bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of a neural stem cell transcriptional program in parenchymal astrocytes
Authors: Magnusson Jens P. , Zamboni Margherita , Santopolo Giuseppe , Mold Jeff E. , Barrientos-Somarribas Mauricio , Talavera-López Carlos , Andersson Björn , Frisén Jonas 
Published: July 2020

AbstractNeural stem cells, located in discrete niches in the adult brain, generate new neurons throughout life. These stem cells are specialized astrocytes, but astrocytes in other brain regions do not generate neurons under physiological conditions. After stroke, however, striatal astrocytes undergo neurogenesis in mice, triggered by decreased Notch signaling. We used single-cell RNA sequencing to characterize neurogenesis by Notch-depleted striatal astrocytesin vivo. Striatal astrocytes were located upstream of neural stem cells in the neuronal lineage. As astrocytes initiated neurogenesis, they became transcriptionally very similar to subventricular zone stem cells and progressed through a nearly identical neurogenic program. Surprisingly, in the non- neurogenic cortex, Notch-depleted astrocytes also initiated neurogenesis. Yet, the cortical astrocytes, and many striatal ones, stalled before entering transit- amplifying divisions. Infusion of epidermal growth factor enabled stalled striatal astrocytes to resume neurogenesis. We conclude that parenchymal astrocytes are latent neural stem cells and that targeted interventions can guide them through their neuronal differentiation.
FER-mediated tyrosine phosphorylation and PIK3R2/p85β recruitment on IRS4 promotes the PI3K-AKT signaling pathway and tumorigenesis in ovarian cancer
Authors: Zhang Yanchun , Xiong Xuexue , Zhu Qi , Zhang Jiali , Wang Yuetong , Cao Jian , Chen Li , Chen Shengmiao , Hou Linjun , Zhao Xi , Hao Piliang , Zhuang Min , Li Dake , Fan Gaofeng 
Published: July 2020

AbstractTyrosine phosphorylation, orchestrated by tyrosine kinases and phosphatases, modulates a multi-layered signaling network in a time and space dependent manner. Dysregulation of this post-translational modification is inevitably associated with pathological diseases. Our previous work has demonstrated that non-receptor tyrosine kinase FER is upregulated in ovarian cancer. Knockdown of the kinase attenuates metastatic phenotypes in tumor cells. Here we employed mass spectrometry and biochemical approaches to identify IRS4 as a novel substrate of FER. Using a proximity-based tagging system, we determined that FER-mediated phosphorylation of Tyr779 enables IRS4 to recruit PIK3R2/p85β, the regulatory subunit of PI-3K, and activate the PI3K-AKT pathway. Rescuing IRS4-null ovarian tumor cells with phosphorylation-defective mutant, but not WT IRS4, delayed tumor cell proliferation bothin vitroandin vivo. Overall, we revealed a kinase-substrate regulatory mode between FER and IRS4, and the pharmacological inhibition of FER kinase may be beneficial for ovarian cancer patients with PI3K-AKT hyperactivation.
Comparative genomics of StAR-related lipid transfer (START) domains across wild and cultivated rice
Authors: Mahtha Sanjeet Kumar , Purama Ravi Kiran , Yadav Gitanjali 
Published: July 2020

AbstractSTART proteins, encoded by a plant amplified family of evolutionary conserved genes, are known to bind lipids/sterols in mammals. In the plant kingdom, they have been reported in proteins involved in lipid binding, transport, signaling, as well as modulation of transcriptional activity, but there is very limited information on sub-functionalization or evolution of new function within the amplified gene family. Availability of ten fully annotated wild and cultivated rice varieties enables a comprehensive analysis of this family across the rice pangenome, across functional categories, as well as across START sub-families. The presence of START domains in all seven wild and three cultivated rice genomes suggests low dispensability and critical functional roles for this family, further supported by chromosomal mapping, duplication analysis and conservation of domain structure. Analysis of synteny highlights a preponderance of segmental and dispersed modes of duplication among STARTs, while transcriptomic investigation of the main cultivated varietyOryza sativa var. japonicareveals sub-functionalization among START genes family members in terms of preferential expression across various developmental stages and anatomical parts, especially flowering related parts. Importance of this family was further supported by Ka/Ks ratios confirming strong negative/purifying selection, implying that START family duplication is strongly constrained and evolutionarily stable.
Braconidae revisited:Bracon brevicornisgenome showcases the potential of linked-read sequencing in identifying a putativecomplementary sex determinergene
Authors: Ferguson K. B. , Pannebakker B. A. , Centurión A. , van den Heuvel J. , Nieuwenhuis R. , Becker F. F. M. , Schijlen E. , Thiel A. , Zwaan B. J. , Verhulst E. C. 
Published: July 2020

