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The immunology of human cytomegalovirus latency： could latent infection be cleared by novel immunotherapeutic strategies？

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Cellular & Molecular Immunology 2015年第2期12卷 128-138页

作者： Mark r Wills Emma Poole Betty Lau Ben Krishna john H Sinclair Department of Medicine University of Cambridge Cambridge UK

While the host immune response following primary human cytomegalovirus （HCMV） infection is generally effective at stopping virus replication and dissemination, virus is never cleared by the host and like all herpesviruses, persists for life. At least in part, this persistence is known to be facilitated by the ability of HCMV to establish latency in myeloid cells in which infection is essentially silent with, importantly, a total lack of new virus production. However, although the viral transcription programme during latency is much suppressed, a number of viral genes are expressed during latent infection at the protein level and many of these have been shown to have profound effects on the latent cell and its environment. Intriguingly, many of these latency-associated genes are also expressed during lyric infection. Therefore, why the same potent host immune responses generated during lytic infection to these viral gene products are not recognized during latency, thereby allowing clearance of latently infected cells, is far from clear. reactivation from latency is also a major cause of HCMV-mediated disease, particularly in the immune compromised and immune naive, and is also likely to be a major source of virus in chronic subclinical HCMV infection which has been suggested to be associated with long-term diseases such as atherosclerosis and some neoplasias. Consequently, understanding latency and why latenUy infected cells appear to be immunoprivileged is crucial for an understanding of the pathogenesis of HCMV and may help to design strategies to eliminate latent virus reservoirs, at least in certain clinical settings.

关键词： Cytomegalovirus latency immune evasion immunotherapeutic

No association between phosphatase and tensin homolog genetic polymorphisms and colon cancer

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World Journal of Gastroenterology 2009年第30期15卷 3771-3775页

作者： Lynette S Phillips Cheryl L Thompson Alona Merkulova Sarah J Plummer Thomas C Tucker Graham case Li Li Department of Epidemiology and Biostatistics and case Comprehensive Cancer Center Case Western Reserve University Cleveland OH 44106-7136 United States Departments of Family Medicine and Epidemiology and Biostatistics Case Center for Transdisciplinary Research on Energetics and Cancer Case Comprehensive Cancer Center Case Western Reserve University Cleveland OH 44106-7136m United States Department of Cancer Biology Cleveland Clinic Foundation Cleveland OH 44195-0001 United States Graham casey Department of Preventive Medicine University of Southern California Los Angeles CA 90033-1006 United States assisted with patient referrals recruitment and reviewed the manuscript coordinated the lab work and reviewed the manuscript Li L led the study design data collection and assisted with the manuscript preparation

AIM: To investigate the association between single nucleotide polymorphisms (SNPs) in the phosphatase and tensin homolog (PTEN) tumor suppressor gene and risk of colon cancer. METHODS: We utilized a population-based casecontrol study of incident colon cancer individuals (n= 421) and controls (n = 483) aged ≥ 30 years to conduct a comprehensive tagSNP association analysis of the PTEN gene. rESULTS: None of the PTEN SNPs were statistically significantly associated with colon cancer when controlled for age, gender, and race, or when additionally adjusted for other known risk factors (P > 0.05). Haplotype analyses similarly showed no association between the PTEN gene and colon cancer. CONCLUSION: Our study does not support PTEN as a colon cancer susceptibility gene.

关键词： Colon cancer Phosphatase and tensinhomolog Candidate gene Genetic polymorphisms Single nucleotide polymorphism association

A global,high-resolution(30-m)inland water body dataset for 2000:first results of a topographic-spectral classification algorithm

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International Journal of Digital Earth 2016年第2期9卷 113-133页

作者： Min Feng Joseph O.Sexton Saurabh Channan john r.Townshend Global Land Cover Facility Department of Geographical SciencesUniversity of MarylandCollege ParkMDUSA

The science and management of terrestrial ecosystems require accurate,high-resolution mapping of surface *** produced a global,30-m-resolution inland surface water dataset with an automated algorithm using Landsat-based surface reflectance estimates,multispectral water and vegetation indices,terrain metrics,and prior coarse-resolution water *** dataset identified 3,650,723 km2 of inland water globally–nearly three quarters of which was located in North America(40.65%)and Asia(32.77%),followed by Europe(9.64%),Africa(8.47%),South America(6.91%),and Oceania(1.57%).Boreal forests contained the largest portion of terrestrial surface water(25.03%of the global total),followed by the nominal‘inland water’biome(16.36%),tundra(15.67%),and temperate broadleaf and mixed forests(13.91%).Agreement with respect to the Moderate-resolution Imaging Spectroradiometer water mask and Landsat-based national land-cover datasets was very high,with commission errorsrrorsrelative to *** of these were accounted for in the seasonality of water cover,snow and ice,and clouds–effects which were compounded by differences in image acquisition date relative to reference *** Global Land Cover Facility(GLCF)inland surface water dataset is available for open access at the GLCF website(http://***).

