bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recalibrating vision-for-action requires years after sight restoration from congenital blindness
Authors: Senna Irene , Piller Sophia , Ben-Zion Itay , Ernst Marc O. 
Published: April 2022

AbstractBeing able to perform goal-directed actions requires predictive, feed-forward control, including a mapping between the visually estimated target locations and the motor commands reaching for them. When the mapping is perturbed, e.g., due to muscle fatigue or optical distortions, we are quickly able to recalibrate the sensorimotor system to update this mapping. Here we investigated whether early visual and visuomotor experience is essential for developing the ability to recalibrate. To this end, we assessed young individuals deprived from vision due to dense congenital bilateral cataracts, who were surgically treated for sight restoration only years after birth. We compared their recalibration performance to such distortion to that of age-matched sighted controls. Their recalibration performance was impaired right after surgery. This finding cannot be explained by their still lower visual acuity, since blurring vision in controls to a matching degree did not lead to comparable behavior. Nevertheless, the recalibration ability of cataract-treated participants improved with experience, matching controls’ performance after around 2 years from surgery. Thus, the lack of early visual experience affects visuomotor recalibration. However, this ability is not lost but slowly develops after sight restoration, highlighting the importance of sensorimotor experience for brain plasticity late in life.
Beta-cell mass expansion during puberty involves serotonin signaling and determines glucose homeostasis in adulthood
Authors: Castell Anne-Laure , Ethier Mélanie , Fergusson Grace , Tremblay Caroline , Goubault Clara , Baltz Marie , Soglio Dorothée Dal , Ghislain Julien , Poitout Vincent 
Published: April 2022

ABSTRACTPuberty is associated with transient insulin resistance that normally recedes at the end of puberty; however, in overweight children insulin resistance persists leading to an increased risk of type 2 diabetes. The mechanisms whereby pancreatic β cells adapt to pubertal insulin resistance, and how they are affected by the metabolic status, have not been investigated. Here we show that puberty is associated with a transient increase in β-cell proliferation in rats and humans of both sexes. In rats, β-cell proliferation correlated with a rise in growth hormone (GH) levels. Serum from pubertal rats and humans promoted β-cell proliferation, suggesting the implication of a circulating factor. In pubertal rat islets, expression of genes of the GH/serotonin (5-HT) pathway underwent changes consistent with proliferative effect. Inhibition of the pro-proliferative 5-HT receptor isoform HTR2b blocked the increase in β-cell proliferation in pubertal islets ex vivo and in vivo. Peri-pubertal metabolic stress blunted β-cell proliferation during puberty and led to altered glucose homeostasis later in life. This study identifies a role of GH/GHR/5-HT/HTR2b signaling in the control of β-cell mass expansion during puberty and a mechanistic link between pubertal obesity and the risk of developing type 2 diabetes.
Markov chains improve the significance computation of overlapping genome annotations
Authors: Gafurov Askar , Brejová Broňa , Medvedev Paul 
Published: April 2022

AbstractMotivationGenome annotations are a common way to represent genomic features such as genes, regulatory elements or epigenetic modifications. The amount of overlap between two annotations is often used to ascertain if there is an underlying biological connection between them. In order to distinguish between true biological association and overlap by pure chance, a robust measure of significance is required. One common way to do this is to determine if the number of intervals in the reference annotation that intersect the query annotation is statistically significant. However, currently employed statistical frameworks are often either inefficient or inaccurate when computing p-values on the scale of the whole human genome.ResultsWe show that finding the p-values under the typically used “gold” null hypothesis is 𝒩𝒫-hard. This motivates us to reformulate the null hypothesis using Markov chains. To be able to measure the fidelity of our Markovian null hypothesis, we develop a fast direct sampling algorithm to estimate the p-value under the gold null hypothesis. We then present an open-source software tool MCDP that computes the p-values under the Markovian null hypothesis in 𝒪 (m2 + n) time and 𝒪 (m) memory, where m and n are the numbers of intervals in the reference and query annotations, respectively. Notably, MCDP runtime and memory usage are independent from the genome length, allowing it to outperform previous approaches in runtime and memory usage by orders of magnitude on human genome annotations, while maintaining the same level of accuracy.AvailabilityThe software is available at https://github.com/fmfi-compbio/mc-overlaps. All data for reproducibility are available at https://github.com/fmfi-compbio/mc-overlaps-reproducibility
A baseline for the genetic stock identification of Atlantic herring, Clupea harengus, in ICES Divisions 6.a, 7.b–c
Authors: Farrell Edward D. , Andersson Leif , Bekkevold Dorte , Campbell Neil , Carlsson Jens , Clarke Maurice W. , Egan Afra , Folkvord Arild , Gras Michaël , Lusseau Susan Mærsk , Mackinson Steven , Nolan Cormac , O’Connell Steven , O’Malley Michael , Pastoors Martin , Pettersson Mats E. , White Emma 
Published: April 2022

