bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oligodendrocytes use postsynaptic proteins to coordinate myelin formation on axons of distinct neurotransmitter classes
Authors: Carey Natalie J. , Doll Caleb A. , Appel Bruce 
Published: October 2024

ABSTRACTAxon myelination can tune neuronal circuits through placement and modulation of different patterns of myelin sheaths on distinct types of axons. How myelin formation is coordinated on distinct axon classes remains largely unknown. Recent work indicates neuronal activity and vesicle release promote myelin formation, and myelin-producing oligodendrocytes express canonical postsynaptic factors that potentially facilitate oligodendrocyte-axon interaction for myelin ensheathment. Here, we examined whether the inhibitory postsynaptic scaffold protein Gephyrin (Gphn) mediates selective myelination of specific axon classes in the larval zebrafish. Consistent with this possibility, Gphn was enriched in myelin on GABAergic and glycinergic axons. Strikingly, ingphnbdeficient larvae, myelin sheaths were longer specifically on GABAergic axons, and the frequency of myelin placement shifted toward glutamatergic axons at the expense of GABAergic axons. Collectively, our results indicate that oligodendrocytes use postsynaptic machinery to coordinate myelin formation in an axon identity-dependent manner.
Theta-gamma transcranial alternating current stimulation enhances motor skill acquisition in healthy young and older adults
Authors: Gamage Nishadi N. , Liao Wei-Yeh , Hand Brodie J. , Atherton Philip J. , Piasecki Mathew , Opie George M. , Semmler John G. 
Published: October 2024

ABSTRACTTheta-gamma transcranial alternating current stimulation (TG tACS) over primary motor cortex (M1) can improve motor skill acquisition in young adults, but the effect on older adults is unknown. This study investigated the effects of TG tACS on motor skill acquisition and M1 excitability in 18 young and 18 older adults. High-definition TG tACS (6 Hz theta, 75 Hz gamma) or sham tACS was applied over right M1 for 20 minutes during a ballistic left-thumb abduction motor training task performed in two experimental sessions. Motor skill acquisition was quantified as changes in movement acceleration during and up to 60 minutes after training. Transcranial magnetic stimulation (TMS) was used to assess changes in M1 excitability with motor-evoked potentials (MEP) and short-interval intracortical inhibition (SICI) before and after training. We found that TG tACS increased motor skill acquisition compared with sham tACS in young and older adults (P< 0.001), with greater effects for young adults (P= 0.01). The improved motor performance with TG tACS lasted at least 60 minutes after training in both age groups. Motor training was accompanied by greater MEP amplitudes with TG tACS compared to sham tACS in young and older adults (P< 0.001), but SICI did not vary between tACS sessions (P= 0.40). These findings indicate that TG tACS over M1 improves motor skill acquisition and alters training-induced changes in M1 excitability in healthy young and older adults. TG tACS may therefore be beneficial to alleviate motor deficits in the ageing population.Key Points SummaryTheta-gamma transcranial alternating current stimulation (TG tACS) can improve motor function in healthy young adults, but the effect on older adults is unknown.We found that TG tACS improved motor skill acquisition with long-lasting effects in healthy young and older adults, but effects were stronger in young adults.Transcranial magnetic stimulation showed that TG tACS altered the training-induced changes in motor cortex excitability, but there was no effect of TG tACS on intracortical inhibition in young or older adults.Our data suggest that TG tACS represents a promising approach to improve motor skill acquisition throughout the lifespan, and may be beneficial in older patient populations that experience motor or cognitive deficits.
A new compression strategy to reduce the size of nanopore sequencing data
Authors: Jayasooriya Kavindu , Jenner Sasha P. , Marasinghe Pasindu , Senanayake Udith , Saadat Hassaan , Taubman David , Ragel Roshan , Gamaarachchi Hasindu , Deveson Ira W. 
Published: October 2024

