bluuebunny/crossref_metadata_2025_split huggingface dataset:
Moderate-term dimethyl fumarate treatment reduces pathology of dystrophic skeletal and cardiac muscle in a mouse model
Authors: Kourakis Stephanie , Timpani Cara A. , Bagaric Ryan M. , Qi Bo , Ali Benazir A. , Boyer Rebecca , Spiesberger Guinevere , Kandhari Nitika , Peterson Amanda L. , Debrincat Didier , Yates Thomas J. , Yan Xu , Kuang Jujiao , de Haan Judy B. , Stupka Nicole , Nijagal Brunda , Deveson-Lucas Deanna , Fischer Dirk , Rybalka Emma 
Published: July 2024

AbstractIn Duchenne muscular dystrophy (DMD), corticosteroids significantly slow disease progression and have been used as a standard of care tool for more than 30 years. However, corticosteroids also impart side effects severe enough to preclude use in some patients. There remains an unmet need for new therapeutics that target the flow-on pathogenic mechanisms of DMD with a more favourable side-effect profile. We have previously demonstrated that short-term treatment with dual-purpose anti-inflammatory, anti-oxidative dimethyl fumarate (DMF), a drug with indication and established safety data in Multiple Sclerosis, more selectively modulates Duchenne (mdx) immunology than the frequently used corticosteroid, prednisone (PRED). Here, we assess the effect of moderate-term DMF treatment over 5 weeks in the typically mildmdxmouse model that we aggravated using exercise. We show that like PRED, DMF maintains anti-inflammatory action but with additional anti-fibrotic and anti-lipogenic effects on muscle with moderate-term use. This study supports our previous work highlighting DMF as a possible repurposing candidate for DMD, especially for patients who cannot tolerate chronic corticosteroid treatment.
Thermodynamics of unicellular life: Entropy production rate as function of the balanced growth rate
Authors: Droste Maarten J. , Remeijer Maaike , Planqué Robert , Bruggeman Frank J. 
Published: July 2024

AbstractIn isothermal chemical reaction networks, reaction rates depend solely on the reactant concentrations setting their thermodynamic driving force. Living cells can, in addition, alter reaction rates in their enzyme-catalysed networks by changing enzyme concentrations. This gives them control over their metabolic activities, as function of conditions. Thermodynamics dictates that the steady-state entropy production rate (EPR) of an isothermal chemical reaction network rises with its reaction rates. Here we ask whether microbial cells that change their metabolism as function of growth rate can break this relation by shifting to a metabolism with a lower thermodynamic driving force at faster growth.We address this problem by focussing on balanced microbial growth in chemostats. Since the driving force can then be determined and the growth rate can be set, chemostats allow for the calculation of the (specific) EPR.First we prove that the EPR of a steady-state chemical reaction network rises with its driving force. Next, we study an example metabolic network with enzyme-catalysed reactions to illustrate that maximisation of specific flux can indeed lead to selection of a pathway with a lower driving force.Following this idea, we investigate microbes that change their metabolic network responsible for catabolism from an energetically-efficient mode to a less efficient mode as function of their growth rate. This happens for instance during a shift from complete degradation of glucose at slow growth to partial degradation at fast growth. If partial degradation liberates less free energy, fast growth can occur at a reduced driving force and possibly a reduced EPR. We analyse these metabolic shifts using three models for chemostat cultivation of the yeastSaccharomyces cerevisiaethat are calibrated with experimental data. We also derive a criterion to predict when EPR drops after a metabolic switch that generalises to other organisms. Both analyses gave however inconclusive results, as current experimental evidence proved insufficient. We indicate which experiments are required to get a better understanding of the behaviour of the EPR during metabolic shifts in unicellular organisms.
Placental-brain axis in females detected within broadly impacted metabolic gene networks protects against prenatal PCB exposure
Authors: Chau Kelly , Neier Kari , Valenzuela Anthony E. , Schmidt Rebecca J. , Durbin-Johnson Blythe , Lein Pamela J. , Korf Ian , LaSalle Janine M. 
Published: July 2024

