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New serological biomarkers of inflammatory bowel disease

World Journal of Gastroenterology 2008年第33期14卷 5115-5124页

作者： Xuhang li laurie Conklin philip Alex Division of Gastro- enterology Department of Medicine Johns Hopkins University School of Medicine Baltimore MD 21205 United States Division of Gastroenterology and Nutrition Department of Pediatrics Johns Hopkins University School of Medicine Baltimore MD 21205 United States

Serological biomarkers in inflammatory bowel disease (IBD) are a rapidly expanding list of non-invasive tests for objective assessments of disease activity, early diagnosis, prognosis evaluation and surveillance. This review summarizes both old and new biomarkers in IBD, but focuses on the development and character-ization of new serological biomarkers (identifi ed since 2007). These include fi ve new anti-glycan antibodies, anti-chitobioside IgA (ACCA), anti-laminaribioside IgG (AlCA), anti-manobioside IgG (AMCA), and antibod-ies against chemically synthesized (∑) two major oligomannose epitopes, Man α-1,3 Man α-1,2 Man (∑Man3) and Man α-1,3 Man α-1,2 Man α-1,2 Man (∑Man4). These new biomarkers serve as valuable complementary tools to existing biomarkers not only in differentiating Crohn's disease (CD), ulcerative colitis (UC), normal and other non-IBD gut diseases, but also in predicting disease involvement (ileum vs colon), IBD risk (as subclinical biomarkers), and disease course (risk of complication and surgery). Interestingly, the prevalence of the antiglycan antibodies, including anti-Saccharomyces cerevisiae antibodies (ASCA), AlCA and AMCA, was found to be associated with single nucleotide polymorphisms (SNPs) of IBD susceptible genes such as NOD2/CARD15, NOD1/CARD4, toll-likereceptors (TlR) 2 and 4, and β-defensin-1. Further-more, a gene dosage effect was observed: anti-glycan positivity became more frequent as the number of NOD2/CARD15 SNPS increased. Other new serum/ plasma IBD biomarkers reviewed include ubiquitination factor E4A (UBE4A), CXCl16 (a chemokine), resistin, and apolipoprotein A-IV. This review also discusses the most recent studies in IBD biomarker discovery by the application of new technologies such as proteomics, fourier transform near-infrared spectroscopy, and mul-tiplex enzyme-linked immunosorbent assay (ElISA)'s (with an emphasis on cytokine/chemokine profiling). Finally, the prospects of developing more clinically use-ful novel diag

关键词： Serological biomarkers Inflammatory bowel disease Ulcerative colitis Crohn's disease Anti-chitobioside IgA Anti-laminaribioside IgG Anti-manobioside IgG Anti-synthetic mannoside antibodies Multiplex enzyme-linked immunosorbent assay Proteomics

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Sediment generation and soil mound denudation in areas of high-density tree throw along a river valley in the Jura Mountains, Switzerland

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Journal of Mountain Science 2021年第2期18卷 377-391页

作者： philip GREENWOOD Jan BAUER Nikolaus J KUHN Physical Geography&Environmental Change Research Group Department of Environmental SciencesUniversity of BaselKlingelbergstrasse 27Basel-4056Switzerland

A preliminary field-based investigation was undertaken in a small(<10 km^(2))river valley located in the mountainous Jura region of northwest *** aims of the work were to assess sediment generation and annual sediment... 详细信息

A preliminary field-based investigation was undertaken in a small(lley located in the mountainous Jura region of northwest *** aims of the work were to assess sediment generation and annual sediment transport rates by tree throw on forested hillslopes,and to document surface hydrology characteristics on four fresh soil mounds associated with recent tree throws over a 24-day monitoring *** the soil mounds,average sediment recovery ranged from 7.7-28.2 g(dry weight),equivalent to a suspended sediment concentration of 145.2-327.8 g l^(-1),and runoff coefficients ranged from 1.0%-4.2%.Based on a soil bulk density value of 1,044 kg m^(-3),upslope runoff generation areas were denuded by an average 0.14 mm by the end of the 24-day monitoring period,representing an erosion rate equivalent to 2.1 mm yr^(-1).A ca.50 cm high soil mound could therefore feasibly persist for around 200-250 *** tree throw work,the dimensions of 215 individual tree throws were measured and their locations mapped in 12 separate locations along the river valley representing a cumulative area equivalent to 5.3 ha(***,43 per ha).Tree throws generated a total of 20.1 m^(3) of fine-sediment(lent of 3.8×10^(-4) m^(3) m^(-2).The process of tree throw was originally attributed to two extreme weather events that occurred in west and central Europe in late December *** the 18-year period since both storms,this represents an annual sediment transport rate of 2.7×10^(-5) m^(3) m^(-1) yr^(-1).Exploring the relationship with wind on fall direction,65.5%of tree throws(143)generally fell in a downslope direction irrespective of hillslope aspect on which they were *** infers that individual storms may not have been responsible for the majority of tree throws,but instead,could be associated with root *** the high density of tree throws and their relative maturity(average age 41 years),we hypothesise that once tr

