bluuebunny/crossref_metadata_2025_split huggingface dataset:
Big Data in Myoelectric Control: Large Multi-User Models Enable Robust Zero-Shot EMG-based Discrete Gesture Recognition
Authors: Eddy Ethan , Campbell Evan , Bateman Scott , Scheme Erik 
Published: July 2024

ABSTRACTMyoelectric control, the use of electromyogram (EMG) signals generated during muscle contractions to control a system or device, is a promising modality for enabling always-available control of emerging ubiquitous computing applications. However, its widespread use has historically been limited by the need for user-specific machine learning models because of behavioural and physiological differences between users. Leveraging the publicly available 612-user EMG-EPN612 dataset, this work dispels this notion, showing that true zero-shot cross-user myoelectric control is achievable without user-specific training. By taking a discrete approach to classification (i.e., recognizing the entire dynamic gesture as a single event), a classification accuracy of 93.0% for six gestures was achieved on a set of 306 unseen users (who provided no training data), showing that big data approaches (compared to most EMG studies, which typically employ only 10-20 users) can enable robust cross-user myoelectric control. By organizing the results into a series of mini-studies, this work provides an in-depth analysis of discrete cross-user models to answer unknown questions and uncover new research directions. In particular, this work explores the number of participants required to build cross-user models, the impact of transfer learning for fine-tuning these models, and the effects of under-represented end-user demographics in the training data, among other issues. Additionally, in order to further evaluate the performance of the created cross-user models, a completely new data set was created (using the same recording device) that includes known covariate factors such as cross-day use and limb-position variability. The results show that the large data models can effectively generalize to new datasets and mitigate the impact of common confounding factors that have historically limited the adoption of EMG-based inputs.
Trichoderma afroharzianumT22 induces rhizobia and flavonoid-driven symbiosis to promote iron deficiency tolerance in garden pea
Authors: Thapa Asha , Hasan Md Rokibul , Kabir Ahmad H. 
Published: July 2024

ABSTRACTIron (Fe) deficiency is a limiting factor for legumes, yet the role of beneficial fungi in mitigating Fe deficiency in garden pea is understudied. In this study,Trichoderma afroharzianumT22 colonized the roots of garden pea cultivars exposed to alkali-mediated Fe-deficiency in a host- specific manner. In Fe-deficient Sugar Snap, T22 improved growth parameters consistent with increased tissue Fe and rhizosphere siderophore. The split-root assay demonstrated that the beneficial effects of T22 on Fe deficiency mitigation are the result of a whole-plant association rather than localized root-specific effects. RNA-seq analysis showed 575 and 818 differentially expressed genes upregulated and downregulated in the roots inoculated with T22 under Fe deficiency. The upregulated genes were mostly involved in the flavonoid biosynthetic pathway (monooxygenase activity, ammonia-lyase activity, 4-coumarate-CoA ligase), along with genes related to mineral transport and redox homeostasis. Further, a flavonoid precursor restored plant health even in the absence of T22, confirming the role of microbial symbiosis in mitigating Fe deficiency. Interestingly, T22 restored the abundance of rhizobia, particularlyRhizobium leguminosarumandRhizobium indicum, along with the induction ofNifA,NifD, andNifHin nodules, suggesting a connection between T22 and rhizobia under Fe-starvation. Further, the elevated rhizosphere siderophore, root flavonoid, expression ofPsCoA(4-coumarate-CoA ligase) as well as the relative abundance ofTaAOX1andR. leguminosarumdiminished when T22 was substituted with exogenous Fe. This suggests that exogenous Fe eliminates the need for microbiome-driven Fe mobilization, while T22-mediated Fe mitigation depends on flavonoid- driven symbiosis andR. leguminosarumabundance. It was further supported by the positive interaction of T22 onR. leguminosarumgrowth in Fe-deficient media. Thus, the beneficial effect of T22 on rhizobia likely stems from their interactions, not just improved Fe status in plants. This study provides the first mechanistic insights into T22 interactions with host and rhizobia, advancing microbiome strategies to alleviate Fe deficiency in peas and other legumes.
Extracellular Vesicles from hiPSC-derived NSCs Protect Human Neurons against Aβ-42 Oligomers Induced Neurodegeneration, Mitochondrial Dysfunction and Tau Phosphorylation
Authors: Rao Shama , Madhu Leelavathi N , Babu Roshni Sara , Nagarajan Advaidhaa , Upadhya Raghavendra , Narvekar Esha , Shetty Ashok K 
Published: July 2024

