Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome-wide association studies reveal distinct genetic correlates and increased heritability of antimicrobial resistance in Vibrio cholerae under anaerobic conditions

The antibiotic formulary is threatened by high rates of antimicrobial resistance (AMR) among enteropathogens. Enteric bacteria are exposed to anaerobic conditions within the gastrointestinal tract, yet little is known about how oxygen exposure influences AMR. The facultative anaerobe Vibrio cholerae was chosen as a model to address this knowledge gap. We obtained V. cholerae isolates from 66 cholera patients, sequenced their genomes, and grew them under anaerobic and aerobic conditions with and without three clinically relevant antibiotics (ciprofloxacin, azithromycin, doxycycline). For ciprofloxacin and azithromycin, the minimal inhibitory concentration (MIC) increased under anaerobic conditions compared to aerobic conditions. Using standard resistance breakpoints, the odds of classifying isolates as resistant increased over 10 times for ciprofloxacin and 100 times for azithromycin under anaerobic conditions compared to aerobic conditions. For doxycycline, nearly all isolates were sensitive under both conditions. Using genome-wide association studies (GWAS), we found associations between genetic elements and AMR phenotypes that varied by oxygen exposure and antibiotic concentrations. These AMR phenotypes were more heritable, and the AMR-associated genetic elements were more often discovered, under anaerobic conditions. These AMR-associated genetic elements are promising targets for future mechanistic research. Our findings provide a rationale to determine if increased MICs under anaerobic conditions are associated with therapeutic failures and/or microbial escape in cholera patients. If so, there may be a need to determine new AMR breakpoints for anaerobic conditions. Impact statement Many bacterial pathogens experience anaerobic conditions in the gut, but antimicrobial resistance (AMR) phenotypes are generally tested under ambient aerobic conditions in the laboratory. To better understand AMR under conditions more similar to natural infections, we used Vibrio cholerae as a model enteric pathogen. We sequenced the genomes and assessed the growth of V. cholerae isolates with different concentrations of three antibiotics, under anaerobic and aerobic conditions. In support of the hypothesis that AMR varies according to oxygen exposure, V. cholerae was more resistant to antibiotics under anaerobic conditions. We found many previously known genes associated with resistance; however, some of these genes were only resistance-associated under aerobic conditions. Resistance to azithromycin and doxycycline only had a detectable genetic component under anaerobic conditions. Together, our results point to distinct genetic mechanisms of resistance under anaerobic conditions and suggest several candidate genes for experimental follow-up. Data summary All sequencing data generated in this study are available in NCBI under BioProject PRJNA818081.
Seasonality of pollinators in Mediterranean montane habitats: cool-blooded bees for early-blooming plants

Understanding the factors that drive community-wide assembly of plant-pollinator systems along environmental gradients has considerable evolutionary, ecological and applied significance. Variation in thermal environments combined with intrinsic differences among pollinators in thermal biology (tolerance limits, thermal optima, thermoregulatory ability) have been proposed as drivers of community-wide pollinator gradients, but this suggestion remains largely speculative. We test the hypothesis that seasonality in bee pollinator composition in montane habitats of southeastern Spain, which largely reflects the prevalence during the early flowering season of mining bees (Andrena), is a consequence of the latter’s thermal biology. Quantitative information on seasonality of Andrena bees in the whole plant community (275 plant species) was combined with field and laboratory data on key aspects of the thermal biology of 30 species of Andrena (endothermic ability, warming constant, relationships of body temperature with ambient and operative temperatures). Andrena bees were a conspicuous, albeit strongly seasonal component of the pollinator assemblage of the regional plant community, visiting flowers of 153 different plant species (57% of total). Proportion of Andrena relative to all bees reached a maximum among plant species which flowered in late winter and early spring, and declined precipitously from May onwards. Andrena were recorded only during the cooler segment of the annual range of air temperatures experienced at flowers by the whole bee assemblage. These patterns can be explained by features of Andrena’s thermal biology: null or negligible endothermy; ability to forage at much lower body temperature than endothermic bees (difference ~10°C); low upper tolerable limit of body temperature, beyond which thermal stress presumably precluded foraging at the warmest period of year; weak thermoregulatory capacity; and high warming constant enhancing ectothermic warming. Our results demonstrate the importance of lineage-specific pollinator traits as drivers of seasonality in community-wide pollinator composition; show that exploitation of cooler microclimates by bees does not require endothermy; falsify the frequent assumption that endothermy and thermoregulation apply to all bees; and suggest that medium- and large-sized ectothermic bees with low upper thermal limits and weak thermoregulatory ability can actually be more adversely affected by climate warming than large endothermic species.
Thinking-for-speaking patterns in the L2 classroom: A mindful conceptual engagement approach to teaching motion events

