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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  • Why are hybrid metal-halide perovskites so defect tolerant? (2021)

    Goñi, Alejandro R. (CSIC - ICMAB)

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    Why are hybrid metal-halide perovskites so defect tolerant?

    Hybrid lead halide perovskites are causing a revolution in photovoltaics, reaching light conversion efficiencies in excess of 25% after less than a decade of intense research. In nanocrystal form, these materials exhibit light-emission quantum yields close to 100%, which make them excellent candidates for light emitting devices too. However, a feature making hybrid perovskites so attractive for commercialization is the fact that they are produced by low-temperature, hence low-cost, scalable solution-based methods. In part as a consequence, hybrid perovskites are mechanically soft ionic solids with low energetic barriers for point-defect formation and yet they exhibit excellent optoelectronic properties. This can be explained if most native point defects (vacancies, interstitials and antisite defects) are shallow. Unlike deep traps, which are highly localized centers exhibiting high charge-carrier trapping rates, shallow defects are benign as far as the charge-carrier recombination is concerned. Shallow defects can be studied by means of low-temperature photoluminescence (PL). In PL experiments, correlated electron-hole pairs, called excitons, are excited with a laser. Excitons move freely through the crystal, like a binary-stars system, but they can become bound to different shallow defects. Free or bound excitons recombine radiatively emitting photons with precise energies, constituting an optical fingerprint (see Fig. 1). 

    In a recent work [1], we performed the first systematic study of the evolution of shallow-defect signatures observed in low-temperature PL spectra of mixed organic-cation lead iodide perovskite single crystals. Based on state-of-the-art ab initio calculations, we were able to provide a first assignment for all PL features to different shallow-defects (vacancies & interstitials) of hybrid perovskites. 

    In this way, our results provide a deeper insight into fundamental aspects of the photo-physics of native shallow defects in metal halide perovskites. This is instrumental for the optimization and further development of photovoltaic as well as light-emitting devices, based on this class of extraordinary semiconductor materials.

  • Controlling brain states with a ray of light (2021)

    Gorostiza Langa, Pau (IBEC)
    Sánchez-Vives, María Victoria (FRCB-IDIBAPS)

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    Controlling brain states with a ray of light

    The brain presents different states depending on the communication between billions of neurons, and this network is the basis of all our perceptions, memories, and behaviours. It is often considered a “black box”, with difficult access for clinicians and researchers, as few tools are available to measure and manipulate brain neuronal networks with spatiotemporal accuracy. Now, a collaboration between the laboratories of Sanchez-Vives (IDIBAPS) and Gorostiza (IBEC) has allowed for the first time to control brain states using a molecule responsive to light, a method called photopharmacology. Results show that the compound PAI (for Phthalimide-Azobenzene-Iperoxo) developed at IBEC can specifically and locally activate muscarinic cholinergic receptors present in the cerebral cortex. They are a specific type of protein that binds acetylcholine, a neuromodulator involved in processes like learning, attention, and memory.

    Transitions between brain states, such as going from being asleep to awake, recovering from anaesthesia, or waking up from a coma, are based on the transmission of chemical and electrical signals between groups of neurons that are activated synchronously, as in waves. Their oscillatory activity is often described as "brain waves" and is an emerging property of the brain cortex. When applying PAI to the intact brain, white light allowed modulating the spontaneous emerging slow oscillations in neuronal circuits and reversibly manipulating the oscillatory frequency. Thus, this molecular tool enables inducing and investigating in a controlled and non-invasive way, the transitions of brain from sleep- to awake-like states using light.

    These results are a breakthrough for neuromodulation technologies to manipulate brain activity patterns, to understand their connections to cognition and behaviour, and could also lead to novel treatments for brain lesions and diseases. Since the method works in intact brain tissue and does not require genetic manipulation, these results open the door to non invasive spatiotemporal control of drug action in the human brain.


  • What big eyes you have! (2021)

    Gorostiza Langa, Pau (IBEC)

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    What big eyes you have!

    Can pupils dilate with light? they usually do the opposite, as they are intended to adjust to the ambient light intensity. That is why a common test performed by eye doctors to examine the optic nerve and retina, or in ophthalmological shops to evaluate visual performance, requires to dilate the pupil with a drug. But pupil dilation is annoying, as it causes blurry vision, increased light sensitivity, and increased ocular pressure long after the test.

    A common way to induce pupil dilation is to use agonists of adrenoceptors, proteins that are expressed on the iris dilator muscle, but also in almost any organ and tissue of the human body, where they regulate important physiological functions such as heart and respiratory rate, digestion, vascular tone, and gland secretion, besides pupil diameter.

    These receptors can now be “turned on and off” locally using a set of photoswitchable molecules that we called “adrenoswitches.” These compounds enable remote control over a variety of physiological functions simply using illumination. And the eye offers a perfect window to demonstrate it. Eye-dilating agents (mydriatics) are used in several ophthalmic procedures. However, post-exam pupil dilation can impede simple everyday tasks like driving or reading for several hours. In order to avoid that, we envisaged a drug that would dilate the pupil only during the examination, and then be deactivated as soon as the lights went off.

