Miracle-dz/UniFAR-FTUs huggingface dataset:
Understanding the Allosteric Transition in Escherichia coli Aspartate Transcarbamoylase through a Novel R-State Structure

A full understanding of an enzyme’s catalytic mechanism and a crystal structure representative of its in vivo form are powerful tools in computational drug screening and design. In the case of aspartate transcarbamoylase (ATCase), an allosteric enzyme, the mechanism and allosteric transition are still being explored. The crystallization of the ATCase mutant Asp236 to alanine, a T-state destabilized mutant, in the presence of phosphonoacetamide (PAM) by microdialysis was successful at pH 5.7. The enzyme crystallized in the R-state in the presence of only one substrate analogue. Globally the enzyme had converted to R, but the active site domains are more open than previously observed. Due to the ordered nature of the reaction, the R-state active site exists with a variety of small molecules bound at different times through out the course of the reaction. This structure shows an R-state active site with only one substrate analogue bound, and may therefore represent the R active site after catalysis has occurred and the active site is binding new substrates to perform its reaction again. Docking studies of small molecules can be conducted using this more open, emptier active site as it may be more representative of an in vivo conformation of the enzyme just before catalysis. Additionally, Arg296, previously unobserved as part of the active site, makes a hydrogen bonding interaction with the PAM molecule. The role of this residue will require further investigation.
An Experimental Study of CSI Management to Preserve Location Privacy

Passive device-free localization of a person exploiting the Channel State Information (CSI) from Wi-Fi signals is quickly becoming a reality. While this capability would enable new applications and services, it also raises concerns about citizens' privacy. In this work, we propose a carefully-crafted obfuscating technique against one of such CSI-based localization methods. In particular, we modify the transmitted I/Q samples by leveraging an irreversible randomized sequence. I/Q symbol manipulation at the transmitter distorts the location-specific information in the CSI while preserving communication, so that an attacker can no longer derive information on user's location. We test this technique against a Neural Network (NN)-based localization system and show that the randomization of the CSI makes undesired localization practically unfeasible. Both the localization system and the randomization CSI management are implemented in real devices. The experimental results obtained in our laboratory show that the considered localization method (first proposed in an MSc thesis) works smoothly regardless of the environment, and that adding random information to the CSI mess up the localization, thus providing the community with a system that preserve location privacy and communication performance at the same time.
A new approach for estimating research impact: An application to French cancer research

Much attention has been paid to estimating the impact of investments in scientific research. Historically, those efforts have been largely ad hoc, burdensome, and error prone. In addition, the focus has been largely mechanical—drawing a direct line between funding and outputs—rather than focusing on the scientists that do the work. Here, we provide an illustrative application of a new approach that examines the impact of research funding on individuals and their scientific output in terms of publications, citations, collaborations, and international activity, controlling for both observed and unobserved factors. We argue that full engagement between scientific funders and the research community is needed if we are to expand the data infrastructure to enable a more scientific assessment of scientific investments.
A Parallel Genetic Algorithm Based on Allied Strategy

Premature convergence has been a main problem in Genetic Algorithms (GAs). In order to prevent premature convergence,the allied strategy of human being is introduce into GAs,and a parallel genetic algorithm based on the allied strategy (PGAAS) is presentod.Excellent performance is showed in compared experiments.A new genetic operator is also used in this paper which establishes the foundation of implementing GAs by hardware.
Comparison of High- vs. Low-Responders Following a 6-Month XC Ski-Specific Training Period: A Multidisciplinary Approach

