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 con las mejors publicaciones del año. 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

  • A human antibody alters memory and behavior (2015)

    Dalmau Obrador, Josep (FRCB-IDIBAPS)

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    A human antibody alters memory and behavior

    In 2007 we discovered a human brain disease mediated by antibodies against the NMDA glutamate receptor (NMDAR). This disorder (named anti-NMDAR encephalitis) was the first of a new category of neuropsychiatric diseases mediated by antibodies against synaptic neurotransmitter receptors. The concept that an antibody could directly alter memory, behavior, cognition, and cause psychosis was novel, and changed the landscape of diagnostic and treatment approaches in neurology and psychiatry. Today, anti-NMDAR encephalitis is considered the most common antibody-mediated CNS disease, ranking in frequency above most viral encephalitis. Over the years, a pathogenic effect of the antibodies had been suggested in studies of cultured neurons and other in vitro models. This year, we reported an animal model that definitively established that patients’ antibodies alter memory and behavior. In this model patient antibodies were continuously infused over 14 days into the cerebroventricular system of mice using catheters connected to osmotic pumps. During and after the infusion multiple memory and behavioral tests were performed. The studies showed that patients’ NMDAR antibodies led to progressive memory impairment, anhedonia and depressive-like behaviors. Molecular studies in the hippocampus of the mice showed a decrease of clusters of total and synaptic NMDAR. These molecular effects, which paralleled behavioral symptoms, gradually reversed after the end of the antibody infusion. This model establishes a link between memory and behavioral deficits and antibody-mediated reduction of NMDAR, provides the biological basis by which removal of antibodies and antibody-producing cells improve neurological function, and offers a model for testing experimental therapies in this and similar disorders.  The work was summarized on the cover of Brain: A Journal of Neurology (Jan 2015).  

  • Graphene enables all-electrical control of energy flow from light emitters (2015)

    de Riedmatten, Hugues (ICFO)
    García de Abajo, Francisco Javier (ICFO)
    Koppens, Frank (ICFO)

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    Graphene enables all-electrical control of energy flow from light emitters

    At the heart of lasers, displays and other light-emitting devices lies the emission of photons. Electrically controlled modulation of this emission is of great importance in applications such as optical communication, sensors and displays. Moreover, electrical control of the light emission pathways opens up the possibility of novel types of nano-photonics devices, based on active plasmonics.

    A collaboration between the groups of ICREA professors at ICFO Frank Koppens, Javier García de Abajo and Hugues de Riedmatten, as well as scientists from  MIT, CNRS, CNISM and Graphenea have now demonstrated active, in-situ electrical control of the energy flow from erbium ions into photons and plasmons. The experiment was implemented by placing the erbium emitters a few tens of nanometers away from the graphene sheet, whose carrier density (Fermi energy) is electrically controlled. Partially funded by the EC Graphene Flagship, this study entitled “Electrical control of optical emitter relaxation pathways enabled by graphene”, has been published in Nature Physics.

    Erbium ions are essentially used for optical amplifiers and emit light at a wavelength of 1.5 micrometers, the so called third telecom window. This is an important window for optical telecommunications because there is very little energy loss in this range, and thus highly efficient information transmission.

    The study has shown that the energy flow from erbium into photons or plasmons can be controlled simply by applying a small electrical voltage. The plasmons in graphene are rather unique, as they are very strongly confined, with a plasmon wavelength that is two orders of magnitude smaller than the wavelength of the emitted photons. As the Fermi energy of the graphene sheet was gradually increased, the erbium emitters went from exciting electrons in the graphene sheet, to emitting photons or plasmons. The experiments revealed the long-sought-after graphene plasmons at near-infrared frequencies, relevant for these telecommunications applications. In addition, the strong concentration of optical energy offers new possibilities for data storage and manipulation through active plasmonic networks.

  • Progress in a New Paradigm to Explain the Magnitude of the Electroweak Scale (2015)

    Espinosa Sedano, José Ramón (IFAE)

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    Progress in a New Paradigm to Explain the Magnitude of the Electroweak Scale

    Our understanding of Nature is based on the empirical evidence that natural phenomena taking place at different energy/distance scales do not influence each other. The parameters of an effective theory are natural if they do not require any special tuning of the parameters of the theory at higher energies. Wilson and 't Hooft gave a quantitative meaning to this naturalness principle by demanding that all dimensionless parameters controlling the different effective theories should be of order unity unless they are associated to the breaking of a symmetry. The Higgs boson mass and the value of the cosmological constant have been long recognized as two notorious challengers of this naturalness principle. Supersymmetry or Higgs compositeness are two prime examples of models trying to associate the Higgs mass to a small symmetry breaking. Recently, however, a radically new approach to explain the smallness of the Higgs mass has been proposed by Graham, Kaplan and Rajendran (Phys. Rev. Lett. 115 (2015) 22, 221801), in reminiscence of the relaxation mechanism of Abbott proposed for explaining the smallness of the cosmological constant.

     

    Technically, the relaxation mechanism exploits the coupling of the Higgs boson to an axionlike field and a long era in the early Universe where the axion unchains a dynamical screening of the Higgs mass. We present a new realization of this idea with the new and outstanding  feature that it leaves no sign of new physics at the electroweak scale, and up to a rather large scale, 109 GeV, except for two very light and weakly coupled axionlike states. One of the scalars can be a viable dark matter candidate. Such a cosmological Higgs-axion interplay could be tested with a number of experimental strategies.

