bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spontaneous enteric nervous system activity precedes maturation of gastrointestinal motility
Authors: Dershowitz Lori B. , Garcia Hassler Bueno , Perley Andrew S. , Coleman Todd P. , Kaltschmidt Julia A. 
Published: August 2023

AbstractSpontaneous neuronal network activity is essential in development of central and peripheral circuits, yet whether this is a feature of enteric nervous system development has yet to be established. Usingex vivogastrointestinal (GI) motility assays with unbiased computational analyses, we identify a previously unknown pattern of spontaneous neurogenic GI motility. We further show that this motility is driven by cholinergic signaling, which may inform GI pharmacology for preterm patients.
Decision-related activity and movement selection in primate visual cortex
Authors: Laamerad Pooya , Liu Liu D. , Pack Christopher C. 
Published: August 2023

AbstractFluctuations in the activity of sensory neurons often predict perceptual decisions. This connection can be quantified with a metric called choice probability (CP), and there has been a longstanding debate about whether CP reflects a causal influence on decisions, or an echo of decision-making activity elsewhere in the brain. Here we show that CP can actually reflect a third variable, namely the movement used to indicate the decision. In a standard visual motion discrimination task, neurons in the middle temporal (MT) area of the primate visual cortex responded more strongly during trials in which the animals executed a saccade toward their receptive fields, and less strongly for saccades directed away from the receptive fields. The resulting trial-to-trial variability accounted for much of the CP observed across the neuronal population, and it arose through training. Surprisingly, the learned association between MT activity and oculomotor selection was causal, as pharmacological inactivation of MT neurons biased behavioral responses away from the corresponding receptive field locations. These results demonstrate that training on a task with fixed sensorimotor contingencies introduces movement-related activity in sensory brain regions, and that this plasticity can shape the neural circuitry of perceptual decision-making.
Comparative study of thermal tolerance and other physiological characteristics inC. briggsaeandC. elegans
Authors: Jhaveri Nikita , Bhullar Harvir , Gupta Bhagwati P. 
Published: August 2023

ABSTRACTThe nematodeCaenorhabditis briggsae(C. briggsae) is routinely used in genetic and evolutionary studies involving its well-known cousin,C. elegans. The two species are morphologically almost identical but exhibit significant developmental, genetic, and genomic differences. The AF16 isolate ofC. briggsaeis an established reference strain. We used additional wild isolates from tropical and temperate regions to perform a comparative study of phenotypic characters. The analysis revealed both intra (betweenC. briggsaeisolates) and inter (compared toC. elegansN2) species variability in dimensions and opacity. Our data also showed thatC. briggsaeisolates prefer higher temperatures for growth, reproduction, and survival thanC. elegansN2. The preference for higher temperatures further translated into a higher tolerance for heat stress, as evidenced by its survival at temperatures lethal to N2. Interestingly, we found that whileC. briggsaeis more resistant to heat and shows greater sensitivity to other forms of stress, namely oxidative and osmotic, compared toC. elegans. The heat resistance ofC. briggsaewas correlated with efficient upregulation of the cytosolic chaperonhsp-16.2. Overall, this work has revealed significant differences in stress sensitivities between the two nematodes and forms the basis to investigate changes in underlying mechanisms that affect their stress responses.
Impacts of early exposure to ethanol on adenosine functioning in zebrafish
Authors: Couto Giovanna Trevisan , da Silva Guilherme Pietro , Rockenbach Liliana , da Silva Jéssica Scheid , Roca Vianna Monica Ryff Moreira , Da Silva Rosane Souza 
Published: August 2023

