bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascular FLRT2 regulates venous-mediated angiogenic expansion and CNS barriergenesis
Authors: Llaó-Cid C. , Peguera B. , Kobialka P. , Decker L. , Vogenstahl J. , Alivodej N. , Srivastava S. , Jin J. , Kirchmaier B. C. , Milla C. , Schlierbach H. , Schänzer A. , Acker T. , Segarra M. , Acker-Palmer A. 
Published: August 2024

AbstractVeins have emerged as the origin of all other endothelial cell subtypes needed to expand vascular networks during developmental and pathological neoangiogenesis. Here, we uncover the significant role of the angioneurin Fibronectin Leucine Rich Transmembrane protein (FLRT) 2 in central nervous system (CNS) vascular development in the mouse. Early postnatal FLRT2 deletion reveals specific defects in retinal veins, impacting endothelial cell proliferation, sprouting and polarity that result in reduced tip cells at the vascular front. FLRT2 interacts with VE-cadherin and together with the endocytic adaptor protein Numb contribute to the modulation of adherens junction morphology in both retina and cerebral cortexin vivo. Utilizing expansion microscopy, we visualize the altered dynamic distribution of VE-cadherin in tissue of FLRT2 endothelial mutants. Additionally, FLRT2 in cortical vessels regulates the crosstalk between adherens and tight junctions, influencing blood-brain barrier development. Our findings position FLRT2 as a vein-specific crucial regulator of CNS vascular development.
Solving the SLoSS debate: Scale-dependent effects of habitat fragmentation on biodiversity loss
Authors: de Jager Monique , Pos Edwin T. 
Published: August 2024

AbstractShould what is left of nature be contained in a Single Large or Several Small (SLoSS) areas? This question of what would minimize the impact severity of habitat destruction on biodiversity loss is much debated, mainly because studies generally focus on different spatial and temporal scales. Using a semi-spatially explicit, (near-)neutral, individual-based model, we investigate the effects of fragmentation on biodiversity loss at two spatial (landscape-versus subcommunity level) and two temporal scales (static versus dynamic effects). Our results show that the role of spatial configuration of habitat destruction depends on when and at what scale we measure biodiversity loss. When considering the more realistic assumption that species differ in dispersal capacity, differences between spatial configurations are likely to be amplified. Our results indicate that the spatial configuration of habitat loss needs to be considered when evaluating the risks of further habitat destruction.
Mitigation of chytrid infection on tadpoles with the antimicrobial metabolites ofXenorhabdus szentirmaii
Authors: Ujszegi János , Boros Zsófia , Harmos Krisztián , Magos Gábor , Tóth Ábris , Vörös Judit , Kásler Andrea 
Published: August 2024

AbstractSurvival of amphibian assemblages is threatened by many factors. Among them, chytridiomycosis, the disease caused by the chytrid fungusBatrachochytrium dendrobatidis(Bd) has great importance, also threatening the populations of the yellow-bellied toad (Bombina variegata), which has a scattered, isolated distribution in Hungary. Treatment with secondary metabolites of the entomopathogenic bacterium,Xenorhabdus szentirmaiiis a promising method in the mitigation of chytridiomycosis, as recently demonstrated. To assess whether it may also be effective for lowering infection intensities inB. variegatatadpoles, we extracted cell-free culture media (CFCM) from liquid cultures ofX. szentirmaiiand tested their antifungal efficacy at a dilution of 0.1 % (v/v), while also measuring possible short-term malign effects on tadpoles experimentally infected with Bd or sham infection. According to our results, CFCM treatment alone did not compromise tadpoles’ survival probability, nor reduced the body mass and developmental speed of the individuals. At the same time, the treatment reduced the intensity and prevalence of Bd infection, but this effect was affected by the population of origin. The antimicrobial metabolites produced byX. szentirmaiimay therefore be suitable for the safe mitigation of chytridiomycosis inB. variegatatadpoles, but further studies are needed, aiming to monitor and increase the efficacy of this method.
High nutritional conditions influence feeding plasticity inPristionchus pacificusand render worms non-predatory
Authors: Piskobulu Veysi , Athanasouli Marina , Witte Hanh , Feldhaus Christian , Streit Adrian , Sommer Ralf J. 
Published: August 2024

