bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linear modeling of brain activity during selective attention to continuous speech: the critical role of the N1 effect in event-related potentials to acoustic edges
Authors: Mai Adrian , Hillyard Steven A. , Strauss Daniel J. 
Published: July 2023

AbstractRecent work in the field of neural speech tracking provided evidence for a cortical rep-resentation of speech through superposition of event-related responses to acoustic edges, an idea closely related to the popular linear modeling approach to study cortical syn-chronization to speech via magneto- or electroencephalography (M/EEG). However, it is still unclear to what extent speech-evoked event-related potentials (ERPs) including well-established phenomena, e.g., the N1 selective attention effect, contribute to the regression-based analyses. Here, we addressed this question by analyzing an EEG dataset obtained during a simple multispeaker selective attention task in which participants were cued to attend to only one of two competing speakers. Segmenting the ongoing EEG based on acoustic edges, we were able to replicate previous findings of event-related responses to speech in MEG data with particularly clear P1-N1-P2 complexes. Crucially, speech-evoked ERPs exhibited significant effects of attention in line with the auditory N1 effect. Comparing speech-evoked ERPs to the linear regression results revealed two major find-ings. First, temporal response functions (TRFs) obtained from forward modeling were strongly temporally as well as spatially correlated with corresponding true ERPs. Sec-ond, effects of attention demonstrated by the stimulus reconstruction (SR) accuracies obtained from backward modeling appeared to be driven by a consistent generation of speech-evoked ERPs including the N1 effect. Taken together, our observations reveal a direct link between ERPs to acoustic edges in speech and the linear TRF and SR mod-eling techniques. We emphasize the enhancement in signal-to-noise ratio provided by repeatedly evoked N1 responses to be a critical factor in facilitating the tracking and subsequent higher-order processing of selectively attended speech. In addition to that, the findings imply a cortical speech representation through superimposed speech-evoked ERPs in accordance with recent arguments promoting the neural evoked-response speech tracking model.
A high-quality reference genome for the common creek chub,Semotilus atromaculatus
Authors: Meuser Amanda V. , Pitura Amy R. , Mandeville Elizabeth G. 
Published: July 2023

AbstractCreek chub (Semotilus atromaculatus) are a leuciscid minnow species commonly found in anthropogenically disturbed environments, making them an excellent model organism to study human impacts on aquatic systems. Genomic resources for creek chub and other leuciscid species are currently limited. However, advancements in DNA sequencing now allow us to create genomic resources at a historically low cost. Here, we present a high quality 239 contig reference genome for the common creek chub, created with PacBio HiFi sequencing. We compared the assembly quality of two pipelines: Pacific Biosciences’ Improved Phase Assembly (IPA; 873 contigs) and Hifiasm (239 contigs). Quality and completeness of this genome is comparable to the zebrafish (Danioninae) and fathead minnow (Leuciscidae) genomes. The creek chub genome is highly syntenic to the zebrafish and fathead minnow genomes, and while our assembly does not resolve into the expected 25 chromosomes, synteny with zebrafish suggests that each creek chub chromosome is likely represented by 1-4 large contigs in our assembly. This reference genome is a valuable resource that will enhance genomic bio-diversity studies of creek chub and other non-model leuciscid species common to disturbed environments.
Genetic dissection of BDNF and TrkB expression in glial cells
Authors: Niu Changran , Yue Xinpei , An Juan Ji , Xu Haifei , Xu Baoji 
Published: July 2023