AbstractExposure to ethanol at the beginning of development can impact the formation of the Nervous System. The set of symptoms resulting from ethanol consumption during pregnancy is called FASD (Fetal Alcohol Spectrum Disorders) and ranges from cognitive alterations to the most severe form called FAS (Fetal Alcohol Syndrome). The effect caused by ethanol on the formation of brain architecture directly affects the adenosine neuromodulation system. In this work, a single exposure regimen of 24 to 26 hpf to 1% ethanol transdermally was used as a model to assess adenosine signaling in the context of seizure susceptibility in zebrafish larvae and adults. To test sensitivity, a 2.5 mM subconvulsant dose of pentylenetetrazole (PTZ) was used, which was not able to increase seizure events in larvae or adults exposed to ethanol during embryonic phase. However, the duration of stage I was increased and the latency to reach stage II was decreased in larvae, showing a possible proconvulsant profile in these ethanol-treated animals. Also, the exposure of larvae to CPA (75 μM) was able to reverse the effect of embryonic ethanol treatment on the latency to reach stage II of seizure. Adenosine and ecto-5’-nucleotidase receptor mRNA expression did not show significant difference in both developmental stages. These results demonstrated that even a short and specific exposure to ethanol can promote, even if mild, effects on neuronal modulation, increasing susceptibility to seizures.
Extensive rewiring of the gene regulatory interactions between in vitro-produced conceptuses and endometrium during attachment
Authors: Biase Fernando H. , Moorey Sarah E. , Schnuelle Julie G. , Rodning Soren , Ortega Marta Sofia , Spencer Thomas E. 
Published: August 2023

ABSTRACTPregnancy loss is a significant problem when embryos producedin vitroare transferred to a synchronized uterus. Currently, mechanisms that underlie losses ofin vitro-producedembryos during implantation are largely unknown. We investigated this problem using cattle as a model of conceptus attachment by analyzing transcriptome data of paired extraembryonic membrane and endometrial samples collected on gestation days 18 and 25, which spans the attachment window in cattle. We identified that the transfer of anin vitro-producedembryo caused a significant alteration in transcript abundance of hundreds of genes in extraembryonic and endometrial tissues on gestation days 18 and 25, when compared to pregnancies initiated by artificial insemination. Many of the genes with altered transcript abundance are associated with biological processes that are relevant to the establishment of pregnancy. An integrative analysis of transcriptome data from the conceptus and endometrium identified hundreds of putative ligand-receptor pairs. There was a limited variation of ligand-receptor pairs in pregnancies initiated byin vitro-producedembryos on gestation day 18, and no alteration was observed on gestation day 25. In parallel, we identified thatin vitroproduction of embryos caused an extensive alteration in the co-expression of genes expressed in the extraembryonic membranes and the corresponding endometrium on both gestation days. Both the transcriptional dysregulation that exists in the conceptus or endometrium independently, and the rewiring of gene transcription between the conceptus and endometrium are a potential component of the mechanisms that contribute to pregnancy losses caused by in vitro production of embryos.SIGNIFICANCE STATEMENTThe successful establishment of pregnancies following the transfer of anin vitroproduced embryo is essential for cattle production and assisted human reproduction. Most of the pregnancies initiated by the transfer of anin vitroproduced embryo fail, in part because of dysfunctional interaction between the embryo and endometrium during pregnancy establishment. Our study identified that conceptuses producedin vitroand their corresponding endometrium have massive dysregulation in gene activity during the peri-implantation window, which affects crucial biological functions necessary for pregnancy. These gene expression alterations are a major contributor to the high rates of pregnancy loss following the transfer of anin vitroproduced embryo. Our findings have implications for improving assisted reproduction in both agriculture and biomedicine.
Non-target Analysis of Wastewater Treatment Plant Effluents: Chemical Fingerprinting as a Monitoring Tool
Authors: Aggerbeck Marie Rønne , Frøkjær Emil Egede , Johansen Anders , Ellegaard-Jensen Lea , Hansen Lars Hestbjerg , Hansen Martin 
Published: August 2023

