RHOA (ras homolog gene family, member A)

Review on RHOA (ras homolog gene family, member A), with data on DNA, on the protein encoded, and where the gene is implicated

No tots els parcs urbans creen benestar relacional en els nens i nenes

Un estudi de dos parcs de Barcelona que han tingut diferents impactes en les habilitats socials dels nens mostra la importància de considerar les estructures socials en la planificació de nous parcs i espais urbans de joc. Aquesta investigació busca ressaltar els vincles entre les formes dominants de reurbanitzacions "verdes" que tenen lloc a les ciutats i les qüestions de justícia ambiental urbana, i els desafiaments i possibilitats que aquestes impliquen per aconseguir espais urbans més justos i ecològics.Un estudio de dos parques de Barcelona que han tenido diferentes impactos en las habilidades sociales de los niños muestra la importancia de considerar las estructuras sociales en la planificación de nuevos parques y espacios urbanos de juego. Esta investigación busca resaltar los vínculos entre las formas dominantes de reurbanizaciones "verdes" que tienen lugar en ciudades y las cuestiones de justicia ambiental urbana, y los desafíos y posibilidades que estas implican para conseguir espacios urbanos más justos y ecológicos.A study of two parks in Barcelona that have had very different impacts on children's social skills shows the importance of considering social structures in the planning of new parks and urban play spaces. This research seeks to highlight the linkages between the dominant forms of "green" redevelopments taking place in cities and questions of urban environmental justice, and the challenges and possibilities these imply for more just and ecological urban spaces

Urban green grabbing : Residential real estate developers discourse and practice in gentrifying Global North neighborhoods

Altres ajuts: Acord transformatiu CRUE-CSICUnidad de excelencia María de Maeztu CEX2019-000940-MIn the movement towards building greener and more sustainable cities, real estate developers are increasingly embracing not only green building construction but broader strategies and action related to urban greening. To date, their motivations and role in this broader urban greening dynamic remains underexplored, yet essential to dissect how greening is sustained and real estate development legitimized in revitalizing neighborhoods. With an eye to better understand green urban capitalist development processes underway amidst financialized nature and urban growth, and the equity impacts they entail, we explore residential real estate developers urban greening discourses and practices. Through a novel dataset of 42 interviews with private and non-profit residential real estate developers in 15 mid-sized American, Western European and Canadian cities, we uncover three differentiated but interconnected discourses around (i) financial benefits, (ii) consumer- or investor-driven demand and (iii) social dimensions behind developers' interest in urban greening. We argue that developers embark on urban green grabbing through "green" discursive and material value appropriation and rent extraction strategies. Urban green grabbing is conceptually useful in depicting who benefits and how/when developers extract additional rent, surplus value, social capital and/or prestige from locating new residential projects adjacent to new or up-and-coming green amenities. Our work contributes to debates about urban greening's perceived position as a value-producing and rent-extracting good from both a political economy and political ecology perspectiv

Gentrification and health in two global cities : a call to identify impacts for socially-vulnerable residents

Unidad de excelencia María de Maeztu MdM-2015-0552In global cities, the impacts of gentrification on the lives and well-being of socially vulnerable residents have occupied political agendas. Yet to date, research on how gentrification affects a multiplicity of health outcomes has remained scarce. While much of the nascent quantitative research helps to identify associations between gentrification and determined health outcomes, it tends to draw from static datasets collected for other studies to draw a posteriori and non-longitudinal conclusions. There is little attention in traditional public health research to purposely understand the health impacts of the complex, multi-layered, and rapid change produced by gentrification. Moreover, few studies examine the pathways and socio-spatial dynamics of the association between gentrification and health. In response, we use qualitative data collected in Boston and Barcelona to comprehensively identify how the health and well-being of long-term residents may be affected by gentrification and to call for new multi-methods research. In this initial assessment, we find a range of potential detrimental factors and potential pathways associated with gentrification, including individual-level physical and mental health outcomes such as obesity, asthma, chronic stress, and depression; neighborhood-level health determinants such as safety and new drug-dealing/use; and institutional-level health determinants such as healthcare precarity and worsened school conditions

Combination of KIR2DS4 and FcγRIIa polymorphisms predicts the response to cetuximab in KRAS mutant metastatic colorectal cancer

