bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tissue remodeling and cell signaling underpin changes in tumor microenvironment heterogeneity in glioma oncogenesis
Authors: Dinevska Marija , Widodo Samuel S. , Furst Liam , Cuzcano Lucero , Fang Yitong , Mangiola Stefano , Neeson Paul J. , Darcy Phillip K. , Ramsay Robert G. , MacKay Fabienne , Stylli Stanley S. , Mantamadiotis Theo 
Published: December 2021

ABSTRACTBrain tumor cells thrive by adapting to the signals in their microenvironment. Understanding how the tumor microenvironment evolves during disease progression is crucial to deciphering the mechanisms underlying the functional behavior of cancer cells. To adapt, cancer cells activate signaling and transcriptional programs and migrate to establish micro-niches, in response to signals from neighboring cells and non-cellular stromal factors. Using multiple tissue analysis approaches to identify and measure immune cell infiltration and extracellular matrix deposition in brain tumors, we show that low-grade glioma is largely devoid of infiltrating immune cells and extracellular matrix proteins, while high-grade glioma exhibits abundant immune cell infiltration and activation, as well as extensive collagen deposition. Spatial analysis shows that most T-cells are sequestered in perivascular nests, but macrophages penetrate deep into tumor cell rich regions. High-grade gliomas exhibit heterogeneous PI3K and MAPK signaling, which correlates with distinct pathological hallmarks, including tumor angiogenesis, tumor cell density and extracellular matrix deposition. Our results also provide compelling evidence that tissue remodeling is an important element in glioma progression, and that targeting the extracellular matrix will be critical to improving GBM therapy.
An ACE2-dependent Sarbecovirus in Russian bats is resistant to SARS-CoV-2 vaccines
Authors: Seifert Stephanie N. , Bai Shuangyi , Fawcett Stephen , Norton Elizabeth B. , Zwezdaryk Kevin J. , Robinson James , Gunn Bronwyn , Letko Michael C. 
Published: December 2021

ABSTRACTSpillover of sarbecoviruses from animals to humans has resulted in outbreaks of severe acute respiratory syndrome SARS-CoVs and the ongoing COVID-19 pandemic. Efforts to identify the origins of SARS-CoV-1 and −2 has resulted in the discovery of numerous animal sarbecoviruses – the majority of which are only distantly related to known human pathogens and do not infect human cells. The receptor binding domain (RBD) on sarbecoviruses engages receptor molecules on the host cell and mediates cell invasion. Here, we tested the receptor tropism and serological cross reactivity for RBDs from two sarbecoviruses found in Russian horseshoe bats. While these two viruses are in a viral lineage distinct from SARS-CoV-1 and −2, one virus, Khosta-2, was capable of using human ACE2 to facilitate cell entry. Viral pseudotypes with a recombinant, SARS-CoV-2 spike encoding for the Khosta 2 RBD were resistant to both SARS-CoV-2 monoclonal antibodies and serum from individuals vaccinated for SARS-CoV-2. Our findings further demonstrate that sarbecoviruses circulating in wildlife outside of Asia also pose a threat to global health and ongoing vaccine campaigns against SARS-CoV-2ONE SENTENCE SUMMARYEuropean bat coronaviruses that are only distantly related to SARS-CoV-2 but use the same cell entry route, escape the immune response against SARS-CoV-2 vaccines, driving the need for broader vaccines.
Efemp1 modulates elastic fiber formation and mechanics of the extrahepatic bile duct
Authors: Llewellyn Jessica , Roberts Emilia , Liu Chengyang , Naji Ali , Assoian Richard K. , Wells Rebecca G. 
Published: December 2021

AbstractEGF-Containing Fibulin Extracellular Matrix Protein 1 (EFEMP1, also called fibulin 3) is an extracellular matrix protein linked in a genome-wide association study to biliary atresia, a fibro-inflammatory disease of the neonatal extrahepatic bile duct. EFEMP1 is expressed in most tissues and Efemp1 null mice have decreased elastic fibers in visceral fascia; however, in contrast to other short fibulins (fibulins 4 and 5), EFEMP1 does not have a role in the development of large elastic fibers, and its overall function remains unclear. We demonstrated that EFEMP1 is expressed in the submucosa of both neonatal and adult mouse and human extrahepatic bile ducts and that, in adult Efemp1+/- mice, elastin organization into fibers is decreased. We used pressure myography, a technique developed to study the mechanics of the vasculature, to show that Efemp1+/- extrahepatic bile ducts are more compliant to luminal pressure, leading to increased circumferential stretch. We conclude that EFEMP1 has an important role in the formation of elastic fibers and mechanical properties of the extrahepatic bile duct. These data suggest that altered expression of EFEMP1 in the extrahepatic bile duct leads to an abnormal response to mechanical stress such as obstruction, potentially explaining the role of EFEMP1 in biliary atresia.
Functional Anatomy of the TDP-43 Redox Sensor
Authors: Zhou Xiaoming , Sumrow Lily , Sutherland Lillian , Liu Daifei , Qin Tian , McKnight Steven L. , Liszczak Glen 
Published: December 2021

