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NOD2/CARD15 , ATG16L1 and IL23R gene polymorphisms and childhood-onset of Crohn’s disease

World Journal of Gastroenterology 2010年第14期16卷 1753-1758页

作者： Maria Gazouli Ioanna pachoula Ioanna panayotou Gerassimos Mantzaris George Chrousos nicholas p Anagnou Eleftheria Roma-Giannikou Department of Biology School of Medicine University of Athens Athens 11527 Greece Laboratory of Cell and Gene Therapy Center of Basic Research Ⅱ Foundation for Biomedical Research of the Academy of Athens (IIBEAA) Athens 11527 Greece First Department of pediatrics "Aghia Sophia" Children's Hospital School of Medicine University of Athens Athens 11527 Greece Department of Gastroenterology Evagelismos Hospital Athens 11521 Greece

AIM: To assess whether the polymorphisms of NOD2/ CARD15 , autophagy-related 16-like 1 (ATG16L1 ), and interleukin-23 receptor (IL23R ) genes play a more critical role in the susceptibility of childhood-onset than in adult-onset Crohn’s disease (CD). METHODS: polymorphisms R702W, G908R, and 3020insC of NOD2/CARD15 ; rs2241880 A/G of ATG16L1 , and rs11209026 (R381Q) of IL23R gene were assessed in 110 childhood-onset CD, 364 adult-onset CD, and 539 healthy individuals. Analysis of polymorphisms R702W, G908R, and 3020insC of NOD2/CARD15 genotyping was performed by allele specific polymerase chain reaction (pCR) or by pCR-restriction fragment length polymor-phism analysis. The polymorphisms rs2241880 A/G of the ATG16L1 , and rs11209026 (R381Q) of the IL23R gene in the children’s cohort were genotyped by pCR and melting curve analysis whereas adult group genotyping was performed using the Affymetrix Genome-Wide Human SNp Array 5.0 (500K). RESULTS: The 3020insC allele in NOD2/CARD15 was significantly higher in childhood than in adult-onset CD (p = 0.0067). Association with at least 1 NOD2/CARD15 variant was specific for ileal disease (with or without co- lonic involvement). Even if the frequency of G allele of the rs2241880 ATG16L1 polymorphism was increased in both paediatric and adult CD patients compared to con- trols (p = 0.017 and p = 0.001, respectively), no difference was observed between the childhood and the adult cohort. The rare Q allele of IL23R rs11209026 polymorphism was underrepresented in both paediatric and adult CD cases (p = 0.0018 and p = 0.04, respectively) and no difference was observed between the childhood and the adult cohort. The presence of the rs2241880 ATG16L1 and rs11209026 IL23R polymorphisms did not influence disease phenotype. CONCLUSION: polymorphism 3020insC in NOD2/ CARD15 occurs statistically significantly more often in patients with childhood-onset CD than in patients with adult-onset CD. The ATG16L1 and IL23R variants are associated

关键词： Genetics Childhood-onset Inflammatory bowel disease Crohn’s disease Genetic susceptibility NOD2/CARD15 ATG16L1 IL23R polymorphisms

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presentation of hepatocellular antigens

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Cellular & Molecular Immunology 2016年第3期13卷 293-300页

作者： Arash Grakoui Ian nicholas Crispe Division of Infectious Diseases Department of Medicine Emory University School of Medicine and Yerkes National Primate Research Center Atlantal GAUSA Department of pathology University of Washington Seattle WA USA.

The liver is an organ in which antigen-specific T-cell responses manifest a bias toward immune tolerance. This is clearly seen in the rejection of allogeneic liver transplants, and multiple other phenomena suggest that this effect is more general. These include tolerance toward antigens introduced via the portal vein, immune failure to several hepatotropic viruses, the lack of natural liverstage immunity to malaria parasites, and the frequent metastasis of cancers to the liver. Here we review the mechanisms by which T cells engage with hepatocellular antigens, the context in which such encounters occur, and the mechanisms that act to suppress a full T-cell response. While many mechanisms play a role, we will argue that two important processes are the constraints on the cross-presentation of hepatocellular antigens, and the induction of negative feedback inhibition driven by interferons. The constant exposure of the liver to microbial products from the intestine may drive innate immunity, rendering the local environment unfavorable for specific T-cell responses through this mechanism. Nevertheless, tolerance toward hepatocellular antigens is not monolithic and under specific circumstances allows both effective immunity and immunopathology.