AbstractThe brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tropomyosin-related kinase receptor B (TrkB) are widely expressed in the central nervous system. It is well documented that neurons express BDNF and full-length TrkB (TrkB.FL), and a lower level of truncated TrkB (TrkB.T). With conflicting results, glial cells also have been reported to express BDNF and TrkB. In the current study, we employed a more sensitive and reliable genetic method to characterize the expression of BDNF and TrkB in glial cells in the mouse brain. We utilized three Cre mouse strains in which Cre recombinase is expressed in the same cells as BDNF, TrkB.FL, or all TrkB isoforms, and crossed them to Cre-dependent EGFP reporter mice to label BDNF- or TrkB-expressing cells. We performed immunohistochemistry with glial cell markers to examine the expression of BDNF and TrkB in microglia, astrocytes, and oligodendrocytes. Surprisingly, we found no BDNF- or TrkB-expressing microglia in the brain and spinal cord. Consistent with previous studies, most astrocytes only express TrkB.T in the adult brain. Moreover, there are a small number of astrocytes and oligodendrocytes that express BDNF, the function of which is to be determined. We also found that oligodendrocyte precursor cells, but not mature oligodendrocytes, express both TrkB.FL and TrkB.T in the adult brain. These results not only clarify the expression of BDNF and TrkB in glial cells, but also open opportunities to investigate previously unidentified roles of BDNF and TrkB in glial cells.
Totally tubular: ASO-mediated knock-down ofG2019S-Lrrk2 modulates lysosomal tubule-associated antigen presentation in macrophages
Authors: Wallings Rebecca L. , Mark Julian R. , Staley Hannah A. , Gillett Drew A. , Neighbarger Noelle , Kordasiewicz Holly , Hirst Warren D. , Tansey Malú Gámez 
Published: July 2023

AbstractGenetic variation around theLRRK2gene affects risk of both familial and sporadic Parkinson’s disease (PD). LRRK2 levels have become an appealing target for potential PD-therapeutics with LRRK2 antisense oligonucleotides (ASOs) now in clinical trials. However, LRRK2 has been suggested to play a fundamental role in peripheral immunity, and it is currently unknown if targeting increased LRRK2 levels in peripheral immune cells will be beneficial or deleterious. Furthermore, the precise role of LRRK2 in immune cells is currently unknown, although it has been suggested that LRRK2-mediated lysosomal function may be crucial to immune responses. Here, it was observed thatG2019Smacrophages exhibited increased stimulation-dependent lysosomal tubule formation (LTF) and MHC-II trafficking from the perinuclear lysosome to the plasma membrane in an mTOR dependent manner with concomitant increases in pro-inflammatory cytokine release. Both ASO-mediated knock down of mutantLrrk2 and LRRK2 kinase inhibition ameliorated this phenotype and decreased these immune responses in control cells. Given the critical role of antigen presentation, lysosomal function, and cytokine release in macrophages, it is likely LRRK2-targetting therapies may have therapeutic value with regards to mutantLRRK2but deleterious effects on the peripheral immune system, such as altered pathogen control and infection resolution.
From Pixels to Phenotypes: Integrating Image-Based Profiling with Cell Health Data Improves Interpretability
Authors: Seal Srijit , Carreras-Puigvert Jordi , Carpenter Anne E , Spjuth Ola , Bender Andreas 
Published: July 2023

SUMMARYCell Painting assays generate morphological profiles that are versatile descriptors of biological systems and have been used to predictin vitroandin vivodrug effects. However, Cell Painting features are based on image statistics, and are, therefore, often not readily biologically interpretable. In this study, we introduce an approach that maps specific Cell Painting features into the BioMorph space using readouts from comprehensive Cell Health assays. We validated that the resulting BioMorph space effectively connected compounds not only with the morphological features associated with their bioactivity but with deeper insights into phenotypic characteristics and cellular processes associated with the given bioactivity. The BioMorph space revealed the mechanism of action for individual compounds, including dual-acting compounds such as emetine, an inhibitor of both protein synthesis and DNA replication. In summary, BioMorph space offers a more biologically relevant way to interpret cell morphological features from the Cell Painting assays and to generate hypotheses for experimental validation.GRAPHICAL ABSTRACTIN BRIEFSeal et al. used machine learning models and feature selection approaches to group cell morphological features from Cell Painting assays and to describe the shared role of these morphological features in various cell health phenotypes. The resulting BioMorph space improves the ability to understand the mechanism of action and toxicity of compounds and to generate hypotheses to guide future experiments.HIGHLIGHTSCombining Cell Painting and Cell Health imaging data defines the BioMorph space.BioMorph space allows detecting less common mechanisms for bioactive compounds.BioMorph space can generate MOA hypotheses to guide experimental validation.BioMorph space is more biologically relevant and interpretable than Cell Painting features.
Integrative and comparative genomic analyses of mammalian macrophage responses to intracellular mycobacterial pathogens
Authors: Hall Thomas J. , McHugo Gillian P. , Mullen Michael P. , Ward James A. , Killick Kate E. , Browne John A. , Gordon Stephen V. , MacHugh David E. 
Published: July 2023