AbstractDevelopmental plasticity, the ability of a genotype to produce different phenotypes in response to environmental conditions, has been subject to intense studies in the last four decades. The self-fertilizing nematodePristionchus pacificushas been developed as a genetic model system for studying developmental plasticity due to its mouth-form polyphenism that results in alternative feeding strategies with a facultative predatory and a non-predatory mouth form. Many studies linked molecular aspects of the regulation of mouth-form polyphenism with investigations of its evolutionary and ecological significance. Also, several environmental factors influencingP. pacificusfeeding structure expression were identified including temperature, culture condition and population density. However, the nutritional plasticity of the mouth form has never been properly investigated although polyphenisms are known to be influenced by changes in nutritional conditions. For instance, studies in eusocial insects and scarab beetles have provided significant mechanistic insights into the nutritional regulation of polyphenisms but also other forms of plasticity. Here, we study the influence of nutrition on mouth-form polyphenism inP. pacificusthrough experiments with monosaccharide and fatty acid supplementation. We show that in particular glucose supplementation renders worms non-predatory. Subsequent transcriptomic and mutant analyses indicate thatde novofatty acid synthesis and peroxisomal beta-oxidation pathways play an important role in the mediation of this plastic response. Finally, the analysis of fitness consequences through fecundity counts suggests that non-predatory animals have an advantage over predatory animals grown in the glucose-supplemented condition.Research highlightsThis study represents the first systematic attempt to investigate the influence of nutrition on mouth-form polyphenism in the genetic model organismPristionchus pacificus. Through glucose and oleic acid supplementation we show that high nutritional conditions influence feeding plasticity and render worms non-predatory. Mutant analysis indicates a role ofde novofatty acid synthesis and peroxisomal beta-oxidation pathways for these responses.
Antibiotics Change the Growth Rate Heterogeneity and Morphology of Bacteria
Authors: Kals Morten , Kals Emma , Kotar Jurij , Donald Allen , Mancini Leonardo , Cicuta Pietro 
Published: August 2024

AbstractA better understanding of the system-level effects of antibiotics is necessary to fight the rise of antibiotic resistance. Utilising the Multipad Agarose Plate (MAP), we monitor the growth rate and cell morphology of three clinically relevant species (E.coli, S.aureusandP.aeruginosa) after exposure to 11 different concentrations of 13 antibiotics (for a total of 24 microbe-antibiotic combinations). As the drug dose approaches the MIC and regardless of the mode of action, our results show a consistent increase in growth rate heterogeneity. Remarkably, drugs that affect protein synthesis consistently show the opposite trend, reducing heterogeneity. We hypothesize that growth rate heterogeneity under antibiotic treatment might therefore depend on the functional distance of the target from ribosomal activity, which is key in determining growth rate. Low heterogeneity is desirable from a clinical perspective, as the opposite is often associated to persistence and antibiotic survival. For all of the antibiotics and species tested, we also find a striking and non-trivial correlation between morphological alterations and growth inhibition. This observation allows us to introduce a new morphological parameter, MOR50, that enables the estimation of minimum inhibitory concentration (MIC) for antibiotic susceptibility testing (AST) with a single snapshot after 2.5 hours of incubation. In addition to introducing a novel, resource-efficient, rapid AST method, our findings shed new light on the effects of antibiotic perturbations on bacteria at the system level that might inform treatment design.
Exosomes can modulate the early hyperexcitability in cortical neurons with ASD-associatedShank3mutation
Authors: Choudhary Ashwani , Rosh Idan , Hussein Yara , Shemen Aviram , Rike Wote Amelo , Zinger Assaf , Offen Daniel , Stern Shani 
Published: August 2024

