bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cervical Spinal Cord Injury Leads to Injury and Metabolic Dysfunction of the Lung
Authors: Huffman Emily E. , Dong Brittany E. , Clarke Harrison A. , Young Lyndsay E.A. , Allison Derek B. , Sun Ramon C. , Waters Christopher M. , Alilain Warren J. 
Published: August 2021

AbstractHigh-cervical spinal cord injury (SCI) often disrupts respiratory motor pathways and disables breathing in the affected population. Moreover, cervically injured individuals are at risk for developing acute lung injury (ALI), which predicts substantial mortality rates. While the correlation between ALI and SCI has been found in the clinical setting, the field lacks an animal model to interrogate the fundamental biology of this relationship. To begin to address this gap, we performed an experimental cervical SCI and assessed lung injury in adult rats. We demonstrate that animals display signs of ALI two weeks post-SCI. We also observed aberrant N-glycan metabolism determined by matrix-assisted laser desorption/ionization mass spectrometry imaging. Collectively, we establish for the first time a model of ALI after SCI at an acute time point that can be used to monitor the progression of lung damage, as well as identify potential targets to ameliorate ALI.
Toxoplasmainfection alters dopamine-sensitive behaviors and host gene expression patterns associated with neuropsychiatric disease
Authors: Cromar Graham L. , Epp Jonathan , Popovic Ana , Gu Yusing , Ha Violet , Walters Brandon , St. Pierre James , Xiong Xuejian , Howland John , Josselyn Sheena , Parkinson John , Frankland Paul W. 
Published: August 2021

ABSTRACTToxoplasma gondiiis a single celled parasite thought to infect 1 in 3 worldwide. During chronic infection,T. gondiican migrate to the brain where it promotes low-grade neuroinflammation with the capacity to induce changes in brain morphology and behavior. Consequently, infection withT. gondiihas been linked with a number of neurocognitive disorders including schizophrenia (SZ), dementia, and Parkinson’s disease. Beyond neuroinflammation, infection withT. gondiican modulate the production of neurotransmitters, such as dopamine. To further dissect these pathways and examine the impact of altered dopaminergic sensitivity inT. gondii-infected mice on both behavior and gene expression, we developed a novel mouse model, based on stimulant-induced (cocaine) hyperactivity. Employing this model, we found that infection withT. gondiidid not alter fear behavior but did impact motor activity and neuropsychiatric-related behaviurs. While both behaviors may help reduce predator avoidance, consistent with previous studies, the latter finding is reminiscent of neurocognitive disorders. Applying RNASeq to two relevant brain regions, striatum and hippocampus, we identified a broad upregulation of immune responses. However, we also noted significant associations with more meaningful neurologically relevant terms were masked due to the sheer number of terms incorporated in multiple testing correction. We therefore performed a more focused analysis using a curated set of neurologically relevant terms revealing significant associations across multiple pathways. We also found thatT. gondiiand cocaine treatments impacted the expression of similar functional pathways in the hippocampus and striatum although, as indicated by the low overlap among differentially expressed genes, largely via different proteins. Furthermore, while most differentially expressed genes reacted to a single condition and were mostly upregulated, we identified gene expression patterns indicating unexpected interactions betweenT. gondiiinfection and cocaine exposure. These include sets of genes which responded to cocaine exposure but not upon cocaine exposure in the context ofT. gondiiinfection, suggestive of a neuroprotective effect advantageous to parasite persistence. Given its ability to uncover such complex relationships, we propose this novel model offers a new perspective to dissect the molecular pathways by whichT. gondiiinfection contributes to neuropsychiatric disorders such as schizophrenia.
C2cd6-encoded CatSperτ Targets Sperm Calcium Channel to Ca2+Signaling Domains in the Flagellar Membrane
Authors: Hwang Jae Yeon , Wang Huafeng , Lu Yonggang , Ikawa Masahito , Chung Jean-Ju 
Published: August 2021

