bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epistasis, aneuploidy, and gain-of-function mutations underlie the evolution of resistance to induced microtubule depolymerization
Authors: Pavani Mattia , Bonaiuti Paolo , Chiroli Elena , Gross Fridolin , Natali Federica , Macaluso Francesca , Poti Adam , Pasqualato Sebastiano , Pompei Simone , Cosentino-Lagomarsino Marco , Rancati Giulia , Szuts David , Ciliberto Andrea 
Published: October 2020

ABSTRACTMicrotubules, polymers of alpha- and beta-tubulin, are essential cellular components. When microtubule polymerization is hindered, cells are delayed in mitosis, but eventually they manage to proliferate with massive chromosome missegregation. Several studies have analyzed the first cell division upon microtubules impairing conditions. Here, we asked how cells cope on the long term. Taking advantage of mutations in beta-tubulin, we evolved in the lab for ∼150 generations 24 populations of yeast cells unable to properly polymerize microtubules. At the end of the evolution experiment, cells re-gained the ability to form microtubules, and were less sensitive to microtubule depolymerizing drugs. Whole genome sequencing allowed us to identify genes recurrently mutated (tubulins and kinesins) as well as the pervasive duplication of chromosome VIII. We confirmed that mutations found in these genes and disomy of chromosome VIII allow cells to compensate for the original mutation in beta-tubulin. The mutations we identified were mostly gain-of-function, likely re-allowing the proper use of the mutated form of beta-tubulin. When we analyzed the temporal order of mutations leading to resistance in independent populations, we observed multiple times the same series of events: disomy of chromosome VIII followed by one additional adaptive mutation in either tubulins or kinesins. Analyzing the epistatic interactions among different mutations, we observed that some mutations benefited from the disomy of chromosome VIII and others did not. Given that tubulins are highly conserved among eukaryotes, our results are potentially relevant for understanding the emergence of resistance to drugs targeting microtubules, widely used for cancer treatment.
MiSiC, a general deep learning-based method for the high-throughput cell segmentation of complex bacterial communities
Authors: Panigrahi Swapnesh , Murat Dorothée , Gall Antoine Le , Martineau Eugénie , Goldlust Kelly , Fiche Jean-Bernard , Rombouts Sara , Nöllmann Marcelo , Espinosa Leon , Mignot Tâm 
Published: October 2020

AbstractStudies of microbial communities by live imaging require new tools for the robust identification of bacterial cells in dense and often inter-species populations, sometimes over very large scales. Here, we developed MiSiC, a general deep-learning-based segmentation method that automatically segments a wide range of spatially structured bacterial communities with very little parameter adjustment, independent of the imaging modality. Using a bacterial predator-prey interaction model, we demonstrate that MiSiC enables the analysis of interspecies interactions, resolving processes at subcellular scales and discriminating between species in millimeter size datasets. The simple implementation of MiSiC and the relatively low need in computing power make its use broadly accessible to fields interested in bacterial interactions and cell biology.
Anterior cingulate cortex hypofunction causes anti-social aggression in mice
Authors: van Heukelum S. , Tulva K. , Geers F. , van Dulm S. , Ruisch I. H. , Mill J. , Viana J. F. , Beckmann C. F. , Buitelaar J. K. , Poelmans G. , Glennon J. C. , Vogt B. A. , Havenith M. N. , França A. S. C. 
Published: October 2020

AbstractControlling aggression is a crucial skill in social species like rodents and humans, and has been associated with anterior cingulate cortex (ACC). Here, we demonstrate a causal link between ACC hypofunction and failed aggression control in BALB/cJ mice. We first show that ACC in BALB/cJ mice is structurally degraded: Neuron density is decreased, with pervasive neuron death and neuro-toxic astroglia. Gene-set enrichment analysis suggested that this process is driven by neuronal degeneration, which then causes toxic astrogliosis. cFos expression across ACC indicated functional consequences: During aggressive encounters, ACC was engaged in control mice, but not BALB/cJ mice. Chemogenetically activating ACC during aggressive encounters drastically suppressed anti-social aggression but left adaptive aggression intact. The network effects of our chemogenetic perturbation suggest that this behavioural rescue is mediated by suppression of amygdala and hypothalamus and activation of mediodorsal thalamus. Together, these findings highlight the causal role of ACC in curbing anti-social aggression.
VPS13D bridges the ER to Miro containing membranes
Authors: Guillén-Samander Andrés , Leonzino Marianna , Hanna Michael G. , Tang Ni , Shen Hongying , De Camilli Pietro 
Published: October 2020

