, concentration, and metal ions) on its stability in aqueous media using a stability-indicating HPLC-UV method. First-order kinetics fitted its degradation under all tested conditions except light and oxygen. In both cases, the established models in chemical kinetics were inappropriate and upgraded with the Weibull model. Metal ions and acidic conditions had the main destabilizing effect on vitamin D3 in aqueous media, but these solutions were successfully stabilized after the addition of ethylenediaminetetraacetic acid (EDTA), ascorbic acid, and citric acid, individually and in combination. EDTA showed the most significant stabilizing effect. Synergism among antioxidants was not observed. Our findings on vitamin D3 instability in aqueous media also correlated with its instability in commercial products. Vitamin D3 aqueous products require proper stabilization, thereby signifying the importance and contribution of the obtained results to the formulation of stable and quality products.
The Serum Uric Acid Level Is Related to the More Severe Renal Histopathology of Female IgA Nephropathy Patients

Hyperuricemia is a significant risk factor for cardiovascular morbidity and chronic kidney disease progression. IgA nephropathy (IgAN) is a well-known primary glomerular nephropathy. Hyperuricemia is associated with a poor prognosis in IgAN patients. We evaluated the association of hyperuricemia with the histopathological severity of IgAN in male and female patients; 658 patients diagnosed with IgAN via kidney biopsy were initially included. Baseline patient data were collected by eight university hospitals affiliated with the College of Medicine of the Catholic University of Korea. Pathological features were independently evaluated by eight expert pathologists working in the hospitals, and the consensus was reached. Of the initial 658 patients, 517 were finally included (253 males and 264 females). Hyperuricemia was defined as a serum uric acid (UA) level >7.0 mg/dL for males and >5.6 mg/dL for females; 108 (42.7%) males and 95 (35.9%) females exhibited hyperuricemia. Compared to the patients with normal UA levels, the global glomerulosclerosis, segmental sclerosis, mesangial matrix expansion (MME), endocapillary proliferation (ECP), interstitial fibrosis (IF), and tubular atrophy (TA) scores were higher in hyperuricemic males and females. In multivariable linear regression, the serum UA level correlated significantly with the MME, ECP, IF, and TA scores of female IgAN patients only.
A Nonsense Variant in Hephaestin Like 1 (HEPHL1) Is Responsible for Congenital Hypotrichosis in Belted Galloway Cattle

Genodermatosis such as hair disorders mostly follow a monogenic mode of inheritance. Congenital hypotrichosis (HY) belong to this group of disorders and is characterized by abnormally reduced hair since birth. The purpose of this study was to characterize the clinical phenotype of a breed-specific non-syndromic form of HY in Belted Galloway cattle and to identify the causative genetic variant for this recessive disorder. An affected calf born in Switzerland presented with multiple small to large areas of alopecia on the limbs and on the dorsal part of the head, neck, and back. A genome-wide association study using Swiss and US Belted Galloway cattle encompassing 12 cases and 61 controls revealed an association signal on chromosome 29. Homozygosity mapping in a subset of cases refined the HY locus to a 1.5 Mb critical interval and subsequent Sanger sequencing of protein-coding exons of positional candidate genes revealed a stop gain variant in the HEPHL1 gene that encodes a multi-copper ferroxidase protein so-called hephaestin like 1 (c.1684A>T; p.Lys562*). A perfect concordance between the homozygous presence of this most likely pathogenic loss-of-function variant and the HY phenotype was found. Genotyping of more than 700 purebred Swiss and US Belted Galloway cattle showed the global spread of the mutation. This study provides a molecular test that will permit the avoidance of risk matings by systematic genotyping of relevant breeding animals. This rare recessive HEPHL1-related form of hypotrichosis provides a novel large animal model for similar human conditions. The results have been incorporated in the Online Mendelian Inheritance in Animals (OMIA) database (OMIA 002230-9913).
Methods for Pain Assessment in Calves and Their Use for the Evaluation of Pain during Different Procedures—A Review

Simple Summary Pain recognition in calves is difficult. Pain is assessed either subjectively or objectively. Subjective pain assessment can be done using ethograms or pain scales, or by evaluation of changes of the facial expression due to pain. The problem with subjective pain assessment is that the evaluation of the amount of pain a calf is experiencing depends on the evaluation and the experience of the observer. Variables for the objective description of pain are assessment of biomarkers in the blood (e.g., cortisol or substance P), use of algometry to measure mechanical nociceptive thresholds, activity measurements by use of accelerometers and pedometers, use of infrared thermography, and the assessment of heart rate, heart rate variability, feed and water intake, or weight gain. Studies about pain recognition and pain management in calves mostly use more than one variable. Often a combination of subjective and objective measures is used to evaluate the level of pain calves are experiencing and to improve pain recognition. Abstract The evaluation and assessment of the level of pain calves are experiencing is important, as the experience of pain (e.g., due to routine husbandry procedures) severely affects the welfare of calves. Studies about the recognition of pain in calves, and especially pain management during and after common procedures, such as castration, dehorning, and disbudding, have been published. This narrative review discusses and summarizes the existing literature about methods for pain assessment in calves. First, it deals with the definition of pain and the challenges associated with the recognition of pain in calves. Then it proceeds to outline the different options and methods for subjective and objective pain assessment in calves, as described in the literature. Research data show that there are several tools suitable for the assessment of pain in calves, at least for research purposes. Finally, it concludes that for research purposes, various variables for the assessment of pain in calves are used in combination. However, there is no variable which can be used solely for the exclusive assessment of pain in calves. Also, further research is needed to describe biomarkers or variables which are easily accessible in the field practice.
Bioactive Ibuprofen-Loaded PLGA Coatings for Multifunctional Surface Modification of Medical Devices