Inspired by sociocultural psychology principles applied to understanding language learning and conceptual development, this participatory action research illustrates a pedagogical intervention to teach motion events as conceptual categories in the Second Language (L2) classroom. The goal is to develop and implement conceptual engagement tasks that promote mindful understanding, application, and internalization of motion events as productive concepts in communicative tasks. This is the basis for a Mindful Conceptual Engagement (MCE) approach to L2 development. We focus on L2 Spanish classroom learners when asking-and-giving-directions. This task is conceptually challenging for First Language (L1) English L2 Spanish learners because it is connected to motion events and how Thinking-for-Speaking (TFS) patterns operate in L2 communication. Twenty-three L2-Spanish students from three different courses participated in the project. A selection of coded data and examples of graphic representations are analyzed. Findings illustrate how to teach motion events conceptually and how MCE promotes conceptual awareness and control of L2 communicative features. We also document the challenges of developing functional conceptual categories of meaning as they only emerge when mindfully applied in conceptual engagement tasks. L2 learners must create their own conceptual representations as learning tools to understand motion events. It is concluded that shifting L1 TFS patterns requires creative and mindful conceptual engagement by L2 learners.
Preliminary prediction of semen quality based on modifiable lifestyle factors by using the XGBoost algorithm

Introduction Semen quality has decreased gradually in recent years, and lifestyle changes are among the primary causes for this issue. Thus far, the specific lifestyle factors affecting semen quality remain to be elucidated. Materials and methods In this study, data on the following factors were collected from 5,109 men examined at our reproductive medicine center: 10 lifestyle factors that potentially affect semen quality (smoking status, alcohol consumption, staying up late, sleeplessness, consumption of pungent food, intensity of sports activity, sedentary lifestyle, working in hot conditions, sauna use in the last 3 months, and exposure to radioactivity); general factors including age, abstinence period, and season of semen examination; and comprehensive semen parameters [semen volume, sperm concentration, progressive and total sperm motility, sperm morphology, and DNA fragmentation index (DFI)]. Then, machine learning with the XGBoost algorithm was applied to establish a primary prediction model by using the collected data. Furthermore, the accuracy of the model was verified via multiple logistic regression following k-fold cross-validation analyses. Results The results indicated that for semen volume, sperm concentration, progressive and total sperm motility, and DFI, the area under the curve (AUC) values ranged from 0.648 to 0.697, while the AUC for sperm morphology was only 0.506. Among the 13 factors, smoking status was the major factor affecting semen volume, sperm concentration, and progressive and total sperm motility. Age was the most important factor affecting DFI. Logistic combined with cross-validation analysis revealed similar results. Furthermore, it showed that heavy smoking (>20 cigarettes/day) had an overall negative effect on semen volume and sperm concentration and progressive and total sperm motility (OR = 4.69, 6.97, 11.16, and 10.35, respectively), while age of >35 years was associated with increased DFI (OR = 5.47). Conclusion The preliminary lifestyle-based model developed for semen quality prediction by using the XGBoost algorithm showed potential for clinical application and further optimization with larger training datasets.
MCPggaac haplotype is associated with poor graft survival in kidney transplant recipients with de novo thrombotic microangiopathy

