bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gastruloids generated without exogenous Wnt activation develop anterior neural tissues
Authors: Girgin Mehmet U. , Lutolf Matthias P. 
Published: October 2020

AbstractWhen stimulated with a pulse from an exogenous WNT pathway activator, small aggregates of mouse embryonic stem cells (ESCs) can undergo embryo-like axial morphogenesis and patterning along the three major body axes. However, these structures, called gastruloids, currently lack the anterior embryonic regions, such as those belonging to the brain. Here we describe an approach to generate gastruloids that have a more complete antero-posterior development. We used bioengineered hydrogel microwell arrays to promote the robust derivation of mouse ESCs into post-implantation epiblast-like (EPI) aggregates in a reproducible and scalable manner. These EPI aggregates break symmetry and axially elongate without external chemical stimulation. Inhibition of WNT signaling in early stages of development leads to the formation of gastruloids with anterior neural tissues. Thus, we provide a new tool to study the development of the mouse after implantationin vitro, especially the formation of anterior neural regions.
Circulating adipokines in non-obese PCOS patients: a systematic review and meta-analysis
Authors: Lin Kainan , Sun Xiaoting , Wang Xiao , Wang Hanchu , Chen Xia 
Published: October 2020

AbstractConcentrations of circulating adipokines in non-obese polycystic ovary syndrome (PCOS) patients had been reported in many researches, however, these results were conflicting. The aim of this meta-analysis was to assess whether the levels of circulating adipokines were changed in non-obese PCOS. To identify eligible studies, literature research was performed in the database of PubMed, Embase, Web of Science without the restriction of region, publication or language. Of the total studies found, only 81 met the inclusion criteria. The meta-analysis showed that circulating levels of adiponectin [-0.95 (95% CI, −1.36 to −0.53)] decreased statistically in non-obese PCOS women. On the contrary, circulating levels of chemerin [1.13 (95% CI, 0.08 to 2.18)], leptin [0.47 (95% CI, 0.13 to 0.81)], resistin [0.45 (95% CI, 0.03 to 0.88)] and visfatin [1.38 (95% CI, 0.68 to 2.09)] increased significantly in non-obese PCOS females. Besides, there was no statistically significant change in the circulating levels of apelin [0.32 (95% CI, −1.34 to 1.99), irisin [1.01(95% CI, −0.68 to 2.70), omentin [-0.37(95% CI, −1.05 to 0.31)] and vaspin [0.09(95% CI, −0.14 to 0.32)] in non-obese PCOS patients. Scientific evidence suggested that the levels of circulating adipokines altered in non-obese PCOS patients compared with controls. Independent of the degree of obesity, the abnormal change of circulating adipokines levels might play an important role in the occurrence and development of PCOS.
SPLICE-q: a Python tool for genome-wide quantification of splicing efficiency
Authors: Costa Verônica R Melo , Pfeuffer Julianus , Louloupi Annita , Ørom Ulf A V , Piro Rosario M 
Published: October 2020

AbstractBackgroundIntrons are generally removed from primary transcripts to form mature RNA molecules in a post-transcriptional process called splicing. An efficient splicing of primary transcripts is an essential step in gene expression and its misregulation is related to numerous human diseases. Thus, to better understand the dynamics of this process and the perturbations that might be caused by aberrant transcript processing it is important to quantify splicing efficiency.ResultsHere, we introduce SPLICE-q, a fast and user-friendly Python tool for genome-wideSPLICingEfficiencyquantification. It supports studies focusing on the implications of splicing efficiency in transcript processing dynamics. SPLICE-q uses aligned reads from strand-specific RNA-seq to quantify splicing efficiency for each intron individually and allows the user to select different levels of restrictiveness concerning the introns’ overlap with other genomic elements such as exons of other genes. We applied SPLICE-q to globally assess the dynamics of intron excision in yeast and human nascent RNA-seq. We also show its application using total RNA-seq from a patient-matched prostate cancer sample.ConclusionsOur analyses illustrate that SPLICE-q is suitable to detect a progressive increase of splicing efficiency throughout a time course of nascent RNA-seq and it might be useful when it comes to understanding cancer progression beyond mere gene expression levels. SPLICE-q is available at:https://github.com/vrmelo/SPLICE-q
Sequences in the cytoplasmic tail of SARS-CoV-2 Spike facilitate expression at the cell surface and syncytia formation
Authors: Cattin-Ortolá Jerome , Welch Lawrence , Maslen Sarah L. , Skehel J. Mark , Papa Guido , James Leo C. , Munro Sean 
Published: October 2020