AbstractThis study aims at discovering and characterizing the plethora of xenobiotic substances released into the environment with wastewater effluents. We present a novel non-targeted screening methodology based on ultra-high resolution Orbitrap mass spectrometry and nanoflow ultra-high performance liquid chromatography together with a new data-processing pipeline. This approach was applied to effluent samples from two state-of-the-art urban, and one small rural wastewater treatment facility. In total, 785 structures were obtained, of these 38 were identified as single compounds, while 480 structures were identified at a putative level. The vast majority of these were therapeutics and drugs, present as parent compounds and metabolites. Using the R packages Phyloseq and MetacodeR, we here present a novel way of visualizing LCMS data while showing significant difference in xenobiotic presence in the wastewater effluents between the three sites.1.SignificanceWe characterized a wide spectrum of xenobiotic substances using ultra-high performance liquid chromatography, and analysed the data with a new data-processing pipeline using microbial ecological tools to visualize and perform statistical testing of the chemical data to reveal trends in compound composition at the three WWTPs. This approach was applied to obtain and analyse data from effluent samples collected at three wastewater treatment facilities. In total, 785 chemical structures were achieved, with a majority identified as therapeutics and drugs. Several of the compounds are suspected endocrine disruptors. The data reveal a significant difference in compound diversity persisting in the wastewater effluents at the three sites. Our findings reveal the presence of undesirable compounds in effluent released into waterways, and address the greatest challenge in environmental chemistry – pinpointing single compounds of interest from masses of data produced.
Investigating the phylogenetic history of toxin tolerance in mushroom-feedingDrosophila
Authors: Erlenbach Theresa , Haynes Lauren , Fish Olivia , Beveridge Jordan , Bingolo Eunice , Giambrone Sarah-Ashley , Kropelin Grace , Rudisill Stephanie , Chialvo Pablo , Reed Laura K. , Dyer Kelly A. , Chialvo Clare Scott 
Published: August 2023

AbstractUnderstanding how and when key novel adaptations evolved is a central goal of evolutionary biology. Within theimmigrans-tripunctataradiation ofDrosophila, many mushroom-feeding species are tolerant of host toxins, such as cyclopeptides, that are lethal to nearly all other eukaryotes. In this study, we used phylogenetic and functional approaches to investigate the evolution of cyclopeptide tolerance in theimmigrans-tripunctataradiation ofDrosophila. We first inferred the evolutionary relationships among 48 species in this radiation using 978 single copy orthologs. Our results resolved previous incongruities within species groups across the phylogeny. Second, we expanded on previous studies of toxin tolerance by assaying 16 of these species for tolerance to α-amanitin and found that six of these species could develop on diet with toxin. Third, we examined fly development on a diet containing a natural mix of toxins extracted from the Death CapAmanita phalloidesmushroom. Both tolerant and susceptible species developed on diet with this mix, though tolerant species survived at significantly higher concentrations. Finally, we asked how cyclopeptide tolerance might have evolved across theimmigrans-tripunctataradiation and inferred that toxin tolerance was ancestral and subsequently lost multiple times. Our results suggest the evolutionary history of cyclopeptide tolerance is complex, and simply describing this trait as present or absent does not fully capture the occurrence or impact on this adaptive radiation. More broadly, the evolution of novelty can be more complex than previously thought, and that accurate descriptions of such novelties are critical in studies examining their evolution.
Functional dissection of KATP channel structures reveals the importance of a conserved interface
Authors: Yang Yaxiong , Chen Lei 
Published: August 2023

AbstractATP-sensitive potassium channels (KATP) are inhibited by ATP but activated by Mg-ADP, coupling the intracellular ATP/ADP ratio to the potassium conductance of the plasma membrane. Although there has been progress in determining the structure of KATP channels, the functional significance of the domain-domain interface in the gating properties of KATP channels is not fully understood. In this study, we propose a new two-module assembly model for the KATP channel. Our mutagenesis experiments, based on this model, indicate that deleting ECL3 on the SUR1 subunit impairs KNtp-independent Mg-ADP activation. This finding demonstrates the essential role of intramolecular interactions between KATPcoreand SURABCin Mg-ADP activation. Notably, this interface is functionally conserved between SUR1 and SUR2. Additionally, the hydrophobic residue F351 on ECL3 of SUR1 is crucial for maintaining the stability of this interface.
RPRM as a potential preventive and therapeutic target for radiation-induced brain injury via multiple mechanisms
Authors: Ye Zhujing , Wang Jin , Shi Wenyu , Zhou Zhou , Zhang Yarui , Wang Jingdong , Yang Hongying 
Published: August 2023