Individual training responses among endurance athletes are determined by a complex interplay between training load, recovery and genetic influence. The present study used a multidisciplinary approach to compare high- and low-responders following a 6-month training period in endurance athletes transferring to cross-country (XC) skiing. Twenty-three endurance-trained athletes (14 runners and 9 rowers/kayakers; 14 men and 9 women) were classified as high (n = 9) or low-responders (n = 11) based on pre- to post changes in treadmill running, roller-ski skating and double-poling ergometry performances following 6-months of standardized XC ski-specific training. Physiological and technical capacities during these same modes were monitored pre and post. In addition, training volume, intensity, mode and session rating of perceived exertion (sRPE) training load were quantified daily. Finally, qualitative interviews of the athlete's personal coaches were performed after the intervention. There were no differences between groups with respect to physiological baseline characteristics. High-responders improved maximum oxygen uptake (VO2max) in treadmill running (5.5 ± 7.0% change from pre- to post) as well as peak oxygen uptake (VO2peak; 7.3 ± 7.0%) and power output at 4 mmol·L−1 (37.7 ± 28.2%) treadmill roller-ski skating which differed from a corresponding non-significant change in low-responders (−1.2 ± 3.6%, −2.7 ± 3.7% and 8.2 ± 12.5%; all P ≤ 0.05). VO2peak in double-poling ergometry did not change in any group, whereas gross efficiency and cycle length in roller-ski skating improved in both groups. High-responders performed greater training loads (weekly load: 3825 ± 1013 vs. 3228 ±.748 and load/volume ratio: 4.9 ± 0.6 vs. 4.2 ± 0.5; both P ≤ 0.05) and had lower incident of injury/illness (5 ± 3 vs. 10 ± 5 days; P = 0.07). Their coaches highlighted high motivation to train and compete, together with the ability to build a strong coach-athlete relationship, to separate high- from low-responders. In conclusion, high-responders to 6-months of standardized XC ski-specific training demonstrates greater improvement in maximal/peak aerobic capacity, which was coincided by higher training loads, greater perceived effort during sessions and lower incidents of injury and illness in comparison to their lower-responding counterparts. Possibly, the higher motivation and stronger coach-athlete relationships in high-responders contributed to more individually optimized training and recovery routines, and thereby more positive performance-development.
The Modified Yale Food Addiction Scale 2.0: Validation Among Non-Clinical and Clinical French-Speaking Samples and Comparison With the Full Yale Food Addiction Scale 2.0

Objectives The modified Yale Food Addiction Scale 2.0 (mYFAS 2.0) was designed to assess food addiction using a shorter version than the YFAS 2.0. We lack data about the psychometric properties of the mYFAS 2.0 in patients with obesity, as well as studies comparing the psychometric properties of the mYFAS 2.0 versus the full YFAS 2.0. This study aimed to validate the French-language mYFAS 2.0 in a non-clinical population (study 1, n = 250), to determine the yet unknown psychometric properties of this scale in patients with obesity (study 2, n = 345), and to compare the full YFAS 2.0 and the mYFAS 2.0 in terms of food addiction (FA) prevalence and symptoms detection in both populations. Method Study 1 included 250 non-clinical individuals (non-underweight and non-obese persons screened negative for eating disorders). Study 2 included 345 bariatric surgery candidates recruited in three centers (Québec, Canada; Reims and Tours, France). The mYFAS 2.0 structure was investigated using confirmatory factorial analyses with tetrachoric correlations. Convergent validity was tested using the full YFAS 2.0, the Binge Eating Scale (both studies), the revised 18-item Three Factor Eating Questionnaire (study 1), the Beck Depression Inventory (study 2), and the body mass index (BMI; both studies). Results The mYFAS 2.0 was unidimensional, and had adequate (study 1: KR-20 = .78) and acceptable (study 2: KR-20 = .73) internal consistency. In study 1, the mYFAS 2.0 had good convergent validity with the YFAS 2.0, BMI, binge eating, cognitive restraint, uncontrolled eating and emotional eating; in study 2, the mYFAS 2.0 had good convergent validity with the YFAS 2.0, binge eating, depression, but not BMI. Participants endorsed fewer symptoms with the mYFAS 2.0 than with the YFAS 2.0; FA prevalences were similar between questionnaires in the non-clinical, but not in the clinical sample. A FA ‘diagnosis’ and risk of binge eating disorder were associated but did not completely overlap. Conclusions The mYFAS 2.0 has close psychometric properties to the YFAS 2.0 in non-clinical and clinical samples. However, the use of the mYFAS 2.0 in bariatric surgery candidates might lead to a significant underestimation of FA prevalence and number of FA symptoms.
Bromodomain Protein BRD4 Is Essential for Hair Cell Function and Survival

