bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automated Protein Function Description for Novel Class Discovery
Authors: Barot Meet , Gligorijevic Vladimir , Bonneau Richard , Cho Kyunghyun 
Published: October 2022

AbstractKnowledge of protein function is necessary for understanding biological systems, but the discovery of new sequences from high-throughput sequencing technologies far outpaces their functional characterization. Beyond the problem of assigning newly sequenced proteins to known functions, a more challenging issue is discovering novel protein functions. The space of possible functions becomes unlimited when considering designed proteins. Protein function prediction, as it is framed in the case of Gene Ontology term prediction, is a multilabel classification problem with a hierarchical label space. However, this framing does not provide guiding principles for discovering completely novel functions. Here we propose a neural machine translation model in order to generate descriptions of protein functions in natural language. In this way, instead of making predictions in a limited label space, our model generates descriptions in the language space, and thus is capable of composing novel functions. Given the novelty of our approach, we design metrics to evaluate the performance of our model: correctness, specificity and robustness. We provide results of our model in the zero-shot classification setting, scoring functional descriptions that the model has not seen before for proteins that have limited homology to those in the training set. Finally, we show generated function descriptions compared to ground truth descriptions for qualitative evaluation.
NIS metastable intermediates provide insights into conformational transition between principal thermodynamic states
Authors: Chakrabarti Mayukh , Amzel L. Mario , Lau Albert Y. 
Published: October 2022

ABSTRACTThe Sodium/Iodide Symporter (NIS), a thirteen-helix transmembrane protein found in the thyroid and other tissues, transports iodide, a required constituent of thyroid hormones T3 and T4. Despite extensive experimental information and clinical data, structural details of the intermediate microstates comprising the conformational transition of NIS between its inwardly and outwardly open states remain unresolved. We present data from a combination of enhanced sampling and transition path molecular dynamics (MD) simulations that elucidate the nature of the principal intermediate states comprising the transition between the inwardly and outwardly open metastable states of fully bound and unbound NIS under an enforced ionic gradient. Our findings suggest that in both the absence and presence of bound physiological ions, NIS principally occupies a proximally inward to inwardly open state, whereas when fully bound, it also occupies a rare but thermodynamically favorable ‘inward occluded’ state. The results of this work provide novel insight into the populations of NIS intermediates and the free energy landscape comprising the conformational transition, adding to a mechanistic understanding of NIS ion transport. Moreover, the knowledge gained from this approach can serve as a basis for studies of NIS mutants to target therapeutic interventions.Abstract FigureFor Table of Contents Only
Rubber needs to be included in deforestation-free commodity legislation
Authors: Warren-Thomas Eleanor , Ahrends Antje , Wang Yunxia , Wang Maria M H , Jones Julia P G 
Published: October 2022

AbstractNatural rubber production uses increasing amounts of land in the tropics and is linked to deforestation. There is debate as to whether current legislative proposals to reduce the import of deforestation-linked commodities into the EU, US and the UK will include rubber. Globally, sustained growth in demand is chiefly driven by tyre production, linked to rising freight and passenger transport flows. Yields of natural rubber remain static, meaning increased plantation area will be required: 2.7 – 5.3 million ha of additional harvested area could be needed by 2030 to meet demand. In order to prevent further deforestation and associated biodiversity loss, millions of smallholder growers producing the majority of rubber globally need support to increase production from existing plantations and close yield gaps, without undermining long-term sustainability through soil or water degradation. Rubber should also be included in legislative proposals to reduce deforestation in supply chains to avoid undermining the impact of these ambitious initiatives on forest loss globally.
Born with intronless ERF transcriptional factors: C4photosynthesis inherits a legacy dating back 450 million years
Authors: Lyu Ming-Ju Amy , Du Huilong , Yao Hongyan , Zhang Zhiguo , Chen Genyun , Chen Faming , Zhao Yong-Yao , Tang Qiming , Miao Fenfen , Wang Yanjie , Zhao Yuhui , Lu Hongwei , Fang Lu , Gao Qiang , Qi Yiying , Zhang Qing , Zhang Jisen , Yang Tao , Cui Xuean , Liang Chengzhi , Lu Tiegang , Zhu Xin-Guang 
Published: October 2022

