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Search Results: 1 - 10 of 6610 matches for " Ramila Philip "
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Investigation of ovarian cancer associated sialylation changes in N-linked glycopeptides by quantitative proteomics
Vivekananda Shetty, Julie Hafner, Punit Shah, Zacharie Nickens, Ramila Philip
Clinical Proteomics , 2012, DOI: 10.1186/1559-0275-9-10
Abstract: In this study, we investigated the N-linked sialylated glycopeptides in serum samples from healthy and ovarian cancer patients using Lectin-directed Tandem Labeling (LTL) and iTRAQ quantitative proteomics methods. We identified 45 N-linked sialylated glycopeptides containing 46 glycosylation sites. Among those, ten sialylated glycopeptides were significantly up-regulated in ovarian cancer patients’ serum samples. LC-MS/MS analysis of the non-glycosylated peptides from the same samples, western blot data using lectin enriched glycoproteins of various ovarian cancer type samples, and PNGase F (+/?) treatment confirmed the sialylation changes in the ovarian cancer samples.Herein, we demonstrated that several proteins are aberrantly sialylated in N-linked glycopeptides in ovarian cancer and detection of glycopeptides with abnormal sialylation changes may have the potential to serve as biomarkers for ovarian cancer.The American Cancer Society estimates that in 2011, about 21,990 new cases of ovarian cancer will be diagnosed and 15,460 women will die of ovarian cancer in the United States (ovariancancer.org) [1-3]. When ovarian cancer is detected early, the five year survival rate is over 90% [4]. Serum measurement of CA125, the current standard, has an early stage detection rate of only about 28% and when combined with ultrasound still only identifies 48% [5,6]. Development of improved diagnostic tools for early detection of ovarian cancer, including the discovery of new ovarian cancer biomarkers, has the potential to significantly improve the survival rate.It has been shown that in the cancer transformation process, changed expression and post translational modification of proteins occurs, resulting in a change in the protein structure and function. Investigating these modifications specific for cancer may provide vital information and serve as biomarkers for the diseased state. Glycosylation is a common and essential form of post translational modification of proteins.
A Ubiquitin Independent Degradation Pathway Utilized by a Hepatitis B Virus Envelope Protein to Limit Antigen Presentation
Yuanjie Liu,James S. Testa,Ramila Philip,Timothy M. Block,Anand S. Mehta
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0024477
Abstract: Hepatitis B virus envelope glycoproteins Large (L), Middle (M) and Small (S) are targets of the host cellular immune system. The extent to which the host recognizes viral antigens presented by infected cells is believed to play a decisive role in determining if an infection will be resolved or become chronic. As with other antigens, HBV envelope polypeptides must be degraded, presumably by cellular proteasomes, to be presented by the MHC I pathway. We have used M as a model to study this process and determine how ER quality control monitors these foreign polymeric proteins and disposes of them through the ER-associated degradation (ERAD) pathway. Using both wild type and mutant HBV M protein, we found that unlike most ERAD substrates, which require ubiquitination for retrotranslocation and degradation, the HBV M protein, which only contains two lysine residues, can undergo rapid and complete, ubiquitin independent, proteasome dependent degradation. The utilization of this pathway had a functional consequence, since proteins degraded through it, were poorly presented via MHC I. To test the hypothesis that the level of ubiquitination, independent of protein degradation, controls the level of antigen presentation, we inserted two additional lysines into both the wild type and mutant M protein. Amazingly, while the addition of the lysine residues dramatically increased the level of ubiquitination, it did not alter the rate of degradation. However and remarkably, the increased ubiquitination was associated with a dramatic increase in the level of antigen presentation. In conclusion, using the HBV surface protein as a model, we have identified a novel ubiquitin independent degradation pathway and determined that this pathway can have implications for antigen presentation and potentially viral pathogenesis.
