Miracle-dz/UniFAR-FTUs huggingface dataset:
Bacillus subtilis YisK possesses oxaloacetate decarboxylase activity and exhibits Mbl-dependent localization

ABSTRACT YisK is an uncharacterized protein in Bacillus subtilis previously shown to interact genetically with the elongasome protein Mbl. YisK overexpression leads to cell widening and lysis, phenotypes that are dependent on mbl and suppressed by mbl mutations. In the present work, we characterize YisK’s localization, structure, and enzymatic activity. We show that YisK localizes as puncta that depend on Mbl. YisK belongs to the fumarylacetoacetate hydrolase (FAH) superfamily, and crystal structures revealed close structural similarity to two oxaloacetate (OAA) decarboxylases: human mitochondrial FAHD1 and Corynebacterium glutamicum Cg1458. We demonstrate that YisK can also catalyze the decarboxylation of OAA (Km = 134 µM, Kcat = 31 min−1). A catalytic dead variant (YisK E148A, E150A) retains wild-type localization and still widens cells following overexpression, indicating these activities are not dependent on YisK catalysis. Conversely, a non-localizing variant (YisK E30A) retains wild-type enzymatic activity in vitro but localizes diffusely and no longer widens cells following overexpression. Together, these results suggest that YisK may be subject to spatial regulation that depends on the cell envelope synthesis machinery. IMPORTANCE The elongasome is a multiprotein complex that guides lengthwise growth in some bacteria. We previously showed that, in B. subtilis, overexpression of an uncharacterized putative enzyme (YisK) perturbed function of the actin-like elongasome protein Mbl. Here, we show that YisK exhibits Mbl-dependent localization. Through biochemical and structural characterization, we demonstrate that, like its mitochondrial homolog FAHD1, YisK can catalyze the decarboxylation of the oxaloacetate to pyruvate and CO2. YisK is the first example of an enzyme implicated in central carbon metabolism with subcellular localization that depends on Mbl. The elongasome is a multiprotein complex that guides lengthwise growth in some bacteria. We previously showed that, in B. subtilis, overexpression of an uncharacterized putative enzyme (YisK) perturbed function of the actin-like elongasome protein Mbl. Here, we show that YisK exhibits Mbl-dependent localization. Through biochemical and structural characterization, we demonstrate that, like its mitochondrial homolog FAHD1, YisK can catalyze the decarboxylation of the oxaloacetate to pyruvate and CO2. YisK is the first example of an enzyme implicated in central carbon metabolism with subcellular localization that depends on Mbl.
No sex differences in oxygen uptake or extraction kinetics in the moderate or heavy exercise intensity domains

The integrative response to exercise differs between sexes, with oxidative energy contribution purported as a potential mechanism. The present study investigated whether this difference was evident in the kinetics of oxygen uptake (V□O2) and extraction (HHb+Mb) during exercise. Sixteen adults (8 males, 8 females, age: 27±5 years) completed three experimental visits. Incremental exercise testing was performed to obtain lactate threshold and V□O2peak. Subsequent visits involved three six-minute cycling bouts at 80% of lactate threshold and one 30-minute bout at a work rate 30% between the lactate threshold and power at V□O2peak. Pulmonary gas exchange and near-infrared spectroscopy of the vastus lateralis were used to continuously sample V□O2 and HHb+Mb, respectively. The phase II V□O2 kinetics were quantified using mono-exponential curves during moderate and heavy exercise. Slow component amplitudes were also quantified for the heavy intensity domain. Relative V□O2peak values were not different between sexes (p=0.111). Males achieved ∼30% greater power outputs (p=0.002). In the moderate and heavy intensity domains, the relative amplitude of the phase II transition was not different between sexes for V□O2 (∼24 and ∼40% V□O2peak, p≥0.179) and HHb+Mb (∼20 and ∼32% ischemia, p≥0.193). Similarly, there were no sex differences in the time constants for V□O2 (∼28 s, p≥0.385) or HHb+Mb (∼10s, p≥0.274). In the heavy intensity domain, neither V□O2 (p≥0.686) or HHb+Mb (p≥0.432) slow component amplitudes were different between sexes. The oxidative response to moderate and heavy intensity exercise did not differ between males and females, suggesting similar dynamic responses of oxidative metabolism during intensity-matched exercise. New and Noteworthy This study demonstrated no sex differences in the oxidative response to moderate and heavy intensity cycling exercise. The change in oxygen uptake and deoxyhaemoglobin were modelled with mono-exponential curve fitting, which revealed no differences in the rate of oxidative energy provision between sexes. This provides insight into previously reported sex differences in the integrative response to exercise.
Cracked actin filaments as mechanosensitive receptors

