bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enabling the execution of large scale workflows for molecular dynamics simulations
Authors: Andrio Pau , Hospital Adam , Ramon-Cortes Cristian , Conejero Javier , Lezzi Daniele , Ejarque Jorge , Gelpi Josep LL. , Badia Rosa M. 
Published: April 2021

AbstractThe usage of workflows has led to progress in many fields of science, where the need to process large amounts of data is coupled with difficulty in accessing and efficiently using High Performance Computing platforms. On the one hand, scientists are focused on their problem and concerned with how to process their data. On top of that, the applications typically have different parts and use different tools for each part, thus complicating the distribution and the reproducibility of the simulations. On the other hand, computer scientists concentrate on how to develop frameworks for the deployment of workflows on HPC or HTC resources; often providing separate solutions for the computational aspects and the data analytic ones.In this paper we present an approach to support biomolecular researchers in the development of complex workflows that i) allow them to compose pipelines of individual simulations built from different tools and interconnected by data dependencies, ii) run them seamlessly on different computational platforms, and iii) scale them up to the large number of cores provided by modern supercomputing infrastructures. Our approach is based on the orchestration of computational building blocks for Molecular Dynamics simulations through an efficient workflow management system that has already been adopted in many scientific fields to run applications on multitudes of computing backends.Results demonstrate the validity of the proposed solution through the execution of massively parallel runs in a supercomputer facility.
Investigating the two regimes of fibrin clot lysis: an experimental and computational approach
Authors: Raynaud Franck , Chopard Bastien , Rousseau Alexandre , Boudjeltia Karim Zouaoui , Monteyne Daniel , Perez-Morga David 
Published: April 2021

AbstractIt has been observedin vitrothat complete clot lysis is generally preceded by a period of latency during which the degradation seems to be inefficient. However, this latency was merely notified but not yet quantitatively discussed. In our experiments we observed that the lysis ubiquitously occurred in two distinct regimes, a slow and a fast lysis regime. We quantified extensively the duration of these regimes for a wide spectrum of experimental conditions and found that on average the slow regime lasts longer than the fast one, meaning that during most of the process the lysis is ineffective. We proposed a computational model in which the two regimes result from a spatially constrained kinetic of clot lysis: first the biochemical reactions take place at the outer core of the fibrin fibers composing the clot, then in the bulk resulting in the observed fast lysis regime. This simple hypothesis appeared to be sufficient to reproduce with a great accuracy the lysis profiles obtained experimentally. Our results shed light on new insights regarding the dynamical aspects of the lysis of fibrin rich clots in a context where the timing is so critical for patient treatment and outcome.SignificanceWhile the interplay between the main components of the fibrinolytic system is well understood, some dynamical aspects of the fibrinolysis remain unclear. Notably, we observe thatin vitrofibrin rich clots undergo a slow and inefficient phase of degradation when subject to endogenous fibrinolysis. In fact, it turns out that a large part of the lysis process operates in this slow regime. To explain this observation, we proposed a computational model in which the properties of the binding of the proteins change during the lysis. First plasminogen and tissue plasminogen activator bind at the surface of the fibers, resulting in a slow lysis, then in the bulk of the fibers thus speeding up the degradation of the clot..
Computational and biochemical analysis of type IV Pilus dynamics and stability
Authors: Karami Yasaman , López-Castilla Aracelys , Ori Andrea , Thomassin Jenny-Lee , Bardiaux Benjamin , Malliavin Therese , Izadi-Pruneyre Nadia , Francetic Olivera , Nilges Michael 
Published: April 2021

SUMMARYType IV pili (T4P) are distinctive dynamic filaments at the surface of many bacteria that can rapidly extend, retract and withstand strong forces. T4P are important virulence factors in many human pathogens, including EnterohemorrhagicEscherichia coli(EHEC). The structure of the EHEC T4P has been determined by integrating Nuclear Magnetic Resonance (NMR) and cryo-electron microscopy data. To better understand pilus assembly, stability and function, we performed a total of 108 μs all-atom molecular dynamics simulations of wild-type and mutant T4P. Extensive characterization of the conformational landscape of T4P in different conditions of temperature, pH and ionic strength was complemented by targeted mutagenesis and biochemical analyses. Our simulations and NMR experiments revealed a conserved set of residues defining a novel calcium-binding site at the interface between three pilin subunits. Calcium binding enhanced T4P stabilityex vivoandin vitro, supporting the role of this binding site as a potential pocket for drug design.
Arf6 is necessary for high level Wingless signalling duringDrosophilawing development
Authors: Marcetteau Julien , Matusek Tamàs , Luton Frédéric , Thérond Pascal P. 
Published: April 2021