SUMMARYIn mammalian sperm cells, regulation of spatiotemporal Ca2+signaling relies on the quadrilinear Ca2+signaling nanodomains in the flagellar membrane. The sperm-specific, multi-subunit CatSper Ca2+channel, which is crucial for sperm hyperactivated motility and male fertility, organizes the nanodomains. Here, we report CatSperτ, theC2cd6-encoded membrane-associating C2 domain protein, can independently migrate to the flagella and serve as a major targeting component of the CatSper channel complex. CatSperτ loss-of-function in mice demonstrates that it is essential for sperm hyperactivated motility and male fertility. CatSperτ targets the CatSper channel into the quadrilinear nanodomains in the flagella of developing spermatids, whereas it is dispensable for functional channel assembly. CatSperτ interacts with ciliary trafficking machinery in a C2-dependent manner. These findings provide insights into the CatSper channel trafficking to the Ca2+signaling nanodomains and the shared molecular mechanisms of ciliary and flagellar membrane targeting.HighlightsCatSperτ encoded byC2cd6is a C2 membrane-associating domain containing proteinCatSperτ loss-of-function impairs sperm hyperactivation and male fertilityCatSperτ adopts ciliary trafficking machineries for flagellar targeting via C2 domainCatSperτ targets the CatSper channel into nanodomains of developing sperm flagella
HAM-ART: An optimised culture-free Hi-C metagenomics pipeline for tracking antimicrobial resistance genes in complex microbial communities
Authors: Kalmar Lajos , Gupta Srishti , Kean Iain R. L. , Ba Xiaoliang , Hadjirin Nazreen , Lay Elizabeth , de Vries Stefan P.W. , Bateman Michael , Bartlett Harriett , Hernandez-Garcia Juan , Tucker Alexander W. , Restiff Olivier , Stevens Mark P , Wood James , Maskell Duncan J , Grant Andrew J , Holmes Mark A 
Published: August 2021

AbstractShotgun metagenomics is a powerful tool to identify antimicrobial resistance (AMR) genes in microbiomes but has the limitation that extrachromosomal DNA, such as plasmids, cannot be linked with the host bacterial chromosome. Here we present a laboratory and bioinformatics pipeline HAM-ART (Hi-C Assisted Metagenomics for Antimicrobial Resistance Tracking) optimised for the generation of metagenome-assembled genomes including both chromosomal and extrachromosomal AMR genes. We demonstrate the performance of the pipeline in a study comparing 100 pig faecal microbiomes from low- and high-antimicrobial use pig farms (organic and conventional farms). We found significant differences in the distribution of AMR genes between low- and high-antimicrobial use farms including a plasmid-borne lincosamide resistance gene exclusive to high-antimicrobial use farms in three species of Lactobacilli.Author SummaryAntimicrobial resistance (AMR) is one of the biggest global health threats humanity is facing. Understanding the emergence and spread of AMR between different bacterial species is crucial for the development of effective countermeasures. In this paper we describe a user-friendly, affordable and comprehensive (laboratory and bioinformatics) workflow that is able to identify, associate and track AMR genes in bacteria. We demonstrate the efficiency and reliability of the method by comparing 50 faecal microbiomes from pig farms with high-antibiotic use (conventional farms), and 50 faecal microbiomes from pig farms with low-antibiotic use (organic farms). Our method provides a novel approach to resistance gene tracking, that also leads to the generation of high quality metagenomic assembled genomes that includes genes on mobile genetic elements, such as plasmids, that would not otherwise be included in these assembled genomes.
In vitro coinfection by influenza A virus and respiratory syncytial virus generates hybrid viral particles with altered structure and tropism
Authors: Haney Joanne , Vijayakrishnan Swetha , Streetley James , Dee Kieran , Goldfarb Daniel Max , Clarke Mairi , Mullin Margaret , Carter Stephen D , Bhella David , Murcia Pablo R 
Published: August 2021

