Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of the core motif of the BRCA2 C-terminal RAD51-binding domain by comparing canine and human BRCA2

Mammary tumors are the most common tumors in women and non-spayed female dogs. One of the reasons for mammary tumors is mutations of the tumor suppressor gene, BRCA2. BRCA2 participates in homologous recombination repair by interacting with the RAD51 recombinase. BRCA2 has two RAD51-binding domains, consisting of BRC repeats and the C-terminal RAD51-binding domain, respectively. Although several studies have addressed the function of the C-terminal RAD51-binding domain of human BRCA2, the amino acid sequences required for the RAD51-interaction activity remain unclear. In this study, the C-terminal RAD51-binding domains of canine and human BRCA2 were compared; the canine domain displayed a weaker interaction with RAD51. This difference was attributed to the C-terminal portion of the domain via a comparison between canine and human domains. Furthermore, peptides shorter than those previously reported displayed RAD51-interacting activity, and a core motif of this domain consisting of 25 amino acids was identified. Since a mutation (S3323N) was reported in the core motif of this domain, the effect of this mutation was evaluated. The mutant exhibited similar RAD51-binding activity as that of the wild-type protein, suggesting that the mutation was functionally neutral. These data suggested that the C-terminal portion of the BRCA2 C-terminal RAD51-binding domain influenced its RAD51-interaction activity, and a minimum core motif of 25 amino acids was identified in this domain. These data may help clarify BRCA2 function, as well as the tumorigenic effects of BRCA2 mutation.
Scale‐dependent signatures of local adaptation in a foundation tree species

Understanding local adaptation is critical for conservation management under rapidly changing environmental conditions. Local adaptation inferred from genotype‐environment associations may show different genomic patterns depending on the spatial scale of sampling, due to differences in the slope of environmental gradients and the level of gene flow. We compared signatures of local adaptation across the genome of mountain ash (Eucalyptus regnans) at two spatial scales: A species‐wide data set and a topographically‐complex subregional data set. We genotyped 367 individual trees at over 3700 single‐nucleotide polymorphisms (SNPs), quantified patterns of spatial genetic structure among populations, and used two analytical methods to identify loci associated with at least one of three environmental variables at each spatial scale. Together, the analyses identified 549 potentially adaptive SNPs at the subregion scale, and 435 SNPs at the range‐wide scale. A total of 39 genic or near‐genic SNPs, associated with 28 genes, were identified at both spatial scales, although no SNP was identified by both methods at both scales. We observed that nongenic regions had significantly higher homozygote excess than genic regions, possibly due to selective elimination of inbred genotypes during stand development. Our results suggest that strong environmental selection occurs in mountain ash, and that the identification of putatively adaptive loci can differ substantially depending on the spatial scale of analyses. We also highlight the importance of multiple adaptive genetic architectures for understanding patterns of local adaptation across large heterogenous landscapes, with comparison of putatively adaptive loci among spatial scales providing crucial insights into the process of adaptation.
Forward-focused coping predicts better mental health outcomes in mid- to late-life during the COVID-19 pandemic

Abstract Objectives: Psychosocial stressors associated with the COVID-19 pandemic may increase the risk of depression and anxiety in the general population. Individuals approaching or within older adulthood may be especially vulnerable to these psychosocial stressors and their impact on mental health outcomes. Consequently, there is an urgent need to identify protective factors for older adults. The purpose of the present study was to determine the relative contribution of coping flexibility (CF) and two distinct coping strategies, forward-focused and trauma-focused, on negative affect in persons 50 years of age and older during the COVID-19 pandemic. Method: Data were collected using an online survey, including questions about demographic information, coping, depression, and anxiety. Participants aged 50 and over were included in our analyses of depression (N = 800) and anxiety (N = 638). Results: Both higher CF and higher forward-focused coping predicted lower depression and lower anxiety. In contrast, higher trauma-focused coping predicted slightly higher depressive symptoms but was not a significant predictor of anxiety. Conclusion: Our findings suggest that higher forward-focused coping may serve as a protective factor in older adults during the pandemic and, therefore, may be an effective treatment target for mental health interventions.
Genetic analysis of a potato (Solanum tuberosum L.) breeding collection for southern Colombia using Single Nucleotide Polymorphism (SNP) markers