AbstractTAR binding protein 43 (TDP-43) is an RNA binding protein that assists in the maturation, export and sub-cellular localization of mRNA. The carboxyl terminal 153 residues of TDP-43 are of low sequence complexity and allow for self-association of the protein in a manner leading to its phase separation from an aqueous environment. These interactions assist TDP-43 in forming cytoplasmic RNA granules involved in the transport of mRNA for localized translation. Self-association of the TDP-43 low complexity (LC) domain is facilitated by a region of twenty five residues that are of extreme evolutionary conservation. The molecular basis for self-adherence of the protein through this region has been illuminated by a combination of structural and biochemical studies, allowing definition of a morphologically specific cross-β structure predicted to be weakly assembled by main chain hydrogen bonds. In this study we have investigated the importance of individual, Pauling hydrogen bonds hypothesized to facilitate self-adherence of the TDP-43 LC domain.
Work-related musculoskeletal disorders and associated factors among cleaners of health institutions in Gondar town, Northwest Ethiopia: an institution based cross-sectional study
Authors: Suleyman Jemal , Gelaw Asmare Yitayeh 
Published: December 2021

AbstractBackgroundMusculoskeletal disorders are growing public health problems both in developed and developing countries including Ethiopia. However, its prevention and control has not yet received due attention. This study aimed to determine.the prevalence and associated factors of musculoskeletal disorders musculoskeletal disorders among cleaners of health institutions in Gondar town, Northwest EthiopiaMethodAn institutional based cross-sectional study was conducted, from April to May 2016 in all health institutions of Gondar town. All the available cleaners of health institutions were taken as study participants. Data were collected by face-to-face interview technique after verbal informed consent. Additionally, weight and height of participants were measured following standard procedures. Data were collected by trained physiotherapists and then entered into a computer using Epi Info version 3.5.3 and exported to SPSS version 20 for analysis. Descriptive statistics was performed to describe the data in percentage and mean. Multiple logistic regressions were fitted and Odds ratios with 95% confidence intervals were calculated to identify associated factors.ResultsA total of 242 participants were included in this study. The majority of the study participants were females (79.3%) and between 25-44 age group (65.3%). Two hundred 0ne (83.1%) of the respondents reported that they had pain in at least one of the body parts in the previous 12 months. Of the nine body parts examined, neck (76%), upper back (40.5%) and lower back (45%) were the most frequently body parts reported to exhibit pain. Job status (AOR = 2.71, 95%CI; 1.37-5.36), and static work habit (AOR = 2.71, 95%CI; 1.37-5.36), were factors associated with musculoskeletal disorders.ConclusionThere is a high prevalence of musculoskeletal disorders among cleaners in the health institutions of Gondar Town. Job status and static work habit were the significant associated factors. Hence, we recommend the design and implementation of institution based screening programs for musculoskeletal disorders
EpyNN: Educational python for Neural Networks
Authors: Malard Florian , Danner Laura , Rouzies Emilie , Meyer Jesse G , Lescop Ewen , Olivier-Van Stichelen Stéphanie 
Published: December 2021

