Immediate early gene expression in dog thyrocytes in response to growth, proliferation, and differentiation stimuli.

In dog thyroid cells, insulin or IGF-1 induces cell growth and is required for the mitogenic action of TSH through cyclic AMP, of EGF, and of phorbol esters. HGF per se stimulates cell proliferation and is thus the only full mitogenic agent. TSH and cAMP enhance, whereas EGF phorbol esters and HGF repress differentiation expression. In this study, we have investigated for each factor and regulatory cascade of the intermediate step of immediate early gene induction, that is, c-myc, c-jun, jun D, jun B, c-fos, fos B, fra-1, fra-2, and egr1; fra-1 and fra-2 expressions were very low. TSH or forskolin increased the levels of c-myc, jun B, jun D, c-fos, and fos B while decreasing those of c-jun and egr1. Phorbol myristate ester stimulated the expression of all the genes. EGF and HGF stimulated the expression of all the genes except jun D and for EGF fos B. All these effects were obtained in the presence and in the absence of insulin, which shows that insulin is not necessary for the effects of the mitogens on immediate early gene expression. The definition of the repertoire of early immediate genes inductible by the various growth cascades provides a framework for the analysis of gene expression in tumors. (1) Insulin was able to induce all the protooncogenes investigated except fos B. This suggests that fos B could be the factor missing for insulin to induce mitogenesis. (2) No characteristic pattern of immediate early gene expression has been observed for insulin, which induces cell hypertrophy and is permissive for the action of the other growth factors. These effects are therefore not accounted for by a specific immediate early gene expression. On the other hand, insulin clearly enhances the effects of TSH, phorbol ester, and EGF on c-myc, junB, and c-fos expression. This suggests that the effect of insulin on mitogenesis might result from quantitative differences in the transcription complexes formed. (3) c-myc, c-fos, and jun B mRNA induction by all stimulating agents, whether inducing cell hypertrophy, or growth and dedifferentiation, or growth and differentiation, suggests that, although these expressions are not sufficient, they may be necessary for the various growth responses of thyroid cells. (4) The inhibition of c-jun and egr1 mRNA expression, and the marked induction of jun D mRNA appear to be specific features of the TSH cAMP pathway. They might be related to its differentiating action. (5) fos B, which is induced by TSH, forskolin, phorbol ester, and HGF but not by insulin, could be involved in the mitogenic action of the former factors.

Developing global trade union "space"

International unions and international solidarity strategies have been changing partly as a response to changes in the global economy. Global union federations have played an important role in expanding communication and developing alliances with other social movements. One of the issues facing trade unions wanting to be effective at an international level is to what extent national concerns can inform and even be transcended by international perspectives. Proposals for studying the global labor force "horizontally", that is, according to different categories and forms of work rather than on a nation-by-nation basis, demonstrates a recognition of global- national dimensions (Harrod and O'Brien 2002:49). This paper will discuss the development of a global trade union "space", which enables national and global unions to work together effectively, using a series of case studies drawn from the experience of global and European public service unions.

Is observed variability in the long-term results of the Continuous Plankton Recorder survey a response to climate change?

In the more than 50 years that the Continuous Plankton Recorder (CPR) survey has operated on a regular monthly basis in the north-east Atlantic and North Sea, large changes have been witnessed in the planktonic ecosystem. These changes have taken the form of long-term trends in abundance for certain species or stepwise changes for others, and in many cases are correlated with a mode of climatic variability in the North Atlantic, either: (1) the North Atlantic Oscillation (NAO), a basin-scale atmospheric alteration of the pressure field between the Azores high pressure cell and the Icelandic Low; or (2) the Gulf Stream Index (GSI), which measures the latitudinal position of the north wall of the Gulf Stream. Recent work has shown that the changes in the GSI are coupled with the NAO and Pacific Southern Oscillation with a 2 year lag. The plankton variability is also possibly linked to changes observed in the distribution and flux of water masses in the surface, intermediate and deep waters of the North Atlantic. For example, in the last two decades, the extent and location of the formation of North Atlantic Deep Water, Labrador Sea Intermediate Water and Norwegian Sea intermediate and upper-layer water has altered considerably. This paper discusses the extent to which observed changes in plankton abundance and distribution may be linked to this basin-scale variability in hydrodynamics. The results are also placed within the context of global climate warming and the possible effects of the observed melting of Arctic permafrost and sea ice on the subpolar North Atlantic.