MHC Class I-Presented T Cell Epitopes Identified by Immunoproteomics Analysis Are Targets for a Cross Reactive Influenza-Specific T Cell Response
James S. Testa,Vivekananda Shetty,Julie Hafner,Zacharie Nickens,Shivali Kamal,Gomathinayagam Sinnathamby,Ramila Philip
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0048484
Abstract: Influenza virus infection and the resulting complications are a significant global public health problem. Improving humoral immunity to influenza is the target of current conventional influenza vaccines, however, these are generally not cross-protective. On the contrary, cell-mediated immunity generated by primary influenza infection provides substantial protection against serologically distinct viruses due to recognition of cross-reactive T cell epitopes, often from internal viral proteins conserved between viral subtypes. Efforts are underway to develop a universal flu vaccine that would stimulate both the humoral and cellular immune responses leading to long-lived memory. Such a universal vaccine should target conserved influenza virus antibody and T cell epitopes that do not vary from strain to strain. In the last decade, immunoproteomics, or the direct identification of HLA class I presented epitopes, has emerged as an alternative to the motif prediction method for the identification of T cell epitopes. In this study, we used this method to uncover several cross-specific MHC class I specific T cell epitopes naturally presented by influenza A-infected cells. These conserved T cell epitopes, when combined with a cross-reactive antibody epitope from the ectodomain of influenza M2, generate cross-strain specific cell mediated and humoral immunity. Overall, we have demonstrated that conserved epitope-specific CTLs could recognize multiple influenza strain infected target cells and, when combined with a universal antibody epitope, could generate virus specific humoral and T cell responses, a step toward a universal vaccine concept. These epitopes also have potential as new tools to characterize T cell immunity in influenza infection, and may serve as part of a universal vaccine candidate complementary to current vaccines.
MHC Class I Presented T Cell Epitopes as Potential Antigens for Therapeutic Vaccine against HBV Chronic Infection
Joseph D. Comber,Aykan Karabudak,Vivekananda Shetty,James S. Testa,Xiaofang Huang,Ramila Philip
Hepatitis Research and Treatment , 2014, DOI: 10.1155/2014/860562
Abstract: Approximately 370 million people worldwide are chronically infected with hepatitis B virus (HBV). Despite the success of the prophylactic HBV vaccine, no therapeutic vaccine or other immunotherapy modality is available for treatment of chronically infected individuals. Clearance of HBV depends on robust, sustained CD8+ T activity; however, the limited numbers of therapeutic vaccines tested have not induced such a response. Most of these vaccines have relied on peptide prediction algorithms to identify MHC-I epitopes or characterization of T cell responses during acute infection. Here, we took an immunoproteomic approach to characterize MHC-I restricted epitopes from cells chronically infected with HBV and therefore more likely to represent the true targets of CD8+ T cells during chronic infection. In this study, we identified eight novel MHC-I restricted epitopes derived from a broad range of HBV proteins that were capable of activating CD8+ T cells. Furthermore, five of the eight epitopes were able to bind HLA-A2 and A24 alleles and activated HBV specific T cell responses. These epitopes also have potential as new tools to characterize T cell immunity in chronic HBV infection and may serve as candidate antigens for a therapeutic vaccine against HBV infection. 1. Introduction Hepatitis B virus (HBV) is a member of the Hepadnaviridae family of viruses which also includes woodchuck hepatitis virus (WHV) and duck hepatitis B virus. These viruses are primarily hepatotropic with infections characterized by fever, fatigue, muscle aches, and yellowing of the eyes and/or skin. The severity of these symptoms can vary with a proportion of cases being asymptomatic [1]. More than 2.5 billion people worldwide have been infected by HBV, but, for the vast majority of adults encountering the virus (>90%), the infection is acute and readily cleared by the immune system [2, 3]. For the remaining 5–10% of adults, and for neonates and unvaccinated children, HBV establishes a chronic infection. Approximately 370 million people worldwide are chronically infected and over 500,000 people die each year due to complications from HBV [1, 4]. These complications include liver cirrhosis, liver failure, and/or hepatocellular carcinoma (HCC) and it is estimated that up to 40% of chronically infected patients will develop at least one of these complications [5]. The primary determinant of whether hepatitis B virus is cleared or establishes a chronic infection is the robustness of the immune response, in particular the CD8+ T cell response [6–9]. Data from both animal models and
