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Alcohol-induced alterations of the hepatocyte cytoskeleton

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World Journal of Gastroenterology 2010年第11期16卷 1358-1365页

作者： Blythe d Shepard pamela L Tuma department of Biology The Catholic University of America

The hepatocyte cytoskeleton consists of three fi lamentous networks: microtubules, actin microfi laments and keratin intermediate filaments. Because of the abundance of the proteins that comprise each system and the central role each network plays in a variety of cellular processes, the three fi lament systems have been the focus of a host of studies aimed at understanding the progression of alcohol-induced liver injury. In this review, we will briefly discuss the hepatic organization of each cytoskeletal network and highlight some components of each system. We will also describe what is known about ethanol-induced changes in the dynamics and distributions of each cytoskeletal system and discuss what is known about changes in protein expression levels and post-translational modifi cations. Finally, we will describe the possible consequences of these cytoskeletal alterations on hepatocyte function and how they might contribute to the progression of liver disease.

关键词： Ethanol Hepatotoxicity Tubulin Actin Keratin

Alcohol-induced protein hyperacetylation: Mechanisms and consequences

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World Journal of Gastroenterology 2009年第10期15卷 1219-1230页

作者： Blythe d Shepard pamela L Tuma department of Biology The Catholic University of America 620 Michigan Avenue NE Washington DC 20064 United States

Although the clinical manifestations of alcoholic liver disease are well-described, little is known about the molecular basis of liver injury. Recent studies have indicated that ethanol exposure induces global protein hyperacetylationo This reversible, post- translational modification on the E-amino groups of lysine residues has been shown to modulate multiple, diverse cellular processes ranging from transcriptional activation to microtubule stability. Thus, alcohol- induced protein hyperacetylation likely leads to major physiological consequences that contribute to alcohol-induced hepatotoxicity. Lysine acetylation is controlled by the activities of two opposing enzymes, histone acetyltransferases and histone deacetylases. Currently, efforts are aimed at determining which enzymes are responsible for the increased acetylation of specific substrates. However, the greater challenge will be to determine the physiological ramifications of protein hyperacetylation and how they might contribute to the progression of liver disease. In this review, we will first list and discuss the proteins known to be hyperacetylated in the presence of ethanol. We will then describe what is known about the mechanisms leading to increased protein acetylation and how hyperacetylation may perturb hepatic function.

关键词： Ethanol Hepatotoxicity Acetylation deacetylases Acetyltransferases

Forecasting the impacts of chemical pollution and climate change interactions on the health of wildlife

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Current Zoology 2015年第4期61卷 669-689页

作者： pamela d. NOYES Sean C. LEMA department of Environmental & Molecular Toxicology Environmental Health Sciences Center Sinnhuber Aquatic ResearchLaboratory Oregon State University Corvallis OR USA Biological Sciences department Center for Coastal Marine Sciences California Polytechnic State University San Luis Obispo CA 93407 USA

Global climate change is impacting organisms, biological communities and ecosystems around the world. While most research has focused on characterizing how the climate is changing, including modeling future climatic conditions and predicting the impacts of these conditions on biodiversity, it is also the case that climate change is altering the environmental impacts of chemical pollution. Future climate conditions are expected to influence both the worldwide distribution of chemicals and the toxi- cological consequences of chemical exposures to organisms. Many of the environmental changes associated with a warming global climate （e.g., increased average - and possibly extreme - temperatures; intense periods of drier and wetter conditions; reduced ocean pH; altered salinity dynamics in estuaries） have the potential to enhance organism susceptibility to chemical toxicity. Addi- tionally, chemical exposures themselves may impair the ability of organisms to cope with the changing environmental conditions of the shifting climate. Such reciprocity in the interactions between climate change and chemicals illustrates the complexity inherent in predicting the toxicological consequences of chemical exposures under future climate scenarios. Here, we summarize what is currently known about the potential reciprocal effects of climate change and chemical toxicity on wildlife, and depict current approaches and ongoing challenges for incorporating climate effects into chemical testing and assessment. Given the rapid pace of new man-made chemistries, the development of accurate and rapid methods to evaluate multiple chemical and non-chemical stressors in an ecologically relevant context will be critical to understanding toxic and endocrine-disrupting effects of chemical pollutants under future climate scenarios [Current Zoology 61 （4）： 669-689, 2015].

