bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell RNA-seq reveals developmental plasticity with coexisting oncogenic states and immune evasion programs in ETP-ALL
Authors: Anand Praveen , Guillaumet-Adkins Amy , Dimitrova Valeriya , Yun Huiyoung , Drier Yotam , Sotudeh Noori , Rogers Anna , Ouseph Madhu M. , Nair Monica , Potdar Sayalee , Isenhart Randi , Kloeber Jake A. , Vijaykumar Tushara , Niu Leili , Vincent Tiffaney , Guo Guangwu , Frede Julia , Harris Marian H. , Place Andrew E. , Silverman Lewis B. , Teachey David T. , Lane Andrew A. , DeAngelo Daniel J. , Aster Jon C. , Bernstein Bradley E. , Lohr Jens G. , Knoechel Birgit 
Published: November 2020

AbstractLineage plasticity and stemness have been invoked as causes of therapy resistance in cancer, because these flexible states allow cancer cells to dedifferentiate and alter their dependencies. We investigated such resistance mechanisms in relapsed/refractory early T-cell progenitor acute lymphoblastic leukemia (ETP-ALL) carrying activating NOTCH1 mutations via full-length single-cell RNA sequencing (scRNA-seq) of malignant and microenvironmental cells. We identified 2 highly distinct stem-like states that critically differed with regard to cell cycle and oncogenic signaling. Fast-cycling stem-like leukemia cells demonstrated Notch activation and were effectively eliminated in patients by Notch inhibition, whereas slow-cycling stem-like cells were Notch independent and rather relied on PI3K signaling, likely explaining the poor efficacy of Notch inhibition in this disease. Remarkably, we found that both stem-like states could differentiate into a more mature leukemia state with prominent immunomodulatory functions, including high expression of the LGALS9 checkpoint molecule. These cells promoted an immunosuppressive leukemia ecosystem with clonal accumulation of dysfunctional CD8+ T cells that expressed HAVCR2, the cognate receptor for LGALS9. Our study identified complex interactions between signaling programs, cellular plasticity, and immune programs that characterize ETP-ALL, illustrating the multidimensionality of tumor heterogeneity. In this scenario, combination therapies targeting diverse oncogenic states and the immune ecosystem seem most promising to successfully eliminate tumor cells that escape treatment through coexisting transcriptional programs.
LncRNA LUADT1 sponges miR-195 to prevent cardiac endothelial cell apoptosis in sepsis
Authors: Zhang Zhimin , Lv Mingzhu , Wang Xiang , Zhao Zheng , Jiang Daolong , Wang Lihua 
Published: November 2020

Abstract
Background
The oncogenic role of the newly identified lncRNA LUADT1 has been revealed in lung adenocarcinoma. It was reported that LUADT1 plays a critical role in multiple human diseases. This study was carried out to investigate the role of LUADT1 in sepsis.

Methods
Sixty patients with sepsis and sixty healthy volunteers were recruited for this study. Plasma samples were collected from all participants. Human primary coronary artery endothelial cells were also used in this study. The expression of Pim-1, miR-195 and LUADT1 were detected by RT-qPCR. The interaction between miR-195 and LUADT1 was determined by overexpression experiments and luciferase activity assay. Cell apoptosis was detected by flow cytometry. The expression of apoptosis-related protein was detected by Western blotting.

Results
Bioinformatics analysis revealed the potential interaction between LUADT1 and miR-195, which was confirmed by dual luciferase reporter assay. LUADT1 was downregulated in patients with sepsis. Moreover, LPS treatment downregulated the expression of LUADT1 in primary cardiac endothelial cells. Overexpression of LUADT1 and miR-195 did not affect the expression of each other in primary cardiac endothelial cells. Interestingly, overexpression of LUADT1 was found to upregulate the expression of Pim-1, a target of miR-195. In addition, it was found that overexpression of LUADT1 and Pim-1 reduced the enhancement effects of miR-195 on LPS-induced cardiac endothelial cell apoptosis.

