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Field cancerization in the colon:a role for aberrant DNA methylation?

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Gastroenterology Report 2014年第1期2卷 16-20页

作者： Yanxin Luo ming Yu william m.grady Department of Colorectal Surgery The Sixth Affiliated HospitalSun Yat-Sen UniversityGuangzhouP.R.China Gastrointestinal Institute Sun Yat-Sen UniversityGuangzhouP.R.China Clinical Research Division Fred Hutchinson Cancer Research CenterSeattleWAUSA Department of medicine University of Washington School of MedicineSeattleWAUSA

Colorectal cancer is the third most common cancer worldwide and arises secondary to the progressive accumulation of genetic and epigenetic alterations in normal colon cells,which results in a polyp-to-cancer progression *** is known that individuals with a personal history of colon adenomas or cancer are at increased risk for metachronous colon *** explanation for this increased risk could be field cancerization,which is a phenomenon in which the histologically normal tissue in an organ is primed to undergo *** alterations appear to be promising markers for field *** this review,we discuss field cancerization in the colon and the data supporting the use of methylated DNA as a biomarker for this phenomenon.

关键词： colorectal cancer field cancerization epigenetic alterations DNA methylation

Survival after inflammatory bowel disease-associated colorectal cancer in the Colon Cancer Family Registry

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World Journal of Gastroenterology 2013年第21期19卷 3241-3248页

作者： Scott V Adams Dennis J Ahnen John A Baron Peter T Campbell Steven Gallinger william m grady Loic Lemarchand Noralane m Lindor John D Potter Polly A Newcomb Cancer Prevention Public Health SciencesFred Hutchinson Cancer Research CenterSeattleWA 98109United States Department of medicine Denver VA Medical Center and University of Colorado School of MedicineDenverCO 80045United States Department of medicine University of North CarolinaChapel HillNC 27599United States Epidemiology Research Program Department of Intramural ResearchAmerican Cancer SocietyAtlantaGA 30303United States Division of General Surgery University of TorontoTorontoON M5G2C4Canada Cancer Research Center of Hawaii University of HawaiiHonoluluHI 96813United States Department of Health Science Research Mayo Clinic ArizonaScottsdaleAZ 85259United States

AIm: To investigate the survival of individuals with colorectal cancer (CRC) with inflammatory bowel disease (IBD-associated CRC) compared to that of individuals without IBD diagnosed with CRC. mETHODS: Epidemiologic, clinical, and follow-up data were obtained from the Colon Cancer Family Registry (Colon CFR). IBD-associated cases were identified from self-report of physician diagnosis. For a subset of participants, medical records were examined to confirm self-report of IBD. Cox proportional hazards regression was applied to estimate adjusted hazard ratios (aHR) and 95%CI of mortality, comparing IBD-associated to non-IBD-associated CRC, adjusted for age at CRC diagnosis, sex, Colon CFR phase, and number of prior endoscopies. Following imputation to complete CRC stage information, adjustment for CRC stage was examined. RESULTS: A total of 7202 CRC cases, including 250 cases of IBD-associated CRC, were analyzed. Over a twelve year follow-up period following CRC diagnosis, 2013 and 74 deaths occurred among non-IBD associated CRC and IBD-associated CRC patients, respectively. The difference in survival between IBD-associated and non-IBD CRC cases was not statistically significant (aHR = 1.08; 95%CI: 0.85-1.36). However, the assumption of proportional hazards necessary for valid inference from Cox regression was not met over the entire follow-up period, and we therefore limited analyses to within five years after CRC diagnosis when the assumption of proportional hazards was met. Over this period, there was evidence of worse prognosis for IBD-associated CRC (aHR = 1.36; 95%CI: 1.05-1.76). Results were similar when adjusted for CRC stage, or restricted to IBD confirmed in medical records. CONCLUSION: These results support the hypothesis that IBD-associated CRC has a worse prognosis than non-IBD-associated CRC.

关键词： Colorectal cancer Inflammatory bowel disease Outcomes research Cancer survival Inflammation

Emerging role of A-kinase anchoring protein 5 signaling in reward circuit function

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Neural Regeneration Research 2025年第10期20卷 2913-2914页

作者： william J.Flerlage mark L.Dell’Acqua Brian m.Cox Fereshteh S.Nugent Uniformed Services University of the Health Sciences Department of Pharmacology and Molecular TherapeuticsBethesdaMDUSA Department of Pharmacology University of Colorado School of MedicineAnschutz Medical CampusAuroraCOUSA

There is a strong evidence supporting the hypothesis of synaptic dysfunction as a major contributor to neural circuit and network disruption underlying emotional and mood dysregulation in psychiatric disorders(Simmons et al.,2024).Diverse sets of distinct molecular signaling pathways converge on the synapse to regulate synaptogenesis,synaptic function,and synaptic plasticity in brain regions and circuits through complex interactions organized by numerous multivalent protein scaffolds,including the family of proteins known as A-kinase anchoring proteins(AKAPs).

