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  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.

LIST OF SCIENTIFIC HIGHLIGHTS

Format: yyyy

  • Chimpanzee and Bonobo ancient hybridization  (2016)

    Marquès Bonet, Tomàs (UPF)

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    Chimpanzee and Bonobo ancient hybridization 

    This year, a study published in Science and led by Tomàs Marquès-Bonet, ICREA researcher at the Institute of Evolutionary Biology (IBE), and the Centro Nacional de Analisis Genomico (CNAG-CRG) revealed novel ancient admixture events among the extant species closest to humans: bonobos and chimpanzees. This study has been then the first study to reveal admixture among the species similar to what has been reported between humans and Neanderthals and shows that admixture might have been a common occurrence during human and primate evolution.

    Between 1,5 and 2 million years ago chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) split from a common ancestor and evolved important strong physical and behavioural differences. To this day, the existence of gene flow between the species has not been considered due to the Congo River that physically separates the geographical distribution ranges of the species. The studied samples, comprising 75 complete genomes of chimpanzees and bonobos sequenced at the CNAG-CRG, cover 10 countries in Africa, from the westernmost to the easternmost region of the chimpanzee range. The results have direct application to the conservation of these species because they permit the detection of the origin of chimpanzees confiscated from illegal trafficking. The researchers have found that central and eastern chimpanzees share significantly more genetic material with bonobos than other chimpanzee subspecies do. Thus, it is believed that the admixture between bonobos and chimpanzees occurred during two different episodes: the first one, less than 500,000 years ago and the second one more recently, less than 200,000 years ago.

    Compared to our knowledge of the origins and population history of humans, much less is known about the extant species closest to humans, and since many predictions suggest the disappearance of chimpanzees and bonobos within the twenty-first century, this is one of the current efforts to pull together all forces in order to understand and protect the chimpanzees and bonobos before they disappear.

  • A mutation that alters the routes of HIV spread in the body (2016)

    Martínez-Picado, Javier (IrsiCaixa)

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    A mutation that alters the routes of HIV spread in the body

    Siglec-1 is a protein that plays a key role in HIV spread in the body that our group identified four years ago, in an article published in PLoS Biology. This protein is the receptor responsible for trans-infection of HIV (the AIDS virus) to CD4 T lymphocytes. Trans-infection occurs when the virus penetrates into a family of immune cells, called myeloid cells, which are supposed to activate the immune response. HIV uses Siglec-1 to penetrate these cells and turn them into "Trojan horses", as the virus prevents them to initiate an adequate immune response and uses them to reach its main target, the CD4 T lymphocytes.

    We have described now in Nature Communications the existence of a genetic variant that prevents the production of Siglec-1. This is a very rare mutation: it is estimated that only 1.3% of the European population has it in at least one allele, and approx 0.05% has it in the two alleles. Despite this low frequency, and after a screening of more than 4,000 people infected with HIV, our study identified for the first time that there are patients who naturally lack this pathway of viral spread: 97 people in the study had the mutation in one of their two alleles, and two had it in both.

    After studying the effect of this alteration in cells taken from patients, we found that the mutation reduces the ability of myeloid cells to capture the virus and transfer it to CD4 T lymphocytes. We observed that Siglec-1 is expressed to a greater extent in people who do not have the mutation, to a lesser extent in those who only have one copy with the mutation, and absolutely nothing in those who have it in both copies. Therefore, the absence of the receptor in people who have the mutation in their two gene copies prevents HIV from entering the myeloid cells and infecting the CD4 T lymphocytes.

    Since the absence of this protein does not seem to have any other effect in people affected by the mutation, these results suggest that it would be feasible to develop drugs, complementary to the current ones, intended to block the function of Siglec-1.

  • Simple patterning of graphene oxide with interest to build electronic devices and biosensors (2016)

    Merkoçi, Arben (ICN2)

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    Simple patterning of graphene oxide with interest to build electronic devices and biosensors

    Fast prototyping of electronic devices including biosensors is of great importance to reach the demand for cost/efficient technologies with interest for industries including “Maker” or “Do It Yourself” communities. Between various nanomaterials, graphene is emerging as a very interesting alternative building block for such devices given advantageous optical and electronic properties beside robustness, low cost and easy to obtain procedures. In this context we developed a simple and versatile graphene oxide printing technology using wax printed membranes for the fast patterning and water activation transfer through pressure- based mechanisms. The wax printed membranes have 50 μm resolution, longtime stability and infinite shaping capability. The use of these membranes complemented with the vacuum filtration of graphene oxide provides the control over the thickness. Our demonstration provides a solvent free methodology for printing graphene oxide devices in all shapes and all substrates using the roll-to-roll automatized mechanism present in the wax printing machine. Graphene oxide was transferred over a wide variety of substrates as textile or plastics in between others. Our patented technology (https://www.google.com/patents/WO2015193486A1?cl=en) on graphene patterning is already in use by Biolin Scientific (Sweden) who already launched the first graphene-based sensors with interest for biosensing applications (http://www.biolinscientific.com/product/q-sense-sensors/). Based on our patented technology (graphene patterning for electronic devices) a Spin Off company (GraphenicaLab) is already created. 

