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High-throughput screening against thioredoxin glutathione reductase identifies novel inhibitors with potential therapeutic value for schistosomiasis

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Infectious Diseases of Poverty 2015年第1期4卷 300-315页

作者： Ting Li Peter D.Ziniel Pan-qing He Valerie P.Kommer Gregory j.crowther Min He Qing Liu Wesley C.Van Voorhis David L.Williams Ming-Wei Wang The National Center for Drug Screening Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Department of Immunology and Microbiology Rush University Medical CenterChicagoIL 60612USA Division of Allergy and Infectious Diseases University of WashingtonSeattleWA 98195USA

Background:Schistosomiasis,a parasitic disease also known as bilharzia and snail fever,is caused by different species of flatworms,such as Schistosoma mansoni(***).Thioredoxin glutathione reductase(TGR)from ***(SmTGR)is a well-characterized drug target for schistosomiasis,yet no anti-SmTGR compounds have reached clinical trials,suggesting that therapeutic development against schistosomiasis might benefit from additional scaffolds targeting this ***:A high-throughput screening(HTS)assay in vitro against SmTGR was developed and applied to a diverse compound *** activity was quantified with ThioGlo®,a reagent that fluoresces upon binding to the free sulfhydryl groups of the reaction product GSH(reduced glutathione).Results:We implemented an HTS effort against 59,360 synthetic *** the primary screening,initial hits(928 or 1.56%)showing greater than 90%inhibition on SmTGR activity at a final concentration of 10μM for each compound were *** tests were carried out to confirm the effects of these hits and to explore the concentration-dependent response *** a result,74 of them(0.12%)representing 17 chemical scaffolds were confirmed and showed a great concentration-dependent inhibitory trend against SmTGR,including structures previously shown to be lethal to schistosomal *** these,two scaffolds displayed a limited structure-activity *** tested in cultured larvae,39 compounds had cidal activity in 48 h,and five of them killed larvae completely at 3.125μ*** these,three compounds also killed adult worms ex vivo at concentrations between 5μM and 10μ***:These confirmed hits may serve as starting points for the development of novel therapeutics to combat schistosomiasis.

关键词： High-throughput screening Schistosomiasis Inhibitor Thioredoxin glutathione reductase

A multi-scale cholera model linking between-host and within-host dynamics

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International journal of Biomathematics 2018年第3期11卷 53-75页

作者： Chayu Yang drew Posny Feng Bao jin Wang Department of Mathematics University of Tennessee at Chattanooga Chattanooga TN 37403 USA NSF Center for Integrated Pest Management North Carolina State University Raleigh NC 27606 USA

We propose a multi-scale modeling framework to investigate the transmission dynamics of cholera. At the population level, we employ a SIR model for the between-host transmission of the disease. At the individual host level, we describe the evolution of the pathogen within the human body. The between-host and within-host dynamics are connected through an environmental equation that characterizes the growth of the pathogen and its interaction with the hosts outside the human body. We put a special emphasis on the within-host dynamics by making a distinction for each individual host. We conduct both mathematical analysis and numerical simulation for our model in order to explore various scenarios associated with cholera transmission and to better understand the complex, multi-scale disease dynamics.

关键词： Cholera equilibrium stability multi-scale modeling

The First Pilot Epigenetic Type Improvement of Neuropsychiatric Symptoms in a Polymorphic Dopamine D2 (-DRD2/ANKK (Taq1A)), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) Compromised Preadolescence Male with Putative PANDAS/CANS: Positive Clinical Outcome with Precision-Guided DNA Testing and Pro-Dopamine Regulation (KB220) and Antibacterial Therapies

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Open journal of Immunology 2024年第3期14卷 60-86页

