bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epithelial morphogenesis in the perinatal mouse uterus
Authors: Vue Zer , Behringer Richard R. 
Published: January 2020

AbstractBackgroundThe uterus is the location where multiple events occur that are required for the start of new life in mammals. The adult uterus contains endometrial or uterine glands that are essential for female fertility. In the mouse, uterine glands are located in the lateral and anti-mesometrial regions of the uterine horn. Previous 3D-imaging of the adult uterus, its glands, and implanting embryos has been performed by multiple groups, using fluorescent microscopy. Adenogenesis, the formation of uterine glands, initiates after birth. Recently, we created a 3D-staging system of mouse uterine gland development at postnatal time points, using light sheet fluorescent microscopy. Here, using a similar approach, we examine the morphological changes in the epithelium of the perinatal mouse uterus.ResultsThe uterine epithelium exhibits mesometrial-antimesometrial (dorsoventral) patterning as early as three days after birth (P3), marked by the presence of the mesometrially-positioned developing uterine rail. Uterine gland buds are present beginning at P4. Novel morphological epithelial structures, including a ventral ridge and uterine segments were identified.ConclusionsThe perinatal mouse uterine luminal epithelium develops mesometrial-antimesometrial (dorsal-ventral) morphologies at 3-4 days post-partum. Between 5-6 days post-partum uterine epithelial folds form, defining alternating left-right segments.Bullet pointsMorphological patterning events in the perinatal uterine epithelium are not well described.Light sheet microscopy was used to generate volumetric reconstructions of the perinatal mouse uterine epithelium.At postnatal day 3 (P3), the uterine epithelium shows the first signs of dorsoventral pattern, with the presence of the forming mesometrially-positioned uterine rail.The first morphological indication of uterine adenogenesis begins at P4.Novel morphological structures were identified from volumetric reconstructions, including the presence of a ventral ridge (another sign of dorsoventral pattern) and uterine segmentation.
The gammaherpesviral TATA-box-binding protein directly interacts with the CTD of host RNA Pol II to direct late gene transcription
Authors: Castañeda Angelica F. , Didychuk Allison L. , Louder Robert K. , McCollum Chloe O. , Davis Zoe H. , Nogales Eva , Glaunsinger Britt A. 
Published: January 2020

ABSTRACTβ- and γ-herpesviruses include the oncogenic human viruses Kaposi’s sarcoma-associated virus (KSHV) and Epstein-Barr virus (EBV), and human cytomegalovirus (HCMV), which is a significant cause of congenital disease. Near the end of their replication cycle, these viruses transcribe their late genes in a manner distinct from host transcription. Late gene transcription requires six virally-encoded proteins, one of which is a functional mimic of host TATA-box-binding protein (TBP) that is also involved in recruitment of RNA polymerase II (Pol II) via unknown mechanisms. Here, we applied biochemical protein interaction studies together with electron microscopy-based imaging of a reconstituted human preinitiation complex to define the mechanism underlying Pol II recruitment. These data revealed that the herpesviral TBP, encoded by ORF24 in KSHV, makes a direct protein-protein contact with the C-terminal domain of host RNA polymerase II (Pol II), which is a unique feature that functionally distinguishes viral from cellular TBP. The interaction is mediated by the N-terminal domain (NTD) of ORF24 through a conserved motif that is shared in its β- and γ-herpesvirus homologs. Thus, these herpesviruses employ an unprecedented strategy in eukaryotic transcription, wherein promoter recognition and polymerase recruitment are facilitated by a single transcriptional activator with functionally distinct domains.SIGNIFICANCE STATEMENTThe β- and γ-herpesviruses mediate their late gene transcription through a set of viral transcriptional activators (vTAs). One of these vTAs, ORF24 in Kaposi’s sarcoma-associated herpesvirus (KSHV), is a mimic of host TATA-box-binding protein (TBP). We demonstrate that the N-terminal domain of ORF24 and its homologs from other β- and γ-herpesviruses directly bind the unstructured C-terminal domain (CTD) of RNA Pol II. This functionally distinguishes the viral TBP mimic from cellular TBP, which does not bind Pol II. Thus, herpesviruses encode a transcription factor that has the dual ability to directly interact with promoter DNA and the polymerase, a property which is unique in eukaryotic transcription and is conceptually akin to prokaryotic transcription factors.
Litterbox - A gnotobiotic zeolite-clay system to investigate Arabidopsis-microbe interactions
Authors: Miebach Moritz , Schlechter Rudolf , Clemens John , Jameson Paula E. , Remus-Emsermann Mitja N.P. 
Published: January 2020

