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El objetivo de este documento es proponer a las bibliotecas universitarias una estrategia tecnológica para adaptarse a los cambios que se están produciendo en los ámbitos del aprendizaje y la investigación. Los principales cambios a los que nos vamos a referir son: la web es la nueva plataforma para la comunicación de la información, esta web está orientada no sólo a los humanos sino también a las máquinas y está potenciando el trabajo en red y en colaboración. Por otra parte, esta forma de trabajar está generando un nuevo concepto de unidad de información, modelada no sólo por la necesidad de representar nuevas formas de publicación (texto, data, simulaciones…) en las nuevas prácticas científicas, sino también por los cambios en la naturaleza de las herramientas de creación y los entornos en que se usan. Finalmente, cada vez más, los usuarios no sólo consumen información, sino que también quieren participar en su generación (blogs, wikis, youtube, slideshare...). Se describen las implicaciones que esos cambios están teniendo en el entorno de las bibliotecas universitarias: la importancia del e-learning, los CRAI y el nuevo modelo de comunicación y publicación científica y se indican algunas líneas de actuación para orientar la estrategia tecnológica de las bibliotecas a la luz de estas transformaciones: nuevo concepto de unidad de información, interoperabilidad, flexibilidad y arquitecturas abiertas.The aim of this paper is to propose a technological strategy that university libraries can use to adapt to changes in the learning and research fields. The following are the most significant of these changes. The Web is the new platform for communicating information, and is aimed at both humans and machines. It promotes working in networks and in collaboration. This way of working is generating a new concept of the information unit. This concept reflects the need to represent new forms of publication (text, data, simulations, etc.) in new scientific practices, and changes in the nature of the tools for creating information and the environments in which they are used. Finally, users not only consume information, but increasingly want to participate in generating it (in blogs, the Wiki systems, YouTube, SlideShare, etc.). We describe the implications of these changes for university libraries: the importance of electronic learning, Learning and Research Resource Centres (CRAI), and the new models of communication and scientific publication. In addition, we propose some lines of action to guide libraries’ technology strategies, in accordance with these changes: the new concept of the information unit, interoperability, flexibility and open architecture.

L'objectiu d'aquest document és proposar a les biblioteques universitàries una estratègia tecnològica per adaptar-se als canvis que es produeixen en els àmbits de l'aprenentatge i la recerca. Els canvis més importants a què ens referirem són els següents: el web és la nova plataforma per comunicar la informació, i aquesta plataforma està orientada no solament als humans, sinó també a les màquines, i alhora potencia el treball en xarxa i en col·laboració. D'altra banda, aquesta manera de treballar està generant un nou concepte d'unitat d'informació, modelat no només per la necessitat de representar noves maneres de publicació (text, dades, simulacions, etc.) en les pràctiques científiques noves, sinó també pels canvis en la naturalesa de les eines de creació i els entorns en els quals s'usen. Finalment, cada vegada més, els usuaris no solament consumeixen informació, sinó que també volen participar a l'hora de generar-la (els blogs, els sistemes wiki, el YouTube, l'SlideShare, etc.). Es descriuen les implicacions que tenen aquests canvis en l'entorn de les biblioteques universitàries: la importància de l'aprenentatge electrònic, els CRAI i el nou model de comunicació i publicació científica. A més, s'indiquen algunes línies d'actuació per orientar l'estratègia tecnològica de les biblioteques d'acord amb aquestes transformacions: el nou concepte d'unitat d'informació, la interoperabilitat, la flexibilitat i les arquitectures obertes.The aim of this paper is to propose a technological strategy that university libraries can use to adapt to changes in the learning and research fields. The following are the most significant of these changes. The Web is the new platform for communicating information, and is aimed at both humans and machines. It promotes working in networks and in collaboration. This way of working is generating a new concept of the information unit. This concept reflects the need to represent new forms of publication (text, data, simulations, etc.) in new scientific practices, and changes in the nature of the tools for creating information and the environments in which they are used. Finally, users not only consume information, but increasingly want to participate in generating it (in blogs, the Wiki systems, YouTube, SlideShare, etc.). We describe the implications of these changes for university libraries: the importance of electronic learning, Learning and Research Resource Centres (CRAI), and the new models of communication and scientific publication. In addition, we propose some lines of action to guide libraries’ technology strategies, in accordance with these changes: the new concept of the information unit, interoperability, flexibility and open architecture.