关键词： liver hepatocytes immunity tolerance

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Heart healthy equals prostate healthy and statins, aspirin, and/or metformin （S.A.M.） are the ideal recommendations for prostate cancer prevention

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Asian Journal of Andrology 2015年第5期17卷 783-791,I0008页

作者： Mark A Moyad nicholas J Vogelzang Department of Urology University of Michigan Medical Center Ann Arbor Michigan USA Developmental Therapeutics Committee and Genitourinary Committee for US Oncology Research Comprehensive Cancer Centers of Nevada Las Vegas Nevada USA

Cardiovascular disease （CVD） has been the number one cause of death in the U.S. for 114 of the last 115 years. Lifestyle factors that promote CVD also appear to increase prostate cancer risk and those that reduce CVD risk also appear to reduce the risk of prostate cancer. The largest randomized trials utilizing dietary supplements or pharmacologic agents for prostate cancer prevention （Selenium and Vitamin E Cancer prevention Trial [SELECT]） have also shed light on the problems and future solutions in this area. Dietary supplements that have not been found to be CVD protective, such as selenium and Vitamin E have not been found to be prostate protective. In addition, over exposure to specific anti-oxidants in nutritionally replete populations may be encouraging cancer growth. Futuretrials of dietary supplements to prevent prostate cancer could be problematic because by the time a definitive trial is initiated the participants will no longer be ＂deficient＂ in the nutrient being tested, which arguably occurred in the SELECT trial. It is also interesting that statins, aspirin, and/or metformin （S.A.M.） are 3 generic, low-cost, heart healthy agents derived from natural sources with separate mechanism of actions, which all appear to have the best benefit to risk ratio compared to any other agent available for prostate cancer prevention, especially aggressive disease, or as an ancillary agent （s） to conventional cancer treatment. It is time to focus on the forest over the trees and recommend proven CVD protective measures for men concerned about their risk of prostate cancer.

关键词： aspirin diet lifestyle metformin prostate cancer statins

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Animal personalities and their implications for complex signaling

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Current Zoology 2014年第3期60卷 381-386页

作者： nicholas DIRIENZO Ann V HEDRICK Department of Neurobiology Physiology & Behavior Animal Behavior Graduate Group University of California Davis CA 95616 USA Department of Neurobiology Physiology & Behavior University of California Davis CA 95616 USA

Animal personalities have been a major focus of behavioral ecology over the past decade. Consistent individual dif ferences in behavior have been found across taxa, and have been shown to influence a range of ecological processes. The role of personalities in sexual selection has been considered, and examples exist that show selection for personality traits with both assortative and disassortative mating patterns between personality types. One overlooked aspect of the personality and sexual se lection literature is the potential for personalitysignaling interactions, specifically with complex signaling. Complex signaling is a diverse topic in itself, and in short, consists of multiple signals within one or more modalities that interact to elicit a receiver response. Research into complex signaling has been thorough, although at times studies discover complex signaling systems that fail to fit into one of the existing hypotheses in the literature. Here, we argue that personalities may interact with complex signal ing, which should be considered by researchers of both personality and sexual selection and communication. We describe several ways in which personalitycomplex signaling interactions could affect both the signaler and receiver, and the way in which they may drive personalityspecific signals as well as receiver preferences. Finally, we discuss how considering personality in com plex signaling studies may inform theory as well as improve the ability of researchers to accurately describe its function.