AbstractMitochondria, which are excluded from the secretory pathway, depend on lipid transport proteins for their lipid supply from the ER, where most lipids are synthesized. In yeast, the outer mitochondrial membrane GTPase Gem1 is an accessory factor of ERMES, an ER-mitochondria tethering complex that contains lipid transport domains and that functions, partially redundantly with Vps13, in lipid transfer between the two organelles. In metazoa, where VPS13, but not ERMES, is present, the Gem1 orthologue Miro was linked to mitochondria dynamics but not to lipid transport. Here we show that Miro, including its peroxisome-enriched splice variant, recruits the lipid transport protein VPS13D, which in turn binds the ER in a VAP-dependent way and thus could provide a lipid conduit between the ER and mitochondria. These findings reveal a so far missing link between function(s) of Gem1/Miro in yeast and higher eukaryotes, where Miro is a Parkin substrate, with potential implications for Parkinson’s disease pathogenesis.SummaryVPS13D mutations result in severe mitochondrial defects. Guillén-Samander et al, show that VPS13D binds VAP in the ER, and interacts with Miro on mitochondria and peroxisomes, so that it can provide a bridge for lipid transport between these organelles.
Social contact behaviors are associated with infection status for whipworm (Trichurissp.) in wild vervet monkeys (Chlorocebus pygerythrus)
Authors: Wren Brandi , Ray Ian S. , Remis Melissa , Gillespie Thomas R. , Camp Joseph 
Published: October 2020

AbstractSocial grooming in the animal kingdom is common and serves several functions, from removing ectoparasites to maintaining social bonds between conspecifics. We examined whether time spent grooming with others in a highly social mammal species was associated with infection status for gastrointestinal parasites. Of six parasites detected, one (Trichurissp.) was associated with social grooming behaviors, but more specifically with direct physical contact with others. Individuals infected withTrichurissp. spent significantly less time grooming conspecifics than those not infected, and time in direct contact with others was the major predictor of infection status. One model correctly predicted infection status forTrichurissp. with a reliability of 95.17% overall when the variables used were time spent in direct contact and time spent grooming others. This decrease in time spent grooming and interacting with others is likely a sickness behavior displayed by individuals with less energy or motivation for non-essential behaviors. This study highlights the need for an understanding of a study population’s parasitic infections when attempting to interpret animal behavior.
Inferring latent temporal progression and regulatory networks from cross-sectional transcriptomic data of cancer samples
Authors: Sun Xiaoqiang , Zhang Ji , Nie Qing 
Published: October 2020