AbstractBackgroundNeurodevelopmental disorders have a strong male bias that is poorly understood. Placenta is a rich source of molecular information about environmental interactions with genetics (including biological sex), that affect the developing brain. We investigated placental-brain transcriptional responses in an established mouse model of prenatal exposure to a human-relevant mixture of polychlorinated biphenyls (PCBs).ResultsTo understand sex, tissue, and dosage effects in embryonic (E18) brain and placenta by RNAseq, we used weighted gene correlation network analysis (WGCNA) to create correlated gene networks that could be compared across sex or tissue. WGCNA revealed that expression within most correlated gene networks was significantly and strongly associated with PCB exposures, but frequently in opposite directions between male-female and placenta-brain comparisons. In both WGCNA and differentially expressed gene analyses, male brain showed more PCB-induced transcriptional changes than male placenta, but the reverse pattern was seen in females. Furthermore, non-monotonic dose responses to PCBs were observed in most gene networks but were most prominent in male brain. The transcriptomic effects of low dose PCB exposure were significantly reversed by dietary folic acid supplementation across both sexes, but these effects were strongest in female placenta. PCB-dysregulated and folic acid-reversed gene networks were commonly enriched in functions in metabolic pathways involved in energy usage and translation, with female-specific protective effects enriched in PPAR, thermogenesis, glycerolipids, and O-glycan biosynthesis, as opposed to toxicant responses in male brain.ConclusionsThe female protective effect in prenatal PCB exposures appears to be mediated by dose-dependent sex differences in transcriptional modulation of metabolism in placenta.Graphical Abstract
Functionally constrained human proteins are less prone to mutational instability caused by single amino acid substitutions
Authors: Andrews T. Daniel , Lehmann Nicole , May Maryam , Goodall Llewelyn , Cho Eun , Chuah Aaron 
Published: July 2024

AbstractIt is well understood that missense mutations that disrupt protein structural stability are a common pathogenic mechanism in human genetic disease. At a proteome-wide scale, we have quantitated potential disruption of protein stability due to amino acid substitution and show that the most functionally constrained proteins are typically less susceptible to large mutational changes in stability. Mechanistically, this relates to greater intrinsic disorder among constrained proteins, but also to increased B-factors in the ordered regions of constrained proteins. This phenomenon means that constrained proteins exhibit smaller stability effects due missense mutations, and partly explains why overtransmission of pathogenic missense variation is less prevalent in genetic disorders characterised with protein truncating variation. From analysis of the predicted protein stability effects of missense genetic variation across all human proteins, we show that the most functionally constrained proteins are depleted of both destabilising (ΔΔG > 0.5 kcal/mol) and overly-stabilising (ΔΔG < -0.5 kcal/mol) amino acid variation in disease-free populations. Despite this, amino acid substitutions with large stability effects in functionally constrained proteins are still highly prevalent among pathogenic human genetic variation. Importantly, we observe that there are approximately five times more missense variants with large stability effects than there are unambiguous loss-of-function mutations. Missense variants with disruption of stability effects recapitulate the per-gene patterns of functional constraint observed with protein truncating loss-of-function variation, yet their relative abundance abrogates difficulties encountered when estimating functional constraint for the shortest human genes.
Evolutionary Dynamics of Lineage-Specific Class-A GPCR Subsets Reveal Widespread Chemosensory Roles and Adaptations in Lophotrochozoa
Authors: Nath Rohan , Panda Biswajit , Siuli Rakesh , Krishnan Arunkumar 
Published: July 2024

ABSTRACTDetecting external chemosensory cues via Class-A G protein-coupled receptors (GPCRs) is essential for behavioral and biological functions, influencing animal evolution and ecological adaptations. While well-studied in vertebrates and echinoderms, their role in major clades like Lophotrochozoa is less understood despite their remarkable ecological adaptations. Utilizing 238 lophotrochozoan genomes across eight phyla, we conducted a large-scale comparative genomics analysis to identify lineage-specifically expanded subsets (LSEs) of Class-A GPCRs adapted for chemoreception. Using phylogeny and orthology-based clustering, we differentiated these expansions from conserved orthogroups of endogenous ligand-binding GPCRs. LSEs correlated with adaptations to diverse habitats, with whole-genome duplications having limited impact. Across phyla, species in coastal, freshwater, and terrestrial habitats exhibited large and diverse LSEs, while those adapted to extreme deep-sea environments, parasitic lifestyles, or alternative chemosensory mechanisms showed consistent reductions. Sequence heterogeneity, positive selection, and ligand-binding pocket flexibility in these LSEs further underscored adaptations to environmental signals. These findings provide foundational insights into Class-A GPCR-mediated chemoreception across Lophotrochozoa.TeaserUnveiling correlations between lophotrochozoans habitat adaptations and lineage-specific changes in Class-A GPCR repertoire.
The barley MLA13-AVRA13heterodimer reveals principles for immunoreceptor recognition of RNase-like powdery mildew effectors
Authors: Lawson Aaron W. , Flores-Ibarra Andrea , Cao Yu , An Chunpeng , Neumann Ulla , Gunkel Monika , Saur Isabel M. L. , Chai Jijie , Behrmann Elmar , Schulze-Lefert Paul 
Published: July 2024

