bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic chemogenetic activation of hippocampal progenitors enhances adult neurogenesis and modulates anxiety-like behavior and fear extinction learning
Authors: Maheshwari Megha , Singla Aastha , Rawat Anoop , Banerjee Toshali , Pati Sthitapranjya , Shah Sneha , Maiti Sudipta , Vaidya Vidita A. 
Published: July 2023

AbstractAdult hippocampal neurogenesis is a lifelong process that involves the integration of newborn neurons into the hippocampal network, and plays a role in cognitive function and the modulation of mood-related behavior. Here, we sought to address the impact of chemogenetic activation of adult hippocampal progenitors on distinct stages of progenitor development, including quiescent stem cell activation, progenitor turnover, differentiation and morphological maturation. We find that hM3Dq-DREADD-mediated activation of nestin-positive adult hippocampal progenitors recruits quiescent stem cells, enhances progenitor proliferation, increases doublecortin-positive newborn neuron number, accompanied by an acceleration of differentiation and morphological maturation, associated with increased dendritic complexity. Behavioral analysis indicated anxiolytic behavioral responses in transgenic mice subjected to chemogenetic activation of adult hippocampal progenitors at timepoints when newborn neurons are predicted to integrate into the mature hippocampal network. Furthermore, we noted an enhanced fear memory extinction on a contextual fear memory learning task in transgenic mice subjected to chemogenetic activation of adult hippocampal progenitors. Our findings indicate that hM3Dq-DREAD-mediated chemogenetic activation of adult hippocampal progenitors impacts distinct aspects of hippocampal neurogenesis, associated with the regulation of anxiety-like behavior and fear memory extinction.
MethNet: a robust approach to identify regulatory hubs and their distal targets in cancer
Authors: Sakellaropoulos Theodore , Do Catherine , Jiang Guimei , Cova Giulia , Meyn Peter , Dimartino Dacia , Ramaswami Sitharam , Heguy Adriana , Tsirigos Aristotelis , Skok Jane A 
Published: July 2023

AbstractAberrations in the capacity of DNA/chromatin modifiers and transcription factors to bind non-coding regions can lead to changes in gene regulation and impact disease phenotypes. However, identifying distal regulatory elements and connecting them with their target genes remains challenging. Here, we present MethNet, a pipeline that integrates large-scale DNA methylation and gene expression data across multiple cancers, to uncover novel cis regulatory elements (CREs) in a 1Mb region around every promoter in the genome. MethNet identifies clusters of highly ranked CREs, referred to as ‘hubs’, which contribute to the regulation of multiple genes and significantly affect patient survival. Promoter-capture Hi-C confirmed that highly ranked associations involve physical interactions between CREs and their gene targets, and CRISPRi based scRNA Perturb-seq validated the functional impact of CREs. Thus, MethNet-identified CREs represent a valuable resource for unraveling complex mechanisms underlying gene expression, and for prioritizing the verification of predicted non-coding disease hotspots.
Aster-dependent non-vesicular transport facilitates dietary cholesterol uptake
Authors: Ferrari Alessandra , Whang Emily , Xiao Xu , Kennelly John P. , Romartinez-Alonso Beatriz , Mack Julia J. , Weston Thomas , Chen Kai , Kim Youngjae , Tol Marcus J. , Bideyan Lara , Nguyen Alexander , Gao Yajing , Cui Liujuan , Bedard Alexander H. , Sandhu Jaspreet , Lee Stephen D. , Fairall Louise , Williams Kevin J. , Song Wenxin , Munguia Priscilla , Russell Robert A. , Martin Martin G. , Jung Michael E. , Jiang Haibo , Schwabe John W.R. , Young Stephen G. , Tontonoz Peter 
Published: July 2023

