Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential Localization of Structural and Non-Structural Proteins during the Bluetongue Virus Replication Cycle

Members of the Reoviridae family assemble virus factories within the cytoplasm of infected cells to replicate and assemble virus particles. Bluetongue virus (BTV) forms virus inclusion bodies (VIBs) that are aggregates of viral RNA, certain viral proteins, and host factors, and have been shown to be sites of the initial assembly of transcriptionally active virus-like particles. This study sought to characterize the formation, composition, and ultrastructure of VIBs, particularly in relation to virus replication. In this study we have utilized various microscopic techniques, including structured illumination microscopy, and virological assays to show for the first time that the outer capsid protein VP5, which is essential for virus maturation, is also associated with VIBs. The addition of VP5 to assembled virus cores exiting VIBs is required to arrest transcriptionally active core particles, facilitating virus maturation. Furthermore, we observed a time-dependent association of the glycosylated non-structural protein 3 (NS3) with VIBs, and report on the importance of the two polybasic motifs within NS3 that facilitate virus trafficking and egress from infected cells at the plasma membrane. Thus, the presence of VP5 and the dynamic nature of NS3 association with VIBs that we report here provide novel insight into these previously less well-characterized processes.
Recent Progress on the Versatility of Virus-Like Particles

Virus-like particles (VLPs) are multimeric nanostructures composed of one or more structural proteins of a virus in the absence of genetic material. Having similar morphology to natural viruses but lacking any pathogenicity or infectivity, VLPs have gradually become a safe substitute for inactivated or attenuated vaccines. VLPs can achieve tissue-specific targeting and complete and effective cell penetration. With highly ordered epitope repeats, VLPs have excellent immunogenicity and can induce strong cellular and humoral immune responses. In addition, as a type of nanocarrier, VLPs can be used to display antigenic epitopes or deliver small molecules. VLPs have thus become powerful tools for vaccinology and biomedical research. This review highlights the versatility of VLPs in antigen presentation, drug delivery, and vaccine technology.
Interaction between Epithelial Sodium Channel γ-Subunit and Claudin-8 Modulates Paracellular Sodium Permeability in Renal Collecting Duct.

BACKGROUND Water and solute transport across epithelia can occur via the transcellular or paracellular pathways. Tight junctions play a key role in mediating paracellular ion reabsorption in the kidney. In the renal collecting duct, which is a typical absorptive tight epithelium, coordination between transcellular sodium reabsorption and paracellular permeability may prevent the backflow of reabsorbed sodium to the tubular lumen along a steep electrochemical gradient. METHODS To investigate whether transcellular sodium transport controls tight-junction composition and paracellular permeability via modulating expression of the transmembrane protein claudin-8, we used cultured mouse cortical collecting duct cells to see how overexpression or silencing of epithelial sodium channel (ENaC) subunits and claudin-8 affect paracellular permeability. We also used conditional kidney tubule-specific knockout mice lacking ENaC subunits to assess the ENaC's effect on claudin-8 expression. RESULTS Overexpression or silencing of the ENaC γ-subunit was associated with parallel and specific changes in claudin-8 abundance. Increased claudin-8 abundance was associated with a reduction in paracellular permeability to sodium, whereas decreased claudin-8 abundance was associated with the opposite effect. Claudin-8 overexpression and silencing reproduced these functional effects on paracellular ion permeability. Conditional kidney tubule-specific ENaC γ-subunit knockout mice displayed decreased claudin-8 expression, confirming the cell culture experiments' findings. Importantly, ENaC β-subunit or α-subunit silencing or kidney tubule-specific β-ENaC or α-ENaC knockout mice did not alter claudin-8 abundance. CONCLUSIONS Our data reveal the specific coupling between ENaC γ-subunit and claudin-8 expression. This coupling may play an important role in preventing the backflow of reabsorbed solutes and water to the tubular lumen, as well as in coupling paracellular and transcellular sodium permeability.
Pioglitazone and Deoxyribonucleoside Combination Treatment Increases Mitochondrial Respiratory Capacity in m.3243A>G MELAS Cybrid Cells