AbstractCo-evolution between cereals and pathogenic grass powdery mildew fungi is exemplified by sequence diversification of an allelic series of barley resistance genes encoding Mildew Locus A (MLA) nucleotide-binding leucine-rich repeat (NLR) immunoreceptors with a N-terminal coiled-coil domain (CNLs). Each immunoreceptor recognises a matching, strain-specific powdery mildew effector encoded by an avirulence gene (AVRa). We present here the cryo-EM structure of barley MLA13 in complex with its cognate effector AVRA13-1. The effector adopts an RNase-like fold when bound to MLA13in planta, similar to crystal structures of other RNase-like AVRA effectors purified fromE. coli. AVRA13-1 interactsviaits basal loops with MLA13 C-terminal leucine rich repeats (LRRs) and the central winged helix domain (WHD). Co-expression of structure-guided MLA13 and AVRA13-1 substitution variants show that the receptor–effector interface plays an essential role in mediating immunity-associated plant cell death. Furthermore, by combining structural information from the MLA13–AVRA13-1 heterocomplex with sequence alignments of other MLA receptors, we designed a single amino acid substitution in MLA7 that enables expanded effector detection of AVRA13-1 and the virulent variant AVRA13-V2. In contrast to the pentameric conformation of previously reported effector-activated CNL resistosomes, MLA13 was purified and resolved as a stable heterodimer from anin plantaexpression system. Our study suggests that the MLA13–AVRA13-1 heterodimer might represent a CNL output distinct from CNL resistosomes and highlights opportunities for the development of designer gain-of-function NLRs.
Spatial patterns of vascular plant species richness in Poland: relations among species group richness and hot spot locations
Authors: Szymura T.H. , Tegegne H. , Szymura M. 
Published: July 2024

AbstractKnowledge of spatial patterns of species richness (SR) is highly relevant for theoretical research in ecology and the development of conservation plans. In Poland, despite a long tradition of botanical surveys, vascular plant SR has not been mapped, nor have the correlations in richness among different plant species groups been explored. Here we used a recently published data set to examine spatial patterns and relationships among the joined SR of vascular plant species, including native species, archeophytes, neophytes, and species with high conservation value (i.e., red list species). The basic spatial unit employed was a 10 × 10 km grid from the Atlas of Distribution of Vascular Plants in Poland (ATPOL). We found that the richness patterns of native species, archeophytes, neophytes, and red-list species were positively correlated. The main patterns of SR and the percentage of particular groups in the joined SR were based on three components: (1) gradient of overall SR, (2) invasion level, and (3) peculiarity of flora in some regions resulting from the high number and proportion of rare species that often have high conservation value. In general, northeastern Poland was species-poor, while the Carpathian Mountain range, the uplands in southern Poland, and some parts of Wisła River valley had the highest SR concentrations. The location of SR hotspots usually did not overlap with the existing system of national parks. The correlations among native SR, high conservation value species, and neophyte SR suggest that biological invasions are among the most important threats to vascular plant diversity in Poland. Finally, we demonstrated that the presented maps, despite likely biases in SR assessments, seem to reflect general ecological gradients influencing vascular plant distribution in Poland.
Towards a Taxonomy Machine – A Training Set of 5.6 Million Arthropod Images
Authors: Steinke D , Ratnasingham S , Agda J , Ait Boutou H , Box I , Boyle M , Chan D , Feng C , Lowe SC , McKeown JTA , McLeod J , Sanchez A , Smith I , Walker S , Wei CY-Y , Hebert PDN 
Published: July 2024

