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.


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  • The Nature of Chance (2019)

    Hoefer, Carl (UB)

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    The Nature of Chance

    Scientists as well as gamblers, insurance actuaries and government planners presuppose the existence of objective chances for certain types of events – for example, a uranium atom decaying, throwing snake-eyes on a craps table, or hospitalizations due to infections increasing by more than 5% in a year.  But when we say that an event of type A has a chance of occurring of 28%, are we really saying something about the world, or rather just saying something about ourselves (that, perhaps, we have a level of expectation or confidence of 28% in an A-type event's happening)?  And if we are in fact saying something about the world itself, exactly what are we saying?  What sort of fact is a chance-fact?  How can one distinguish a world in which A-type events have 28% chance from a world in which they have 35% chance?

    Culminating many years of thinking and development, Carl Hoefer's book Chance in the World (Oxford University Press) offers definitive answers to questions such as these.  Hoefer argues that objective chances are pattern-facts, that is, facts about the overall patterns that are discernible in the totality of events that take place in the world.  Hoefer's theory, which can be viewed as a sophisticated revision and refinement of traditional frequency-based definitions of chance, overcomes the problems of earlier accounts of chance and offers an understanding that is demonstrably compatible with the uses of chance found in the sciences and in daily life.

  • The evolutionary origin of neuronal microexons (2019)

    Irimia, Manuel (CRG)
    Valcárcel Juárez, Juan (CRG)

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    The evolutionary origin of neuronal microexons

    The mechanisms by which entire programs of gene regulation arose are poorly understood, and very rarely can be traced back to singular genomic novelties (e.g. the appearance of a specific regulator or protein domain). In this study, we elucidated the mechanism underlying the emergence of a particularly intriguing and evolutionarily conserved program of alternative splicing: the one of neural-specific microexons.

    Microexons are tiny (3-27-nt long) exons that are critical for nervous system development and that have been implicated in autism spectrum disorders. The finding in mammals of large, tightly regulated programs of microexons came as a major surprise. It was widely assumed that very short exons were largely not accessible to the cellular machinery, as their minute size would preclude the spliceosomal interactions needed for exon definition. Therefore, these findings raised a major question: when and how in evolution did animal cells acquire the ability to recognize and splice-in microexons?

    Here, we demonstrated that neural microexon programs originated in bilaterian ancestors, more than 600 million years ago, through the emergence of a distinct genomic novelty occurring in a pan-eukaryotic core spliceosomal gene. This genomic novelty generated an alternative isoform encoding a new protein interaction domain with a unique functional property: microexon splicing. We named this domain the "enhancer of microexons" (eMIC). We showed that the eMIC domain is necessary and sufficient for the specific inclusion of neural microexons in both vertebrates and invertebrates, and that it does so by interacting with some of the earliest factors required for spliceosomal assembly.

    After its origin, the eMIC domain qualitatively expanded the regulatory toolkit of animals by enabling the recognition and subsequent selection of tiny exons that were not previously available to the splicing machineries of ancestral species. The functional importance of this mechanism is illustrated by the neurodevelopmental and behavioral defects of mouse models depleted of microexons, and also by the deregulation of this program in autistic patients.

  • Peering Beyond the Horizon: Revealing The Hidden Sector of the Universe (2019)

    Jiménez Tellado, Raúl (UB)
    Verde, Licia (UB)

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    Peering Beyond the Horizon: Revealing The Hidden Sector of the Universe

    For the first time scientists, led by ICREA  Prof. Raul Jimenez, have developed a method to look into our past Universe. The so-called "past-light-cone" are those regions of the Universe that remain unconected from us because it would take light longer than the age of the Universe to travel. In principle we cannot explore this vast region of our Universe. However, by using galaxy clusters as "cosmic mirrors" Jimenez et al. have shown that one could actually view these regions of our past. The technique involves making "movies" of the cosmic microwave background: the relic of the most distant light in the early Universe. This new observational window could open new avenues to understand nature as  we do not know if the Universe in its past is like ours or different. It would allow us to peer into causaly disconnected regions from us and thus understand if the pillars of physical cosmology (which received the nobel prize this year) are correct or we will discover new physics.

