bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hair follicle stem cell progeny heal blisters while pausing skin development
Authors: Fujimura Yu , Watanabe Mika , Ohno Kota , Kobayashi Yasuaki , Takashima Shota , Nakamura Hideki , Kosumi Hideyuki , Wang Yunan , Mai Yosuke , Lauria Andrea , Proserpio Valentina , Ujiie Hideyuki , Iwata Hiroaki , Nishie Wataru , Nagayama Masaharu , Oliviero Salvatore , Donati Giacomo , Shimizu Hiroshi , Natsuga Ken 
Published: April 2020

AbstractInjury in adult tissue generally reactivates developmental programs to foster regeneration, but it is not known whether this paradigm applies to growing tissue. Here, by employing blisters, we show that epidermal wounds heal at the expense of skin development. The regenerated epidermis suppresses the expression of tissue morphogenesis genes accompanied by delayed hair follicle (HF) growth. Lineage tracing experiments, cell proliferation dynamics, and mathematical modeling reveal that the progeny of HF junctional zone stem cells, which undergo a morphological transformation, repair the blisters while not promoting HF development. In contrast, the contribution of interfollicular stem cell progeny to blister healing is small. These findings demonstrate that tissue development can be sacrificed for the sake of wound regeneration and suggest that tissue repair does not coincide with the reactivation of developmental programs in all regenerative contexts. Our study elucidates the key cellular mechanism of wound healing in skin blistering diseases.
Continuous manipulation of mental representations is compromised in cerebellar degeneration
Authors: McDougle Samuel D. , Tsay Jonathan , Pitt Benjamin , King Maedbh , Saban William , Taylor Jordan A. , Ivry Richard B. 
Published: April 2020

ABSTRACTHere we test the hypothesis that the cerebellum aids in the dynamic transformation of mental representations. We report a series of neuropsychological experiments comparing the performance of individuals with cerebellar degeneration (CD) on cognitive tasks that either entail continuous, movement-like mental operations or more discrete mental operations. In visual cognition, individuals with CD exhibited an impaired rate of mental rotation, an operation hypothesized to require the continuous manipulation of a visual representation. In contrast, individuals with CD showed a normal processing rate when scanning items in visual working memory, an operation hypothesized to require the maintenance and retrieval of representations. In mathematical cognition, individuals with CD were impaired at single-digit addition, an operation hypothesized to require iterative manipulations along a mental number-line; this group was not impaired on arithmetic tasks requiring memory retrieval (e.g., single-digit multiplication). These results, obtained in tasks from two disparate domains, suggest one potential constraint on the contribution of the cerebellum to cognitive tasks. This constraint may parallel the cerebellum’s role in motor control, involving coordinated dynamic transformations in a mental workspace.
Mosquito cellular immunity at single-cell resolution
Authors: Raddi Gianmarco , Barletta Ana Beatriz F , Efremova Mirjana , Ramirez Jose Luis , Cantera Rafael , Teichmann Sarah A. , Barillas-Mury Carolina , Billker Oliver 
Published: April 2020

AbstractInsect hemocytes are the functional equivalents of leukocytes and limit the capacity of mosquitoes to transmit human pathogens through phagocytosis, encapsulation, secretion of immune factors and immune priming (1,2). Here we profile the transcriptomes of 8506 hemocytes ofAnopheles gambiaeandAedes aegypti, two important mosquito vectors. Blood feeding, infection with malaria parasites and other immune challenges reveal a previously unknown functional diversity of hemocytes, with different types of granulocytes expressing distinct and evolutionarily conserved subsets of effector genes. A new cell type, which we term megacyte, is defined inAnophelesby a unique transmembrane protein marker (TM7318) and high expression of LPS-Induced TNF-alpha transcription factor 3 (LL3). Knock-down experiments indicate that LL3 mediates hemocyte differentiation during immune priming. We identify two main hemocyte lineages and find evidence of proliferating granulocyte populations. We validate our analysis with RNA in-situ hybridization and highlight the mobilization of sessile hemocytes into circulation upon infection. Our data (https://hemocytes.cellgeni.sanger.ac.uk/) provide the first atlas of medically relevant invertebrate immune cells at single cell resolution. It provides an important resource for invertebrate immunology by identifying cellular events that underpin mosquito immunity to malaria infection.
Complete and validated genomes from a metagenome
Authors: Giguere Daniel J , Bahcheli Alexander T , Joris Benjamin R , Paulssen Julie M , Gieg Lisa M , Flatley Martin W , Gloor Gregory B 
Published: April 2020

