Every year, a committee of experts sits down with a tough job to do: from among all ICREA publications, they must find a handful that stand out from all the others. This is indeed a challenge. The debates are sometimes heated and always difficult but, in the end, a shortlist of  the most outstanding publications of the year is produced. No prize is awarded, and the only additional acknowledge is the honour of being chosen and highlighted by ICREA. Each piece has something unique about it, whether it be a particularly elegant solution, the huge impact it has in the media or the sheer fascination it generates as a truly new idea. For whatever the reason, these are the best of the best and, as such, we are proud to share them here.


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  • Simple detection of circulating cancer cells using gold nanoparticles (2012)

    Merkoçi, Arben (ICN2)

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    Simple detection of circulating cancer cells using gold nanoparticles

    Circulating tumor cells (CTCs) are traveling cells in physiological fluids that are released from a main tumor or from metastasis. CTC quantification is of great interest for evaluating cancer dissemination, predicting patient prognosis, and also for the evaluation of therapeutic treatments representing a reliable potential alternative to invasive biopsies and subsequent proteomic and functional genetic analysis. In fact, isolation of CTCs from peripheral blood, as a "liquid biopsy", is expected to be able to complement conventional tissue biopsies of metastatic tumors for therapy guidance. A particularly important aspect of a "liquid biopsy" is that it is safe and can be performed frequently, because repeated invasive procedures may be responsible for limited sample accessibility. The main techniques reported for CTC detection consist in their labeling with tagged antibodies (immunocytometry) followed by fluorescence analysis or the detection of the expression of tumor markers by reverse-transcriptase polymerase chain reaction (RT-PCR). However, the required previous isolation of CTCs from the human fluids is limited to complex analytic approaches that often result in a low yield and purity. Merkoçi's groups in collaboration with colleagues at UAB have achieved a novel and rapid and simple detection of cancer circulating cells using gold nanoparticles (AuNP). The electrochemical detection and the characterization results demonstrate that this method is selective to Caco2 CTC and that the electrochemical signal is not affected by the presence of other circulating cells. The achieved detection is selective for the target tumor cells and can exclude the false positive results. The main advantages of the presented method compared with the already reported for CTC detection rely on the sensitive and quantitative electrochemical detection technique used in addition to the excellent properties of the AuNPs labels. The sensitivity, simplicity, low cost, easy-to-use mode, and miniaturization/portability of the electrochemical detection system make it ideal for point-of-care applications.

  • Oceans acidifying at unprecedented speed, at least over the past 300 million years (2012)

    Pelejero Bou, Carles (CSIC - ICM)

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    Oceans acidifying at unprecedented speed, at least over the past 300 million years

    In addition to causing global warming, anthropogenic emissions of CO2 are altering the chemistry of Earth's oceans, turning them more acidic. This change has important implications for marine organisms and ecosystems. Important insights on this have been obtained from laboratory experiments, in which marine organisms are exposed to future levels of ocean pH. This experimental approach, however, is limited by their reduced ecologic complexity compared to the real world and by the duration of the experiments. Crucial issues such as the possibility of acclimation or evolutionary adaptation of marine organisms is hard to be assessed from this perspective. In this context, a valuable complementary approach consists in scrutinizing the geological record, which contains signatures for a variety of global environmental perturbations, including ocean acidification, plus their associated biotic responses. In this study, we review the record of the past ~300 million years of Earth's history, which contain events that exhibit evidence for elevated atmospheric CO2, global warming, ocean acidification and deoxygenation, some of them with contemporaneous extinction or evolutionary turnover among marine calcifiers. An important event within this period of time is the so-called Paleocene-Eocene thermal Maximum, 56 million years ago, an event characterized by global warming, which caused ocean acidification and extinction of marine biota, mostly from the deep ocean. In this case, estimations indicate that, even though the amounts of carbon released into the system are of a magnitude similar to the current human perturbation, the injection of carbon then was at least 10 times slower than the current one. Further back in time, other major shocks include the asteroid impact at the end of the Cretaceous, 65 million years ago which, in addition to other major environmental changes, also involved a rapid acidification of the oceans. Other extinction events, such as the Permo-Triassic, 200 million years ago, and the end-Permian, 252 million years ago, could have also involved significant acidification. However, all these extinctions were also associated with decreases in the oxygen content of the oceans and major warming. In fact, these are the three main environmental pressures that are currently affecting in a more global way global oceans: warming, acidification and deoxygenation. Although similarities exist with past events in the geological record, our study concludes that, at least over the last 300 million years, none of the change

  • Sequencing of pig genomes (2012)

    Pérez Enciso, Miguel (UAB)

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    Sequencing of pig genomes

    Analyses of pig genomes provide insight into porcine demography and evolution: For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars ~1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model.

  • Understanding the evolution of genomes and the regulation of the proteome. (2012)

    Ribas de Pouplana, Lluís (IRB Barcelona)

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    Understanding the evolution of genomes and the regulation of the proteome.

    We have discovered a new mechanism for protein synthesis control (Novoa et al., Cell 2012). More specifically, we have described the role of two tRNA anticodon modifications in genome evolution and proteome regulation across the complete tree of life. We have shown that these modifications contributed to the evolution of genomes, and currently play a part in the control of protein synthesis in extant species.

