bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gut microbiota and maternal immune transfer at birth influence pre-allergic clinical outcome
Authors: Villette Remy , Traore Djelika , Dhilly Elise , Foucault Pierre , Parisel Eleonore , Sauce Delphine , Gorochov Guy , Kayem Gilles , Schuhmacher Marta , Annesi-Maesano Isabella , Larsen Martin ,   EarlyFOOD study group
Published: April 2023

SummaryThe gut microbiota of 2-3 month-old infants is associated with later pre-allergic signs, while the microbiota at the time of allergic manifestation is not. We hypothesized that the infant gut microbiota and immune system are primed shortly after birth, and that this is influenced by maternal transfer of humoral immunity. We investigated the association between allergic outcomes and composition and humoral immunity to gut microbiota at birth, 2 months, and 2 years-of-age. Meconium microbiota clustered into three groups dominated byEscherichia,Enterococcus, and mixed genera, respectively. TheEscherichiacluster was associated with protection against later allergic manifestations. We moreover studied the proportion and specificity of humoral immunity to gut microbiota. Humoral immunity to gut microbiota at birth was associated with future allergies. Future studies should evaluate whether interventions to alter gut microbiota and humoral immunity in early-life protects against allergy.
Phylogenomic Analyses Reveal Widespread Gene Flow During the Early Radiation of Oaks and Relatives (Fagaceae: Quercoideae)
Authors: Liu Shuiyin , Yang Yingying , Tian Qin , Yang Zhiyun , Li Shufeng , Valdes Paul J. , Farnsworth Alex , Kates Heather R. , Siniscalchi Carolina M. , Guralnick Robert P. , Soltis Douglas E. , Soltis Pamela S. , Stull Gregory W. , Folk Ryan A. , Yi Tingshuang 
Published: April 2023

AbstractOaks (Quercus), one of the most species-rich and ecologically dominant woody plant clades in the Northern Hemisphere, are well known for their propensity to hybridize and form syngameons, complexes where alleles are readily exchanged among closely related species. While hybridization has been extensively studied towards the tips of the oak phylogeny, the extent, timeline, and evolutionary scenarios of hybridization during the early radiation of oaks and related genera (Quercoideae) remain poorly known. Using an expansive new dataset of nuclear and chloroplast sequences (including up to 431 spp.), we conducted a multifaceted phylogenomic investigation ofQuercusaimed at characterizing gene-tree and cytonuclear (chloroplast-nuclear) discordance and identifying ancient reticulation in the early evolution of the group. We document extensive nuclear gene-tree and cytonuclear discordance at deep nodes inQuercusand Quercoideae, withQuercusrecovered as non-monophyletic in the chloroplast phylogeny. Analyses recovered clear signatures of gene flow against a backdrop of incomplete lineage sorting, with gene flow most prevalent among major lineages ofQuercusand Quercoideae during their initial radiation, dated to the early-middle Eocene. Ancestral reconstructions including fossil data suggest that the ancestors ofCastanea+Castanopsis,Lithocarpus, and the Old World oak clade co-occurred in North America and Eurasia, while the ancestors ofChrysolepis, Notholithocarpus,and the New World oak clade co-occurred in North America, offering ample opportunity for hybridization in each region. Following this initial phase of radiation and reticulation, we detected multiple niche shifts inQuercusand other Quercoideae genera that likely facilitated their expansion into new habitats arising from post-Eocene climatic changes. Our study shows that hybridization—perhaps in the form of ancient syngameons similar to those seen today—has been a common and important process throughout the evolutionary history of oaks and their close relatives.
DEGAP: Dynamic Elongation of a Genome Assembly Path
Authors: Huang Yicheng , Wang Ziyuan , Schmidt Monica A. , Zhang Jianwei 
Published: April 2023