Background: We have shown that pre-reperfusion metoprolol reduces infarct size in humans (METOCARD-CNIC trial). Preclinical data suggest that this strategy reduces myocardial neutrophil infiltration. Here we evaluated the potential involvement of circulating cells in the cardioprotection afforded by metoprolol.Methods: WT and b1AR-KO mice were subjected to myocardial IRI (45min/24h Ischemia/Reperfusion). Ten minutes before reperfusion, animals were randomized to receive either i.v. metoprolol or vehicle through the femoral vein. In a different experiment, b1AR-KO mice were subjected to lethal irradiation and bone marrow transplant from WT donors. Once fully recovered, animals with more than an 80% engraftment were subjected to IRI and randomized to i.v.metoprolol or vehicle. At the end of the procedure, infarct size was evaluated by TTC/Evans blue staining. Additionally, intravital microscopy was performed in the cremaster muscle of WT and b1AR-KO mice after neutrophil and platelet labeling.Results: Infarct size was 30% smaller in WT animals receiving i.v. metoprolol compared to vehicle. Conversely, metoprolol had no effect on b1KO mice. In b1KO mice transplanted with WT bone marrow, the cardioprotective phenotype of metoprolol was rescued. Metoprolol massively inhibited neutrophil-platelet interactions after TNFa challenging and this effect was absent in b1KO mice.Conclusion: Circulating cells mediates the cardioprotection afforded by i.v. metoprolol. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) play a crucial role in orchestrating immune responses, particularly in promoting IFNγ-producing-CD8 cytotoxic T lymphocytes (CTLs) and IFNγ-producing-CD4 T helper 1 (Th1) cells, which are essential for defending against viral infections. Additionally, the nuclear envelope protein lamin A/C has been implicated in T cell immunity. Nevertheless, the intricate interplay between innate and adaptive immunity in response to viral infections, particularly the role of lamin A/C in DC functions within this context, remains poorly understood. In this study, we demonstrate that mice lacking lamin A/C in myeloid LysM promoter-expressing cells exhibit a reduced capacity to induce Th1 and CD8 CTL responses, leading to impaired clearance of acute primary Vaccinia virus (VACV) infection. Remarkably, in vitro-generated granulocyte macrophage colony-stimulating factor bone marrow-derived DCs (GM-CSF BMDCs) show high levels of lamin A/C. Lamin A/C absence on GM-CSF BMDCs does not affect the expression of costimulatory molecules on the cell membrane but it reduces the cellular ability to form immunological synapses with naïve CD4 T cells. Lamin A/C deletion induces alterations in NFκB nuclear localization, thereby influencing NF-κB-dependent transcription. Furthermore, lamin A/C ablation modifies the gene accessibility of BMDCs, predisposing these cells to mount a less effective antiviral response upon TLR stimulation. This study highlights the critical role of DCs in interacting with CD4 T cells during antiviral responses and proposes some mechanisms through which lamin A/C may modulate DC function via gene accessibility and transcriptional regulation., (© 2024. The Author(s).)