Synchronous response of marine plankton ecosystems to climate in the Northeast Atlantic and the North Sea

Over the last few decades, global warming has accelerated both the rate and magnitude of changes observed in many functional units of the Earth System. In this context, plankton are sentinel organisms because they are sensitive to subtle levels of changes in temperature and might help in identifying the current effects of climate change on pelagic ecosystems. In this paper, we performed a comparative approach in two regions of the North Atlantic (i.e. the Northeast Atlantic and the North Sea) to explore the relationships between changes in marine plankton, the regional physico-chemical environment and large-scale hydro-climatic forcing using four key indices: the North Atlantic Oscillation (NAO), the Atlantic Multidecadal Oscillation (AMO), the East Atlantic (EA) pattern and Northern Hemisphere Temperature (NHT) anomalies. Our analyses suggest that long-term changes in the states of the two ecosystems were synchronous and correlated to the same large-scale hydro-climatic variables: NHT anomalies, the AMO and to a lesser extent the EA pattern. No significant correlation was found between long-term ecosystem modifications and the state of the NAO. Our results suggest that the effect of climate on these ecosystems has mainly occurred in both regions through the modulation of the thermal regime.

Zooplankton response to a warmer northern Wadden Sea

Weekly measurements of mesozooplankton (>76 mu m) and hydrographic parameters have been carried out since 1984 in the List Tidal Basin (northern Wadden Sea). Monthly water temperature significantly increased by 0.04 degrees C year. The largest increase by 3 degrees C in 22 years occurred in September, implying, an extension of the warm summer period. Mean annual copepod abundance and length of copepod season correlated significantly with mean temperature from January to May. Except for an increasing Acartia sp. abundance during spring (April-May), no longterm trends in copepod abundance were observed. The percentage of carnivorous zooplankton increased significantly since 1984 mainly due to a sudden increase in the cyclopoid copepod Oithona similis in 1997. We expect that global warming will lead to a longer copepod season and higher copepod abundances in the northern Wadden Sea.

Response to Comments on "Impacts of Biodiversity Loss on Ocean Ecosystem Services"

We show that globally declining fisheries catch trends cannot be explained by random processes and are consistent with declining stock abundance trends. Future projections are inherently uncertain but may provide a benchmark against which to assess the effectiveness of conservation measures. Marine reserves and fisheries closures are among those measures and can be equally effective in tropical and temperate areas—but must be combined with catch-, effort-, and gear restrictions to meet global conservation objectives.

Vulnerability of coastal ecosystems to changes in harmful algal bloom distribution in response to climate change: projections based on model analysis

Harmful algal blooms (HABs), those proliferations of algae that can cause fish kills, contaminate seafood with toxins, form unsightly scums, or detrimentally alter ecosystem function have been increasing in frequency, magnitude, and duration worldwide. Here, using a global modeling approach, we show, for three regions of the globe, the potential effects of nutrient loading and climate change for two HAB genera, pelagic Prorocentrum and Karenia, each with differing physiological characteristics for growth. The projections (end of century, 2090-2100) are based on climate change resulting from the A1B scenario of the Intergovernmental Panel on Climate Change Institut Pierre Simon Laplace Climate Model (IPCC, IPSL-CM4), applied in a coupled oceanographic-biogeochemical model, combined with a suite of assumed physiological 'rules' for genera-specific bloom development. Based on these models, an expansion in area and/or number of months annually conducive to development of these HABs along the NW European Shelf-Baltic Sea system and NE Asia was projected for both HAB genera, but no expansion (Prorocentrum spp.), or actual contraction in area and months conducive for blooms (Karenia spp.), was projected in the SE Asian domain. The implications of these projections, especially for Northern Europe, are shifts in vulnerability of coastal systems to HAB events, increased regional HAB impacts to aquaculture, increased risks to human health and ecosystems, and economic consequences of these events due to losses to fisheries and ecosystem services.