ABSTRACTBracon brevicornisis an ectoparasitoid of a wide range of larval-stage Lepidopterans, including several pests of important crops, such as the corn borer,Ostrinia nubilalis. It is also one of the earliest documented cases of complementary sex determination in Hymenoptera. Here, we present the linked-read genome ofB. brevicornis, complete with anab initio-derived annotation and protein comparisons with fellow braconids,Fopius arisanusandDiachasma alloem. We demonstrate the potential of linked-read assemblies in exploring regions of heterozygosity and search for structural and homology-derived evidence of thecomplementary sex determinergene (csd).
Temporal dynamics of neural activity in macaque frontal cortex assessed with large-scale recordings
Authors: Decramer Thomas , Premereur Elsie , Caprara Irene , Theys Tom , Janssen Peter 
Published: July 2020

AbstractWe make eye movements to objects before grasping these objects, and the gaze direction generally indicates where the object will be grasped. Hence, the brain has to coordinate eye-, arm- and hand movements. We performed large-scale recordings (more than 2000 responsive sites) in frontal cortex of monkeys during a saccade-reach-grasp task. When an object appeared in peripheral vision, the first burst of activity emerged in prearcuate areas (the FEF and area 45B), followed by dorsal and ventral premotor cortex, and a buildup of activity in primary motor cortex. After the saccade, prearcuate activity remained elevated while primary motor and premotor activity rose in anticipation of the upcoming arm and hand movement. Some premotor and prearcuate sites were equally active when the object appeared in peripheral vision and at the fovea, suggesting a role in eye-hand coordination. Thus, a large part of lateral frontal cortex is active during a saccade-reach-grasp task.
A Method for the Automatic Normalization and 3D Facial Mesh Extraction from Head Magnetic Resonance Imaging
Authors: Sevillano Xavier , Ureña David , Gonzàlez Rubèn , Fatjó-Vilas Mar , Salvador Raymond , Pomarol-Clotet Edith , Martínez-Abadías Neus 
Published: July 2020

AbstractThe analysis of 3D facial shape in medicine is motivated by the fact that certain diseases and syndromes are associated to specific facial dysmorphologies. In this context, 3D facial shape analysis constitutes a promising and non-invasive support to traditional diagnostic methods. In this work, we explore the use of head magnetic resonances to obtain accurate 3D facial meshes that enable subsequent facial shape analysis. We present a fully automatic method that normalizes the orientation and alignment of 3D point clouds corresponding to head magnetic resonances by detecting salient facial features. Moreover, using clustering techniques, our method also allows to eliminate noise and artifacts appearing in magnetic resonance imaging. Finally, through bidirectional ray tracing, we obtain a dense 3D facial mesh that accurately captures facial shape. The proposed method has been built and evaluated on a dataset of 185 head magnetic resonances, and it has demonstrated its ability to successfully orient, align and obtain a dense 3D facial mesh with a high accuracy rate.
The mechanism underlying J-waves and T-waves in the electrocardiogram of mice and zebra finches
Authors: Offerhaus Joost A. , Snelderwaard Peter C. , Faber Jaeike W. , Riebe Katharina , Jensen Bjarke , Boukens Bas J. 
Published: July 2020