作者： Kenneth Blum Igor Elman David Han Colin Hanna David Baron Ashim Gupta Shan Kazmi jag Khalsa Debasis Bagchi Thomas McLaughlin Rajendra D. Badgaiyan Edward j. Modestino drew Edwards Catherine A. Dennen Eric R. Braverman Abdalla Bowirrat Keerthy Sunder Kevin Murphy Nicole jafari Foojan Zeine Paul R. Carney Mark S. Gold Kai-Uwe Lewandowski Alireza Sharafshah Aryeh R. Pollack Panayotis K. Thanos Division of Addiction Research & Education Center for Sports and Mental Health Western University of Health Sciences Pomona CA USA Department of Psychiatry Boonshoft School of Medicine Wright State University and Dayton VA Medical Centre Dayton OH USA Division of Nutrigenomics Victory Nutrition International Lederoch PA USA Institute of Psychology ELTE Etvs Lornd University Budapest Hungary Department of Psychiatry School of Medicine University of Vermont Burlington VT USA The Kenneth Blum Behavioral & Neurogenetic Institute LLC. Austin TX USA Department of Molecular Biology Adelson School of Medicine Ariel University Ariel Israel Division of Neuromodulation Research Karma Doctors & Karma TMS Palm Springs CA USA Division of Personalized Interventions Peak Logic Del Mar CA USA Division of Personalized Medicine Cross-Cultural Research & Educational Institute San Clemente CA USA Awareness Integration Institute San Clemente CA USA Division of Personalized Pain Therapy Center for Advanced Spine Care of Southern Arizona Tucson AZ USA Department of Psychiatry Harvard School of Medicine Cambridge MA USA Department of Management Science and Statistics University of Texas San Antonio TX USA Behavioral Neuropharmacology and Neuroimaging Laboratory Clinical Research Institute on Addictions Department of Pharmacology and Toxicology Jacobs School of Medicine and Biomedical Sciences University at Buffalo Buffalo NY USA Future Biologics Lawrenceville GA USA Department of Microbiology Immunology & Tropic Diseases School of Medicine Georgetown University Washington DC USA Department of Pharmaceutical Sciences College of Pharmacy Texas Southern University Houston TX USA Department of Psychiatry School of Medicine Case Western University Cleveland OH USA Brain and Behavior Laboratory Curry College Milton MA USA The Neurogenesis Project Jacksonville FL USA Department of Family Medicine Jefferson Health Northeast Philadelphia PA USA Departmen

Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy regarding treatment approaches, especially related to the behavioral sequelae, we have hypothesized in other published work that it is characterized by the rapid onset of Reward Deficiency Syndrome (RDS) in children. We propose utilizing a multi-systems biological approach involving the coupling of genetic addiction risk testing and pro-dopamine regulation (KB220/POLYGEN®) to help induce “dopamine homeostasis” in patients with PANDAS, especially those with known DNA-induced hypodopaminergia. This case study examines a 12-year-old Caucasian male with no prior psychiatric issues who presented with a sudden onset of severe anxiety, depression, emotional liability, and suicidal ideation. The patient underwent genotyping and the genetic addiction risk score (GARS) testing, which revealed risk polymorphisms in the dopamine D2 (-DRD2/ANKK (Taq1A), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) genes. These polymorphisms have been linked to hypodopaminergia. The patient was subsequently placed on research ID-KB220ZPBMPOLY (POLYGEN®), and albeit the possibility of bias, based upon self and parental assessment, a marked rapid improvement in psychiatric symptoms was observed. In the second phase of treatment (102 days utilizing KB220), the patient received standard antibody testing, which was positive for Lyme. Antibacterial therapy started immediately, and KB220z was discontinued to provide a wash-out period. A monotonic trend analysis was performed on each outcome measure, and a consistently decreasing trend was observed utilizing antibacterial therapy. Our recommendation, albeit only one case, is to utilize and further research a combined therapeutic approach, involving precision-guided DNA testing and pro-dopamine regulation along with antibacterial therapy, as well as

关键词： PANDAS CANS Genetic Addiction Risk Testing (GARS) Pro-Dopamine Regulation Hypodopaminergia Polymorphisms Antibacterial Therapy Infections

Fabrication of Polymeric Visual Decoys for the Male Emerald Ash Borer （Agrilus planipennis）

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journal of Bionic Engineering 2013年第2期10卷 129-138页

作者： drew P. Pulsifer Akhlesh Lakhtakia Mahesh S. Narkhede Michael j. Domingue Beverly G. Post jayant Kumar Raul j. Martln-Palma Thomas C. Baker Department of Engineering Science & Mechanics Pennsylvania State University University Park Pennsylvania 16802 USA Center for Advanced Materials and Department of Plastics Engineering University of Massachusetts Lowell Lowell MA 01854 USA Department of Entomology Pennsylvania State University University Park PA 16802 USA Center for Advanced Materials and Department of Physics & Applied Physics University of Massachusetts Lowell Lowell MA 01854 USA Department of Materials Science & Engineering Pennsylvania State University University Park Pennsylvania 16802 USA

Through a bioreplication approach, we have fabricated artificial visual decoys for the invasive species Agrilus planipen- nis--commonly known as the Emerald Ash Borer （EAB）. The mating behavior of this species involves an overflying EAB male pouncing on an EAB female at rest on an ash leaflet before copulating. The male spots the female on the leaflet by visually detecting the iridescent green color of the female＇s elytra. As rearing EAB and then deploying dead females as decoys for trapping is both arduous and inconvenient, we decided to fabricate artificial decoys. We used a dead female to make a negative die of nickel and a positive die of epoxy. Decoys were then made by first depositing a quarter-wave-stack Bragg reflector on a polymer sheet and then stamping it with a pair of matched negative and positive dies to take the shape of the upper surface of an EAB female. As nearly 100 artificial decoys were fabricated from just one EAB female, this bioreplication process is industrially scalable. Preliminary results from a field trapping test are indicative of success.