0.1AbstractThe assembly and binning of metagenomically-assembled genomes (MAGs) using Illumina sequencing has improved the genomic characterization of unculturable communities. However, short-read-only metagenomic assemblies rarely result in completed genomes because of the difficulty assembling repetitive regions. Here, we present a strategy to complete and validate multiple MAGs from a bacterial community using a combination of short and ultra long reads (N50 > 25 kb). Our strategy is to perform an initial long read-only metagenomic assembly using metaFlye, followed by multiple rounds of polishing using both long and short reads. To validate the genomes, we verified that longs reads spanned the regions that were not supported by uniquely mapped paired-end Illumina sequences. We obtained multiple complete genomes from a naphthenic acid-degrading community, including one from the recently proposed Candidate Phyla Radiation. The majority of the population is represented by the assembled genomes; recruiting 63.77 % of Nanopore reads, and 64.38 % of Illumina reads. The pipeline we developed will enable researchers to validate genomes from metagenomic assemblies, increasing the quality of metagenomically assembled genomes through additional scrutiny.
Dynamics of the cell-free DNA methylome of metastatic prostate cancer during androgen-targeting treatment
Authors: Peter Madonna R. , Bilenky Misha , Isserlin Ruth , Bader Gary D. , Shen Shu Yi , De Carvalho Daniel D. , Hansen Aaron R. , Hu Pingzhao , Fleshner Neil E. , Joshua Anthony M. , Hirst Martin , Bapat Bharati 
Published: April 2020

AbstractAimWe examined methylation changes in cell-free DNA (cfDNA) in metastatic castration resistant prostate cancer (mCRPC) during treatment.Materials and MethodsGenome-wide methylation analysis of sequentially collected cfDNA samples derived from mCRPC patients undergoing androgen-targeting therapy was performed.ResultsAlterations in methylation states previously implicated in prostate cancer progression were observed and patients that maintained methylation changes throughout therapy tended to have a longer time to clinical progression (TTP). Importantly, we also report that markers associated with a highly aggressive form of the disease, Neuroendocrine-CRPC, were associated with a faster TTP.ConclusionOur findings highlight the potential of monitoring cfDNA methylome during therapy in mCRPC, which may serve as predictive markers of response to androgen-targeting agents.
Testing the ‘caves as islands’ model in two cave-obligate invertebrates with a genomic approach
Authors: Balogh Andras , Ngo Lam , Zigler Kirk S. , Dixon Groves 
Published: April 2020

AbstractCaves offer selective pressures that are distinct from the surface. Organisms that have evolved to exist under these pressures typically exhibit a suite of convergent characteristics, including a loss or reduction of eyes and pigmentation. As a result, cave-obligate taxa, termed troglobionts, are no longer viable on the surface. This circumstance has led to a “caves as islands” model of troglobiont evolution that predicts extreme genetic divergence between cave populations even across relatively small areas. An effective test of this model would involve (1) common troglobionts from (2) nearby caves in a cave-dense region, (3) good sample sizes per cave, (4) multiple taxa, and (5) genome-wide characterization. With these criteria in mind, we used RAD-seq to genotype an average of ten individuals of the troglobiotic spiderNesticus barriand the troglobiotic beetlePtomaphagus hatchi, each from four closely located caves (ranging from 3-13 km apart) in the cave-rich southern Cumberland Plateau of Tennessee, USA. Consistent with the caves as islands model, we find that populations from separate caves are indeed highly genetically isolated. In addition, nucleotide diversity was correlated to cave length, suggesting that cave size is a dominant force shaping troglobiont population size and genetic diversity. Our results support the idea of caves as natural laboratories for the study of parallel evolutionary processes.
Genome-wide CRISPR synthetic lethality screen identifies a role for the ADP-ribosyltransferase PARP14 in replication fork stability controlled by ATR
Authors: Dhoonmoon Ashna , Schleicher Emily M. , Nicolae Claudia M. , Clements Kristen E. , Moldovan George-Lucian 
Published: April 2020

