Impacts of climate change and fisheries on the Celtic Sea ecosystem

Climate change and fisheries have affected marine environments worldwide leading to impacts on ecosystem structure and functioning. However there is clear evidence of spatial variability in the response of these impacts both within and among marine ecosystems. Although several studies have tried to explain the effect of these impacts on marine food webs, it is unclear how they interact, and how they may affect marine ecosystems remains an important unanswered question. This suggests the urgent need for multiple-trophic level and ecosystem-based management approaches to account for both fisheries and climate change impacts at ocean basins across the globe. Marine apex predators, such as seabirds, are vulnerable to the effects of both climate and fishing impacts, and can be used as reliable and sensitive bio-indicators of the status of the marine ecosystem. The Celtic Sea ecosystem is a productive shelf region in the Northeast Atlantic. It is characterized by high fish and invertebrate biodiversity. In addition, internationally important numbers of seabirds, such as Northern gannet Morus bassanus (L.), Manx shearwater Puffinus puffinus (B.), Common guillemot Uria aalge (P.) and Black-legged kittiwake Rissa tridactyla (L.), breed along the Celtic Sea coasts. In recent years, fisheries from across Europe have intensively exploited the Celtic Sea, leading to changes in stock structure. Moreover, the increase in annual average Sea Surface Temperature by 0.67 oC over the past two decades has altered the composition of plankton communities. These impacts, independently and in tandem, are likely to have had dramatic effects upon the Celtic Sea food web emphasizing the need to enhance our understanding of this important marine ecosystem. In this thesis the effects of climate change and fisheries on the Celtic Sea pelagic food web are evaluated, in particular focussing on the response of seabird populations. This is in part because of recent declines in the breeding success of many seabird colonies in the northeast Atlantic, particularly around the North Sea. Long-term data across four trophic levels (phytoplankton, zooplankton, mid-trophic level fish and seabirds) and different modelling approaches are used to determine factors influencing seabird productivity at different geographical scales. First, I review the direct and indirect effects of climate change and fisheries upon marine ecosystems, as well as their impacts upon marine birds. Second, I use data collected during 1986-2007 from a single seabird colony, across four trophic levels, to investigate long-term direct and indirect climate effects. The results suggest only a weak climate signal in the Celtic Sea, and this is only evident between mid-trophic level fish and certain species of seabird. Third, a similar multi-trophic level approach across three nearby regions in the southwest UK (Irish Sea, Celtic Sea, and English Channel) reveal no evidence of a bottom-up signal during the period 1991-2007. These findings are in contrast with the nearby North Sea region, where a strong bottom-up effect was found to affect seabird populations, highlighting the importance of regional-based studies across multiple trophic levels. Finally, to provide a more complete picture of the Celtic Sea, and how it might respond to changes in fisheries management and climatic variation, I use the complex tropho-dynamic ecosystem model Ecopath with Ecosim. The main focus is on how seabird biomass changes in response to the application of different fisheries regimes likely to be implemented under forthcoming reforms to the Common Fisheries Policy (e.g. the application of quotas and discard bans), as well as future climate change scenarios, in order to provide guideline support for resource management and seabird conservation in the Celtic Sea. The results suggest that some seabird guilds (gulls and some other scavengers) may be negatively affected by a reduction in discards, while other species (offshore divers) will benefit from a decrease in the fishing of pelagic fish species. Climate change is likely to have a negative impact across all trophic levels with a strong negative impact upon seabird populations. Therefore seabirds are likely to show species-specific responses to both climate variation (bottom-up effect) and changes in fishing practices, in particular our findings suggest that for some species climate may outweigh the fisheries impacts even when fisheries pressure is reduced by 50%. In summary, this study suggests that despite the generally negative impact of climate described for some regions in the Northeast Atlantic, the Celtic Sea ecosystem seems to be more resilient. However, both climate and fisheries and the interactions between these factors should be taken into account in the formulation of future management plans for the Celtic Sea ecosystem. The use of multiple-trophic level and ecosystem-based approaches over multiple spatial and temporal scales has helped to elucidate possible trophic mechanisms that are the response to future fishing and climate impacts in the Celtic Sea. The results of this study could have implications for both management plans and conservation policy.Natural Englan