关键词： inland water Landsat global high resolution MODIS

Correlation between rpoB gene mutation in Mycobacterium avium subspecies paratuberculosis and clinical rifabutin and rifampicin resistance for treatment of Crohn’s disease

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World Journal of Gastroenterology 2008年第17期14卷 2723-2730页

作者： Daniel r Beckler Sammer Elwasila George Ghobrial john F Valentine Saleh A Naser Department of Molecular Biology and Microbiology Burnett School of Biomedical Sciences Center for Biomolecular Sciences College of Medicine University of Central Florida Department of Medicine University of Florida Gainesville

AIM： To investigate overlapping regions of the rpoB gene previously involved with rifamycin resistance in M. tuberculosis and seek correlation between rpoB mutations in dinical MAP strains with susceptibility to rIF and rFB. METHODS： We designed a molecular-based PCr method for the evaluation of rifabutin （rFB） and rifampicin （rIF） resistance based on probable determinant regions within the rpoB gene of MAP, including the 81 bp variable site located between nucleotides 1363 and 1443. The minimum inhibitory concentration （MIC） for rIF was also determined against 11 MAP isolates in attempt to seek correlation with rpoB sequences. rESULTS： We determined that MAP strain 18 had an MIC of 〉 30 mg/L and ≤ 5 mg/L for rIF and rFB respectively, and a significant and novel rpoB mutation C1367T, compared to an MIC of ≤ 1.0 mg/L for both drugs in the wild type MAP. The 30-fold increase in the MIC was a direct result of the rpoB mutation C1367T, which caused an amino acid change Thr456 to Ile456 in the drug＇s binding site. In addition, MAP strain 185 contained five silent rpoB mutations and exhibited an MIC comparable to the wild-type. Moreover, our in vitro selected mutation in MAP strain UCF5 resulted in the generation of a new resistant strain （UCF5-rIF16r） that possessed T1442C rpoB mutation and an MIC 〉 30 mg/L and 〉 10 mg/L for rIF and rFB respectively. Sequencing of the entire rpoB gene in MAP strains UCF4, 18, and UCF5-rIF16r revealed an rpoB mutation A2284C further downstream of the 81 bp variable region in UCF4, accounting for observed slight increase in MIC. In addition, no other significant mutations were found in strains 18 and UCF-rIF16r. CONCLUSION： The data clearly illustrates that clinical and in vitro-selected MAP mutants with rpoB mutations result in resistance to rIF and rFB, and that a single amino acid change in the beta subunit may have a significant impact on rIF resistance. Unconventional drug susceptibility testing such as our molecular approach wi

关键词： Mycobacterium paratuberculosis Crohn's disease rifabutin rifampicin rpoB Minimum inhibitoryconcentration

Intermittent suckling with or without comingling of non-littermate piglets before weaning improves piglet performance in the immediate post-weaning period when compared with conventional weaning

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Journal of Animal Science and Biotechnology 2017年第3期8卷 721-732页

作者： Diana L.Turpin Pieter Langendijk Kate Plush john r.Pluske School of Veterinary and Life Sciences Murdoch UniversityMurdochWA 6150Australia Trouw Nutrition Veerstraat 38Boxmeer 5831 iNThe Netherlands South Australian research and Development Institute Roseworthy CampusJS Davis BuildingRoseworthySA 5371Australia Present address:SunPork Farms 563 Coleman RoadPinkerton PlainsSA 5400Australia