AbstractSummaryArtificial Neural Networks (ANNs) have achieved unequaled performance for numerous problems in many areas of Science, Business, Public Policy, and more. While experts are familiar with performance-oriented software and underlying theory, ANNs are difficult to comprehend for non-experts because it requires skills in programming, background in mathematics and knowledge of terminology and concepts. In this work, we release EpyNN, an educational python resource meant for a public willing to understand key concepts and practical implementation of scalable ANN architectures from concise, homogeneous and idiomatic source code. EpyNN contains an educational Application Programming Interface (API), educational workflows from data preparation to ANN training and a documentation website setting side-by-side code, mathematics, graphical representation and text to facilitate learning and provide teaching material. Overall, EpyNN provides basics for python-fluent individuals who wish to learn, teach or develop from scratch.AvailabilityEpyNN documentation is available at https://epynn.net and repository can be retrieved from https://github.com/synthaze/epynn.ContactStéphanie Olivier-Van-Stichelen, solivier@mcw.edu.Supplementary InformationSupplementary files and listings.
IL-21 signaling promotes the establishment of KSHV infection in human tonsil lymphocytes by increasing early targeting of plasma cells
Authors: Alomari Nedaa , Aalam Farizeh , Nabiee Romina , Castano Jesus Ramirez , Totonchy Jennifer 
Published: December 2021

AbstractFactors influencing Kaposi’s sarcoma-associated herpesvirus (KSHV) transmission and the early stages of KSHV infection in the human immune system remain poorly characterized. KSHV is known to extensively manipulate the host immune system and the cytokine milieu, and cytokines are known to influence the progression of KSHV-associated diseases. Here, using our unique model of KSHV infection in tonsil lymphocytes, we investigate the influence of host cytokines on the establishment of KSHV infection in human B cells. Our data demonstrate that KSHV manipulates the host cytokine microenvironment during early infection and susceptibility is generally associated with downregulation of multiple cytokines. However, we show that IL-21 signaling promotes KSHV infection by promoting both plasma cell numbers and increasing KSHV infection in plasma cells as early as 3 days post-infection. Our data reveal that this phenotype is dependent upon a specific milieu of T cells, that includes IL-21 producing Th17, Tc17 and CD8+ central memory T cells. These results suggest that IL-21 plays a significant role in the early stages of KSHV infection in the human immune system and that specific immunological states favor the initial establishment of KSHV infection by increasing infection in plasma cells.
panModule: detecting conserved modules in the variable regions of a pangenome graph
Authors: Bazin Adelme , Medigue Claudine , Vallenet David , Calteau Alexandra 
Published: December 2021

AbstractThe recent years have seen the rise of pangenomes as comparative genomic tools to better understand the evolution of gene content among microbial genomes in close phylogenetic groups such as species. While the core or persistent genome is often well-known as it includes essential or ubiquitous genes, the variable genome is usually less characterized and includes many genes with unknown functions even among the most studied organisms. It gathers important genes for strain adaptation that are acquired by horizontal gene transfer. Here, we introduce panModule, an original method to identify conserved modules in pangenome graphs built from thousands of microbial genomes. These modules correspond to synteny blocks composed of consecutive genes that are conserved in a subset of the compared strains. Identifying conserved modules can provide insights on genes involved in the same functional processes, and as such is a very helpful tool to facilitate the understanding of genomic regions with complex evolutionary histories. The panModule method was benchmarked on a curated dataset of conserved modules in Escherichia coli genomes. Its use was illustrated through a study of a high pathogenicity island in Klebsiella pneumoniae that allowed a better understanding of this region. panModule is freely available and accessible through the PPanGGOLiN software suite (https://github.com/labgem/PPanGGOLiN).
Among-individual variation of risk-taking behaviour in group and solitary context is uncorrelated but independently repeatable in a juvenile Arctic charr (Salvelinus alpinus) aquaculture strain
Authors: Philip Joris , Dellinger Marion , Benhaïm David 
Published: December 2021

AbstractBehavioural traits have been shown to have implications in fish welfare and growth performances in aquaculture. If several studies have demonstrated the existence of repeatable and heritable behavioural traits (i.e., animal personality), the methodology to assess personality in fishes is often carried out in solitary context, which appears to somewhat limit their use from a selective breeding perspective because these tests are too time consuming. To address this drawback, group-based tests have been developed. In Nordic country, Arctic charr (Salvelinus alpinus) is widely used in aquaculture, but no selection effort on behavioural traits has yet been carried out. Specifically, in this study we examined if risk-taking behaviour was repeatable and correlated in group and solitary context and if the early influences of physical environment affect the among-individual variation of behavioural trait across time in order to verify whether a group risk-taking test could be used as a selective breeding tool. Here, we found that in both contexts and treatments, the risk-taking behaviour was repeatable across a short period of 6 days. However, no cross-context consistency was found between group and solitary, which indicates that Arctic charr express different behavioural trait in group and solitary.
Mutational cascade of SARS-CoV-2 leading to evolution and emergence of omicron variant
Authors: Bansal Kanika , Kumar Sanjeet 
Published: December 2021