关键词： function supporting

modelling the smart farm

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Information Processing in Agriculture 2017年第3期4卷 179-187页

作者： michael J.O’grady Gregory m.P.O’Hare School of Computer Science University College DublinBelfieldDublin 4Ireland Earth Institute University College DublinBelfieldDublin 4Ireland

Smart farming envisages the harnessing of Information and Communication Technologies as an enabler of more efficient,productive,and profitable farming *** technologies do not suffice on their own;rather they must be judiciously combined to deliver meaningful information in near ***-support tools incorporating models of disparate farming activities,either on their own or in combination with other models,offer one popular approach;exemplars include GPFARm,APSIm,GRAZPLAN amongst many *** models tend to be generic in nature and their adoption by individual farmers is *** technologies offer an opportunity to remedy this situation;farm-specific models that can reflect near real-time events become tractable using such *** on the development,and application of farm-specific models is at a very early *** paper thus presents an overview of models within the farming enterprise;it then reviews the state-of the art in smart technologies that promise to enable a new generation of enterprise-specific models that will underpin future smart farming enterprises.

关键词： Smart agriculture modelling Sensing Internet of things

The Aerosol-monsoon Climate System of Asia:A New Paradigm

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Journal of meteorological Research 2016年第1期30卷 1-11页

作者： william K.m.Lau Earth Science Interdisciplinary Center University of MarylandCollege Park

This commentary is based on a series of recent lectures on aerosol-monsoon interactions I gave at the Beijing Normal University in August 2015. A main theme of the lectures is on a new paradigm of ＂An Aerosol-monsoon-Climate-System＂, which posits that aerosol, like rainfall, cloud, and wind, is an integral component of the monsoon climate system, influencing monsoon weather and climate on m1 timescales. Here, salient issues discussed in my lectures and my personal perspective regarding interactions between atmospheric dynamics and aerosols from both natural and anthropogenic sources are summarized. my hope is that under this new paradigm, we can break down traditional disciplinary barriers, advance a deeper understanding of weather and climate in monsoon regions, as well as entrain a new generation of geoscientists to strive for a sustainable future for one of the most complex and challenging human-natural climate sub-system of the earth.

关键词： aerosol monsoon climate system interaction new paradigm

A pilot study of the association between genetic polymorphisms involved in estrogen signaling and infant male genital phenotypes

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Asian Journal of Andrology 2012年第5期14卷 766-772页

作者： Sheela Sathyanarayana Shanna H Swan Federico m Farin Hui-Wen Wilkerson michael Bamshad Richard grady Chuan Zhou Stephen m Schwartzy Department of Pediatrics University of WashingtonSeattleWA 98195USA Center for Child Health Behaviorand DevelopmentSeattle Children's Research InstituteSeattleWA 98105USA Department of Preventive medicine Mount Sinai School of MedicineNew YorkNY 10029USA Department of Environmental and Occupational Health Sciences University of WashingtonSeattleWA 98195USA Department of Genome Sciences University of WashingtonSeattleWA 98195USA Division of Pediatric Urology Seattle Children's HospitalSeattleWA 98105USA Department of Epidemiology University of WashingtonSeattleWA 98195USA Epidemiology Program Fred Hutchinson Cancer Research CenterSeattleWA 98109USA

