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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  • The second law of thermodynamics assists the study of the brain. (2022)

    Deco, Gustavo (UPF)

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    The second law of thermodynamics assists the study of the brain.

    The principles of thermodynamics are applicable to any system including the study of brain states.

    Deco's group and international collaborators study how brain dynamics change in different states, for example, sleep, wakefulness, coma, or neurological diseases. The idea is that the brain works like an orchestra, with a conductor and section leaders (violins, wind, strings...) and depending on our state, these hierarchies change and transform. A hierarchical system is where one or more zones take the baton, to lead other areas.

    This hierarchy was quantified, not only by measuring the interactions between parts of the brain using fMRI, which allows seeing brain activity, but also by using a trick based on the second law of thermodynamics that says a system tends to go from ordered to more random behaviour or entropy as time passes.

    With time, if entropy increases, it means that the system is not in equilibrium and is non-reversible in time, so, we cannot know at what point it is. Conversely, if entropy does not grow or does not occur, then it is a system in equilibrium and reversible in time.

    An example of the increase in entropy, where the system is irreversible, would be a video of a breaking glass. If we see the film backward or forward we easily know if it is before or after the glass breaks.

    In contrast, a system where entropy does not increase, which is reversible, would be a video of a billiards game at the moment when two balls collide and rebound away from each other. Playing the video forward or backward provides identical images, so we cannot know at which point we are.

    By quantifying the relationship between different parts of the brain, symmetry is broken. By moving the series of signals back and forth, and compare them as with the films, we know which system it is: a reversible one is not hierarchical, a non-reversible one is hierarchical.

    The technique is a good biomarker of brain consciousness. This is very practical as the classification of states helps define patient treatments and expectations.

  • Twins shed light on the genetic and environmental factors shaping our speech organs (2022)

    Dediu, Dan (UB)

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    Twins shed light on the genetic and environmental factors shaping our speech organs

    Most people take for granted that the organs we use to speak, such as the tongue, lips, teeth and the bony roof of the mouth (hard palate), somehow emerge during development and then pretty much "quietly" do their job. However, on a closer inspection (or a chat with your dentist while the anaesthetic kicks in) will soon reveal that they vary tremendously, in more or less subtle ways, between "normal" people: some have longer tongues that can touch the tip of their nose, some have smaller teeth, and yet some have high, domed hard palates.

    Does this variation matter for speech, and where does it come from? To the first question, the answer suggested by recent studies is that, at least in some cases, it might. To the second, the answer is largely unknown given the complexity of the interplay between genes, environment and culture, and the lack of large scale-studies using adequate methodology and data.

    To remedy this, an international consortium, initiated by Dan Dediu and Dorret Boomsma, has combined 3D structural magnetic resonance imaging (MRI) of the speech organs from more than 600 identical and non-identical twins. These data were collected across almost two decades and five different studies at the Netherlands Twin Register, Vrije Universiteit Amsterdam, and allowed the team an in-depth analysis of the interplay between genes and environment for 140 aspects of the vocal tract. This interplay is captured by their so-called heritability which can vary between 0% and 100%, and expresses the proportion of the observed variation between individuals due to variation in their genes.

    The results are complex and suggest that the interplay between genes and environment varies dramatically between components of the vocal tract, from the unexpectedly low heritability of the hard palate to the unexpectedly high heritability of the position of the voice box (larynx). Overall, the results are consonant with observations that cultural practices (including the food consumed) do matter. The study opens new directions in the "hunt" for the genes and environmental and cultural factors at play by focusing future research, with potential therapeutic applications.

  • Untangling genomic architecture reveals new therapeutic target for leukemia (2022)

    Di Croce, Luciano (CRG)
    Martí-Renom, Marc (CNAG)

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    Untangling genomic architecture reveals new therapeutic target for leukemia

    Acute Promyelocytic Leukaemia (APL) is an aggressive type of blood cancer that is responsible for 5-15% of all types of leukaemia, which occurs because of chromosomal translocations, in which a chromosome breaks and a portion of it reattaches to a different chromosome. In APL, this results in a gene fusion event between the promyelocytic leukemia (PML) and retinoic acid receptor alpha (RARα) genes. The expression a new protein – PML/RARα – in hematopoietic stem cells blocks their differentiation. Eventually, the bone marrow fills up with abnormal white blood cells known as promyelocytes that lead to a shortage of other types of blood cells and prevent normal blood production.
    We found that PML-RARα initiates a series of alterations that result in specific changes chromatin organization and the repression of transcription.
    One of the genes most affected by these changes at an early stage was KLF4, which codes for a protein that binds to DNA to control the rate of transcription of genetic information, also known as a transcription factor. Klf4 activity was inactivated during the progression of APL. We found that, when cells were manipulated to overexpress Klf4 many traits of cancerous cells were reversed.
    The findings pave the way for the development of drugs that boost the reactivation of the genes repressed at the earliest stages of cancer formation (such as Klf4), intercepting the disease before it becomes uncontrollable.
    The method, developed in our laboratory, can also be used to study changes to the genomic architecture of other types of cancer, which could reveal other possible therapeutic targets yet to be discovered.


