bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Biogeography ofDromiciopsin Southern South America: middle Miocene transgressions, speciation and associations withNothofagus
Authors: Quintero-Galvis Julian F. , Saenz-Agudelo Pablo , Celis-Diez Juan L. , Amico Guillermo C. , Vazquez Soledad , Shafer Aaron B.A. , Nespolo Roberto F. 
Published: August 2020

AbstractAimSeveral geological events affecting Southern South America during the middle Miocene climatic optimum acted as important drivers of diversification to the biota. This is the case of Microbiotheria, for whichDromiciopsis considered the sole surviving lineage, the sister group of Eomarsupialia (Australian marsupials). Three mainDromiciopsgenetic lineages are known, whose divergence was initially attributed to recent Pleistocene glaciations. Using fossil-calibrated dating on nuclear and mitochondrial genes, here we reevaluate this hypothesis and report an older (Miocenic) biogeographic history for the genus.LocationSouthern South America.MethodsPhylogenetic reconstruction using sequences from two mitochondrial DNA and four nuclear DNA genes in 159 specimens, from 31 sites across Chile and Argentina. Divergence time estimation using fossil calibration.ResultsOur phylogenetic analysis resolved four well supported clades with discrete geographic distributions. The oldest and most differentiated clade corresponds to that of the northern distribution (35.2°S to 39.3°S), which would be a different species (D. bozinovici, sensu D’elia et al. 2016). According to our estimations, this species shared a common ancestor withD. gliroides(southern clades) about 13 million years ago (95% CI: 6.4-25.3). The southern clades (39.6°S to 42.0°S), showed a divergence time ranging from 9.57 to 6.5 Mya. Strong genetic structure was detected from north to south but not across the Andes, or between Chiloé island/ mainland. Demographic equilibrium is inferred to the northern clade, and recent demographic expansions was detected in the central and southern clades.Main conclusionsThe whole diversification ofDromiciopsoccurred within the Miocene, being the Middle Miocene transgression (MMT), the massive marine flooding that covered several lowlands of the western face of los Andes between 38-48° S, the most likely diversifying force. This was the result of an increase in global sea levels due to the Miocene climatic optimum, which shaped the biogeographic origin of several species, includingNothofagusforests, the habitat main ofDromiciops.
Bio-informatic Analysis of Missense Single Nucleotide Polymorphisms (SNPs) in Human CD38 Gene Associated with B-Chronic Lymphocytic Leukemia
Authors: Fadl Hiba Awadelkareem Osman , Abdelmoneim Abdelrahman Hamza , Elbager Sahar Gamal 
Published: August 2020

ABSTRACTBackgroundCLL: Chronic lymphocytic leukemia is a chronic type of haematological malignancies that evoked from lymph proliferative origin of bone marrow and secondary lymphoid tissue, resultant in proliferation and progressive accumulation of distinct monoclonal CD5 /CD19 /CD23 B lymphocytes in the bone marrow, peripheral blood, and lymphatic organs.CD38is a multifunctional ecto-enzyme, known to be a direct contributor in pathogenesis of CLL by poorly understood mechanism. Even though, it highly expressed in CLL. At specific position of CD38 gene sequence, substitution of single nucleotide may result in change in amino acid that ends by consequent alteration of protein structure.AimTo study CD38 polymorphism and to predict its effect on structure and subsequently function of CD38 molecule.Methodology and ResultThe bioinformatic analysis of CD38 gene had been carried out by using several soft wares. Functional analysis by SIFT, Polyphen2, and PROVEAN reveled 12 deleterious SNPs. These SNPs were further analyzed by SNAP2, SNP@GO. PMut, STRING and other soft wars. Furthermore, Stability analysis was done using I-Mutant and MUpro software where seven SNPs were found to decrease the stability of the protein by I-Mutant, while two SNPs increase it. At the same time, eight SNPs were found to decrease the stability by Mupro software while only one SNP is predicted to increase it. Finally, Physiochemical analysis was done using Project Hope.ConclusionIn summary, CD38 genotype seems to have twelve SNP that possibly will result in deleterious effect on Protein Structure. This genetic variation eventually will lead to alteration in potential molecule functions. Which effect the progression of CLL By the end.
A Sub-Minute Resolution Prediction of Brain Temperature Based on Sleep-Wake State in the Mouse
Authors: Sela Yaniv , Hoekstra Marieke M.B. , Franken Paul 
Published: August 2020