Conclusion
In summary, LUADT1 may protect cardiac endothelial cells against apoptosis in sepsis by regulating the miR-195/Pim-1 axis.
Illuminating the complexities of conflict with evolution: validation of the scales of evolutionary conflict measure (SECM)
Authors: Sbeglia Gena C. , Nehm Ross H. 
Published: November 2020

AbstractBackgroundAlthough personal, familial, and community conflict with evolution have been documented in the literature, these scales require conceptualization as a construct and operationalization as a measure. The Scales of Conflict with Evolution Measure (SECM) instrument was developed in response to these needs. Using a construct validity framework, the content, internal structure, convergent, and substantive validity of the SECM were evaluated using Rasch analysis, Structural Equation Modeling (SEM), and follow up questioning. The conceptual utility of the instrument was explored by examining whether it added explanatory insights into evolution acceptance above and beyond religiosity, evolution knowledge, and background variables.ResultsA literature review and expert consultation indicated that construct of evolutionary conflict perception should (i) encompass the hierarchical nature of human social structures (personal, family, community) and (ii) probe conflict as it relates to human values, cultures, and beliefs. A three-dimensional construct was operationalized as a nine-item rating scale measure. Using Rasch analyses of SECM responses from a diverse sample of > 1000 students studying evolution, the instrument met criteria of robust measurement, including: fit to model expectations; three-dimensional structure; high reliability; good rating scale function; measurement invariance with time; and convergence with a similar construct. SEM showed that: (i) family and community conflict had unique causal contributions to personal conflict, with family showing a stronger and modest impact, and (ii) personal conflict had a significant and modest causal impact on evolution acceptance above and beyond the contributions of religiosity, evolution knowledge, and background variables.ConclusionThe SECM is an easy-to-administer instrument to measure conflict with evolution and is supported by several forms of validity evidence. The SECM has potential for facilitating measurement of evolutionary conflict in educational settings, thereby raising instructor awareness of conflict levels in students, promoting rigorous evaluations of educational interventions designed to reduce conflict, and fostering conceptual advances in the field of evolution education. Future work is needed to gather additional forms of validity evidence and to test current validity claims in additional participant samples. SECM measures should also be incorporated into more complex SEM models that treat evolution knowledge and religiosity as part of the structural paths to evolution acceptance. Such models could provide insights into the most worthwhile targets for the development of educational interventions to mitigate conflict at multiple scales.
MADloy: robust detection of mosaic loss of chromosome Y from genotype-array-intensity data
Authors: González Juan R. , López-Sánchez Marcos , Cáceres Alejandro , Puig Pere , Esko Tonu , Pérez-Jurado Luis A. 
Published: November 2020

AbstractBackgroundAccurate protocols and methods to robustly detect the mosaic loss of chromosome Y (mLOY) are needed given its reported role in cancer, several age-related disorders and overall male mortality. Intensity SNP-array data have been used to infer mLOY status and to determine its prominent role in male disease. However, discrepancies of reported findings can be due to the uncertainty and variability of the methods used for mLOY detection and to the differences in the tissue-matrix used.ResultsWe created a publicly available software tool calledMADloy(Mosaic Alteration Detection for LOY) that incorporates existing methods and includes a new robust approach, allowing efficient calling in large studies and comparisons between methods.MADloyoptimizes mLOY calling by correctly modeling the underlying reference population with no-mLOY status and incorporating B-deviation information. We observed improvements in the calling accuracy to previous methods, using experimentally validated samples, and an increment in the statistical power to detect associations with disease and mortality, using simulation studies and real dataset analyses. To understand discrepancies in mLOY detection across different tissues, we appliedMADloyto detect the increment of mLOY cellularity in blood on 18 individuals after 3 years and to confirm that its detection in saliva was sub-optimal (41%). We additionally applied MADloy to detect the down-regulation genes in the chromosome Y in kidney and bladder tumors with mLOY, and to perform pathway analyses for the detection of mLOY in blood.ConclusionsMADloyis a new software tool implemented in R for the easy and robust calling of mLOY status across different tissues aimed to facilitate its study in large epidemiological studies.
Mixed logistic regression in genome-wide association studies
Authors: Milet Jacqueline , Courtin David , Garcia André , Perdry Hervé 
Published: November 2020

