bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the “cost of generating force” hypothesis across frequency in human running and hopping
Authors: Allen Stephen P. , Beck Owen N. , Grabowski Alena M. 
Published: March 2022

AbstractThe volume of active muscle and duration of extensor muscle force well-explain the associated metabolic energy expenditure across body mass and speed during level-ground running and hopping. However, if these parameters fundamentally drive metabolic energy expenditure, then they should pertain to multiple modes of locomotion and provide a simple framework for relating biomechanics to metabolic energy expenditure in bouncing gaits. Therefore, we evaluated the ability of the ‘cost of generating force’ hypothesis to link biomechanics and metabolic energy expenditure during human running and hopping across step frequencies. We asked participants to run and hop at 0%, ±8% and ±15% of preferred step frequency. We calculated changes in active muscle volume, force duration, and metabolic energy expenditure. Overall, as step frequency increased, active muscle volume decreased due to postural changes via effective mechanical advantage (EMA) or duty factor. Accounting for changes in EMA and muscle volume better related to metabolic energy expenditure during running and hopping at different step frequencies than assuming a constant EMA and muscle volume. Thus, to ultimately develop muscle mechanics models that can explain metabolic energy expenditure across different modes of locomotion, we suggest more precise measures of muscle force production that include the effects of EMA.
Analysis of the persistence and particle size distributional shift of sperm-derived environmental DNA to monitor Jack Mackerel spawning activity
Authors: Tsuji Satsuki , Murakami Hiroaki , Masuda Reiji 
Published: March 2022

AbstractEnvironmental DNA (eDNA) analysis holds great promises as an efficient and noninvasive method to monitor not only the presence and biomass of organisms but also their spawning activity. In eDNA analysis-based monitoring of spawning activity, the detection of sperm-derived eDNA is a key point; however, its characteristics and dynamics are completely unknown. The present study focuses on the persistence and particle size distribution (PSD) of eDNA derived from the sperm of Japanese jack mackerel. First, we investigated the time-dependent degradation and the PSD of sperm-derived eDNA by artificially adding sperm to fish eDNA-free seawater. Next, we kept fish in tanks and examined the changes in DNA concentration and PSD before and after spawning. The data obtained from the two experiments showed that the degradation of sperm-derived eDNA proceeded rapidly, with PSD shifting to a smaller size, regardless of the DNA region (Cyt b or ITS1). Additionally, it was shown that the nuclei and mitochondria released from sperm through degradation had a size distribution that was not simply dependent on each organelle size. The results of this study will contribute to elucidating the characteristics and dynamics of eDNA specifically during the spawning season and to further developing eDNA analysis as a powerful tool for the monitoring of spawning activity.Abstract Figure
Thymus formation in uncharted embryonic territories
Authors: Alcobia Isabel , Gama-Carvalho Margarida , Magalhães Leonor , Proa Vitor , Henrique Domingos , Neves Hélia 
Published: March 2022

ABSTRACTThe thymus is a conserved organ among vertebrates, derived from the endoderm of distinct pharyngeal pouches (PP), whose location and number vary across species. Together with reports of sporadic ectopic thymus locations in mice and humans, this suggests that the potential to make a thymus resides in a broader region of the PP endoderm than previously ascribed.Using the chick-quail chimera system, we explore this hypothesis and test the capacity of non-canonical pouches to participate in thymus formation. We further ask if the local mesenchyme of pharyngeal arches (PA) could also play a role in the regulation of thymus formation. After testing several embryonic tissue associations, we mapped the pharyngeal endoderm regions with thymus potential to the second and third/fourth pharyngeal pouches (2PP and 3/4PP). We further identified mesenchyme regions that regulate this potential to the 3/4 pharyngeal arches and to the dorsal region of the second arch, with positive and negative influences, respectively. Transcriptomic analysis of these tissues helped us revealing a common genetic program in the PP endoderm linked to thymus potential in addition to finding distinct signalling pathways involved in the cellular interactions with the mesenchyme of the pharyngeal arches that result in modulating this potential.Together, these results provide new information about the initial specification of thymus primordia in the embryo that may contribute to improving the development of thymus organoid systems.Graphical abstract
MitoSearch: Construction of fish species composition database with environmental DNA using public databases
Authors: Ito Takumi , Mizobata Hideaki , Yoshitake Kazutoshi , Kinoshita Shigeharu , Asakawa Shuichi 
Published: March 2022

