Search results for "unity"
showing 10 items of 3852 documents
A Potent Tumor-Reactive p53-Specific Single-Chain TCR without On- or Off-Target Autoimmunity In Vivo
2018
Genetic engineering of T cells with a T cell receptor (TCR) targeting tumor antigen is a promising strategy for cancer immunotherapy. Inefficient expression of the introduced TCR due to TCR mispairing may limit the efficacy and adversely affect the safety of TCR gene therapy. Here, we evaluated the safety and therapeutic efficiency of an optimized single-chain TCR (scTCR) specific for an HLA-A2.1-restricted (non-mutated) p53(264–272) peptide in adoptive T cell transfer (ACT) models using our unique transgenic mice expressing human p53 and HLA-A2.1 that closely mimic the human setting. Specifically, we showed that adoptive transfer of optimized scTCR-redirected T cells does not induce on-tar…
Impairment of TGF-β signaling in T cells increases susceptibility to experimental autoimmune hepatitis in mice
2002
In autoimmune hepatitis, strong TGF-beta1 expression is found in the inflamed liver. TGF-beta overexpression may be part of a regulatory immune response attempting to suppress autoreactive T cells. To test this hypothesis, we determined whether impairment of TGF-beta signaling in T cells leads to increased susceptibility to experimental autoimmune hepatitis (EAH). Transgenic mice of strain FVB/N were generated expressing a dominant-negative TGF-beta type II receptor in T cells under the control of the human CD2 promoter/locus control region. On induction of EAH, transgenic mice showed markedly increased portal and periportal leukocytic infiltrations with hepatocellular necroses compared wit…
Chronic inflammatory cardiomyopathy of interferon γ-overexpressing transgenic mice is mediated by tumor necrosis factor-α.
2011
We recently described a model of inflammatory cardiomyopathy in interferon (IFN)-γ overexpressing transgenic mice stably circulating IFN-γ in the serum referred to as SAP–-IFN-γ mice. SAP–IFN-γ transgenic mice show cardiac infiltration by mononuclear leukocytes, culminating in dilated cardiomyopathy characterized by an increase of left ventricular end diastolic diameter and reduction of fractional shortening. We hypothesized that the pathological mechanism underlying SAP–IFN-γ cardiomyopathy might be mediated by (auto)immune processes or tumor necrosis factor (TNF)-α synthesis from IFN-γ–activated macrophages. To verify these hypotheses, we crossed SAP–IFN-γ transgenic mice with immunodefic…
Disrupting immune regulation incurs transient costs in male reproductive function.
2014
9 pages; International audience; BACKGROUND: Immune protection against pathogenic organisms has been shown to incur costs. Previous studies investigating the cost of immunity have mostly focused on the metabolic requirements of immune maintenance and activation. In addition to these metabolic costs, the immune system can induce damage to the host if the immune response is mis-targeted or over-expressed. Given its non-specific nature, an over-expressed inflammatory response is often associated with substantial damage for the host. Here, we investigated the cost of an over-expressed inflammatory response in the reproductive function of male mice. METHODOLOGY/PRINCIPAL FINDINGS: We experimenta…
Recognition of Specified RNA Modifications by the Innate Immune System
2015
Microbial nucleic acids have been described as important activators of human innate immune responses by triggering so-called pattern recognition receptors (PRRs) that are expressed on innate immune cells, including plasmacytoid dendritic cells and monocytes. Although host and microbial nucleic acids share pronounced chemical and structural similarities, they significantly differ in their posttranscriptional modification profile, allowing the host to discriminate between self and nonself. In this regard, ribose 2'-O-methylation has been discovered as suppressor of RNA-induced PRR activation. Although 2'-O-methylation occurs with higher frequencies in eukaryotic than in prokaryotic RNA, the i…
RB1 in cancer: Different mechanisms of RB1 inactivation and alterations of pRb pathway in tumorigenesis
2013
Loss of RB1 gene is considered either a causal or an accelerating event in retinoblastoma. A variety of mechanisms inactivates RB1 gene, including intragenic mutations, loss of expression by methylation and chromosomal deletions, with effects which are species-and cell type-specific. RB1 deletion can even lead to aneuploidy thus greatly increasing cancer risk. The RB1gene is part of a larger gene family that includes RBL1 and RBL2, each of the three encoding structurally related proteins indicated as pRb, p107, and p130, respectively. The great interest in these genes and proteins springs from their ability to slow down neoplastic growth. pRb can associate with various proteins by which it …
CENPA overexpression promotes genome instability in pRb-depleted human cells
2009
Abstract Background Aneuploidy is a hallmark of most human cancers that arises as a consequence of chromosomal instability and it is frequently associated with centrosome amplification. Functional inactivation of the Retinoblastoma protein (pRb) has been indicated as a cause promoting chromosomal instability as well centrosome amplification. However, the underlying molecular mechanism still remains to be clarified. Results Here we show that pRb depletion both in wild type and p53 knockout HCT116 cells was associated with the presence of multipolar spindles, anaphase bridges, lagging chromosomes and micronuclei harbouring whole chromosomes. In addition aneuploidy caused by pRb acute loss was…
La explicación del riesgo de sequía en la Geografía escolar. Una exploración desde los manuales escolares de Ciencias Sociales (Educación Primaria)
2021
espanolEn la region mediterranea uno de los principales riesgos naturales son las sequias. Este fenomeno se ha agravado en las ultimas decadas debido al incremento de la vulnerabilidad asociadas a actividades humanas y, segun los escenarios futuros de cambio climatico, se preve que aumente la peligrosidad (mayor intensidad y frecuencia de los periodos secos). El objetivo de este trabajo es llevar a cabo un analisis de como se explica el riesgo de sequia en los manuales escolares de Ciencias Sociales (3er ciclo de Educacion Primaria) en la Comunidad Valenciana (Espana). A partir de la consulta de estos recursos (las 5 editoriales mas utilizadas), los resultados obtenidos indican que esta tem…
Geobotanical approach to detect land-use change of a Mediterranean landscape: a case study in Central-Western Sicily
2018
A landscape is a palimpsest of the interactions between human activities and ecological dynamics. In an interdisciplinary perspective of dialogue between the ‘Two Cultures’ (Natural Sciences and Humanities), a study of a rural area has been carried out through a reading of plant ecosystems as signs of human impact. The purpose of this paper—as part of the project ‘Harvesting Memories’: Ecology and landscape archaeology of Castro/Giardinallo Valley and Mt. Barrau district (Corleone, Palermo, Sicily)—is to analyse the formative-processes of a Sicilian rural landscape and its changes in the last century. A key element in the reconstruction of the formation of the present landscape is the serie…
Gobernanza democrática para el desarrollo: Las estructuras de cooperación en los municipios en riesgo de despoblación de la Comunitat Valenciana
2020
[ES] La muerte anunciada de muchos municipios del interior montañoso y rural de España pone de relieve la catástrofe que puede suponer en términos de pérdida poblacional, patrimonial, cultural, económica y medioambiental. La toma de conciencia de ese problema obliga a poner en marcha políticas que modifiquen esta deriva. Nuestro propósito en último término es diseñar una política de desarrollo integral para estos territorios. A este fin, el objeto concreto de este trabajo es realizar un diagnóstico territorial en relación a las estructuras de cooperación existentes en los territorios en riesgo de despoblación de la Comunidad Valenciana.