Detailed knowledge on genetic parameters such as diversity, structure, and linkage disequilibrium (LD) and identification of duplicates in a germplasm bank and/or breeding collection are essential to conservation and breeding strategies in any crop. Therefore, the potato genetic breeding collection at the Universidad de Nariño in Colombia, which is made up of diploid and tetraploid genotypes in two of the more diverse genebanks in the world, was analyzed with 8303 single nucleotide polymorphisms (SNP) from SolCAP version 1. In total, 144 genotypes from this collection were analyzed identifying an 57.2% of the polymorphic markers that allowed establishing two and three subpopulations that differentiated the diploid genotypes from the tetraploids. These subpopulations had high levels of heterozygosity and linkage disequilibrium. The diversity levels were higher in the tetraploid genotypes, while the LD levels were higher in the diploid genotypes. For the tetraploids, the genotypes from Peru had greater diversity and lower linkage disequilibrium than those from Colombia, which had slightly lower diversity and higher degrees of LD. The genetic analysis identified, adjusted and/or selected diploid and tetraploid genotypes under the following characteristics: 1) errors in classification associated with the level of ploidy; 2) presence of duplicates; and 3) genotypes with broad genetic distances and potential use in controlled hybridization processes. These analyses suggested that the potato genetic breeding collection at the Universidad de Nariño has a genetic base with a potential use in breeding programs for this crop in the Department of Nariño, in southern Colombia.
Associations of firearm dealer openings with firearm self-harm deaths and injuries: A differences-in-differences analysis

Background Firearm dealer density is correlated with firearm interpersonal violence, but no quasi-experimental studies have assessed whether changes in dealer density lead to changes in firearm self-harm injuries and deaths. We assessed whether openings of firearm dealers are associated with short-term changes in local firearm self-harm injury rates. Methods We identified 718 openings of firearm dealers in California using licensing data, 2014–2016. We defined exposure regions based on aggregations of zip codes defined by proximity to firearm dealer openings and matched each opening to four control regions on time and determinants of firearm injury. We applied a differences-in-differences approach to compare rates of firearm self-harm, in the month before and after each opening, in places with and without openings. Results Firearm dealer openings were not associated with acute, local changes in firearm self-harm relative to places without openings (ratio of rate ratio: 0.90 [95% CI:0.68–1.19]). Results were robust to numerous sensitivity and secondary analyses. Conclusion We found no associations of firearm dealer openings with acute, localized firearm self-harm deaths and injuries. Our focus on acute, local effects; broad availability of dealers and firearms; durability of firearms; or strong confounding-control may explain these null findings.
Emotion regulation, mindfulness, and self-compassion among patients with borderline personality disorder, compared to healthy control subjects

Objectives Emotion regulation difficulties are a major characteristic of personality disorders. Our study investigated emotion regulation difficulties that are characteristic of borderline personality disorder (BPD), compared to a healthy control group. Methods Patients with BPD (N = 59) and healthy participants (N = 70) filled out four self-report questionnaires (Cognitive Emotion Regulation Questionnaire, Difficulties in Emotion Regulation Scale, Five Facet Mindfulness Questionnaire, Self-Compassion Scale) that measured the presence or lack of different emotion-regulation strategies. Differences between the BPD and the healthy control group were investigated by Multivariate Analysis of Variance (MANOVA) and univariate post-hoc F-test statistics. Results People suffering from BPD had statistically significantly (p<0.05) higher levels of emotional dysregulation and used more maladaptive emotion-regulation strategies, as well as lower levels of mindfulness and self-compassion compared to the HC group. Conclusion In comparison to a healthy control group, BPD patients show deficits in the following areas: mindfulness, self-compassion and adaptive emotion-regulation strategies. Based on these results, we suggest that teaching emotion-regulation, mindfulness, and self-compassion skills to patients can be crucial in the treatment of borderline personality disorder.
The beneficial effects of cinnamon among patients with metabolic diseases: A systematic review and dose-response meta-analysis of randomized-controlled trials