Background： In this experiment, intermittent suckling（IS） with or without the co-mingling（Co M） of piglets was studied as a method to stimulate solid feed intake and reduce post-weaning ***： Three weaning regimes using 30 multiparous sows were compared：（1） conventional weaning（CW）（n = 10 litters）, where piglets had continuous access to the sow until weaning（d 0, farrowing = d-25 relative to weaning）;（2） intermittent suckling（IS）（n = 10 litters）, where piglets were separated from the sow for 8 h/d starting at d-7（relative to weaning）; and（3） intermittent suckling with co-mingling（ISCo）（n = 10 litters） where IS started at d-7 and two litters were housed together during separation and then returned to their original sow. Ad libitum creep feed was available from d-17. At weaning pigs were housed in pens of 11 pigs, 27 pens in total. The ISCo treatment was divided in half to examine effects of different mixing strategies after weaning. Half of the ISCo litters were kept in familiar groups（ISCo F, familiar, n = 4） and the other half were mixed within treatment resulting in groups of unfamiliar pigs（ISCo NF, not familiar, n = 5）, the same as IS（n = 9） and CW（n = 9） ***： The ISCo piglets ate more creep feed in the week before weaning（P 〈 0.01）, but also showed more aggressive and manipulative behaviour on first day of Co M compared with CW piglets（P 〈 0.05）. IS with or without Co M increased exploratory and play behaviour on the first day of treatment intervention（P 〈 0.001） and increased sleeping behaviour on the last day of treatment intervention compared with CW（P 〈 0.001）. Mixing strategy at weaning had an effect on performance data with the highest growth and feed intake seen in ISCo F pigs 2 to 8 d after weaning（P 〈0.001）. IS and ISCo NF pigs also grew faster and ate more than CW pigs 2 to 8 d after weaning（P 〈 0.001）. Post-weaning injury scores suggested reduced aggression in ISCo as evidenced by reduced redness（skin irritation）（P 〈 0.05）, a

关键词： Behaviour Co-mingling Intermittent suckling Piglet Weaning

The ruminal microbiome associated with methane emissions from ruminant livestock

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Journal of Animal Science and Biotechnology 2017年第2期8卷 289-299页

作者： Ilma Tapio Timothy J.Snelling Francesco Strozzi r.john Wallace Green Technology Natural Resources Institute FinlandJokioinenFinland rowett Institute of Nutrition and Health University of AberdeenForesterhillAberdeen AB16 5BDUK. PTP Via Einstein-Loc.Cascina Codazza26900 Lodiltaly

Methane emissions from ruminant livestock contribute significantly to the large environmental footprint of *** rumen is the principal source of methane, and certain features of the microbiome are associated with low/high methane phenotypes. Despite their primary role in methanogenesis, the abundance of archaea has only a weak correlation with methane emissions from individual animals. The composition of the archaeal community appears to have a stronger effect, with animals harbouring the Methanobrevibacter gottschalki clade tending to be associated with greater methane emissions. Ciliate protozoa produce abundant H_2, the main substrate for methanogenesis in the rumen,and their removal（defaunation） results in an average 11% lower methane emissions in vivo, but the results are not consistent. Different protozoal genera seem to result in greater methane emissions, though community types（A, AB, B and O） did not differ. Within the bacteria, three different ‘ruminotypes＇ have been identified, two of which predispose animals to have lower methane emissions. The two low-methane ruminotypes are generally characterized by less abundant H_2-producing bacteria. A lower abundance of Proteobacteria and differences in certain Bacteroidetes and anaerobic fungi seem to be associated with high methane emissions. rumen anaerobic fungi produce abundant H_2 and formate, and their abundance generally corresponds to the level of methane emissions. Thus, microbiome analysis is consistent with known pathways for H_2 production and methanogenesis, but not yet in a predictive manner. The production and utilisation of formate by the ruminal microbiota is poorly understood and may be a source of variability between animals.

关键词： Archaea Methane Microbiome rumen

Online single-session interventions for Kenyan adolescents:study protocol for a comparative effectiveness randomised controlled trial

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General Psychiatry 2021年第3期34卷 163-168页

作者： Akash r Wasil Tom Lee Osborn john r Weisz robert J Derubeis Department of Psychology University of PennsylvaniaPhiladelphiaPennsylvaniaUSA Shamiri Institute NairobiKenya Department of Psychology Harvard UniversityCambridgeMassachusettsUSA