AbstractIntestinal cholesterol absorption is an important contributor to systemic cholesterol homeostasis. Niemann-Pick C1 Like 1 (NPC1L1), the target of the drug ezetimibe (EZ), assists in the initial step of dietary cholesterol uptake. However, how cholesterol moves downstream of NPC1L1 is unknown. Here we show that Aster-B and Aster-C are critical for non-vesicular cholesterol movement in enterocytes, bridging NPC1L1 at the plasma membrane (PM) and ACAT2 in the endoplasmic reticulum (ER). Loss of NPC1L1 diminishes accessible PM cholesterol in enterocytes and abolishes Aster recruitment to the intestinal brush border. Enterocytes lacking Asters accumulate cholesterol at the PM and display evidence of ER cholesterol depletion, including decreased cholesterol ester stores and activation of the SREBP-2 transcriptional pathway. Aster-deficient mice have impaired cholesterol absorption and are protected against diet-induced hypercholesterolemia. Finally, we show that the Aster pathway can be targeted with a small molecule inhibitor to manipulate dietary cholesterol uptake. These findings identify the Aster pathway as a physiologically important and pharmacologically tractable node in dietary lipid absorption.One-Sentence SummaryIdentification of a targetable pathway for regulation of dietary cholesterol absorption
A framework for Frizzled-G protein coupling and implications to the Wnt-PCP signaling pathways
Authors: Zhang Zhibin , Lin Xi , Wei Ling , Wu Yiran , Xu Lu , Wu Lijie , Wei Xiaohu , Wang Arthur , Zhao Suwen , Zhu Xiangjia , Xu Fei 
Published: July 2023

AbstractThe ten Frizzled receptors (FZDs) are essential in Wnt signaling and play important roles in embryonic development and tumorigenesis. Among these, FZD6 is closely associated with lens development. Understanding FZD activation mechanism is key to unlock these emerging targets. Here we present the cryo-EM structures of FZD6 and FZD3 which are known to relay non-canonical Wnt-PCP (planar cell polarity) signaling pathways as well as FZD1 in their G protein-coupled (active) and G protein-free (inactive) states, respectively. Comparison of the three inactive/active pairs unveiled a shared activation framework among all ten FZDs. Mutagenesis along with imaging and functional analysis on the human lens epithelial tissues suggested potential crosstalk between G-protein binding and Wnt-PCP signaling pathways. Together, this study provides an integrated understanding of FZD structure and function, and lays the foundation for developing therapeutic modulators to activate or inhibit FZD signaling for a range of disorders including cancers and cataracts.
Impact of COVID-19 on the cascade of care for tuberculosis: A systematic review
Authors: Fapohunda Tomiwa , Mapahla Lovemore , Taha Reham Amin Khidir , Chivese Tawanda 
Published: July 2023

AbstractObjectivesTo describe the impact of the COVID-19 pandemic on the TB care cascade.MethodsIn this systematic review, the Cochrane library, Scopus, CINAHL, Ebscohost, and PubMed databases were comprehensively searched from the onset of the pandemic, till May 5th, 2022. Eligible studies were those reporting on changes in the TB cascade of care one year before and one year during the COVID-19 pandemic. Due to the expected differences in the contexts of the included studies, a narrative synthesis was conducted.ResultsTwenty-seven studies, from Asia, North America, Africa, South America, and Europe were included. TB screening decreased by between 1% - 50%, and multidrug resistance tuberculosis (MDR-TB) screening decreased by between 15%-17%. Diagnostic delay increased by between 35 - 45 days, contact tracing decreased by up to 36.1%, and case notification decreased by between 3%-63%. TB treatment enrolment decreased by between 16%-35.0%, treatment completion decreased by around 8.0% and treatment success decreased by up to 17.0%.ConclusionCOVID-19 had a detrimental impact on the TB care cascade and these findings suggest a need for policies to protect healthcare systems for TB and other communicable diseases in future health emergencies.Protocol registration - PROSPERO: CRD42021272456Ethics approvalThis systematic review used data from published studies and aggregated data, thus, ethics approval was not required.
Increased interhemispheric functional connectivity during non-dominant hand movement in right-handed subjects
Authors: Tsurugizawa Tomokazu , Taki Ai , Zalesky Andrew , Kasahara Kazumi 
Published: July 2023

AbstractHand preference is one of the behavioral expressions of lateralization in the brain. Previous fMRI studies, using conventional task-based functional MRI (fMRI), investigated the lateralization of brain function, and several regions including the motor cortex, putamen, thalamus, and cerebellum were activated during the single-hand movement. However, lateralization of functional connectivity related to hand preference has not been investigated. Here, we used the generalized psychophysiological interaction (gPPI) approach to investigate the alteration of functional connectivity during single-hand movement from the resting state in right-hand subjects. The functional connectivity in interhemispheric motor-related regions including the supplementary motor area, putamen, precentral gyrus, and cerebellum was significantly increased during non-dominant hand movement, while functional connectivity was not increased during dominant hand movement. The general linear model (GLM) showed activation in the left supplementary motor area, left precentral gyrus, and right cerebellum during right hand movement and activation in the right supplementary motor area, right precentral gyrus, and left cerebellum during left hand movement. These results indicate that a combination of GLM and gPPI analysis can detect the lateralization of hand preference more clearly in right-handed subjects.
Microengineering 3D Collagen Matrices with Tumor-Mimetic Gradients in Fiber Alignment
Authors: Joshi Indranil M. , Mansouri Mehran , Ahmed Adeel , Simon Richard A. , Bambizi Poorya Esmaili , Desa Danielle E. , Elias Tresa M. , Brown Edward B. , Abhyankar Vinay V. 
Published: July 2023

