bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digital Twin Brain Simulator: Harnessing Primate ECoG Data for Real-Time Consciousness Monitoring and Virtual Intervention
Authors: Takahashi Yuta , Idei Hayato , Komatsu Misako , Tani Jun , Tomita Hiroaki , Yamashita Yuichi 
Published: May 2024

ABSTRACTAt the forefront of bridging computational brain modeling with personalized medicine, this study introduces a novel, real-time, electrocorticogram (ECoG) simulator based on the digital twin brain concept. Utilizing advanced data assimilation techniques, specifically a Variational Bayesian Recurrent Neural Network model with hierarchical latent units, the simulator dynamically predicts ECoG signals reflecting real-time brain latent states. By assimilating broad ECoG signals from Macaque monkeys across awake and anesthetized conditions, the model successfully updated its latent states in real-time, enhancing the precision of ECoG signal simulations. Behind the successful data assimilation, a self-organization of latent states in the model was observed, reflecting brain states and individuality. This self-organization facilitated simulation of virtual drug administration and uncovered functional networks underlying changes in brain function during anesthesia. These results show that the proposed model is not only capable of simulating brain signals in real-time with high accuracy, but is also useful for revealing underlying information processing dynamics.
Dynamic changes in mitochondria support phenotypic flexibility of microglia
Authors: Espinoza Katherine , Schaler Ari W. , Gray Daniel T. , Sass Arielle R. , Moore Kamilia , Yu Megan E. , Chamorro Casandra G. , De Biase Lindsay M. 
Published: May 2024

ABSTRACTMicroglial capacity to adapt to local tissue needs is a hallmark feature of these cells. Yet, a full understanding of the intracellular machinery that allows them to rapidly adjust their cellular phenotype is lacking. New studies show that macrophage ability to alter cellular phenotype is critically regulated by their mitochondria. Indeed, mitochondria are increasingly recognized as key intracellular signaling and regulatory hubs, in addition to their well-established role as ATP producers. Surprisingly little is known about microglial mitochondriain vivoand whether they play similar roles in regulating microglial capacity to alter cellular phenotype. Here, we generated novel transgenic crosses for accurate visualization of microglial mitochondria and found, unexpectedly, that mitochondria did not appear to regulate microglial tissue surveillance. However, brain regions where microglia show early responses to aging also showed early changes in microglial mitochondria. Microglial mitochondria were also altered within hours of LPS injections and microglial expression of inflammation-, trophic-, and phagocytosis-relevant genes was strongly correlated with expression levels of specific mitochondria-relevant genes. Finally, direct genetic manipulation of microglial mitochondria altered microglial morphology and led to brain-region specific effects on microglial gene expression. Overall, this study provides foundational information about microglial mitochondria and their relationship to differences in cell phenotype that occur across brain region, during pathological insults, and during aging.
Identification of distinct rodent-associated adenovirus lineages from a mixed-use landscape in the Western Ghats biodiversity hotspot
Authors: Ansil B.R. , Sanyal Avirup , Sreenivas Darshan , Garg Kritika M. , Ramakrishnan Uma , Chattopadhyay Balaji 
Published: May 2024