关键词： Global wanning Toxicology Metals Endocrine disruptors Risk assessment

Expression of HER2 and bradykinin B_1 receptors in precursor lesions of gallbladder carcinoma

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World Journal of Gastroenterology 2012年第11期18卷 1208-1215页

作者： Cesar Toledo Carola E Matus Ximena Barraza pamela Arroyo pamela Ehrenfeld Carlos d Figueroa Kanti d Bhoola Maeva del Pozo Maria T Poblete Laboratorio de Patologia Celular Instituto de AnatomiaHistologia y PatologiaUniversidad Austral de ChileValdivia Box 567Chile Servicio de Anatomia Patologica Hospital Base Lung Institute of Western AustraliaCentre for Asthma and Allergy Research InstituteUniversity of Western Australia

AIM： To determine the expression of HER2 and bradykinin B1 receptors （B1R） in the two pathogenic models of gallbladder cancer： the metaplasia dysplasia carcino ma and the adenoma carcinoma pathways.METHOdS： Receptor proteins were visualized by immunohistochemistry on 5-μm sections of paraffin-embedded tissue. Expression of both receptors was studied in biopsy samples from 92 patients （6 males and 86 females; age ranging from 28 to 86 years, mean 56 years）. High HER2 expression in specimens was additionally investigated by fluorescence in situ hybridization. Cell proliferation in each sample was assessed by using the Ki-67 proliferation marker.RESULTS： HER2 receptor protein was absent in adenomas and in normal gallbladder epithelium. On the contrary, there was intense staining for HER2 on the basolateral membrane of epithelial cells of intestinal metaplasia （22/24; 91.7%） and carcinoma in situ （9/10; 90%）, the lesions that displayed a significantly high proliferation index. Protein up-regulation of HER2 in the epithelium with metaplasia or carcinoma in s/tu was not accompanied by HER2 gene amplification. A similar result was observed in invasive carcinomas （0/12）. The B1R distribution pattern mirrored that of HER2 except that B1R was additionally observed in the adenomas. The B1R appeared either as cytoplasmic dots or labeling on the apical cell membrane of the cells composing the epithelia with intestinal metaplasia （24/24; 100%） and carcinoma in situ （10/10; 100%） and in the epithelial cells of adenomas. In contrast, both HER2 （4/12; 33%） and B1R （1/12; 8.3%） showed a low expression in inva- sive gallbladder carcinomas.CONCLUSION： The up-regulation of HER2 and B1R in precursor lesions of gallbladder carcinoma suggests cross-talk between these two receptors that may be of importance in the modulation of cell proliferation in gallbladder carcinogenesis,

关键词： Bradykinin BI receptor HER2 Gallbladderadenoma Gallbladder dysplasia Intestinal metaplasia Gallbladder cancer

Heating Up the Environmental Context of Chemical Pollution： Ecotoxicology in a Changing Global Climate

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Current Zoology 2015年第4期61卷 614-616页

作者： pamela d. NOYES Sean C. LEMA Guest Editors department of Environmental & Molecular Toxicology Sinnhuber Aquatic Research Laboratory Oregon State University Corvallis OR USA Biological Sciences department Center for Coastal Marine Sciences California Polytechnic State University San Luis Obispo CA USA

Humans and wildlife are exposed to an ever-increasing array of man-made chemicals that are now meas-ured in every habitat on our planet from the Earth＇s highest mountain peaks to sediments in the deep ocean （e.g., Farrington and Takada, 2014; Quiroz et al., 2009; Veron et al., 1987; Villa et al., 2006）. In addition to the expanding variety of synthetic chemistries in use, there are many substances that are components of the Earth that may through human activities concentrate at high- levels or be released into the environment in forms that enhance their bioavailability, exposure, and toxicity potential.

关键词：光环境生态毒理学全球气候化学污染加热化学物质人类活动生物利用度

Impact of a physician-supervised exercise-nutrition program with testosterone substitution in partial androgen-deficient middle-aged obese men

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Journal of Geriatric Cardiology 2011年第4期8卷 201-206页

作者： Ernst R Schwarz Robert d Willix jr Cenegenics Education and Research Foundation Las Vegas and Heart Institute of Southern CaliforniaBeverly Hills348 S Oakhurst DrBeverly HillsCA 90212USA

Background Partial androgen deficiency syndrome in the aging male is associated with signs of aging such as a development of abdominal obesity,sexual dysfunction,increase body fat,weight gain and the development of cardiac *** We assessed the outcome of a commercially available physician supervised nutrition and exercise program with concomitant testosterone replacement therapy in middle age obese men with partial androgen deficiency in order to reduce cardiac risks *** Fifty-six self referred men without diabetes mellitus,hypertension,or cardiovascular disease(ages 52.3±7.8 years)were randomly selected from a large *** weight,body fat composition,fasting glucose,hemoglobin A1c and fasting lipid levels,as well as free and total testosterone levels were *** patients were assessed and followed 6–18 months after initiation of the *** program consisted of a low glycemic load balanced nutrition diet,a recommended structured daily exercise program of 30–60 minutes,as well as once to twice weekly intramuscular testosterone injections(113.0±27.8 mg).Results At follow up,weight was reduced from 233.9±30.0 pounds(lbs)to 221.3±25.1 lbs(Pduced from 33.2±3.3 kg/m2 to 31.3±2.8 kg/m^(2)(Pdy fat was 27.1%±5.2%vs.34.3%±5.7%at baseline(Pduced from 95.3±14.4 mg/dL to 87.5±12.6 mg/dL(Pduced from 195.4±33.0 mg/dL to 172.7±35.0 mg/dL(Pdverse events were *** Testosterone replacement therapy in middle aged obese men with partial androgen deficiency appeared safe and might have promoted the effects of a weight reduction diet and daily exercise program as long as an adequate physician supervision and follow up was *** combination therapy significantly reduced coronary risk factors such as glucose intolerance and hyperlipidemia.

