bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post-2020 Kunming 30% target can easily protect all endemic sharks and rays in the Western Indian Ocean and more
Authors: Cheok Jessica , Jabado Rima W. , Ebert David A. , Dulvy Nicholas K. 
Published: March 2021

SummarySharks and rays are possibly the most threatened Class of marine fishes and their declines can be halted if protected areas are optimised to benefit these species. We identify spatial priorities for all 63 endemic sharks and rays in the marine biodiversity hotspot, the Western Indian Ocean (WIO). Collectively, while the WIO nations currently surpass the 10% Aichi ocean protection target, this amounts to a dismal protection of only 1.57% of each species’ distribution range. We show that the entire ranges of all endemics can be achieved by protecting 11% of EEZs of WIO nations, well within reach of the new 30% of oceans by 2030 target. Regional management bodies exist, which if taken advantage of to implement shark and ray management, provide opportunities to implement more efficient management across the region. We recommend key management actions to implement and explicit incentivisation of international cooperation in the post-2020 biodiversity framework.Science for SocietyThe past decade has seen massive growth in the establishment of marine protected areas (MPAs), driven by the Aichi biodiversity target of protecting 10% of all ocean areas. This expansion of MPAs, however, has largely occurred in areas residual to extractive uses, often coinciding with less threatened areas of lower conservation value. This coming decade will see a further push to ensure 30% of the oceans are protected by 2030. It is important to understand how existing and future MPAs should be placed to benefit threatened biodiversity. Currently this is unclear for sharks and rays, comprising a species group that is the most evolutionarily distinct vertebrate radiation in the world and also one of the most threatened. We identify both regional and national conservation priorities for expanding marine protected areas to benefit all 63 endemic sharks and rays occurring in the Western Indian Ocean region. We find that the region has already exceeded the 10% ocean protection target, but this amounts to an average of only 1.57% protection of the distribution ranges of these species. We show that protecting the top 10% priority sites will conserve almost half of the geographic range of each species yet require only 1.16% of the total EEZ – a tiny fraction of the 30% by 2030 target. We also show that regional collaboration among all nations can result in more spatially efficient conservation priorities. We recommend that the post-2020 biodiversity framework needs to explicitly incentivise regional cooperation between nations to efficiently achieve urgent targets and maximise benefits to biodiversity.
The effect of task demands on the neural patterns generated by novel instruction encoding
Authors: Sobrado Alberto , Palenciano Ana F. , González-García Carlos , Ruz María 
Published: March 2021

AbstractVerbal instructions allow fast and optimal implementation of novel behaviors. Previous research has shown that different control-related variables structure neural activity in frontoparietal regions during the encoding of novel instructed tasks. However, it is uncertain whether different task goals modulate the organizing effect of these variables. In this study, we investigated whether the neural encoding of three task-relevant variables (dimension integration, response set complexity and target category) is modulated by implementation and memorization demands. To do so, we combined functional Magnetic Resonance Imaging (fMRI), an instruction-following paradigm and multivariate analyses. We addressed how and where distributed activity patterns encoded the instructions’ variables and the impact of the implementation and memorization demands on the fidelity of these representations. We further explored the nature of the neural code underpinning this process. Our results reveal, first, that the content of to-be-implemented and to-be-memorized instructions is represented in overlapping brain regions, flexibly using a common neural code across tasks. Importantly, they also suggest that preparing to implement the instructions increases the decodability of task-relevant information in frontoparietal areas, in comparison with memorization demands. Overall, our work emphasizes both similarities and differences in task coding under the two contextual demands. These findings qualify the previous understanding of novel instruction processing, suggesting that representing task attributes in a generalizable code, together with the increase in encoding fidelity induced by the implementation goals, could be key mechanisms for proactive control in novel scenarios.
Spike-frequency dependent coregulation of multiple ionic conductances in fast-spiking cells forces a metabolic tradeoff
Authors: Ban Yue , Maltby Rosalie , Markham Michael R. 
Published: March 2021