ABSTRACTNanopore sequencing is an increasingly central tool for genomics. Despite rapid advances in the field, large data volumes and computational bottlenecks continue to pose major challenges. Here we introduceex-zd, a new data compression strategy that helps address the large size of raw signal data generated during nanopore experiments.Ex-zdencompasses both a lossless compression method, which modestly outperforms all current methods for nanopore signal data compression, and a ‘lossy’ method, which can be used to achieve dramatic additional savings. The latter component works by reducing the number of bits used to encode signal data. We show that the three least significant bits in signal data generated on instruments from Oxford Nanopore Technologies (ONT) predominantly encode noise. Their removal reduces file sizes by half without impacting downstream analyses, including basecalling and detection of DNA methylation.Ex-zdcompression saves hundreds of gigabytes on a single ONT sequencing experiment, thereby increasing the scalability, portability and accessibility of nanopore sequencing.
Adaptation, not prediction, drives neuronal spiking responses in mammalian sensory cortex
Authors: Westerberg Jacob A. , Xiong Yihan S. , Nejat Hamed , Sennesh Eli , Durand Séverine , Hardcastle Ben , Cabasco Hannah , Belski Hannah , Bawany Ahad , Gillis Ryan , Loeffler Henry , Peene Carter R. , Han Warren , Nguyen Katrina , Ha Vivian , Johnson Tye , Grasso Conor , Young Ahrial , Swapp Jackie , Ouellette Ben , Caldejon Shiella , Williford Ali , Groblewski Peter A. , Olsen Shawn R. , Kiselycznyk Carly , Lecoq Jerome A. , Maier Alexander , Bastos André M. 
Published: October 2024

SummaryPredictive coding (PC) hypothesizes that the brain computes internal models of predicted events and that unpredicted stimuli are signaled with prediction errors that feed forward. We tested this hypothesis using a visual oddball task. A repetitive sequence interrupted by a novel stimulus is a “local” oddball. “Global” oddballs defy predictions while repeating the local context, thereby dissociating genuine prediction errors from adaptation-related responses. We recorded neuronal spiking activity across the visual hierarchy in mice and monkeys viewing these oddballs. Local oddball responses largely followed PC: they were robust, emerged early in layers 2/3, and fed forward. Global oddball responses challenged PC: they were weak, absent in most visual areas, more robust in prefrontal cortex, emerged in non-granular layers, and did not involve inhibitory interneurons relaying predictive suppression. Contrary to PC, genuine predictive coding does not emerge early in sensory processing, and is instead exclusive to more cognitive, higher-order areas.HighlightsCore principles of Predictive Coding explain local, but not global oddball brain responsesGlobal oddballs are sparsely encoded in visual cortex and do not engage feedforward mechanismsParvalbumin and somatostatin interneurons do not support sensory global oddball detectionGlobal oddballs are earliest, and most robustly encoded, in prefrontal brain areasSignificanceGlobal oddballs defy our expectations without standing out from their local context. Whether they are encoded in sensory brain areas was uncertain. Through multiarea neurophysiological recordings in mice and monkeys, Westerberg et al. show that global oddballs neuronal responses contradicts predictive coding hypotheses and emerge in higher order areas.
Pharmacological inhibition of Fms-like kinase 3 (FLT3) promotes neuronal maturation and suppresses seizure in a mouse model
Authors: Cruite Kate , Moore Madeline , Gallagher Michael D. , Coleman Emanuel M. , Yin Yuqin , Lin Shuqi , Shahbo Ellie , Lungjangwa Tenzin , Hovestadt Volker , Jaenisch Rudolf , Maguire Jamie , Tang Xin 
Published: October 2024