关键词： Tree throw Hillslope processes Sediment generation mechanism Sediment transport rate Soil mound Ibach river valley

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Analyses of publicly available genomics resources define FGF-2-expressing bladder carcinomas as EMT-prone, proliferative tumors with low mutation rates and high expression of CTlA-4, PD-1 and PD-l1

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Signal Transduction and Targeted Therapy 2017年第1期2卷 258-265页

作者： Elizabeth A McNiel philip N Tsichlis Molecular Oncology Research Institute Tufts Medical CenterBostonMAUSA Cummings School of Veterinary Medicine Tufts UniversityNorth GraftonMAUSA.

Fibroblast growth factor 2(FGF-2)is overexpressed in a subset of invasive bladder carcinomas and its overexpression correlates with poor *** of publicly available databases addressing the molecular mechanisms that may be responsible for the poor prognosis of these tumors,revealed that FGF-2 expression correlates positively with the expression of epithelial to mesenchymal transition(EMT)-promoting transcription factors and with changes in gene expression that are characteristic of *** same analyses also revealed that FGF-2 correlates negatively with the expression,mutation and copy number variations of FGFR-3,all of which are associated with noninvasive bladder ***,they showed that FGF-2 expression correlates with the expression of FGFR-1,the expression of the IIIc variant of FGFR-2 and with the expression of *** latter observation is significant because our earlier studies had shown that Akt3 regulates FGFR-2 alternative splicing,shifting the balance toward the IIIc relative to the IIIb FGFR-2 splice *** the IIIc variant is recognized by FGF-2,while the IIIb variant is not,we conclude that Akt3 may facilitate the FGF-2 ***-2 is known to promote the expression of KDM2B,which functions in concert with EZH2 to repress the EZH2-targeting microRNA miR-101,activating a switch,which stably upregulates *** cancer genome atlas(TCGA)data showing a correlation between KDM2B and EZH2 expression and Oncomine data,showing a correlation between KDM2B and tumor progression,strongly support the role of the FGF-2/KDM2B/miR-101/EZH2 pathway in bladder *** observations combined,suggest a model according to which FGF-2 induces EMT,cell proliferation and cancer stem cell self-renewal by coupling the Akt3 and KDM2B-controlled pathways outlined above,in bladder *** analyses of publicly available databases,revealed that FGF-2-expressing bladder carcinomas carry fewer genetic alterations and they tend to expr

关键词： bladder carcinomas alterations

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Glucose transporter 4 can be inserted in the membrane without exposing its catalytic site for photolabeling from the medium

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Science China(life Sciences) 2007年第2期50卷 147-154页

作者： Manabu ISHIKI philip J BIlAN Programme in Cell Biology Hospital for Sick Children Toronto Canada M5G 1×8

Insulin stimulates the production of PI(3,4,5)P3 in muscle cells, and this is required to stimulate GlUT4 fusion with the plasma membrane. Introduction of exogenous PI(3,4,5)P3 to muscle cells recapitulates insulin's effects on GlUT4 fusion with the plasma membrane, but not glucose uptake. This study aims to explore the mechanism behind this difference. In l6-GlUT4myc muscle cells, the availability of the GlUT4 intracellular C-terminus and extracellular myc epitopes for immunoreactivity on plasma membrane lawns was detected with the corresponding antibody. The availability of the active site of GlUT4 from extracellular medium was assessed by affinity photolabeling with the cell impermeant compound Bio-lC-ATB-BMPA. 100nmol/l insulin and 10μmol/l PI(3,4,5)P3 caused myc signal gain on the plasma membrane lawns by 1.64-fold and 1.58-fold over basal, respectively. Insulin, but not PI(3,4,5)P3, increased photolabeling of GlUT4 and immunolabeling with C-terminus antibody by 2.47-fold and 2.04-fold over basal, respectively. Upon insulin stimulation, the C-terminus signal gain was greater than myc signal gain (2.04-fold vs. 1.64-fold over basal, respectively) in plasma membrane lawns. These results indicate that (i) PI(3,4,5)P3 does not make the active site of GlUT4 available from the extracellular surface despite causing GlUT4 fusion with the plasma membrane; (ii) the availability of the active site of GlUT4 from the extracellular medium and availability of the C-terminus from the cytosolic site are correlated; (iii) in addition to stimulating GlUT4 translocation, insulin stimulation displaces a protein which masks the GlUT4 C-terminus. We propose that a protein which masks the C-terminus also prevents the active site from being available for photolabelling and possibly glucose uptake after treatment with PI(3,4,5)P3.

