bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV-1-envelope trimer transitions from prefusion-closed to CD4-bound-open conformations through an occluded-intermediate state
Authors: Lee Myungjin , Lu Maolin , Zhang Baoshan , Zhou Tongqing , Katte Revansiddha , Han Yang , Rawi Reda , Kwong Peter D. 
Published: July 2024

ABSTRACTHIV-1 infection is initiated by the interaction between the gp120 subunit in the envelope (Env) trimer and the cellular receptor CD4 on host cells. This interaction induces substantial structural rearrangement of the Env trimer. Currently, static structural information for prefusion-closed trimers, CD4-bound prefusion-open trimers, and various antibody-bound trimers is available. However, dynamic features between these static states (e.g., transition structures) are not well understood. Here, we investigate the full transition pathway of a site specifically glycosylated Env trimer between prefusion-closed and CD4-bound-open conformations by collective molecular dynamics and single-molecule Förster resonance energy transfer (smFRET). Our investigations reveal and confirm important features of the transition pathway, including movement of variable loops to generate a glycan hole at the trimer apex and formation or rearrangements of α-helices and β-strands. Notably, by comparing the transition pathway to known Env-structures, we uncover evidence for a transition intermediate, with four antibodies, Ab1303, Ab1573, b12, and DH851.3, recognizing this intermediate. Each of these four antibodies induce population shifts of Env to occupy a newly observed smFRET state: the “occluded-intermediate” state. We propose this occluded-intermediate state to be both a prevalent state of Env and an on-path conformation between prefusion-closed and CD4-bound-open states, previously overlooked in smFRET analyses.
A focal traumatic injury to the spinal cord causes an immediate and massive spreading depolarization sustained by chloride ions, with transient network dysfunction and remote cortical glia changes
Authors: Mohammadshirazi Atiyeh , Mazzone Graciela L. , Zylberberg Benjamín A. , Mio Luca , Pistorio Giulio , Falcone Carmen , Taccola Giuliano 
Published: July 2024

AbstractIn clinics, physical injuries to the spinal cord cause a temporary motor areflexia below lesion, known as spinal shock. This topic is still underexplored due to the lack of preclinical SCI models that do not use anesthesia, which would affect spinal excitability. Our innovative design considered a custom-made micro impactor that provides localized and calibrated strikes to the ventral surface of the thoracic spinal cord of the entire CNS isolated from neonatal rats. Before and after injury, multiple ventral root (VR) recordings continuously traced respiratory rhythm, baseline spontaneous activities, and electrically-induced reflex responses. As early as 200 ms after impact, an immediate transient depolarization spread from the injury site to the whole spinal cord with distinct segmental velocities. Stronger strikes induced higher potentials causing, at the site of injury, a transient drop in tissue oxygen levels and a massive cell death with complete disconnection of longitudinal tracts. Below the impact site, expiratory rhythm and spontaneous lumbar activity were suppressed. On lumbar VRs, reflex responses transiently halted but later recovered to control values, while electrically-induced fictive locomotion remained perturbed. Moreover, low-ion modified Krebs solutions differently influenced impact-induced depolarizations, the magnitude of which amplified in low-Cl−. Moreover, remote changes in cortical glia occurred soon after spinal damage. Overall, our novel in vitro platform traces the immediate functional consequences of impacts to the spinal cord during development. This basic study provides insights on the SCI pathophysiology, unveiling an immediate chloride dysregulation and transient remote glial changes in the cortex.
Subcellular ToF-SIMS imaging of the snow algaSanguina nivaloidesby combining high mass and high lateral resolution acquisitions
Authors: Seydoux Claire , Ezzedine Jade A. , Larbi Grégory Si , Ravanel Stéphane , Maréchal Eric , Barnes Jean-Paul , Jouneau Pierre-Henri 
Published: July 2024

