Miracle-dz/UniFAR-FTUs huggingface dataset:
Loss of Nobox prevents ovarian differentiation from juvenile ovaries in zebrafish

Abstract As a species without master sex-determining genes, zebrafish displays high plasticity in sex differentiation, making it an excellent model for studying the regulatory mechanisms underlying gonadal differentiation and gametogenesis. Despite being a gonochorist, zebrafish is a juvenile hermaphrodite that undergoes a special phase of juvenile ovary before further differentiation into functional testis and ovary. The mechanisms underlying juvenile ovary formation and subsequent gonadal differentiation remain largely unknown. In this study, we explored the role of Nobox/nobox (new born ovary homeobox protein), another oocyte-specific transcription factor in females, in early zebrafish gonadogenesis using CRISPR/Cas9 technology. As in mammals, nobox is specifically expressed in zebrafish gonads with a dimorphic pattern at juvenile stage. In contrast to the mutant of figla (factor in the germline alpha, another oocyte-specific transcription factor), the nobox mutants showed formation of typical perinucleolar (PN) follicles at primary growth (PG) stage in juvenile gonads, suggesting occurrence of follicle assembly from cystic oocytes (chromatin nucleolar stage, CN). These follicles, however, failed to develop further to form functional ovaries, resulting in all-male phenotype. Despite its expression in adult testis, the loss of nobox did not seem to affect testis development, spermatogenesis and male spawning. In summary, our results indicate an important role for Nobox in zebrafish ovarian differentiation and early folliculogenesis. Graphical Abstract Using genome-editing method, we demonstrated that Nobox, an oocyte-specific transcriptional factor, plays an essential role in ovarian formation during zebrafish gonadal differentiation and folliculogenesis in females. Although follicles could be seen to some extent in the absence of Nobox, their formation and further development are both retarded.
McvR, a single domain response regulator regulates motility and virulence in the plant pathogen Xanthomonas campestris

Abstract Signal transduction pathways mediated by sensor histidine kinases and cognate response regulators control a variety of physiological processes in response to environmental conditions in most bacteria. Comparatively little is known about the mechanism(s) by which single‐domain response regulators (SD‐RRs), which lack a dedicated output domain but harbour a phosphoryl receiver domain, exert their various regulatory effects in bacteria. Here we have examined the role of the SD‐RR proteins encoded by the phytopathogen Xanthomonas campestris pv. campestris (Xcc). We describe the identification and characterization of a SD‐RR protein named McvR (motility, chemotaxis, and virulence‐related response regulator) that is required for virulence and motility regulation in Xcc. Deletion of the mcvR open reading frame caused reduced motility, chemotactic movement, and virulence in Xcc. Global transcriptome analyses revealed the McvR had a broad regulatory role and that most motility and pathogenicity genes were down‐regulated in the mcvR mutant. Bacterial two‐hybrid and protein pull‐down assays revealed that McvR did not physically interact with components of the bacterial flagellum but interacts with other SD‐RR proteins (like CheY) and the subset of DNA‐binding proteins involved in gene regulation. Site‐directed mutagenesis and phosphor‐transfer experiments revealed that the aspartyl residue at position 55 of the receiver domain is important for phosphorylation and the regulatory activity of McvR protein. Taken together, the findings describe a previously unrecognized class of SD‐RR protein that contributes to the regulation of motility and virulence in Xcc.
Risk-adjusted analysis of survival variability among hospitals treating biliary malignancy

Abstract Biliary tract cancer’s (BTC) treatment main stone for advanced stages is constituted by chemotherapy. Surgical centralization and physicians’ confidence in the use of new technologies and molecular analysis turned out to be of interest and potentially influencing survival. After applying a random-effect model, the relationship between each clinical variable on the main outcome was investigated through multilevel mixed-effects logistic regression. The risk-standardized outcomes were calculated for each centre involved. In the unadjusted cohort the median survival was 8.6 months (95%C.I.: 7.8–9.3) with a 9-month survival rate of 48.3% (95%C.I.: 45.0–51.5). A substantial heterogeneity across hospitals was found (I2: 70.3%). In multilevel mixed effect logistic regression, male, being treated for gallbladder cancer, higher ECOG, increased NLR, CEA and Ca 19.9 and low value of haemoglobin showed to increase the odds for 9-month mortality. The model estimated that the residual variance observed in 9-month mortality was attributable for the 2.6% to the treating hospital. Through a multilevel mixed effect model, average risk-standardized mortality within 9 months was 50.1%. As noticeable, all hospital’s risk-standardized mortality falls within 95%C.I. , thus all participating centres provided similar outcomes when adjusted for patient case-mix. Heterogenicity between hospital did not affect the outcome in term of overall survival.
Research on the evaluation method for modelling and simulation of infrared imaging sensor

