Miracle-dz/UniFAR-FTUs huggingface dataset:
RhoA/ROCK Regulates Prion Pathogenesis by Controlling Connexin 43 Activity

Scrapie infection, which converts cellular prion protein (PrPC) into the pathological and infectious isoform (PrPSc), leads to neuronal cell death, glial cell activation and PrPSc accumulation. Previous studies reported that PrPC regulates RhoA/Rho-associated kinase (ROCK) signaling and that connexin 43 (Cx43) expression is upregulated in in vitro and in vivo prion-infected models. However, whether there is a link between RhoA/ROCK and Cx43 in prion disease pathogenesis is uncertain. Here, we investigated the role of RhoA/ROCK signaling and Cx43 in prion diseases using in vitro and in vivo models. Scrapie infection induced RhoA activation, accompanied by increased phosphorylation of LIM kinase 1/2 (LIMK1/2) at Thr508/Thr505 and cofilin at Ser3 and reduced phosphorylation of RhoA at Ser188 in hippocampal neuronal cells and brains of mice. Scrapie infection-induced RhoA activation also resulted in PrPSc accumulation followed by a reduction in the interaction between RhoA and p190RhoGAP (a GTPase-activating protein). Interestingly, scrapie infection significantly enhanced the interaction between RhoA and Cx43. Moreover, RhoA and Cx43 colocalization was more visible in both the membrane and cytoplasm of scrapie-infected hippocampal neuronal cells than in controls. Finally, RhoA and ROCK inhibition reduced PrPSc accumulation and the RhoA/Cx43 interaction, leading to decreased Cx43 hemichannel activity in scrapie-infected hippocampal neuronal cells. These findings suggest that RhoA/ROCK regulates Cx43 activity, which may have an important role in the pathogenesis of prion disease.
Food Insecurity and Micronutrient Status among Ghanaian Women Planning to Become Pregnant

We examined the association between food insecurity (FIS) and micronutrient status among Ghanaian women planning to become pregnant. A cross-sectional analysis was completed of 95 women aged 18–35 years, living in the Upper Manya Krobo District in the Eastern Region of Ghana. Questionnaires were administered to collect sociodemographic and food security data; weight and height were measured. Blood was drawn from an antecubital vein; one drop was used to assess hemoglobin via Hemocue. Zinc and copper were analyzed using flame atomic spectrophotometry while iron biomarkers, retinol and 25-hydroxyvitamin D were analyzed using ELISA, ultra-performance liquid chromatography and liquid chromatography-tandem mass spectrometry, respectively. Logistic regression models were used to determine the relationship between food insecurity (FIS) and micronutrient deficiencies. FIS was reported among 23% of the households, while micronutrient deficiencies ranged from 7–28% irrespective of FIS status. Retinol concentrations were negatively associated with FIS (p = 0.043) after controlling for covariates, although levels were within the normal range in both groups. No statistically significant associations between FIS and micronutrient deficiencies were found. Among those with FIS, 59% were deficient in at least one nutrient with 18% deficient in two nutrients. Unmarried women were at higher risk of FIS (p = 0.017) than married women. FIS was associated with retinol concentrations but not other micronutrient biomarkers in Ghanaian women expecting to become pregnant in the next 6 months.
A cell type‐specific expression map of NCoR1 and SMRT transcriptional co‐repressors in the mouse brain

