bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-omics map revealed PPARαactivation protecting against myocardial ischemia-reperfusion injury by maintaining cardiac metabolic homeostasis
Authors: Gao Yun , Huang Fei , Ruan Fanwei , Lai Dongwu , Zhang Zhe , Zhang Yuan , Zhu Jun , Lu Yuwen , Shen Liyin , He Jin , Liu Yan , Fu Guosheng , Zhu Yang , Shen Li , Zhuang Lenan 
Published: August 2023

ABSTRACTTimely percutaneous coronary intervention is the most effective initial therapy for the acute myocardial infarction (MI). However, the mechanism in energy metabolism underlying time-dependent coronary reperfusion remains largely unknown. Here, we generated an integrative map of cardiac cells using bulk and single-nucleus RNA-seq combined with metabolomics profiling of hearts with reperfusion at distinct time points post MI in rat. We found early time reperfusion (ETR), but not late time reperfusion (LTR) reduced myocardial injury by maintaining cardiac energy homeostasis. PPARα was identified as a key regulator for maintaining fatty acid metabolism after MI/R injury. Importantly, pretreatment with FDA-approved PPARα agonist, fenofibrate, improved the transcriptional signatures, and ameliorated the function of the MI/R injured hearts, particularly in the ETR. Together, our data not only deciphered the protective effect of ETR by maintaining cardiac energy homeostasis, but also provided insights into the translational potential of PPARα activation in alleviating MI/R injury.
CryptoCEN: A Co-Expression Network forCryptococcus neoformansreveals novel proteins involved in DNA damage repair
Authors: O’Meara Matthew J. , Rapala Jackson R. , Nichols Connie B. , Alexandre Christina , Billmyre R. Blake , Steenwyk Jacob L , Alspaugh J. Andrew , O’Meara Teresa R. 
Published: August 2023

ABSTRACTElucidating gene function is a major goal in biology, especially among non-model organisms. However, doing so is complicated by the fact that molecular conservation does not always mirror functional conservation, and that complex relationships among genes are responsible for encoding pathways and higher-order biological processes. Co-expression, a promising approach for predicting gene function, relies on the general principal that genes with similar expression patterns across multiple conditions will likely be involved in the same biological process. ForCryptococcus neoformans,a prevalent human fungal pathogen greatly diverged from model yeasts, approximately 60% of the predicted genes in the genome lack functional annotations. Here, we leveraged a large amount of publicly available transcriptomic data to generate aC. neoformansCo-Expression Network (CryptoCEN), successfully recapitulating known protein networks, predicting gene function, and enabling insights into the principles influencing co-expression. With 100% predictive accuracy, we used CryptoCEN to identify 13 new DNA damage response genes, underscoring the utility of guilt-by-association for determining gene function. Overall, co-expression is a powerful tool for uncovering gene function, and decreases the experimental tests needed to identify functions for currently under-annotated genes.
Temperate gut phages are prevalent, diverse, and predominantly inactive
Authors: Dahlman Sofia , Avellaneda-Franco Laura , Kett Ciaran , Subedi Dinesh , Young Remy B. , Gould Jodee A. , Rutten Emily L. , Gulliver Emily L. , Turkington Christopher J.R. , Nezam-Abadi Neda , Grasis Juris A. , Lyras Dena , Edwards Robert A. , Forster Samuel C. , Barr Jeremy J. 
Published: August 2023

AbstractLarge-scale metagenomic and data mining efforts have uncovered an expansive diversity of bacteriophages (phages) within the human gut1–3. These insights include broader phage populational dynamics such as temporal stability4, interindividual uniqueness5,6and potential associations to specific disease states7,8. However, the functional understanding of phage-host interactions and their impacts within this complex ecosystem have been limited due to a lack of cultured isolates for experimental validation. Here we characterise 125 active prophages originating from 252 diverse human gut bacterial isolates using seven different induction conditions to substantially expand the experimentally validated temperate phage-host pairs originating from the human gut. Importantly, only 17% of computationally predicted prophages were induced with common induction agents and these exhibited distinct gene patterns compared to non-induced predictions. Active Bacteroidota prophages were among the most prevalent members of the gut virome, with extensive use of diversity generating retroelements and exhibiting broad host ranges. Moreover, active polylysogeny was present in 52% of studied gut lysogens and led to coordinated prophage induction across diverse conditions. This study represents a substantial expansion of experimentally validated gut prophages, providing key insights into their diversity and genetics, including a genetic pathway for prophage domestication and demonstration that differential induction was complex and influenced by divergent prophage integration sites. More broadly, it highlights the importance of experimental validation alongside genomic based computational prediction to enable further functional understanding of these commensal viruses within the human gut.
Metabolism of glucose and trehalose by cyclic pentose phosphate pathway is essential for effective immune response inDrosophila
Authors: Kazek Michalina , Chodáková Lenka , Lehr Katharina , Strych Lukáš , Nedbalová Pavla , McMullen Ellen , Bajgar Adam , Šimek Petr , Moos Martin , Doležal Tomáš 
Published: August 2023