To modulate the biofunctionality of implantable medical devices commonly used in clinical practice, their surface modification with bioactive polymeric coatings is an attractive and successful emerging strategy. Biodegradable coatings based on poly(lactic acid-co-glycolic acid), PLGA, represent versatile and safe candidates for surface modification of implantable biomaterials and devices, providing additional tunable ability for topical delivery of desired therapeutic agents. In the present study, Ibuprofen-loaded PLGA coatings (PLGA/IBUP) were obtained by using the dip-coating and drop-casting combined protocol. The composite materials demonstrated long-term drug release under biologically simulated dynamic conditions. Reversible swelling phenomena of polymeric coatings occurred in the first two weeks of testing, accompanied by the gradual matrix degradation and slow release of the therapeutic agent. Irreversible degradation of PLGA coatings occurred after one month, due to copolymer’s hydrolysis (evidenced by chemical and structural modifications). After 30 days of dynamic testing, the cumulative release of IBUP was ~250 µg/mL. Excellent cytocompatibility was revealed on human-derived macrophages, fibroblasts and keratinocytes. The results herein evidence the promising potential of PLGA/IBUP coatings to be used for surface modification of medical devices, such as metallic implants and wound dressings.
Use of Anti-Diabetic Agents in Non-Diabetic Kidney Disease: From Bench to Bedside

New drugs were recently developed to treat hyperglycemia in patients with type 2 diabetes mellitus (T2D). However, metformin remains the first-line anti-diabetic agent because of its cost-effectiveness. It has pleiotropic action that produces cardiovascular benefits, and it can be useful in diabetic nephropathy, although metformin-associated lactic acidosis is a hindrance to its use in patients with kidney failure. New anti-diabetic agents, including glucagon-like peptide-1 receptor (GLP-1R) agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium-glucose transporter-2 (SGLT-2) inhibitors, also produce cardiovascular or renal benefits in T2D patients. Their glucose-independent beneficial actions can lead to cardiorenal protection via hemodynamic stabilization and inflammatory modulation. Systemic hypertension is relieved by natriuresis and improved vascular dysfunction. Enhanced tubuloglomerular feedback can be restored by SGLT-2 inhibition, reducing glomerular hypertension. Patients with non-diabetic kidney disease might also benefit from those drugs because hypertension, proteinuria, oxidative stress, and inflammation are common factors in the progression of kidney disease, irrespective of the presence of diabetes. In various animal models of non-diabetic kidney disease, metformin, GLP-1R agonists, DPP-4 inhibitors, and SGLT-2 inhibitors were favorable to kidney morphology and function. They strikingly attenuated biomarkers of oxidative stress and inflammatory responses in diseased kidneys. However, whether those animal results translate to patients with non-diabetic kidney disease has yet to be evaluated. Considering the paucity of new agents to treat kidney disease and the minimal adverse effects of metformin, GLP-1R agonists, DPP-4 inhibitors, and SGLT-2 inhibitors, these anti-diabetic agents could be used in patients with non-diabetic kidney disease. This paper provides a rationale for clinical trials that apply metformin, GLP-1R agonists, DPP-4 inhibitors, and SGLT-2 inhibitors to non-diabetic kidney disease.
Environmental Impact on Seaweed Phenolic Production and Activity: An Important Step for Compound Exploitation

Seaweeds are a potential source of bioactive compounds that are useful for biotechnological applications and can be employed in different industrial areas in order to replace synthetic compounds with components of natural origin. Diverse studies demonstrate that there is a solid ground for the exploitation of seaweed bioactive compounds in order to prevent illness and to ensure a better and healthier lifestyle. Among the bioactive algal molecules, phenolic compounds are produced as secondary metabolites with beneficial effects on plants, and also on human beings and animals, due to their inherent bioactive properties, which exert antioxidant, antiviral, and antimicrobial activities. The use of phenolic compounds in pharmaceutical, nutraceutical, cosmetics, and food industries may provide outcomes that could enhance human health. Through the production of healthy foods and natural drugs, bioactive compounds from seaweeds can help with the treatment of human diseases. This review aims to highlight the importance of phenolic compounds from seaweeds, the scope of their production in nature and the impact that these compounds can have on human and animal health through nutraceutical and pharmaceutical products.