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Obesity-induced sperm DNA methylation changes at satellite repeats are reprogrammed in rat offspring

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Asian Journal of Andrology 2016年第6期18卷 930-936页

作者： Neil A Youngson Virginie Lecomte Christopher A Maloney preston Leung Jia Liu Luke B Hesson Fabio Luciani Lutz Krause Margaret J Morris Department of Pharmacology School of Medical Sciences UNSW Australia Sydney NSW 2052 Australia Inflammation and Infection Research School of Medical Sciences UNSW Australia Sydney NSW 2052 Australia Adult Cancer Program Lowy Cancer Research Centre and Prince of Wales Clinical School UNSW Australia Sydney NSW 2052 Australia QIMR Berghofer Medical Research Institute Herston Brisbane Queensland 4006 Australia University of Queensland Diamantina Institute Translational Research Institute University of Queensland 37 Kent Street Woolleongabba Queensland 4102 Australia

There is now strong evidence that the paternal contribution to offspring phenotype at fertilisation is more than just DNA. However, the identity and mechanisms of this nongenetic inheritance are poorly understood. One of the more important questions in this research area is： do changes in sperm DNA methylation have phenotypic consequences for offspring？ We have previously reported that offspring of obese male rats have altered glucose metabolism compared with controls and that this effect was inherited through nongenetic means. Here, we describe investigations into sperm DNA methylation in a new cohort using the same protocol. Male rats on a high-fat diet were 30% heavier than control-fed males at the time of mating （16-19 weeks old, n = 14/14）. A small （0.25%） increase in total 5-methyl-2＇-deoxycytidine was detected in obese rat spermatozoa by liquid chromatography tandem mass spectrometry. Examination of the repetitive fraction of the genome with methyI-CpG binding domain protein-enriched genome sequencing （MBD-Seq） and pyrosequencing revealed that retrotransposon DNA methylation states in spermatozoa were not affected by obesity, but methylation at satellite repeats throughout the genome was increased. However, examination of muscle, liver, and spermatozoa from male 27-week-old offspring from obese and control fathers （both groups from n = 8 fathers） revealed that normal DNA methylation levels were restored during offspring development. Furthermore, no changes were found in three genomic imprints in obese rat spermatozoa. Our findings have implications for transgenerational epigenetic reprogramming. They suggest that postfertilization mechanisms exist for normalising some environmentally-induced DNA methylation changes in sperm cells.

关键词： methylation obesity spermatozoa

An Induced Demand Model for High Speed 1 in UK

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Journal of Transportation Technologies 2013年第1期3卷 44-51页

作者： Francesca Pagliara John preston 不详

Induced travel is an important component of travel demand and increasing attention has been paid to building analytical model to get more precise travel demand forecasting. In general, induced demand can be defined in terms of additional trips that would be made if travel conditions improved (less congested, lower vehicle costs or tolls). In this paper the induced demand resulting from higher design speeds and, therefore by less travel time, for the High Speed 1 in UK will be modelled on the basis of the relationship between existing High Speed Rail demand (dependent variable) to existing High Speed Rail travel times and costs. The covariates include socioeconomic variables related to population and employment in the zones connected by the High Speed Rail services. This model has been calibrated by mean of a before and after study carried on the corridor, when the new High Speed Rail services was introduced. Elasticities of induced travel (trips and VMT) have been computed with respect to fares, travel time and service frequency.

关键词： High Speed Rail Induced Demand Regression Models Elasticities

E-selectin ligand complexes adopt an extended high-affinity conformation

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分子细胞生物学报:英文版 2016年第1期8卷 62-72页

作者： Roland C.preston Roman P.Jakob Florian P.C.Binder Christoph P.Sager Beat Ernst Timm Maier Institute of Molecular Pharmacy Universitat Basel4056 BaselSwitzerland Biozentrum Universitat Basel4056 BaselSwitzerland

