FAK signaling is critical for ErbB-2/ErbB-3 receptor cooperation for oncogenic transformation and invasion

The overexpression of members of the ErbB tyrosine kinase receptor family has been associated with cancer progression. We demonstrate that focal adhesion kinase (FAK) is essential for oncogenic transformation and cell invasion that is induced by ErbB-2 and -3 receptor signaling. ErbB-2/3 overexpression in FAK-deficient cells fails to promote cell transformation and rescue chemotaxis deficiency. Restoration of FAK rescues both oncogenic transformation and invasion that is induced by ErbB-2/3 in vitro and in vivo. In contrast, the inhibition of FAK in FAK-proficient invasive cancer cells prevented cell invasion and metastasis formation. The activation of ErbB-2/3 regulates FAK phosphorylation at Tyr-397, -861, and -925. ErbB-induced oncogenic transformation correlates with the ability of FAK to restore ErbB-2/3–induced mitogen-activated protein kinase (MAPK) activation; the inhibition of MAPK prevented oncogenic transformation. In contrast, the inhibition of Src but not MAPK prevented ErbB–FAK-induced chemotaxis. In migratory cells, activated ErbB-2/3 receptors colocalize with activated FAK at cell protrusions. This colocalization requires intact FAK. In summary, distinct FAK signaling has an essential function in ErbB-induced oncogenesis and invasiveness

Implementing Green Infrastructure for the Spatial Planning of Peri-Urban Areas in Geneva, Switzerland

The concept of green infrastructure (GI) seeks to identify and prioritize areas of high ecological value for wildlife and people, to improve the integration of natural values in landscape planning decisions. In 2018, the canton of Geneva, Switzerland, established a roadmap for biodiversity conservation, which includes the operationalization of GI covering 30% of the territory by 2030. In this paper, we demonstrate a GI mapping framework in the canton of Geneva. Our approach is based on the combined assessment of three 'pillars', namely species' distribution, landscape structure and connectivity, and ecosystem services, to optimize the allocation of conservation actions using the spatial prioritization software, Zonation. The identified priority conservation areas closely overlap existing natural reserves. Including the three pillars in the landscape prioritization should also improve adhesion to the GI idea, without undermining the protection of threatened species. With regards to land use planning, public and private land parcels with high values for GI may require specific incentives to maintain their desirable characteristics, as they are more likely to be degraded than areas with more building restrictions. Visualizing priority conservation areas in a spatially explicit manner will support decision-makers in Geneva to optimally allocate limited resources for ecosystem preservation.Peer reviewe

HIV-Specific Cellular Immune Response Is Inversely Correlated with Disease Progression as Defined by Decline of CD4+ T Cells in Relation to HIV RNA Load

The average time between infection with human immunodeficiency virus (HIV) and development of acquired immune deficiency syndrome is ∼8 years. However, progression rates vary widely, depending on several determinants, including HIV-specific immunity, host genetic factors, and virulence of the infecting strain. In untreated HIV-infected patients with different progression rates, we examined HIV-specific T cell responses in combination with host genetic markers, such as chemokine/chemokine-receptor (CCR) polymorphisms and human leukocyte antigen (HLA) genotypes. HIV-specific CD4+ T cell responses and, to a lesser extent, HIVspecific CD8+ T cell responses were inversely correlated with progression rate. Slower progression was not related to polymorphisms in CCR genes, HLA genotype, or GB virus C coinfection. These data suggest that HIV-specific T cell responses are involved in protecting the host from disease progressio

Introduced Mammalian Predators Induce Behavioural Changes in Parental Care in an Endemic New Zealand Bird

The introduction of predatory mammals to oceanic islands has led to the extinction of many endemic birds. Although introduced predators should favour changes that reduce predation risk in surviving bird species, the ability of island birds to respond to such novel changes remains unstudied. We tested whether novel predation risk imposed by introduced mammalian predators has altered the parental behaviour of the endemic New Zealand bellbird (Anthornis melanura). We examined parental behaviour of bellbirds at three woodland sites in New Zealand that differed in predation risk: 1) a mainland site with exotic predators present (high predation risk), 2) a mainland site with exotic predators experimentally removed (low risk recently) and, 3) an off-shore island where exotic predators were never introduced (low risk always). We also compared parental behaviour of bellbirds with two closely related Tasmanian honeyeaters (Phylidonyris spp.) that evolved with native nest predators (high risk always). Increased nest predation risk has been postulated to favour reduced parental activity, and we tested whether island bellbirds responded to variation in predation risk. We found that females spent more time on the nest per incubating bout with increased risk of predation, a strategy that minimised activity at the nest during incubation. Parental activity during the nestling period, measured as number of feeding visits/hr, also decreased with increasing nest predation risk across sites, and was lowest among the honeyeaters in Tasmania that evolved with native predators. These results demonstrate that some island birds are able to respond to increased risk of predation by novel predators in ways that appear adaptive. We suggest that conservation efforts may be more effective if they take advantage of the ability of island birds to respond to novel predators, especially when the elimination of exotic predators is not possible

