Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel polyadenylylation-dependent neutralization mechanism of the HEPN/MNT toxin/antitoxin system

Abstract The two-gene module HEPN/MNT is predicted to be the most abundant toxin/antitoxin (TA) system in prokaryotes. However, its physiological function and neutralization mechanism remains obscure. Here, we discovered that the MntA antitoxin (MNT-domain protein) acts as an adenylyltransferase and chemically modifies the HepT toxin (HEPN-domain protein) to block its toxicity as an RNase. Biochemical and structural studies revealed that MntA mediates the transfer of three AMPs to a tyrosine residue next to the RNase domain of HepT in Shewanella oneidensis. Furthermore, in vitro enzymatic assays showed that the three AMPs are transferred to HepT by MntA consecutively with ATP serving as the substrate, and this polyadenylylation is crucial for reducing HepT toxicity. Additionally, the GSX10DXD motif, which is conserved among MntA proteins, is the key active motif for polyadenylylating and neutralizing HepT. Thus, HepT/MntA represents a new type of TA system, and the polyadenylylation-dependent TA neutralization mechanism is prevalent in bacteria and archaea.
Can soy isoflavones plus soy protein change serum levels of interlukin‐6? A systematic review and meta‐analysis of randomized controlled trials

In the present review, we aimed to summarize the effect of soy isoflavones plus soy protein on circulating interlukin‐6 (IL‐6) in adult participants. Databases including ISI Web of Science, PubMed, Scopus, Cochrane Library, and clinicaltrials.gov were searched up to 23 March 2020. The mean change from baseline of IL‐6 concentrations and its SD for intervention and comparison groups were used to calculate the effect size. If the heterogeneity test was statistically significant, DerSimonian and Laird random effects model was used. Cochran's Q test and I‐squared statistic were also used to compute the statistical heterogeneity of the intervention's effects. Eighteen studies were known to be eligible for systematic review and 14 studies were selected for meta‐analysis. Our meta‐analysis results indicated a non‐significant effect in serum IL‐6 concentrations compared to the comparison group (WMD = 0.03 pg/ml, 95% CI: −0.06, 0.12; p = .459). In subgroup analysis, based on soy isoflavones dosage, it was observed that this combination could reduce IL‐6 levels in studies that used isoflavones with dose >84 mg/day (WMD = −0.12 pg/ml 95% CI: −0.24, −0.004; p = .042, I2 = 82.7%) and in articles with a good quality (WMD = −0.15 pg/ml 95% CI: −0.24, −0.05; p = .003, I2 = 62.3%). Performing well‐designed intervention studies using a high dose of soy isoflavones is recommended to confirm the beneficial effects of soy ingredients on IL‐6.
MiR‐140‐5p promotes osteogenic differentiation of mouse embryonic bone marrow mesenchymal stem cells and post‐fracture healing of mice

MiR‐140‐5p is high expressed in normal fracture healing, but its specific role and mechanism in tissue‐to‐bone healing are rarely reported. Therefore, this study investigated the effects of miR‐140‐5p on tissue‐to‐bone healing. Clone formation experiment, flow cytometry, Alizarin Red S Staining and Oil Red O Staining were performed to investigate the biological characteristics of mouse embryonic bone marrow mesenchymal stem cells C3H10T1/2. MiR‐140‐5p mimic was transfected into osteogenic medium (OS)‐treated C3H10T1/2 cells to investigate the effects of miR‐140‐5p on osteogenic differentiation. MiR‐140‐5p transgenic mouse model and the transgenic fracture model were established, and the effects of miR‐140‐5p on osteogenic differentiation, bone mineral density (BMD) and bone mass of bone tissues were detected by haematoxylin and eosin staining and computed tomography scan. The expressions of osteocalcin, differentiation‐related genes (Runx2, ALP, Spp1 and Bglap3) and miR‐140‐5p were determined by quantitative real‐time polymerase chain reaction. C3H10T1/2 cells showed the abilities of forming cloned differentiation of osteogenesis, fat cells, and its phenotypes including CD44, CD90.1 and Sca‐1 but excluding CD45 haematopoietic stem cell marker. Overexpression of miR‐140‐5p promoted the expressions of differentiation‐related genes and calcium deposition of OS‐treated C3H10T1/2 cells. MiR‐140‐5p increased the expression of osteocalcin, BMD and bone mass and promoted bone healing of miR‐140‐5p‐transgenic mice with fracture. MiR‐140‐5p promoted osteogenic differentiation of mouse embryonic bone marrow mesenchymal stem cells and post‐fracture healing in mice.
Abundance of Indo-Pacific bottlenose dolphins (Tursiops aduncus) along the south coast of South Africa

