Risks in the North Caucasus: Potential or Real Escalation of the Ethnopolitical Situation

Introduction. Positive dynamics in the ethnopolitical sphere of the North Caucasus does not mean that there are no further risks of the escalation of the ethnopolitical tension and stabilizing processes are irreversible. The goal and objectives of the article are the identification of the current ethnopolitical situation in the North Caucasus and assessment of the achievements or failures of the decade-long implementation of programs of reconstructiong the region. The authors identify risk factors of the ethnopolitical tension in the North Caucasus as a key approach to conflict forecasting, develop a hierarchy of risk factors, and assess the optimality of management decisions. Methods and discussion. In the context of the discussion the most relevant is understanding risks as an inevitable product of decision-making (Luhmann). The analysis of risk generating processes in the North Caucasus is most effective from the standpoint of the conflict studies (conflict resolution) approach (Burton). Empirical data was obtained by series of expert surveys, the Delphi method, content analysis of media sources (the Internet, printed press, radio, television) and analysis of official statistical data. The conclusion was made that during the past three years positive results have been achieved mainly due to administrative resources and activities of the institutions of force (“siloviki”), but those resources are close to exhaustion. All “classical” risk factors identified by the country’s leadership in 2009 remain and “new” risk factors are actualized. Among the “classical” risks, the first positions are occupied by the low level of industrial production, the critical dependence of the North Caucasus republics on federal budget subsidies, the lag in life standards in these republics from the average in Russia, the retention of a high unemployment rate. These risks are to a large extent due to such factor as the low efficiency of regional authorities. The “new” risk factors include those that were in a latent state, but now can turn into manifest conflicts. This is, above all, a land-use problem that has various modifications: ethnic, territorial, economic, historical. Further studies of the problems of the North Caucasus are related to the analysis of the effectiveness of the system of ethnopolitical security and centre-peripheral relations, to the new non-trivial approaches in the theory of Russian federalism, to the choice of a model of spatial development of the Russian Federation. Analysis and results. Despite the general improvement of the climate of ethnic relations, risk factors in the ethnopolitical situation in the North Caucasus can result in the return of the region to the negative conflict scenario. The modern North Caucasus can be characterized as a risk society, in which risks appear as a result of decision making more and more frequently. Some positive “shifts” in the economic and social basis of life in the region are not sufficient for irreversible changes of the situation for the better. The specificity of current problems in the North Caucasus is that their conflict potential can be implemented “unexpectedly” through various indirect links

Global Proteomic Analysis Reveals an Exclusive Role of Thylakoid Membranes in Bioenergetics of a Model Cyanobacterium

Cyanobacteria are photosynthetic microbes with highly differentiated membrane systems. These organisms contain an outer membrane, plasma membrane, and an internal system of thylakoid membranes where the photosynthetic and respiratory machinery are found. This existence of compartmentalization and differentiation of membrane systems poses a number of challenges for cyanobacterial cells in terms of organization and distribution of proteins to the correct membrane system. Proteomics studies have long sought to identify the components of the different membrane systems in cyanobacteria, and to date about 450 different proteins have been attributed to either the plasma membrane or thylakoid membrane. Given the complexity of these membranes, many more proteins remain to be identified, and a comprehensive catalogue of plasma membrane and thylakoid membrane proteins is needed. Here we describe the identification of 635 differentially localized proteins in Synechocystis sp. PCC 6803 by quantitative iTRAQ isobaric labeling; of these, 459 proteins were localized to the plasma membrane and 176 were localized to the thylakoid membrane. Surprisingly, we found over 2.5 times the number of unique proteins identified in the plasma membrane compared with the thylakoid membrane. This suggests that the protein composition of the thylakoid membrane is more homogeneous than the plasma membrane, consistent with the role of the plasma membrane in diverse cellular processes including protein trafficking and nutrient import, compared with a more specialized role for the thylakoid membrane in cellular energetics. Thus, our data clearly define the two membrane systems with distinct functions. Overall, the protein compositions of the Synechocystis 6803 plasma membrane and thylakoid membrane are quite similar to that of the plasma membrane of Escherichia coli and thylakoid membrane of Arabidopsis chloroplasts, respectively. Synechocystis 6803 can therefore be described as a Gram-negative bacterium with an additional internal membrane system that fulfills the energetic requirements of the cell

Dynamic proteomic profiling of a unicellular cyanobacterium Cyanothece ATCC51142 across light-dark diurnal cycles