  • Incorrect number of chromosomes, gene-dosage imbalance and cancer (2016)

    Milán Kalbfleisch, Marco (IRB Barcelona)
    Rodriguez Nebreda, Angel (IRB Barcelona)

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    Incorrect number of chromosomes, gene-dosage imbalance and cancer

    Genomic instability was originally proposed to cause cancer over 100 years ago and it has been observed in most solid tumors. There are various forms of genomic instability and the most common in cancer is chromosomal instability (CIN), which refers to the high rate by which chromosome structure and number changes over time in cancer cells compared to normal cells. While CIN contributes to the gain or loss of chromosomes carrying oncogene or tumor-suppressor genes, respectively, errors in chromosome segregation cause DNA damage and chromosomal rearrangements, and the resulting aneuploidy, defined as an abnormal number of chromosomes or parts of them, compromises cell fitness.

    Marco Milán and colleagues have used the wing primordia of Drosophila to molecularly dissect the cellular and tissue-wide effects of CIN-induced aneuploidy. These wing primordia grow from 20 to 30,000 cells in 4 days and provide the advantage that individual cells can be tracked and the tissue can be manipulated genetically in a temporal and spatial manner. Previous work from the lab has shown that CIN-induced aneuploid cells are removed from the tissue by JNK-dependent apoptosis. When highly aneuploid cells are prevented from entering apoptosis, JNK drives the expression of mitogenic molecules and matrix-metalloproteases and induces tumor-like tissues that grow extensively, cause malignancy to the host and metastasize when transplanted into the abdomen of adult hosts.

    Authors have now made use of the inherent aneuploidy in male flies to unravel a role of chromosome-wide gene dosage imbalance to the effects of CIN in vivo. Authors also identify several mechanisms that buffer the deleterious effects of CIN in proliferative tissues, including activation of the DNA-damage response pathway, induction of p38 MAPK signaling to protect against reactive oxygen species (ROS), and expression of mitogenic cytokines to promote compensatory cell proliferation and restore tissue loss. Compromising the activity of these buffering mechanisms enhances the deleterious and pro-tumorigenic effects of CIN. 

  • Uncovering the relevant role of autophagy in restoring tissue regeneration during aging (2016)

    Muñoz-Cánoves, Pura (UPF)

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    Uncovering the relevant role of autophagy in restoring tissue regeneration during aging

    Dr. Pura Muñoz-Cánoves’ Group recently published in Nature one possible explanation for the loss of tissue regenerative capacity with aging. In tissues with little turnover, stem cells (which repair tissues and organs) remain in a dormant, quiescent state. The stem cells of skeletal muscle (also called satellite cells) were thought to be quiescent throughout life, only activating in response to damage or stress. Dr. Muñoz-Cánoves and colleagues hypothesized that satellite cells would progressively accumulate intracellular toxic debris over their lifespan, and would therefore need an efficient ‘clean-up’ system to maintain protein homeostasis (proteostasis). These ideas led them to investigate the possible role of autophagy, a system used by cells to degrade damaged proteins and organelles in vesicular structures called lysosomes. Recent evidence shows that, at advanced, geriatric life stages, satellite cells lose quiescence and enter an irreversible state of proliferative block called senescence, leading to defective muscle regeneration. Using autophagy-reporting mice, these researchers found that adult satellite cells, despite their dormant state, maintain a basal autophagic activity. In old age, however, this activity is lost, causing accumulation of damaged mitochondria. Mitochondria are the essential organelles of energy production, and the accumulated dysfunctional mitochondria generate high levels of reactive oxygen species (ROS), causing further damage to proteins and DNA. This loss of proteostasis provokes senescence entry and impairs satellite cell functions. By reactivating autophagy or inhibiting ROS production in aged satellite cells, they were able to prevent senescence, restore stem-cell self-renewal, and reboot the capacity to form new muscle fibres. The identification of autophagy as an obligatory activity for maintaining stem-cell fitness, despite these cells’ low metabolic activity, not only advances the understanding of stem-cell biology, but also suggests research avenues into potential regenerative medicine applications.

  • How nanoparticles give electrons away (2016)

    Neyman, Konstantin M (UB)

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    How nanoparticles give electrons away

    Whether it is in catalytic processes, new types of solar cells or advanced electronic components, nanoparticles are everywhere in modern production and environmental technologies. Their remarkable properties ensure efficiency and save resources. Specialproperties of nanoparticles often arise from chemical interactions with the support material on which they are placed. Such interactions change the electronic structure of the nanoparticle when electrical charge is exchanged between the particle and the support.

    Scientists led by ICREA Professor Konstantin Neyman (Universitat de Barcelona) and Professor Jörg Libuda (Universität Erlangen-Nürnberg, Germany) have succeeded in quantifying the charge that is lost by a platinum nanoparticle when it is deposited onto a typical oxide support. Their work brings the possibility of designing nanoparticles with tailor-made properties a step closer.

    In order to measure the electrical charge exchanged between metal particles and supports the international research team from Germany, Spain, Italy and Czech Republic funded by the European Commission prepared a clean, atomically well-defined oxide surface, on which platinum nanoparticles have been placed. Using a highly sensitive detection method at Elettra Sincrotrone Trieste the researchers were able to quantify the effect for the first time. Studying particles with various numbers of atoms, from dozens to several hundreds, they measured the number of electrons transferred to the support and showed that the effect is most pronounced for small particles with around 50 atoms.

    The effect for such particles is surprisingly large: approximately every tenth metal atom loses an electron when the particle is in contact with the oxide. Using theoretical methods and computational modelling the researchers revealed how the effect can be controlled, allowing the chemical properties to be adapted to better suit the intended application. This research, published in Nature Materials magazine, should enable more efficient usage of valuable raw materials and energy, for instance, in catalytic processes.

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