AbstractBackgroundMixed linear models (MLM) have been widely used to account for population structure in case-control genome-wide association studies, the status being analyzed as a quantitative phenotype. Chen et al. proved in 2016 that this method is inappropriate in some situations and proposed GMMAT, a score test for the mixed logistic regression (MLR). However, this test does not produces an estimation of the variants’ effects. We propose two computationally efficient methods to estimate the variants’ effects. Their properties and those of other methods (MLM, logistic regression) are evaluated using both simulated and real genomic data from a recent GWAS in two geographically close population in West Africa.ResultsWe show that, when the disease prevalence differs between population strata, MLM is inappropriate to analyze binary traits. MLR performs the best in all circumstances. The variants’ effects are well evaluated by our methods, with a moderate bias when the effect sizes are large. Additionally, we propose a stratified QQ-plot, enhancing the diagnosis ofpvalues inflation or deflation when population strata are not clearly identified in the sample.ConclusionThe two proposed methods are implemented in the R packagemilorGWASavailable on the CRAN. Both methods scale up to at least 10,000 individuals. The same computational strategies could be applied to other models (e.g. mixed Cox model for survival analysis).
Intrinsic laws of k-mer spectra of genome sequences and evolution mechanism of genomes
Authors: Yang Zhenhua , Li Hong , Jia Yun , Zheng Yan , Meng Hu , Bao Tonglaga , Li Xiaolong , Luo Liaofu 
Published: November 2020

Abstract
Background
K-mer spectra of DNA sequences contain important information about sequence composition and sequence evolution. We want to reveal the evolution rules of genome sequences by studying the k-mer spectra of genome sequences.

Results
The intrinsic laws of k-mer spectra of 920 genome sequences from primate to prokaryote were analyzed. We found that there are two types of evolution selection modes in genome sequences, named as CG Independent Selection and TA Independent Selection. There is a mutual inhibition relationship between CG and TA independent selections. We found that the intensity of CG and TA independent selections correlates closely with genome evolution and G + C content of genome sequences. The living habits of species are related closely to the independent selection modes adopted by species genomes. Consequently, we proposed an evolution mechanism of genomes in which the genome evolution is determined by the intensities of the CG and TA independent selections and the mutual inhibition relationship. Besides, by the evolution mechanism of genomes, we speculated the evolution modes of prokaryotes in mild and extreme environments in the anaerobic age and the evolving process of prokaryotes from anaerobic to aerobic environment on earth as well as the originations of different eukaryotes.

Conclusion
We found that there are two independent selection modes in genome sequences. The evolution of genome sequence is determined by the two independent selection modes and the mutual inhibition relationship between them.
Genome-wide association studies for methane emission and ruminal volatile fatty acids using Holstein cattle sequence data
Authors: Jalil Sarghale Ali , Moradi Shahrebabak Mohammad , Moradi Shahrebabak Hossein , Nejati Javaremi Ardeshir , Saatchi Mahdi , Khansefid Majid , Miar Younes 
Published: November 2020

Abstract
Background
Methane emission by ruminants has contributed considerably to the global warming and understanding the genomic architecture of methane production may help livestock producers to reduce the methane emission from the livestock production system. The goal of our study was to identify genomic regions affecting the predicted methane emission (PME) from volatile fatty acids (VFAs) indicators and VFA traits using imputed whole-genome sequence data in Iranian Holstein cattle.

Results
Based on the significant-association threshold (p < 5 × 10− 8), 33 single nucleotide polymorphisms (SNPs) were detected for PME per kg milk (n = 2), PME per kg fat (n = 14), and valeric acid (n = 17). Besides, 69 genes were identified for valeric acid (n = 18), PME per kg milk (n = 4) and PME per kg fat (n = 47) that were located within 1 Mb of significant SNPs. Based on the gene ontology (GO) term analysis, six promising candidate genes were significantly clustered in organelle organization (GO:0004984, p = 3.9 × 10− 2) for valeric acid, and 17 candidate genes significantly clustered in olfactory receptors activity (GO:0004984, p = 4 × 10− 10) for PME traits. Annotation results revealed 31 quantitative trait loci (QTLs) for milk yield and its components, body weight, and residual feed intake within 1 Mb of significant SNPs.

