bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Scalable Staining Strategy for Whole-Brain Connectomics
Authors: Lu Xiaotang , Wu Yuelong , Schalek Richard L. , Meirovitch Yaron , Berger Daniel R. , Lichtman Jeff W. 
Published: September 2023

AbstractMapping the complete synaptic connectivity of a mammalian brain would be transformative, revealing the pathways underlying perception, behavior, and memory. Serial section electron microscopy, via membrane staining using osmium tetroxide, is ideal for visualizing cells and synaptic connections but, in whole brain samples, faces significant challenges related to chemical treatment and volume changes. These issues can adversely affect both the ultrastructural quality and macroscopic tissue integrity. By leveraging time-lapse X-ray imaging and brain proxies, we have developed a 12-step protocol, ODeCO, that effectively infiltrates osmium throughout an entire mouse brain while preserving ultrastructure without any cracks or fragmentation, a necessary prerequisite for constructing the first comprehensive mouse brain connectome.
Sleep and circadian rhythm disruption by NPTX2 loss of function
Authors: Roh Seung-Eon , Xiao Meifang , Delgado Ana , Kwak Chuljung , Savonenko Alena , Bakker Arnold , Kwon Hyung-Bae , Worley Paul 
Published: September 2023

AbstractSleep and circadian rhythm disruption (SCRD) is commonly observed in aging, especially in individuals who experience progressive cognitive decline to mild cognitive impairment (MCI) and Alzheimer’s disease (AD). However, precise molecular mechanisms underlying the association between SCRD and aging are not fully understood. Orexin A is a well-characterized “sleep neuropeptide” that is expressed in hypothalamic neurons and evokes wake behavior. The importance of Orexin is exemplified in narcolepsy where it is profoundly down-regulated. Interestingly, the synaptic immediate early gene NPTX2 is co-expressed in Orexin neurons and is similarly reduced in narcolepsy. NPTX2 is also down-regulated in CSF of some cognitively normal older individuals and predicts the time of transition from normal cognition to MCI. The association between Orexin and NPTX2 is further evinced here where we observe that Orexin A and NPTX2 are highly correlated in CSF of cognitively normal aged individuals and raises the question of whether SCRD that are typically attributed to Orexin A loss of function may be modified by concomitant NPTX2 down-regulation. Is NPTX2 an effector of sleep or simply a reporter of orexin-dependent SCRD? To address this question, we examined NPTX2 KO mice and found they retain Orexin expression in the brain and so provide an opportunity to examine the specific contribution of NPTX2 to SCRD. Our results reveal that NPTX2 KO mice exhibit a disrupted circadian onset time, coupled with increased activity during the sleep phase, suggesting difficulties in maintaining states. Sleep EEG indicates distinct temporal allocation shifts across vigilance states, characterized by reduced wake and increased NREM time. Evident sleep fragmentation manifests through alterations of event occurrences during Wake and NREM, notably during light transition periods, in conjunction with an increased frequency of sleep transitions in NPTX2 KO mice, particularly between Wake and NREM. EEG spectral analysis indicated significant shifts in power across various frequency bands in the wake, NREM, and REM states, suggestive of disrupted neuronal synchronicity. An intriguing observation is the diminished occurrence of sleep spindles, one of the earliest measures of human sleep disruption, in NPTX2 KO mice. These findings highlight the effector role of NPTX2 loss of function as an instigator of SCRD and a potential mediator of sleep disruption in aging.
Evolution of wheat blast resistance geneRmg8accompanied by differentiation of variants recognizing the powdery mildew fungus
Authors: Asuke Soichiro , Morita Kohei , Shimizu Motoki , Abe Fumitaka , Terauchi Ryohei , Nago Chika , Takahashi Yoshino , Shibata Mai , Yoshioka Motohiro , Iwakawa Mizuki , Kishi-Kaboshi Mitsuko , Su Zhuo , Nasuda Shuhei , Handa Hirokazu , Fujita Masaya , Tougou Makoto , Hatta Koichi , Mori Naoki , Matsuoka Yoshihiro , Kato Kenji , Tosa Yukio 
Published: September 2023

