bluuebunny/crossref_metadata_2025_split huggingface dataset:
C. elegansLIN-66 mediates EIF-3.G-dependent protein translation via a cold-shock domain
Authors: Blazie Stephen M. , Fortunati Daniel , Zhao Yan , Jin Yishi 
Published: February 2024

SummaryProtein translation initiation is a complex and conserved process involving many proteins acting in concert. The eukaryotic initiation factor 3 (eIF3) complex is essential for the assembly of the pre-initiation complex that scans and positions mRNA at the initiation codon. eIF3 complex consists of 13 subunits. In addition to their essential roles in general translation initiation, emerging studies suggest that individual subunits of eIF3 can provide specialized functions in response to specific stimuli. We have previously reported that a gain-of-function (gf) mutation in the G subunit ofC. eleganseIF3 complex,eif-3.g(gf),selectively modulates protein translation in the ventral cord cholinergic motor neurons. Here, through unbiased genetic suppressor screening, we have identified thelin-66gene that mediates theeif-3.g(gf)-dependent protein translation in the motor neurons. LIN-66 is previously reported to be a nematode-specific protein composed of largely low complexity amino acid sequences with unknown functional domains. We combined bioinformatic analysis within vivofunctional dissection and identified a cold-shock domain in LIN-66 to be critical for its function. In the cholinergic motor neurons, LIN-66 shows somatic cytoplasmic localization and close association with EIF-3.G. The low complexity amino acid sequences of LIN-66 modulate its subcellular pattern. Cold-shock-domains are known to interact with RNA and have broad functions in RNA metabolism and protein translation. We propose that LIN-66 mediates stimuli-dependent protein translation by facilitating the interaction of mRNAs with EIF-3.G.
Effects of time-dependent ATP consumption caused by neuron firing on ATP concentrations in synaptic boutons containing and lacking a stationary mitochondrion
Authors: Kuznetsov Andrey V. 
Published: February 2024

AbstractThe precise mechanism behind the absence of a stationary mitochondrion in approximately half of presynaptic release sites in axons, and how these sites lacking a stationary mitochondrion receive ATP, is not fully understood. This paper presents a mathematical model designed to simulate the transient ATP concentration in presynapticen passantboutons. The model is utilized to investigate how the ATP concentration responds to increased ATP demand during neuronal firing in boutons with a stationary mitochondrion and those without one. The analysis suggests that neuron firing may cause oscillations in the ATP concentrations, with peak-to-peak amplitudes ranging from 0.06% to 5% of their average values. However, this does not deplete boutons lacking a mitochondrion of ATP; for physiologically relevant values of model parameters, their concentration remains approximately 3.75 times higher than the minimum concentration required for synaptic activity. The variance in average ATP concentrations between boutons containing a stationary mitochondrion and those lacking one ranges from 0.3% to 0.8%, contingent on the distance between the boutons. The model indicates that diffusion-driven ATP transport is rapid enough to adequately supply ATP molecules to boutons lacking a stationary mitochondrion.
Streptococcus pneumoniaeaugments circadian clock gene expression in zebrafish cells
Authors: Fénero Camila Morales , Sacksteder Raina E. , Kimmey Jacqueline M. 
Published: February 2024

AbstractThe circadian clock is a highly coordinated, cell-autonomous process that regulates the daily internal rhythms of biological organisms. Circadian clocks have been identified in various organisms, including mammals, invertebrates, cyanobacteria, and plants. The zebrafish (Danio rerio) is a practical model for studying the vertebrate circadian clock due to its small size, ease of manipulation, gene tractability, and direct light responsiveness. Several studies have revealed that bacterial, viral, and parasitic infections can impact the expression of circadian genes in mammals. While some evidence suggests that this may also be the case in zebrafish, no studies have investigated the direct effects of bacterial exposure on the zebrafish clock. Here, using zebrafish Z3 cells, we show that exposure to heat-killedStreptococcus pneumoniae(HK-Spn) can augment the expression of core repressive factors, includingper1b, per2, per3,andcry1a. Further investigation demonstrated that HK-Spn induces the production of reactive oxygen species (ROS) in Z3 cells and that the addition of NAC, a ROS antioxidant, blocks Spn-mediated induction ofper2,cry1a, andper3. Additionally, HK-Spn augmented the expression oftefaandtefb,an effect NAC suppressed. These results suggest the involvement of a ROS-dependent pathway in the augmentation ofper2,cry1a, and per3by HK-Spn. Moreover, the activation oftefaandtefbby HK-Spn represents promising new targets for further investigation of the regulation of these genes.
Testing the evolutionary potential of an alpine plant: Phenotypic plasticity in response to growth temperature far outweighs parental environmental effects and other genetic causes of variation
Authors: Arnold Pieter A. , Wang Shuo , Notarnicola Rocco F. , Nicotra Adrienne B. , Kruuk Loeske E. B. 
Published: February 2024