AbstractBackgroundEmergence of new variant of SARS-CoV-2, namely omicron, has posed a global concern because of its high rate of transmissibility and mutations in its genome. Researchers worldwide are trying to understand the evolution and emergence of such variants to understand the mutational cascade events.MethodsWe have considered all omicron genomes (n = 302 genomes) available till 2nd December 2021 in the public repository of GISAID along with representatives of variants of concern (VOC), i.e., alpha, beta, gamma, delta, and omicron; variant of interest (VOI) mu and lambda; and variant under monitoring (VUM). Whole genome-based phylogeny and mutational analysis were performed to understand the evolution of SARS CoV-2 leading to emergence of omicron variant.ResultsWhole genome-based phylogeny depicted two phylogroups (PG-I and PG-II) forming variant specific clades except for gamma and VUM GH. Mutational analysis detected 18,261 mutations in the omicron variant, majority of which were non-synonymous mutations in spike (A67, T547K, D614G, H655Y, N679K, P681H, D796Y, N856K, Q954H), followed by RNA dependent RNA polymerase (rdrp) (A1892T, I189V, P314L, K38R, T492I, V57V), ORF6 (M19M) and nucleocapsid protein (RG203KR).ConclusionDelta and omicron have evolutionary diverged into distinct phylogroups and do not share a common ancestry. While, omicron shares common ancestry with VOI lambda and its evolution is mainly derived by the non-synonymous mutations.
Stepwise evolution of a butterfly supergene via duplication and inversion
Authors: Kim Kang-Wook , De-Kayne Rishi , Gordon Ian J. , Omufwoko Kennedy Saitoti , Martins Dino J. , ffrench-Constant Richard , Martin Simon H. 
Published: December 2021

ABSTRACTSupergenes maintain adaptive clusters of alleles in the face of genetic mixing. Although usually attributed to inversions, supergenes can be complex, and reconstructing the precise processes that led to recombination suppression and their timing is challenging. We investigated the origin of the BC supergene, which controls variation in warning colouration in the African Monarch butterfly,Danaus chrysippus. By generating chromosome-scale assemblies for all three alleles, we identified multiple structural differences. Most strikingly, we find that a region of >1 million bp underwent several segmental duplications at least 7.5 million years ago. The resulting duplicated fragments appear to have triggered four inversions in surrounding parts of the chromosome, resulting in stepwise growth of the region of suppressed recombination. Phylogenies for the inversions are incongruent with the species tree, and suggest that structural polymorphisms have persisted for at least 4.1 million years. In addition to the role of duplications in triggering inversions, our results suggest a previously undescribed mechanism of recombination suppression through independent losses of divergent duplicated tracts. Overall, our findings add support for a stepwise model of supergene evolution involving a variety of structural changes.
Rab40c Regulates Focal Adhesions and Protein Phosphatase 6 Activity by Controlling ANKRD28 Ubiquitylation and Degradation
Authors: Han Ke-Jun , Prekeris Rytis 
Published: December 2021

ABSTRACTRab40c is a SOCS box–containing protein which binds Cullin5 to form a ubiquitin E3 ligase complex (Rab40c/CRL5) to regulate protein ubiquitylation. However, the exact functions of Rab40c remain to be determined, and what proteins are the targets of Rab40c-Cullin5 mediated ubiquitylation in mammalian cells are unknown. Here we showed that in migrating MDA-MB-231 cells Rab40c regulates focal adhesion’s number, size, and distribution. Mechanistically, we found that Rab40c binds the protein phosphatase 6 (PP6) complex and ubiquitylates one of its subunits, ankyrin repeat domain 28 (ANKRD28), thus, leading to its lysosomal degradation. Furthermore, we identified that phosphorylation of FAK and MOB1 is decreased in Rab40c knock-out cells, which may contribute to focal adhesion site regulation by Rab40c. Thus, we propose a model where Rab40c/CRL5 regulates ANKRD28 ubiquitylation and degradation, leading to a decrease in PP6 activity, which ultimately affects FAK and Hippo pathway signaling to alter focal adhesion dynamics.
Transactive response DNA-binding Protein (TDP-43) regulates early HIV-1 entry and infection
Authors: Cabrera-Rodríguez Romina , Pérez-Yanes Silvia , González-Montelongo Rafaela , Lorenzo-Salazar José M. , Estévez-Herrera Judith , García-Luis Jonay , Íñigo-Campos Antonio , Rubio-Rodríguez Luis A. , Muñoz-Barrera Adrián , Trujillo-González Rodrigo , Dorta-Guerra Roberto , Casado Concha , Pernas María , Blanco Julià , Flores Carlos , Valenzuela-Fernández Agustín 
Published: December 2021