    When tested in blind mice, whose pupils do not respond to illumination, adrenoswitch-1 evoked a pupil dilation that reversed upon removal of the activating light source. In wild type animals, it inhibited the pupil contraction reflex when this was induced by violet light.

  • A biosensor made of photosynthetic complexes from plants (2021)

    Gorostiza Langa, Pau (IBEC)
    van Hulst, Niek F. (ICFO)

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    A biosensor made of photosynthetic complexes from plants

    Photosynthetic reactions in plants, algae, and cyanobacteria are driven by photosystem protein complexes, which exchange electrons with partner biomolecules. Photosynthetic complexes can also bind synthetic organic molecules, which mediates their photoactivity and enables sensing of herbicides and algicides, or the study of electron transport chains. Thus, development, characterization, and sensing of photosystem complexes bears both fundamental and applied interest. Binding to the plastoquinone sites of photosystem-I provides a promising route to biosensing, and would enable identifying novel substances displaying phytotoxic effects, including those obtained from natural product extracts. To this end, we have devised a procedure to attach photo- and redox-active photosystem I complexes to the surface of transparent gold, and we obtained reproducible electrochemical photo-responses with direct current readout. Using this novel biosensing platform, we measured photocurrents in the presence of the viologen derivative paraquat at concentrations as low as 100 nM, with a biosensor dynamic range spanning six orders of magnitude up to 100 mM concentration.


  • How do plants and animals use alternative splicing? (2021)

    Irimia, Manuel (CRG)

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    How do plants and animals use alternative splicing?

    Alternative splicing is a pre-translational process by which eukaryotic cells can generate multiple transcripts from a single gene, often in response to specific developmental and/or environmental cues. This can lead to the generation of either multiple protein isoforms, expanding proteome diversity, or of a subset of non-functional transcripts, effectively contributing to downregulate gene expression.

    Alternative splicing exists since the last common ancestor of eukaryotes and it is particularly prevalent in animals and plants, the two major multicellular domains of life. However, a major question remained: how do these two lineages make use of this mechanism? What differences and commonalities do they have?

    To answer this question, we profiled alternative splicing patterns across tissues and environmental conditions in the model plant Arabidopsis thaliana and compared them with those of animal models. We observed that Arabidopsis display high levels of alternative splicing, similar to those of fruit flies, which have complex organs and behaviors. Remarkably, however, we found that Arabidopsis often uses this mechanism to adapt its transcriptome in response to environmental stress, modulating gene expression levels, whereas animals employ it mainly to shape and sculpt their proteomes in a tissue-specific manner (Fig. 1). These divergent patterns are consistent with the different lifestyles of each lineage: whereas plants are sessile and need to respond to any unfavorable condition in situ, animals can run away from those conditions. In turn, animals need highly specialized tissues to accomplish and coordinate these responses, particularly muscle and nervous systems, which show the highest levels of tissue-specific splicing in animals.


  • Strengthening evidence for four-top-quark production at the LHC (2021)

    Juste, Aurelio (IFAE)

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    Strengthening evidence for four-top-quark production at the LHC

    One of the main goals of the ATLAS experiment at CERN’s Large Hadron Collider (LHC) is to challenge the predictions of the Standard Model (SM), our most successful theory of elementary particles. To this end, a promising direction is the study of the production of four top quarks at once, a very rare process that happens only once every 1012 proton-proton collisions. Once produced, each top quark decays into a W boson and a bottom quark, with the W boson decaying into a charged lepton (electron, muon, or tau) and a neutrino, or a quark-antiquark pair. This results in some of the most spectacular signatures ever produced at the LHC.

    In 2020, the ATLAS Collaboration reported strong evidence for this process [1]. To confirm it, ATLAS physicists performed a new study focused on events with one charged lepton or two leptons with opposite electric charge [2, 3]. Despite accounting for the lion’s share of four-top-quark events, these signatures are easily overshadowed by other, much more-common SM processes with similar decay products, requiring the use of sophisticated multivariate techniques to discriminate them. The measured four-top-quark rate is compatible with the previous result [1] and their combination is a factor of two larger than the SM prediction, although still consistent with it within 2.0 standard deviations (s.d.). The existence of the four-top-quark process is therefore favoured with an observed significance of 4.7 s.d. This provides stronger evidence for this process than expected (2.6 s.d.), and is just shy of the conventional requirement of 5 s.d. to claim an observation.

    Since 2015, researchers at IFAE, under A. Juste’s leadership, are playing a major role in the search for four-top-quark production in ATLAS. The team has not only contributed to the recent results [1-3], but is also leading dedicated searches for beyond-the-SM four-top-quark production via a new heavy Higgs boson, which could potentially explain the measured excess. Additional data from the next LHC run, to start in 2022, along with further analysis improvements, will hopefully allow drawing definite conclusions on whether the breakdown of the SM is finally in sight.