RESUMEN
Disease comorbidity is a result of complex epigenetic interplay. A disease is rarely a consequence of an abnormality in a single gene; complex pathways to disease patterns emerge from gene-gene interactions and gene-environment interactions. Understanding these mechanisms of disease and comorbidity development, breaking down them into clusters and disentangling the epigenetic - actionable - components, is of utter importance from a public health perspective. With the increase in the average life expectancy, healthy aging becomes a primary objective, from both an individual (i.e. quality of life) and a societal (i.e. healthcare costs) standpoint. Many studies have analyzed disease networks based on common altered genes, on protein-protein interactions, or on shared disease comorbidites, i.e. phenotypic disease networks. In this work we aim at studying the relations between genotypic and phenotypic disease networks, using a large statewide cohort of individuals (100, 000+ from California, USA) with linked clinical and genotypic information, the Genetic Epidemiology Research on Adult Health and Aging (GERA). By comparing their phenotypic and genotypic networks, we try to disentangle the epigenetic component of disease comorbidity.
RESUMEN
AIMS: This study examined the development of bacterial biofilms within a metropolitan distribution system. The distribution system is fed with different source water (i.e. groundwater, GW and surface water, SW) and undergoes different treatment processes in separate facilities. METHODS AND RESULTS: The biofilm community was characterized using 16S rRNA gene clone libraries and functional potential analysis, generated from total DNA extracted from coupons in biofilm annular reactors fed with onsite drinking water for up to 18 months. Differences in the bacterial community structure were observed between GW and SW. Representatives that explained the dissimilarity were associated with the classes Betaproteobacteria, Alphaproteobacteria, Actinobacteria, Gammaproteobacteria and Firmicutes. After 9 months the biofilm bacterial community from both GW and SW were dominated by Mycobacterium species. The distribution of the dominant operational taxonomic unit (OTU) (Mycobacterium) positively correlated with the drinking water distribution system (DWDS) temperature. CONCLUSIONS: In this study, the biofilm community structure observed between GW and SW were dissimilar, while communities from different locations receiving SW did not show significant differences. The results suggest that source water and/or the water quality shaped by their respective treatment processes may play an important role in shaping the bacterial communities in the distribution system. In addition, several bacterial groups were present in all samples, suggesting that they are an integral part of the core microbiota of this DWDS. SIGNIFICANCE AND IMPACT OF THE STUDY: These results provide an ecological insight into biofilm bacterial structure in chlorine-treated drinking water influenced by different water sources and their respective treatment processes.
Asunto(s)
Bacterias/aislamiento & purificación , Biodiversidad , Biopelículas , Agua Potable/microbiología , Bacterias/clasificación , Bacterias/genética , Cloro/análisis , Agua Potable/análisis , Agua Subterránea/análisis , Agua Subterránea/microbiología , Purificación del Agua , Calidad del Agua , Abastecimiento de Agua/normasRESUMEN
The zero-mean circular complex Gaussian field statistics of a random medium are experimentally demonstrated in the optical domain, thus verifying this key assumption of statistical optics. Using a frequency-tunable laser source in a fixed-path-length interferometer, we obtain optical field fluctuations in the time and frequency domains that clearly show that the ensemble-averaged temporal intensity converges to the photon transit time distribution, which for the samples used is in excellent agreement with a diffusion model.