AbstractThe transactive response DNA-binding protein (TDP-43) is an important regulator of mRNA, being reported to stabilize the anti-HIV factor, histone deacetylase 6 (HDAC6). However, little is known about the role of TDP-43 in HIV infection. In this work, we seek for the TDP-43 function on regulating CD4+ T cell permissibility to HIV infection. We observed that over-expression of wt-TDP-43 in CD4+ T cells stabilized HDAC6, increasing mRNA and the protein levels of this antiviral enzyme. Under this experimental condition, HIV-1 infection was impaired, independently of the viral envelope glycoprotein (Env) complex tropism. The results obtained by using an HIV-1 Env-mediated cell-to-cell fusion model, under the same experimental conditions, suggest that the increase in TDP-43 levels negatively affects the viral Env fusion capacity. Moreover, the specific siRNA silencing of endogenous TDP-43 in target cells lead to a significant decrease in the levels of HDAC6 which consistently induces an increase in the fusogenic and infection activities of the HIV-1 Env. These observations were confirmed by using primary viral Envs from HIV+ individuals with different clinical phenotypes. An increase in the level of expression of wt-TDP-43 strongly reduced the Envs infection activity of viremic non-progressors (VNP) and rapid progressors (RP) HIV+ individuals down to the levels of the inefficient HIV-1 Envs from long-term non-progressor elite controllers (LTNP-EC) individuals. On the contrary, low levels of endogenous TDP-43, obtained after specific siRNA-TDP-43 knocking-down, significantly favors the infection activity of primary HIV-1 Envs of VNP and RP individuals, leading to an increase in the infection ability of the primary HIV-1/LTNP-EC Envs. Based on this evidence, we interpret that TDP-43 conditions cell permissibility to HIV infection by affecting viral Env fusion and infection capacities, at least by altering the cellular levels of the antiviral enzyme HDAC6.
miR-199-3p Suppresses Cellular Migration and Viability and Promotes Progesterone Production in Goose Ovarian Follicles Before Selection by Targeting ITGB8 and Regulating Other ECM-related Genes
Authors: Li Qin , Zhang Keshan , Zhao Xianzhi , Li Jing , Xie Youhui , Zhong Hang , Wang Qigui 
Published: December 2021

ABSTRACTThe extracellular matrix (ECM) constitutes the follicular basal lamina and is also present between follicular cells. Remodeling of the ECM is believed to be a key event in follicular development, especially follicular selection, and plays important roles in cell migration, survival, and steroidogenesis. miR-199-3p is differentially expressed in the goose follicular granulosa layer during follicular selection and is reported to play a primary role in inhibiting cell migration and invasion. Nevertheless, the effect of miR-199-3p on ovarian follicles and its role in follicular cellular migration are not understood. In this study, we demonstrated by qRT-PCR that miR-199-3p was differentially expressed in the granulosa layer from goose ovarian follicles before and after follicular selection. Additionally, we found that miR-199-3p overexpression could significantly suppress cell viability and migration, as well as elevate both the concentration of progesterone and the expression of key progesterone production genes in cultured granulosa cells (GCs) from goose pre-hierarchical follicles. Furthermore, using dual-fluorescence reporter experiments on 293T cells, we confirmed that miR-199-3p downregulated the expression of the ECM gene ITGB8 by directly targeting its mRNA three prime untranslated region (3′ UTR). Finally, we found that miR-199-3p overexpression in the GCs of goose pre-hierarchical follicles inhibited the expression of two ECM-related genes (MMP9 and MMP15) yet promoted the expression of another two ECM-related genes (COL4A1 and LAMA1). Taken together, these findings suggest that miR-199-3p participates in granulosa cell migration, viability, and steroidogenesis in goose ovarian follicles before selection by targeting ITGB8 and modulating other ECM-related genes. These data highlight the key roles of miR-199-3p in follicular cell migration, viability, and steroidogenesis by regulating ECM-related genes and thus contribute to a better understanding of the mechanisms underlying follicle selection in birds.