Abstract This systematic review and meta-analysis aims to summarize and conclude the clinical evidence regarding the use of cinnamon among patients with metabolic diseases. A comprehensive literature search without any limitation on language was conducted using the following bibliographical databases: ISI Web of Science, Embase, Scopus, PubMed, and Google Scholar. Search was conducted up to 23 January 2020. A total of 35 clinical trials were included for final analysis. Pooling of results showed a significant reducing effect of cinnamon on total cholesterol (TC) (weighted mean difference (WMD) = −11.67 mg/dL; P = 0.010), triglyceride (TG) (WMD = −16.27 mg/dL; P < 0.001), low density lipoprotein-cholesterol (LDL-C) (WMD = −6.36 mg/dL; P < 0.001), serum glucose (WMD = −11.39 mg/dL; P < 0.001), serum insulin (WMD = −1.27 μIU/mL; P = 0.028), and waist circumstance (WC) (WMD = −1.68 cm; P = 0.016). These lowering effects on TG, TC, LDL-C, and serum glucose levels were robust in studies that used cinnamon supplementation dose ≤1.5 g. Also, our findings of the present meta-analysis showed that cinnamon supplementation could have favorable effects on high density lipoprotein-cholesterol (HDL-C, WMD = 1.35; P = 0.038) as well as systolic (WMD = −3.95 mmHg; P = 0.018) and diastolic (WMD = −3.36; P = 0.001) blood pressure among patients with metabolic diseases. The present meta-analysis suggests that cinnamon might exert beneficial effects on various cardiometabolic risk factors among patients with metabolic diseases.
Reduced Reaction Mechanisms for Methanol-Air Diffusion Flames

Abstract Reduced reaction mechanisms for methanol-air diffusion fiames are developed by systematic reduction of a skeletal mechanism. By examining the magnitude of the net production rates for the intermediate species, it is shown that for stagnation point diffusion flames the steady state assumption is reasonable for CH2OH, HCO, O, OH, H02, and H2O2, but not for CH2O. By eliminating these species from the skeletal mechanism, a five-step reduced mechanism is derived CH3OH + 2H = CH2O + 2H2, (R1) CH2O = CO + H2, (R2) CO + H2O = CO2 + H2,(R3) 2H2 + O, + M = 2H2O + M, (R4)O2 + 3H2 = 2H + 2H2O. (R5) To explore the impact of making the steady state assumption for CH2O, this five-step mechanism is further reduced to four steps by eliminating CH2O from the mechanism. Comparisons of calculated results for the stagnation point diffusion flame show a reasonable agreement among the different mechanisms. However, the four-step mechanism yields peak CH2O concentrations about six limes those predicted by the skeletal m.
Does local injection of reveromycin A inhibit tooth movement without causing systemic side effects?

OBJECTIVE To determine the feasibility of local inhibition of osteoclast activity and control of tooth movement with local intraoral reveromycin A (RMA) injection in model mice for experimental tooth movement. MATERIALS AND METHODS Eight-week-old wild-type mice (n = 6 per group) were divided into four groups consisting of two non-RMA groups that received normal saline for 14 (14-day non-RMA group) or 21 consecutive days (21-day non-RMA group) and 2 RMA groups that received RMA (1.0 mg/kg of weight) for 14 (14-day RMA group) or 21 consecutive days (21-day RMA group). RMA was injected locally into the buccal mucosa of the left first maxillary molar twice daily starting 3 days before placement of the 10-gf Ni-Ti closed coil spring. Tooth movement distance was analysed using micro-computed tomography. The effects on surrounding alveolar bone were evaluated by measuring the ratio of bone surface area to tissue surface area with haematoxylin-eosin-stained sections and counting the number of osteoclasts in periodontal tissue with TRAP-stained sections. Blood tests were performed and bone volume and trabecular separation at the tibial neck were measured to analyse systemic side effects. RESULTS Local RMA injection inhibited tooth movement by 40.6 per cent, promoted alveolar bone volume maintenance by 37.4 per cent, and inhibited osteoclast activity around the tooth root at 21 days by 40.8 per cent. Systemic effects on osteoclasts or osteoblasts were not observed. CONCLUSION Local injection of RMA enabled control of tooth movement without systemic side effects in a mouse model.
Noradrenergic Signaling Disengages Feedforward Transmission in the Nucleus Accumbens Shell

