bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of the imprinted allele of the p57Kip2 gene in mouse neocortical development
Authors: Imaizumi Yui , Furutachi Shohei , Watanabe Tomoyuki , Miya Hiroaki , Kawaguchi Daichi , Gotoh Yukiko 
Published: August 2019

AbstractImprinted genes are expressed from only one allele in a parent of origin–specific manner. The cyclin-dependent kinase inhibitor p57Kip2 (p57) is encoded by an imprinted gene, with the paternal allele being silenced. The possible expression and function of the paternal allele of p57 have remained little studied, however. We now show that the paternal allele of the p57 gene is expressed at a low level in the developing mouse neocortex. Surprisingly, the central nervous system-specific conditional deletion of the paternal allele (pat cKO) at the p57 locus resulted in a marked reduction in brain size. Furthermore, pat cKO gradually reduced the number of neural stem-progenitor cells (NPCs) during neocortical development, and thus reduced the number of upper-layer neurons, which were derived from late-stage NPCs. Our results thus show that the paternal allele of the p57 locus plays a key role in maintenance of NPCs during neocortical development.
Gene prediction in heterogeneous cancer tissues and establishment of Least Absolute Shrinking and Selection Operator model of lung squamous cell carcinoma
Authors: Khaliq Ateeq Muhammed , Rg SharathChandra , Rajamohan Meenakshi 
Published: August 2019

AbstractBackgroundThis study is aimed to establish a Least Absolute Shrinking and Selection Operator (LASSO) model based on tumor heterogeneity to predict the best features of LUSC in various cancer subtypes.MethodsThe RNASeq data of 505 LUSC cancer samples were downloaded from the TCGA database. Subsequent to the identification of differentially expressed genes (DEGs), the samples were divided into two subtypes based on the consensus clustering method. The subtypes were estimated with the abundance of immune and non-immune stromal cell populations which infiltrated tissue. LASSO model was established to predict each subtype’s best genes. Enrichment pathway analysis was then carried out. Finally, the validity of the LUSC model for identifying features was established by the survival analysis.Results240 and 262 samples were clustered in Subtype-1 and Subtype-2 groups respectively. DEG analysis was performed on each subtype. A standard cutoff was applied and in total, 4586 genes were upregulated and 1495 were downregulated in case of subtype-1 and 5016 genes were upregulated and 3224 were downregulated in case of subtype-2. LASSO model was established to predict the best features from each subtypes, 49 and 34 most relevant genes were selected in subtype-1 and subtype-2. The abundance of tissue-infiltrates analysis distinguished the subtypes based on the expression pattern of immune infiltrates. Survival analysis showed that this model could effectively predict the best and distinct features in cancer subtypes.DiscussionThis study suggests that the unsupervised clustering and LASSO model-based feature selection can be effectively used to predict relevant genes which might play an important role in cancer diagnosis.
Modelling the effects of leaky predator-exclusion fences and their surrounding halo
Authors: Agarwal Kanupriya , Bode Michael 
Published: August 2019

ABSTRACTTerrestrial fauna of the southern hemisphere, particularly Australia and New Zealand, have suffered significant declines and extinctions due to predation by introduced red foxesVulpes vulpesand catsFelis catus. Predator-exclusion fences offer protection to these threatened species and allow their populations to persist and even flourish within their boundaries. These fences have traditionally been designed to stop the movement of both the invasive predators (into the fence), and the native animals (out of the fence). However, recent theory and evidence suggest that when native animals are able to move across the fence, they can create a population beyond the fence boundary. This phenomena has been called a “halo effect”, and has the potential to both expand the direct and indirect benefits of predator-exclusion fences, and to reduce their negative effects. However, the conditions under which such an effect can be achieved are uncertain. They include questions about which native species could support a meaningful halo, what levels of predation outside the fence can be tolerated, and how permeable the fence would need to be. Here, we formulate this problem as both a simple two-patch model and a spatial partial differential equation model. We use the two approaches to explore the conditions under which a halo can deliver conservation benefits, and offer clear insights into the problem.
Time-resolved single-cell transcriptomics uncovers dynamics of cardiac neutrophil diversity in murine myocardial infarction
Authors: Vafadarnejad Ehsan , Rizzo Giuseppe , Krampert Laura , Arampatzi Panagiota , Nugroho Vallery Audy , Schulz Dirk , Roesch Melanie , Alayrac Paul , Vilar Jose , Silvestre Jean-Sébastien , Zernecke Alma , Saliba Antoine-Emmanuel , Cochain Clément 
Published: August 2019

