bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cue-specific remodeling of the neuronal transcriptome through intron retention programs
Authors: Mazille Maxime , Scheiffele Peter , Mauger Oriane 
Published: October 2021

AbstractSub-cellular compartmentalization through the nuclear envelope has for a long time been primarily considered a physical barrier that separates nuclear and cytosolic contents. More recently, nuclear compartmentalization has emerged to harbor key regulatory functions in gene expression. A sizeable proportion of protein-coding mRNAs is more prevalent in the nucleus than in the cytosol reflecting the existence of mechanisms to control mRNA release into the cytosol. However, the biological relevance of the nuclear retention of mRNAs remains unclear. Here, we provide a comprehensive map of the subcellular localization of mRNAs in mature neurons and reveal that transcripts stably retaining introns are broadly targeted for nuclear retention. We systematically probed these transcripts upon neuronal stimulation and found that sub-populations of nuclear-retained transcripts are bi-directionally regulated in response to cues: some appear targeted for degradation while others undergo splicing completion to generate fully mature mRNAs which are exported to the cytosol to increase functional gene expression. Remarkably, different forms of stimulation mobilize distinct groups of intron-retaining transcripts and this selectivity arises from the activation of specific signaling pathways. Overall, our findings uncover cue-specific control of intron retention as a major regulator of acute remodeling of the neuronal transcriptome.
The photobiology of the human circadian clock
Authors: Schoonderwoerd Robin A. , de Rover Mischa , Janse Jan A.M. , Hirschler Lydiane , Willemse Channa R. , Scholten Leonie , Klop Ilse , van Berloo Sander , van Osch Matthias J.P. , Swaab Dick F. , Meijer Johanna H. 
Published: October 2021

AbstractIn modern society, the widespread use of artificial light at night disrupts the suprachiasmatic nucleus (SCN), which serves as our central circadian clock. Existing models describe excitatory responses of the SCN to primarily blue light, but direct measures in humans are absent. The combination of state-of-the-art neuroimaging techniques and custom-made MRI compatible LED devices allowed to directly measure the light response of the SCN. In contrast to the general expectation, we found that SCN activity was suppressed by light. The suppressions were observed not only in response to narrowband blue light (λmax: 470nm) but remarkably, also in response to green (λmax: 515nm) and orange (λmax: 590nm), but not to violet light (λmax: 405nm). The broadband sensitivity of the SCN implies that strategies on light exposure should be revised: enhancement of light levels during daytime is possible with wavelengths other than blue, while during nighttime, all colors are potentially disruptive.
Polymer-Assisted Condensation: A Mechanism for Hetero-Chromatin Formation and Epigenetic Memory
Authors: Sommer Jens-Uwe , Merlitz Holger , Schiessel Helmut 
Published: October 2021

AbstractWe consider the formation of droplets from a 2-component liquid mixture induced by a large polymer chain that has preferential solubility with one of the components. We assume that the liquid mixture is in a fully miscible state, but far above the critical interaction limit of the two species. We show that the polymer coil acts as a chemical potential trap, which can shift the mixture inside the polymer volume into the partially miscible state and thus triggers the formation of a polymer-bound droplet of the preferred solvent phase which we denote as polymer-assisted condensation (PAC). We propose a simple mean-field model which can predict the essential feature of PAC and perform molecular-dynamics simulations to show that the predicted phase behavior is robust against fluctuation effects. Our model aims to understand the formation of macromolecular condensates inside the cell nucleus, such as those formed by heterochromatin 1 (HP1). We propose that such droplets organize the spatial structure of chromatin into hetero- and euchromatin and ensure the propagation of epigenetic information through the cell generations.
Increased mTOR signaling, impaired autophagic flux and cell-to-cell viral transmission are hallmarks of SARS-CoV-2 infection
Authors: Maktura Grazielle Celeste , Dias Thomaz Luscher , Zambalde Érika Pereira , Brenha Bianca , Amorim Mariene R. , Santos Luana Nunes , Buscaratti Lucas , de Angeli Elston João Gabriel , Mara Cynthia , Mancini Mariana Camargo Silva , Pavan Isadora Carolina Betim , Toledo-Teixeira Daniel A. , Bispo-dos-Santos Karina , Parise Pierina L. , Muraro Stefanie Primon , de Souza Gabriela Fabiano , Morelli Ana Paula , da Silva Luiz Guilherme Salvino , de Castro Ícaro Maia Santos , Barbosa Guilherme O. , Ludwig Raissa G. , Knittel Thiago L. , Saccon Tatiana D. , Mori Marcelo A. , Granja Fabiana , Carvalho Hernandes F. , da Silva Luis Lamberti Pinto , Nakaya Helder I. , Proenca-Modena Jose Luiz , Simabuco Fernando Moreira , Marques-Souza Henrique 
Published: October 2021