The nucleus accumbens shell (NAcSh) receives extensive monoaminergic input from multiple midbrain structures. However, little is known how norepinephrine (NE) modulates NAc circuit dynamics. Using a dynamic electrophysiological approach with optogenetics, pharmacology, and drugs acutely restricted by tethering (DART), we explored microcircuit-specific neuromodulatory mechanisms recruited by NE signaling in the NAcSh of parvalbumin (PV)-specific reporter mice. Surprisingly, NE had little direct effect on modulation of synaptic input at medium spiny projection neurons (MSNs). In contrast, we report that NE transmission selectively modulates glutamatergic synapses onto PV-expressing fast-spiking interneurons (PV-INs) by recruiting postsynaptically-localized α2-adrenergic receptors (ARs). The synaptic effects of α2-AR activity decrease PV-IN-dependent feedforward inhibition onto MSNs evoked via optogenetic stimulation of cortical afferents to the NAcSh. These findings provide insight into a new circuit motif in which NE has a privileged line of communication to tune feedforward inhibition in the NAcSh. SIGNIFICANCE STATEMENT The nucleus accumbens (NAc) directs reward-related motivational output by integrating glutamatergic input with diverse neuromodulatory input from monoamine centers. The present study reveals a synapse-specific regulatory mechanism recruited by norepinephrine (NE) signaling within parvalbumin-expressing interneuron (PV-IN) feedforward inhibitory microcircuits. PV-IN-mediated feedforward inhibition in the NAc is instrumental in coordinating NAc output by synchronizing the activity of medium spiny projection neurons (MSNs). By negatively regulating glutamatergic transmission onto PV-INs via α2-adrenergic receptors (ARs), NE diminishes feedforward inhibition onto MSNs to promote NAc output. These findings elucidate previously unknown microcircuit mechanisms recruited by the historically overlooked NE system in the NAc.
Effect of fluid resuscitation on acute lung injury in a rat model of sepsis.

AIM Sepsis is a systemic infection reaction and intravascular volume therapy plays a crucial role in it's treatment. Acute respiratory distress syndrome (ARDS) occurs in the lungs, the most affected organ. This study aimed to investigate the different effects of fluid therapy on ARDS caused by sepsis. METHOD To form a sepsis model, cecal ligation and puncture (CLP) procedure were performed on 44 adult rats. Divided into six groups; normal, CLP group, those treated with 40 ml/kg 0.9 % NaCl, 3 % NaCl (hypertonic saline), Ringer Lactate and Hydroxyethyl starch. After 24 hours treatments, histopathological examination of the lungs were done, and the plasma levels of CRP, TNF-α and IL-6 and paO2 were measured. RESULTS The scores of all histological parameters of the group treated with hypertonic saline were significantly lower than of the other groups (p < 0.001). Likewise, according to the arterial blood gas results, paO2 was significantly higher (p < 0.01) in the hypertonic saline group compared to the other groups, and paCO2 was significantly lower (p < 0.01). CRP, TNF-α and IL-6 levels of inflammatory markers were also significantly lower in hypertonic saline groups compared to other groups (p < 0.001). CONCLUSIONS Our study shows that treatment with hypertonic saline reduces the progression of ARDS in sepsis (Tab. 3, Fig. 4, Ref. 49).
Incidence and maternal-fetal risk factors of stillbirth. A population-based historical cohort and a nested casecontrol study.