Cetuximab is a standard-of-care treatment for RAS wild-type metastatic colorectal cancer (mCRC) but not for those harbor a KRAS mutation since MAPK pathway is constitutively activated. Nevertheless, cetuximab also exerts its effect by its immunomodulatory activity despite the presence of RAS mutation. The aim of this study was to determine the impact of polymorphism FcγRIIIa V158F and killer immunoglobulin-like receptor (KIR) genes on the outcome of mCRC patients with KRAS mutations treated with cetuximab. This multicenter Phase II clinical trial included 70 mCRC patients with KRAS mutated. We found KIR2DS4 gene was significantly associated with OS (HR 2.27; 95% CI, 1.08–4.77; P = 0.03). In non-functional receptor homozygotes the median OS was 2.6 months longer than in carriers of one copy of full receptor. Multivariate analysis confirmed KIR2DS4 as a favorable prognostic marker for OS (HR 6.71) in mCRC patients with KRAS mutation treated with cetuximab. These data support the potential therapeutic of cetuximab in KRAS mutated mCRC carrying non-functional receptor KIR2DS4 since these patients significantly prolong their OS even after heavily treatment. KIR2DS4 typing could be used as predictive marker for identifying RAS mutated patients that could benefit from combination approaches of anti-EGFR monoclonal antibodies and other immunotherapies to overcome the resistance mediated by mutation in RAS.This clinical trial was approved and supported by Merck S.L., an affiliate of Merck KGaA, Darmstadt. Germany [research project number 2010-023580-18, date: 05-06-2014

Exploring green gentrification in 28 global North cities : the role of urban parks and other types of greenspaces

Unidad de excelencia María de Maeztu CEX2019-000940-MAlthough cities globally are increasingly mobilizing re-naturing projects to address diverse urban socio-environmental and health challenges, there is mounting evidence that these interventions may also be linked to the phenomenon known as green gentrification. However, to date the empirical evidence on the relationship between greenspaces and gentrification regarding associations with different greenspace types remains scarce. This study focused on 28 mid-sized cities in North America and Western Europe. We assessed improved access to different types of greenspace (i.e. total area of parks, gardens, nature preserves, recreational areas or greenways [i] added before the 2000s or [ii] added before the 2010s) and gentrification processes (including [i] gentrification for the 2000s; [ii] gentrification for the 2010s; [iii] gentrification throughout the decades of the 2000s and 2010s) in each small geographical unit of each city. To estimate the associations, we developed a Bayesian hierarchical spatial model foreach city and gentrification time period (i.e. a maximum of three models per city). More than half of our models showed that parks-together with other factors such as proximity to the city center-are positively associated with gentrification processes, particularly in the US context, except in historically Black disinvested postindustrial cities with lots of vacant land. We also find than in half of our models newly designated nature preserves are negatively associated with gentrification processes, particularly when considering gentrification throughout the 2000s and the 2010s and in the US. Meanwhile, for new gardens, recreational spaces and greenways, our research shows mixed results (some positive, some negative and some no effect associations). Considering the environmental and health benefits of urban re-naturing projects, cities should keep investing in improving park access while simultaneously implementing anti-displacement and inclusive green policies

An apicobasal gradient of Rac activity determines protrusion form and position

Each cell within a polarised epithelial sheet must align and correctly position a wide range of subcellular structures, including actin-based dynamic protrusions. Using in vivo inducible transgenes that can sense or modify Rac activity, we demonstrate an apicobasal gradient of Rac activity that is required to correctly form and position distinct classes of dynamic protrusion along the apicobasal axis of the cell. We show that we can modify the Rac activity gradient in genetic mutants for specific polarity proteins, with consequent changes in protrusion form and position and additionally show, using photoactivatable Rac transgenes, that it is the level of Rac activity that determines protrusion form. Thus, we demonstrate a mechanism by which polarity proteins can spatially regulate Rac activity and the actin cytoskeleton to ensure correct epithelial cell shape and prevent epithelial-to-mesenchymal transitions

Cell Culture Replication of a Genotype 1b Hepatitis C Virus Isolate Cloned from a Patient Who Underwent Liver Transplantation