AbstractThe COVID-19 disease caued by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has two characteristics that distinguish it from other viral infections. It affects more severely people with pre-existing comorbidities and viral load peaks prior to the onset of the symptoms. Investigating factors that could contribute to these characteristics, we found increased mTOR signaling and suppressed genes related to autophagy, lysosome, and vesicle fusion in Vero E6 cells infected with SARS-CoV-2. Transcriptomic data mining of bronchoalveolar epithelial cells from severe COVID-19 patients revealed that COVID-19 severity is associated with increased expression of genes related to mTOR signaling and decreased expression of genes related to autophagy, lysosome function, and vesicle fusion. SARS-CoV-2 infection in Vero E6 cells also resulted in virus retention inside the cells and trafficking of virus-bearing vesicles between neighboring cells. Our findings support a scenario where SARS-CoV-2 benefits from compromised autophagic flux and inhibited exocytosis in individuals with chronic hyperactivation of mTOR signaling, which might relate to undetectable proliferation and evasion of the immune system.
Differential and synergistic effects of low birth weight and Western diet on skeletal muscle vasculature, mitochondrial lipid metabolism and insulin signaling in male guinea pigs
Authors: Dunlop Kristyn , Sarr Ousseynou , Stachura Nicole , Zhao Lin , Nygard Karen , Thompson Jennifer A. , Hadway Jennifer , Richardson Bryan S. , Bureau Yves , Borradaile Nica , Lee Ting-Yim , Regnault Timothy R.H. 
Published: October 2021

AbstractLow birth weight (LBW) offspring are at increased risk for developing insulin resistance, a key precursor in metabolic syndrome and type 2 diabetes mellitus. Altered skeletal muscle vasculature, extracellular matrix, amino acid and mitochondrial lipid metabolism, and insulin signaling are implicated in this pathogenesis. Using uteroplacental insufficiency (UPI) to induce intrauterine growth restriction (IUGR) and LBW in the guinea pig, we investigated the relationship between UPI-induced IUGR/LBW and later life skeletal muscle arteriole density, fibrosis, amino acid and mitochondrial lipid metabolism, markers of insulin signaling and glucose uptake, and how a postnatal high-fat, high-sugar “Western” diet (WD) modulates these changes. Muscle of 145-day-old male LBW glucose tolerant offspring displayed diminished vessel density and altered acylcarnitine levels. Disrupted muscle insulin signaling despite maintained whole-body glucose homeostasis also occurred in both LBW and WD-fed male ‘lean’ offspring. Additionally, postnatal WD unmasked LBW-induced impairment of mitochondrial lipid metabolism as reflected by increased acylcarnitine accumulation. This study provides evidence that early markers of skeletal muscle metabolic dysfunction appear to be influenced by the in utero environment and interact with a high fat-sugar postnatal environment to exacerbate altered mitochondrial lipid metabolism promoting mitochondrial overload.
Development and Application of Multidimensional Lipid Libraries to Investigate Lipidomic Dysregulation Related to Smoke Inhalation Injury Severity
Authors: Kirkwood Kaylie I. , Christopher Michael W. , Burgess Jefferey L. , Littau Sally R. , Pratt Brian S. , Shulman Nicholas , Tamura Kaipo , MacCoss Michael J. , MacLean Brendan X. , Baker Erin S. 
Published: October 2021

