bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneity and developmental dynamics of LYVE-1 perivascular macrophages distribution in the mouse brain
Authors: Karam Marie , Malkinson Guy , Brunet Isabelle 
Published: October 2021

AbstractBrain perivascular macrophages (PVMs) belong to border-associated macrophages. PVMs are situated along blood vessels in the Virchow-Robin space and are thus found at a unique anatomical position between the endothelium and the parenchyma. Owing to their location and phagocytic capabilities, PVMs are regarded as important components that regulate various aspects of brain physiology in health and pathophysiological states. Here, used LYVE-1 to identify PVMs in the mouse brain. We used brain-tissue sections and cleared whole-brains to learn how they are distributed within the brain and across different developmental postnatal stages. We find that LYVE-1+ PVMs associate with the vasculature in a brain-region-dependent manner, where the hippocampus shows the highest density of LYVE-1+ PVMs. We show that their postnatal distribution is developmentally dynamic and peaks at P10-P20 depending on the brain region. We further demonstrate that their density is reduced in the APP/PS1 mouse model of Alzheimer’s Disease. In conclusion, our results show an unexpected heterogeneity and dynamics of LYVE-1+ PVMs, and support an important role for this population of PVMs during development and in regulating brain functions in steady-state and disease conditions.
Age-related change in task-evoked amygdala—prefrontal circuitry: a multiverse approach with an accelerated longitudinal cohort aged 4-22 years
Authors: Bloom Paul Alexander , VanTieghem Michelle , Gabard-Durnam Laurel , Gee Dylan G. , Flannery Jessica , Caldera Christina , Goff Bonnie , Telzer Eva H. , Humphreys Kathryn L. , Fareri Dominic S. , Shapiro Mor , Algharazi Sameah , Bolger Niall , Aly Mariam , Tottenham Nim 
Published: October 2021

AbstractThe amygdala and its connections with medial prefrontal cortex (mPFC) play central roles in the development of emotional processes. While several studies have suggested that this circuitry exhibits functional changes across the first two decades of life, findings have been mixed – perhaps resulting from differences in analytic choices across studies. Here we used multiverse analyses to examine the robustness of task-based amygdala–mPFC function findings to analytic choices within the context of an accelerated longitudinal design (4-22 years- old; N=98; 183 scans; 1-3 scans/participant). Participants, recruited from the greater Los Angeles area, completed an event-related emotional face (fear, neutral) task. Parallel analyses varying in preprocessing and modeling choices found that age-related change estimates for amygdala reactivity were more robust than task-evoked amygdala–mPFC functional connectivity to varied analytical choices. Specification curves indicated evidence for age-related decreases in amygdala reactivity to faces, though within-participant changes in amygdala reactivity could not be differentiated from between-participant differences. In contrast, amygdala—mPFC functional connectivity results varied across methods much more, and evidence for age-related change in amygdala–mPFC connectivity was not consistent. Generalized psychophysiological interaction (gPPI) measurements of connectivity were especially sensitive to whether a deconvolution step was applied. Our findings demonstrate the importance of assessing the robustness of findings to analysis choices, although the age-related changes in our current work cannot be overinterpreted given low test-retest reliability. Together, these findings highlight both the challenges in estimating developmental change in longitudinal cohorts and the value of multiverse approaches in developmental neuroimaging for assessing robustness of results. (Preprint: https://www.biorxiv.org/content/10.1101/2021.10.08.463601v1).Key PointsMultiverse analyses applied to fMRI data are valuable for determining the robustness of findings to varied analytical choicesIn the current study, age-related change estimates for amygdala reactivity were relatively robust to analytical decisions, though gPPI functional connectivity analyses were much more sensitive, leading some estimates to flip signBoth test-retest reliability and robustness to analytical choices are important considerations for developmental research
Prediction and Expression Analysis of Deleterious Nonsynonymous SNPs of Arabidopsis ACD11 Gene by Combining Computational Algorithms and Molecular Docking Approach
Authors: Rifat Mahmudul Hasan , Ahmed Jamil , Ahmed Milad , Ahmed Foeaz , Gulsan Airin , Hasan Mahmudul 
Published: October 2021