AbstractThe DNA damage response is essential to maintain genomic stability, suppress replication stress, and protect against carcinogenesis. The ATR-CHK1 pathway is an essential component of this response, which regulates cell cycle progression in the face of replication stress. PARP14 is an ADP-ribosyltransferase with multiple roles in transcription, signaling, and DNA repair. To understand the biological functions of PARP14, we catalogued the genetic components that impact cellular viability upon loss of PARP14 by performing an unbiased, comprehensive, genome-wide CRISPR knockout genetic screen in PARP14-deficient cells. We uncovered the ATR-CHK1 pathway as essential for viability of PARP14-deficient cells, and identified regulation of replication fork stability as an important mechanistic contributor to the synthetic lethality observed. Our work shows that PARP14 is an important modulator of the response to ATR-CHK1 pathway inhibitors.
Decoding Predictions and Violations of Object Position and Category in Time-resolved EEG
Authors: Whyte Christopher J. , Robinson Amanda K. , Grootswagers Tijl , Hogendoorn Hinze , Carlson Thomas A. 
Published: April 2020

AbstractClassic models of predictive coding propose that sensory systems use information retained from prior experience to predict current sensory input. Any mismatch between predicted and current input (prediction error) is then fed forward up the hierarchy leading to a revision of the prediction. We tested this hypothesis in the domain of object vision using a combination of multivariate pattern analysis and time-resolved electroencephalography. We presented participants with sequences of images that stepped around fixation in a predictable order. On the majority of presentations, the images conformed to a consistent pattern of position order and object category order, however, on a subset of presentations the last image in the sequence violated the established pattern by either violating the predicted category or position of the object. Contrary to classic predictive coding when decoding position and category we found no differences in decoding accuracy between predictable and violation conditions. However, consistent with recent extensions of predictive coding, exploratory analyses showed that a greater proportion of predictions was made to the forthcoming position in the sequence than to either the previous position or the position behind the previous position suggesting that the visual system actively anticipates future input as opposed to just inferring current input.
Mycobacteria tolerate carbon monoxide by remodelling their respiratory chain
Authors: Bayly Katherine , Cordero Paul R. F. , Huang Cheng , Schittenhelm Ralf B. , Grinter Rhys , Greening Chris 
Published: April 2020

AbstractCarbon monoxide (CO) is a gas infamous for its acute toxicity. The toxicity of CO predominantly stems from its tendency to form carbonyl complexes with transition metals, thus inhibiting the heme-prosthetic groups of proteins, including the terminal oxidases of the respiratory chain. While CO has been proposed as an antibacterial agent, the evidence supporting its toxicity towards bacteria is equivocal, and its cellular targets remain poorly defined. In this work, we investigate the physiological response of mycobacteria to CO. We show thatMycobacterium smegmatisis highly resistant to the toxic effects of CO, exhibiting normal growth parameters when cultured in its presence. We profiled the proteome ofM. smegmatisduring growth in CO, identifying strong induction of cytochromebdoxidase and members of thedosregulon, but relatively few other changes. We show that the activity of cytochromebdoxidase is resistant to CO, whereas cytochromebcc-aa3oxidase is strongly inhibited by this gas. Consistent with these findings, growth analysis shows thatM. smegmatislacking cytochromebdoxidase displays a significant growth defect in the presence of CO, while induction of thedosregulon appears to be unimportant for adaption to CO. Altogether, our findings suggest thatM. smegmatishas considerable resistance to CO and benefits from respiratory flexibility to withstand its inhibitory effects.ImportanceCarbon monoxide has an infamous reputation as a toxic gas and it has been suggested that it has potential as an antibacterial agent. Despite this, the means by which bacteria resist its toxic effects are not well understood. In this study we determine the physiological response ofMycobacterium smegmatisto growth in CO. We show for the first time that the cytochromebdoxidase is inherently resistant to CO and is deployed byM. smegmatisto tolerate the presence of this gas. Further, we show that aside from this remodelling of its respiratory chain,M. smegmatismakes few other functional changes to its proteome, suggesting it has a high level of inherent resistance to CO.
Translational inhibition and phase separation primes the epigenetic silencing of transposons
Authors: Kim Eun Yu , Wang Ling , Lei Zhen , Li Hui , Fan Wenwen , Cho Jungnam 
Published: April 2020