Hair cells (HCs) play crucial roles in perceiving sound, acceleration, and fluid motion. The tonotopic architecture of the sensory epithelium recognizes mechanical stimuli and convert them into electrical signals. The expression and regulation of the genes in the inner ear is very important to keep the sensory organ functional. Our study is the first to investigate the role of the epigenetic reader Brd4 in the mouse inner ear. We demonstrate that HC specific deletion of Brd4 in vivo in the mouse inner ear is sufficient to cause profound hearing loss (HL), degeneration of stereocilia, nerve fibers and HC loss postnatally in mouse; suggesting an important role in hearing function and maintenance.
Tobacco Smoke and Inhaled Drugs Alter Expression and Activity of Multidrug Resistance-Associated Protein-1 (MRP1) in Human Distal Lung Epithelial Cells in vitro

Multidrug resistance-associated protein-1 (MRP1/ABCC1) is highly expressed in human lung tissues. Recent studies suggest that it significantly affects the pulmonary disposition of its substrates, both after pulmonary and systemic administration. To better understand the molecular mechanisms involved, we studied the expression, subcellular localization and activity of MRP1 in freshly isolated human alveolar epithelial type 2 (AT2) and type 1-like (AT1-like) cells in primary culture, and in the NCI-H441 cell line. Moreover, the effect of cigarette smoke extract (CSE) and a series of inhaled drugs on MRP1 abundance and activity was investigated in vitro. MRP1 expression levels were measured by q-PCR and immunoblot in AT2 and AT1-like cells from different donors and in several passages of the NCI-H441 cell line. The subcellular localization of the transporter was studied by confocal laser scanning microscopy and cell surface protein biotinylation. MRP1 activity was assessed by bidirectional transport and efflux experiments using the MRP1 substrate, 5(6)-carboxyfluorescein [CF; formed intracellularly from 5(6)-carboxyfluorescein-diacetate (CFDA)] in AT1-like and NCI-H441 cell monolayers. Furthermore, the effect of CSE as well as several bronchodilators and inhaled corticosteroids on MRP1 abundance and CF efflux was investigated. MRP1 protein abundance increased upon differentiation from AT2 to AT1-like phenotype, however, ABCC1 gene levels remained unchanged. MRP1 abundance in NCI-H441 cells were comparable to those found in AT1-like cells. The transporter was detected primarily in basolateral membranes of both cell types which was consistent with net basolateral efflux of CF. Likewise, bidirectional transport studies showed net apical-to-basolateral transport of CF which was sensitive to the MRP1 inhibitor MK-571. Budesonide, beclomethasone dipropionate, salbutamol sulfate, and CSE decreased CF efflux in a concentration-dependent manner. Interestingly, CSE increased MRP1 abundance, whereas budesonide, beclomethasone dipropionate, salbutamol sulfate did not have such effect. CSE and inhaled drugs can reduce MRP1 activity in vitro, which implies the transporter being a potential drug target in the treatment of chronic obstructive pulmonary disease (COPD). Moreover, MRP1 expression level, localization and activity were comparable in human AT1-like and NCI-H441 cells. Therefore, the cell line can be a useful alternative in vitro model to study MRP1 in distal lung epithelium.
The Probable, Possible, and Novel Functions of ERp29

The luminal endoplasmic reticulum (ER) protein of 29 kDa (ERp29) is a ubiquitously expressed cellular agent with multiple critical roles. ERp29 regulates the biosynthesis and trafficking of several transmembrane and secretory proteins, including the cystic fibrosis transmembrane conductance regulator (CFTR), the epithelial sodium channel (ENaC), thyroglobulin, connexin 43 hemichannels, and proinsulin. ERp29 is hypothesized to promote ER to cis-Golgi cargo protein transport via COP II machinery through its interactions with the KDEL receptor; this interaction may facilitate the loading of ERp29 clients into COP II vesicles. ERp29 also plays a role in ER stress (ERS) and the unfolded protein response (UPR) and is implicated in oncogenesis. Here, we review the vast array of ERp29’s clients, its role as an ER to Golgi escort protein, and further suggest ERp29 as a potential target for therapies related to diseases of protein misfolding and mistrafficking.
Effects of Nicotine Gum Administration on Vision (ENIGMA-Vis): Study Protocol of a Double-Blind, Randomized, and Controlled Clinical Trial