AbstractMycobacterium tuberculosis, the causative agent of human tuberculosis (hTB), is currently classed as the thirteenth leading cause of death worldwide.Mycobacterium bovis, a close evolutionary relative ofM. tuberculosis, causes bovine tuberculosis (bTB) and is one of the most damaging infectious diseases to livestock agriculture. Previous studies have shown that the pathogenesis of bTB disease is comparable to hTB disease, and that the bovine and human alveolar macrophage (bAM and hAM, respectively) transcriptomes are extensively reprogrammed in response to infection with these intracellular mycobacterial pathogens. However, althoughM. bovisandM. tuberculosisshare over 99% identity at the genome level, the innate immune responses to these pathogens have been shown to be different in human or cattle hosts.In this study, a multi-omics integrative approach was applied to encompass functional genomics and GWAS data sets across the two primary hosts (Bos taurusandHomo sapiens) and both pathogens (M. bovisandM. tuberculosis). Four different experimental infection groups were used, each with parallel non-infected control cells: 1) bAM infected withM. bovis, 2) bAM infected withM. tuberculosis, 3) hAM infected withM. tuberculosis, and 4) human monocyte-derived macrophages (hMDM) infected withM. tuberculosis. RNA-seq data from these experiments 24 hours post-infection (24 hpi) was analysed using three separate computational pipelines: 1) differentially expressed genes, 2) differential gene expression interaction networks, and 3) combined pathway analysis. The results of these analyses were then integrated with high-resolution bovine and human GWAS data sets to detect novel quantitative trait loci (QTLs) for resistance to mycobacterial infection and resilience to disease. Results from this study revealed common and unique response macrophage pathways for both pathogens and identified 32 genes (12 bovine and 20 human) significantly enriched for SNPs associated with disease resistance, the majority of which encode key components of the NF-κB signalling pathway and that also drive formation of the granuloma.
Co-adaptation improves performance in a dynamic human-machine interface
Authors: Yamagami Momona , Madduri Maneeshika M. , Chasnov Benjamin J. , Chou Amber H.Y. , Peterson Lauren N. , Burden Samuel A. 
Published: July 2023

AbstractDespite the growing prevalence of adaptive systems in daily life, methods for analysis and synthesis of these systems are limited. Here we find theoretical obstacles to creating optimization-based algorithms that co-adapt with people in the presence of dynamic machines. These theoretical limitations motivate us to conduct human subjects experiments with adaptive interfaces, where we find an interface that decreases human effort while improving closed-loop system performance during interaction with a machine that has complex dynamics. Finally, we conduct computational simulations and find a parsimonious model for the human’s adaptation strategy in our experiments, providing a hypothesis that can be tested in future studies. Our results highlight major gaps in understanding of co-adaptation in dynamic human-machine interfaces that warrant further investigation. New theory and algorithms are needed to ensure interfaces are safe, accessible, and useful.
Integrative epigenomic and functional characterization assay based annotation of regulatory activity across diverse human cell types
Authors: Dincer Tevfik Umut , Ernst Jason 
Published: July 2023

AbstractWe introduce ChromActivity, a computational framework for predicting and annotating regulatory activity across the genome through integration of multiple epigenomic maps and various functional characterization datasets. ChromActivity generates genomewide predictions of regulatory activity associated with each functional characterization dataset across many cell types based on available epigenomic data. It then for each cell type produces (1) ChromScoreHMM genome annotations based on the combinatorial and spatial patterns within these predictions and (2) ChromScore tracks of overall predicted regulatory activity. ChromActivity provides a resource for analyzing and interpreting the human regulatory genome across diverse cell types.
TriTan: An efficient triple non-negative matrix factorisation method for integrative analysis of single-cell multiomics data
Authors: Ma Xin , Lin Lijing , Zhao Qian , Iqbal Mudassar 
Published: July 2023