AbstractUnraveling molecular regulatory networks underlying disease progression is critically important for understanding disease mechanisms and identifying drug targets. The existing methods for inferring gene regulatory networks (GRNs) rely mainly on time-course gene expression data. However, most available omics data from cross-sectional studies of cancer patients often lack sufficient temporal information, leading to a key challenge for GRN inference. Through quantifying the latent progression using random walks-based manifold distance, we propose a latent-temporal progression-based Bayesian method, PROB, for inferring GRNs from the cross-sectional transcriptomic data of tumor samples. The robustness of PROB to the measurement variabilities in the data is mathematically proved and numerically verified. Performance evaluation on real data indicates that PROB outperforms other methods in both pseudotime inference and GRN inference. Applications to bladder cancer and breast cancer demonstrate that our method is effective to identify key regulators of cancer progression or drug targets. The identified ACSS1 is experimentally validated to promote epithelial-to-mesenchymal transition of bladder cancer cells, and the predicted FOXM1-targets interactions are verified and are predictive of relapse in breast cancer. Our study suggests new effective ways to clinical transcriptomic data modeling for characterizing cancer progression and facilitates the translation of regulatory network-based approaches into precision medicine.Author summaryReconstructing gene regulatory network (GRN) is an essential question in systems biology. The lack of temporal information in sample-based transcriptomic data leads to a major challenge for inferring GRN and its translation to precision medicine. To address the above challenge, we propose to decode the latent temporal information underlying cancer progression via ordering patient samples based on transcriptomic similarity, and design a latent-temporal progression-based Bayesian method to infer GRNs from sample-based transcriptomic data of cancer patients. The advantages of our method include its capability to infer causal GRNs (with directed and signed edges) and its robustness to the measurement variability in the data. Performance evaluation using both simulated data and real data demonstrate that our method outperforms other existing methods in both pseudotime inference and GRN inference. Our method is then applied to reconstruct EMT regulatory networks in bladder cancer and to identify key regulators underlying progression of breast cancer. Importantly, the predicted key regulators/interactions are experimentally validated. Our study suggests that inferring dynamic progression trajectory from static expression data of tumor samples helps to uncover regulatory mechanisms underlying cancer progression and to discovery key regulators which may be used as candidate drug targets.
Crumbs and the Apical Spectrin Cytoskeleton Regulate R8 Cell Fate in theDrosophilaeye
Authors: Pojer Jonathan M. , Kondo Shu , Harvey Kieran F. 
Published: October 2020

ABSTRACTThe Hippo pathway is an important regulator of organ growth and cell fate. In the R8 photoreceptor cells of theDrosophila melanogastereye, the Hippo pathway controls the fate choice between one of two subtypes that express either the blue light-sensitive Rhodopsin 5 (Hippo inactive) or the green light-sensitive Rhodopsin 6 (Hippo active). The degree to which the mechanism of Hippo signal transduction and the proteins that mediate it are conserved in organ growth and R8 cell fate choice is currently unclear. Here, we identify Crumbs and the apical spectrin cytoskeleton as regulators of R8 cell fate. By contrast, other proteins that influence Hippo-dependent organ growth, such as the basolateral spectrin cytoskeleton and Ajuba, are dispensable for the R8 cell fate choice. Surprisingly, Crumbs promotes the Rhodopsin 5 cell fate, which is driven by Yorkie, rather than the Rhodopsin 6 cell fate, which is driven by Warts and the Hippo pathway, which contrasts with its impact on Hippo activity in organ growth. Furthermore, neither the apical spectrin cytoskeleton nor Crumbs regulate the Hippo pathway through mechanisms that have been reported to operate in growing organs. Together, these results show that only a subset of Hippo pathway proteins regulate the R8 binary cell fate decision and that aspects of Hippo pathway signalling appear to differ between growing organs and post-mitotic R8 cells.
Relationships between climate and phylogenetic community structure of fossil pollen assemblages are not constant during the last deglaciation
Authors: Pradhan Kavya , Nieto-Lugilde Diego , Fitzpatrick Matthew C. 
Published: October 2020

AbstractDisentangling the influence of environmental drivers on community assembly is important to understand how multiple processes influence biodiversity patterns and can inform understanding of ecological responses to climate change. Phylogenetic Community Structure (PCS) is increasingly used in community assembly studies to incorporate evolutionary perspectives and as a proxy for trait (dis)similarity within communities. Studies often assume a stationary relationship between PCS and climate, though few if any studies have tested this assumption over long time periods with concurrent community data. We estimated Nearest Taxon Index (NTI) and Net Relatedness index (NRI), two PCS metrics, of fossil pollen assemblages of angiosperms in eastern North America data over the last 21 ka BP at 1ka intervals. We analyzed spatiotemporal relationships between PCS and seven climate variables, evaluated the potential impact of deglaciation on PCS, and tested for the stability of climate-PCS relationships. The broad scale patterns of PCS, with overdispersion increasing towards the southern and eastern parts of the study area, remained largely stable across time. Most importantly, we found that significant relationships between climate variables and PCS (slope) were unstable as climate changed during the last deglaciation and new ice-free regions were colonized. We also found weak, but significant, relationships between both PCS metrics (i.e., NTI and NRI) and climate and time-since-deglaciation, which were stable even though the baselines (intercepts) changed through time. Overall, our results suggest that (1) PCS of fossil Angiosperm assemblages during the last 21ka BP have had predictable spatial patterns, but (2) the instability in the relationships between PCS and climate brings into question their usefulness in predictive modeling of community assembly.
Bathyarchaeota Occurrence in Shallow Marine Methane-rich Sediments (Saco do Mamanguá, Rio de Janeiro, Brazil)
Authors: Romano R. G. , Bendia A. G. , Franco D. C. , Signori C. N. , Yu T. , Wang F. , Jovane L. , Pellizari V. H. 
Published: October 2020

