Destacados

Cada año, un comité de expertos debe acometer una ardua tarea: de entre todas las publicaciones de ICREA, debe escoger unas cuantas que destaquen del resto. Es todo un reto: a veces los debates se acaloran, y siempre son difíciles, pero acaba saliendo una lista de 24 publicaciones. No se concede ningún premio, y el único reconocimiento adicional es el honor de ser resaltado en la web de ICREA. Cada publicación tiene algo especial, ya sea una solución especialmente elegante, un éxito espectacular en los medios de comunicación o la simple fascinación por una idea del todo nueva. Independientemente de la razón, se trata de los mejores de los mejores y, como tales, nos complace compartirlos aquí.

LIST OF SCIENTIFIC HIGHLIGHTS

Format: yyyy
  • Higgs Hunting at the LHC (2011)

    Martínez Pérez, Mario (IFAE)

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    Since 2009, the Large Hadron Collider (LHC) at CERN (Geneva, Switzerland) collides protons at a center-of-mass energy of 7 TeV, the highest energy ever reached by a particle accelerator. One of the main goals of the LHC is the search for the Higgs boson, the last piece of the Standard Model that remains undiscovered. The so-called Higgs mechanism was introduced in 1964 to explain the breaking of the electroweak symmetry, leading to a massless photon, mediator of the electromagnetic force, and very heavy W and Z bosons, mediators of the weak interaction. The Higgs mechanism would also explain the mass of fermions as the Higgs field permeates the Universe and interacts with all particles endowing them with their mass. Finally, the existence of a Higgs boson associated with the Higgs field is postulated, although its mass is not predicted and must be determined experimentally.

    During the last four decades, particle physicists have searched for the Higgs boson. In the 90's, the LEP electron-positron collider at CERN concluded that the Higgs boson, if it exists, should have a mass larger than 114.4 GeV at 95% confidence level (C.L). Since 2002, the quest for the Higgs boson was mainly undertaken by the CDF and D0 experiments at the 1.96 TeV proton-antiproton Tevatron collider at Fermilab (near Chicago, USA). The experiments were able to extend the excluded mass range at 95% C.L. to 156-177 GeV, still leaving much room for the Higgs boson to hide.

    The analysis of the data delivered in 2011 by the LHC to the ATLAS and CMS experiments has translated into a huge step forward in the quest for the Higgs boson. In particular, the combination of searches at the ATLAS experiment has excluded at 95% C.L. the presence of a Higgs boson with mass in the ranges: 112.7-115.5 GeV, 131-237 GeV, and 251-453 GeV [1-4]. Most importantly, the experiment observes a suggestive excess of events around 126 GeV (see Fig. 1) which would be consistent with the potential signal of a Higgs boson, although the observation is not yet statistically significant. It corresponds to a 3.6 standard deviation from the background-only hypothesis (see Fig. 2) but, after including look-elsewhere effects, it translates into a 1% probability to be a simple background fluctuation.
    In 2012 the LHC experiments will collect much more data, which should allow them to either discover the Higgs boson or completely exclude its existence. A. Juste and M. Martínez lead the analysis effort of the ATLAS data at IFAE, playing a central role in those channels whe

  • New clues into AIDS pathogenesis: the case of genes similarly regulated after retroviral infection in human and nonhuman primates (2011)

    Martínez Picado, Javier (IrsiCaixa)

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    High levels of Human Immunodeficiency Virus (HIV-1) replication during the chronic phase of infection usually correlate with rapid progression to severe immunodeficiency. However, a minority of highly viremic individuals remains asymptomatic and maintains high CD4+ T lymphocytes. This tolerant profile is poorly understood and reminiscent of the widely studied nonprogressive disease model of Simian Immunodeficiency Virus (SIV) infection in natural hosts. In a study co-led by researchers at the University of Lausanne and the AIDS Research Institute -IrsiCaixa-, we identified transcriptome differences between rapid progressors and viremic nonprogressors and highlight several genes relevant for the understanding of HIV-1-induced immunosuppression. Rapid progressors were characterized by a specific transcriptome profile of CD4+ and CD8+ T cells similar to that observed in pathogenic SIV-infected rhesus macaques. In contrast, viremic nonprogressors exhibited lower expression of interferon-stimulated genes and shared a common gene regulation profile with nonpathogenic SIV-infected sooty mangabeys. A short list of genes associated with viremic nonprogressors, including CASP1, CD38, LAG3, TNFSF13B, SOCS1, and EEF1D, showed significant correlation with time to disease progression when evaluated in an independent set of CD4+ T cell expression data. This work characterizes 2 minimally studied clinical patterns of progression to AIDS, whose analysis may inform our understanding of HIV pathogenesis. The study is presently exploring the phenotypic traits that differentiate HIV-1/AIDS disease in extended cohorts of rapid progressors (approx. 8% of all HIV-1 infected individuals) and viremic nonprogressors (approx. 0.1% of all HIV-1 infected individuals).