De novo thrombotic microangiopathy (TMA) is associated with poor kidney graft survival, and as we previously described, it is a recipient driven process with suspected genetic background. Direct Sanger sequencing was performed in 90 KTR with de novo TMA and 90 corresponding donors on selected regions in CFH, CD46, C3, and CFB genes that involve variations with a functional effect or confer a risk for aHUS. Additionally, 37 recipients of paired kidneys who did not develop TMA were analyzed for the MCPggaac haplotype. Three-years death-censored graft survival was assessed using Kaplan-Meier and Cox regression models. The distribution of haplotypes in all groups was in the Hardy-Weinberg equilibrium and there was no clustering of haplotypes in any group. In the TMA group, we found that MCPggaac haplotype carriers were at a significantly higher risk of graft loss compared to individuals with the wild-type genotype. Worse 3-year death-censored graft survival was associated with longer cold ischemia time (HR 1.20, 95% CI 1.06, 1.36) and recipients’ MCPggaac haplotype (HR 3.83, 95% CI 1.42, 10.4) in the multivariable Cox regression model. There was no association between donor haplotypes and kidney graft survival. Similarly, there was no effect of the MCPggaac haplotype on 3-year graft survival in recipients of paired kidneys without de novo TMA. Kidney transplant recipients carrying the MCPggaac haplotype with de novo TMA are at an increased risk of premature graft loss. These patients might benefit from therapeutic strategies based on complement inhibition.
Familiarization with meaningless sound patterns facilitates learning to detect those patterns among distracters

Initially “meaningless” and randomly generated sounds can be learned over exposure. This is demonstrated by studies where repetitions of randomly determined sound patterns are detected better if they are the same sounds presented on previous trials than if they are novel. This experiment posed two novel questions about this learning. First, does familiarization with a sound outside of the repetition detection context facilitate later performance? Second, does familiarization enhance performance when repeats are interleaved with distracters? Listeners were first trained to categorize a unique pattern of synchronous complex tone trains (210 ms in duration) from other tone trains with similar qualities (familiarization phase). They were then tasked to detect repeated pattern presentations interleaved with similar distracters in 4.2 s long excerpts (repetition detection phase). The familiarized pattern (Familiar Fixed – FF), an unfamiliar pattern that remained fixed throughout (Unfamiliar Fixed – UF), or patterns that were uniquely determined on each trial (Unfamiliar Unfixed – UU) could be presented as repeats. FF patterns were learned at a faster rate and achieved higher repetition detection sensitivity than UF and UU patterns. Similarly, FF patterns also showed steeper learning slopes in their response times (RTs) than UF patterns. The data show that familiarity with a “meaningless” sound pattern on its own (i.e., without repetition) can facilitate repetition detection even in the presence of distracters. Familiarity effects become most apparent in the potential for learning.
Cellular senescence and abdominal aortic aneurysm: From pathogenesis to therapeutics

As China’s population enters the aging stage, the threat of abdominal aortic aneurysm (AAA) mainly in elderly patients is becoming more and more serious. It is of great clinical significance to study the pathogenesis of AAA and explore potential therapeutic targets. The purpose of this paper is to analyze the pathogenesis of AAA from the perspective of cellular senescence: on the basis of clear evidence of cellular senescence in aneurysm wall, we actively elucidate specific molecular and regulatory pathways, and to explore the targeted drugs related to senescence and senescent cells eliminate measures, eventually improve the health of patients with AAA and prolong the life of human beings.
Anti-DFS70 antibodies in systemic lupus erythematosus: Prevalence in a large Chinese cohort and an unexpected association with anti-dsDNA antibodies by a long-term follow-up