AbstractThe taxonomic identification of organisms from images is an active research area within the machine learning community. Current algorithms are very effective for object recognition and discrimination, but they require extensive training datasets to generate reliable assignments. This study releases 5.6 million images with representatives from 10 arthropod classes and 26 insect orders. All images were taken using a Keyence VHX-7000 Digital Microscope system with an automatic stage to permit high-resolution (4K) microphotography. Providing phenotypic data for 324,000 species derived from 48 countries, this release represents, by far, the largest dataset of standardized arthropod images. As such, this dataset is well suited for testing the efficacy of machine learning algorithms for identifying specimens to higher taxonomic categories.
Convolvulaceae of Guinea: taxonomy, conservation and useful plants
Authors: Davis Becca , Couch Charlotte , Bidault Ehoarn , Simbiano Faya Julien , Moumou Denise , Felipe Almeida Rafael , Simões Ana Rita G. 
Published: July 2024

ABSTRACTConvolvulaceae is a diverse and economically important plant family in Tropical Africa, including the crop sweet potato (Ipomoea batatas(L.) Lam.) and its wild relatives, morning glories (IpomoeaL.), bindweeds (ConvolvulusL.), invasive weeds (e.g.CuscutaL.) and several other species with food, medicinal, or traditional uses. A taxonomic treatment of Convolvulaceae for Guinea is here presented, including comprehensive morphological descriptions, identification keys to genera and species, distribution and ecological information, specimen data, and documentation of known uses. A total of 51 species belonging to 16 genera are documented, 38 of which are native, and 13 presumed introduced; 33 of these are used as medicine, 18 as ornamental, 12 as food and 15 with a range of other uses. Preliminary IUCN Red List assessments were carried out for 45 species for which there were no previous assessments All 45 preliminary conservation assessments were categorised as Least Concern for the global Red List, with 61% of native species having at least one occurrence point falling within protected areas.
Comparison of black soldier fly, cricket, and superworm on growth performance, nutrient utilization and fatty acid profiles of rainbow trout
Authors: Drosdowech Sonja , Chiasson Marcia , Ma David , Huyben David , Rooney Neil 
Published: July 2024

AbstractInclusion of fishmeal and fish oil in feeds for farmed fish is not sustainable and alternatives need to be evaluated. The aim of this study was to determine the effect of diets including defatted black soldier fly larvae (Hermetia illucens), adult cricket (Gryllodes sigillatus) and superworm (Zophobas morio) on the growth performance, apparent nutrient digestibility, nutrient retention, and fatty acid profiles of juvenile rainbow trout (Oncorhynchus mykiss). Triplicate tanks of fish (100.5 ± 0.6 g; mean ± SD) were fed one of four diets, a control diet with 20% fishmeal, and three experimental diets containing either 15% defatted black soldier fly meal, 15% full-fat adult cricket meal or 15% full-fat superworm meal, where each insect meal partially replaced fishmeal and fish oil. After 84 days of feeding, no significant differences were observed between diets for growth performance indicators or body indices. Fish fed the control and superworm diets had a higher protein content and retention in whole-body carcass compared to the cricket and black soldier fly diet groups. No significant effects between diets were found on whole-body carcass regarding fatty acid classes SFA, MUFA, PUFA n-3 and PUFA n-6, although lauric acid and myristic acid were significantly higher in fish fed black soldier fly diet and linoleic acid was higher in fish fed superworm and cricket diets. Retention of fatty acids was higher for most classes in fish fed the black soldier fly diet, yet whole carcass lipid content did not differ significantly between diets. Additionally, apparent digestibility of phosphorous was significantly improved for all insect diets compared to the control. These results indicate that insect meals can partially replace fishmeal and fish oil in diets for rainbow trout without compromising growth performance and fatty acid composition, while improving phosphorous utilization.
Mixtures of Intrinsically Disordered Neuronal Protein Tau and Anionic Liposomes Reveal Distinct Anionic Liposome-Tau Complexes Coexisting with Tau Liquid-Liquid Phase Separated Coacervates
Authors: Tchounwou Christine , Jobanputra Anjali J. , Lasher Dylan , Fletcher Bretton J. , Jacinto Jorge , Bhaduri Arjun , Best Rebecca L. , Fisher William S. , Ewert Kai K. , Li Youli , Feinstein Stuart C. , Safinya Cyrus R. 
Published: July 2024