AbstractExisting fish species distribution databases have the following problems: the possibility of species identification errors due to plasticity of morphological characteristics, the impossibility of quantitative composition, and the difficulty of geographically and time-series integrated interpretation. To solve the above problems, we constructed MitoSearch database. It is a fish species distribution database using 2,160 samples of variable regions of 12S rRNA genes amplified by MiFish primers registered at NCBI/EBI/DDBJ, and visualizes the fish species composition data on a map. By integrating a large amount of data registered in public databases, MitoSearch was aimed to provide the comprehensive understanding of spatial and temporal distribution of organisms on a global scale.
Allosteric inhibitors of Zika virus NS2B-NS3 protease targeting protease in super-open conformation
Authors: Meewan Ittipat , Shiryaev Sergey A. , Huang Chun-Teng , Lin Yi-Wen , Chuang Chiao-Han , Terskikh Alexey V. , Abagyan Ruben 
Published: March 2022

ABSTRACTZika virus (ZIKV) is a member of the Flaviviridae family and is considered a major health threat causing cases of microcephaly in newborns and Guillain-Barré syndrome in adults. Here we targeted a transient deep and hydrophobic pocket of the super-open conformation of ZIKV NS2B-NS3 protease to overcome the limitations of the orthosteric inhibitors. After virtual docking screening of approximately 7 million compounds against the novel allosteric site we selected the top seven candidates and tested them in an enzymatic assay. Six out of seven top candidates selected by the docking screen inhibited ZIKV NS2B-NS3 protease proteolytic activity at low micromolar concentrations, as well as suppressing viral replication. These six compounds, targeting the selected protease pocket conserved in ZIKV as well as several other Flaviviruses, have opened an opportunity for a new kind of drug candidate that might be useful to treat several flaviviral infections.
Circadian-period variation underlies the local adaptation of photoperiodism in the short-day plant Lemna aequinoctialis
Authors: Muranaka Tomoaki , Ito Shogo , Kudoh Hiroshi , Oyama Tokitaka 
Published: March 2022

SummaryPhenotypic variation is the basis for trait adaptation via evolutionary selection.1, 2, 3 However, the driving forces behind the quantitative trait variations remain unclear owing to their complexity at the molecular level.4, 5, 6 This study focused on the natural variation of the free-running period (FRP) of the circadian clock because FRP is a determining factor of the internal clock phase (chronotype), which is responsible for physiological timing during a day.7 Although natural variations in FRP have been widely reported,8, 10, 11 few studies have shown the association between FRP and adaptive temporal traits. As a clock-dependent physiological process, photoperiodism is a typical target of local adaptation.12, 13Lemna aequinoctialis in Japan is a paddy-field duckweed exhibiting a latitudinal cline of critical day-lengths (CDLs) for short-day flowering.14 To investigate the relationship between FRP and CDL, we collected 72 strains of L. aequinoctialis within a latitudinal range between 31.5°N to 43.8°N. We found a significant correlation (P = 7.5E-8) between FRPs and locally adaptive CDLs, confirming that the variation in FRP-dependent chronotypes underlies geographically differentiated photoperiodism. Diel transcriptome analysis revealed that the induction timing of a florigen gene is key for connecting chronotypes to photoperiodism at the molecular level. Based on these results, we propose a fundamental rule concerning the “chronotype effect” in evolution: the variation of FRP functions as a resource for the variation of temporal traits. This study highlights the adaptive significance of FRP variation and provides a reason for the maintenance of FRP variation in natural populations.
Niche-based deterministic assembly processes strengthen the effects of β-diversity on metacommunity functioning of marine bacterioplankton
Authors: Chang Feng-Hsun , Yang Jinny Wu , Liu Ariana Chih-Hsien , Lu Hsiao-Pei , Gong Gwo Ching , Shiah Fuh-Kwo , Hsieh Chih-hao 
Published: March 2022