MotivationSingle-cell multi-omics have opened up tremendous opportunities for understanding gene regulatory networks underlying cell states by simultaneously profiling transcriptomes, epigenomes and proteomes of the same cell. However, existing computational methods for integrative analysis of these high-dimensional multi-modal data are either computationally expensive or limited in interpretation ans scope. These limitations pose challenges in the implementation of these methods in large-scale studies and hinder a more in-depth understanding of the underlying regulatory mechanisms.ResultsHere, we propose TriTan (Triple inTegrative fast non-negative matrix factorisation), an efficient joint factorisation method for single-cell multiomics data. TriTan implements a highly efficient triple non-negative matrix factorisation algorithm which greatly enhances its computational speed, and facilitates interpretation by clustering both the cells and features simultaneously as well as identifying signature feature sets for each cell cluster. Additionally, three matrix factorisation produced by TriTan helps in finding associations of features across modalities, facilitating the prediction of cell type specific regulatory networks. We applied TriTan to single-cell multi-modal data obtained from different technologies and benchmarked it against the state-of-the-art methods where it shows highly competitive performance. Furthermore, we showed a range of downstream analyses that can be conducted utilising the outputs from TriTan.Availabilityhttps://github.com/maxxxxxxxin/TriTanonline.
Rewiring the carbon cycle: a theoretical framework for animal-driven ecosystem carbon sequestration
Authors: Rizzuto Matteo , Leroux Shawn J. , Schmitz Oswald J. 
Published: July 2023

AbstractMost carbon cycle models do not consider animal-mediated effects, focusing instead on carbon exchanges among plants, microbes, and the atmosphere. Yet, a growing body of empirical evidence from diverse ecosystems points to pervasive animal effects on ecosystem carbon cycling and shows that ignoring them could lead to misrepresentation of an ecosystem’s carbon cycle. We develop a new theoretical framework to account for animal effects on ecosystem carbon cycling. We combine a classic ecosystem compartment modeling approach with a classic carbon model to account for carbon flux and storage among plant, animal, and soil microbial trophic compartments. We show, by way of numerical analyses of steady state conditions, that herbivore presence alters the dominant pathways of control over carbon storage and capture. This altered control arises via direct, consumptive effects and especially via indirect, non-consumptive pathways by instigating faster nutrient recycling. This leads to a quantitative change in the ecosystem’s carbon balance, increasing the amount of carbon captured and stored in the ecosystem by 2–3 fold. The modeling shows that animals could play a larger role in ecosystem carbon cycle than previously thought. Our framework provides further guidance for empirical research aimed at quantifying animal-mediated control of carbon cycling and to inform the development of nature-based climate change solutions that leverage animal influence on the carbon cycle to help mitigate climate change.
Tissue tension permits β-catenin phosphorylation to drive mesoderm specification in human embryonic stem cells
Authors: Ayad Nadia M.E. , Lakins Johnathon N. , Ghagre Ajinkya , Ehrlicher Allen J. , Weaver Valerie M. 
Published: July 2023

SummaryThe role of morphogenetic forces in cell fate specification is an area of intense interest. Our prior studies suggested that the development of high cell-cell tension in human embryonic stem cells (hESC) colonies permits the Src-mediated phosphorylation of junctional β-catenin that accelerates its release to potentiate Wnt-dependent signaling critical for initiating mesoderm specification. Using an ectopically expressed nonphosphorylatable mutant of β-catenin (Y654F), we now provide direct evidence that impeding tension-dependent Src-mediated β-catenin phosphorylation impedes the expression of Brachyury (T) and the epithelial-to-mesenchymal transition (EMT) necessary for mesoderm specification. Addition of exogenous Wnt3a or inhibiting GSK3β activity rescued mesoderm expression, emphasizing the importance of force dependent Wnt signaling in regulating mechanomorphogenesis. Our work provides a framework for understanding tension-dependent β-catenin/Wnt signaling in the self-organization of tissues during developmental processes including gastrulation.
Oral immunization with rVSV bivalent vaccine elicits protective immune responses, including ADCC, against both SARS-CoV-2 and Influenza A viruses
Authors: Ouyang Maggie Jing , Ao Zhujun , Olukitibi Titus A. , Lawrynuik Peter , Shieh Christopher , Kung Sam , Fowke Keith , Kobasa Darwyn , Yao Xiaojian 
Published: July 2023