AbstractShifts in land-use patterns and increased human-livestock-wildlife interactions have generated numerous possibilities for pathogen spillover. This demands increased efforts of pathogen surveillance in wildlife, especially in changing landscapes with high biodiversity. We investigated adenovirus diversity in small mammals, an understudied host taxon, from a forest-plantation mosaic in the Western Ghats biodiversity hotspot. Using PCR-based screening followed by Sanger sequencing and phylogenetic analyses, we attempted to detect and characterize adenovirus diversity in seven species of small mammals. We observed high prevalence (up to 38.8%) and identified five lineages of adenoviruses with unique mutations in the endemic and dominant small mammal species,Rattus satarae. These lineages significantly differed from other known Murine adenoviruses (p-distance > 25%), indicating the likelihood of novel adenovirus diversity in this endemic small mammal. Collectively, our results highlight the potential for unexplored diversity of DNA viruses like adenovirus in poorly explored host taxa inhabiting human-used landscapes and its zoonotic implications.
Renal L-2-hydroxyglutarate dehydrogenase activity promotes hypoxia tolerance and mitochondrial metabolism inDrosophila melanogaster
Authors: Mahmoudzadeh Nader H. , Heidarian Yasaman , Tourigny Jason P. , Fitt Alexander J. , Beebe Katherine , Li Hongde , Luhur Arthur , Buddika Kasun , Mungcal Liam , Kundu Anirban , Policastro Robert A. , Brinkley Garrett J. , Zentner Gabriel E. , Nemkov Travis , Pepin Robert , Chawla Geetanjali , Sudarshan Sunil , Rodan Aylin R. , D’Alessandro Angelo , Tennessen Jason M. 
Published: May 2024

ABSTRACTThe mitochondrial enzyme L-2-hydroxyglutarate dehydrogenase (L2HGDH) regulates the abundance of L-2-hydroxyglutarate (L-2HG), a potent signaling metabolite capable of influencing chromatin architecture, mitochondrial metabolism, and cell fate decisions. Loss of L2hgdh activity in humans induces ectopic L-2HG accumulation, resulting in neurodevelopmental defects, altered immune cell function, and enhanced growth of clear cell renal cell carcinomas. To better understand the molecular mechanisms that underlie these disease pathologies, we used the fruit flyDrosophila melanogasterto investigate the endogenous functions of L2hgdh. Our studies revealed that while L2hgdh is not essential for growth or viability under standard culture conditions,L2hgdhmutants are hypersensitive to hypoxia and expire during the reoxygenation phase with severe disruptions of mitochondrial metabolism. Moreover, we find that the fly renal system (Malpighian tubules; MTs) is a key site of L2hgdh activity, asL2hgdhmutants that express a rescuing transgene within the MTs survive hypoxia treatment and exhibit normal levels of mitochondrial metabolites. We also demonstrate that even under normoxic conditions,L2hgdhmutant MTs experience significant metabolic stress and are sensitized to aberrant growth upon Egfr activation. Overall, our findings present a model in which renal L2hgdh activity limits systemic L-2HG accumulation, thus indirectly regulating the balance between glycolytic and mitochondrial metabolism, enabling successful recovery from hypoxia exposure, and ensuring renal tissue integrity.
Circadian Coupling Orchestrates Cell Growth
Authors: Gutu Nica , Nordentoft Malthe S. , Kuhn Marlena , Ector Carolin , Finger Anna-Marie , Heltberg Mathias Spliid , Jensen Mogens Høgh , Keilholz Ulrich , Kramer Achim , Herzel Hanspeter , Granada Adrián E. 
Published: May 2024

SummarySingle-cell circadian oscillators exchange extracellular information to sustain coherent circadian rhythms at the tissue level. Within cells, the circadian clock and the cell cycle couple, yet the mechanisms governing this interplay remain poorly elucidated. Here, we study the role of extracellular circadian communication in the intracellular coordination between the circadian clock and the cell cycle. We demonstrate that the loss of extracellular circadian synchronization disrupts circadian and cell cycle coordination within individual cells, impeding collective tissue growth. Coherent circadian rhythms yield oscillatory growth patterns, unveiling a global timing regulator of tissue dynamics. Knocking down core circadian elements abolishes observed effects, highlighting the central role of circadian clock regulation. Our research underscores the significance of tissue-level circadian disruption in regulating proliferation, thereby linking disrupted circadian clocks with oncogenic processes. These findings illuminate the intricate interplay between circadian rhythms, cellular signaling, and tissue physiology, enhancing our understanding of tissue homeostasis and growth regulation in both health and disease contexts.
WITHDRAWN: Prevalence ofkatGandinhAmutations in genes associated with isoniazid resistance inMycobacterium tuberculosisclinical isolates in Cameroon
Authors: Nono Vanessa Ninkeh , Nantia Edouard Akono , Mutshembele Awelani Miranda , Teagho Sorelle Nguimfack , Simo Yannick Willy Kamdem , Takong Brenda Shile , Djieugoue Yvonne Josiane , Assolo Yannick Patrick , Ongboulal Suzanne Magloire , Awungafac Stanley Nkemnji , Eyangoh Sara , Makhado Ndivuhu Agnes , Mensah Eric , Donfack Valerie Flore Donkeng 
Published: May 2024

