bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuron secreted chemokine-like Orion is involved in the transformation of glial cells into phagocytes in different neuronal remodeling paradigms
Authors: Perron Clarisse , Carme Pascal , Rosell Arnau Llobet , Minnaert Eva , Demoulin Salomé Ruiz , Szczkowski Héloïse , Neukomm Lukas Jakob , Dura Jean-Maurice , Boulanger Ana 
Published: December 2022

SummaryDuring animal development, neurons often form exuberant or incorrect axons and dendrites at early stages, followed by the refinement of neuronal circuits at late stages. Neural circuit refinement leads to the production of large amounts of neuronal debris in the form of neuronal cell corpses, fragmented axons and dendrites, and pruned synapses requiring disposal. In particular, the predominant phagocytes acting during the neuronal remodeling and degeneration are glial cells and critical signaling pathways between neurons and glia leading to phagocytosis are required. Chemokine-like mushroom body neuron secreted Orion ligand was shown to be essential to the astrocyte infiltration into the γ axon bundle leading to γ axon pruning and clearance of debris left from axon fragmentation. Here we show a role oforionalso in debris engulfment and phagocytosis. Interestingly, we show thatorionis also involved in the overall transformation of astrocytes into phagocytes. In addition, analysis of several neuronal paradigms demonstrates the role oforionin the elimination of both peptidergic vCrz+and PDF-Tri neuronsviaadditional phagocytic glial cells as cortex and/or ensheathing glia. Our results suggest that Orion is essential for phagocytic activation of three different types of glial cells: astrocytes, cortex and ensheathing glia and point to Orion as a trigger not only of glial infiltration but also engulfment and phagocytosis.
Improved humoral immunity and protection against influenza virus infection with a 3D porous biomaterial vaccine
Authors: Miwa Hiromi , Antao Olivia Q , Kelly-Scumpia Kindra M. , Baghdasarian Sevana , Mayer Daniel P. , Shang Lily , Sanchez Gina M. , Archang Maani M , Scumpia Philip O. , Weinstein Jason S , Carlo Dino Di 
Published: December 2022

AbstractNew vaccine platforms that properly activate humoral immunity and generate neutralizing antibodies are required to combat emerging and re-emerging pathogens, including influenza virus. Biomaterial scaffolds with macroscale porosity have demonstrated tremendous promise in regenerative medicine where they have been shown to allow immune cell infiltration and subsequent activation, but whether these types of materials can serve as an immunization platform is unknown. We developed an injectable immunization platform that uses a slurry of antigen-loaded hydrogel microparticles that anneal to form a porous scaffold with high surface area for antigen uptake by infiltrating immune cells as the biomaterial degrades to maximize humoral immunity. Antigen-loaded-microgels elicited a robust cellular humoral immune response, with increased CD4+T follicular helper (Tfh) cells and prolonged germinal center (GC) B cells comparable to the commonly used adjuvant, aluminum hydroxide (Alum). By simply increasing the weight fraction of polymer material, we enhanced material stiffness and further increased antigen-specific antibody titers superior to Alum. Vaccinating mice with inactivated influenza virus loaded into this more highly crosslinked formulation elicited a strong antibody response and provided better protection against a high dose viral challenge than Alum. Thus, we demonstrate that by tuning physical and chemical properties alone, we can enhance adjuvanticity and promote humoral immunity and protection against a pathogen, leveraging two different types of antigenic material: individual protein antigen and inactivated virus. The flexibility of the platform may enable design of new vaccines to enhance innate and adaptive immune cell programming to generate and tune high affinity antibodies, a promising approach to generate long-lasting immunity against specific pathogens.
novoRNABreak: local assembly for novel splice junction and fusion transcript detection from RNA-seq data
Authors: Tan Yukun , Mohanty Vakul , Liang Shaoheng , Ma Jun , Kim Kun Hee , Bonder Marc Jan , Shi Xinghua , Lee Charles ,   Human Genome Structural Variation Consortium, Chong Zechen , Chen Ken 
Published: December 2022

