T-cell trans-synaptic vesicles are distinct and carry greater effector content than constitutive extracellular vesicles

The immunological synapse is a molecular hub that facilitates the delivery of three activation signals, namely antigen, costimulation/corepression and cytokines, from antigen-presenting cells (APC) to T cells. T cells release a fourth class of signaling entities, trans-synaptic vesicles (tSV), to mediate bidirectional communication. Here we present bead-supported lipid bilayers (BSLB) as versatile synthetic APCs to capture, characterize and advance the understanding of tSV biogenesis. Specifically, the integration of juxtacrine signals, such as CD40 and antigen, results in the adaptive tailoring and release of tSV, which differ in size, yields and immune receptor cargo compared with steadily released extracellular vesicles (EVs). Focusing on CD40L+ tSV as model effectors, we show that PD-L1 trans-presentation together with TSG101, ADAM10 and CD81 are key in determining CD40L vesicular release. Lastly, we find greater RNA-binding protein and microRNA content in tSV compared with EVs, supporting the specialized role of tSV as intercellular messenger

Clathrin mediates both internalization and vesicular release of triggered T cell receptor at the immunological synapse

Ligation of T cell receptor (TCR) to peptide-MHC (pMHC) complexes initiates signaling leading to T cell activation and TCR ubiquitination. Ubiquitinated TCR is then either internalized by the T cell or released toward the antigen-presenting cell (APC) in extracellular vesicles. How these distinct fates are orchestrated is unknown. Here, we show that clathrin is first recruited to TCR microclusters by HRS and STAM2 to initiate release of TCR in extracellular vesicles through clathrin- and ESCRT-mediated ectocytosis directly from the plasma membrane. Subsequently, EPN1 recruits clathrin to remaining TCR microclusters to enable trans-endocytosis of pMHC-TCR conjugates from the APC. With these results, we demonstrate how clathrin governs bidirectional membrane exchange at the immunological synapse through two topologically opposite processes coordinated by the sequential recruitment of ecto- and endocytic adaptors. This provides a scaffold for direct two-way communication between T cells and APCs

Modulation of Tumor Immunity by Soluble and Membrane-Bound Molecules at the Immunological Synapse

To circumvent pathology caused by infectious microbes and tumor growth, the host immune system must constantly clear harmful microorganisms and potentially malignant transformed cells. This task is accomplished in part by T-cells, which can directly kill infected or tumorigenic cells. A crucial event determining the recognition and elimination of detrimental cells is antigen recognition by the T cell receptor (TCR) expressed on the surface of T cells. Upon binding of the TCR to cognate peptide-MHC complexes presented on the surface of antigen presenting cells (APCs), a specialized supramolecular structure known as the immunological synapse (IS) assembles at the T cell-APC interface. Such a structure involves massive redistribution of membrane proteins, including TCR/pMHC complexes, modulatory receptor pairs, and adhesion molecules. Furthermore, assembly of the immunological synapse leads to intracellular events that modulate and define the magnitude and characteristics of the T cell response. Here, we discuss recent literature on the regulation and assembly of IS and the mechanisms evolved by tumors to modulate its function to escape T cell cytotoxicity, as well as novel strategies targeting the IS for therapy

Interfaces no convencionales aplicadas a la captura de datos en procesos productivos industriales aplicados a las PyMEs

El proyecto que se lleva a cabo en la Universidad Nacional de Luján, se propone estudiar y desarrollar interfaces de usuario no convencionales aplicables en la captura de datos en procesos productivos industriales en PyMES, con el objetivo de contribuir al mejoramiento de la calidad y eficiencia del sector.Eje: Innovación en sistemas de software.Red de Universidades con Carreras en Informátic

Recombinant BCG Vaccines Reduce Pneumovirus-Caused Airway Pathology by Inducing Protective Humoral Immunity