AbstractWnt signalling is a core pathway involved in a wide range of developmental processes throughout the metazoa.In vitrostudies have suggested that the small GTP binding protein Arf6 regulates upstream steps of Wnt transduction, by promoting the phosphorylation of the Wnt co-receptor, LRP6, and the release of β-catenin from the adherens junctions. To assess the relevance of these previous findingsin vivo, we analyse the consequence of the absence of Arf6 activity onDrosophilawing patterning, a developmental model of Wnt/Wingless signalling. We observed a dominant loss of wing margin bristles and Senseless expression in Arf6 mutant flies, phenotypes characteristic of a defect in high level Wingless signalling. In contrast to previous findings, we show that Arf6 is required downstream of Armadillo/β-catenin stabilisation in Wingless signal transduction. Our data suggest that Arf6 modulates the activity of a downstream nuclear regulator of Pangolin activity in order to control the induction of high level Wingless signalling. Our findings represent a novel regulatory role for Arf6 in Wingless signalling.
Opening of a Cryptic Pocket in β-lactamase Increases Penicillinase Activity
Authors: Knoverek Catherine R , Mallimadugula Upasana L , Singh Sukrit , Rennella Enrico , Frederick Thomas E , Yuwen Tairan , Raavicharla Shreya , Kay Lewis E , Bowman Gregory R 
Published: April 2021

AbstractUnderstanding the functional role of protein excited states has important implications in protein design and drug discovery. However, because these states are difficult to find and study, it is still unclear if excited states simply result from thermal fluctuations and generally detract from function or if these states can actually enhance protein function. To investigate this question, we consider excited states in β-lactamases and particularly a subset of states containing a cryptic pocket which forms under the Ω-loop. Given the known importance of the Ω-loop and the presence of this pocket in at least two homologs, we hypothesized that these excited states enhance enzyme activity. Using thiol labeling assays to probe Ω-loop pocket dynamics and kinetic assays to probe activity, we find that while this pocket is not completely conserved across β-lactamase homologs, those with the Ω-loop pocket have a higher activity against the substrate benzylpenicillin. We also find that this is true for TEM β-lactamase variants with greater open Ω-loop pocket populations. We further investigate the open population using a combination of NMR CEST experiments and molecular dynamics simulations. To test our understanding of the Ω-loop pocket’s functional role, we designed mutations to enhance/suppress pocket opening and observed that benzylpenicillin activity is proportional to the probability of pocket opening in our designed variants. The work described here suggests that excited states containing cryptic pockets can be advantageous for function and may be favored by natural selection, increasing the potential utility of such cryptic pockets as drug targets.
Soil composition and plant genotype determine benzoxazinoid-mediated plant-soil feedbacks in cereals
Authors: Cadot Selma , Gfeller Valentin , Hu Lingfei , Singh Nikhil , Sánchez-Vallet Andrea , Glauser Gaétan , Croll Daniel , Erb Matthias , van der Heijden Marcel G. A. , Schlaeppi Klaus 
Published: April 2021