SummaryThe genusFlaveria, containing species at different evolutionary stages of the progression from C3to C4photosynthesis, is used as a model system to study the evolution of C4photosynthesis. Here, we report chromosome-scale genome sequences for fiveFlaveriaspecies, including C3, C4, and intermediate species. Our analyses revealed that both acquiring additional gene copies and recruiting ethylene responsive factor (ERF)cis-regulatory elements (CREs) contributed to the emergence of C4photosynthesis. ERF transcriptional factors (TFs), especially intronless ERF TFs, were co-opted in dicotyledonous C4species and monocotyledonous C4species in parallel. These C4species co-opted intronless ERF TFs originated from the Late Ordovician mass extinction that occurred ∼450 million years ago in coping with environmental stress. Therefore, this study demonstrated that intronless ERF TFs were acquired during the early evolution of plants and provided the molecular toolbox facilitating multiple subsequent independent evolutions of C4photosynthesis.
A new framework for detecting copy number variants from single nucleotide polymorphism data: ‘rCNV’, a versatile R package for paralogs and CNVs detection
Authors: Karunarathne Piyal , Zhou Qiujie , Schliep Klaus , Milesi Pascal 
Published: October 2022

AbstractStudies show that copy number variants (CNVs), due to their ubiquitous presence in eukaryotes, contribute to phenotypic variation, environmental adaptation, and fuel species divergence at a previously unknown rate. However, the detection of CNVs in genomes, especially in non-model organisms is challenging due to the need for costly genomic resources and complex computational infrastructure. Therefore, to provide researchers with a low-cost and easily accessible resource, we developed a robust statistical framework and an R software package to detect CNVs using allelic-read depth from SNPs data.The core of the framework exploits i) the allelic-read depth ratio distribution in heterozygotes for individual SNPs and testing it against an expected distribution under a binomial sampling, and ii) SNPs showing an apparent excess of heterozygotes under Hardy-Weinberg equilibrium, to detect alleles in putatively multi-copy regions. The use of multiple statistical tests to find the deviation in allelic-read depth ratio distribution makes our method sensitive to sampling and aware of reference biases thereby minimizing false detection of CNVs.Our framework is well-catered for high throughput short-reads data, hence, most GBS technologies (e.g., RADseq, Exome-capture, WGS). As such, it allows calling CNVs from genomes of varying complexity. The framework is implemented in the R package “rCNV” which effortlessly automates the analysis. We trained our models on simulated data and tested on four datasets obtained from different sequencing technologies (i.e., RADseq: Chinook salmon –Oncorhynchus tshawytscha, American lobster –Homarus americanus, Exome-capture: Norway Spruce –Picea abies, and WGS: Malaria mosquito -Anopheles gambiae).
Hill-type models of skeletal muscle and neuromuscular actuators: a systematic review
Authors: Caillet Arnault H. , Phillips Andrew T.M. , Carty Christopher , Farina Dario , Modenese Luca 
Published: October 2022

AbstractBacked by a century of research and development, Hill-type models of skeletal muscle, often including a muscle-tendon complex and neuromechanical interface, are widely used for countless applications. Lacking recent comprehensive reviews, the field of Hill-type modelling is, however, dense and hard-to-explore, with detrimental consequences on innovation. Here we present the first systematic review of Hill-type muscle modelling. It aims to clarify the literature by detailing its contents and critically discussing the state-of-the-art by identifying the latest advances, current gaps, and potential future directions in Hill-type modelling. For this purpose, fifty-seven criteria-abiding Hill-type models were assessed according to a completeness evaluation, which identified the modelled muscle properties, and a modelling evaluation, which considered the level of validation and reusability of the models, as well as their modelling strategy and calibration. It is concluded that most models (1) do not significantly advance beyond historical gold standards, (2) neglect the importance of parameter identification, (3) lack robust validation, and (4) are not reusable in other studies. Besides providing a convenient tool supported by extensive supplementary material for navigating the literature, the results of this review highlight the need for global recommendations in Hill-type modelling to optimize inter-study consistency, knowledge transfer, and model reusability.
Robustness vs productivity during evolutionary community assembly: short-term synergies and long-term trade-offs
Authors: Lepori Vasco J. , Loeuille Nicolas , Rohr Rudolf P. 
Published: October 2022

AbstractThe realization that evolutionary feedbacks need to be considered to fully grasp ecological dynamics has sparked interest in the effect of evolution on community properties like coexistence and productivity. However, little is known about the evolution of community robustness and productivity along diversification processes in species-rich systems. We leverage the recent structural approach to coexistence together with adaptive dynamics to study such properties and their relationships in a general trait-based model of competition on a niche axis. We show that the effects of coevolution on coexistence are two-fold and contrasting depending on the timescale considered. In the short term, evolution of niche differentiation strengthens coexistence, while long-term diversification leads to niche packing and decreased robustness. Moreover, we find that co-evolved communities tend to be on average more robust and more productive than non-evolutionary assemblages. We illustrate how our theoretical predictions echo in observed empirical patterns and the implications of our results for empiricists and applied ecologists. We suggest that some of our results such as the improved robustness of Evolutionary Stable Communities could be tested experimentally in suitable model systems.
Versatile and automated workflow for the analysis of oligodendroglial calcium signals in preclinical mouse models of myelin repair
Authors: Maas Dorien A. , Manot-Saillet Blandine , Bun Philippe , Habermacher Chloé , Poilbout Corinne , Rusconi Filippo , Angulo Maria Cecilia 
Published: October 2022