AbstractBrief cardiac cycles are required to achieve high heart rates as seen in endothermic animals. A main determinant of the cardiac cycle is the repolarization phase of the cardiac action potential, which is visible in the ECG as a T-wave. In mammals with high heart rates – such as rodents – the repolarization phase is short and the ECG is characterized by a positive deflection following the QRS-complex, the J-wave. It is unclear whether birds with high heart rates show similar ECG characteristics. Here we study cardiac repolarization and the ECG in the zebra finch which has high heart rates. Inex vivohearts of zebra finch (N=5) and mouse (N=5), pseudo-ECGs and optical action potentials were measured. In both species, total ventricular activation was fast with QRS durations shorter than 10ms. Ventricular activation progressed from the left to the right ventricle in zebra finch whereas the activation pattern was apex-to-base in mouse. In both species, phase 1 early repolarization followed the activation front, causing a positive J-wave in the pseudo-ECG. In zebra finch, late repolarization was directed from the right ventricle to the left ventricle, whereas late repolarization was directed opposite in mouse. Accordingly, on the zebra finch ECG, the J-wave and the T-wave have the same direction, whereas in the mouse the J-wave and the T-wave are discordant. Our findings demonstrate early repolarization and the associated J-wave are not restricted to mammals and that they also occur within birds. Early repolarization may have evolved by convergence in association with high heart rates.Summary statementZebra finches are small birds with high heart rates. Similar to small rodents, the zebra finch ECG contains a J-wave, which is caused by early repolarization
Sexual differences in genetic architecture in UK Biobank
Authors: Bernabeu Elena , Canela-Xandri Oriol , Rawlik Konrad , Talenti Andrea , Prendergast James , Tenesa Albert 
Published: July 2020

ABSTRACTSex is arguably the most important differentiating characteristic in most mammalian species, separating populations into different groups, with varying behaviors, morphologies, and physiologies based on their complement of sex chromosomes. In humans, despite males and females sharing nearly identical genomes, there are differences between the sexes in complex traits and in the risk of a wide array of diseases. Gene by sex interactions (GxS) are thought to account for some of this sexual dimorphism. However, the extent and basis of these interactions are poorly understood.Here we provide insights into both the scope and mechanism of GxS across the genome of circa 450,000 individuals of European ancestry and 530 complex traits in the UK Biobank. We found small yet widespread differences in genetic architecture across traits through the calculation of sex-specific heritability, genetic correlations, and sex-stratified genome-wide association studies (GWAS). We also found that, in some cases, sex-agnostic GWAS efforts might be missing loci of interest, and looked into possible improvements in the prediction of high-level phenotypes. Finally, we studied the potential functional role of the dimorphism observed through sex-biased eQTL and gene-level analyses.This study marks a broad examination of the genetics of sexual dimorphism. Our findings parallel previous reports, suggesting the presence of sexual genetic heterogeneity across complex traits of generally modest magnitude. Our results suggest the need to consider sex-stratified analyses for future studies in order to shed light into possible sex-specific molecular mechanisms.
Mycobacterial HelD is a nucleic acids-clearing factor for RNA polymerase
Authors: Kouba Tomáš , Koval’ Tomáš , Sudzinová Petra , Pospíšil Jiří , Brezovská Barbora , Hnilicová Jarmila , Šanderová Hana , Janoušková Martina , Šiková Michaela , Halada Petr , Sýkora Michal , Barvík Ivan , Nováček Jiří , Trundová Mária , Dušková Jarmila , Skálová Tereza , Chon URee , Murakami Katsuhiko S. , Dohnálek Jan , Krásný Libor 
Published: July 2020

SUMMARYRNA synthesis is central to life, and RNA polymerase depends on accessory factors for recovery from stalled states and adaption to environmental changes. Here we investigated the mechanism by which a helicase-like factor HelD recycles RNA polymerase. We report a cryo-EM structure of an unprecedented complex between theMycobacterium smegmatisRNA polymerase and HelD. The crescent-shaped HelD simultaneously penetrates deep into two RNA polymerase channels that are responsible for DNA binding and substrate delivery to the active site, thereby locking RNA polymerase in an inactive state. We show that HelD prevents non-specific interactions between RNA polymerase and DNA and dissociates transcription elongation complexes, but does not inhibit RNA polymerase binding to the initiation σ factor. The liberated RNA polymerase can either stay dormant, sequestered by HelD, or upon HelD release, restart transcription. Our results provide insights into the architecture and regulation of the highly medically-relevant mycobacterial transcription machinery and define HelD as a clearing factor that removes undesirable nucleic acids from RNA polymerase.
ALG-2 interacting protein-X (Alix) is required for activity-dependent bulk endocytosis at brain synapses
Authors: Laporte Marine H. , Chi Kwang Il , Caudal Laura C. , Zhao Na , Rolland Marta , Martinez-Hernandez José , Martineau Magalie , Chatellard Christine , Denarier Eric , Mercier Vincent , Lemaître Florent , Blot Béatrice , Moutaux Eve , Cazorla Maxime , Perrais David , Lanté Fabien , Fraboulet Sandrine , Hemming Fiona J. , Kirchhoff Frank , Sadoul Rémy 
Published: July 2020