Studies reported that tobacco addiction was related to visual impairments, but one unresolved issue is whether the impairments are related to the many compounds existing in the cigarettes or to the effects of nicotine. On the other hand, nicotine gum can be used as replacement therapy or as a neuroprotective agent for some diseases. The main purpose of this controlled trial is to investigate the effects of nicotine gum on vision. The ENIGMA-Vis trial aims to compare two dosages of nicotine gum (2 and 4 mg) and a placebo gum in a randomized, double-blind, placebo-controlled trial of 100 participants to be allocated into a single group assignment of repeated measures (two studies; N = 50 for each one). Eligibility criteria are healthy non-smokers not diagnosed with substance abuse and without an acute or chronic medical condition. Intervention will last three sessions for each participant with a window frame of 1 week per session. Study outcomes are (1) short-term effects of nicotine gum on contrast sensitivity; (2) short-term effects of nicotine gum on chromatic contrast discrimination; and (3) whether demographics, body mass index, or serum cotinine predicts response of visual processing. This study addresses an important gap in the effects of nicotine on vision. One of the main takeaways of this study is to understand the effects of nicotine on contrast sensitivity and chromatic contrast discrimination. This information will provide a further understanding of how nicotine interacts with early visual processes and help determine how the different components present during smoking can affect vision. Clinical Trial Registration Number: RBR-46tjy3.
Gestures in Storytelling by Preschool Chinese-Speaking Children With and Without Autism

Previous findings on gestural impairment in autism are inconsistent, while scant evidence came from Chinese-speaking individuals. In the present study, preschool Chinese-speaking children with typical development and with autism were asked to generate stories from a set of wordless Cartoon pictures. Two groups were matched in chronological age and language developmental age. Their speech and gestures were coded. Compared to children with typical development, children with autism produced fewer gestures and showed lower gesture rate. Besides, children with autism produced fewer emblems and fewer supplementary gestures compared to their TD peers. Unlike children with typical development, children with autism tend to produce emblems for reinforcing, rather than supplementing information not conveyed in speech. Results showed the impairments in integrating the cross-modal semantic information in children with autism.
Effects of Recombinant Spidroin rS1/9 on Brain Neural Progenitors After Photothrombosis-Induced Ischemia

The existence of niches of stem cells residence in the ventricular–subventricular zone and the subgranular zone in the adult brain is well-known. These zones are the sites of restoration of brain function after injury. Bioengineered scaffolds introduced in the damaged loci were shown to support neurogenesis to the injury area, thus representing a strategy to treat acute neurodegeneration. In this study, we explored the neuroprotective activity of the recombinant analog of Nephila clavipes spidroin 1 rS1/9 after its introduction into the ischemia-damaged brain. We used nestin–green fluorescent protein (GFP) transgenic reporter mouse line, in which neural stem/progenitor cells are easily visualized and quantified by the expression of GFP, to determine the alterations in the dentate gyrus (DG) after focal ischemia in the prefrontal cortex. Changes in the proliferation of neural stem/progenitor cells during the first weeks following photothrombosis-induced brain ischemia and in vitro effects of spidroin rS1/9 in rat primary neuronal cultures were the subject of the study. The introduction of microparticles of the recombinant protein rS1/9 into the area of ischemic damage to the prefrontal cortex leads to a higher proliferation rate and increased survival of progenitor cells in the DG of the hippocampus which functions as a niche of brain stem cells located at a distance from the injury zone. rS1/9 also increased the levels of a mitochondrial probe in DG cells, which may report on either an increased number of mitochondria and/or of the mitochondrial membrane potential in progenitor cells. Apparently, the stimulation of progenitor cells was caused by formed biologically active products stemming from rS1/9 biodegradation which can also have an effect upon the growth of primary cortical neurons, their adhesion, neurite growth, and the formation of a neuronal network. The high biological activity of rS1/9 suggests it as an excellent material for therapeutic usage aimed at enhancing brain plasticity by interacting with stem cell niches. Substances formed from rS1/9 can also be used to enhance primary neuroprotection resulting in reduced cell death in the injury area.
Cerebral Functional Manipulation of Repetitive Transcranial Magnetic Stimulation in Cognitive Impairment Patients After Stroke: An fMRI Study