ABSTRACTHigh-frequency action potentials (APs) allow rapid information acquisition and processing in neural systems, but create biophysical and metabolic challenges for excitable cells. The electric fishEigenmannia virescensimages its world and communicates with high-frequency (200-600 Hz) electric organ discharges (EODs) produced by synchronized APs generated at the same frequency in the electric organ cells (electrocytes). We cloned three previously unidentified Na+-activated K+channel isoforms from electroctyes (eSlack1, eSlack2, and eSlick1). In electrocytes, mRNA transcript levels of the rapidly-activating eSlick, but not the slower eSlack1 or eSlack2, correlated with EOD frequency across individuals. In addition, transcript levels of an inward-rectifier K+channel, a voltage-gated Na+channel, and Na+,K+-ATPases also correlated with EOD frequency while a second Na+channel isoform did not. Computational simulations showed that maintaining electrocyte AP waveform integrity as firing rates increase requires scaling conductances in accordance with these mRNA expression correlations, causing AP metabolic costs to increase exponentially.
Diversification, Spread, and Admixture of Octoploid Strawberry in the Western Hemisphere
Authors: Bird Kevin A. , Hardigan Michael A. , Ragsdale Aaron P. , Knapp Steven J. , VanBuren Robert , Edger Patrick P. 
Published: March 2021

Premise of the studyOctoploid strawberry (Fragaria sp.) has a complex evolutionary history that has until recently been intractable due to limitations of available genomic resources. While recent work has further uncovered the evolutionary history of the octoploid strawberry, there are still open questions. Much is still unknown about the evolutionary relationship of the wild octoploid species,Fragaria virginianaandFragaria chiloensis, and gene flow within and among species after the original formation of the octoploid genome.MethodsWe leveraged a diversity collection of wild octoploid eco-types of strawberry representing the recognized subspecies and ranging from Alaska to Southern Chile, and a high density SNP array to investigate wild octoploid strawberry evolution. Evolutionary relationships are interrogated with phylogenetic analysis and genetic clustering algorithms. Additionally, admixture among and within species is assessed with model-based and tree-based approaches.Key ResultsPhylogenetic analysis revealed that the two octoploid strawberry species are monophyletic sister lineages. The genetic clustering results show substructure between North Americana and South AmericanF. chiloensispopulations. Additionally, model-based and tree-based methods support gene flow within and among the two octoploid species, including newly identified admixture in the HawaiianF. chiloensissubsp.sandwicensispopulation that appears to be from an ancestralF. chiloensispopulation.ConclusionF. virginianaandF. chiloensisare supported as monophyletic and sister lineages. All but one of the subspecies recognized within both octoploid species show extensive paraphyly. Furthermore, the phylogenetic relationship amongF. chiloensispopulations supports a single population range expansion southward from North America. The inter- and intraspecific relationships of octoploid strawberry are complex and suggest substantial and deep gene flow between sympatric populations among and within species.
Antimalarial mass drug administration in large populations and the evolution of drug resistance
Authors: Nguyen Tran Dang , Tran Thu Nguyen-Anh , Parker Daniel M. , White Nicholas J , Boni Maciej F 
Published: March 2021

AbstractMass drug administration (MDA) with antimalarials has been shown to reduce prevalence and interrupt transmission in small populations, in populations with reliable access to antimalarial drugs, and in populations where sustained improvements in diagnosis and treatment are possible. Effective MDA eliminates drug-resistant parasites which has the long-term benefit of extending the useful therapeutic life of first-line therapies for all populations, not just the focal population where MDA was carried out. However, in order to plan elimination measures effectively, it is necessary to characterize the conditions under which failed MDA could exacerbate resistance. We use an individual-based stochastic model ofPlasmodium falciparumtransmission to evaluate this risk in large populations (>40K) where access to antimalarial treatments may not be uniformly high and where re-importation of drug-resistant parasites may be common. We find that drug-resistance evolution can be accelerated by MDA when all three of the following conditions are met: (1) strong genetic bottlenecking that falls short of elimination, (2) re-importation of resistant genotypes, and (3) continued selection pressure during routine case management post-MDA. Accelerated resistance levels are not immediate but follow the rebound of malaria cases post-MDA, if this is allowed to occur. Crucially, resistance is driven by the selection pressure during routine case management post-MDA and not the selection pressure exerted during the MDA itself. Second, we find that increasing treatment coverage post-MDA increases the probability of local elimination in low-transmission regions (PfPR < 2%) in scenarios with both low and high levels of drug-resistance importation. This emphasizes the importance of preparation and planning to ensure that MDA has a high probability of leading to elimination, and the necessity of supporting public health infrastructure to provide high coverage of diagnosis and treatment post-MDA.
How Stimulus Statistics Affect The Receptive Fields of V1 Cells
Authors: Almasi Ali , Sun Shi Hai , Yunzab Molis , Jung Young Jun , Meffin Hamish , Ibbotson Michael R. 
Published: March 2021