AbstractIn the tumor microenvironment (TME), collagen fibers facilitate tumor cell migration through the extracellular matrix. Previous studies have focused on studying the responses of cells on uniformly aligned or randomly aligned collagen fibers. However, the in vivo environment also features spatial gradients in alignment, which arise from the local reorganization of the matrix architecture due to cell-induced traction forces. Although there has been extensive research on how cells respond to graded biophysical cues, such as stiffness, porosity, and ligand density, the cellular responses to physiological fiber alignment gradients have been largely unexplored. This is due, in part, to a lack of robust experimental techniques to create controlled alignment gradients in natural materials. In this study, we image tumor biopsy samples and characterize the alignment gradients present in the TME. To replicate physiological gradients, we introduce a first-of-its-kind biofabrication technique that utilizes a microfluidic channel with constricting and expanding geometry to engineer 3D collagen hydrogels with tunable fiber alignment gradients that range from sub-millimeter to millimeter length scales. Our modular approach allows easy access to the microengineered gradient gels, and we demonstrate that HUVECs migrate in response to the fiber architecture. We provide preliminary evidence suggesting that MDA-MB-231 cell aggregates, patterned onto a specific location on the alignment gradient, exhibit preferential migration towards increasing alignment. This finding suggests that alignment gradients could serve as an additional taxis cue in the ECM. Importantly, our study represents the first successful engineering of continuous gradients of fiber alignment in soft, natural materials. We anticipate that our user-friendly platform, which needs no specialized equipment, will offer new experimental capabilities to study the impact of fiber-based contact guidance on directed cell migration.
Efficient Functions for Energetic Least-Cost Analysis over Land and Water in thelbmechpackage forR
Authors: Mejía Ramón Andrés G. 
Published: July 2023

AbstractCurrent least-cost tools for behavioral scientists are computationally insufficient and lack methods to independently derive animal-specific energetic cost functions based on locational data. Moreover, topologically-valid approaches only measure the biomechanical cost of movement, when sometimes net metababolical expediture may be a more-important consideration. In this paper, I first derive generalizable cost functions for energetic expenditure for any arbitrary biped or quadruped, versus the currently-employed regressed functions with limited cross-taxa or behavioral mode applicability. I then describe the cost-distance functions of the R package lbmech, designed to (1) regress the parameters describing behavioral sensitivity to slope from GPS tracking data; and (2) calculate the costs of movement in terms of time, kinetic work, and net metabolic expenditure. Finally, I demonstrate the utility of this package using publicly-available GPS, ocean current velocity, and elevation data from the Balearic Islands of Spain. This approach greatly facilitates the collection of field-based data given the reliance on GPS data. Moreover, it allows us to identify and consider individual- and group-level effects and variances that may lead to differential movement-related fitness with evolutionary consequences.
A Robust Combination Test Using the Normal Distribution, with Application to Phylogenetic Inference
Authors: Haque Md Rejuan , Kubatko Laura 
Published: July 2023

AbstractCombination tests are used to combine P-values from individual studies to test a global null hypothesis. These types of tests can also be applied to combine P-values from testing separate null hypotheses within the same study in cases for which the procedure for testing a global null hypothesis is unavailable. One such application of a combination test is to detect the presence of hybrid species within a set of species. Although many combination tests have been proposed in the literature, there is no uniformly most powerful test applicable for all conditions. For instance, in the hybrid detection application, it is expected that only a few of the species within a set species might have truly arisen via hybridization, and thus when tested, only a few of the individual P-values are expected to be significant. Thus, a desirable property of a combination test for this situation is to be able to reject the global null hypothesis even if only a small fraction of the individual P-values are significant. In this paper, we propose a new combination test based on the normal distribution that assigns weight to each test adaptively, thereby providing powerful results even when only a small fraction of the individual null hypotheses are false. A comprehensive simulation study, as well as real data applications, demonstrate that the proposed test is powerful in detecting false global null hypotheses under several situations for which existing tests have low power.
IFNγ modestly contributes to disease progression in theNdufs4(-/-) model of Leigh syndrome while IP10 is dispensable
Authors: Hanaford Allison R , Khanna Asheema , James Katerina , Truong Vivian , Liao Ryan , Chen Yihan , Mulholland Michael , Kayser Bernhard , Hsieh Erin Shien , Sedensky Margaret , Morgan Phil , Kalia Vandana , Sarkar Surojit , Johnson Simon C 
Published: July 2023