ABSTRACTTime-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging has demonstrated great potential for metabolic imaging, yet achieving sufficiently high lateral and mass resolution to reach the organelle scale remains challenging. We have developed an approach by combining ToF-SIMS imaging acquisitions at high lateral resolution (> 150 nm) and high mass resolution (9,000). The data were then merged and processed using multivariate analysis (MVA), allowing for the precise identification and annotation of 85% of the main contributors to the multivariate analysis components at high lateral resolution. Insights into the electron microscopy sample preparation are provided, especially as we reveal that at least three different osmium-containing complexes can be found depending on the specific chemical environment of organelles. In cells of the snow algaSanguina nivaloides, living in a natural environment limited in nutrients such as phosphorus (P), we were able to map elements and molecules within their subcellular context, allowing for the molecular fingerprinting of organelles at a resolution of 100 nm, as confirmed by correlative electron microscopy. It was thus possible to highlight thatS. nivaloideslikely absorbed selectively some inorganic P forms provided by P-rich dust deposited on the snow surface.S. nivaloidescells could maintain phosphorylations in the stroma of the chloroplast, consistently with the preservation of photosynthetic activity. The presented method can thus overcome the current limitations of ToF-SIMS for subcellular imaging and contribute to the understanding of key questions such as P homeostasis and other cell physiological processes.
NanoLAS 2.0: A Comprehensive Update on a Nanobody-Focused Platform with Advanced Visualization and Docking Simulation Features
Authors: Zheng Zebiao , Qin Wei , Yu Kangrui , Hong Yangqi , Tang Yongqi , Wang Tiantai , Liang Lixin , Huang Bingding , Wang Xin 
Published: July 2024

AbstractSummaryNanobodies, a unique subclass of antibodies initially discovered in camelids, characterized by the absence of light chains and consisting solely of a heavy chain variable region. This distinctive structure endows nanobodies with inherent advantages in the realms of disease treatment and biopharmaceutical applications. Presently, research and applications concerning nanobodies are experiencing rapid growth. However, existing databases suffer from non-uniform data sources and a lack of data standardization. To address these issues, we developed the NanoLAS database in 2023. Despite the progress in data integration made by NanoLAS, there was room for improvement in search functionality, three-dimensional structural display, and other areas. Building upon this foundation, we introduce the comprehensively updated NanoLAS 2.0. This version offers updates to data sources, precise 3D structural presentation, and molecular docking simulation capabilities, refines the multi-condition search mechanism, and incorporates a brand-new sequence viewer as well as epitope prediction functionality. Additionally, to cater to the needs of researchers, we have designed a user-friendly and intuitive interface. In summary, we anticipate that NanoLAS 2.0 will serve as a powerful and easy-to-use research tool, facilitating researchers in their exploration of nanobodies and propelling advancements in the field of nanobody research and application.AvailabilityNanoLAS 2.0 is available athttps://www.nanolas2.onlineContactbingdinghuang@sztu.edu.cnandwangxin@sztu.edu.cn
Optimal sigmoid function models for analysis of transspinal evoked potential recruitment curves recorded from different muscles
Authors: Skiadopoulos Andreas , Knikou Maria 
Published: July 2024

AbstractRecruitment input-output curves of transspinal evoked potentials that represent the net spinal motor output of alpha motor neurons, and those of cortically, spinally or peripherally induced responses are used extensively in research as neurophysiological biomarkers to establish physiological or pathological behavior of neuronal networks as well as post-treatment recovery. A comparison between different sigmoidal models to fit the transspinal evoked potentials recruitment curve and estimate the parameters of physiological importance has not been performed. This study sought to address this gap by fitting eight sigmoidal models (Boltzmann, Hill, Log-Logistic, Log-Normal, Weibull-1, Weibull-2, Gompertz, Extreme Value Function) to the transspinal evoked potentials recruitment curves of soleus and tibialis anterior recorded under four different cathodal stimulation settings. The sigmoidal models were ranked based on the Akaike information criterion, and their performance was assessed in terms of Akaike differences and weights values. Additionally, an interclass correlation coefficient between the predicted parameters derived from the best models fitted to the recruitment curves was also established. A Bland-Altman analysis was conducted to evaluate the agreement between the predicted parameters from the best models. The findings revealed a muscle dependency, with the Boltzmann and Hill models identified as the best fits for the soleus, while the Extreme Value Function and Boltzmann models were optimal for the tibialis anterior transspinal evoked potentials recruitment curves. Excellent agreement for the upper asymptote, slope, and inflection point parameters was found between Boltzmann and Hill models for the soleus, and for slope and inflection point parameters between Extreme Value Function and Boltzmann models for the tibialis anterior. Notably, the Boltzmann model for soleus and the Extreme Value Function model for tibialis anterior exhibited less susceptibility to inaccuracies in estimated parameters. Based on these findings, we suggest the Boltzmann and the Extreme Value Function models for fitting the soleus and the tibialis anterior transspinal evoked potentials recruitment curve, respectively.
A novel repressor-activator-competitor module comprising C2H2zinc finger and NAC transcription factors regulates rice grain development
Authors: Jaiswal Priya , Priyadarshini Richa , Yadav Antima , Aswathi P V , Mahto Arunima , Mathew Iny Elizebeth , Das Upasana , Qasim Falah , Vichitra Ankur , Panwar Akanksha , Verma Ankit , Tyagi Akhilesh K. , Agarwal Pinky 
Published: July 2024