AbstractIn chemical synapses undergoing high frequency stimulation, vesicle components can be retrieved from the plasma membrane via a clathrin-independent process called activity dependent bulk endocytosis (ADBE). Alix (ALG-2 interacting protein X)/ PDCD6IP) is an adaptor protein binding to ESCRT and endophilin-A proteins which is required for clathrin-independent endocytosis in fibroblasts. Alix is expressed in neurons and concentrates at synapses during epileptic seizures. Here, we used cultured neurons to show that Alix is recruited to presynapses where it interacts with, and concentrates endophilin-A during conditions triggering ADBE. Using Alix knockout (ko) neurons we showed that this recruitment, which requires interaction with the calcium-binding protein ALG-2, is necessary for ABDE. We also found that presynaptic compartments of Alix ko hippocampi display subtle morphological defects compatible with flawed synaptic activity and plasticity detected electrophysiologically. Furthermore, mice lacking Alix in the forebrain undergo less seizures during kainate-induced status epilepticus and reduced propagation of the epileptiform activity. These results thus show that impairment of ADBE due to the lack of neuronal Alix alters synaptic recovery during physiological or pathological repeated stimulations.
Sortase-mediated site-specific modification of interleukin-2 for the generation of a tumor targeting acetazolamide-cytokine conjugate
Authors: Gouyou Baptiste , Millul J , Villa A , Cazzamalli S , Neri D , Matasci M 
Published: July 2020

1.AbstractSmall ligands specific to tumor-associated antigens can be used as alternatives to antibodies for the delivery of small payloads such as radionuclides, cytotoxic drugs and fluorophores. Their use as delivery moiety of bioactive proteins like cytokines remains largely unexplored. Here, we describe the preparation andin vivocharacterization of the first small molecule-cytokine conjugate targeting carbonic anhydrase IX (CAIX), a marker of renal cell carcinoma and hypoxia. Site-specific conjugation between interleukin-2 and acetazolamide was obtained by Sortase A-mediated transpeptidation. Binding of the conjugate to the cognate CAIX antigen was confirmed by surface plasmon resonance. Thein vivotargeting of structures expressing carbonic anhydrase IX was assessed by biodistribution experiments in tumor bearing mice. Optimization of manufacturability and tumor targeting performance of acetazolamide-cytokine products will be required in order to enable industrial applications.Graphical abstract
Geographic drivers of diversification in loliginid squids with an emphasis on the western Atlantic species
Authors: Genty Gabrielle , Pardo-De la Hoz Carlos J , Montoya Paola , Ritschard Elena A. 
Published: July 2020

ABSTRACTAimIdentifying the mechanisms driving divergence in marine organisms is challenging as opportunities for allopatric isolation are less conspicuous than in terrestrial ecosystems. Here, we aim to estimate a dated phylogeny of the squid family Loliginidae, and perform ecological niche analyses to explore biogeographic and evolutionary patterns giving rise to extant lineages in this group, with particular focus on cryptic species with population structure along the western Atlantic coast.LocationWorld-wide.TaxonClass Cephalopoda, Family LoliginidaeMethodsWe used three loci to infer gene trees and perform species delimitation analysis to detect putative cryptic speciation events. We then estimated a dated species tree under the Bayesian multispecies coalescent and used it to reconstruct ancestral distributions based on the currently known ranges of the species. Also, we tested the hypothesis of niche divergence in three recently diverged species subpopulations of the northwestern and southwestern Atlantic Ocean by ecological niche modeling and niche overlap measurement from occurrence data.ResultsThe phylogenetic analyses confirmed the monophyly for the current twenty-six species of the Loliginidae family. Our ancestral area reconstruction and divergence estimation revealed the origin and geographical dispersal of loliginid lineages. Additionally, the phylogenetic analysis and the species delimitation analysis supported geographic structure withinD. pleii, D. pealeiiandL. brevis.The ecological niche models revealed unsuitable habitat in the immediately adjacent area of the Amazonian Orinoco Plume, yet suitable habitat characteristics beyond this area.Main conclusionsOur study allowed us to confirm the monophyly of all currently recognized species within the Loliginidae family and we corroborate the biogeographical origin being the Indo-Pacific region in the Cretaceous. We found a possible new cryptic lineage and show evidence of the Amazon-Orinoco Plume as an ecological barrier, which influenced the diversification of this particular group of marine organisms.
Myofibroblast Forms Atherosclerotic Plaques
Authors: Wang Xinggang , Ge Junbo 
Published: July 2020