AbstractPhenotypic plasticity and rapid evolution are fundamental processes by which organisms can maintain their function and fitness in the face of environmental changes. Here we quantified the plasticity and evolutionary potential of an alpine herbWahlenbergia ceracea. Utilising its mixed-mating system, we generated outcrossed and self-pollinated families that were grown in either cool or warm environments, and that had parents that had also been grown in either cool or warm environments. We then analysed the contribution of environmental and genetic factors to variation in a range of phenotypic traits including phenology, leaf mass per area, photosynthetic function, thermal tolerance, and reproductive fitness. The strongest effect was that of current growth temperature, indicating strong phenotypic plasticity. All traits except thermal tolerance were plastic, whereby warm-grown plants flowered earlier, grew larger, produced more reproductive stems compared to cool-grown plants. Flowering onset and biomass were heritable and under selection, with early flowering and larger plants having higher relative fitness. There was little evidence for transgenerational plasticity, maternal effects, or genotype-by-environment interactions. Inbreeding delayed flowering and reduced reproductive fitness and biomass. Overall, we found thatW. ceraceahas the capacity to respond rapidly to climate warming via plasticity, and the potential for evolutionary change.HighlightWe found strong plasticity to growth environment in many phenotypic traits, but little effect of parental environment, revealing capacity to respond rapidly to climate warming, and potential for evolutionary change.
Augmentation of DNA exonuclease TREX1 in macrophages as a therapy for cardiac ischemic injury
Authors: Ibrahim Ahmed Gamal-Eldin , Ciullo Alessandra , Miyamoto Kazutaka , Liao Ke , Jones Xaviar M. , Yamaguchi Shukuro , Li Chang , Rannou Alice , Nawaz Asma , Morris Ashley , Tsi Kara , Marbán Cristina H. , Lee Jamie , Manriquez Nancy , Hong Yeojin , Kumar Arati Naveen , Dawkins James F. , Rogers Russell G. , Marbán Eduardo 
Published: February 2024

AbstractNoncoding RNAs (ncRNAs) are increasingly recognized as bioactive. Here we report the development of TY1, a synthetic ncRNA bioinspired by a naturally-occurring human small Y RNA with immunomodulatory properties. TY1 upregulates TREX1, an exonuclease that rapidly degrades cytosolic DNA. In preclinical models of myocardial infarction (MI) induced by ischemia/reperfusion, TY1 reduced scar size. The cardioprotective effect of TY1 was abrogated by prior depletion of macrophages and mimicked by adoptive transfer of macrophages exposed either to TY1 or TREX1. Inhibition of TREX1 in macrophages blocked TY1 cardioprotection. Consistent with a central role for TREX1, TY1 attenuated DNA damage in the post-MI heart. This novel mechanism—pharmacologic upregulation of TREX1 in macrophages—establishes TY1 as the prototype for a new class of ncRNA drugs with disease-modifying bioactivity.One Sentence SummaryUpregulation of three prime exonuclease, TREX1, in macrophages enhances tissue repair post myocardial infarction.
Sarcomeric SRX:DRX Equilibrium in Alport and LDLR/P407 Mouse Models of HFpEF
Authors: Kamiar Ali , Williams Monique , Capcha Jose M. , Kazmierczak Katarzyna , Liang Jingsheng , Lopaschuk Gary D. , Webster Keith A , Szczesna-Cordary Danuta , Shehadeh Lina A 
Published: February 2024