AbstractObjectiveAfter myocardial infarction, neutrophils rapidly and massively infiltrate the heart, where they can promote both tissue healing and damage. Here, we investigated the dynamics of cardiac neutrophil heterogeneity after infarction.Methods and resultsWe employed single-cell transcriptomics (scRNA-seq) to investigate temporal neutrophil heterogeneity in the heart after murine myocardial infarction. At day 1, 3, and 5 after infarction, neutrophils could be delineated into six distinct clusters with specific time-dependent patterning and proportions. While the majority of neutrophils at day 1 were characterized by high expression of chemokines (e.g.Cxcl3,Ccl6), and putative activity of transcriptional regulators involved in hypoxic response (Hif1a) and emergency granulopoiesis (Cebpb), two major subsets ofSiglecfhi(enriched for e.g.Icam1andTnf) andSiglecflow(Slpi, Ifitm1) neutrophils were found at 3 and 5 days. Flow cytometry analysis confirmed the presence of LY6G+SIGLECFhiand LY6G+SIGLECFlowneutrophils in the heart from 3 days after infarction onwards. LY6G+SIGLECFhineutrophils were absent from the bone marrow, blood and spleen, suggesting local acquisition of surface SIGLECF. Acquisition of the SIGLECFhistate was paralleled by features of neutrophil ageing and activation (ICAM1hiCXCR4hiCD49dhiCD62Llow). scRNA-seq of atherosclerotic aortas revealed two neutrophil subsets with gene expression patterns reminiscent of the majorSiglecfhiandSiglecflowcardiac neutrophil subpopulations, revealing that these populations may be present across distinct contexts of cardiovascular inflammation.ConclusionAltogether, our data provide a time-resolved census of neutrophil diversity and gene expression dynamics in the mouse ischemic heart at the single-cell level, and suggests that temporal neutrophil heterogeneity is in part driven by local transition to a SIGLECFhistate.
Release of stem cells from quiescence reveals multiple gliogenic domains in the adult brain
Authors: Delgado Ana C. , Maldonado-Soto Angel R. , Silva-Vargas Violeta , Mizrak Dogukan , Känel Thomas von , Paul Alex , Madar Aviv , Cuervo Henar , Kitajewski Jan , Lin Chyuan-Sheng , Doetsch Fiona 
Published: August 2019

AbstractQuiescent neural stem cells (NSCs) in the adult ventricular-subventricular zone (V-SVZ) have a regional identity and undergo activation to generate neurons. The domains for gliogenesis are less explored. Here we show that Platelet-Derived Growth Factor Receptor beta (PDGFRβ) is expressed by adult V-SVZ NSCs that generate olfactory bulb interneurons and glia with slow baseline kinetics. Selective deletion of PDGFRβ in adult V-SVZ NSCs leads to their release from quiescence uncovering multiple domains in the septal wall for oligodendrocyte and astrocyte formation. Unexpectedly, we identify a novel intraventricular oligodendrocyte progenitor inside the brain ventricles. Together our findings reveal different NSC spatial domains for gliogenesis in the adult V-SVZ that are largely quiescent under homeostasis and may have key functions for brain plasticity.
Optogenetic inhibition of Delta reveals digital Notch signaling output during tissue differentiation
Authors: Viswanathan Ranjith , Necakov Aleksandar , Trylinski Mateusz , Harish Rohit Krishnan , Krueger Daniel , Esposito Emilia , Schweisguth Francois , Neveu Pierre , De Renzis Stefano 
Published: August 2019