AbstractPlants are colonised by millions of microorganisms representing thousands of species with varying effects on plant growth and health. The microbial communities found on plants are compositionally consistent and their overall positive effect on the plant is well known. However, the effects of individual microbiota members on plant hosts andvice versa, as well as the underlying mechanisms remain largely unknown. Here, we describe ‘Litterbox’, a highly controlled system to investigate plant-microbe interactions. Plants were grown gnotobiotically on zeolite-clay, an excellent soil replacement that retains enough moisture to avoid subsequent watering. Plants grown on zeolite phenotypically resemble plants grown under environmental conditions. Further, bacterial densities on leaves in the Litterbox system resembled those in temperate environments. A PDMS sheet was used to cover the zeolite, thereby significantly lowering the bacterial load in the zeolite and rhizosphere. This reduced the likelihood of potential systemic responses in leaves induced by microbial rhizosphere colonisation. We present results of example experiments studying the transcriptional responses of leaves to defined microbiota members and the spatial distribution of bacteria on leaves. We anticipate that this versatile and affordable plant growth system will promote microbiota research and help in elucidating plant-microbe interactions and their underlying mechanisms.
Genetic diversity and evolution of Hantaan virus in China and its neighbors
Authors: Li Naizhe , Li Aqian , Liu Yang , Wu Wei , Li Chuan , Yu Dongyang , Zhu Yu , Li Jiandong , Li Dexin , Wang Shiwen , Liang Mifang 
Published: January 2020

AbstractBackgroudHantaan virus(HTNV), as one of the pathogenic hantaviruses of HFRS, has raised serious concerns in Eurasia. China and its neighbors, especially Russia and South Korea, are seriously suffered HTNV infections. Recent studies reported genetic diversity and phylogenetic features of HTNV in different parts of China, but the analyses from the holistic perspective are rare.Methodology and Principal FindingsTo better understand HTNV genetic diversity and dynamics, we analyzed all available complete sequences derived from the S and M segments with bio-informatic tools. Our study revealed 11 phylogroups and sequences showed obvious geographic clustering. We found 42 significant amino acid variants sites and 18 of them located in immune epitopes. Nine recombination events and seven reassortment isolates were deteced in our study. Sequences from Guizhou were highly genetic divergent, characterized by the emergence of multiple lineages, recombination and reassortment events. We found that HTNV probably emerged in Zhejiang about 1,000 years ago and the population size expanded from 1980s to 1990s. Bayesian stochastic search variable selection analysis revealed that Heilongjiang, Shaanxi and Guizhou played important roles in HTNV evolution and migration.Conclusions/SignificanceThese findings reveal the original and evolution features of HTNV which might assist in understanding Hantavirus epidemics and would be useful for disease prevention and control.Author summaryHemorrhagic Fever with Renal Syndrome (HFRS) and Hantavirus Pulmonary Syndrome (HPS) are endemic zoonotic infectious diseases caused by hantaviruses that belong to the Family Bunyaviridae. Hantaviruses have gained worldwide attention as etiological agents of emerging zoonotic diseases, with fatality rates ranging from <10% up to 60%. However, our knowledge about the emergence and evolution of HTNV is limited. To get more information about HTNV genetic diversity and phylogenetic features in holistic perspective, we investigated the genetic diversity and spatial distribution of HTNV using all available whole genomic sequences of S and M segments. We also gain insights into the genetic diversity and spatial-temporal dynamics of HTNV. These data can augment traditional approach to infectious disease surveillance and control.
Localization of neutral evolution: selection for mutational robustness and the maximal entropy random walk
Authors: Smerlak Matteo 
Published: January 2020