The introduction of the genotype 2a isolate JFH1 was a major breakthrough in the field of hepatitis C virus (HCV), allowing researchers to study the complete life cycle of the virus in cell culture. However, fully competent culture systems encompassing the most therapeutically relevant HCV genotypes are still lacking, especially for the highly drug-resistant genotype 1b. For most isolated HCV clones, efficient replication in cultured hepatoma cells requires the introduction of replication-enhancing mutations. However, such mutations may interfere with viral assembly, as occurs in the case of the genotype 1b isolate Con1. In this study, we show that a clinical serum carrying a genotype 1b virus with an exceptionally high viral load was able to infect Huh7.5 cells. Similar to previous reports, inoculation of Huh7.5 cells by natural virus is very inefficient compared to infection by cell culture HCV. A consensus sequence of a new genotype 1b HCV isolate was cloned from the clinical serum (designated Barcelona HCV1), and then subjected to replication studies. This virus replicated poorly in a transient fashion in Huh7.5 cells after electroporation with in vitro transcribed RNA. Nonetheless, approximately 3 weeks post electroporation and thereafter, core protein-positive cells were detected by immunofluorescence. Surprisingly, small amounts of core protein were also measurable in the supernatant of electroporated cells, suggesting that HCV particles might be assembled and released. Our findings not only enhance the current method of cloning in vitro HCV replication-competent isolates, but also offer valuable insights for the realization of fully competent culture systems for HCV

Essential Role of Cdc42 in Ras-Induced Transformation Revealed by Gene Targeting

The ras proto-oncogene is one of the most frequently mutated genes in human cancer. However, given the prevalence of activating mutations in Ras and its association with aggressive forms of cancer, attempts to therapeutically target aberrant Ras signaling have been largely disappointing. This lack of progress highlights the deficiency in our understanding of cellular pathways required for Ras-mediated tumorigenesis and suggests the importance of identifying new molecular pathways associated with Ras-driven malignancies. Cdc42 is a Ras-related small GTPase that is known to play roles in oncogenic processes such as cell growth, survival, invasion, and migration. A pan-dominant negative mutant overexpression approach to suppress Cdc42 and related pathways has previously shown a requirement for Cdc42 in Ras-induced anchorage-independent cell growth, however the lack of specificity of such approaches make it difficult to determine if effects are directly related to changes in Cdc42 activity or other Rho family members. Therefore, in order to directly and unambiguously address the role of Cdc42 in Ras-mediated transformation, tumor formation and maintenance, we have developed a model of conditional cdc42 gene in Ras-transformed cells. Loss of Cdc42 drastically alters the cell morphology and inhibits proliferation, cell cycle progression and tumorigenicity of Ras-transformed cells, while non-transformed cells or c-Myc transformed cells are largely unaffected. The loss of Cdc42 in Ras-transformed cells results in reduced Akt signaling, restoration of which could partially rescues the proliferation defects associated with Cdc42 loss. Moreover, disruption of Cdc42 function in established tumors inhibited continued tumor growth. These studies implicate Cdc42 in Ras-driven tumor growth and suggest that targeting Cdc42 is beneficial in Ras-mediated malignancies

Tumor-suppressor activity of RRIG1 in breast cancer

<p>Abstract</p> <p>Background</p> <p>Retinoid receptor-induced gene-1 (RRIG1) is a novel gene that has been lost in several types of human cancers. The aim of this study was to determine whether RRIG1 plays a role in breast cancer, such as in the suppression of breast cancer cell growth and invasion.</p> <p>Methods</p> <p>Immunohistochemistry was used to detect RRIG1 expression in breast tissue specimens. Gene transfection was used to restore or knock down RRIG1 expression in breast cancer cell lines for analysis of cell viability, colony formation, and migration/invasion potential. Reverse-transcription polymerase chain reaction and western blot assays were used to detect the changes in gene expression. The RhoA activation assay was used to assess RRIG1-induced inhibition of RhoA activity.</p> <p>Results</p> <p>The immunohistochemical data showed that <it>RRIG1 </it>expression was reduced in breast cancer tissues compared with normal and atypical hyperplastic breast tissues. <it>RRIG1 </it>expression was inversely correlated with lymph node metastasis of breast cancer but was not associated with the status of hormone receptors, such as estrogen receptor, progesterone receptor, or HER2. Furthermore, restoration of <it>RRIG1 </it>expression inhibited proliferation, colony formation, migration, and invasion of breast cancer cells. Expression of RRIG1 also reduced phosphorylated Erk1/2 and Akt levels; c-Jun, MMP9, and Akt expressions; and RhoA activity. In contrast, knockdown of RRIG1 expression promoted breast cancer cell proliferation, colony formation, migration, and invasion potential.</p> <p>Conclusion</p> <p>The data from the current study indicated that <it>RRIG1 </it>expression was reduced or lost in breast cancer and that restoration of RRIG1 expression suppressed breast cancer cell growth and invasion capacity. Future studies will determine the underlying molecular mechanisms and define RRIG1 as a tumor-suppressor gene in breast cancer.</p