Antigen-Induced Immunomodulation in the Pathogenesis of Atherosclerosis

Atherosclerosis is a chronic inflammatory disorder characterised by the accumulation of monocytes/macrophages, smooth muscle cells, and lymphocytes within the arterial wall in response to the release of proinflammatory molecules. Such accumulation results in the formation of the atherosclerotic plaque, which would eventually evolve to complications such as total artery occlusion, rupture, calcification, or aneurysm. Although the molecular mechanism responsible for the development of atherosclerosis is not completely understood, it is clear that the immune system plays a key role in the development of the atherosclerotic plaque and in its complications. There are multiple antigenic stimuli that have been associated with the pathogenesis of atherosclerosis. Most of these stimuli come from modified self-molecules such as oxidised low-density lipoproteins (oxLDLs), beta2glycoprotein1 (β2GP1), lipoprotein a (LP(a)), heat shock proteins (HSPs), and protein components of the extracellular matrix such as collagen and fibrinogen in the form of advanced glycation-end (AGE) products. In addition, several foreign antigens including bacteria such as Porphyromonas gingivalis and Chlamydia pneumoniae and viruses such as enterovirus and cytomegalovirus have been associated with atherosclerosis as potentially causative or bystander participants, adding another level of complexity to the analysis of the pathophysiology of atherosclerosis. The present review summarises the most important scientific findings published within the last two decades on the importance of antigens, antigen stimulation, and adaptive immune responses in the development of atherosclerotic plaques

Surveillance for Neisseria meningitidis Disease Activity and Transmission Using Information Technology

Background While formal reporting, surveillance, and response structures remain essential to protecting public health, a new generation of freely accessible, online, and real-time informatics tools for disease tracking are expanding the ability to raise earlier public awareness of emerging disease threats. The rationale for this study is to test the hypothesis that the HealthMap informatics tools can complement epidemiological data captured by traditional surveillance monitoring systems for meningitis due to Neisseria meningitides (N. meningitides) by highlighting severe transmissible disease activity and outbreaks in the United States. Methods Annual analyses of N. meningitides disease alerts captured by HealthMap were compared to epidemiological data captured by the Centers for Disease Control’s Active Bacterial Core surveillance (ABCs) for N. meningitides. Morbidity and mortality case reports were measured annually from 2010 to 2013 (HealthMap) and 2005 to 2012 (ABCs). Findings HealthMap N. meningitides monitoring captured 80-90% of alerts as diagnosed N. meningitides, 5-20% of alerts as suspected cases, and 5-10% of alerts as related news articles. HealthMap disease alert activity for emerging disease threats related to N. meningitides were in agreement with patterns identified historically using traditional surveillance systems. HealthMap’s strength lies in its ability to provide a cumulative “snapshot” of weak signals that allows for rapid dissemination of knowledge and earlier public awareness of potential outbreak status while formal testing and confirmation for specific serotypes is ongoing by public health authorities. Conclusions The underreporting of disease cases in internet-based data streaming makes inadequate any comparison to epidemiological trends illustrated by the more comprehensive ABCs network published by the Centers for Disease Control. However, the expected delays in compiling confirmatory reports by traditional surveillance systems (at the time of writing, ABCs data for 2013 is listed as being provisional) emphasize the helpfulness of real-time internet-based data streaming to quickly fill gaps including the visualization of modes of disease transmission in outbreaks for better resource and action planning. HealthMap can also contribute as an internet-based monitoring system to provide real-time channel for patients to report intervention-related failures.National Library of Medicine (U.S.) (Grant 5 R01 LM010812-04

Analisis Proses Seleksi Tenaga Kerja Di De Boliva Café Surabaya Town Square

Penelitian ini dilakukan di De Boliva Café Surabaya Town Square. Tujuan dalam penelitian ini adalah untuk mengetahui proses seleksi tenaga kerja. Teknik analisis yang digunakan dalam penelitian ini adalah analisis kualitatif deksriptif. Hasil analisis menunjukkan bahwa proses seleksi tenaga kerja di De Boliva adalah seleksi curriculum vitae (CV) beserta surat lamaran, tes tulis, wawancara video, dan wawancara akhir

A novel transport mechanism for MOMP in Chlamydophila pneumoniae and its putative role in immune-therapy

Major outer membrane proteins (MOMPs) of Gram negative bacteria are one of the most intensively studied membrane proteins. MOMPs are essential for maintaining the structural integrity of bacterial outer membranes and in adaptation of parasites to their hosts. There is evidence to suggest a role for purified MOMP from Chlamydophila pneumoniae and corresponding MOMP-derived peptides in immune-modulation, leading to a reduced atherosclerotic phenotype in apoE−/− mice via a characteristic dampening of MHC class II activity. The work reported herein tests this hypothesis by employing a combination of homology modelling and docking to examine the detailed molecular interactions that may be responsible. A three-dimensional homology model of the C. pneumoniae MOMP was constructed based on the 14 transmembrane β-barrel crystal structure of the fatty acid transporter from Escherichia coli, which provides a plausible transport mechanism for MOMP. Ligand docking experiments were used to provide details of the possible molecular interactions driving the binding of MOMP-derived peptides to MHC class II alleles known to be strongly associated with inflammation. The docking experiments were corroborated by predictions from conventional immuno-informatic algorithms. This work supports further the use of MOMP in C. pneumoniae as a possible vaccine target and the role of MOMP-derived peptides as vaccine candidates for immune-therapy in chronic inflammation that can result in cardiovascular events