AbstractThe Spike (S) protein of SARS-CoV-2 binds ACE2 to direct fusion with host cells. S comprises a large external domain, a transmembrane domain (TMD) and a short cytoplasmic tail. Understanding the intracellular trafficking of S is relevant to SARS-CoV-2 infection, and to vaccines expressing full-length S from mRNA or adenovirus vectors. We have applied proteomics to identify cellular factors that interact with the cytoplasmic tail of S. We confirmed interactions with the COPI and COPII vesicle coats, ERM family actin regulators, and the WIPI3 autophagy component. The COPII binding-site promotes exit from the endoplasmic reticulum (ER), and although COPI-binding should retain S in the early Golgi where viral budding occurs, there is a suboptimal histidine residue in the recognition motif. As a result, S leaks to the surface where it accumulates and can direct the formation of multinucleate syncytia. Thus, the trafficking signals in the tail of S indicate that syncytia play a role in the SARS-CoV-2 lifecycle.
TRAF4 inhibits bladder cancer progression by promoting BMP/SMAD signalling pathway
Authors: Iyengar Prasanna Vasudevan , Marvin Dieuwke Louise , Lama Dilraj , Tan Tuan Zea , Suriyamurthy Sudha , Xie Feng , van Dinther Maarten , Mei Hailiang , Verma Chandra Shekhar , Zhang Long , Ritsma Laila , ten Dijke Peter 
Published: October 2020

AbstractBladder cancer is one of the most prevalent cancer types in the world, frequently exhibiting invasion and metastasis and therefore associated with poor prognosis. It is a progressive disease with high recurrence rates even after surgery, which calls for the urgent need for early intervention and diagnosis. The E3 ubiquitin ligase TNF Receptor Associated Factor 4 (TRAF4) has been largely implicated as a tumour-promoting element in a wide range of cancers. Over-expression and amplification of this gene product has been a common observation in breast and other metastatic tumours. In contrast, we observed that expression of TRAF4 negatively correlated with overall patient survival. Moreover, its expression was repressed at epigenetic levels in aggressive bladder cancer cells. We also describe an ERK kinase phosphorylation site on TRAF4 that inhibits its stability and localization to plasma membrane in such cells. Furthermore, knockdown of TRAF4 in epithelial bladder cancer cell lines leads to gain of mesenchymal genes and a loss of epithelial integrity. Reciprocally, stable over-expression of TRAF4 in mesenchymal cells leads to decreased migratory and invasive properties. Transcriptomic analysis upon TRAF4 mis-expression in bladder cancer cell lines revealed that higher TRAF4 expression enhanced BMP/SMAD and dampened NF-κB signalling pathways. Importantly, this notion was confirmed in bladder cancer patient material. Mechanistically, we showed that TRAF4 targets the E3 ubiquitin ligase SMURF1, a negative regulator of BMP/SMAD signalling, for proteasomal degradation in bladder cancer cells. We show that genetic and pharmacological inhibition of SMURF1 or its function inhibited migration of aggressive (mesenchymal) bladder cancer cells.
Imaging stable isotope labelling kinetics (iSILK) for following spatial Aβ plaque aggregation dynamics in evolving Alzheimer’s disease pathology
Authors: Michno Wojciech , Stringer Katie , Enzlein Thomas , Passarelli Melissa K. , Escrig Stephane , Blennow Kaj , Zetterberg Henrik , Meibom Anders , Hopf Carsten , Edwards Frances A. , Hanrieder Jörg 
Published: October 2020