AbstractPlant-soil feedbacks refer to effects on plants that are mediated by soil modifications caused by the previous plant generation. Maize conditions the surrounding soil by secretion of root exudates including benzoxazinoids (BXs), a class of bioactive secondary metabolites. Previous work found that a BX- conditioned soil microbiota enhances insect resistance while reducing biomass in the next generation of maize plants. Whether these BX-mediated and microbially driven feedbacks are conserved across different soils and response species is unknown. We found the BX-feedbacks on maize growth and insect resistance conserved between two arable soils, but absent in a more fertile grassland soil, suggesting a soil-type dependence of BX feedbacks. We demonstrated that wheat also responded to BX-feedbacks. While the negative growth response to BX-conditioning was conserved in both cereals, insect resistance showed opposite patterns, with an increase in maize and a decrease in wheat. Wheat pathogen resistance was not affected. Finally and consistent with maize, we found the BX-feedbacks to be cultivar specific. Taken together, BX- feedbacks affected cereal growth and resistance in a soil and genotype dependent manner. Cultivar-specificity of BX-feedbacks is a key finding, as it hides the potential to optimize crops that avoid negative plant-soil feedbacks in rotations.
Custom long non-coding RNA capture enhances detection sensitivity in different human sample types
Authors: Morlion Annelien , Everaert Celine , Nuytens Justine , Hulstaert Eva , Vandesompele Jo , Mestdagh Pieter 
Published: April 2021

AbstractLong non-coding RNAs (lncRNAs) are a heterogeneous group of transcripts that lack protein coding potential and display regulatory functions in various cellular processes. As a result of their cell- and cancer-specific expression patterns, lncRNAs have emerged as potential diagnostic and therapeutic targets. The accurate characterization of lncRNAs in bulk transcriptome data remains challenging due to their low abundance compared to protein coding genes. To tackle this issue, we describe a unique short-read custom lncRNA capture sequencing approach that relies on a comprehensive set of 565,878 capture probes for 49,372 human lncRNA genes. This custom lncRNA capture approach was evaluated on various sample types ranging from artificial high-quality RNA mixtures to more challenging formalin-fixed paraffin-embedded tissue and biofluid material. The custom enrichment approach allows the detection of a more diverse repertoire of lncRNAs, with better reproducibility and higher coverage compared to classic total RNA-sequencing.
Serum levels of tissue factor pathway inhibitor: Potential association with Raynaud’s phenomenon and telangiectasia in patients with systemic sclerosis
Authors: Norimatsu Yuta , Miyagawa Takuya , Fukui Yuki , Omatsu Jun , Toyama Satoshi , Awaji Kentaro , Ikawa Tetsuya , Watanabe Yusuke , Yoshizaki Ayumi , Sato Shinichi , Asano Yoshihide 
Published: April 2021

AbstractVasculopathy is a critical step of systemic sclerosis (SSc) development, bridging between autoimmune inflammation and tissue fibrosis. Impaired coagulation system is a part of SSc vasculopathy, but the role of tissue factor pathway inhibitor (TFPI), a critical regulator of the extrinsic coagulation pathway, remained unknown. Therefore, we evaluated the clinical correlation of serum TFPI levels in SSc patients. Serum TFPI levels were comparable between SSc and control participants, but SSc patients with Raynaud’s phenomenon and telangiectasia had significantly lower serum TFPI levels than those without. Importantly, there was a significant positive correlation between serum TFPI levels and protein S activity. These results support the critical role of impaired coagulation system in SSc.
The best of both worlds: Apomixis and sexuality co‐occur in species of Microlicia, Melastomataceae
Authors: Viana Matheus Lacerda , Oliveira Paulo Eugênio , Romero Rosana , Caetano Ana Paula Souza 
Published: April 2021

AbstractApomixis, the asexual formation of embryos and seeds, occurs in approximately 18% of angiosperm families. Melastomataceae exhibits a remarkable number of apomictic species, distributed among different tribes. This mode of reproduction has been elucidated in Miconieae, but remains unclarified for other groups, such as Microlicieae. Although apomixis has been previously described for Microlicieae species, the cytological basis for this phenomenon is entirely unknown in this group. Thus, populations of Microlicia fasciculata and M. polystemma were used in order to (a) investigate the presence of autonomous apomixis; (b) verify if this mode of reproduction leads to polyembryony; and (c) investigate whether apomixis may occur in parallel with the sexual process. We tested these species for autonomous fruit set and polyembryony, and pollen viability, and analyzed pollen tube growth. Anatomical techniques were used to elucidate the micro‐ and megasporogenesis and gametogenesis. The species showed autonomous fruit and seed formation and exhibited polyembryony. Apospory and adventitious embryony were the developmental mechanisms of apomixis in M. fasciculata and M. polystemma, respectively. Both species exhibited low pollen viability. However, some viable pollen, reduced embryo sac formation, natural pollination and pollen tube growth enable sexual reproduction and characterize these species as facultative apomicts. The independence of pollinators for fruit set, uniparental reproduction and the possibility of sexual reproduction, confer reproductive assurance and flexibility, bringing together advantages of sexual and asexual reproduction. In this sense, apomixis may have played an important role in the evolution and diversification of Microlicia, a widely distributed genus in the Brazilian Cerrado.
Microbiology of a NaCl stalactite ‘salticle’ in Triassic halite
Authors: Thompson Thomas P. , Kelly Stephen A. , Skvortsov Timofey , Plunkett Gill , Ruffell Alastair , Hallsworth John E. , Hopps Jason , Gilmore Brendan F. 
Published: April 2021