关键词： glucose transport 4 (GlUT4) insulin phosphatidylinositol 3 4 5-trisphosphate (PI(3 4 5)P3) photolabel

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Insulin sensitivity and inhibition by forskolin,dipyridamole and pentobarbital of glucose transport in three l6 muscle cell lines

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Science China(life Sciences) 2007年第6期50卷 739-747页

作者： philip J BIlAN Michiko HAYASHI Programme in Cell Biology Hospital for Sick Children Toronto Canada M5G 1X8

l6 skeletal muscle myoblasts stably overexpressing glucose transporter GlUT1 or GlUT4 with exofa- cial myc-epitope tags were characterized for their response to insulin. In clonally selected cultures, 2-deoxyglucose uptake into l6-GlUT1myc myoblasts and myotubes was linear within the time of study. In l6-GlUT1myc and l6-GlUT4myc myoblasts, 100 nmol/l insulin treatment increased the GlUT1 content of the plasma membrane by 1.58±0.01 fold and the GlUT4 content 1.96±0.11 fold, as well as the 2-deoxyglucose uptake 1.53±0.09 and 1.86±0.17 fold respectively, all by a wortmannin-inhibitable manner. The phosphorylation of Akt in these two cell lines was increased by insulin. l6-GlUT1myc myoblasts showed a dose-dependent stimulation of glucose uptake by insulin, with unaltered sensitiv- ity and maximal responsiveness compared with wild type cells. By contrast, the improved insulin re- sponsiveness and sensitivity of glucose uptake were observed in l6-GlUT4myc myoblasts. Earlier studies indicated that forskolin might affect insulin-stimulated GlUT4 translocation. A 65% decrease of insulin-stimulated 2-deoxyglucose uptake in GlUT4myc cells was not due to an effect on GlUT4 mobi- lization to the plasma membrane, but instead on direct inhibition of GlUT4. Forskolin and dipyridamole are more potent inhibitors of GlUT4 than GlUT1. Alternatively, pentobarbital inhibits GlUT1 more than GlUT4. The use of these inhibitors confirmed that the overexpressed GlUT1 or GlUT4 are the major functional glucose transporters in unstimulated and insulin-stimulated l6 myoblasts. Therefore, l6-GlUT1myc and l6-GlUT4myc cells provide a platform to screen compounds that may have differ- ential effects on GlUT isoform activity or may influence GlUT isoform mobilization to the cell surface of muscle cells.

关键词： l6 muscle cells, glucose transporter (GlUT), insulin, 2-deoxyglucose uptake

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Joint effects of weather and interspecific competition on foraging behavior and survival of a mountain herbivore

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Current Zoology 2019年第2期65卷 165-175页

作者： Francesco FERRETTI Sandro lOVARI philip A. STEPHENS Research Unit of Behavioural Ecology Ethology and Wildlife Management Department of Life Sciences University of Siena Via P.A. Mattioli 4 53100 Siena Italy Conservation Ecology Group Department of Biosciences Durham University South Road Durham DH1 3LE UK Maremma Natural History Museum Strada Corsini 5 58100 Grosseto Italy

Weather variations have the potential to in fluence species interactions, although effects on competitive interactions between species are poorly known. Both weather and competition can influence foraging behavior and survival of herbivores during nursing/weaning, a critical period in the herbivore life cycle. We evaluated the joint effects of weather and competition with red deer Cervus elaphus on the foraging behavior of adult female Apen nine chamois Rupicapra pyrenaica ornata in summer, and on winter survival of chamois kids. High temperature and low rainfall during the growing seas on of vegetation had negative effects on bite rate. Effects of weather were greater in forb patches, including cold-adapted, nutritious plants of key importanee to chamois, than in graminoid ones. Our results confirm previous indications of a negative effect of competition on bite rate of female chamois and on kid survival. Furthermore, harsh weather conditions and competition with deer had additive, negative roles on foraging behavior and survival of chamois. Growing temperatures are expected to influence distribution, growth, and/or nutritional quality of plants;competition would reduce pasture quality and food availability through resource depletion. Both factors would limit food/energy intake rates during summer, reducing survival of the youngest cohorts in winter. We suggest that interspecific competition can be an important additive factor to the effects of weather changes on behavior and demography.