Conclusions
Our results identified 33 SNPs associated with PME and valeric acid traits, as well as 17 olfactory receptors activity genes for PME traits related to feed intake and preference. Identified SNPs were close to 31 QTLs for milk yield and its components, body weight, and residual feed intake traits. In addition, these traits had high correlations with PME trait. Overall, our findings suggest that marker-assisted and genomic selection could be used to improve the difficult and expensive-to-measure phenotypes such as PME. Moreover, prediction of methane emission by VFA indicators could be useful for increasing the size of reference population required in genome-wide association studies and genomic selection.
Systemic paralogy and function of retinal determination network homologs in arachnids
Authors: Gainett Guilherme , Ballesteros Jesús A. , Kanzler Charlotte R. , Zehms Jakob T. , Zern John M. , Aharon Shlomi , Gavish-Regev Efrat , Sharma Prashant P. 
Published: November 2020

AbstractBackgroundArachnids are important components of cave ecosystems and display many examples of troglomorphisms, such as blindness, depigmentation, and elongate appendages. Little is known about how the eyes of arachnids are specified genetically, let alone the mechanisms for eye reduction and loss in troglomorphic arachnids. Additionally, duplication of Retinal Determination Gene Network (RDGN) homologs in spiders has convoluted functional inferences extrapolated from single-copy homologs in pancrustacean models.ResultsWe investigated a sister species pair of Israeli cave whip spiders,Charinus ioanniticusandC. israelensis(Arachnopulmonata, Amblypygi), of which one species has reduced eyes. We generated embryonic transcriptomes for both Amblypygi species, and discovered that several RDGN homologs exhibit duplications. We show that duplication of RDGN homologs is systemic across arachnopulmonates (arachnid orders that bear book lungs), rather than being a spider-specific phenomenon. A differential gene expression (DGE) analysis comparing the expression of RDGN genes in field-collected embryos of both species identified candidate RDGN genes involved in the formation and reduction of eyes in whip spiders. To ground bioinformatic inference of expression patterns with functional experiments, we interrogated the function of three candidate RDGN genes identified from DGE using RNAi in the spiderParasteatoda tepidariorum. We provide functional evidence that one of these paralogs,sine oculis/Six1 A(soA), is necessary for the development of all arachnid eye types.ConclusionsOur work establishes a foundation to investigate the genetics of troglomorphic adaptations in cave arachnids, and links differential gene expression to an arthropod eye phenotype for the first time outside of Pancrustacea. Our results support the conservation of at least one RDGN component across Arthropoda and provide a framework for identifying the role of gene duplications in generating arachnid eye diversity.
Chicken cecal DNA methylome alteration in the response to Salmonella enterica serovar Enteritidis inoculation
Authors: Wang Yuanmei , Liu Liying , Li Min , Lin Lili , Su Pengcheng , Tang Hui , Fan Xinzhong , Li Xianyao 
Published: November 2020

Abstract
Background
Salmonella enterica serovar Enteritidis (SE) is one of the pathogenic bacteria, which affects poultry production and poses a severe threat to public health. Chicken meat and eggs are the main sources of human salmonellosis. DNA methylation is involved in regulatory processes including gene expression, chromatin structure and genomic imprinting. To understand the methylation regulation in the response to SE inoculation in chicken, the genome-wide DNA methylation profile following SE inoculation was analyzed through whole-genome bisulfite sequencing in the current study.

Results
There were 185,362,463 clean reads and 126,098,724 unique reads in the control group, and 180,530,750 clean reads and 126,782,896 unique reads in the inoculated group. The methylation density in the gene body was higher than that in the upstream and downstream regions of the gene. There were 8946 differentially methylated genes (3639 hypo-methylated genes, 5307 hyper-methylated genes) obtained between inoculated and control groups. Methylated genes were mainly enriched in immune-related Gene Ontology (GO) terms and metabolic process terms. Cytokine-cytokine receptor interaction, TGF-beta signaling pathway, FoxO signaling pathway, Wnt signaling pathway and several metabolism-related pathways were significantly enriched. The density of differentially methylated cytosines in miRNAs was the highest. HOX genes were widely methylated.