Withdrawal statementThis manuscript has been withdrawn by the authors as it was submitted and made public without the full consent of all the authors. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Fructosamine and Triglycerides - Developing an Index for Assessing Insulin Resistance
Authors: de Oliveira Andrade Luís Jesuíno , Matos de Oliveira Gabriela Correia , Matos de Oliveira Luísa Correia , Moreno de Brito Luiz Felipe , Matos de Oliveira Luís 
Published: May 2024

ABSTRACTIntroductionInsulin resistance (IR) is a metabolic condition where cells become less responsive to insulin, affecting glucose absorption and leading to diseases like type 2 diabetes. Factors like obesity and high triglycerides worsen IR. Fructosamine is a key marker for short-term glycemic control and can indicate IR. Various methods, like the euglycemic clamp and HOMA-IR index, assess IR, with the TyG index emerging as a simple and reliable tool due to its strong correlation with IR.ObjectiveTo develop and evaluate a novel IR index that incorporates both fructosamine and triglyceride levels, aiming to improve the accuracy of IR assessment compared to existing methods.MethodsThis study investigated IR using established methods and proposed a novel TrigFruc index incorporating fructosamine. Data from 200 individuals was analyzed to assess the TrigFruc index’s performance compared to existing methods (HOMA-IR and TyG index). Descriptive statistics summarized participant demographics, and Pearson’s correlation evaluated the relationship between TrigFruc and HOMA-IR and between TrigFruc and TyG index. A receiver operating characteristic (ROC) analysis identified the optimal TrigFruc cut-off point for IR detection, comparing its sensitivity and specificity to HOMA-IR and TyG index.ResultsStudy with 200 participants (63% female, avg. age 46.6 years), the established HOMA-IR index identified IR in 32% (64 individuals) while the TyG index found it in 66% (132). The new TrigFruc index showed a weaker correlation with HOMA-IR (r=0.28) compared to the TyG index (r=0.44). For detecting IR based on HOMA-IR, the optimal TrigFruc cut-off (Ln 4.57) had just 50% sensitivity (correctly identifying half of true IR cases) but low specificity (23%, high misclassification of non-IR cases). When compared to the TyG index, the optimal TrigFruc cut-off (Ln 4.74) showed excellent performance with high sensitivity (85%, strong ability to identify true IR) and specificity (95%, low misclassification of non-IR).ConclusionThe TrigFruc index, incorporating fructosamine, shows promise for IR assessment. Compared to HOMA-IR, it exhibits better correlation with the TyG index and superior sensitivity and specificity for IR detection when using the TyG index as a reference.
Use of assistive technology to assess distal motor function in subjects with neuromuscular disease
Authors: Vincent-Genod Dominique , Roche Sylvain , Barrière Aurélie , de Lattre Capucine , Tinat Marie , Venema Eelke , Lagrange Emmeline , de Souza Adriana Gomes Lisboa , Thomann Guillaume , Coton Justine , Gautheron Vincent , Féasson Léonard , Rippert Pascal , Vuillerot Carole 
Published: May 2024