AbstractStudies at a local community (α) level have shown that biodiversity positively affects ecosystem functioning due to niche-based deterministic processes like resource partitioning. Extending to a metacommunity (β) level, we hypothesize that β diversity also positively affects metacommunity functioning. We further hypothesize that the β diversity effect is stronger (more positive) when β diversity is increased by deterministic/non-random assembly processes. To test the hypotheses, we collected bacterioplankton along a transect of 6 stations in the southern East China Sea in 14 cruises. All 6 stations within a cruise were regarded as a metacommunity. For any pairs of the 6 stations, the Bray-Curtis index and summed bacterial biomass were calculated to represent β diversity and metacommunity functioning, respectively. We also calculated deviation of observed mean pairwise phylogenetic similarities among species from random to represent the deterministic influences of assembly processes. We found that bacterial β diversity generally positively affects metacommunity functioning; however, the β diversity effect varied among cruises. Cross-cruise comparison indicates that the β diversity effect increased with the deterministic assembly processes selecting for phylogenetically dissimilar species. This study extends the biodiversity-ecosystem functioning research to a metacommunity level, complementing the current framework by considering community assembly in natural environments.
Placental inflammation leads to abnormal embryonic heart development
Authors: Ward Eleanor J , Bert Serena , Fanti Silvia , Dufton Neil P , Malone Kerri M , Maughan Robert T , Prin Fabrice , Volpato Lia Karina , Piovezan Anna Paula , Perretti Mauro , Marelli-Berg Federica M , Nadkarni Suchita 
Published: March 2022

AbstractPlacental and embryonic heart development occurs in parallel, and these organs have been proposed to exert reciprocal regulation during gestation. Poor placentation has been associated with congenital heart disease (CHD), an important cause of infant mortality. However, the mechanisms by which altered placental development can lead to CHD remain unresolved. In the current study we show that neutrophil-driven placental inflammation leads to inadequate placental development and loss of barrier function. Consequently, placental inflammatory monocytes of maternal origin become capable to migrate to the embryonic heart and alter the normal composition of resident cardiac macrophages and cardiac tissue structure. This cardiac impairment continues into postnatal life, hindering normal tissue architecture and function. Finally, we demonstrate that tempering placental inflammation can rescue this fetal cardiac defect and is sufficient to promote normal cardiac function in postnatal life. Taken together, our observations provide a mechanistic paradigm whereby neutrophil-driven inflammation in pregnancy can preclude normal embryonic heart development as a direct consequence of poor placental development.
Focusing the GWASLenson days to flower using latent variable phenotypes derived from global multi-environment trials
Authors: Neupane Sandesh , Wright Derek M , Martinez Raul O , Butler Jakob , Weller James L , Bett Kirstin E 
Published: March 2022

AbstractAdaptation constraints within crop species have resulted in limited genetic diversity in some breeding programs and/or areas where new crops have been introduced,e.g.,lentil(Lens culinarisMedik.) in North America. An improved understanding of the underlying genetics involved in phenology-related traits is valuable knowledge to aid breeders in overcoming limitations associated with unadapted germplasm and expanding their genetic diversity by introducing new, exotic material. We used a large, 18 site-year, multi-environment dataset, phenotyped for phenology-related traits across nine locations and over three years, along with accompanying latent variable phenotypes derived from a photothermal model and principal component analysis (PCA) of days from sowing to flower (DTF) data for a lentil diversity panel (324 accessions) which has also been genotyped with an exome capture array. Genomewide association studies (GWAS) on DTF across multiple environments helped confirm associations with known flowering time genes and identify new quantitative trait loci (QTL), which may contain previously unknown flowering time genes. Additionally, the use of latent variable phenotypes, which can incorporate environmental data such as temperature and photoperiod as both GWAS traits and as covariates, strengthened associations, revealed additional hidden associations, and alluded to potential roles of the associated QTL. Our approach can be replicated with other crop species, and the results from our GWAS serve as a resource for further exploration into the complex nature of phenology-related traits across the major growing environments for cultivated lentil.
Microscope Alignment Using Real-Time Imaging FCS
Authors: Aik Daniel Y. K. , Wohland Thorsten 
Published: March 2022