<p>Abstract</p> <p>Background</p> <p>Unicellular cyanobacteria of the genus <it>Cyanothece </it>are recognized for their ability to execute nitrogen (N₂)-fixation in the dark and photosynthesis in the light. An understanding of these mechanistic processes in an integrated systems context should provide insights into how <it>Cyanothece </it>might be optimized for specialized environments and/or industrial purposes. Systems-wide dynamic proteomic profiling with mass spectrometry (MS) analysis should reveal fundamental insights into the control and regulation of these functions.</p> <p>Results</p> <p>To expand upon the current knowledge of protein expression patterns in <it>Cyanothece </it>ATCC51142, we performed quantitative proteomic analysis using partial ("unsaturated") metabolic labeling and high mass accuracy LC-MS analysis. This dynamic proteomic profiling identified 721 actively synthesized proteins with significant temporal changes in expression throughout the light-dark cycles, of which 425 proteins matched with previously characterized cycling transcripts. The remaining 296 proteins contained a cluster of proteins uniquely involved in DNA replication and repair, protein degradation, tRNA synthesis and modification, transport and binding, and regulatory functions. Functional classification of labeled proteins suggested that proteins involved in respiration and glycogen metabolism showed increased expression in the dark cycle together with nitrogenase, suggesting that N₂-fixation is mediated by higher respiration and glycogen metabolism. Results indicated that <it>Cyanothece </it>ATCC51142 might utilize alternative pathways for carbon (C) and nitrogen (N) acquisition, particularly, aspartic acid and glutamate as substrates of C and N, respectively. Utilization of phosphoketolase (PHK) pathway for the conversion of xylulose-5P to pyruvate and acetyl-P likely constitutes an alternative strategy to compensate higher ATP and NADPH demand.</p> <p>Conclusion</p> <p>This study provides a deeper systems level insight into how <it>Cyanothece </it>ATCC51142 modulates cellular functions to accommodate photosynthesis and N₂-fixation within the single cell.</p

Antibody‐independent targeted quantification of TMPRSS2‐ERG fusion protein products in prostate cancer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135707/1/mol22014871169-sup-mmc1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135707/2/mol22014871169.pd

Comprehensive Proteomics Analysis of Stressed Human Islets Identifies GDF15 as a Target for Type 1 Diabetes Intervention

Type 1 diabetes (T1D) results from the progressive loss of β cells, a process propagated by pro-inflammatory cytokine signaling that disrupts the balance between pro- and anti-apoptotic proteins. To identify proteins involved in this process, we performed comprehensive proteomics of human pancreatic islets treated with interleukin-1β and interferon-γ, leading to the identification of 11,324 proteins, of which 387 were significantly regulated by treatment. We then tested the function of growth/differentiation factor 15 (GDF15), which was repressed by the treatment. We found that GDF15 translation was blocked during inflammation, and it was depleted in islets from individuals with T1D. The addition of exogenous GDF15 inhibited interleukin-1β+interferon-γ-induced apoptosis of human islets. Administration of GDF15 reduced by 53% the incidence of diabetes in NOD mice. Our approach provides a unique resource for the identification of the human islet proteins regulated by cytokines and was effective in discovering a potential target for T1D therapy

Integrative Analysis of the Mitochondrial Proteome in Yeast

In this study yeast mitochondria were used as a model system to apply, evaluate, and integrate different genomic approaches to define the proteins of an organelle. Liquid chromatography mass spectrometry applied to purified mitochondria identified 546 proteins. By expression analysis and comparison to other proteome studies, we demonstrate that the proteomic approach identifies primarily highly abundant proteins. By expanding our evaluation to other types of genomic approaches, including systematic deletion phenotype screening, expression profiling, subcellular localization studies, protein interaction analyses, and computational predictions, we show that an integration of approaches moves beyond the limitations of any single approach. We report the success of each approach by benchmarking it against a reference set of known mitochondrial proteins, and predict approximately 700 proteins associated with the mitochondrial organelle from the integration of 22 datasets. We show that a combination of complementary approaches like deletion phenotype screening and mass spectrometry can identify over 75% of the known mitochondrial proteome. These findings have implications for choosing optimal genome-wide approaches for the study of other cellular systems, including organelles and pathways in various species. Furthermore, our systematic identification of genes involved in mitochondrial function and biogenesis in yeast expands the candidate genes available for mapping Mendelian and complex mitochondrial disorders in humans

Diurnal Rhythms Result in Significant Changes in the Cellular Protein Complement in the Cyanobacterium Cyanothece 51142