AbstractPurposeAmong the 32 items of the Motor Function Measure scale, 3 concern the assessment of hand function on a paper-based support. Their characteristics make it possible to envisage the use of a tablet instead of the original paper-based support for their completion. This would then make it possible to automate the score to reduce intra- and inter-individual variability.The main objective of the present study was to validate the digital completion of items 18, 19, and 22 by measuring the agreement of the scores obtained using a digital tablet with those obtained using the original paper-based support in children and adults with various neuromuscular diseases (NMD). The secondary objective is to calibrate an algorithm for the automatic items scoring.DesignProspective, multicentre, non-interventional study.MethodsNinety-eight subjects aged 5 to 60 years with a confirmed NMD completed MFM items 18, 19, and 22 both on a paper support and a digital tablet.ResultsThe median age of included subjects was 16.2 years. Agreement between scores as assessed using the weighted Kappa coefficient was almost perfect for the scores of items 18 and 22 (K=0.93, and 0.95, respectively) and substantial for item 19 (K=0.70). In all cases of disagreement, the difference was of 1 point. The most frequent disagreement concerned item 19; mainly in the direction of a scoring of 1 point less on the tablet. An automatic analysis algorithm was tested on 82 recordings to suggest improvements.ConclusionThe switch from original paper-based support to the tablet results in minimal and acceptable differences, and maintains a valid and reproducible measure of the 3 items. The developed algorithm for automatic scoring appears feasible with the perspective to include them in a digital application that will make it easier to monitor patients.
Viral methyltransferase inhibitors: berbamine, venetoclax, and ponatinib as efficacious antivirals against Chikungunya virus
Authors: Bhutkar Mandar , Saha Ankita , Tomar Shailly 
Published: May 2024

AbstractChikungunya virus (CHIKV), transmitted by mosquitoes, poses a significant global health threat. Presently, no effective treatment options are available to reduce the disease burden. The lack of approved therapeutics against CHIKV and the complex spectrum of chronic musculoskeletal and neurological manifestations raise significant concerns, and repurposing drugs could offer swift avenues in the development of effective treatment strategies. RNA capping is a crucial step meditated by non-structural protein 1 (nsP1) in CHIKV replication. In this study, FDA-approved antivirals targeting CHIKV nsP1 methyltransferase (MTase) have been identified by structure-based virtual screening. Berbamine Hydrochloride (BH), ABT199/Venetoclax (ABT), and Ponatinib (PT) were the top hits, which exhibited robust binding energies. Tryptophan fluorescence spectroscopy-based assay confirmed binding of BH-, ABT-, and PT to purified nsP1 with KDvalues ∼5.45 μM, ∼161.3 μM, and ∼3.83μM, respectively. A dose-dependent decrease in CHIKV nsP1 MTase activity was observed in a capillary electrophoresis-based assay. Treatment with BH, ABT, and PT lead to a dose-dependent reduction in the virus titer with IC50<100, ∼3.46, and <3.9 nM, respectively, and reduced viral mRNA levels. The nsP1 MTases are highly conserved among alphaviruses; therefore, BH, ABT, and PT, as expected, inhibited replication machinery in Sindbis virus (SINV) replicon assay with IC50∼1.94, ∼0.23, and >1.25 μM, respectively. These results underscore the efficacy and promise of repurposing drugs as rapid and effective antiviral therapeutics against CHIKV.HighlightsBerbamine Hydrochloride (BH), ABT199/Venetoclax (ABT), and Ponatinib (PT) identified as inhibitors of Chikungunya virus (CHIKV) nsP1Molecules BH, ABT and PT make moelcular interactions with nsP1: KDvalues ∼5.45, ∼161.3, and ∼3.83 in μM, respectively and effectively inhibit methyltransferase activity.BH, ABT, and PT exhibited potent antiviral activity against CHIKV in cell-based assays, with IC50<100, ∼3.46, and <3.9 nM.BH, ABT, and PT also inhibit Sindbis virus, the prototype alphavirus with IC50∼1.94, ∼0.23, and >1.25 μM respectively demonstrating broad spectrum antiviral efficacy.Graphical Abstract
The exoproteome and surfaceome of toxigenicCorynebacterium diphtheriae1737 and its response to iron-restriction and growth on human hemoglobin
Authors: Goring Andrew K. , Hale Scott T. , Dasika Poojita , Chen Yu , Clubb Robert T. , Loo Joseph A. 
Published: May 2024