AbstractBackgroundOne of the hallmarks of Alzheimer’s disease (AD) is the buildup of amyloid beta-42 (Aβ-42) in the brain, which leads to various adverse effects. Therefore, therapeutic interventions proficient in reducing Aβ-42-induced toxicity in AD are of great interest. One promising approach is to use extracellular vesicles from human induced pluripotent stem cell-derived neural stem cells (hiPSC-NSC-EVs) because they carry multiple therapeutic miRNAs and proteins capable of protecting neurons against Aβ-42-induced pathological changes. Therefore, thisin vitrostudy investigated the proficiency of hiPSC-NSC-EVs to protect human neurons derived from two distinct hiPSC lines from Aβ-42o-induced neurodegeneration.MethodsWe isolated hiPSC-NSC-EVs using chromatographic methods and characterized their size, ultrastructure, expression of EV-specific markers and proficiency in getting incorporated into mature human neurons. Next, mature human neurons differentiated from two different hiPSC lines were exposed to 1 µM Aβ-42 oligomers (Aβ-42o) alone or with varying concentrations of hiPSC-NSC-EVs. The protective effects of hiPSC-NSC-EVs against Aβ-42o-induced neurodegeneration, increased oxidative stress, mitochondrial dysfunction, impaired autophagy, and tau phosphorylation were ascertained using multiple measures and one-way ANOVA with Newman-Keuls multiple comparisons post hoc tests.ResultsSignificant neurodegeneration was observed when human neurons were exposed to Aβ-42o alone. Notably, neurodegeneration was associated with elevated levels of oxidative stress markers malondialdehyde (MDA) and protein carbonyls (PCs), increased expression of proapoptotic Bax and Bad genes and proteins, reduced expression of the antiapoptotic gene and protein Bcl-2, increased expression of genes encoding mitochondrial complex proteins, decreased expression of autophagy-related proteins Beclin-1 and microtubule-associated protein 1 light chain 3B, and increased phosphorylation of tau. However, the addition of an optimal dose of hiPSC-NSC-EVs (6 x 109EVs) to human neuronal cultures exposed to Aβ-42o significantly reduced the extent of neurodegeneration, along with diminished levels of MDA and PCs, normalized expressions of Bax, Bad, and Bcl-2, and genes linked to mitochondrial complex proteins, and reduced tau phosphorylation.ConclusionsThe findings demonstrate that an optimal dose of hiPSC-NSC-EVs could significantly decrease the degeneration of human neurons induced by Aβ-42o. The results also support further research into the effectiveness of hiPSC-NSC-EVs in AD, particularly their proficiency in preserving neurons and slowing disease progression.
AoUPRS: A Cost-Effective and Versatile PRS Calculator for theAll of UsProgram
Authors: Khattab Ahmed , Chen Shang-Fu , Wineinger Nathan , Torkamani Ali 
Published: July 2024

ABSTRACTBackgroundThe All of Us (AoU) Research Program provides a comprehensive genomic dataset to accelerate health research and medical breakthroughs. Despite its potential, researchers face significant challenges, including high costs and inefficiencies associated with data extraction and analysis. AoUPRS addresses these challenges by offering a versatile and cost-effective tool for calculating polygenic risk scores (PRS), enabling both experienced and novice researchers to leverage the AoU dataset for significant genomic discoveries.ResultsAoUPRS is implemented in Python and utilizes the Hail framework for genomic data analysis. It offers two distinct approaches for PRS calculation: the Hail MatrixTable (MT) and the Hail Variant Dataset (VDS). The MT approach provides a dense representation of genotype data, while the VDS approach offers a sparse representation, significantly reducing computational costs. In performance evaluations, the VDS approach demonstrated a cost reduction of up to 99.51% for smaller scores and 85% for larger scores compared to the MT approach. Both approaches yielded similar predictive power, as shown by logistic regression analyses of PRS for coronary artery disease, atrial fibrillation, and type 2 diabetes. The empirical cumulative distribution functions (ECDFs) for PRS values further confirmed the consistency between the two methods.ConclusionsAoUPRS is a versatile and cost-effective tool that addresses the high costs and inefficiencies associated with PRS calculations using the AoU dataset. By offering both dense and sparse data processing approaches, AoUPRS allows researchers to choose the approach best suited to their needs, facilitating genomic discoveries. The tool’s open-source availability on GitHub, coupled with detailed documentation and tutorials, ensures accessibility and ease of use for the scientific community.
Pulsatile dynamics propagate crystalline order in the developingDrosophila eye
Authors: Couturier Lydie , Luna-Escalante Juan , Mazouni Khallil , Mestdagh Claire , Phan Minh-Son , Tinevez Jean-Yves , Schweisguth François , Corson Francis 
Published: July 2024