AbstractFor our understanding of Alzheimer’s disease (AD) pathophysiology, it is of critical importance to determine how key pathological factors, specifically amyloid β (Aβ) plaque formation, are interconnected and implicated in neurodegeneration, disease progression and the development of clinical symptoms. Exactly how Aβ plaque formation is initiated and how the ongoing plaque deposition proceeds is not well understood. This is partly because we can only examine details of the molecular pathology after death in humans, and in mice, we can only examine a particular point in time without any longitudinal information on the fate of individually formed deposits. Herein, we used metabolic labelling of proteins with stable isotopes, together with multimodal imaging mass spectrometry (IMS) for imaging stable isotope labelling kinetics (iSILK) in the APPNL-G-Fknock-in mouse model of AD. The aim was to monitor the earliest seeds of Aβ deposition through ongoing plaque development and track the deposition of Aβ that is produced later in relation to already deposited plaques. This allowed us to visualize Aβ peptide aggregation dynamics within individual deposits across different brain regions. We identified the cortex as a primary site of deposition in precipitating plaque pathology. Further, our data show that structural plaque heterogeneity is associated with differential peptide deposition. Specifically, Aβ1-42 is forming an initial core seed followed by radial outgrowth and late secretion and deposition of Aβ1-38.Together these data prove the potential of iSILK for probing amyloid protein secretion, processing and aggregation dynamics in AD pathology.
Everything Under Control? Comparing Knepp Estate rewilding project with ‘traditional’ nature conservation
Authors: Dempsey Benedict Edward 
Published: October 2020

Abstract‘Rewilding’ is an increasingly prominent concept in conservation, but one that has attracted controversy. Debate frequently focuses on ‘control,’ with rewilding presented as reducing human control of nature. Opposition to rewilding often stems from a perceived lack of control – and associated perception of increased risk and uncertainty.I explore the concept of control in conservation. I identify that control is not a simple, linear concept, but consists of multiple dimensions. Using a lens of control, I compare two ethnographic case studies: the Sussex Wildlife Trust’s Old Lodge nature reserve; and Knepp Estate, one of the most influential rewilding projects in the UK. These sites ostensibly represent ‘high-control’ and ‘low-control’ examples of conservation.I outline how Old Lodge does not exert precise control in all respects, but rather involves elements of uncertainty and negotiation. I describe how Knepp’s model of rewilding reduces control in some dimensions but increases it in others. I conclude that, while Knepp’s ‘rewilding’ does represent a significant conceptual departure from ‘traditional’ conservation, it should not be characterised simplistically as an approach that reduces control.Based on this analysis, I argue that reduction of control should not be assumed to underpin the concept of rewilding. Rather, there is interplay between different control dimensions that combine to form different configurations of control. With this understanding, debate about rewilding – and conservation more broadly – can avoid simplistic characterisations of ‘reducing control’ and become instead an active discussion of what configuration of control is desired.This analysis could be seen negatively by those who argue that Knepp’s version of rewilding does not sufficiently reduce human control of nature. In contrast, Knepp’s approach can be seen positively as opening new conceptual space while retaining human involvement. It supports the argument that versions of rewilding can be legitimate, innovative components of plural conservation strategies.
Differential gene expression in the interactome of the Human Dopamine transporter in the context of Parkinson’s disease
Authors: Quiroz Roberto Navarro , Scott Ana Ligia , Philot Eric Allison , Atencio Linda , Ponce Cecilia Fernandez , Martinez Gustavo Aroca , Bonfanti Andres Cadena , Escorcia Lorena Gomez , Quiroz Elkin Navarro 
Published: October 2020