ABSTRACTLipids play many biological roles including membrane formation, protection, insulation, energy storage, and cell division. These functions have brought great interest to lipidomic studies for understanding their dysregulation in toxic exposure, inflammation, and diseases. However, lipids have shown to be analytically challenging due to their highly isomeric nature and vast concentration ranges in biological matrices. Therefore, powerful multidimensional techniques such as those integrating liquid chromatography, ion mobility spectrometry, collision induced dissociation, and mass spectrometry (LC-IMS-CID-MS) have recently been implemented to separate lipid isomers as well as provide structural information and increased feature identification confidence. These multidimensional datasets are however extremely large and highly complex, resulting in challenges in data processing and annotation. Here, we have overcome these challenges by developing sample-specific multidimensional libraries using the freely available software Skyline. Specifically, the human plasma library developed for this work contains over 500 unique, experimentally validated lipids, which is combined with adapted Skyline functions for highly confident lipid annotations such as indexed retention time (iRT) for retention time prediction and IMS drift time filtering for increased sensitivity and selectivity. For broad comparison with other lipidomic studies, this human plasma database was initially used to annotate LC-IMS-CID-MS data from a NIST SRM 1950 extract, giving comparable results to previous studies. This workflow was then utilized to assess matched plasma and bronchoalveolar lavage fluid (BALF) samples from patients with varying degrees of smoke inhalation injury to identify potential lipid-based patient prognostic and diagnostic markers.Abstract Figure
Gaussian curvature dilutes the nuclear lamina, favoring nuclear rupture, especially at high strain rate
Authors: Pfeifer Charlotte R. , Tobin Michael P. , Cho Sangkyun , Vashisth Manasvita , Dooling Larry , Vazquez Lizeth Lopez , Ricci-De Lucca Emma G. , Simon Keiann T. , Discher Dennis E. 
Published: October 2021

ABSTRACTNuclear rupture has long been associated with deficits or defects in lamins, with recent results also indicating a role for actomyosin stress, but key physical determinants of rupture remain unclear. Here, lamin-B stably interacts with the nuclear membrane at sites of low Gaussian curvature yet dilutes at high-curvature to favor rupture, whereas lamin-A depletes similarly but only at high strain-rates. Live cell imaging of lamin-B1 gene-edited cancer cells is complemented by fixed-cell imaging of ruptured nuclei in: iPS-derived cells from progeria patients, cells within beating chick embryo hearts, and cancer cells that develop multiple ruptures in migrating through small pores. Dilution and curvature-dependent rupture fit a parsimonious model of a stiff filament that detaches from a curved surface, suggesting an elastic-type response of lamin-B, but rupture is also modestly suppressed by inhibiting myosin-II and by hypotonic stress, which slow the strain rates. Lamin-A dilution and nuclear rupture likelihood indeed increase above a threshold rate of pulling into small pipettes, suggesting a viscoplastic coupling to the envelope for protection against nuclear rupture.Summary statementHigh nuclear curvature drives lamina dilution and nuclear envelope rupture even when myosin stress is inhibited. Stiff filaments generally dilute from sites of high Gaussian curvature, providing mathematical fits of experiments.
The secreted neuronal signal Spock1 regulates the blood-brain barrier
Authors: O’Brown Natasha M. , Patel Nikit B. , Hartmann Ursula , Klein Allon M. , Gu Chenghua , Megason Sean G. 
Published: October 2021

ABSTRACTThe blood-brain barrier (BBB) is a unique set of properties of the brain vasculature which severely restricts its permeability to proteins and small molecules. Classic chick-quail chimera studies showed that these properties are not intrinsic to the brain vasculature but rather are induced by surrounding neural tissue. Here we identify Spock1 as a candidate neuronal signal for regulating BBB permeability in zebrafish and mice. Mosaic genetic analysis shows that neuronally-expressed Spock1 is cell non-autonomously required for a functional BBB. Leakage inspock1mutants is associated with altered extracellular matrix (ECM), increased endothelial transcytosis, and altered pericyte-endothelial interactions. Furthermore, a single dose of recombinant SPOCK1 partially restores BBB function inspock1mutants by quenching gelatinase activity and restoring vascular expression of BBB genes includingmcamb. These analyses support a model in which neuronally secreted Spock1 induces BBB properties by altering the ECM, thereby regulating pericyte-endothelial interactions and downstream vascular gene expression.One-Sentence SummarySpock1 is a signal secreted by neurons that induces barrier properties in the brain vasculature
CAR modulates plasma membrane nano-organization and immune signaling downstream of RALF1-FERONIA signaling pathway
Authors: Chen Weijun , Zhou Huina , Xu Fan , Yu Meng , Coego Alberto , Rodriguez Lesia , Lu Yuqing , Xie Qijun , Fu Qiong , Chen Jia , Xu Guoyun , Wu Dousheng , Li Xiushan , Li Xiaojuan , Jaillais Yvon , Rodriguez Pedro L. , Zhu Sirui , Yu Feng 
Published: October 2021