AbstractModern EMCCD and sCMOS cameras read out fluorescence data with single-molecule sensitivity at a rate of thousands of frames per second. Exploiting these capabilities in full requires data evaluation in real-time. The direct camera-read-out tool presented here allows access to the data while the camera is recording. This provides simplified and accurate alignment procedures for Total Internal Reflection and Light Sheet Fluorescence Microscopy (TIRFM, LSFM), and simplifies and accelerates fluorescence experiments. The tool handles a range of widely used EMCCD and sCMOS cameras and uses Imaging Fluorescence Correlation Spectroscopy (Imaging FCS) for its evaluation. It is easily extendable to other camera models and other techniques and is a base for automated TIRMF and LSFM data acquisition.SignificanceWe developed a direct camera readout (DCR) software tool that allows access to camera data during acquisition and provides real-time Imaging Fluorescence Correlation Spectroscopy (Imaging FCS) analysis. DCR displays live feedback and due to the sensitivity of correlation analysis provides a sensitive tool for microscope alignment using simple solutions of fluorescent particles. DCR is adaptable to different cameras and evaluation strategies, reduces alignment time, accelerates experiments, and can be used for automation.
Using Local Genetic Correlation Improves Polygenic Score Prediction Across Traits
Authors: Pain Oliver , Lewis Cathryn M. 
Published: March 2022

AbstractIntroductionThe predictive utility of polygenic scores (PGS) is steadily increasing as genome-wide association studies (GWAS) increase in sample size and diversity, and as PGS methodology is further developed. Multivariate PGS approaches incorporate GWAS results for secondary phenotypes which are genetically correlated with the target phenotype. These improve prediction over using PGS for only the target phenotype. However, previous methods have only considered the genome-wide estimates of SNP-based heritability (h2SNP) and genetic correlation (rg) between target and secondary phenotypes. In this study, we assess the impact of localh2SNPandrgwithin specific loci on cross-trait prediction.MethodsWe evaluate PGS using three target phenotypes (depression, intelligence, BMI) in the UK Biobank, with GWAS summary statistics matching the target phenotypes and 14 genetically correlated secondary phenotypes. PGS SNP-weights were derived using MegaPRS. Localh2SNPandrgwere estimated using LAVA. We then evaluated PGS after reweighting SNP-weights according to localh2SNPandrgestimates between the target and secondary phenotypes. Elastic net models containing PGS for multiple phenotypes were evaluated using nested 10-fold cross validation.ResultsModelling target and secondary PGS significantly improved target phenotype prediction over the target PGS alone, with relative improvements ranging from 0.8-12.2%. Furthermore, we show reweighting PGS by localh2SNPandrgestimates can enhance the predictive utility of PGS across phenotypes, with additional relative improvements of 0.2%-2.8%. Reweighting PGS by localh2SNPandrgimproved target phenotype prediction most when there was a mixture of positive and negative localrgestimates between target and secondary phenotypes.ConclusionModelling PGS for secondary phenotypes consistently improves prediction of target phenotypes, and this approach can be further enhanced by incorporating localh2SNPandrgestimates to highlight relevant genetic effects across phenotypes.
A critical role for heme synthesis and succinate in the regulation of pluripotent states transitions
Authors: Detraux Damien , Caruso Marino , Feller Louise , Fransolet Maude , Meurant Sébastien , Mathieu Julie , Arnould Thierry , Renard Patricia 
Published: March 2022

AbstractUsing embryonic stem cells (ESCs) in regenerative medicine or in disease modeling requires a complete understanding of these cells. Two main distinct developmental states of ESCs have been stabilized in vitro, a naïve pre-implantation stage and a primed post-implantation stage. Based on two recently published CRISPR-Cas9 knockout functional screens, we show here that the exit of the naïve state is impaired upon heme biosynthesis pathway blockade, linked to the incapacity to activate MAPK- and TGFβ-dependent signaling pathways. In addition, heme synthesis inhibition promotes the acquisition of 2 cell-like cells in a heme-independent manner caused by a mitochondrial succinate accumulation and leakage out of the cell. We further demonstrate that extra-cellular succinate acts as a paracrine/autocrine signal, able to trigger the 2C-like reprogramming through the activation of its plasma membrane receptor, SUCNR1. Overall, this study unveils a new mechanism underlying the maintenance of pluripotency under the control of heme synthesis.
Genetic mapping of APP and amyloid-β biology modulation by trisomy 21
Authors: Mumford Paige , Tosh Justin , Anderle Silvia , Wikberg Eleni Gkanatsiou , Lau Gloria , Noy Sue , Cleverley Karen , Saito Takashi , Saido Takaomi C , Yu Eugene Y. , Brinkmalm Gunnar , Portelius Erik , Blennow Kaj , Zetterberg Henrik , Tybulewicz Victor , Fisher Elizabeth M.C. , Wiseman Frances K. 
Published: March 2022

