1,721,021 research outputs found
El mundo de custodio II: Basado en hechos surrealistas
No full textThis is the second book of the El Mundo de Custodio's collection, with the surreal adventures of Custodio - a character who reminds us of the famous Don Quixote - someone who does not live in his time but in an ideal reality away from the modern life that started to change his world at the time of La Transición in Spain
Custodio Garcia, para salvarles
No full textthis is the third book of the collection "El mundo de Custodio" which tell the story of a big family in Spain in post Franco times
MicroRNAs and respiratory diseases
No full textMicroRNAs (miRNA) are a family of endogenous, small, noncoding RNA molecules that modulate physiological and pathological processes by post-transcriptional inhibition of gene expression. They were first recognised as regulators of development in worms and fruitflies. In recent years extensive research has explored their pivotal role in the pathogenesis of human diseases. Over 1000 human miRNAs have been discovered to date, however the biological function and protein targets for the majority remain to be uncovered. Within the respiratory system, miRNAs are important in normal pulmonary development and maintaining lung homeostasis. Recent studies have also begun to reveal that altered miRNA expression profiles may be associated with pathological processes within the lung and lead to the development of various pulmonary diseases ranging from inflammatory diseases to lung cancers. Advancing our understanding of the role of miRNAs in the respiratory system will help provide new perspectives on disease mechanisms and reveal intriguing therapeutic targets and diagnostics for respiratory disorders
El papel higiénico y otros asuntos de suma importancia. El Mundo de Custodio, libro I
No full textThis is a novel based in the Spain, in the period of the transition to democracy (seventies), thorough the original life of Custodio and his big family. Custodio, reminds us to Don Quijote, from the 17th century novel by Miguel de Cervantes. Custodio will follow Don Quijote’s dream of saving the world, in a surrealistic battle against the advances of the modern world. He will devote his life in saving money and avoiding unnecessary spending of his seven children (since he has to provide for a big family) and saving people from all possible sickness (preparing original and incredible cures for them
Single-cell RNA sequencing datasets from human foetal cardiac fibroblasts
No full textPre-filtered, tagged, h5ad files derived from single-cell RNA sequencing data from foetal cardiac fibroblasts used in Chapters 3 and 6 of PhD thesis entitled: "Investigating the role of NR2F2 in fibroblast during human heart development"</span
MicroRNA-155 targets SMAD2 and modulates the response of macrophages to transforming growth factor-{beta}
No full textTransforming growth factor-beta (TGF-?) is a pleiotropic cytokine with important effects on processes such as fibrosis, angiogenesis, and immunosupression. Using bioinformatics, we identified SMAD2, one of the mediators of TGF-? signaling, as a predicted target for a microRNA, microRNA-155 (miR-155). MicroRNAs are a class of small non-coding RNAs that have emerged as an important class of gene expression regulators. miR-155 has been found to be involved in the regulation of the immune response in myeloid cells. Here, we provide direct evidence of binding of miR-155 to a predicted binding site and the ability of miR-155 to repress SMAD2 protein expression. We employed a lentivirally transduced monocyte cell line (THP1-155) containing an inducible miR-155 transgene to show that endogenous levels of SMAD2 protein were decreased after sustained overexpression of miR-155. This decrease in SMAD2 led to a reduction in both TGF-?-induced SMAD-2 phosphorylation and SMAD-2-dependent activation of the expression of the CAGA(12)LUC reporter plasmid. Overexpression of miR-155 altered the cellular responses to TGF-? by changing the expression of a set of genes that is involved in inflammation, fibrosis, and angiogenesis. Our study provides firm evidence of a role for miR-155 in directly repressing SMAD2 expression, and our results demonstrate the relevance of one of the two predicted target sites in SMAD2 3'-UTR. Altogether, our data uncover an important role for miR-155 in modulating the cellular response to TGF-? with possible implications in several human diseases where homeostasis of TGF-? might be altered
The interleukin 13 (IL-13) pathway in human macrophages is modulated by microRNA-155 via direct targeting of interleukin 13 receptor ?1 (IL13R?1)