Objective Monospecific autoantibodies to dense fine speckles 70 (DFS70) antigen are purported to aid in excluding systemic autoimmune rheumatic diseases (SARD) such as systemic lupus erythematosus (SLE). However, the non-isolated anti-DFS70 still has a certain prevalence in SLE patients, and the clinical significance remains unclear. We aimed to investigate the prevalence, clinical relevance, and value of long-term monitoring of anti-DFS70 antibodies in SLE patients. Methods Anti-DFS70 antibodies were measured by enzyme-linked immunosorbent assay (ELISA) in 851 SLE patients, 211 healthy individuals, and 194 patients with other SARD (except SLE). Demographic, serological, and clinical associations of anti-DFS70 antibodies were analyzed by a stepwise multivariable logistic regression model. The correlation of anti-DFS70 with anti-dsDNA, anti-C1q, and SLE Disease Activity Index 2000 (SLEDAI-2K) was analyzed. Sixty-one SLE patients with follow-up time ranging from 2 to 57 months were measured anti-DFS70 antibodies using both ELISA and line immunoassay. The dynamic variations of anti-DFS70 antibodies were evaluated with anti-dsDNA, anti-C1q, and SLEDAI-2K during the follow-up. Results The prevalence of anti-DFS70 was significantly higher in SLE (20.7% (176/851)) than in healthy individuals (9.5% (20/211), p = 0.0002) and other SARD (10.8% (21/194), p = 0.002). Multivariable analysis revealed that anti-DFS70-positive SLE patients were associated with younger age (odds ratio (OR) = 0.982; 95% confidence interval (CI) = 0.969, 0.995), higher frequencies of anti-dsDNA (OR 1.598; 95% CI 1.107, 2.306) and anti-PCNA (OR 6.101; 95% CI 2.534, 14.688), and higher levels of serum IgG (OR 1.097; 95% CI 1.067, 1.129) and were more likely to be accompanied by mucosal ulcers (OR 5.921; 95% CI 1.652, 21.215). The O.D. value of anti-DFS70 positively correlated with levels of anti-dsDNA (r = 0.183, p < 0.0001) and anti-C1q (r = 0.181, p < 0.0001), respectively, but not with SLEDAI-2K (p = 0.920). During the follow-up, 49 (42 negative and 7 positive) patients remained stable with anti-DFS70 levels. The other 12 patients experienced significant changes in anti-DFS70, and 83.3% (10/12) of them showed similar trends between anti-DFS70 and anti-dsDNA by evaluation of dynamic variations. Conclusion Anti-DFS70 antibodies seem to be prevalent in Chinese SLE patients. The positive association of anti-DFS70 with anti-dsDNA and consistent dynamic variation between anti-DFS70 and anti-dsDNA during the follow-up suggested a potential relationship between anti-DFS70 and anti-dsDNA in patients with SLE.
Pathogenic gain-of-function mutations in the prodomain and C-terminal domain of PCSK9 inhibit LDL binding

Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a secreted protein that binds and mediates endo-lysosomal degradation of low-density lipoprotein receptor (LDLR), limiting plasma clearance of cholesterol-rich LDL particles in liver. Gain-of-function (GOF) point mutations in PCSK9 are associated with familial hypercholesterolemia (FH). Approximately 30%–40% of PCSK9 in normolipidemic human plasma is bound to LDL particles. We previously reported that an R496W GOF mutation in a region of PCSK9 known as cysteine-histidine–rich domain module 1 (CM1) prevents LDL binding in vitro [Sarkar et al., J. Biol. Chem. 295 (8), 2285–2298 (2020)]. Herein, we identify additional GOF mutations that inhibit LDL association, localized either within CM1 or a surface-exposed region in the PCSK9 prodomain. Notably, LDL binding was nearly abolished by a prodomain S127R GOF mutation, one of the first PCSK9 mutations identified in FH patients. PCSK9 containing alanine or proline substitutions at amino acid position 127 were also defective for LDL binding. LDL inhibited cell surface LDLR binding and degradation induced by exogenous PCSK9-D374Y but had no effect on an S127R-D374Y double mutant form of PCSK9. These studies reveal that multiple FH-associated GOF mutations in two distinct regions of PCSK9 inhibit LDL binding, and that the Ser-127 residue in PCSK9 plays a critical role.
Tannic acid reduced apparent protein digestibility and induced oxidative stress and inflammatory response without altering growth performance and ruminal microbiota diversity of Xiangdong black goats

The present study was performed to evaluate the impacts of tannic acid (TA) supplementation at different levels on the growth performance, physiological, oxidative and immunological metrics, and ruminal microflora of Xiangdong black goats. Twenty-four goats were randomly assigned to four dietary treatments: the control (CON, basal diet), the low-dose TA group [TAL, 0.3 % of dry matter (DM)], the mid-dose TA group (TAM, 0.6 % of DM), and the high-dose TA group (TAH, 0.9 % of DM). Results showed that the growth performance was unaffected (P > 0.05) by adding TA, whilst the 0.3 % and 0.6 % TA supplementation significantly decreased (P < 0.05) the apparent digestibility of crude protein (CP) and ruminal NH3-N concentration, and raised (P < 0.05) the level of total volatile fatty acid (TVFA) in rumen. The increments of alanine aminotransferase (ALT), triglyceride (TG), cortisol (CORT), total antioxidant capacity (T-AOC), interleukin (IL)-1β, IL-6, and serumamyloid A (SAA), and decrements of globulin (GLB), immunoglobulin G (IgG), cholinesterase (CHE), glutathione reductase (GR), creatinine (CRE), growth hormone (GH), high-density lipoprotein cholesterol (HDLC), and insulin-like growth factor 1 (IGF-1) to different extents by TA addition were observed. Although the Alpha and Beta diversity of rumen bacterial community remained unchanged by supplementing TA, the relative abundance of the predominant genus Prevotella_1 was significantly enriched (P < 0.05) in TAL. It could hence be concluded that the TA supplementation in the present trial generally decreased CP digestion and caused oxidative stress and inflammatory response without influencing growth performance and ruminal microbiota diversity. More research is needed to explore the premium dosage and mechanisms of effects for TA addition in the diet of goats.
Genetic substructure of Guizhou Tai-Kadai-speaking people inferred from genome-wide single nucleotide polymorphisms data