Objective: Recently, the area of repetitive transcranial magnetic stimulation (rTMS) targeting neurological rehabilitation has been advanced as a potential treatment for post-stroke cognitive impairment (PSCI). However, the underlying mechanisms remains to be elusived. This study aims to figure out cerebral functional manipulation of rTMS in patients with PSCI through using the resting-state functional magnetic resonance imaging (rs-fMRI). Methods: Thirty patients with PSCI were recruited and randomly allocated into two groups: the rTMS intervention group and control group. The rTMS intervention group was given 20 min of 5 Hz rTMS (or control) over left dorsolateral prefrontal cortex (DLPFC) besides routine cognitive intervention training for 3 consecutive weeks, five times per week, on weekdays. Cognition performance was assessed by the Minimum Mental State Examination (MMSE) and Montreal cognitive assessment (MoCA). Neural activity and functional connectivity (FC) changes were acquired by rs-fMRI with fractional amplitude of low-frequency fluctuation (fALFF) and seed-based correlation analysis. Results: Cognition improvements were observed both in rTMS intervention group and control group (P < 0.01), while the rTMS group got more significant improvent than control group (P < 0.05). To be specified, compared with the control group, the rTMS group got higher fALFF values in these brain regions including superior temporal gyrus, inferior frontal gyrus and parahippocampal gyrus, while lower fALFF values in middle temporal gyrus, middle frontal gyrus and fusiform gyrus. In addition, the rTMS group showed increased FC between LDPFC and toprecuneus, inferior temporal gyrus, middle and inferior frontal gyrus and marginal gyrus, while decreased FC between LDPFC and middle temporal gyrus and thalamus. Conclusion: The increase and decrease of neural activity and FC in cognition-related regions detected by rs-fMRI are good indicators to clarify the underlining mechanisms of rTMS on PSCI.
Peripartum Phenomenon in Crioula Lanada Sheep Susceptible and Resistant to Gastrointestinal Nematodes

This study aimed at evaluating parasitological and blood variables in native breed Crioula Lanada sheep belonging to the same herd, to identify and compare susceptible or resistant individuals to gastrointestinal nematodes during gestation and lactation phases. For this purpose, 18 Crioula sheep were used within 2 years of evaluation, in which blood and feces samples and weight of the animals were taken from their 4th month of gestation until the weaning of their lambs, in the 4th month postpartum. Feces samples were used for counting eggs per gram of feces (EPG) and, thus, to identify 12 resistant ewes (EPG < 1,000) and 6 susceptible (EPG > 1,000) to gastrointestinal nematodes. The identification of infective larvae was also performed. Blood was used for analysis of packed cell volume (PCV), eosinophil count, total plasma protein, and immunoglobulin G level against Haemonchus contortus infective larvae. The Kruskal–Wallis non-parametric comparison test was used to evaluate the differences between days of parturition and linear mixed-effects model using package lme4 in R to evaluate the groups. The main parasite species observed in the feces samples were Haemonchus, Trichostrongylus, Oesophagostomum, Ostertagia, and Cooperia in similar proportions in both groups. Susceptible ewes presented peaks of EPG at the beginning of lactation and lower PCV values throughout the study. No difference between groups was observed concerning other blood variables or body weight, but some changes were observed along with the gestation and lactation phases within each group. The physiological response of sheep to nematode infection is a useful tool to identify the most susceptible individuals within the same breed and herd and to select the most genetically resistant individuals.