No full textMacrophages play a central role in the balance and efficiency of the immune response and are at the interface between innate and adaptive immunity. Their phenotype is a delicate equilibrium between the M1 (classical, pro-Th(1)) and M2 (alternative, pro-Th(2)) profiles. This balance is regulated by cytokines such as interleukin 13 (IL-13), a typical pro-M2-Th(2) cytokine that has been related to allergic disease and asthma. IL-13 binds to IL-13 receptor ?1 (IL13R?1), a component of the Type II IL-4 receptor, and exerts its effects by activating the transcription factor signal transducer and activator of transcription 6 (STAT6) through phosphorylation. MicroRNAs are short (?22 nucleotide) inhibitory non-coding RNAs that block the translation or promote the degradation of their specific mRNA targets. By bioinformatics analysis, we found that microRNA-155 (miR-155) is predicted to target IL13R?1. This suggested that miR-155 might be involved in the regulation of the M1/M2 balance in macrophages by modulating IL-13 effects. miR-155 has been implicated in the development of a healthy immune system and function as well as in the inflammatory pro-Th(1)/M1 immune profile. Here we have shown that in human macrophages, miR-155 directly targets IL13R?1 and reduces the levels of IL13R?1 protein, leading to diminished activation of STAT6. Finally we also demonstrate that miR-155 affects the IL-13-dependent regulation of several genes (SOCS1, DC-SIGN, CCL18, CD23, and SERPINE) involved in the establishment of an M2/pro-Th(2) phenotype in macrophages. Our work shows a central role for miR-155 in determining the M2 phenotype in human macrophages
Bag-of-words is competitive with sum-of-embeddings language-inspired representations on protein inference
No full textInferring protein function is a fundamental and long-standing problem in biology. Laboratory experiments in this field are often expensive, and therefore large-scale computational protein inference from readily available amino acid sequences is needed to understand in more detail the mechanisms underlying biological processes in living organisms. Recently, studies have utilised mathematical ideas from natural language processing and self-supervised learning, to derive features based on protein sequence information. In the area of language modelling, it has been shown that learnt representations from self-supervised pre-training can capture the semantic information of words well for downstream applications. In this study, we tested the ability of sequence-based protein representations learnt using self-supervised pre-training on a large protein database, on multiple protein inference tasks. We show that simple baseline representations in the form of bag-of-words histograms perform better than those based on self-supervised learning, on sequence similarity and protein inference tasks. By feature selection we show that the top discriminant features help bag-of-words capture important information for data-driven function prediction. These findings could have important implications for self-supervised learning models on protein sequences, and might encourage the consideration of alternative pre-training schemes for learning representations that capture more meaningful biological information from the sequence alone
Enhancing natural killer cell anti-tumour activity through macrophage manipulation
Full text linkThe tumour microenvironment (TME) is a complex and dynamic environment containing diverse cellular, stromal and soluble factors, that collectively influence cancer progression, immune evasion and therapeutic resistance. Among the immune components of the TME, macrophages and natural killer (NK) cells are key players, whose interactions, particularly their crosstalk, critically shape anti-tumour immunity. The macrophage–NK cell interplay can either promote or suppress immune responses depending on the context, representing both a challenge and a therapeutic opportunity. NK cells are key effectors capable of recognising and eliminating malignant cells without prior sensitisation, whereas macrophages exhibit remarkable plasticity, functioning as either promoters or suppressors of tumour immunity depending on their activation state. This review focuses on current strategies to harness macrophages in cancer therapy, including phenotype repolarisation, selective depletion, and disruption or enhancement of the macrophage-NK cell crosstalk to enhance NK cell-mediated tumour surveillance. Finally, we highlight emerging technologies, such as single-cell RNA sequencing, spatial transcriptomics, and proteomics, as powerful tools to elucidate the dynamic interplay between macrophages and NK cells and inform the next generation of immunotherapeutic interventions
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