Miracle-dz/UniFAR-FTUs huggingface dataset:
Flagella-dependent inhibition of biofilm formation by sub-inhibitory concentration of polymyxin B in Vibrio cholerae

Biofilm formation is a common strategy used by bacteria in order to survive and persist in the environment. In Vibrio cholerae (V. cholerae), a Gram-negative pathogen responsible for the cholera disease, biofilm-like aggregates are important for the pathogenesis and disease transmission. Biofilm formation is initiated by the attachment of the bacteria to a surface, followed by maturation stages involving the formation of a biofilm matrix. In V. cholerae, flagella are essential for the initial step of biofilm formation, allowing the bacteria to swim and to detect a surface. In this study, we explored the effect of polymyxin B (PmB), a cationic bacterial antimicrobial peptide, on biofilm formation in pathogenic V. cholerae strains belonging to the O1 and O139 serotypes. We found that sub-inhibitory concentration of PmB induces a reduction of the biofilm formation by V. cholerae O1 and O139. Experiment on preformed biofilm demonstrated that the biofilm formation inhibition occurs at the initial step of biofilm formation, where the flagella are essential. We further characterize the effect of PmB on V. cholerae flagellation. Our results demonstrate that the flagellin expression is not reduced in presence of sub-inhibitory concentration of PmB. However, a decrease of the abundance of flagellin associated with the bacterial cells together with an increase in the secretome was observed. Electron microscopy observations also suggest that the abundance of aflagellated bacteria increases upon PmB supplementation. Finally, in agreement with the effect on the flagellation, a reduction of the bacterial motility is observed. Altogether, our results suggest that the PmB affect V. cholerae flagella resulting in a decrease of the motility and a compromised ability to form biofilm.
A Brief Review of the Application of Neuroergonomics in Skilled Cognition During Expert Sports Performance

The elite sports environment provides a unique setting for studying human performance, where both cognitive and physical demands are high. Successful performance in sport is contingent upon key cognitive skills such as attention, perception, working memory and decision-making. The demands of competitive sport also increase loading on the central nervous system (CNS). Neuroimaging methods such as functional magnetic resonance imaging (fMRI), functional near infrared spectroscopy (fNIRS) and electroencephalography (EEG) offer the potential to investigate the cognitive demands of sport, neuroplasticity of athletes, and biofeedback training. However, practical and technical limitations of these methods have generally limited their use to laboratory-based studies of athletes during simulated sporting tasks. This review article, provides a brief overview of research that has applied neuroimaging technology to study various aspects of cognitive function during sports performance in athletes, alternative methods for measuring CNS loading [e.g., direct current (DC) potential], possible solutions and avenues of focus for future neuroergonomics research in sport.
Characterization of the CACNA1C-R518C Missense Mutation in the Pathobiology of Long-QT Syndrome Using Human Induced Pluripotent Stem Cell Cardiomyocytes Shows Action Potential Prolongation and L-Type Calcium Channel Perturbation.

BACKGROUND The CACNA1C-encoded cardiac L-type calcium channel (Cav1.2) is essential for cardiocyte action potential duration (APD). We previously reported the CACNA1C-p.R518C variant associated with prolonged QT intervals, cardiomyopathy, and sudden cardiac death in several pedigrees. METHODS To characterize a patient-derived human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) CACNA1C-p.R518C model, CACNA1C-p.R518C hiPSC-CMs were generated from a 13-year-old man (QTc, >480 ms) with a family history of sudden cardiac death. An isogenic hiPSC-CM gene-corrected control was created using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9). APD and calcium handling were assessed by live cell imaging with Arclight voltage and Fluo-4 calcium indicators, respectively. The APD and L-type calcium channel biophysical properties were further assessed by whole-cell patch clamp technique. RESULTS The Bazett formula-corrected, Arclight-measured APD90 of CACNA1C-p.R518C hiPSC-CMs was significantly longer (622±11 ms; n=92) than the isogenic control hiPSC-CMs (453±5 ms; n=62; P<0.0001). Patch clamp assessment of CACNA1C-p.R518C hiPSC-CMs paced at 1 Hz confirmed a prolonged APD90 (689±29 ms; n=10) compared with the patient's isogenic control hiPSC-CMs (434±30 ms; n=8; P<0.05). Fluo-4-measured calcium transient decay time suggested calcium mishandling in CACNA1C-p.R518C. Patch clamp analysis revealed increased L-type calcium channel window current, slow decay time at various voltages, and increased late calcium current for CACNA1C-p.R518C hiPSC-CMs when compared with isogenic control hiPSC-CMs. CONCLUSIONS Using patient-specific hiPSC-CM mutant and isogenic control lines, we demonstrate that the CACNA1C-p.R518C variant is the self-sufficient, monogenetic substrate for the patient's long-QT syndrome phenotype. These data further bolster the conclusion that CACNA1C is a bona fide, definite evidence long-QT syndrome susceptibility gene.
4-Couv, a Backcover Treebank