The lack of effective treatments for mitochondrial disease has seen the development of new approaches, including those that aim to stimulate mitochondrial biogenesis to boost ATP generation above a critical disease threshold. Here, we examine the effects of the peroxisome proliferator-activated receptor γ (PPARγ) activator pioglitazone (PioG), in combination with deoxyribonucleosides (dNs), on mitochondrial biogenesis in cybrid cells containing >90% of the m.3243A>G mutation associated with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). PioG + dNs combination treatment increased mtDNA copy number and mitochondrial mass in both control (CON) and m.3243A>G (MUT) cybrids, with no adverse effects on cell proliferation. PioG + dNs also increased mtDNA-encoded transcripts in CON cybrids, but had the opposite effect in MUT cybrids, reducing the already elevated transcript levels. Steady-state levels of mature oxidative phosphorylation (OXPHOS) protein complexes were increased by PioG + dNs treatment in CON cybrids, but were unchanged in MUT cybrids. However, treatment was able to significantly increase maximal mitochondrial oxygen consumption rates and cell respiratory control ratios in both CON and MUT cybrids. Overall, these findings highlight the ability of PioG + dNs to improve mitochondrial respiratory function in cybrid cells containing the m.3243A>G MELAS mutation, as well as their potential for development into novel therapies to treat mitochondrial disease.
The Coronavirus and the Risks to the Elderly in Long-Term Care

ABSTRACT The elderly in long-term care (LTC) and their caregiving staff are at elevated risk from COVID-19. Outbreaks in LTC facilities can threaten the health care system. COVID-19 suppression should focus on testing and infection control at LTC facilities. Policies should also be developed to ensure that LTC facilities remain adequately staffed and that infection control protocols are closely followed. Family will not be able to visit LTC facilities, increasing isolation and vulnerability to abuse and neglect. To protect residents and staff, supervision of LTC facilities should remain a priority during the pandemic.
Curcumin and Endometriosis

Endometriosis is one of the main common gynecological disorders, which is characterized by the presence of glands and stroma outside the uterine cavity. Some findings have highlighted the main role of inflammation in endometriosis by acting on proliferation, apoptosis and angiogenesis. Oxidative stress, an imbalance between reactive oxygen species and antioxidants, could have a key role in the initiation and progression of endometriosis by resulting in inflammatory responses in the peritoneal cavity. Nevertheless, the mechanisms underlying this disease are still unclear and therapies are not currently efficient. Curcumin is a major anti-inflammatory agent. Several findings have highlighted the anti-oxidant, anti-inflammatory and anti-angiogenic properties of curcumin. The purpose of this review is to summarize the potential action of curcumin in endometriosis by acting on inflammation, oxidative stress, invasion and adhesion, apoptosis and angiogenesis.
Portable Ultrasound-Based Device for Detecting Older Adults’ Sit-to-Stand Transitions in Unsupervised 30-Second Chair–Stand Tests

Lower-limb strength is a marker of functional decline in elders. This work studies the feasibility of using the quasi-periodic nature of the distance between a subjects’ back and the chair backrest during a 30-s chair–stand test (CST) to carry out unsupervised measurements based on readings from a low-cost ultrasound sensor. The device comprises an ultrasound sensor, an Arduino UNO board, and a Bluetooth module. Sit-to-stand transitions are identified by filtering the signal with a moving minimum filter and comparing the output to an adaptive threshold. An inter-rater reliability (IRR) study was carried out to validate the device ability to count the same number of valid transitions as the gold-standard manual count. A group of elders (age: mean (m) = 80.79 years old, SD = 5.38; gender: 21 female and seven male) were asked to perform a 30-s CST using the device while a trained nurse manually counted valid transitions. Ultimately, a moving minimum filter was necessary to cancel the effect of outliers, likely produced because older people tend to produce more motion artefacts and, thus, noisier signals. While the intra-class correlation coefficient (ICC) for this study was good (ICC = 0.86, 95% confidence interval (CI) = 0.73, 0.93), it is not yet clear whether the results are sufficient to support clinical decision-making.
Recent Strategic Advances in CFTR Drug Discovery: An Overview

Cystic fibrosis transmembrane conductance regulator (CFTR)-rescuing drugs have already transformed cystic fibrosis (CF) from a fatal disease to a treatable chronic condition. However, new-generation drugs able to bind CFTR with higher specificity/affinity and to exert stronger therapeutic benefits and fewer side effects are still awaited. Computational methods and biosensors have become indispensable tools in the process of drug discovery for many important human pathologies. Instead, they have been used only piecemeal in CF so far, calling for their appropriate integration with well-tried CF biochemical and cell-based models to speed up the discovery of new CFTR-rescuing drugs. This review will give an overview of the available structures and computational models of CFTR and of the biosensors, biochemical and cell-based assays already used in CF-oriented studies. It will also give the reader some insights about how to integrate these tools as to improve the efficiency of the drug discovery process targeted to CFTR.
A Novel Predictive Model for In-Hospital Mortality Based on a Combination of Multiple Blood Variables in Patients with ST-Segment-Elevation Myocardial Infarction