SummaryLarge regions of Earth's surface are underlain by salt deposits that evaporated from ancient oceans and are populated by extreme halophilic microbes. Some of these halophiles may have been preserved over geological timescales within hypersaline fluid inclusions, but ingresses of water and/or anthropogenic activities can lead to the formation of alternative habitats, including NaCl stalactites or other speleothems. While the microbiology of ancient evaporites has been well studied, the ecology of these recently formed structures is less‐well understood. Here, the microbiology of a NaCl stalactite (‘salticle’) in a Triassic halite mine is characterized. The specific aims were to determine the presence of fluid inclusions, determine the microbial structure of the salticle compared with a nearby brine‐pool and surficial soil, and characterize the ecophysiological capabilities of this unique ecosystem. The salticle contained fluid inclusions, and their microbiome was composed of Euryarchaetota, Proteobacteria, and Actinobacteria, with Haloarchaea in greater abundance than brine‐pool or soil microbiomes. The salticle metagenome exhibited a greater abundance of genes involved in osmoregulation, anaerobic respiration, UV resistance, oxidative stress, and stress‐protein synthesis relative to the soil microbiome. We discuss the potential astrobiological implications of salticles as enclosed salt‐saturated habitats that are protected from ionizing radiation and have a stable water activity.
Everyday geoeconomics: The belt and road initiative in Oceania
Authors: Szadziewski Henryk 
Published: April 2021

AbstractAcademic writing on geoeconomics often neglects the lived experiences of local scale actors. This commentary develops the idea of ‘everyday geoeconomics’ to broaden the conceptual and methodological tools available to scholars when examining state‐led geoeconomic initiatives. Everyday geoeconomics includes a range of local responses to policies. It can be used to view these social practices as forms of text that are as important as formal, practical, popular texts referred to in critical geopolitics when analysing the spatial dimensions of economic change. Deemphasising lived experiences in geoeconomic work denotes the return of power/knowledge in human geography after its deconstruction within critical geopolitics. The commentary is enriched by reference to China's Belt and Road Initiative, a state policy held up as a model geoeconomic strategy. The work situates the Belt and Road Initiative in Oceania, where popular and academic debate has polarised around a statist discourse of China's presence as a positive or negative force. This polarisation relegates the lived experiences of residents and newly arrived Chinese as irrelevant to the Belt and Road and leaves us with an incomplete understanding about how those transactions and reactions are shaping global politics.
The association of energy and macronutrient intake at dinner vs breakfast with the incidence of type 2 diabetes mellitus in a cohort study: The China Health and Nutrition Survey, 1997‐2011
Authors: Ren Xiyun , Yang Xue , Jiang Haiyang , Han Tianshu , Sun Changhao 
Published: April 2021