We introduce 4-Couv, a treebanking project aiming at develop a large multipurpose treebank for French language. The main characteristic of this project is to provide adequate material for both linguistic and psycholinguistic research. The treebank is made of short and self-contained texts selected from a corpus of backcovers coming from different editors and different genres. Such material makes possible classical linguistic research (especially in syntax and discourse), but offers also new perspectives in experimental linguistics: being short texts and semantically coherent, they perfectly fit with the requirements of eye-tracking or electro-encephalographic recordings. At this stage, 4-Couv contains 3,500 trees automatically tagged and parsed, and manually corrected. Its format is compatible with other standard French treebanks. We present in this paper, the treebank, its annotation and the different treebanking tools that have been developed for the different stages of its elaboration: text selection, tagging, parsing and manual correction.
Subtle selectivity in a pheromone sensor triumvirate desynchronizes competence and predation in a human gut commensal

Constantly surrounded by kin or alien organisms in nature, eukaryotes and prokaryotes developed various communication systems to coordinate adaptive multi-entity behavior. In complex and overcrowded environments, they require to discriminate relevant signals in a myriad of pheromones to execute appropriate responses. In the human gut commensal Streptococcus salivarius, the cytoplasmic Rgg/RNPP regulator ComR couples competence to bacteriocin-mediated predation. Here, we describe a paralogous sensor duo, ScuR and SarF, which circumvents ComR in order to disconnect these two physiological processes. We highlighted the recurring role of Rgg/RNPP in the production of antimicrobials and designed a robust genetic screen to unveil potent/optimized peptide pheromones. Further mutational and biochemical analyses dissected the modifiable selectivity toward their pheromone and operating sequences at the subtle molecular level. Additionally, our results highlight how we might mobilize antimicrobial molecules while silencing competence in endogenous populations of human microflora and temper gut disorders provoked by bacterial pathogens.
Association Mapping for 24 Traits Related to Protein Content, Gluten Strength, Color, Cooking, and Milling Quality Using Balanced and Unbalanced Data in Durum Wheat [Triticum turgidum L. var. durum (Desf).]

Durum wheat [Triticum durum (Desf). ] is mostly used to produce pasta, couscous, and bulgur. The quality of the grain and end-use products determine its market value. However, quality tests are highly resource intensive and almost impossible to conduct in the early generations in the breeding program. Modern genomics-based tools provide an excellent opportunity to genetically dissect complex quality traits to expedite cultivar development using molecular breeding approaches. This study used a panel of 243 cultivars and advanced breeding lines developed during the last 20 years to identify SNPs associated with 24 traits related to nutritional value and quality. Genome-wide association study (GWAS) identified a total of 179 marker–trait associations (MTAs), located in 95 genomic regions belonging to all 14 durum wheat chromosomes. Major and stable QTLs were identified for gluten strength on chromosomes 1A and 1B, and for PPO activity on chromosomes 1A, 2B, 3A, and 3B. As a large amount of unbalance phenotypic data are generated every year on advanced lines in all the breeding programs, the applicability of such a dataset for identification of MTAs remains unclear. We observed that ∼84% of the MTAs identified using a historic unbalanced dataset (belonging to a total of 80 environments collected over a period of 16 years) were also identified in a balanced dataset. This suggests the suitability of historic unbalanced phenotypic data to identify beneficial MTAs to facilitate local-knowledge-based breeding. In addition to providing extensive knowledge about the genetics of quality traits, association mapping identified several candidate markers to assist durum wheat quality improvement through molecular breeding. The molecular markers associated with important traits could be extremely useful in the development of improved quality durum wheat cultivars using marker-assisted selection (MAS).
A Simple Metal-Free Cyclization for the Synthesis of 4-Methylene-3-Substituted Quinazolinone and Quinazolinthione Derivatives: Experiment and Theory