Proteomic identification and characterization of hepatic glyoxalase 1 dysregulation in non-alcoholic fatty liver disease

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. However, its molecular pathogenesis is incompletely characterized and clinical biomarkers remain scarce. The aims of these experiments were to identify and characterize liver protein alterations in an animal model of early, diet-related, liver injury and to assess novel candidate biomarkers in NAFLD patients. Methods: Liver membrane and cytosolic protein fractions from high fat fed apolipoprotein E knockout (ApoE−/−) animals were analyzed by quantitative proteomics, utilizing isobaric tags for relative and absolute quantitation (iTRAQ) combined with nano-liquid chromatography and tandem mass spectrometry (nLC-MS/MS). Differential protein expression was confirmed independently by immunoblotting and immunohistochemistry in both murine tissue and biopsies from paediatric NAFLD patients. Candidate biomarkers were analyzed by enzyme-linked immunosorbent assay in serum from adult NAFLD patients. Results: Through proteomic profiling, we identified decreased expression of hepatic glyoxalase 1 (GLO1) in a murine model. GLO1 protein expression was also found altered in tissue biopsies from paediatric NAFLD patients. In vitro experiments demonstrated that, in response to lipid loading in hepatocytes, GLO1 is first hyperacetylated then ubiquitinated and degraded, leading to an increase in reactive methylglyoxal. In a cohort of 59 biopsy-confirmed adult NAFLD patients, increased serum levels of the primary methylglyoxal-derived advanced glycation endproduct, hydroimidazolone (MG-H1) were significantly correlated with body mass index (r = 0.520, p < 0.0001). Conclusion: Collectively these results demonstrate the dysregulation of GLO1 in NAFLD and implicate the acetylation-ubquitination degradation pathway as the functional mechanism. Further investigation of the role of GLO1 in the molecular pathogenesis of NAFLD is warranted. Keywords: Non-alcoholic fatty liver disease, Glyoxalase, Methylglyoxal, Proteomics, iTRA

Gestión del conocimiento: perspectiva multidisciplinaria. Volumen 11

El libro “Gestión del Conocimiento. Perspectiva Multidisciplinaria”, Volumen 11, de la Colección Unión Global, es resultado de investigaciones. Los capítulos del libro, son resultados de investigaciones desarrolladas por sus autores. El libro cuenta con el apoyo de los grupos de investigación: Universidad Sur del Lago “Jesús María Semprúm” (UNESUR), Zulia – Venezuela; Universidad Politécnica Territorial de Falcón Alonso Gamero (UPTAG), Falcón – Venezuela; Universidad Politécnica Territorial de Mérida Kleber Ramírez (UPTM), Mérida – Venezuela; Universidad Guanajuato (UG) - Campus Celaya - Salvatierra - Cuerpo Académico de Biodesarrollo y Bioeconomía en las Organizaciones y Políticas Públicas (C.A.B.B.O.P.P), Guanajuato – México; Centro de Altos Estudios de Venezuela (CEALEVE), Zulia – Venezuela, Centro Integral de Formación Educativa Especializada del Sur (CIFE - SUR) - Zulia - Venezuela, Centro de Investigaciones Internacionales SAS (CIN), Antioquia - Colombia.y diferentes grupos de investigación del ámbito nacional e internacional que hoy se unen para estrechar vínculos investigativos, para que sus aportes científicos formen parte de los libros que se publiquen en formatos digital e impreso

Gap junctions and connexins: potential contributors to the immunological synapse

Gap junctional communication is a widespread mechanism for metabolic coupling of adjoining cells. In the immune system, evidence has built up showing that lymphocytes possess the protein building blocks of gap junctions, the connexins. The most widespread is connexin 43, but connexin 40 is also present in secondary lymphoid organs. Inhibitors of gap junctional communication, especially the highly specific connexin mimetic peptides, have been shown to decrease the secretion of immunoglobulins and cytokines by T and B lymphocyte cocultures, indicating that connexins may play a fundamental role in lymphocyte physiology. Traditionally, connexins function when assembled into gap junction-intercellular channels. However, the possibility is now arising that gap junction hemichannels, previously viewed as plasma membrane precursors of gap junctions, are also involved in the release from cells of small metabolites, e.g., adenosine 5'-triphosphate and nicotinamide adenine dinucleotide(+), and this opens up a second, possible paracrine function for connexins detected in lymphocytes. The increasing structural and functional evidence points to a potential role that lymphocyte gap junctional intercellular communication may play within the complex signaling components of the immunological synapse