AbstractTransposons are mobile DNAs that can cause fatal mutations. To counteract these genome invaders, the host genomes deploy small interfering (si) RNAs to initiate and establish the epigenetic silencing. However, the regulatory mechanisms for the selective recognition of transposons by the host genomes remain still elusive. Here we show that plant transposon RNAs undergo frequent ribosome stalling caused by their inherently unfavourable codon sequence usage. The ribosome stalling then causes the RNA truncation and the localization to siRNA bodies, which are both critical prerequisites for the siRNA processing. In addition, SGS3, the key protein in the siRNA biogenesis pathway, forms liquid dropletsin vitrothrough its prion-like domains implicating the role of liquid-liquid phase separation in the formation of the siRNA bodies. Our study provides a novel insight into the regulatory mechanisms for the recognition of invasive genetic elements which is essential for the maintenance of genome integrity.
A Rapid Pathogenicity Assay ofR. solanacearumin 10-12 Days Old Eggplant (Solanum melongena) Seedlings by Root Inoculation Approach
Authors: Singh Niraj 
Published: April 2020

1.AbstractThis study has reported standardization of pathogenicity assay ofRalstonia solancearumin eggplant seedlings by root inoculation approach. Though the approach is similar to my earlier published work that done with tomato seedlings, in case of eggplant, duration of the seed germination, age of the seedlings, symptom timing and progression rate of the disease are different. In an introductory observation,R. solanacearumF1C1 inoculation was performed in to 10-12 days old eggplant seedlings resulted in lethal infection in eggplant seedlings and subsequently most of these infected seedlings got wilted within 10 days of post-inoculation. Colonization studies ofR. solanacearumin wilted as well as infected eggplant seedlings were confirmed by GUS staining as well as fluorescence microscopy. In addition, we also observed that wrapping of the eggplant seedlings root by a thin layer of cotton soon after the pathogen inoculation in the root, enhanced the disease progression and wilting of the inoculated seedlings. The standardized root inoculation protocol in eggplant seedlings was found to be efficient to distinguish mutant strains of different virulence genes such ashrpB, phcAandpilTfrom wild-typeR. solanacearum. Due to its reproducibility and consistency in different eggplant cultivars, the standardized protocol described here is practically observed as an useful and rapid approach to investigateR. solanacearumpathogenicity and disease progression at the early seedling stage of eggplant.
Pharmacological activation of the circadian component REV-ERB inhibits HIV-1 replication
Authors: Borrmann Helene , Davies Rhianna , Dickinson Matthew , Pedroza-Pacheco Isabela , Schilling Mirjam , Vaughan-Jackson Alun , James William , Balfe Peter , Borrow Persephone , McKeating Jane A , Zhuang Xiaodong 
Published: April 2020