    We have demonstrated that the codon composition of highly expressed genes is enriched in triplets recognized by modified tRNAs. Thus, a new mechanism for the control of gene expression arises based on the relationship between the codon composition of any given gene and the existing pool of modified tRNAs in the cell. We want to explore this relationship and characterize how levels of modified tRNAs may affect gene expression levels. For that purpose we have chosen two experimental models that represent extreme cases either in the levels of modification activity or in the numbers of tRNA genes in the genome.

    More specificaly, we propose to study the biological significance of extreme variations in the levels of tRNAmodification that are reported between normal and transformed mammalian cells. On the other hand, we propose to study the biological role of these modifying enzymes in organisms that contain a dramatically simplified complement of tRNA genes. Specifically, we will be investigating their role in Plasmodium falciparum, the causing agent of malaria and the eukaryotic organisms with the simplest set of tRNA genes in its genome. Given the simplicity of tRNA gene composition, and the extreme codon usage bias of Plasmodium, we suspect that the function of tRNA modification is particularly important to allow a proper match between tRNA content and genetic codon composition.

  • Network structure of the plant circadian clock. (2012)

    Riechmann Fernández, Jose Luis (CRAG)

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    Network structure of the plant circadian clock.

    Molecular circadian clocks are ubiquitous endogenous mechanisms that allow organisms to temporally organize biological activities, coordinating them with the daily environmental cycle. In plants, the circadian clock regulates processes such as growth rate, primary and secondary metabolism, hormone biosynthesis and responses, stomatal opening, water stress responses, water uptake, leaf movement, petal opening, seed dormancy, and pathogen defense. In addition, the circadian clock forms the basis for one of the genetic pathways that control the timing of the transition from vegetative to reproductive growth, or flowering.

    In an article published in Science -a collaboration with the group of CSIC Professor Paloma Mas, also at CRAG- we describe our efforts to understand the molecular mechanisms underlying the function of TIMING OF CAB EXPRESSION1 (TOC1). In many organisms, the circadian clock is composed of functionally coupled morning and evening oscillators. In Arabidopsis, oscillator coupling relies on a core loop in which the evening oscillator component TOC1 was proposed to activate a subset of morning-expressed oscillator genes. We showed that TOC1 does not function as an activator but as a general repressor of oscillator gene expression. Repression occurs through TOC1 rhythmic association to the promoters of all oscillator genes. Hormone-dependent induction of TOC1 and analysis of RNAi plants showed that TOC1 prevents the activation of morning-expressed genes at night. Thus, the morning and evening oscillator loops are connected through the repressing activity of TOC1.

    These results overturn the canonical, long-standing model of the plant circadian clock, in which TOC1 was presumed to be an activator of a reduced number of oscillator genes, not a general repressor of oscillator gene transcription, as has now been demonstrated.

  • Structural edge instabilities and Robustness of the Quantum Hall effect in Graphene : Mystery solved (2012)

    Roche, Stephan (ICN2)

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    Structural edge instabilities and Robustness of the Quantum Hall effect in Graphene : Mystery solved

    Together with some colleagues from the Graphene Research Center in Singapore, the ICMM-CSIC in Madrid and the IMEP-LAHC (Grenoble INP), we have proposed an explanation for an enigma in graphene: the fact that when using conventional methods of electric current detection with low to medium intensity applied magnetic fields (2 to 20 Tesla), scientists have repeatedly failed to observe the quantum Hall effect in graphene samples with scrolled edges (see Figure), known as graphene nanoscrolls. This issue was raised by Andre Geim, the 2011 Physics Nobel Laureate for the discovery of groundbreaking properties of this carbon-based two-dimensional material with exceptional physical properties.

    In the quantum Hall effect, a fundamental mesoscopic quantum phenomenon in 2D materials, the application of an external magnetic field forces the electric charges in the sample to segregate outwards to the sample´s edges (referred as chiral edge states), much like a referee forcing the players of two brawling football teams to separate onto either side of the pitch. This establishes a quantized Hall conductance together with a vanishing longitudinal conductivity.

    When researchers study the quantum behaviour of electronic excitations in graphene (and other materials), they typically create a simple circuit in which current travels from a source contact at one end (or edge) of the material to a drain contact at the opposing end (or edge). This technique gives clear readings of the quantum Hall effect in completely flat graphene (such as samples that are bound to a substrate); in contrast, in free-standing graphene (see Figure (b)), which generally shows scrolled edges, the effect seems to be quenched.

    By measuring the magnetic field along the length and depth of the scrolled edges as well as in the flat portion of graphene samples of this type, we have deduced that these edges basically short circuit the very drains used to measure current in these types of experiment, jeopardizing the formation of chiral current generation at the edges. Non-chiral edges current propagate inside the scrolls whereas chiral currents are formed deeper inside the bulk, hence more sensitive to disorder and scattering. Accordingly, the observation of the Quantum Hall regime in suspended graphene is prohibited in presence of such structural edge instabilities.