AbstractFms-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase predominantly expressed in blood and brain cells. While the FLT3 signaling pathway has been extensively studied in blood cell development and leukemia, its role in the brain remains largely unexplored. Through our group’s previous high-throughput drug screening work unexpectedly found that several small molecule FLT3 inhibitors (FLT3i), including KW-2449 and Sunitinib, enhance expression of the gene encoding chloride transporter KCC2 in neurons. KCC2 is crucial for brain development and function, and its dysregulation is linked to many brain diseases. These findings suggest previously unrecognized roles of FLT3 signaling in brain health and disease that have yet to be systematically studied. In this study, we utilized a functional genomics approach to investigate the transcriptomic changes induced by pharmacological inhibition of the FLT3 pathway in brain cells, including cultured primary mouse neurons, a human stem cell-derived neuronal model of Rett syndrome (RTT), and human stem cell-derived microglia cultures. Our results show that treating human or mouse neurons with FLT3i drugs significantly upregulates genes crucial for brain development while downregulating genes linked to neuroinflammation. In contrast, FLT3i treatment of human microglia, which do not express FLT3, has no effect on their gene expression, highlighting the cell type-specific roles of FLT3 signaling in the brain. To further understand how FLT3 signaling regulates the expression of neuronal maturation genes such as KCC2, we conducted a curated CRISPR screen that identified a number of transcription factors involved in FLT3i-mediated KCC2 activation in neurons. The mRNA and protein levels of several neurodevelopmental disorder (NDD) risk genes are significantly upregulated in FLT3i-treated neurons, indicating potential therapeutic applications of FLT3i in rescuing underexpression and/or haploinsufficiency of disease-associated genes. In ourin vivostudies, we evaluated the efficacy of the FLT3i drug KW-2449 in mice, demonstrating that it can effectively cross the blood-brain barrier, induce KCC2 protein expression for up to 24 hours after a single injection, and reduces seizure activity in a chemoconvulsant-induced mouse model of temporal lobe epilepsy. Collectively, our findings uncover previously unrecognized roles of neuron-specific FLT3 signaling in promoting neuronal maturation and reducing neuroinflammation. These results suggest that FLT3 kinase signaling regulates a transcriptional program vital for brain development and function, position it as a promising therapeutic target for NDD treatment.
Tissue-specific transcriptomics uncovers novel craniofacial genes underlying jaw divergence in specialist pupfishes
Authors: Palominos M. Fernanda , Muhl Vanessa , Martin Christopher H. 
Published: October 2024

AbstractThe regulation of gene expression is one of the key evolutionary processes driving phenotypic divergence among species. Here, we investigate the tissue-specific gene expression of a non-model adaptive radiation ofCyprinodonpupfishes, characterized by their divergent dietary niches and exceptionally fast rates of craniofacial evolution. By comparing tissue-specific gene expression in the most morphologically divergent skeletal structure, the oral jaws, with the relatively morphologically conserved caudal tail region, we identified genes that were differentially expressed exclusively in the developing jaws of each of the three trophic specialists at hatching (8 dpf) and not in any other species. We then assessed their overlap (as transcriptionally-regulated genes) with adaptive regulatory variants identified in previous genomic studies. Our analysis identifiedpycr3andatp8a1as the most promising for craniofacial evolution in the scale-eaters, both genes with no known previous craniofacial function. We functionally confirmed the craniofacial expression of these genes byin situmRNA hybridization chain reaction and demonstrated their species-specific expression in branchial and muscle tissues between sister species of this young radiation. Our work underscores the power of integrating tissue-specific transcriptomics with speciation genomics to identify novel craniofacial candidate genes controlling divergent morphogenesis in a natural ‘evolutionary mutant’ system.
BoMBR: An Annotated Bone Marrow Biopsy Dataset for Segmentation of Reticulin Fibers
Authors: Raina Panav , Dharamdasani Satyender , Chinnam Dheeraj , Sharma Praveen , Gupta Sukrit 
Published: October 2024

AbstractBone marrow reticulin fibrosis is associated with varied benign as well as malignant hematological conditions. The assessment of reticulin fibrosis is important in the diagnosis, prognostication and management of such disorders. The current methods for quantification of reticulin fibrosis are inefficient and prone to errors. Therefore, there is a need for automated tools for accurate and consistent quantification of reticulin. However, the lack of standardized datasets has hindered the development of such tools. In this study, we present a comprehensive dataset that comprises of 201BoneMarrowBiopsy images forReticulin (BoMBR) quantification. These images were meticulously annotated for semantic segmentation, with the focus on performing reticulin fiber quantification. This annotation was done by two trained hematopathologists who were aided by Deep Learning (DL) models and image processing techniques that generated a rough automated annotation for them to start with. This ensured precise delineation of the reticulin fibers alongside other cellular components such as bony trabeculae, fat, and cells. This is the first publicly available dataset in this domain with the aim to catalyze advancements the development of computational models for improved reticulin quantification. Further, we show that our annotated dataset can be used to train a DL model for a multi-class semantic segmentation task for robust reticulin fiber detection task (Mean Dice score: 0.92). We use these model outputs for the Marrow Fibrosis (MF) grade detection and obtained a Mean Weighted Average F1 score of 0.656 with our trained model. Our code for preprocessing the dataset is available athttps://github.com/AI-in-Medicine-IIT-Ropar/BoMBR_dataset_preprocessing.
Metagenomic Insights into the Spatio-temporal Variation of Metal and Antibiotic Resistance Genes in Lake Erie
Authors: Reddy Saahith , Kiledal E. Anders 
Published: October 2024