AbstractCOVID-19 and influenza both cause enormous disease burdens, and vaccines are the primary measures for their control. Since these viral diseases are transmitted through the mucosal surface of the respiratory tract, developing an effective and convenient mucosal vaccine should be a high priority. We previously reported a recombinant vesicular stomatitis virus (rVSV)-based bivalent vaccine (v-EM2/SPΔC1Delta) that protects animals from both SARS-CoV-2 and influenza viruses via intramuscular and intranasal immunization. Here, we further investigated the immune response induced by oral immunization with this vaccine and its protective efficacy in mice. The results demonstrated that the oral cavity delivery, like the intranasal route, elicited strong and protective systemic immune responses against SARS-CoV-2 and influenza A virus. This included high levels of neutralizing antibodies (NAbs) against SARS-CoV-2, as well as strong anti-SARS-CoV-2 spike protein (SP) antibody-dependent cellular cytotoxicity (ADCC) and anti-influenza M2 ADCC responses in mice sera. Furthermore, it provided efficient protection against challenge with influenza H1N1 virus in a mouse model, with a 100% survival rate and a significant low lung viral load of influenza virus. All these findings provide substantial evidence for the effectiveness of oral immunization with the rVSV bivalent vaccine.
Absence of SARS-CoV-2 in Wildlife of Northeastern Minnesota and Isle Royale National Park
Authors: Castañeda David , Isaac Edmund J. , Kautz Todd , Romanski Mark C. , Moore Seth A. , Aliota Matthew T. 
Published: July 2023

AbstractWe investigated the presence of SARS-CoV-2 in free-ranging wildlife populations in Northeastern Minnesota on the Grand Portage Indian Reservation and Isle Royale National Park. 120 nasal samples were collected from white-tailed deer, moose, gray wolves, and black bears monitored for conservation efforts during 2022-2023. Samples were tested for viral RNA by RT-qPCR using the CDC N1/N2 primer set. Our data indicate that no wildlife samples were positive for SARS-CoV-2 RNA. Continued surveillance is therefore crucial to better understand the changing landscape of zoonotic SARS-CoV-2 in the Upper Midwest.
Crystal Structure of the 4-Hydroxybutyryl-CoA Synthetase (ADP-forming) from Nitrosopumilus maritimus
Authors: Johnson Jerome , Tolar Bradley B. , Tosun Bilge , Yoshikuni Yasuo , Francis Christopher A. , Wakatsuki Soichi , DeMirci Hasan 
Published: July 2023

AbstractThe 3-hydroxypropionate/4-hydroxybutyrate (3HP/4HB) cycle from ammonia-oxidizing Thaumarchaeota is currently considered the most energy-efficient aerobic carbon fixation pathway. TheNitrosopumilus maritimus4-hydroxybutyryl-CoA synthetase (ADP-forming; Nmar_0206) represents one of several enzymes from this cycle that exhibit increased efficiency over crenarchaeal counterparts. This enzyme reduces energy requirements on the cell, reflecting thaumarchaeal success in adapting to low-nutrient environments. Here we show the structure of Nmar_0206 fromNitrosopumilus maritimusSCM1, which reveals a highly conserved interdomain linker loop between the CoA-binding and ATP-grasp domains. Phylogenetic analysis suggests the widespread prevalence of this loop and highlights both its underrepresentation within the PDB and structural importance within the (ATP-forming) acyl- CoA synthetase (ACD) superfamily. This linker is shown to have a possible influence on conserved interface interactions between domains, thereby influencing homodimer stability. These results provide a structural basis for the energy efficiency of this key enzyme in the modified 3HP/4HB cycle of Thaumarchaeota.