AbstractCardiac myosin energetic states that regulate heart contractility define interactions of myosin cross-bridges with actin-containing thin filaments have been functionally linked with the pathology of hypertrophic cardiomyopathy (HCM). In particular, the balance between the disordered relaxed (DRX) and super relaxed (SRX) states that correlate respectively with enhanced force and energy conservation significantly determine myocardial performance and energy utilization. Compelling evidence suggests that a balanced SRX and DRX states proportion is a prerequisite for long-term cardiac health. Whereas roles for altered SRX: DRX proportions in HCM have been studied in depth, the mechanics of sarcomeric dysfunction and SRX: DRX proportions have not been reported in models of acquired heart failure (HF) including HF with preserved ejection fraction (HFpEF). Here, we quantified SRX andDRX myosin populations in two mouse models of HFpEF, including Alport and LDLR/P407 mice that represent cardiorenal/hypertensive and cardiometabolic/hyperlipidemic mouse models of HFpEF, respectively. We report significant changes in the SRX:DRX in both HFpEF mouse models, with an increased DRX state associated with Alport mice and a stabilized SRX state associated with LDLR/P407 mice. These findings correlate respectively with the hypercontractility and metabolic dysregulation with bradycardia phenotypes.
Peptide Amphiphiles Hitchhike on Endogenous Biomolecules for Enhanced Cancer Imaging and Therapy
Authors: Fischer Jared M. , Stewart Morgan , Dai Mingchong , Drennan Samuel , Holland Samantha , Quentel Arnaud , Sabuncu Sinan , Kingston Benjamin R. , Dengos Isabel , Xiang Li , Bonic Karla , Goncalves Florian , Yi Xin , Ranganathan Srivathsan , Branchaud Bruce P. , Muldoon Leslie L. , Barajas Ramon F. , Yildirim Adem 
Published: February 2024

AbstractThe interactions of nanomaterials with biomolecules in vivo determine their biological fate. Here, we show that a self-assembled peptide amphiphile nanostructure (namely SA-E) dynamically interacts with endogenous biomolecules and takes advantage of naturally occurring processes to target a broad range of solid tumors. Upon in vivo administration, self-assembled nanostructures of SA-E disassemble and reassemble with lipoproteins in circulation. Hitchhiking on lipoproteins prolongs the blood circulation of SA-E and allows it to cross endothelial barriers through transcytosis. At the tumor site, SA-E internalizes into cancer cells by mainly interacting with lipid-raft domains on cell membranes. By exploiting these endogenous interactions, SA-E demonstrated high tumor accumulation with extended retention in various xenograft, syngeneic, patient-derived xenograft, or transgenic mouse and rat models. In addition, SA-E enabled the effective delivery of highly potent chemotherapy to breast and glioma tumors with reduced side effects. With its simple and modular design and universal tumor accumulation mechanism, SA-E represents a promising platform for broad applications in cancer imaging and therapy.
Plant Root Expansion Microscopy (ROOT-ExM): A streamlined super resolution method for plants
Authors: Grison Magali S. , Maucort Guillaume , Dumazel Amandine , Champelovier Dorian , Boutté Yohann , Fernández-Monreal Mónica , Bayer Emmanuelle M. 
Published: February 2024

AbstractExpansion microscopy (ExM) has revolutionized biological imaging by physically enlarging samples, surpassing the light diffraction limit and enabling nanoscale visualization using standard microscopes. While extensively employed across a wide range of biological samples, its application to plant tissues is sparse. In this work, we present ROOT-ExM, an expansion method suited for stiff and intricate multicellular plant tissues, focusing on the primary root of Arabidopsis thaliana. ROOT-ExM achieves isotropic expansion with a fourfold increase in resolution, enabling super-resolution microscopy comparable to STimulated Emission Depletion (STED) microscopy. Labelling is achieved through immunolocalization, compartment-specific dyes, and native fluorescence preservation, while N-Hydroxysuccinimide (NHS) ester-dye conjugates reveal the ultrastructural context of cells alongside specific labelling. We successfully applied ROOT-ExM to image various cellular structures, including the Golgi apparatus, the endoplasmic reticulum, the cytoskeleton, and wall-embedded structures such as plasmodesmata. When combined with lattice light sheet microscopy (LLSM), ROOT-ExM achieves 3D quantitative analysis of nanoscale cellular process, revealing increased vesicular fusion in close proximity of the cell plate during cell division. Achieving super-resolution fluorescence imaging in plant biology remains a formidable challenge. Our findings underscore that ROOT-ExM provides a remarkable, cost-effective solution to this challenge, paving the way for unprecedented insights into plant cellular subcellular architecture.One sentence summaryROOT-ExM achieves super-resolution expansion microscopy in plants
Epigenetic regulation by TET1 in gene-environmental interactions influencing susceptibility to congenital malformations
Authors: van der Veer Bernard K. , Chen Lehua , Tsaniras Spyridon Champeris , Brangers Wannes , Chen Qiuying , Schroiff Mariana , Custers Colin , Kwak Harm H.M. , Khoueiry Rita , Cabrera Robert , Gross Steven S. , Finnell Richard H. , Lei Yunping , Koh Kian Peng 
Published: February 2024