ABSTRACTShank3, a scaffolding protein, is critical for synaptic structure and function, particularly for the formation and maintenance of dendritic spines.Shank3mutations are strongly implicated in autism spectrum disorder (ASD) and related neuropsychiatric conditions such as Phelan-McDermid Syndrome (PMS) also known as the 22q13.3 deletion syndrome. Previous work has recognized early hyperexcitability in cortical neurons derived from ASD patients with various gene mutations as a potential common endophenotype. In this study, we examined the effects of exosomes extracted from several cell types on the neurophysiological properties of cortical neurons derived fromShank3(c.3679insG mutation) induced pluripotent stem cells (iPSCs). First, we sought to understand the implications of exosome-based intercellular communication on the neurophysiology ofShank3mutant and control neurons by switching their respective exosomes. We found that while control neuron-derived exosomes do not change the neurophysiology ofShank3neurons, theShank3neuron-derived exosomes transfer the early hyperexcitability and other ASD-related phenotypes to control neurons. Next, we also explored the therapeutic potential of mesenchymal stem cells (MSC) and iPSC-derived exosomes from healthy donors in theShank3cortical neurons. We demonstrate that both MSC and iPSC-derived exosomes rescue the early hyperexcitability and accelerated maturation ofShank3neurons. Proteomic analysis of exosomes derived fromShank3mutant and control neurons, as well as from exosomes derived from MSCs and iPSCs, revealed distinct protein cargoes that may cause changes in the neurophysiological properties of the recipient neurons. Our results hence provide novel insights into the pathophysiology of ASD emphasizing the importance of exosomes in intercellular communication and their potential to influence intrinsic and network properties of neurons. Moreover, our findings support the need for further exploration of exosome-based interventions as potential therapeutics for treating neurodevelopmental disorders.
Allogenic platelet-rich plasma and platelet-rich plasma extracellular vesicles alter the proteome of tenocytes in an in vitro equine model of tendon inflammation: A pilot study
Authors: Clarke Emily J , Jensen Anders , Gillen Alexandra M , Bardell David , Senior Mark , Anderson James R , Peffers Mandy J 
Published: August 2024

AbstractBackgroundTendon injuries are common in horses, often resulting in a high risk of reinjury. Hemoderivative therapeutics including platelet-rich plasma (PRP) show promise but outcomes vary due to inconsistent composition. PRP is rich in soluble growth factors and extracellular vesicles (EVs), the latter facilitate cell-to-cell communication by delivering biologically active cargo. This pilot study profiled the proteome of PRP and PRP-derived EVs and examined their effects on an equine tendon inflammatory modelin vitro.MethodsPlasma was isolated via double centrifugation and PRP produced using a commercial filtration kit. EVs were isolated from PRP and plasma using differential ultracentrifugation and characterised with the Exoview Tetraspanin assay. Equine tenocytes were stimulated with interleukin 1β and tumor necrosis factor α, then treated with PRP or PRP-derived EVs. Proteomic analysis was conducted on cell lysates, PRP and PRP-EVs using data-dependent acquisition liquid chromatography-tandem mass spectrometry and the data analyzed using multivariate and univariate approaches.ResultsPRP contained 575 quantifiable proteins and PRP-derived EVs 209 proteins. When compared to plasma and plasma derived EVs respectively, PRP and PRP-EVs were enriched in proteins associated with cellular waste disposal and inhibition of lipid metabolism. Experimental factors (inflammatory stimulation and/or treatments) significantly affected the abundance of 18 proteins as expressed in equine tenocytes including col1a1 (col1a1) and sequestosome 1, associated with collagen metabolism and nuclear factor kappa B signaling.DiscussionThe findings from this study suggest PRP-derived EVs influence inflammatory tenocytes and may be crucial to the efficacy of PRP.
Uncovering novel functions of the enigmatic, abundant and activeAnaerolineaein a salt marsh ecosystem
Authors: Payne Paige E. , Knobbe Loren N. , Chanton Patricia , Zaugg Julian , Mortazavi Behzad , Mason Olivia U. 
Published: August 2024

