bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bowel Colonization by Non-Commensal Fungi in Neonatal Obstructive Cholangitis and Biliary Atresia
Authors: Huang Song-Wei , Lin Chia-Ray , Chang Ya-Hui , Ni Yen-Hsuan , Chen Huey-Ling , Liu Hong-Hsing 
Published: March 2023

AbstractUp to two-thirds of biliary atresia (BA) patients need liver transplantation after the standard Kasai portoenterostomy treatment. Unrelenting cholangitis often precedes the full-blown presentation of BA. Using ribosomal 18S sequencing, here we report bowel colonization by non-commensalAspergillusfungi in one case of neonatal obstructive cholangitis. Continuous oral fluconazole treatment resolved obstructive cholangitis completely. Colonization by non-commensalAspergillusandCerrenawere additionally identified in 2 BA cases. In brief, bowel colonization by non-commensal fungi could be a treatable cause of neonatal obstructive cholangitis and potentially BA at an early stage.
Exploring the vomeronasal organ in an endangered antelope species
Authors: Torres Mateo V. , Ortiz-Leal Irene , Ferreiro Andrea , Rois José Luis , Sanchez-Quinteiro Pablo 
Published: March 2023

ABSTRACTThe dama gazelle is a threatened and scarcely studied species of northern Africa. Human pressure has depleted the population of dama gazelles from tens of thousands to a few hundred individuals. Since 1970, after deriving from a founder population of the last 17 surviving individuals in the Western Sahara, it has been reproduced naturally in captivity. Although certain aspects of the reproductive biology of the dama gazelle have been established in preparation for the future implementation of assisted reproductive technology there is a lack of information regarding the role of semiochemical-mediated communication in the sexual behavior of the dama gazelle. This is partially due to the lack of a neuroanatomical and morphofunctional characterization of the dama gazelle vomeronasal organ (VNO); the sensory organ responsible for the processing of pheromones. This study aims to determine the presence in the dama gazelle of a VNO fully equipped to carry out its neurosensory function and to contribute to the understanding of the interspecific variability of the VNO of ruminants. Employing histological, lectin-histochemical and immunohistochemical techniques we have performed a detailed morphofunctional evaluation of the dama gazelle VNO along its entire longitudinal axis. The findings suggest that studies of the VNO should take a similar approach, as there are significant structural and neurochemical transformations that the organ exhibits as a whole. This study contributes to the understanding of the VNO in dama gazelles and provides a basis for future studies on semiochemical-mediated communication and reproductive management of this species.
Unveiling Convergent and Divergent Intrinsic Brain Network Alternations in Depressed Adolescents Engaged Non-Suicidal Self-Injurious Behaviors with and without Suicidal Attempts
Authors: Li Linling , Liang Zhen , Li Guohua , Xu Hong , Yang Xing , Liu Xia , Zhang Xin , Wang Jianhong , Zhang Zhiguo , Zhou Yongjie 
Published: March 2023

AbstractNonsuicidal self-injury (NSSI) and suicidal attempt (SA) frequently occur during depressed adolescents, but the underlying neurobiological mechanisms are poorly understood. The maturation of network connectivity is a central feature of brain development during adolescence. However, few researchers have used resting-state functional magnetic resonance imaging (fMRI) to investigate the similarities and differences in the intrinsic brain networks between NSSI with NSSI+SA in depressed adolescent populations. In this study, we collected self-reported questionnaires and resting-state (fMRI data from a sample of depressed adolescents (N = 114), categorized into three groups: clinical control (non-self-harm), NSSI-only, and NSSI+SA based on their self-harm history. The alternations of FC patterns were identified through support vector machine-based classification, as machine learning approaches can help to overcome the multiple-comparison problems of their multivariate nature. Referring to the convergent alternations between adolescent NSSI with or without a history of SA, the alternations of intra-/inter-network FCs among the Control, SalVAtten, Limbic, and Default networks. Besides, divergent alternations were also observed for depressed adolescents with a history of SA, involving the Limbic, DorsAttn, Visual, and Subcortical networks. Besides, the severity of depressive symptoms only showed a significant correlation with altered FCs in Limbic-DorAttn and Limbic-Visual networks, strengthening the fact that these observed alternations of FC could not all be explained by increased depression severity. The emphasis of this study on the network basis could extend the existing evidence at a circuit level and the observed convergent alternations may explain an underlying neurobiological mechanism pertaining to the continuum of self-destructiveness in adolescents. In addition, our discovery of divergent alternations could help to identify biomarkers that will aid in differentiating those at risk for SA among those engaging in NSSI and contribute to the development of neurobiologically informed interventions.
Transcriptional characterization of iPSC-derived microglia as a model for therapeutic development in neurodegeneration
Authors: Ramaswami Gokul , Yuva-Aydemir Yeliz , Akerberg Brynn , Matthews Bryan , Williams Jenna , Golczer Gabriel , Huang Jiaqi , Huh Dann , Burkly Linda C. , Engle Sandra J. , Sehgal Alfica , Sigova Alla A. , Fremeau Robert T. , Liu Yuting , Bumcrot David 
Published: March 2023

AbstractBackgroundMicroglia are the resident immune cells in the brain that play a key role in driving neuroinflammation, a hallmark of neurodegenerative disorders. Inducible microglia-like cells have been developed as an in vitro platform for molecular and therapeutic hypothesis generation and testing. However, there has been no systematic assessment of similarity of these cells to primary human microglia along with their responsiveness to external cues expected of primary cells in the brain.MethodsIn this study, we performed transcriptional characterization of commercially available human inducible pluripotent stem cell (iPSC)-derived microglia-like (iMGL) cells by bulk and single cell RNA sequencing to assess their similarity with primary human microglia. To evaluate their stimulation responsiveness, iMGL cells were treated with Liver X Receptor (LXR) pathway agonists and their transcriptional responses characterized by bulk and single cell RNA sequencing.ResultsBulk transcriptome analyses demonstrate that iMGL cells have a similar overall expression profile to freshly isolated human primary microglia and express many key microglial transcription factors and functional and disease-associated genes. Notably, at the single-cell level, iMGL cells exhibit distinct transcriptional subpopulations, representing both homeostatic and activated states present in normal and diseased primary microglia. Treatment of iMGL cells with LXR pathway agonists induces robust transcriptional changes in lipid metabolism and cell cycle at the bulk level. At the single cell level, we observe heterogeneity in responses between cell subpopulations in homeostatic and activated states and deconvolute bulk expression changes into their corresponding single cell states.ConclusionsIn summary, our results demonstrate that iMGL cells exhibit a complex transcriptional profile and responsiveness, reminiscent of in vivo microglia, and thus represent a promising model system for therapeutic development in neurodegeneration.
High fidelity sensory-evoked responses in neocortex after intravenous injection of genetically encoded calcium sensors
Authors: Leikvoll Austin , Kara Prakash 
Published: March 2023

AbstractTwo-photon imaging of genetically-encoded calcium indicators (GECIs) has traditionally relied on intracranial injections of adeno-associated virus (AAV) or transgenic animals to achieve expression. Intracranial injections require an invasive surgery and result in a relatively small volume of tissue labeling. Transgenic animals, although they can have brain-wide GECI expression, often express GECIs in only a small subset of neurons, may have abnormal behavioral phenotypes, and are currently limited to older generations of GECIs. Inspired by recent developments in the synthesis of AAVs that readily cross the blood brain barrier, we tested whether an alternative strategy of intravenously injecting AAV-PhP.eB is suitable for two-photon calcium imaging of neurons over many months after injection. We injected young (postnatal day 23 to 31) C57BL/6J mice with AAV-PhP.eB-Synapsin-jGCaMP7s via the retro-orbital sinus. After allowing 5 to 34 weeks for expression, we performed conventional and widefield two-photon imaging of layers 2/3, 4 and 5 of the primary visual cortex. We found reproducible trial-by-trial neural responses and tuning properties consistent with known feature selectivity in the visual cortex. Thus, intravenous injection of AAV-PhP.eB does not interfere with the normal processing in neural circuits.In vivoand histological images show no nuclear expression of jGCaMP7s for at least 34 weeks post-injection.
Diet-Induced Glial Insulin Resistance Impairs The Clearance Of Neuronal Debris
Authors: Alassaf Mroj , Rajan Akhila 
Published: March 2023

AbstractObesity significantly increases the risk of developing neurodegenerative disorders, yet the precise mechanisms underlying this connection remain unclear. Defects in glial phagocytic function are a key feature of neurodegenerative disorders, as delayed clearance of neuronal debris can result in inflammation, neuronal death, and poor nervous system recovery. Mounting evidence indicates that glial function can affect feeding behavior, weight, and systemic metabolism, suggesting that diet may play a role in regulating glial function. While it is appreciated that glial cells are insulin sensitive, whether obesogenic diets can induce glial insulin resistance and thereby impair glial phagocytic function remains unknown. Here, using aDrosophilamodel, we show that a chronic obesogenic diet induces glial insulin resistance and impairs the clearance of neuronal debris. Specifically, obesogenic diet exposure downregulates the basal and injury-induced expression of the glia-associated phagocytic receptor, Draper. Constitutive activation of systemic insulin release fromDrosophilaInsulin-producing cells (IPCs) mimics the effect of diet-induced obesity on glial draper expression. In contrast, genetically attenuating systemic insulin release from the IPCs rescues diet-induced glial insulin resistance and draper expression. Significantly, we show that genetically stimulating Phosphoinositide 3-kinase (PI3K), a downstream effector of Insulin receptor signaling, rescues HSD-induced glial defects. Hence, we establish that obesogenic diets impair glial phagocytic function and delays the clearance of neuronal debris.
Sex differences in neural representations of social and nonsocial reward in the medial prefrontal cortex
Authors: Isaac Jennifer , Karkare Sonia , Balasubramanian Hymavathy , Schappaugh Nicholas , Javier Jarildy , Rashid Maha , Murugan Malavika 
Published: March 2023

AbstractThe reinforcing nature of social interactions is necessary for the maintenance of appropriate social behavior. However, the neural substrates underlying social reward processing and how they might differ based on the sex and internal state of the animal remains unknown. It is also unclear whether these neural substrates are shared with those involved in nonsocial rewarding processing. We developed a fully automated, novel two choice (social-sucrose) operant assay in which mice choose between social and nonsocial rewards to directly compare the reward-related behaviors associated with two competing stimuli. We performed cellular resolution calcium imaging of medial prefrontal cortex (mPFC) neurons in male and female mice across varying states of water restriction and social isolation. We found that mPFC neurons maintain largely non-overlapping, flexible representations of social and nonsocial reward that vary with internal state in a sex-dependent manner. Additionally, optogenetic manipulation of mPFC activity during the reward period of the assay disrupted reward-seeking behavior across male and female mice. Thus, using a novel operant assay, we have identified sex-dependent, non-overlapping neural representations of social and nonsocial reward in the mPFC that vary with internal state and that are essential for appropriate reward-seeking behavior.
Icariin prevents depression-like behaviors in chronic unpredictable mild stress-induced rats through Bax/cytoplasm C/caspase-3 axis to alleviate neuronal apoptosis
Authors: Wu Xiao , Zhang Xiaona , Sun Lulu , Lu Xiaomin , Shen Cunsi 
Published: March 2023

AbstractMajor depressive disorder (MDD) affects approximately 16% of the global population. Our previous study has demonstrated that icariin (ICA) exhibits anti-depressant activity by increasing the expression of Brain Derived Neurotrophic Factor (BDNF) in a rat model of chronic unpredictable mild stress (CUMS). In this study, we investigated whether and how ICA can prevent CUMS-induced depression-like behaviors in rats by modulating hippocampus neuronal apoptosis. Forty male rats were randomly divided into control, CUMS, CUMS-fluoxetine (Flx) (10 mg/kg), and CUMS-ICA (20 mg/kg) groups. Behavior tests including sucrose preference test (SPT), open field test (OFT), elevated plus-maze (EPM), and forced swimming tests (FST) were performed. The Nissl staining and TUNNEL assay were used to determine neuronal apoptosis. Subsequently, expression of glucocorticoid receptor (GR), Bcl-2, cytochrome C, caspase-3 and Bax in the hippocampus were tested by western blot. Our results show that a chronic administration of ICA (20 mg/kg) can prevent CUMS-induced depressant-like behaviors in male model rats. Additionally, ICA significantly inhibited mitochondrial translocation of GR, reduced mitochondrial outer membrane permeabilization (MOMP) to suppress the release of cytochrome C, and then inhibit the activation of caspase-3. In conclusion, our research provides new evidence to understand the anti-depressant activity of ICA, which relates to its inhibition of neuronal apoptosis in hippocampus through mitochondrial apoptotic pathway.
Dynamics of an incoherent feedforward loop drive ERK-dependent pattern formation in the earlyDrosophilaembryo
Authors: Ho Emily K. , Oatman Harrison R. , McFann Sarah E. , Yang Liu , Johnson Heath E. , Shvartsman Stanislav Y. , Toettcher Jared E. 
Published: March 2023

AbstractPositional information in developing tissues often takes the form of stripes of gene expression that mark the boundaries of a particular cell type or morphogenetic process. How stripes form is still in many cases poorly understood. Here we use optogenetics and live-cell biosensors to investigate one such pattern: the posterior stripe ofbrachyenteron (byn)expression in the earlyDrosophilaembryo. Thisbynstripe depends on interpretation of an upstream signal – a gradient of ERK kinase activity – and the expression of two target genestailless (tll)andhuckebein (hkb)that exert antagonistic control overbyn. We find that high or low doses of ERK signaling produce either transient or sustainedbynexpression, respectively. These ERK stimuli also regulatetllandhkbexpression with distinct dynamics:tlltranscription is rapidly induced under both low and high stimuli, whereashkbtranscription converts graded ERK inputs into an output switch with a variable time delay. Antagonistic regulatory paths acting on different timescales are hallmarks of an incoherent feedforward loop architecture, which is sufficient to explain transient or sustainedbyndynamics and adds temporal complexity to the steady-state model ofbynstripe formation. We further show that an all-or-none stimulus can be ‘blurred’ through intracellular diffusion to non-locally produce a stripe ofbyngene expression. Overall, our study provides a blueprint for using optogenetic inputs to dissect developmental signal interpretation in space and time.
Microbiota Succession Influences Nematode Physiology in a Beetle Microcosm Ecosystem
Authors: Han Ziduan , Sommer Ralf J. , Lo Wen-Sui 
Published: March 2023

AbstractResearch during the last decade has generated a substantial understanding of the role of microbiota in animal development, metabolism and immunity, including humans. However, many organismal interactions involve microbial successions, such as in animal decay but also human health and disease. The complexity of most microbiota makes it difficult to obtain insight into such microbial successions, resulting in a limited understanding of microbiota for ecosystem functioning. One potential, relatively simple, model system for the analysis of microbial successions is insect decay in soil ecosystems, a highly abundant process that has however, not been investigated in detail. For example, microbiota and nematodes are the two most abundant groups of organisms in soil systems, but their interplay and successions during the decomposition of insects are currently unknown. Here, we use a semi-artificial decaying rose chafer grub microcosm to study the reciprocal interactions between microbiota and nematodes through metagenomics and transcriptomic studies. We show that the controlled addition of nematodes to beetle grub carcasses will strongly influence the microbial succession and result in a massive increase in microbial diversity. Nematodes select microbes of high nutritional value for consumption, thereby influencing the composition of microbiota on the decaying insect. Reciprocally, the activity of nematode metabolic pathways strongly responds to their microbial diet and affects fat metabolism and the formation of dauer larvae, the nematode dispersal stage. These results indicate the importance of microbial successions and their reciprocal interactions with nematodes for insect decay in soil ecosystems.
Dysregulation of Prefrontal Oligodendrocyte Lineage Cells Across Mouse Models of Adversity and Human Major Depressive Disorder
Authors: Sharma Sumeet , Ma Wenjing , Ressler Kerry J. , Anderson Thea , Li Dan. C. , Jin Peng , Gourley Shannon L. , Qin Zhaohui 
Published: March 2023

AbstractAnimal models of adversity have yielded few molecular mechanisms that translate to human stress-related diseases like major depressive disorder (MDD). We congruently analyze publicly available bulk-tissue transcriptomic data from prefrontal cortex (PFC) in multiple mouse models of adversity and in MDD. We apply strategies, to quantify cell-type specific enrichment from bulk-tissue transcriptomics, utilizing reference single cell RNA sequencing datasets. These analyses reveal conserved patterns of oligodendrocyte (OL) dysregulation across animal experiments, including susceptibility to social defeat, acute cocaine withdrawal, chronic unpredictable stress, early life stress, and adolescent social isolation. Using unbiased methodologies, we further identify a dysregulation of layer 6 neurons that associate with deficits in goal-directed behavior after social isolation. Human post-mortem brains with MDD show similar OL transcriptome changes in Brodmann Areas 8/9 in both male and female patients. This work assesses cell type involvement in an unbiased manner from differential expression analyses across animal models of adversity and human MDD and finds a common signature of OL dysfunction in the frontal cortex.
CXCR4 blockade alleviates pulmonary and cardiac outcomes in early COPD
Authors: Dupin Isabelle , Henrot Pauline , Maurat Elise , Abohalaka Reshed , Chaigne Sébastien , El Hamrani Dounia , Eyraud Edmée , Prevel Renaud , Esteves Pauline , Campagnac Maryline , Dubreuil Marielle , Cardouat Guillaume , Bouchet Clément , Ousova Olga , Dupuy Jean-William , Trian Thomas , Thumerel Matthieu , Bégueret Hugues , Girodet Pierre-Olivier , Marthan Roger , Zysman Maeva , Freund-Michel Véronique , Berger Patrick 
Published: March 2023

ABSTRACTChronic obstructive pulmonary disease (COPD) is a prevalent respiratory disease lacking effective treatment. Focusing on early COPD should help to discover disease modifying therapies. We aimed to examine the role of the CXCL12/CXCR4 axis in early COPD from both human samples and murine models. Blood samples and lung tissues of early COPD patients and controls were obtained in order to analyse CXCL12 and CXCR4 levels. To generate an early COPD model, ten-week-old male C57BL/6J mice were exposed to cigarette smoke (CS) for 10 weeks and intranasal instillations of polyinosinic–polycytidylic acid (poly(I:C)) for the last 5 weeks to mimic exacerbations. CXCR4 expressing cells number was increased in the blood of patients with COPD, as well as in the blood of exposed mice. Lung CXCL12 expression was higher in both early COPD patients and exposed mice. Exposed mice presented mild airway obstruction, peri-bronchial fibrosis and right heart thickening. The density of fibrocytes expressing CXCR4 was increased in the bronchial submucosa of these mice. Conditional inactivation of CXCR4 at adult stage as well as pharmacological inhibition of CXCR4 with plerixafor injections improved lung function, reduced inflammation, and protected against CS and poly-(I:C)-induced airway and cardiac remodeling. CXCR4-/-and plerixafor-treated mice also had less CXCR4-expressing circulating cells and a lower density of peri-bronchial fibrocytes. We demonstrate that targeting CXCR4 has beneficial effects in an animal model of early COPD and provide a framework to translate these preclinical findings to clinical settings in a drug repurposing approach.Clinical relevanceWe demonstrate that CXCL12/CXCR4 axis plays an important role in the pathogenesis of early COPD. Inhibition of this axis improves lung function and cardiac tissue remodeling, supporting the future use of CXCR4 inhibitors to slow down the progression of the disease.
An adaptive behavioral control motif mediated by cortical axo-axonic inhibition
Authors: Jung Kanghoon , Chang Minhyeok , Steinecke André , Berke Benjamin , Choi Youngjin , Oisi Yasuhiro , Fitzpatrick David , Taniguchi Hiroki , Kwon Hyung-Bae 
Published: March 2023

AbstractNeural circuits are reorganized with specificity during learning. Genetically-defined subgroups of inhibitory interneurons are thought to play distinct roles in learning, but heterogeneity within these subgroups has limited our understanding of the scope and nature of their specific contributions to learning. Here we reveal that the chandelier cell (ChC), an interneuron type that specializes in inhibiting the axon-initial segment (AIS) of pyramidal neurons, establishes cortical microcircuits for organizing neural coding through selective axo-axonic synaptic plasticity. We find that organized motor control is mediated by enhanced population coding of direction-tuned premotor neurons, whose tuning is refined through suppression of irrelevant neuronal activity. ChCs are required for learning-dependent refinements via providing selective inhibitory control over pyramidal neurons rather than global suppression. Quantitative analysis on structural plasticity of axo-axonic synapses revealed that ChCs redistributed inhibitory weights to individual pyramidal neurons during learning. These results demonstrate an adaptive logic of the inhibitory circuit motif responsible for organizing distributed neural representations. Thus, ChCs permit efficient cortical computation in a target cell specific manner, which highlights the significance of interneuron diversity.