Single nucleotide polymorphisms （SNPs） in genes that influence development of the male reproductive tract have been associated with male genitourinary abnormalities. However, no studies have tested the relationship between SNPs and intermediate phenotypes such as anogenital distance （AGD）, anoscrotal distance （ASD） and penile width （PW）. We tested whether 24 common SNPs in eight genes that influence male genital development were associated with intermediate phenotypes in 106 healthy male infants from the Study for Future Families. We used DNA from buccal smears and linear regression models to assess the relationship between anogenital measurements and SNP genotypes with adjustment for covariates. We found that the rs2077647 G allele, located in the coding region of estrogen receptor alpha （ESR1）, was associated with a shorter AGD （P=0.02; -7.3 mm, 95% confidence interval （CI）： -11.6 to -3.1）, and the rs10475 T allele, located in the 3＇ untranslated region of activating transcription factor 3 （ATF3）, was associated with a shorter ASD （-4.3 mm, 95% Ch -7.2 to -1.4）, although this result was not significant （P=0.07） after controlling for multiple comparisons. We observed no association between PW and the SNPs tested. minor alleles for two SNPs in genes that regulate estrogen signaling during male genital development were associated with AGD and ASD, although the significance of the association was marginal. Our findings suggest that AGD and ASD are influenced by heritable factors in genes known to be associated with frank male genital abnormalities such as hvpospadias and crvotorchidism.

关键词： gene hypospadias male phenotype polymorphism reproductive

Assessment of mercury(II) bioavailability using a bioluminescent bacterial biosensor: Practical and theoretical challenges

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Journal of Environmental Sciences 2010年第8期22卷 1137-1143页

作者： Paulo R G Barrocas william m Landing Robert J m Hudson Department of Sanitation and Environmental Health National School of Public Health Oswaldo Cruz Foundation Department of Oceanography Florida State University. Tallahassee Department of Natural Resources and Environmental Sciences University of Illinois

Critical methodological challenges in the microbial biosensor approach to assessing Hg（II） bioavailability were evaluated from the perspective of analytical chemists. The main challenge stems from the fact that the chemical speciation of Hg（II） in natural waters exerts a major control on its bioavailability, yet its natural complexation equilibria are extensively altered during conventional bioassays. New data, obtained using a bioluminescent Hg（II）-biosensor, that illustrate these challenges are presented and potential solutions proposed.

关键词： mercury bioavailability biosensor chemical speciation bioluminescent

Predictive value of hypo-osmotic swelling test to identifyviable non-motile sperm

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Asian Journal of Andrology 2003年第3期5卷 209-212页

作者： william m.Buckett University of Liverpool and the Reproductive medicine Unit Liverpool Women's Hospital Liverpool UK

Aim: To determine the predictive value of the hypo-osmotic swelling (HOS) test to identify viable, non-motile sperm. methods: Semen samples from 20 men with severe asthenozoospermia underwent traditional seminal analysis, eosin-nigrosin (EN) staining and the HOS test. A further EN stain was then performed on a HOS pre-treated aliquot and a total of 2000 further sperm examined. Results: The median sperm density was 5.1 million/mL (IQR 4.3-13.1) and the median motility was 3.0 % (IQR 0-7). Seven samples showed complete asthenozoospermia. Initial EN staining showed 59 % viability (range 48-69) despite the poor standard parameters and 47 % (range 33-61) in the complete asthenozoospermia subgroup. The HOS test showed 49.9 % reacted overall (range 40-59) and 41.7 % (range 22-61) in the complete asthenozoospermia subgroup. The combined HOS/EN stain showed the positive predictive value of the HOS test to identify viable sperm was 84.2 % overall and 79.7 % in the complete asthenozoospermia subgroup. Conclusion: The HOS test can effectively predict sperm viability in patients with severe and complete asthenozoospermia.

关键词： azoospermia sperm spermmotility hypo-osmotic swelling (HOS) test sperm viability predictive value

Reproductive biology of an old endemic murid rodent of Australia, the Spinifex hopping mouse, Notomys alexis:adaptations for life in the arid zone

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Integrative Zoology 2011年第4期6卷 321-333页

作者： william G.BREED Chris m.LEIGH Discipline of Anatomy and Pathology University of AdelaideAdelaideAustralia

The Spinifex hopping mouse(Notomys alexis Thomas,1922)is an arid adapted Australo–Papuan old endemic rodent that undergoes boom and bust population *** this communication,we review our findings on the timing of reproduction and the potential reproductive rate of this *** investigate the first question,the reproductive condition of adult females,and occurrence of immatures,in a population on a cattle station in central Australia was determined and,for the second,data from a laboratory colony compared to those previously published on closely related species in other *** findings show that,at least in the population at the times that monitoring was performed,reproductive activity was only taking place in spring and early summer,whereas the laboratory study indicates that females have a similar gestation length and litter size to those of most close relatives occurring in other *** have extremely small testes and store relatively few *** findings suggest that Notomys alexis might show some seasonality of reproduction at least in this region of central Australia and that this species does not have a higher reproductive rate than that of related species in other,more predictable,environments.

关键词： arid environment hopping mouse reproduction