bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stereopy: modeling comparative and spatiotemporal cellular heterogeneity via multi-sample spatial transcriptomics
Authors: Fang Shuangsang , Xu Mengyang , Cao Lei , Liu Xiaobin , Bezulj Marija , Tan Liwei , Yuan Zhiyuan , Li Yao , Xia Tianyi , Guo Longyu , Kovacevic Vladimir , Hui Junhou , Guo Lidong , Liu Chao , Cheng Mengnan , Lin Li’ang , Wen Zhenbin , Josic Bojana , Milicevic Nikola , Qiu Ping , Lu Qin , Li Yumei , Wang Leying , Hu Luni , Zhang Chao , Kang Qiang , Chen Fengzhen , Deng Ziqing , Li Junhua , Li Mei , Li Shengkang , Zhao Yi , Fan Guangyi , Zhang Yong , Chen Ao , Li Yuxiang , Xu Xun 
Published: December 2023

AbstractTracing cellular dynamic changes across conditions, time, and space is crucial for understanding the molecular mechanisms underlying complex biological systems. However, integrating multi-sample data in a unified and flexible way to explore cellular heterogeneity remains a major challenge. Here, we present Stereopy, a flexible and versatile framework for modeling and dissecting comparative and spatiotemporal patterns in multi-sample spatial transcriptomics with interactive data visualization. To optimize this flexible framework, we have developed three key components: a multi-sample tailored data container, a scope controller, and an analysis transformer. Furthermore, Stereopy showcases three transformative applications supported by pivotal algorithms. Firstly, the multi-sample cell community detection (CCD) algorithm introduces an innovative capability to detect specific cell communities and identify genes responsible for pathological changes in comparable datasets. Secondly, the spatially resolved temporal gene pattern inference (TGPI) algorithm represents a notable advancement in detecting important spatiotemporal gene patterns while concurrently considering spatial and temporal features, which enhances the identification of important genes, domains and regulatory factors closely associated with temporal datasets. Finally, the 3D niche-based regulation inference tool, named NicheReg3D, reconstructs the 3D cell niches to enable the inference of cell-gene interaction network within the spatial texture, thus bridging intercellular communications and intracellular regulations to unravel the intricate regulatory mechanisms that govern cellular behavior. Overall, Stereopy serves as both a bioinformatics toolbox and an extensible framework that provides researchers with enhanced data interpretation abilities and new perspectives for mining multi-sample spatial transcriptomics data.
fastDFE: fast and flexible inference of the distribution of fitness effects
Authors: Sendrowski Janek , Bataillon Thomas 
Published: December 2023

AbstractEstimating the distribution of fitness effects (DFE) of new mutations is of fundamental importance in evolutionary biology, ecology, and conservation. However, existing methods for DFE estimation suffer from limitations, such as slow computation speed and limited scalability. To address these issues, we introduce fastDFE, a Python-based software package, offering fast and flexible DFE inference from site-frequency spectrum (SFS) data. Apart from providing efficient joint inference of multiple DFEs that share parameters, it offers the feature of introducing genomic covariates that influence the DFEs, and testing their significance. To further simplify usage, fastDFE is equipped with comprehensive VCF-to-SFS parsing utilities. These include options for site filtering and stratification, as well as site-degeneracy annotation and probabilistic 11 ancestral-allele inference. fastDFE thereby covers the entire workflow of DFE inference from the moment of acquiring a raw VCF file. Despite its Python foundation, fastDFE comprises a full R interface, including native R visualization capabilities. The package is comprehensively tested, and documented atfastdfe.readthedocs.io.
Adenosinergic modulation of layer 6 microcircuitry in the medial prefrontal cortex is specific to presynaptic cell type
Authors: Ding Chao , Yang Danqing , Feldmeyer Dirk 
Published: December 2023