The ability to rapidly change gene expression patterns is essential for differentiation, development, and functioning of the brain. Throughout development, or in response to environmental stimuli, gene expression patterns are tightly regulated by the dynamic interplay between transcription activators and repressors. Nuclear receptor corepressor 1 (NCoR1) and silencing mediator for retinoid or thyroid‐hormone receptors (SMRT) are the best characterized transcriptional co‐repressors from a molecular point of view. They mediate epigenetic silencing of gene expression in a wide range of developmental and homeostatic processes in many tissues, including the brain. For instance, NCoR1 and SMRT regulate neuronal stem cell proliferation and differentiation during brain development and they have been implicated in learning and memory. However, we still have a limited understanding of their regional and cell type‐specific expression in the brain. In this study, we used fluorescent immunohistochemistry to map their expression patterns throughout the adult mouse brain. Our findings reveal that NCoR1 and SMRT share an overall neuroanatomical distribution, and are detected in both excitatory and inhibitory neurons. However, we observed striking differences in their cell type‐specific expression in glial cells. Specifically, all oligodendrocytes express NCoR1, but only a subset express SMRT. In addition, NCoR1, but not SMRT, was detected in a subset of astrocytes and in the microglia. These novel observations are corroborated by single cell transcriptomics and emphasize how NCoR1 and SMRT may contribute to distinct biological functions, suggesting an exclusive role of NCoR1 in innate immune responses in the brain.
Thermosensitive Chitosan–Gelatin–Glycerol Phosphate Hydrogels as Collagenase Carrier for Tendon–Bone Healing in a Rabbit Model

Healing of an anterior cruciate ligament graft in bone tunnel yields weaker fibrous scar tissue, which may prolong an already prolonged healing process within the tendon–bone interface. In this study, gelatin molecules were added to thermosensitive chitosan/β-glycerol phosphate disodium salt hydrogels to form chitosan/gelatin/β-glycerol phosphate (C/G/GP) hydrogels, which were applied to 0.1 mg/mL collagenase carrier in the tendon–bone junction. New Zealand white rabbit’s long digital extensor tendon was detached and translated into a 2.5-mm diameter tibial plateau tunnel. Thirty-six rabbits underwent bilateral surgery and hydrogel injection treatment with and without collagenase. Histological analyses revealed early healing and more bone formation at the tendon–bone interface after collagenase partial digestion. The area of metachromasia significantly increased in both 4-week and 8-week groups after collagenase treatment (p < 0.01). Micro computed tomography showed a significant increase in total bone volume and bone volume/tissue volume in the 8 weeks after collagenase treatment, compared with the control group. Load-to-failure was significantly higher in the treated group at 8 weeks (23.8 ± 8.13 N vs 14.3 ± 3.9 N; p = 0.008). Treatment with collagenase digestion resulted in a 66% increase in pull-out strength. In conclusion, injection of C/G/GP hydrogel with collagenase improves tendon-to-bone healing in a rabbit model.
The associations of CYP19A1 rs700518 polymorphism with bone mineral density and risk of osteoporosis: a meta-analysis

Abstract Osteoporosis is now a worldwide public health problem that seriously endangers human health, but its causes have not yet been fully clarified. Recently, increasing evidence suggested that polymorphisms in CYP19A1 gene were associated with osteoporosis risk and bone mineral density (BMD), but results remained conflicting. We herein performed a meta-analysis based on evidence currently available from the literature to make a more precise estimation of these relationships. The PubMed, Embase, Cochrane library, CNKI (China National Knowledge Infrastructure), and Wan Fang databases were searched for eligible studies. Odds ratio (OR), mean difference (MD), and 95% confidence interval (CI) were applied to assess the strength of these relationships. A total of 8 studies involving 2632 subjects were included in our meta-analysis. We observed that the AG genotype of CYP19A1 rs700518 was significantly associated with lower BMD values of lumbar spine and femoral neck (AG vs. GG: p = .001 and.01, respectively). However, this polymorphism had no obvious impacts on osteoporosis risk according to current available data. In conclusion, the present meta-analysis showed that CYP19A1 rs700518 polymorphism may be a potential candidate biomarker for osteoporosis screening, early diagnosis, and treatment, which will help improve individualized therapy of osteoporosis patients in clinics.
Structure, Function, Diversity, and Composition of Fungal Communities in Rhizospheric Soil of Coptis chinensis Franch under a Successive Cropping System