  • Solving protein structures using genetics (2019)

    Lehner, Ben (CRG)

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    Solving protein structures using genetics

    Determining the three-dimensional structures of macromolecules is a major goal of biological research because of the close relationship between structure and function.   Structure determination usually relies on physical techniques including X-ray crystallography, NMR spectroscopy and cryo-electron microscopy. We have developed an alternative method that allows the high-resolution three-dimensional backbone structure of a biological macromolecule to be determined only from measurements of the activity of mutant variants of the molecule. This genetic approach to structure determination relies on the quantification of genetic interactions (epistasis) between mutations and the discrimination of direct from indirect interactions. This provides an alternative experimental strategy for structure determination and one that allows the power of high throughput genomics to be applied to structural biology. It also allows the structures of molecules to be determined as they are performing their functions inside cells.

  • Multicolored light twists in new knotted ways (2019)

    Lewenstein, Maciej Andrzej (ICFO)

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    Multicolored light twists in new knotted ways

    Around age six, we start learning how to tie our shoelaces, making knots that look like ribbons — or possibly more complex forms, if we are a little clumsy. We use knots every day, but the type of knots we generally use is associated with physical objects, things we can touch. In a recent study, published in two papers, joint collaborations by ICREA/ICFO researchers demonstrated multicolored light twists in new knotted ways. They have broken theoretical and experimental ground in this new field, uncovering new types of knots for twisted light and a new type of angular momentum.

    In the first paper, published in Nature Photonics, ICFO researchers Emilio Pisanty, Gerard Jiménez Machado, Veronica Vicuña-Hernández, Antonio Picón, and Alessio Celi, led by ICREA Prof. at ICFO Maciej Lewenstein and UPC Prof. at ICFO Juan P. Torres, have designed a beam of light with a polarization state that forms three-lobed trefoils at each point, by combining light of different frequencies, and making the trefoils connect to each other in a way such that the light beam, as a whole, has the shape of a knot. These beams also exhibit a new kind of angular momentum, associated with the unusual symmetry of the beams, which remain unchanged when they’re rotated — but only when the polarization is rotated by a specific portion of the rotation in space. This new quantity is termed the torus-knot angular momentum, because of the type of knot in the beams, and the researchers were able to experimentally confirm its presence.

    In the second paper, published in Physical Review Letters, ICFO researchers Emilio Pisanty and Antonio Picón, led by ICREA Professor at ICFO Maciej Lewenstein, in collaboration with researchers from the University of Salamanca and from CU Boulder, show that the new type of angular momentum is conserved in interactions. They show, via theoretical simulations, that at extremely high intensities, many photons of light can be combined into single photons with high energy, and that these new, bigger photons carry the combined torus-knot angular momentum of the original, smaller photons.

  • The Mutational Footprints of Cancer Therapies (2019)

    López-Bigas, Núria (IRB Barcelona)

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    The Mutational Footprints of Cancer Therapies

    As we age our cells accumulate mutations due to a number of different processes.  The source of these mutations can be exogenous (e.g., solar radiation, tobacco smoke or some toxic substance) or endogenous (e.g., errors in DNA copying). Each of these mutational processes leave a specific footprint in the DNA, which we call its mutational signature or footprint.

    Since many cancer treatments affect DNA, we reasoned that they may leave a specific mutational footprint in the DNA of the cells of treated patients.

    We analyzed the mutations identified in the genomes of more than 3500 metastases of formerly treated patients and using ad hoc bioinformatic analyses, we identified the mutational footprints of six therapies widely used for the treatment of cancer (five based on drugs used as chemotherapies, and radiotherapy).

    Using these footprints, we then can quantified the mutations likely caused by each kind of chemotherapy. We expect that these findings will allow for precise assessment of the mutational risk of different cancer therapies to understand their long-term side effects.