A Therapeutic Perspective

AF was funded by a Ph.D. fellowship (PD/BD/135506/2018) from the Fundação para a Ciência e a Tecnologia (FCT) and DB by the FCT Investigator Program (IF/00501/2014/CP1252/CT0001).The Adenosine diphosphate-Ribosylation Factor (ARF) family belongs to the RAS superfamily of small GTPases and is involved in a wide variety of physiological processes, such as cell proliferation, motility and differentiation by regulating membrane traffic and associating with the cytoskeleton. Like other members of the RAS superfamily, ARF family proteins are activated by Guanine nucleotide Exchange Factors (GEFs) and inactivated by GTPase-Activating Proteins (GAPs). When active, they bind effectors, which mediate downstream functions. Several studies have reported that cancer cells are able to subvert membrane traffic regulators to enhance migration and invasion. Indeed, members of the ARF family, including ARF-Like (ARL) proteins have been implicated in tumorigenesis and progression of several types of cancer. Here, we review the role of ARF family members, their GEFs/GAPs and effectors in tumorigenesis and cancer progression, highlighting the ones that can have a pro-oncogenic behavior or function as tumor suppressors. Moreover, we propose possible mechanisms and approaches to target these proteins, toward the development of novel therapeutic strategies to impair tumor progression.publishersversionpublishe

Arl13b interferes with α-tubulin acetylation

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Commensal-to-pathogen transition: One-single transposon insertion results in two pathoadaptive traits in Escherichia coli -macrophage interaction

There are no funders and sponsors indicated explicitly in the document. This deposit is composed by the main article plus the supplementary materials of the publication.Escherichia coli is both a harmless commensal in the intestines of many mammals, as well as a dangerous pathogen. The evolutionary paths taken by strains of this species in the commensal-to-pathogen transition are complex and can involve changes both in the core genome, as well in the pan-genome. One way to understand the likely paths that a commensal strain of E. coli takes when evolving pathogenicity is through experimentally evolving the strain under the selective pressures that it will have to withstand as a pathogen. Here, we report that a commensal strain, under continuous pressure from macrophages, recurrently acquired a transposable element insertion, which resulted in two key phenotypic changes: increased intracellular survival, through the delay of phagosome maturation and increased ability to escape macrophages. We further show that the acquisition of the pathoadaptive traits was accompanied by small but significant changes in the transcriptome of macrophages upon infection. These results show that under constant pressures from a key component of the host immune system, namely macrophage phagocytosis, commensal E. coli rapidly acquires pathoadaptive mutations that cause transcriptome changes associated to the host-microbe duet.There are no funders and sponsors indicated explicitly in the document.info:eu-repo/semantics/publishedVersio

On the fringe: tracking and evaluating changes in land use in the areas surrounding three national parks in Spain and Portugal

Naturbanization analyses territorial changes in the surroundings of national parks brought about by the arrival of new settlers and economic activities, both of which are attracted by the value of the environment and landscape. This paper presents a comparison of the naturbanization processes in three national parks in Spain and Portugal (Doñana and Sierra Nevada National Parks, and Peneda-Gêres National Park, respectively) and in their areas of influence. Data is taken from Corine-Land Cover (1990-2006), which is the only available source of information about land use and land cover changes in the whole of the European Union. These changes have been interpreted and analysed using the Cross Tabulation Matrix developed by Pontius (2004). Land use changes connected to naturbanization processes are measured using Gains and Loss measurements. The intensification of changes in land use is one of the most significant developments associated with these processes, which have implications for the sustainable development and conservation of these areas

Assessment of human influenza pandemic scenarios in Europe

The response to the emergence of the 2009 influenza A(H1N1) pandemic was the result of a decade of pandemic planning, largely centred on the threat of an avian influenza A(H5N1) pandemic. Based on a literature review, this study aims to define a set of new pandemic scenarios that could be used in case of a future influenza pandemic. A total of 338 documents were identified using a searching strategy based on seven combinations of keywords. Eighty-three of these documents provided useful information on the 13 virus-related and health-system-related parameters initially considered for describing scenarios. Among these, four parameters were finally selected (clinical attack rate, case fatality rate, hospital admission rate, and intensive care admission rate) and four different levels of severity for each of them were set. The definition of six most likely scenarios results from the combination of four different levels of severity of the four final parameters (256 possible scenarios). Although it has some limitations, this approach allows for more flexible scenarios and hence it is far from the classic scenarios structure used for pandemic plans until 2009