Background and Aims: Somatic mutations in the TET2 gene that lead to clonal haematopoiesis (CH) are associated with accelerated atherosclerosis development in mice and a higher risk of atherosclerotic disease in humans. Mechanistically, these observations have been linked to exacerbated vascular inflammation. This study aimed to evaluate whether colchicine, a widely available and inexpensive anti-inflammatory drug, prevents the accelerated atherosclerosis associated with TET2-mutant CH., Methods: In mice, TET2-mutant CH was modelled using bone marrow transplantations in atherosclerosis-prone Ldlr-/- mice. Haematopoietic chimeras carrying initially 10% Tet2-/- haematopoietic cells were fed a high-cholesterol diet and treated with colchicine or placebo. In humans, whole-exome sequencing data and clinical data from 37 181 participants in the Mass General Brigham Biobank and 437 236 participants in the UK Biobank were analysed to examine the potential modifying effect of colchicine prescription on the relationship between CH and myocardial infarction., Results: Colchicine prevented accelerated atherosclerosis development in the mouse model of TET2-mutant CH, in parallel with suppression of interleukin-1β overproduction in conditions of TET2 loss of function. In humans, patients who were prescribed colchicine had attenuated associations between TET2 mutations and myocardial infarction. This interaction was not observed for other mutated genes., Conclusions: These results highlight the potential value of colchicine to mitigate the higher cardiovascular risk of carriers of somatic TET2 mutations in blood cells. These observations set the basis for the development of clinical trials that evaluate the efficacy of precision medicine approaches tailored to the effects of specific mutations linked to CH., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Group 3 innate lymphoid cells (ILC3s) are vital for defending tissue barriers from invading pathogens. Hypoxia influences the production of intestinal ILC3-derived cytokines by activating HIF. Yet, the mechanisms governing HIF-1α in ILC3s and other innate RORγt + cells during in vivo infections are poorly understood. In our study, transgenic mice with specific Hif-1a gene inactivation in innate RORγt + cells (RAG1KO HIF-1α ▵Rorc ) exhibit more severe colitis following Citrobacter rodentium infection, primarily due to the inability to upregulate IL-22. We find that HIF-1α ▵Rorc mice have impaired IL-22 production in ILC3s, while non-ILC3 innate RORγt + cells, also capable of producing IL-22, remain unaffected. Furthermore, we show that IL-18, induced by Toll-like receptor 2, selectively triggers IL-22 in ILC3s by transcriptionally upregulating HIF-1α, revealing an oxygen-independent regulatory pathway. Our results highlight that, during late-stage C. rodentium infection, IL-18 induction in the colon promotes IL-22 through HIF-1α in ILC3s, which is crucial for protection against this pathogen., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Somatic mutations in blood indicative of clonal hematopoiesis of indeterminate potential (CHIP) are associated with an increased risk of hematologic malignancy, coronary artery disease, and all-cause mortality. Here we analyze the relation between CHIP status and incident peripheral artery disease (PAD) and atherosclerosis, using whole-exome sequencing and clinical data from the UK Biobank and Mass General Brigham Biobank. CHIP associated with incident PAD and atherosclerotic disease across multiple beds, with increased risk among individuals with CHIP driven by mutation in DNA Damage Repair (DDR) genes such as TP53 and PPM1D . To model the effects of DDR-induced CHIP on atherosclerosis, we used a competitive bone marrow transplantation strategy, and generated atherosclerosis-prone Ldlr -/- chimeric mice carrying 20% p53-deficient hematopoietic cells. The chimeric mice were analyzed 13-weeks post-grafting and showed increased aortic plaque size and accumulation of macrophages within the plaque, driven by increased proliferation of p53-deficient plaque macrophages. In summary, our findings highlight the role of CHIP as a broad driver of atherosclerosis across the entire arterial system beyond the coronary arteries, and provide genetic and experimental support for a direct causal contribution of TP53-mutant CHIP to atherosclerosis.