AbstractBackgroundThe human dopamine transporter is the main regulator of dopamine tone and an intricate network exists to regulate the expression, conformation, and kinetics of the hDAT. hDAT dysfunction is directly related to Parkinson’s disease. The objective of this work is to evaluate the differential gene expression in the interactome of the Dopamine transporter in the context of Parkinson’s disease.MethodsTo do this, we evaluated hDAT interaction data in string-db, mint.bio, IntAct, reactome, hprd and BioGRID, subsequently, data was obtained from the differential gene expression of mRNA and miRNAs for this hDAT interactome in the context of PD.ResultsThe analysis of the differential expression changes of genes of the hDAT interactome in tissues of patients with PD compared with tissues of individuals without PD, allowed to identify an expression pattern of 32 components of the hDAT interactome, of which 31 presented a negative change proportion in PD.ConclusionsWe found a total of 90 miRNAs that could regulate the expression of 27 components of the hDAT interactome, at the same time, 39 components of the hDAT interactome may participate in 40 metabolic pathways. Together, these findings show a systematic effect on the hDAT-mediated dopamine internalization process in patients with Parkinson’s, which would contribute to a greater susceptibility to neuronal oxidative stress in PD patients.
Spleen glia are a transcriptionally unique glial subtype interposed between immune cells and sympathetic axons
Authors: Lucas Tawaun A. , Zhu Li , Buckwalter Marion S. 
Published: October 2020

AbstractGlia are known to play important roles in the brain, the gut, and around the sciatic nerve. While the gut has its own specialized nervous system, other viscera are innervated solely by autonomic nerves. The functions of glia that accompany autonomic innervation are not well known, even though they are one of the most abundant cell types in the peripheral nervous system. Here, we focused on non-myelinating Schwann Cells in the spleen, spleen glia. The spleen is a major immune organ innervated by the sympathetic nervous system, which modulates immune function. This interaction is known as neuroimmune communication. We establish that spleen glia can be visualized using both immunohistochemistry for S100B and GFAP and with a reporter mouse. Spleen glia ensheath sympathetic axons and are localized to the lymphocyte-rich white pulp areas of the spleen. We sequenced the spleen glia transcriptome and identified genes that are likely involved in axonal ensheathment and communication with both nerves and immune cells. Spleen glia express receptors for neurotransmitters made by sympathetic axons (adrenergic, purinergic, and Neuropeptide Y), and also cytokines, chemokines, and their receptors that may communicate with immune cells in the spleen. We also established similarities and differences between spleen glia and other glial types. While all glia share many genes in common, spleen glia differentially express immune genes, including genes involved in cytokine-cytokine receptor interactions, phagocytosis, and the complement cascade. Thus, spleen glia are a unique glial type, physically and transcriptionally poised to participate in neuroimmune communication in the spleen.Table of ContentsMain PointsSpleen glia maintain tight associations with splenic nerves and come in close contact with immune cellsSpleen glia express genes required for communication with nerves and immune cellsSpleen glia are a transcriptionally unique glial type
Genome-enabled inference of functional genetic variants in the face, brain and behavior
Authors: Patil Chinar , Sylvester Jonathan B. , Abdilleh Kawther , Norsworthy Michael W. , Pottin Karen , Malinsky Milan , Bloomquist Ryan F. , Johnson Zachary V. , McGrath Patrick T. , Streelman Jeffrey T. 
Published: October 2020

AbstractLake Malawi cichlid fishes exhibit extensive divergence in form and function among closely related species separated by a relatively small number of genetic changes. During the past million years, hundreds of species have diversified along an ecological axis in rock vs. sand habitats. We compared the genomes of rock- and sand-dwelling species and asked which genetic variants in which genes differed among the groups. We found that 96% of differentiated variants reside in non-coding sequence but these non-coding diverged variants are evolutionarily conserved. The majority of divergent coding variants are missense and/or loss of function. Regions near differentiated variants are enriched for craniofacial, neural and behavioral functional categories. To follow up experimentally, we used rock- vs. sand-species and their hybrids to (i) clarify the push-pull roles of BMP signaling andirx1bin the specification of forebrain territories during gastrulation and (ii) reveal striking context-dependent brain gene expression during adult social behavior. Our results suggest compelling ties between early brain development and adult behavior and highlight the promise of evolutionary reverse genetics – the identification of functional variants from genome sequencing in natural populations.
A high-throughput amplicon sequencing approach for population-wide species diversity and composition survey
Authors: Tay WT , Court LN , Macfadyen S , Jacomb F , Vyskočilová S , Colvin J , De Barro PJ 
Published: October 2020