AbstractIf many mutations confer no immediate selective advantage, they can pave the way for the discovery of fitter phenotypes and their subsequent positive selection. Understanding the reach of neutral evolution is therefore a key problem linking diversity, robustness and evolvability at the molecular scale. While this process is usually described as a random walk in sequence space with clock-like regularity, new effects can arise in large microbial or viral populations where new mutants arise before old ones can fix. Here I show that the clonal interference of neutral variants shuts off the access to neutral ridges and thus induces localization within the robust cores of neutral networks. As a result, larger populations can be less effective at exploring sequence space than smaller ones—a counterintuitive limitation to evolvability which invalidates analogies between evolution and percolation. I illustrate these effects by revisiting Maynard Smith’s word-game model of protein evolution. Interestingly, the phenomenon of neutral interference connects evolutionary dynamics to a Markov process known in network science as the maximal-entropy random walk; its special properties imply that, when many neutral variants interfere in a population, evolution chooses mutational paths—not individual mutations—uniformly at random.
Oct4 regulates embryonic pluripotency via metabolic mechanisms and Stat3 signalling
Authors: Stirparo Giuliano Giuseppe , Kurowski Agata , Strawbridge Stanley Eugene , Stuart Hannah , Boroviak Thorsten Edwin , Yanagida Ayaka , Nichols Jennifer 
Published: January 2020

AbstractOCT4 is a fundamental component of the molecular circuitry governing pluripotencyin vivoandin vitro. To determine how OCT4 protects the pluripotent lineage from differentiation into trophoblast, we used single cell transcriptomics and quantitative immunofluorescence on blastocysts and established differentially expressed genes and pathways between control and OCT4 null cells. Activation of most pluripotency-associated transcription factors in the early mouse inner cell mass appears independent of OCT4, whereas JAK/STAT signalling requires OCT4, via activation of IL6ST. Single cell deconvolution, diffusion component and trajectory inference dissected the process of differentiation of OCT4 null cells by activating specific gene-network and transcription factors. Downregulation of glycolytic and oxidative metabolism was observed. CHIPseq analysis suggests OCT4 directly targets rate-limiting glycolytic enzymes. Concomitant with significant disruption of the STAT3 pathway, oxidative respiration is significantly diminished in OCT4 null cells. Upregulation of the lysosomal pathway detected in OCT4 null embryos is likely attributable to aberrant metabolism.Highlights and noveltyMajor pluripotency-associated transcription factors are activated in OCT4-deficient early mouse ICM cells, coincident with ectopic expression of trophectoderm markersJAK/STAT signalling is defective in OCT4 null embryosOCT4 promotes expression of KATS enzymes by means of glycolytic production of Acetyl CoA to secure chromatin accessibility for acquisition of epiblast identityOCT4 regulates the metabolic and biophysical processes required for establishment of embryonic pluripotency
Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody
Authors: Tian Xiaolong , Li Cheng , Huang Ailing , Xia Shuai , Lu Sicong , Shi Zhengli , Lu Lu , Jiang Shibo , Yang Zhenlin , Wu Yanling , Ying Tianlei 
Published: January 2020

ABSTRACTThe newly identified 2019 novel coronavirus (2019-nCoV) has caused more than 800 laboratory-confirmed human infections, including 25 deaths, posing a serious threat to human health. Currently, however, there is no specific antiviral treatment or vaccine. Considering the relatively high identity of receptor binding domain (RBD) in 2019-nCoV and SARS-CoV, it is urgent to assess the cross-reactivity of anti-SARS-CoV antibodies with 2019-nCoV spike protein, which could have important implications for rapid development of vaccines and therapeutic antibodies against 2019-nCoV. Here, we report for the first time that a SARS-CoV-specific human monoclonal antibody, CR3022, could bind potently with 2019-nCoV RBD (KD of 6.3 nM). The epitope of CR3022 does not overlap with the ACE2 binding site within 2019-nCoV RBD. Therefore, CR3022 has the potential to be developed as candidate therapeutics, alone or in combination with other neutralizing antibodies, for the prevention and treatment of 2019-nCoV infections. Interestingly, some of the most potent SARS-CoV-specific neutralizing antibodies (e.g., m396, CR3014) that target the ACE2 binding site of SARS-CoV failed to bind 2019-nCoV spike protein, indicating that the difference in the RBD of SARS-CoV and 2019-nCoV has a critical impact for the cross-reactivity of neutralizing antibodies, and that it is still necessary to develop novel monoclonal antibodies that could bind specifically to 2019-nCoV RBD.
Foveal pRF properties in the visual cortex depend on the extent of stimulated visual field
Authors: Prabhakaran Gokulraj , Carvalho Joana , Invernizzi Azzurra , Kanowski Martin , Renken Remco J. , Cornelissen Frans W. , Hoffmann Michael B. 
Published: January 2020