Gender Differences in Post-Traumatic Stress

Acute stress can trigger cardiovascular events and disease. The earthquake is an \u2018\u2018ideal\u2019\u2019 natural experiment for acute and chronic stress, with impact mainly on the cardiovascular system. On May 20th and 29th, 2012, two earthquakes of magnitude 5.9! to 6.4! on the Richter scale, hit the province of Modena and Reggio Emilia, an area of the north-center of Italy never considered at seismic risk. The purpose of our study was to assess whether there were gender-specific differences in stress-induced incidence of cardiovascular events and age of patients who arrived at the Emergency Departments (ED) of the three main teaching hospitals of the University of Modena and Reggio Emilia. Global access of patients, divided in relation to age, gender, and diagnosis was compared with that one detected in the same departments and in the same interval of time in 2010. The data collected were relative to consecutive cases derived by retrospective chart and acute cardiovascular events were classified according to ICD-9 (International Classification of Diseases, ninth revision). A total of 1,401 accesses were recorded in the year of earthquake versus 530 in 2010 ( p \ua3 0.05), with no statistically significant differences in number of cases and mean age in relation to gender, despite the number of women exceeded that of men in 2012 (730 vs. 671); the opposite occurred, in 2010 (328 vs. 202). The gender analysis of 2012 showed a prevalence of acute coronary syndromes (ACSs 177 vs. 73, p \ua3 0.03) in men, whereas women presented more strokes and transient ischemic attacks (TIAs) (90 vs. 94, p \ua3 0.05), atrial fibrillation (120 vs. 49, p \ua3 0.05), deep venous thrombosis and pulmonary embolism (DVT/PE; 64 vs. 9, p \ua3 0.05), panic attacks (124 vs. 26, p \ua3 0.03), aspecific chest pain (122 vs. 18, p \ua3 0.05), TakoTsubo cardiomyopathy (10 vs. 0, p \ua3 0.05), and DVT/PE (61 vs. 3, p \ua3 0.03). The gender analysis of 2010 showed no difference in number of accesses and age, with higher incidence of ACS in men (130 vs. 34, p \ua3 0.05) and aspecific chest pain in women (42 vs. 5, p \ua3 0.05). The analysis between 2012 and the standard period (2010) showed women recurring to ED in larger number with more panic attacks (124 vs. 3, p \ua3 0.01), more atrial fibrillation (120 vs. 40, p \ua3 0.01) and, as a possible consequence, more TIAs and strokes (190 vs. 25, p \ua3 0.005), more TakoTsubo (10 vs. 0, p \ua3 0.05), DVT/PE (61 vs. 3, p \ua3 0.05), and aspecific chest pain (122 vs. 5, p \ua3 0.01). The difference between men\u2019s accesses to ED was less striking, but in 2012 men reported more panic attacks (26 vs. none, p \ua3 0.05), more atrial fibrillations, TIAs, and strokes (49 vs. 13, p \ua3 0.05 and 94 vs. 18, p \ua3 0.03). In conclusion, clinical (stress induced) events recorded during and immediately after the 2012 earthquakes were quite different between women and men, although the pathophysiological mechanism was probably the same, consisting acute sympathetic nervous activation, with elevation of blood pressure and heart rate, endothelial dysfunction, platelet and hemostatic activation, increased blood viscosity, and hypercoagulation. Women, in our observation, appeared to be more sensitive and responsive to acute stress, although men also appeared to suffer from stress effects when compared with a standard period, which, nevertheless, reflects in our population the most common epidemiology of gender difference in ED accesses for cardiovascular events

Design and synthesis of high affinity compounds for the Hsp60 expression control in carcinogenic processes

First observed in cells exposed to high temperatures, Heat shock proteins (Hsps) are nowadays considered the most important cell “chaperone” complexes over-­expressed in response to a number of cell stress stimuli.1 The chaperone activity is the main function of the eukaryotic Heat shock protein 60 kDa (Hsp60), involved in the capture and refold of unfolded or misfolded proteins. Additional roles in signal transduction,2 senescence activation3 and apoptosis4 have been ascribed to cytosolic Hsp60. During the carcinogenIc process, in vivo studies demonstrated increased levels of human Hsp60 in several organs, such as uterine exocervix,5 large bowel,6 and prostate.6 In this context, our study aims to elucidate the structural details of the interaction between Hsp60 and novel designed antagonists able to specifically block this chaperonine. A preliminary virtual screening of 24 million molecules, available in the Zinc database, was carried out on the ATP-­binding site of a bacterial Hsp60 monomer, the coordinates of which were taken from Protein Data Bank (ID: 1WE3), figure 1. Compounds with high affinity were further refined by other in silico protocols previously and successfully applied by us in the study of several biological targets.7The analysis of virtual screening results highlights the N-­{5-­[1H-­imidazol-­4-­yl-­methyl)-­ amino]-­benzofuran-­3-­yl}-­benzamides of type 1 as interesting series for the inhibition of Hsp60 ATP-­binding site. Selected compounds were prepared in excellent yields, following appropriate synthetic pathways. All compounds are currently tested in order to proof they potential anticancer activity as modulator of Hsp60 function in tumor cells