AbstractManagement of agricultural pests requires an understanding of pest species diversity, their interactions with beneficial insects and spatial-temporal patterns of pest abundance. Invasive and agriculturally important insect pests can build up very high populations, especially in cropping landscapes. Traditionally, sampling effort for species identification involves small sample sizes and is labour intensive. Here, we describe a multi-primer high throughput sequencing (HTS) metabarcoding method and associated analytical workflow for a rapid, intensive, high-volume survey of pest species compositions. We demonstrate our method using the taxonomically challenging Bemisia pest cryptic species complex as examples. The whiteflies Bemisia including the ‘tabaci’ species are agriculturally important capable of vectoring diverse plant viruses that cause diseases and crop losses. Our multi-primer metabarcoding HTS amplicon approach simultaneously process high volumes of whitefly individuals, with efficiency to detect rare (i.e., 1%) test-species, while our improved whitefly primers for metabarcoding also detected beneficial hymenopteran parasitoid species from whitefly nymphs. Field-testing our redesigned Bemisia metabarcoding primer sets across the Tanzania, Uganda and Malawi cassava cultivation landscapes, we identified the sub-Saharan Africa 1 Bemisia putative species as the dominant pest species, with other cryptic Bemisia species being detected at various abundances. We also provide evidence that Bemisia species compositions can be affected by host crops and sampling techniques that target either nymphs or adults. Our multi-primer HTS metabarcoding method incorporated two over-lapping amplicons of 472bp and 518bp that spanned the entire 657bp 3’ barcoding region for Bemisia, and is particularly suitable to molecular diagnostic surveys of this highly cryptic insect pest species complex that also typically exhibited high population densities in heavy crop infestation episodes. Our approach can be adopted to understand species biodiversity across landscapes, with broad implications for improving trans-boundary biosecurity preparedness, thus contributing to molecular ecological knowledge and the development of control strategies for high-density, cryptic, pest-species complexes.
Shared developmental gait disruptions across two mouse models of neurodevelopmental disorders
Authors: Rahn Rachel M. , Weichselbaum Claire T. , Gutmann David H. , Dougherty Joseph D. , Maloney Susan E. 
Published: October 2020

AbstractMotor deficits such as abnormal gait are an underappreciated yet characteristic phenotype of many neurodevelopmental disorders (NDDs), including Williams Syndrome (WS) and Neurofibromatosis Type 1 (NF1). Compared to cognitive phenotypes, gait phenotypes are readily and comparably assessed in both humans and model organisms, and are controlled by well-defined CNS circuits. Discovery of a common gait phenotype between NDDs might suggest shared cellular and molecular deficits and highlight simple outcome variables to potentially quantify longitudinal treatment efficacy in NDDs. We therefore characterized gait using the DigiGait assay in two different NDD models: the complete deletion (CD) mouse, which models hemizygous loss of the complete WS locus, and theNf1+/R681Xmouse, which models a patient-derived heterozygous germlineNF1mutation. We collected longitudinal data across five developmental time points (postnatal days 21-30) and one early adulthood time point. Compared to wild type littermate controls, both models displayed markedly similar spatial, temporal, and postural gait abnormalities during development. Developing CD mice also displayed significant decreases in variability metrics. Multiple gait abnormalities observed acrossNf1+/R681Xmouse development persisted into early adulthood, including increased stride length and decreased stride frequency, while developmental abnormalities in CD mice largely resolved by adulthood. These findings suggest that gait subcomponents affected in NDDs show overlap between disorders as well as some disorder-specific features, which may change over the course of development. Our incorporation of spatial, temporal, and postural gait measures also provides a template for gait characterization in other NDD models, and a platform to examining circuits or longitudinal therapeutics.Lay SummaryGait changes have been reported in Williams Syndrome and Neurofibromatosis Type 1, but how these changes develop over time has not been explored. We therefore studied gait in mouse models of these two disorders across time. We found multiple shared differences in gait as compared to healthy controls at the younger ages in both models. However, those differences were resolved in the Williams Syndrome model by adulthood, yet persisted in the Neurofibromatosis Type 1 model.