关键词： bioreplication conformal-evaporated-film-by-rotation method electroforming negative die positive die stampingCopyright ~ 2013 jilin University. Published by Science Press and Elsevier Limited. All rights reserved.

Field testing innovative differential geospatial and photogrammetric monitoring technologiesin mountainous terrain near Ashcroft,British Columbia,Canada

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journal of Mountain Science 2021年第1期18卷 1-20页

作者： David HUNTLEY Peter BOBROWSKY Roger MACLEOD Robert COCKING jamel jOSEPH drew ROTHERAM-CLARKE Geological Survey of Canada 1500-605 Robson StreetVancouverBritish ColumbiaV6B 5J3Canada Geological Survey of Canada 9860 West Saanich RoadSidneyBritish ColumbiaV8L 4B2Canada

This paper presents a novel approach to continuously monitor very slow-moving translational landslides in mountainous terrain using conventional and experimental differential global navigation satellite system(d-GNSS)technologies.A key research question addressed is whether displacement trends captured by a radio-frequency“mobile”d-GNSS network compare with the spatial and temporal patterns in activity indicated by satellite interferometric synthetic aperture radar(InSAR)and unmanned aerial vehicle(UAV)*** testing undertaken at Ripley Landslide,near Ashcroft in south-central British Columbia,Canada,demonstrates the applicability of new geospatial technologies to monitoring ground control points(GCPs)and railway infrastructure on a landslide with small and slow annual displacements(<10 cm/yr).Each technique records increased landslide activity and ground displacement in late winter and early *** this interval,river and groundwater levels are at their lowest levels,while ground saturation rapidly increases in response to the thawing of surficial earth materials,and the infiltration of snowmelt and runoff occurs by way of deep-penetrating tension cracks at the head scarp and across the main slide *** over the last decade provides vital information for government agencies,national railway companies,and other stakeholders to understand geohazard risk,predict landslide movement,improve the safety,security,and resilience of Canada’s transportation infrastructure;and reduce risks to the economy,environment,natural resources,and public safety.

关键词： Landslide Change detection monitoring Global Navigation Satellite System Real-Time Kinematic System GeocubeTM Bathymetric Survey Unmanned Aerial Vehicle Interferometric Synthetic Aperture Radar

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Methylation of TIMP3 in esophageal squamous cell carcinoma

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World journal of Gastroenterology 2008年第2期14卷 203-210页

作者： Eric Smith Neville j De Young Zi-Qiang Tian Maria Caruso a.drew R Ruszkiewicz jun-Feng Liu Glyn G jamieson Paul a.drew Discipline of Surgery School of Medicine Faculty of Health Sciences TheUniversity of Adelaide Royal Adelaide Hospital South Australia5005 Australia Department of Thoracic Surgery Fourth Hospital of Hebei Medical University Shijiazhuang050011 Hebei Province China Division of Tissue Pathology Institute of Medical and Veterinary Science AdelaideSouth Australia 5000 Australia School of Nursing and Midwifery Flinders University Bedford Park South Australia 5042 Australia

AIM: To measure the frequency of DNA methylation of the tissue inhibitor of metalloproteinase 3 (TIMP3) promoter and relate this to any change of gene expression in esophageal squamous cell carcinoma in patients from a region of high incidence in ***: Cancer cell lines were treated with or without the demethylating reagent 5-aza-2’-deoxycytidine. Methylation of the TIMP3 promoter was assessed in three regions by melt curve analysis and its expression was assessed by real-time RT-PCR. Tumors and proximal resection margins were obtained from 64 patients with esophageal squamous cell carcinoma from a region of high incidence in China. Methylation was assessed by melt curve analysis and expression by ***: Methylation in one of the three promoter regions assessed correlated with gene silencing in esophageal cell lines. A degree of methylation of TIMP3 was found in only four esophageal squamous cell carcinomas, and partial loss of TIMP3 protein expression in just ***: Methylation and loss of expression of TIMP3 occurs infrequently in esophageal squamous cell carcinoma in a region of high incidence in China.

关键词： Esophageal squamous cell carcinoma Immunohistochemistry Methylation TIMP3

Cover Crop and Irrigation Effects on Soil Microbial Communities and Enzymes in Semiarid Agroecosystems of the Central Great Plains of North America

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Pedosphere 2016年第2期26卷 192-205页

作者： Francisco j. CALDERON David NIELSEN Veronica ACOSTA-MARTINEZ Merle F. VIGIL drew LYON USDA-ARS Central Great Plains Research Station Akron CO 80720 USA USDA-ARS Cropping Systems Research Laboratory Wind Erosion and Water Conservation Unit Lubbock TX 79415 USA Department of Crop and Soil Sciences Washington State University Pullman WA 99164-6420 USA

