Cada any, un comitè d'experts s'ha d'enfrontar a la difícil tasca d'escolllir, d'entre totes les publicacions ICREA, unes poques que destaquin sobre la resta. És tot un repte: de vegades els debats s'acaloren, i sempre són difícils, però acaba sortint-ne una llista amb les millors publicacions de l'any. No es concedeix cap premi, i l'únic reconeixement addicional és l'honor d'ésser presentat com a Highlight. Cada publicació té alguna cosa especial, sia una solució especialment elegant a un vell problema, un resó espectacular als mitjans de comunicació o simplement, la fascinació d'una idea revolucionària. Independentment del motiu, es tracta dels millors dels millors i, com a tals, ens plau compartir-los aquí.
LIST OF SCIENTIFIC HIGHLIGHTS
Mucus enhances gut homeostasis and oral tolerance by delivering tolerogenic signals
(2013)
Mucus enhances gut homeostasis and oral tolerance by delivering tolerogenic signals
The gastrointestinal tract is home to the highest density of commensal bacteria in the human body and is a primary site of pathogen exposure. Understanding how the immune system recognizes and responds to friend or foe in the gut is central to developing treatments for allergic and inflammatory diseases. A mucus layer covers the entire gastrointestinal tract, physically separating the microbiota from host tissue and preventing pathogen invasion. We now show that mucus does more than act as a shield—it also influences the function of intestinal antigen-presenting cells and epithelial cells to sustain the ability of the host to maintain tolerance toward food and commensal antigens. We found that the gut mucus educates dendritic cells (DCs) to develop tolerance toward food and commensal antigens. DCs lie beneath the intestinal epithelial cell layer and present antigens to other cells of the immune system. Exposure of DCs to mucin-2 (MUC2), a major mucus component, subdues their responses to microbe-derived signals and also promotes their capacity to stimulate the production of regulatory T cells (Tregs), key determinants of oral tolerance. In particular, we observed that MUC2 increased the expression of factors by DCs that allow them to induce Treg production such as transforming growth factor–β (TGF-β) and retinaldehyde dehydrogenase, an enzyme involved in generating retinoic acid. Moreover, MUC2 also acted directly on epithelial cells to stimulate their release of molecules that support DC regulatory function. The ability of MUC2 to promote regulatory responses depends on the interaction of glycan moieties present on MUC2 with galectin-3 (a carbohydrate-binding protein) and the capacity of this complex to engage Dectin-1 on the surface of DCs. The downstream effect of Dectin-1 interaction with MUC-2 is the expression of β-catenin, a factor that can control the tolerogenic function of gut DCs. These results imply that by amplifying various aspects of the gut regulatory network, mucus may be a central determinant of gut immune specification and immune tolerance. Our findings are of particular relevance to understanding severe inflammatory conditions such as inflammatory bowel diseases. Changes to mucus glycosylation can occur during inflammatory responses, and altered glycosylation of mucus has been associated with colitis. Because of the physical protection afforded by mucus, strategies that restore its integrity in inflammatory diseases a
The connectivity between motor and auditory areas mediates word learning abilities
(2013)
de Diego Balaguer, Ruth (UB) Rodríguez Fornells, Antoni (IDIBELL)
The connectivity between motor and auditory areas mediates word learning abilities
Humans are endowed with an amazing capacity to learn words throughout the lifespan. However great individual differences characterise the word learning abilities. This differences may rely on the integration between auditory and motor information that allow the translation of the linguistic auditory information into articulatory gestures. We combined diffusion imaging tractography to dissect the fiber tracts connecting auditory and motor brain areas and functional magnetic resonance imaging to study whether the strength of anatomical and functional connectivity between auditory and motor language networks is associated with word learning ability. We showed that performance in word learning correlates with microstructural properties and strength of functional connectivity of the direct connections between Broca’s and Wernicke’s territories in the left hemisphere. The participants were scanned while listening to an artificial language made of a fluent speech built with nine trisyllabic words that were randomly repeated during four minutes. Word recognition of these words was tested immediately after language learning. The study suggests that our ability to learn new words relies on an efficient and fast communication between temporal and frontal areas responsible of auditory and motor processing respectively. The results of this study may have also implications in evolutionary terms. The absence of these connections in other animals may explain the unique ability of learning words in humans.
Biosensing of individual molecules: Catching one within millions with optical antennas inside nano-boxes.
(2013)
Biosensing of individual molecules: Catching one within millions with optical antennas inside nano-boxes.
A single cell in our body is composed by thousands of millions of different biomolecules that work together in an extreme coordinated manner. Likewise, many biological and biochemical reactions occur only if molecules are present at very high concentrations. Understanding how all these molecules interact with each other is key to advance our knowledge in molecular and cell biology. Unfortunately, detecting one molecule within millions of other neighbouring molecules has been technically impossible until now. The key to succeed relies on foreseeing a device that shrinks the observation region to a tiny size that is comparable to the size of the molecule itself, that is, only a few nanometres. Together with the Fresnel Institute in Marseille we have conceived and fabricated the smallest optical device that can detect and sense individual biomolecules at concentrations that are similar to those found in the cellular context. The device called “antenna-in-a-box” consists on a tiny dimer antenna made out of two gold semi-spheres and separated from each other by a gap as small as 15nm. Light sent to this antenna is enormously amplified in the gap region where the actual detection of the biomolecule of interest occurs. Because amplification of the light is confined to the dimensions of the gap, only molecules present in this tiny region are detected. As additional trick, we embed the dimer antennas inside boxes also of nanometric dimensions. The box screens out the unwanted contribution of millions of other surrounding molecules, reducing the background and improving as a whole the detection of individual biomolecules. When tested under different sample concentrations, this novel antenna-in-box device allowed for 1100-fold fluorescence brightness enhancement together with detection volumes down to 58 zeptoliters (1 zL = 10-21L), i.e., the smallest observation volume in the world. Our antenna-in-box offers a highly efficient platform for performing a multitude of nanoscale biochemical assays with single molecule sensitivity at physiological conditions. It could be used for ultrasensitive sensing of minute amount of molecules, becoming an exquisite early diagnosis device for biosensing of many disease markers. It could be also used as an ultra-bright optical nanosource to lighten up molecular processes in living cells and ultimately watch how individual biomolecules interact with each other, a long awaited dream of biologists.