ABSTRACTToxin-producingCorynebacterium diphtheriaestrains are the etiological agent of the severe upper respiratory disease, diphtheria. A global phylogenetic analysis revealed that biotype gravis is particularly lethal as it produces diphtheria toxin and a range of other virulence factors, particularly when it encounters low levels of iron at sites of infection. To gain insight into how it colonizes its host we have identified iron-dependent changes in the exoproteome and surfaceome ofC. diphtheriaestrain 1737 using a combination of whole-cell fractionation, intact cell surface proteolysis, and quantitative proteomics. In total, we identified 1,425 of the predicted 2,265 (63%) proteins encoded by its reference genome. For each protein we quantified its degree of secretion and surface-exposure, revealing that exoproteases and hydrolases predominate in the exoproteome, while the surfaceome is enriched with adhesins, particularly DIP2093. Our analysis provides insight into how components in the heme-acquisition system are positioned, showing pronounced surface-exposure of the strain-specific ChtA/ChtC paralogues and high secretion of the species-conserved heme-binding HtaA protein suggesting it functions as a hemophore. Profiling the response of the exoproteome and surfaceome after microbial exposure to human hemoglobin and iron limitation reveals potential virulence factors that may be expressed at sites of infection. Data are available via ProteomeXchange with identifier PXD051674.
Alzheimer’s disease and neurodegeneration in symptomatic cerebral small vessel disease
Authors: Arndt Philipp , Pfister Malte , Perosa Valentina , Mattern Hendrik , Bernal Jose , John Anna-Charlotte , Dörner Marc , Müller Patrick , Braun-Dullaeus Rüdiger C. , Garz Cornelia , Nelke Christopher , Kokott Alma , Jansen Robin , Gliem Michael , Meuth Sven G. , Henneicke Solveig , Vielhaber Stefan , Neumann Katja , Schreiber Stefanie 
Published: May 2024

AbstractBackgroundCo-occurrence of cerebral small vessel disease (CSVD) is common in aging and Alzheimer’s disease (AD) dementia, but, in symptomatic CSVD prevalence and role of AD and neurodegenerative co-pathologies have been less explored.MethodsIn vivodetermination of prevalence, predictors and relevance for cognition of AD and neurodegenerative co-pathologies in symptomatic CSVD, including deep perforator arteriopathy (DPA) and cerebral amyloid angiopathy (CAA), utilizing cerebrospinal fluid (CSF) biomarkers. Cross-sectional study from October 2010 to September 2021 of participants with magnetic resonance imaging (MRI) and CSF biomarkers (amyloid-β 42/40 ratio, phosphorylated-tau, total-tau, neurofilament light). Biomarker levels were compared among groups; prevalence of ATN classification subtypes was estimated and related to clinical phenotype, CSVD MRI markers and global cognition.ResultsThe study comprised 229 individuals (median age 74 years; 47% females), 70 with AD dementia, 79 with probable CAA, 62 with DPA patients and 18 healthy controls. Participants were categorized based on the ATN classification: normal biomarkers (A-T-N-), AD pathology continuum (A+T±N±), and non-AD pathological changes, including primary age-related tauopathy (PART, A-T+N+) or isolated neurodegeneration (A-T-N+). Of 141 CSVD patients, 43 (30%) were A-T-N-, 39 (28%) A+T±N±, with lower prevalence in DPA than CAA (15% vs. 38%, p = .003), 18 (13%) A-T+N+, and 41 (29%) A-T-N+, with higher prevalence in DPA than CAA (42% vs. 19%, p = .002). A+T±N± was associated with increasing age, female sex, lobar hemorrhages and low burden of deep white matter hyperintensities and lacunes. A-T-N+ was related to younger age, symptomatic stroke and lacunes. A-T+N+ had no specific predictors, except advanced age. Each pathological ATN profile was independently related to lower Mini Mental State Examination scores (A+T±N±: B = -2.7, p = .013; A-T+N+: B = -4.6, p = .002; A-T-N+: B = -2.3, p = .034), accounting for demographics, clinical phenotype and MRI CSVD severity.ConclusionsUsing biomarkers, this study confirmsin vivothat CSVD frequently co-occurs with AD or neurodegenerative pathologies, exerting independent effects on cognitive health. As disease-modifying therapies emerge, integrating interacting biomarkers will be crucial for the selection of patients with the greatest benefit.
All-optical source size and emittance measurements of laser-accelerated electron beams
Authors: Salgado F. C. , Kozan A. , Seipt D. , Hollatz D. , Hilz P. , Kaluza M. , Sävert A. , Seidel A. , Ullmann D. , Zhao Y. , Zepf M. 
Published: May 2024