AbstractAtlantic herring in ICES Divisions 6.a, 7.b-c comprises at least three populations, distinguished by temporal and spatial differences in spawning, which have until recently been managed as two stocks defined by geographic delineators. Outside of spawning the populations form mixed aggregations, which are the subject of acoustic surveys. The inability to distinguish the populations has prevented the development of separate survey indices and separate stock assessments. A panel of 45 SNPs, derived from whole genome sequencing, were used to genotype 3,480 baseline spawning samples (2014-2021). A temporally stable baseline comprising 2,316 herring from populations known to inhabit Division 6.a was used to develop a genetic assignment method, with a self-assignment accuracy >90%. The long-term temporal stability of the assignment model was validated by assigning archive (2003-2004) baseline samples (270 individuals) with a high level of accuracy. Assignment of non-baseline samples (1,514 individuals) from Division 6.a, 7.b-c indicated previously unrecognised levels of mixing of populations outside of the spawning season. The genetic markers and assignment models presented constitute a ‘toolbox’ that can be used for the assignment of herring caught in mixed survey and commercial catches in Division 6.a into their population of origin with a high level of accuracy.
The phosphoproteome is a first responder in tiered cellular adaptation to chemical stress followed by proteomics and transcriptomics alteration
Authors: Chen Peiru , Li Yuan , Xu Feng , Zhang Zhenpeng , Zuo Tao , Guo Jiabin , Li Kaixuan , Liu Shu , Li Suzhen , Yin Jian , Chang Lei , Kukic Predrag , Liddell Mark , Tulum Liz , Carmichael Paul , Peng Shuangqing , Li Jin , Zhang Qiang , Xu Ping 
Published: April 2022

AbstractNext-generation risk assessment for environmental chemicals and ingredients in consumer products involves a weight of evidence (WoE) framework integrating a suite of new approach methodologies (NAMs) based on points of departure (PoD) obtained fromin vitroassays. Omics techniques provide broad coverages of the molecular toxicity pathway space. Transcriptomics assays especially play a leading role by providing relatively conservative PoDs in comparison with apical endpoints. However, it is unclear whether and how parameters measured using other omics technicquesparticipate in the cellular response to chemical perturbations, especially at exposure levels below the transcriptomically defined PoD. Multi-omics coverage may provide additional sensitive or confirmative biomarkers to complement and reduce the uncertainty in safety decisions made using targeted and transcriptomics assays. In the present study, we compared changes in transcriptomics, proteomics and phosphoproteomics with two prototype compounds, coumarin, as a main study and doxorubicin, as a complementary study to understand the sensitivity of the three omics techniques in response to chemically-induced changes in HepG2 and AC16 cells. With measurements obtained for multiple chemical concentrations and time points, we demonstrated that, compared with proteomics and transcriptomics, phosphoproteomics alterations occur not only earlier in time as expected, but also at much lower chemical concentrations and hence are proximal to the very early effects induced by chemical exposure. The phosphoproteomics changes appear to approach maximum when the transcriptomics alterations begin to be initiated. The results are consistent with a tiered framework of cellular response to chemical insults, where posttranslational modification of preexisting proteins is first seen before transcriptomics induction is engaged to launch a more energy-expensive defense that defines a useful PoD. We conclude that as the cost becomes more affordable, proteomics covering posttranslational modifications can be utilized to provide a more complete coverage of chemical-induced cellular alteration and supplement transcriptomics-based health safety decision making.
Acod1 negatively impacts osteoclastogenesis via GPR91-mediated NFATc1 activation
Authors: Gao Yue , Kraus Franziska V. , Seebach Elisabeth , Chakraborty Sushmita , Schaack Dominik , Schenz Judith , Wagner Willi , Kubatzky Katharina F. 
Published: April 2022

AbstractImmune cells undergo metabolic reprogramming upon exposure to inflammatory stimuli. The immuneresponsive gene 1 (Irg1) encodes aconitate decarboxylase (Acod1), an enzyme that generates itaconate from cis-aconitate in the TCA cycle and is one of the most highly induced genes in macrophages during inflammation. Itaconate inhibits succinate dehydrogenase activity leading to the accumulation of succinate. As the adjustment of energy metabolism also plays an important role during the formation of bone-resorbing osteoclasts, we investigated if Irg1 is regulated during osteoclastogenesis. We show that M-CSF/RANKL treatment induces Irg1 at an early time-point in bone marrow-derived macrophages (BMDM) as well as in the RAW264.7 macrophage cell line. Next, we stably overexpressed Acod1 in RAW264.7 cells. The metabolism of these Acod1 cells shifted towards glycolysis, as indicated by an increase in mTOR activation, subsequent 4EB-P1 phosphorylation and reduced ATP levels. When we investigated the ability of Acod1 cells to differentiate into osteoclasts, we observed a remarkable suppression of osteoclast-associated genes and the number of TRAP-positive, multi-nucleated osteoclasts was greatly reduced but not completely abrogated. Surprisingly, NFATc1 was detectable in nuclear extracts in untreated Acod1 cells leading to residual transcriptional NFAT activity in luciferase assays. This is caused by the elevated levels of succinate in Acod1 cells, as succinate can bind extracellularly to its cognate receptor GPR91 leading to Gq-mediated activation of NFATc1. When we investigated the expression of Gpr91, we found RANKL-mediated induction of Gpr91 to be severely reduced in Acod1 cells and we suggest that GPR91 is a target of RANKL-mediated NFATc1 activation. However, on the protein level, the receptor was still expressed at the cell surface. The observed repression of Gpr91 in Acod1 overexpressing cells was also detected by treatment with octyl-itaconate, showing that this is an itaconate-mediated effect. We hypothesize that the itaconate-mediated increase in succinate levels causes activation of NFATc1 signalling, although the transcriptional activity does not lead to osteoclastogenesis. In the presence of RANKL, these pre-activated cells are slow in switching to RANKL-mediated induction of osteoclast genes, which decreases their ability to differentiate into osteoclasts.
Unmasking hidden changes in intrinsic properties in neurons that coordinate oscillatory networks
Authors: Schneider Anna C. , Smarandache-Wellmann Carmen 
Published: April 2022

2.AbstractNeurons utilize gain control to efficiently encode shifting inputs with maximum sensitivity. While gain control is present in a multitude of neurons, research on the underlying mechanisms is still sparse. We focused on one coordinating neuron (ASCE) in the crayfish swimmeret system that is both necessary and sufficient to coordinate distributed motor circuits. This neuron encodes properties of the motor activity in its home ganglion and sends the information as burst of spikes to its anterior target ganglia. Previous research has shown that ASCE encodes the strength of the motor activity by its spike number, and that the range of the number of spikes per burst adapts to the average motor activity. In turn, the motor activity can be activated and modulated via cholinergic pathways.We explored ASCE’s response to changing levels of motor system excitation, which was induced with cholinergic agonists, both when the neuron was part of the full swimmeret system’s circuit and when it was isolated from the network. The cholinergic agonist carbachol directly depolarized ASCE’s membrane potential via nicotinic receptors when the neuron was isolated. In the intact circuit, ASCE’s membrane potential did not change but its input resistance decreased. This indicated an additional indirect action of carbachol, presumably via presynaptic central pattern generating neurons at the core of each motor circuit. The balance of direct and indirect effects could allow ASCE to match its spiking range to the system’s excitation level.1.Summary statementA balance of direct and indirect cholinergic effects precisely controls the membrane potential, and therefore the gain, of a neuron that is involved in the coordination of distributed motor circuits.
Population genomics unravels the Holocene history of Triticum-Aegilops species
Authors: Zhao Xuebo , Guo Yafei , Kang Lipeng , Bi Aoyue , Xu Daxing , Zhang Zhiliang , Zhang Jijin , Yang Xiaohan , Xu Jun , Xu Song , Song Xinyue , Zhang Ming , Li Yiwen , Kear Philip , Wang Jing , Yin Changbin , Liu Zhiyong , Fu Xiangdong , Lu Fei 
Published: April 2022