AbstractPatients receiving cranial radiotherapy for primary and metastatic brain tumors may experience radiation-induced brain injury (RIBI). So far there is a lack of effective preventive and therapeutic strategies for RIBI. Due to its complicated underlying pathogenic mechanisms, it is rather difficult to develop a single approach to target them simultaneously. We have recently reported that Reprimo (RPRM), a tumor suppressor gene, is a critical player in DNA damage repair, and RPRM deletion significantly confers radioresistance to mice. Here in this study, by using RPRM knockout (KO) mouse model established in our laboratory, we found that RPRM deletion alleviated RIBI in mice via targeting its multiple underlying mechanisms. Specifically, RPRM knockout significantly reduced hippocampal DNA damage and apoptosis shortly after mice were exposed to whole brain irradiation (WBI). For the late-delayed effect of WBI, RPRM knockout obviously ameliorated radiation-induced decline in neurocognitive function and dramatically diminished WBI-induced neurogenesis inhibition. Moreover, RPRM KO mice exhibited a significantly lower level of acute and chronic inflammation response and microglial activation than wild type (WT) mice did post WBI. Finally, we uncovered that RPRM knockout not only protected microglia against radiation-induced damage, thus prevented microglial activation, but also protected neurons and decreased the induction of CCL2 in neurons after irradiation, in turn attenuating the activation of microglial cells nearby through paracrine CCL2. Taken together, Our results indicate that RPRM plays a crucial role in the occurrence of RIBI, suggesting that RPRM may serve as a novel potential target for the prevention and treatment of RIBI.
SiCR: Web application for single-cell repertoire analysis and immune profiling
Authors: Ishikawa Masakazu , Matsumoto Kaoru , Okuzaki Daisuke 
Published: August 2023

AbstractBackgroundSingle-cell RNA sequencing (scRNA-seq) allows analysis of complete sequences of antigen receptors in individual cells. However, it is a complex technique that requires multiple analyses to obtain accurate results. Although several user-friendly tools for scRNA-seq are available, none are specifically designed for immune profiling.ResultsWe developed a web application called SiCR that is based on the Shiny framework of the R package and specializes in single-cell immune profiling. SiCR allows clustering and cell typing required for both general single-cell and immune profiling analyses, such as predicting whether the chronotype is expanding in each group and the antigen the expanding chronotype targets. These analyses can be performed using a cursor control. SiCR also allows for detailed figure settings, enabling immediate publication of results.ConclusionsSiCR is a comprehensive workbench that can be used by biologists for single-cell immune profiling. Currently, it is the only web application that allows single-cell repertoire analysis using both raw and preprocessed data. Moreover, SiCR significantly reduces the time and effort required to analyze and interpret information in single-cell immune profiling. Therefore, SiCR is a potential reference application for interactive analysis and investigation of biological data, especially for immune profiling.
Learning produces a hippocampal cognitive map in the form of an orthogonalized state machine
Authors: Sun Weinan , Winnubst Johan , Natrajan Maanasa , Lai Chongxi , Kajikawa Koichiro , Michaelos Michalis , Gattoni Rachel , Stringer Carsen , Flickinger Daniel , Fitzgerald James E. , Spruston Nelson 
Published: August 2023