E-selectin is a cell-adhesion molecule of the vascular endothelium that promotes essential leukocyte rolling in the early inflammatory response by binding to glycoproteins containing the tetrasaccharide sialyl Lewisx(sLex).Efficient leukocyte recruitment under vascular flow conditions depends on an increased lifetime of E-selectin/ligand complexes under tensile force in a so-called catch-bond binding ***-crystal structures of a representative fragment of the extracellular E-selectin region with sLex and a glycomimetic antagonist thereof reveal an extended E-selectin conformation,which is identified as a high-affinity binding state of E-selectin by molecular dynamics ***-angle X-ray scattering experiments demonstrate a direct link between ligand binding and E-selectin conformational transition under static conditions in *** permits tracing a series of concerted structural changes connecting ligand binding to conformational stretching as the structural basis of E-selectin catch-bond-mediated leukocyte *** detailed molecular view of the binding site paves the way for the design of a new generation of selectin *** is of special interest,since their therapeutic potentialwas recently demonstrated with the pan-selectin antagonists GMI-1070(Rivipansel).

关键词： inﬂammation leukocyte adhesion E-selectin glycomimetic antagonist sialyl Lewisx conformational change

急性炎症性脱髓鞘性多发性神经病早期电诊断的新标准

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世界核心医学期刊文摘（神经病学分册） 2005年第10期1卷 44-45页

作者： Al-Shekhlee A. Hachwi R.N. preston D.C. KatirjiB. 陈海 EMG Laboratory University Hospitals of Cleveland 960 Clague Road Westlake OH 4 4145 United States Dr.

A variety of electrodiagnostic methods are used to confirm the diagnosis of a cute inflammatory demyelinating polyneuropathy (AIDP), but difficulties are freq uent during the first few weeks of weakness. We compared the nerve conduction st udies (NCS) of patients with AIDP to those with critical illness polyneuropathy (CIP), a subacute axonal polyneuropathy. New electrodiagnostic criteria with gra ded certainty (normal, nondiagnostic, suggestive, highly suggestive, and definit e) were designed and applied in a blinded manner to both groups. Among the AIDP patients, 64% met the highly suggestive and definite criteria (specificity 95 - 100% , P < .0.01), whereas 80% of the CIP group fell in the nondiagnostic criteria (P < 0.001). The relative preservation of the sural sensory response in spite of at least two abnormal sensory NCS in the upper limb suggested acute de myelination (sensitivity 48% , specificity 96% , P < 0.001) and was even more conclusive when associated with absent or prolonged F waves. Motor and sensory r esponse amplitudes were lower in the CIP group, with comparable mean motor and s ensory distal latencies and motor conduction velocities. Motor conduction blocks were present in 10% of nerves in AIDP and were not encountered in CIP. The fr equency of absent or delayedFwaves and absent H reflex was similar in both group s. The correlation coefficient of the cerebrospinal fluid protein concentration with the designed criteria was higher in the AIDP group (r=0.9). We conclude tha t a new criterion with graded certainty is of higher specificity in the majority of patients with early AIDP.

关键词：电诊断暗示性多发性神经病脱髓鞘危重病远端潜伏期神经传导诊断标准运动传导速度腓肠神经

The transcription factor RelB restrains group 2 innate lymphoid cells and type 2 immune pathology in vivo

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Cellular & Molecular Immunology 2021年第1期18卷 230-242页

作者： Lei Zhang Yuanlin Ying Shuqiu Chen preston R.Arnold Fafa Tian Laurie J.Minze Xiang Xiao Xian C.Li Immunobiology and Transplant Science Center and Department of SurgeryHouston Methodist HospitalTexas Medical CenterHoustonTexasUSA Department of Neurology Xiangya HospitalCentral South UniversityChangshaChina Department of Urology Southeast University Zhongda HospitalNanjingChina Department of Surgery Weill Cornell Medical College of Cornell UniversityNew YorkNYUSA