AbstractWhile brain temperature is of neurobiological and clinical importance, it is still unclear which factors contribute to its daily dynamics and to what degree. We recorded cortical temperature in mice alongside sleep-wake state during 4 days including a 6h sleep deprivation, and developed a mathematical tool to simulate temperature based on the sleep-wake sequence. The model estimated temperature with remarkable precision accounting for 91% of its variance based on three main factors with the sleep-wake sequence accounting for most of the variance (74%) and time-of-day (‘circadian’) the least (9%). As third factor, prior wake prevalence, was discovered to up-regulate temperature, explaining 43% of the variance. With similar accuracy the model predicted cortical temperature in a second, independent cohort using the parameters optimized for the first. Our model corroborates the profound influence of sleep-wake state on brain temperature, and can help differentiate thermoregulatory from sleep-wake driven effects in experiments affecting both.
Endothelial Cell Cycle State Determines Propensity for Arterial-Venous Fate
Authors: Chavkin Nicholas W. , Genet Gael , Poulet Mathilde , Genet Nafiisha , Marziano Corina , Vasavada Hema , Nelson Elizabeth A. , Kour Anupreet , McDonnell Stephanie P. , Huba Mahalia , Walsh Kenneth , Hirschi Karen K. 
Published: August 2020

SummaryFormation and maturation of a functional blood vascular system is required for the development and maintenance of all tissues in the body. During the process of blood vessel development, primordial endothelial cells are formed and become specified toward arterial or venous fates to generate a circulatory network that provides nutrients and oxygen to, and removes metabolic waste from, all tissues1-3. Specification of arterial and venous endothelial cells occurs in conjunction with suppression of endothelial cell cycle progression4,5, and endothelial cell hyperproliferation is associated with potentially lethal arterial-venous malformations6. However, the mechanistic role that cell cycle state plays in arterial-venous specification is unknown. Herein, studying retinal vascular development in Fucci2aR reporter mice7, we found that venous and arterial endothelial cells are in distinct cell cycle states during development and in adulthood. That is, venous endothelial cells reside in early G1 state, while arterial endothelial cells reside in late G1 state. Endothelial cells in early vs. late G1 exhibited significant differences in gene expression and activity, especially among BMP/TGF-β signaling components. The early G1 state was found to be essential for BMP4-induced venous specification, whereas late G1 state is essential for TGF-β1-induced arterial specification. In a mouse model of endothelial cell hyperproliferation and disrupted vascular remodeling, pharmacological inhibition of endothelial cell cycle rescues the arterial-venous specification defects. Collectively, our results show that endothelial cell cycle control plays a key role in arterial-venous network formation, and distinct cell cycle states provide distinct windows of opportunity for the molecular induction of arterial vs. venous specification.
MACMIC Reveals Dual Role of CTCF in Epigenetic Regulation of Cell Identity Genes
Authors: Wang Guangyu , Xia Bo , Zhou Man , Lv Jie , Zhao Dongyu , Li Yanqiang , Bu Yiwen , Wang Xin , Cooke John P. , Cao Qi , Lee Min Gyu , Zhang Lili , Chen Kaifu 
Published: August 2020