Cover crops can have beneficial effects on soil microbiology by increasing carbon （C） supply, but these beneficial effects can be modulated by precipitation conditions. The objective of this study was to compare a fallow-winter wheat （Triticum aestivum L.） rotation to several cover crop-winter wheat rotations under rainfed and irrigated conditions in the semiarid US High Plains. Experiments were carried out at two sites, Sidney in Nebraska, and Akron in Colorado, USA, with three times of soil sampling in 2012--2013 at cover crop termination, wheat planting, and wheat maturity. The experiments included four single-species cover crops, a 10-species mixture, and a fallow treatment. The variables measured were soil C and nitrogen （N）, soil community structure by fatty acid methyl ester （FAME） profiles, and soil β-glucosidase,β-glucosaminidase, and phosphodiesterase activities. The fallow treatment, devoid of living plants, reduced the concentrations of most FAMEs at cover crop termination. The total FAME concentration was correlated with cover crop biomass （R = 0.62 at Sidney and 0.44 at Akron）. By the time of wheat planting, there was a beneficial effect of irrigation, which caused an increase in myeorrhizal and protozoan markers. At wheat maturity, the cover crop and irrigation effects on soil FAMEs had subsided, but irrigation had a positive effect on the β-glucosidase and phosphodiesterase activities at Akron, which was the drier of the two sites. Cover crops and irrigation were slow to impact soil C concentration. Our results show that cover crops had a short-lived effect on soil microbial communities in semiarid wheat-based rotations and irrigation could enhance soil enzyme activity. In the semiarid environment, longer time spans may have been needed to see beneficial effects of cover crops on soil microbial community structure, soil enzyme activities, and soil C sequestration.

关键词： crop rotation enzyme activity FAME profile fatty acid methyl ester winter wheat

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Who＇s your neighbor？ Acoustic cues to individual identity in red squirrel Tamiasciurus hudsonicus rattle calls

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Current Zoology 2012年第5期58卷 758-764页

作者： Shannon M. DIGWEED drew RENDALL Teana IMBEAU Departments of Psychology and Biological Science Grant MacEwan University Edmonton Alberta T5J 2P2 Canada Department of Psychology University of Lethbridge Lethbridge Alberta T1K 3M4 Canada Department of Biological Science Grant MacEwan University Edmonton Alberta T5J 2P2 Canada

North American red squirrels Tamiasciurus hudsonicus often produce a loud territorial rattle call when conspecifics enter or invade a territory. Previous playback experiments suggest that the territorial rattle call may indicate an invader＇s identity as squirrels responded more intensely to calls played from strangers than to calls played from neighbors. This dear-enemy effect is well known in a variety of bird and mammal species and functions to reduce aggressive interactions between known neighbors. However, although previous experiments on red squirrels suggest some form of individual differentiation and thus recognition, detailed acoustic analysis of potential acoustic cues in rattle calls have not been conducted. If calls function to aid in conspecific identifi- cation in order to mitigate aggressive territorial interactions, we would expect that individual recognition cues would be acoustically represented. Our work provides a detailed analysis of acoustic cues to identity within rattle calls. A total of 225 calls across 32 in- dividual squirrels from Sheep River Provincial Park, Kananaskis, AB, Canada, were analyzed with discriminant function analysis for potential acoustic cues to individual identity. Initial analysis of all individuals revealed a reliable acoustic differentiation across individuals. A more detailed analysis of clusters of neighboring squirrels was performed and results again indicated a statistically significant likelihood that calls were assigned correctly to specific squirrels （55%-75% correctly assigned）; in other words squirrels have distinct voices that should allow for individual identification and discrimination by conspecifics [Current Zoology 58 （5）： 758-764, 2012].

关键词： Vocal communication Territory calls Red squirrel Dear-enemy Individual identity

用电子模拟乘法器测量功率、无功功率、伏安的新方案

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电测与仪表 1967年第2期 11-14+18页

作者： A.j.drew

引言测量导彼中的电压和电流,以及自一远距离遥测这些量,是一相当简单的事情,但测量功率却不这样简单。在本地测量功率时,古典的西门子功率表是通用的一种形式,但用这种仪表作遥测功率指示时需要有复杂的伺服系毓,它可以是力矩平衡式或... 详细信息

引言测量导彼中的电压和电流,以及自一远距离遥测这些量,是一相当简单的事情,但测量功率却不这样简单。在本地测量功率时,古典的西门子功率表是通用的一种形式,但用这种仪表作遥测功率指示时需要有复杂的伺服系毓,它可以是力矩平衡式或位置追随式的。另一通用的基于积算能量表的功率遥测法,是由能量表圆盘的旋蒋产生一系列脉冲,脉冲的频率是线路中功率的度量。可惜这种方法在被测量变化时响应缓慢,譬如在到达新数值的80%时,需要15～30秒。

关键词：无功功率倍频电流道流霍尔相敏整流器乘法器