AbstractPattern formation in developing tissues often involves self-organization guided by positional information. In most tissues, however, its dynamics, and therefore the underlying logic, remain unknown. Examining self-organized patterning of the fly eye, we combine experiments and modeling to elucidate how rows of light-receiving units emerge in the wake of a traveling differentiation front to form a crystal-like array. Live imaging of the proneural factor Atonal reveals unanticipated oscillations at the front, which are produced by the successive activation of two distinct enhancers and associated with pulsatile Notch signaling. Our observations are inconsistent with current models of eye patterning, whereby each row of differentiating cells provides a negative template for the next. Instead, they inform a new relay model in which transient Notch signaling from differentiating cells provides a positive template for the onset of differentiation two rows ahead, conveying both temporal and spatial information to propagate oscillations and crystal-like order.
Composite Hedges Nanopores: A High INDEL-Correcting Codec System for Rapid and Portable DNA Data Readout
Authors: Zhao Xuyang , Li Junyao , Fan Qingyuan , Dai Jing , Long Yanping , Liu Ronghui , Zhai Jixian , Pan Qing , Li Yi 
Published: July 2024

AbstractDNA, as the origin for the genetic information flow, has also been a compelling alternative to non-volatile information storage medium. Reading digital information from this highly dense but lightweighted medium nowadays relied on conventional next-generation sequencing (NGS), which involves ‘wash and read’ cycles for synchronization and the indel (insertion and deletion) errors rarely occur. However, these time-consuming cycles hinder the future of real-time data retrieval. Nanopore sequencing holds the promise to overcome the efficiency problem, but high indel error rates lead to the requirement of large amount of high-quality data for accurate readout using emerging NGS-based codec systems. Here we introduce Composite Hedges Nanopores (CHN), a nanopore-based codec scheme tailored for real-time data retrieval, capable of handling indel rates up to 15.9% and substitution rates up to 7.8%. The overall information density can be doubled from 0.59 to 1.17 by utilizing a degenerated eight-letter alphabet, where one composite strand will be projected into eight normal strands. We demonstrate that sequencing times of 20 and 120 minutes were sufficient for processing representative text and image files (7 and 115 composite strands), respectively. The time-diminishing deviations are mainly originated from the extremely uneven abundance among the composite strands (cross-group variation) as well as the huge inequality among the normal strands (in-group variation). Moreover, to achieve complete data recovery, it is estimated that text and image data require 4× and 8× physical redundancy (coverage) of composite strands, respectively. Our CHN codec system excels on both molecular design and equalized dictionary usage, laying a solid foundation for nucleic acid-based data retrieval and encoding approaching to real-time, applicable in both cloud and edge computing systems.
Direct non-transcriptional link between brassinosteroid perception and cortical microtubule reorientation drives hypocotyl growth
Authors: Delesalle Charlotte , Montiel-Jorda Alvaro , Neveu Julie , Fujita Satoshi , Vert Grégory 
Published: July 2024