AbstractAccelerated cell death 11 (ACD11) is an autoimmune gene that suppresses pathogen infection in plants by preventing plant cells from becoming infected by any pathogen. This gene is widely known for growth inhibition, premature leaf chlorosis, and defense-related programmed cell death (PCD) in seedlings before flowering in Arabidopsis plant. Specific amino acid changes in the ACD11 protein’s highly conserved domains are linked to autoimmune symptoms including constitutive defensive responses and necrosis without pathogen awareness. The molecular aspect of the aberrant activity of the ACD11 protein is difficult to ascertain. The purpose of our study was to find the most deleterious mutation position in the ACD11 protein and correlate them with their abnormal expression pattern. Using several computational methods, we discovered PCD vulnerable single nucleotide polymorphisms (SNPs) in ACD11. We analysed the RNA-Seq data, identified the detrimental nonsynonymous SNPs (nsSNP), built genetically mutated protein structures and used molecular docking to assess the impact of mutation. Our results demonstrated that the A15T and A39D variations in the GLTP domain were likely to be extremely detrimental mutations that inhibit the expression of the ACD11 protein domain by destabilizing its composition, as well as disrupt its catalytic effectiveness. When compared to the A15T mutant, the A39D mutant was more likely to destabilize the protein structure. In conclusion, these mutants can aid in the better understanding of the vast pool of PCD susceptibilities connected to ACD11 gene GLTP domain activation.
Development of transcriptomics-based eukaryotes growth rate indices
Authors: Kong Wye-Lup , Machida Ryuji J. 
Published: October 2021

AbstractGrowth rate estimation is important to understand the flow of energy and nutrient elements in an ecosystem, but it has remained challenging, especially on microscopic organisms.In this study, we propose four growth rate indices that use mRNA abundance ratios between nuclear and mitochondrial genes: (1) total nuclear and mitochondrial mRNA ratio (Nuc:Mito-TmRNA), (2) nuclear and mitochondrial ribosomal protein mRNA ratio (Nuc:Mito-RPmRNA), (3) gene ontology (GO) terms and total mitochondrial mRNA ratios and (4) nuclear and mitochondrial specific gene mRNA ratio. We examine these proposed ratios using RNA-Seq datasets of Daphnia magna and Saccharomyces cerevisiae.The results showed that both Nuc:Mito-TmRNA and Nuc:Mito-RPmRNA ratio indices showed significant correlations with the growth rate for both species. A large number of GO terms mRNA ratios showed significant correlations with the growth rate of S. cerevisiae. Lastly, we identified mRNA ratios of several specific nuclear and mitochondrial gene pairs that showed significant correlations.We foresee future implications for the proposed mRNA ratios used in metatranscriptome analyses to estimate the growth rate of communities and species.
Social information use for spatial decision inZootoca vivipara
Authors: Brevet M. , Jacob S. , Rutschmann A. , Richard M. , Cote J. , Clobert J. 
Published: October 2021

AbstractMovements of individuals are conditioned by information acquisition coming from either personal or social sources. Yet, little is known about the processes used by individuals to make movement decisions when facing multiple sources of social information simultaneously. This study aimed to test experimentally how social information from multiple sources is used to make movement decisions, and whether a contrast in this information allows individuals to orientate in space. We used common lizards (Zootoca vivipara) in a replicated experimental setting: one focal individual received information from two other individuals coming from peripheral environments, before being given the opportunity to relocate in one or another of the peripheral environments.Our analyses revealed that the behavior of informants, their mother’s morphology, as well as the quality of informants’ environment, affected movement decisions: the probability to relocate from the focal area increased when informants displayed traits associated with low resources (no food intake, poor maternal condition) or high competition (high activity). The physical condition of individuals also mediated the use of social information about food intake, with a match between resource availability in informants and personal condition. Conversely, spatial orientation was not affected by the contrast of phenotype between informants nor by spatial variability in resource availability.This study highlights that multiple social information sources can be used for movement decisions, likely because these information sources reflect the quality of the surrounding environment (e.g., competition level or resources availability). It also emphasizes that social information use for movement is conditioned by individual phenotype.
Immune cell multi-omics analysis reveals contribution of oxidative phosphorylation to B cell functions and organ damage of lupus
Authors: Takeshima Yusuke , Iwasaki Yukiko , Nakano Masahiro , Narushima Yuta , Ota Mineto , Nagafuchi Yasuo , Sumitomo Shuji , Okamura Tomohisa , Elkon Keith B , Ishigaki Kazuyoshi , Suzuki Akari , Kochi Yuta , Yamamoto Kazuhiko , Fujio Keishi 
Published: October 2021

AbstractObjectiveSystemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disease, with a poor long-term prognosis. The type I interferon (IFN) signature, a prominent feature of SLE, is not an ideal therapeutic target or outcome predictor. To explore immunological pathways in SLE more precisely, we performed integrative analysis of transcriptomics, epigenomics, and genomics using each immune cell subset from peripheral blood.MethodsWe sorted 18 immune cell subsets and identified the mRNA expression profiles and genetic polymorphisms in 107 SLE patients and 92 healthy controls. Open chromatin information was also taken by ATAC-seq analysis. Combined differentially expressed genes (DEGs) and expression quantitative trait loci (eQTL) analysis was conducted to find key driver genes in SLE pathogenesis.ResultsWe found transcriptomic, epigenetic, and genetic importance of oxidative phosphorylation (OXPHOS)/mitochondrial dysfunction in SLE memory B cells. Particularly, we identified an OXPHOS-regulating gene, PRDX6, as a key driver in SLE B cells. Prdx6–deficient B cells showed upregulated mitochondrial respiration as well as antibody production. We revealed OXPHOS signature was associated with type I IFN signaling-related genes (ISRGs) signature in SLE memory B cells. Furthermore, the gene sets related to innate immune signaling among ISRGs presented correlation with OXPHOS and these two signatures showed associations with SLE organ damage as well as specific clinical phenotypes.ConclusionThis work elucidated the potential prognostic marker for SLE. Since OXPHOS consists of the electron transport chain, a functional unit in mitochondria, these findings suggest the importance of mitochondrial dysfunction as a key immunological pathway involved in SLE.
A COMPARATIVE ANALAYSIS OF INTER-SITE GENE EXPRESSION HETEROGENICITY OF NORMAL HUMAN BUCCAL MUCOSA WITH NORMAL GINGIVAL MUCOSA
Authors: Rooban Thavarajah , Ranganathan Kannan 
Published: October 2021

ABSTRACTBACKGROUNDDescription of heterogeneity of gene expression of various human intraoral sites are not adequate. The aim of this study was to explore the difference of gene expression profiles of whole tissue obtained from apparently normal human gingiva and buccal mucosa (HGM, HBM).MATERIALS AND METHODSGene sets fulfilling inclusion and exclusion criteria of HGM and HBM in gene Expression Omnibus(GEO) database were identified, segregated, filtered and analysed using the ExAtlas online web tool using pre-determined cut-off. The differentially expressed genes were studied for epithelial keratinization related, housekeeping(HKG), extracellular matrix related(ECMRG) and epithelial-mesenchymal transition related genes(EMTRGs).RESULTSIn all 40 HBM and 64 HGM formed the study group. In all there were 18012 significantly expressed genes. Of this, 1814 were over-expressed and 1862 under-expressed HBM genes as compared to HGM. One in five of all studied genes significantly differed between HBM and HGM. For the keratinization genes, 1 in 6 differed. One of every 5 HKG-proteomics genes differed between HBM and HGM, while this ratio was 1-in 4 for all ECMRGs and EMTRGs.DISCUSSIONThis difference in the gene expression between the HBM and HGM could possibly influence a multitude of biological pathways. This result could explain partly the difference in clinicopathological features of oral lesions occurring in HBM and HGM. The innate genotypic difference between the two intra-oral niches could serve as confounding factor in genotypic studies. Hence studies that compare the HBM and HGM should factor-in these findings while evaluating their results.
Lpnet: Reconstructing Phylogenetic Networks from Distances Using Integer Linear Programming
Authors: Guo Mengzhen , Grünewald Stefan 
Published: October 2021

