The efficacy of sanctuary areas for the management of fish stocks and biodiversity in WA waters

Debate concerning the relative benefits of marine protected areas (MPAs) for the management of marine resources can often reflect unrecognized differences in the scope, scale and definitions of the objectives being sought by various Government or community bodies. There can also be different opinions on the level of protection required for an area to be considered an ‘MPA’ and functional definitions for both the biological diversity and ecosystems within these areas are often lacking. This paper seeks to outline the relative efficiency and effectiveness of MPAs, especially no-take sanctuary areas, compared to other strategies currently employed to help achieve the main objective of the Western Australian (WA) Fish Resources Management Act (FRMA) 1994, which is “to conserve fish* and protect their environment”. This objective covers the conservation of most of the marine resources of the WA coast, including fish stock management; habitat protection and biodiversity generally out to the 200 m depth contour

Lovastatin induces apoptosis of ovarian cancer cells and synergizes with doxorubicin: potential therapeutic relevance

<p>Abstract</p> <p>Background</p> <p>Ovarian carcinoma is a rarely curable disease, for which new treatment options are required. As agents that block HMG-CoA reductase and the mevalonate pathway, the statin family of drugs are used in the treatment of hypercholesterolemia and have been shown to trigger apoptosis in a tumor-specific manner. Recent clinical trials show that the addition of statins to traditional chemotherapeutic strategies can increase efficacy of targeting statin-sensitive tumors. Our goal was to assess statin-induced apoptosis of ovarian cancer cells, either alone or in combination with chemotherapeutics, and then determine these mechanisms of action.</p> <p>Methods</p> <p>The effect of lovastatin on ovarian cancer cell lines was evaluated alone and in combination with cisplatin and doxorubicin using several assays (MTT, TUNEL, fixed PI, PARP cleavage) and synergy determined by evaluating the combination index. The mechanisms of action were evaluated using functional, molecular, and pharmacologic approaches.</p> <p>Results</p> <p>We demonstrate that lovastatin induces apoptosis of ovarian cancer cells in a p53-independent manner and synergizes with doxorubicin, a chemotherapeutic agent used to treat recurrent cases of ovarian cancer. Lovastatin drives ovarian tumor cell death by two mechanisms: first, by blocking HMG-CoA reductase activity, and second, by sensitizing multi-drug resistant cells to doxorubicin by a novel mevalonate-independent mechanism. This inhibition of drug transport, likely through inhibition of P-glycoprotein, potentiates both DNA damage and tumor cell apoptosis.</p> <p>Conclusions</p> <p>The results of this research provide pre-clinical data to warrant further evaluation of statins as potential anti-cancer agents to treat ovarian carcinoma. Many statins are inexpensive, off-patent generic drugs that are immediately available for use as anti-cancer agents. We provide evidence that lovastatin triggers apoptosis of ovarian cancer cells as a single agent by a mevalonate-dependent mechanism. Moreover, we also show lovastatin synergizes with doxorubicin, an agent administered for recurrent disease. This synergy occurs by a novel mevalonate-independent mechanism that antagonizes drug resistance, likely by inhibiting P-glycoprotein. These data raise important issues that may impact how statins can best be included in chemotherapy regimens.</p

Ion-beam sputtered amorphous silicon films for cryogenic precision measurement systems

Thermal noise resulting from the mechanical loss of multilayer dielectric coatings is expected to impose a limit to the sensitivities of precision measurement systems used in fundamental and applied science. In the case of gravitational wave astronomy, future interferometric gravitational wave detectors are likely to operate at cryogenic temperatures to reduce such thermal noise and ameliorate thermal loading effects, with the desirable thermomechanical properties of silicon making it an attractive mirror substrate choice for this purpose. For use in such a precision instrument, appropriate coatings of low thermal noise are essential. Amorphous silicon (a−Si) deposited by e-beam and other techniques has been shown to have low mechanical loss. However, to date, the levels of mechanical and optical loss for a−Si when deposited by ion-beam sputtering (the technique required to produce amorphous mirrors of the specification for gravitational wave detector mirrors) are unknown. In this paper results from measurements of the mechanical loss of a series of IBS a−Si films are presented which show that reductions are possible in coating thermal noise of a factor of 1.5 at 120 K and 2.1 at 20 K over the current best IBS coatings (alternating stacks of silica and titania-doped tantala), with further reductions feasible under appropriate heat treatments

Brief Report: Feasibility of Social Cognition and Interaction Training for Adults with High Functioning Autism

The goal of this study was to evaluate the feasibility and utility of a group-based cognitive behavioral intervention to improve social-cognitive functioning in adults with high-functioning autism (HFA). We modified the treatment manual of a previously validated intervention, Social Cognition and Interaction Training (SCIT), for optimal use with HFA adults (SCIT-A). We then conducted a pilot study to compare SCIT-A (n = 6) to treatment as usual (TAU) (n = 5) for adults with HFA. Feasibility was supported; attendance was high (92%) and satisfaction reports were primarily positive. Participants in SCIT-A showed significant improvement in theory-of-mind skills and trend level improvements in social communication skills; TAU participants did not show these improvements. Findings indicate SCIT-A shows promise as an intervention for adults with HFA

Pharmacologic and Genetic Manipulation of MMP-2 and -9 Affects Retinal Neovascularization in Rodent Models of OIR

PURPOSE. The efficacy of three matrix metalloproteinase (MMP) inhibitors with various selectivities (Ro-31-9790, AG3340, and DPC-A37668) was investigated in a rat model of retinopathy of prematurity, to examine the roles of MMP-2 and -9 in retinal neovascularization. The susceptibilities of MMP-2 Ϫ/Ϫ and -9 Ϫ/Ϫ mice to preretinal neovascularization were investigated in a mouse model of oxygen-induced retinopathy. METHODS. Sprague-Dawley newborn rats were exposed to alternating episodes of 50% and 10% oxygen (variable oxygen exposure) to induce retinal neovascularization. Three MMP inhibitors with various selectivity profiles were administered to variable oxygen-exposed rats via local or systemic routes. Antineovascular efficacy was determined in drug-treated versus vehicle-treated rat pups by computerized imaging of adenosine diphosphatase (ADPase)-stained retinal flatmounts. Wild-type C57BL/6J and isogenic MMP-2 Ϫ/Ϫ and -9 Ϫ/Ϫ mice were exposed to 75% oxygen followed by normoxia. The mice were killed immediately before or after the normoxic exposure, and eyes were either harvested for retinal dissection and flatmounting or were paraffin embedded and sectioned. Retinal vascular area and retinal neovascularization were assessed by adenosine diphosphatase staining of retinal flatmounts and by counting preretinal nuclei of hematoxylin and eosin-stained retinal sections, respectively. RESULTS. Ro-31-9790, AG3340, and DPC-A37668 had no effect on normal development of the rat retinal vasculature, regardless of dose or route of administration. Intravitreal injection of Ro-31-9790 (broad-spectrum) immediately after variable-oxygen exposure and 2 days after exposure resulted in 78% and 82% inhibition of retinal neovascularization, respectively. AG3340 (MMP-2-and -9-selective inhibitor) and DPC-A37668 (MMP-2-selective inhibitor) resulted in 65% and 52% inhibition, respectively, when administered by intravitreal injection immediately after variable-oxygen exposure. Intraperitoneal injection of 5, 15, and 50 mg/mL AG3340 or DPC-A37668 for 6 days after variable oxygen exposure resulted in 22% to 39% and 0% to 31% inhibition of neovascularization, respectively. AG3340 and DPC-A37668 administered by oral gavage at doses of 3, 10, or 30 mg/mL provided up to 42% and 86% inhibition of neovascularization, respectively. The average vascular areas of retinas from MMP-2 Ϫ/Ϫ or -9 Ϫ/Ϫ mice at postnatal day 12 were not significantly different from the wild-type control. There was a 75% (P Ͻ 0.001) and 44% (P Ͻ 0.01) reduction in preretinal neovascularization in oxygen-exposed MMP-2 Ϫ/Ϫ and -9 Ϫ/Ϫ mice at postnatal day 19, respectively, compared with wild-type control mice. CONCLUSIONS. The results of this study suggest that MMP-2 plays a predominant role in retinal angiogenesis in both the mouse and rat models of oxygen-induced retinopathy. Furthermore, MMP-2 inhibition may be a viable therapeutic approach for ocular diseases characterized by retinal neovascularization. (Invest Ophthalmol Vis Sci. 2007;48:907-915) DOI:10.1167/ iovs.06-0082 T he term angiogenesis refers to the growth of new capillaries from preexisting blood vessels. The initial events of angiogenesis involve proteolytic basement membrane degradation; extracellular matrix remodeling; and endothelial cell (EC) proliferation, migration, and differentiation. The integration of these events in physiologic angiogenesis involves complex interactions among cells, growth factors, cytokines, and extracellular matrix components. 1 Matrix metalloproteinases (MMPs) comprise a family of proteolytic enzymes of more than 20 members that are zinc and calcium dependent. Most MMPs are secreted in the inactive proenzyme form, some of them by endothelial cells of the angiogenic phenotype. 2 MMP proenzymes are activated, in part, by the plasminogen activator (PA) system, giving rise to active forms that digest and remodel the basement membrane and extracellular matrix. 6 Although tPA is secreted by established vessels, 7 studies in a guinea pig corneal neovascularization (NV) model demonstrated that endothelial cells in new vessel sprouts secrete uPA exclusively (Jerdan JA et al. IOVS 1988;29:ARVO Abstract 109). uPA and tPA activities are rigidly controlled by plasminogen activator inhibitor (PAI)-1. MMP-2 and -9 degrade gelatin; elastin; and collagens IV (a major basement membrane component), V, VII, and X. 2 MMP-2 and -9 are most likely involved in tumor angiogenesis, 9 -11 and recent studies indicate that MMP-2 and -9 are critical for NV in the posterior segment of the eye. For example, experiments From th