SummaryThe receptor-like kinase (RLK) FERONIA (FER) senses peptide ligands in the plasma membrane (PM), modulates plant growth and development, and integrates biotic and abiotic stress signaling for downstream adaptive response. However, the molecular interplay of these diverse processes is largely unknown.Here, we show that FER, the receptor of Rapid Alkalinization Factor 1 (RALF1), physically interacts with C2 domain ABA–related (CAR) proteins to control the nano-organization of the PM inArabidopsis.During this process, the RALF1–FER pathway upregulates CAR protein translation, and then more CAR proteins are recruited to PM. This acts as a rapid feedforward loop to stabilize PM liquid-ordered phase. FER interacts with and phosphorylates CARs, and reducing their lipid-binding ability, which breaks the feedback regulation CAR activity at latter time point.Similar to FER mutant, pentuplecar14569mutants inhibit flg22-induced FLS2-BAK1 immune complex formation, which depends on the integrity of nanodomains.Together, we propose that the FER-CAR module controls the formation of the PM nano-organization during RALF signaling through a self-contained amplifying loop including both positive and negative feedbacks.
The PRO model accounts for the anterior cingulate cortex role in risky decision-making and monitoring
Authors: Woo Jae Hyung , Azab Habiba , Jahn Andrew , Hayden Benjamin , Brown Joshua W. 
Published: October 2021

ABSTRACTThe anterior cingulate cortex (ACC) has been implicated in a number of functions including performance monitoring and decision making involving effort. The prediction of responses and outcomes (PRO) model has provided a unified account of much human and monkey ACC data involving anatomy, neurophysiology, EEG, fMRI, and behavior. Here we explore the computational nature of ACC with the PRO model, extending it to account specifically for both human and macaque monkey decision-making under risk, including both behavioral and neural data. We show that the PRO model can account for a number of additional effects related to outcome prediction, decision-making under risk, gambling behavior, and we show that the ACC represents the variance of uncertain outcomes, suggesting a link between ACC function and mean-variance theories of decision making. The PRO model provides a unified account of a large set of data regarding the ACC.
Micro-aggregation of a pristine grassland soil selects for bacterial and fungal communities and changes in nitrogen cycling potentials
Authors: Keuschnig Christoph , Martins Jean M.F. , Navel Aline , Simonet Pascal , Larose Catherine 
Published: October 2021

AbstractMicrobial analysis at the micro scale of soil is essential to the overall understanding of microbial organization and interactions, and necessary for a better understanding of soil ecosystem functioning. While bacterial communities have been extensively described, little is known about the organization of fungal communities as well as functional potentials at scales relevant to microbial interactions. Fungal and bacterial communities and changes in nitrogen cycling potentials in the pristine Rothamsted Park Grass soil (bulk soil) as well as in its particle size sub-fractions (PSFs; > 250 μm, 250-63 μm, 63-20 μm, 20-2 μm, < 2 μm and supernatant) were studied. The potential for nitrogen reduction was found elevated in bigger aggregates. The relative abundance of Basidiomycota deceased with decreasing particle size, Ascomycota showed an increase and Mucoromycota became more prominent in particles less than 20 μm.Bacterial community structures changed below 20 μm at the scale where microbes operate. Strikingly, only members of two bacterial and one fungal phyla (Proteobacteria, Bacteroidota and Ascomycota, respectively) were washed-off the soil during fractionation and accumulated in the supernatant fraction where most of the detected bacterial genera (e.g., Pseudomonas, Massilia, Mucilaginibacter, Edaphobaculum, Duganella, Janthinobacterium and Variovorax) were previously associated with exopolysaccharide production and biofilm formation.Overall, the applied method shows potential to study soil microbial communities at micro scales which might be useful in studies focusing on the role of specific fungal taxa in soil structure formation as well as research on how and by whom biofilm-like structures are distributed and organized in soil.ImportanceIntensive exploitation of soils has led to increasing environmental concerns such as pollution, erosion, emission of greenhouse gases and, in general, the weakening of its ecosystem services that are mainly regulated by microbial activity. Microbial activity and metabolism drive the formation of soil aggregates, ranging in size from a few micrometres to several millimetres. Understanding biological mechanisms related to aggregate size classes can provide insight into large-scale processes, but most research has focused on macroaggregates. Here, we investigated the microbial community and its functional changes at these smaller scales that are clearly more relevant for assessing microbial activity. We demonstrated that fungal communities are more sensitive to bigger size classes than bacteria, suggesting their dominant role in soil structure formation and turnover. We also identified preferential niches for reductive processes within the nitrogen cycle and a selection of specific taxa by analysing the water used for the wet-fractionation approach.
Deep phylogenetic-based clustering analysis uncovers new and shared mutations in SARS-CoV-2 variants as a result of directional and convergent evolution
Authors: Nunes Danilo Rosa , Braconi Carla Torres , Ludwig-Begall Louisa F. , Arns Clarice Weis , Durães-Carvalho Ricardo 
Published: October 2021