AbstractWheat blast, a devastating disease having spread recently from South America to Asia and Africa, is caused byPyricularia oryzaepathotypeTriticumwhich emerged in 1985.Rmg8andRmg7, genes for resistance to wheat blast found in common wheat and tetraploid wheat, respectively, recognize the same avirulence gene,AVR-Rmg8. Here, we show an evolutionary process in which resistance gene(s), which had obtained an ability to recognizeAVR-Rmg8before the differentiation ofTriticumandAegilops, has expanded its target pathogens. Molecular cloning revealed thatRmg7was one of alleles ofPm4(Pm4a), a gene for resistance to wheat powdery mildew on 2AL, whereasRmg8was its homoeolog on 2BL ineffective against wheat powdery mildew.Rmg8variants with the ability to recognizeAVR-Rmg8were distributed not only inTriticumspp. but also inAegilops speltoides,Ae. umbellulata,andAe. comosa. This result suggests that the origin of resistance gene(s) recognizingAVR-Rmg8dates back to the time before differentiation of A, B, S, U, and M genomes, that is, ∼5 million years before the emergence of its current target, the wheat blast fungus. Phylogenetic analyses suggested that, in the evolutionary process thereafter, some of their variants gained the ability to recognize the wheat powdery mildew fungus and evolved into genes for resistance to wheat powdery mildew.
The origin, divergence and inter-subspecies hybridization of house mice (Mus musculus)
Authors: Jing Meidong , Chen Yingjie , Yuan Wenbo , Song Ying , Bi Xiaoxin , Huang Ling 
Published: September 2023

AbstractHouse mice (Mus musculus) are the ancestors of laboratory mouse strains and an excellent model for evolutionary biology. The origin, divergence and inter-subspecies hybridization of the three main subspecies (Mus musculus domesticus,M. m. musculus,M. m. castaneus) were not well-resolved. Population genomic analyses with 349 samples from Eurasia confirmed the Himalayas-India-Pakistan junctional region as the origin centre. The divergence ofM. m. domesticus,M. m. musculusandM. m. castaneusoccurred ∼333.6, 308.3 and 134.4 thousand years ago, respectively, which located in different interglacial stages in Pleistocene. Hybridization amongM. m. domesticus,M. m. musculus, andM. m. castaneusafter secondary contact during spread and gene flow between the ancestral population and different subspecies produced distinct genomic mixtures in populations from different regions of Eurasia. Long-distance introgression fromM. m. musculusintoM. m. castaneusand fromM. m. castaneusintoM. m. musculushappened in southern China and northern China, respectively. And extensive genomic introgression occurred on both autosomes and the X chromosomes. Genomic introgression in hybrids from East Asia and Europe revealed that the level of genomic differentiation, recombination rate and benefits for the survival and reproduction of hybrids determined the introgression capability of distinct genomic regions in inter-subspecies hybridization of house mice. Unidirectional introgression of the Y chromosome made all wild mice in East Asia hold themusculus-type Y chromosome. Our study provided comprehensive insights into the origin, divergence and inter-subspecies’ genomic introgression of house mice.
Multimodal delineation of a layer of effector function among exhausted CD8 T cells in tumors
Authors: Ray Arja , Bassette Molly , Hu Kenneth H. , Pass Lomax F. , Courau Tristan , Samad Bushra , Combes Alexis , Johri Vrinda , Davidson Brittany , Wai Katherine , Ha Patrick , Hernandez Grace , Zaleta-Linares Itzia , Krummel Matthew F. 
Published: September 2023

AbstractThe anti-tumor function of CD8 T cells is limited through well-established pathways of T cell exhaustion (TEX). Strategies to capture emergent functional states amongst this dominant trajectory of dysfunction are necessary to find pathways to durable anti-tumor immunity. By leveraging transcriptional reporting (by the fluorescent protein TFP) of the T cell activation markerCd69,related to upstream AP-1 transcription factors, we define a classifier for potent versus sub-optimal CD69+ activation states arising from T cell stimulation. In tumors, this delineation acts an additional functional readout along the TEXdifferentiation trajectory, within and across TEXsubsets, marked by enhanced effector cytokine and granzyme B production. The more potent state remains differentially prominent in a T cell-mediated tumor clearance model, where they also show increased engagement in the microenvironment and are superior in tumor cell killing. Employing multimodal CITE-Seq in human head and neck tumors enables a similar strategy to identify Cd69RNAhiCD69+ cells that also have enhanced functional features in comparison to Cd69RNAloCD69+ cells, again within and across intratumoral CD8 T cell subsets. Refining the contours of the T cell functional landscape in tumors in this way paves the way for the identification of rare exceptional effectors, with imminent relevance to cancer treatment.Graphical Abstract
MMORF—FSL’s MultiMOdal Registration Framework
Authors: Lange Frederik J. , Arthofer Christoph , Bartsch Andreas , Douaud Gwenaëlle , McCarthy Paul , Smith Stephen M. , Andersson Jesper L. R. 
Published: September 2023