关键词： Animal personalities Sexual Selection Complex Signaling Multimodal Communication Communication

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Articulating China's Science and Technology:Knowledge Collaboration Networks Within and Beyond the Yangtze River Delta Megalopolis in China

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Chinese Geographical Science 2018年第2期28卷 247-260页

作者： LI Yingcheng nicholas A.pHELpS School of Architecture Southeast University Bartlett School of planning University College London

In this paper, we reconsider the defining but often overlooked ‘hinge' function of megalopolises by analyzing how megalopolises have articulated national and international urban systems in the context of a globalizing knowledge economy. Taking the case of China's Yangtze River Delta(YRD) region, we particularly focus on knowledge circulation within and beyond the YRD region by analyzing the pattern and process of knowledge collaboration at different geographical scales during the 2004–2014 period. Results show that the structure of scientific knowledge collaboration as reflected by co-publications has been strongest at the national scale whereas that of technological knowledge collaboration as measured by co-patents has been strongest at the global scale. Despite this difference, the structure of both scientific and technological knowledge collaboration has been functionally polycentric at the megalopolitan scale but become less so at the national and global scales. The ‘globally connected but locally disconnected' pattern of Shanghai's external knowledge collaboration suggests that the gateway role of the YRD megalopolis in promoting knowledge collaboration at different geographical scales will take time before it is fully realized.

关键词： urban network publication patent scale gateway Yangtze River Delta (YRD)

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Effects of Exhaust Gas Recirculation on the Homogeneous Charge Combustion process of n-Heptane at Different Load Conditions

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Transactions of Tianjin University 2005年第4期11卷 262-267页

作者：刘德新冯洪庆郑进才 MILLER David L CERNANSKY nicholas p State Key Laboratory of Engines School of Mechanical Engineering Tianjin University Tianjin 300072 China Department of Mechanical Engineering Drexel University Philadelphia PA19104-2875 USA

Effects of exhaust gas recirculation （EGR） on homogeneous charge combustion of n-heptane was studied through simulation and experiment. Experiments were carried out in a single cylinder, four-stroke, air cooled engine and a single cylinder, two-stroke, water cooled engine. In the four-stroke engine, experiments of the effects of EGR were examined using heated N2 addition as a surrogate for external EGR and modifying engine to increase internal EGR. The ignition timing was sensitive to EGR due to thermal and chemical effects. EGR or extra air is a key factor in eliminating knock during mid-load conditions. For higher load operation the only way to avoid knock is to control reaction timing through the use of spark ignition. Experimental and modeling results from the two-stroke engine show that auto-ignition can be avoided by increasing the engine speed. The two-stroke engine experiments indicate that high levels of internal EGR can enable spark ignition at lean conditions. At higher load conditions, increasing the engine speed is an effective method to control transition from homogeneous charge compression ignition （HCCI） operation to non-HCCI operation and successful spark ignition of a highly dilute mixture can avoid serious knock.

关键词： homogeneous charge combustion exhaust gas recirculation n-heptane auto-ignition

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purines:From Diagnostic Biomarkers to Therapeutic Agents in Brain Injury

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Neuroscience Bulletin 2020年第11期36卷 1315-1326页

作者： Bruno G.Frenguelli nicholas Dale School of Life Sciences The University WarwickCoventry CV47ALUK

The purines constitute a family of inter-related compounds that serve a broad range of important intracellular and extracellular biological *** particular,adenosine triphosphate(ATp)and its metabolite and precursor,adenosine,regulate a wide variety of cellular and systems-level physiological processes extending from ATp acting as the cellular energy currency,to the adenosine arising from the depletion of cellular ATp and responding to reduce energy demand and hence to preserve ATp during times of metabolic *** inter-relationship provides opportunities for both the diagnosis of energy depletion during conditions such as stroke,and the replenishment of ATp after such *** this review we address these opportunities and the broad potential of purines as diagnostics and restorative agents.