AbstractNearly two decades after the last epidemic caused by a severe acute respiratory syndrome coronavirus (SARS-CoV), newly emerged SARS-CoV-2 quickly spread in 2020 and precipitated an ongoing global public health crisis. Both the continuous accumulation of point mutations, owed to the naturally imposed genomic plasticity of SARS-CoV-2 evolutionary processes, as well as viral spread over time, allow this RNA virus to gain new genetic identities, spawn novel variants and enhance its potential for immune evasion. Here, through an in-depth phylogenetic clustering analysis of upwards of 200,000 whole-genome sequences, we reveal the presence of not previously reported and hitherto unidentified mutations and recombination breakpoints in Variants of Concern (VOC) and Variants of Interest (VOI) from Brazil, India (Beta, Eta and Kappa) and the USA (Beta, Eta and Lambda). Additionally, we identify sites with shared mutations under directional evolution in the SARS-CoV-2 Spike-encoding protein of VOC and VOI, tracing a heretofore-undescribed correlation with viral spread in South America, India and the USA. Our evidence-based analysis provides well-supported evidence of similar pathways of evolution for such mutations in all SARS-CoV-2 variants and sub-lineages. This raises two pivotal points: the co-circulation of variants and sub-lineages in close evolutionary environments, which sheds light onto their trajectories into convergent and directional evolution (i), and a linear perspective into the prospective vaccine efficacy against different SARS-CoV-2 strains (ii).Author summaryIn this study, through analysis of very robust and comprehensive datasets, we identify a plethora of mutations in the SARS-CoV-2 Spike cell surface protein of several variants of concern and multiple variants of interest. We trace an association of such mutations with viral spread in different countries. We further infer the presence of new SARS-CoV-2 sublineages and show that the vast majority of mutations identified in the SARS-CoV-2 Spike protein are under convergent evolution. If we consider every color of a Rubik’s cube’s face to represent a different mutation of a particular variant, evolutionary convergence can be achieved only when all composite pieces of a single face are of the same color and every face has one unique color. Overall, this raises two important points: we provide insight into the presence of SARS-CoV-2 variants and sub-lineages circulating in very close evolutionary environments and our analyses can serve to facilitate an outlook into the prospective vaccine efficacy against different SARS-CoV-2 strains.
Differential immunogenicity of homologous versus heterologous boost in Ad26.COV2.S vaccine recipients
Authors: Kim Huat Nicholas Khoo , Er Lim Joey Ming , Gill Upkar S. , de Alwis Ruklanthi , Tan Nicole , Nan Toh Justin Zhen , Abbott Jane E. , Usai Carla , Ooi Eng Eong , Hong Low Jenny Guek , Le Bert Nina , Kennedy Patrick T. F. , Bertoletti Antonio 
Published: October 2021

AbstractProtection offered by COVID-19 vaccines wanes over time, requiring an evaluation of different boosting strategies to revert such a trend and enhance the quantity and quality of Spike-specific humoral and cellular immune responses. These immunological parameters in homologous or heterologous vaccination boosts have thus far been studied for mRNA and ChAdOx1 nCoV-19 vaccines, but knowledge on individuals who received a single dose of Ad26.COV2.S is lacking.We studied Spike-specific humoral and cellular immunity in Ad26.COV2.S vaccinated individuals (n=55) who were either primed with Ad26.COV2.S only (n=13), or boosted with a homologous (Ad26.COV2.S, n=28) or heterologous (BNT162b2, n=14) second dose. We compared our findings with the results found in individuals vaccinated with a single (n=16) or double (n=44) dose of BNT162b2. We observed that a strategy of heterologous vaccination enhanced the quantity and breadth of both, Spike-specific humoral and cellular immunity in Ad26.COV2.S vaccinated. In contrast, the impact of homologous boost was quantitatively minimal in Ad26.COV2.S vaccinated and Spike-specific antibodies and T cells were narrowly focused to the S1 region. Although a direct association between quantity and quality of immunological parameters and in vivo protection has not been demonstrated, the immunological features of Spike-specific humoral and cellular immune responses support the utilization of a heterologous strategy of vaccine boost in individuals who received Ad26.COV2.S vaccination.