Source, sea and sink—A holistic approach to understanding plastic pollution in the Southern Caribbean

Marine plastics are considered to be a major threat to the sustainable use of marine and coastal resources of the Caribbean, on which the region relies heavily for tourism and fishing. To date, little work has quantified plastics within the Caribbean marine environment or examined their potential sources. This study aimed to address this by holistically integrating marine (surface water, subsurface water and sediment) and terrestrial sampling and Lagrangian particle tracking to examine the potential origins, flows and quantities of plastics within the Southern Caribbean. Terrestrial litter and the microplastics identified in marine samples may arise from the maritime and tourism industries, both of which are major contributors to the economies of the Caribbean region. The San Blas islands, Panama had the highest abundance of microplastics at a depth of 25 m, and significantly greater quantities in surface water than recorded in the other countries. Modelling indicated the microplastics likely arose from mainland Panama, which has some of the highest levels of mismanaged waste. Antigua had among the lowest quantities of terrestrial and marine plastics, yet the greatest diversity of polymers. Modelling indicated the majority of the microplastics in Antiguan coastal surface were likely to have originated from the wider North Atlantic Ocean. Ocean currents influence the movements of plastics and thus the relative contributions arising from local and distant sources which become distributed within a country's territorial water. These transboundary movements can undermine local or national legislation aimed at reducing plastic pollution. While this study presents a snapshot of plastic pollution, it contributes towards the void of knowledge regarding marine plastic pollution in the Caribbean Sea and highlights the need for international and interdisciplinary collaborative research and solutions to plastic pollution

Developing a typology for peer education and peer support delivered by prisoners

Peer interventions delivered for prisoners by prisoners offer a means to improve health and reduce risk factors for this population. The variety of peer programs poses challenges for synthesizing evidence. This paper presents a typology developed as part of a systematic review of peer interventions in prison settings. Peer interventions are grouped into four modes: peer education, peer support, peer mentoring and bridging roles, with the addition of a number of specific interventions identified through the review process. The paper discusses the different modes of peer delivery with reference to a wider health promotion literature on the value of social influence and support. In conclusion, the typology offers a framework for developing the evidence base across a diverse field of practice in correctional health care