In emergency clinical settings, it may be beneficial to use rapidly measured objective variables for the risk assessment for patient outcome. This study sought to develop an easy-to-measure and objective risk-score prediction model for in-hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI). A total of 1027 consecutive STEMI patients were recruited and divided into derivation (n = 669) and validation (n = 358) cohorts. A risk-score model was created based on the combination of blood test parameters obtained immediately after admission. In the derivation cohort, multivariate analysis showed that the following 5 variables were significantly associated with in-hospital death: estimated glomerular filtration rate <45 mL/min/1.73 m2, platelet count <15 × 104/μL, albumin ≤3.5 g/dL, high-sensitivity troponin I >1.6 ng/mL, and blood sugar ≥200 mg/dL. The risk score was weighted for those variables according to their odds ratios. An incremental change in the scores was significantly associated with elevated in-hospital mortality (p < 0.001). Receiver operating characteristic curve analysis showed adequate discrimination between patients with and without in-hospital death (derivation cohort: area under the curve (AUC) 0.853; validation cohort: AUC 0.879), and there was no significant difference in the AUC values between the laboratory-based and Global Registry of Acute Coronary Events (GRACE) score (p = 0.721). Thus, our laboratory-based model might be helpful in objectively and accurately predicting in-hospital mortality in STEMI patients.
Clinical Evaluation of the Nasopalatine Canal in Implant-Prosthetic Treatment: A Pilot Study

Implant-prosthetic rehabilitation of missing teeth in the anterior maxilla is often challenging due to ongoing bone resorption and remodeling events and may require regeneration procedures involving the nasopalatine canal (NPC). We describe a surgical approach with a block graft in relation to the NPC and evaluate clinical performance, sensory perception, and aesthetic result of the implant-prosthetic treatment over a two- to nine-year (mean: 3.5 years) follow-up. Ten implants (six in the right central incisor and four in the left central incisor) were, respectively, placed in 10 consecutive patients with bone defects affecting the NPC and unfavorable widening of the incisive foramen. Treatment stages included: (1) Diagnosis: evaluation of clinical-aesthetic parameters using Cone Beam Computed Tomography; (2) Surgery: block graft placement by palatine and incisal with simultaneous guided bone regeneration, and late (6–10 months) implant placement; (3) Prosthetics: placement of a screw-retained crown (torque of 32 N/cm). At treatment initiation, all the NPCs evaluated in our study were free of pathologies. Treatment evaluation included bone crest thickness, neurosensory status, patients’ treatment perception, and pink and white aesthetic scores (PES/WES). Pre-surgery, anterior ridge thickness at the level of the incisive foramen was (mean ± SD) 3.5 ± 2 mm, 5.4 ± 1.5 mm, and 6.1 ± 1.9 mm at heights of 4, 8, and 14 mm apical to the marginal bone crest, respectively. Post-treatment values were, respectively, 10.1 ± 2.0 mm, 10.5 ± 1.0 mm, and 13.4 ± 3.0 mm. The perception of treatment with the aesthetic pink and white indices (PES/WES) was an average of 7.5 and 7 points, respectively, out of a total of 10 each index, with a recovery of 100% of the neurosensory perception of the area. We propose that bone augmentation using block and particulate graft material can compensate for anatomical variations in the NPC, optimize implant’s three-dimensional positioning and improve facial contour, providing tissue and implant stability and good aesthetic outcomes.
Safety and Feasibility of PARP1/2 Imaging with 18F-PARPi in Patients with Head and Neck Cancer

