PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth.

BackgroundProgesterone Receptor Membrane Component 1 (PGRMC1) is expressed in many cancer cells, where it is associated with detrimental patient outcomes. It contains phosphorylated tyrosines which evolutionarily preceded deuterostome gastrulation and tissue differentiation mechanisms.ResultsWe demonstrate that manipulating PGRMC1 phosphorylation status in MIA PaCa-2 (MP) cells imposes broad pleiotropic effects. Relative to parental cells over-expressing hemagglutinin-tagged wild-type (WT) PGRMC1-HA, cells expressing a PGRMC1-HA-S57A/S181A double mutant (DM) exhibited reduced levels of proteins involved in energy metabolism and mitochondrial function, and altered glucose metabolism suggesting modulation of the Warburg effect. This was associated with increased PI3K/AKT activity, altered cell shape, actin cytoskeleton, motility, and mitochondrial properties. An S57A/Y180F/S181A triple mutant (TM) indicated the involvement of Y180 in PI3K/AKT activation. Mutation of Y180F strongly attenuated subcutaneous xenograft tumor growth in NOD-SCID gamma mice. Elsewhere we demonstrate altered metabolism, mutation incidence, and epigenetic status in these cells.ConclusionsAltogether, these results indicate that mutational manipulation of PGRMC1 phosphorylation status exerts broad pleiotropic effects relevant to cancer and other cell biology

Ecological and evolutionary consequences of alternative sex-change pathways in fish

Sequentially hermaphroditic fish change sex from male to female (protandry) or vice versa (protogyny), increasing their fitness by becoming highly fecund females or large dominant males, respectively. These life-history strategies present different social organizations and reproductive modes, from near-random mating in protandry, to aggregate- and harem-spawning in protogyny. Using a combination of theoretical and molecular approaches, we compared variance in reproductive success (V k*) and effective population sizes (N e) in several species of sex-changing fish. We observed that, regardless of the direction of sex change, individuals conform to the same overall strategy, producing more offspring and exhibiting greater V k* in the second sex. However, protogynous species show greater V k*, especially pronounced in haremic species, resulting in an overall reduction of N e compared to protandrous species. Collectively and independently, our results demonstrate that the direction of sex change is a pivotal variable in predicting demographic changes and resilience in sex-changing fish, many of which sustain highly valued and vulnerable fisheries worldwide

A systematic review of patient reported factors associated with uptake and completion of cardiovascular lifestyle behaviour change

Background: Healthy lifestyles are an important facet of cardiovascular risk management. Unfortunately many individuals fail to engage with lifestyle change programmes. There are many factors that patients report as influencing their decisions about initiating lifestyle change. This is challenging for health care professionals who may lack the skills and time to address a broad range of barriers to lifestyle behaviour. Guidance on which factors to focus on during lifestyle consultations may assist healthcare professionals to hone their skills and knowledge leading to more productive patient interactions with ultimately better uptake of lifestyle behaviour change support. The aim of our study was to clarify which influences reported by patients predict uptake and completion of formal lifestyle change programmes. Methods: A systematic narrative review of quantitative observational studies reporting factors (influences) associated with uptake and completion of lifestyle behaviour change programmes. Quantitative observational studies involving patients at high risk of cardiovascular events were identified through electronic searching and screened against pre-defined selection criteria. Factors were extracted and organised into an existing qualitative framework. Results: 374 factors were extracted from 32 studies. Factors most consistently associated with uptake of lifestyle change related to support from family and friends, transport and other costs, and beliefs about the causes of illness and lifestyle change. Depression and anxiety also appear to influence uptake as well as completion. Many factors show inconsistent patterns with respect to uptake and completion of lifestyle change programmes. Conclusion: There are a small number of factors that consistently appear to influence uptake and completion of cardiovascular lifestyle behaviour change. These factors could be considered during patient consultations to promote a tailored approach to decision making about the most suitable type and level lifestyle behaviour change support