AbstractHuman immunodeficiency virus 1 (HIV-1) is a life-threatening pathogen that still lacks a curative therapy or vaccine. Despite the reduction in AIDS-related deaths achieved by current antiretroviral therapies, drawbacks including drug resistance and the failure to eradicate infection highlight the need to identify new pathways to target the infection. Circadian rhythms are endogenous 24-hour oscillations which regulate physiological processes including immune responses to infection, and there is an emerging role for the circadian components participating viral replication. The molecular clock consists of transcriptional/translational feedback loops that generate rhythms. In mammals, CLOCK and BMAL1 activate rhythmic transcription of genes including the nuclear receptor REV-ERBα, which represses BMAL1 and plays an essential role in sustaining a functional clock. We investigated whether REV-ERB activity regulates HIV-1 replication, and found REV-ERB agonists inhibited HIV-1 promoter activity in cell lines, primary human CD4 T cells and macrophages, whilst antagonism or genetic disruption of REV-ERB increased promoter activity. Furthermore, the REV-ERB agonist SR9009 inhibited promoter activity of different HIV-subtypes and HIV-1 replication in primary T cells. This study shows a role for REV-ERB synthetic ligands to inhibit HIV-1 LTR promoter activity and viral replication, supporting a role for circadian clock transcription factors in regulating HIV-1 replication.
From Substance to Computation: Internalization and Hierarchical Structure in Evolutionary Phonology
Authors: Tanaka Shin-ichi 
Published: April 2020

AbstractIn the history of phonological theory, the paradigm of computational systems has shifted in tandem with a better understanding of substantive issues such as typology, acquisition, social variation, and historical change in sound structure. The paradigm shift in the past 50 years can simply be characterized as the one from ‘serial derivation by rules’ to ‘parallel evaluation by constraints,’ and now Optimality Theory (OT) focusses on substantive issues by improving its phonetic groundings and has ceased groping for a better mode of computation. This is because OT is primarily a substantive theory of CON, and at least in its standard version, the computational systems of Eval and GEN are merely ‘given assumptions.’In this article, we will overview some arguments against OT in substantive respects. As an ultimate problem in substance, it cannot solve ‘the poverty paradox,’ which means the paradox of ‘the poverty of the stimulus’ in ontogeny and ‘the poverty of the inheritance’ in phylogeny. Moreover, as a proximate problem in substance, certain gaps to be missed in syllable typology would erroneously be predicted to exist by OT. Alternatively, we will rethink the mode of computation in phonology and propose a new paradigm for phonology from the viewpoint of language evolution under a minimalist lens. Our proposal is based on Fujita’s (2016a, 2017) Hypothesis on Motor Control Origin of Merge in Language Evolution, which solves ‘the poverty paradox’ and thus satisfies both explanatory and evolutionary adequacy. We will demonstrate that substantive findings in OT can successfully be carried over to this scenario, in which the empirical problem concerning the typological gap is offered a reasonable explanation. We will also show that phonology has a vital role in computation and is not merely a subsidiary issue at the interface of the Sensory-Motor systems in linearization or externalization. We will take up one case for this claim: the English syllable CCVC has structural ambiguity, which means that phonology involves internalization with some mechanisms in order to create different hierarchical structures.
Microrheology reveals microscale viscosity gradients in planktonic systems
Authors: Guadayol Òscar , Mendonca Tania , Segura-Noguera Mariona , Wright Amanda J. , Tassieri Manlio , Humphries Stuart 
Published: April 2020

AbstractMicrobial activity in planktonic systems creates a dynamic and heterogeneous microscale seascape that harbours a diverse community of microorganisms and ecological interactions of global significance. In recent decades a great effort has been put into understanding this complex system, particularly focusing on the role of chemical patchiness, while overlooking a physical parameter that governs microbial life and is affected by biological activity: viscosity. Here we use microrheological techniques to measure viscosity at length scales relevant to microorganisms. Our results reveal the viscous nature and the spatial extent of the phycosphere, the microenvironment surrounding phytoplankton cells, and show heterogeneity in viscosity at the microscale. Such heterogeneity affects the distribution of chemicals and microorganisms, with pervasive and profound implications for the functioning of the planktonic ecosystem.One Sentence SummaryMicrorheology measurements unveil the existence of layers of increased viscosity surrounding phytoplankton cells and within aggregates.