Modelling the future biogeography of North Atlantic zooplankton communities in response to climate change

Advances in habitat and climate modelling allow us to reduce uncertainties of climate change impacts on species distribution. We evaluated the impacts of future climate change on community structure, diversity, distribution and phenology of 14 copepod species in the North Atlantic. We developed and validated habitat models for key zooplankton species using continuous plankton recorder (CPR) survey data collected at mid latitudes of the North Atlantic. Generalized additive models (GAMs) were applied to relate the occurrence of species to environmental variables. Models were projected to future (2080–2099) environmental conditions using coupled hydroclimatix–biogeochemical models under the Intergovernmental Panel on Climate Change (IPCC) A1B climate scenario, and compared to present (2001–2020) conditions. Our projections indicated that the copepod community is expected to respond substantially to climate change: a mean poleward latitudinal shift of 8.7 km per decade for the overall community with an important species range variation (–15 to 18 km per decade); the species seasonal peak is expected to occur 12–13 d earlier for Calanus finmarchicus and C. hyperboreus; and important changes in community structure are also expected (high species turnover of 43–79% south of the Oceanic Polar Front). The impacts of the change expected by the end of the century under IPCC global warming scenarios on copepods highlight poleward shifts, earlier seasonal peak and changes in biodiversity spatial patterns that might lead to alterations of the future North Atlantic pelagic ecosystem. Our model and projections are supported by a temporal validation undertaken using the North Atlantic climate regime shift that occurred in the 1980s: the habitat model built in the cold period (1970–1986) has been validated in the warm period (1987–2004).

BRCA1 regulates the interferon gamma-mediated apoptotic response

BRCA1 is a tumor suppressor gene implicated in transcriptional regulation. We have generated cell lines with inducible expression of BRCA1 as a tool to identify downstream targets that may be important mediators of BRCA1 function. Oligonucleotide array-based expression profiling identified 11 previously described interferon regulated genes that were up-regulated following inducible expression of BRCA1. Northern blot analysis revealed that a subset of the identified targets including IRF-7, MxA, and ISG-54 were synergistically up-regulated by BRCA1 in the presence of interferon gamma (IFN-gamma) but not interferons alpha or beta. Importantly, IFN-gamma-mediated induction of IRF-7 and MxA was attenuated in the BRCA1 mutant cell line HCC1937, an effect that was rescued following reconstitution of exogenous wild type BRCA1 in these cells. Furthermore, reconstituted BRCA1 sensitized HCC1937 cells to IFN-gamma-induced apoptotic cell death. This study identifies BRCA1 as a component of the IFN-gamma-regulated signaling pathway and suggests that BRCA1 may play a role in the regulation of IFN-gamma-mediated apoptosis.

Role played by BRCA1 in regulating the cellular response to stress

BRCA1 (breast-cancer susceptibility gene 1) is a tumour suppressor gene that is mutated in the germline of women with a genetic predisposition to breast and ovarian cancer. In this review, we examine the role played by BRCA1 in mediating the cellular response to stress. We review the role played by BRCA1 in detecting and signalling the presence of DNA damage, particularly double-strand DNA breaks, and look at the evidence to support a role for BRCA1 in regulating stress response pathways such as the c-Jun N-terminal kinase/stress-activated protein kinase pathway. in addition, we examine the role played by BRCA1 in mediating both cell-cycle arrest and apoptosis following different types of cellular insult, and how this may be modulated by the presence or absence of associated proteins such as p53. Finally, we explore the possibility that many of the functions associated with BRCA1 may be based on transcriptional regulation of key downstream genes that have been implicated in the regulation of these specific cellular pathways.

The construction of a whole-cell biosensor for phosphonoacetate, based on the LysR-like transcriptional regulator PhnR from Pseudomonas fluorescens 23F

The phnA gene that encodes the carbon-phosphorus bond cleavage enzyme phosphonoacetate hydrolase is widely distributed in the environment, suggesting that its phosphonate substrate may play a significant role in biogeochemical phosphorus cycling. Surprisingly, however, no biogenic origin for phosphonoacetate has yet been established. To facilitate the search for its natural source we have constructed a whole-cell phosphonoacetate biosensor. The gene encoding the LysR-type transcriptional activator PhnR, which controls expression of the phosphonoacetate degradative operon in Pseudomonas fluorescens 23F, was inserted in the broad-host-range promoter probe vector pPROBE-NT, together with the promoter region of the structural genes. Cells of Escherichia coli DH5a that contained the resultant construct, pPANT3, exhibited phosphonoacetate-dependent green fluorescent protein fluorescence in response to threshold concentrations of as little as 0.5 µM phosphonoacetate, some 100 times lower than the detection limit of currently available non-biological analytical methods; the pPANT3 biosensor construct in Pseudomonas putida KT2440 was less sensitive, although with shorter response times. From a range of other phosphonates and phosphonoacetate analogues tested, only phosphonoacetaldehyde and arsonoacetate induced green fluorescent protein fluorescence in the E. coli DH5a (pPANT3) biosensor, although at much-reduced sensitivities (50 µM phosphonoacetaldehyde and 500 µM arsonoacetate).