ABSTRACTAntibiotic resistance and metal toxicity in freshwater bodies have human health impacts and carry economic implications worldwide. The presence of metal and antibiotic resistance genes within microbial communities can be informative about both issues. The Laurentian Great Lakes contain nearly 20% of the world’s supply of freshwater; however, it is unclear how these genes are changing over time in this system. In this study, we characterized these genes in nearly two hundred metagenomes collected from multiple sites in western Lake Erie at a five-year time interval: 2014-2019. 11 metal resistance genes (MRGs) and nine antibiotic resistance genes (ARGs) were characterized and demonstrated significant changes in diversity and spatial distribution. Increased abundance was observed for genes likeaac(3)andTEM-1Bconferring resistance to aminoglycoside (gentamicin) and β-lactam antibiotics, respectively. MRGs associated with mercury, lead, and arsenic also increased in abundance over the five years. Collectively, our data point to a notable increase in both ARGs and MRGs in Lake Erie over five years, with a specific and significant increase in the abundance of genes conferring resistance to aminoglycoside and β-lactam antibiotic resistance and mercury contamination. Future integrated and systematic freshwater microbiome and public health investigations are needed to assess the potential impact on humans and environmental health from increasing microbial antibiotic and metal resistance in large freshwater reservoirs like the Great Lakes.IMPORTANCEAntibiotic and metal resistance genes (ARGs and MRGs) in microbial communities of the Laurentian Great Lakes have significant human and environmental health implications. However, an assessment of the Great Lakes’ microbiome for ARGs and MRGs is lacking. The abundance of 11 MRGs and 9 ARGs was characterized between 2014 and 2019 and showed significant abundance differences. Specifically, we observed an increase in genes conferring resistance to aminoglycoside (gentamicin) and β-lactam antibiotics (amongst the most commonly utilized antibiotics in humans), such asaac(3)andTEM-1B,respectively. MRGs conferring resistance to mercury, lead, and arsenic also increased in abundance, with the largest increase observed for mercury resistance genes such asMerA, MerP,andMerT. Collectively, these findings point to a concerning increased abundance of both ARGs and MRGs in Lake Erie. Further studies to assess the causes for the increase and the direct impact on human and environmental health are needed.
Interaction hierarchy among Cdv proteins drives recruitment to membrane necks
Authors: De Franceschi Nicola , Blanch-Jover Alberto , Dekker Cees 
Published: October 2024

AbstractCell division in the crenarchaea is accomplished by the Cdv system. In Sulfolobus cells, it was observed that an initial non-contractile ring of CdvA and CdvB forms at the mid location of the cell, which is followed by a second ring of CdvB1 and CdvB2 that appear to drive the constriction of the cell membrane. Here, we use anin vitroreconstituted system to explore how protein interactions among these Cdv proteins govern their recruitment to the membrane. We show that CdvA does not bind the membrane unless in complex with CdvB. We find that CdvB2 can polymerize if its self-inhibitory domain is removed, and that by itself is exhibits poor binding to the membrane. However, CdvB2 can be efficiently recruited to the membrane by both CdvB1 and CdvB. Furthermore, the CdvB1:CdvB2 co-polymer can be recruited to the membrane by CdvA:CdvB. By reconstituting these proteins in dumbbell-shaped liposomes, we show that Cdv proteins have a strong preference to localize at membrane necks of high curvature. Our findings clarify many of the mutual protein interactions of the Cdv system and their interaction with the membrane, thus helping to build a mechanistic understanding of cell division in archaeal cells.
Quantum tomography with
τ
leptons at the FCC-ee: Entanglement, Bell inequality violation,
sinθW
, and anomalous couplings
Authors: Fabbrichesi M. , Marzola L. 
Published: October 2024

The Future Circular Collider (FCC)—in its first incarnation as a lepton collider—will produce, according to the proposed design, more than 100 billion pairs of τ leptons after working for four years at the energy of the Z-boson resonance. The τ lepton is special because its relatively long lifetime makes it possible to reconstruct the momenta of neutrinos emitted in the single pion decay mode. The resulting large number of events is an ideal source for a full quantum tomography of the process that will test quantum entanglement and the violation of Bell inequality with unprecedented precision. In addition, the study of polarizations and spin correlations can provide a competitive determination of the Weinberg angle θW and constrain possible anomalous couplings in the neutral electroweak current. We utilize analytic results and Monte Carlo simulations to explore to what extent these goals might be accomplished.