Human aging is frequently accompanied by the acquisition of somatic mutations in the hematopoietic system that induce clonal hematopoiesis, leading to the development of a mutant clone of hematopoietic progenitors and leukocytes. This somatic-mutation-driven clonal hematopoiesis has been associated with an increased incidence of cardiovascular disease and type 2 diabetes, but whether this epidemiological association reflects a direct, causal contribution of mutant hematopoietic and immune cells to age-related metabolic abnormalities remains unexplored. Here, we show that inactivating mutations in the epigenetic regulator TET2, which lead to clonal hematopoiesis, aggravate age- and obesity-related insulin resistance in mice. This metabolic dysfunction is paralleled by increased expression of the pro-inflammatory cytokine IL-1β in white adipose tissue, and it is suppressed by pharmacological inhibition of NLRP3 inflammasome-mediated IL-1β production. These findings support a causal contribution of somatic TET2 mutations to insulin resistance and type 2 diabetes., Competing Interests: Declaration of Interests K.W. and J.J.F. are co-inventors on a patent related to the treatment of cardiometabolic diseases associated with somatic TET2 mutations. M.A.C. is co-founder and chief executive officer of Inflazome, a company developing drugs that target inflammasomes. These authors have no additional conflicts of interest. Other authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The mechanisms by which lamin A/C in CD4 + T-cells control intestinal homeostasis and can cause inflammatory bowel disease (IBD) are unknown. Here, we explore lamin A/C in a mouse model of IBD. Adoptive transfer to Rag1 -/- mice of Lmna -/- CD4 + T-cells, which have enhanced regulatory T-cells (Treg) differentiation and function, induced less severe IBD than wild-type T-cells. Lamin A/C deficiency in CD4 + T-cells enhanced transcription of the Treg master regulator FOXP3, thus promoting Treg differentiation, and reduced Th1 polarization, due to epigenetic changes in the Th1 master regulator T-bet. In mesenteric lymph nodes, retinoic acid (RA) released by CD103 + dendritic cells downregulated lamin A/C in CD4 + T-cells, enhancing Treg differentiation. However, non-RA-producing CD103 - dendritic cells predominated in peripheral lymph nodes, facilitating lamin A/C expression in CD4 + T-cells and therefore Th1 differentiation. Our findings establish lamin A/C as a key regulator of Th differentiation in physiological conditions and show it as a potential immune-regulatory target in IBD. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (© 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Quantification of naïve CD4 T cell activation, proliferation, and differentiation to T helper 1 (Th1) cells is a useful way to assess the role played by T cells in an immune response. This protocol describes the in vitro differentiation of bone marrow (BM) progenitors to obtain granulocyte macrophage colony-stimulating factor (GM-CSF) derived-dendritic cells (DCs). The protocol also describes the adoptive transfer of ovalbumin peptide (OVAp)-loaded GM-CSF-derived DCs and naïve CD4 T cells from OTII transgenic mice in order to analyze the in vivo activation, proliferation, and Th1 differentiation of the transferred CD4 T cells. This protocol circumvents the limitation of purely in vivo methods imposed by the inability to specifically manipulate or select the studied cell population. Moreover, this protocol allows studies in an in vivo environment, thus avoiding alterations to functional factors that may occur in vitro and including the influence of cell types and other factors only found in intact organs. The protocol is a useful tool for generating changes in DCs and T cells that modify adaptive immune responses, potentially providing important results to understand the origin or development of numerous immune associated diseases.

The original version of this Article contained an error in the spelling of the author José María González-Granado, which was incorrectly given as José María Gozález-Granado. This has now been corrected in both the PDF and HTML versions of the Article.

Differentiation of naive CD4 + T-cells into functionally distinct T helper (Th) subsets is critical to immunity against pathogen infection. Little is known about the role of signals emanating from the nuclear envelope for T-cell differentiation. The nuclear envelope protein lamin A/C is induced in naive CD4 + T-cells upon antigen recognition and acts as a link between the nucleus and the plasma membrane during T-cell activation. Here we demonstrate that the absence of lamin A/C in naive T-cell reduces Th1 differentiation without affecting Th2 differentiation in vitro and in vivo. Moreover, Rag1 -/- mice reconstituted with Lmna -/- CD4 + CD25 - T-cells and infected with vaccinia virus show weaker Th1 responses and viral removal than mice reconstituted with wild-type T-cells. Th1 responses and pathogen clearance upon Leishmania major infection were similarly diminished in mice lacking lamin A/C in the complete immune system or selectively in T-cells. Lamin A/C mediates Th1 polarization by a mechanism involving T-bet and IFNγ production. Our results reveal a novel role for lamin A/C as key regulator of Th1 differentiation in response to viral and intracellular parasite infections.