AbstractAdenosinergic modulation in the PFC is recognised for its involvement in various behavioural aspects including sleep homoeostasis, decision-making, spatial working memory and anxiety. While the principal cells of layer 6 (L6) exhibit significant morphological diversity, the detailed cell-specific regulatory mechanisms of adenosine in L6 remain unexplored. Here, we quantitatively analysed the morphological and electrophysiological parameters of L6 neurons in the rat medial prefrontal cortex (mPFC) using whole-cell recordings combined with morphological reconstructions. We were able to identify two different morphological categories of excitatory neurons, those with a leading dendrite that was oriented either upright (towards the dial surface) or inverted (towards the white matter). These two excitatory neuron subtypes exhibited different electrophysiological and synaptic properties. Adenosine at a concentration of 30 µM indiscriminately suppressed connections with either an upright or an inverted presynaptic excitatory neuron. However, using lower concentrations of adenosine (10 µM) revealed that synapses originating from L6 upright neurons have a higher sensitivity to adenosine-induced inhibition of synaptic release. Adenosine receptor activation causes a reduction in the probability of presynaptic neurotransmitter release that could be abolished by specifically blocking A1adenosine receptors (A1ARs) using 8-cyclopentyltheophylline (CPT). Our results demonstrate a differential expression level of A1ARs at presynaptic sites of two functionally and morphologically distinct subpopulations of L6 principal neurons, suggesting that they may play distinct roles in the maintenance of sleep homoeostasis by adenosine.
KGRACDA: A Model Based on Knowledge Graph from Recursion and Attention Aggregation for CircRNA-disease Association Prediction
Authors: Wang Ying , Ma Maoyuan , Xie Yanxin , Peng Qinke , Lyu Hongqiang , Sun Hequan , Fu Laiyi 
Published: December 2023

SUMMARYCircRNA has been found to exhibit with human diseases, rendering the investigation of the circRNA-disease association (CDA) of significant importance. Deep learning provides a novel avenue for predicting CDA, however, due to the limited availability of comprehensive CDA datasets, most existing methods operate by directly reasoning over triplets of embedded entities and relations, neglecting the explicit capture local depth information. In this study, we propose a novel approach called Knowledge Graph-Enhanced Recursive Aggregation for CDA (KGRACDA), which enables the querying of explicit local structures surrounding triplets, thereby serving as crucial evidence for predicting CDA. First, we construct a comprehensive CDA knowledge graph utilizing a large-scale, multi-source heterogeneous dataset. Subsequently, we develop a graph neural network using recursive techniques and employ attention aggregation to generate CDA prediction scores. Experimental results demonstrate that KGRACDA surpasses other state-of-the-art methods by explicitly capturing local depth information related to CDA. To improve the convenience of CDA prediction, we have updated an interactive web platform named HNRBase v2.0, which provides rich visualization of circRNA data, and allows users to easily download data and predict CDA using KGRACDA. The code and datasets are publicly available athttps://github.com/maoyuanma/KGRACDA.
ANDROMEDA by Prosilico and log D outperform human hepatocytes for the prediction of intrinsic hepatic metabolic clearance of carboxylic acids
Authors: Fagerholm Urban 
Published: December 2023