ABSTRACTCognitive maps confer animals with flexible intelligence by representing spatial, temporal, and abstract relationships that can be used to shape thought, planning, and behavior. Cognitive maps have been observed in the hippocampus, but their algorithmic form and the processes by which they are learned remain obscure. Here, we employed large-scale, longitudinal two-photon calcium imaging to record activity from thousands of neurons in the CA1 region of the hippocampus while mice learned to efficiently collect rewards from two subtly different versions of linear tracks in virtual reality. The results provide a detailed view of the formation of a cognitive map in the hippocampus. Throughout learning, both the animal behavior and hippocampal neural activity progressed through multiple intermediate stages, gradually revealing improved task representation that mirrored improved behavioral efficiency. The learning process led to progressive decorrelations in initially similar hippocampal neural activity within and across tracks, ultimately resulting in orthogonalized representations resembling a state machine capturing the inherent structure of the task. We show that a Hidden Markov Model (HMM) and a biologically plausible recurrent neural network trained using Hebbian learning can both capture core aspects of the learning dynamics and the orthogonalized representational structure in neural activity. In contrast, we show that gradient-based learning of sequence models such as Long Short-Term Memory networks (LSTMs) and Transformers do not naturally produce such orthogonalized representations. We further demonstrate that mice exhibited adaptive behavior in novel task settings, with neural activity reflecting flexible deployment of the state machine. These findings shed light on the mathematical form of cognitive maps, the learning rules that sculpt them, and the algorithms that promote adaptive behavior in animals. The work thus charts a course toward a deeper understanding of biological intelligence and offers insights toward developing more robust learning algorithms in artificial intelligence.
Mechanism of Phosphate Release from Actin Filaments
Authors: Wang Yihang , Wu Jiangbo , Zsolnay Vilmos , Pollard Thomas D. , Voth Gregory A. 
Published: August 2023

AbstractAfter ATP-actin monomers assemble filaments, the ATP’s γ-phosphate is hydrolyzed within seconds and dissociates over minutes. We used all-atom molecular dynamics simulations to sample the release of phosphate from filaments and study residues that gate release. Dissociation of phosphate from Mg2+is rate limiting and associated with an energy barrier of 20 kcal/mol, consistent with experimental rates of phosphate release. Phosphate then diffuses in an internal cavity toward a gate formed by R177 suggested in prior computational studies and cryo-EM structures. The gate is closed when R177 hydrogen bonds with N111 and is open when R177 forms a salt bridge with D179. Most of the time interactions of R177 with other residues occludes the phosphate release pathway. Machine learning analysis reveals that the occluding interactions fluctuate rapidly, underscoring the secondary role of backdoor gate opening in Pirelease, in contrast with the previous hypothesis that gate opening is the primary event.Significance StatementThe protein actin assembles into filaments that participate in muscle contraction and cellular movements. An ATP bound to the actin monomer is hydrolyzed rapidly during filament assembly, but the γ-phosphate dissociates slowly from the filament. We identified phosphate dissociation from Mg2+as the rate-limiting step in phosphate release from actin based on an energy barrier that aligns with the experimentally determined release rate. The release of phosphate from the protein requires opening a gate in the actin molecule formed by the interaction between sidechains of arginine 177 and asparagine 111. Surprisingly, simulations revealed other interactions of the sidechain of arginine 177 that occlude the release pathway most of the time but have not been observed in low-temperature cryo-EM structures.
Comprehensive Assessment of Isoform Detection Methods for Third-Generation Sequencing Data
Authors: Su Yaqi , Yu Zhejian , Jin Siqian , Ai Zhipeng , Yuan Ruihong , Chen Xinyi , Xue Ziwei , Guo Yixin , Chen Di , Liang Hongqing , Liu Zuozhu , Liu Wanlu 
Published: August 2023

AbstractThe advancement of Third-Generation Sequencing (TGS) techniques has significantly increased the length of sequencing to several kilobases, thereby facilitating the identification of alternative splicing (AS) events and isoform expressions. Recently, numerous computational methods for isoform detection using long-read sequencing data have been developed. However, there is lack of prior comparative studies that systemically evaluates the performance of these software tools, implemented with different algorithms, under various simulations that encompass potential influencing factors. In this study, we conducted a benchmarking analysis of eleven methods implemented in eight computational tools capable of identifying isoform structures from TGS RNA sequencing data. We evaluated their performances using simulated data, which represented diverse sequencing platforms generated by an in-house simulator, as well as experimental data. Our comprehensive results demonstrate the guided mode of StringTie2 and Bambu achieved the best performance in sensitivity and precision, respectively. This study provides valuable guidance for future research on AS analysis and the ongoing improvement of tools for isoform detection using TGS data.