AbstractWe present MMORF—FSL’s MultiMOdal Registration Framework—a newly released nonlinear image registration tool designed primarily for application to MRI images of the brain. MMORF is capable of simultaneously optimising both displacement and rotational transformations within a single registration framework by leveraging rich information from multiple scalar and tensor modalities. The regularisation employed in MMORF promotes local rigidity in the deformation, and we have previously demonstrated how this effectively controls both shape and size distortion, and leads to more biologically plausible warps. The performance of MMORF is benchmarked against three established nonlinear registration methods—FNIRT, ANTs and DR-TAMAS—across four domains: FreeSurfer label overlap, DTI similarity, task-fMRI cluster mass, and distortion. Results show that MMORF performs as well as or better than all other methods across every domain—both in terms of accuracy and levels of distortion. MMORF is available as part of FSL, and its inputs and outputs are fully compatible with existing workflows. We believe that MMORF will be a valuable tool for the neuroimaging community, regardless of the domain of any downstream analysis, providing state-of-the-art registration performance that integrates into the rich and widely adopted suite of analysis tools in FSL.
Species-specific epigenetic responses to drought stress of two sympatric oak species reflect their ecological preferences
Authors: Rubio B , Provost G Le , Brachi B , Gerardin T , Brendel O , Tost J. , Daviaud Christian , Gallusci P 
Published: September 2023

SummaryIn a context of climate change, it is necessary to decipher the strategies established by plants to cope with limited water supply.Transcriptome, methylome and small RNA data were generated for two oak species with contrasting levels of drought tolerance (Quercus roburandQuercus petraea), under control and drought stress conditionsAll data are in line with a species-specific response to drought stress consistent with their ecological preferences. The biological processes associated with genomic regions identified in all datasets were mainly associated with parietal processes inQ. petraea,which may explain in part its better tolerance to water deprivation.A significant proportion of DNA methylation differences observed in control conditions between the two oak species were maintained during DS which may constitute a pool of epigenetic markers discriminating these two oak species. These markers were enriched in highly differentiated SNPs suggesting that some of them may be associated both with the ecological differences or intrinsic barriers to reproduction between the two species.An integrative approach of the three datasets revealed genomic co-locations of potential importance for forest three adaptation to drought stress.
Randomness impacts specific priors building, visual exploration, and perception in object recognition
Authors: Gal Cécile , Țincaș Ioana , Moca Vasile V. , Ciuparu Andrei , Dan Loredana E. , Smith Marie L. , Gliga Teodora , Mureșan Raul C. 
Published: September 2023

1.AbstractRecognising objects is a vital skill on which humans heavily rely to respond quickly and adaptively to their environment. Yet, we lack understanding on the role visual information sampling plays in this process, and its relation to the individual’s priors. To bridge this gap, the eye-movements of 18 adult participants were recorded during a free-viewing object-recognition task usingDotsstimuli (Moca et al., 2011). Participants viewed the stimuli in one of three orders: from most visible to least (Descending), least visible to most (Ascending) or in a randomised order (Random). This dictated the strength of their priors along the experiment. Adding to Moca et al.’s original finding that visibility order influenced participants’ recognition performance and visual exploration, we found that while orders allowing for stronger priors generally led participants to visually sample more informative locations, this was not the case ofRandomparticipants. Indeed, they appeared to behave naïvely, and their use of specific object-related priors seemed fully impaired, while they seemed to maintain the ability to use general task-related priors to guide their exploration. These findings have important implications for our understanding of perception, which appears markedly subjective even at the basic level of visual sampling and object perception.
Altered hierarchical gradients of intrinsic neural timescales in mild cognitive impairment and Alzheimer’s disease
Authors: Zhang Aiying , Wengler Kenneth , Zhu Xi , Horga Guillermo , Goldberg Terry E. , Lee Seonjoo ,   Alzheimer’s Disease Neuroimaging Initiative
Published: September 2023