AbstractInteractions between respiratory viruses impact viral transmission dynamics and clinical outcomes. To identify and characterize virus-virus interactions at the cellular level, we coinfected human lung cells with influenza A virus (IAV) and respiratory syncytial virus (RSV). Super-resolution microscopy, live-cell imaging, scanning electron microscopy, and cryo-electron tomography revealed extracellular and membrane-associated filamentous structures consistent with hybrid viral particles (HVPs). We show that HVPs harbor surface glycoproteins and ribonucleoproteins of IAV and RSV, and use the RSV fusion glycoprotein to evade anti-IAV neutralising antibodies and to infect and spread among cells lacking IAV receptors. Finally, we show evidence of IAV and RSV coinfection within cells of the bronchial epithelium, with viral proteins from both viruses co-localising at the apical surface. Our observations have profound implications for infection biology as they define a previously unknown interaction between respiratory viruses that might affect virus pathogenesis by expanding virus tropism and facilitating immune evasion.
Haploinsufficiency of the mouse Tshz3 gene leads to kidney dysfunction
Authors: Sanchez-Martin Irene , Magalhães Pedro , Fatmi Ahmed , Richard Fabrice , Vu Manh Thien Phong , Saurin Andy , Feuillet Guylène , Denis Colette , Schanstra Joost P. , Zürbig Petra , Caubit Xavier , Fasano Laurent 
Published: August 2021

AbstractRenal tract defects and autism spectrum disorder (ASD) deficits represent the phenotypic core of the 19q12 deletion syndrome caused by the loss of one copy of the TSHZ3 gene. While a proportion of Tshz3 heterozygous (Tshz3+/lacZ) mice display ureteral defects, no kidney defects have been reported in these mice. The purpose of this study was to characterize the expression of Tshz3 in adult kidney as well as the renal physiological consequences of embryonic haploinsufficiency of Tshz3 by analyzing the morphology and function of Tshz3 heterozygous adult kidney. Here, we described Tshz3 expression in the smooth muscle and stromal cells lining the renal pelvis, the papilla and glomerular endothelial cells (GEnCs) of the adult kidney. Histological analysis showed that Tshz3+/lacZ adult kidney had an average of 29% fewer glomeruli than wild type kidney. Transmission electron microscopy (TEM) of Tshz3+/lacZ glomeruli revealed ultrastructural defects. Compared to wild type, Tshz3+/lacZ mice showed no difference in their urine parameters but lower blood urea, phosphates, magnesium and potassium at 2 months of age. At the molecular level, transcriptome analysis identified differentially expressed genes related to inflammatory processes in Tshz3+/lacZ compare to wild type (WT; control) adult kidneys. Lastly, analysis of the urinary peptidome revealed 33 peptides associated with Tshz3+/lacZ adult mice. These results provide the first evidence that in the mouse Tshz3 haploinsufficiency leads to cellular, molecular and functional abnormalities in the adult mouse kidney.
Functional Connectivity of the World’s Protected Areas
Authors: Brennan A. , Naidoo R. , Greenstreet L. , Mehrabi Z. , Ramankutty N. , Kremen C. 
Published: August 2021

AbstractRapid environmental change threatens to isolate the world’s wildlife populations and intensify biodiversity loss. Global policies have called for expanding and connecting the world’s protected areas (PAs) to curtail the crisis, yet how well PA networks currently support wildlife movement, and where connectivity conservation or restoration is most critical, have never been mapped globally. Here, we map the functional connectivity (how animals move through landscapes) of the world’s terrestrial PAs for the first time. Also, going beyond existing global connectivity indices, we quantify national PA-connectedness using an approach that meaningfully represents animal movement through anthropogenic landscapes. We find that reducing the human footprint may improve national PA-connectivity more than adding new PAs; however, both strategies are critical for improving and preserving connectivity in places where the predicted flow of animal movement is highly concentrated. We show that the majority of critical connectivity areas (CCAs) (defined as globally important areas of concentrated animal movements) remain unprotected. Of these, 72% overlap with previously-identified global conservation priority areas, while 3% of CCAs occur within moderate to heavily modified lands. Conservation and restoration of CCAs could safeguard connectivity of the world’s PAs, and dovetail with previously identified global conservation priorities.
Columnar localization and laminar origin of cortical surface electrical potentials
Authors: Baratham Vyassa L. , Dougherty Maximilian E. , Ledochowitsch Peter , Maharbiz Michel M. , Bouchard Kristofer E. 
Published: August 2021