AbstractSpatio-temporal regulation of signalling pathways plays a key role in generating diverse responses during the development of multicellular organisms. The role of signal dynamics in transferring signalling informationin vivois incompletely understood. Here we employ genome engineering inDrosophila melanogasterto generate a functional optogenetic allele of the Notch ligand Delta (opto-Delta), which replaces both copies of the endogenous wild type locus. Using clonal analysis, we show that optogenetic activation blocks Notch activation through cis-inhibition in signal-receiving cells. Signal perturbation in combination with quantitative analysis of a live transcriptional reporter of Notch pathway activity reveals differential tissue- and cell-scale regulatory modes. While at the tissue-level the duration of Notch signalling determines the probability with which a cellular response will occur, in individual cells Notch activation acts through a switch-like mechanism. Thus, time confers regulatory properties to Notch signalling that exhibit integrative digital behaviours during tissue differentiation.
Xanthomonas sontii sp. nov., a non-pathogenic bacterium isolated from healthy basmati rice (Oryza sativa) seeds from India
Authors: Bansal Kanika , Kaur Amandeep , Midha Samriti , Kumar Sanjeet , Korpole Suresh , Patil Prabhu B. 
Published: August 2019

AbstractThree yellow pigmented, Gram negative, aerobic, rod shaped, motile bacterial strains designated as PPL1, PPL2 and PPL3 were isolated from healthy basmati rice seeds. Phenotypic, biochemical and 16S rRNA gene sequence analysis assigned these strains to the genus Xanthomonas. The 16S rRNA gene sequence was having 99.59% similarity with X. sacchari CFBP4641T. However, whole genome based phylogenomic analysis revealed that these strains formed a distinct monophyletic clade with X. sacchari CFBP4641T as their closest neighbour. Taxonogenomic studies based on average nucleotide identity (orthoANI) and digital DNA-DNA hybridization (dDDH) values of these strains with type strains (or representative strains) of different Xanthomonas species including X. sacchari showed below recommended threshold values of ANI (<96%) and dDDH (70%) for species delineation. Furthermore, at the whole genome level, PPL1 and PPL2 were found to be clonal, while PPL3 was not a clonal, but belonging to the same species. Our in planta pathogenicity studies revealed that the strains PPL1, PPL2 and PPL3 are non-pathogenic to rice plants. Hence, based on the present study, they form a novel lineage and species associated with rice seeds for which the name Xanthomonas sontii sp. nov. is proposed. The type strain for the X. sontii sp. nov. is PPL1T (CFBP8688T = ICMP23426T = MTCC12491T) and strains PPL2 (CFBP8689 = ICMP23427 = MTCC12492) and PPL3 (CFBP8690 =ICMP23428 = MTCC12492) as other strains of the species.
Meta-analysis of problematic alcohol use in 435,563 individuals identifies 29 risk variants and yields insights into biology, pleiotropy and causality
Authors: Zhou Hang , Sealock Julia M. , Sanchez-Roige Sandra , Clarke Toni-Kim , Levey Daniel , Cheng Zhongshan , Li Boyang , Polimanti Renato , Kember Rachel L. , Smith Rachel Vickers , Thygesen Johan H. , Morgan Marsha Y. , Atkinson Stephen R. , Thursz Mark R. , Nyegaard Mette , Mattheisen Manuel , Børglum Anders D. , Johnson Emma C. ,   the VA Million Veteran Program, Justice Amy C. , Palmer Abraham A. , McQuillin Andrew , Davis Lea K. , Edenberg Howard J. , Agrawal Arpana , Kranzler Henry R. , Gelernter Joel 
Published: August 2019

AbstractProblematic alcohol use (PAU) is a leading cause of death and disability worldwide. Although genome-wide association studies (GWASs) have identified PAU risk genes, the genetic architecture of this trait is not fully understood. We conducted a proxy-phenotype meta-analysis of PAU combining alcohol use disorder and problematic drinking in 435,563 European-ancestry individuals. We identified 29 independent risk variants, 19 of them novel. PAU was genetically correlated with 138 phenotypes, including substance use and psychiatric traits. Phenome-wide polygenic risk score analysis in an independent biobank sample (BioVU, n=67,589) confirmed the genetic correlations between PAU and substance use and psychiatric disorders. Genetic heritability of PAU was enriched in brain and in genomic conserved and regulatory regions. Mendelian randomization suggested causal effects on liability to PAU of substance use, psychiatric status, risk-taking behavior, and cognitive performance. In summary, this large PAU meta-analysis identified novel risk loci and revealed genetic relationships with numerous other outcomes.
The basal level of gene expression associated with chromatin loosening shapes Waddington landscapes and controls cell differentiation
Authors: Flouriot Gilles , Jehanno Charly , le Page Yann , le Goff Pascale , Boutin Benjamin , Michel Denis 
Published: August 2019