  • A new mechanism of gene expression reprogramming in cancer (2011)

    Méndez de la Iglesia, Raúl (IRB Barcelona)

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    Proteins are the ultimate mediators of cellular functions in physiological and pathological conditions. However, much more efforts have been dedicated to study tumor-associated changes in transcription rather than in translation (protein synthesis). In collaboration with Pilar Navarro (IMIM/PRBB) and Paco Real (CNIO), we have found that the RNA-binding protein, and translational regulator, CPEB4 is up regulated in pancreatic ductal adenocarcinomas (PDAs), unveiling a new role for tumor-specific expression of factors that promote tumor growth and vascularization. CPEB4 controls the translation a wide spectra of mRNAs whose translation is reprogrammed in tumors, compared with normal tissues. Among these, a key mRNA encodes for the protease tPA (tissue plasminogen activator). tPA mRNA is stored as a deadenylated repressed mRNA in normal pancreas but becomes cytoplasmically polyadenylated, and translationally activated, in PDAs. Depletion of CPEB4, in vivo and in vitro, prevents tPA expression, malignant transformation of tumoral cells, and tumoral growth, invisibility and vascularization. Preliminary data suggest that the relevance of these findings goes beyond pancreatic cancer. CPEB4 plays a similar role in glioblastoma and the public databases contain information indicating that it is overexpressed in a wide variety of human tumors. Altogether this finding opens a new window of opportunity to generate tools with diagnostic and even therapeutical potential.

    * in collaboration with Eduardo Eyras (ICREA at UPF)

  • Cancer biomarkers detection using nanochannels (2011)

    Merkoçi, Arben (ICN2)

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    A rapid nanochannel-based immunoassay capable of the filtering and subsequent detection of proteins in whole blood without any sample preparation is described. This is accomplished by using a nanoporous/nanochannel membrane modifi ed with antibodies, the conductivity of which toward a redox indicator is tuned by primary and secondary immunoreactions with proteins and gold nanoparticles. This interesting nanopore blockage by gold nanoparticles is enhanced by silver deposition that further decreases the diffusion of the signaling indicator through the nanochannel. The effi ciency of the nanochannels to act as immunoreaction platforms including the use of nanoparticles is also monitored by microscopic techniques. Successful detection of immunoglobulins including a cancer biomarker is achieved in buffer as well as in whole blood. This system constitutes an effi cient immunoassay capable of detecting up to 52 U mL-1 of CA15-3. The developed nanochannel/nanoparticle-based device can be used for several other proteins and extended also to DNA detection with interest not only for diagnostics but also environmental monitoring, food analysis, safety, and security applications. In this work we combine for the first time the capability of current tuning of a nanopore/nanochannel-based platform upon immunoblocking through nanoparticles for the detection of proteins, by taking advantage of an electrotransducer fabricated by screen-printing technology and a simple voltammetric detection mode. In addition, we show that the use of AuNP tags as blocking agents improves the detection limits of the label-free immunosensor. The catalytic properties of AuNPs upon silver deposition, applied also for protein detection, are examined for the in-nanochannel enhancement of AuNPs, which increases to a very high extent the pore-blocking efficiency and consequently the sensitivity of the assays. We also demonstrate for the
    first time the efficiency of the developed nanochannel/nanoparticle device for future applications in the direct detection of cancer biomarkers in whole blood, where the membranes act as both "filtering" and sensing platforms and thus avoid matrix effects.