AbstractGenome assembly remains to be a major task in genomic research. Despite the development over the past decades of different assembler software programs and algorithms, it is still a great challenge to assemble a complete genome with no gaps. With the latest DNA Circular Consensus Sequencing (CCS) technology, several assembler programs now can build a genome from raw sequencing data to contigs, however, some complex sequence regions remain as unresolved gaps. Here, we present a novel gap-filling software DEGAP that can resolve gap regions in genomes by utilizing the dual advantages of accuracy and length of high-fidelity (HiFi) reads. DEGAP optimizes HiFi reads by identifying the differences between reads and provides ‘GapFiller’ or ‘CtgLinker’ modes to eliminate or shorten gaps in genomes. DEGAP adopts a cyclic elongation strategy that automatically and dynamically adjusts parameters according to the complexity of the sequences and selects the optimal extension path. DEGAP has already been successfully applied to decipher complex genomic regions in several projects and may be widely employed to generate more gap-free genomes.
SnRK2-mediated phosphorylation of SIZ1 enhances global SUMOylation under osmotic stress in Arabidopsis
Authors: Sang Tian , Jia Bei , Wang Pengcheng 
Published: April 2023

AbstractSUMOylation is a highly dynamic posttranslational modification that plays a critical role in regulating plant stress responses. The global SUMOylation is quickly induced by dehydration and hyperosmotic stresses in plants, while the detailed mechanism underlying such SUMOylation dynamics is largely unknown. Here, we report that the SNF1-related protein kinase 2 (SnRK2) and SUMO E3 ligase SIZ1 module is crucial for the stress-induced increment of SUMOylation in Arabidopsis. Under osmotic stress, or application of phytohormone Abscisic Acid (ABA), the rapidly activated SnRK2s physically interact with and phosphorylate SIZ1, enhancing its stability. The Ser820 residue in C-terminal region of SIZ1 proteins is a functional SnRK2 phosphosite, whose phosphorylation is abolished in the high-order mutant ofSnRK2s. The non-phosphorylatable SIZ1S820Ais unstable bothin vivoandin vitro. We also noticed the degradation of SIZ1 is largely darkness-dependent, interestingly, independent of COP1, a key ubiquitin E3 ligase regulating photomorphogenesis. Multiple SUMOylation, Ubiquitination, and phosphorylation sites in SIZ1 proteins, which may coordinate the dynamics of SIZ1 proteins and global SUMOylation upon environmental changes. Our findings highlight the critical role of the SnRK2-SIZ1 module in regulating SUMOylation dynamics during plant stress responses and provide new insights into the regulatory mechanisms underlying this essential posttranslational modification.
The potential of Senicapoc, a KCNN4 inhibitor, for the prevention and treatment of breast cancer
Authors: Xiao Christos , Miranda Mariska , Shi Wei , Beesley Jonathan , Saunus Jodi M. , Civitarese Andrew , Black Debra M. , Ruppert Meagan , Pereira Melrine , Jackson Susan , Teale Zachary , Carter-Cusack Dylan , Kalinowski Lauren , Kutasovic Jamie R. , McCart Reed Amy E. , Handoko Herlina Y. , Chen XiaoQing , Bessette Darrell , MacDonald Kelli , Lakhani Sunil R. , Chenevix-Trench Georgia , Britt Kara , Al-Ejeh Fares 
Published: April 2023

AbstractBackgroundGenome-wide association studies have identified a breast cancer risk locus at 19q13.31. The candidate causal variants at this locus are located in the first exon ofKCNN4.KCNN4, which regulates membrane potential and Ca2+signaling, is a good candidate for drug repositioning because its inhibitor, Senicapoc, has been shown to be well tolerated in Phase-II and -III clinical trials for asthma and sickle cell anemia.MethodsWe evaluated public mRNA expression data to determine whether the allele at 19q13.31 associated with increased breast cancer risk was associated withKCNN4expression. We also used immunohistochemistry to evaluate the relationship between KCNN4 protein expression and breast cancer survival. We then used Senicapoc in two murine mammary tumor models to determine if it would delay tumor development. We also treated mice bearing 4T1 mammary tumors with Senicapoc, by subcutaneous injection and by oral gavage. Finally we used gene editing to make deletions withinKcnn4in 4T1 to determine whether Senicapoc had off-target effects on tumor growth.ResultsAnalysis of the Genotype-Tissue Expression Project showed that the allele at 19q13.31 associated with increased breast cancer risk is associated with increasedKCNN4expression, suggesting that inhibiting KCNN4 might reduce breast cancer risk. Using immunohistochemistry in a large breast cancer cohort, we found that membrane and cytoplasmic expression is a marker of poor prognosis in triple negative breast cancer. We then tested the efficacy of Senicapoc to prevent and treat breast cancer. This showed that it delays the development of mammary tumors in two murine models, and slows growth of a syngeneic (4T1) model of triple negative breast cancer. Senicapoc monotherapy showed similar efficacy to anthracycline/taxane-based chemotherapy in these studies, with a stronger effect when they were combined.ConclusionsThese results provide a rationale for clinical testing of Senicapoc for treating, and even preventing, breast cancer.
The mitochondrial Ca2+channel MCU is critical for tumor growth by supporting cell cycle progression and proliferation
Authors: García Emily Fernández , Paudel Usha , Noji Michael C. , Bowman Caitlyn E. , Pitarresi Jason R. , Rustgi Anil K. , Wellen Kathryn E. , Arany Zolt , Weissenrieder Jillian S. , Foskett J. Kevin 
Published: April 2023