Actin filament networks are exposed to mechanical stimuli, but the effect of strain on actin filament structure has not been well-established in molecular detail. This is a critical gap in understanding because the activity of a variety of actin-binding proteins have recently been determined to be altered by actin filament strain. We therefore used all-atom molecular dynamics simulations to apply tensile strains to actin filaments and find that changes in actin subunit organization are minimal in mechanically strained, but intact, actin filaments. However, a conformational change disrupts the critical D-loop to W-loop connection between longitudinal neighboring subunits, which leads to a metastable cracked conformation of the actin filament, whereby one protofilament is broken prior to filament severing. We propose that the metastable crack presents a force-activated binding site for actin regulatory factors that specifically associate with strained actin filaments. Through protein-protein docking simulations, we find that 43 evolutionarily-diverse members of the dual zinc finger containing LIM domain family, which localize to mechanically strained actin filaments, recognize two binding sites exposed at the cracked interface. Furthermore, through its interactions with the crack, LIM domains increase the length of time damaged filaments remain stable. Our findings propose a new molecular model for mechanosensitive binding to actin filaments. SIGNIFICANCE STATEMENT Cells continually experience mechanical strain, which has been observed to alter the interactions between actin filaments and mechanosensitive actin-binding proteins in recent experimental studies. However, the structural basis of this mechanosensitivity is not well understood. We used molecular dynamics and protein-protein docking simulations to investigate how tension alters the actin filament binding surface and interactions with associated proteins. We identified a novel metastable cracked conformation of the actin filament, whereby one protofilament breaks before the other, presenting a unique strain-induced binding surface. Mechanosensitive LIM domain actin-binding proteins can then preferentially bind the cracked interface, and this association stabilizes damaged actin filaments.
Operational forecast framework applied to extreme sea levels at regional and local scales

ABSTRACT The design, implementation and demonstration of a novel and generic computational forecast framework for multi-scale prediction of extreme sea levels and associated flooding is presented. Denoted Water Information Forecast Framework (WIFF), it integrates process-based models for waves, tides and surges from regional to local scales, predicting the flooding of coastal areas, and supporting the routine and emergency management of coastal resources. WIFF manages the simulations and the real-time monitoring data, archives the data and makes the information available through a WebGIS that targets users with distinct access privileges. Additionally, the web component of WIFF adapts automatically and transparently to any device. WIFF also provides ways to assess the model accuracy and generates tailored products based on model results and observations. WIFF is demonstrated in the prediction of extreme water levels in the Portuguese coast, simulating processes at different scales: at basin scales, waves are simulated in the North Atlantic and in the Portuguese shelf, and sea levels due to tides and atmospheric forcings are simulated in the Northeast Atlantic; at estuarine scales, high-resolution, fully coupled wave/circulation predictions are performed in the Tagus estuary to account for wave–current interactions. User-oriented georeferenced products are generated, including automatic model/data comparisons, targeting the needs of civil protection agents and combining for the first time an agile, service-oriented platform with high-resolution, process-rich predictions of the Tagus dynamics.
Meningococcal Antibiotic Resistance: Molecular Characterization of Isolates from Patients with Invasive Meningococcal Disease (IMD) in Greece

