Search results for "privilege"
showing 10 items of 46 documents
2,3-Dihydrobenzofuran privileged structures as new bioinspired lead compounds for the design of mPGES-1 inhibitors
2016
International audience; 2,3-Dihydrobenzofurans are proposed as privileged structures and used as chemical platform to design small compound libraries. By combining molecular docking calculations and experimental verification of biochemical interference, we selected some potential inhibitors of microsomal prostaglandin E2 synthase (mPGES)-1. Starting from low affinity natural product 1, by our combined approach we identified the compounds 19 and 20 with biological activity in the low micromolar range. Our data suggest that the 2,3-dihydrobenzofuran derivatives might be suitable bioinspired lead compounds for development of new generation mPGES-1 inhibitors with increased affinity.
Human limbal fibroblast-like stem cells induce immune-tolerance in autoreactive T lymphocytes from female patients with Hashimoto’s thyroiditis
2017
Background Due to their “natural immune privilege” and immunoregulatory properties human fibroblast-like limbal stem cells (f-LSCs) have acquired great interest as a potential tool for achieving immunotolerance. Hashimoto’s thyroiditis (HT) is the most common thyroid autoimmune disease and cause of hypothyroidism. To date, conventional hormone replacement therapy and unspecific immunosuppressive regimens cannot provide a definitive cure for HT subjects. We explored the immunosuppressant potential of human f-LSCs on circulating lymphomonocytes (PBMCs) collected from healthy donors and female HT patients. Methods We assessed the immunophenotyping of f-LSCs, both untreated and after 48 h of pr…
Time for a “Plan B” in Peritoneal Metastatic Disease
2019
Abstract Peritoneal involvement in cancer is the harbinger of a particularly unfavorable prognosis. The peritoneal cavity microenvironment is skewed toward immunoregulatory conditions promoted by macrophage populations and innate-like B-1 B cells, which provide immune privilege to malignant cell foci. In this issue of Cancer Research, Haro and colleagues demonstrate that triggering innate IgM-mediated B-1a immune responses via pathogen- or danger-associated molecular pattern recognition exerts antitumor effects on peritoneal metastases by inducing classical complement cascade activation. Exploitation of innate B-1 humoral responses and noncellular immunity is a promising strategy to counter…
Immunobiology of Uveal Melanoma: State of the Art and Therapeutic Targets
2019
Uveal Melanoma (UM) represents the most common primary intraocular malignant tumor in adults. Although it originates from melanocytes as cutaneous melanoma, it shows significant clinical and biological differences with the latter, including high resistance to immune therapy. Indeed, UM can evade immune surveillance via multiple mechanisms, such as the expression of inhibitory checkpoints (e.g., PD-L1, CD47, CD200) and the production of IDO-1 and soluble FasL, among others. More in-depth understanding of these mechanisms will suggest potential targets for the design of novel and more effective management strategies for UM patients.
Meningeal γδ T cell-derived IL-17 controls synaptic plasticity and short-term memory
2019
The notion of "immune privilege" of the brain has been revised to accommodate its infiltration, at steady state, by immune cells that participate in normal neurophysiology. However, the immune mechanisms that regulate learning and memory remain poorly understood. Here, we show that noninflammatory interleukin-17 (IL-17) derived from a previously unknown fetal-derived meningeal-resident γδ T cell subset promotes cognition. When tested in classical spatial learning paradigms, mice lacking γδ T cells or IL-17 displayed deficient short-term memory while retaining long-term memory. The plasticity of glutamatergic synapses was reduced in the absence of IL-17, resulting in impaired long-term poten…
Galerías de «mujeres ilustres» o el sinuoso camino de la excepción a la norma cotidiana (ss. XV-XVIII).
2000
Between the fifteenth and the eighteenth centuries, collections of «illustrious women» were a very widely spread genre all over Europe. Humanistic and courtly in their origins, they were linked to the discourse of women´s «excellence» and they transmitted the values of privilege and aristocratic ethics. At the same time, they showed ambivalent, disturbing and powerful images of «women on top». The fact that its popularity seems to have increased during the eighteenth century and that they took more widespread forms such as articles in the periodicals raises interesting questions about the meanings those images, opposed in many ways to Enlightenment values and attitudes, could have for eight…
Tourist Gaze Reconsidered
2021
The term tourist gaze was coined initially to represent those superficial expectations that tourists have on destination communities; tourists impute their ideas of authentic experience upon destination residents and their social structure and see what they have predetermined to see. This is made more real when local communities consciously act out the desired roles for financial reasons. Thus, gaze leads to surreally authentic experiences. However, does this always happen? Say, in community-centered tourism where empowered destination communities choose tourists, tourists do not have the privilege to gaze. These communities might even be able to apply their own versions of gaze upon the to…
The ius liberorum of non-Roman citizens in Egypt. Some notes on an old Taubenschlag’s hypothesis
2019
Abstract Normally the ius liberorum is associated with Roman citizens, but in the lex Irnitana we have evidence of non-Roman members of the curial class of Baetica who took advantage of this privilege. In Roman Egypt, the constitution of the boulai in the nome capitals could have provided a similar context for the selection of local elites in which Romanized Egyptians obtained that privilege.
Family Matters : Abusing Family Refresh Tokens to Gain Unauthorised Access to Microsoft Cloud Services Exploratory Study of Azure Active Directory Fa…
2022
Azure Active Directory (Azure AD) is an identity and access management service used by Microsoft 365 and Azure services and thousands of third-party service providers. Azure AD uses OIDC and OAuth protocols for authentication and authorisation, respectively. OAuth authorisation involves four parties: client, resource owner, resource server, and authorisation server. The resource owner can access the resource server using the specific client after the authorisation server has authorised the access. The authorisation is presented using a cryptographically signed Access Token, which includes the identity of the resource owner, client, and resource. During the authorisation, Azure AD assigns Ac…
CD40 provides immune privilege to the bone marrow hematopoietic niche
2020
AbstractAllogeneic bone marrow transplantation remains the only therapeutic option for a wide range of hematological malignancies despite the risk of possible adverse, immune-related events, such as infection and acute graft-versus-host disease (aGVHD). aGVHD is characterized by T-cell activation, defective B-cell development and osteoblastic niche destruction in bone marrow (BM) among other issues. Transplant conditioning regimens cause excessive inflammatory cytokines production and impaired regulatory T-cell control of aberrant T-cell activation. Here, we show that mesenchymal cells (MSCs) upregulated CD40 upon irradiation at the expense of mesenchymal markers, and that CD40 endows MSC o…