AbstractThe baseline level of transcription is variable and seriously complicates the normalization of comparative transcriptomic data, but its biological importance remains unappreciated. We show that this ingredient is in fact crucial for the interpretation of molecular biology results. It is correlated to the degree of chromatin loosening measured by DNA accessibility, and systematically leads to cellular dedifferentiation as assessed by transcriptomic signatures, irrespective of the molecular and cellular tools used. A theoretical analysis of gene circuits formally involved in differentiation, reveals that the epigenetic landscapes of Waddington are restructured by the level of non-specific expression, such that the attractors of progenitor and differentiated cells can be mutually exclusive. Together, these results unveil a generic principle of epigenetic landscape remodeling in which the basal gene expression level, notoriously important in pluripotent cells, allows the maintenance of stemness by generating a specific landscape and in turn, its reduction favors multistability and thereby differentiation. This study highlights how heterochromatin maintenance is essential for preventing pathological cellular reprogramming, age-related diseases and cancer.
Global H-NS counter-silencing by LuxR activates quorum sensing gene expression
Authors: Chaparian Ryan R. , Tran Minh L. N. , Conrad Laura C. Miller , Rusch Douglas B. , Kessel Julia C. van 
Published: August 2019

AbstractBacteria coordinate cellular behaviors using a cell-cell communication system termed quorum sensing. In Vibrio harveyi, the master quorum sensing transcriptional factor LuxR directly regulates >100 genes in response to changes in population density. Here, we show that LuxR derepresses quorum sensing loci by competing with H-NS, a global transcriptional repressor that oligomerizes on DNA to form filaments and bridges. We first identified H-NS as a repressor of bioluminescence gene expression, for which LuxR is a required activator. In an hns deletion strain, LuxR is no longer necessary for transcription activation of the bioluminescence genes, suggesting that the primary role of LuxR is to displace H-NS to derepress gene expression. Using RNA-seq and ChIP-seq, we determined that H-NS and LuxR co-regulate and co-occupy 28 promoters driving expression of 63 genes across the genome. ChIP-PCR assays show that as autoinducer concentration increases, LuxR protein accumulates at co-occupied promoters while H-NS protein disperses. LuxR is sufficient to evict H-NS from promoter DNA in vitro, which is dependent on LuxR DNA binding activity. From these findings, we propose a model in which LuxR serves as a counter-silencer at H-NS-repressed quorum sensing loci by disrupting H-NS nucleoprotein complexes that block transcription.
Crystal structure of the TbBILBO1 N-terminal domain reveals a ubiquitin fold with a long rigid loop for the binding of its partner
Authors: Vidilaseris Keni , Landrein Nicolas , Pivovarova Yulia , Lesigang Johannes , Aeksiri Niran , Robinson Derrick R. , Bonhivers Melanie , Dong Gang 
Published: August 2019

ABSTRACTBILBO1 was the first characterized component of the flagellar pocket collar (FPC) in trypanosomes. The N-terminal domain (NTD) of BILBO1 plays an essential role in Trypanosoma brucei FPC biogenesis and is thus vital for the parasite’s survival. Here we report a 1.6-Å resolution crystal structure of TbBILBO1-NTD, which revealed a conserved horseshoe-like hydrophobic pocket formed by an unusually long loop. Mutagenesis studies suggested that another FPC protein, FPC4, interacts with TbBILBO1 via mainly contacting the three conserved aromatic residues W71, Y87 and F89 at the center of this pocket. Overall, we have determined the binding site of TbFPC4 on TbBILBO1-NTD, which may provide a basis for rational drug design in the future.
Rad51 Interaction Analysis Reveals a Functional Interplay Among Recombination Auxiliary Factors
Authors: Argunhan Bilge , Sakakura Masayoshi , Afshar Negar , Kurihara Misato , Ito Kentaro , Maki Takahisa , Kanamaru Shuji , Murayama Yasuto , Tsubouchi Hideo , Takahashi Masayuki , Takahashi Hideo , Iwasaki Hiroshi 
Published: August 2019