ABSTRACTGrain size and quality are crucial agronomic traits. We have characterized a seed-preferential C2H2zinc finger transcriptional repressor,ZOS1-15. Its overexpression, knock-down and knock-out plants indicated a negative control over grain size due to altered cell expansion. ZOS1-15 homodimerized and directly interacted with co-repressor TOPLESS and histone deacetylases to form a repression complex. ZOS1-15 also interacted with Mediator subunit MED14_1 and a seed-preferential transcriptional activator, ONAC024, with three alternatively spliced isoforms. The ectopic expression ofONAC024negatively affected plant growth and development. Seed-preferential overexpression and knock-down plants showed ONAC024 as a positive regulator of grain length due to increased cell proliferation and expansion. CRES-T generated transgenic rice plants indicated a functional divergence amongst ONAC024 isoforms. Tandem interactions were observed between ONAC024-ONAC023-ONAC026-ONAC020. ZOS1-15 and ONAC024 functioned antagonistically to regulate grain amylose and SSP accumulation while ONAC023 affected only amylose. ZOS1-15 and ONAC024 directly regulated the expression of two SSP encoding genes. Binding of ONAC024 was competed by ONAC025-MADS29 complex. The seed-preferential overexpression of SS1/ ONAC025 resulted in decreased grain size and amylose content, but higher yield. This study proposes a ’repressor-activator-competitor’ module, wherein ZOS1-15, ONAC024, ONAC023, ONAC025 along with their interactors synergistically and antagonistically regulate multiple aspects of rice grain development.
Vesicle Picker: A tool for efficient identification of membrane protein complexes in vesicles
Authors: Karimi Ryan , Coupland Claire E. , Rubinstein John L. 
Published: July 2024

AbstractElectron cryomicroscopy (cryo-EM) has recently allowed determination of near-atomic resolution structures of membrane proteins and protein complexes embedded in lipid vesicles. However, particle selection from electron micrographs of these vesicles can be challenging due to the strong signal contributed from the lipid bilayer. This challenge often requires iterative and laborious particle selection workflows to generate a dataset of high-quality particle images for subsequent analysis. Here we present Vesicle Picker, an open-source program built on the Segment Anything model. Vesicle Picker enables automatic identification of vesicles in cryo-EM micrographs with high recall and precision. It then exhaustively selects all potential particle locations, either at the perimeter or uniformly over the surface of the projection of the vesicle. The program is designed to interface with cryoSPARC, which performs both upstream micrograph processing and downstream single particle image analysis. We demonstrate Vesicle Picker’s utility by determining a high-resolution map of the vacuolar-type ATPase from micrographs of native synaptic vesicles (SVs) and identifying an additional protein or protein complex in the SV membrane.
Systematically investigating and identifying bacteriocins in the human gut microbiome
Authors: Zhang Dengwei , Zou Yinai , Shi Yuqi , Zhang Junliang , Liu Jing , Wu Gengfan , Zhang Jian , Gao Ying , Chen Muxuan , Li Yong-Xin 
Published: July 2024