The Human Respiratory Syncytial Virus (hRSV) and the Human Metapneumovirus (hMPV) are two pneumoviruses that are leading agents causing acute lower respiratory tract infections (ALRTIs) affecting young infants, the elderly, and immunocompromised patients worldwide. Since these pathogens were first discovered, many approaches for the licensing of safe and effective vaccines have been explored being unsuccessful to date. We have previously described that immunization with recombinant strains of Mycobacterium bovis Bacillus Calmette-Guérin (rBCG) expressing the hRSV nucleoprotein (rBCG-N) or the hMPV phosphoprotein (rBCG-P) induced immune protection against each respective virus. These vaccines efficiently promoted viral clearance without significant lung damage, mainly through the induction of a T helper 1 cellular immunity. Here we show that upon viral challenge, rBCG-immunized mice developed a protective humoral immunity, characterized by production of antibodies specific for most hRSV and hMPV proteins. Further, isotype switching from IgG1 to IgG2a was observed in mice immunized with rBCG vaccines and correlated with an increased viral clearance, as compared to unimmunized animals. Finally, sera obtained from animals immunized with rBCG vaccines and infected with their respective viruses exhibited virus neutralizing capacity and protected naïve mice from viral replication and pulmonary disease. These results support the notion that the use of rBCG strains could be considered as an effective vaccination approach against other respiratory viruses with similar biology as hRSV and hMPV

Dung removal increases under higher dung beetle functional diversity regardless of grazing intensification

Dung removal by macrofauna such as dung beetles is an important process for nutrient cycling in pasturelands. Intensification of farming practices generally reduces species and functional diversity of terrestrial invertebrates, which may negatively affect ecosystem services. Here, we investigate the effects of cattle-grazing intensification on dung removal by dung beetles in field experiments replicated in 38 pastures around the world. Within each study site, we measured dung removal in pastures managed with low- and high-intensity regimes to assess between-regime differences in dung beetle diversity and dung removal, whilst also considering climate and regional variations. The impacts of intensification were heterogeneous, either diminishing or increasing dung beetle species richness, functional diversity, and dung removal rates. The effects of beetle diversity on dung removal were more variable across sites than within sites. Dung removal increased with species richness across sites, while functional diversity consistently enhanced dung removal within sites, independently of cattle grazing intensity or climate. Our findings indicate that, despite intensified cattle stocking rates, ecosystem services related to decomposition and nutrient cycling can be maintained when a functionally diverse dung beetle community inhabits the human-modified landscape

Supporting information: The EICAT+ framework enables classification of positive impacts of alien taxa on native biodiversity [dataset]

Supporting information A in S1 File. Glossary of additional key terms. Supporting information B in S1 File. Table reporting contrasting arguments and approaches used to define how alien taxa are considered and should be managed in accordance with different conservation values/motivations. As multiple values/motivations exist and determine which entities we are interested in (see also Supporting information A), distinct conservation targets can be identified. Note that here, we only consider conservation values/motivations that are expressed regardless of any nature’s instrumental (utilitarian) value, i.e., regardless of nature’s contributions to human well-being (see “nature for itself” framing [9]). Also, note that such contrasting arguments and approaches are not necessarily mutually exclusive and have been occasionally combined to find a middle ground to achieve broader conservation goals [10–13]. Supporting information C in S1 File. Circumstances under which the prevention/mitigation of a decreasing change is considered as a positive change under EICAT+. In EICAT+, we also consider as positive impacts (i.e., increasing changes) cases in which an alien species prevents/mitigates decreasing changes, e.g., when the performance of a native individual, the size of a native population, or the occupancy of a native species would have decreased, or decreased to a greater extent, if the alien species had not been introduced. Although some of these positive impacts can be inferred, the prevention of a decreasing change should be assessed under EICAT+ only when there is convincing evidence that a certain biodiversity attribute (e.g., population size) would have decreased, or decreased to a greater extent, in the absence of the alien species. In the case of extinction prevention, for instance, it must be clear that (i) the population was locally heading toward extinction before the introduction of the alien; and (ii) the alien taxon prevented, through a specific impact mechanism, an extinction that would have occurred in its absence [41,42] (Fig 2b). Other cases where an alien species may prevent or mitigate decreasing changes are, for instance, those in which the abundance (i.e., a proxy for population size) of a native species declined in the uninvaded (i.e., control) plots but not, or to a lesser extent, in the plots invaded by the alien. Note that positive impacts associated with the prevention/mitigation of a decreasing change will generally be more difficult to study and identify than those associated with actual increasing changes, as the former require extensive data regarding the temporal trend of individual performance, population size, or area of occupancy. Supporting information D in S1 File. EICAT+ mechanisms and submechanisms by which an alien taxon can cause positive impacts on native biodiversity attributes and examples of positive impacts sourced from the literature and assessed under EICAT+ (ML+ = Minimal positive impact, MN+ = Minor positive impact, MO+ = Moderate positive impact, MR+ = Major positive impact, MV+ = Massive positive impact). Rationales behind the formulation of the mechanisms and submechanisms can be found in the main text and in Supporting information G, H, and J. Supporting information E in S1 File. Table reporting examples sourced from the literature and classified as information that cannot be classified under EICAT+, but that contain information about mechanisms and might set the stage for future studies. Although these studies described the existence of mechanisms by which alien taxa may cause positive impacts on native taxa, such literature is considered as nonrelevant, as it did not measure, or provide information on, biodiversity attributes used in EICAT+ (e.g., performance of individuals or population size). Rationales behind the formulation of the mechanisms and submechanisms can be found in the main text and in Supporting information G, H, and J. Supporting information F in S1 File. How to attribute a confidence score in EICAT+. Supporting information G in S1 File. Additional information around the rationale behind the formulation of the EICAT+ mechanisms and submechanisms. Supporting information H in S1 File. Additional information about how alien species can cause positive impacts on native biodiversity through overcompensation. Supporting information J in S1 File. Additional information about how alien species can cause positive impacts on native biodiversity through hybridization. Supporting information K in S1 File. References used in the Supporting information.Peer reviewe

Anales del III Congreso Internacional de Vivienda y Ciudad "Debate en torno a la nueva agenda urbana"

Acta de congresoEl III Congreso Internacional de Vivienda y Ciudad “Debates en torno a la NUEVa Agenda Urbana”, ha sido una apuesta de alto compromiso por acercar los debates centrales y urgentes que tensionan el pleno ejercicio del derecho a la ciudad. Para ello las instituciones organizadoras (INVIHAB –Instituto de Investigación de Vivienda y Hábitat y MGyDH-Maestría en Gestión y Desarrollo Habitacional-1), hemos convidado un espacio que se concretó con potencia en un debate transdisciplinario. Convocó a intelectuales de prestigio internacional, investigadores, académicos y gestores estatales, y en una metodología de innovación articuló las voces académicas con las de las organizaciones sociales y/o barriales en el Foro de las Organizaciones Sociales que tuvo su espacio propio para dar voz a quienes están trabajando en los desafíos para garantizar los derechos a la vivienda y los bienes urbanos en nuestras ciudades del Siglo XXI

Cation-chloride cotransporters and GABA-ergic innervation in the human epileptic hippocampus

Intracellular chloride concentration, [Cl-]i, determines the polarity of GABAA-induced neuronal Cl- currents. In neurons, [Cl-]i is set by the activity of Na+, K+, 2Cl- cotransporters (NKCC) such as NKCC1, which physiologically accumulate Cl- in the cell, and Cl - extruding K+, Cl- cotransporters like KCC2. Alterations in the balance of NKCC1 and KCC2 activity may determine the switch from hyperpolarizing to depolarizing effects of GABA, reported in the subiculum of epileptic patients with hippocampal sclerosis. We studied the expression of NKCC (putative NKCC1) and KCC2 in human normal temporal neocortex by Western blot analysis and in normal and epileptic regions of the subiculum and the hippocampus proper using immunocytochemistry. Western blot analysis revealed NKCC and KCC2 proteins in adult human neocortical membranes similar to those in rat neocortex. NKCC and KCC2 immunolabeling of pyramidal and nonpyramidal cells was found in normal and epileptic hippocampal formation. In the transition between the subiculum with sclerotic regions of CA1, known to exhibit epileptogenic activity, double immunolabeling of NKCC and KCC2 revealed that approximately 20% of the NKCC-immunoreactive neurons do not express KCC2. In these same areas some neurons were distinctly hyperinnervated by parvalbumin (PV) positive hypertrophic basket formations that innervated mostly neurons expressing NKCC (74%) and to a lesser extent NKCC-immunonegative neurons (26%). Hypertrophic basket formations also innervated KCC2-positive (76%) and -negative (24%) neurons. The data suggest that changes in the relative expression of NKCC1 and KCC2 in neurons having aberrant GABA-ergic hyperinnervation may contribute to epileptiform activity in the subicular regions adjacent to sclerotic areas of the hippocampus. © 2007 International League Against Epilepsy.Peer Reviewe