The exact relationships between group 2 innate lymphoid cells(ILC2s)and Th2 cells in type 2 pathology,as well as the mechanisms that restrain the responses of these cells,remain poorly *** we examined the roles of ILC2s and Th2 cells in type 2 lung pathology in vivo using germline and conditional fie/b-deficient *** found that mice with germline deletion of Relb^(-/-)spontaneously developed prominent type 2 pathology in the lung,which contrasted sharply with mice with T-cell-specific Relb deletion(Relb^(f/f)Cd4-Cre),which were healthy with no observed autoimmune *** also found that in contrast to wild-type B6 mice,Rel6-defident mice showed markedly expanded ILC2s but not ILC1s or ***,adoptive transfer of naive CD4^(+)T cells into Rag1^(-/-)Relb^(-/-)hosts induced prominent type 2 lung pathology,which was inhibited by depletion of ***,we showed that Relb deletion led to enhanced expression of Bcl11b,a key transcription factor for *** concluded that RelB plays a critical role in restraining ILC2s,primarily by suppressing Bcl11b activity,and consequently inhibits type 2 lung pathology in vivo.

关键词： Allergic inflammation Innate lymphoid cells NF-kB RelB Th2 cells type 2 pathology

使用初级保健数据预测最易受寒冷天气影响的人群:病例交叉分析

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中国全科医学 2018年第12期 1391-1391页

作者： TAMMES P SARTINI C preston I 本刊编辑部

背景美国国家卫生与护理研究所(NICE)建议全科医生通过现有常规数据识别出在寒冷家庭中死亡和患病风险高的患者。目的调查社会人口学特征、临床因素和房屋能量效率特征是否可以预测寒冷相关死亡率。设计与场所从临床实践研究数据链中,选... 详细信息

背景美国国家卫生与护理研究所(NICE)建议全科医生通过现有常规数据识别出在寒冷家庭中死亡和患病风险高的患者。目的调查社会人口学特征、临床因素和房屋能量效率特征是否可以预测寒冷相关死亡率。设计与场所从临床实践研究数据链中,选取2012年4月—2014年3月死亡的34 777名年龄≥65岁的患者进行病例交叉分析。根据气象局数据,给出死亡当天和死亡前3天的平均温度,计算死亡日期之前/之后第28天的3 d平均温度。方法采用条件Logistic回归分析来估算温度相关死亡的OR值,以及表示温度与社会人口学特征、临床因素和房屋能量效率特征之间相互作用的ROR。结果较低3 d温度与较高死亡风险相关[OR=1.011/1℃下降,95%CI(1.007,1.015),P<0.001]。社会人口学特征、临床因素和房屋能量效率特征没有修正效应。分析与过冬死亡率(n=7 710)相关的冬季死亡原因,结果显示较低3 d温度对女性影响较弱[ROR=0.980/1℃下降,95%CI(0.959,1.002),P=0.082],对居住在英格兰北部的患者影响更大[ROR=1.040/1℃下降,95%CI(1.013,1.066),P=0.002]。结论全科医生不太可能通过现有常规数据识别出寒冷相关死亡的高风险老年患者。NICE可能需要完善其指导指南。

关键词：全科医生临床因素交叉分析社会人口学能量效率

冻干血球间接血凝试验诊断耕牛血吸虫病的研究

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湖南农业大学学报(自然科学版) 1980年第2期 53-57页

作者：周庆堂冯德南

我省诊断耕牛血吸虫病历来都采用粪孵检查。粪孵法要求每头牛做到三粪六检,每普查一次,花的人工多,费的时间长,瓶罐损耗大,而检出率却不高,许多患血吸虫的病牛查不出来。因此,研究一种方法简便、快速、低耗,灵敏度高、特异性强、查病效... 详细信息

我省诊断耕牛血吸虫病历来都采用粪孵检查。粪孵法要求每头牛做到三粪六检,每普查一次,花的人工多,费的时间长,瓶罐损耗大,而检出率却不高,许多患血吸虫的病牛查不出来。因此,研究一种方法简便、快速、低耗,灵敏度高、特异性强、查病效果好且易于推广的诊断方法,是耕牛血防迫切需要解决的课题之一。人医方面,首先提出间接血凝试验报告的是Kagan(1955),我国扬赞元等(1975)进行了冻干血球间接血凝试验研究。1975年preston和Duffus将血凝试验应用于诊断牛的血吸虫病。国内迄今尚无血凝试验诊断耕牛血吸虫病的公开报道。1977年10月,我们将间接血凝