ABSTRACTMethane gas (CH4) reservoirs have previously been reported in tropical marine sediments of Saco do Mamanguá ria (Rio de Janeiro, Brazil). It is known that a methane microbiome can be established in methane seeps sites; however, they are still poorly characterised. In this study, we aimed to investigate the spatial and vertical distribution of the bacterial and archaeal composition and the community structure in the sediments of Saco do Mamanguá ria. For this purpose, we collected sediment samples through 100 cm long gravity corer at three different sites and performed community analysis based on 16S rRNA gene sequencing, quantification of the methyl coenzyme M reductase-encoding gene (mcrA) and geochemical analysis, including CH4stable isotope. Our results revealed a biogenic trend for CH4isotopic signature and a high proportion of archaeal sequences assigned as Bathyarchaeota, with a spatial distribution throughout the inner areas of the channel and the deepest strata. OTUs classified within Bathyarchaeota and Chloroflexi (Dehalococcoidia) showed positive correlation with methane concentrations, sediment depth and oxidation-reduction potential. Due to their prevalence in the microbial community, we also performed phylogenetic analysis to understand the closeness of our Bathyarchaeota OTUs with Bathyarchaeota subgroups, and the results demonstrated a close relationship particularly with Bathy-8 and Bathy-13, which possess genes for acetogenesis and methanogenesis. Although direct relations between microbial populations and the biogenic methane emissions in Saco do Mamanguá cannot be assured, our results emphasize the importance of further investigations about the potential role of Bathyarchaeota in the carbon cycling in methane-rich tropical shallow ecosystems.
SARS-CoV-2 has observably higher propensity to accept uracil as nucleotide substitution: Prevalence of amino acid substitutions and their predicted functional implications in circulating SARS-CoV-2 in India up to July, 2020
Authors: Roy Subrata , Nath Himadri , Mallick Abinash , Biswas Subhajit 
Published: October 2020

AbstractSARS-CoV-2 has emerged as pandemic all over the world since late 2019. In this study, we investigated the diversity of the virus in the context of SARS-CoV-2 spread in India. Full-length SARS-CoV-2 genome sequences of the circulating viruses from all over India were collected from GISAID, an open data repository, until 25thJuly, 2020. We have focused on the non-synonymous changes across the genome that resulted in amino acid substitutions. Analysis of the genomic signatures of the non-synonymous mutations demonstrated a strong association between the time of sample collection and the accumulation of genetic diversity. Most of these isolates from India belonged to the A2a clade (63.4%) which has overcome the selective pressure and is spreading rapidly across several continents. Interestingly a new clade I/A3i has emerged as the second-highest prevalent type among the Indian isolates, comprising 25.5% of the Indian sequences. Emergence of new mutations in the S protein was observed. Major SARS-CoV-2 clades in India have defining mutations in the RdRp. Maximum accumulation of mutations was observed in ORF1a.Other than the clade-defining mutations, few representative non-synonymous mutations were checked against the available crystal structures of the SARS-CoV-2 proteins in the DynaMut server to assess their thermodynamic stability. We have observed that SARS-CoV-2 genomes contain more uracil than any other nucleotide. Furthermore, substitution of nucleotides to uracil was highest among the non-synonymous mutations observed. The A+U content in SARS-CoV-2 genome is much higher compared to other RNA viruses, suggesting that the virus RdRp has a propensity towards uracil incorporation in the genome. This implies that thymidine analogues may have a better chance to competitively inhibit SARS-CoV-2 RNA replication than other nucleotide analogues.
Metabolic Plasticity drives Development during Mammalian Embryogenesis
Authors: Sharpley Mark S. , Chi Fangtao , Banerjee Utpal 
Published: October 2020