RESUMEN
BACKGROUND: In ulcerative colitis (UC) the activation (i.e. nuclear translocation) of nuclear factor kappa B (NF-kappaB) is an important step in the regulation of cytokines secreted by lamina propria macrophages. Clinical trials suggest anti-inflammatory effects of locally administered butyrate in UC. The potential effects of butyrate on NF-kappaB activation in lamina propria macrophages of UC patients were investigated. METHODS: Eleven patients with distal UC were treated for up to 8 weeks with butyrate at 100 mM (n = 6) or placebo (n = 5) enemas. At entry and after 4 and 8 weeks, clinical status was noted and intestinal inflammation was graded endoscopically and histologically. Double-staining with antibodies against NF-kappaB (p65) and CD68 was employed to detect NF-kappaB and macrophages, respectively. RESULTS: In untreated patients, nuclear translocation of NF-kappaB was detectable in virtually all macrophages. Butyrate treatment for 4 and 8 weeks resulted in a significant reduction in the number of macrophages being positive for nuclear translocated NF-kappaB. In addition, butyrate significantly reduced both the number of neutrophils in crypt and surface epithelia and of the lamina propria lymphocytes/plasma cells. These findings correlated with a significant decrease in the Disease Activity Index (DAI). CONCLUSIONS: The decrease in DAI and mucosal inflammation in butyrate-treated patients is associated with a reduction of NF-kappaB translocation in lamina propria macrophages. Since the inflammatory process in UC is mainly sustained by macrophage-derived cytokines, the known anti-inflammatory effects of butyrate may in part be mediated by an inhibition of NF-kappaB activation in these macrophages.
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Butiratos/uso terapéutico , Colitis Ulcerosa/metabolismo , Mucosa Intestinal/patología , Macrófagos/metabolismo , FN-kappa B/metabolismo , Adulto , Butiratos/administración & dosificación , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/patología , Colon/patología , Enema , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , FN-kappa B/efectos de los fármacosRESUMEN
Nuclear factor-kappa B (NF-kappaB) is a critical transcription factor for the inducible expression of multiple genes involved in inflammation. NF-kappaB is sequestered in the cytoplasm by inhibitory IkappaB proteins. Extracellular stimuli, notably interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) activate NF-kappaB nuclear translocation via IkappaB phosphorylation and degradation. Since previous reports suggest that the short chain fatty acid butyrate has antiinflammatory properties, the effects of butyrate on NF-kappaB nuclear translocation in human epithelial cells (HeLa229) were tested. In cells pretreated with butyrate, a time- and dose-dependent inhibition of IL-1beta-mediated NF-kappaB nuclear translocation was observed. However, IkappaB alpha phosphorylation and degradation occurred rapidly in both butyrate pretreated and nonpretreated cells, respectively. These data indicate that inhibition of IL-1beta-induced NF-kappaB activation by butyrate does not require an intact IkappaB alpha protein.
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Butiratos/farmacología , Interleucina-1/fisiología , FN-kappa B/fisiología , Translocación Genética/efectos de los fármacos , Células HeLa , Humanos , Inmunohistoquímica , FN-kappa B/genética , FosforilaciónRESUMEN
Butyrate, a short-chain fatty acid, is generated by anaerobic fermentation within the colon. Clinical trials suggest that short-chain fatty acids ameliorate inflammation in ulcerative colitis. Nuclear factor (NF) kappaB, an inducible transcription factor that is activated in inflamed colonic tissue, is sequestered to the cytoplasm by its inhibitory IkappaB proteins. The anti-inflammatory effects of butyrate are associated with an inhibition of NF-kappaB nuclear translocation. To investigate the mechanism of NF-kappaB inhibition we examined the effects of butyrate on IkappaBalpha. Human adenocarcinoma cells (SW480, SW620, and HeLa229) were treated with butyrate for up to 48 h followed by tumor necrosis factor (TNF) alpha stimulation. NF-kappaB was detected by immunofluorescence staining with an antibody against its p65 subunit. Levels of IkappBalpha and phosphorylated IkappaBalpha were determined by western blot. Stimulation with TNFalpha resulted in rapid phosphorylation and degradation of IkappaBalpha followed by NF-kappaB nuclear translocation. Butyrate pretreatment successfully inhibited NF-kappaB activation. Pretreatment of adenocarcinoma cells with butyrate is associated with inhibition of TNFalpha-mediated phosphorylation and degradation of IkappaBalpha and effective blocking of NF-kappaB nuclear translocation. The anti-inflammatory effects of butyrate may at least in part be mediated by an inhibition of IkappaBalpha mediated activation of NF-kappaB.