Highlights

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 24 publications 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.

LIST OF SCIENTIFIC HIGHLIGHTS

Format: 2017
  • On genetic differentiation between domestic pigs and Tibetan wild boars. (2015)

    Pérez Enciso, Miguel (UAB)

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    In this work, Pérez Enciso et al. challenge the conclusion from a previous report on Tibetan pigs by Li et al. (2013), which claimed that Tibetan pigs had diverged from other pigs several million years ago. Perez-­Enciso et al. reanalyzed that and other public data from 65 complete pig genomes to prove that Tibetan pigs are no more divergent than any other Chinese breed, thus resetting the landscape for pig evolutionary studies. This report was accompanied by another one by Frantz et al. who, using completely different arguments, reached the same conclusion and, together with another paper on Chinese pig genomes, was featured in the Nature Genetics cover.

  • High relevance of asymptomatic individuals for malaria propagation and the dual role of climate in endemic and epidemic settings in Africa. (2015)

    Rodó i López, Xavier (IC3)

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    A new study published in the Proceedings of the National Academy of Sciences of the United States of America by scientists from CONICET Bariloche, Institut Pasteur both at Paris and Dakar, IRD-Dakar and the Institut Català de Ciències del Clima (IC3) at Barcelona, shows unequivocally how the incidence of clinical malaria is both influenced by climatic factors and immunity. Disentangling the relative contributions of these factors is a major challenge. The study benefits from a unique long-term follow-up of 2 adjacent populations spanning two decades in Senegal, that have very different levels of malaria endemicity. By using  recently developed mathematical modelling techniques and extremely detailed records from both malaria incidence, parasite inoculation variability within hosts by mosquito population, and local climate data, the study was able to demonstrate how the influence of immunity and climatic factors varies according to the force of infection. A common modelling framework elucidates important information on how immunity influences transmission of the parasite from men to mosquitoes. Notably, the models show how individuals, who are infected without symptoms or infected with parasites at an undetectable level by classical diagnostic methods, contribute significantly to the infectious population. Undetectable but infectious individuals are likely to present a problem for elimination of the parasite reservoir in humans, which is the final step towards elimination of the malaria in a population.

  • Quantum analyses reveal secrets of wiggly sugars (2015)

    Rovira Virgili, Carme (UB)

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    Carbohydrates are critical macromolecules in biochemistry and cell biology, notably in immunity and intercellular communication. Enzymes that help build, degrade, and modify these sugars are attractive targets for drug development, and also find major use in industrial biotechnology. But carbohydrates are often highly complex and flexible structures, ones that are synthetically challenging, and studying their intimate chemistry has proved difficult. If we are to harness their potential as drug targets, better tools for the study of their interactions with enzymes are required.

    In this Perspective, we review new molecular dynamics simulations using quantum mechanics/molecular mechanics (QM/MM) techniques that have fostered understanding of the mechanisms and conformational dynamics of two important classes of carbohydrate-active enzymes in the past decade. The two classes, glycosyl hydrolases and glycosyltransferases, catalyze the hydrolysis and synthesis, respectively, of glycosidic bonds between carbohydrates and their partner molecules.

    Simulations have revealed the conformational dynamics of distinct reaction pathways taken by different families of glycoside hydrolases and characterized their transition states, findings that will aid inhibitor design. The results have also fueled ongoing debate over which of two proposed mechanisms certain classes of glycosyltransferases follow.  It is shown that QM/MM techniques are now at the forefront of carbohydrate enzymology, providing insights not amenable by other techniques.

  • Liquid biopsy of cerebrospinal fluid for less invasive and more effective characterization of brain tumors (2015)

    Seoane Suárez, Joan (VHIO)

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    In November 2015, Dr. Joan Seoane's group at the Vall d’Hebron Institute of Oncology (VHIO) published a study in Nature Communications proposing that the cerebrospinal fluid could be used as a liquid biopsy for the early diagnosis, prognosis, therapeutic management and tracking of brain cancer.

     

    The identification of each and every tumor type along with each respective individual molecular makeup is critical in tackling cancer with greater precision. Moreover, the study of how the tumor complexity evolves with time is crucial for the correct treatment of cancer. To date, the analysis of brain tumors has consisted of a biopsy or surgical sampling. Such approaches suppose risk per se and do not necessarily facilitate access to a representative part of the tumor. A new technique, liquid biopsy, has been recently and successfully developed which detects a tumor's specific mutations by means of the analysis of circulating tumor cell-free DNA. 