Unique and differential protein signatures within the mononuclear cells of HIV-1 and HCV mono-infected and co-infected patients
Nawal Boukli, Vivekananda Shetty, Luis Cubano, Martha Ricaurte, Jordana Coelho-dos-Reis, Zacharie Nickens, Punit Shah, Andrew H. Talal, Ramila Philip, pooja Jain
Clinical Proteomics , 2012, DOI: 10.1186/1559-0275-9-11
Abstract: In this study, we investigated the proteome profiles of peripheral blood mononuclear cells from HIV-1 mono-, HCV mono-, and HIV-1/HCV co-infected patients. The results of high-resolution 2D gel electrophoresis and PD quest software quantitative analysis revealed that several proteins were differentially expressed in HIV-1, HCV, and HIV-1/HCV co-infection. Liquid chromatography-mass spectrometry and Mascot database matching (LC-MS/MS analysis) successfully identified 29 unique and differentially expressed proteins. These included cytoskeletal proteins (tropomyosin, gelsolin, DYPLSL3, DYPLSL4 and profilin-1), chaperones and co-chaperones (HSP90-beta and stress-induced phosphoprotein), metabolic and pre-apoptotic proteins (guanosine triphosphate [GTP]-binding nuclear protein Ran, the detoxifying enzyme glutathione S-transferase (GST) and Rho GDP-dissociation inhibitor (Rho-GDI), proteins involved in cell prosurvival mechanism, and those involved in matrix synthesis (collagen binding protein 2 [CBP2]). The six most significant and relevant proteins were further validated in a group of mono- and co-infected patients (n = 20) at the transcriptional levels. Conclusions: The specific pro and anti- apoptotic protein signatures revealed in this study could facilitate the understanding of apoptotic and protective immune-mediated mechanisms underlying HIV-1 and HCV co-infection and their implications on liver disease progression in co-infected patients.
Understanding India, globalisation and health care systems: a mapping of research in the social sciences
Ramila Bisht, Emma Pitchforth, Susan F Murray
Globalization and Health , 2012, DOI: 10.1186/1744-8603-8-32
Abstract: Current globalisation is regarded as a new phase of world integration with increased density and frequency of international or global social interactions relative to local or national ones. In these new dynamics, nation states are influenced by transnational processes occurring on multiple economic, political and cultural levels [1]. Much public health literature still assumes a default model of a ‘healthcare system’ bounded by a nation state which to varying degrees takes responsibility for the four essential functions of service provision, resource generation, financing and stewardship [2], but there is increasing awareness that globalisation processes are shaping local health systems in important ways [3]. In this article we set out to map through the lens of India’s healthcare and its relationship to transnational health care systems, the current extent and form of the social science approaches to an understanding of this field.India is an illuminating case for which one would expect to find a considerable body of literature. The country has emerged as one of the so-called ‘Rising Powers’ which represent drivers of global economic and social change. Healthcare is one of India’s largest sectors in terms of revenue and employment, and is expanding rapidly. The private sector accounts for more than 80% of total healthcare spending within India [4]. Since ‘liberalisation’ of economic policies in the late 1980s, India has also become increasingly attractive to foreign investors with its low costs and large, English-speaking, workforce. During the 1990s, Indian healthcare grew at a compound annual rate of 16% and today the total value of the sector is more than $34 billion and projected to grow to nearly $40 billion by 2012. The consultancy group Pricewaterhouse Coopers’ Emerging Market Report on Healthcare in India[5] listed a number of ‘flourishing market opportunities’ for foreign as well as national companies: medical tourism (often combining elective surgery and
Understanding health systems, health economies and globalization: the need for social science perspectives
Susan F Murray, Ramila Bisht, Rama Baru, Emma Pitchforth
Globalization and Health , 2012, DOI: 10.1186/1744-8603-8-30