ABSTRACTNumerous studies of relationship between epigenomic features have focused on their strong correlation across the genome, likely because such relationship can be easily identified by many established methods for correlation analysis. However, two features with little correlation may still colocalize at many genomic sites to implement important functions. There is no bioinformatic tool for researchers to specifically identify such feature pair. Here, we develop a method to identify feature pair in which two features have maximal colocalization but minimal correlation (MACMIC) across the genome. By MACMIC analysis of 3,385 feature pairs in 15 cell types, we reveal a dual role of CTCF in epigenetic regulation of cell identity genes. Although super-enhancers are associated with activation of target genes, only a subset of super-enhancers colocalized with CTCF regulate cell identity genes. At super-enhancers colocalized with CTCF, the CTCF is required for the active marker H3K27ac in cell type requiring the activation, and also required for the repressive marker H3K27me3 in other cell types requiring the repression. Our work demonstrates the biological utility of the MACMIC analysis and reveals a key role for CTCF in epigenetic regulation of cell identity.
Correlative single-molecule fluorescence barcoding of gene regulation inSaccharomyces cerevisiae
Authors: Shashkova Sviatlana , Nyström Thomas , Leake Mark C , Wollman Adam JM 
Published: August 2020

AbstractMost cells adapt to their environment by switching combinations of genes on and off through a complex interplay of transcription factor proteins (TFs). The mechanisms by which TFs respond to signals, move into the nucleus and find specific binding sites in target genes is still largely unknown. Single-molecule fluorescence microscopes, which can image single TFs in live cells, have begun to elucidate the problem. Here, we show that different environmental signals, in this case carbon sources, yield a unique single-molecule fluorescence pattern of foci of a key metabolic regulating transcription factor, Mig1, in the nucleus of the budding yeast,Saccharomyces cerevisiae. This pattern serves as a ‘barcode’ of the gene regulatory state of the cells which can be correlated with cell growth characteristics and other biological function.HighlightsSingle-molecule microscopy of transcription factors in live yeastBarcoding single-molecule nuclear fluorescenceCorrelation with cell growth characteristicsGrowth in different carbon sources
Suppression of MDA5-mediated antiviral immune responses by NSP8 of SARS-CoV-2
Authors: Yang Ziwei , Zhang Xiaolin , Wang Fan , Wang Peihui , Kuang Ersheng , Li Xiaojuan 
Published: August 2020

AbstractMelanoma differentiation-associated gene-5 (MDA5) acts as a cytoplasmic RNA sensor to detect viral dsRNA and mediates type I interferon (IFN) signaling and antiviral innate immune responses to infection by RNA viruses. Upon recognition of viral dsRNA, MDA5 is activated with K63-linked polyubiquitination and then triggers the recruitment of MAVS and activation of TBK1 and IKK, subsequently leading to IRF3 and NF-κB phosphorylation. Great numbers of symptomatic and severe infections of SARS-CoV-2 are spreading worldwide, and the poor efficacy of treatment with type I interferon and antiviral agents indicates that SARS-CoV-2 escapes from antiviral immune responses via an unknown mechanism. Here, we report that SARS-CoV-2 nonstructural protein 8 (NSP8) acts as an innate immune suppressor and inhibits type I IFN signaling to promote infection of RNA viruses. It downregulates the expression of type I IFNs, IFN-stimulated genes and proinflammatory cytokines by binding to MDA5 and impairing its K63-linked polyubiquitination. Our findings reveal that NSP8 mediates innate immune evasion during SARS-CoV-2 infection and may serve as a potential target for future therapeutics for SARS-CoV-2 infectious diseases.ImportanceThe large-scale spread of COVID-19 is causing mass casualties worldwide, and the failure of antiviral immune treatment suggests immune evasion. It has been reported that several nonstructural proteins of severe coronaviruses suppress antiviral immune responses; however, the immune suppression mechanism of SARS-CoV-2 remains unknown. Here, we revealed that NSP8 protein of SARS-CoV-2 directly blocks the activation of the cytosolic viral dsRNA sensor MDA5 and significantly downregulates antiviral immune responses. Our study contributes to our understanding of the direct immune evasion mechanism of SARS-CoV-2 by showing that NSP8 suppresses the most upstream sensor of innate immune responses involved in the recognition of viral dsRNA.
KIAA1841, a novel SANT and BTB domain-containing protein, inhibits class switch recombination
Authors: Zheng Simin , Matthews Allysia J. , Rahman Numa , Herrick-Reynolds Kayleigh , Choi Jee Eun , Sible Emily , Ng Yan Kee , Rhodes Daniela , Elledge Stephen J. , Vuong Bao Q. 
Published: August 2020