关键词： aging heart disease androgen deficiency testosterone

Ecological succession of benthic organisms on niche-type artificial reefs

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Ecological Processes 2020年第1期9卷 433-442页

作者： María-Isabel Toledo pamela Torres Cristina díaz Victor Zamora Jesús López Germán Olivares Escuela de Ciencias del Mar Facultad de Ciencias del Mar y GeografíaPontificia Universidad Católica de ValparaísoValparaísoChile

As part of efforts to restore fishery resources and recover damaged coastal ecosystems,artificial reefs are often anchored on the seafloor in coastal zones,to provide new habitats for marine *** aim of the study was to describe the structure of a community of benthic invertebrates colonising a niche-type artificial reef(AATN in Spanish).Nine structures were anchored at depths of 16±1.5 m for 99 weeks(22 months)in the Area of Benthic Resource Management and Exploitation(AMERB)in coastal waters of the Region of Bio Bio,*** results showed that,at 3 months from submersion of the NTAR,much of the artificial substrate remained bare and there were only low levels of specimens of Balanus ***,showing mean coverage of 11.26%,and even lower proportions of Rhodophyta,with mean coverage of 0.34%.At 6 months,the presence of hydrozoans was seen,decreasing the coverage of the barnacles,which was aided further at 8 months with the arrival of barnacle predatory *** 8 months,new benthic invertebrates appeared and competed for the *** included sponges and *** 99 weeks,the hydrozoans dominated the substrate,followed by barnacles and Rhodophyta,the first colonising organisms,leading to colonisation by motile macro-invertebrates,mainly consisting of crustaceans,echinoderms and *** AATN artificial system provides an ideal substrate for the development of early ecological succession and the use of this technology should be feasible in the recovery process of habitat damaged by anthropogenic actions and climate change.

关键词： Artificial reefs Ecological succession Colonisation Benthic organisms Balanus sp. Rhodophyta Hydrozoans

Improved speciation of dissolved organic nitrogen in natural waters: amide hydrolysis with fluorescence derivatization

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Journal of Environmental Sciences 2008年第10期20卷 1273-1280页

作者： Ryan L.Fimmen Tamara d.Trouts daniel d.Richter jr. dharni Vasudevan School of Earth Sciences The Ohio State University 125 S.Oval MallColumbus OH 43210 USA.Nicholas School of the Environment and Earth Sciences Duke University Durham NC 27708 USA School of Earth Sciences The Ohio State University 125 S.Oval MallColumbus OH 43210 USA Nicholas School of the Environment and Earth Sciences Duke UniversityDurham NC 27708 USA. Nicholas School of the Environment and Earth Sciences Duke UniversityDurham NC 27708 USA.Department of Chemistry Bowdoin CollegeBrunswick ME 04011 USA

The objective of this study was to improve primary-amine nitrogen (1°-N) quantification in dissolved organic matter (dOM) originating from natural waters where inorganic forms of N, which may cause analytical interference, are commonly encountered. Efforts were targeted at elucidating organic-N structural criteria influencing the response of organic amines to known colorimetric and fluorescent reagents and exploring the use of divalent metal-assisted amide hydrolysis in combination with fluorescence analyse...

关键词： dissolved organic matter/nitrogen (dOM/dON) o-phthaldialdehyde fluorescamine ninhydrin amino acids amide hydrolysis peptides

Tracking Power System State Evolution with Maximum-correntropy-based Extended Kalman Filter

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Journal of Modern Power Systems and Clean Energy 2020年第4期8卷 616-626页

作者： Julio A.d.Massignan João B.A.London jr. Vladimiro Miranda IEEE department of Electrical and Computing Engineering School of Engineering of São CarlosUniversity of São PauloSão CarlosBrazil Faculty of Engineering University of Porto and INESC TECPortoPortugal

This paper develops a novel approach to track power system state evolution based on the maximum correntropy criterion,due to its robustness against non-Gaussian *** includes the temporal aspects on the estimation process within a maximum-correntropy-based extended Kalman filter(MCEKF),which is able to deal with both nonlinear supervisory control and data acquisition(SCAdA)and phasor measurement unit(PMU)measurement *** representing the behavior of the state variables with a nonparametric model within the kernel density estimation,it is possible to include abrupt state transitions as part of the process noise with non-Gaussian ***,a novel strategy to update the size of Parzen windows in the kernel estimation is proposed to suppress the effects of suspect *** properly adjusting the kernel bandwidth,the proposed MCEKF keeps its accuracy during sudden load changes and contingencies,or in the presence of bad *** with IEEE test systems and the Brazilian interconnected system are carried *** results show that the method deals with non-Gaussian noises in both the process and measurement,and provides accurate estimates of the system state under normal and abnormal conditions.

关键词： Tracking state estimation Kalman filter maximum correntropy power system Parzen window