Background For parents, stillbirth is a tragic experience; thus, identifying the associated risk factors can be beneficial in order to prevent this event. This study aimed to investigate the incidence and risk factors associated with stillbirth. Methods In this historical cohort study, a total of 18,129 birth records were investigated. The outcome variable was having or not having stillbirth. For each case of stillbirth, three live birth infants on the same day and same hospital were selected as controls, which were matched for gestational age. The data were collected using a researcher-made checklist. Finally, data were analyzed using STATA, 13.0 with Cox proportional hazards regression model at the significance level of 0.05. Results The cumulative incidence of stillbirth was 9.48 per 1,000 live births. Based on multivariate Cox regression model, five risk factors for stillbirth were identified, including male gender, fetal diseases, gestational hypertension, gestational diabetes, and maternal hypothyroidism, (all hazard ratios > 1 and p<0.05), and - for the first time in Iran - maternal hypothyroidism, oligohydramnios, and polyhydramnios were shown as risk factors for stillbirth, which were not evaluated in any previous study. Conclusion The findings of this study suggest that some maternal and fetal risk factors can be recognized as predictors of stillbirth, which might help to detect and prevent high-risk parents at early stages in order to avoid adverse health consequences in the mother and her neonate.
Stress and perceived discrimination among the Arab population in Israel: the mediation role of the perceived COVID-19 threat and trust in the healthcare system

ABSTRACT During pandemics, minorities may experience high stress levels, which could harm their mental and physical health. However, to the best of our knowledge, this has not been examined among minorities in Israel during the COVID-19 pandemic. This study, therefore, explores stress among the Arab minority in Israel during the first wave of the COVID-19 outbreak, and its association with the population’s perceived COVID-19 threat, trust in the healthcare system, adherence to preventative guidelines, and perceived discrimination. The study analyzed a cross-sectional online survey of 626 Israeli Arabs. Most participants (65%) reported moderate levels of stress, and 10% reported severe levels. The Bedouin population reported significantly higher levels of stress compared to other minority groups. The participants also reported a high degree of perceived threat, a moderate-to-high level of discrimination, a moderate level of trust in the healthcare system, and very high adherence to guidelines. Hierarchical regression analysis showed that age, religion, trust in the healthcare system, perceived threat, and adherence to guidelines were all significant predictors of stress [F(11,600), p < . 001]. The model explained 24% of the variance in stress. Structural equation modeling (SEM) revealed that the participants’ perceived threat and trust mediated the association between their perceived discrimination and stress [indirect effect = 0.13, SE = 0.03 CI = (0.08, 0.18)], whereby discrimination was negatively associated with trust (β = −0.52), which, in turn, was negatively associated with stress (β = −0.10). Furthermore, discrimination was positively associated with perceived threat (β = 0.21), which, in turn, was positively associated with stress (β = 0.35). Discrimination is an important social determinant of health – especially during health emergencies when trust in healthcare systems and perceived threats are crucial. As such, our findings could assist policymakers in developing fair policies that are tailored to various population groups and that may reduce stress levels among minorities, thereby improving both their mental and physical health.
Grapevine red blotch virus is transmitted by the three-cornered alfalfa hopper in a circulative, nonpropagative mode with unique attributes.

The transmission mode of grapevine red blotch virus (GRBV, genus Grablovirus, family Geminiviridae) by Spissistilus festinus, the three-cornered alfalfa hopper, is unknown. By analogy with other members in the family Geminiviridae, we hypothesized circulative, nonpropagative transmission. Time course experiments revealed GRBV in dissected guts, hemolymph and heads with salivary glands following a 5-, 8- and 10-day exposure to infected grapevines, respectively. After a 15-day acquisition on infected grapevines and subsequent transfer on alfalfa, a non-host of GRBV, the virus titer decreased over time in adult insects, as shown by qPCR. Snap bean proved to be a feeding host of S. festinus and a pseudo-systemic host of GRBV following Agrobacterium tumefaciens-mediated delivery of an infectious clone. The virus was efficiently transmitted by S. festinus from infected snap bean plants to excised snap bean trifoliates (90%) or grapevine leaves (100%) but less efficiently from infected grapevine plants to excised grapevine leaves (10%) or snap bean trifoliates (67%). Transmission of GRBV also occurred transstadially but not via seeds. The virus titer was significantly higher in guts and hemolymph relative to heads with salivary glands, and in adults emanating from third compared with first instars that emerged on infected grapevine plants and developed on snap bean trifoliates. This study demonstrated circulative, nonpropagative transmission of GRBV by S. festinus with an extended acquisition access period compared with other viruses in the family Geminiviridae and marked differences in transmission efficiency between grapevine, the natural host, and snap bean, an alternative herbaceous host.