ABSTRACTWe present novoRNABreak, a unified framework for cancer specific novel splice junction and fusion transcript detection in RNA-seq data obtained from human cancer samples. novoRNABreak is based on a local assembly model, which offers a tradeoff between the alignment-based and de novo whole transcriptome assembly (WTA) approaches, namely, being more sensitive in assembling novel junctions that cannot be directly aligned, and more efficient due to the strategy that focuses on junctions rather than full-length transcripts. The performance of novoRNABreak is demonstrated by a comprehensive set of experiments using synthetic data generated based on genome reference, as well as real RNA-seq data from breast cancer and prostate cancer samples. The results show that novoRNABreak can detect novel splice junctions and fusion transcripts efficiently with high sensitivity and reasonable specificity.
Primary infection with Zika virus provides one-way heterologous protection against Spondweni virus infection in rhesus macaques
Authors: Jaeger Anna S. , Crooks Chelsea M. , Weiler Andrea M. , Bliss Mason I. , Rybarczyk Sierra , Richardson Alex , Einwalter Morgan , Peterson Eric , Capuano Saverio , Barkhymer Alison , Becker Jordan T. , Greene Joseph T. , Freedman Tanya S. , Langlois Ryan A. , Friedrich Thomas C. , Aliota Matthew T. 
Published: December 2022

AbstractSpondweni virus (SPONV) is the closest known relative of Zika virus (ZIKV). SPONV pathogenesis resembles that of ZIKV in pregnant mice, and both viruses are transmitted byAedes aegyptimosquitoes. We aimed to develop a translational model to further understand SPONV transmission and pathogenesis. We found that cynomolgus macaques (Macaca fascicularis) inoculated with ZIKV or SPONV were susceptible to ZIKV, but resistant to SPONV infection. In contrast, rhesus macaques (Macaca mulatta) supported productive infection with both ZIKV and SPONV and developed robust neutralizing antibody responses. Crossover serial challenge in rhesus macaques revealed that SPONV immunity did not protect against ZIKV infection, whereas ZIKV immunity was fully protective against SPONV infection. These findings establish a viable model for future investigation into SPONV pathogenesis, and suggest the risk of SPONV emergence is low in areas with high ZIKV seroprevalence due to one-way cross-protection between ZIKV and SPONV.TeaserIdentification of asymmetric immune interactions between Zika and Spondweni viruses in macaque monkeys.
The microRNomes of Chinese Hamster Ovary (CHO) cells and their extracellular vesicles, and how they respond to osmotic and ammonia stress
Authors: Belliveau Jessica , Papoutsakis Eleftherios T. 
Published: December 2022

AbstractA new area of focus in Chinese Hamster Ovary (CHO) biotechnology is the role of small (exosomes) and large (microvesicles or microparticles) extracellular vesicles (EVs). CHO cells in culture exchange large quantities of proteins and RNA through these EVs, yet the content and role of these EVs remain elusive. MicroRNAs (miRs) are central to adaptive responses to stress and more broadly to changes in culture conditions. Given that EVs are highly enriched in miRs, and that EVs release large quantities of miRs bothin vivoandin vitro, EVs and their miR content likely play an important role in adaptive responses. Here we report the miRNA landscape of CHO cells and their EVs under normal culture conditions and under ammonia and osmotic stress. We show that both cells and EVs are highly enriched in five miRs (among over 600 miRs) that make up about half of their total miR content, and that these highly enriched miRs differ significantly between normal and stress culture conditions. Notable is the high enrichment in mir-92a and miR-23a under normal culture conditions, in contrast to the high enrichment in let-7 family miRs (let-7c, let-7b and let-7a) under both stress conditions. The latter suggests a preserved stress-responsive function of the let-7 miR family, one of the most highly preserved miR families across species, where among other functions, let-7 miRs regulate core oncogenes, which, depending on the biological context, may tip the balance between cell cycle arrest and apoptosis. While the expected –based on their profound enrichment – important role of these highly enriched miRs remains to be dissected, our data and analysis constitute an important resource for exploring the role of miRs in cell adaptation as well as for synthetic applications.
Census of exposed aggregation-prone regions in proteomes
Authors: Falgarone Théo , Villain Etienne , Richard Francois , Osmanli Zarifa , Kajava Andrey V. 
Published: December 2022

