The gathering storm: optimizing management of coastal ecosystems in the face of a climate-driven threat

© The Author(s) 2019. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: [email protected]. BACKGROUND: The combination of rising sea levels and increased likelihood of extreme storm events poses a major threat to our coastlines and as a result, many ecosystems recognized and valued for their important contribution to coastal defence face increased damage from erosion and flooding. Nevertheless, only recently have we begun to examine how plant species and communities, respond to, and recover from, the many disturbances associated with storm events. SCOPE: We review how the threats posed by a combination of sea level rise and storms affects coastal sub-, inter- and supra-tidal plant communities. We consider ecophysiological impacts at the level of the individual plant, but also how ecological interactions at the community level, and responses at landscape scale, inform our understanding of how and why an increasing frequency and intensity of storm damage are vital to effective coastal management. While noting how research is centred on the impact of hurricanes in the US Gulf region, we take a global perspective and consider how ecosystems worldwide (e.g. seagrass, kelp forests, sand dunes, saltmarsh and mangroves) respond to storm damage and contribute to coastal defence. CONCLUSIONS: The threats posed by storms to coastal plant communities are undoubtedly severe, but, beyond this obvious conclusion, we highlight four research priority areas. These call for studies focusing on (1) how storm disturbance affects plant reproduction and recruitment; (2) plant response to the multiple stressors associated with anthropogenic climate change and storm events; (3) the role of ecosystem-level interactions in dictating post-disturbance recovery; and (4) models and long-term monitoring to better predict where and how storms and other climate change-driven phenomena impact coastal ecosystems and services. In so doing, we argue how plant scientists must work with geomorphologists and environmental agencies to protect the unique biodiversity and pivotal contribution to coastal defence delivered by maritime plant communities

The pestivirus N terminal protease N(pro) redistributes to mitochondria and peroxisomes suggesting new sites for regulation of IRF3 by N(pro.)

The N-terminal protease of pestiviruses, N(pro) is a unique viral protein, both because it is a distinct autoprotease that cleaves itself from the following polyprotein chain, and also because it binds and inactivates IRF3, a central regulator of interferon production. An important question remains the role of N(pro) in the inhibition of apoptosis. In this study, apoptotic signals induced by staurosporine, interferon, double stranded RNA, sodium arsenate and hydrogen peroxide were inhibited by expression of wild type N(pro), but not by mutant protein N(pro) C112R, which we show is less efficient at promoting degradation of IRF3, and led to the conclusion that N(pro) inhibits the stress-induced intrinsic mitochondrial pathway through inhibition of IRF3-dependent Bax activation. Both expression of N(pro) and infection with Bovine Viral Diarrhea Virus (BVDV) prevented Bax redistribution and mitochondrial fragmentation. Given the role played by signaling platforms during IRF3 activation, we have studied the subcellular distribution of N(pro) and we show that, in common with many other viral proteins, N(pro) targets mitochondria to inhibit apoptosis in response to cell stress. N(pro) itself not only relocated to mitochondria but in addition, both N(pro) and IRF3 associated with peroxisomes, with over 85% of N(pro) puncta co-distributing with PMP70, a marker for peroxisomes. In addition, peroxisomes containing N(pro) and IRF3 associated with ubiquitin. IRF3 was degraded, whereas N(pro) accumulated in response to cell stress. These results implicate mitochondria and peroxisomes as new sites for IRF3 regulation by N(pro), and highlight the role of these organelles in the anti-viral pathway

A mechanism for the inhibition of DNA-PK-mediated DNA sensing by a virus

The innate immune system is critical in the response to infection by pathogens and it is activated by pattern recognition receptors (PRRs) binding to pathogen associated molecular patterns (PAMPs). During viral infection, the direct recognition of the viral nucleic acids, such as the genomes of DNA viruses, is very important for activation of innate immunity. Recently, DNA-dependent protein kinase (DNA-PK), a heterotrimeric complex consisting of the Ku70/Ku80 heterodimer and the catalytic subunit DNA-PKcs was identified as a cytoplasmic PRR for DNA that is important for the innate immune response to intracellular DNA and DNA virus infection. Here we show that vaccinia virus (VACV) has evolved to inhibit this function of DNA-PK by expression of a highly conserved protein called C16, which was known to contribute to virulence but by an unknown mechanism. Data presented show that C16 binds directly to the Ku heterodimer and thereby inhibits the innate immune response to DNA in fibroblasts, characterised by the decreased production of cytokines and chemokines. Mechanistically, C16 acts by blocking DNA-PK binding to DNA, which correlates with reduced DNA-PK-dependent DNA sensing. The C-terminal region of C16 is sufficient for binding Ku and this activity is conserved in the variola virus (VARV) orthologue of C16. In contrast, deletion of 5 amino acids in this domain is enough to knockout this function from the attenuated vaccine strain modified vaccinia virus Ankara (MVA). In vivo a VACV mutant lacking C16 induced higher levels of cytokines and chemokines early after infection compared to control viruses, confirming the role of this virulence factor in attenuating the innate immune response. Overall this study describes the inhibition of DNA-PK-dependent DNA sensing by a poxvirus protein, adding to the evidence that DNA-PK is a critical component of innate immunity to DNA viruses