Purpose: We performed a first-in-human clinical trial. The aim of this study was to determine safety and feasibility of PET imaging with 18F-PARPi in patients with head and neck cancer. Patients and Methods: Eleven patients with newly diagnosed or recurrent oral and oropharyngeal cancer were injected with 18F-PARPi (331 ± 42 MBq), and dynamic PET/CT imaging was performed between 0 and 25 minutes postinjection. Static PET/CT scans were obtained at 30, 60, and 120 minutes postinjection. Blood samples for tracer concentration and metabolite analysis were collected. Blood pressure, ECG, oxygen levels, clinical chemistry, and complete blood count were obtained before and after tracer administration. Results: 18F-PARPi was well-tolerated by all patients without any safety concerns. Of the 11 patients included in the analysis, 18F-PARPi had focal uptake in all primary lesions (n = 10, SUVmax = 2.8 ± 1.2) and all 18F-FDG–positive lymph nodes (n = 34). 18F-PARPi uptake was seen in 18F-FDG–negative lymph nodes of 3 patients (n = 6). Focal uptake of tracer in primary and metastatic lesions was corroborated by CT alone or in combination with 18F-FDG. The overall effective dose with 18F-PARPi PET was 3.9 mSv – 5.2 mSv, contrast was high [SUVmax(lesion)/SUVmax(trapezius muscle) = 4.5] and less variable than 18F-FDG when compared with the genioglossus muscle (1.3 vs. 6.0, P = 0.001). Conclusions: Imaging of head and neck cancer with 18F-PARPi is feasible and safe. 18F-PARPi detects primary and metastatic lesions, and retention in tumors is longer than in healthy tissues.
Fungal communities differentially respond to warming and drought in tropical grassland soil

Climate change is predicted to cause more extreme events, such as heatwaves, and different precipitation patterns. The effects of warming and short‐term drought on soil microbial communities, in particular fungal communities, remain largely unexplored under field conditions. Here, we evaluated how the fungal community of a tropical grassland soil responds to these changes. A field experiment was carried out in a temperature free‐air controlled enhancement (T‐FACE) facility in Ribeirão Preto, Brazil. The isolated and combined effects of drought and a 2°C increase in temperature were investigated. Based on metabarcoding of the ITS2 region, a total of 771 operational taxonomic units were observed. While warming affected the community structure, drought affected the alpha diversity, and the interaction between warming and drought affected both diversity and structure. The change in community composition driven by warming affected only the less abundant species (>1% of the total sequences). The aspect of the fungal communities that was most affected was diversity, which was increased by drought (p < .05), mostly by reducing the dominance of a single species, as observed in the watered plots. In a phylogenetic context, some fungal taxa were favoured by changes in temperature (Hypocreales) and drought (Sordariales) or disadvantaged by both (Pleosporales). It was of note that a water deficit increased the abundance of phytopathogenic fungi, such as Curvularia, Thielavia and Fusarium species. Overall, our results provide evidence that fungal communities in tropical grassland soils have greater sensitivity to drought than to temperature, which might increase the incidence of certain soil‐borne diseases.
Enhanced Adsorptive Bioremediation of Heavy Metals (Cd2+, Cr6+, Pb2+) by Methane-Oxidizing Epipelon

Cadmium (Cd), chromium (Cr) and lead (Pb) are heavy metals that have been classified as priority pollutants in aqueous environment while methane-oxidizing bacteria as a biofilter arguably consume up to 90% of the produced methane in the same aqueous environment before it escapes into the atmosphere. However, the underlying kinetics and active methane oxidizers are poorly understood for the hotspot of epipelon that provides a unique micro-ecosystem containing diversified guild of microorganisms including methane oxidizers for potential bioremediation of heavy metals. In the present study, the Pb2+, Cd2+and Cr6+ bioremediation potential of epipelon biofilm was assessed under both high (120,000 ppm) and near-atmospheric (6 ppm) methane concentrations. Epipelon biofilm demonstrated a high methane oxidation activity following microcosm incubation amended with a high concentration of methane, accompanied by the complete removal of 50 mg L−1 Pb2+ and 50 mg L−1 Cd2+ (14 days) and partial (20%) removal of 50 mg L−1 Cr6+ after 20 days. High methane dose stimulated a faster (144 h earlier) heavy metal removal rate compared to near-atmospheric methane concentrations. DNA-based stable isotope probing (DNA-SIP) following 13CH4 microcosm incubation revealed the growth and activity of different phylotypes of methanotrophs during the methane oxidation and heavy metal removal process. High throughput sequencing of 13C-labelled particulate methane monooxygenase gene pmoA and 16S rRNA genes revealed that the prevalent active methane oxidizers were type I affiliated methanotrophs, i.e., Methylobacter. Type II methanotrophs including Methylosinus and Methylocystis were also labeled only under high methane concentrations. These results suggest that epipelon biofilm can serve as an important micro-environment to alleviate both methane emission and the heavy metal contamination in aqueous ecosystems with constant high methane fluxes.
Involvement of Enteric Glia in Small Intestine Neuromuscular Dysfunction of Toll-Like Receptor 4-Deficient Mice