Published by the American Physical Society
2024
Consumer-based brand equity of US domestic and global wine tourism destinations from the American market perspective
Authors: Milman Ady , Tasci Asli D.A. , Back Robin M. 
Published: October 2024

Purpose
This study aims to measure and compare consumer-based brand equity (CBBE) of several US and global wine tourism destinations from an American market point of view.

Design/methodology/approach
An online randomized experimental design was used to assign respondents to different wine tourism destination contexts and measure their perceptions and intentions. A structured survey was designed with CBBE scale items related to the most commonly studied components of CBBE, namely, familiarity, perceived quality, image, consumer value, brand value and brand loyalty.

Findings
The study revealed that respondents were unfamiliar with multi-regional and global wine-growing destinations and their wines, implying that wine tourists belong to different market segments that seek different experiences. Among the US wine tourism destinations, Napa Valley is the destination with the strongest CBBE, with the highest overall ratings in all five CBBE components, on average. In terms of country-level wine tourism destinations, the US has the strongest CBBE, with the highest overall ratings in familiarity and brand loyalty.

Research limitations/implications
Wine tourism destination CBBE is shown to include components that may not relate exclusively to wine and variations in perceptions concerning global wine-growing regions may be associated with consumer familiarity. Future studies may include respondents from different countries to determine the generalizability of the current findings.

Originality/value
To the best of the authors’ knowledge, the current study is the first to assess consumer-based brand equity of wine tourism destinations in the US and globally from a US resident perspective.
When does newcomer get feedback? Relationship between supervisor perceived organizational support and supervisor developmental feedback
Authors: Zhao Junzhe , Wang Minghui , Li Yongxin , Zhao Guoxiang 
Published: October 2024

PurposeUsing social exchange theory, this paper explores the relationship between supervisor perceived organizational support and supervisor developmental feedback. It verifies the mediating role of supervisor felt obligation to organization and the moderating role of supervisor core self-evaluation in this relationship.Design/methodology/approachA two-wave survey sampling method was applied to collect 247 pieces of paired data (supervisors-new employees) in organizations in China.FindingsThe results show that supervisor felt obligation to organization mediates the relationship between supervisor perceived organizational support and supervisor developmental feedback. The findings suggest that a high level of supervisor core self-evaluation strengthens the relationship between supervisor perceived organizational support and supervisor felt obligation to organization and then facilitates supervisor developmental feedback.Originality/valueThis study combines two perspectives, organizational factor and supervisor trait, to reveal the occurrence mechanism of supervisor developmental feedback and complements the research on the influencing factors of supervisor developmental feedback. In addition, it provides some theoretical guidance and practical insights into how organizations can motivate supervisors to provide developmental feedback to new employees.
Abnormal Temperatures, Climate Risk Disclosures and Bank Loan Pricing: International Evidence
Authors: Ge Wenxia , Qi Zhen , Wu Zhenyu , Yu Li 
Published: October 2024

AbstractThis paper examines the effect of abnormal‐temperature‐related climate risk on bank loan pricing. Using a sample of syndicated loans from 35 countries and jurisdictions, we find that banks charge higher interest rates for borrowers with higher climate risk. We also find that climate risk affects loan spreads of both long‐term and short‐term loans, and this effect is more pronounced for short‐term loans. Our cross‐sectional analyses reveal that voluntary climate risk disclosures in conference calls by borrowers mitigate the impact of climate risk on loan spreads, especially when lead banks have less climate‐risk‐related lending experience. In addition, the borrowing cost of high‐climate‐risk borrowers in the United States decreases after the SEC issued climate risk disclosure guidance. However, the ESG disclosure requirements in 19 other countries, which are not climate‐risk‐specific, do not alter the effect of climate risk on bank loan pricing.