ABSTRACTAlthough Rad51 is the key protein in homologous recombination (HR), a major DNA double-strand break repair pathway, several auxiliary factors interact with Rad51 to promote productive HR. Here, we present an interdisciplinary characterization of the interaction between Rad51 and Swi5-Sfr1, a widely conserved auxiliary factor. NMR and site-specific crosslinking experiments revealed two distinct sites within the intrinsically disordered N-terminus of Sfr1 that cooperatively bind to Rad51. Although disruption of this binding severely impaired Rad51 stimulation in vitro, interaction mutants did not show any defects in DNA repair. Unexpectedly, in the absence of the Rad51 paralogs Rad55-Rad57, which constitute another auxiliary factor complex, these interaction mutants were unable to promote DNA repair. Our findings provide molecular insights into Rad51 stimulation by Swi5-Sfr1 and suggest that, rather than functioning in an independent subpathway of HR as was previously proposed, Rad55-Rad57 facilitates the recruitment of Swi5-Sfr1 to Rad51.
Context-dependent and dynamic functional influence of corticothalamic pathways to first- and higher-order visual thalamus
Authors: Kirchgessner Megan A. , Franklin Alexis D. , Callaway Edward M. 
Published: August 2019

AbstractLayer 6 (L6) is the sole purveyor of corticothalamic (CT) feedback to first-order thalamus and also sends projections to higher-order thalamus, yet how it engages the full corticothalamic circuit to contribute to sensory processing in an awake animal remains unknown. We sought to elucidate the functional impact of L6CT projections from primary visual cortex to visual thalamic nuclei dLGN (first-order) and pulvinar (higher-order) using optogenetics and extracellular electrophysiology in awake mice. While sustained L6CT photostimulation suppresses activity in both visual thalamic nuclei in vivo, moderate-frequency (10Hz) stimulation powerfully facilitates thalamic spiking. We show that each stimulation paradigm differentially influences the balance between monosynaptic excitatory and disynaptic inhibitory corticothalamic pathways to dLGN and pulvinar as well as the prevalence of burst versus tonic firing. Altogether, our results support a model in which L6CTs modulate first- and higher-order thalamus through parallel excitatory and inhibitory pathways that are highly dynamic and context-dependent.SignificanceLayer 6 corticothalamic (L6CT) projections play important modulatory roles in thalamic processing, yet how this modulation is executed is unclear. While some studies suggest fundamentally inhibitory influence of L6CTs over first-order thalamus, potential complex, frequency-dependent effects have not been investigated in vivo. Moreover, how L6CTs affect higher-order nuclei in vivo has not been explored. This study utilizes various optogenetic manipulations of L6CTs with single-unit recordings from multiple thalamic nuclei in awake mice to address these questions. Our results illustrate similar effects of L6CTs on first- and higher-order visual thalamic nuclei, yet very different effects within-nucleus depending on how L6CTs are engaged. These findings suggest that L6CT modulation is not simply inhibitory by nature, but instead is dynamic and context-dependent.
Considering founding and variable genomes is critical in studying polyploid evolution
Authors: Ye Xueling , Hu Haiyan , Zhou Hong , Jiang Yunfeng , Gao Shang , Yuan Zhongwei , Stiller Jiri , Li Chengwei , Chen Guoyue , Liu Yaxi , Wei Yuming , Zheng You-Liang , Liu Chunji 
Published: August 2019

AbstractA wide range of differences between the subgenomes, termed as subgenome asymmetry or SA, has been reported in various polyploids and different species seem to have different responses to polyploidization. We compared subgenome differences in gene ratio and relative diversity between artificial and natural genotypes of several allopolyploid species. Surprisingly, consistent differences in neither gene ratio nor relative diversity between the subgenomes were detected between these two types of polyploid genotypes although they differ in times exposed to evolutional selection. As expected, the estimated ratio of retained genes between a subgenome and its diploid donor was invariably higher for the artificial allopolyploid genotypes due likely to the presence of variable genome components (VGC). Clearly, the presence of VGC means that exaggerated differences between a donor and a subgenome in a polyploid are inevitable when random genotypes were used to represent species of either a polyploid or its donors. SA was also detected in genotypes before the completion of the polyploidization events as well as in those which were not formed via polyploidization. Considering that significant changes during and following polyploidization have been detected in previous studies, our results suggest that the influence of VGC needs to be considered in evaluating SA and that diploid donors may define changes in polyploid evolution.