AbstractElectrocorticography (ECoG) methodologically bridges basic neuroscience and understanding of human brains in health and disease. However, the localization of ECoG signals across the surface of the brain and the spatial distribution of their generating neuronal sources are poorly understood. To address this gap, we recorded from rat auditory cortex using customized μECoG, and simulated cortical surface electrical potentials with a full-scale, biophysically detailed cortical column model. Experimentally, μECoG-derived auditory representations were tonotopically organized and signals were anisotropically localized to ≤±200 μm, i.e., a single cortical column. Biophysical simulations reproduce experimental findings, and indicate that neurons in cortical layers V and VI contribute ∼85% of evoked high-gamma signal recorded at the surface. Cell number and synchronicity were the primary biophysical properties determining laminar contributions to evoked μECoG signals, while distance was only a minimal factor. Thus, evoked μECoG signals primarily originate from neurons in the infragranular layers of a single cortical column.In BriefBaratham et al., investigated the localization and origins of sensory evoked ECoG responses. They experimentally found that ECoG responses were anisotropically localized ≤±200 μm, i.e., a single cortical column. Biophysically detailed simulations revealed that neurons in layers V &VI were the primary sources of evoked ECoG responses, in contrast to common thinking.HighlightsEvoked μECoG signals are localized on the surface to a cortical column.Neurons in cortical layers V and VI constitute the vast majority of the signal recorded at the surface.Different laminar contributions to ECoG signal are driven by cell density and synchronicity.
Third-order motifs are sufficient to fully and uniquely characterize spatiotemporal neural network activity
Authors: Deshpande Sarita S. , Smith Graham A. , van Drongelen Wim 
Published: August 2021

AbstractNeuroscientific analyses balance between capturing the brain’s complexity and expressing that complexity in meaningful and understandable ways. Here we present a novel approach that fully characterizes neural network activity and does so by uniquely transforming raw signals into easily interpretable and biologically relevant metrics of network behavior. We first prove that third-order, or triple, correlation describes network activity in its entirety using the triple correlation uniqueness (TCU) theorem. Triple correlation quantifies the relationships among three events separated by spatial and temporal lags, which are triplet motifs. Classifying these motifs by their event sequencing leads to fourteen qualitatively distinct motif classes that embody well-studied network behaviors such as synchrony, feedback, feedforward, convergence, and divergence. Within these motif classes, the summed triple correlations provide novel metrics of network behavior, as well as being inclusive of commonly used analyses. We demonstrate the power of this approach on a range of networks with increasingly obscured signals, from ideal noiseless simulations to noisy experimental data. This approach can be easily applied to any recording modality, so existing neural datasets are ripe for reanalysis. Triple correlation is an accessible signal processing tool with a solid theoretical foundation capable of revealing previously elusive information within recordings of neural networks.
Fission and PINK-1-mediated mitophagy are required for Insulin/IGF-1 signaling mutant reproductive longevity
Authors: Cota Vanessa , Murphy Coleen T. 
Published: August 2021

AbstractWomen’s reproductive cessation is the earliest sign of human aging and is caused by decreasing oocyte quality. Similarly, C. elegans’ reproduction declines with age and is caused by oocyte quality decline. Aberrant mitochondrial dynamics are a hallmark of age-related dysfunction, but the role of mitochondrial morphology in reproductive aging is largely unknown. We examined the requirements for mitochondrial fusion and fission in oocytes of both wild-type worms and the long-lived, long-reproducing insulin-like receptor mutant daf-2. We find that normal reproduction requires both fusion and fission. By contrast, daf-2 mutants require fission, but not fusion, for reproductive span extension. daf-2 mutant oocytes’ mitochondria are punctate (fissioned) and may be primed for mitophagy, as loss of the mitophagy regulator PINK-1 shortens daf-2’s reproductive span. Our data suggest that daf-2 maintain oocyte mitochondria quality with age via a shift toward punctate mitochondrial morphology and mitophagy to extend reproductive longevity.
DeepANIS: Predicting antibody paratope from concatenated CDR sequences by integrating bidirectional long-short-term memory and transformer neural networks
Authors: Zhang Pan , Zheng Shuangjia , Chen Jianwen , Zhou Yaoqi , Yang Yuedong 
Published: August 2021