AbstractIntracellular Ca2+signals of oligodendroglia, the myelin-forming cells of the central nervous system, regulate vital cellular processes including myelination. However, studies on oligodendroglia Ca2+signal dynamics are still scarce, especially during myelin repair, and there are no software solutions to properly analyze the unique Ca2+signal characteristics in these cells. Here, we provide a comprehensive experimental and analytical workflow to acquire and analyze Ca2+imaging data of oligodendroglia at the population and single-cell levels in preclinical mouse models of myelin repair. We report diverseex vivoandin vivoexperimental protocols to obtain reproducible Ca2+imaging data from oligodendroglia in demyelinated lesions. Importantly, we provide an analytical pipeline containing two free, open source and cross-platform software programs, Occam and post-prOccam, that enable the fully automated analysis of one- and two-photon Ca2+imaging datasets from oligodendroglia obtained by eitherex vivoorin vivoCa2+imaging techniques. This versatile and accessible experimental and analytical framework, which revealed significant but uncorrelated spontaneous Ca2+activity in oligodendroglia inside demyelinated lesions, should facilitate the elucidation of Ca2+-mediated mechanisms underlying remyelination and therefore help to accelerate the development of therapeutic strategies for the many myelin-related disorders, such as multiple sclerosis.
SCTC: inference of developmental potential from single-cell transcriptional complexity
Authors: Lin Hai , Hu Huan , Feng Zhen , Xu Fei , Lyu Jie , Shuai Jianwei 
Published: October 2022

AbstractInference of single-cell developmental potential from scRNA-Seq data enables us to reconstruct the pseudo-temporal path of cell development, which is an important and challenging task for single-cell analysis. Single-cell transcriptional diversity (SCTD), measured by the number of expressed genes per cell, has been found to be negatively correlated with the development time, and thus can be considered as a hallmark of developmental potential. However, in some cases, the gene expression level of the cells in the early stages of development may be lower than that of the later stages, which may lead to incorrect estimation of differentiation states by gene diversity-based inference. Here we refer to the economic complexity theory and propose single-cell transcriptional complexity (SCTC) metrics as a measure of single-cell developmental potential, given the intrinsic similarities between biological and economic complex systems. We take into account not only the number of genes expressed by cells, but also the more sophisticated structure information of gene expression by treating the scRNA-seq count matrix as a bipartite network. We show that complexity metrics characterize the developmental potential more accurately than the diversity metrics. Especially, in the early stages of development, cells typically have lower gene expression level than that in the later stages, while their complexity in the early stages is significantly higher than that in the later stages. Based on the measurement of SCTC, we provide an unsupervised method for accurate, robust, and transferable inference of single-cell pseudotime. Our findings suggest that the complexity emerging from the interaction between cells and genes determines the developmental potential, which may bring new insights into the understanding of biological development from the perspective of the complexity theory.
Alternating selection for dispersal and multicellularity favors regulated life cycles
Authors: Barrere Julien , Nanda Piyush , Murray Andrew W. 
Published: October 2022

SummaryThe evolution of complex multicellularity opened paths to increased morphological diversity and organizational novelty. This transition involved three processes: cells remained attached to one another to form groups, cells within these groups differentiated to perform different tasks, and the groups evolved new reproductive strategies1–5. Recent experiments identified selective pressures and mutations that can drive the emergence of simple multicellularity and cell differentiation6–11but the evolution of life cycles, in particular, how simple multicellular forms reproduce has been understudied. The selective pressure and mechanisms that produced a regular alternation between single cells and multicellular collectives are still unclear12. To probe the factors regulating simple multicellular life cycles, we examined a collection of wild isolates of the budding yeast,S. cerevisiae12,13. We found that all these strains can exist as multicellular clusters, a phenotype that is controlled by the mating type locus and strongly influenced by the nutritional environment. Inspired by this variation, we engineered inducible dispersal in a multicellular laboratory strain and demonstrated that a regulated life cycle has an advantage over constitutively single-celled or constitutively multicellular life cycles when the environment alternates between favoring intercellular cooperation (a low sucrose concentration) and dispersal (a patchy environment generated by emulsion). Our results suggest that the separation of mother and daughter cells is under selection in wild isolates and is regulated by their genetic composition and the environments they encounter and that alternating patterns of resource availability may have played a role in the evolution of life cycles.Visual abstract
Microrobots Powered by Concentration Polarization Electrophoresis (CPEP)
Authors: Katzmeier Florian , Simmel Friedrich C. 
Published: October 2022