Synthesizing plausible futures for biodiversity and ecosystem services in Europe and Central Asia using scenario archetypes

Scenarios are a useful tool to explore possible futures of social-ecological systems. The number of scenarios has increased dramatically over recent decades, with a large diversity in temporal and spatial scales, purposes, themes, development methods, and content. Scenario archetypes generically describe future developments and can be useful in meaningfully classifying scenarios, structuring and summarizing the overwhelming amount of information, and enabling scientific outputs to more effectively interface with decision-making frameworks. The Intergovernmental Platform for Biodiversity and Ecosystem Services (IPBES) faced this challenge and used scenario archetypes in its assessment of future interactions between nature and society. We describe the use of scenario archetypes in the IPBES Regional Assessment of Europe and Central Asia. Six scenario archetypes for the region are described in terms of their driver assumptions and impacts on nature (including biodiversity) and its contributions to people (including ecosystem services): business-as-usual, economic optimism, regional competition, regional sustainability, global sustainable development, and inequality. The analysis shows that trade-offs between nature’s contributions to people are projected under different scenario archetypes. However, the means of resolving these trade-offs depend on differing political and societal value judgements within each scenario archetype. Scenarios that include proactive decision making on environmental issues, environmental management approaches that support multifunctionality, and mainstreaming environmental issues across sectors, are generally more successful in mitigating trade-offs than isolated environmental policies. Furthermore, those scenario archetypes that focus on achieving a balanced supply of nature’s contributions to people and that incorporate a diversity of values are estimated to achieve more policy goals and targets, such as the UN Sustainable Development Goals and the Convention on Biological Diversity Aichi targets. The scenario archetypes approach is shown to be helpful in supporting science-policy dialogue for proactive decision making that anticipates change, mitigates undesirable trade-offs, and fosters societal transformation in pursuit of sustainable development

Synthesizing plausible futures for biodiversity and ecosystem services in europe and central asia using scenario archetypes

Scenarios are a useful tool to explore possible futures of social-ecological systems. The number of scenarios has increased dramatically over recent decades, with a large diversity in temporal and spatial scales, purposes, themes, development methods, and content. Scenario archetypes generically describe future developments and can be useful in meaningfully classifying scenarios, structuring and summarizing the overwhelming amount of information, and enabling scientific outputs to more effectively interface with decision-making frameworks. The Intergovernmental Platform for Biodiversity and Ecosystem Services (IPBES) faced this challenge and used scenario archetypes in its assessment of future interactions between nature and society. We describe the use of scenario archetypes in the IPBES Regional Assessment of Europe and Central Asia. Six scenario archetypes for the region are described in terms of their driver assumptions and impacts on nature (including biodiversity) and its contributions to people (including ecosystem services): Business-as-usual, economic optimism, regional competition, regional sustainability, global sustainable development, and inequality. The analysis shows that trade-offs between nature’s contributions to people are projected under different scenario archetypes. However, the means of resolving these trade-offs depend on differing political and societal value judgements within each scenario archetype. Scenarios that include proactive decision making on environmental issues, environmental management approaches that support multifunctionality, and mainstreaming environmental issues across sectors, are generally more successful in mitigating tradeoffs than isolated environmental policies. Furthermore, those scenario archetypes that focus on achieving a balanced supply of nature’s contributions to people and that incorporate a diversity of values are estimated to achieve more policy goals and targets, such as the UN Sustainable Development Goals and the Convention on Biological Diversity Aichi targets. The scenario archetypes approach is shown to be helpful in supporting science-policy dialogue for proactive decision making that anticipates change, mitigates undesirable trade-offs, and fosters societal transformation in pursuit of sustainable development. © 2019 by the author(s)

Focal Adhesion Kinase contributes to insulin-induced actin reorganization into a mesh harboring Glucose transporter-4 in insulin resistant skeletal muscle cells