Transcriptional upregulation of SOCS 1 and suppressors of cytokine signaling 3 mRNA in the absence of suppressors of cytokine signaling 2 mRNA after infection with West Nile virus or tick-borne encephalitis virus.

Suppressors of cytokine signaling (SOCS) proteins are a family of proteins that are able to act in a classic negative feedback loop to regulate cytokine signal transduction. The regulation of the immune response by SOCS proteins may contribute to persistent infection or even a fatal outcome. In this study, we have investigated the induction of SOCS 1-3 after peripheral infection with West Nile virus (WNV) or tick-borne encephalitis virus (TBEV) in the murine model. We have shown that the cytokine response after infection of mice with WNV or TBEV induces an upregulation in the brain of mRNA transcripts for SOCS 1 and SOCS 3, but not SOCS 2. We hypothesize that SOCS proteins may play a role in limiting cytokine responses in the brain as a neuroprotective mechanism, which may actually enhance the ability of neuroinvasive viruses such as WNV and TBEV to spread and cause disease.

Comparative proteome analysis of triclabendazole response in the liver fluke, Fasciola hepatica.

Control of Fasciola hepatica infections of livestock in the absence of vaccines depends largely on the chemical triclabendazole (TCBZ) because it is effective against immature and adult parasites. Overdependence on a single drug and improper application is considered a significant factor in increasing global reports of fluke resistant to TCBZ. The mode(s) of action and biological target(s) of TCBZ are not confirmed, delaying detection and the monitoring of early TCBZ resistance. In this study, to further understand liver fluke response to TCBZ, the soluble proteomes of TCBZ-resistant and TCBZ-susceptible isolates of F. hepatica were compared with and without in vitro exposure to the metabolically active form of the parent drug triclabendazole sulphoxide (TCBZ-SO), via two-dimensional gel electrophoresis (2-DE). Gel image analysis revealed proteins displaying altered synthesis patterns and responses both between isolates and under TCBZ-SO exposure. These proteins were identified by mass spectrometry supported by a F. hepatica expressed sequence tag (EST) data set. The TCBZ responding proteins were grouped into three categories; structural proteins, energy metabolism proteins, and “stress” response proteins. This single proteomic investigation supported the reductionist experiments from many laboratories that collectively suggest TCBZ has a range of effects on liver fluke metabolism. Proteomics highlighted differences in the innate proteome profile of different fluke isolates that may influence future therapy and diagnostics design. Two of the TCBZ responding proteins, a glutathione transferase and a fatty acid binding protein, were cloned, produced as recombinants, and both found to bind TCBZ-SO at physiologically relevant concentrations, which may indicate a role in TCBZ metabolism and resistance.

The Paediatric Rheumatology International Trials Organisation provisional criteria for the evaluation of response to therapy in juvenile dermatomyositis.

Objective To develop a provisional definition for the evaluation of response to therapy in juvenile dermatomyositis (DM) based on the Paediatric Rheumatology International Trials Organisation juvenile DM core set of variables. Methods Thirty-seven experienced pediatric rheumatologists from 27 countries achieved consensus on 128 difficult patient profiles as clinically improved or not improved using a stepwise approach (patient's rating, statistical analysis, definition selection). Using the physicians' consensus ratings as the “gold standard measure,” chi-square, sensitivity, specificity, false-positive and-negative rates, area under the receiver operating characteristic curve, and kappa agreement for candidate definitions of improvement were calculated. Definitions with kappa values >0.8 were multiplied by the face validity score to select the top definitions. Results The top definition of improvement was at least 20% improvement from baseline in 3 of 6 core set variables with no more than 1 of the remaining worsening by more than 30%, which cannot be muscle strength. The second-highest scoring definition was at least 20% improvement from baseline in 3 of 6 core set variables with no more than 2 of the remaining worsening by more than 25%, which cannot be muscle strength (definition P1 selected by the International Myositis Assessment and Clinical Studies group). The third is similar to the second with the maximum amount of worsening set to 30%. This indicates convergent validity of the process. Conclusion We propose a provisional data-driven definition of improvement that reflects well the consensus rating of experienced clinicians, which incorporates clinically meaningful change in core set variables in a composite end point for the evaluation of global response to therapy in juvenile DM.