Role of 26S Proteasome and Regulator of G-Protein Signaling 10 in Regulating Neuroinflammation in the Central Nervous System

Major histocompatibility complex molecules (MHCII) are cell surface glycoproteins that present extracellular antigens to CD4+ T lymphocytes and initiate adaptive immune responses. Apart from their protective role, overexpression of MHCII contributes to autoimmune disorders where the immune system attacks our own tissues. Autoimmune diseases are characterized by self-reactive responses to autoantigens, promoting tissue damage, inflammation mediated by proinflammatory cytokines, autoreactive lymphocytes, and autoantibodies. MHCII molecules are tightly regulated at the level of transcription by Class II transactivator (CIITA). CIITA associates with an enhanceosome complex at MHCII promoters and regulates the expression of MHCII. It is thus crucial to understand the regulation of CIITA expression in order to regulate MHCII in autoimmune diseases. Our lab has shown that the 19S ATPases of the 26S proteasome associate with MHCII and CIITA promoters and play important roles in gene transcription, regulate covalent modifications to histones, and are involved in the assembly of activator complexes in mammalian cells. The mechanisms by which the proteasome influences transcription remain unclear. Here, we define novel roles of the 19S ATPases Sug1, S7, and S6a in expression of CIITApIV genes. These ATPases are recruited to CIITApIV promoters and coding regions, interact with the elongation factor PTEFb, and with Ser5 phosphorylated RNA Pol II. Both the generation of CIITApIV transcripts and efficient recruitment of RNA Pol II to CIITApIV are negatively impacted by knockdown of 19S ATPases. Alternatively, inflammation is also suppressed via the Regulator of G-protein signaling 10 (RGS10) in microglial cells which express high levels of RGS10 and promote homeostasis in the central nervous system. However, chronic activation of microglial cells leads to release of cytokines which cause neuroinflammation. Our investigation of roles played by RGS10 in chronically activated microglial cells indicates that RGS10 binds to promoters of IL-1β, and TNF-α and regulates these genes, while the molecular mechanism remains to be investigated. Together, our observations indicate roles for the UPS in modulating gene expression and for RGS10 in regulating proinflammatory cytokines in microglial cells, each of which provides novel therapeutic targets to combat inflammation in autoimmune and neurodegenerative diseases

Oggetti finzionali. L’astrazione straniante in Historias de cronopios y de famas di Julio Cortázar

Oggetti finzionali. L’astrazione straniante in Historias de cronopios y de famas di Julio Cortázar Tesi di Alice Nagini RELATORE: prof.ssa Emilia Perassi CORRELATORE: prof.ssa Laura Scarabelli CORSO DI LAUREA: Laurea Magistrale in Lettere Moderne UNIVERSITA': Università degli Studi di Milano ANNO ACCADEMICO: 2017-201

Improve the Security and Usability of User Session using Continuous Authentication Protocol

Session organization of distributed web applications is usually depends on textual passwords and biometric verification at the starting of session, but here single authentication is happening. In this the problem is client identity is not verifying during the whole session. To overcome this problem a new approach continuous authentication protocol and the architecture CASHMA (context aware security by hierarchical multilevel architecture) are proposed for user verification. The advantage of the proposed system is to increase usability and security of session with biometric data. Experimental studies have been implemented using java

An Inverted Index Structure for the Social Image Dataset To Accelerate the Searching Process

We suggest a social re-ranking system for tag-based image recovery with the thought of image’s bearing and variety. We purpose at re-ranking images giving to their pictorial information, semantic information and social clues. The original results embrace images underwrote by diverse social users. Regularly each operator underwrites several images. First we type these images by inter-user re-ranking. Users that have higher involvement to the prearranged query rank complex. Then we chronologically instrument intra-user re-ranking on the ranked user’s image set, and first the most appropriate image from each user’s image set is selected. These certain images unite the final retrieved results. We form an inverted index structure for the societal image dataset to fast-track the incisive route

A Concrete Construction of RS IBF In Defined Security Model

We propose a thought called revocable-storage identity-based encryption (RS-IBE), which can give the forward/in reverse security of ciphertext by presenting the functionalities of client repudiation and ciphertext refresh all the while. Besides, we exhibit a solid development of RS-IBE, and demonstrate its security in the characterized security model. The execution examinations demonstrate that the proposed RS-IBE scheme has focal points as far as usefulness and productivity, and in this way is plausible for a pragmatic and financially savvy data sharing framework. At long last, we give usage consequences of the proposed plan to show its practicability

A new distributed storage evaluating with irrefutable outsourcing of key upgrades

In this worldview, key updates can be securely redistributed to some approved gathering, and along these lines the key-refresh trouble on the customer will be kept negligible. In particular, we use the third party auditor (TPA) in many existing open evaluating structures, let it assume the job of approved gathering for our situation, and make it accountable for both the capacity reviewing and the protected key updates for key-introduction obstruction. In our structure, TPA just needs to hold a scrambled variant of the customer's secret key, while doing all these oppressive errands in the interest of the customer. The customer just needs to download the scrambled secret key from the TPA while transferring new documents to cloud. Plus, our structure additionally outfits the customer with ability to additionally confirm the legitimacy of the scrambled secret keys given by TPA