Three Strategies for Changing Attributions about Severe Mental Illness

The effects of three strategies for changing stigmatizing attitudes—education (which replaces myths about mental illness with accurate conceptions), contact (which challenges public attitudes about mental illness through direct interactions with persons who have these disorders), and protest (which seeks to suppress stigmatizing attitudes about mental illness)—were examined on attributions about schizophrenia and other severe mental illnesses. One hundred and fifty-two students at a community college were randomly assigned to one of the three strategies or a control condition. They completed a questionnaire about attributions toward six groups—depression, psychosis, cocaine addiction, mental retardation, cancer, and AIDS—prior to and after completing the assigned condition. As expected, results showed that education had no effect on attributions about physical disabilities but led to improved attributions in all four psychiatric groups. Contact produced positive changes that exceeded education effects in attributions about targeted psychiatric disabilities: depression and psychosis. Protest yielded no significant changes in attributions about any group. This study also examined the effects of these strategies on processing information about mental illness

Identifying molecular features that distinguish fluvastatin-sensitive breast tumor cells

Statins, routinely used to treat hypercholesterolemia, selectively induce apoptosis in some tumor cells by inhibiting the mevalonate pathway. Recent clinical studies suggest that a subset of breast tumors is particularly susceptible to lipophilic statins, such as fluvastatin. To quickly advance statins as effective anticancer agents for breast cancer treatment, it is critical to identify the molecular features defining this sensitive subset. We have therefore characterized fluvastatin sensitivity by MTT assay in a panel of 19 breast cell lines that reflect the molecular diversity of breast cancer, and have evaluated the association of sensitivity with several clinicopathological and molecular features. A wide range of fluvastatin sensitivity was observed across breast tumor cell lines, with fluvastatin triggering cell death in a subset of sensitive cell lines. Fluvastatin sensitivity was associated with an estrogen receptor alpha (ERa)-negative, basal-like tumor subtype, features that can be scored with routine and/or strong preclinical diagnostics. To ascertain additional candidate sensitivity-associated molecular features, we mined publicly available gene expression datasets, identifying genes encoding regulators of mevalonate production, nonsterol lipid homeostasis, and global cellular metabolism, including the oncogene MYC. Further exploration of this data allowed us to generate a 10-gene mRNA abundance signature predictive of fluvastatin sensitivity, which showed preliminary validation in an independent set of breast tumor cell lines. Here, we have therefore identified several candidate predictors of sensitivity to fluvastatin treatment in breast cancer, which warrant further preclinical and clinical evaluation.Fil: Goard, Carolyn A.. University Health Network. Princess Margaret Cancer Centre. Ontario Cancer Institute and Campbell Family Institute for Breast Cancer Research; Canadá. University Of Toronto; CanadáFil: Chan Seng Yue, Michelle . University Health Network. Princess Margaret Cancer Centre. Ontario Cancer Institute and Campbell Family Institute for Breast Cancer Research; Canadá. Ontario Institute of Cancer Research. Informatics and Biocomputing Platform; CanadáFil: Mullen, Peter J.. University Health Network. Princess Margaret Cancer Centre. Ontario Cancer Institute and Campbell Family Institute for Breast Cancer Research; CanadáFil: Quiroga, Ariel Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; Argentina. University of Alberta; CanadáFil: Wasylishen, Amanda R.. University Health Network. Princess Margaret Cancer Centre. Ontario Cancer Institute and Campbell Family Institute for Breast Cancer Research; Canadá. University Of Toronto; CanadáFil: Clendening, James W.. University Health Network. Princess Margaret Cancer Centre. Ontario Cancer Institute and Campbell Family Institute for Breast Cancer Research; Canadá. University Of Toronto; CanadáFil: Sendorek, Dorota H. S.. Ontario Institute of Cancer Research. Informatics and Biocomputing Platform; CanadáFil: Haider, Syed. Ontario Institute of Cancer Research. Informatics and Biocomputing Platform; CanadáFil: Lehner, Richard. University of Alberta; CanadáFil: Boutros, Paul C.. University Of Toronto; Canadá. Ontario Institute of Cancer Research. Informatics and Biocomputing Platform; CanadáFil: Penn, Linda Z.. University Health Network. Princess Margaret Cancer Centre. Ontario Cancer Institute and Campbell Family Institute for Breast Cancer Research; Canadá. University Of Toronto; Canad