Enteric glial cells (EGCs) influence nitric oxide (NO)− and adenosine diphosphate (ADP)− mediated signaling in the enteric nervous system (ENS). Since Toll-like receptor 4 (TLR4) participates to EGC homoeostasis, this study aimed to evaluate the possible involvement of EGCs in the alterations of the inhibitory neurotransmission in TLR4−/− mice. Ileal segments from male TLR4−/− and wild-type (WT) C57BL/6J mice were incubated with the gliotoxin fluoroacetate (FA). Alterations in ENS morphology and neurochemical coding were investigated by immunohistochemistry whereas neuromuscular responses were determined by recording non-adrenergic non-cholinergic (NANC) relaxations in isometrically suspended isolated ileal preparations. TLR4−/− ileal segments showed increased iNOS immunoreactivity associated with enhanced NANC relaxation, mediated by iNOS-derived NO and sensitive to P2Y1 inhibition. Treatment with FA diminished iNOS immunoreactivity and partially abolished NO− and ADP− mediated relaxation in the TLR4−/− mouse ileum, with no changes of P2Y1 and connexin-43 immunofluorescence distribution in the ENS. After FA treatment, S100β and GFAP immunoreactivity in TLR4−/− myenteric plexus was reduced to levels comparable to those observed in WT. Our findings show the involvement of EGCs in the alterations of ENS architecture and in the increased purinergic and nitrergic-mediated relaxation, determining gut dysmotility in TLR4−/− mice.
Role of Chitin Deacetylase 1 in the Molting and Metamorphosis of the Cigarette Beetle Lasioderma serricorne

Chitin deacetylases (CDAs) are chitin-modifying enzymes known to play vital roles in insect metamorphosis and development. In this study, we identified and characterized a chitin deacetylase 1 gene (LsCDA1) from the cigarette beetle Lasioderma serricorne. LsCDA1 contains a 1614 bp open reading frame encoding a protein of 537 amino acids that includes domain structures typical of CDAs. LsCDA1 was mainly expressed in the late larval and late pupal stages. In larval tissues, the highest level of LsCDA1 was detected in the integument. The expression of LsCDA1 was induced by 20-hydroxyecdysone (20E) in vivo, and it was significantly suppressed by knocking down the expression of ecdysteroidogenesis genes and 20E signaling genes. RNA interference (RNAi)-aided silencing of LsCDA1 in fifth-instar larvae prevented the larval–pupal molt and caused 75% larval mortality. In the late pupal stage, depletion of LsCDA1 resulted in the inhibition of pupal growth and wing abnormalities, and the expression levels of four wing development-related genes (LsDY, LsWG, LsVG, and LsAP) were dramatically decreased. Meanwhile, the chitin contents of LsCDA1 RNAi beetles were significantly reduced, and expressions of three chitin synthesis pathway genes (LsTRE1, LsUAP1, and LsCHS1) were greatly decreased. The results suggest that LsCDA1 is indispensable for larval–pupal and pupal–adult molts, and that it is a potential target for the RNAi-based control of L. serricorne.
Training with blood flow restriction increases femoral artery diameter and thigh oxygen delivery during knee‐extensor exercise in recreationally trained men

Endurance‐type training with blood flow restriction (BFR) increases maximum oxygen uptake ( V̇O2max ) and exercise endurance of humans. However, the physiological mechanisms behind this phenomenon remain uncertain. In the present study, we show that BFR‐interval training reduces the peripheral resistance to oxygen transport during dynamic, submaximal exercise in recreationally‐trained men, mainly by increasing convective oxygen delivery to contracting muscles. Accordingly, BFR‐training increased oxygen uptake by, and concomitantly reduced net lactate release from, the contracting muscles during relative‐intensity‐matched exercise, at the same time as invoking a similar increase in diffusional oxygen conductance compared to the training control. Only BFR‐training increased resting femoral artery diameter, whereas increases in oxygen transport and uptake were dissociated from changes in the skeletal muscle content of mitochondrial electron‐transport proteins. Thus, physically trained men benefit from BFR‐interval training by increasing leg convective oxygen transport and reducing lactate release, thereby improving the potential for increasing the percentage of V̇O2max that can be sustained throughout exercise.