AbstractThe etiology of neural tube defects (NTDs) involves complex gene-environmental interactions. Folic acid (FA) prevents NTDs, but the mechanisms remain poorly understood and at least 30% of human NTDs resist the beneficial effects of FA supplementation. Here, we identify the DNA demethylase TET1 as a nexus of folate-dependent one-carbon metabolism and genetic risk factors post-neural tube closure. We determine that cranial NTDs inTet1-/-embryos occur at two to three times higher penetrance in genetically heterogeneous than in homogeneous genetic backgrounds, suggesting a strong impact of genetic modifiers on phenotypic expression. Quantitative trait locus mapping identified a strong NTD risk locus in the 129S6 strain, which harbors missense and modifier variants at genes implicated in intracellular endocytic trafficking and developmental signaling. NTDs acrossTet1-/-strains are resistant to FA supplementation. However, both excess and depleted maternal FA diets modify the impact ofTet1loss on offspring DNA methylation primarily at neurodevelopmental loci. FA deficiency reveals susceptibility to NTD and other structural brain defects due to haploinsufficiency ofTet1. In contrast, excess FA inTet1-/-embryos drives promoter DNA hypermethylation and reduced expression of multiple membrane solute transporters, including a FA transporter, accompanied by loss of phospholipid metabolites. Overall, our study unravels interactions between modified maternal FA status,Tet1gene dosage and genetic backgrounds that impact neurotransmitter functions, cellular methylation and individual susceptibilities to congenital malformations, further implicating that epigenetic dysregulation may underlie NTDs resistant to FA supplementation.
Contracted Functional Connectivity Profiles in Autism
Authors: Weber Clara F. , Kebets Valeria , Benkarim Oualid , Lariviere Sara , Wang Yezhou , Ngo Alexander , Jiang Hongxiu , Chai Xiaoqian , Park Bo-yong , Milham Michael P. , Di Martino Adriana , Valk Sofie , Hong Seok-Jun , Bernhardt Boris C. 
Published: February 2024

ABSTRACTObjectiveAutism spectrum disorder (ASD) is a pervasive neurodevelopmental condition that is associated with atypical brain network organization, with prior work suggesting differential connectivity alterations with respect to functional connection length. Here, we tested whether functional connectopathy in ASD specifically relates to disruptions in long-relative to short-range functional connectivity profiles. Our approach combined functional connectomics with geodesic distance mapping, and we studied associations to macroscale networks, microarchitectural patterns, as well as socio-demographic and clinical phenotypes.MethodsWe studied 211 males from three sites of the ABIDE-I dataset comprising 103 participants with an ASD diagnosis (mean±SD age=20.8±8.1 years) and 108 neurotypical controls (NT, 19.2±7.2 years). For each participant, we computed cortex-wide connectivity distance (CD) measures by combining geodesic distance mapping with resting-state functional connectivity profiling. We compared CD between ASD and NT participants using surface-based linear models, and studied associations with age, symptom severity, and intelligence scores. We contextualized CD alterations relative to canonical networks and explored spatial associations with functional and microstructural cortical gradients as well as cytoarchitectonic cortical types.ResultsCompared to NT, ASD participants presented with widespread reductions in CD, generally indicating shorter average connection length and thus suggesting reduced long-range connectivity but increased short-range connections. Peak reductions were localized in transmodal systems (i.e., heteromodal and paralimbic regions in the prefrontal, temporal, and parietal and temporo-parieto-occipital cortex), and effect sizes correlated with the sensory-transmodal gradient of brain function. ASD-related CD reductions appeared consistent across inter-individual differences in age and symptom severity, and we observed a positive correlation of CD to IQ scores.ConclusionsOur study showed reductions in CD as a relatively stable imaging phenotype of ASD that preferentially impacted paralimbic and heteromodal association systems. CD reductions in ASD corroborate previous reports of ASD-related imbalance between short-range overconnectivity and long-range underconnectivity.
Super-resolution expansion microscopy in plant roots
Authors: Gallei Michelle , Truckenbrodt Sven , Kreuzinger Caroline , Inumella Syamala , Vistunou Vitali , Sommer Christoph , Tavakoli Mojtaba R. , Agudelo-Dueñas Nathalie , Vorlaufer Jakob , Jahr Wiebke , Randuch Marek , Johnson Alexander , Benková Eva , Friml Jiří , Danzl Johann G. 
Published: February 2024

AbstractSuper-resolution methods enable spatial resolution far better than the optical diffraction limit of about half the wavelength of light (∼200-300 nm) but have yet to attain widespread use in plants, owing in large part to plants’ challenging optical properties. Expansion microscopy improves effective resolution by isotropically increasing physical distances between sample structures while preserving relative spatial arrangements, and clears the sample. However, its application to plants has been hindered by the rigid, mechanically cohesive structure of plant tissues. Here, we report on whole-mount expansion microscopy ofArabidopsis thalianaroot tissues (PlantEx), achieving 4-fold resolution increase over conventional microscopy, highlighting microtubule cytoskeleton organization and interaction between molecularly defined cellular constituents. By combining PlantEx with STED microscopy, we increase nanoscale resolution further and visualize the complex organization of subcellular organelles from intact tissues by example of the densely packed COPI-coated vesicles associated with the Golgi apparatus and put these into cellular structural context.
MATEdb2, a collection of high-quality metazoan proteomes across the Animal Tree of Life to speed up phylogenomic studies
Authors: Martínez-Redondo Gemma I. , Vargas-Chávez Carlos , Eleftheriadi Klara , Benítez-Álvarez Lisandra , Vázquez-Valls Marçal , Fernández Rosa 
Published: February 2024

AbstractRecent advances in high throughput sequencing have exponentially increased the number of genomic data available for animals (Metazoa) in the last decades, with high-quality chromosome-level genomes being published almost daily. Nevertheless, generating a new genome is not an easy task due to the high cost of genome sequencing, the high complexity of assembly, and the lack of standardized protocols for genome annotation. The lack of consensus in the annotation and publication of genome files hinders research by making researchers lose time in reformatting the files for their purposes but can also reduce the quality of the genetic repertoire for an evolutionary study. Thus, the use of transcriptomes obtained using the same pipeline as a proxy for the genetic content of species remains a valuable resource that is easier to obtain, cheaper, and more comparable than genomes. In a previous study, we presented the Metazoan Assemblies from Transcriptomic Ensembles database (MATEdb), a repository of high-quality transcriptomic and genomic data for the two most diverse animal phyla, Arthropoda and Mollusca. Here, we present the newest version of MATEdb (MATEdb2) that overcomes some of the previous limitations of our database: (1) we include data from all animal phyla where public data is available, (2) we provide gene annotations extracted from the original GFF genome files using the same pipeline. In total, we provide proteomes inferred from high-quality transcriptomic or genomic data for almost 1000 animal species, including the longest isoforms, all isoforms, and functional annotation based on sequence homology and protein language models, as well as the embedding representations of the sequences. We believe this new version of MATEdb will accelerate research on animal phylogenomics while saving thousands of hours of computational work in a plea for open, greener, and collaborative science.
Identifying cancer cells from calling single-nucleotide variants in scRNA-seq data
Authors: Marot-Lassauzaie Valérie , Beneyto-Calabuig Sergi , Obermayer Benedikt , Velten Lars , Beule Dieter , Haghverdi Laleh 
Published: February 2024

AbstractSingle cell RNA sequencing (scRNA-seq) data is widely used to study cancer cell states and their heterogeneity. However, the tumour microenvironment is usually a mixture of healthy and cancerous cells and it can be difficult to fully separate these two populations based on transcriptomics alone. If available, somatic single nucleotide variants (SNVs) observed in the scRNA-seq data could be used to identify the cancer population. However, calling somatic SNVs in scRNA-seq data is a challenging task, as most variants seen in the short read data are not somatic, but can instead be germline variants, RNA edits or transcription, sequencing or processing errors. Additionally, only variants present in actively transcribed regions for each individual cell will be seen in the data. To address these challenges, we develop CCLONE (Cancer Cell Labelling On Noisy Expression), an interpretable tool adapted to handle the uncertainty and sparsity of SNVs called from scRNA-seq data. CCLONE jointly identifies cancer clonal populations, and their associated variants. We apply CCLONE on two acute myeloid leukaemia datasets and one lung adenocarcinoma dataset and show that CCLONE captures both genetic clones and somatic events for multiple patients. These results show how CCLONE can be used to gather insight into the course of the disease and the origin of cancer cells in scRNA-seq data.