The validity of infrared image guidance simulation is determined by the fidelity and the accuracy of modelling and simulation of infrared imaging sensor system, and the research on assessment of modelling and simulation of infrared imaging sensor is important to design and assess the IR system. A method is proposed to evaluate simulation of infrared sensor effect based on full reference quality assessment method, the evaluation index system is established to evaluate simulation fidelity of infrared imaging sensor. The accuracy of irradiance and contrast of infrared simulation image can be assessed with one-dimension histogram analysis, and the spatial correlation of image is assessed with two-dimension histogram analysis, and geometrical and gray distribution characteristics are assessed with fidelity function. With the method, modelling and simulation of infrared imaging sensor can be effectively assessed.
Self-Assessed Severity as a Determinant of Coronavirus Disease 2019 Symptom Specificity: A Longitudinal Cohort Study

Abstract Coronavirus disease 2019 symptom definitions rarely include symptom severity. We collected daily nasal swab samples and symptom diaries from contacts of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) case patients. Requiring ≥1 moderate or severe symptom reduced sensitivity to predict SARS-CoV-2 shedding from 60.0% (95% confidence interval [CI], 52.9%−66.7%) to 31.5% (95% CI, 25.7%− 38.0%) but increased specificity from 77.5% (95% CI, 75.3%−79.5%) to 93.8% (95% CI, 92.7%−94.8%).
Does a school snack make a difference? An evaluation of the World Food Programme emergency school feeding programme in Lebanon among Lebanese and Syrian refugee children

Abstract Objective: To investigate the effects of providing a daily healthy school snack on children’s nutritional, social and educational outcomes and explore stakeholders’ perceptions of an emergency school feeding programme (SFP). Design: Convergence triangulation mixed-methods study design. Associations were examined between receiving the school feeding intervention and children’s outcomes using multivariable regression models. Quantitative data were complemented with interviews and focus group discussions with parents and staff. Setting: In vulnerable communities in Lebanon, the World Food Programme has implemented an emergency SFP targeting Lebanese (attending morning sessions) and Syrian refugee children (attending afternoon sessions) in public schools. Participants: Children from ten intervention schools (morning n 403; afternoon n 379) and ten matched control schools (morning n 399; afternoon n 401), as well as twenty-nine parents and twenty-two school staff members. Results: Diet diversity was higher in intervention schools as compared with control with a significantly higher consumption of dairy products, nuts and fruit in both sessions. Child-reported food insecurity experience was lower in children attending the afternoon session of intervention v. control schools. The SFP intervention was associated with higher school engagement and sense of school community in the morning session only. While the SFP was significantly associated with higher attendance for children in afternoon sessions only, it was significantly associated with school retention of children in both sessions. Conclusions: A daily healthy snack potentially acts as an incentive to improve children’s nutritional outcomes, school engagement, sense of belonging, equality between students and improvement in children’s attendance and retention in public schools.
Neural correlates of negative emotion processing in subthreshold depression

Abstract Subthreshold depression (SD) is regarded as a major risk factor for major depression. However, little is known about the neural mechanism of negative emotion processing in SD. The study aimed to examine the different neural correlates for negative emotion processing in SD and health controls (HCs) and to investigate changes in functional connectivity in SD compared with HC. Blood oxygenation level-dependent (BOLD) responses of SD and HC were captured while performing a passive viewing task, which comprised a negative condition and a masked condition. A total of 42 SD and 32 HC adolescents participated in the study. Between-group comparisons revealed significant reduced activations in the superior frontal gyrus (SFG), middle frontal gyrus and middle cingulate gyrus. Region of interest (ROI) analyses did not find correlations between contrast values of the ROIs and depressive symptoms. In addition, we found a significant increased functional connectivity between the SFG and caudate, pallidum and insula, which was significantly correlated with depressive symptoms in the SD group (P < 0.05). Altered functional connectivity between the SFG and caudate, pallidum and insula may underlie the pathology of SD. This is the first study to investigate neural mechanisms of negative emotion processing in SD using task-based functional magnetic resonance imaging.
Selection signatures of Qinchuan cattle based on whole-genome sequences

