Growth factors in idiopathic pulmonary fibrosis: relative roles

Treatment of idiopathic pulmonary fibrosis patients has evolved very slowly; the fundamental approach of corticosteroids alone or in combination with other immunosuppressive agents has had little impact on long-term survival. The continued use of corticosteroids is justified because of the lack of a more effective alternative. Current research indicates that the mechanisms driving idiopathic pulmonary fibrosis reflect abnormal, dysregulated wound healing within the lung, involving increased activity and possibly exaggerated responses by a spectrum of profibrogenic growth factors. An understanding of the roles of these growth factors, and the way in which they modulate events at cellular level, could lead to more targeted therapeutic strategies, improving patients' quality of life and survival

A role for peroxisome proliferator-activated receptors in the immunopathology of schistosomiasis?

Peroxisome proliferator-activated receptors (PPARs) have been demonstrated to have a role in immune regulation. In general, they are anti-inflammatory and promote Th2 type responses, and they are associated with the alternative activation of macrophages. Interestingly, helminth infections, such as the schistosome blood flukes that cause schistosomiasis, are characterised by a Th2 response and the accumulation of alternative activated macrophages. This would suggest that at some level, PPARs could have a role in the modulation of the immune response in schistosomiasis. This paper discusses possible areas where PPARs could have a role in this disease

Hepatic stellate cells and parasite-induced liver fibrosis

ABSTRACT: Fibrogenesis is a common feature of many diseases where there is severe insult to the liver. The hepatic stellate cell trans-differentiation into a myofibroblast has been identified as an important event in liver fibrogenesis and has been well investigated over the last few years in a number of liver diseases. The trans-differentiation process can be monitored in vitro by evaluation of biomarkers that are characteristic of normal quiescent hepatic stellate cells or activated myofibroblasts. Two major parasitic diseases associated with liver injury and fibrosis are schistosomiasis and echinococcosis. Recent studies have highlighted a role for activated hepatic stellate cells in both murine and human schistosomiasis as well as demonstrating that schistosome antigens are able to regulate this trans-differentiation process. Study of the hepatic stellate cell and its interaction with parasite-derived antigens may be pivotal in our understanding of the pathology associated with schistosomiasis and other parasitic diseases, including echinococcosis, as well as revealing new information on the trans-differentiation process in this cell type

Does hydatid cyst fluid from Echinococcus granulosus cysts have any effect on cells involved in fibrosis in cystic echinococcosis?

Cystic echinococcosis is characterized by the presence of slow growing hydatid cysts, usually in the liver or lungs. Survival of the parasite is based on an interaction of the host immune system and a range of parasite immune-evasive strategies. Fibrosis in the tissues surrounding the cysts can be seen as a host protective response isolating the parasite and restricting its growth or from another perspective fibrosis may be protective for the parasite by providing a barrier to more effective immunological responses. In this study the adenocarcinomic human alveolar basal epithelial cell line (A549) was used as model system. This cell line can be involved in fibrosis as cells can transform into mesenchymal cells and differentiate later to fibroblasts and/or myofibroblasts which can ultimately secrete collagen. Cells were initially cultured in vitro in RPMI-1640 medium containing 1-10% hydatid cyst fluid (HCF). The possible effect of the parasite extracts on cell migration was investigated using a wound healing assay. The ability of HCF components to modify cell surface markers of mesenchymal transition was also investigated by fluorescence microscopy. Results showed that there was a dose-dependent increase in cell growth in the presence of cyst fluid after 5 days of culture. The migratory response of cells was also enhanced by the presence of HCF. Both the enhanced growth and migratory activity were still evident when the HCF had been boiled indicating that the components responsible were thermostable. Semi-purified extracts of a major HCF component, antigen B showed a similar high stimulatory effect similar to that of HCF. The fluorescence microscopy showed a significant expression in the fibronectin and E-cadherin cell markers in cells treated with HCF. These results indicate that components within HCF have a stimulatory effect in the possible enhancement of fibrosis

Heartbeat of the Southern Oscillation explains ENSO climatic resonances

This is the final version. Available from the publisher via the DOI in this record.The El Nino-Southern Oscillation (ENSO) nonlinear oscillator phenomenon has a far reaching ~ influence on the climate and human activities. The up to 10 year quasi-period cycle of the El Nino and ~ subsequent La Nina is known to be dominated in the tropics by nonlinear physical interaction of wind with ~ the equatorial waveguide in the Pacific. Long-term cyclic phenomena do not feature in the current theory of the ENSO process. We update the theory by assessing low (>10 years) and high (<10 years) frequency coupling using evidence across tropical, extratropical, and Pacific basin scales. We analyze observations and model simulations with a highly accurate method called Dominant Frequency State Analysis (DFSA) to provide evidence of stable ENSO features. The observational data sets of the Southern Oscillation Index (SOI), North Pacific Index Anomaly, and ENSO Sea Surface Temperature Anomaly, as well as a theoretical model all confirm the existence of long-term and short-term climatic cycles of the ENSO process with resonance frequencies of {2.5, 3.8, 5, 12–14, 61–75, 180} years. This fundamental result shows long-term and short-term signal coupling with mode locking across the dominant ENSO dynamics. These dominant oscillation frequency dynamics, defined as ENSO frequency states, contain a stable attractor with three frequencies in resonance allowing us to coin the term Heartbeat of the Southern Oscillation due to its characteristic shape. We predict future ENSO states based on a stable hysteresis scenario of short-term and long-term ENSO oscillations over the next century.Natural Environment Research Council (NERC)Plymouth Marine Laboratory (PML

Mitotic instability in triploid and tetraploid one-year-old eastern oyster, Crassostrea virginica, assessed by cytogenetic and flow cytometry techniques