AbstractAlzheimer’s disease (AD) is a devastating neurodegenerative disease that affects millions of older adults in the US and worldwide. Resting-state functional magnetic resonance imaging (rs-fMRI) has become a widely used neuroimaging tool to study neurophysiology in AD and its prodromal condition, mild cognitive impairment (MCI). The intrinsic neural timescale (INT), which can be estimated through the magnitude of the autocorrelation of intrinsic neural signals using rs-fMRI, is thought to quantify the duration that neural information is stored in a local cortical circuit. The heterogeneity of the timescales is considered to be a basis of the functional hierarchy in the brain. In addition, INT captures an aspect of circuit dynamics relevant to excitation/inhibition (E/I) balance, which is thought to be broadly relevant for cognitive functions. Here we examined its relevance to AD. We used rs-fMRI data of 904 individuals from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. The subjects were divided into 4 groups based on their baseline and end-visit clinical status, which were cognitively normal (CN), stable MCI, Converter, and AD groups. Linear mixed effect model and pairwise comparison were implemented to investigate the large-scale hierarchical organization and local differences. We observed high similarities between AD and Converter groups. Specifically, among the eight identified ROIs with distinct INT alterations in AD, three ROIs (inferior temporal, caudate, pallidum areas) exhibit stable and significant alteration in AD converter. In addition, distinct INT related pathological changes in stable MCI and AD/Converter were found. For AD and Converter groups, neural information is stored for a longer time in lower hierarchical order areas, while higher levels of hierarchy seem to be preferentially impaired in stable MCI leading to a less pronounced hierarchical gradient effect. These results inform that the INT holds great potential as an additional measure for AD prediction, a stable biomarker for clinical diagnosis and an important therapeutic target in AD.
Development of a mutant aerosolized ACE2 that neutralizes SARS-CoV-2 in vivo
Authors: Kober Daniel L. , Caballero Van Dyke Marley C. , Eitson Jennifer L. , Boys Ian N. , McDougal Matthew B. , Rosenbaum Daniel M. , Schoggins John W. 
Published: September 2023

AbstractThe rapid evolution of SARS-CoV-2 variants highlights the need for new therapies to prevent disease spread. SARS-CoV-2, like SARS-CoV-1, uses the human cell surface protein angiotensin-converting enzyme 2 (ACE2) as its native receptor. Here, we design and characterize a mutant ACE2 that enables rapid affinity purification of a dimeric protein by altering the active site to prevent autoproteolytic digestion of a C-terminal His10epitope tag. In cultured cells, mutant ACE2 competitively inhibits lentiviral vectors pseudotyped with spike from multiple SARS-CoV-2 variants, and infectious SARS-CoV-2. Moreover, the protein can be nebulized and retains virus-binding properties. We developed a system for delivery of aerosolized ACE2 to K18-hACE2 mice and demonstrate protection by our modified ACE2 when delivered as a prophylactic agent. These results show proof-of-concept for an aerosolized delivery method to evaluate anti-SARS-CoV-2 agentsin vivoand suggest a new tool in the ongoing fight against SARS-CoV-2 and other ACE2-dependent viruses.
Convergent generation of atypical prions in knock-in mouse models of genetic prion disease
Authors: Mehra Surabhi , Bourkas Matthew E.C. , Kaczmarczyk Lech , Stuart Erica , Arshad Hamza , Griffin Jennifer K. , Frost Kathy L. , Walsh Daniel J. , Supattapone Surachai , Booth Stephanie A. , Jackson Walker S. , Watts Joel C. 
Published: September 2023