AbstractWe present Lpnet, a variant of the widely used Neighbor-net method that approximates pairwise distances between taxa by a circular phylogenetic network. We first apply standard methods to construct a binary phylogenetic tree and then use integer linear programming to compute an optimal circular orderings that agrees with all tree splits. This approach achieves an improved approximation of the input distance for the clear majority of experiments that we have run for simulated and real data. We release an implementation in R that can handle up to 94 taxa and usually needs about one minute on a standard computer for 80 taxa. For larger taxa sets, we include a top-down heuristic which also tends to perform better than Neighbor-net.
HyINDEL – A Hybrid approach for Detection of Insertions and Deletions
Authors: Thatikunta Alok , Parekh Nita 
Published: October 2021

AbstractInsertion and deletion (INDELs) mutations, the most common type of structural variation in the human genome, have been implicated in numerous human traits and diseases including rare genetic disorders and cancer. Next generation sequencing (NGS) technologies have drastically reduced the cost of sequencing whole genomes, greatly contributing to genome-wide detection of structural variants. However, due to large variations in INDEL sizes and presence of low complexity and repeat regions, their detection remains a challenge. Here we present a hybrid approach, HyINDEL, which integrates clustering, split-mapping and assembly-based approaches, for the detection of INDELs of all sizes (from small to large) and also identifies the insertion sequences. The method starts with identifying clusters of discordant and soft-clip reads which are validated by depth-of-coverage and alignment of soft-clip reads to identify candidate INDELs, while the assembly -based approach is used in identifying the insertion sequence. Performance of HyINDEL is evaluated on both simulated and real datasets and compared with state-of-the-art tools. A significant improvement in recall and F-score metrics as well as in breakpoint support is observed on using soft-clip alignments. It is freely available at https://github.com/alok123t/HyINDEL.
Trait-environment relationship in tadpoles of the southern Atlantic Forest
Authors: dos Santos Roseli Coelho , Brum Diego , Dalmolin Diego , Farina Renata Krentz , Lucas Elaine Maria , Tozetti Alexandro Marques 
Published: October 2021

AbstractEnvironmental predictors select individuals by their functional traits, shaping the anuran assembly patterns. Individuals respond to environmental filters that can be on a local or regional scale.In this study, we investigated the association between local (water and microhabitat) and landscape variables and the morphological traits of tadpoles of ponds and streams. The study was conducted in the southern region of the Brazilian Atlantic Forest. We sampled 28 waterbodies and recorded 22 anurans species. We performed RLQ and fourth-corner analyses to determine the patterns of trait-environment relationships and determine which environmental and landscape variables influence the morphological characteristics of tadpoles from streams and ponds.We found that the morphological traits of tadpoles are influenced mainly by physicochemical and microhabitat attributes, being distinct between ponds and streams. In ponds, water depth, pH, and the presence of vegetation influence the morphological traits of the tadpoles, while in the streams water pH, temperature, conductivity, total alkalinity, Alk HCO3, and microhabitat variables played a major role in defining the traits.Our results indicate that local components of habitat (water characteristics and microhabitat) influence functional traits of tadpoles in both ponds and streams, especially those supposedly related to locomotory, foraging and prey-detection abilities.
Anti-cancer potential of cannabis terpenes in a taxol-resistant model of breast cancer
Authors: Tomko Andrea M. , Whynot Erin G. , O’Leary Lauren F. , Dupré Denis J. 
Published: October 2021

AbstractChemotherapeutic resistance can limit breast cancer outcomes; therefore, the exploration of novel therapeutic options is warranted. Isolated compounds found in cannabis have previously been shown to exhibit anti-cancer effects, but little is known about their effects in resistant breast cancer. Our study aims to evaluate the effects of terpenes found in cannabis in in vitro chemotherapy-resistant model of breast cancer. We aimed to identify whether five terpenes found in cannabis produced anti-cancer effects, and if their effects were improved upon co-treatment with cannabinoids and flavonoids also found in cannabis. Nerolidol and β-caryophyllene produced the greatest cytotoxic effects, activated the apoptotic cascade and reduced cellular invasion. Combinations with the flavonoid kaempferol potentiated the cytotoxic effects of ocimene, terpinolene, and β-myrcene. Combinations of nerolidol and Δ9-tetrahydrocannabinol or cannabidiol produced variable responses ranging from antagonism and additivity to synergy, depending on concentrations used. Our results indicate that cannabis terpenes, alone or combined with cannabinoids and flavonoids, produced anti-cancer effects in chemotherapy-resistant breast cancer cell lines. This study is a first step in the identification of compounds that could have therapeutic potential in the treatment of resistant breast cancer.
Precise control of microtubule disassembly in living cells
Authors: Liu Grace Y. , Chen Shiau-Chi , Shaiv Kritika , Hong Shi-Rong , Yang Wen-Ting , Huang Shih-Han , Chang Ya-Chu , Cheng Hsuan , Lin Yu-Chun 
Published: October 2021