For commercial oyster aquaculture, triploidy has significant advantages. To produce triploids, the principal technology uses diploid x tetraploid crosses. The development of tetraploid brood stock for this purpose has been successful, but as more is understood about tetraploids, it seems clear that chromosome instability is a principal feature in oysters. This paper is a continuation of work to investigate chromosome instability in polyploid Crassostrea virginica. We established families between tetraploids-apparently stable (non-mosaic) and unstable (mosaic)-and normal reference diploids, creating triploid groups, as well as tetraploids between mosaic and non-mosaic tetraploids. Chromosome loss was about the same for triploid juveniles produced from either mosaic or non-mosaic tetraploids or from either male or female tetraploids. However, there was a statistically significant difference in chromosome loss in tetraploid juveniles produced from mosaic versus non-mosaic parents, with mosaics producing more unstable progeny. These results confirm that chromosome instability, as manifested in mosaic tetraploids, is of little concern for producing triploids, but it is clearly problematic for tetraploid breeding. Concordance between the results from cytogenetics and flow cytometry was also tested for the first time in oysters, by assessing the ploidy of individuals using both techniques. Results between the two were non-concordant

A re-evaluation of the Earth’s surface temperature response to radiative forcing

This is the final version. Available on open access from IOP Publishing via the DOI in this recordData availability statement: All the time-series data used in this analysis is freely available for research: http://cdiac.ornl.gov/trends/temp/jonescru/jones.html; www.pik-potsdam.de/~mmalte/rcps/; www.cgd.ucar.edu/cas/catalog/climind/AMO.html. The models in this paper have been inferred statistically from the data record available when the present study was initiated and they can change over time. The data that support the findings of this study are available upon reasonable request from the authorsThere is much current debate about the way in which the earth's climate and temperature are responding to anthropogenic and natural forcing. In this paper we re-assess the current evidence at the globally averaged level by adopting a generic 'data-based mechanistic' modelling strategy that incorporates statistically efficient parameter estimation. This identifies a low order, differential equation model that explains how the global average surface temperature variation responds to the influences of total radiative forcing (TRF). The model response includes a novel, stochastic oscillatory component with a period of about 55 years (range 51.6–60 years) that appears to be associated with heat energy interchange between the atmosphere and the ocean. These 'quasi-cycle' oscillations, which account for the observed pauses in global temperature increase around 1880, 1940 and 2001, appear to be related to ocean dynamic responses, particularly the Atlantic multidecadal oscillation. The model explains 90% of the variance in the global average surface temperature anomaly and yields estimates of the equilibrium climate sensitivity (ECS) (2.29 compfnC with 5%–95% range 2.11 compfnC to 2.49 compfnC) and the transient climate response (TCR) (1.56 compfnC with 5%–95% range 1.43 compfnC to 1.68 compfnC), both of which are smaller than most previous estimates. When a high level of uncertainty in the TRF is taken into account, the ECS and TCR estimates are unchanged but the ranges are increased to 1.43 compfnC to 3.14 compfnC and 0.99 compfnC to 2.16 compfnC, respectively.Engineering and Physical Sciences Research Council (EPSRC)Natural Environment Research Council (NERC)Newton Funded China Services Partnership (CSSP

Heterogeneity of impacts of high CO2 on the North Western European Shelf

The increase in atmospheric CO2 is a dual threat to the marine environment: from one side it drives climate change, leading to modifications in water temperature, circulation patterns and stratification intensity; on the other side it causes a decrease in marine pH (ocean acidification, or OA) due to the increase in dissolved CO2. Assessing the combined impact of climate change and OA on marine ecosystems is a challenging task. The response of the ecosystem to a single driver can be highly variable and remains still uncertain; additionally the interaction between these can be either synergistic or antagonistic. In this work we use the coupled oceanographic–ecosystem model POLCOMS-ERSEM driven by climate forcing to study the interaction between climate change and OA. We focus in particular on carbonate chemistry, primary and secondary production. The model has been run in three different configurations in order to assess separately the impacts of climate change on net primary production and of OA on the carbonate chemistry, which have been strongly supported by scientific literature, from the impact of biological feedbacks of OA on the ecosystem, whose uncertainty still has to be well constrained. The global mean of the projected decrease of pH at the end of the century is about 0.27 pH units, but the model shows significant interaction among the drivers and high variability in the temporal and spatial response. As a result of this high variability, critical tipping point can be locally and/or temporally reached: e.g. undersaturation with respect to aragonite is projected to occur in the deeper part of the central North Sea during summer. Impacts of climate change and of OA on primary and secondary production may have similar magnitude, compensating in some area and exacerbating in others

What can ecosystem models tell us about the risk of eutrophication in the North Sea?

Eutrophication is a process resulting from an increase in anthropogenic nutrient inputs from rivers and other sources, the consequences of which can include enhanced algal biomass, changes in plankton community composition and oxygen depletion near the seabed. Within the context of the Marine Strategy Framework Directive, indicators (and associated threshold) have been identified to assess the eutrophication status of an ecosystem. Large databases of observations (in situ) are required to properly assess the eutrophication status. Marine hydrodynamic/ecosystem models provide continuous fields of a wide range of ecosystem characteristics. Using such models in this context could help to overcome the lack of in situ data, and provide a powerful tool for ecosystem-based management and policy makers. Here we demonstrate a methodology that uses a combination of model outputs and in situ data to assess the risk of eutrophication in the coastal domain of the North Sea. The risk of eutrophication is computed for the past and present time as well as for different future scenarios. This allows us to assess both the current risk and its sensitivity to anthropogenic pressure and climate change. Model sensitivity studies suggest that the coastal waters of the North Sea may be more sensitive to anthropogenic rivers loads than climate change in the near future (to 2040)