ABSTRACTLoss of solubility usually leads to the detrimental elimination of protein function. In some cases, the protein aggregation is also required for beneficial functions. Given the duality of this phenomenon, it remains a fundamental question how natural selection controls the aggregation. The exponential growth of genomic sequence data and recent progress within silicopredictors of the aggregation allows approaching this problem by a large-scale bioinformatics analysis. Most of the aggregation-prone regions are hidden within the 3D structures and, therefore, they cannot realize their potential to aggregate. Thus, the most realistic census of the aggregation prone regions requires crossing aggregation prediction with information about the location of the natively unfolded regions. This allows us to detect so-called “Exposed Aggregation-prone Regions” (EARs). Here, we analyzed the occurrence and distribution of the EARs in 76 full reference proteomes from the three kingdoms of life. For this purpose, we used a bioinformatics pipeline, which provides a consensual result based on several predictors of aggregation. Our analysis revealed a number of new statistically significant correlations about the presence of EARs in different organisms, their dependence on protein length, cellular localizations, co-occurrence with short linear motifs, and the level of protein expression. We also obtained a list of proteins with the conserved aggregation-prone sequences for further experimental tests. Insights gained from this work led to a deeper understanding of the functional and evolutionary relations of the protein aggregation.
Drug-induced changes in connectivity to midbrain dopamine cells revealed by rabies monosynaptic tracing
Authors: Bartas Katrina , Hui May , Derdeyn Pieter , Tian Guilian , Vasquez Jose J. , Azouz Ghalia , Yamamoto Cindy M. , Beier Kevin T. 
Published: December 2022

ABSTRACTDrugs of abuse cause long-lasting changes in connectivity from inputs onto ventral tegmental area dopamine cells (VTADA) that contribute to drug-induced behavioral adaptations. However, it is not known which inputs are altered. Here we used a rabies virus-based mapping strategy to quantify rabies-labeled inputs to VTA cells after a single exposure to one of a variety of abused drugs – cocaine, amphetamine, methamphetamine, morphine, and nicotine – and compared the relative global input labeling across conditions. We observed that all tested drugs of abuse elicited similar input changes onto VTADAcells, in particular onto DA cells projecting to the lateral shell of the nucleus accumbens and amygdala. In addition, repeated administration of ketamine/xylazine to induce anesthesia induces a change in inputs to VTADAcells that is similar to but different from those elicited by a single exposure to drugs of abuse, suggesting that caution should be taken when using ketamine/xylazine-based anesthesia in rodents when assessing motivated behaviors. Furthermore, comparison of viral tracing data to an atlas of gene expression in the adult mouse brain showed that the basal expression patterns of several gene classes, especially calcium channels, were highly correlated with the extent of both addictive drug- or ketamine/xylazine-induced changes in rabies-labeled inputs to VTADAcells. Reducing expression levels of the voltage-gated calcium channelCacna1ein cells in the nucleus accumbens lateral shell reduced rabies-mediated input labeling of these cells into VTADAcells. These results directly link genes controlling cellular excitability and the extent of input labeling by the rabies virus.
Lung extracellular matrix modulates KRT5+basal cell activity in pulmonary fibrosis
Authors: Hewitt Richard J. , Puttur Franz , Gaboriau David C. A. , Fercoq Frédéric , Fresquet Maryline , Traves William J. , Yates Laura L. , Walker Simone A. , Molyneaux Philip L. , Kemp Samuel V. , Nicholson Andrew G. , Rice Alexandra , Lennon Rachel , Carlin Leo M. , Byrne Adam J. , Maher Toby M. , Lloyd Clare M. 
Published: December 2022

AbstractAberrant expansion of KRT5+basal cells in the distal lung accompanies progressive alveolar epithelial cell loss and tissue remodelling during fibrogenesis in idiopathic pulmonary fibrosis (IPF). The mechanisms determining activity of KRT5+cells in IPF have not been delineated. Here, we reveal a potential mechanism by which KRT5+cells migrate within the fibrotic lung, navigating regional differences in collagen topography.In vitro, KRT5+cell migratory characteristics and expression of remodelling genes are modulated by extracellular matrix (ECM) composition and organisation. Mass spectrometry-based proteomics revealed compositional differences in ECM components secreted by primary human lung fibroblasts (HLF) from IPF patients compared to controls. Over-expression of ECM glycoprotein, Secreted Protein Acidic and Cysteine Rich (SPARC) in the IPF HLF matrix restricts KRT5+cell migrationin vitro. Together, our findings demonstrate how changes to the ECM in IPF directly influence KRT5+cell behaviour and function contributing to remodelling events in the fibrotic niche.
A chromosome-scale high-contiguity genome assembly of the threatened cheetah (Acinonyx jubatus)
Authors: Winter Sven , Meißner René , Greve Carola , Hamadou Alexander Ben , Horin Petr , Prost Stefan , Burger Pamela A. 
Published: December 2022