AbstractMicrotubules (MTs) are components of the evolutionarily conserved cytoskeleton, which tightly regulates various cellular activities. Our understanding of MTs is largely based on MT-targeting agents, which, however, are insufficient to dissect the dynamic mechanisms of specific MT populations due to their slow effects on the entire pool of MTs in cells. To address this limitation, we have used chemogenetics and optogenetics to disassemble specific MT subtypes by rapid recruitment of engineered MT-cleaving enzymes. Acute MT disassembly swiftly halted vesicular trafficking and lysosome dynamics. We also used this approach to disassemble MTs specifically modified by tyrosination and several MT-based structures including primary cilia, mitotic spindles, and intercellular bridges. These effects were rapidly reversed by inhibiting the activity or MT association of the cleaving enzymes. The disassembly of targeted MTs with spatial and temporal accuracy enables to uncover new insights of how MTs precisely regulate cellular architectures and functions.
Quantitative multiplex immunohistochemistry reveals inter-patient lymphovascular and immune heterogeneity in primary cutaneous melanoma
Authors: Femel Julia , Booth Jamie L. , Asnaashari Tina G. , Leachman Sancy A. , Tsujikawa Takahiro , White Kevin P. , Chang Young H. , Lund Amanda W. 
Published: October 2021

ABSTRACTPurposeQuantitative, multiplexed imaging is revealing complex spatial relationships between phenotypically diverse tumor infiltrating leukocyte populations and their prognostic implications. The underlying mechanisms and tissue structures that determine leukocyte distribution within and around tumor nests, however, remain poorly understood. While presumed players in metastatic dissemination, new preclinical data demonstrates that blood and lymphatic vessels (lymphovasculature) also dictate leukocyte trafficking within tumor microenvironments and thereby impact anti-tumor immunity. Here we interrogate these relationships in primary human cutaneous melanoma.Experimental DesignWe established a quantitative, multiplexed imaging platform to simultaneously detect immune infiltrates and tumor-associated vessels in formalin-fixed paraffin embedded patient samples. We performed a discovery, retrospective analysis of 28 treatment-naïve, primary cutaneous melanomas.ResultsHere we find that the lymphvasculature and immune infiltrate is heterogenous across patients in treatment naïve, primary melanoma. We categorized five lymphovascular subtypes that differ by functionality and morphology and mapped their localization in and around primary tumors. Interestingly, the localization of specific vessel subtypes, but not overall vessel density, significantly associated with the presence of lymphoid aggregates, regional progression, and intratumoral T cell infiltrates.ConclusionsWe describe a quantitative platform to enable simultaneous lymphovascular and immune infiltrate analysis and map their spatial relationships in primary melanoma. Our data indicate that tumor-associated vessels exist in different states and that their localization may determine potential for tumor cell exit (metastasis) or leukocyte trafficking (immune response).This platform will support future efforts to map tumor-associated lymphovascular evolution across stage, assess its prognostic value, and stratify patients for adjuvant therapy.TRANSLATIONAL RELEVANCEThis report describes a quantitative, image-based method to investigate the relationship between the tumor-associated lymphovasculature and immune landscape in treatment naïve, primary human melanoma. The research shows that melanoma-associated blood and lymphatic vessels display context-dependent phenotypes that associate both with the risk of regional progression and immune infiltration. These findings indicate that stromal/vascular heterogeneity may underlie regional differences in immunogenicity and thus present opportunities for future biomarker development and therapeutic intervention.