Alterations in the insulin-like growth factor system during treatment with diethylstilboestrol in patients with metastatic breast cancer

Alterations in the insulin-like growth factor (IGF)-system were evaluated in 16 patients treated with diethylstilboestrol 5 mg 3 times daily. Fasting blood samples were obtained before treatment and after 2 weeks, 1 month and/or 2–3 months on therapy. Insulin-like growth factor (IGF)-I, IGF-II, free IGF-I, IGF-binding protein (IGFBP)-1, IGFBP-2 and IGFBP-3 were measured by radioimmuno-/immunoradiometric-assays. All samples were subjected to Western ligand blotting as well as immunoblotting for IGFBP-3. We observed a significant decrease (percentage of pretreatment levels with 95 confidence intervals of the mean) in IGF-I [2 weeks 63% (49–79); 1 month 56% (44–73); 2–3 months 66% (53–82)], IGF-II [2 weeks 67% (56–80); 1 month 60% (52–68); 2–3 months 64% (55–75)], free IGF-I [2 weeks 29% (19–42); 1 month 25% (18–36); 2–3 months 31% (21–46)], IGFBP-2 [2 weeks 53% (18–156); 1 month 69% (61–78); 2–3 months 66% (57–78)], IGFBP-3 [2 weeks 74% (63–85); 1 month 69% (62–76); 2–3 months 71% (63–80)], as well as IGFBP-3 protease activity [2 weeks 71% (54–95); 1 month 78% (64–94); 2–3 months 71% (54–93)]. Contrary, the plasma levels (percentage of pretreatment levels with 95 confidence intervals of the mean) of IGFBP-1 [2 weeks 250% (127–495); 1 month 173% (138–542); 2–3 months 273% (146–510)] and IGFBP-4 [2 weeks 146% (112–192); 1 month 140% (116–169); 2–3 months 150% (114–198)] increased significantly. While this study confirms previous observations during treatment with oral oestrogens in substitution doses, the reduction in plasma IGF-II, free IGF-I, IGFBP-2 and -3 are all novel findings. A profound decrease in free IGF-I suggests a reduced bioavailability of IGFs from plasma to the tissues. These observations may be of significance to understand the mechanisms of the antitumour effect of diethylstilboestrol in pharmacological doses. © 2001 Cancer Research Campaign http://www.bjcancer.co

Community change within a Caribbean coral reef Marine Protected Area following two decades of local management

© The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS ONE 8 (2013): e54069, doi:10.1371/journal.pone.0054069.Structural change in both the habitat and reef-associated fish assemblages within spatially managed coral reefs can provide key insights into the benefits and limitations of Marine Protected Areas (MPAs). While MPA zoning effects on particular target species are well reported, we are yet to fully resolve the various affects of spatial management on the structure of coral reef communities over decadal time scales. Here, we document mixed affects of MPA zoning on fish density, biomass and species richness over the 21 years since establishment of the Saba Marine Park (SMP). Although we found significantly greater biomass and species richness of reef-associated fishes within shallow habitats (5 meters depth) closed to fishing, this did not hold for deeper (15 m) habitats, and there was a widespread decline (38% decrease) in live hard coral cover and a 68% loss of carnivorous reef fishes across all zones of the SMP from the 1990s to 2008. Given the importance of live coral for the maintenance and replenishment of reef fishes, and the likely role of chronic disturbance in driving coral decline across the region, we explore how local spatial management can help protect coral reef ecosystems within the context of large-scale environmental pressures and disturbances outside the purview of local MPA management.Funding was provided by the Saba Conservation Foundation ((SCF), King Abdullah University of Science and Technology, The Australian National University and Australian Research Council

Evidence for protandry in Polydactylus quadrifilis in the Kwanza Estuary, Angola, and its implications for local fisheries