The genome-wide characteristics and admixture history of the Tai-Kadai-speaking populations are essential for understanding the population genetic diversity in southern China. We genotyped about 700,000 single nucleotide polymorphisms (SNPs) of 239 individuals from six Tai-Kadai-speaking populations residing in the mountainous Guizhou Province of southwestern China. We merged the genome-wide data with available populations and ancients in East and Southeast Asia to infer Tai-Kadai-speaking populations’ admixture history and genetic structure. We observed a genetic substructure within the studied six populations in the PCA, ADMIXTURE, ChromoPainter, GLOBETROTTER, f-statistics, and qpWave analysis. The Dong, Zhuang, and Bouyei people had a strong genetic affinity with other Tai-Kadai-speaking and Austronesian groups in the surrounding area. However, Gelao showed an affinity to Sino-Tibetan groups, and Mulao people were genetically close to Hmong-Mien populations. qpAdm further illuminated that Gelao and Dong_Tongren composited more Han-related ancestry than Dong, Zhuang, Bouyei, and Mulao people. Meanwhile, we observed high frequencies of Y-chromosome haplogroup O in studied Tai-Kadai-speaking groups except for Gelao people with a high haplogroup N frequency. From the maternal side, haplogroup M7 was frequent in studied populations except for Tongren Dong, who had a high frequency of haplogroup B5. Our newly reported data are helpful for further exploring population dynamics in southern China.
Long-term postural control in elite athletes following mild traumatic brain injury

Background Traumas to the head and neck are common in sports and often affects otherwise healthy young individuals. Sports-related concussions (SRC), defined as a mild traumatic brain injury (mTBI), may inflict persistent neck and shoulder pain, and headache, but also more complex symptoms, such as imbalance, dizziness, and visual disturbances. These more complex symptoms are difficult to identify with standard health care diagnostic procedures. Objective To investigate postural control in a group of former elite athletes with persistent post-concussive symptoms (PPCS) at least 6 months after the incident. Method Postural control was examined using posturography during quiet stance and randomized balance perturbations with eyes open and eyes closed. Randomized balance perturbations were used to examine motor learning through sensorimotor adaptation. Force platform recordings were converted to reflect the energy used to maintain balance and spectrally categorized into total energy used, energy used for smooth corrective changes of posture (i.e., <0.1 Hz), and energy used for fast corrective movements to maintain balance (i.e., >0.1 Hz). Results The mTBI group included 20 (13 males, mean age 26.6 years) elite athletes with PPCS and the control group included 12 athletes (9 males, mean age 26.4 years) with no history of SRC. The mTBI group used significantly more energy during balance perturbations than controls: +143% total energy, p = 0.004; +122% low frequency energy, p = 0.007; and +162% high frequency energy, p = 0.004. The mTBI subjects also adapted less to the balance perturbations than controls in total (18% mTBI vs. 37% controls, p = 0.042), low frequency (24% mTBI vs. 42% controls, p = 0.046), and high frequency (6% mTBI vs. 28% controls, p = 0.040). The mTBI subjects used significantly more energy during quiet stance than controls: +128% total energy, p = 0.034; +136% low-frequency energy, p = 0.048; and +109% high-frequency energy, p = 0.015. Conclusion Athletes with previous mTBI and PPCS used more energy to stand compared to controls during balance perturbations and quiet stance and had diminished sensorimotor adaptation. Sports-related concussions are able to affect postural control and motor learning.