    This work is highlighted by By Michael Berger. Copyright 2011 Nanowerk:
    http://www.nanowerk.com/spotlight/spotid=20257.php

  • Teamwork between tiny catalyst nanoparticles (2011)

    Neyman, Konstantin M (UB)

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    Every football fan knows very well that a successful team needs players with different talents. It seems to be similar for complex chemical processes, which are accelerated by catalytic materials. These catalysts are composed of various components, only a few nanometers in size, whose cooperation is crucial: when the teamwork succeeds, the catalyst is modified and thus can become much more efficient than the individual active component.

    This was demonstrated by a group of researchers in an international collaboration of five European countries led by ICREA Professor Dr. Konstantin Neyman (Universitat de Barcelona) and Prof. Dr. Jörg Libuda (Universität Erlangen-Nürnberg, Germany) also involving groups from Sofia, Prague and Trieste. The results of the investigation have been published in the journal Nature Materials, 2011.

    Heterogeneous catalytic processes play a decisive role in efficient production of most chemicals and advanced materials, as well as in emerging key technologies for energy and the environment. The industrial catalysts are commonly extremely complex and it is very difficult to obtain insights at the microscopic level into the way they work. For this reason, most catalysts are optimised empirically, by a trial and error approach, so that making them is often close to "black magic".

    The international research team has managed to make systems, which model these catalysts. These permit on the one hand analysis by the most modern methods, such as by the synchrotron light, and on the other hand the use of modern, so-called quantum mechanical theoretical methods. Together, theory and experiment enable to obtain a detailed knowledge on these complex materials. It was then found that it was exactly this structure, which created the new properties of the material: the catalysts consist of oxide and metal particles of only a few nanometers in size, but they must be in close contact. The special chemical activity then is due to cooperation between the different components. Only when the components exist in the special form of nanoparticles can the highly reactive oxygen species be exchanged and open up new reaction paths. A catalyst made solely of metal or oxide does not work: like a football team that is all goal-keepers or all strikers.

  • A cocktail of antioxidants as a therapeutic hope for Lorenzo's oil disease (2011)

    Pujol Onofre, Aurora (IDIBELL)

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    Adrenoleukodystrophy (X-ALD) is a rare, lethal neurodegenerative disease of brain white matter caused by loss of function of the ABCD1 peroxisomal transporter of very long-chain fatty acids (VLCFA). There is currently no satisfactory therapy as a dietary approach, Lorenzo's oil, is not able to prevent or halt disease progression. The mouse model for X-ALD exhibits a late-onset neurological phenotype with axonal degeneration in spinal cords and associated locomotor disability, resembling the most common clinical presentation of X-ALD. Recently, we have identified oxidative damage as an early event in life, and the excess of VLCFA as a generator of radical oxygen species (ROS) and oxidative damage to proteins in X-ALD. To find the proof of principle for oxidative damage as main contributor to pathology, we have tested a combination of FDA-approved antioxidants: N-acetyl-cysteine, alpha-lipoic acid and alpha-tocopherol. In vitro, the three drugs act in a synergistic manner to scavenge VLCFA-dependent ROS generation. Further, in a preclinical setting, the cocktail of the three compounds reversed: i) oxidative stress and lesions to proteins, ii) immunohistological signs of axonal degeneration and iii) locomotor impairment in bar cross and treadmill tests (1). Thus, we have established a direct link between oxidative stress and axonal damage in a mouse model of neurodegenerative disease, and paved the way for translation into clinical trials. Currently, 20 X-ALD patients are enrolled on an open phase II clinical trial financed by the Spanish Ministry of Health and Hesperia Foundation (clinicaltrials.org NCT01495260). Endpoints include biochemical measures such as biomarkers of oxidative damage previously identified in our laboratory (2), and clinical outcomes, such as evaluation of spasticity scales and MRI images. As axonal degeneration is a main contributor to disability in progressive neurodegerative diseases in which oxidative stress is often associated as pathogenic factor, such as sclerosis multiple or Alzheimer disease, our results invites re-assessment of this combination of antioxidants in highly prevalent neurological disorders.

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