AbstractMost cases of human prion disease arise due to spontaneous misfolding of wild-type or mutant prion protein. Though recapitulating spontaneous prion conversion in animal models has proven challenging, transgenic mice expressing the misfolding-prone bank vole prion protein (BVPrP) recreate certain key aspects of sporadic and genetic prion disease. However, it remains unclear whether spontaneous prion generation can occur in the absence of protein over-expression and how disease-causing mutations affect prion strain properties. To address these issues, we generated knock-in mice expressing physiological levels of either wild-type or mutant BVPrP with isoleucine at codon 109. While mice expressing wild-type BVPrP remained free from neurological disease, a subset of knock-in mice expressing BVPrP with mutations that cause either fatal familial insomnia (D178N) or familial Creutzfeldt-Jakob disease (E200K) developed progressive neurological illness. Brains from spontaneously ill knock-in mice contained prion disease-specific neuropathological changes as well as atypical protease-resistant prion protein. Moreover, brain extracts from spontaneously ill D178N- or E200K-mutant BVPrP knock-in mice transmitted disease to mice expressing wild-type BVPrP. Surprisingly, the properties of the D178N- and E200K-mutant prions appeared identical both pre- and post-transmission, suggesting that both mutations guide the formation of a highly similar atypical prion strain. These findings imply that knock-in mice expressing mutant BVPrP spontaneously develop abona fideprion disease and that mutations causing prion diseases may share a uniform initial mechanism of action. Therefore, these mice represent useful tools for studying the early stages of genetic prion diseases.
Gamma-burst cortical activity in awake behaving macaques
Authors: Acland Benjamin T. , Palanca Ben Julian A. , Bijsterbosch Janine , Snyder Lawrence H. 
Published: September 2023

AbstractElectrophysiological recordings during ketamine anesthesia have revealed a slow alternating pattern of high- and low- frequency activity (a “gamma-burst” pattern) that develops with the onset of general anesthesia. We examine the role of NMDA receptor antagonism in generating the gamma-burst pattern and the link between gamma-bursts and dissociative anesthesia. We compare the effects of ketamine with those of the highly selective NMDA receptor antagonist CGS 19755 on multi-site intracranial electrophysiology and behavior in rhesus macaques. Remarkably, we find that animals given a moderate dose of CGS 19755 are able to perform a difficult memory task, while at the same time showing electrophysiological activity similar to ketamine anesthesia, with one key difference: a lack of delta-band LFP modulation. This difference demonstrates that ketamine’s ability to drive strong delta-band oscillations relies on additional mechanisms beyond NMDA receptor antagonism alone, and points to a key role for the activity underlying delta-band oscillations in causing anesthesia.
survInTime - Exploring surveillance methods and data analysis on Brazilian respiratory syndrome dataset and community mobility changes
Authors: Martins Yasmmin Côrtes , da Silva Ronaldo Francisco 
Published: September 2023

AbstractBackgroundThe covid-19 pandemic brought negative impacts in almost every country in the world. These impacts were observed mainly in the public health sphere, with a rapid raise and spread of the disease and failed attempts to restrain it while there was no treatment. However, in developing countries, the impacts were severe in other aspects such as the intensification of social inequality, poverty and food insecurity. Specifically in Brazil, the miscommunication among the government layers conducted the control measures to a complete chaos in a country of continental dimensions. Brazil made an effort to register granular informative data about the case reports and their outcomes, while this data is available and can be consumed freely, there are issues concerning the integrity and inconsistencies between the real number of cases and the number of notifications in this dataset.ResultsWe projected and implemented four types of analysis to explore the Brazilian public dataset of Severe Acute Respiratory Syndrome (srag dataset) notifications and the google dataset of community mobility change (mobility dataset). These analysis provides some diagnosis of data integration issues and strategies to integrate data and experimentation of surveillance analysis. The first type of analysis aims at describing and exploring the data contained in both datasets, starting by assessing the data quality concerning missing data, then summarizing the patterns found in this datasets. The Second type concerns an statistical experiment to estimate the cases from mobility patterns organized in periods of time. We also developed, as the third analysis type, an algorithm to help the understanding of the disease waves by detecting them and compare the time periods across the cities. Lastly, we build time series datasets considering deaths, overall cases and residential mobility change in regular time periods and used as features to group cities with similar behavior.ConclusionThe exploratory data analysis showed the under representation of covid-19 cases in many small cities in Brazil that were absent in the srag dataset or with a number of cases very low than real projections. We also assessed the availability of data for the Brazilian cities in the mobility dataset in each state, finding out that not all the states were represented and the best coverage occurred in Rio de Janeiro state. We compared the capacity of place categories mobility change combination on estimating the number of cases measuring the errors and identifying the best components in mobility that could affect the cases. In order to target specific strategies for groups of cities, we compared strategies to cluster cities that obtained similar outcomes behavior along the time, highlighting the divergence on handling the disease.Availabilityhttps://github.com/YasCoMa/dashboard-srag-mobility