AbstractThe mitochondrial uniporter (MCU) Ca2+ion channel represents the primary means for Ca2+uptake into mitochondria. Here we employedin vitroandin vivomodels with MCU genetically eliminated to understand how MCU contributes to tumor formation and progression. Transformation of primary fibroblastsin vitrowas associated with increased MCU expression, enhanced mitochondrial Ca2+uptake, suppression of inactivating-phosphorylation of pyruvate dehydrogenase, a modest increase of basal mitochondrial respiration and a significant increase of acute Ca2+-dependent stimulation of mitochondrial respiration. Inhibition of mitochondrial Ca2+uptake by genetic deletion of MCU markedly inhibited growth of HEK293T cells and of transformed fibroblasts in mouse xenograft models. Reduced tumor growth was primarily a result of substantially reduced proliferation and fewer mitotic cellsin vivo, and slower cell proliferationin vitroassociated with delayed progression through S-phase of the cell cycle. MCU deletion inhibited cancer stem cell-like spheroid formation and cell invasionin vitro, both predictors of metastatic potential. Surprisingly, mitochondrial matrix Ca2+concentration, membrane potential, global dehydrogenase activity, respiration and ROS production were unchanged by genetic deletion of MCU in transformed cells. In contrast, MCU deletion elevated glycolysis and glutaminolysis, strongly sensitized cell proliferation to glucose and glutamine limitation, and altered agonist-induced cytoplasmic Ca2+signals. Our results reveal a dependence of tumorigenesis on MCU, mediated by a reliance on mitochondrial Ca2+uptake for cell metabolism and Ca2+dynamics necessary for cell-cycle progression and cell proliferation.
MitoSort: robust demultiplexing of pooled single-cell genomics data using endogenous germline mitochondrial variants
Authors: Tang Zhongjie , Zhang Weixing , Shi Peiyu , Li Sijun , Li Xinhui , Xu Yicong , Shu Yaqing , Xu Jin 
Published: April 2023

ABSTRACTMultiplexing across donors has emerged as a popular strategy to increase throughput, reduce costs, overcome technical batch effects, and improve doublet detection in single-cell genomic studies. Using endogenous genetic barcodes eliminates the need for additional experimental processing steps. Among the available choices for endogenous barcodes, the unique features of mtDNA variants render them a more computationally efficient and robust option compared to genome variants. Here we present MitoSort, a method that uses mtDNA germline variants to assign cells to their donor of origin and identify cross-genotype doublets. We evaluated the performance of MitoSort byin silicopooled mtscATAC-seq libraries and experimentally multiplexed data using cell hashing method. MitoSort achieve both high accuracy and efficiency on genotype clustering and doublet detection for mtscATAC-seq data, which fills a void left by the inadequacies of current computational techniques tailored for scRNA-seq data. Moreover, MitoSort exhibits versatility and can be applied to various single-cell sequencing approaches beyond mtscATAC-seq, as long as the mtDNA variants can be reliably detected. Furthermore, through a case study, we demonstrated that demultiplexing 8 individuals assayed at the same time with MitoSort, enables the comparison of cell composition without batch effects.
A SREBF2-dependent gene program drives an immunotolerant dendritic cell population during cancer progression
Authors: Plebanek Michael P. , Xue Yue , Nguyen Y-Van , DeVito Nicholas C. , Wang Xueying , Holtzhausen Alisha , Beasley Georgia M. , Yarla Nagendra , Thievanthiran Bala , Hanks Brent A. 
Published: April 2023

