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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  • White paper on astrocytes in diseases of the central nervous system (2021)

    Galea, Elena (UAB)

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    White paper on astrocytes in diseases of the central nervous system

    Astrocytes are a type of cell in the central nervous system (CNS) with homeostatic and computational roles in neural circuits. Hypertrophy of astrocytes was recognized in the mid XIXth century as an almost universal sign of CNS pathology, and the term ‘reactive astrocytes’ was coined to describe astrocytic remodeling in response to pathologic conditions. In the decade of the 90s of the XXth century, the study of reactive astrocytes exploded as part of the so-called ‘neuroinflammation’ in CNS pathologies; however, thirty years later the field is stagnated. There are no therapies derived from research on ‘inflammatory’ astrocytes, data from highly influential studies cannot be reproduced, and, importantly, astrocyte experts do not agree on basic issues including what reactive astrocytes are. A few of us capitalized on this discontent by fostering a necessary debate. The result is a working consensus of 80+ authors on reactive astrocytes. We take positions on controversies regarding the impact of astrocytes in CNS diseases, we discuss nomenclature, provide definitions, and we outline a systematic approach to unraveling the contribution of astrocytes to disorders of the CNS aging. This article is expected to inform clinical thinking and research on astrocytes and to promote the development of astrocyte-based biomarkers and therapies.

  • Complete coupling of light to optical surface excitations (2021)

    García de Abajo, Francisco Javier (ICFO)

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    Complete coupling of light to optical surface excitations

    Confining optical modes well below the size determined by the light wavelength at the same frequency is beneficial for the design of compact and efficient optical devices because light concentration impacts the electromagnetic energy density, the ability of light to interact with analytes in sensors, and the nonlinear response of materials in all-optical light modulators. However, such confinement comes at the prize that coupling of propagating light to those modes is made more inefficient because of the mismatch with the light wavelength. Light coupling in and out of confined modes is in fact a major pending problem that limits the practical applicability of the optical confinement strategy in nanophotonics.

    Small scatterers are commonly employed to assist light coupling because they allow targeting designated spatial regions in space, matching the area occupied by the confined modes. However, when those scatterers are placed close to the materials supporting the optical modes, the coupling is reduced by losses introduced through the coupling itself, acting as a loss channel. In this work, we have proposed the use of small scatterers placed at a suitable distance from a surface supporting optical modes as a strategy to realize complete optical coupling into such optical modes. By employing lossless, resonant scatterers such as silica particles supporting dipolar Mie resonances, and illuminating the system with focused light, we demonstrate through rigorous theory the possibility of achieving complete optical coupling, provided the angular profile of the incident light is appropriately shaped, and the surface-scatterer distance is fixed to satisfy the so-called critical coupling conditions.

    The solution here proposed to solve the in and out optical coupling problem has general applicability in nanophotonics and provides a viable route toward the design of compact optical devices in which suitably engineered optical scatterers are used to funnel light into the surface modes of a planar surface, where they can be used for optical sensing or signal processing, and eventually coupled out into propagating light following the same scheme.

  • New breast cancer precision medicine approach to prevent metastasis: from bench to bedside (2021)

    Gomis, Roger (IRB Barcelona)

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    New breast cancer precision medicine approach to prevent metastasis: from bench to bedside

    Currently, bisphosphonates are not regulatory approved for its use in adjuvant treatment of early-stage breast cancer patients. However, they are recommended in the ASCO/ESMO guidance for clinical practice for adjuvant treatment of breast cancer of postmenopausal patients.


    The results from this study show that, independent of menopausal status, patients with MAF-negative (non-amplified) tumors treated with Clodronate had a longer survival than untreated patients (HROS= 0·59, (95% CI 0·37–0·93), p=0·02), whereas patients who had MAF-positive tumors had no benefit. The risk of death at 5 years in MAF-negative patients was reduced by 41% with clodronate adjuvant treatment. MAF-negative patients who benefited from clodronate adjuvant treatment in this study represented around 80% of all breast cancer patients.


    Our results indicate that the clinical benefit of adjuvant clodronate use is restricted to MAF-negative patients. The assessment of MAF status has the potential to become an objective approach to selection of breast cancer patients for adjuvant clodronate treatment, improving the clinical outcome of the patients.


    The MAF gene amplification acts like an orchestra conductor, activating and blocking a large number of genes, and it plays a key role in breast cancer metastasis, particularly in the spread to the bone. It regulates processes such as cell survival, the initiation of metastasis, metabolic rewiring, and also adhesion to cells from the bone marrow, and the formation of osteoclasts, a cell types responsible for remodeling bone.

    The MAF test is developed by Inbiomotion, a spin-off from IRB Barcelona and ICREA, the test has been successfully assayed in two clinical trials, involving a total of 6,500 patients.

  • 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.