Coastally distributed dolphin species are vulnerable to a variety of anthropogenic pressures, yet a lack of abundance data often prevents data-driven conservation management strategies from being implemented. We investigated the abundance of Indo-Pacific bottlenose dolphins (Tursiops aduncus) along the south coast of South Africa, from the Goukamma Marine Protected Area (MPA) to the Tsitsikamma MPA, between 2014 and 2016. During this period, 662.3h of boat-based photo-identification survey effort was carried out during 189 surveys. The sighting histories of 817 identified individuals were used to estimate abundance using capture-recapture modelling. Using open population (POPAN) models, we estimated that 2,155 individuals (95% CI: 1,873–2,479) occurred in the study area, although many individuals appeared to be transients. We recorded smaller group sizes and an apparent decline in abundance in a subset of the study area (Plettenberg Bay) compared to estimates obtained in 2002–2003 at this location. We recorded declines of more than 70% in both abundance and group size for a subset of the study area (Plettenberg Bay), in relation to estimates obtained in 2002–2003 at this location. We discuss plausible hypotheses for causes of the declines, including anthropogenic pressure, ecosystem change, and methodological inconsistencies. Our study highlights the importance of assessing trends in abundance at other locations to inform data-driven conservation management strategies of T. aduncus in South Africa.
Severity and Consolidation Quantification of COVID-19 From CT Images Using Deep Learning Based on Hybrid Weak Labels

Early and accurate diagnosis of Coronavirus disease (COVID-19) is essential for patient isolation and contact tracing so that the spread of infection can be limited. Computed tomography (CT) can provide important information in COVID-19, especially for patients with moderate to severe disease as well as those with worsening cardiopulmonary status. As an automatic tool, deep learning methods can be utilized to perform semantic segmentation of affected lung regions, which is important to establish disease severity and prognosis prediction. Both the extent and type of pulmonary opacities help assess disease severity. However, manually pixel-level multi-class labelling is time-consuming, subjective, and non-quantitative. In this article, we proposed a hybrid weak label-based deep learning method that utilize both the manually annotated pulmonary opacities from COVID-19 pneumonia and the patient-level disease-type information available from the clinical report. A UNet was firstly trained with semantic labels to segment the total infected region. It was used to initialize another UNet, which was trained to segment the consolidations with patient-level information using the Expectation-Maximization (EM) algorithm. To demonstrate the performance of the proposed method, multi-institutional CT datasets from Iran, Italy, South Korea, and the United States were utilized. Results show that our proposed method can predict the infected regions as well as the consolidation regions with good correlation to human annotation.
Effects of Acute Exercise on Drug Craving, Self-Esteem, Mood, and Affect in Adults with Polysubstance Use Disorder: Protocol for a Multicenter Randomized Controlled Trial

Background Novel treatments for substance use disorders are needed. Acute bouts of exercise can improve mood states and craving in nonclinical populations. Exercise effects in those with polysubstance dependence are understudied; controlled trials are needed. Objective This protocol describes a clinical study examining the short-term psychological effects of 2 types of physical activity, soccer and circuit training, in patients with substance use disorders. Effects will be compared with a nonexercise control group. Specific aims are to investigate whether there are differences between the activities and the duration of changes. Methods This study is a short-term multicenter randomized control trial with a crossover design. Patients consecutively admitted to 4 inpatient treatment centers were invited to participate in 3 conditions, each lasting 45 minutes, within one week. The order of the conditions was randomized. There were a total of 5 assessments, taken at baseline, immediately before each condition, immediately after each condition, and 1, 2, and 4 hours postintervention, enabling patterns of change over time to be observed. Psychological effects were assessed with self-report questionnaires, which included scales for craving, state anxiety, positive and negative affect, self-esteem, and mood. Exercise intensity was assessed with the Borg Rating of Perceived Exertion scale and a heart rate monitor (Polar M200; Polar Electro Ltd). Cortisol was assessed in saliva before and 4 hours after the intervention. Results A total of 39 patients were included in the study. Data collection was completed in 2019. Conclusions We anticipate larger improvements in the intervention groups than among controls, indicating positive psychological effects during and after exercise. The study will add clinically relevant information about the short-term psychological effects of exercise in the treatment of substance use disorders, using activities that are easily accessible in different clinical settings. Trial Registration German Clinical Trials Register DRKS00018869; https://www.drks. de/drks_web/navigate.do? navigationId=trial.HTML&TRIAL_ID=DRKS00018869 International Registered Report Identifier (IRRID) DERR1-10.2196/18553
Transcription cofactor GRIP1 differentially affects myeloid cell–driven neuroinflammation and response to IFN-β therapy