     

    The liquid biopsy 'policing' of cancer is not only facilitating a more precise treatment selection for each individual patient, but could also help us to be steps ahead of the cancer's next move. Compared to traditional tissue biopsy, it is a much less invasive technique, and represents a significant step forward towards a better detection of cancer mutations, tracking the evolution of the disease, as well as predicting the response to therapy. 

     

    Joan Seoane’s group has discovered that the cerebrospinal fluid is highly enriched in circulating tumor DNA and allows for the characterization of brain tumors. The cerebrospinal fluid flows through the brain parenchyma and the spinal cord and can be sampled by a lumbar puncture (similar to an epidural puncture). The cerebrospinal fluid liquid biopsy opens a novel, pioneering line of research into biomarkers that enable to monitor the progress of the disease and ultimately help to evaluate the effect of treatment and drug effectiveness as the cancer progresses.  

  • Pulsating news of 2015 (2015)

    Torres, Diego F. (CSIC - ICE)

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    Pulsars, being even more massive than the Sun, are very dense neutron stars that are the size of a city. Like lighthouses for the universe, emit radio to gamma-ray waves when they rotate up to hundreds of times per second. This year has been quite busy for pulsar research at ICREA.

    We found the most energetic pulsed photons from a pulsar to date, at TeV energies, and produced the most precise measurement of a pulsar nebula along several orders of magnitude in energy, with the MAGIC telescopes. We worked on detailed theoretical models for the latter emission. We witnessed the first pulsar discovered in another galaxy, as well as orbitally recurrent flaring in a pulsar binary, with Fermi-LAT. Transitional pulsars (which we discovered in 2013) are gamma-ray sources depending on the state they live, and we developed a propeller model that explains how.

    In a series of five theoretical papers published in Monthly Notices of the Royal Astronomical Society this year, we examined synchro-curvature radiation as a mechanism for gamma-ray emission in pulsars. We found that a relatively simple model can reproduce the spectra of practically all gamma-ray pulsars detected by the Fermi-LAT satellite, and that significant correlations arise for the model parameters that can be used to predict the gamma-ray brightness. Fig. 1 below is the main result of this research.

    Magnetars, among pulsars, usually possess very powerful magnetic fields. In 2013, we announced the discovery of a magnetar exceptionally close to the supermassive black hole at the center of the Galaxy. At a distance of 0.3 light years, this magnetar is by far the closest neutron star to a supermassive black hole ever discovered and is likely in its gravitational grip, see Fig. 2. We monitored the magnetar with X-ray satellites since, and this year we revealed that its brightness is dropping more slowly than any other previously observed, and its surface is hotter than expected. We considered starquakes and the bombardment of the surface of the magnetar by charged particles trapped in twisted bundles of magnetic fields above the surface as a way to provide heating, but the mystery still persists.

     

  • The forces that stick cells together (2015)

    Trepat, Xavier (IBEC)
    Guimerà Manrique, Roger (URV)

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    Communication between cells is key to the coordinated functioning of organs, and a breakdown in communication is one of the characteristic features of cancer and chronic inflammatory diseases. Traditionally, such loss of communication between cells had been understood to result from purely biochemical factors, such as growth factors and chemokines. Recently, however, this traditional view has been challenged; physics of communication between cells is as important as the chemistry behind it.

    In this study, Roger Guimerà and Xavier Trepat – together withcolleagues at the Technical University of Catalonia (UPC) and the Rovira i Virgili University (URV) – combined molecular biology, nanotechnology and mathematical models to identify the molecules involved in the physical communication between cells. We developed technologies to map in parallel the main physical properties that govern tissue dynamics, including cellular velocities and deformations, as well as inter-, intra-, and extra-cellular forces. We used these tools to study epithelial dynamics while systematically knocking down the main proteins that comprise the intercellular adhesome.

    Global analysis of our data challenged several aspects of the current wisdom in the field. Firstly, we showed that force transmission at cell-cell junctions is not solely mediated by adherens junctions but also by proteins from tight junctions, desmosomes and gap junctions. Secondly, we established that P-cadherin (rather than E-cadherin) controls how much tension is supported by a cell-cell junction. E-cadherin, by contrast, controls how fast tension builds up. Finally, we demonstrated that simple models based on measured concentrations of cadherins and catenins are able to predict intercellular forces with high statistical significance.

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