A total of 141 Polydactylus quadrifilis were sampled from the Kwanza Estuary in Angola ranging in size from 436 to 1360 mm fork-length (FL). Of these, 124 were male, six intersex and 11 female. Female fish were significantly longer (mm, FL) and heavier (kg) than males and had significantly higher gonadosomatic indices (GSI’s) than those of males and intersex fish. Transitional (intersex) gonads were delimited, with testicular and ovarian regions separated by connective tissue. The first signs of ovarian tissue appeared on the outer ventral surface of the gonad. A second layer of ovarian tissue was first noticeable at either end of the initial ovarian region and developed back towards the centre of the ventral wall to form a luminal space. Early-stage oocytes were commonly found in the outer area of male regions and residual late-stage spermatids and spermatozoa were found in the luminal space of ovarian regions, suggesting a process of sex change from the outside inwards. A loss of male function was noted with increased ovarian prevalence. Based on this evidence it is suggested that P. quadrifilis in the Kwanza Estuary are protandrous. Owing to the reliance of P. quadrifilis on large highly fecund females for egg production, it is likely that they will be sensitive to fishing practices that target larger individuals within the population

The Role of Tourism and Recreation in the Spread of Non-Native Species: A Systematic Review and Meta-Analysis

Managing the pathways by which non-native species are introduced and spread is considered the most effective way of preventing species invasions. Tourism and outdoor recreation involve the frequent congregation of people, vehicles and vessels from geographically diverse areas. They are therefore perceived to be major pathways for the movement of non-native species, and ones that will become increasingly important with the continued growth of these sectors. However, a global assessment of the relationship between tourism activities and the introduction of non-native species–particularly in freshwater and marine environments–is lacking. We conducted a systematic review and meta-analysis to determine the impact of tourism and outdoor recreation on non-native species in terrestrial, marine and freshwater environments. Our results provide quantitative evidence that the abundance and richness of non-native species are significantly higher in sites where tourist activities take place than in control sites. The pattern was consistent across terrestrial, freshwater and marine environments; across a variety of vectors (e.g. horses, hikers, yachts); and across a range of taxonomic groups. These results highlight the need for widespread biosecurity interventions to prevent the inadvertent introduction of invasive non-native species (INNS) as the tourism and outdoor recreation sectors grow

Abrolhos Bank Reef Health Evaluated by Means of Water Quality, Microbial Diversity, Benthic Cover, and Fish Biomass Data

The health of the coral reefs of the Abrolhos Bank (southwestern Atlantic) was characterized with a holistic approach using measurements of four ecosystem components: (i) inorganic and organic nutrient concentrations, [1] fish biomass, [1] macroalgal and coral cover and (iv) microbial community composition and abundance. The possible benefits of protection from fishing were particularly evaluated by comparing sites with varying levels of protection. Two reefs within the well-enforced no-take area of the National Marine Park of Abrolhos (Parcel dos Abrolhos and California) were compared with two unprotected coastal reefs (Sebastião Gomes and Pedra de Leste) and one legally protected but poorly enforced coastal reef (the “paper park” of Timbebas Reef). The fish biomass was lower and the fleshy macroalgal cover was higher in the unprotected reefs compared with the protected areas. The unprotected and protected reefs had similar seawater chemistry. Lower vibrio CFU counts were observed in the fully protected area of California Reef. Metagenome analysis showed that the unprotected reefs had a higher abundance of archaeal and viral sequences and more bacterial pathogens, while the protected reefs had a higher abundance of genes related to photosynthesis. Similar to other reef systems in the world, there was evidence that reductions in the biomass of herbivorous fishes and the consequent increase in macroalgal cover in the Abrolhos Bank may be affecting microbial diversity and abundance. Through the integration of different types of ecological data, the present study showed that protection from fishing may lead to greater reef health. The data presented herein suggest that protected coral reefs have higher microbial diversity, with the most degraded reef (Sebastião Gomes) showing a marked reduction in microbial species richness. It is concluded that ecological conditions in unprotected reefs may promote the growth and rapid evolution of opportunistic microbial pathogens