Dinámica espaciotemporal a largo plazo de comunidades de cefalópodos en el mar Mediterráneo

The Mediterranean Sea shows a trend of increasing temperature and decreasing productivity from the western to the eastern basin. In this work we investigate whether this trend is reflected in the cephalopod assemblages found throughout the Mediterranean. Data obtained with bottom trawl surveys carried out during the last 22 years by EU Mediterranean countries were used. In addition to analysing spatial differences in cephalopod assemblages, we also analysed putative temporal changes during the last two decades. For this purpose, the basin was spatially divided into bioregions, the trawling grounds were subdivided into depth strata, and the dataset was split into two time series of 11 years each. All analyses were done using PRIMER software. The species richness did not vary with the longitudinal gradient, though in most bioregions it showed a mild decrease with depth before plummeting in the deepest waters. Cluster analysis revealed four different bathymetric assemblages in all bioregions. Despite the contrasting conditions between basins and the claims of biodiversity loss, our study revealed that spatial and temporal differences during the last two decades were restricted to changes in the relative abundance of species from a common pool of species inhabiting the whole Mediterranean.El mar Mediterráneo muestra un patrón de aumento de la temperatura y disminución de la productividad de la cuenca occidental a la oriental. En este trabajo se investiga si este patrón se refleja en las comunidades de cefalópodos que habitan el Mediterráneo. Se utilizaron datos obtenidos en campañas de arrastre de fondo realizadas durante los últimos 22 años por la mayoría de países mediterráneos de la UE. Junto con el análisis de las diferencias espaciales en las comunidades de cefalópodos, también se analizaron cambios temporales durante las dos últimas décadas. Para ello, la cuenca se dividió espacialmente en diferentes bioregiones, mientras que el conjunto de datos se dividió en dos series temporales de 11 años cada una. Todos los análisis se realizaron utilizando el software PRIMER. La riqueza específica no varió con el gradiente longitudinal, aunque en la mayoría de las bioregiones mostró una leve disminución con la profundidad antes de desplomarse en el estrato más profundo. El análisis cluster reveló cuatro comunidades batimétricas diferentes en todas las bioregiones. A pesar de las contrastadas condiciones ambientales entre las cuencas y las afirmaciones de pérdida de biodiversidad, nuestro estudio reveló que las diferencias espaciales y temporales durante las dos últimas décadas se limitaron a cambios en la abundancia relativa de las especies a partir de un conjunto faunístico común que habita todo el Mediterráneo

Higher Frequency of T-Cell Response to M. tuberculosis Latency Antigen Rv2628 at the Site of Active Tuberculosis Disease than in Peripheral Blood

RATIONALE: Due to the invasive nature of the procedures involved, most studies of Mycobacterium tuberculosis (Mtb)-specific immunity in humans have focused on the periphery rather than the site of active infection, the lung. Recently, antigens associated with Mtb-latency and -dormancy have been described using peripheral blood (PB) cells; however their response in the lung is unknown. The objective of this report was to evaluate, in patients prospectively enrolled with suspected active tuberculosis (TB), whether the latency antigen Rv2628 induces local-specific immune response in bronchoalveolar lavage (BAL) cells compared to PB cells. MATERIAL/METHODS: Among the 41 subjects enrolled, 20 resulted with active TB. Among the 21 without active disease, 9 were defined as subjects with latent TB-infection (LTBI) [Quantiferon TB Gold In-tube positive]. Cytokine responses to Rv2628 were evaluated by enzyme linked immunospot (ELISPOT) assay and flow cytometric (FACS) analysis. RD1-secreted antigen stimulation was used as control. RESULTS: There was a significantly higher frequency of Rv2628- and RD1-specific CD4+ T-cells in the BAL of active TB patients than in PB. However the trend of the response to Rv2628 in subjects with LTBI was higher than in active TB in both PB and BAL, although this difference was not significant. In active TB, Rv2628 and RD1 induced a cytokine-response profile mainly consisting of interferon (IFN)-γ-single-positive over double-IFN-γ/interleukin (IL)-2 T-cells in both PB and BAL. Finally, BAL-specific CD4+ T-cells were mostly effector memory (EM), while peripheral T-cell phenotypes were distributed among naïve, central memory and terminally differentiated effector memory T-cells. CONCLUSIONS: In this observational study, we show that there is a high frequency of specific T-cells for Mtb-latency and RD1-secreted antigens (mostly IFN-γ-single-positive specific T-cells with an EM phenotype) in the BAL of active TB patients. These data may be important for better understanding the pathogenesis of TB in the lung

Metabolic control of DNA methylation in naive pluripotent cells.