关键词：间接血凝试验被动血凝反应耕牛役牛血凝抗原虫卵抗原血吸虫病裂体吸虫病地方病血球冻干

关节置换术后手术部位感染细菌的抗生素敏感性研究

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骨科动态 2006年第4期2卷 205-210页

作者： ERIC FULKERSON CRAUG J DELLA VALLE BRENT WISE MICHAEL WALSH CHARLES preston PAUL E DI CESARE 张晖（译）裴福兴（校） Investigation performed at the Musculoskeletal Research Center New York University Hospital for Joint Diseases New York NY and Rush University Medical Center Midwest Orthopaedics Chicago Illinois 四川大学华西医院骨科 610041

背景：目前，对于治疗疑似全髋或全膝关节置换术后假体周围感染的抗生素使用原则还没有共识。本研究旨在建立这样一个用药原则。方法：对146例患者进行回顾性研究。在这些患者进行全髋或全膝关节置换术后的翻修术时，共194个标本得到了... 详细信息

背景：目前，对于治疗疑似全髋或全膝关节置换术后假体周围感染的抗生素使用原则还没有共识。本研究旨在建立这样一个用药原则。方法：对146例患者进行回顾性研究。在这些患者进行全髋或全膝关节置换术后的翻修术时，共194个标本得到了细菌培养阳性结果。患者的一般信息、并存疾病情况、细菌种类、抗生素敏感性资料以及翻修术后细菌培养出现阳性结果所需要的天数均被记录。结果：共110髋、84膝得到的标本培养结果为阳性。其中70％为慢性感染，17％为急性术后局部感染，13％为急性血源性感染。翻修术后出现阳性培养结果的平均时间为3天。革兰氏阳性菌感染占绝大多数。在这些细菌中，88％对庆大霉素敏感，96％对万古霉素敏感，61％对头孢唑林敏感。多数的耐药菌来自于先前有过抗生素治疗失败史的患者。术后急性感染的菌株比慢性感染或血源性感染的菌株更易发生耐药。血源性感染患者分离得到的菌株对庆大霉素和头孢唑林都有高度的敏感性。结论：对疑似假体周围感染的经验性抗生素用药应该在对感染进行分类和确定革兰氏染色结果的指导下进行。我们认为，在得到培养结果之前，急性血源性感染应该一开始就使用头孢唑林和庆大霉素的联合治疗。所有术后慢性或急性革兰氏阳性菌感染或不能明确革兰氏染色结果的细菌感染都应该用万古霉素。革兰氏阴性菌感染应该用第三代或第四代头孢霉素。革兰氏阳性菌和阴性菌的混合感染应该联合使用万古霉素和第三代或第四代头孢霉素。另外，我们认为如果在术后第4天还没有得到细菌培养或是其他确诊的阳性结果就应该结束经验性抗生素治疗。可信水平：诊断性研究，Ⅳ级。进一步可信度参见作者介绍。

关键词：抗生素敏感性全膝关节置换感染细菌术后革兰氏阳性菌感染手术部位革兰氏阴性菌感染经验性抗生素治疗

The Unrecognized Value of Bio-Medical Engineers in Healthcare Projects in Developing Countries

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International Journal of Clinical Medicine 2014年第6期5卷 293-296页

作者： Carl E. Bartecchi Robert preston Catholic Health Initiatives (CHI) St. Anthony’s Hospital Lakewood USA School of Medicine University of Colorado Denver USA Bach Mai Hospital Project Denver USA

The healthcare needs of developing countries are great and ever increasing as their populations grow. Few assistance programs have recognized the value of the bio-medical engineer as part of the approach to the provision of healthcare in developing countries. An example of a program, the Bach Mai Hospital Project, in Vietnam, utilizing the talents of the bio-medical engineer, attests to the potential value of bio-medical engineers as part of the healthcare team. Their inclusion in such efforts can result in the saving of lives, time and money. Knowledge of their hospital's excess equipment inventory and their ability to restore medical equipment badly needed in a developing country makes them valuable additions to any medical assistance program.

关键词： Healthcare Developing Country Medical Equipment Volunteerism