AbstractBackgroundThis study aims to investigate the association of energy and macronutrient intake at dinner vs breakfast with the incidence of type 2 diabetes mellitus (T2DM).MethodsA total of 11 153 adults, including 811 with T2DM, completed a questionnaire about energy and macronutrient intake in the China Health and Nutrition Survey (1997‐2011). The differences (Δ) in energy and macronutrient intake between dinner and breakfast (Δ = dinner − breakfast) were categorized into quintiles. Cox proportional hazards regression models were performed to explore the association between Δ and the risk of T2DM and to investigate the change of the risk when 5% total energy or energy provided by macronutrients at dinner was substituted with total energy or energy provided by macronutrients at breakfast by isocaloric substitution models.ResultsAfter adjustment for potential confounders, compared with participants in the lowest quintile, participants in the highest quintile were more likely to develop T2DM (hazard ratio [HR]Δenergy 1.46, 95% CI 1.13‐1.87; HRΔfat 1.85, 95% CI 1.43‐2.41; HRΔprotein 1.37, 95% CI 1.06‐1.78). Isocalorically replacing 5% energy at dinner with energy at breakfast was associated with a 7% lower T2DM risk. Replacing 5% energy provided by fat at dinner with energy provided by carbohydrate, protein, and fat at breakfast was associated with a 9%, 5%, and 7% lower T2DM risk, respectively. Replacing 5% energy provided by protein at dinner with energy provided by carbohydrate or protein at breakfast was associated with a 5% lower T2DM risk.ConclusionsHigher intake of energy, protein, and fat at dinner than at breakfast increased the risk of T2DM.
Debut of an endangered bird in zoos raises public interest, awareness and conservation knowledge of the species
Authors: Fukano Y. , Soga M. , Fukuda M. , Takahashi Y. , Koyama M. , Arakawa Y. , Miyano N. , Akiba Y. , Horiguchi M. 
Published: April 2021

AbstractRaising public awareness and support for endangered species is critical for global biodiversity conservation. However, we know little about which factors drive public interest in wildlife and how an increase in people's interest shapes their behaviours towards wildlife conservation. The animal debut of ex situ endangered species at zoos may raise general public interest in the conservation of these species. We assessed the impact of an animal debut using a case study of ex situ‐bred Japanese rock ptarmigan, a bird subspecies locally endangered in Japan, on people's awareness, knowledge and behaviours regarding Japanese ptarmigan conservation. The public's reactions to ptarmigans were measured by using an online questionnaire survey and online sources of information (Google Trends, Wikipedia, Twitter and the donation website visits). The animal debut events generated a nationwide increase in information‐seeking and sharing behaviours on the web and in conservation‐oriented behaviour (measured by the number of donation website page visits). A significant increase in knowledge of ptarmigans was evident only among people living in prefectures where ptarmigans occurred. Overall, our results suggest that the debut of ex situ‐bred endangered animals has the potential to promote public awareness, knowledge and behaviours for their conservation on a nationwide scale. Policy makers and practitioners should view zoos as important conservation centres and encourage conservation agencies to collaborate with them to reinforce public support for conservation programmes.
Assessing the threat of landscape transformation and habitat fragmentation in a global biodiversity hotspot
Authors: Ntshanga Nasiphi K. , Procheş Serban , Slingsby Jasper A. 
Published: April 2021

AbstractHabitat loss and habitat fragmentation are amongst the major drivers of biodiversity loss globally. Although habitat fragmentation poses additional threats to biodiversity beyond habitat loss alone, the IUCN’s Red List of Ecosystems (RLE) does not provide guidance on how to assess these threats. This study develops an approach for incorporating habitat fragmentation into the RLE threat assessment and investigates additional insights such an analysis could provide beyond the analysis of distribution trends. This is achieved by quantifying RLE criteria A and B (distribution reduction, restricted distribution and decline) and comparing outcomes with indices of habitat fragmentation (core area, Largest Patch Index, Patch Cohesion Index and Aggregation Index) in the Cape Floristic Region of South Africa. Results revealed that much of the Cape Floristic Region is severely threatened by both landscape transformation and habitat fragmentation, but that treating the habitat fragmentation indices as additional RLE criteria did not alter the ecosystem threat assessment outcomes. Whilst this suggests that the existing RLE criteria implicitly account for habitat fragmentation, the relationship between fragmentation indices and RLE criteria were weak and highly variable in some cases, indicating that the RLE criteria alone do not sufficiently account for the threat of habitat fragmentation. Supplementing the RLE with habitat fragmentation measures highlights additional, unique information on threats to ecosystems. This simple approach has the potential to assist in setting conservation priorities and management goals, particularly in fragmented ecosystems.