  • Reducing uncertainty of near-term climate change estimates (2022)

    Donat, Markus G. (BSC-CNS)
    Doblas Reyes, Francisco Javier (BSC-CNS)

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    Reducing uncertainty of near-term climate change estimates

    Estimates of future changes in climate are typically derived from complex climate model simulations driven by the expected changes in anthropogenic emissions including greenhouse gases that warm the planet. These simulations of future climate are widely referred to as so-called climate projections. Climate projections are affected by a range of different uncertainties, whereby internal variability is the dominant source of uncertainty in regional near-term climate change estimates for the next 10-20 years.


    We have developed a new method to reduce the uncertainty from internal climate variability in estimates of near-term climate change. We use large ensembles of hundreds of climate projections and in each year sub-select those simulations for which the global patterns of ocean temperature anomalies are most similar to observed anomaly patterns. These ocean temperature anomaly patterns include signatures from different modes of climate variability, and the selection aligns the phasing of the simulated and observed climate variations. This method improves the accuracy of near-term climate projections in large parts of the globe, most notably the tropical Pacific, the tropical and sub-polar North Atlantic, the Indian ocean and land regions in Africa, Asia, southwestern Europe, and Australia among others. The skill improvements in the Pacific region are particularly remarkable, as this is an area where state-of-the-art climate models struggle to reproduce the observed climate variations, limiting the usefulness of climate projections there. The new constraint based on the phasing of climate variability therefore provides more accurate climate information in these regions and addresses some of the previous limitations in projecting and predicting future climate.


  • Extreme points of the unit balls in spaces of functions (2022)

    Dyakonov, Konstantin (UB)

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    Extreme points of the unit balls in spaces of functions

    А point of a convex set S is said to be extreme (for S) if it is not an interior point of any line segment contained in S. For instance, if S is a closed convex polygon in the plane, then the extreme points of S are precisely its vertices. Also, if S is a closed ball in the usual Euclidean space − think of an orange or a watermelon − then every point of the boundary sphere is extreme for S (and these are the only extreme points).

    However, the situation may change dramatically if we consider balls in more general normed vector spaces. In particular, various function spaces are worth looking at. One striking example is offered by L1, the space of integrable functions on the interval [0,1], say. The (closed) unit ball of L1 is the set of those functions f  for which the integral of |f| over [0,1] does not exceed 1, and it turns out that this set has no extreme points at all. Thus, the unit ball of L1 is no longer "round"; it is actually pretty "flat"!

    Now, we turn to more sophisticated function spaces whose members have prescribed gaps (or holes) in their Fourier spectra. This means that only certain selected harmonics show up in the function's Fourier series, while others are forbidden. Our lacunary function spaces are then normed appropriately (the norm being either uniform or inherited from L1), and we determine the extreme points of the unit balls that arise.

  • Epigenetics predicts the efficacy of T-lymphocyte treatments in hematological malignancies (2022)

    Esteller Badosa, Manel (IJC)

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    Epigenetics predicts the efficacy of T-lymphocyte treatments in hematological malignancies

    One in five cancers affects blood cells and lymph nodes, causing leukemias and lymphomas, respectively. Although their treatment with drugs has led to a great advance in their cure, there are cases where there is no clinical response or resistance to them is generated. For a few years there has been an alternative for these cases: a cell therapy that collects the T-lymphocytes of these patients, modifies them through genetic engineering in the laboratory and they are again administered to the patient so that they more effectively attack the cancer. This innovative new cellular medicine, also called chimeric antigen receptor T-lymphocyte therapy (CAR-T), is not without problems that can be summarized in the appearance of side effects, cases that are insensitive to the therapy and its high economic cost. Therefore, it would be very important to be able to select which patients are likely to benefit from the use of CAR-T cells. Dr Esteller’s group decided to look in detail at the molecular characteristics of more than 100 samples of CAR-T cells provided to patients with leukemias and lymphomas. They discovered that there was a genetic regulation profile (epigenome) that was associated with the absence of disease relapse and an improved overall survival of these people. In addition, it was observed that this epigenetic pattern wass typical of young T lymphocytes that, as they have a long life ahead and a greater capacity to remain in the patient's bloodstream, perhaps for this reason they are more efficient CAR-T cells. It is worth investigating now whether these cell subpopulations would be ideal to be selected and administered, or if they can be enriched using epigenetic drugs that are given in the context of other leukemias and lymphomas.