关键词： chamois foraging behavior global changes interspecific interactions resource exploitation ungulates

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Oral mucosal lipids are antibacterial against Porphyromonas gingivalis, induce ultrastructural damage, and alter bacterial lipid and protein compositions

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International Journal of Oral Science 2013年第3期5卷 130-140页

作者： Carol l Fischer Katherine S Walters David R Drake Deborah V Dawson Derek R Blanchette Kim A Brogden philip W Wertz Dows Institute for Dental Research College of Dentistry The University of Iowa Central Microscopy Research Facility College of Dentistry The University of Iowa Department of Endodontics College of Dentistry The University of Iowa Department of Pediatric Dentistry College of Dentistry The University of Iowa Department of Periodontics College of Dentistry The University of Iowa Department of Oral Pathology Radiology & Medicine College of Dentistry The University of Iowa

Oral mucosal and salivary lipids exhibit potent antimicrobial activity for a variety of Gram-positive and Gram-negative bacteria;however,little is known about their spectrum of antimicrobial activity or mechanisms of action against oral *** this study,we examine the activity of two fatty acids and three sphingoid bases against Porphyromonas gingivalis,an important colonizer of the oral cavity implicated in *** inhibitory concentrations,minimal bactericidal concentrations,and kill kinetics revealed variable,but potent,activity of oral mucosal and salivary lipids against ***,indicating that lipid structure may be an important determinant in lipid mechanisms of activity against bacteria,although specific components of bacterial membranes are also likely *** micrographs showed ultrastructural damage induced by sapienic acid and phytosphingosine and confirmed disruption of the bacterial plasma *** information,coupled with the association of treatment lipids with *** lipids revealed via thin layer chromatography,suggests that the plasma membrane is a likely target of lipid antibacterial *** a combination of two-dimensional in-gel electrophoresis and Western blot followed by mass spectroscopy and N-terminus degradation sequencing we also show that treatment with sapienic acid induces upregulation of a set of proteins comprising a unique *** stress response,including proteins important in fatty acid biosynthesis,metabolism and energy production,protein processing,cell adhesion and *** or therapeutic lipid treatments may be beneficial for intervention of infection by supplementing the natural immune function of endogenous lipids on mucosal surfaces.

关键词： antimicrobial lipid fatty acid Porphyromonasgingivalis sphingoid base sphingolipid ultrastructure

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Changes in human hepatic metabolism in steatosis and cirrhosis

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World Journal of Gastroenterology 2017年第15期23卷 2685-2695页

作者： Zoe Schofield Michelle AC Reed philip N Newsome David H Adams Ulrich l Günther Patricia F lalor Sci-Phy-4-Health EPSRC Research and Training Centre in Physical Sciences for HealthCollege of Engineering and Physical Sciences School of Cancer Sciences at the University of Birmingham Centre for liver Research and National Institute for Health Research(NIHR)Birmingham liver Biomedical Research Unit 不详

AIMTo understand the underlying metabolic changes in human liver disease we have applied nuclear magnetic resonance (NMR) metabolomics analysis to human liver *** have carried out pilot study using 1H-NMR to derive metabolomic signatures from human liver from patients with steatosis, nonalcoholic steatohepatitis (NASH) or alcohol-related liver damage (ARlD) to identify species that can predict outcome and discriminate between alcohol and metabolic-induced liver *** in branched chain amino acid homeostasis, tricarboxylic acid cycle and purine biosynthesis intermediates along with betaine were associated with the development of cirrhosis in both ARlD and nonalcoholic fatty liver disease. Species such as propylene glycol and as yet unidentified moieties that allowed discrimination between NASH and ARlD samples were also detected using our *** high throughput, non-destructive technique for multiple analyte quantification in human liver specimens has potential for identification of biomarkers with prognostic and diagnostic significance.