Mimouna et al. use functional and transcriptomic approaches in a mouse model of multiple sclerosis to show that a transcriptional coregulator, GRIP1, known for anti-inflammatory actions, promotes macrophage- and microglia-driven neuroinflammation but also mediates therapeutic efficacy of type I IFN.
In vitro evaluation of the effect of different disinfectants on the biofilm of Staphylococcus epidermidis and Staphylococcus aureus formed on acrylic ocular prostheses

The aim of this study was to evaluate the effect of disinfectants on the biofilm of Staphylococcus aureus and Staphylococcus epidermidis formed on the acrylic surface of ocular prostheses. In this study, 396 acrylic specimens were manufactured (50% for Staphylococcus epidermidis, and 50% for Staphylococcus aureus). For each bacterium, 66 specimens were subjected to biofilm formation on their surfaces for 24 hours, 66 specimens were subjected to biofilm formation on their surfaces for 48 hours, and 66 specimens were subjected to biofilm formation on their surfaces for 72 hours. Then, they were divided into groups according to disinfection method (n = 6): sterile distilled water for 10, 15, 30 min, and 6 hours (control); soap for 30 min (NES30); Opti-Free for 30 min (OPF30) and 6 h (OPF6); Efferdent for 15 min (EFF15); and 0.5%, 2%, and 4% chlorhexidine for 10 min (0.5% CHX10, 2% CHX10, and 4% CHX10). After the treatments, the specimens were vortexed to release the biofilm and the counting of bacterial colonies was performed (CFU/mL). Three-way ANOVA and the Tukey-Kramer HSD test were used (α = 0.05). For Staphylococcus epidermidis, there was no significant difference between NES30, OPF30, and OPF6 with their respective control groups; nor between NES30, OPF30, and OPF6 themselves, regardless of the biofilm development period (P >0.05). For Staphylococcus aureus, there was no significant difference between NES30 and OPF30 with their control group; nor between NES30 and OPF30 themselves, regardless of the biofilm development period (P >0.05). For Staphylococcus aureus, OPF6 showed a significant reduction in the number of CFU/mL when compared with its control group, NES30, and OPF30, regardless of the biofilm development period (P <0.05). For both bacteria, 0.5% CHX10, 2% CHX10,4% CHX10, and EFF15 showed a significant reduction in the number of CFU/mL when compared with their control groups, NES30, OPF30, and OPF6, regardless of the biofilm development period (P <0.05). Therefore, EFF15 and CHX (0.5%, 2% and 4%) were effective in reducing Staphylococcus epidermidis and Staphylococcus aureus on acrylic surfaces. NES30 and OPF (30 and 6) are not recommended.
Influência de técnicas de enriquecimento ambiental no aumento do bem-estar de Callithrix penicillata (E. Geoffroy, 1812) (Primates: Callitrichidae)