AbstractLeigh syndrome (LS) is the most common pediatric presentation of genetic mitochondrial disease. LS is a multi-system disease characterized by severe neurologic and metabolic abnormalities. The defining feature of the disease is the presence of symmetric, bilateral, progressive necrotizing lesions in the brain stem, cerebellum, and basal ganglia. The pathogenic mechanisms underlying disease initiation and progression in LS have yet to be elucidated. Recent evidence demonstrates that the immune system plays a key role in LS pathogenesis. Treatment with the macrophage-depleting Csf1r inhibitor pexidartinib prevents disease in theNdufs4(-/-) mouse model of LS, but the mechanisms leading to immune activation and governing disease progression remain to be elucidated. In recent work, the cytokines IFNγ and IFNγ-induced protein 10 (IP10) were found to be significantly elevated inNdufs4(-/-) brainstem. Given their role as macrophage-activating factors, here we sought to assess the role of IFNγ and IP10 in LS using by generatingNdufs4(-/-)/Ifng(-/-) andNdufs4(-/-)/IP10(-/-) double knockout lines. We find that IP10 alone does not significantly impact the onset or progression of disease in theNdufs4(-/-) model, while IFNγ loss significantly, but modestly, improves survival. These data indicate that IFNγ contributes to pathology, but that IFNγ and IP10 are both dispensable for overall disease course of LS. Our findings support some role for IFNγ targeting therapies in the management of mitochondrial disease, but suggest they may provide only modest benefits, at least in LS.
Proteome profiling of nasopharynx reveals pathophysiological signature of COVID-19 disease severity
Authors: Ooi Amanda , Esau Luke E. , Pugachev Artyom , Groen Arnoud , Mfarrej Sara , Salunke Rahul P. , Subudhi Amit K. , Ben-Rached Fathia , Alofi Fadwa , Alsomali Afrah , Alquthami Khaled , Khogeer Asim , Hashem Anwar M. , Almontashiri Naif , Magistretti Pierre J. , Hala Sharif , Pain Arnab 
Published: July 2023

SummaryAn aberrant innate immune system caused by the beta coronavirus SARS-CoV-2 is a characteristic manifestation of severe coronavirus disease 2019 (COVID-19). Here, we performed proteome profiling of nasopharyngeal (NP) swabs from 273 hospitalized patients with mild and severe COVID-19 symptoms, including non-survivors. We identified depletion in STAT1-mediated type I interferon response, retinol metabolism and NRF2 antioxidant system that are associated with disease severity in our patient demography. We found that the dysregulation of glucocorticoid signaling and renin-angiotensin-aldosterone system (RAAS) contribute to the pathophysiology of COVID-19 fatality. Hyperactivation of host innate immune system was observed in severe patients, marked by elevated proteins involved in neutrophil degranulation and platelet aggregation. Our study using high-throughput proteomics on the nasopharynx of COVID-19 patients provides additional evidence on the SARS-CoV-2-induced pathophysiological signatures of disease severity and fatality.
Periodontitis promotes bacterial extracellular vesicle-induced neuroinflammation in the brain and trigeminal ganglion
Authors: Ha Jae Yeong , Seok Jiwon , Kim Suk-Jeong , Jung Hye-Jin , Ryu Ka-Young , Nakamura Michiko , Jang Il-Sung , Hong Su-Hyung , Lee Youngkyun , Lee Heon-Jin 
Published: July 2023

