bluuebunny/crossref_metadata_2025_split huggingface dataset:
Senescent-like microglia limit remyelination through the senescence associated secretory phenotype
Authors: Gross Phillip S. , Laforet Violeta Duran , Manavi Zeeba , Zia Sameera , Lee Sung Hyun , Shults Nataliia , Selva Sean , Alvarez Enrique , Plemel Jason R. , Schafer Dorothy P. , Huang Jeffrey K. 
Published: May 2024

ABSTRACTThe capacity to regenerate myelin in the central nervous system (CNS) diminishes with age. This decline is particularly evident in multiple sclerosis (MS), which has been suggested to exhibit features of accelerated biological aging. Whether cellular senescence, a hallmark of aging, contributes to remyelination impairment remains unknown. Here, we show that senescent cells (SCs) accumulate within demyelinated lesions after injury, and their elimination enhances remyelination in young mice but not in aged mice. In young mice, we observed the upregulation of senescence-associated transcripts primarily in microglia after demyelination, followed by their reduction during remyelination. However, in aged mice, senescence-associated factors persisted within lesions, correlating with inefficient remyelination. We found that SC elimination enhanced remyelination in young mice but was ineffective in aged mice. Proteomic analysis of senescence-associated secretory phenotype (SASP) revealed elevated levels of CCL11/Eotaxin-1 in lesions, which was found to inhibit efficient oligodendrocyte maturation. These results suggest therapeutic targeting of SASP components, such as CCL11, may improve remyelination in aging and MS.
RF coil design strategies for improving SNR at the ultrahigh magnetic field of 10.5 Tesla
Authors: Waks Matt , Lagore Russell L. , Auerbach Edward , Grant Andrea , Sadeghi-Tarakameh Alireza , DelaBarre Lance , Jungst Steve , Tavaf Nader , Lattanzi Riccardo , Giannakopoulos Ilias , Moeller Steen , Wu Xiaoping , Yacoub Essa , Vizioli Luca , Schmidt Simon , Metzger Gregory J. , Eryaman Yigitcan , Adriany Gregor , Uğurbil Kamil 
Published: May 2024

AbstractPurposeTo develop multichannel transmit and receive arrays towards capturing the ultimate-intrinsic-SNR (uiSNR) at 10.5 Tesla (T) and to demonstrate the feasibility and potential of whole-brain, high-resolution human brain imaging at this high field strength.MethodsA dual row 16-channel self-decoupled transmit (Tx) array was converted to a 16Tx/Rx transceiver using custom transmit/receive switches. A 64-channel receive-only (64Rx) array was built to fit into the 16Tx/Rx array. Electromagnetic modeling and experiments were employed to define safe operation limits of the resulting 16Tx/80Rx array and obtain FDA approval for human use.ResultsThe 64Rx array alone captured approximately 50% of the central uiSNR at 10.5T while the identical 7T 64Rx array captured ∼76% of uiSNR at this lower field strength. The 16Tx/80Rx configuration brought the fraction of uiSNR captured at 10.5T to levels comparable to the performance of the 64Rx array at 7T. SNR data obtained at the two field strengths with these arrays displayeddependent increases over a large central region. Whole-brain high resolution T2* and T1weighted anatomical and gradient-recalled echo EPI BOLD fMRI images were obtained at 10.5T for the first time with such an advanced array, illustrating the promise of >10T fields in studying the human brain.ConclusionWe demonstrated the ability to approach the uiSNR at 10.5T over the human brain with a novel, high channel count array, achieving large SNR gains over 7T, currently the most commonly employed ultrahigh field platform, and demonstrate high resolution and high contrast anatomical and functional imaging at 10.5T.
Digital cognitive assessments as low-burden markers for predicting future cognitive decline and tau accumulation across the Alzheimer’s spectrum
Authors: Vanderlip Casey R. , Stark Craig E.L. ,   Alzheimer’s Disease Neuroimaging Initiative
Published: May 2024