For effective case management and chemoprophylaxis of Invasive Meningococcal Disease (IMD), prompt antibiotic treatment is required. N. meningitidis is usually susceptible to antibiotics, but reduced susceptibility to penicillin, ciprofloxacin, and rifampicin is increasing worldwide, jeopardizing patients’ outcome. We assessed, phenotypically and genotypically, the antimicrobial resistance patterns of 192 strains isolated from IMD cases from all over Greece during 2010–2021. Antimicrobial susceptibility to penicillin, rifampicin, and ciprofloxacin was determined using the E-test. All isolates were genotyped by Multilocus Sequence Typing (MLST). penA, rpoB, and gyrA genes were amplified by PCR and sequenced. Of the 192 isolates, 37% (72/192) were penicillin-susceptible/had increased exposure, and 11% (21/192) were penicillin-resistant. Among those, 40 penA alleles were identified; penA1, penA27, and penA3 were highly associated with susceptibility to penicillin; penA14, penA25, and penA22 related to reduced susceptibility to penicillin, while penA9, penA910, and penA295 had resistance to penicillin. Two ciprofloxacin-resistant isolates harbored the gyrA346 allele, while one rifampicin-resistant isolate harbored the rpoB5 allele. Resistance to ciprofloxacin and rifampicin remains rare. As Greece is one of the countries with high antimicrobial resistance, continued monitoring of antibiotic resistance is important to ensure timely detection of emerging resistance for treatment and prevention guidelines.
Chromosome‐level genome assembly and whole‐genome resequencing of topmouth culter (Culter alburnus) provide insights into the intraspecific variation of its semi‐buoyant and adhesive eggs

Topmouth culter (Culter alburnus) is an ecologically and economically important species belonging to the subfamily Culterinae that is native to and widespread in East Asia. Intraspecific variation of semi‐buoyant and adhesive eggs in topmouth culter provides an ideal opportunity to investigate the genetic mechanisms of spawning habits underlying the adaptive radiation of cyprinids in East Asia. In this study, we present a chromosome‐level genome assembly of topmouth culter and re‐sequenced 158 individuals from six locations in China covering three geographical groups and two egg type variations. The topmouth culter genome size was 1.05 Gb, with a contig N50 length of 17.8 Mb and anchored onto 24 chromosomes. Phylogenetic analysis showed that the divergence time of the Culterinae was coinciding with the time of initiation of the Asian monsoon intensification. Gene family evolutionary analysis indicated that the expanded gene families in topmouth culter were associated with dietary adaptation. Population‐level genetic analysis indicated clear differentiation among the six populations, which were clustered into three distinct clusters, consistent with their geographical divergence. The historical effective population size of topmouth culter correlated with the Tibetan Plateau uplifting according to the demographic history reconstruction. A selective sweep analysis between adhesive and semi‐buoyant egg populations revealed the genes associated with the hydration and adhesiveness of eggs, indicating divergent selection towards different hydrological environments. This study offers a high‐resolution genetic resource for further studies on evolutionary adaptation, genetic breeding and conservation of topmouth culter, providing insights into the molecular mechanisms for egg type variation of East Asian cyprinids.
The Impact of Marketization on Enterprise Performance from the Perspective of Enterprise Debt

The problem of corporate debt is a hidden danger to China’s economic growth and financial stability. This paper studies the effect of regional marketization on the debt burden of the local enterprises based on a fixed effects model. The result demonstrates that the higher the market-oriented degree, the lower the debt burden of the enterprises in that region. Further analysis demonstrates that the improvement of marketization not only directly reduces the enterprise debt, but also reduces debt burden by increasing the enterprise productivity and promoting the enterprise property rights reform. Improving the level of regional marketization is conducive to the enterprise debt issue, and this provides some suggestions to the policy makers.
Mortality Caused by Candida auris Bloodstream Infections in Comparison with Other Candida Species, a Multicentre Retrospective Cohort

Candida auris is an emerging pathogen considered to be critical in the World Health Organization fungal organisms list. The study aims to determine the mortality and hospital stays attributed to Candida auris (C. auris) compared to other Candida species in adult patients with candidemia. A retrospective cohort of adults with candidemia was examined from seven centres in Colombia between 2016 and 2021. The primary outcome was 30-day mortality, and the secondary outcome was the length of hospital stay among survivors. Adjustment of the confounding variables was performed using inverse probability weights of exposure propensity score (candidemia by C. auris), survival regression models (Weibull distribution), and a counting model (negative binomial distribution). A value of 244 (47.6%) of the 512 patients with candidemia died within the first 30 days. The crude mortality in C. auris was 38.1% vs. 51.1% in Candida non-auris (CNA). In the Weibull model, mortality in the C. auris group was lower (adjusted HR: aHR- 0.69, 95% CI: 0.53–0.90). Antifungal treatment also decreased mortality, with an aHR of 0.36 (95% CI 0.27–0.47), while the presence of septic shock on patient progression increased it, with an aHR of 1.73 (95% CI 1.41–2.13). Among the patients who survived, no differences in the length of hospital stay were observed between the C. auris and the CNA groups, with an incidence rate ratio of 0.92 (95% CI: 0.68–1.22). Mortality in patients with C. auris bloodstream infections appears lower when adjusted for numerous confounding variables regarding treatment and the presence of septic shock in patient progression. We identified no significant effect of C. auris on the length of hospital stay in surviving patients.
Effect of low iron stress on root growth and iron uptake and utilization of different maize cultivars at seedling stage *