Key protein in stem cell division identified
(2013)
Our group has published a new study in Nature Cell Biology that contributes one important step towards elucidating the molecular mechanisms that some stem cells use to renew themselves while generating daughters that differentiate. Using as a model system the Drosophila neuroblast, the neural stem cell that generates the fly’s neural tissue, we identified a protein, named Centrobin that plays a key role in stem cell division.The study focuses on the cell organelle known as “centrosome”, which organises the microtubule network. In most animal cells, from worms to humans, a typical centrosome is composed of two barrel-shaped structures called “centrioles” surrounded by pericentriolar material that has a strong microtubule nucleation activity. For each centriole pair, one of the centrioles, called “mother”, is one cell cycle older than the other, called “daughter”. Previous results from our lab have shown that in Drosophila neuroblasts during interphase only the daughter centriole is embedded in pericentriolar material, forming a structure that organises a large microtubule array that plays a key role in instructing the orientation of the next cell division. When the cell divides, the daughter centriole is retained by the renewed neuroblast.This new study reports that Centrobin is both necessary and sufficient to enable daughter centrioles to bind the pericentriolar material that organises the interphase microtubule aster in Drosophila neuroblasts. Centrobin is present in daugther centrioles and absent in mother centrioles (Figure 1). The published article shows that daughter centrioles experimentally depleted of Centrobin cannot bind pericentriolar material while mother centrioles modified to carry Centrobin can. We also show that Centrobin physically binds to a set of known centriolar and pericentriolar material proteins, thus identifying a molecular pathway that might account for Centrobin’s function. Remarkably Centrobin can only perform its function if phosphorylated by Polo, hence revealing an interphase role of this essential kinase in daughter centriole retention by Drosophila neural stem cells.An article published last year by scientists working in the Division of Cancer Diagnosis in the Saitaman Cancer Center, in Japan, showed that when human neuroblastoma cells divide, the daughter cell that retains higher self-renewal potential frequently inherits the daughter centro
Light-regulated stapled peptides to inhibit protein-protein interactions involved in clathrin-mediated endocytosis
(2013)
Light-regulated stapled peptides to inhibit protein-protein interactions involved in clathrin-mediated endocytosis
Most biological processes are mediated by protein-protein interactions (PPIs), which have emerged as important pharmacological targets. Peptide inhibitors with nanomolar affinities were recently developed and demonstrated anticancer activity in vivo. In order to dissect the precise orchestration of PPIs in cells, it would be very useful to complement the pharmacologic selectivity of inhibitors with a means of remotely controlling their kinetics and site of action. Here, we present a peptide design and screening method to obtain photoswitchable inhibitors of protein-protein interactions, and we apply it to photo-regulate clathrin-mediated endocytosis (CME) in living cells. The selective manipulation of CME with light using these peptides, named Traffic Lights (TL) because they act as stop & go signals for membrane traffic, constitutes a novel tool to control cell signaling in spatiotemporally defined patterns. TL peptides can be applied to dissect the role of CME in complex cellular functions like receptor internalization, cell growth, division and differentiation.
Uncovering and preserving South Africa's rich precolonial heritage
(2013)
Uncovering and preserving South Africa's rich precolonial heritage
“The Archaeology of the West Coast of South Africa” is a peer-reviewed volume that presents updated contributions from specialists in the fields of coastal shell midden archaeology, zooarchaeological studies, GIS spatial analyses, geoarchaeology, ceramic and lithic technology, physical anthropology, historical archaeology, and heritage management. An introductory chapter discusses the role and history of archaeological research in this region followed by ten chapters focusing in different sub-regions and above topics. As reflected in this book, the West Coast of South Africa holds one of the largest, most ancient and richest archives of the human history in the world. Spreading 1 million years and a diversity of environments, this record of human presence represents a privileged window into the various stages of technological and behavioral evolution. The cultural heritage of the West Coast of South Africa includes also some of the most ancient rock art in southern Africa. This constellation of distinctive factors makes this region a vital source of discussions for international scholars in diverse topics such as: Pleistocene tool manufacture and mobility, the emergence of modern human behavior, forager and herder land use patterns and cultural contact situations as well as possible competition between these groups, population dynamics and funerary contexts, human impact on marine and terrestrial resources, emergent social complexity among initial egalitarian hunter-gatherer groups, and the irreversible impact of colonial presence that brought a new social and economic order that shapes the South African nation today. About twenty separate and major research projects (academic and contract archaeology (CA)) in collaboration with North American and European research institutions have been conducted over the last fifteen years in this geographic area. Although several of these CA projects have been described in less accessible accounts and in the so-called “grey literature”, these reports are now reflected in this book. The many contributing authors are leaders in their respective fields and have ensured a high and consistent academic quality throughout its length.