AbstractDigital cognitive assessments, particularly those that can be done at home, present as low burden biomarkers for participants and patients alike, but their effectiveness in diagnosis of Alzheimer’s or predicting its trajectory is still unclear. Here, we assessed what utility or added value these digital cognitive assessments provide for identifying those at high risk for cognitive decline. We analyzed >500 ADNI participants who underwent a brief digital cognitive assessment and Aβ/tau PET scans, examining their ability to distinguish cognitive status and predict cognitive decline. Performance on the digital cognitive assessment were superior to both cortical Aβ and entorhinal tau in detecting mild cognitive impairment and future cognitive decline, with mnemonic discrimination deficits emerging as the most critical measure for predicting decline and future tau accumulation. Digital assessments are effective in identifying at-risk individuals, supporting their utility as low-burden tools for early Alzheimer’s detection and monitoring.
Characterization of immunity-inducing rhizobacteria highlights diversity in plant-microbe interactions
Authors: Loranger Mackenzie Eli William , Yim Winfield , Toffoli Matthew , Groleau Marie-Christine , Nickzad Arvin , Morales-Lizcano Nadia , Berleth Thomas , Moeder Wolfgang , Déziel Eric , Yoshioka Keiko 
Published: May 2024

AbstractThe narrow region of soil surrounding roots (rhizosphere) contains an astonishing diversity of microorganisms. Some rhizosphere bacteria can improve plant health and immunity, via direct competition with pathogens or by establishing heightened immunity in aboveground tissues, a phenomenon known as Induced Systemic Resistance (ISR). We screened a bacterial library from agricultural soils to identify strains that, after root treatment, induce immunity inSolanum lycopersicum(tomato) against the fungal pathogenBotrytis cinerea. Here, we report the establishment of a screening method and characterization of a subset of five strains, belonging to the speciesBacillus velezensis, Paenibacillus peoriaeandPseudomonas parafulva, that induced systemic resistance in tomato. However interestingly, only two of them triggered canonical ISR in Arabidopsis, indicating plant host specificity and/or alternative modes of actions. Furthermore, some of the strains displayed direct anti-microbial activity. We also found the requirement of the lipid-binding protein DIR1 in ISR establishment, indicating a possible convergence of SAR and ISR signaling. Finally, we found thatP. parafulvaTP18m, also displayed strong effects on root development. Taken together, we have identified taxonomically diverse immunity-inducing bacteria. Our characterization revealed diverse features, highlighting the complexity of bacteria- host interaction in the rhizosphere.HighlightWe identified taxonomically diverse rhizobacteria that induce systemic resistance in tomato plants to Botrytis after application to the root. These bacteria display diverse modes of action to improve plant health.
Assessing Plasticity in the Primary Sensory Cortex and Its Relation with Atypical Tactile Reactivity in Autism: A TMS-EEG Protocol
Authors: Kariminezhad Shohreh , Zomorrodi Reza , Zrenner Christoph , Blumberger Daniel M. , Ameis Stephanie H. , Lin Hsiang-Yuan , Lai Meng-Chuan , Rajji Tarek K. , Lunsky Yona , Sanches Marcos , Desarkar Pushpal 
Published: May 2024

AbstractBackgroundAtypical sensory reactivity is a cardinal presentation in autism. Within the tactile domain, atypical tactile reactivity (TR) is common, it emerges early, persists into adulthood, and impedes social interaction and daily functioning. Hence, atypical TR is a key target for biological intervention to improve outcomes. Brain mechanisms informing biological interventions for atypical TR remains elusive. We previously reported hyper-plasticity in the motor cortex in autistic adults and found that repetitive transcranial magnetic stimulation (rTMS), designed to strengthen inhibitory processes in the brain, reduced hyper-plasticity. Whether the primary sensory cortex (S1) is characterized by hyper-plasticity, which may underlie atypical TR in autism is unknown.ObjectivesWe aim to test whether hyper-plasticity in the S1 underlies atypical TR in autism, and investigate if a single session of rTMS can safely reduce hyper-plasticity in S1 in autistic adults.MethodPlasticity will be assessed in the left S1 with integrated paired associative stimulation and electroencephalography (PAS-EEG) paradigm in 32 autistic adults and 32 age-, sex-, and intelligence quotient-matched controls. Autistic participants will be further randomized (double-blind, 1:1) to receive a single-session of either sham or active 20 Hz bilateral rTMS over the S1 and the plasticity will be re-assessed over the left S1 on the same day.ConclusionsAtypical TR has been identified as one of the top clinical research priorities that can influence outcome in autistic population. The study findings can be highly valuable to further elucidate the mechanism underlying atypical TR, which in turn can help with developing a mechanism-driven intervention.
A connectome manipulation framework for the systematic and reproducible study of structure–function relationships through simulations
Authors: Pokorny Christoph , Awile Omar , Isbister James B. , Kurban Kerem , Wolf Matthias , Reimann Michael W. 
Published: May 2024