<p>Abstract</p> <p>Background</p> <p>Focal Adhesion Kinase (FAK) is recently reported to regulate insulin resistance by regulating glucose uptake in C2C12 skeletal muscle cells. However, the underlying mechanism for FAK-mediated glucose transporter-4 translocation (Glut-4), responsible for glucose uptake, remains unknown. Recently actin remodeling was reported to be essential for Glut-4 translocation. Therefore, we investigated whether FAK contributes to insulin-induced actin remodeling and harbor Glut-4 for glucose transport and whether downregulation of FAK affects the remodeling and causes insulin resistance.</p> <p>Results</p> <p>To address the issue we employed two approaches: gain of function by overexpressing FAK and loss of function by siRNA-mediated silencing of FAK. We observed that overexpression of FAK induces actin remodeling in skeletal muscle cells in presence of insulin. Concomitant to this Glut-4 molecules were also observed to be present in the vicinity of remodeled actin, as indicated by the colocalization studies. FAK-mediated actin remodeling resulted into subsequent glucose uptake via PI3K-dependent pathway. On the other hand FAK silencing reduced actin remodeling affecting Glut-4 translocation resulting into insulin resistance.</p> <p>Conclusion</p> <p>The data confirms that FAK regulates glucose uptake through actin reorganization in skeletal muscle. FAK overexpression supports actin remodeling and subsequent glucose uptake in a PI3K dependent manner. Inhibition of FAK prevents insulin-stimulated remodeling of actin filaments resulting into decreased Glut-4 translocation and glucose uptake generating insulin resistance. To our knowledge this is the first study relating FAK, actin remodeling, Glut-4 translocation and glucose uptake and their interrelationship in generating insulin resistance.</p

Nothing a Hot Bath Won't Cure: Infection Rates of Amphibian Chytrid Fungus Correlate Negatively with Water Temperature under Natural Field Settings

Dramatic declines and extinctions of amphibian populations throughout the world have been associated with chytridiomycosis, an infectious disease caused by the pathogenic chytrid fungus Batrachochytrium dendrobatidis (Bd). Previous studies indicated that Bd prevalence correlates with cooler temperatures in the field, and laboratory experiments have demonstrated that Bd ceases growth at temperatures above 28°C. Here we investigate how small-scale variations in water temperature correlate with Bd prevalence in the wild. We sampled 221 amphibians, including 201 lowland leopard frogs (Rana [Lithobates] yavapaiensis), from 12 sites in Arizona, USA, and tested them for Bd. Amphibians were encountered in microhabitats that exhibited a wide range of water temperatures (10–50°C), including several geothermal water sources. There was a strong inverse correlation between the water temperature in which lowland leopard frogs were captured and Bd prevalence, even after taking into account the influence of year, season, and host size. In locations where Bd was known to be present, the prevalence of Bd infections dropped from 75–100% in water <15°C, to less than 10% in water >30°C. A strong inverse correlation between Bd infection status and water temperature was also observed within sites. Our findings suggest that microhabitats where water temperatures exceed 30°C provide lowland leopard frogs with significant protection from Bd, which could have important implications for disease dynamics, as well as management applications

Meta-Review of Metanalytic Studies with Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Major Depression

BACKGROUND: Major Depression (MD) and treatment-resistant depression (TRD) are worldwide leading causes of disability and therapeutic strategies for these impairing and prevalent conditions include pharmacological augmentation strategies and brain stimulation techniques. In this perspective, repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique with a favorable profile of tolerability which, despite being recently approved by the Food and Drug Administration (FDA) for the treatment of patients with medication-refractory unipolar depression, still raises some doubts about most effective parameters of stimulation.METHODS: A literature search was performed using PubMed for the years 2001 through February 2011 in order to review meta-analytic studies assessing efficacy and safety issues for rTMS in depressive disorders. Fifteen meta-analyses were identified and critically discussed in order to provide an updated and comprehensive overview of the topic with specific emphasis on potentially optimal parameters of stimulation.RESULTS: First meta-analyses on the efficacy of rTMS for the treatment of MD and TRD have shown mixed results. On the other hand, more recent meta-analytic studies seem to support the antidepressant efficacy of the technique to a greater extent, also in light of longer periods of stimulation (e.g. > 2 weeks).CONCLUSION: rTMS seems to be an effective and safe brain stimulation technique for the treatment of medication refractory depression. Nevertheless, further studies are needed to better define specific stimulation-related issues, such as duration of treatment as well as durability of effects and predictors of response