AbstractClass switch recombination (CSR) enables B cells to produce different immunoglobulin isotypes and mount an effective immune response against pathogens. Timely resolution of CSR prevents damage due to an uncontrolled and prolonged immune response. While many positive regulators of CSR have been described, negative regulators of CSR are relatively unknown. Using a shRNA library screen in a mouse B cell line, we have identified the novel protein KIAA1841 (NM_027860) as a negative regulator of CSR. KIAA1841 is an uncharacterized protein of 82kD containing SANT and BTB domains. The BTB domain of KIAA1841 exhibited characteristic properties such as self-dimerization and interaction with co-repressor proteins. Overexpression of KIAA1841 inhibited CSR in primary mouse splenic B cells, and inhibition of CSR is dependent on the BTB domain while the SANT domain is largely dispensable. Thus, we have identified a new member of the BTB family that serves as a negative regulator of CSR.
Relations between hemispheric asymmetries of grey matter and auditory processing of spoken syllables in 281 healthy adults
Authors: Guadalupe Tulio , Kong Xiang-Zhen , Akkermans Sophie E. A. , Fisher Simon E. , Francks Clyde 
Published: August 2020

AbstractMost people have a right-ear advantage for the perception of spoken syllables, consistent with left hemisphere dominance for speech processing. However, there is considerable variation, with some people showing left-ear advantage. The extent to which this variation is reflected in brain structure remains unclear. We tested for relations between hemispheric asymmetries of auditory processing and of grey matter in 281 adults, using dichotic listening and voxel-based morphometry. This was the largest study of this issue to date. Per-voxel asymmetry indexes were derived for each participant following registration of brain magnetic resonance images to a template that was symmetrized. The asymmetry index derived from dichotic listening was related to grey matter asymmetry in clusters of voxels corresponding to the amygdala and cerebellum lobule VI. There was also a smaller, non-significant cluster in the posterior superior temporal gyrus, a region of auditory cortex. These findings contribute to the mapping of asymmetrical structure-function links in the human brain, and suggest that subcortical structures should be investigated in relation to hemispheric dominance for speech processing, in addition to auditory cortex.
Shedding light on the underlying characteristics of genomes using Kronecker model families of codon evolution
Authors: Zaheri Maryam , Salamin Nicolas 
Published: August 2020

AbstractThe mechanistic models of codon evolution rely on some simplistic assumptions in order to reduce the computational complexity of estimating the high number of parameters of the models. This paper is an attempt to investigate how much these simplistic assumptions are misleading when they violate the nature of the biological dataset in hand. We particularly focus on three simplistic assumptions made by most of the current mechanistic codon models including: 1) only single substitutions between nucleotides within codons in the codon transition rate matrix are allowed. 2) mutation is homogenous across nucleotides within a codon. 3) assuming HKY nucleotide model is good enough at the nucleotide level. For this purpose, we developed a framework of mechanistic codon models, each model in the framework hold or relax some of the mentioned simplifying assumptions. Holding or relaxing the three simplistic assumptions results in total to eight different mechanistic models in the framework. Through several experiments on biological datasets and simulations we show that the three simplistic assumptions are unrealistic for most of the biological datasets and relaxing these assumptions lead to accurate estimation of evolutionary parameters such as selection pressure.
Disparate regulation ofimddrives sex differences in infection pathology inDrosophila melanogaster
Authors: Vincent Crystal M. , Dionne Marc S. 
Published: August 2020