ABSTRACTIntroductionExtrahepatic metabolism/conjugation, deconjugation of their metabolites, and low and varying unbound fraction in plasma (fu), is characteristic for carboxylic drugs. Thus, it is comparably difficult to estimate theirin vivointrinsic hepatic metabolic clearance (CLint) and hepatic CL (CLH) and to predict theirin vivoCLint, CLHand CL. One objective was to investigate the laboratory variability of fuand CLintfor carboxylic acids. Another objective was to compare human hepatocytes, measured log D and the software ANDROMEDA with regards to prediction of humanin vivoCLintof carboxylic acids.Materials and MethodsMeasured unbound hepatocyte CLint, non-renal CL (surrogate for CLH), non-renal CLint(surrogate for hepatic metabolic CLint), log D and fudata were taken from studies in the literature. ANDROMEDA (by Prosilico; version 1.0) prediction software was used forin silicopredictions of CLintfor carboxylic acids not used in the training set of its CLint-model.Results and DiscussionMean and maximum differences between highest and lowest reportedin vivoCLintpredicted from hepatocyte CLintwere 210- and 1,476-fold (n=8), respectively. Corresponding estimates forin vitrofuwere 19- and 50-fold, respectively. The data set with the apparently highest number of carboxylic acids contains 39 carboxylic acids within vitroCLintand log D (both measured at the same laboratory),in vivoCLintandin vitrofu. 18 carboxylic acids were excluded as theirin vitroCLintwas below the limit of quantification. The correlation coefficient (R2) for log hepatocyte predictedin vivoCLintvslogin vivoCLintwas 0.34. The corresponding R2for log Dvslogin vivoCLintwas 0.40 (0.47 for 64 carboxylic acids). The Q2(forward-looking R2) forin silico(ANDROMEDA) predicted and measured login vivoCLintfor 12 carboxylic acids was 0.86. The corresponding R2for hepatocytes and log D were 0.67 and 0.66, respectively. ANDROMEDA produced a lower maximum prediction error compared to hepatocytes and also predicted thein vivoCLintfor all carboxylic acids out of reach for the hepatocyte assay.ConclusionVery large interlaboratory variability was demonstrated for plasma protein binding and hepatocyte assays. Log D, and especially ANDROMEDA, outperformed the hepatocyte assay for the prediction of CLintof carboxylic acidsin vivoin man.
Motor unit discharge rate modulation during isometric contractions to failure is intensity and task dependent
Authors: Valenčič Tamara , Ansdell Paul , Brownstein Callum G , Spillane Padraig M , Holobar Aleš , Škarabot Jakob 
Published: December 2023

AbstractThe nature of neuromuscular decrements associated with contractions to task failure is known to dependent on task demands. Task-specificity of the associated adjustments in motor unit discharge rate (MUDR) behaviour, however, remains unclear. This study examined MUDR adjustments during different submaximal isometric knee-extension tasks to failure. Participants performed a sustained and an intermittent task at 20 and 50% of maximal voluntary torque (MVT), respectively (Experiment 1). High-density surface electromyography signals were recorded from vastus lateralis (VL) and medialis (VM) and decomposed into individual MU discharge timings, with the identified MUs tracked from recruitment to task failure. MUDR was quantified and normalised to intervals of 10% of contraction time (CT). MUDR of both muscles exhibited distinct modulation patterns in each task. During 20% MVT sustained task, MUDR decreased until ∼50% CT, after which it gradually returned to baseline. Conversely, during the 50% MVT intermittent task, MUDR remained stable until ∼40-50% CT, after which it started to continually increase until task failure. To explore the effect of contraction intensity on the observed patterns, VL and VM MUDR was quantified during sustained contractions at 30 and 50% MVT (Experiment 2). During the 30% MVT sustained task, MUDR remained stable until ∼80-90% CT in both muscles, after which it continually increased until task failure. During the 50% MVT sustained task the increase in MUDR occurred earlier, after ∼70-80% CT. Our results suggest that adjustments in MUDR during submaximal isometric contractions to failure are task- and intensity-dependent.
Extracellular symbiont colonizes insect during embryo development
Authors: Porras Miguel Ángel González , Pons Inès , García-Lozano Marleny , Jagdale Shounak , Emmerich Christiane , Weiss Benjamin , Salem Hassan 
Published: December 2023

AbstractInsects typically acquire their beneficial microbes early in development. Endosymbionts housed intracellularly are commonly integrated during oogenesis or embryogenesis, whereas extracellular microbes are only known to be acquired after hatching by immature instars such as larvae or nymphs. Here, however, we report on an extracellular symbiont that colonises its host during embryo development. Tortoise leaf beetles (Chrysomelidae: Cassidinae) host their digestive bacterial symbiontStammeraextracellularly within foregut symbiotic organs, and in ovary-associated glands to ensure its vertical transmission. We outline the initial stages of symbiont colonization and observe that while the foregut symbiotic organs develop three days prior to larval emergence, they remain empty until the final 24 hours of embryo development. Infection byStammeraoccurs during that timeframe, and prior to hatching. By experimentally manipulating symbiont availability to embryos in the egg, we describe a 12-hour developmental window governing colonization byStammera. Symbiotic organs form normally in aposymbiotic larvae, demonstrating that theseStammera-bearing structures develop autonomously. In adults, the foregut symbiotic organs are already colonized following metamorphosis and host a stableStammerapopulation to facilitate folivory. The ovary-associated glands, however, initially lackStammera. Symbiont abundance subsequently increases within these transmission organs, thereby ensuring sufficient titers at the onset of oviposition ∼29 days following metamorphosis. Collectively, our findings reveal thatStammeracolonization precedes larval emergence, where its proliferation is eventually decoupled in adult beetles to match the nutritional and reproductive requirements of its host.
Common types of microdebris affect the physiology of reef-building corals
Authors: Reichert Jessica , Tirpitz Vanessa , Plaza Katherine , Wörner Elisabeth , Bösser Luisa , Kühn Susanne , Primpke Sebastian , Schubert Patrick , Ziegler Maren , Wilke Thomas 
Published: December 2023