AbstractActivation of immune cells requires the remodeling of cell metabolism in order to support immune function. We study these metabolic changes through the infection ofDrosophilalarvae by parasitoid wasp. Neutralization of the parasitoid egg involves the differentiation of lamellocytes, which encapsulate the egg. A melanization cascade is initiated, producing toxic molecules to destroy the egg; meanwhile the capsule created also protects the host from the toxic reaction. We combine transcriptomics and metabolomics, including 13C-labeled glucose and trehalose tracing, as well as genetic manipulation of sugar metabolism to study changes in metabolism, specifically inDrosophilahemocytes. We found that hemocytes increase the expression of several carbohydrate transporters, and accordingly uptake of sugar during infection. These carbohydrates are metabolized by increased glycolysis, associated with lactate production, and cyclic pentose phosphate pathway (PPP), in which glucose-6-phosphate is re-oxidized to maximize NADPH production. Oxidative PPP is required for lamellocyte differentiation and resistance, as is systemic trehalose metabolism. In addition, fully differentiated lamellocytes use a cytoplasmic form of trehalase to cleave trehalose to glucose, within the cell, to fuel cyclic PPP. Intracellular trehalose metabolism is not required for resistance, but may be associated with host protection from its own toxic response. Thus, our results suggest that sugar metabolism within immune cells, and specifically in cyclic PPP, may be important for not only fighting infection, but also for protecting the host from its own immune response and ensuring sufficient fitness of the survivor.
Biocompatible hydrogel electrodeposition enables the simultaneous preparation of multi-microinterfaces for ligand bioconjugation and multiplexed electrochemical detection
Authors: Juska Vuslat B. , Moukri Nadia , Estrela Pedro , Maxwell Graeme D. , Hendriks Stacey , Santillan-Urquiza Esmeralda , O’Brien Bernadette , Patella Bernardo , Inguanta Rosalinda , O’Riordan Alan 
Published: August 2023

AbstractAffinity based electrochemical biosensing systems with integrated miniaturised interfaces has enabled key advancement toward rapid, sensitive, precise and deployable detection platforms. Manufacturing silicon micro/nano devices for biology interface has been a highly promising platform to design and develop electrochemical sensors for the detection of very low concentrations of the target molecules. However, the biofouling challenge of the biosensors when the surface is exposed to a complex matrix such as blood, serum, milk, has been a road blocker. Here we introduce a simple, rapid formation of an anti-biofouling coating onto several electroactive surface areas present on a single chip simultaneously. Using such a multiplexed surface, we were able to investigate the optimum working conditions on-chip. Concentrating on two individual bioassay platforms for stress biomarkers, haptoglobin and cortisol, we demonstrate the broad applicability of the developed universal platform with excellent performance in bovine serum and correlation with conventional ELISA using milk samples.
Calcium regulation of theArabidopsisNa+/K+transporter HKT1;1 improves seed germination under salt stress
Authors: Chandran Ancy E.J. , Finkler Aliza , Hait Tom Aharon , Kiere Yvonne , David Sivan , Pasmanik-Chor Metsada , Shkolnik Doron 
Published: August 2023