AbstractWe studied the changes that neuronal RF models undergo when the statistics of the stimulus are changed from those of white Gaussian noise (WGN) to those of natural scenes (NS). Fitting the model to data estimates both a cascade of linear filters on the stimulus, as wells as the static nonlinearities that map the output of the filters to the neuronal spike rates. We found that cells respond differently to these two classes of stimuli, with mostly higher spike rates and shorter response latencies to NS than to WGN. The most striking finding was that NS resulted in RFs that had additional uncovered filters than did WGN. This finding was not an artefact of the higher spike rates but rather related to a change in coding. Our results reveal a greater extent of nonlinear processing in V1 neurons when stimulated using NS compared to WGN. Our findings indicate the existence of nonlinear mechanisms that endow V1 neurons with context-dependent transmission of visual information.
Trajectory inference across multiple conditions with condiments: differential topology, progression, differentiation, and expression
Authors: de Bézieux Hector Roux , Van den Berge Koen , Street Kelly , Dudoit Sandrine 
Published: March 2021

AbstractIn single-cell RNA-sequencing (scRNA-seq), gene expression is assessed individually for each cell, allowing the investigation of developmental processes, such as embryogenesis and cellular differentiation and regeneration, at unprecedented resolutions. In such dynamic biological systems, grouping cells into discrete groups is not reflective of the biology. Cellular states rather form a continuum, e.g., for the differentiation of stem cells into mature cell types. This process is often represented via a trajectory in a reduced-dimensional representation of the scRNA-seq dataset.While many methods have been suggested for trajectory inference, it is often unclear how to handle multiple biological groups or conditions, e.g., inferring and comparing the differentiation trajectories of wild-type and knock-out stem cell populations.In this manuscript, we present a method for the estimation and downstream interpretation of cell trajectories across multiple conditions. Our framework allows the interpretation of differences between conditions at the trajectory, cell population, and gene expression levels. We start by integrating datasets from multiple conditions into a single trajectory. By comparing the conditions along the trajectory’s path, we can detect large-scale changes, indicative of differential progression. We also demonstrate how to detect subtler changes by finding genes that exhibit different behaviors between these conditions along a differentiation path.
rdacca.hp: an R package for generalizing hierarchical and variation partitioning in multiple regression and canonical analysis
Authors: Lai Jiangshan , Zou Yi , Zhang Jinlong , Peres-Neto Pedro 
Published: March 2021

SummaryCanonical analysis, a generalization of multiple regression to multiple response variables, is widely used in ecology. Because these models often involve large amounts of parameters (one slope per response per predictor), they pose challenges to model interpretation. Currently, multi-response canonical analysis is constrained by two major challenges. Firstly, we lack quantitative frameworks for estimating the overall importance of single predictors. Secondly, although the commonly used variation partitioning framework to estimate the importance of groups of multiple predictors can be used to estimate the importance of single predictors, it is currently computationally constrained to a maximum of four predictor matrices.We established that commonality analysis and hierarchical partitioning, widely used for both estimating predictor importance and improving the interpretation of single-response regression models, are related and complementary frameworks that can be expanded for the analysis of multiple-response models.In this application, we aim at: a) demonstrating the mathematical links between commonality analysis, variation and hierarchical partitioning; b) generalizing these frameworks to allow the analysis of any number of responses, predictor variables or groups of predictor variables in the case of variation partitioning; and c) introducing and demonstrating the usage of the R packagerdacca.hpthat implements these generalized frameworks.
Generation of human blastocyst-like structures from pluripotent stem cells
Authors: Fan Yong , Min Zhe-Ying , Alsolami Samhan , Ma Zheng-Lai , Zhong Ke , Pei Wen-Di , Zhang Pu-Yao , Kang Xiang-Jin , Zhang Ying-Ying , Zhu Hai-Ying , Qiao Jie , Li Mo , Yu Yang 
Published: March 2021