Protein kinase A-mediated CREB phosphorylation is an oxidant-induced survival pathway in alveolar type II cells

Oxidant stress plays a role in the pathogenesis of pulmonary diseases, including fibrotic lung disease and cancer. We previously found that hydrogen peroxide (H2O2) initiates an increase in Ca2+/cAMP-response element binding protein (CREB) phosphorylation in C10 alveolar type II cells that requires activation of extracellular regulated kinases 1/2 (ERK1/2). Here, we investigated the role of crosstalk between protein kinase A (PKA) and epidermal growth factor receptor (EGFR) in oxidant-induced signaling to ERK1/2 and CREB in C10 cells. Application of H2O2 increased nuclear accumulation of PKA, and inhibition of PKA with H89 reduced oxidant-mediated phosphorylation of both CREB and ERK1/2. Single cell measurements of cAMP and redox status, using a FRET-based biosensor and a redox-sensitive GFP, respectively, indicated that H2O2 increases production of cAMP that correlates with redox state. Inhibition of EGFR activity decreased both H2O2-induced CREB phosphorylation and translocation of PKA to the nucleus, suggesting that crosstalk between PKA and EGFR underlies the oxidant-induced CREB response. Furthermore, knockdown of CREB expression using siRNA led to a decrease in bcl-2 and an increase in oxidant-induced apoptosis. Together these data reveal a novel role for crosstalk between PKA, ERK1/2 and CREB that mediates cell survival during oxidant stress

The Photodynamic Effect of Different Size ZnO Nanoparticles on Cancer Cell Proliferation In Vitro

Nanomaterials have widely been used in the field of biological and biomedicine, such as tissue imaging, diagnosis and cancer therapy. In this study, we explored the cytotoxicity and photodynamic effect of different-sized ZnO nanoparticles to target cells. Our observations demonstrated that ZnO nanoparticles exerted dose-dependent and time-dependent cytotoxicity for cancer cells like hepatocellular carcinoma SMMC-7721 cells in vitro. Meanwhile, it was observed that UV irradiation could enhance the suppression ability of ZnO nanoparticles on cancer cells proliferation, and these effects were in the size-dependent manner. Furthermore, when ZnO nanoparticles combined with daunorubicin, the related cytotoxicity of anticancer agents on cancer cells was evidently enhanced, suggesting that ZnO nanoparticles could play an important role in drug delivery. This may offer the possibility of the great potential and promising applications of the ZnO nanoparticles in clinical and biomedical areas like photodynamic cancer therapy and others

Synergistic Effect of Functionalized Nickel Nanoparticles and Quercetin on Inhibition of the SMMC-7721 Cells Proliferation

The effect of functionalized nickel (Ni) nanoparticles capped with positively charged tetraheptylammonium on cellular uptake of drug quercetin into hepatocellular carcinoma cells (SMMC-7721) has been explored in this study via microscopy and electrochemical characterization as well as MTT assay. Meanwhile, the influence of Ni nanoparticles and/or quercetin on cell proliferation has been further evaluated by the real-time cell electronic sensing (RT-CES) study. Our observations indicate that Ni nanoparticles could efficiently improve the permeability of cancer cell membrane, and remarkably enhance the accumulation of quercetin in SMMC-7721 cells, suggesting that Ni nanoparticles and quercetin would facilitate the synergistic effect on inhibiting proliferation of cancer cells

An anthropogenic habitat facilitates the establishment of non-native birds by providing underexploited resources

Anthropogenic modification of habitats may reduce the resources available for native species, leading to population declines and extinction. These same habitats often have the highest richness of non-native species. This pattern may be explained if recently human-modified habitats provide novel resources that are more accessible to non-native species than native species. Using non-native birds in the Iberian Peninsula as a case study, we conduct a large-scale study to investigate whether non-native species are positively associated with human modified habitats, and to investigate whether this positive association may be driven by the presence of resources that are not fully exploited by native species. We do this by comparing the functional diversity and resource use of native and non-native bird communities in a recently human-modified habitat (rice fields) and in more traditional habitats in the Iberian Peninsula. The functional diversity of native bird communities was lower in rice fields, but non-native birds were positively associated with rice fields and plugged this gap. Differences in resource use between native and non-native species allowed non-native species to exploit resources that were plentiful in rice fields, supporting the role of underexploited resources in driving the positive association of non-native birds with rice fields. Our results provide a potential mechanism explaining the positive association of non-native species with anthropogenic habitats, and further work is needed to test if this applies more generally

