Seagrass can mitigate negative ocean acidification effects on calcifying algae

The ultimate effect that ocean acidification (OA) and warming will have on the physiology of calcifying algae is still largely uncertain. Responses depend on the complex interactions between seawater chemistry, global/local stressors and species-specific physiologies. There is a significant gap regarding the effect that metabolic interactions between coexisting species may have on local seawater chemistry and the concurrent effect of OA. Here, we manipulated CO2 and temperature to evaluate the physiological responses of two common photoautotrophs from shallow tropical marine coastal ecosystems in Brazil: the calcifying alga Halimeda cuneata, and the seagrass Halodule wrightii. We tested whether or not seagrass presence can influence the calcification rate of a widespread and abundant species of Halimeda under OA and warming. Our results demonstrate that under elevated CO2, the high photosynthetic rates of H. wrightii contribute to raise H. cuneata calcification more than two-fold and thus we suggest that H. cuneata populations coexisting with H. wrightii may have a higher resilience to OA conditions. This conclusion supports the more general hypothesis that, in coastal and shallow reef environments, the metabolic interactions between calcifying and non-calcifying organisms are instrumental in providing refuge against OA effects and increasing the resilience of the more OA-susceptible species.E.B. would like to thank the Coordenação de Aperfeiçoamento de Pessoas de Nível Superior (CAPES) for Masters funding. Funding for this project came from the Synergism grant (CNPq 407365/2013-3). We extend our thanks to the Brazil-based Projeto Coral Vivo and its sponsor PetroBras Ambiental for providing the Marine Mesocosm structure and experimental assistance.info:eu-repo/semantics/publishedVersio

Potentiating Oncolytic Virus-Induced Immune-Mediated Tumor Cell Killing Using Histone Deacetylase Inhibition

A clinical oncolytic herpes simplex virus (HSV) encoding granulocyte-macrophage colony-stimulating factor (GMCSF), talimogene laherparepvec, causes regression of injected and non-injected melanoma lesions in patients and is now licensed for clinical use in advanced melanoma. To date, limited data are available regarding the mechanisms of human anti-tumor immune priming, an improved understanding of which could inform the development of future combination strategies with improved efficacy. This study addressed direct oncolysis and innate and adaptive human immune-mediated effects of a closely related HSV encoding GM-CSF (HSVGM-CSF) alone and in combination with histone deacetylase inhibition. We found that HSVGM-CSF supported activation of antimelanoma immunity via monocyte-mediated type I interferon production, which activates NK cells, and viral maturation of immature dendritic cells (iDCs) into potent antigen-presenting cells for cytotoxic T lymphocyte (CTL) priming. Addition of the histone deacetylase inhibitor valproic acid (VPA) to HSVGM-CSF treatment of tumor cells increased viral replication, viral GM-CSF production, and oncolysis and augmented the development of anti-tumor immunity. Mechanistically, VPA increased expression of activating ligands for NK cell recognition and induced expression of tumor-associated antigens, supporting innate NK cell killing and CTL priming. These data support the clinical combination of talimogene laherparepvec with histone deacetylase inhibition to enhance oncolysis and anti-tumor immunity

High and Low Molecular Weight Hyaluronic Acid Differentially Regulate Human Fibrocyte Differentiation

Following tissue injury, monocytes can enter the tissue and differentiate into fibroblast-like cells called fibrocytes, but little is known about what regulates this differentiation. Extracellular matrix contains high molecular weight hyaluronic acid (HMWHA; ∼2×10(6) Da). During injury, HMWHA breaks down to low molecular weight hyaluronic acid (LMWHA; ∼0.8-8×10(5) Da).In this report, we show that HMWHA potentiates the differentiation of human monocytes into fibrocytes, while LMWHA inhibits fibrocyte differentiation. Digestion of HMWHA with hyaluronidase produces small hyaluronic acid fragments, and these fragments inhibit fibrocyte differentiation. Monocytes internalize HMWHA and LMWHA equally well, suggesting that the opposing effects on fibrocyte differentiation are not due to differential internalization of HMWHA or LMWHA. Adding HMWHA to PBMC does not appear to affect the levels of the hyaluronic acid receptor CD44, whereas adding LMWHA decreases CD44 levels. The addition of anti-CD44 antibodies potentiates fibrocyte differentiation, suggesting that CD44 mediates at least some of the effect of hyaluronic acid on fibrocyte differentiation. The fibrocyte differentiation-inhibiting factor serum amyloid P (SAP) inhibits HMWHA-induced fibrocyte differentiation and potentiates LMWHA-induced inhibition. Conversely, LMWHA inhibits the ability of HMWHA, interleukin-4 (IL-4), or interleukin-13 (IL-13) to promote fibrocyte differentiation.We hypothesize that hyaluronic acid signals at least in part through CD44 to regulate fibrocyte differentiation, with a dominance hierarchy of SAP>LMWHA≥HMWHA>IL-4 or IL-13

Systematic review of the epidemiological evidence comparing lung cancer risk in smokers of mentholated and unmentholated cigarettes