ABSTRACTCalcium is known to improve seed-germination rates under salt stress. We investigated the involvement of calcium ions (Ca2+) in regulatingHIGH-AFFINITY K+TRANSPORTER 1(HKT1;1), which encodes a Na+/K+transporter, and its post-translational regulatorTYPE 2C PROTEIN PHOSPHATASE 49(PP2C49), in germinatingArabidopsis thalianaseedlings. Germination rates ofhkt1mutant seeds under salt stress remained unchanged by CaCl2treatment in wild-typeArabidopsis, whereaspp2c49mutant seeds displayed improved salt-stress tolerance in the absence of CaCl2supplementation. Analysis ofHKT1;1andPP2C49promoter activity revealed that CaCl2treatment results in radicle-focused expression ofHKT1;1and reduction of the native radicle-exclusive expression ofPP2C49. Ion-content analysis indicated that CaCl2treatment improves K+retention in germinating wild-type seedlings under salt stress, but not inhkt1seedlings. Transgenic seedlings designed to exclusively expressHKT1;1in the radicle during germination displayed higher germination rates under salt stress than the wild type in the absence of CaCl2treatment. Transcriptome analysis of germinating seedlings treated with CaCl2, NaCl, or both revealed 118 upregulated and 94 downregulated genes as responsive to the combined treatment. Bioinformatics analysis of the upstream sequences of CaCl2–NaCl-treatment-responsive upregulated genes revealed the abscisic acid response element CACGTGTC, a potential CaM-binding transcription activator-binding motif, as most prominent. Our findings suggest a key role for Ca2+in mediating salt-stress responses during germination by regulating genes that function to maintain Na+and K+homeostasis, which is vital for seed germination under salt stress.
A model of sediment retention by vegetation for Great Britain: new methodologies & validation
Authors: Hooftman Danny A.P. , Bullock James M. , Evans Paul M. , Redhead John W. , Ridding Lucy E. , Varma Varun , Pywell Richard F. 
Published: August 2023

AbstractSoil erosion is an substantial environmental concern worldwide. It has been historically and is of increasingly concern currently. Next to natural processes, over 2 million hectares of soil are at risk of erosion through intensifying agriculture in the Great Britain (England, Wales, Scotland and their territorial islands). Predictive soil erosion models, in the form of Ecosystem Service tools, aid in helping to identify areas that are vulnerable to soil erosion. Yet, no predictions for erosion or sediment retention by vegetation based on local data have been developed for Great Britain or the United Kingdom as a whole.Here we develop an erosion retention model using the InVEST platform, which is based on the RUSLE mathematical framework. We parameterise the model, as far as feasible, with GB specific input data. The developed model estimations are validated against suspended solids concentrations (sediments) in throughout England and Wales.Next to presenting the first GB wide estimate of erosion and erosion retention using the InVEST SDR module, we test three approaches here that differ from more widely applicable RUSLE model inputs, such as created for Europe as a whole. Here, we incorporate (1) periodicity to allow erosion to potentially fluctuate within years; (2) GB-specific cover periodic management factors estimates, including a range of crop types, based on observed satellite NDVI values (3) soil erosivity under heavy rainfall following GB estimates for 2000-2019.We conclude that both the GB created erosivity layer as the added periodicity do not seem to be provide substantial improvement over non-periodic estimated created with more widely available data, when validated against this set of suspended solids in rivers. In contrast, the observed cover management factors calculated from NDVI are a good improvement affecting the ranking order among catchments. Therefore, the generating of cover management factors using NDVI data could be promoted as method for InVEST SDR model development and in more general for developing RUSLE-based erosion estimates worldwide.
Reward contingency modulates olfactory bulb output via pathway-dependent peri-somatic inhibition
Authors: Lindeman Sander , Fu Xiaochen , Reinert Janine K , Fukunaga Izumi 
Published: August 2023

AbstractAssociating values to environmental cues is a critical aspect of learning from experiences, allowing animals to predict and maximise future rewards. Value-related signals in the brain were once considered a property of higher sensory regions, but its wide distribution across many brain regions is increasingly recognised. Here, we investigate how reward-related signals begin to be incorporated, mechanistically, at the earliest stage of olfactory processing, namely, in the olfactory bulb. In head-fixed mice performing Go/No-Go discrimination of closely related olfactory mixtures, rewarded odours evoke widespread inhibition in one class of output neurons, that is, in mitral cells but not tufted cells. The temporal characteristics of this reward-related inhibition suggest it is odour-driven, but it is also context-dependent since it is absent during pseudo-conditioning and pharmacological silencing of the piriform cortex. Further, the reward-related modulation is present in the somata but not in the apical dendritic tuft of mitral cells, suggesting an involvement of circuit component located deep in the olfactory bulb. Depth-resolved imaging from granule cell dendritic gemmules suggests that granule cells that target mitral cells receive a reward-related extrinsic drive. Our results support the notion that value-related modulation appears at the early stages of sensory processing and provide constraints on long-range and local circuit mechanisms.
Loss of Carnitine Palmitoyltransferase 1a Reduces Docosahexaenoic Acid-Containing Phospholipids and Drives Sexually Dimorphic Liver Disease in Mice
Authors: Zelows Mikala M. , Cady Corissa , Dharanipragada Nikitha , Mead Anna E. , Kipp Zachary A. , Bates Evelyn A. , Varadharajan Venkateshwari , Banerjee Rakhee , Park Se-Hyung , Shelman Nathan R. , Clarke Harrison A. , Hawkinson Tara R. , Medina Terrymar , Sun Ramon C. , Lydic Todd A. , Hinds Terry D. , Brown J. Mark , Softic Samir , Graf Gregory A. , Helsley Robert N. 
Published: August 2023

