Seasonal and microclimatic influences on the ecophysiology of Mediterranean coastal dune plants

The coastal dune environment, due to the complex coast-to-inland gradient, contributes greatly to plant bio- diversity. The ability of plants to withstand the harsh conditions of this habitat leads to a peculiar vegetation profile which may be affected by the natural and artificial degradation of the coast. Given that these disturbances are likely to increase in the future, there is a great interest in increasing the knowledge of resistance mechanisms allowing plants to colonize this stressful environment. Our focus was on physiological stress markers that could be early signals of changes before ecological disturbances become evident. Three representative species of the different dune zones, Achillea maritima, Ammophila arenaria and Helichrysum stoechas were studied during the four seasons. Winter and summer were confirmed as the most critical seasons with different levels of stress depending on the coast profile where plants grew. The shoreline-inland gradient of stress conditions was evident only for A. arenaria, whose physiology was negatively affected in foredune during summer and for this reason this species could be a useful indicator of increasingly harsh environmental conditions. Physiological perfor- mances of the studied species changed across the seasons and the occupied niches, in accordance with the respective strategies of resistance

Delivery of a Salmonella Typhi Exotoxin from a Host Intracellular Compartment

SummarySalmonella Typhi, an exclusive human pathogen and the cause of typhoid fever, expresses a functional cytolethal distending toxin for which only the active subunit, CdtB, has been identified. Here, we show that PltA and PltB, which are encoded in the same pathogenicity islet as cdtB, associate with CdtB to form a multipartite toxin. PltA and PltB are homologs of components of the pertussis toxin, including its ADP-ribosyl transferase subunit. We also show that PltA and PltB are required for the delivery of CdtB from an intracellular compartment to target cells via autocrine and paracrine pathways. We hypothesize that this toxin, which we have named “typhoid toxin,” and its delivery mechanism may contribute to S. Typhi's unique virulence properties

A Small-Scale shRNA Screen in Primary Mouse Macrophages Identifies a Role for the Rab GTPase Rab1b in Controlling Salmonella Typhi Growth

Acknowledgments We are very grateful to Leigh Knodler for her generous gift of P22 phages from a S. Typhimurium glmS::Cm::mCherry strain. We thank the Microscopy and Histology Core Facility, the Centre for Genome-Enabled Biology and Medicine (CGEBM), the Iain Fraser Cytometry Centre and the qPCR Facility (University of Aberdeen) for their support and assistance in this work. We thank members of the Spanò/Baldassarre laboratory for their feedback throughout this project. The content of this manuscript has been posted as a preprint on bioRxiv (Solano-Collado et al., 2020). Funding This work was supported by the European Union’s Horizon 2020 research and innovation program Marie Skłodowska-Curie Fellowship (706040_KILLINGTYPHI) to VS-C, the Wellcome Trust (Seed Award 109680/Z/15/Z), the European Union’s Horizon 2020 ERC consolidator award (2016-726152-TYPHI), the BBSRC (BB/N017854/1) and Tenovus Scotland (G14/19) to SS.Peer reviewedPublisher PD

VARP and Rab9 are dispensable for the Rab32/BLOC-3 dependent salmonella killing in mouse macrophages

Salmonella enterica serovar Typhi (S. Typhi) is the causative agent of typhoid fever, a disease that kills an estimated 200,000 people annually. Previously, we discovered an antimicrobial pathway dependent on Rab32 and BLOC-3 (BRAM) that is critical to kill S. Typhi in murine macrophages. The BLOC-3 complex is comprised of the two sub-units HPS1 and HPS4 and exhibits guanine-nucleotide exchange factor (GEF) activity to Rab32. In melanocytes, Rab9 has been shown to interact with HPS4 and RUTBC1, a Rab32 GTPase activating (GAP) protein, and regulate the Rab32-mediated melanosome biogenesis. Intriguingly, Rab9-deficient melanocytes exhibit hypopigmentation, a similar phenotype to Rab32 or BLOC-3 deficient melanocytes. Additionally, VPS9-ankyrin-repeat-protein (VARP) has been shown to regulate melanocytic enzyme trafficking into the melanosomes through interaction with Rab32. Although Rab32, Rab9 and VARP are a part of melanogenesis in melanocytes, whether Rab9 and VARP are required for the BRAM mediated killing in macrophages is currently unknown. Here we showed that HPS4 is recruited to the Salmonella-containing vacuoles (SCV) and over-expression of BLOC-3 significantly increased Rab32-positive bacteria vacuoles. We found that SCV acquire Rab9, however over-expressing Rab9 did not change HPS4 localisation on bacteria vacuoles. Importantly, we used shRNA to knock-down Rab9 and VARP in macrophages and showed that these proteins are dispensable for Rab32 recruitment to the SCV. Furthermore, we assessed the survival of S. Typhimurium in macrophages deficient for Rab9 or VARP and demonstrated that these proteins are not essential for BRAM pathway-dependent killing

A 14-3-3γ dimer-based scaffold bridges CtBP1-S/BARS to PI(4)KIIIβ to regulate post-Golgi carrier formation

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The Rab32/BLOC-3-dependent pathway mediates host defense against different pathogens in human macrophages.

Macrophages provide a first line of defense against microorganisms, and while some mechanisms to kill pathogens such as the oxidative burst are well described, others are still undefined or unknown. Here, we report that the Rab32 guanosine triphosphatase and its guanine nucleotide exchange factor BLOC-3 (biogenesis of lysosome-related organelles complex-3) are central components of a trafficking pathway that controls both bacterial and fungal intracellular pathogens. This host-defense mechanism is active in both human and murine macrophages and is independent of well-known antimicrobial mechanisms such as the NADPH (reduced form of nicotinamide adenine dinucleotide phosphate)-dependent oxidative burst, production of nitric oxide, and antimicrobial peptides. To survive in human macrophages, Salmonella Typhi actively counteracts the Rab32/BLOC-3 pathway through its Salmonella pathogenicity island-1-encoded type III secretion system. These findings demonstrate that the Rab32/BLOC-3 pathway is a novel and universal host-defense pathway and protects mammalian species from various pathogens

EtG Quantification in Hair and Different Reference Cut-Offs in Relation to Various Pathologies: A Scoping Review

CC BY 4.0Ethyl glucuronide (EtG) is a non-volatile, non-oxidative, hydrophilic, and stable ethanol phase II metabolite. EtG is produced through ethanol glucuronidation by UDP-glucuronosyltransferase (UGT), a phase II enzyme. EtG can be extracted from different biological matrices, including keratin ones, such as hair or nails. The purpose of this scoping review is to describe the relationship between EtG levels in hair and some of the most common and frequent pathological conditions and verify whether different reference cut-offs in relation to various pathologies have been identified in the scientific literature. In fact, in-depth knowledge of the influence of pathologies, such as diabetes mellitus, hepatic and renal dysfunction, on EtG production and its storage in keratin matrices would allow a more appropriate interpretation of obtained data and rule out false positives or false negatives. This scoping review is based on bibliographic research carried out on PubMed regarding the quantification of EtG in hair of subjects affected by different pathological conditions. According to the scientific literature, the main and most common pathologies that can affect the concentration of EtG in hair are liver and kidney diseases and diabetes. The EtG quantification analytical data should be interpreted carefully as they may have a great impact in both forensic and clinical contexts

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements