Tubulin and Actin Interplay at the T Cell and Antigen-Presenting Cell Interface

T cells reorganize their actin and tubulin-based cytoskeletons to provide a physical basis to the immune synapse. However, growing evidence shows that their roles on T cell activation are more dynamic than merely serving as tracks or scaffold for different molecules. The crosstalk between both skeletons may be important for the formation and movement of the lamella at the immunological synapse by increasing the adhesion of the T cell to the antigen-presenting cells (APC), thus favoring the transport of components toward the plasma membrane and in turn regulating the T-APC intercellular communication. Microtubules and F-actin appear to be essential for the transport of the different signaling microclusters along the membrane, therefore facilitating the propagation of the signal. Finally, they can also be important for regulating the endocytosis, recycling, and degradation of the T cell receptor signaling machinery, thus helping both to sustain the activated state and to switch it off

Desafios do Ensino Superior em Moçambique

INTRODUÇÃO Qualquer leitura sobre o ensino superior em África deve ter sempre como pano de fundo a relação intrínseca e incontornável entre ciência e desenvolvimento. Partilhando uma história semelhante profundamente marcada pela dominação colonial, as nações africanas acabaram por perseguir, depois das independências políticas, uma trajectória própria, segundo os casos, de forma mais ou menos bem conseguida. Trajectória que significasse, por um lado, superar as assimetrias históricas produzi..

HUMANITIES: BETWEEN CONTINUITY AND FINITUDE OR BETWEEN UNREST AND CHALLENGES

“O QUE SIGNIFICA SER HUMANO NUM TEMPO EM QUE O MENOS IMPORTANTE PARECE SER O PRÓPRIO HOMEM?”. PARTINDO DESTE QUESTIONAMENTO, O TEXTO PERCORE OS CAMINHOS QUE CONDUZEM À CRISE DE PRESTÍGIO QUE PERCORE AS CIÊNCIAS HUMANAS NO MUNDO CONTEMPORÂNEO. COMO LUGAR DE COEXISTÊNCIA DO MUNDO E DO POSÍVEL, A LITERATURA ABRE HOJE, COMO NO PASSADO, OS ESPAÇOS DE LIBERDADE E CRIATIVIDADE, NOS QUAIS A HUMANIDADE SE PODE RENCONTRAR E QUE URGE SEREM CULTIVADOS.“WHAT IS THE MEANING OF BEING HUMAN IN AN ERA WHERE THE LES IMPORTANT IS MANKIND”? FROM THIS QUESTION, THE TEXT FLOWS THROUGH THE ARGUMENTS THAT EXPLAIN THE CRISIS OF HUMAN SCIENCES PRESTIGE IN CONTEMPORARY WORLD. LITERATURE, IN WHICH THE REAL WORLD AND THE POSIBLE WORLD COEXIST, OPENS SPACE FOR FREDOM AND CREATIVITY WHERE MANKIND CAN MET WITH ITSELF. IT IS VITAL THAT THESE SPACES ARE PROPERLY CULTIVATED

O sortilégio do conto: entre o fragmento e a totalidade

Texto fragmentário e semanticamente plástico, o conto literário reassume nas literaturas africanas a sua natureza comunitária e totalizadora, em sintonia com uma específica visão do mundo

Ensino superior em Moçambique - Políticas, formação de quadros e construção da cidadania

Reflectir sobre o ensino implica necessariamente rastrear um ideal de cidadania. Este artigo incide sobre o caso concreto de Moçambique, onde o projecto do ensino superior acaba por estar intrinsecamente ligado ao projecto de construção da própria nação, em que as particularidades inerentes a este subsistema educativo acabam por traduzir, de forma sensível, por um lado, a visão que está subjacente ao processo de formação dos quadros que devem fazer a diferença no mercado de trabalho e no desenvolvimento da sociedade moçambicana, em geral. Por outro lado, pela dependência recorrente que todo o sistema de ensino superior apresenta em relação ao apoio externo, à imagem, afinal, do próprio país, é possível perceber as oscilações de percurso e de maior ou menor capacidade de resposta àqueles que são os grandes desafios que se colocam para a construção de uma cidadania activa e consequente, propulsora de um progresso real e auto-sustentado

A LITERATURA MOÇAMBICANA E A REINVENÇÃO DA CONTEMPORANEIDADE

RESUMO: Neste artigo, estabelecemos uma reflexão a respeito da experiênciada contemporaneidade na África, questionando em que medidaas sociedades e a arte africanas, em especial a literatura, participam dacontemporaneidade que tem como fulcro o Ocidente; em que medida osuniversos de recepção, instaurados na e através da literatura que se fazem Moçambique nos permitem viver a contemporaneidade dos outros.Nesse caso, se não funcionará, a escrita literária, como o manto de Penélope,tecido e desconstruído, ato contínuo, tal como a própria ideia decontemporaneidade, ou, então, como reinvenção dessa mesmacontemporaneidade.PALAVRAS-CHAVE: contemporaneidade, literatura, reinvençãoABSTRACT: In this article, we establish a reflection on the contemporaryexperience in Africa, questioning the extent to which African societiesand arts take part in the contemporaneity whose fulcrum is the West. Towhat extent do the universes of reception created through the literaturethat is made in Mozambique allow us to live the others’ contemporaneity?In this case, will the literary writings not act as Penelope’s mantle,constantly weaved and undone, as the very idea of contemporaneity?Or will they function, otherwise, as a reinvention of thatcontemporaneity?KEYWORDS: contemporaneity, literature, reinventio