ABSTRACTSynaptic connectivity at the neuronal level is characterized by highly non-random features. Hypotheses about their role can be developed by correlating structural metrics to functional features. But to prove causation, manipula- tions of connectivity would have to be studied. However, the fine-grained scale at which non-random trends are expressed makes this approach challenging to pursue experimentally. Simulations of neuronal networks provide an alternative route to study arbitrarily complex manipulations in morphologically and biophysically detailed models. Here, we present Connectome-Manipulator, a Python framework for rapid connectome manipulations of large- scale network models in SONATA format. In addition to creating or manipulating the connectome of a model, it provides tools to fit parameters of stochastic connectivity models against existing connectomes. This enables rapid replacement of any existing connectome with equivalent connectomes at different levels of complexity, or transplantation of connectivity features from one connectome to another, for systematic study. We employed the framework in a detailed model of rat somatosensory cortex in two exemplary use cases: transplanting interneuron connectivity trends from electron microscopy data and creating simplified connectomes of excitatory connectivity. We ran a series of network simulations and found diverse shifts in the activity of individual neuron populations causally linked to these manipulations.
Two germ granule eIF4E isoforms reside in different mRNPs to hand offC elegansmRNAs from translational repression to activation
Authors: Gajjar Gita , Huggins Hayden P. , Kim Eun Suk , Huang Weihua , Bonnet Frederic X. , Updike Dustin L. , Keiper Brett D. 
Published: May 2024

AbstractWe studied the function of translation factor eIF4E isoforms in regulating mRNAs in germ cell granules/condensates. Translational control of mRNAs plays an essential role in germ cell gene regulation. Messenger ribonucleoprotein (mRNP) complexes assemble on mRNAs as they move from the nucleus into perinuclear germ granules to exert both positive and negative post-transcriptional regulation in the cytoplasm. InC. elegans, germ granules are surprisingly dynamic mRNP condensates that remodel during development. Two eIF4E isoforms (called IFE-1 and IFE-3), eIF4E-Interacting Proteins (4EIPs), RBPs, DEAD-box helicases, polyadenylated mRNAs, Argonautes and miRNAs all occupy positions in germ granules. Affinity purification of IFE-1 and IFE-3 allowed mass spectrometry and mRNA-Seq to identify the proteins and mRNAs that populate stable eIF4E mRNPs. We find translationally controlled mRNAs (e.g.pos-1, mex-3, spn-4,etc.) enriched in IFE-3 mRNPs, but excluded from IFE-1 mRNPs. These mRNAs also require IFE-1 for efficient translation. The findings support a model in which oocytes and embryos utilize the two eIF4Es for opposite purposes on critically regulated germline mRNAs. Careful colocalization of the eIF4Es with other germ granule components suggests an architecture in which GLH-1, PGL-1 and the IFEs are stratified to facilitate sequential interactions for mRNAs. Biochemical characterization demonstrates opposing yet cooperative roles for IFE-3 and IFE-1 to hand-off of translationally controlled mRNAs from the repressed to the activated state, respectively. The model involves eIF4E mRNPs shuttling mRNAs through nuclear pore-associated granules/condensates to cytoplasmic ribosomes.
Genome-wide nucleosome and transcription factor responses to genetic perturbations reveal chromatin-mediated mechanisms of transcriptional regulation
Authors: Moyung Kevin , Li Yulong , Hartemink Alexander J. , MacAlpine David M. 
Published: May 2024

AbstractEpigenetic mechanisms contribute to gene regulation by altering chromatin accessibility through changes in transcription factor (TF) and nucleosome occupancy throughout the genome. Despite numerous studies focusing on changes in gene expression, the intricate chromatin-mediated regulatory code remains largely unexplored on a comprehensive scale. We address this by employing a factor-agnostic, reverse-genetics approach that uses MNase-seq to capture genome-wide TF and nucleosome occupancies in response to the individual deletion of 201 transcriptional regulators inSaccharomyces cerevisiae, thereby assaying nearly one million mutant-gene interactions. We develop a principled approach to identify and quantify chromatin changes genome-wide, observing differences in TF and nucleosome occupancy that recapitulate well-established pathways identified by gene expression data. We also discover distinct chromatin signatures associated with the up- and downregulation of genes, and use these signatures to reveal regulatory mechanisms previously unexplored in expression-based studies. Finally, we demonstrate that chromatin features are predictive of transcriptional activity and leverage these features to reconstruct chromatin-based transcriptional regulatory networks. Overall, these results illustrate the power of an approach combining genetic perturbation with high-resolution epigenomic profiling; the latter enables a close examination of the interplay between TFs and nucleosomes genome-wide, providing a deeper, more mechanistic understanding of the complex relationship between chromatin organization and transcription.
Perception of task duration affects metabolic cost during split-belt adaptation
Authors: Jeffcoat S.N. , Aragon A. , Kuch A. , Farrokhi S. , Sanchez N. 
Published: May 2024

