HPV16 Oncoproteins Induce MMPs/RECK-TIMP-2 Imbalance in Primary Keratinocytes: Possible Implications in Cervical Carcinogenesis

Cervical cancer is the third most common cancer in women worldwide. Persistent infection with high-risk HPV types, principally HPV16 and 18 is the main risk factor for the development of this malignancy. However, the onset of invasive tumor occurs many years after initial exposure in a minority of infected women. This suggests that other factors beyond viral infection are necessary for tumor establishment and progression. Tumor progression is characterized by an increase in secretion and activation of matrix metalloproteinases (MMPs) produced by either the tumor cells themselves or tumor-associated fibroblasts or macrophages. Increased MMPs expression, including MMP-2, MMP-9 and MT1-MMP, has been observed during cervical carcinoma progression. These proteins have been associated with degradation of ECM components, tumor invasion, metastasis and recurrence. However, few studies have evaluated the interplay between HPV infection and the expression and activity of MMPs and their regulators in cervical cancer. We analyzed the effect of HPV16 oncoproteins on the expression and activity of MMP-2, MMP-9, MT1-MMP, and their inhibitors TIMP-2 and RECK in cultures of human keratinocytes. We observed that E7 expression is associated with increased pro-MMP-9 activity in the epithelial component of organotypic cultures, while E6 and E7 oncoproteins co-expression down-regulates RECK and TIMP-2 levels in organotypic and monolayers cultures. Finally, a study conducted in human cervical tissues showed a decrease in RECK expression levels in precancer and cancer lesions. Our results indicate that HPV oncoproteins promote MMPs/RECK-TIMP-2 imbalance which may be involved in HPV-associated lesions outcome

The democracy of Green Infrastructure

With the understanding of nature in terms of ecosystem services and the recognition of the vital role these play for human wellbeing (Millennium Assessment, 2005), the value of the natural realm is scientifically and socially defined while at the same time institutionalised. Within this frame of interpretation, nature is a supplier of provision-ing, regulating, supporting welfare and cultural services, thus becoming not only a life-enabling factor for humanity but also a conceptual construct comparable to cornerstones of democracy, such as equality, freedom and citizenship. The idea of green infrastructure is another recently coined term envisioning nature in cities in the form of a net-work and enabling a broad life-furthering vision of society. Standards for green open spaces embedded in some planning frameworks further state the right for all to a common good. Yet, evidence shows that this common right is not always met. Within the current context of advanced and neoliberal capitalism, green areas are sometimes used as an added financial value for real estate, thus increasing restrictions to their free access and full utilization. In developing countries with young democracies, such as Brazil, this process implies another significant factor of social inequality insofar the restricted access to nature by the poorest people means also diminished food safety, and the jeopardizing of certain cultural practices. In developed countries, loss of land for food production and movements reclaiming the right to the city by squatting unoccupied open spaces to initiate community gar-dens, demonstrates that the access to green spaces is also problematic, although in different ways if compared to developing countries. This chapter contributes to this topic by discussing the inequality in provision of green spaces in informal settlements and social housing development in Brazil, as well as in the globalised north. The chapter concludes with recommendations to enhance democracy through a just provision of nature in cities

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Project DIAPICNA -DIAzotrophic PIco-Cyanobacteria in the North Atlantic open ocean: their abundance and importance as a source of new nitrogen at the Azores Front/Current

International audienceNutrient concentrations indicate an oligotrophic area with nutrient bottom regeneration at the North of the Azores Current Front (Station 4, 35°N, Graph 2, Left). Nitrate isotopes indicate nitrate assimilation at Station 4, while depleted signatures South of the Front might result from N 2 fixation (Graph 2, Right)