<p>Abstract</p> <p>Background</p> <p>US mentholated cigarette sales have increased considerably over 50 years. Preference for mentholated cigarettes is markedly higher in Black people. While menthol itself is not genotoxic or carcinogenic, its acute respiratory effects might affect inhalation of cigarette smoke. This possibility seems consistent with the higher lung cancer risk in Black men, despite Black people smoking less and starting smoking later than White people. Despite experimental data suggesting similar carcinogenicity of mentholated and non-mentholated cigarettes, the lack of convincing evidence that mentholation increases puffing, inhalation or smoke uptake, and the similarity of lung cancer rates in Black and White females, a review of cigarette mentholation and lung cancer is timely given current regulatory interest in the topic.</p> <p>Methods</p> <p>Epidemiological studies comparing lung cancer risk in mentholated and non-mentholated cigarette smokers were identified from MedLine and other sources. Study details were extracted and strengths and weaknesses assessed. Relative risk estimates were extracted, or derived, for ever mentholated use and for long-term use, overall and by gender, race, and current/ever smoking, and meta-analyses conducted.</p> <p>Results</p> <p>Eight generally good quality studies were identified, with valid cases and controls, and appropriate adjustment for age, gender, race and smoking. The studies afforded good power to detect possible effects. However, only one study presented results by histological type, none adjusted for occupation or diet, and some provided no results by length of mentholated cigarette use.</p> <p>The data do not suggest any effect of mentholation on lung cancer risk. Adjusted relative risk estimates for ever use vary from 0.81 to 1.12, giving a combined estimate of 0.93 (95% confidence interval 0.84-1.02, n = 8), with no increase in males (1.01, 0.84-1.22, n = 5), females (0.80, 0.67-0.95, n = 5), White people (0.87, 0.75-1.03, n = 4) or Black people (0.90, 0.73-1.10, n = 4). Estimates for current and ever smokers are similar. The combined estimate for long-term use (0.95, 0.80-1.13, n = 4) again suggests no effect of mentholation.</p> <p>Conclusion</p> <p>Higher lung cancer rates in Black males cannot be due to their greater preference for mentholated cigarettes. While some study weaknesses exist, the epidemiological evidence is consistent with mentholation having no effect on the lung carcinogenicity of cigarettes.</p

Developmental Stability Covaries with Genome-Wide and Single-Locus Heterozygosity in House Sparrows

Fluctuating asymmetry (FA), a measure of developmental instability, has been hypothesized to increase with genetic stress. Despite numerous studies providing empirical evidence for associations between FA and genome-wide properties such as multi-locus heterozygosity, support for single-locus effects remains scant. Here we test if, and to what extent, FA co-varies with single- and multilocus markers of genetic diversity in house sparrow (Passer domesticus) populations along an urban gradient. In line with theoretical expectations, FA was inversely correlated with genetic diversity estimated at genome level. However, this relationship was largely driven by variation at a single key locus. Contrary to our expectations, relationships between FA and genetic diversity were not stronger in individuals from urban populations that experience higher nutritional stress. We conclude that loss of genetic diversity adversely affects developmental stability in P. domesticus, and more generally, that the molecular basis of developmental stability may involve complex interactions between local and genome-wide effects. Further study on the relative effects of single-locus and genome-wide effects on the developmental stability of populations with different genetic properties is therefore needed

Effect of Inorganic and Organic Carbon Enrichments (DIC and DOC) on the Photosynthesis and Calcification Rates of Two Calcifying Green Algae from a Caribbean Reef Lagoon

Coral reefs worldwide are affected by increasing dissolved inorganic carbon (DIC) and organic carbon (DOC) concentrations due to ocean acidification (OA) and coastal eutrophication. These two stressors can occur simultaneously, particularly in near-shore reef environments with increasing anthropogenic pressure. However, experimental studies on how elevated DIC and DOC interact are scarce and fundamental to understanding potential synergistic effects and foreseeing future changes in coral reef function. Using an open mesocosm experiment, the present study investigated the impact of elevated DIC (pHNBS: 8.2 and 7.8; pCO2: 377 and 1076 ?atm) and DOC (added as 833 ?mol L-1 of glucose) on calcification and photosynthesis rates of two common calcifying green algae, Halimeda incrassata and Udotea flabellum, in a shallow reef environment. Our results revealed that under elevated DIC, algal photosynthesis decreased similarly for both species, but calcification was more affected in H. incrassata, which also showed carbonate dissolution rates. Elevated DOC reduced photosynthesis and calcification rates in H. incrassata, while in U. flabellum photosynthesis was unaffected and thalus calcification was severely impaired. The combined treatment showed an antagonistic effect of elevated DIC and DOC on the photosynthesis and calcification rates of H. incrassata, and an additive effect in U. flabellum. We conclude that the dominant sand dweller H. incrassata is more negatively affected by both DIC and DOC enrichments, but that their impact could be mitigated when they occur simultaneously. In contrast, U. flabellum can be less affected in coastal eutrophic waters by elevated DIC, but its contribution to reef carbonate sediment production could be further reduced. Accordingly, while the capacity of environmental eutrophication to exacerbate the impact of OA on algal-derived carbonate sand production seems to be species-specific, significant reductions can be expected under future OA scenarios, with important consequences for beach erosion and coastal sediment dynamics

Biodiversity and Health: Implications for Conservation

The human health and well-being benefits of contact with nature are becoming increasingly recognised and well understood, yet the implications of nature experiences for biodiversity conservation are far less clear. Theoretically, there are two plausible pathways that could lead to positive conservation outcomes. The first is a direct win-win scenario where biodiverse areas of high conservation value are also disproportionately beneficial to human health and well-being, meaning that the two sets of objectives can be simultaneously and directly achieved, as long as such green spaces are safeguarded appropriately. The second is that experiencing nature can stimulate people’s interest in biodiversity, concern for its fate, and willingness to take action to protect it, therefore generating conservation gains indirectly. To date, the two pathways have rarely been distinguished and scarcely studied. Here we consider how they may potentially operate in practice, while acknowledging that the mechanisms by which biodiversity might underpin human health and well-being benefits are still being determined