AbstractDeep knowledge of crop biodiversity is essential to improve global food security. Despite bread wheat serving as a keystone crop worldwide, the population history of bread wheat and its wild relatives (a.k.a. wheats) remains elusive. By analyzing whole-genome sequences of 795 wheats, we found that bread wheat originated southwest of the Caspian Sea ∼11,700 years ago and underwent a slow speciation process, lasting ∼3,300 years due to persistent gene flow from wild relatives. Soon after, bread wheat spread across Eurasia and reached Europe, South Asia, and East Asia ∼7,000 to ∼5,000 years ago, shaping a diversified but occasionally convergent adaptive landscape of bread wheat in novel environments. Opposite to cultivated wheat, wild wheat populations have declined by ∼82% in the past ∼2,000 years due to the food choice shift of humans, and likely continue to drop because of the changing climate. These findings will guide future efforts in protecting and utilizing wheat biodiversity to improve global food security.
Identification ofYAB11-NGAL1controlling leaf serrations through enhanced genome-wide association studies ofPopulus
Authors: Liu Peng , Bu Chenhao , Chen Panfei , Zhang Deqiang , Song Yuepeng 
Published: April 2022

AbstractLeaf margins are complex plant morphological features and contribute to the diversity of leaf shapes which effect on plant structure, yield and adaptation. Although several regulators of leaf margins have been identified, the genetic basis of natural variation therein has not been fully elucidated. We first profiled two distinct types (serration and smooth) of leaf morphology using the persistent homology mathematical framework (PHMF) in poplar. Combined genome-wide association studies (GWAS) and expression quantitative trait nucleotide (eQTN) mapping to create a module of leaf morphology controlling using data fromPopulus tomentosaandP. simoniiassociation population, respectively. Natural variation of leaf margins is associated with transcript abundances ofYABBY11(YAB11) in poplar. InP. tomentosa,PtoYAB11carries premature stop codon (PtoYAB11PSC) resulting in lost its positive regulation inPtoNGAL-1,PtoRBCL,PtoATPA,PtoATPE, andPtoPSBB. Overexpression ofPtoYAB11PSCserrated leaf margin, enlarged leaves, promoted photosynthesis and increased biomass. Overexpression ofPsiYAB11inP. tomentosacould rescue leaf margin serration and increase stomatal density and light damage repair ability. In poplar, YAB11-NGAL1is sensitive to environmental conditions and play positive regulator of leaf margin serration. It might be important regulator which bridge environment signaling to leaf morphological plasticity.
Hairy root transformation system as a tool for CRISPR/Cas9-directed genome editing in oilseed rape (Brassica napus)
Authors: Jedličková Veronika , Mácová Kateřina , Štefková Marie , Butula Jan , Staveníková Jana , Sedláček Marek , Robert Hélène S. 
Published: April 2022

AbstractOur study examined the mutation efficiency of the CRISPR/Cas9 method for tryptophan aminotransferase BnaTAA1 genes involved in the auxin biosynthesis pathway. We made nine CRISPR/Cas9 constructs with various promoters driving the expression of a Cas9 from Staphylococcus aureus (SaCas9) or a plant codon-optimized Streptococcus pyogenes Cas9 (pcoCas9). We developed a fast and efficient system for evaluating the variety and frequency of mutations caused by each construct using Brassica napus hairy roots. We showed that pcoCas9 is more efficient in mutating the targeted loci than SaCas9 and the presence of the NLS signal enhanced the chance of mutagenesis by 25%. The mutations were studied further in regenerated lines, and we determined the BnaTAA1 gene expression and heritability of the gene modifications in transgenic plants. Hairy root transformation combined with CRISPR/Cas9-mediated gene editing represents a fast and straightforward system for studying target gene function in the important oilseed crop Brassica napus.One-sentence summaryThe hairy root transformation system of Brassica napus generates stable transformants and is a tool for efficiently identifying CRISPR/Cas9-induced genome editing.
Mapping CAR T-cell design space using agent-based models
Authors: Prybutok Alexis N. , Yu Jessica S. , Leonard Joshua N. , Bagheri Neda 
Published: April 2022