AbstractMale and female animals exhibit differences in infection outcomes. One possible source of sexually dimorphic immunity is sex-specific costs of immune activity or pathology, but little is known about the independent effects of immune-induced versus microbe-induced pathology, and whether these may differ for the sexes. Here, through measuring metabolic and physiological outputs in wild-type and immune-compromisedDrosophila melanogaster, we test whether the sexes are differentially impacted by these various sources of pathology and identify a critical regulator of this difference. We find that the sexes exhibit differential immune activity but similar bacteria-derived metabolic pathology. We show that female-specific immune-inducible expression ofPGRP-LB, a negative regulator of the Imd pathway, enables females to reduce immune activity in response to reductions in bacterial numbers. In the absence ofPGRP-LB, females are more resistant of infection, confirming the functional importance of this regulation and suggesting that female-biased immune restriction comes at a cost.
Cell-Scale Biophysical Cues from Collagen Fiber Architecture Instruct Cell Behavior and the Propagation of Mechanosensory Signals
Authors: Szulczewski Joseph M. , Inman David R. , Proestaki Maria , Notbohm Jacob , Burkel Brian M. , Ponik Suzanne M. 
Published: August 2020

AbstractMechanosensory cues from the extracellular matrix underpin numerous cellular behaviors including tumor cell migration yet are influenced by the local structure and organization of the matrix in unknown ways. To investigate mechanical cues with respect to local collagen organization, we used a combination of intravital imaging of the mammary tumor microenvironment and 3D collagen gel systems with both migratory MDA-MB-231 cells and acellular pNIPAAm beads. We identified that fiber organization directs a bias in cell response along the axis of alignment. Using innovative methodology, we determined that local collagen alignment resulted in a 30-fold difference in directional cell-scale stiffness and also dramatically altered the rate at which cell-induced fiber displacements decayed over distance. Our results reveal differential mechanical properties across orthogonal directions in aligned matrices that provide sizeable cues to the cell and have important implications for cellular mechanosensing and cell-cell communication within the tissue microenvironment.
Detecting potential reference list manipulation within a citation network
Authors: Wren Jonathan D. , Georgescu Constantin 
Published: August 2020

AbstractAlthough citations are used as a quantifiable, objective metric of academic influence, cases have been documented whereby references were added to a paper solely to inflate the perceived influence of a body of research. This reference list manipulation (RLM) could take place during the peer-review process (e.g., coercive citation from editors or reviewers), or prior to it (e.g., a quid-pro-quo between authors). Surveys have estimated how many people may have been affected by coercive RLM at one time or another, but it is not known how many authors engage in RLM, nor to what degree. Examining a subset of active, highly published authors (n=20,803) in PubMed, we find the frequency of non-self citations (NSC) to one author coming from one paper approximates Zipf’s law. We propose the Gini Index as a simple means of quantifying skew in this distribution and test it against a series of “red flag” metrics that are expected to result from RLM attempts. We estimate between 81 (FDR <0.05) and 231 (FDR<0.10) authors are outliers on the curve, suggestive of chronic, repeated RLM. Based upon the distribution, we estimate approximately 3,284 (16%) of all authors may have engaged in RLM to some degree, possibly opportunistically. Finally, we find authors who use 18% or more of their references for self-citation are significantly more likely to have NSC Gini distortions, suggesting their desire to see their work cited carries over into their peer-review activity.
Pleistocene stickleback genomes reveal the constraints on parallel evolution
Authors: Kirch Melanie , Romundset Anders , Gilbert M. Thomas P. , Jones Felicity C. , Foote Andrew D. 
Published: August 2020

Parallel evolution is typically studied by comparing modern populations from contrasting environments, therefore the chronology of adaptive changes remains poorly understood. We applied a paleogenomics approach to investigate this temporal component of adaptation by sequencing the genomes of 11-13,000-year-old stickleback recovered from the transitionary layer between marine and freshwater sediments of two Norwegian isolation lakes, and comparing them with 30 modern stickleback genomes from the same lakes and adjacent marine fjord. The ancient stickleback shared genome-wide ancestry with the modern fjord population, whereas modern lake populations have lost substantial ancestral variation following founder effects. We found modern lake stickleback had lost freshwater-adaptive alleles found in the ancient stickleback genomes, and showed incomplete adaptation, revealing the hitherto underappreciated stochastic nature of selection on standing variation present in founder populations.One Sentence Summary‘Pleistocene threespine stickleback genomes reveal insights into the earliest stages of freshwater adaptation’