Search results for "CLO"
showing 10 items of 9986 documents
Metabolism via arginase or nitric oxide synthase: two competing arginine pathways in macrophages
2014
Macrophages play a major role in the immune system, both as antimicrobial effector cells and as immunoregulatory cells, which induce, suppress or modulate adaptive immune responses. These key aspects of macrophage biology are fundamentally driven by the phenotype of macrophage arginine metabolism that is prevalent in an evolving or ongoing immune response. M1 macrophages express the enzyme nitric oxide synthase (NOS), which metabolizes arginine to nitric oxide (NO) and citrulline. NO can be metabolized to further downstream reactive nitrogen species, while citrulline might be reused for efficient NO synthesis via the citrulline-NO cycle. M2 macrophages are characterized by expression of the…
eIF2α confers cellular tolerance to S. aureus α-toxin
2015
We report on the role of conserved stress-response pathways for cellular tolerance to a pore forming toxin. First, we observed that small molecular weight inhibitors including of eIF2α-phosphatase, jun-N-terminal kinase (JNK), and PI3-kinase sensitized normal mouse embryonal fibroblasts (MEFs) to the small pore forming S. aureus α-toxin. Sensitization depended on expression of mADAM10, the murine ortholog of a proposed high-affinity receptor for α-toxin in human cells. Similarly, eIF2α (S51A/S51A) MEFs, which harbor an Ala knock-in mutation at the regulated Ser51 phosphorylation site of eukaryotic translation initiation factor 2α, were hyper-sensitive to α-toxin. Inhibition of translation w…
Tolerogenic Dendritic Cells for Regulatory T Cell Induction in Man.
2015
Dendritic cells are (DC) highly specialized professional antigen-presenting cells (APC) that regulate immune responses, maintaining the balance between tolerance and immunity. Mechanisms via which they can promote central and peripheral tolerance include clonal deletion, inhibition of memory T cell responses, T cell anergy and induction of regulatory T cells. These properties have led to the analysis of human tolerogenic DC as a therapeutic strategy for induction or re-establishment of tolerance. In the recent years, numerous protocols for the generation of human tolerogenic DC have been developed and their tolerogenic mechanisms, including induction of regulatory T cells, are relatively we…
Immunological Markers for PML Prediction in MS Patients Treated with Natalizumab
2015
International audience; Natalizumab (NTZ), a monoclonal antibody recognizing the alpha4 integrin chain, has been approved for the treatment of active multiple sclerosis, but expose to the onset of a rare side effect, progressive multifocal leukoencephalopathy (PML). Estimating the individual risk of PML in NTZ-treated patients is a major challenge, and therapeutic strategies are mainly guided by the overall PML risk assessed by identified risk factors: JC virus (JCV) seropositivity, treatment duration (with peak incidence after 24 months), and the previous use of immunosuppressive therapies. Given that this stratification does not yet allow a precise individual prediction of PML, other pred…
Molecular epidemiology of HIV-1 subtype B in the Basque Country (Spain)
2012
The goal of this work was to study the HIV-1 subtype B epidemic in the Basque Country (Spain). For this, we used HIV samples submitted for genotypic testing of anti-retroviral resistance mutations from 2005 until 2008. Consequently, 2115 HIV-1 sequences comprising protease and retrotranscriptase (PR/RT) coding regions were analyzed. HIV transmission groups were identified by phylogenetic analysis. The 10 largest such groups were subsequently subjected to Bayesian phylogenetic and coalescent reconstructions, using a relaxed molecular clock model. The results obtained show that these groups have been long-standing: most of them were originated in the late 70s or early 80s, and none after the …
Blood Transfusion Management for Patients Treated With Anti-CD38 Monoclonal Antibodies
2018
Daratumumab has proven to be highly efficacious for relapsed and refractory multiple myeloma (MM) and has recently been approved in the frontline setting for MM patients ineligible for transplantation. In the future, expanded indications are possible for daratumumab and other anti-CD38 monoclonal antibodies in development. For several years, it has been recognized that these therapies interfere with blood bank testing by binding to CD38 on red blood cells and causing panagglutination on the Indirect Antiglobulin Test. This can lead to redundant testing and significant delays in patient care. Given the anticipated increase in utilization of anti-CD38 monoclonal antibodies, as well as the tra…
A Conceptual Framework for Using and Evaluating Web-Based Learning Resources in School Education
2010
Published version of an article from the journal:Journal of Information Technology Education. Also available from the publisher: http://www.jite.org/documents/Vol9/JITEv9p053-079Hadjerrouit743.pdf Web-based learning resources (WBLRs) have provided teachers with a wide range of new teachingexperiences that are not possible in traditional classroom. However, little research has beendone as to which approach to WBLRs is suitable to address issues that are pertinent to learning.This paper proposes a conceptual framework to explore the design and evaluation of WBLRs inschool education. The paper also examines the way in which the framework is used to evaluatestudents? and teachers? perceptions o…
Una poética de las ruinas. Testimonio y alegoría de Aníbal Quijada
2009
El texto de Aníbal Quijada Cerco de púas ejemplifica la doble vinculación de los testimonios del exilio chileno. Por una parte, éstos debieron inscribirse en las estrategias internacionales de denuncia contra la dictadura militar y, por otra, la comunidad cultural latinoamericana hizo de los testimonios un elemento esencial para la redefinición del concepto mismo de lo literario. El testimonio de Quijada desarrolla, en ese contexto, unas estrategias narrativas y de representación que alejan su textura de la mayoría de los testimonios de la época.The text of Aníbal Quijada Cerco de púas, is a good example of the double filiation of the testimonies of Chilean exile. In one hand these testimon…
Evaluation of the inverse electron demand Diels-Alder reaction in rats using a scandium-44-labelled tetrazine for pretargeted PET imaging
2019
Background Pretargeted imaging allows the use of short-lived radionuclides when imaging the accumulation of slow clearing targeting agents such as antibodies. The biotin-(strept)avidin and the bispecific antibody-hapten interactions have been applied in clinical pretargeting studies; unfortunately, these systems led to immunogenic responses in patients. The inverse electron demand Diels-Alder (IEDDA) reaction between a radiolabelled tetrazine (Tz) and a trans-cyclooctene (TCO)-functionalized targeting vector is a promising alternative for clinical pretargeted imaging due to its fast reaction kinetics. This strategy was first applied in nuclear medicine using an 111In-labelled Tz to image TC…
“One Ring to Bind Them All”—Part II: Identification of Promising G-Quadruplex Ligands by Screening of Cyclophane-Type Macrocycles
2010
A collection of 26 polyammonium cyclophane-type macrocycles with a large structural diversity has been screened for G-quadruplex recognition. A two-step selection procedure based on the FRET-melting assay was carried out enabling identification of macrocycles of high affinity (ΔT1/2up to30°C) and high selectivity for the human telomeric G-quadruplex. The four selected hits possess sophisticated architectures, more particularly the presence of a pendant side-arm as well as the existence of a particular topological arrangement appear to be strong determinants of quadruplex binding. These compounds are thus likely to create multiple contacts with the target that may be at the origin of their h…