SummaryHuman gut microbiota produces unmodified bacteriocins, natural antimicrobial peptides that protect against pathogens and regulate host physiology. However, current bioinformatic tools limit the comprehensive investigation of bacteriocins’ biosynthesis, obstructing research into their biological functions. Here, we introduce IIBacFinder, a superior analysis pipeline for identifying unmodified class II bacteriocins. Through large-scale bioinformatic analysis and experimental validation, we demonstrate their widespread distribution across the bacterial kingdom, with being niche-specific and enriched in the human microbiome. Analyzing over 280,000 bacterial genomes, we reveal the diverse potential of human gut bacteria to produce these bacteriocins. Guided by meta-omics analysis, we synthesized 26 hypothetical bacteriocins from gut commensal species, with 16 showing antibacterial activities. Furtherex vivotests show minimal impact of narrow-spectrum bacteriocins on human fecal microbiota. Our study highlights the huge biosynthetic potential of unmodified bacteriocins in the human gut, paving the way for understanding their biological functions and health implications.
Adaptive Dynamic Social Networks Using an Agent-Based Model to Study the Role of Social Awareness in Infectious Disease Spread
Authors: López Leonardo , Giovanini Leonardo 
Published: July 2024

AbstractThe synergy between the spread of infectious diseases and individual behavior is widely recognized. Our pioneering methodology introduces a model based on agents embedded within adaptive temporal networks, providing a nuanced portrayal of daily interactions through an agent-based paradigm. Each agent encapsulates the interactions of individuals, with external stimuli and environmental cues influencing their conduct. Comprising three intertwined elements—individual behavior, social dynamics, and epidemiological factors—the model has been validated against real-world influenza outbreaks, demonstrating superior performance compared to traditional methodologies. Our framework exhibits extensive versatility and applicability by encapsulating individual-level dynamics through elementary rules and simulating complex social behaviors such as social consciousness.
CARDIO-QVARK Diagnose Ischemic Myocardiocyte!
Authors: Marzoog Basheer Abdullah , Chomakhidze Peter , Suvorov Alexander , Kopylov Philipp 
Published: July 2024

AbstractBackgroundIschemic heart disease (IHD) has the highest mortality rate in the globe. This returns to the poor diagnostic and therapeutic strategies including the early prevention methods.AimsTo assess the changes in the single channel electrocardiography (SCECG) at rest and on exercise test in patients with vs without IHD confirmed by stress computed tomography myocardial perfusion (CTP) imaging with vasodilatation stress-test.ObjectivesIHD frequently have preventable risk factors and causes that lead to the disease appearance. However, the lack of the proper diagnostic and prevention tools remains a global challenge in or era despite the current scientific advances.Material and methodsA single center observational study included 80 participants from Moscow. The participants aged ≥ 40 years and given a written consent to participate in the study. Both groups, G1=31 with vs G2=49 without post stress induced myocardial perfusion defect, passed cardiologist consultation, anthropometric measurements, blood pressure and pulse rate, echocardiography, cardio-ankle vascular index, performing bicycle ergometry, recording 3-minutes SCECG (using CARDO-QVARK) before and just after bicycle ergometry, and then performing CTP. The LASSO regression with nested cross-validation was used to find association between CARDO-QVARK parameters and the existence of the perfusion defect. Statistical processing carried out using the R programming language v4.2, Python v.3.10 [^R], and Statistica 12 programme.ResultsThe CARDO-QVARK parameters analysis have a specificity 75.5 % [95 % confidence interval (CI); 0.628; 0.88], sensitivity 51.6 % [95 % CI; 0.333; 0.695], area under the curve (AUC) 67 % [95 % CI; 0.530; 0.801] in compare to bicycle ergometry AUC; 50.7 % [95 % CI; 0.388; 0.625], specificity 53.1 % [95 % CI; 0.392; 0.673], sensitivity 48.4 % [95 % CI; 0.306; 0.657], based on our study results.ConclusionThe SCECG have no statistically significant higher diagnostic accuracy in compare to bicycle ergometry. However, CARDO-QVARK has the potential to improve the diagnostic accuracy of the bicycle ergometry.OtherFurther investigations required to uncover the hidden capabilities of CARDO-QVARK in the diagnosis of ischemic heart disease.
CLINICAL AND COGNITIVE PHENOTYPING OF COPY NUMBER VARIANTS PATHOGENIC FOR NEURODEVELOPMENTAL DISORDERS FROM A MULTI-ANCESTRY BIOBANK
Authors: Zaks Nina , Mahjani Behrang , Reichenberg Abraham , Birnbaum Rebecca 
Published: July 2024