Abstract: The peer-reviewed, online open-access journal Globalization and Health was established in [2005] with the aim of providing an international forum for high quality original research, knowledge sharing and debate on the topic of globalization and its effects on health, both positive and negative. Within its stated scope the journal recognises the complexity and breadth of topics and the range of disciplinary perspectives required to understand the relationship between globalization and health. In this editorial and special issue we pay attention to the particular contribution of social science. Social scientists, including economists, political scientists and sociologists, have undoubtedly been key contributors to the discussions and theorising about globalization processes since they began to use the term in the [1960]s, long its current widespread use. That theoretical armoury is combined with research approaches that lend themselves well to exploration of the micro, meso and macro forces that confront health systems in the globalizing world, and one would expect to see prominent participation of these disciplines in current published research in this field. The review paper by Bisht et al. [] published in this special issue examines the broader ‘state of the art’ in this regard using the case of research on India, and gives suggestions for future ways forward. [1] We also undertook a mapping of this journal’s own content in order to track trends, emphases, commonalities and differences in the work published over the first six full years of its operation ( [2005,2010]) and to locate the place of social science within its content so far. Ninety four papers were reviewed for topic, author’s institution, disciplinary perspective, geographical focus, methodology and funding. Topics were then grouped into more general themes.The topic areas of HIV/AIDS and globalization and food, diet and obesity have been consistent themes throughout the early years of the journal, as h
Reducing consumption to avert catastrophic global climate change: The case of aviation  [PDF]
Philip Cafaro
Natural Science (NS) , 2013, DOI: 10.4236/ns.2013.51A016

Avoiding potentially catastrophic global climate change is a moral imperative, demanding significant reductions in greenhouse gas emissions from all important transport sectors, including aviation. However, because passenger flights and freight traffic are increasing much faster than efficiency improvements, the aviation sector will not be able to reduce emissions, or even stabilize them at current levels, without direct, forceful action to reduce demand. This paper reviews the ethical principles and empirical realities supporting the case for reducing worldwide aviation traffic. It argues that most passenger air travel and air freight shipping represents unnecessary luxury consumption, which responsible moral agents should willingly reduce in order to mitigate global climate change. It considers several mechanisms for doing so, and contends that they may succeed, but only if combined with an explicit recognition and binding commitment that for the foreseeable future, aviation must be a slow-growth or no-growth sector of the world economy.

Linking Regional Science and Urban Economics: Long-Run Interactions among Preferences for Amenities and Public Goods  [PDF]
Philip E. Philip E. Graves
Modern Economy (ME) , 2012, DOI: 10.4236/me.2012.33035
Abstract: The linked nature of long-term patterns of urban deconcentration and regional change (from rustbelt to sunbelt in the U.S., but with similar phenomena increasingly world-wide) is analyzed in a framework that emphasizes heterogeneous human preferences. The focus is on the important interactions that exist between local and regional amenities, whether exogenous or endogenous. The central thesis is that persistent exogenous amenity variation among regions provides an underlying pattern of regional growth and decline. However, inappropriate provision of local public goods in central cities is seen to lead both to non-optimally large levels of suburbanization and to rates of regional change that are also non-optimally large.
Economic Growth and Business Cycles: The Labor Supply Decision with Two Types of Technological Progress  [PDF]
Philip E. Graves
Modern Economy (ME) , 2011, DOI: 10.4236/me.2011.23033
Abstract: An informal model is described that leads to multiple macroeconomic equilibria as a consequence of random variation in the relative amounts of technological change for new and existing goods. The novel observation is that the rate of introduction and market penetration of new goods (sometimes called product innovation) vis-à-vis technological advance for existing goods (sometimes called process innovation) importantly affects the labor supply decision. A relatively rapid influx of new goods will generally increase labor supply, while relatively more technological advance for existing goods will reduce labor supply to the market. These impacts are seen to provide insights into Rostow’s stages of growth. Short run variations in the relative importance of the two types of technological change are seen to imply unpredictable business cycle behavior of the type we observe. The welfare implications of national income accounting that fails to consider changes in leisure are discussed.
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