The effects of mutant Ras proteins on the cell signalome

The genetic alterations in cancer cells are tightly linked to signaling pathway dysregulation. Ras is a key molecule that controls several tumorigenesis-related processes, and mutations in RAS genes often lead to unbiased intensification of signaling networks that fuel cancer progression. In this article, we review recent studies that describe mutant Ras-regulated signaling routes and their cross-talk. In addition to the two main Ras-driven signaling pathways, i.e., the RAF/MEK/ERK and PI3K/AKT/mTOR pathways, we have also collected emerging data showing the importance of Ras in other signaling pathways, including the RAC/PAK, RalGDS/Ral, and PKC/PLC signaling pathways. Moreover, microRNA-regulated Ras-associated signaling pathways are also discussed to highlight the importance of Ras regulation in cancer. Finally, emerging data show that the signal alterations in specific cell types, such as cancer stem cells, could promote cancer development. Therefore, we also cover the up-to-date findings related to Ras-regulated signal transduction in cancer stem cells. © 2020, The Author(s)

Climate Impacts, Political Institutions, and Leader Survival: Effects of Drought and Flooding Precipitation.

We explore how the political survival of leaders in different political regimes is affected by drought and flooding precipitation, which are the two major anticipated impacts of anthropogenic climate change. Using georeferenced climate data for the entire world and the Archigos dataset for the period of 1950-2010, we find that irregular political exits, such as coups or revolutions, are not significantly affected by climate impacts. Similarly, drought has a positive but insignificant effect on all types of political exits. On the other hand, we find that floods increase political turnover through the regular means such as elections or term limits. Democracies are better able to withstand the pressures arising from the economic and social disruptions associated with high precipitation than other institutional arrangements. Our results further suggest that, in the context of floods, political institutions play a more important role than economic development for the leaders’ political survival

Oxidative stress and metabolic markers in pre- and postnatal polycystic ovary syndrome rat protocols

Lady Serrano Mujica,1 Alessandra Bridi,1,2 Ricardo Della Méa,1 Vitor Braga Rissi,1 Naiara Guarda,3 Rafael Noal Moresco,3 Melissa Orlandin Premaor,4 Alfredo Quites Antoniazzi,1 Paulo Bayard Dias Gonçalves,1 Fabio Vasconcellos Comim1,4 1Laboratory of Biotechnology and Animal Reproduction, BioRep, Federal University of Santa Maria, Santa Maria, Rio Grande do Sul, 2Department of Veterinary Medicine, University of São Paulo, São Paulo, 3Laboratory of Clinical Biochemistry, Department of Clinical and Toxicological Analysis, 4Department of Clinical Medicine, Federal University of Santa Maria, Santa Maria, Rio Grande do Sul, Brazil Background: Several studies have described an enhanced inflammatory status and oxidative stress balance disruption in women with polycystic ovary syndrome (PCOS). However, there is scarce information about redox markers in the blood of androgenized animal models. Here, we evaluated the serum/plasma oxidative stress marker and metabolic parameter characteristics of prenatal (PreN) and postnatal (PostN) androgenized rat models of PCOS. Materials and methods: For PreN androgenization (n=8), 2.5 mg of testosterone propionate was subcutaneously administered to dams at embryonic days 16, 17, and 18, whereas PostN androgenization (n=7) was accomplished by subcutaneously injecting 1.25 mg of testosterone propionate to animals at PostN day 5. A unique control group (n=8) was constituted for comparison. Results: Our results indicate that PostN group rats exhibited particular modifications in the oxidative stress marker, an increased plasma ferric-reducing ability of plasma, and an increased antioxidant capacity reflected by higher albumin serum levels. PostN animals also presented increased total cholesterol and triglyceride–glucose levels, suggesting severe metabolic disarrangement. Conclusion: Study findings indicate that changes in oxidative stress could be promoted by testosterone propionate exposure after birth, which is likely associated with anovulation and/or lipid disarrangement. Keywords: animal models of PCOS, oxidative stress, prenatal, postnata

Oxidative stress and biochemical markers in prenatally androgenized sheep after neonatal treatment with GnRH agonist

Jandui Escariãoda Nóbrega,1 Joabel Tonelotto dos Santos,1 Lady K Serrano-Mujica,1 Guilherme Bochi,2 Rafael Noal Moresco,2 Vitor Braga Rissi,1 Werner Giehl Glanzner,1 Felipe W Langer,3 Alfredo Quites Antoniazzi,1 Paulo Bayard Dias Gonçalves,1 Melissa O Premaor,3 Fabio V Comim1,3 1Laboratory of Biotechnology and Animal Reproduction – BioRep, Federal University of Santa Maria (UFSM), Santa Maria, RS, Brazil; 2Laboratory of Clinical Biochemistry, Department of Clinical and Toxicological Analysis, Federal University of Santa Maria (UFSM), Santa Maria, RS, Brazil; 3Department of Clinical Medicine, Federal University of Santa Maria (UFSM), Santa Maria, RS, Brazil Background: Disruption of the balance between the production of ROS and their removal through enzymatic and non-enzymatic (antioxidant) processes has been proposed as a new mechanism in the pathology of polycystic ovary syndrome (PCOS). Evidence from animal models of PCOS (prenatally androgenized sheep) has suggested that treatment with insulin sensitizers, but not antiandrogens, can reduce increases in ROS.Materials and methods: In the present study, we investigated the effects of neonatal treatment with a gonadotropin-releasing hormone (GnRH) agonist (leuprolide acetate) on prenatally androgenized sheep with testosterone propionate to determine its impact on oxidative stress molecules (ferric reducing antioxidant power [FRAP], advanced oxidation protein product [AOPP], nitric oxide [NOx], albumin) at 8, 12, and 18 months of age.Results: Androgenized ewes (but not leuprolide-treated ewes) showed reduced total cholesterol levels associated with a decrease in the ratio of visceral to subcutaneous adiposity (adjusted to abdominal area) as determined by computed tomography. In androgenized ewes at 12 months of age, an increase in subcutaneous fat and relative decrease in the visceral fat compartment did not affect the expression of REDOX markers. At 18 months of age, however, the levels of NOx metabolites decreased in androgenized animals, but remained close to normal in ewes subjected to neonatal treatment with leuprolide acetate. Other oxidative stress parameters (FRAP, AOPP, albumin) did not vary among groups.Conclusion: Our results demonstrate that the GnRH agonist leuprolide (as a single dose after birth) had weak effects on markers of the oxidative stress balance. Keywords: animal model of polycystic ovary syndrome, oxidative stress, gonadotropin-releasing hormone agonist, sheep, metabolis

LGBTQ perspectives in peacebuilding

Feminist scholars have long touted the necessity of employing a gender lens to better understand power and violence in global politics. Sexuality is an important dimension of these gendered power dynamics. LGBTQ (lesbian, gay, bisexual, transgender, and queer) perspectives in peacebuilding unsettle the assumptions about what is the “correct” or “normal” sexual orientation, gender identity, or family structure. Drawing on a multiplicity of LGBTQ voices to inform post-conflict responses allows for a more expansive approach to understanding what gendered insecurities look like and how best to respond to them