Soil types and cropping systems influence the diversity and composition of the rhizospheric microbial communities. Coptis chinensis Franch is one of the most important medicinal plants in China. In the current study, we provide detailed information regarding the diversity and composition of rhizospheric fungal communities of the C. chinensis plants in continuous cropping fields and fallow fields in two seasons (winter and summer), using next-generation sequencing. Alpha diversity was higher in the five-year C. chinensis field and lower in fallow fields. Significant differences analysis confirmed more fungi in the cultivated field soil than in fallow fields. Additionally, PCoA of beta diversity indices revealed that samples associated with the cultivated fields and fallow fields in different seasons were separated. Five fungal phyla (Ascomycota, Basidiomycota, Chytridiomycota, Glomeromycota and Mucoromycota) were identified from the soil samples in addition to the unclassified fungal taxa and Cryptomycota, and among these phyla, Ascomycota was predominantly found. FUNGuild fungal functional prediction revealed that saprotroph was the dominant trophic type in all two time-series soil samples. Redundancy analysis (RDA) of the dominant phyla data and soil physiochemical properties revealed the variations in fungal community structure in the soil samples. Knowledge from the present study could provide a valuable reference for solving the continuous cropping problems and promote the sustainable development of the C. chinensis industry.
Acute rule-out of non–ST-segment elevation acute coronary syndrome in the (pre)hospital setting by HEART score assessment and a single point-of-care troponin: rationale and design of the ARTICA randomised trial

Introduction Because of the lack of prehospital protocols to rule out a non-ST-segment elevation acute coronary syndrome (NSTE-ACS), patients with chest pain are often transferred to the emergency department (ED) for thorough evaluation. However, in low-risk patients, an ACS is rarely found, resulting in unnecessary healthcare consumption. Using the HEART (History, ECG, Age, Risk factors and Troponin) score, low-risk patients are easily identified. When a point-of-care (POC) troponin measurement is included in the HEART score, an ACS can adequately be ruled out in low-risk patients in the prehospital setting. However, it remains unclear whether a prehospital rule-out strategy using the HEART score and a POC troponin measurement in patients with suspected NSTE-ACS is cost-effective. Methods and analysis The ARTICA trial is a randomised trial in which the primary objective is to investigate the cost-effectiveness after 30 days of an early rule-out strategy for low-risk patients suspected of a NSTE-ACS, using a modified HEART score including a POC troponin T measurement. Patients are included by ambulance paramedics and 1:1 randomised for (1) presentation at the ED (control group) or (2) POC troponin T measurement (intervention group) and transfer of the care to the general practitioner in case of a low troponin T value. In total, 866 patients will be included. Follow-up will be performed after 30 days, 6 months and 12 months. Ethics and dissemination This trial has been accepted by the Medical Research Ethics Committee region Arnhem-Nijmegen. The results of this trial will be disseminated in one main paper and in additional papers with subgroup analyses. Trial registration number Netherlands Trial Register (NL7148).
Discrimination of various amine vapors by a tri-emissive MOF composite via a combination of three dimensional ratiometric approach and confinement-induced enhancement effect.

Multi-emissive sensors are being actively pursued owning to their ratiometric luminescent detection capability which demonstrates better sensitivity and selectivity than conventional single-emission sensors. Herein we present a trichromatic white-light-emitting MOF composite (Z3) by simultaneously incorporating red/green-emitting platinum/ruthenium complex cations into porous blue-emitting bio-MOF-1 through post-synthetic modification. With the help of three-dimensional (3-D) dual-ratiometric luminescence recognition method, and unique turn on responses of the red emission toward amine compounds (ACs) , including NH3 and aliphatic amines, via confinement-induced luminescence enhancement effect, Z3 can work as a dual-ratiometric luminescent sensor for discrimination 7 out of 11 AC vapors. This work not only provides a new AC sensing mechanism (confinement effect) that can induce "turn on" response but also proves that the accuracy and selectivity of composite sensor can be greatly improved through the combination of 3-D recognition method and the confinement effect. Thus it open up fresh opportunities to develop composite sensors with excellent sensing and differentiating ability.
Group Conflict Questionnaire: Adaptation and Evidences of Validity for Portuguese-Speaking Athletes