Abstract Qinchuan cattle has gradually improved in body shape and growth rate in the long-term breeding process from the draft cattle to beef cattle. As the head of the five local yellow cattle in China, the Qinchuan cattle has been designated as a specialized beef cattle breed. We investigated the selection signatures using whole genome sequencing data in Qinchuan cattle. Based on Fst, we detected hundreds of candidate genes under selection across Qinchuan, Red Angus, and Japanese Black cattle. Through protein-protein interaction analysis and functional annotation of candidate genes, the results revealed that KMT2E, LTBP1 and NIPBL were related to brain size, body characteristics, and limb development, respectively, suggesting that these potential genes may affect the growth and development traits in Qinchuan cattle. ARIH2, DACT1 and DNM2, et al. are related to meat quality. Meanwhile, TBXA2R can be used as a gene associated with reproductive function, and USH2A affect coat color. This provided a glimpse into the formation of breeds and molecular genetic breeding. Our findings will promote genome-assisted breeding to improve animal production and health.
Divergence in Heliconius flight behaviour is associated with local adaptation to different forest structures.

1. Micro-habitat choice plays a major role in shaping local patterns of biodiversity. In butterflies, stratification in flight height has an important role in maintaining community diversity. Despite its presumed importance, the role of behavioural shifts in early stages of speciation in response to differences in habitat structure is yet to be established. 2. Here, we investigated variation in flight height behaviour in two closely related Heliconius species, H. erato cyrbia and H. himera, which produce viable hybrids but are isolated across an environmental gradient, spanning lowland wet forest to high altitude scrub forest. Speciation in this pair is associated with strong assortative mating, but ecological isolation and local adaptation are also considered essential for complete reproductive isolation. 3. We quantified differences in flight height and forest structure across the environmental gradient and test the importance of resource distribution in explaining flight behaviour. We then use common garden experiments to test whether differences in flight height reflect individual responses to resource distribution or genetically determined shifts in foraging behaviour. 4. We found that the two species fly at different heights in the wild, and demonstrate that this can be explained by differences in the vertical distribution of plant resources. In both the wild and captivity, H. himera choose to fly lower and feed at lower positions, closely mirroring differences in resource availability in the wild. 5. Given expectations that foraging efficiency contributes to survival and reproductive success, we suggest that foraging behaviour may reflect local adaptation to divergent forest structures. Our results highlight the potential role of habitat-dependent divergence in behaviour during the early stages of speciation.
Construction and performance of exendin-4-loaded chitosan–PLGA microspheres for enhancing implant osseointegration in type 2 diabetic rats

Abstract The updating and optimization of drug delivery systems is critical for better in vivo behaviors of drugs, as well as for improving impaired implant osseointegration in diabetes. Numerous studies have reported the benefits of exendin-4 on diabetic bone, with the potential to enhance osseointegration in diabetes. To construct an appropriate sustained-release system of exendin-4 targeting implant osseointegration in diabetes, this study fabricated exendin-4-loaded microspheres using poly(lactic-co-glycolic acid) (PLGA) and chitosan. The morphology, size, encapsulation efficiency, and drug release behavior of microspheres were investigated. The bioactivity of drug-loaded microspheres on cell proliferation and osteogenic differentiation of diabetic BMSCs was investigated to examine the pharmacologic action of exendin-4 loaded into chitosan–PLGA microspheres. Further, the influence of microspheres on osseointegration was evaluated using type 2 diabetes mellitus (T2DM) rat implant model. After 4 weeks, the samples were evaluated by radiological and histological analysis. The results of in vitro experiments showed that the prepared exendin-4-loaded chitosan–PLGA microspheres have good properties as a drug delivery system, and the chitosan could improve the encapsulation efficiency and drug release of PLGA microspheres. In addition, exendin-4-loaded microspheres could enhance the proliferation and osteogenic differentiation of diabetic BMSCs. The results of in vivo experiments showed the exendin-4-loaded microspheres significantly improved the impaired osseointegration and bone formation around implants in T2DM rats without affecting blood glucose levels. Thus, the local application of exendin-4-loaded chitosan–PLGA microspheres might be a promising therapeutic strategy for improving the efficacy of dental implants in T2DM individuals.
High throughput virtual screening and molecular dynamics simulation analysis of phytomolecules against BfmR of Acinetobacter baumannii: anti-virulent drug development campaign