Background Mental health problems are the leading cause of disability among adolescents worldwide,yet access to treatment is *** digital interventions have been shown to improve youth mental health,but little is known about which digital interventions are most *** To evaluate the effectiveness of two digital single-session interventions(Shamiri-Digital and Digital-CBT(cognitive-behavioural therapy))among Kenyan *** We will perform a school-based comparative effectiveness randomised controlled *** 926 Kenyan adolescents will be randomly assigned to one of three conditions:Shamiri-Digital(focused on gratitude,growth mindsets and values),Digital-CBT(focused on behavioural activation,cognitive restructuring and problem solving)or a study-skills control condition(focused on note-taking and essay writing skills).The primary outcomes include depressive symptoms(measured by the Patient Health Questionnaire-8),anxiety symptoms(Generalized Anxiety Disorder Screener-7)and subjective well-being(Short Warwick-Edinburgh Mental Well-being Scale).The secondary outcomes include acceptability,appropriateness,primary control and secondary *** and appropriateness will be measured immediately post-intervention;other outcomes will be measured 2 weeks,4 weeks and 12 weeks *** We hypothesise that adolescents assigned to Shamiri-Digital and adolescents assigned to Digital-CBT will experience greater improvements(assessed via hierarchical linear models)than those assigned to the control *** will also compare Shamiri-Digital with Digital-CBT,although we do not have a preplanned *** Our findings will help us evaluate two digital single-session interventions with different theoretical *** effective,such interventions could be disseminated to reduce the public health burden of common mental health problems.

关键词： assigned behaviour Edinburgh

Targeting Ageing to Decrease Complex Non-Communicable Human Diseases

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Journal of Genetics and Genomics 2014年第9期41卷 457-458页

作者： Jing-Dong J.Han john r.Speakman Chinese Academy of Sciences Key Laboratory of Computational Biology Chinese Academy of Sciences-Max Planck Partner Institute for Computational BiologyShanghai Institutes for Biological SciencesChinese Academy of Sciences State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of Sciences Institute of Biological and Environmental Sciences University of Aberdeen

During the last two centuries, there have been many spectacular advances in medical science, the main consequence of which has been the dramatically reduced burden of infectious diseases. While in the 1800s many people died before reaching adult- hood, nowadays most people survive. Hence average life ex- pectancy in 1800s was around 30-40, which was barely higher than it had been in Greek and roman times （Finch, 2010）, but nowadays life expectancy in most modernised economies is around 75 - 80. This demographic shift, which has happened in only 200 years, has created a dramatic change in the causes of mortality. The major killers in the modern world are non- communicable diseases （NCDs）： principally cardiovascular disease, cancer and neurodegenerative disorders such as Alz- heimer＇s disease. A major factor that influences susceptibility to all these diseases is age. As we get older, our risk of developing these NCDs increases enormously. For example, the rate of breast cancer in females at age 15-19 is less than 10 per 100,000 population, but this increases to 100 at age 40-44, 275 at age 55--59 and 450 at age 85 ＋（http：//***/ cancer-info/cancerstats/types/breast/incidence/#age）. Ageing has consequently become a major medical, social and economic burden to many countries.

关键词： Targeting Ageing to Decrease Complex Non-Communicable Human Diseases

Three cases of uncommon medication-associated osteonecrosis of temporal bone

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第3期10卷 237-240页

作者： Hunter VanDolah Jason r.Crossley H.Jeffrey Kim Georgetown University School of Medicine Washington DCUSA Department of Otolaryngology–Head and Neck Surgery MedStar Georgetown University HospitalWashington DCUSA

Introduction:Medication-related osteonecrosis of the temporal bone is rare and has been reported to be associated with the use of anti-resorptive and biologic ***,we present the first case of tyrosine-kinase inhibitor-related external auditory canal(EAC)osteonecrosis as well as two cases related to anti-resorptive ***:A retrospective case ***:case one:an 84-year-old female presented with chronic otitis externa and osteonecrosis of EACs *** had a history of osteoporosis treated with denosumab and risedronic *** successfully underwent left EAC reconstruction using an inferiorly-based pedicle periosteal flap while the right ear canal was managed *** two:a 69-year-old male presented with osteonecrosis of the right *** had a history of osteoporosis treated with alendronic acid and zoledronic *** osteonecrosis is conservatively managed with local debridement and antibiotic *** three:a 60-year-old male presented with osteonecrosis of the right inferior *** had a history of chronic myelogenous leukemia treated with a tyrosine-kinase inhibitor,*** failing conservative therapy,he underwent right ear canal reconstruction using a periosteal vascular pedicle flap without complication and experienced complete resolution to his ***:Anti-resorptive agents and/or tyrosine kinase inhibitors may lead to dysregulation of bone remodeling and result in rare cases of temporal bone *** a local debridement and antibiotic therapy fail,definitive surgical excision of necrotic bone with subsequent reconstruction of the EAC may offer patients a possible resolution in symptoms.

关键词： bisphosphonates denosumab external auditory canal imatinib medication-related osteonecrosis osteonecrosis temporal bone tyrosine-kinase Inhibitors