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Mashup Score: 0
Antarctica harbours some of the most isolated and extreme environments on Earth, concealing a largely unexplored and unique component of the global animal virosphere. To understand the diversity and evolutionary histories of viruses in these polar species we determined the viromes of 11 Antarctic fish species with 248 samples collected from the Ross Sea region spanning the Perciformes, Gadiformes, and Scorpaeniformes orders. The continent’s shift southward and cooling temperatures over 20 million years ago led to a reduction in biodiversity and subsequent radiation of some marine fauna, such as the notothenioid fishes. Despite decreased host species richness in polar regions, we revealed a surprisingly complex virome diversity in Ross Sea fish, with the types and numbers of viruses per host species and individuals sampled comparable to that of fish in warmer marine environments with higher host community diversity. We also observed a higher number of closely related viruses likely repr
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Mashup Score: 0Lithic bacterial communities: ecological aspects focusing on Tintenstrich communities - 1 day(s) ago
Tintenstrich communities (TC) are mainly composed by Cyanobacteria developing on rock substrates and forming physical structures strictly connected to the rock itself. Endolithic and epilithic bacterial communities are important because they contribute to nutrients release within run-off waters flowing on the rock surface. Despite them being ubiquitous, little information about their ecology and main characteristics is available. In this paper, we characterized the bacterial communities of rock surfaces of TC in Switzerland through Illumina sequencing and investigated their bacterial community composition on two substrate types (silicious and limestone rocks) through multivariate models. Our results show that Cyanobacteria and Proteobacteria are the predominant phyla in this environment. Bacterial alpha diversity was higher on limestone than on siliceous rock, and beta diversity of siliceous rock varied with changes in rock surface structure. Here we provide novel insights into the bac
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Mashup Score: 4
Innate immunity, the first line of defense against pathogens, relies on efficient elimination of invading agents by phagocytes. In the co-evolution of host and pathogen, pathogens developed mechanisms to dampen and evade phagocytic clearance. Here, we report that bacterial pathogens can evade clearance by macrophages through mimicry at the mammalian anti-phagocytic signaling axis between CD47 (ligand) and SIRPα (receptor). We identified a protein, P66, on the surface of Borrelia burgdorferi that, like CD47, is necessary and sufficient to bind the macrophage receptor SIRPα. Expression of the gene encoding the protein is required for bacteria to bind SIRPα or a high-affinity CD47 reagent. Genetic deletion of p66 increases phagocytosis by macrophages. Blockade of P66 during infection promotes clearance of the bacteria. This study demonstrates that mimicry of the mammalian anti-phagocytic protein CD47 by B. burgdorferi inhibits macrophage-mediated bacterial clearance. Such a mechanism has
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Mashup Score: 2Complementary methods for the study of interactions between eosinophils and cancer cells. - 1 day(s) ago
Eosinophils are a rare immune cell subset with important roles in Th2 immunity and, recently, in cancer. Interleukin IL-33 (IL-33) is well recognized for its important roles in the activation of eosinophils in Th2 immunity. On the other hand, IL-33 has been recently discovered to play central roles in cancer, in particular by activating eosinophils and increase their degranulation consequent to an intrinsic tumor cell killing function. We propose a dual approach methodology to extrapolate functional interactions of eosinophils with tumor cells, as a result of eosinophil stimulation. Human eosinophils (Eos) isolated from the blood of healthy donors by dextran sedimentation followed by magnetic sorting are exposed to IL-33 (Eos33) or IL-5 (Eos5, control) for 18 h. These pre-conditioned cells are then co-cultured with A375P melanoma cells to monitor cell-cell interactions. Acoustic focusing flow cytometry analysis is employed to evaluate the presence of Eos-tumor cell conjugates after 1h
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Mashup Score: 4
Cancer remains a formidable global health challenge, with metastasis being a key contributor to its lethality. Abundant high molecular mass hyaluronic acid, a major non-protein component of extracellular matrix, protects naked mole rats from cancer and reduces cancer incidence in mice. Hyaluronidase plays a critical role in degrading hyaluronic acid and is frequently overexpressed in metastatic cancer. Here we investigated the potential of targeting hyaluronidases to reduce metastasis. High throughput screen identified delphinidin, a natural plant compound found in fruits and vegetables, as a potent hyaluronidase inhibitor. Delphinidin-mediated inhibition of hyaluronidase activity led to an increase in high molecular weight hyaluronic acid in cell culture and in mouse tissues, and reduced migration and invasion behavior of breast, prostate, and melanoma cancer cells. Moreover, delphinidin treatment suppressed melanoma metastasis in mice. Our study provides a proof of principle that inh
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Mashup Score: 0Validation of ferroptosis in canine cancer cells to enable comparative oncology and translational medicine - 1 day(s) ago
