Biology subjects

Ware, J.

Publications and source records attributed to Ware, J..

6 recordsLinked to original sources

bioRxiv2025

A GPVI-platelet-neutrophil-NET axis drives systemic sclerosis

Systemic sclerosis (SSc) is immune-mediate inflammatory disease characterized by progressive tissue fibrosis. We observed that circulating neutrophils from patients with diffuse SSc exhibit an activated phenotype, a finding echoed in blood and skin transcriptomes. Neutrophil depletion abrogated experimental SSc induced by cutaneous injection of hypochlorous acid (HOCl) or bleomycin (BLM), and adoptive transfer of HOCl and BLM neutrophils induced skin and lung fibrosis in healthy mice, establishing neutrophils as necessary and sufficient for fibrosis. We noted that SSc patients exhibited platelet activation, a phenotype that preceded neutrophil activation in mice, suggesting an upstream role. Indeed, platelet depletion abrogated neutrophil activation and tissue fibrosis, and exposure to HOCl or BLM platelets conferred upon wild-type neutrophils the capacity to induce skin and lung fibrosis via neutrophil extracellular traps (NETs). Genetic and therapeutic blockade of the platelet collagen receptor GPVI attenuated platelet and neutrophil activation, reduced circulating NETs, and protected animals from skin and lung fibrosis. These findings identify the GPVI-platelet-neutrophil-NET as a new source of therapeutic targets in SSc.

immunology↗

bioRxiv2022

Tropical origin, global diversification and dispersal in the pond damselflies (Coenagrionoidea) revealed by a new molecular phylogeny

The processes responsible for the formation of Earths most conspicuous diversity pattern, the latitudinal diversity gradient (LDG), remain unexplored for many clades in the Tree of Life. Here, we present a densely-sampled and dated molecular phylogeny for the most speciose clade of damselflies worldwide (Odonata: Coenagrionoidea), and investigate the role of time, macroevolutionary processes and biome-shift dynamics in shaping the LDG in this ancient insect superfamily. We used process-based biogeographic models to jointly infer ancestral ranges and speciation times, and to characterise within-biome dispersal and biome-shift dynamics across the cosmopolitan distribution of Coenagrionoidea. We also investigated temporal and biome-dependent variation in diversification rates. Our results uncover a tropical origin of pond damselflies and featherlegs [~] 105 Ma, while highligthing uncertainty of ancestral ranges within the tropics in deep time. Even though diversification rates have declined since the origin of this clade, global climate change and biome-shifts have slowly increased diversity in warm- and cold-temperate areas, where lineage turnover rates have been relatively higher. This study underscores the importance of biogeographic origin and time to diversify as important drivers of the LDG in pond damselflies and their relatives, while diversification dynamics have instead resulted in the formation of ephemeral species in temperate regions. Biome-shifts, although limited by tropical niche conservatism, have been the main factor reducing the steepness of the LDG in the last 30 Myr. With ongoing climate change and increasing northward range expansions of many damselfly taxa, the LDG may become less pronounced. Our results support recent calls to unify biogeographic and macroevolutionary approaches to increase our understanding of how latitudinal diversity gradients are formed and why they vary across time and among taxa.

evolutionary biology↗

bioRxiv2020

How old are dragonflies and damselflies? Odonata (Insecta) transcriptomics resolve familial relationships

Dragonflies and damselflies, representing the insect order Odonata, are among the earliest flying insects with living (extant) representatives. However, unravelling details of their long evolutionary history, such as egg laying (oviposition) strategies, is impeded by unresolved phylogenetic relationships, an issue particularly prevalent in damselfly families and fossil lineages. Here we present the first transcriptome-based phylogenetic reconstruction of Odonata, analyzing 2,980 protein-coding genes in 105 species representing nearly all of the orders families (except Austropetaliidae and Neopetaliidae). All damselfly families and most dragonfly families are recovered as monophyletic groups. Our Molecular clock estimates suggest that crown-Zygoptera (damselflies) and -Anisoptera (dragonflies) both arose during the late Triassic. Several of the observed long inner branches in our topology are indicative of the extinction of once flourishing lineages. We also find that exophytic egg laying behaviour with a reduced ovipositor evolved in certain dragonflies during the late Jurassic / early Cretaceous. Lastly, we find that certain fossils have an unexpected deterring impact in divergence dating analysis.

evolutionary biology↗

bioRxiv2020

Calcium ion chelation preserves platelet function during cold storage

ObjectivePlatelet transfusion is a life-saving therapy to prevent or treat bleeding in patients with thrombocytopenia or platelet dysfunction. However, for more than six decades, safe and effective strategies for platelet storage have been an impediment to widespread use of platelet transfusion. Refrigerated platelets are cleared rapidly from circulation, precluding cold storage of platelets for transfusion. Consequently, platelets are stored at room temperature (RT) with an upper limit of 5 days due to risks of bacterial contamination and loss of platelet function. This practice severely limits platelet availability for transfusion. This study is to identify the mechanism of platelet clearance after cold storage and develop a method for platelet cold storage. Approach and ResultsWe found that rapid clearance of cold-stored platelets was largely due to integrin activation and apoptosis. Deficiency of integrin {beta}3 or caspase-3 prolonged cold-stored platelets in circulation. Pre-treatment of platelets with EGTA, a cell impermeable calcium ion chelator, reversely inhibited cold storage-induced platelet activation and consequently prolonged circulation of cold-stored platelets. Moreover, transfusion of EGTA-treated, cold-stored platelets, but not RT-stored platelets, into the mice deficient in glycoprotein Ib significantly shortened tail-bleeding times and diminished blood loss. ConclusionIntegrin activation and apoptosis is the underlying mechanism of rapid clearance of platelets after cold storage. Addition of a cell impermeable calcium ion chelator to platelet products is potentially a simple and effective method to enable cold storage of platelets for transfusion.

cell biology↗

bioRxiv2019

Genomics of Egyptian Healthy Volunteers: The EHVol Study

Comprehensive genomic databases offer unprecedented opportunities towards effective tailored strategies for the prevention and treatment of disease. The integration of genomic and phenotypic data from diverse ethnic populations is also key to advancements in precision medicine and novel diagnostic technologies. Current reference genomic databases, however, are not representative of the global human population, making variant interpretation challenging and uncertain, especially in underrepresented populations such as the North African population. To address this, a study of 391 Egyptian healthy volunteers (EHVols) was initiated as a milestone towards establishing the 1000 Egyptian Genomes project.

genomics↗

bioRxiv2017

Gene family information facilitates variant interpretation and identification of disease-associated genes

Differentiating risk-conferring from benign missense variants, and therefore optimal calculation of gene-variant burden, represent a major challenge in particular for rare and genetic heterogeneous disorders. While orthologous gene conservation is commonly employed in variant annotation, approximately 80% of known disease-associated genes are paralogs and belong to gene families. It has not been thoroughly investigated how gene family information can be utilized for disease gene discovery and variant interpretation. We developed a paralog conservation score to empirically evaluate whether paralog conserved or nonconserved sites of in-human paralogs are important for protein function. Using this score, we demonstrate that disease-associated missense variants are significantly enriched at paralog conserved sites across all disease groups and disease inheritance models tested. Next, we assessed whether gene family information could assist in discovering novel disease-associated genes. We subsequently developed a gene family de novo enrichment framework that identified 43 exome-wide enriched gene families including 98 de novo variant carrying genes in more than 10k neurodevelopmental disorder patients. 33 gene family enriched genes represent novel candidate genes which are brain expressed and variant constrained in neurodevelopmental disorders.

genetics↗