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Search Results: 1 - 10 of 210 matches for " Iryna Shanina "
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Gammaherpesvirus Latency Accentuates EAE Pathogenesis: Relevance to Epstein-Barr Virus and Multiple Sclerosis
Costanza Casiraghi,Iryna Shanina,Sehyun Cho,Michael L. Freeman,Marcia A. Blackman,Marc S. Horwitz
PLOS Pathogens , 2012, DOI: 10.1371/journal.ppat.1002715
Abstract: Epstein-Barr virus (EBV) has been identified as a putative environmental trigger of multiple sclerosis (MS), yet EBV's role in MS remains elusive. We utilized murine gamma herpesvirus 68 (γHV-68), the murine homolog to EBV, to examine how infection by a virus like EBV could enhance CNS autoimmunity. Mice latently infected with γHV-68 developed more severe EAE including heightened paralysis and mortality. Similar to MS, γHV-68EAE mice developed lesions composed of CD4 and CD8 T cells, macrophages and loss of myelin in the brain and spinal cord. Further, T cells from the CNS of γHV-68 EAE mice were primarily Th1, producing heightened levels of IFN-γ and T-bet accompanied by IL-17 suppression, whereas a Th17 response was observed in uninfected EAE mice. Clearly, γHV-68 latency polarizes the adaptive immune response, directs a heightened CNS pathology following EAE induction reminiscent of human MS and portrays a novel mechanism by which EBV likely influences MS and other autoimmune diseases.
Lack of IL-6 during Coxsackievirus Infection Heightens the Early Immune Response Resulting in Increased Severity of Chronic Autoimmune Myocarditis
Maya C. Poffenberger,Nadine Straka,Nahida El Warry,Dianne Fang,Iryna Shanina,Marc S. Horwitz
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0006207
Abstract: Chronic myocarditis is often initiated by viral infection, the most common of which is coxsackievirus infection. The precise mechanism by which viral infection leads to chronic autoimmune pathology is poorly understood, however it is clear that the early immune response plays a critical role. Previous results have shown that the inflammatory cytokine interleukin (IL)-6 is integral to the development of experimental-induced autoimmune myocarditis. However, the function of IL-6 during viral-mediated autoimmunity has yet to be elucidated.
Toll-Like Receptor 3 Signaling on Macrophages Is Required for Survival Following Coxsackievirus B4 Infection
Martin J. Richer, Danielle J. Lavallée, Iryna Shanina, Marc S. Horwitz
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0004127
Abstract: Toll-like receptor 3 (TLR3) has been proposed to play a central role in the early recognition of viruses by sensing double stranded RNA, a common intermediate of viral replication. However, several reports have demonstrated that TLR3 signaling is either dispensable or even harmful following infection with certain viruses. Here, we asked whether TLR3 plays a role in the response to coxsackievirus B4 (CB4), a prevalent human pathogen that has been associated with pancreatitis, myocarditis and diabetes. We demonstrate that TLR3 signaling on macrophages is critical to establish protective immunity to CB4. TLR3 deficient mice produced reduced pro-inflammatory mediators and are unable to control viral replication at the early stages of infection resulting in severe cardiac damage. Intriguingly, the absence of TLR3 did not affect the activation of several key innate and adaptive cellular effectors. This suggests that in the absence of TLR3 signaling on macrophages, viral replication outpaces the developing adaptive immune response. We further demonstrate that the MyD88-dependent signaling pathways are not only unable to compensate for the loss of TLR3, they are also dispensable in the response to this RNA virus. Our results demonstrate that TLR3 is not simply part of a redundant system of viral recognition, but rather TLR3 plays an essential role in recognizing the molecular signatures associated with specific viruses including CB4.
Immunomodulation of Antigen Presenting Cells Promotes Natural Regulatory T Cells That Prevent Autoimmune Diabetes in NOD Mice
Martin J. Richer, Danielle J. Lavallée, Iryna Shanina, Marc S. Horwitz
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0031153
Abstract: Progression towards type 1 diabetes (T1D) in susceptible patients is linked to a progressive decline in the capacity of regulatory T cells (Treg) to maintain tolerance. As such, therapies aimed at redressing the failing Treg compartment have been the subject of intense investigation. Treg dysfunction in T1D has recently been linked to a reduced capacity of antigen presenting cells (APCs) to maintain Treg function rather than Treg intrinsic defects. This suggests that therapies aimed simply at addressing the failing Treg compartment are unlikely to provide long-term protection. Here, we demonstrate that modulation of the inflammatory status of CD11b+CD11c? APCs favors the upregulation of protective Tregs in a mouse model of T1D. We further demonstrate that reduced expression of the costimulatory molecule CD40 plays a role in this increased immunoregulatory capacity. Strikingly, Treg upregulation resulted exclusively from an increase in natural Tregs rather than the peripheral conversion of conventional T cells. This suggests that modulation of CD11b+ CD11c? APCs inflammatory properties favors the establishment of natural Treg responses that, unlike adaptive Treg responses, are likely to maintain tolerance to a broad range of antigens. As such, modulation of this APC subset represents a potential therapeutic avenue to reestablish peripheral tolerance and protect from autoimmune diseases such as T1D.
