Cutting edge: Regulation of exosome secretion by the integral MAL protein in T cells

Exosomes secreted by T cells play an important role in coordinating the immune response. HIV-1 Nef hijacks the route of exosome secretion of T cells to modulate the functioning of uninfected cells. Despite the importance of the process, the protein machinery involved in exosome biogenesis is yet to be identified. In this study, we show that MAL, a tetraspanning membrane protein expressed in human T cells, is present in endosomes that travel toward the plasma membrane for exosome secretion. In the absence of MAL, the release of exosome particles and markers was greatly impaired. This effect was accompanied by protein sorting defects at multivesicular endosomes that divert the exosomal marker CD63 to autophagic vacuoles. Exosome release induced by HIV-1 Nef was also dependent on MAL expression. Therefore,MAL is a critical element of the machinery for exosome secretion andmay constitute a target for modulating exosome secretion by human T cells. The Journal of Immunology, 2015, 195: 810–814.Peer Reviewe

Seafloor deformation related to Quaternary tectonics in the Majorca Channel, Balearic Promontory (Western Mediterranean)

El análisis morfotectónico del sector central del Promontorio Balear, entre las islas de Ibiza y Mallorca, mediante batimetría multihaz y perfiles sísmicos de muy alta resolución ha permitido diferenciar varios rasgos morfológicos relacionados con la tectónica a dos escalas. Los elementos de gran escala, de dirección NE-SO, son: i) el escarpe Émile Baudot; ii) el monte submarino Émile Baudot, y iii) la alineación de montes submarinos Ausiàs March y Ses Olives. Los elementos de pequeña escala son: i) dos elevaciones longitudinales (ENE-OSO); ii) escarpes rectilíneos (NO-SE a NE-SO); iii) depresiones tectónicas (NNE SSO a NE-SO); y iv) alineaciones rectilíneas de pockmarks (NO-SE a NNE-SSO). Los elementos de mayor tamaño responden a la configuración estructural neógeno-cuaternaria. El escarpe Émile Baudot limita el Promontorio Balear y la cuenca oceánica del Mediterráneo Occidental. La alineación de montes submarinos Ausiàs March y Ses Olives está generada por una fase extensional, y el monte submarino Émile Baudot forma parte de una alineación volcánica NO-SE asociada a la Zona de Fractura de Ibiza. Los elementos de pequeña escala están relacionados con estructuras tectónicas activas que deforman las unidades sedimentarias del Cuaternario y el fondo marino. Las elevaciones longitudinales están generadas por pliegues anticlinales, mientras que el resto de estructuras están asociadas a la actividad de fallas normales de buzamiento alto.A morphotectonic analysis has been carried out between the islands of Ibiza and Majorca in the central sector of the Balearic Promontory using multibeam bathymetry and very high-resolution seismic profiles. Several morphological features related to tectonics at two different scales have been differentiated. The large-scale features have a NE-SW direction, they are: i) the Émile Baudot Escarpment; ii) the Émile Baudot seamount, and iii) the Ausiàs March and Ses Olives seamounts alignment. The differentiated small-scale elements are i) two longitudinal elevations (ENE-WSW); ii) rectilinear scarps (NW-SE to NE-SW); iii) tectonic depressions limited by one or two scarps (NNE-SSW to NE-SW), and iv) rectilinear pockmarks alignments (NW-SE to NNE-SSW). The largest elements respond to the Neogene-Quaternary structural configuration. The Émile Baudot escarpment is the limit between the Balearic Promontory and the Western Mediterranean oceanic basin. The alignment of the Ausiàs March and Ses Olives seamounts respond to the last extensional phase, and the Émile Baudot seamount forms part of a NW-SE volcanic alignment that could be associated with the Ibiza Fracture Zone. The smaller elements are related to active tectonic structures that deform Quaternary sedimentary units and the seafloor. The longitudinal elevations correspond to anticlinal folds, while the rest of the structures are associated to the activity of near vertical normal faults.En prens

COVID-19 Immunisation Strategy: Priority Populations

Additional support from ISGlobal’s Antoni Plasència and Josep M. AntóWith a limited initial supply of COVID-19 vaccines doses and an expected delay for the universal vaccination of those eligible to receive it, it is relevant to analyse how best to prioritise the first available doses to achieve the greatest impact, both in terms of protecting individuals and minimising community transmission. Ethical issues are key in guiding a fair distribution. Different scenarios on vaccine implementation are summarised in this report. After a critical review of the documents and considering that these criteria are applied to Spanish citizens, the members of theGCMSC establish a priority vaccination list based on ethical principles and adapted to our count

INF2 promotes the formation of detyrosinated microtubules necessary for centrosome reorientation in T cells

T cell antigen receptor-proximal signaling components, Rho-family GTPases, and formin proteins DIA1 and FMNL1 have been implicated in centrosome reorientation to the immunological synapse of T lymphocytes. However, the role of these molecules in the reorientation process is not yet defined. Here we find that a subset of microtubules became rapidly stabilized and that their α-tubulin subunit posttranslationally detyrosinated after engagement of the T cell receptor. Formation of stabilized, detyrosinated microtubules required the formin INF2, which was also found to be essential for centrosome reorientation, but it occurred independently of T cell receptor-induced massive tyrosine phosphorylation. The FH2 domain, which was mapped as the INF2 region involved in centrosome repositioning, was able to mediate the formation of stable, detyrosinated microtubules and to restore centrosome translocation in DIA1-, FMNL1-, Rac1-, and Cdc42-deficient cells. Further experiments indicated that microtubule stabilization was required for centrosome polarization. Our work identifies INF2 and stable, detyrosinated microtubules as central players in centrosome reorientation in T cellsThis work was supported by grants BFU2009-07886 and CONSOLIDER COAT CSD2009-00016 to M.A. Alonso, and BFU2011-22859 to I. Correas (all of them from the Ministerio de Economía y Competitividad, Spain), and grant S2010/BMD-2305 from the Comunidad de Madrid to I. Correa