Naive epiblast and embryonic stem cells (ESCs) give rise to all cells of adults. Such developmental plasticity is associated with genome hypomethylation. Here, we show that LIF-Stat3 signaling induces genomic hypomethylation via metabolic reconfiguration. Stat3-/- ESCs show decreased α-ketoglutarate production from glutamine, leading to increased Dnmt3a and Dnmt3b expression and DNA methylation. Notably, genome methylation is dynamically controlled through modulation of α-ketoglutarate availability or Stat3 activation in mitochondria. Alpha-ketoglutarate links metabolism to the epigenome by reducing the expression of Otx2 and its targets Dnmt3a and Dnmt3b. Genetic inactivation of Otx2 or Dnmt3a and Dnmt3b results in genomic hypomethylation even in the absence of active LIF-Stat3. Stat3-/- ESCs show increased methylation at imprinting control regions and altered expression of cognate transcripts. Single-cell analyses of Stat3-/- embryos confirmed the dysregulated expression of Otx2, Dnmt3a and Dnmt3b as well as imprinted genes. Several cancers display Stat3 overactivation and abnormal DNA methylation; therefore, the molecular module that we describe might be exploited under pathological conditions

Metabolic control of DNA methylation in naive pluripotent cells.

Naive epiblast and embryonic stem cells (ESCs) give rise to all cells of adults. Such developmental plasticity is associated with genome hypomethylation. Here, we show that LIF-Stat3 signaling induces genomic hypomethylation via metabolic reconfiguration. Stat3-/- ESCs show decreased α-ketoglutarate production from glutamine, leading to increased Dnmt3a and Dnmt3b expression and DNA methylation. Notably, genome methylation is dynamically controlled through modulation of α-ketoglutarate availability or Stat3 activation in mitochondria. Alpha-ketoglutarate links metabolism to the epigenome by reducing the expression of Otx2 and its targets Dnmt3a and Dnmt3b. Genetic inactivation of Otx2 or Dnmt3a and Dnmt3b results in genomic hypomethylation even in the absence of active LIF-Stat3. Stat3-/- ESCs show increased methylation at imprinting control regions and altered expression of cognate transcripts. Single-cell analyses of Stat3-/- embryos confirmed the dysregulated expression of Otx2, Dnmt3a and Dnmt3b as well as imprinted genes. Several cancers display Stat3 overactivation and abnormal DNA methylation; therefore, the molecular module that we describe might be exploited under pathological conditions

Methylated HBHA produced in <i>M. smegmatis</i> discriminates between active and non-active tuberculosis disease among RD1-responders

Background. A challenge in tuberculosis (TB) research is to develop a new immunological test that can help distinguish, among subjects responsive to QuantiFERON TB Gold In tube (QFT-IT), those who are able to control Mtb replication (remote LTBI, recent infection and past TB) from those who cannot (active TB disease). IFN-γ; response to the Heparin-binding-hemagglutinin (HBHA) of Mtb has been associated with LTBI, but the cumbersome procedures of purifying the methylated and immunological active form of the protein from Mtb or M. bovis Bacillus Calmette et Guerin (BCG) have prevented its implementation in a diagnostic test. Therefore, the aim of the present study was to evaluate the IFN-γ response to methylated HBHA of Mtb produced in M. smegmatis (rHBHAms) in individuals at different stages of TB who scored positive to QFT-IT. Methodology/Principal Findings. 87 individuals at different stages of TB who scored positive to QFT-IT were selected. IFN-γ response to in vitro whole blood stimulation with rHBHAms was evaluated by short-term and long-term tests and detected by ELISA or flow cytometry. We demonstrated that the IFN-γ response to rHBHAms is mediated by CD4+ T-cells with an effector-memory phenotype. This response, evaluated by short-term-tests, is significantly lower in active TB than in remote LTBI (p = 0.0010) and past TB (p = 0.0152). These results were confirmed by long-term tests. The qualitative data confirmed that IFN-γ responses higher than the cut-off point identified by ROC analysis are associated with the status of non-active disease. Conclusions. In this study we show that the T-cell response to a recombinant and methylated HBHA of Mtb produced in M. smegmatis is useful to discriminate between active and non-active TB disease among those responsive to QFT-IT in a whole blood system. Further studies are needed to improve the accuracy of the assay