AbstractPrevious studies demonstrated that alterations in functional MRI derived receptive field (pRF) properties in cortical projection zones of retinal lesions can erroneously be mistaken for cortical large-scale reorganization in response to visual system pathologies. We tested, whether such confounds are also evident in the normal cortical projection zone of the fovea for simulated peripheral visual field defects. We applied fMRI-based visual field mapping of the central visual field at 3 Tesla in eight controls to compare the pRF properties of the central visual field of a reference condition (stimulus radius: 14°) and two conditions with simulated peripheral visual field defect, i.e., with a peripheral gray mask, stimulating only the central 7° or 4° radius. We quantified, for the cortical representation of the actually stimulated visual field, the changes in the position and size of the pRFs associated with reduced peripheral stimulation using conventional and advanced pRF modeling. We found foveal pRF-positions (≤3°) to be significantly shifted towards the periphery (p<0.05, corrected). These pRF-shifts were largest for the 4° condition [visual area (mean eccentricity shift): V1 (0.9°), V2 (0.9°), V3 (1.0°)], but also evident for the 7° condition [V1 (0.5°), V2 (0.5°), V3 (0.9°)]. Further, an overall enlargement of pRF-sizes was observed. These findings indicate the dependence of foveal pRF parameters on the spatial extent of the stimulated visual field. Consequently, our results imply that, previously reported similar findings in patients with actual peripheral scotomas need to be interpreted with caution and indicate the need for adequate control conditions in investigations of visual cortex reorganization.HighlightsFoveal pRF properties change in controls with restricted peripheral stimulationpRFs shift in position and enlarge in size for reduced stimulation extentAlterations in pRF characteristics in patients should be interpreted with cautionAdequate control conditions needed in investigations of visual cortex plasticity
Creld2 function during unfolded protein response is essential for liver metabolism homeostasis
Authors: Kern Paul , Balzer Nora R. , Bender Franziska , Frolov Alex , Wunderling Klaus , Sowa Jan-Peter , Bonaguro Lorenzo , Ulas Thomas , Thiele Christoph , Schultze Joachim L. , Canbay Ali , Bauer Reinhard , Mass Elvira 
Published: January 2020

AbstractThe unfolded protein response (UPR) is associated with the hepatic metabolic function, yet it is not well understood how endoplasmic reticulum (ER) disturbance might influence metabolic homeostasis. Here, we describe the physiological function of Cysteine-rich with EGF-like domains 2 (Creld2), previously characterized as a downstream target of the ER-stress signal transducer Atf6. To this end we generatedCreld2-deficient mice and induced UPR by injection of tunicamycin. Creld2 augments protein folding and creates an interlink between the UPR axes through its interaction with proteins involved in UPR. Thereby, Creld2 promotes tolerance to ER stress and recovery from acute stress.Creld2-deficiency leads to a dysregulated UPR, and causes the development of hepatic steatosis during ER stress conditions. Moreover, Creld2 enhancement of the UPR assists in the regulation of energy expenditure. Furthermore, we observed a sex dimorphism in humans with fatty liver disease, with only males showing an accumulation of CRELD2 protein in the liver. These results reveal a Creld2 function at the intersection between UPR and metabolic homeostasis and suggest a mechanism in which chronic ER stress underlies fatty liver disease in males.
A mysterious 80 nm amoeba virus with a near-complete “ORFan genome” challenges the classification of DNA viruses
Authors: Boratto Paulo V. M. , Oliveira Graziele P. , Machado Talita B. , Andrade Ana Cláudia S. P. , Baudoin Jean-Pierre , Klose Thomas , Schulz Frederik , Azza Saïd , Decloquement Philippe , Chabrière Eric , Colson Philippe , Levasseur Anthony , La Scola Bernard , Abrahão Jônatas S. 
Published: January 2020