European Registry on Helicobacter pylori Management: Effectiveness of First and Second-Line Treatment in Spain

The management of Helicobacter pylori infection has to rely on previous local effectiveness due to the geographical variability of antibiotic resistance. The aim of this study was to evaluate the effectiveness of first and second-line H. pylori treatment in Spain, where the empirical prescription is recommended. A multicentre prospective non-interventional registry of the clinical practice of European gastroenterologists concerning H. pylori infection (Hp-EuReg) was developed, including patients from 2013 until June 2019. Effectiveness was evaluated descriptively and through a multivariate analysis concerning age, gender, presence of ulcer, proton-pump inhibitor (PPI) dose, therapy duration and compliance. Overall, 53 Spanish hospitals were included, and 10,267 patients received a first-line therapy. The best results were obtained with the 10-day bismuth single-capsule therapy (95% cure rate by intention-to-treat) and with both the 14-day bismuth-clarithromycin quadruple (PPI-bismuth-clarithromycin-amoxicillin, 91%) and the 14-day non-bismuth quadruple concomitant (PPI-clarithromycin-amoxicillin-metronidazole, 92%) therapies. Second-line therapies were prescribed to 2448 patients, with most-effective therapies being the triple quinolone (PPI-amoxicillin-levofloxacin/moxifloxacin) and the bismuth-levofloxacin quadruple schemes (PPI-bismuth-levofloxacin-amoxicillin) prescribed for 14 days (92%, 89% and 90% effectiveness, respectively), and the bismuth single-capsule (10 days, 88.5%). Compliance, longer duration and higher acid inhibition were associated with higher effectiveness. "Optimized" H. pylori therapies achieve over 90% success in Spain

Native diversity buffers against severity of non-native tree invasions

Determining the drivers of non-native plant invasions is critical for managing native ecosystems and limiting the spread of invasive species$^{1,2}$. Tree invasions in particular have been relatively overlooked, even though they have the potential to transform ecosystems and economies$^{3,4}$. Here, leveraging global tree databases$^{5,6,7}$, we explore how the phylogenetic and functional diversity of native tree communities, human pressure and the environment influence the establishment of non-native tree species and the subsequent invasion severity. We find that anthropogenic factors are key to predicting whether a location is invaded, but that invasion severity is underpinned by native diversity, with higher diversity predicting lower invasion severity. Temperature and precipitation emerge as strong predictors of invasion strategy, with non-native species invading successfully when they are similar to the native community in cold or dry extremes. Yet, despite the influence of these ecological forces in determining invasion strategy, we find evidence that these patterns can be obscured by human activity, with lower ecological signal in areas with higher proximity to shipping ports. Our global perspective of non-native tree invasion highlights that human drivers influence non-native tree presence, and that native phylogenetic and functional diversity have a critical role in the establishment and spread of subsequent invasions

Native diversity buffers against severity of non-native tree invasions.

Determining the drivers of non-native plant invasions is critical for managing native ecosystems and limiting the spread of invasive species1,2. Tree invasions in particular have been relatively overlooked, even though they have the potential to transform ecosystems and economies3,4. Here, leveraging global tree databases5-7, we explore how the phylogenetic and functional diversity of native tree communities, human pressure and the environment influence the establishment of non-native tree species and the subsequent invasion severity. We find that anthropogenic factors are key to predicting whether a location is invaded, but that invasion severity is underpinned by native diversity, with higher diversity predicting lower invasion severity. Temperature and precipitation emerge as strong predictors of invasion strategy, with non-native species invading successfully when they are similar to the native community in cold or dry extremes. Yet, despite the influence of these ecological forces in determining invasion strategy, we find evidence that these patterns can be obscured by human activity, with lower ecological signal in areas with higher proximity to shipping ports. Our global perspective of non-native tree invasion highlights that human drivers influence non-native tree presence, and that native phylogenetic and functional diversity have a critical role in the establishment and spread of subsequent invasions

Native diversity buffers against severity of non-native tree invasions

Determining the drivers of non-native plant invasions is critical for managing native ecosystems and limiting the spread of invasive species1,2. Tree invasions in particular have been relatively overlooked, even though they have the potential to transform ecosystems and economies3,4. Here, leveraging global tree databases5-7, we explore how the phylogenetic and functional diversity of native tree communities, human pressure and the environment influence the establishment of non-native tree species and the subsequent invasion severity. We find that anthropogenic factors are key to predicting whether a location is invaded, but that invasion severity is underpinned by native diversity, with higher diversity predicting lower invasion severity. Temperature and precipitation emerge as strong predictors of invasion strategy, with non-native species invading successfully when they are similar to the native community in cold or dry extremes. Yet, despite the influence of these ecological forces in determining invasion strategy, we find evidence that these patterns can be obscured by human activity, with lower ecological signal in areas with higher proximity to shipping ports. Our global perspective of non-native tree invasion highlights that human drivers influence non-native tree presence, and that native phylogenetic and functional diversity have a critical role in the establishment and spread of subsequent invasions