AbstractDendritic cells (cDCs) are essential mediators of anti-tumor immunity. Cancers have developed mechanisms to render DCs dysfunctional within the tumor microenvironment. Utilizing CD63 as a unique surface marker, we demonstrate that mature regulatory DCs (mregDCs) suppress DC antigen cross-presentation while driving TH2 and regulatory T cell differentiation within tumor-draining lymph node tissues. Transcriptional and metabolic studies show that mregDC functionality is dependent upon the mevalonate biosynthetic pathway and the master transcription factor, SREBP2. Melanoma-derived lactate activates DC SREBP2 in the tumor microenvironment (TME) and drives mregDC development from conventional DCs. DC-specific genetic silencing and pharmacologic inhibition of SREBP2 promotes anti-tumor CD8+T cell activation and suppresses melanoma progression. CD63+mregDCs reside within the sentinel lymph nodes of melanoma patients. Collectively, this work describes a tumor-driven SREBP2-dependent program that promotes CD63+mregDC development and function while serving as a promising therapeutic target for overcoming immune tolerance in the TME.One Sentence SummaryThe metabolic transcription factor, SREBF2, regulates the development and tolerogenic function of the mregDC population within the tumor microenvironment.
Deconstructing the brain bases of emotion regulation: A systems-identification approach using Bayes factors
Authors: Bo Ke , Kraynak Thomas E. , Kwon Mijin , Sun Michael , Gianaros Peter J. , Wager Tor D. 
Published: April 2023

AbstractCognitive reappraisal is fundamental to cognitive therapies and everyday emotion regulation. Analyses using Bayes factors and an axiomatic systems-identification approach identified four reappraisal-related components encompassing distributed neural activity patterns across two independent fMRI studies (n=182 and n=176): (1) An anterior prefrontal system selectively involved in cognitive reappraisal; (2) A fronto-parietal-insular system engaged by both reappraisal and emotion generation, demonstrating a general role in appraisal; (3) A largely subcortical system activated during negative emotion generation but unaffected by reappraisal, including amygdala, hypothalamus, and periaqueductal gray; and (4) a posterior cortical system of negative emotion-related regions down-regulated by reappraisal. These systems covaried with individual differences in reappraisal success and were differentially related to neurotransmitter binding maps, implicating cannabinoid and serotonin systems in reappraisal. These findings challenge ‘limbic’-centric models of reappraisal and provide new systems-level targets for assessing and enhancing emotion regulation.
Dedifferentiating germ cells regain stem-cell specific polarity checkpoint prior to niche reentry
Authors: Bener Muhammed Burak , Twillie Autumn , Chadha Rakshan , Patel Naiya , Inaba Mayu 
Published: April 2023

AbstractIn the Drosophila germline stem cell system, maintenance of the stem cell pool requires “dedifferentiation”, in which differentiating cells reattach to the niche and reacquire stem cell properties. However, the mechanism of dedifferentiation remains poorly understood. Here, using long-term live imaging, we show that dedifferentiated cells immediately re-enter mitosis with correct spindle orientation after reattachment to the niche. Analysis of cell cycle markers revealed that these dedifferentiating cells are all in G2 phase. In addition, we found that the observed G2 block during dedifferentiation likely corresponds to a centrosome orientation checkpoint (COC), a previously reported polarity checkpoint. We show that re-activation of a COC is likely required for the dedifferentiation thus ensuring asymmetric division even in dedifferentiated stem cells. Taken together, our study demonstrates the remarkable ability of dedifferentiating cells to reacquire the ability to divide asymmetrically.
The first two chromosome-scale genome assemblies of American hazelnut enable comparative genomic analysis of the genusCorylus
Authors: Brainard Scott H. , Sanders Dean M. , Bruna Tomas , Shu Shengqiang , Dawson Julie C. 
Published: April 2023