Iron, as a mineral element necessary for plant growth, has a significant effect on chlorophyll synthesis, REDOX reaction, plant photosynthesis, respiration, and substance/energy metabolism. Low content of effective iron in soil can easily cause iron deficiency (chlorosis) in maize planted in calcareous soils of arid/semi-arid regions. The study of the ability/mechanism of maize to resist low iron stress is critical for solving chlorosis due to iron deficiency. In order to determine the mechanism of resistant maize cultivars to low iron stress at seedling stage, ‘Zhenghong 2’ (resistant to low iron) and ‘Chuandan 418’ (sensitive to low iron) were selected for the study. For genetic improvement of the maize varieties resistant to ch in aX iv :2 01 71 1. 02 16 1v 1 ChinaXiv合作期刊 1164 中国生态农业学报 2017 第 25卷 http://www.ecoagri. ac.cn low iron stress, three-leaf maize seedlings were treated with different levels of iron solution with severe (10 μmol·L), medium (30 μmol·L), light (50 μmol·L) iron stress and control (100 μmol·L). Analysis of low iron stress for different maize varieties to low iron showed that the low iron stress had significant effects on root growth and iron uptake of maize seedlings after 14 and 28 days of treatments. As iron concentration decreased, root length, root volume, root vitality, dry matter, iron content, iron accumulation and relative absorption capacity of maize seedlings significantly dropped. However, iron treatment increased root-washing mugineic acid, iron distribution in aboveground parts and iron physiological efficiency of the seedlings. This was one of the most important physiological mechanisms of maize adaptation to low iron stress. Although iron accumulation had significant positive correlation with iron absorption ability of maize, iron absorption capacity under moderate and severe low iron stress in maize cultivars with different low iron resistances were not significant. Thus the difference in iron absorption ability was not the main cause of high iron accumulation in ‘Zhenghong 2’. Iron accumulation was also significantly positively correlated with root length, root volume, root dry weight and root activity. Compared with ‘Chuandan 418’ low iron resistant variety ‘Zhenghong 2’ had longer root length, larger root volume, heavier root dry weight, higher root vitality and higher iron accumulation. There was a positive correlation between mugineic acid and iron distribution in stems and leaves of maize seedlings. Also a positive correlation was observed between iron physiology efficiency and iron distribution in stems and leaves of maize seedlings. The enhancement of root secretion of mugineic acid improved iron allocation rate in the shoot system of maize so as to improve the efficiency of iron physiology. The rate of increase in mugineic acid was higher for ‘Zhenghong 2’ under moderate and severe low iron stress and that was the main reason for the high iron physiological efficiency.
Serum 5-Methyltetrahydrofolate Status Is Associated with One-Carbon Metabolism-Related Metabolite Concentrations and Enzyme Activity Indicators in Young Women

Maintaining optimal one-carbon metabolism (OCM) is essential for health and pregnancy. In this cross-sectional study, folate status was assessed based on 5-methyltetrahydrofolate (5-MTHF) levels, and the association between 5-MTHF and OCM-related metabolites was investigated in 227 female Japanese university students aged 18–25 years. The participants were divided into high and low 5-MTHF groups based on their folate status. Serum samples of the participants were collected while they were fasting, and 18 OCM-related metabolites were measured using stable-isotope dilution liquid chromatography–electrospray tandem mass spectrometry. The association between serum 5-MTHF and OCM-related metabolite concentrations was assessed using Spearman’s rank correlation coefficient. Serum 5-MTHF concentrations were negatively correlated with total homocysteine (tHcy) concentrations and positively correlated with S-adenosylmethionine (SAM) and total cysteine (tCys) concentrations. Serum 5-MTHF concentrations demonstrated a stronger negative correlation with tHcy/tCys than with tHcy alone. The negative correlation between betaine and tHcy concentrations was stronger in the low 5-MTHF group than in the high 5-MTHF group. The 5-MTHF status could be linked to Hcy flux into the transsulfuration pathway via SAM. Therefore, the tHcy/tCys ratio may be a more sensitive indicator of the 5-MTHF status than tHcy alone. Furthermore, a low 5-MTHF status can enhance Hcy metabolism via betaine.
CLA+ memory T cells in atopic dermatitis