AbstractSecond-order electrokinetic flow around colloidal particles caused by concentration polarization electro-osmosis (CPEO) can result in a phoretic motion of asymmetric particle dimers in a homogeneous AC electrical field, which we refer to as concentration polarization electro-phoresis (CPEP). To demonstrate this actuation mechanism, we created particle dimers from micron-sized silica spheres with sizes 1.0 µm and 2.1 µm by connecting them with DNA linker molecules. The dimers can be steered along arbitrarily chosen paths within a 2D plane by controlling the orientation of the AC electric field in a fluidic chamber with the joystick of a gamepad. Further utilizing induced dipole-dipole interactions, we demonstrate that particle dimers can be used to controllably pick up monomeric particles and release them at any desired position, and also to assemble several particles into groups. Systematic experiments exploring the dependence of the dimer migration speed on the electric field strength, frequency, and buffer composition align with the theoretical framework of CPEO and provide parameter ranges for the operation of our microrobots.
A review of the International Seabed Authority database DeepData: challenges and opportunities in the UN Ocean Decade
Authors: Rabone M. , Horton T. , Jones D. O. B. , Simon-Lledó E. , Glover A. G. 
Published: October 2022

1.AbstractThere is an urgent need for quality biodiversity data in the context of rapid environmental change. Nowhere is this more urgent than in the deep ocean, with the possibility of seabed mining moving from exploration to exploitation, but where vast knowledge gaps persist. Regions of the seabed beyond national jurisdiction, managed by the International Seabed Authority (ISA) are undergoing intensive mining exploration, including the Clarion-Clipperton Zone. In 2019 the ISA launched its database ‘DeepData’, publishing environmental (including biological) data; and since June 2021, DeepData records have been harvested by OBIS (Ocean Biodiversity Information System) via the ISA node. Here we explore how DeepData could support biological research and environmental policy development in the CCZ (and wider ocean regions); and whether data are Findable, Accessible, Interoperable and Reusable (FAIR). Given the direct connection of DeepData with the regulator of a rapidly developing potential industry, this review is particularly timely. We found evidence of extensive duplication of datasets; an absence of unique record identifiers and significant taxonomic data quality issues, compromising FAIRness of the data. The publication of DeepData records on the OBIS ISA node has led to large-scale improvements in data quality and availability. However, limitations in usage of identifiers and issues with taxonomic information were also evident in datasets published on the node, stemming from mis-mapping of data from the ISA environmental data template to the data standard Darwin Core prior to data harvesting by OBIS. While notable data quality issues remain, these changes signal a rapid evolution for the database and significant movement towards integrating with global systems through usage of data standards and publication on global aggregators. This is exactly what has been needed for biological datasets held by the ISA. We provide recommendations for future development of the database to support this evolution towards FAIR.
Glycolytic reprogramming underlies immune cell activation by polyethylene wear particles
Authors: Maduka Chima V. , Habeeb Oluwatosin M. , Kuhnert Maxwell M. , Hakun Maxwell , Goodman Stuart B. , Contag Christopher H. 
Published: October 2022

AbstractPrimary total joint arthroplasties (TJAs) are widely and successfully applied reconstructive procedures to treat end-stage arthritis. Nearly 50% of TJAs are now performed in young patients, posing a new challenge: performing TJAs which last a lifetime. The urgency is justified because subsequent TJAs are costlier and fraught with higher complication rates, not to mention the toll taken on patients and their families. Polyethylene particles, generated by wear at joint articulations, drive aseptic loosening by inciting insidious inflammation associated with surrounding bone loss. Down modulating polyethylene particle-induced inflammation enhances integration of implants to bone (osseointegration), preventing loosening. A promising immunomodulation strategy could leverage immune cell metabolism, however, the role of immunometabolism in polyethylene particle-induced inflammation is unknown. Our findings reveal that immune cells exposed to sterile or contaminated polyethylene particles show fundamentally altered metabolism, resulting in glycolytic reprogramming. Inhibiting glycolysis controlled inflammation, inducing a pro-regenerative phenotype that could enhance osseointegration.