Development of an HIV-1 Specific Microbicide Using Caulobacter crescentus S-Layer Mediated Display of CD4 and MIP1α
John F. Nomellini,Carmen Li,Danielle Lavallee,Iryna Shanina,Lisa A. Cavacini,Marc S. Horwitz,John Smit
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0010366
Abstract: The development of alternative strategies to prevent HIV infection is a global public health priority. Initial efforts in anti-HIV microbicide development have met with poor success as the strategies have relied on a non-specific mechanism of action. Here, we report the development of a microbicide aimed at specifically blocking HIV entry by displaying molecular components of the HIV/host cell attachment complex on the surface of Caulobacter crescentus, a harmless aquatic bacterium. This bacterium can be readily manipulated to present heterologous proteins at high density on its surface by genetic insertion into its crystalline surface layer protein [1], [2]. In separate constructions, we generated bacteria displaying domain 1 of CD4 and MIP1α. Each moiety reacted with specific antibodies by Western immunoblot and immuno-fluorescence microscopy. Microbicide functionality was assessed using an HIV pseudotype virus assay system representing Clade B subtypes. Bacteria displaying MIP1α reduced infectivity by 35–78% depending on the specific subtype while CD4 display reduced infection by as much as 56%. Combinations of both constructs reduced infectivity by nearly 98%. We demonstrated that HIV infection could be inhibited using a strategy aimed at HIV-specific molecular interactions with Caulobacter surface protein display, and that sufficient protein folding and conformation could be mimicked to bind and block entry. Further, this is the first demonstration that Caulobacter surface protein display may be a useful approach to preventing HIV infection or other viruses as a microbicide. We propose that this harmless bacterium, which is inexpensive to produce and formulate, might be suitable for topical applications as a viable alternative in the search for effective microbicides to counteract the world wide incidence of HIV infection.
Development of an HIV-1 Microbicide Based on Caulobacter crescentus: Blocking Infection by High-Density Display of Virus Entry Inhibitors
Christina Farr, John F. Nomellini, Evan Ailon, Iryna Shanina, Sassan Sangsari, Lisa A. Cavacini, John Smit, Marc S. Horwitz
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0065965
Abstract: The HIV/AIDS pandemic remains an enormous global health concern. Despite effective prevention options, 2.6 million new infections occur annually, with women in developing countries accounting for more than half of these infections. New prevention strategies that can be used by women are urgently needed. Topical microbicides specific for HIV-1 represent a promising prevention strategy. Conceptually, using harmless bacteria to display peptides or proteins capable of blocking entry provides an inexpensive approach to microbicide development. To avoid the potential pitfalls of engineering commensal bacteria, our strategy is to genetically display infection inhibitors on a non-native bacterium and rely on topical application of stabilized bacteria before potential virus exposure. Due to the high density cell-surface display capabilities and the inherent low toxicity of the bacterium, the S-layer mediated protein display capabilities of the non-pathogenic bacterium Caulobacter crescentus has been exploited for this approach. We have demonstrated that C. crescentus displaying MIP1α or CD4 interfered with the virus entry pathway and provided significant protection from HIV-1 pseudovirus representing clade B in a standard single cycle infection assay. Here we have expanded our C. crescentus based microbicide approach with additional and diverse classes of natural and synthetic inhibitors of the HIV-1 entry pathway. All display constructs provided variable but significant protection from HIV-1 infection; some with protection as high as 70%. Further, we describe protection from infection with additional viral clades. These findings indicate the significant potential for engineering C. crescentus to be an effective and readily adaptable HIV-1 microbicide platform.