AbstractHumans continuously adapt locomotor patterns. Whether metabolic cost reduction is the primary objective or a by-product of the observed biomechanical changes during adaptation is not known. The main goal of our study is to determine if perception of task duration affects the adaptation of locomotor patterns to reduce energetic cost during split-belt walking. We tested the hypothesis that individuals who believe they will sustain a locomotor adaptation task for a prolonged time will reduce metabolic cost by adapting toward a walking pattern associated with lower mechanical work. N=14 participants walked on a split-belt treadmill for 10 minutes with knowledge of task duration (group K), while N=15 participants performed the task under the assumption that they would walk for 30 minutes (group U). Both groups walked for 10 minutes with the belts moving at 1.5 and 0.5 m/s, followed by 6 minutes of walking with both belts at 1.0 m/s. We observed a significant main effect of Time (p<0.001, observed power 1.0) and the interaction of Time×Group (p=0.004, observed power 0.84) on metabolic cost. Participants in the U group had a metabolic cost that was 12% lower during adaptation compared to the K group, which did not reduce metabolic cost during adaptation. The metabolic cost reduction observed in group U was not associated with biomechanical changes during adaptation. Our results indicate that metabolic cost reduction has a primary role in tasks that need to be sustained for a prolonged time, and this reduction is not only related to biomechanical factors.New and NoteworthyIndividuals can markedly reduce the metabolic cost of a walking adaptation task if they believe they must sustain the task for a prolonged time. The variables typically used to track adaptation do not track the reductions in metabolic cost observed in our study. Metabolic cost reduction can occur without clear changes in biomechanical factors.
Single-cell landscapes of long non-coding RNAs in early vascular endothelial development and hemogenic specification
Authors: Chen Xupeng , Ning Xiaowei , Lu Chenguang , He Han , Yao Yingpeng , Ni Yanli , Zhou Jie , Liu Bing , Hou Siyuan , Lan Yu , Li Zongcheng 
Published: May 2024

AbstractUnderstanding the molecular regulation of arterial and hemogenic specification during early embryonic vascular development is crucial for guiding vascular and hematopoietic regeneration. Accumulating evidence emphasizes the role of long non-coding RNAs (lncRNAs) in cell fate decision. However, the dynamic expression and the potential roles of lncRNAs in early vascular development are still unknown. Here, we first constructed a single-cell landscape of lncRNA expression based on the deeply sequenced tag-based single-cell transcriptome data of early embryonic vascular endothelial cells (VECs). We revealed the contribution of lncRNAs to VEC heterogeneity and identified 295 lncRNAs with specific expression in eight VEC populations. Furthermore, we identified a series of lncRNAs potentially involved in regulating the two waves of arterial specification and hemogenic specification. We uncovered a transient downregulation ofH19in the hemogenic endothelial population during endothelial-to-hematopoietic transition. Additionally, we constructed a transcription factor regulatory network composed of 287 regulons for early VEC development. We further revealed differential activation patterns of regulons and modules in the eight VEC populations, and predicted potential lncRNA-regulon regulatory network. Moreover, unsupervised analysis of the lncRNA expression profile revealed novel VEC subpopulations strongly associated with the maturation of VECs, suggesting the prominent roles of lncRNAs in endothelial maturation. In summary, our study fills the gap in understanding of lncRNA regulatory networks in early vascular development and provides insights into the fields of vascular and hematopoietic regeneration research.
Muscle-derived miR-200a-3p through light-intensity exercise may contribute to improve memory dysfunction in type 2 diabetic mice
Authors: Shima Takeru , Onishi Hayate , Terashima Chiho 
Published: May 2024