A new series of 3-substituted 4-methylene-quinazolinthiones and 4-methylene-quinazolinones were synthesized in moderate to excellent yield through a simple reaction of 2-aminoacetophenones with isocyanates or isothiocyanates. The reaction shows good tolerance of many important functional groups in the presence of air and water under metal-free conditions. Only water is produced as a coproduct, rendering this “green” methodology a highly versatile and eco-friendly alternative to the existing methods for the construction of the quinazolinone/quinazolinthione framework. We have interpreted the reaction mechanism by use of quantum chemical calculations on the basis of state-of-the-art computational methods SMD-B3LYP-D3(BJ)/BS1//B3LYP/BS1.
Multi-method Fusion of Cross-Subject Emotion Recognition Based on High-Dimensional EEG Features

Emotion recognition using electroencephalogram (EEG) signals has attracted significant research attention. However, it is difficult to improve the emotional recognition effect across subjects. In response to this difficulty, in this study, multiple features were extracted for the formation of high-dimensional features. Based on the high-dimensional features, an effective method for cross-subject emotion recognition was then developed, which integrated the significance test/sequential backward selection and the support vector machine (ST-SBSSVM). The effectiveness of the ST-SBSSVM was validated on a dataset for emotion analysis using physiological signals (DEAP) and the SJTU Emotion EEG Dataset (SEED). With respect to high-dimensional features, the ST-SBSSVM average improved the accuracy of cross-subject emotion recognition by 12.4% on the DEAP and 26.5% on the SEED when compared with common emotion recognition methods. The recognition accuracy obtained using ST-SBSSVM was as high as that obtained using sequential backward selection (SBS) on the DEAP dataset. However, on the SEED dataset, the recognition accuracy increased by ~6% using ST-SBSSVM from that using the SBS. Using the ST-SBSSVM, ~97% (DEAP) and 91% (SEED) of the program runtime was eliminated when compared with the SBS. Compared with recent similar works, the method developed in this study for emotion recognition across all subjects was found to be effective, and its accuracy was 72% (DEAP) and 89% (SEED).
Remote Ischemic Preconditioning Has No Short Term Effect on Blood Pressure, Heart Rate, and Arterial Stiffness in Healthy Young Adults

Objective Remote ischemic preconditioning (RIPC) are short episodes of ischemia and reperfusion applied to remote tissue to trigger responses in a specific organ or cardiovascular bed. This study investigates whether RIPC has a short-term effect on blood pressure (BP), heart rate, and arterial stiffness. Patients and Methods From March 2018 to August 2018, we included 40 healthy volunteers (23 female, age 25.6 ± 2.8 years) into this single-blinded randomized-controlled crossover trial. After measuring BP, heart rate, and arterial stiffness in supine position participants were randomized into intervention or SHAM group. The intervention group then underwent a RIPC protocol (3 cycles of 5 min of 200 mmHg ischemia followed by 5 min reperfusion) at the thigh. The SHAM group followed the same protocol just on the upper arm with 40 mmHg pressure inflation. Directly after this 30-min procedure a reassessment of hemodynamic measures was conducted. Results There were no significant changes in all five outcome parameters when comparing the effect of RIPC to SHAM. In peripheral systolic BP the mean difference between groups was Δ1. 14 ± 6.5 mmHg (p = 0.672), and for diastolic BP Δ−0.69 ± 4.5 mmHg (p = 0.507). Heart rate shoed a Δ−0.8 ± 4.7 beats/min (p = 0.397). Regarding arterial stiffness measures, there was also no significant improvements thru RIPC. The mean difference between RIPC and SHAM for central systolic BP was Δ0. 40 ± 7.2 mmHg (p = 0.951) and for PWV Δ0. 01 ± 0.26 m/s (p = 0.563). Conclusion This study could not find any short-term effects of RIPC on arterial stiffness, BP, and heart rate in a RCT in young healthy adults.
Precise Short Sequence Insertion in Zebrafish Using a CRISPR/Cas9 Approach to Generate a Constitutively Soluble Lrp2 Protein