AbstractHere we report the discovery of Yaravirus, a new lineage of amoebal virus with a puzzling origin and phylogeny. Yaravirus presents 80 nm-sized particles and a 44,924 bp dsDNA genome encoding for 74 predicted proteins. More than 90% (68) of Yaravirus predicted genes have never been described before, representing ORFans. Only six genes had distant homologs in public databases: an exonuclease/recombinase, a packaging-ATPase, a bifunctional DNA primase/polymerase and three hypothetical proteins. Furthermore, we were not able to retrieve viral genomes closely related to Yaravirus in 8,535 publicly available metagenomes spanning diverse habitats around the globe. The Yaravirus genome also contained six types of tRNAs that did not match commonly used codons. Proteomics revealed that Yaravirus particles contain 26 viral proteins, one of which potentially representing a novel capsid protein with no significant homology with NCLDV major capsid proteins but with a predicted double-jelly roll domain. Yaravirus expands our knowledge of the diversity of DNA viruses. The phylogenetic distance between Yaravirus and all other viruses highlights our still preliminary assessment of the genomic diversity of eukaryotic viruses, reinforcing the need for the isolation of new viruses of protists.Significance statementMost of the known viruses of amoeba have been seen to share many features that eventually prompted authors to classify them into common evolutionary groups. Here we describe Yaravirus, an entity that could represent either the first isolated virus ofAcanthamoebaspp. out of the group of NCLDVs or, in alternative evolutive scenario, it is a distant and extremely reduced virus of this group. Contrary to what is observed in other isolated viruses of amoeba, Yaravirus is not represented by a large/giant particle and a complex genome, but at the same time carries an important number of previously undescribed genes, including one encoding a novel major capsid protein. Metagenomic approaches also testified for the rarity of Yaravirus in the environment.
Molecular characterization of a novel cytorhabdovirus with a unique genomic organization infecting yerba mate (Ilex paraguariensis) in Argentina
Authors: Bejerman Nicolás , Acevedo Raúl Maximiliano , de Breuil Soledad , Ruiz Oscar A. , Sansberro Pedro , Dietzgen Ralf G. , Nome Claudia , Debat Humberto 
Published: January 2020

AbstractThe genome of a novel rhabdovirus was detected in yerba mate (Ilex paraguariensisSt. Hil.). The newly identified virus, tentatively named yerba mate virus A (YmVA), has a genome of 14,961 nucleotides. Notably, eight open reading frames were identified in the antigenomic orientation of the negative-sense, single-stranded viral RNA, including two novel accessory genes, in the order 3’-N-P-3-4-M-G-L-8-5’. Sequence identity of the encoded proteins as well as phylogenetic analysis suggest that YmVA is a new member of the genusCytorhabdovirus, familyRhabdoviridae. YmVA unique genomic organization and phylogenetic relationships indicate that this virus likely represents a distinct evolutionary lineage within the cytorhabdoviruses.
Simulation based optimal evacuation plan in vertical ship lift: a case study
Authors: Wang Jian-Ping , Wang Mei-Ru , Zhou Jian-Lan , Zuo Qing-Jun , Shi Xun-Xian 
Published: January 2020

Purpose
The purpose of this study is to develop optimal evacuation plan to provide valuable theoretical and practical insight in the fire evacuation work of similar structures, by proposing a systematic simulation-based guided-evacuation agent-based model (GAM) and a three-stage mathematical evacuation model to investigate how to simulate, assess and improve the performance efficiency of the evacuation plan.

Design/methodology/approach
The authors first present the self-evacuation and guided-evacuation models to determine the optimal evacuation plan in ship chamber. Three key performance indicators are put forward to quantitatively assess the evacuation performance within the two fire scenarios. The evacuation model in tower is built to obtain the dividing points of the three different fire evacuation plans.

Findings
The study shows that the optimal evacuation plan determined by the GAM considering social relationships effectively relieves the congestion or collision of evacuees and improves the evacuation uniformity. The optimal evacuation plan not only solves the crush caused by congestion or collision of evacuees but also can greatly shorten the evacuation time for passenger ship fire.

Originality/value
This study establishes the GAM considering the interactive evacuee characteristics and the proportion of evacuees guided by the crew members to make the optimal evacuation plan more time-efficient. The self-evacuation process is simulated to assess the performance of the guided-evacuation strategies, which are used to verify the effectiveness and feasibility of the optimal evacuation plan in this research.