AbstractMarine debris, particularly microdebris (< 1 mm) poses a potential threat to marine life, including reef-building corals. While previous research has mainly focused on the impact of single polymer microplastics, the effects of natural microdebris, composed of a mixture of materials, have not been explored. Therefore, this study aimed to assess the effects of different microdebris, originating from major sources of pollution, on reef-building corals. For this, we exposed two scleractinian coral species,Pocillopora verrucosaandStylophora pistillata, known to frequently ingest microplastics, to four types of microdebris in an 8-week laboratory experiment: fragmented environmental plastic debris, artificial fibers from clothing, residues from the automobile sector consisting of tire wear, brake abrasion, and varnish flakes, a single polymer microplastic treatment consisting of polyethylene particles, and a microdebris-free control treatment. Specifically, we (I) compared the effects of the different microdebris on coral growth, necrosis, and photosynthesis, (II) investigated the difference between the microdebris mixtures and the exposure to the single polymer treatment, and (III) identified potential mechanisms causing species-specific effects by contrasting the feeding responses of the two coral species on microdebris and natural food. We show that the fibers and tire wear had the strongest effects on coral physiology, withP. verrucosabeing more affected thanS. pistillata. Both species showed increased volume growth in response to the microdebris treatments, accompanied by decreased calcification inP. verrucosa. Photosynthetic efficiency of the symbionts was enhanced in both species. The species-specific physiological responses might be attributed to feeding reactions, withP. verrucosaresponding significantly more often to microdebris thanS. pistillata. These findings highlight the effect of different microdebris on coral physiology and the need for future studies to use particle mixtures to better mimic naturally occurring microdebris and assess its effect on corals in more detail.HighlightsThe effects of major sources of microdebris pollution on coral physiology were compared.Overall, microdebris had only minor impacts on coral physiology.Artificial fibers and tire wear caused the strongest effect on coral physiology.Single polymer and complex microdebris caused similar, yet species-specific effects.Species-specific effects might be due to different feeding behaviors.Graphical abstract
Influenza infected macrophages release viral ribonucleoproteins that shape the local host response
Authors: Fritzlar Svenja , Lakdawala Seema S. , Roberts Jason A. , Coin Lachlan J. M. , Deng Yi-Mo , Moselen Jean , Le Sage Valerie M. , Mackenzie Jason M. , Labzin Larisa I. , Brooks Andrew G. , Reading Patrick C. , Londrigan Sarah L. 
Published: December 2023

SummaryAirway epithelial cells and macrophages (MΦ) represent cellular targets of infection by influenza A virus (IAV). Epithelial cells support IAV infection and replication by enabling the generation and release of new viral particles (productive replication). In contrast, MΦ are susceptible to initial IAV infection but the release of infectious viral particles is inhibited through abortive replication. Despite the lack of infectious virions released from infected MΦ, we detected newly synthesised viral RNA and nucleoprotein (NP) in MΦ supernatants. We show that viral RNA is released from infected MΦ as viral ribonucleoprotein (vRNP) complexes which elicits potent inflammatory responses when exposed to uninfected cells. These vRNPs specifically induced IL-1β, CXCL13, IL-32, CCL4 and CXCL10 in uninfected cells and were at least partially sensed through the RIG-I/MDA5 pathway. While MΦ represent a dead-end for IAV infection through abortive replication, the release of vRNPs shapes immune repsonses of uninfected cells in the local microenvironment.
Fecal bacterial communities of the platypus (Ornithorhynchus anatinus) reflect captivity status – implications for conservation and management
Authors: Dungan Ashley M. , Thomas Jessica L. 
Published: December 2023