关键词： purines Adenosine ATp Biomarker Stroke Cerebral ischemia Traumatic brain injury Adenine D-ribose

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Teleseismic waves reveal anisotropic poroelastic response of wastewater disposal reservoir

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Earth and planetary physics 2021年第6期5卷 547-558页

作者： Andrew J Barbour nicholas M Beeler u.s.geological survey earthquake science centerusa

Connecting earthquake nucleation in basement rock to fluid injection in basal,sedimentary reservoirs,depends heavily on choices related to the poroelastic properties of the fluid-rock system,thermo-chemical effects *** constraints on these parameters outside of laboratory settings are rare,and it is commonly assumed that the rock layers are *** the Arbuckle wastewater disposal reservoir in Osage County,Oklahoma,high-frequency formation pressure changes and collocated broadband ground velocities measured during the passing of large teleseismic waves show a poroelastic response of the reservoir that is both azimuthally variable and anisotropic;this includes evidence of static shifts in pressure that presumably relate to changes in local *** azimuthal dependence in both the static response and shear coupling appears related to tectonic stress and strain indicators such as the orientations of the maximum horizontal stress and faults and *** dynamic strains from a nearby borehole strainmeter,we show that the ratio of shear to volumetric strain coupling is~0.41 which implies a mean Skempton's coefficient of A=0.24 over the plausible range of the undrained poisson's *** these observations are made at relatively low confining pressure and differential stress,we suggest that the hydraulically conductive fracture network is a primary control on the coupling between pore pressure diffusion and elastic stresses in response to natural or anthropogenic sources.

关键词： poroelasticity dynamic strain anisotropy wastewater disposal Oklahoma induced seismicity

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So you aspire to be a professor?

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World Journal of Gastroenterology 2009年第44期15卷 5626-5627页

作者： nicholas J Talley Department of Internal Medicine Mayo Clinic Jacksonville Professor of Medicine and EpidemiologyDivision of Gastroenterology & HepatologyMayo Clinic College of Medicine Consultant200 First Street S.W.PL-6-56Rochester MN 55905United States

＂The truth is that life is delicious, horrible, charming, frightful, sweet, bitter, and that is everything.＂ Anatole France （Francois-Anatole Thibault, 1844-1924）.

关键词：胃疾病临床治疗疗效

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Identifying migrant remains in South Texas:policy and practice

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Forensic Sciences Research 2019年第1期4卷 60-68页

作者： M.Katherine Spradley nicholas p.Herrmann Courtney B.Siegert Chloe p.McDaneld Department of Anthropology Texas State UniversitySan Marcos(TX)USA

In 2012, Texas surpassed Arizona in migrant deaths. The majority of deaths occurred in the Rio Grande Valley, specifically in Brooks County, Texas. Brooks County is one of the poorest in the state and was overwhelmed with deaths, without appropriate resources to follow the state laws pertaining to the investigation of unidentified human remains. Until 2013, most remains that were not immediately identified were buried without collecting DNA samples and the location of burials was not recorded. Our paper outlines the difficulties searching for these burials, the struggles of the families of the missing, and the collaborative approaches to facilitating identifications in South Texas. Community outreach combined with geophysical surveys guide which cemeteries are in need of exhumations. Once ceme-teries are surveyed, archaeological methods are employed to exhume remains and docu-ment burials. Remains are taken to the Forensic Anthropology Center at Texas State for processing, analysis, and identification efforts. Undergraduate and graduate students clean remains and wash clothing and personal *** skeletal analysis, all information regarding the remains, including photographs of per-sonal effects, are uploaded to the National Missing and Unidentified persons System (NamUs) and a DNA sample is submitted to the University of North Texas for inclusion in the Combined DNA Index System (CODIS) DNA database. However, CODIS lacks DNA family reference samples from many families of the missing due to families living outside the US or because they do not feel comfortable providing a DNA sample in the presence of law enforcement. Therefore, it is necessary to work with non-governmental organizations who specialize in collecting missing persons reports and DNA samples from the families of the missing. Working collaboratively with multiple agencies, identification of migrant remains is possible.

关键词： Forensic anthropology migrant migration positive identification geophys-ical survey

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