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Giralt M.,Institute Salud Carlos III | Villarroya F.,University of Barcelona
Endocrinology | Year: 2013

Brown adipose tissue (BAT) is a major site of nonshivering thermogenesis in mammals. Rodent studies indicated that BAT thermogenic activity may protect against obesity. Recent findings using novel radiodiagnosis procedures revealed unanticipated high activity of BAT in adult humans. Moreover, complex processes of cell differentiation leading to the appearance of active brown adipocytes have been recently identified. The brown adipocytes clustered in defined anatomical BAT depots of rodents arise from mesenchymal precursor cells common to the myogenic cell lineage. They are being called "classical" or "developmentally programmed" brown adipocytes. However, brown adipocytes may appear after thermogenic stimuli at anatomical sites corresponding to white adipose tissue (WAT). This process is called the "browning" of WAT. The brown adipocytes appearing in WAT derive from precursor cells different from those in classical BAT and are closer to the white adipocyte cell lineage. The brown adipocytes appearing in WAT are often called "inducible, beige, or brite." The appearance of these inducible brown adipocytes in WAT may also involve transdifferentiation processes of white-to-brown adipose cells. There is no evidence that the ultimate thermogenic function of the beige/brite adipocytes differs from that of classical brown adipocytes, although some genetic data in rodents suggest a relevant role of the browning process in protection against obesity. Although the activation of classical BAT and the browning process sharecommonmechanisms of induction (eg, noradrenergic-mediated induction by cold), multiple novel adrenergic-independent endocrine factors that activate BAT and the browning of WAT have been identified recently. In adult humans, BAT is mainly composed of beige/brite adipocytes, although recent data indicate the persistence of classical BAT at some anatomical sites. Understanding the biological processes controlling brown adipocyte activity and differentiation could help the design of BAT-focused strategies to increase energy expenditure and fight against obesity.


Cuenca-Estrella M.,Institute Salud Carlos III
Clinical Microbiology and Infection | Year: 2014

The phenotypic methods for identification of antifungal resistance are reliable procedures, and MIC determination by reference techniques is the gold standard to detect resistant clinical isolates. In recent years, progress has been made towards the description of resistance mechanisms at molecular level. There are methods of detection that can be useful for clinical laboratories, but lack of standardization precludes their full and effective integration in the routine daily practice. The molecular detection of Candida resistance to azoles and to echinocandins and of Aspergillus resistance to triazoles can be clinically relevant and could help to design more efficient prevention and control strategies. This text reviews the present state of the detection of mechanisms of resistance at the molecular level in Candida spp. and Aspergillus spp. and its relevance to clinical practice. © 2013 The Authors. Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.


Zaragoza O.,Institute Salud Carlos III | Nielsen K.,University of Minnesota
Current Opinion in Microbiology | Year: 2013

Cryptococcus neoformans is a pathogenic yeast that commonly infects immunocompromised individuals, yet has developed multiple adaptation mechanisms to the host. Several virulence factors (capsule and melanin) have been known for many years. However, this yeast also possesses a morphogenetic program that is still not well characterized. C. neoformans has the ability to dramatically enlarge its size during infection to form 'titan cells' that can reach up to 100. μm in cell body diameter, in contrast to typical size cells of 5-7. μm. These titan cells pose a problem for the host because they contribute to fungal survival, dissemination to the central nervous system, and possibly even latency. In this review, we will provide an overview of these cells, covering current knowledge about their phenotypic features, mechanism of formation, and their significance during infection. © 2013 Elsevier Ltd.


Forastiero A.,Institute Salud Carlos III
Antimicrobial agents and chemotherapy | Year: 2013

Candida tropicalis ranks between third and fourth among Candida species most commonly isolated from clinical specimens. Invasive candidiasis and candidemia are treated with amphotericin B or echinocandins as first-line therapy, with extended-spectrum triazoles as acceptable alternatives. Candida tropicalis is usually susceptible to all antifungal agents, although several azole drug-resistant clinical isolates are being reported. However, C. tropicalis resistant to amphotericin B is uncommon, and only a few strains have reliably demonstrated a high level of resistance to this agent. The resistance mechanisms operating in C. tropicalis strains isolated from clinical samples showing resistance to azole drugs alone or with amphotericin B cross-resistance were elucidated. Antifungal drug resistance was related to mutations of the azole target (Erg11p) with or without alterations of the ergosterol biosynthesis pathway. The antifungal drug resistance shown in vitro correlated very well with the results obtained in vivo using the model host Galleria mellonella. Using this panel of strains, the G. mellonella model system was validated as a simple, nonmammalian minihost model that can be used to study in vitro-in vivo correlation of antifungals in C. tropicalis. The development in C. tropicalis of antifungal drug resistance with different mechanisms during antifungal treatment has potential clinical impact and deserves specific prospective studies.


Grant
Agency: Cordis | Branch: H2020 | Program: ERA-NET-Cofund | Phase: HCO-07-2014 | Award Amount: 30.95M | Year: 2015

Over 12 million people in Europe suffer from neurodegenerative diseases (ND), yet treatments that prevent or stop the progression of neurodegeneration are still lacking. Tackling this grand challenge requires enhanced coordination of national efforts to accelerate discovery. Such synergies have been created among 28 countries in the pilot EU JPI on Neurodegenerative Disease Research (JPND). JPND has a long standing experience in collaborative action with 75 million of additional national funds being successfully mobilized between 2011 and 2014 to support transnational research programs. The JPND Research Strategy is now ripe for further enhancement in tight coordination with the EC through an ERA-Net Cofund instrument JPco-fuND with an unprecedented commitment of 30 million of national funds associated to a highly incentivizing EC top-up fund. Among the most burning questions, three priority topics have emerged through a consultative process between researchers and JPND members in order to unlock several major issues within ND research: the identification of genetic, epigenetic and environmental risk and protective factors, the development and maintenance of longitudinal cohorts, the creation of advanced experimental models. These are key questions of equal priority to increase understanding of ND mechanisms that will be addressed through a common joint transnational call allowing a significant acceleration of the execution of the JPND research strategy. Moreover, to expand the impact of JPco-fuND, JPND will continue to implement other actions without EU co-funding such as aligning national research strategies, making databases more accessible and interoperable, developing enabling capacities such as supportive infrastructure and platforms, capacity building, education and training. These actions are required in parallel to achieve the highest impact for the patients, their carers and for society as whole and address this grand challenge in the coming years.

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