AbstractBrassinosteroids (BRs) are steroid-type phytohormones that are essential for plant growth, development and adaptation to environmental stresses. BRs promote cell wall remodelling through extensive reprogramming of gene expression, thus impacting on cell elongation and hypocotyl growth. The existence of non-genomic responses to BRs is however still unclear. Here we identified and characterized a new family of BRI1-interacting proteins identified by yeast two hybrid named MBAPs. We confirmed using several complementary approaches that MBAPs are genuine BRI1 partners in plant cells. We demonstrated that MBAPs are localized to cortical microtubules (CMTs) underlying the plasma membrane using a short conserved helix and where they contact with and are phosphorylated by BRI1. Combinations ofmbaploss-of-function mutants showed hypersensitivity to BRs and establish MBAPs as negative regulators of BR responses. Surprisingly,mbapmutants showed unaffected typical downstream BR signaling readouts and BR target gene expression. Rather,mbapmutants displayed disordered CMT network and enhanced CMT reorganization upon BR perception. Altogether, our work shed light on the direct non-transcriptional connection between BR perception at the cell surface and CMT organization in the control of hypocotyl elongation.
Caenorhabditis elegansSynMuv B gene activity is down-regulated during a viral infection to enhance RNA interference
Authors: Seetharaman Ashwin , Galagali Himani , Linarte Elizabeth , Liu Mona H.X. , Cohen Jennifer D. , Chetal Kashish , Sadreyev Ruslan , Tate Alex J. , Montgomery Taiowa A. , Ruvkun Gary 
Published: July 2024

ABSTRACTSmall RNA pathways regulate eukaryotic antiviral defense. Many of theCaenorhabditis elegansmutations that were identified based on their enhanced RNAi, the synMuv B genes, also emerged from unrelated genetic screens for increased growth factor signaling. The dozen synMuv B genes encode homologues of the mammalian dREAM complex found in nearly all animals and plants, which includes thelin-35/retinoblastoma oncogene. We show that a set of highly induced mRNAs in synMuv B mutants is congruent with mRNAs induced by Orsay RNA virus infection ofC. elegans. In wild type animals, a combination of a synMuv A mutation and a synMuv B mutation are required for the Muv phenotype of increased growth factor signaling. But we show that Orsay virus infection of a single synMuv A mutant can induce a Muv phenotype, unlike the uninfected single synMuv A mutant. This suggests that decreased synMuv B activity, which activates the antiviral RNAi pathway, is a defense response to viral infection. Small RNA deep sequencing analysis of various dREAM complex mutants uncovers distinct siRNA profiles indicative of such an siRNA response. We conclude that the synMuv B mutants maintain an antiviral readiness state even in the absence of actual infection. The enhanced RNAi and conservation of the dREAM complex mutants suggests new therapeutic avenues to boost antiviral defenses.
Spatial Transcriptomics and Single-Nucleus Multi-omics Analysis Revealing the Impact of High Maternal Folic Acid Supplementation on Offspring Brain Development
Authors: Xu Xiguang , Lin Yu , Yin Liduo , Serpa Priscila da Silva , Conacher Benjamin , Pacholac Christina , Carvallo Francisco , Hrubec Terry , Farris Shannon , Zimmerman Kurt , Wang Xiaobin , Xie Hehuang 
Published: July 2024

ABSTRACTFolate, an essential vitamin B9, is crucial for diverse biological processes including neurogenesis. Folic acid (FA) supplementation during pregnancy is a standard practice for preventing neural tube defects (NTDs). However, concerns are growing over the potential risks of excessive maternal FA intake. Here, we employed mouse model and spatial transcriptomics and single-nucleus multi-omics approaches to investigate the impact of high maternal FA supplementation during the periconceptional period on offspring brain development. Maternal high FA supplementation affected gene pathways linked to neurogenesis and neuronal axon myelination across multiple brain regions, as well as gene expression alterations related to learning and memory in thalamic and ventricular regions. Single-nucleus multi-omics analysis revealed that maturing excitatory neurons in the dentate gyrus (DG) are particularly vulnerable to high maternal FA intake, leading to aberrant gene expressions and chromatin accessibility in pathways governing ribosomal biogenesis critical for synaptic formation. Our findings provide new insights into specific brain regions, cell types, gene expressions and pathways that can be affected by maternal high FA supplementation.
Denoising, Deblurring, and optical Deconvolution for cryo-ET and light microscopy with a physics-informed deep neural network DeBCR
Authors: Li Rui , Yushkevich Artsemi , Chu Xiaofeng , Kudryashev Mikhail , Yakimovich Artur 
Published: July 2024