AbstractThe cheetah (Acinonyx jubatus, SCHREBER 1775) is a large felid and is considered the fastest land animal. Historically, it inhabited open grassland across Africa, the Arabian Peninsula, and southwestern Asia; however, only small and fragmented populations remain today. Here, we present a de novo genome assembly of the cheetah based on PacBio continuous long reads and Hi-C proximity ligation data. The final assembly (VMU_Ajub_asm_v1.0) has a total length of 2.38 Gb, of which 99.7% are anchored into the expected 19 chromosome-scale scaffolds. The contig and scaffold N50 values of 96.8 Mb and 144.4 Mb, respectively, a BUSCO completeness of 95.4% and a k-mer completeness of 98.4%, emphasize the high quality of the assembly. Furthermore, annotation of the assembly identified 23,622 genes and a repeat content of 40.4%. This new highly contiguous and chromosome-scale assembly will greatly benefit conservation and evolutionary genomic analyses and will be a valuable resource, e.g., to gain a detailed understanding of the function and diversity of immune response genes in felids.
A computational model ofPseudomonas syringaemetabolism unveils the role of branched-chain amino acids in virulence expression at the early stages of Arabidopsis colonization
Authors: Tubergen Philip J. , Medlock Greg , Moore Anni , Zhang Xiaomu , Papin Jason A. , Danna Cristian H. 
Published: December 2022

ABSTRACTLeaf mesophyll-colonizing bacterial pathogens infect their plant hosts by adjusting their metabolism to the leaf mesophyll environment. Soon after the inoculation of naïve, susceptible plants, the model bacterial pathogenPseudomonas syringaepv.tomatoDC3000 (PstDC3000) expresses virulence factors that suppress plant immunity, a requirement to produce robust infections. However, if plant immunity was elicited with Microbe-Associated Molecular-Patterns (MAMPs) prior to bacterial inoculation,PstDC3000 slows down virulence expression and only produces symptomless mild infections. To understand how bacterial metabolism adapts to these two contrasting conditions, we created iPst19, anin silicoensemble of genome-scale metabolic reconstructions. Constraining thein silicogrowth of iPst19 within planta PstDC3000 gene expression data revealed that sugar catabolism is highly active in bacteria that have been inoculated in mock-treated plants. In contrast, branched-chain amino acids (BCAAs) catabolism is highly active in bacteria that have been inoculated in MAMP-pretreated plants. Bacterial growth and gene expression analysis showed that BCAAs suppress virulence gene expression without affecting bacterial growthin vitro. In planta, however, BCAAs suppress the expression of virulence genes at the early stages of the infection and significantly impair leaf colonization of the host plantArabidopsis thaliana. While the overexpression of the conserved bacterial leucine-responsive transcriptional regulatorLrpinduced the expression of virulence genes, its downregulation had the opposite effect, suggesting that BCAA-free Lrp induces virulence while BCAA-Lrpdoes not. Overall, our data provide mechanistic connections to understand how plant immunity impactsPstDC3000 metabolism and virulence, furthering our understanding of bacterial pathogenesis and plant disease.
A data assimilation method to track time-varying changes in the excitation-inhibition balance using scalp EEG
Authors: Yokoyama Hiroshi , Kitajo Keiichi 
Published: December 2022

AbstractRecent neuroscience studies have suggested that controlling the excitation and inhibition (E/I) balance is essential for maintaining normal brain function. However, while control of time-varying E/I balance is considered essential for perceptual and motor learning, an efficient method for estimating E/I balance changes has yet to be established. To tackle this issue, we propose a new method to estimate E/I balance changes by applying neural-mass model-based tracking of the brain state using the Ensemble Kalman Filter. In this method, the parameters of synaptic E/I gains in the model are estimated from observed electroencephalography (EEG) signals. Moreover, the index of E/I balance was defined by calculating the ratio between synaptic E/I gains based on estimated parameters. The method was validated by showing that it could estimate E/I balance changes from human EEG data at the sub-second scale, indicating that it has the potential to quantify how time-varying changes in E/I balance influence changes in perceptual and motor learning. Furthermore, this method could be used to develop an E/I balance-based neurofeedback training method for clinical use.
LRRK2 Suppresses Lysosome Degradative Activity in Macrophages and Microglia Through MiT-TFE Transcription Factor Inhibition
Authors: Yadavalli Narayana , Ferguson Shawn M. 
Published: December 2022