Abstract Acinetobacter baumannii is a notorious multidrug resistant bacterium responsible for several hospital acquired infections assisted by its capacity to develop biofilms. A. baumannii BfmR (RstA), a response regulator from the BfmR/S two-component signal transduction system, is the major controller of A. baumannii biofilm development and formation. As a result, BfmR represents a novel target for anti-biofilm treatment against A. baumannii. The discovery of the high-resolution crystal structure of BfmR provides a good chance for computational screening of its probable inhibitors. Therefore, in this study we aim to search new, less toxic, and natural BfmR inhibitors from 8450 phytomolecules available in the Indian Medicinal Plants, Phytochemistry and Therapeutic (IMPPAT) database by analyzing molecular docking against BfmR (PDB ID: 6BR7). Out of these 8450 phytomolecules 6742 molecules were successfully docked with BfmR with the docking score range −6.305 kcal/mol to +5.120 kcal/mol. Structure based-molecular docking (SB-MD) and ADMET (absorption, distribution, metabolism, excretion, & toxicity) profile examination revealed that Norepinephrine, Australine, Calystegine B3, 7,7 A-Diepialexine, and Alpha-Methylnoradrenaline phytocompounds strongly binds to the active site residues of BfmR. Furthermore, molecular dynamics simulation (MDS) studies for 100 ns and the binding free energy (MM/GBSA) analysis elucidated the binding mechanism of Calystegine B3, 7,7 A-Diepialexine, and Alpha-Methylnoradrenaline to BfmR. In summary, these phytocompounds seems to have the promising molecules against BfmR, and thus necessitates further verification by both in vitro and in vivo experiments. Highlights BfmR plays a key role in biofilm development and exopolysaccharide (EPS) synthesis in A. baumannii. Computational approach to search for promising BfmR inhibitors from IMPAAT database. The lead phytomolecules such as Calystegine B3, 7,7 A-Diepialexine, and Alpha-Methylnoradrenaline displayed significant binding with BfmR active site. The outcome of BfmR binding phytomolecules has broadened the scope of hit molecules validation. Communicated by Ramaswamy H. Sarma
Staying connected in old age: associations between bonding social capital, loneliness and well-being and the value of digital media

Abstract Objectives We examined associations between age, bonding social capital (BSC), loneliness and psychological, social and emotional well-being in old age. As in theory digital media can support both preservation of and access to someone’s social capital, we also explored associations between the use of WhatsApp, social network sites (SNS) and Internet applications and respectively BSC and loneliness. Method In this cross-sectional study a sample of 349 older adults (range = 70y–93y; Mean(SD)=74.8y(4.9y); 59.6% male) filled out a questionnaire including the bonding social capital subscale of the personal social capital scale for elderly (PSCSE), validated scales measuring social, emotional, and psychological well-being and loneliness, the SNS intensity scale and items measuring frequencies of Whatsapp use and use of various Internet functions. Also relevant demographic and other covariates were included. Results Regression analyses including relevant covariates confirmed our hypotheses, finding negative associations between BSC and both age and loneliness, and positive associations between BSC and psychological, social and emotional well-being. WhatsApp and Internet use were both found positively associated with BSC, whilst a negative association between WhatsApp use and loneliness was found. SNS use was not associated with BSC nor with loneliness. Conclusion Our findings indicate BSC as an important factor in positive aging and illustrate a widening gap between the need for socio-emotional resources versus their availability. With regard to digital media, we conclude that its value in old age should be sought in providing access to one’s bonding social capital rather than adding to it by expanding the number of social relations.
The impact of COVID-19 lockdown on the general health status of people with chronic health conditions in Belgium: a cross-sectional survey study

ABSTRACT Background Patients with chronic health conditions risk aggravation of their health status due to reduced access to health services during the COVID-19 related lockdown. Objectives To investigate the impact of Belgian COVID-19 measures on general health status (i.e. worse or stable/better) of patients, adult and pediatric, with chronic health conditions and how this change in health status relates to personal and health behavior-related factors. Design A cross-sectional study using an online survey was conducted during the first COVID-19 related lockdown in Belgium. Methods Associations between change in health status since the lockdown and (change in) personal and health behavior-related factors (including physical activity, access to health-care services and social activities) were investigated. Results In adults (n = 561), almost all personal factors, including feelings of distress, depression, anxiety, somatization, and low self-efficacy, were significantly worse in patients with a worse health status during the lockdown (n = 293, 52%) compared to patients reporting a stable/better health status (p < .001–0.002). Also, these patients reported lower physical activity levels, more tele-consultations and less social activities (p < .001–0.006). In children (n = 55), all surveys were completed by a proxy (parent(s)/guardian) who reported a worse health status in 38% of the children. Level of distress of the child (p = .005) since the lockdown and somatization of the parent(s) (p = .0018) were significantly worse in children with a worse versus a stable/better health status. Conclusion Fifty-two percent of the adults and 38% of children with chronic health conditions reported worsening of their general health status during the lockdown in March–May 2020 in Belgium. Negative personal factors and unhelpful health behavior seems to be associated with a worse health status.