LRP2 is a large transmembrane receptor expressed on absorptive epithelia where it binds many extracellular ligands to control several signaling pathways. Mutations in LRP2 are associated with buphthalmic eye enlargement, myopia and other non-ocular symptoms. Though studies have clearly shown that absence of LRP2 causes these phenotypes, and that overexpression of individual LRP2 domains can exacerbate eye enlargement caused by the absence of Lrp2, the relationship between soluble LRP2 fragments and full-length membrane-bound LRP2 is not completely understood. Here we use a CRISPR/Cas9 approach to insert a stop codon cassette into zebrafish lrp2 to prematurely truncate the protein before its transmembrane domain while leaving the entire extracellular domain intact. The resulting mutant line will be a useful tool for examining Lrp2 function in the eye, and testing hypotheses regarding its extracellular processing.
Performance Expectancies Moderate the Effectiveness of More or Less Generative Activities Over Time

We examined if the benefits of generation for long-term learning depend on individual differences in performance expectancies (PEs) prior to learning. We predicted that a greater generative activity (problem-solving) compared to less generative activity (worked-examples) should be more effective for pupils with higher PEs, especially in the long run. As a comparison group for problem-solving, we implemented a special type of worked-examples that decreased engaging in self-explanations, because our main prediction focused on PEs moderating the long-term effectivity of less versus greater generative activities. We tested students’ immediate and delayed performance (after 3 months) using coherent curricular materials on linear functions in a sample of eighth graders (advanced school track). The results were partly in line with our predictions: Although we found no moderation of PE and generative activity, we obtained the predicted 3-way interaction of PE, generative activity, and time. Immediately, greater generative activity (problem-solving) was beneficial for pupils with higher PEs, while for pupils with lower PEs, problem-solving versus worked-examples did not differ. In the delayed test, this pattern reversed: for lower PEs, greater generative activity outperformed less generative activities, but there was no difference for higher PEs. Unexpectedly, the initial advantage of problem-solving for higher PEs could not be maintained, decreasing over three subsequent months, whereas the performance in the worked-example condition remained at a comparable level for higher PEs. The change in performance in the problem-solving condition for lower PEs was descriptively less pronounced than in the worked-example condition, but statistically not different. We further investigated the effects of problem-solving and worked-examples on changes in PEs after learning and after testing, hinting at gradual decrease in PEs and greater metacognitive accuracy in the problem-solving condition due to a reduction of overconfidence.
Effects and Mechanisms of Cognitive, Aerobic Exercise, and Combined Training on Cognition, Health, and Brain Outcomes in Physically Inactive Older Adults: The Projecte Moviment Protocol

Introduction Age-related health, brain, and cognitive impairment is a great challenge in current society. Cognitive training, aerobic exercise and their combination have been shown to benefit health, brain, cognition and psychological status in healthy older adults. Inconsistent results across studies may be related to several variables. We need to better identify cognitive changes, individual variables that may predict the effect of these interventions, and changes in structural and functional brain outcomes as well as physiological molecular correlates that may be mediating these effects. Projecte Moviment is a multi-domain randomized trial examining the effect of these interventions applied 5 days per week for 3 months compared to a passive control group. The aim of this paper is to describe the sample, procedures and planned analyses. Methods One hundred and forty healthy physically inactive older adults will be randomly assigned to computerized cognitive training (CCT), aerobic exercise (AE), combined training (COMB), or a control group. The intervention consists of a 3 month home-based program 5 days per week in sessions of 45 min. Data from cognitive, physical, and psychological tests, cardiovascular risk factors, structural and functional brain scans, and blood samples will be obtained before and after the intervention. Results Effects of the interventions on cognitive outcomes will be described in intention-to-treat and per protocol analyses. We will also analyze potential genetic, demographic, brain, and physiological molecular correlates that may predict the effects of intervention, as well as the association between cognitive effects and changes in these variables using the per protocol sample. Discussion Projecte Moviment is a multi-domain intervention trial based on prior evidence that aims to understand the effects of CCT, AE, and COMB on cognitive and psychological outcomes compared to a passive control group, and to determine related biological correlates and predictors of the intervention effects. Clinical Trial Registration: www.ClinicalTrials. gov, identifier NCT03123900.
BlsA Is a Low to Moderate Temperature Blue Light Photoreceptor in the Human Pathogen Acinetobacter baumannii