Este estudo aplicou tecnicas de enriquecimento ambiental em um grupo cativo de Callithrix penicillata (saguis-de-tufos-pretos) com o objetivo de aumentar o bem-estar desses animais. O enriquecimento foi realizado com seis animais, tres machos e tres femeas, do Zoologico do Parque Municipal do Sabia (Uberlândia, MG, Brasil). Os dados foram coletados em tres fases, pre-enriquecimento, enriquecimento e pos-enriquecimento, cada uma com 40h de observacoes quantitativas. Foram utilizados dois modelos de enriquecimento sensorial e quatro modelos de enriquecimento alimentar. A resposta comportamental ao enriquecimento foi positiva. Foi observado aumento em alguns comportamentos, como exploratorios, de forrageio, sociais e territoriais, ao passo que outros diminuiram como os estereotipos (indicativos de estresse). Durante e apos o enriquecimento houve exibicao de comportamentos antes nao expressos, principalmente os relacionados a reproducao e socializacao. As mudancas comportamentais observadas indicam que o enriquecimento promoveu uma melhora na qualidade de vida dos animais.
Sex/gender modifies the association between the MC4R p.Ile269Asn mutation and type 2 diabetes in the Mexican population.

CONTEXT Studies in mice and humans suggest that melanocortin-4 receptor (MC4R) deficiency impacts body weight in a sex/gender-dependent manner. However, similar evidence for type 2 diabetes (T2D) is scarce. OBJECTIVE AND DESIGN We investigated whether sex/gender modifies the association between the loss-of-function MC4R p.Ile269Asn mutation and T2D in 6,929 Mexican adults (3,175 T2D cases and 3,754 normal glucose tolerance (NGT) controls). The 2003 American Diabetes Association criteria were used to define NGT and T2D. The MC4R p.Ile269Asn mutation was genotyped in all participants using the TaqMan technology. RESULTS The MC4R p.Ile269Asn mutation was associated with T2D in 6,929 Mexican adults (Ncontrols=3,754, Ncases=3,175, odds ratio (OR)=2.00, 95% confidence interval (CI) [1.35-2.97], p=5.7x10 -4). The MC4R p.Ile269Asn mutation had a frequency of 0.86 and 1.05% in women with NGT and T2D, and 0.78 and 1.32% in men with NGT and T2D, respectively. We identified a significant interaction between the MC4R p.Ile269Asn mutation and sex/gender on T2D risk (p=0.049). While a strong association between the mutation and T2D was observed in men (Ncontrols=2,418, Ncases=1,807, OR=2.63, 95%CI [1.62-4.28], p=9.3x10 -5), results were not significant in women (Ncontrols=1,336, Ncases=1,368, OR=1.16, 95%CI [0.60-2.26], p=0.65). Further adjustment for body mass index in the logistic regression model did not alter the sex/gender-specific pattern of association (men: OR=2.22, 95%CI [1.34-3.67], p=0.0019; women: OR = 1.02, 95%CI [0.51-2.02], p=0.95). CONCLUSION This is the first report of a male-specific association between the MC4R p.Ile269Asn loss-of-function mutation and T2D in the Mexican population.
Correction for Fraser, Detecting selection with a genetic cross

Distinguishing which traits have evolved under natural selection, as opposed to neutral evolution, is a major goal of evolutionary biology. Several tests have been proposed to accomplish this, but these either rely on false assumptions or suffer from low power. Here, I introduce an approach to detecting selection that makes minimal assumptions and only requires phenotypic data from ∼ 10 individuals. The test compares the phenotypic difference between two populations to what would be expected by chance under neutral evolution, which can be estimated from the phenotypic distribution of an F 2 cross between those populations. Simulations show that the test is robust to variation in the number of loci affecting the trait, the distribution of locus effect sizes, heritability, dominance, and epistasis. Comparing its performance to the QTL sign test — an existing test of selection that requires both genotype and phenotype data — the new test achieves comparable power with 50- to 100-fold fewer individuals (and no genotype data). Applying the test to empirical data spanning over a century shows strong directional selection in many crops, as well as on naturally selected traits such as head shape in Hawaiian Drosoph- ila and skin color in humans. Applied to gene expression data, the test reveals that the strength of stabilizing selection acting on mRNA levels in a species is strongly associated with that species ’ effective population size. In sum, this test is applicable to pheno- typic data from almost any genetic cross, allowing selection to be detected more easily and powerfully than previously possible.
Macroevolutionary dynamics of parasite diversification: A reality check