Conclusions
The genome-wide DNA methylation profile in the response to SE inoculation in chicken was analyzed. SE inoculation promoted the DNA methylation in the chicken cecum and caused methylation alteration in immune- and metabolic- related genes. Wnt signal pathway, miRNAs and HOX gene family may play crucial roles in the methylation regulation of SE inoculation in chicken. The findings herein will deepen the understanding of epigenetic regulation in the response to SE inoculation in chicken.
Extensive gene rearrangements in the mitogenomes of congeneric annelid species and insights on the evolutionary history of the genus Ophryotrocha
Authors: Tempestini Astrid , Massamba-N’Siala Gloria , Vermandele Fanny , Beaudreau Nicholas , Mortz Mathieu , Dufresne France , Calosi Piero 
Published: November 2020

AbstractBackgroundAnnelids are one the most speciose and ecologically diverse groups of metazoans. Although a significant effort has been recently invested in sequencing genomes of a wide array of metazoans, many orders and families within the phylum Annelida are still represented by a single specimen of a single species. The genus of interstitial annelidsOphryotrocha(Dorvilleidae, Errantia, Annelida) is among these neglected groups, despite its extensive use as model organism in numerous studies on the evolution of life history, physiological and ecological traits. To compensate for the paucity of genomic information in this genus, we here obtained novel complete mitochondrial genomes of sixOphryotrochaspecies using next generation sequencing. In addition, we investigated the evolution of the reproductive mode in theOphryotrochagenus using a phylogeny based on two mitochondrial markers (COXI and 16S rDNA) and one nuclear fragment (Histone H3).ResultsSurprisingly, gene order was not conserved among the sixOphryotrochaspecies investigated, and varied greatly as compared to those found in other annelid species within the class Errantia. The mitogenome phylogeny for the sixOphryotrochaspecies displayed a separation of gonochoric and hermaphroditic species. However, this separation was not observed in the phylogeny based on the COX1, 16S rDNA, and H3 genes. Parsimony and Bayesian ancestral trait reconstruction indicated that gonochorism was the most parsimonious ancestral reproductive mode inOphryotrochaspp.ConclusionsOur results highlight the remarkably high level of gene order variation among congeneric species, even in annelids. This encourages the need for additional mitogenome sequencing of annelid taxa in order to properly understand its mtDNA evolution, high biodiversity and phylogenetic relationships.
Immune challenge reduces gut microbial diversity and triggers fertility-dependent gene expression changes in a social insect
Authors: Negroni Matteo Antoine , Segers Francisca H. I. D. , Vogelweith Fanny , Foitzik Susanne 
Published: November 2020

AbstractBackgroundThe gut microbiome can influence life history traits associated with host fitness such as fecundity and longevity. In most organisms, these two life history traits are traded-off, while they are positively linked in social insects. In ants, highly fecund queens can live for decades, while their non-reproducing workers exhibit much shorter lifespans. Yet, when fertility is induced in workers by death or removal of the queen, worker lifespan can increase. It is unclear how this positive link between fecundity and longevity is achieved and what role the gut microbiome and the immune system play in this. To gain insights into the molecular regulation of lifespan in social insects, we investigated fat body gene expression and gut microbiome composition in workers of the antTemnothorax rugatulusin response to an experimental induction of fertility and an immune challenge.ResultsFertile workers upregulated several molecular repair mechanisms, which could explain their extended lifespan. The immune challenge altered the expression of several thousand genes in the fat body, including many immune genes, and, interestingly, this transcriptomic response depended on worker fertility. For example, only fertile, immune-challenged workers upregulated genes involved in the synthesis ofalpha-ketoglutarate, an immune system regulator, which extends the lifespan inCaenorhabditis elegansby down-regulating the TOR pathway and reducing oxidant production. Additionally, we observed a dramatic loss in bacterial diversity in the guts of the ants within a day of the immune challenge. Yet, bacterial density did not change, so that the gut microbiomes of many immune challenged workers consisted of only a single or a few bacterial strains. Moreover, the expression of immune genes was linked to the gut microbiome composition, suggesting that the ant host can regulate the microbiome in its gut.ConclusionsImmune system flare-ups can have negative consequence on gut microbiome diversity, pointing to a previously underrated cost of immunity. Moreover, our results provide important insights into shifts in the molecular regulation of fertility and longevity associated with insect sociality.