AbstractChimeric antigen receptor (CAR) T-cell therapy shows promise for treating liquid cancers and increasingly for solid tumors as well. While potential design strategies exist to address translational challenges, including the lack of unique tumor antigens and the presence of an immunosuppressive tumor microenvironment, testing all possible design choicesin vitroandin vivois prohibitively expensive, time consuming, and laborious. To address this gap, we extended the modeling framework ARCADE (Agent-based Representation of Cells And Dynamic Environments) to include CAR T-cell agents (CAR T-cell ARCADE, or CARCADE). We conductedin silicoexperiments to investigate how clinically relevant design choices and inherent tumor features—CAR T-cell dose, CD4+:CD8+CAR T-cell ratio, CAR-antigen affinity, cancer and healthy cell antigen expression—individually and collectively impact treatment outcomes. Our analysis revealed that tuning CAR affinity modulates IL-2 production by balancing CAR T-cell proliferation and effector function. It also identified a novel multi-feature tuned treatment strategy for balancing selectivity and efficacy and provided insights into how spatial effects can impact relative treatment performance in different contexts. CARCADE facilitates deeper biological understanding of treatment design and could ultimately enable identification of promising treatment strategies to accelerate solid tumor CAR T-cell design-build-test cycles.
Spring haul-out behavior of seals in the Bering and Chukchi seas
Authors: London Josh M. , Conn Paul B. , Koslovsky Stacie M. , Richmond Erin L. , Ver Hoef Jay M. , Cameron Michael F. , Crawford Justin A. , Von Duyke Andrew L. , Quakenbush Lori , Boveng Peter L. 
Published: April 2022

ABSTRACTIce-associated seals rely on sea ice for a variety of activities, including pupping, breeding, molting, and resting. In the Arctic, many of these activities occur in spring (April – June) as sea ice begins to melt and retreat northward. Rapid acceleration of climate change in Arctic ecosystems is therefore of concern as the quantity and quality of suitable habitat is forecast to decrease. Improved estimates of seal population abundance are needed to properly monitor the impacts of these changes over time. In this paper, we use hourly percent-dry data from satellite-linked bio-loggers deployed between 2005 and 2021 to quantify the proportion of seals hauled out on ice. This information is needed to accurately estimate abundance from aerial survey counts of ice-associated seals (i.e., to correct for the proportion of animals that are in the water while surveys are conducted). In addition to providing essential data for survey ‘availability’ calculations, our analysis also provides insights into the seasonal timing and environmental factors affecting haul-out behavior by ice-associated seals. We specifically focused on bearded (Erignathus barbatus), ribbon (Histriophoca fasciata), and spotted seals (Phoca largha) in the Bering and Chukchi seas. Because ringed seals (Phoca (pusa) hispida) can be out of the water but hidden from view in snow lairs analysis of their ‘availability’ to surveys requires special consideration; therefore,they were not included in this analysis. Using generalized linear mixed pseudo-models to properly account for temporal autocorrelation, we fit models with covariates of interest (e.g., day-of-year, solar hour, age-sex class, wind speed, barometric pressure, temperature, precipitation) to examine their ability to explain variation in haul-out probability. We found evidence for strong diel and within-season patterns in haul-out behavior, as well as strong weather effects (particularly wind and temperature). In general, seals were more likely to haul out on ice in the middle of the day and when wind speed was low and temperatures were higher. Haul-out probability increased through March and April, peaking in May and early June before declining again. The timing and frequency of haul-out events also varied based on species and age-sex class. For ribbon and spotted seals, models with year effects were highly supported, indicating that the timing and magnitude of haul-out behavior varied among years. However, we did not find broad evidence that haul-out timing was linked to annual sea-ice extent. Our analysis emphasizes the importance of accounting for seasonal and temporal variation in haul-out behavior, as well as associated environmental covariates, when interpreting the number of seals counted in aerial surveys.