AbstractThe duck-billed platypus (Ornithorhynchusanatinus) is currently listed as ‘Near-Threatened’ under the International Union for Conservation of Nature (IUCN) Red List based on observed population declines and local extinctions. A key part of the conservation strategy for this species is its captive maintenance; however, captive animals often undergo significant changes in their gut microbiome. The study of the gut microbiome in threatened wildlife species has enormous potential to improve conservation efforts and gain insights into host-microbe coevolution. Here, for the first time, we characterize the gut microbiome of wild platypus via fecal samples using high-throughput sequencing of the bacterial 16S rRNA gene and identify microbial biomarkers of captivity in this species. At the phylum level, Firmicutes (50.4%) predominated among all platypuses, followed by Proteobacteria (28.7%), Fusobacteria (13.4%), and Bacteroidota (6.9%), with twenty-one ‘core’ bacteria identified. Captive individuals did not differ in their microbial α-diversity compared to wild platypus but had significantly different community composition (β-diversity) and exhibited higher abundances ofEnterococcus, which are potential pathogenic bacteria. Four taxa were identified as biomarkers of wild platypus, includingRickettsiella, Epulopiscium, Clostridium, and Cetobacterium. This contrast in gut microbiome composition between wild and captive platypus is an essential insight for guiding conservation management as the rewilding of captive animal microbiomes is a new and emerging tool to improve captive animal health, maximize captive breeding efforts, and give reintroduced or translocated animals the best chance of survival.
Tardigrade secretory proteins protect biological structures from desiccation
Authors: Lim Samuel , Reilly Charles B. , Barghouti Zeina , Marelli Benedetto , Way Jeffrey C. , Silver Pamela A. 
Published: December 2023

AbstractTardigrades, microscopic animals that survive a broad range of environmental stresses, express a unique set of proteins termed tardigrade-specific intrinsically disordered proteins (TDPs). TDPs are often expressed at high levels in tardigrades upon desiccation, and appear to mediate stress adaptation. Here, we focused on the proteins belonging to the secretory family of tardigrade proteins termed secreted-abundant heat soluble (“SAHS”) proteins, and investigated their ability to protect diverse biological structures. Recombinantly expressed SAHS proteins prevented desiccated liposomes from fusion, and enhanced desiccation tolerance ofE. coliandRhizobium tropiciupon extracellular application. Molecular dynamics simulation and comparative structural analysis suggest a model by which SAHS proteins may undergo a structural transition upon desiccation, in which removal of water and solutes from a large internal cavity in SAHS proteins destabilizes the beta-sheet structure. These results highlight the potential application of SAHS proteins as stabilizing molecules for preservation of cells.
Dorsal hippocampal oxytocin receptor regulates adult peer bonding in rats
Authors: Hu Yufei , Li Wensi , Zhao Yinji , Liu Yuying , Sun Wenyu , Yan Yi , Liu Laixin , Deng Bowen , Fan Pu 
Published: December 2023

AbstractHealthy social relationships are beneficial whereas their breakdown is often linked to psychiatric disorders. Parental care and bonding between sexual partners have been well studied both at the level of behavioral analysis and underlying neuronal mechanisms. By contrast, little is known about the neural and molecular basis of peer bonding, defined as social bonds formed between unrelated individuals of the same sex, due to the lack of a suitable experimental paradigm. We found that adult Sprague Dawley (SD) rats of the same sex form strong peer bonds with each other following co-housing. Peer bonded rats exhibit affiliative displays toward their cagemates who are distressed whereas they exhibit agonistic behaviors toward strangers in these situations. Using innovative, genetic strategies in rats, we show that both oxytocin receptor (OXTR) bearing neurons andOxtrsignaling in the dorsal hippocampus are essential for peer bonds to form. Together, we have developed a new platform for studying peer bonding and demonstrate a neural pathway that governs this behavior.