Novel schemes for generating ultralow emittance electron beams have been developed in past years and promise compact particle sources with excellent beam quality suitable for future high-energy physics experiments and free-electron lasers. Recent theoretical work has proposed a laser-based method capable of resolving emittances in the sub 0.1 mm mrad regime by modulating the electron phase space ponderomotively. Here we present the first experimental demonstration of this scheme using a laser wakefield accelerator. The observed emittance and source size are consistent with published values. We also show calculations demonstrating that tight bounds on the upper limit for emittance and source size can be derived from the “laser-grating” method even in the presence of low signal to noise and uncertainty in laser-grating parameters.

Published by the American Physical Society
2024
Verification of wave turbulence theory in the kinetic limit
Authors: Hrabski Alexander , Pan Yulin 
Published: May 2024

Using the 1D Majda-McLaughlin-Tabak model as an example, we develop numerical experiments to study the validity of the wave kinetic equation (WKE) at the kinetic limit (i.e., small nonlinearity and large domain). We show that the dynamics converge to the WKE prediction, in terms of the closure model and energy flux, when the kinetic limit is approached. When the kinetic limit is combined with a process of widening the inertial range, the theoretical Kolmogorov constant can be recovered numerically to a very high precision.

Published by the American Physical Society
2024
Doping dependence of scattering rate for linear-in-temperature resistivity in cuprate superconductors
Authors: Qin Mingyang , Zhang Ruozhou , Miao Chaoran , Wei Zhongxu , Shi Yujun , Yao Yixuan , Wang Haowen , Li Yangmu , Jin Kui , Xiang Xiaodong 
Published: May 2024

The origin of the linear-in-temperature (T-linear) resistivity in cuprate superconductors remains a profound mystery in condensed matter physics. Here, we investigate the dependence of the T-linear resistivity coefficient on doping, i.e., A1(p), for three typical regions in the temperature versus doping phase diagram of hole-doped cuprates, from which the doping dependence of the scattering rate, i.e., α1(p), is further derived. It is found that for region I (p<p* and T>T*), α1(p) is almost a constant; for region II (p>p* and T>Tcoh), α1(p)∝p; for region III (p>p* and T<Tcoh), α1(p)∝p(pc−p), where T* is the onset temperature of the pseudogap phase, p* indicates the doping at which T* goes to zero, Tcoh marks the onset of antinodal quasiparticle coherence, and pc is the doping where the low-temperature linear behavior in the overdoped regime vanishes. Moreover, the deduced α1(p) relations are verified with the experimental data from previous reports. The discovered scattering rate versus doping relationship will shed light on the scattering mechanism underlying the T-linear resistivity in cuprate superconductors.

Published by the American Physical Society
2024