Circulating skin‐homing cutaneous lymphocyte‐associated antigen (CLA)+ T cells constitute a small subset of human memory T cells involved in several aspects of atopic dermatitis: Staphylococcus aureus related mechanisms, the abnormal Th2 immune response, biomarkers, clinical aspects of the patients, pruritus, and the mechanism of action of targeted therapies. Superantigens, IL‐13, IL‐31, pruritus, CCL17 and early effects on dupilumab‐treated patients have in common that they are associated with the CLA+ T cell mechanisms in atopic dermatitis patients. The function of CLA+ T cells corresponds with the role of T cells belonging to the skin‐associated lymphoid tissue and could be a reason why they reflect different mechanisms of atopic dermatitis and many other T cell mediated skin diseases. The goal of this review is to gather all this translational information of atopic dermatitis pathology.
FedLEGO: Enabling Heterogenous Model Cooperation via Brick Reassembly in Federated Learning

This paper focuses on addressing the practical yet challenging problem of model heterogeneity in federated learning, where clients possess models with different network structures. To track this problem, we propose a novel framework called FedLEGO , which treats each client model as a LEGO toy, reassembles it into bricks, and assembles bricks back into personalized models accordingly. Moreover, FedLEGO automatically and dynamically generates informative and diverse personalized candidates with minimal human intervention. Furthermore, our proposed heterogeneous model reassembly technique mitigates the adverse impact introduced by using public data with different distributions from the client data to a certain extent. Experimental results demonstrate that FedLEGO outperforms baselines on three datasets under both IID and Non-IID settings. Additionally, FedLEGO effectively reduces the adverse impact of using different public data and dynamically generates diverse personalized models in an automated manner.
CLEP_A_401726 743..752

Purpose: (i) To report the prevalence of participants to a first-line intervention for OA in Sweden using over-the-counter (OTC) and/ or prescribed NSAIDs; (ii) To estimate the accuracy of dispensed prescriptions of NSAIDs recorded in a Swedish health-care register to capture the use of NSAID considering clinician-report as reference standard. Methods: Register-based study. We used data from OA individuals who participated in the Swedish first-line intervention recorded in the Swedish Osteoarthritis Register (SOAR). SOAR includes clinician-reported use of NSAIDs in the three months preceding the intervention. We used the Prescribed Drug Register to retrieve data on NSAID prescriptions dispensed in the same period. We estimated the prevalence of OTC users (individuals with clinicians-reported use of NSAID but no prescription dispensed), prescription users (individuals with clinicians-reported use of NSAID and a prescription dispensed) and non-users (neither of the previous). We calculated sensitivity, specificity, positive predictive value, and negative predictive value of dispensed prescriptions of NSAIDs vs clinician-report. Results: We included 116,162 individuals (mean age [Standard Deviation]: 66 [9.6] years, 79% women, 77% knee OA). Overall, 24.7% (95% Confidence Intervals [CI] 24.5%; 25.0%) used OTC NSAIDs only, 18.2% (18.0%; 18.5%) used prescribed NSAIDs, 6.6% (6–4%; 6.7%) reported not using NSAIDs while having an NSAID prescription dispensed. Of the 49,913 individuals with clinician-reported use of NSAIDs, 21,190 had a prescription dispensed (sensitivity: 42.5% [95% CI 42.0%, 42.9%]; positive predictive value: 73.5% [73.0%, 74.0%]). Of the 66,249 individuals reporting not using NSAIDs, 58,617 did not have a prescription dispensed (specificity: 88.5% [88.2%, 88.7%]; negative predictive value: 67.1% [66.8%, 67.4%]). Conclusion: Overall, 24.7% of participants in a first-line intervention for OA used OTC NSAIDs only while 18.2% used prescribed NSAIDs. Dispensed prescriptions of NSAIDs have high specificity but low sensitivity and can correctly identify about 70% of both the non-users and users in this population.