AbstractHuman blastocysts are comprised of the first three cell lineages of the embryo: trophectoderm, epiblast, and primitive endoderm, all of which are essential for early development and organ formation1,2. However, due to ethical concerns and restricted access to human blastocysts, we lack a comprehensive understanding of early human embryogenesis. To bridge this knowledge gap, we need a reliable model system that recapitulates early stages of human embryogenesis. Here we report a ∼three-dimensional (3D), two-step induction protocol for generating blastocyst-like structures (EPS-blastoids) from human extended pluripotent stem (EPS) cells. Morphological and single-cell transcriptomic analyses revealed that EPS-blastoids contain key cell lineages and are transcriptionally similar to human blastocysts. Furthermore, EPS-blastoids also exhibited the developmental potential to undergo post-implantation morphogenesis in vitro to form structures with a cellular composition and transcriptome signature similar to human embryos that had been cultured in vitro for 8 or 10 days. In conclusion, human EPS-blastoids provide a new experimental platform for studying early developmental stages of the human embryo.HighlightsA method for generating human blastoids from EPS cells.Human blastoids resemble blastocysts in terms of morphology and cell lineage composition.Single-cell transcriptomic analyses reveal EPI, PE, and TE cell lineages in human blastoids.Human blastoids mimic in vitro the morphogenetic events of pre- and early post-implantation stages.
End-to-end Learning of Evolutionary Models to Find Coding Regions in Genome Alignments
Authors: Mertsch Darvin , Stanke Mario 
Published: March 2021

1AbstractMotivationThe comparison of genomes using models of molecular evolution is a powerful approach for finding or towards understanding functional elements. In particular, comparative genomics is a fundamental building brick in building high-quality, complete and consistent annotations of ever larger sets of alignable genomes.ResultsWe here present our new program ClaMSA that classifies multiple sequence alignments using a phylogenetic model. It uses a novel continuous-time Markov chain machine learning layer, named CTMC, that is learned end-to-end together with (recurrent) neural networks for a learning task. We trained ClaMSA discriminately to classify aligned codon sequences that are candidates of coding regions into coding or non-coding and obtained six times fewer false positives for this task on vertebrate and fly alignments than existing methods at the same true positive rate. ClaMSA and the CTMC layer are general tools that could be used for other machine learning tasks on tree-related sequence data.AvailabilityFreely fromhttps://github.com/Gaius-Augustus/clamsa.
Direct sulphate-TOR signalling controls transcriptional reprogramming for shoot apex activation inArabidopsis
Authors: Yu Yongdong , Zhong Zhaochen , Ma Liuyin , Xiang Chengbin , Xu Ping , Xiong Yan 
Published: March 2021

AbstractPhotosynthetic plants play a primary role for the global sulphur cycle in the earth ecosystems by reduction of inorganic sulphate from the soil to organic sulphur-containing compounds. How plants sense and transduce the sulphate availability in soil to mediate their growth remains largely unclear. The target of rapamycin (TOR) kinase is an evolutionarily conserved master regulator of nutrient sensing and metabolic signalling to control cell proliferation and growth in all eukaryotes. Here, we discovered that inorganic sulphate exhibits higher potency than organic cysteine and glutathione for activation of TOR and cell proliferation in the leaf primordium to promote true leaf development inArabidopsis. Chemical genetic analyses further revealed that this sulphate activation of TOR is independent of the sulphate-assimilation process and glucose-energy signalling. Significantly, tissue specific transcriptome analyses uncovered previously unknown sulphate-orchestrating genes involved in DNA replication, cell proliferation, autophagy and various secondary metabolism pathways, which are completely depending on TOR signalling. Systematic comparison between the sulphate- and glucose-TOR controlled transcriptome further revealed that, as the central growth integrator, TOR kinase can sense different upstream nutrient signals to control both shared and unique transcriptome networks, therefore, precisely modulate plant proliferation, growth and stress responses.
The first multi-tissue diel genome-scale metabolic model of a woody plant highlights suberin biosynthesis pathways inQuercus suber
Authors: Cunha Emanuel , Silva Miguel , Chaves Ines , Demirci Huseyin , Lagoa Davide Rafael , Lima Diogo , Rocha Miguel , Rocha Isabel , Dias Oscar 
Published: March 2021