ABSTRACTBackground and AimsGenome and epigenome wide association studies identified variants in carnitine palmitoyltransferase 1a (CPT1a) that associate with lipid traits. The goal of this study was to determine the impact by which liver-specific CPT1a deletion impacts hepatic lipid metabolism.Approach and ResultsSix-to-eight-week old male and female liver-specific knockout (LKO) and littermate controls were placed on a low-fat or high-fat diet (HFD; 60% kcal fat) for 15 weeks. Mice were necropsied after a 16 hour fast, and tissues were collected for lipidomics, matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI), kinome analysis, RNA-sequencing, and protein expression by immunoblotting. Female LKO mice had increased serum alanine aminotransferase (ALT) levels which were associated with greater deposition of hepatic lipids, while male mice were not affected by CPT1a deletion relative to male control mice. Mice with CPT1a deletion had reductions in DHA-containing phospholipids at the expense of monounsaturated fatty acids (MUFA)-containing phospholipids in both whole liver and at the level of the lipid droplet (LD). Male and female LKO mice increased RNA levels of genes involved in LD lipolysis (Plin2,Cidec,G0S2) and in polyunsaturated fatty acid (PUFA) metabolism (Elovl5, Fads1, Elovl2), while only female LKO mice increased genes involved in inflammation (Ly6d, Mmp12, Cxcl2). Kinase profiling showed decreased protein kinase A (PKA) activity, which coincided with increased PLIN2, PLIN5, and G0S2 protein levels and decreased triglyceride hydrolysis in LKO mice.ConclusionsLiver-specific deletion of CPT1a promotes sexually dimorphic steatotic liver disease (SLD) in mice, and here we have identified new mechanisms by which females are protected from HFD-induced liver injury.Graphical Summary
Spider mites collectively avoid plants with cadmium irrespective of their frequency or the presence of competitors
Authors: Godinho Diogo Prino , Fragata Inês , de la Masselière Maud Charlery , Magalhães Sara 
Published: August 2023

AbstractAccumulation of heavy metals by plants can serve as a defence against herbivory. Herbivores, in turn, may avoid feeding on contaminated tissues. Such avoidance, however, may hinge upon the specific conditions faced by herbivores. Here, we tested whether the spider miteTetranychus urticaeavoids tomato plants contaminated with cadmium in presence of conspecifics or heterospecifics and depending on the frequency of contaminated plants. We show that individual spider mite females do not preferentially move to leaf tissues with or without cadmium, despite clear costs on their performance. However, in a set-up where 200 mites were simultaneously given the choice between four plants with or without cadmium, they collectively avoided plants with cadmium, irrespective of the proportion of plants with cadmium. In addition,T. urticaedid not discriminate between plants infested with its competitorT. evansiand other uncontaminated plants but they preferred plants with competitors when the other plants contained cadmium. Our results show that aggregation may facilitate avoidance of contaminated plants. They also indicate that cadmium accumulation in plants is a stronger selective pressure than interspecific competition withT. evansi.Therefore, collective avoidance of metal-accumulating plants by herbivores is robust to environmental conditions and may have important consequences for species distribution and interactions in metal contaminated sites.
Reinforcement motor learning after cerebellar damage is related to state estimation
Authors: White Christopher M. , Snow Evan C. , Therrien Amanda S. 
Published: August 2023