Ferroptosis is a cell death mechanism that has attracted significant attention as a potential basis for the development of new cancer therapies. Validation of ferroptosis biology in species commonly used in translation and pre-clinical development is a necessary foundation for enabling the advancement of such ferroptosis modulating drugs. Here, we demonstrate that canine cancer cells exhibit sensitivity to a wide range of ferroptosis-inducing perturbations in a manner indistinguishable from human cancer cells, and recapitulate characteristic patterns of ferroptotic response across tumor types seen in the human setting. The foundation provided herein establishes the dog as a relevant efficacy and toxicology model for ferroptosis and creates new opportunities to leverage the canine comparative oncology paradigm to accelerate the development of ferroptosis-inducing drugs for human cancer patients. ### Competing Interest Statement V.S.V. is a co-founder and equity holder of Kojin Therapeut
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Mashup Score: 3The enzyme glutamate-cysteine ligase (GCL) is a target for ferroptosis induction in cancer - 1 day(s) ago
Despite glutathione’s long-recognized role as a major cellular antioxidant and its central role in ferroptosis defense, inhibition of glutathione biosynthetic enzymes has received little attention as a target for the therapeutic induction of ferroptosis. Here, we report that small-molecule inhibition of glutamate-cysteine ligase (GCL), the rate-limiting enzyme of glutathione biosynthesis, selectively and potently kills cancer cells by ferroptosis. We further describe novel GCL inhibitors including KOJ-1 and KOJ-2, compounds with excellent cellular potency and pharmacological properties, representing valuable tools to study the biology of ferroptosis and glutathione. ### Competing Interest Statement V.S.V is a co-founder and equity holder of Kojin Therapeutics. All authors are equity holders of Kojin Therapeutics and are either current or past employees of Kojin Therapeutics. J.K.E, L.F., J.H.J. and V.S.V. are inventors of patents related to ferroptosis and GCL.
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Mashup Score: 3GREMLIN1 disrupts intestinal epithelial-mesenchymal crosstalk to induce a wnt-dependent ectopic stem cell niche via stromal remodelling - 1 day(s) ago
In homeostasis, counterbalanced morphogen signalling gradients along the vertical axis of the intestinal mucosa regulate the fate and function of epithelial and stromal cell compartments. Here, we used a disease-positioned mouse, and human tissue, to explore the consequences of pathological Bone Morphogenetic Protein (BMP) signalling dysregulation on epithelial-mesenchymal interaction. Aberrant pan-epithelial expression of the secreted BMP antagonist GREM1, resulted in ectopic crypt formation with lineage tracing demonstrating the presence of Lgr5(-) stem/progenitor cells. Isolated epithelial cell Grem1 expression had no effect on individual cell fate, indicating an intercompartmental impact of mucosal-wide BMP antagonism. Treatment with a novel anti-Grem1 antibody abrogated the polyposis phenotype, and triangulation of specific pathway inhibitors defined a pathological sequence of events, with wnt-ligand dependent ectopic stem cell niches formed through stromal remodelling following B
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Mashup Score: 11
Pancreatic ductal adenocarcinoma (PDAC) contains an extensive stroma that modulates response to therapy, contributing to the dismal prognosis associated with this cancer. Evidence suggests that the stromal composition of PDAC is shaped by mutations within malignant cells; however, most pre-clinical models of PDAC are driven by KrasG12D and mutant Trp53 and have not assessed the contribution of other known oncogenic drivers, including KRASG12V and alterations in CDKN2A and SMAD4. To increase understanding of malignant cell-stroma crosstalk in PDAC, we analyzed Trp53-mutant mouse models driven by KrasG12D or KrasG12V in which Smad4 was wild-type or deleted. KrasG12D; Smad4-deleted PDAC developed a fibro-inflammatory rich stroma with increased JAK/STAT malignant cell signaling and an enhanced therapeutic response to JAK/STAT inhibition. In stark contrast, the stroma of Smad4-deleted KrasG12V PDAC was differently altered, and the malignant compartment lacked JAK/STAT signaling dependency.
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Mashup Score: 4Receptor binding and tissue architecture explain the morphogen local-to-global mobility transition - 1 day(s) ago
Morphogens are intercellular signaling molecules providing spatial information to cells in developing tissues to coordinate cell fate decisions. The spatial information is encoded within long-ranged concentration gradients of the morphogen. Direct measurement of morphogen dynamics in a range of systems suggests that local and global diffusion coefficients can differ by orders of magnitude. Further, local diffusivity can be large, which would potentially abolish any concentration gradient rapidly. Such observations have led to alternative transport models being proposed, including transcytosis and cytonemes. Here, we show that accounting for tissue architecture combined with receptor binding is sufficient to hinder the diffusive dynamics of morphogens, leading to an order of magnitude decrease in the effective diffusion coefficient from local to global scales. In particular, we built a realistic in silico architecture of the extracellular spaces of the zebrafish brain using light and el
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Viromes of Antarctic fish resembles the diversity found at lower latitudes https://t.co/W6y1dr21fI #bioRxiv