AbstractMotivationAntibodies are a type of important biomolecules in the humoral immunity system, which can bind tightly to potential antigens with high affinity and specificity. An accurate identification of the paratope, the binding sites with antigens, is crucial for antibody mechanistic research and design. Although many methods have been developed for paratope prediction, further improvement of their accuracy is necessary.ResultsIn this study, we concatenated the sequences of Complementarity Determining Regions (CDRs) within a single antibody to better capture nonlocal interactions between different CDRs and loop type-specific features for improving paratope prediction. We further integrated BiLSTM and transformer networks to gain the dependencies among the residues within the concatenated CDR sequences and to increase the interpretability of the model. The new method called DeepANIS (Antibody Interacting Site prediction) outperforms other antibody paratope prediction methods compared.AvailabilityThe DeepANIS method is freely available as a webserver at https://biomed.nscc-gz.cn:9094/apps/DeepANIS and for download at https://github.com/HideInDust/DeepANISContactyangyd25@mail.sysu.edu.cn or zhouyq@szbl.ac.cnSupplementary informationSupplementary data are available at Bioinformatics online.
Comprehensive species sampling and sophisticated algorithmic approaches refute the monophyly of Arachnida
Authors: Ballesteros Jesús A. , Santibáñez-López Carlos E. , Baker Caitlin M. , Benavides Ligia R. , Cunha Tauana J. , Gainett Guilherme , Ontano Andrew Z. , Setton Emily V.W. , Arango Claudia P. , Gavish-Regev Efrat , Harvey Mark S. , Wheeler Ward C. , Hormiga Gustavo , Giribet Gonzalo , Sharma Prashant P. 
Published: August 2021

AbstractDeciphering the evolutionary relationships of Chelicerata (arachnids, horseshoe crabs, and allied taxa) has proven notoriously difficult, due to their ancient rapid radiation and the incidence of elevated evolutionary rates in several lineages. While conflicting hypotheses prevail in morphological and molecular datasets alike, the monophyly of Arachnida is nearly universally accepted. Though a small number of phylotranscriptomic analyses have recovered arachnid monophyly, these did not sample all living chelicerate orders. We generated a dataset of 506 high-quality genomes and transcriptomes, sampling all living orders of Chelicerata with high occupancy and rigorous approaches to orthology inference. Our analyses consistently recovered the nested placement of horseshoe crabs within a paraphyletic Arachnida. This result was insensitive to variation in evolutionary rates of genes, complexity of the substitution models, and alternatives algorithmic approaches to species tree inference. Investigation of systematic bias showed that genes and sites that recover arachnid monophyly are enriched in noise and exhibit low information content. To test the effect of morphological data, we generated a 514-taxon morphological data matrix of extant and fossil Chelicerata, analyzed in tandem with the molecular matrix. Combined analyses recovered the clade Merostomata (the marine orders Xiphosura, Eurypterida, and Chasmataspidida), but nested within Arachnida. Our results suggest that morphological convergence resulting from adaptations to life in terrestrial habitats has driven the historical perception of arachnid monophyly, paralleling the history of numerous other invertebrate terrestrial groups.
Collective computation and the emergence of hunter-gatherer small-worlds
Authors: Hamilton Marcus J. 
Published: August 2021

AbstractTwo defining features of human sociality are large brains with neurally-dense cerebral cortices and the propensity to form complex social networks with non-kin. Large brains and the social networks in which they are embedded facilitate flows of fitness-enhancing information at multiple scales, but are also energetically expensive. In this paper, we consider how flows of energy and information interact to shape the macroscopic features of hunter-gatherer socioecology. Collective computation is the processing of information by complex adaptive systems to generate inferences in order to solve adaptive problems. In hunter-gatherer societies the adaptive problem is how to maximize fitness by optimizing information processing given the energy constraints of complex environments. The solution is the emergent macroscopic structure of the socioecology. Here we show how computation is extended across social networks to form the decentralized knowledge systems characteristic of hunter-gatherer societies. Data show that hunter-gatherer bands of co-residing families constitute computationally powerful networks that are embedded within hierarchically modular social networks that form complex metapopulations bound by fission-fusion dynamics at multiple scales facilitating the flow of information far beyond local interactions. These dynamics lead to the emergence of hunter-gatherer small-worlds where highly clustered local interactions are embedded within much larger, but sparsely connected metapopulations. Hunter-gatherers optimize local energy budgets in small groups but maintain interactions with much larger social networks while avoiding many of the ecological costs.