关键词： Human liver Metabolomics Steatosis Nuclear magnetic resonance Alcohol

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Outcomes of Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding

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World Journal of Gastroenterology 2013年第36期19卷 6035-6043页

作者： Nam Q Nguyen philip Game Justin Bessell Tamara l Debreceni Melissa Neo Carly M Burgstad Pennie Taylor Gary A Wittert Department of Gastroenterology and Hepatology Royal Adelaide Hospital Discipline of Medicine University of Adelaide Department of Surgery Royal Adelaide Hospital Adelaide Obesity Surgery Calvary Wakefield Hospital Department of Surgery Flinders University

AIM:To evaluate weight loss and surgical outcomes of Roux-en-Y gastric bypass(RYGB)and laparoscopic adjustable gastric band(lAGB).METHODS:Data relating to changes in body mass index(BMI)and procedural complications after RYGB(1995-2009;n=609;116M:493F;42.4±0.4 years)or lAGB(2004-2009;n=686;131M:555F;37.2±0.4years)were extracted from prospective ***:Pre-operative BMI was higher in RYGB than lAGB patients(46.8±7.1 kg/m2vs 40.4±4.2 kg/m2,PlAGB than RYGB(17.1%vs 4.1%,Plationships between weight loss and pre-operative BMI(Plthough there was no difference in weight loss between genders during the first 3-year post-surgery,male lAGB patients had greater BMI reduction than females(-8.2±4.3 kg/m2vs-3.9±1.9kg/m2,P=0.02).Peri-operative complications occurred more frequently following RYGB than lAGB(8.0%vs0.5%,Plated to wound *** had more long-term complications requiring corrective procedures than RYGB(8.9%vs 2.1%,Plted in greater BMI reduction(-9.5±3.8 kg/m2)compared to removal and replacement of the band(-6.0±3.0 kg/m2).Twelve months post-surgery,fasting glucose,total cholesterol and low density lipoprotein levels were significantly lower with the magnitude of reduction greater in RYGB ***:RYGB produces substantially greater weight loss than *** peri-operative complications are greater after RYGB,long-term complication rate is higher following lAGB.

关键词： Bariatric surgery Gastric bypass Gastric banding Weight loss Complications Co-morbidity Outcomes

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Experimental,analytical and numerical studies on concrete encased trapezoidally web profiled cold-formed steel beams by varying depth-thickness ratio

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Frontiers of Structural and Civil Engineering 2020年第4期14卷 930-946页

作者： Divahar RAVI Aravind Raj PONSUBBIAH Sangeetha Sreekuniar PRABHA Joanna philip SARATHA Department of Civil Engineering Aarupadai Veedu Institute of TechnologyChennai 603104India Department of Civil Engineering Hindustan Institute of Technology and ScienceChennai 603103India

Concrete encased with trapezoidally corrugated web profiled cold-formed steel beams are used worldwide to improve resistance toward fire and corrosion,higher load carrying capacity as well as significant increase in the bending stiffness by encasing concrete on the beam *** present work gives a detailed description on the experimental,analytical and numerical investigation on the flexural behavior of concrete encased trapezoidally corrugated web profiled cold-formed steel beams which were simply supported at both ends and subjected to two point symmetric *** flexural behavior of such structure has been experimentally tested to failure under pure *** find the effct of concrete encasement in the web,12 experiments were conducted by two different *** having three different web corrugation angles of 0°,30°,and 45°with two different web depth-thickness(dw/tw)ratios of 60 and 80 were *** results such as load-deflection relationship,ultimate capacity,load-strain relationship,moment-curvature curves,ductility and failure mode indices of the specimens are *** the static bending tests the concrete encased trapezoidally corugated web beam showed improved moment carrying capacity,ductility bchavior and the resistance to transverse deflections in comparison to concrete encased with plain web *** for the beams with concrete encased 30°trapezoidally corrugated web having(dw/tw)ratio 60 and 80,the loading capacity was improved about 54%and 67.3%and the ductility also increased about l.6 and 3.6 times,when compared to concrete encased beams with plain *** research should contribute to the future engineering applications on seismic resistant structures and efficient usage of concrete encased with cold-formed steel beams by exhibiting its super elasto-plastic *** analytical and numerical results showed good agreement with the experimental results at yield load,which indicates that the proposed analyti

关键词： concrete encased beam trapezoidally corrugated web loading capacity super elasto-plastic

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