SummaryThe native, perennial shrub American hazelnut (Corylus americana) is cultivated in the Midwestern U.S. for its significant ecological benefits, as well as its high-value nut crop. Implementation of modern breeding methods and quantitative genetic analyses ofC. americanarequires high-quality reference genomes, a resource that is currently lacking. We therefore developed the first chromosome-scale assemblies for this species using the accessions ‘Rush’ and ‘Winkler’. Genomes were assembled using HiFi PacBio reads and Arima Hi-C data, and Oxford Nanopore reads and a high-density genetic map were used to perform error correction. N50 scores are 31.9 Mb and 35.3 Mb, with 90.2% and 97.1% of the total genome assembled into the 11 pseudomolecules, for ‘Rush’ and ‘Winkler’, respectively. Gene prediction was performed using custom RNAseq libraries and protein homology data. ‘Rush’ has a BUSCO score of 99.0 for its assembly and 99.0 for its annotation, while ‘Winkler’ had corresponding scores of 96.9 and 96.5, indicating high-quality assemblies. These two independent assemblies enable unbiased assessment of structural variation withinC. americana, as well as patterns of syntenic relationships across theCorylusgenus. Furthermore, we identified high-density SNP marker sets from genotyping-by-sequencing data using 1,343C. americana, C. avellana, andC. americanaxC. avellanahybrids, in order to assess population structure in natural and breeding populations. Finally, the transcriptomes of these assemblies, as well as several other recently publishedCorylusgenomes, were utilized to perform phylogenetic analysis of sporophytic self-incompatibility (SSI) in hazelnut, providing evidence of unique molecular pathways governing self-incompatibility inCorylus.
Dispersal in Kentish plovers (Charadrius alexandrinus): Adult females perform furthest movements
Authors: Cimiotti Dominic V. , Eberhart-Hertel Luke , Audevard Aurélien , Garcias Salas Pere Joan , Gelinaud Guillaume , Günther Klaus , Rocha Afonso , Schulz Rainer , van der Winden Jan , Schmaljohann Heiko , Küpper Clemens 
Published: April 2023

AbstractDispersal is an important behavioural process that plays a significant role in, among others, speciation, population viability, and individual fitness. Despite progress in avian dispersal research, there are still many knowledge gaps. For example, it is of interest to study how movement propensity (i.e., nomadic vs. philopatric) relates to age- and/or sex-specific patterns of dispersal. Here, we investigated the role of sex and life-stage on natal (i.e., displacement between birth site and first breeding site) and breeding dispersal (i.e., displacement between sequential breeding sites) in the Kentish plover (Charadrius alexandrinus). This small and inconspicuous wader is characterised by flexible mating behaviour that includes monogamy, and serial polygyandry. Using a continent-wide dataset of ringing and re-encounter data throughout the species’ range in Europe, we found that adult females generally dispersed further than adult males between seasons, but we detected no sex-difference in natal dispersal distances and no general difference between natal and breeding dispersal distances. Furthermore, females were the main group exhibiting ‘long-distance’ breeding dispersal, which we defined as breeding movements greater than ≥108 km (i.e., upper 10% percentile of our dataset). Our work detected two females breeding in the Mediterranean before dispersing and breeding at the North Sea in the subsequent year, distances of 1,290 and 1,704 km, respectively – this represents the longest known breeding dispersal within the genusCharadrius. The long-distance dispersal records we identified are consistent with low genetic differentiation between mainland populations shown in previous work. The dispersive nature of the Kentish plover is likely attributed to its breeding behaviour: polyandrous females exhibit extensive mate searching and habitat prospecting. We recommend that the dispersal traits of Kentish plover be incorporated into the species’ conservation and management planning to more accurately inform models of population connectivity and metapopulation dynamics.
ANDA: An open-source tool for automated image analysis of neuronal differentiation
Authors: Wæhler Hallvard Austin , Labba Nils-Anders , Paulsen Ragnhild Elisabeth , Sandve Geir Kjetil , Eskeland Ragnhild 
Published: April 2023

AbstractBackgroundImaging ofin vitroneuronal differentiation and measurements of cell morphologies has led to novel insights into neuronal development. Live-cell imaging techniques and large datasets of images has increased the demand for automated pipelines for quantitative analysis of neuronal morphological metrics.ResultsWe present ANDA, an analysis workflow for quantification of various aspects of neuronal morphology from high-throughput live-cell imaging screens. This tool automates the analysis of neuronal cell numbers, neurite lengths and neurite attachment points. We used rat, chicken and humanin vitromodels for neuronal differentiation and have demonstrated the accuracy, versatility, and efficiency of the tool.ConclusionsANDA is an open-source tool that is easy to use and capable of automated processing from time-course measurements of neuronal cells. The strength of this pipeline is the capability to analyse high-throughput imaging screens.