AbstractAnaerolineae, particularly uncultured representatives, are one of the most abundant microbial groups in coastal salt marshes, dominating the belowground rhizosphere, where over half of plant biomass production occurs. However, this class generally remains poorly understood, particularly in a salt marsh context. Here, novelAnaerolineaemetagenome assembled genomes (MAGs) were generated from the salt marsh rhizosphere representingAnaerolineales,Promineifilales,JAAYZQ01, B4-G1, JAFGEY01, UCB3, andCaldilinealesorders. Metagenome and metatranscriptome reads were mapped to annotated MAGs, revealing nearly allAnaerolineaeencoded and transcribed genes required for oxidation of simple sugars to complex carbon compounds, fermentation, and carbon fixation. Further, the majority ofAnaerolineaeexpressed genes involved in anaerobic and aerobic respiration and secondary metabolite production. The data revealed that the belowground salt marshAnaerolineaein the rhizosphere are important players in carbon cycling, including degradation of simple carbon compounds to more recalcitrant plant material, such as cellulose, using a diversity of electron acceptors and represent an unexplored reservoir of novel secondary metabolites.ImportanceGiven that coastal salt marshes are recognized as biogeochemical hotspots, it is fundamentally important to understand the functional role of the microbiome in this ecosystem. In particular,Anaerolineaeare abundant members of the salt marsh rhizosphere and have been identified as core microbes, suggesting they play a particularly important functional role. Yet, little is known about the metabolic pathways encoded and expressed in this abundant salt marsh clade. Using an ‘omics based approach we determined thatAnaerolineaeare capable of oxidizing a range of carbon compounds, including simple sugars to complex carbon compounds, while also encoding fermentation and carbon fixation. Surprisingly,Anaerolineaeencoded and transcribed genes involved in aerobic respiration, which was unexpected given the reduced nature of the salt marsh rhizosphere. Finally, the majority ofAnaerolineaeappear to be involved in secondary metabolite production, suggesting that this group represents an unexplored reservoir of novel and important secondary metabolites.
Cell type-specific impact of aging and Alzheimer disease on hippocampal CA1 perforant path input
Authors: Santoro Bina , Srinivas Kalyan V. , Reyes Isabel , Tian Chengju , Masurkar Arjun V. 
Published: August 2024

ABSTRACTThe perforant path (PP) carries direct inputs from entorhinal cortex to CA1 pyramidal neurons (PNs), with an impact dependent on PN position across transverse (CA1a–CA1c) and radial (superficial/deep) axes. It remains unclear how aging and Alzheimer disease (AD) affect PP input, despite its critical role in memory and early AD. Applyingex vivorecordings and two-photon microscopy in slices from mice up to 30 months old, we interrogated PP responses across PN subpopulations and compared them to Schaffer collateral and intrinsic excitability changes. We found that aging uniquely impacts PP excitatory responses, abolishing transverse and radial differences via a mechanism independent of presynaptic and membrane excitability change. This is amplified in aged 3xTg-AD mice, with further weakening of PP inputs to CA1a superficial PNs associated with distal dendritic spine loss. This demonstrates a unique feature of aging-related circuit dysfunction, with mechanistic implications related to memory impairment and synaptic vulnerability.
Morphological Profiling Dataset of EU-OPENSCREEN Bioactive Compounds Over Multiple Imaging Sites and Cell Lines
Authors: Wolff Christopher , Neuenschwander Martin , Beese Carsten Jörn , Sitani Divya , Ramos Maria C. , Srovnalova Alzbeta , Varela María José , Polishchuk Pavel , Skopelitou Katholiki E. , Škuta Ctibor , Stechmann Bahne , Brea José , Clausen Mads Hartvig , Dzubak Petr , Fernández-Godino Rosario , Genilloud Olga , Hajduch Marian , Loza María Isabel , Lehmann Martin , von Kries Jens Peter , Sun Han , Schmied Christopher 
Published: August 2024

AbstractMorphological profiling with the Cell Painting assay has emerged as a promising method in drug discovery research. The assay captures morphological changes across various cellular compartments enabling the rapid identification of the effect of compounds. We present a comprehensive morphological profiling dataset using the carefully curated and well-annotated EU-OPENSCREEN Bioactive Compound Set.Our profiling dataset was generated across multiple imaging sites with high-throughput confocal microscopes using the Hep G2 as well as the U2 OS cell line. We employed an extensive assay optimization process to achieve high data quality across the different imaging sites. An analysis of the four replicates validates the robustness of the generated data. We compare morphological features of the different cell lines and map the profiles to activity, toxicity, and basic compound targets to further describe the dataset as well as to demonstrate the potential of this dataset to be used for mechanism of action exploration.
Circuit firing homeostasis following synaptic perturbation ensures robust behavior
Authors: Hoagland Adam , Newman Zachary Louis , Cai Zerong , Isacoff Ehud Y. 
Published: August 2024