AbstractGram-negative bacteria derived extracellular vesicles (EVs), also known as outer membrane vesicles, have attracted significant attention due to their pathogenic roles in various inflammatory diseases. We recently demonstrated that EVs secreted by the periodontopathogenAggregatibacter actinomycetemcomitans(Aa) can cross the blood–brain barrier (BBB) and that their extracellular RNA cargo can promote the secretion of proinflammatory cytokines, such as IL-6 and TNF-α, in the brain. To gain more insight into the relationship between periodontal disease (PD) and neuroinflammatory diseases, we investigated the effect of Aa EVs in a mouse model of ligature-induced PD. When EVs were administered through intragingival injection or EV-soaked gel, proinflammatory cytokines were strongly induced in the brains of PD mice. The use of TLR (Toll-like receptor)-reporter cell lines andMyD88knockout mice confirmed that the increased release of cytokines was triggered by Aa EVs via TLR4 and TLR8 signaling pathways and their downstream MyD88 pathway. Furthermore, the injection of EVs through the epidermis and gingiva resulted in the direct retrograde transfer of Aa EVs from axon terminals to the cell bodies of trigeminal ganglion (TG) neurons and the subsequent activation of TG neurons. We also found that the Aa EVs changed the action potential of TG neurons. These findings suggest that EVs derived from periodontopathogens such as Aa might be involved in pathogenic pathways for neuroinflammatory diseases, neuropathic pain, and other systemic inflammatory symptoms as a comorbidity of periodontitis.Author summaryExtracellular vesicles (EVs) secreted from bacterial cells play a key role in microbe-host cell communication. Bacterial EVs (bEVs) may be closely linked to the pathogenesis underlying neuroinflammatory diseases. In the current experiments, bEVs caused the brain to release proinflammatory cytokines by activating the host TLR signaling pathway. This induction of neuroinflammation was significantly more prominent in the periodontitis disease model, implying a substantial link between periodontal and neuroinflammatory diseases through bEVs. We also show that bEVs are translocated to the neuronal cell body via retrograde axonal transport, where they directly activate neuronal proinflammatory signals (Fig 8). Our findings reveal that bEVs are a pathogenic pathway for neurological conditions potentially linked to periodontitis, such as Alzheimer’s disease and trigeminal neuropathic pain.
Pasa: Leverage population pangenome graph to scaffold prokaryote genome assemblies
Authors: Do Van Hoan , Nguyen Son Hoang , Le Duc Quang , Nguyen Tam Thi , Nguyen Canh Hao , Ho Tho Huu , Nam Vo Sy , Nguyen Trang , Nguyen Hoang Anh , Cao Minh Duc 
Published: July 2023

AbstractWhole genome sequencing has increasingly become the essential method for studying the genetic mechanisms of antimicrobial resistance and for surveillance of drug-resistant bacterial pathogens. The majority of bacterial genomes sequenced to date have been sequenced with Illumina sequencing technology, owing to its high-throughput, excellent sequence accuracy, and low cost. However, because of the short-read nature of the technology, these assemblies are fragmented into large numbers of contigs, hindering the obtaining of full information of the genome. We develop Pasa, a graph-based algorithm that utilizes the pangenome graph and the assembly graph information to improve scaffolding quality. By leveraging the population information of the bacteria species, Pasa is able to utilize the linkage information of the gene families of the species to resolve the contig graph of the assembly. We show that our method outperforms the current state of the art in terms of accuracy, and at the same time, is computationally efficient to be applied to a large number of existing draft assemblies.
Improving the Circularization Efficiency, Stability and Translatability of Circular RNA by circDesign
Authors: Xu Congcong , Zhang Liang , Wang Weiyun , Tang Yuying , Wang Qiuhe , An Jinqi , Xu Heng , Ge Yun , Zhu Hanfei , Wang He , Li Bin , Wang Xiaotian , Qiu Xuhui , Shen Mingyun , Chen Geng , Shen Haifa , Huang Liang , Li Hangwen 
Published: July 2023

AbstractSynthetic circular RNA (circRNA) has recently emerged as the next generation RNA technology for vaccine and drug development, featuring its uniqueness in a closed-loop structure and cap-independent translation mechanism. However, rational design and optimization of circRNA to improve its stability and protein coding potential remains challenging due to lack of structure prediction tool and sequence design algorithm for endless circular-shaped RNA. In this study, we presented circDesign, a computational approach to achieve optimal design of the circRNA with enhanced circularization efficiency, stability, and translatability. Using rabies virus glycoprotein (RABV-G) and varicella-zoster virus (VZV) glycoprotein gE as the exemplified antigens, we demonstrated that optimized circRNAs encoding corresponding antigens exhibited higher stability and protein translation efficiencyin vitro. Formulated by proprietary delivery system lipopolyplex (LPP), the optimized circRNA vaccines encoding RABV-G or VZV gE antigen further elicited enhanced humoral and cellularin vivoimmune responses in mice. Taken together, this circular RNA design approach provided a general strategy to leverage the capability of circRNA as next generation vaccines or therapeutics.