Ligand Mobility Modulates Immunological Synapse Formation and T Cell Activation

T cell receptor (TCR) engagement induces clustering and recruitment to the plasma membrane of many signaling molecules, including the protein tyrosine kinase zeta-chain associated protein of 70 kDa (ZAP70) and the adaptor SH2 domain-containing leukocyte protein of 76 kDa (SLP76). This molecular rearrangement results in formation of the immunological synapse (IS), a dynamic protein array that modulates T cell activation. The current study investigates the effects of apparent long-range ligand mobility on T cell signaling activity and IS formation. We formed stimulatory lipid bilayers on glass surfaces from binary lipid mixtures with varied composition, and characterized these surfaces with respect to diffusion coefficient and fluid connectivity. Stimulatory ligands coupled to these surfaces with similar density and orientation showed differences in their ability to activate T cells. On less mobile membranes, central supramolecular activation cluster (cSMAC) formation was delayed and the overall accumulation of CD3ζ at the IS was reduced. Analysis of signaling microcluster (MC) dynamics showed that ZAP70 MCs exhibited faster track velocity and longer trajectories as a function of increased ligand mobility, whereas movement of SLP76 MCs was relatively insensitive to this parameter. Actin retrograde flow was observed on all surfaces, but cell spreading and subsequent cytoskeletal contraction were more pronounced on mobile membranes. Finally, increased tyrosine phosphorylation and persistent elevation of intracellular Ca2+ were observed in cells stimulated on fluid membranes. These results point to ligand mobility as an important parameter in modulating T cell responses

USP18-Based Negative Feedback Control Is Induced by Type I and Type III Interferons and Specifically Inactivates Interferon α Response

Type I interferons (IFN) are cytokines that are rapidly secreted upon microbial infections and regulate all aspects of the immune response. In humans 15 type I IFN subtypes exist, of which IFN α2 and IFN β are used in the clinic for treatment of different pathologies. IFN α2 and IFN β are non redundant in their expression and in their potency to exert specific bioactivities. The more recently identified type III IFNs (3 IFN λ or IL-28/IL-29) bind an unrelated cell-type restricted receptor. Downstream of these two receptor complexes is a shared Jak/Stat pathway. Several mechanisms that contribute to the shut down of the IFN-induced signaling have been described at the molecular level. In particular, it has long been known that type I IFN induces the establishment of a desensitized state. In this work we asked how the IFN-induced desensitization integrates into the network built by the multiple type I IFN subtypes and type III IFNs. We show that priming of cells with either type I IFN or type III IFN interferes with the cell's ability to further respond to all IFN α subtypes. Importantly, primed cells are differentially desensitized in that they retain sensitivity to IFN β. We show that USP18 is necessary and sufficient to induce differential desensitization, by impairing the formation of functional binding sites for IFN α2. Our data highlight a new type of differential between IFNs α and IFN β and underline a cross-talk between type I and type III IFN. This cross-talk could shed light on the reported genetic variation in the IFN λ loci, which has been associated with persistence of hepatitis C virus and patient's response to IFN α2 therapy

Mitochondrial and Plasma Membrane Pools of Stomatin-Like Protein 2 Coalesce at the Immunological Synapse during T Cell Activation

Stomatin-like protein 2 (SLP-2) is a member of the stomatin – prohibitin – flotillin – HflC/K (SPFH) superfamily. Recent evidence indicates that SLP-2 is involved in the organization of cardiolipin-enriched microdomains in mitochondrial membranes and the regulation of mitochondrial biogenesis and function. In T cells, this role translates into enhanced T cell activation. Although the major pool of SLP-2 is associated with mitochondria, we show here that there is an additional pool of SLP-2 associated with the plasma membrane of T cells. Both plasma membrane-associated and mitochondria-associated pools of SLP-2 coalesce at the immunological synapse (IS) upon T cell activation. SLP-2 is not required for formation of IS nor for the re-localization of mitochondria to the IS because SLP-2-deficient T cells showed normal re-localization of these organelles in response to T cell activation. Interestingly, upon T cell activation, we found the surface pool of SLP-2 mostly excluded from the central supramolecular activation complex, and enriched in the peripheral area of the IS where signalling TCR microclusters are located. Based on these results, we propose that SLP-2 facilitates the compartmentalization not only of mitochondrial membranes but also of the plasma membrane into functional microdomains. In this latter location, SLP-2 may facilitate the optimal assembly of TCR signalosome components. Our data also suggest that there may be a net exchange of membrane material between mitochondria and plasma membrane, explaining the presence of some mitochondrial proteins in the plasma membrane