ABSTRACTTau, an intrinsically disordered neuronal protein and polyampholyte with an overall positive charge, is a microtubule (MT) associated protein, which binds to anionic domains of MTs and suppresses their dynamic instability. Aberrant tau-MT interactions are implicated in Alzheimer’s and other neurodegenerative diseases. Here, we studied the interactions between full length human protein tau and other negatively charged binding substrates, as revealed by differential-interference-contrast (DIC) and fluorescence microscopy. As a binding substrate, we chose anionic liposomes (ALs) containing either 1,2-dioleoyl-sn-glycero-3-phosphatidylserine (DOPS, −1e) or 1,2-dioleoyl-sn-glycero-3-phosphatidylglycerol (DOPG, −1e) mixed with zwitterionic 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) to mimic anionic plasma membranes of axons where tau resides. At low salt concentrations (0 to 10 mM KCl or NaCl) with minimal charge screening, reaction mixtures of tau and ALs resulted in the formation of distinct states of AL-tau complexes coexisting with liquid-liquid phase separated tau self-coacervates arising from the polyampholytic nature of tau containing cationic and anionic domains. AL-tau complexes exhibited distinct types of morphologies. This included, large ≈20-30 micron tau-decorated giant vesicles with additional smaller liposomes with bound tau attached to the giant vesicles, and tau-mediated finite-size assemblies of small liposomes. As the ionic strength of the solution was increased to near and above physiological salt concentrations for 1:1 electrolytes (≈150 mM), AL-tau complexes remained stable while tau self-coacervate droplets were found to dissolve indicative of breaking of (anionic/cationic) electrostatic bonds between tau chains due to increased charge screening. The findings are consistent with the hypothesis that distinct cationic domains of tau may interact with anionic lipid domains of the lumen facing monolayer of the axon plasma membrane suggesting the possibility of transient yet robust interactions at physiologically relevant ionic strengths.
CD24a knockout transforms the tumor microenvironment from cold to hot by promoting tumor-killing immune cell infiltration in a murine triple-negative breast cancer model
Authors: Chan Shih-Hsuan , Tseng Hsuan-Jung , Wang Lu-Hai 
Published: July 2024

AbstractBackgroundCD24 plays a crucial role not only in promoting tumor progression and metastasis but also in modulating macrophage-mediated anti-tumor immunity. However, the impact of tumor CD24 on the immune landscape of the tumor microenvironment (TME) remains poorly explored. Here, we investigated the role of CD24a, murine CD24 gene, in the progression and immune dynamics of the tumor microenvironment (TME) in the 4T1 murine model of triple-negative breast cancer (TNBC).Methods:We employed Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 technology to perform a gene knockout of Cd24a in 4T1 cells. Flow cytometry was utilized to analyze the distribution and number of immune cells, including myeloid-derived suppressor cells (MDSCs), natural killer (NK) cells, T cells, and macrophages, within tumors, spleens, and bone marrow. Immunofluorescence (IF) staining was used to detect these immune cells in tumor sections. Additionally, ANDOR Dragonfly High-Speed Confocal was used to perform three-dimensional (3D) mapping of mouse tumors.ResultsOur study showed that knocking out CD24a significantly impeded tumor progression and prolonged mouse survival. Flow cytometry and IF analysis revealed that the loss of CD24a transformed tumor microenvironment from cold to hot by promoting the infiltration of M1 macrophages, cytotoxic CD8+T cells, and CD49b+natural killer (NK) cells while reducing the recruitment and expansion of granulocytic myeloid-derived suppressor cells (gMDSCs) in the TME. Additionally, the 3D mapping of TME further validated the “hot state” of CD24a knockout tumors.ConclusionsOur study provides the first evidence that targeting CD24a could effectively reprogram the TME, enhancing its immunogenicity, and transforming immune cold tumors into hot tumors. This strategy may offer a promising therapeutic strategy for enhancing the immune response against poorly immunogenic tumors.