     

    The relaxion idea pursued here represent a new twist in the long and fruitful history of the interplay between particle physics and cosmology. While in the past particle physics has been a crucial ingredient to understand the cosmological history of our universe, if these new ideas were correct, cosmological evolution would be a crucial ingredient in the understanding of some key parameters of particle physics.

  • The switch of cancer (2015)

    Eyras Jiménez, Eduardo (UPF)

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    The switch of cancer

    For many years, scientists have struggled to understand and cure cancer. The study of the genome of multiple tumors has been fundamental to detect relevant alterations in cancer. These studies have highlighted the heterogeneity of genetic alterations in patients suffering from the same type of cancer, motivating the development of individualized treatments. Tumors frequently lack known actionable alterations, making thus necessary to expand the catalogue of cancer signatures to integrate other molecular alterations.

    There is increasing evidence that alterations in the splicing regulatory program play an important role in tumor transformation. Splicing is a process by which the long RNA molecule transcribed from the gene in the genome is processed to remove segments called introns, giving rise to an RNA transcript. Alternative splicing provides a mechanism to generate multiple RNA transcripts from the same gene by eliminating introns in different ways. This process is tightly regulated and can give rise to molecules with very different functions. This dramatic change is generally called a splicing switch.

    Splicing switches can induce altered cellular states, leading to disease. Accordingly, the identification of these switches can be fundamental for prognosis and therapy. This analysis is generally hindered by the heterogeneity of tumors of the same origin from different individuals, as well as by the normal variability between individuals. We have developed a new computational method, robust to biological and technical variability, which identifies significant splicing switches across a large number of tumor samples and shows high accuracy. 

    This is the first published large-scale analysis describing the splicing alterations in 9 cancer types using RNA sequencing data for more than 4000 patient samples. In this work, we have discovered that there exist many splicing switches in patients with the same cancer type that can separate with high accuracy tumor and normal samples, and different types of cancer from each other, providing potential novel molecular targets for prognosis and therapy.

  • How did yeast double its genome? (2015)

    Gabaldón Estevan, Toni (CRG)

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    How did yeast double its genome?

    The model yeast Saccharomyces cerevisiae was the first eukaryotic organism to be sequenced. From the initial analyses it appeared that the organism seemed to have two very different versions of many of its genes, implying an ancestral duplication of the whole genome. Since then, the scientific community has accepted the theory that yeast underwent a whole genome duplication, a phenomenon that is not isolated and can also be found in other species. For instance, we know that whole genome duplications were important in the early evolution of vertebrates and that it is a very common phenomenon in plants, especially cultivated ones. However the mechanism by which this whole genome duplication occurred remained unknown, and highly debated.

    In this article Gabaldón's team shows that the appearance of duplicated genes was not caused by a simple duplication of the whole genome but rather by a hybridization of two different species. Their proposal, which is at odds with the currently most widely accepted theory in the scientific community, provides new insight into this key process during genome evolution and the origins of species.The researchers analyzed genomic data with computational tools, based on cutting-edge phylogenomic methods, and designed by the Gabaldón group, to study the family gene trees. This allowed the researchers to reconstruct gene duplications and to determine what happened in evolutionary time, making it a computational equivalent of carbon-14 dating for fossils. To their surprise, they found that the age of some duplicated genes seemed to be much greater than that predicted by the theory for the whole genome duplication event. Rather than supporting a genome duplication event at the time when yeast evolved to have twice the number of chromosomes, their data indicated that the duplicated genes had begun to diverge long before. This result suggested the possibility of hybridization between species. In this case, the genes that have been duplicated still differ from each other, so that their divergence preceded the duplication of the chromosome.

     

  • Mathematical analyses of astrocyte topology in a transgenic mouse model of Alzheimer's disease (2015)

    Galea, Elena (UAB)

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    Mathematical analyses of astrocyte topology in a transgenic mouse model of Alzheimer's disease

    We sought to identify forces shaping the interaction between astrocytes and amyloid-beta plaques by performing a spatial analysis using mathematical analyses borrowed from statistical physics, and 3D images from living transgenic mice. We discovered that astrocytes are repelled by other astrocytes and by plaques. The study is relevant for three reasons. First, our conclusions contradict the current thinking about astrocytes in Alzheimer's disease. A key issue is what causes accumulation of amyloid beta plaques, and the physiological removal thereof. Plaque removal is indeed among the most highly pursued therapeutic avenues in Alzheimer's disease. Since it is widely (and wrongly) believed that astrocytes naturally migrate to plaques and eat them up, there is a line of research aimed at potentiating this capacity with drugs. After this study, people will realize that astrocytes barely move in Alzheimer's disease. This study is going to stir debate and oblige the field to reassess astrocytes as a target in Alzheimer's disease therapeutics. Second, we have identified a previously unknown aspect of astrocyte organization: the absolute minimum allowable distance between astrocytes. This demonstrates spatial organization in astrocytes. Finally, the study fills a major void in the neurosciences today, i.e., the incapability to analyze new data in meaningful ways. The advent and widespread use of imaging technologies like 2-photon microscopy has produced a wealth of increasingly complex materials, which clearly beg for computer-based analytical approaches. But these have lagged behind. There is a serious lack of tools and theoretical elaborations to help process and interpret the mass of new information. Here, we use mathematics and computer modeling to examine with great spatial precision—around 1 micron—the interactions of astrocytes and amyloid beta plaques. Although applying mathematics to biology and medicine has a long history, this study will reinforce the notion that mathematics is all the more instrumental to understand the newly-obtained information from the living brain.

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