AbstractHomeostatic regulation of excitability and synaptic transmission ensures stable neural circuit output under changing conditions. We find that pre- or postsynaptic weakening of motor neuron (MN) to muscle glutamatergic transmission inDrosophilalarva has little impact on locomotion, suggesting non-synaptic compensatory mechanisms.In vivoimaging of MN to muscle synaptic transmission and MN activity both show that synaptic weakeningincreasesactivity in tonic type Ib MNs, but not in the phasic type Is MN that innervate the same muscles. Additionally, an inhibitory class of pre-MNs that innervates type Ib—but not Is—MNsdecreasesactivity. Our experiments suggest that weakening of MN evoked synaptic release onto the muscle is compensated for by an increase in MN firing due to a combined cell-autonomous increase in excitability and decreased inhibitory central drive. Selectivity for type Ib MNs may serve to restore tonic drive while absence of firing adjustment in the convergent Is MN can maintain the contraction wave dynamics needed for locomotion.
Diseased skin dermal proteomic profiles reflect shared extracellular matrix dysregulation patterns
Authors: Martins Luís , Malta Mariana D. , Chaves Sara , Osório Hugo , Guttmann-Gruber Christina , Kocher Thomas , Marques Alexandra P. 
Published: August 2024

ABSTRACTExtracellular matrix (ECM) plays a major role in the maintenance of skin homeostasis and modifications in its structure are commonly linked with skin diseases of different origins. Recent evidence shows that epidermal fibroblasts can be important regulators of epidermal pathology. However, despite recent advances, the intricate mechanisms responsible for the ECM defects in a wide range of skin pathologies are still evasive.In this work we used Dystrophic Epidermolysis Bullosa, Pemphigus vulgaris and Squamous Cell Carcinoma, as the models for epidermal diseases of distinct etiology, in order to explore potential shared alterations in diseased dermal fibroblasts.Our proteome analysis revealed that differentially expressed proteins in all diseases are commonly enriched in processes related to supramolecular fiber organization, complex of collagen trimers and actomyosin, however with opposite patterns. Nevertheless, Collagen XII is significantly downregulated in all diseases. Additionally, an algorithmic pipeline predicts that MAPKs and CDKs are major regulators of dermal proteome alterations across all diseases.Altogether, our results highlight a possible shared mechanism where downregulation of Collagen XII mediates ECM organization disruption leading to diverse disease phenotypes.
Prenatal glyphosate exposure disrupts the gut-brain axis across several generations in mice
Authors: Barnett J.A. , Josephson J.K. , Haskey N. , Hart M.M. , Soma K.K. , Bandy M.L. , McComb C.J. , Verdugo A. , Ghosh S. , Letef C. , Copp A. , Gibon J. , Ye J. , Giebelhaus R.T. , Murch S.J. , Jung M.M. , Gibson D.L. 
Published: August 2024

AbstractGlyphosate, a widely used herbicide in North America, has become prevalent in the food supply due to preharvest applications, raising concerns about potential health impacts. This study investigated the effects of prenatal glyphosate exposure on the gut bacteriome, colitis, metabolic health, and behavior across generations in mice. In healthy mice, glyphosate decreased goblet cell numbers and mucin-2 expression in the colon and dysregulated cytokines in F1 and F2 progeny at levels below the EPA acceptable daily limit. Glyphosate also disrupted metabolism, including impaired glucose tolerance, increased insulin resistance and reduced serum GLP-1 levels. Moreover, prenatal glyphosate exposure induced behavioral deficits, including reduced locomotor activity and impaired working memory, which are associated with alterations in the gut microbiome composition and key gut-brain axis mediators. These data underscore the potential risks associated with glyphosate exposure, highlighting the need for further research and regulatory consideration.