AbstractIndividuals who have Down syndrome frequently develop early onset Alzheimer’s disease, a neurodegenerative condition caused by the build-up of aggregated amyloid-β and tau proteins in the brain. Amyloid-β is produced by APP, a gene located on chromosome 21. People who have Down syndrome have three copies of chromosome 21 and thus also an additional copy of APP; this genetic change drives the early development of Alzheimer’s disease in these individuals. Here we use a combination of next-generation mouse models of Down syndrome (Tc1, Dp3Tyb, Dp(10)2Yey and Dp(17)3Yey) and a knockin mouse model of amyloid-β accumulation (AppNL-F) to determine how chromosome 21 genes other than APP modulate APP/amyloid-β in the brain when in three copies. We demonstrate that three copies of other chromosome 21 genes are sufficient to partially ameliorate amyloid-β accumulation in the brain. We go on to identify a subregion of chromosome 21 that contains the gene/genes causing this decrease in amyloid-β accumulation and investigate the role of two lead candidate genes Dyrk1a and Bace2. Thus an additional copy of chromosome 21 genes, other than APP, can modulate APP/amyloid-β in the brain under physiological conditions. This work provides critical mechanistic insight into the development of disease and an explanation for the typically later age of onset of dementia in people who have AD-DS compared to those who have familial AD caused by triplication of APP.
Insight into Polyproline II Helical Bundle Stability and Folding from NMR Spectroscopic Characterization of the Snow Flea Antifreeze Protein Denatured State
Authors: Treviño Miguel Á. , Moya María Redondo , Sánchez Rubén López , Pantoja-Uceda David , Mompeán Miguel , Laurents Douglas V. 
Published: March 2022

AbstractThe use of PPII helices in protein design is currently hindered by limitations in our understanding of their conformational stability and folding. Recent studies of the snow flea antifreeze protein (sfAFP), a useful model system composed of six PPII helices, suggested that a low denatured state entropy contributes to folding thermodynamics. To get atomic level information on the conformational ensemble and entropy of the reduced denatured state of sfAFP, we have analyzed its chemical shifts and {1H}-15N relaxation parameters by NMR spectroscopy at three experimental conditions. No significant populations of preferred secondary structure were detected. The stiffening of certain N-terminal residues at neutral versus acidic pH leads us to suggest that favorable charge-charge interactions could bias the conformational ensemble to favor the formation of the two disulfide bonds during nascent folding. Despite a high content of flexible glycine residues, the mobility of the sfAFP denatured ensemble is similar for denatured α/β proteins both on fast ps/ns as well as slower μs/ms timescales. These results are in line with a conformational entropy in the denatured ensemble resembling that of typical proteins and suggest that new structures based on PPII helical bundles should be amenable to protein design.
Mechanical stress driven by rigidity sensing governs epithelial stability
Authors: Sonam Surabhi , Balasubramaniam Lakshmi , Lin Shao-Zhen , Ivan Ying Ming Yow , Jaumà Irina Pi , Jebane Cecile , Karnat Marc , Toyama Yusuke , Marcq Philippe , Prost Jacques , Mège René-Marc , Rupprecht Jean-François , Ladoux Benoît 
Published: March 2022

AbstractEpithelia act as a barrier against environmental stress and abrasion and in vivo they are continuously exposed to environments of various mechanical properties. The impact of this environment on epithelial integrity remains elusive. By culturing epithelial cells on 2D hydrogels, we observe a loss of epithelial monolayer integrity through spontaneous hole formation when grown on soft substrates. Substrate stiffness triggers an unanticipated mechanical switch of epithelial monolayers from tensile on soft to compressive on stiff substrates. Through active nematic modelling, we find unique patterns of cell shape texture called nematic topological defects that underpin large isotropic stress fluctuations at certain locations thereby triggering mechanical failure of the monolayer and hole opening. Our results show that substrate stiffness provides feedback on monolayer mechanical state and that topological defects can trigger stochastic mechanical failure, with potential application towards a mechanistic understanding of compromised epithelial integrity in bacterial infection, tumor progression and morphogenesis.