Light is an environmental signal that produces extensive effects on the physiology of the human pathogen Acinetobacter baumannii. Many of the bacterial responses to light depend on BlsA, a bluelight using FAD (BLUF)-type photoreceptor, which also integrates temperature signals. In this work, we disclose novel mechanistic aspects of the function of BlsA. First, we show that light modulation of motility occurs only at temperatures lower than 24°C, a phenotype depending on BlsA. Second, blsA transcript levels were significantly reduced at temperatures higher than 25°C, in agreement with BlsA protein levels in the cell which were undetectable at 26°C and higher temperatures. Also, quantum yield of photo-activation of BlsA (lBlsA) between 14 and 37°C, showed that BlsA photoactivity is greatly compromised at 25°C and absent above 28°C. Fluorescence emission and anisotropy of the cofactor together with the intrinsic protein fluorescence studies suggest that the FAD binding site is more susceptible to structural changes caused by increments in temperature than other regions of the protein. Moreover, BlsA itself gains structural instability and strongly aggregates at temperatures above 30°C. Overall, BlsA is a low to moderate temperature photoreceptor, whose functioning is highly regulated in the cell, with control points at expression of the cognate gene as well as photoactivity.
Bacterial Heavy-Metal and Antibiotic Resistance Genes in a Copper Tailing Dam Area in Northern China

Heavy metal resistance genes (MRGs) and antibiotic resistance genes (ARGs) in bacteria can respond to the inducement of heavy metals. However, the co-occurrence of MRGs and ARGs in the long-term heavy metal contaminated area is still poorly understood. Here, we investigated the relationship between the abundance of soil bacteria MRGs, ARGs and heavy metal pollution in a copper tailing dam area of northern China. We found that arsC and ereA genes coding for resistance mechanisms to arsenic and to macrolides, respectively, are the most abundant MRG and ARG in the study area. The abundance of MRGs is positively correlated with cadmium (Cd) concentration, and this indicates the importance of Cd in the selection of MRGs. The network analysis results show that sulII and MRGs co-occur and copB occur with ARGs, which suggests that MRGs and ARGs can be co-selected in the soil contaminated by heavy metal. The network analysis also reveals the co-occurrence of Cd and MRGs, and thus heavy metal with a high ‘toxic-response’ factor can be used as the indicator of MRGs. This study improves the understanding of the relationship between bacterial resistance and multi-metal contamination, and underlies the exploration of the adaptive mechanism of microbes in the multi-metal contaminated environment.
Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma

Glioblastoma multiforme (GBM) is a grade 4 and the most aggressive form of glioma, with a poor response to current treatments. The expression of microRNAs (miRNAs) is widely dysregulated in various cancers, including GBM. One of the overexpressed miRNAs in GBM is miR-21 which promotes proliferation, invasion and metastatic behaviors of tumor cells. With a size of 30–100 nm, the extracellular vesicles “exosomes” have emerged as a novel and powerful drug delivering systems. Recently, exosomal transfer of miRNAs or anti-miRNAs to tumor cells has introduced a new approach for therapeutic application of miRNAs to combat cancer. Here, we have tried to down-regulate miR-21 expression in glioma cell lines, U87-MG, and C6, by using engineered exosomes, packed with a miR-21-sponge construct. Our data revealed that the engineered exosomes have the potential to suppress miR-21 and consequently to upregulate miR-21 target genes, PDCD4 and RECK. Interestingly, in cells treated with miR-21-sponge exosomes we observed a decline in proliferation and also an elevation in apoptotic rates. Finally, in a rat model of glioblastoma, administrating exosomes loaded with a miR-21-sponge construct leads to a significant reduction in the volume of the tumors. In brief, our findings suggest a new therapeutic strategy to use engineered exosomes to deliver a miR-21-sponge construct to GBM cells, in order to block its malignant behavior.