ABSTRACTRecent work showed that individuals with cerebellar degeneration could leverage intact reinforcement learning (RL) to alter their movement. However, there was marked inter-individual variability in learning, and the factors underlying it were unclear. Cerebellum-dependent sensory prediction may contribute to RL in motor contexts by enhancing body state estimates, which are necessary to solve the credit-assignment problem. The objective of this study was to test the relationship between the predictive component of state estimation and RL in individuals with cerebellar degeneration. Individuals with cerebellar degeneration and neurotypical control participants completed two tasks: an RL task that required them to alter the angle of reaching movements and a state estimation task that tested the somatosensory perception of active and passive movement. The state estimation task permitted calculation of the active benefit shown by each participant, which is thought to reflect the cerebellum-dependent predictive component of state estimation. We found that the cerebellar and control groups showed similar magnitudes of learning with reinforcement and active benefit on average, but there was substantial variability across individuals. Using multiple regression, we assessed potential predictors of RL. Our analysis included active benefit, somatosensory acuity, clinical ataxia severity, movement variability, movement speed, and age. We found a significant relationship in which greater active benefit predicted better learning with reinforcement in the cerebellar, but not the control group. No other variables showed significant relationships with learning. Overall, our results support the hypothesis that the integrity of sensory prediction is a strong predictor of RL after cerebellar damage.
Soft extracellular matrix drives an endoplasmic reticulum stress-dependent S quiescence underlying molecular traits of pulmonary basal cells
Authors: Laval Pierre-Alexandre , Piecyk Marie , Le Guen Pauli , Ilie Mirela-Diana , Fauvre Joelle , Coste Isabelle , Renno Toufic , Aznar Nicolas , Hadji Celine , Migdal Camille , Duret Cedric , Bertolino Philippe , Ferraro-Peyret Carole , Nicolas Alice , Chaveroux Cedric 
Published: August 2023

AbstractCell culture on soft matrix, either in 2D and 3D, preserves the characteristics of progenitors. However, the mechanism by which the mechanical microenvironment determines progenitor phenotype, and its relevance to human biology, remains poorly described. Here we designed multi-well hydrogel plates with a high degree of physico-chemical uniformity to reliably address the molecular mechanism underlying cell state modification driven by physiological stiffness. Cell cycle, differentiation and metabolic activity could be studied in parallel assays, showing that the soft environment promotes an atypical S-phase quiescence and prevents cell drift, while preserving the differentiation capacities of human bronchoepithelial cells. These softness-sensitive responses are driven by defects in proteostasis and enhanced basal endoplasmic reticulum stress. The analysis of available single cell data of the human lung also showed that this non-conventional state coming from the soft extracellular environment is indeed consistent with molecular feature of pulmonary basal cells. Overall, this study demonstrates that mechanical mimicry in 2D culture supports allows to maintain progenitor cells in a state of high physiological relevance for characterizing novel molecular events that govern progenitor biology in human tissues.
SPTF-3/SP1 orchestrates mitochondrial biogenesis upon ribosomal stress and acute starvation
Authors: Hemerling Johannes CW , Pavlenko Victor , Herholz Marija , Baumann Linda , Zečić Aleksandra , Kukat Alexandra , Popovic Milica , Szczepanowska Karolina , Cores Estela Cepeda , Vilchez David , Kurian Leo , Trifunovic Aleksandra 
Published: August 2023

AbstractWhen cells have increased energy demand, they respond by elevating the production of new mitochondria through the process of mitochondrial biogenesis. This complex physiological undertaking requires precise coordination of mitochondrial and nuclear gene expression to extend the existing mitochondrial network in the cell. Using C. elegans as a model system we have identified stress-induced transcription factor SPTF-3 as a novel regulator of mitochondrial biogenesis on-demand upon increased heat stress, dietary restriction, and acute starvation. We show that SPTF-3 also regulates ATFS-1, the main transcriptional regulator of UPRmt(mitochondrial unfolded protein response). Thus, by orchestrating two parallel programs – mitochondrial biogenesis and UPRmt, SPTF-3 safeguards mitochondrial wellbeing and function upon stress, thus allowing survival in unfavorable conditions. Mitochondrial biogenesis is induced by disturbances in cytoplasmic ribosomal assembly, which leads to preferential translation of SPTF-3. Importantly, we demonstrated that the role of SPTF-3 in the regulation of mitochondrial biogenesis upon nutrient deprivation is conserved in mammals through its homolog SP1.