AbstractFor decades, smooth muscle cells (SMCs) and macrophages are considered as the main contributors to atherosclerotic plaques. However, we found that in the human coronary atherosclerotic plaques, SMCs were few, while lots of myofibroblasts infiltrated in the intima near the lumen (fibrous cap) and their distribution was highly positive related to intimal thickness. In addition to lots of foam cells formation, collagen fibers were forming in the thickening intima near the lumen (fibrous cap), and denaturing or calcifying gradually far from the lumen, which evolved into various complex plaques. In vitro, myofibroblasts could actively take lots of low-density lipoprotein (LDL) to enhance proliferation. Lots of collagen fibers, foam cells and extracellular lipids accumulation emerged in myofibroblasts cultured with 5% FBS high glucose DMEM without adding modified LDL. It is consistent with the characteristics of human coronary atherosclerotic plaques. It is the first time that lipid rich plaques with lots of foam cells, extracellular lipids and collagen fibers formed in vitro. It demonstrated that myofibroblast should be the direct and main source of collagen fibers, foam cells and extracellular lipids. This suggests that atherosclerosis is not as complicated as previously considered, and it might be mainly a process of myofibroblast remodeling to vascular injury caused by various risk factors. This study made the pathogenesis of atherosclerosis clearer. It would provide a target cell for future treatments of atherosclerotic diseases. In vitro atherosclerotic plaques model formed by human myofibroblasts would be an efficient and convenient way to study atherosclerosis.
Minimal net loss of vegetation via interior pond dynamics in an extensive unditched salt marsh
Authors: Smith Joseph , Pellew Michael 
Published: July 2020

AbstractPonds in salt marshes are often interpreted as a symptom of degradation, yet ponds can also be part of a cyclical process of pool formation, expansion, tidal breaching and vegetation recovery. Pond dynamics may be altered by accelerated sea level rise, with consequences for the long-term stability of ecosystems. We test the prediction that ponds are in dynamic equilibrium across one the largest expanses of unditched salt marsh in the Northeast USA by (1) examining change in pond and marsh area between 1970 and present and (2) by tracking individual pool dynamics across an 87-year time series. We found that net pond area has remained unchanged since 1970 because the amount of marsh conversion to ponds is equivalent to the amount pond recovery to marsh. The ratio of tidally-connected ponds is increasing relative to non-tidal ponds which suggests that some rates of change may be decoupling, which may be related to a decline in the rate of pond formation. A nuanced understanding of marsh pools needs to be incorporated into marsh condition assessments and establishment of restoration priorities so that ponds are not interpreted as evidence of degradation when they are exhibiting a recovery cycle. Unditched marshes around the world are a rare resource that remains essential for advancing scientific understanding and serving as reference sites for restoration of marshes altered by past management.
Comparative analysis of single-cell RNA Sequencing Platforms and Methods
Authors: Ashton John M. , Rehrauer Hubert , Myers Jason , Myers Jacqueline , Zanche Michelle , Balys Malene , Foox Jonathan , Mason Chistopher E. , Steen Robert , Kuentzel Marcy , Aquino Catharine , Garcia-Reyero Natàlia , Chittur Sridar V. 
Published: July 2020

ABSTRACTSingle-cell RNA sequencing (scRNA-seq) offers great new opportunities for increasing our understanding of complex biological processes. In particular, development of an accurate Human Cell Atlas is largely dependent on the rapidly advancing technologies and molecular chemistries employed in scRNA-seq. These advances have already allowed an increase in throughput for scRNA-seq from 96 to 80,000 cells on a single instrument run by capturing cells within nano-liter droplets. While this increase in throughput is critical for many experimental questions, a thorough comparison between microfluidic-, plate-, and droplet-based technologies or between multiple available platforms utilizing these technologies is largely lacking. Here, we report scRNA-seq data from SUM149PT cells treated with the histone deacetylase inhibitor TSA vs. untreated controls across several scRNA-seq platforms (Fluidigm C1, WaferGen iCell8, 10X Genomics Chromium Controller, and Illumina/BioRad ddSEQ). The primary goal of this project was to demonstrate RNA sequencing (RNA-seq) methods for profiling the ultra-low amounts of RNA present in individual cells, and this report discusses the results of the study as well as technical challenges/lesson learned and present general guidelines for best practices in sample preparation and analysis.