SummaryPreimplantation mouse embryos interact minimally with their environment, and development is largely driven by metabolic processes. During the earliest cleavage stages, metabolism is rigid, with maternal deposits enforcing a redox state that facilitates zygotic genome activation. As maternal control falls, metabolic shuttles are activated, increasing glycolysis and equilibrating the TCA cycle. The resulting flexibility of nutrient utilization and metabolic plasticity facilitates unidirectional developmental progression such that later stage embryos proceed to form blastocysts without any exogenously added nutrients. We explore the mechanisms that govern this choreographed sequence that balances the deposition, degradation, synthesis and function of metabolic enzymes with redox control, bioenergetics and biosynthesis. Cancer cells follow a distinct metabolic strategy from that of the preimplantation embryo. However, important shared features emerge under reductive stress. We conclude that metabolic plasticity drives normal development while stress conditions mimic hallmark events in Cancer Metabolism.
Selective translation of epigenetic modifiers drives the developmental clock of neural stem cells
Authors: Wu Quan , Shichino Yuichi , Abe Takaya , Suetsugu Taeko , Omori Ayaka , Kiyonari Hiroshi , Iwasaki Shintaro , Matsuzaki Fumio 
Published: October 2020

AbstractThe cerebral cortex is formed by diverse neurons generated sequentially from neural stem cells (NSCs). A clock mechanism has been suggested to underlie the temporal progression of NSCs, which is mainly defined by the transcriptome and the epigenetic state. However, what drives such a developmental clock remains elusive. We show that translational control of histone H3 trimethylation at Lys27 (H3K27me3) modifiers is part of this clock. We found that depletion of Fbl, an rRNA methyltransferase, reduces translation of both the Ezh2 methyltransferase and Kdm6b demethylase of H3K27me3 and delays progression of the NSC state. These defects are phenocopied by simultaneous inhibition of H3K27me3 methyltransferase and demethylase, indicating the role of Fbl in the genome-wide H3K27me3 pattern. Fbl selectively enhances the translation of H3K27me3 modifiers via a cap-independent mechanism. We thus propose that Fbl drives the intrinsic clock through the translational enhancement of H3K27me3 modifiers that predominantly define the NSC state.
A qualitative study on money, well-being and serial crowdfunding
Authors: Sherman Arie , Axelrad Hila 
Published: October 2020

PurposeThe paper aims to examine the unique nature of crowdfunding and its association with supporters' well-being, measured by Seligman's (2011) well-being theory and its five elements of PERMA: positive emotions, engagement, relationships, meaning and accomplishment.Design/methodology/approach22 structured interviews were conducted with supporters of crowdfunding projects. The interviews were analyzed using deduction, generating themes and assigning them to the relevant PERMA elements.FindingsAlmost all interviews included five or four PERMA elements, supporting the hypothesis about crowdfunding as a form of economic behavior that is triggered by the desire for fulfillment in life. The authors found that the tendency to become a serial crowdfunder is triggered by PERMA and a sense of trust.Originality/valueThis is the first study that presents a well-being theory of non-investment crowdfunding contributions. Based on the interviews, we suggest a theory linking the motivation for backing current and future projects with PERMA elements, sense of trust and the nature of adaption to activities with intrinsic attributes.
Disaster justice for people with disabilities
Authors: Ton Khanh That , Adamson Carole 
Published: October 2020

PurposeThe purpose of this article is to examine disaster justice for people with disabilities (PWD).Design/methodology/approachDrawing on the capability approach, the article explores distributive injustice that PWD face in dealing with disasters. It discusses procedural justice with a focus on the agency of PWD and their participation in decision-making processes concerning disaster risk reduction.FindingsIt argues that disaster injustice faced by PWD can be construed as the inequalities of capabilities that they experience in coping with disasters. Furthermore, although social structures play an important role in creating and perpetuating disaster injustice, PWD, as agents of change, have power to transform social structures that, in turn, bring about justice for themselves.Originality/valueThe article raises the need for considering the equality of capabilities and human agency in achieving disaster justice for PWD.