ABSTRACTBackgroundRare copy number variants (CNVs) are pathogenic for neurodevelopmental disorders (NDDs) and effect neurocognitive impairment. In aggregate, NDD CNVs may present in up to 2% of population cohorts with implications for neuropsychiatric disease risk and cognitive health. However, analyses of NDD CNVs in biobanks or population cohorts have been hindered by limited clinical or cognitive phenotypes, and a lack of ancestral diversity. In the current proof-of-concept study, NDD CNV carriers were recontacted from BioMe, a multi-ancestry biobank derived from the Mount Sinai healthcare system, to enable ‘deep phenotyping’ beyond electronic health record outcomes.MethodsFrom BioMebiobank, 892 adult participants were recontacted, including 335 harboring NDD CNVs, 217 with schizophrenia and 340 neurotypical controls as comparators. Clinical and cognitive assessments were administered to each recruited participant.ResultsSeventy-three participants completed study assessments (mean age=48.8 years; 66% female; 36% African, 26% European, 34% Hispanic), or 8% of the recontacted subset, including 30 NDD CNV carriers across 15 loci. Among NDD CNV carriers, assessments indicated 40% with mood and anxiety disorders, 30% with learning disorders, and 13% with a history of special education. NDD CNV carriers were significantly cognitively impaired compared to controls on digit span backwards (Beta=-1.76, FDR=0.04) and digit span sequencing (Beta=-2.01, FDR=0.04).ConclusionsFeasibility of “recall-by-genotype” from a multi-ancestry biobank was established for NDD CNV carriers, along with comparator groups. The current study corroborated past reports of NDD CNVs effects of cognitive impairment, while elucidating clinical phenotypes for recalled individuals. Future “recall-by-genotype” studies may further facilitate clinical characterization of disease-relevant genomic variants.
Apathy, intentions, explicit attitudes, and approach-avoidance tendencies in physical activity behavior
Authors: Farajzadeh Ata , Jabouille François , Benoit Nickolas , Bezeau Olivier , Bourgie Tristan , Gerro Benjamin , Ouimet Jacob , Boisgontier Matthieu P. 
Published: July 2024

ABSTRACTBackgroundGreater behavioral apathy has been shown to be associated with lower engagement in physical activity. However, the mechanisms underlying this association remain overlooked and poorly understood. Intentions, explicit attitudes, and approach-avoidance tendencies toward physical activity may play a central role in the relationship, given their strong links to motivation and physical activity.MethodsAn online study was conducted in 365 participants aged 54±18 years. All measures were assessed using questionnaires, except approach-avoidance tendencies, which were derived from reaction times in an approach-avoidance task. Component mediation analyses based on multiple linear regressions were conducted to examine whether the intention to be physically active mediated the relationship between behavioral apathy levels and usual physical activity levels, and whether explicit attitudes and approach-avoidance tendencies mediated the relationship between behavioral apathy and the intention.ResultsResults showed that weaker intentions to be physically active mediated the association between higher behavioral apathy and lower usual weekly levels of moderate-to-vigorous physical activity. In addition, explicit attitudes mediated the effect of behavioral apathy on intentions to be physically active. Results on approach-avoidance tendencies showed a significant three-way interaction between apathy, stimulus (physical activity vs. sedentary behavior), and action direction (approach vs. avoidance) on corrected reaction time (b = 19.6; 95CI = 2.0 to 37.3; p = .029), with higher apathy being associated with a greater tendency to avoid physical activity stimuli and to approach sedentary stimuli. However, we found no evidence suggesting that these tendencies mediated the effect of apathy on intentions or habitual physical activity. Based on our data, a mean item score greater than 34.5% of the scale range (e.g., >3.07 on a 1–7 scale) is indicative of behavioral apathy.ConclusionThis study provides new insights into the role of intentions, explicit attitudes, and approach-avoidance tendencies toward physical activity in the relationship between behavioral apathy levels and the engagement in physical activity.