AbstractComputational image-quality enhancement for microscopy (deblurring, denoising, and optical deconvolution) provides researchers with detailed information on samples. Recent general-purpose deep learning solutions advanced in this task. Yet, without consideration of the underlying physics, they may yield unrealistic and non-existent details and distortions during image restoration, requiring domain expertise to discern true features from artifacts. Furthermore, the large expressive capacity of general-purpose deep learning models requires more resources to train and use in applications. We introduce DeBCR, a physics-informed deep learning model based on wavelet theory to enhance microscopy images. DeBCR is a light model with a fast runtime and without hallucinations. We evaluated the image restoration performance of DeBCR and 12 current state-of-the-art models over 6 datasets spanning crucial modalities in advanced light microscopy and cryo-electron tomography. Leveraging optic models, DeBCR demonstrates superior performance in denoising, optical deconvolution, and deblurring tasks across both LM and cryo-ET modalities.
Functional analysis of conservedC. elegansbHLH family members uncovers lifespan control by a peptidergic hub neuron
Authors: Aguilar G. Robert , Vidal Berta , Ji Hongzhu , Evenblij Joke , Ji Hongfei , Valperga Giulio , Liao Chien-Po , Fang-Yen Christopher , Hobert Oliver 
Published: July 2024

ABSTRACTThroughout the animal kingdom, several members of the basic helix-loop-helix (bHLH) family act as proneural genes during early steps of nervous system development. Roles of bHLH genes in specifying terminal differentiation of postmitotic neurons have been less extensively studied. We analyze here the function of fiveC. elegansbHLH genes, falling into three phylogenetically conserved subfamilies, which are continuously expressed in a very small number of postmitotic neurons in the central nervous system. We show (a) that two orthologs of the vertebrate bHLHb4/b5 genes, calledhlh-17andhlh-32,function redundantly to specify the identity of a single head interneuron (AUA), as well as an individual motor neuron (VB2), (b) that thePTF1aorthologhlh-13acts as a terminal selector to control terminal differentiation and function of the sole octopaminergic neuron class inC. elegans, RIC, and (c) that the NHLH1/2 orthologhlh-15controls terminal differentiation and function of the peptidergic AVK head interneuron class, a known neuropeptidergic signaling hub in the animal. Strikingly, through null mutant analysis and cell-specific rescue experiments, we find that loss ofhlh-15/NHLHin the peptidergic AVK neurons and the resulting abrogation of neuropeptide secretion causes a substantially expanded lifespan of the animal, revealing an unanticipated impact of a central, peptidergic hub neuron in regulating lifespan, which we propose to be akin to hypothalamic control of lifespan in vertebrates. Taken together, our functional analysis reveals themes of bHLH gene function during terminal differentiation that are complementary to the earlier lineage specification roles of other bHLH family members. However, such late functions are much more sparsely employed by members of the bHLH transcription factor family, compared to the function of the much more broadly employed homeodomain transcription factor family.
A wavelet-based approach generates quantitative, scale-free and hierarchical descriptions of 3D genome structures and new biological insights
Authors: Pellow Ryan , Comeron Josep M 
Published: July 2024

ABSTRACTEukaryotes fold their genomes within nuclei in three-dimensional space, with coordinated multiscale structures including loops, topologically associating domains (TADs), and higher-order chromosome territories. This 3D organization plays essential roles in gene regulation and development, responses to physiological stress, and disease. However, current methodologies to infer these 3D structures from genomic data have limitations. These include varying outcomes depending on the resolution of the analysis and sequencing depth, qualitative results that hinder statistical comparisons, lack of insight into the frequency of the structures in samples with many genomes, and no direct inference of hierarchical structures. These shortcomings can make it difficult for the rigorous comparison of 3D properties across genomes, between experimental conditions, or species. To address these challenges, we developed a wavelet transform-based method (WaveTAD) that describes the 3D nuclear organization in a resolution-free, probabilistic, and hierarchical manner. WaveTAD generates probabilities that capture the variable frequency within samples and shows increased accuracy and sensitivity compared to current approaches. We applied WaveTAD to multiple datasets fromDrosophila, mouse, and humans to illustrate new biological insights that our more sensitive and quantitative approach provides, such as the widespread presence of embryonic 3D organization before zygotic genome activation, the effect of multiple CTCF units on the stability of loops and TADs, and the association between gene expression and TAD structures in COVID-19 patients or sex-specific transcription inDrosophila.