AbstractBackgroundMemory dysfunction associated with type 2 diabetes mellitus (T2DM) poses a considerable threat to overall well-being. Engaging in light-intensity exercise has been shown to exert favorable effects on hippocampal function and molecular profiles, includingMct2mRNA and miR-200a-3p. Nonetheless, a comprehensive understanding of the mechanisms underlying the positive impact of light-intensity exercise remains elusive. Here, we assessed the influence of exosomal miR-200a-3p secretion from gastrocnemius muscles in T2DM mice undergoing light-intensity exercise intervention, focusing on its potential to ameliorate memory dysfunction.Basic proceduresWe initially assessed the effects of light-intensity exercise (7.0 m/min for healthy mice, 5.0 m/min for ob/ob mice, 30 min/day, five days/week, over a four-week period) on memory function, hippocampal mRNA associated with memory function, and the secretion of exosomal miR-200a-3p from their gastrocnemius muscle. Subsequently, the impact of a daily intraperitoneal injection of the miR-200a-3p mimic over a four-week duration was investigated, focusing on its influence on hippocampal dysregulation in ob/ob mice.Main findingsThe light-intensity exercise intervention increased gastrocnemius muscle-derived and plasma exosomal miR-200a-3p levels in ob/ob mice, concomitant with improved memory dysfunction. Intriguingly, the daily intraperitoneal injection of mmu-miR-200a-3p mimic also demonstrated an ameliorative effect on memory function in ob/ob mice. Notably, both the exercise intervention and miR-200a-3p mimic treatment induced downregulation in hippocampalKeap1mRNA and upregulation in mRNA ofHsp90aa1andMct2in ob/ob mice.Principal conclusionsThe current results imply that the augmentation of exosomal miR-200a-3p derived from the gastrocnemius muscle contributes to the amelioration of memory dysfunction in T2DM undergoing light-intensity exercise. Additionally, it is proposed that miR-200a-3p emulates the effects of light-intensity exercise, suggesting a potential therapeutic pathway for addressing hippocampal complications in the context of T2DM.
Molecular Specializations Underlying Phenotypic Differences in Inner Ear Hair Cells of Zebrafish and Mice
Authors: Giffen Kimberlee P. , Liu Huizhan , Yamane Kacey L. , Li Yi , Chen Lei , Kramer Ken L. , Zallocchi Marisa , He David Z.Z. 
Published: May 2024

AbstractHair cells (HCs) are the sensory receptors of the auditory and vestibular systems in the inner ears of vertebrates that selectively transduce mechanical stimuli into electrical activity. Although all HCs have the hallmark stereocilia bundle for mechanotransduction, HCs in non-mammals and mammals differ in their molecular specialization in the apical, basolateral and synaptic membranes. HCs of non-mammals, such as zebrafish (zHCs), are electrically tuned to specific frequencies and possess an active process in the stereocilia bundle to amplify sound signals. Mammalian cochlear HCs, in contrast, are not electrically tuned and achieve amplification by somatic motility of outer HCs (OHCs). To understand the genetic mechanisms underlying differences among adult zebrafish and mammalian cochlear HCs, we compared their RNA-seq-characterized transcriptomes, focusing on protein-coding orthologous genes related to HC specialization. There was considerable shared expression of gene orthologs among the HCs, including those genes associated with mechanotransduction, ion transport/channels, and synaptic signaling. For example, both zebrafish and mouse HCs expressTmc1, Lhfpl5, Tmie, Cib2, Cacna1d, Cacnb2, Otof, PcloandSlc17a8. However, there were some notable differences in expression among zHCs, OHCs, and inner HCs (IHCs), which likely underlie the distinctive physiological properties of each cell type.Tmc2 and Cib3were not detected in adult mouse HCs buttmc2aandbandcib3were highly expressed in zHCs. Mouse HCs expressKcna10,Kcnj13,Kcnj16, andKcnq4, which were not detected in zHCs.Chrna9andChrna10were expressed in mouse HCs. In contrast,chrna10was not detected in zHCs. OHCs highly expressSlc26a5which encodes the motor protein prestin that contributes to OHC electromotility. However, zHCs have only weak expression ofslc26a5, and subsequently showed no voltage dependent electromotility when measured. Notably, the zHCs expressed more paralogous genes including those associated with HC-specific functions and transcriptional activity, though it is unknown whether they have functions similar to their mammalian counterparts. There was overlap in the expressed genes associated with a known hearing phenotype. Our analyses unveil substantial differences in gene expression patterns that may explain phenotypic specialization of zebrafish and mouse HCs. This dataset also includes several protein-coding genes to further the functional characterization of HCs and study of HC evolution from non-mammals to mammals.