Bacterial phagocytosis and antigen cross-presentation to activate CD8 + T cells are principal functions of professional antigen presenting cells. However, conventional CD4 + T cells also capture and kill bacteria from infected dendritic cells in a process termed transphagocytosis (also known as transinfection). Here, we show that transphagocytic T cells present bacterial antigens to naive CD8 + T cells, which proliferate and become cytotoxic in response. CD4 + T-cell-mediated antigen presentation also occurs in vivo in the course of infection, and induces the generation of central memory CD8 + T cells with low PD-1 expression. Moreover, transphagocytic CD4 + T cells induce protective anti-tumour immune responses by priming CD8 + T cells, highlighting the potential of CD4 + T cells as a tool for cancer immunotherapy.

Antigen presentation by dendritic cells (DCs) stimulates naive CD4 + T cells, triggering T cell activation and the adaptive arm of the immune response. Newly synthesized major histocompatibility complex class II (MHC-II) molecules accumulate at MHC-II-enriched endosomal compartments and are transported to the plasma membrane of DCs after binding to antigenic peptides to enable antigen presentation. In DCs, MHC-II molecules are included in tetraspanin-enriched microdomains (TEMs). However, the role of tetraspanin CD9 in these processes remains largely undefined. Here, we show that CD9 regulates the T cell-stimulatory capacity of granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent bone marrow-derived DCs (BMDCs), without affecting antigen presentation by fms-like tyrosine kinase 3 ligand (Flt3L)-dependent BMDCs. CD9 knockout (KO) GM-CSF-dependent BMDCs, which resemble monocyte-derived DCs (MoDCs), induce lower levels of T cell activation than wild-type DCs, and this effect is related to a reduction in MHC-II surface expression in CD9-deficient MoDCs. Importantly, MHC-II targeting to the plasma membrane is largely impaired in immature CD9 KO MoDCs, in which MHC-II remains arrested in acidic intracellular compartments enriched in LAMP-1 (lysosome-associated membrane protein 1), and MHC-II internalization is also blocked. Moreover, CD9 participates in MHC-II trafficking in mature MoDCs, regulating its endocytosis and recycling. Our results demonstrate that the tetraspanin CD9 specifically regulates antigenic presentation in MoDCs through the regulation of MHC-II intracellular trafficking., (Copyright © 2017 American Society for Microbiology.)

We report the proteomic analysis of the Atlantic bushmaster, Lachesis muta rhombeata, from Brazil. Along with previous characterization of the venom proteomes of L. stenophrys (Costa Rica), L. melanocephala (Costa Rica), L. acrochorda (Colombia), and L. muta muta (Bolivia), the present study provides the first overview of the composition and distribution of venom proteins across this wide-ranging genus, and highlights the remarkable similar compositional and pharmacological profiles across Lachesis venoms. The paraspecificity of two antivenoms, produced at Instituto Vital Brazil (Brazil) and Instituto Clodomiro Picado (Costa Rica) using different conspecific taxa in the immunization mixtures, was assessed using genus-wide comparative antivenomics. This study confirms that the proteomic similarity among Lachesis sp. venoms is mirrored in their high immunological conservation across the genus. The clinical and therapeutic consequences of genus-wide venomics and antivenomics investigations of Lachesis venoms are discussed., Biological Significance: The proteomics characterization of L. m. rhombeata venom completes the overview of Lachesis venom proteomes and confirms the remarkable toxin profile conservation across the five clades of this wide-ranging genus. Genus-wide antivenomics showed that two antivenoms, produced against L. stenophrys or L. m. rhombeata, exhibit paraspecificity towards all other congeneric venoms. Our venomics study shows that, despite the broad geographic distribution of the genus, monospecific antivenoms may achieve clinical coverage for any Lachesis sp. envenoming., (Copyright © 2013 Elsevier B.V. All rights reserved.)