Parasitism is often invoked as a factor explaining the variation in diversification rates across the tree of life, while also representing up to half of Earth's diversity. Yet, patterns and processes of parasite diversification remain mostly unknown. In this study, we assess the patterns of parasite diversification and specifically determine the role of life‐history traits (i.e. life cycle complexity and host range) and major coevolutionary events in driving diversification across eight phylogenetic datasets spanning taxonomically different parasite groups. Aware of the degree of incomplete sampling among all parasite phylogenies, we also tested the impact of sampling bias on estimates of diversification. We show that the patterns and rates of parasite diversification differ among taxa according to life cycle complexity and to some extent major host transitions. Only directly transmitted parasites were found to be influenced by an effect of major host transitions on diversification rates. Although parasitism may be a main factor responsible for heterogeneity in diversification among the tree of life, the high degree of incomplete parasite phylogenies remains an obstacle when modelling diversification dynamics. Nevertheless, we provide the first comparative test of parasite diversification, revealing some consistent patterns and insight into the processes that shape it.
Diet during early life defines testicular lipid content and sperm quality in adulthood.

Childhood obesity is a serious concern associated with ill health later in life. Emerging data suggest that obesity has long-term adverse effects upon male sexual and reproductive health but few studies addressed this issue. We hypothesized that exposure to high-fat diet during early life alters testicular lipid content and metabolism leading to permanent damage to sperm parameters. After weaning (day 21 after birth), 36 male mice were randomly divided into 3 groups and fed with different diet regimen for 200 days: CTRL-standard chow; HFD-high-fat diet (Carbohydrate: 35.7%, Protein: 20.5%, Fat: 36.0%); HFDt-high-fat diet for 60 days then replaced by standard chow. Biometric and metabolic data were monitored. Animals were then sacrificed, and tissues collected. Epididymal sperm parameters and endocrine parameters were evaluated. Testicular metabolites were extracted and characterized by 1H-NMR and GC-MS. Testicular mitochondrial and antioxidant activity were evaluated. Our results show that mice fed with high-fat diet, even if only until early adulthood, had lower sperm viability and motility, and higher incidence of head and tail defects. Although diet reversion with weight loss during adulthood prevents the progression of metabolic syndrome, testicular content in fatty acids is irreversibly affected. Excessive fat intake promoted an over-accumulation of pro-inflammatory n-6 polyunsaturated fatty acids in testis, which are strongly correlated with negative effects upon sperm quality. Therefore, the adoption of high-fat diets during early life correlates to irreversible changes in testicular lipid content and metabolism, which are related to permanent damage to sperm quality later in life.
Onset of action of inhaled glucocorticoids on bronchial and alveolar nitric oxide output

Fractional exhaled nitric oxide (FENO) is a marker of airway inflammation. Measuring FENO at multiple flow rates enables calculation of NO parameters: bronchial NO output (J awNO), bronchial wall (C awNO) and alveolar (C ANO) NO concentrations, and bronchial diffusion factor of NO (D awNO). FENO is known to rapidly reduce after the commencement of inhaled corticosteroid (ICS) treatment. However, little is known on the effect of ICS on the other NO parameters. We assessed (1) the onset of action of ICS treatment on the NO parameters and (2) whether the changes in bronchial NO output are due to changes in bronchial wall NO concentration or diffusion factor. FENO and other NO parameters were measured at baseline and after 1, 3 and 7 d of treatment with inhaled fluticasone propionate 250 μg b.i. d. in 23 allergic children with a history of asthma-like symptoms. There was a decrease in J awNO (from 680 (244/1791) (median (1st/3rd quartile)) to 357 (165/753) pl s−1, p < 0.001) and FENO50( from 13.8 (7.5/35) to 8.3 (5.36/17.0) ppb, p < 0.001) in 3 d from the first dose of ICS. Also, C awNO seemed to reduce after 3 d (from 171 (89/328) to 79 (54/157) ppb, p = 0.041), while D awNO remained unchanged. Furthermore, C ANO reduced during the 7 d treatment (from 3.0 (2.0/5.0) to 2.3 (1.9/2.6) ppb, p = 0.004). ICS treatment reduced FENO50 and J awNO rapidly and the decline was caused by decreased bronchial wall NO concentration while bronchial NO diffusion factor remained unchanged. These findings suggest that C awNO could be a more specific marker of airway inflammation and treatment response than J awNO or FENO50, which are both determined also by D awNO that seems to be resistant to the treatment with ICS.