AbstractCells maintain optimal levels of lysosome degradative activity to protect against pathogens, clear waste and generate nutrients. Here we show that LRRK2, a protein that is tightly linked to Parkinson’s disease, negatively regulates lysosome degradative activity in macrophages and microglia via a transcriptional mechanism. Depletion of LRRK2 and inhibition of LRRK2 kinase activity enhanced lysosomal proteolytic activity and increased the expression of multiple lysosomal hydrolases. Conversely, the kinase hyperactive LRRK2 G2019S Parkinson’s disease mutant suppressed lysosomal degradative activity and gene expression. We identified MiT-TFE transcription factors (TFE3, TFEB and MITF) as mediators of LRRK2-dependent control of lysosomal gene expression. LRRK2 negatively regulated the abundance and nuclear localization of these transcription factors and their depletion prevented LRRK2-dependent changes in lysosome protein levels. These discoveries define a role for LRRK2 in controlling lysosome degradative activity and support a model wherein LRRK2 hyperactivity may increase Parkinson’s disease risk by suppressing lysosome degradative activity.Significance StatementThis study defines a homeostatic mechanism that allows macrophages and microglia to match the degradative activity of their lysosomes to ongoing changes in cellular demand. It shows that the leucine rich repeat kinase 2 (LRRK2) protein suppresses lysosome degradative activity by inhibiting the expression and nuclear localization of the MiT-TFE family of transcription factors that control the expression of multiple genes that encode lysosome proteins. It further demonstrates that a Parkinson’s disease mutation that hyperactivates LRRK2 kinase activity limits the degradative activity of lysosomes more strongly. These findings support a model wherein LRRK2 protects cells from excessive lysosome degradative activity and suggest that overactivation of this pathway may increase Parkinson’s disease risk by limiting the degradative activity of lysosomes.
Evaluation ofMycobacterium Tuberculosisenrichment in metagenomic samples using ONT adaptive sequencing and amplicon sequencing for identification and variant calling
Authors: Su Junhao , Lui Wui Wang , Lee YanLam , Zheng Zhenxian , Siu Gilman Kit-Hang , Ng Timothy Ting-Leung , Zhang Tong , Lam Tommy Tsan-Yuk , Lao Hiu-Yin , Yam Wing-Cheong , Tam Kingsley King-Gee , Leung Kenneth Siu-Sing , Lam Tak-Wah , Leung Amy Wing-Sze , Luo Ruibang 
Published: December 2022

AbstractSensitive detection ofMycobacterium Tuberculosis(TB) in small percentages in metagenomic samples is essential for microbial classification and drug resistance prediction, and assisting in diagnosis and treatment planning. However, traditional methods, such as bacterial culture and microscopy, are time-consuming and sometimes have limited TB detection sensitivity. Oxford Nanopore Technologies’ MinION sequencing allows rapid and simple sample preparation for whole genome and amplicon sequencing. Its recently developed adaptive sequencing selects reads from targets, while allowing real-time base-calling during sequencing to achieve sequence enrichment or depletion. Another common enrichment method is PCR amplification of the target TB genes. In this study, we compared both methods with MinION sequencing for TB detection and variant calling in metagenomic samples using both simulation runs and those with synthetic and patient samples. We found that both methods effectively enrich TB reads from a high percentage of human and other microbial DNA. We provide a simple automatic analysis framework, including quality filtering, taxonomic classification, variant calling, and antimicrobial resistance prediction, to support these detection workflows for clinical use, openly available athttps://github.com/HKU-BAL/ONT-TB-NF. Depending on the patient’s medical condition and sample type (commonly including bronchoalveolar lavage fluid, blood samples, sputum, and tissues), we discuss the findings and recommend that users optimize their workflow to improve the detection limit.