Cyanothece sp. ATCC 51142 is a diazotrophic cyanobacterium notable for its ability to perform oxygenic photosynthesis and dinitrogen fixation in the same single cell. Previous transcriptional analysis revealed that the existence of these incompatible cellular processes largely depends on tightly synchronized expression programs involving ∼30% of genes in the genome. To expand upon current knowledge, we have utilized sensitive proteomic approaches to examine the impact of diurnal rhythms on the protein complement in Cyanothece 51142. We found that 250 proteins accounting for ∼5% of the predicted ORFs from the Cyanothece 51142 genome and 20% of proteins detected under alternating light/dark conditions exhibited periodic oscillations in their abundances. Our results suggest that altered enzyme activities at different phases during the diurnal cycle can be attributed to changes in the abundance of related proteins and key compounds. The integration of global proteomics and transcriptomic data further revealed that post-transcriptional events are important for temporal regulation of processes such as photosynthesis in Cyanothece 51142. This analysis is the first comprehensive report on global quantitative proteomics in a unicellular diazotrophic cyanobacterium and uncovers novel findings about diurnal rhythms

The cerebrospinal fluid proteome in HIV infection: change associated with disease severity

<p>Abstract</p> <p>Background</p> <p>Central nervous system (CNS) infection is a nearly universal feature of untreated systemic HIV infection with a clinical spectrum that ranges from chronic asymptomatic infection to severe cognitive and motor dysfunction. Analysis of cerebrospinal fluid (CSF) has played an important part in defining the character of this evolving infection and response to treatment. To further characterize CNS HIV infection and its effects, we applied advanced high-throughput proteomic methods to CSF to identify novel proteins and their changes with disease progression and treatment.</p> <p>Results</p> <p>After establishing an <it>accurate mass and time </it>(AMT) tag database containing 23,141 AMT tags for CSF peptides, we analyzed 91 CSF samples by LC-MS from 12 HIV-uninfected and 14 HIV-infected subjects studied in the context of initiation of antiretroviral therapy and correlated abundances of identified proteins a) within and between subjects, b) with all other proteins across the entire sample set, and c) with "external" CSF biomarkers of infection (HIV RNA), immune activation (neopterin) and neural injury (neurofilament light chain protein, NFL). We identified a mean of 2,333 +/- 328 (SD) peptides covering 307 +/-16 proteins in the 91 CSF sample set. Protein abundances differed both between and within subjects sampled at different time points and readily separated those with and without HIV infection. Proteins also showed inter-correlations across the sample set that were associated with biologically relevant dynamic processes. One-hundred and fifty proteins showed correlations with the external biomarkers. For example, using a threshold of cross correlation coefficient (Pearson's) ≤ -0.3 and ≥0.3 for potentially meaningful relationships, a total of 99 proteins correlated with CSF neopterin (43 negative and 56 positive correlations) and related principally to neuronal plasticity and survival and to innate immunity. Pathway analysis defined several networks connecting the identified proteins, including one with amyloid precursor protein as a central node.</p> <p>Conclusions</p> <p>Advanced CSF proteomic analysis enabled the identification of an array of novel protein changes across the spectrum of CNS HIV infection and disease. This initial analysis clearly demonstrated the value of contemporary state-of-the-art proteomic CSF analysis as a discovery tool in HIV infection with likely similar application to other neurological inflammatory and degenerative diseases.</p

Coupled transcriptome and proteome analysis of human lymphotropic tumor viruses: insights on the detection and discovery of viral genes

<p>Abstract</p> <p>Background</p> <p>Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are related human tumor viruses that cause primary effusion lymphomas (PEL) and Burkitt's lymphomas (BL), respectively. Viral genes expressed in naturally-infected cancer cells contribute to disease pathogenesis; knowing which viral genes are expressed is critical in understanding how these viruses cause cancer. To evaluate the expression of viral genes, we used high-resolution separation and mass spectrometry coupled with custom tiling arrays to align the viral proteomes and transcriptomes of three PEL and two BL cell lines under latent and lytic culture conditions.</p> <p>Results</p> <p>The majority of viral genes were efficiently detected at the transcript and/or protein level on manipulating the viral life cycle. Overall the correlation of expressed viral proteins and transcripts was highly complementary in both validating and providing orthogonal data with latent/lytic viral gene expression. Our approach also identified novel viral genes in both KSHV and EBV, and extends viral genome annotation. Several previously uncharacterized genes were validated at both transcript and protein levels.</p> <p>Conclusions</p> <p>This systems biology approach coupling proteome and transcriptome measurements provides a comprehensive view of viral gene expression that could not have been attained using each methodology independently. Detection of viral proteins in combination with viral transcripts is a potentially powerful method for establishing virus-disease relationships.</p