Adhesive Interactions Delineate the Topography of the Immune Synapse

T cells form adhesive contacts with antigen-presenting cells (APCs) as part of the normal surveillance process that occurs in lymph nodes and other tissues. Most of these adhesive interactions are formed by integrins that interact with ligands expressed on the surface of the APC. The interactive strength of integrins depends on their degree of membrane proximity as well as intracellular signals that dictate the conformation of the integrin. Integrins appear in different conformations that endow them with different affinities for their ligand(s). Integrin conformation and thus adhesive strength between the T cell and the APC is tuned by intracellular signals that are turned on by ligation of the T cell receptor (TCR) and chemokine receptors. During the different stages of the process, integrins, the TCR and chemokine receptors may be interconnected by the actin cytoskeleton underneath the plasma membrane, forming a chemical and physical network that facilitates the spatiotemporal dynamics, positioning, and function of these receptors and supports cell-cell adhesion during T cell activation, allowing it to perform its effector function

The swing of lipids at peroxisomes and endolysosomes in t cell activation

The immune synapse (IS) is a well-known intercellular communication platform, organized at the interphase between the antigen presenting cell (APC) and the T cell. After T cell receptor (TCR) stimulation, signaling from plasma membrane proteins and lipids is amplified by molecules and downstream pathways for full synapse formation and maintenance. This secondary signaling event relies on intracellular reorganization at the IS, involving the cytoskeleton and components of the secretory/recycling machinery, such as the Golgi apparatus and the endolysosomal system (ELS). T cell activation triggers a metabolic reprogramming that involves the synthesis of lipids, which act as signaling mediators, and an increase of mitochondrial activity. Then, this mitochondrial activity results in elevated reactive oxygen species (ROS) production that may lead to cytotoxicity. The regulation of ROS levels requires the concerted action of mitochondria and peroxisomes. In this review, we analyze this reprogramming and the signaling implications of endolysosomal, mitochondrial, peroxisomal, and lipidic systems in T cell activation.This review was funded by grant SAF2017-82886-R from the Spanish Ministry of Economy and Competitiveness (MINECO), grant S2017/BMD-3671-INFLAMUNE-CM from the Comunidad de Madrid, a grant from the Ramón Areces Foundation “Ciencias de la Vida y la Salud” (CIVP19A5941 XIX Concurso-2018) and a grant from Ayudas Fundación BBVA a Equipos de Investigación Científica (BIOMEDICINA-2018), the Fundació Marató TV3 (grant 122/C/2015) and “La Caixa” Banking Foundation (HR17-00016). BIOIMID (PIE13/041) from Instituto de Salud Carlos III, CIBER Cardiovascular (CB16/11/00272, Fondo de Investigación Sanitaria del Instituto de Salud Carlos III and co-funding by Fondo Europeo de Desarrollo Regional FEDER). SGD and ARG are funded by fellowship FPU and FPI programs, from Ministry of Science and Universities, respectively

ReCom: A semi-supervised approach to ultra-tolerant database search for improved identification of modified peptides.

Open-search methods allow unbiased, high-throughput identification of post-translational modifications in proteins at an unprecedented scale. The performance of current open-search algorithms is diminished by experimental errors in the determination of the precursor peptide mass. In this work we propose a semi-supervised open search approach, called ReCom, that minimizes this effect by taking advantage of a priori known information from a reference database, such as Unimod or a database provided by the user. We present a proof-of-concept study using Comet-ReCom, an improved version of Comet-PTM. Comet-ReCom increased identification performance of Comet-PTM by 68%. This increased performance of Comet-ReCom to score the MS/MS spectrum comes in parallel with a significantly better assignation of the monoisotopic peak of the precursor peptide in the MS spectrum, even in cases of peptide coelution. Our data demonstrate that open searches using ultra-tolerant mass windows can benefit from using a semi-supervised approach that takes advantage from previous knowledge on the nature of protein modifications. SIGNIFICANCE: The present study introduces a novel approach to ultra-tolerant database search, which employs prior knowledge of post-translational modifications (PTMs) to improve identification of modified peptides. This method addresses the limitations related to experimental errors and precursor mass assignation of previous open-search methods. Thus, it enables the study of the biological significance of a wider variety of PTMs, including unknown or unexpected modifications that may have gone unnoticed using non-supervised search methods.This study was supported by competitive grants from the Spanish Ministry of Science, Innovation and Universities (PGC2018-097019-B-I00, PID2021-122348NB-I00, PLEC2022-009235 and PLEC2022-009298), the Instituto de Salud Carlos III (Fondo de Investigación Sanitaria grant PRB3 (PT17/0019/0003- ISCIIISGEFI / ERDF, ProteoRed), Comunidad de Madrid (IMMUNO-VAR, P2022/BMD-7333) and “la Caixa” Banking Foundation (project codes HR17-00247 and HR22-00253). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation), and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033).S