This research adapted the Group Conflict Questionnaire (GCQ) into Portuguese and provided evidence for its construct validity. Study 1 included four translators and five academics who developed a Portuguese version of the GCQ (P-GCQ). In this phase, we provided evidence for content and construct validity for the scale and for each item using an expert panel in a pilot study with 20 youth athletes. Study 2 included two participant samples (Sample 1, n = 254; Sample 2, n = 351) of Brazilian youth and adult athletes who completed the adapted P-GCQ, providing evidence for the structural aspect of its construct validity via factor analyses. Study 3 included 162 Brazilian athletes who completed the P-GCQ and a measure of team cohesion, from which we provided further evidence of the P-GCQ’s internal and external construct validity, showing that both task and social cohesion were negatively associated with the athletes’ perceptions of group conflict. Overall, we found that the P-GCQ produces valid and reliable scores for Portuguese-speaking athletes; it may now be used confidently by researchers and practitioners interested in assessing group conflict within this population.
Activation of mTOR Signaling Pathway in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and occurs mainly in patients with liver cirrhosis. The mammalian target of rapamycin (mTOR) signaling pathway is involved in many hallmarks of cancer including cell growth, metabolism re-programming, proliferation and inhibition of apoptosis. The mTOR pathway is upregulated in HCC tissue samples as compared with the surrounding liver cirrhotic tissue. In addition, the activation of mTOR is more intense in the tumor edge, thus reinforcing its role in HCC proliferation and spreading. The inhibition of the mTOR pathway by currently available pharmacological compounds (i.e., sirolimus or everolimus) is able to hamper tumor progression both in vitro and in animal models. The use of mTOR inhibitors alone or in combination with other therapies is a very attractive approach, which has been extensively investigated in humans. However, results are contradictory and there is no solid evidence suggesting a true benefit in clinical practice. As a result, neither sirolimus nor everolimus are currently approved to treat HCC or to prevent tumor recurrence after curative surgery. In the present comprehensive review, we analyzed the most recent scientific evidence while providing some insights to understand the gap between experimental and clinical studies.
A Rapid Robust Method for Subgrouping Non-NF2 Meningiomas According to Genotype and Detection of Lower Levels of M2 Macrophages in AKT1 E17K Mutated Tumours

The majority of meningiomas are grade I, but some grade I tumours are clinically more aggressive. Recent advances in the genetic study of meningiomas has allowed investigation into the influence of genetics on the tumour microenvironment, which is important for tumorigenesis. We have established that the endpoint genotyping method Kompetitive Allele Specific PCR (KASP™) is a fast, reliable method for the screening of meningioma samples into different non-NF2 mutational groups using a standard real-time PCR instrument. This genotyping method and four-colour flow cytometry has enabled us to assess the variability in the largest immune cell infiltrate population, M2 macrophages (CD45+HLA-DR+CD14+CD163+) in 42 meningioma samples, and to suggest that underlying genetics is relevant. Further immunohistochemistry analysis comparing AKT1 E17K mutants to WHO grade I NF2-negative samples showed significantly lower levels of CD163-positive activated M2 macrophages in meningiomas with mutated AKT1 E17K, signifying a more immunosuppressive tumour microenvironment in NF2 meningiomas. Our data suggested that underlying tumour genetics play a part in the development of the immune composition of the tumour microenvironment. Stratifying meningiomas by mutational status and correlating this with their cellular composition will aid in the development of new immunotherapies for patients.
Wing kinematic and aerodynamic compensations for unilateral wing damage in a small phorid fly.