AbstractIn the last decade, genome-scale metabolic models have been increasingly used to study plant metabolic behavior at the tissue and multi-tissue level under different environmental conditions.Quercus suber, also known as the cork oak tree, is one of the most important forest communities of the Mediterranean/Iberian region. In this work, we present the genome-scale metabolic model of theQ. suber(iEC7871), the first of a woody plant. The metabolic model comprises 7871 genes, 6231 reactions, and 6481 metabolites across eight compartments. Transcriptomics data was integrated into the model to obtain tissue-specific models for the leaf, inner bark, and phellogen, with specific biomass compositions. The tissue-specific models were merged into a diel multi-tissue metabolic model to predict interactions among the three tissues at the light and dark phases. The metabolic models were also used to analyze the pathways associated with the synthesis of suberin monomers. Nevertheless, the models developed in this work can provide insights into other aspects of the metabolism ofQ. suber, such as its secondary metabolism and cork formation.
Towards a broad-spectrum antiviral, the myristoyltransferase inhibitor IMP-1088 suppresses viral replication – the Yellow fever NS5 is myristoylated
Authors: Immerheiser Melissa , Zimniak Melissa , Hilpert Helen , Geiger Nina , König Eva-Maria , Bodem Jochen 
Published: March 2021

AbstractAlthough a potent Yellow fever vaccine is available since 1937, up to 200.000 severe cases are reported per year, which indicates that virus vaccines require additional support by antiviral therapies. Direct-acting antiviral drugs against severe and widespread diseases, such as DENV and Yellow fever infections with more than millions of diagnosed diseases per year, are still not available. Since antivirals’ development against neglected diseases is uneconomical, a broadspectrum antiviral compound would be of public benefit. Here, we show that IMP-1088, a recently published myristoyltransferase-1/2 inhibitor suppressing Rhino- and Polioviruses, inhibits replication of HIV-1, Yellow fever virus, Dengue virus, Vaccinia virus, CMV, and human Herpesvirus 8 in the low nanomolar range, indicating that IMP-1088 has broad-range activity against different pathogenic virus families. The inhibition relies on virally encoded myristoylation signals since Zika, Chikungunya, and Enterovirus 71 are not affected by IMP-1088. Furthermore, we show that the Yellow fever NS5 protein is myristoylated and IMP-1088 treatment of Dengue and Yellow fever infected cells leads to a re-localisation of the viral NS5 proteins.Author SummaryTreatment of viral diseases requires the development of tailored drugs specific to inhibit certain virus families. This specificity results in missing treatment options for important human pathogens such as Yellow fever and Dengue virus infection since the development is laborious and costly. Substances acting on various virus families could solve this problem. Here, we describe that IMP-1088, an inhibitor of the cellular myristoyltransferase, inhibits HIV-1, Dengue virus, Yellow fever viruses, Vaccinia virus, and Herpesviruses at low concentrations, which do not affect cell proliferation. Viruses without predicated myristoylation sites, such as Zika viruses, were not inhibited by IMP-1088. Since no experimental evidence was provided that Yellow fever virus proteins are myristoylated, we analysed the post-translational modification of Yellow fever NS5 protein. We determined the subcellular localisation to understand the mechanism of the IMP-1088 mediated suppression and could show that both the Dengue and the Yellow fever NS5 proteins are re-localised by IMP-1088 treatment.