Prediction of Multiphase Alternative of Acute Disseminated Encephalomyelitis Course Development  [PDF]
Iryna Lobanova, Olena Myalovitska
World Journal of Neuroscience (WJNS) , 2014, DOI: 10.4236/wjns.2014.42011
Abstract:

Prediction of development of the multi-phase alternative for the course inherent to acute disseminated encephalomyelitis (ADEM) is of great clinical importance, as it enables timely determination of the treatment tactics as well as volume of respective therapeutic interventions. This work is aimed at ascertaining the prognostic factors that determine the risk of development of the multi-phase course in disseminated encephalomyelitis. We have examined 101 patients with the diagnosis ADEM, namely: 28 men and 73 women in the age from 17 up to 53 years (average value 31.7 ± 1.01 years). To ascertain the prognostic meaning of clinic-paraclinic indices corresponding to patients with ADEM, we estimated the cumulative part of absence of relapses in the group of patients by using the Kaplan-Meyer method with estimating the Fisher criterion and using the most important clinic-paraclinic data. Development of the multiphase course in ADEM is reliably related to the following prognostic signs: changes in the neurologic status of patients with ADEM, degree of disability in accord with the EDSS scale as well as sizes of demyelination focuses determined using MRT. Criteria for congenial prediction in disease development with delayed appearance of ADEM relapses in the form of the multi-phase course are as follows: domination of motor impairments over coordinative impairments in neurological status, slight degree (in EDSS scale) of disability and small sizes (up to 4 mm) of demyelination focuses (MRT data). Our analysis of the main clinic-paraclinic indices obtained using the Kaplan-Meyer method indicates reliability of results and enables us to find a number of important prognostic criteria for appearance of the multiphase course in ADEM.

The peculiaryties and prerequisites origin conflicts in the region
Iryna Sivchuk
Socìal?no-ekonomì?nì Problemì ì Der?ava , 2010,
Abstract: Research of having the collective working discussion in the organization Ternopil region, it is defined their cores cause occurrence that methods overcoming of negative consequences.
From specialization to diversification
Shuran, Iryna
Socìal?no-ekonomì?nì Problemì ì Der?ava , 2012,
Abstract: The main types of corporate diversification strategy were considered. Strategic opportunities to diversify the company's were given. The main advantages and disadvantages of diversification strategies in related and unrelated fields of activity were identified. The examples of companies that have implemented the strategic approaches to diversification were given. The most common approach of this strategy in the domestic industrial market was identified.
Bibliographic Data Towards the Semantic Web: A Review of Key Issues and Recent Experiences = Bibliyografik Verilerin lenmesinde Yenilik i Yakla mlar: Semantik Web’e Do ru
Solodovnik, Iryna
Bilgi Dünyas? , 2012,
Abstract: This article intends to review the underlying concepts and technologies of the Semantic Web and the potential they provide for metadata management covering bibliographic resources. To get closer to a semantic web data space, different libraries are adhering to the initiatives making their traditional Knowledge Organization Systems (KOS) operational on the web through SKOS techniques, as well as releasing bibliographic data under open licenses (open bibliographic data)and publishing it with Linked Data (LD) mechanisms. LD meaningful semantic connections createthe Web of Data, a global database representing the first practical step to the Semantic Web.Here interoperable data can be processed independently of application, platform or domain,providing rich retrieval results produced by powerful query languages. From a library perspective,a problem statement is a global promotion within the Library community of understandingand of adoption of Linked Open Data (LOD), of LODe-BD recommendations, as well as releasing bibliographic data as Linked Library Data (LLD). In this way, different bibliographic datasets could become full members of the Semantic Web making interoperable different knowledge datasets of heterogeneous web communities. / Son y llarda, verilerini Web üzerinden payla an global Web topluluklar nda, bibliyografik,bilimsel ve y netsel verilerin y netilmesi bak m ndan dijital bilgi sistemleri, yeni bilginin üretiminde merkezi bir rol oynamaya ba lam t r. Dijital materyallerin hacmi büyüdük e ve kullan mlar yayg nla t k a, dijital ge mi ve gelece imizin irtibatland r lmas nemli bir ba ar mücadelesi gerektirmektedir. Geleneksel Bilgiyi organize eden sistemler, dijital evrede veri yay nlanmas n n yeni ortaya kan y ntemleri, verileri serbest eri ime a ma ve ili kilendirerek “a k veri” haline getirme, farkl toplumlar n yenilik i yakla mlar n destekleyen i birli i al malar olu turma, bibliyografik veri taban y netimine zgü yeni yakla mlard r. Ayn ekilde, dijital i eri in düzenlenmesinde gittik e karma kla an ortamlara ihtiya duyulmas , metaveri modellemesinde yeni rlar a maktad r. Bu al man n temel amac , dijital enformasyon ve veri y netimindekiyeni kuramsal ve pratik kullan m olan paradigmalardan okuru haberdar etmek ve zellikle de Semantik Web kapsam ndaki bibliyografik verilere odaklanmakt r.
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