To investigate the way in which very small insects compensate for unilateral wing damage, we measured the wing kinematics of a very small insect, a phorid fly (Megaselia scalaris), with 16.7% wing area loss in the outer part of the left wing and a normal counterpart, and we computed the aerodynamic forces and power expenditures of the phorid flies. Our major findings are the following. The phorid fly compensates for unilateral wing damage by increasing the stroke amplitude and the deviation angle of the damaged wing (the large deviation angle gives the wing a deep U-shaped wing path), unlike the medium and large insects studied previously, which compensate for the unilateral wing damage mainly by increasing the stroke amplitude of the damaged wing. The increased stroke amplitude and the deep U-shaped wing path give the damaged wing a larger wing velocity during its flapping motion and a rapid downward acceleration in the beginning of the upstroke, which enable the damaged wing to generate the required vertical force for weight support. However, the larger wing velocity of the damaged wing also generates larger horizontal and side forces, increasing the resultant aerodynamic force of the damaged wing. Due to the larger aerodynamic force and the smaller wing area, the wing loading of the damaged wing is 25% larger than that of the wings of the normal phorid fly; this may greatly shorten the life of the damaged wing. Furthermore, because the damaged wing has much larger angular velocity and produces larger aerodynamic moment compared with the intact wing of the damaged phorid fly, the aerodynamic power consumed by the damaged wing is 38% larger than that by the intact wing, i.e., the energy distribution between the damaged and intact wings is highly asymmetrical; this may greatly increase the muscle wastage of the damaged side.
Factors associated with intrauterine contraceptive device use among women of reproductive age group in Addis Ababa, Ethiopia: A case control study

Background Intrauterine Contraceptive Device (IUCD) is a highly effective and reversible modern contraceptive, which is still significantly underutilized in Ethiopia. The aim of this study was to identify factors affecting the use of IUCDs among women of reproductive age group in Addis Ababa. Methods Facility-based, unmatched case-control study was employed among randomly selected cases and controls in selected health centers in Addis Ababa from August to October 2017. The cases (n = 128) were women of reproductive age group who were IUCD users and controls (n = 256) were women of reproductive age group who were users of oral or injectable contraceptives during the study period. After randomly selecting two health center from each sub-city the number of cases and controls were equally allocated to each of the selected health centers. In each selected health center, all eligible cases were enrolled consecutively until the sample size was achieved. Two consecutive controls were selected for each case. Data was collected face-to-face by trained nurses by using structured questionnaire. Factors associated with IUCD use were identified by multi-variable binary logistic regression models using the backward conditional stepwise method. Results In the multi-variable analysis, IUCD use was strongly associated with husbands/partners being supportive of IUCD use (Adjusted OR = 13.24, 95% CI; 5.30–33.02), being literate women (Adjusted OR = 5.31, 95% CI; 1.05–26.93), women having a perception of IUCD does not cause infection (Adjusted OR = 4.38, 95% CI; 1.45–13.26) and the source of information about IUCD being mass-media (Adjusted OR = 3.81, 95% CI; 1.49–9.74). Conclusions The findings of the study reinforce the need of husbands/partners involvement in the interventions to enhance utilization of IUCD. Moreover, due attention should also be provided for delivering IUCD-related messages in the public mass-media.
Evolution of Distinct Responses to Low NAD+ Stress by Rewiring the Sir2 Deacetylase Network in Yeasts

Evolutionary adaptation increases the fitness of a species in its environment. It can occur through rewiring of gene regulatory networks, such that an organism responds appropriately to environmental changes. We investigated whether sirtuin deacetylases, which repress transcription and require NAD+ for activity, serve as transcriptional rewiring points that facilitate the evolution of potentially adaptive traits. If so, bringing genes under the control of sirtuins could enable organisms to mount appropriate responses to stresses that decrease NAD+ levels. To explore how the genomic targets of sirtuins shift over evolutionary time, we compared two yeast species, Saccharomyces cerevisiae and Kluyveromyces lactis, that display differences in cellular metabolism and life cycle timing in response to nutrient availability. We identified sirtuin-regulated genes through a combination of chromatin immunoprecipitation and RNA expression. In both species, regulated genes were associated with NAD+ homeostasis, mating, and sporulation, but the specific genes differed. In addition, regulated genes in K. lactis were associated with other processes, including utilization of nonglucose carbon sources, detoxification of arsenic, and production of the siderophore pulcherrimin. Consistent with the species-restricted regulation of these genes, sirtuin deletion affected relevant phenotypes in K. lactis but not S. cerevisiae. Finally, sirtuin-regulated gene sets were depleted for broadly conserved genes, consistent with sirtuins regulating processes restricted to a few species. Taken together, these results are consistent with the notion that sirtuins serve as rewiring points that allow species to evolve distinct responses to low NAD+ stress.