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Neurofibromatosis:The role of guanosine triphosphatase activating proteins in sensory neuron function

生理学报 2008年第5期60卷 581-583页

作者： cynthia m.hingtgen Departments of Neurology and Pharmacology and Toxicology Indiana University School of MedicineIndianapolisIndianaUSA

Neurofibromatosis type 1(NF1) is a common autosomal dominant disease characterized by formation of multiple benign and malignant *** with this disorder also experience chronic pain,which can be ***,the protein product of the Nf1 gene,is a guanosine triphosphatase activating protein(GAP) for p21Ras(Ras).Loss of Nf1 results in an increase in activity of the Ras transduction *** of the growing evidence suggesting involvement of downstream components of the Ras transduction cascade in the sensitization of nociceptive sensory neurons,we examined the stimulus-evoked release of the neuropeptides,substance P(SP) and calcitonin gene-related peptide(CGRP),from primary sensory neurons of mice with a mutation of the Nf1 gene(Nf1+/-).measuring the levels of SP and CGRP by radioimmunoassay,we demonstrated that capsaicinstimulated release of neuropeptides is 3-5 folds higher in spinal cord slices from Nf1+/-mice than that from wildtype mouse *** addition,the potassium-and capsaicin-stimulated release of CGRP from the culture of sensory neurons isolated from Nf1+/-mice was more than double that from the culture of wildtype *** patch-clamp electrophysiological techniques,we also examined the excitability of capsaicin-sensitive sensory *** was found that the number of action potentials generated by the neurons from Nf1+/-mice,responsing to a ramp of depolarizing current,was more than three times of that generated by wildtype *** with that observation,neurons from Nf1+/-mice had lower firing thresholds,lower rheobase currents and shorter firing latencies compared with wildtype *** data clearly demonstrate that GAPs,such as neurofibromin,can alter the excitability of nociceptive sensory *** augmented response of sensory neurons with altered Ras signaling may explain the abnormal pain sensations experienced by people with NF1 and suggests an important role of GAPs in the mechanism of sensor

关键词：感觉神经元神经系统蛋白质多发性神经纤维瘤临床分析

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Effects of temperature and hydric environment on survival of the Panamanian Golden Frog infected with a pathogenic chytrid fungus

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Integrative Zoology 2010年第2期5卷 143-153页

作者： Heidi m.BUSTAmANTE Lauren J.LIVO cynthia CAREY Department of Integrative Physiology University of ColoradoBoulderColoradoUSA

Considerable controversy exists concerning whether or not climate changes(particularly global warming)are causing outbreaks of a lethal amphibian pathogen,the chytrid fungus Batrachochytrium dendrobatidis(Longcore,Pessier&*** 1999).In the present study,groups of Panamanian golden frogs(Atelopus zeteki Dunn,1993),a critically endangered amphibian thought to be nearly extinct in Panama,were exposed to varying dosages of zoospores of Batrachochytrium dendrobatidis,temperatures and hydric environments in order to learn whether this species is susceptible to this pathogen and,if so,how environmental factors affect *** pathogen proved to be highly lethal for *** exposed to a dosage of 100 Bd zoospores survived significantly(Pmate change and the decline of these frogs in the field,but they inform the discussion about how environmental conditions can have an impact on the interaction between a susceptible amphibian and this *** data do not support the contention that rising global temperatures are necessary to cause the death of amphibians infected with this pathogen because the pathogen was equally lethal at 17 as at 23℃,and frogs at the warmer temperature lived significantly longer than those at the cooler one.

关键词： amphibian declines Atelopus zeteki Batrachochytrium dendrobatidis chytridiomycosis climatelinked-epidemic hypothesis

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NETosis,complement,and coagulation:a triangular relationship

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Cellular & molecular Immunology 2019年第1期16卷 19-27页

作者： cynthia m.de Bont Wilbert C.Boelens Ger J.m.Pruijn Department of Biomolecular Chemistry Institute for Molecules and Materials(IMM)Radboud UniversityNijmegenThe Netherlands

NETosis is a regulated form of neutrophil cell death that contributes to the host defense against pathogens and was linked to various diseases soon after its first description in *** NETosis,neutrophils release neutrophil extracellular traps(NETs),which can capture and kill bacteria and other pathogens to prevent them from *** substantial progress has been made in our understanding of NETosis,the precise mechanism underlying NETosis is still a matter of *** continues to elucidate the molecular pathways involved in *** recent years,interactions with the complement and coagulation systems have become increasingly *** complement proteins can stimulate NET formation,and NETs,in turn,can serve as a platform for complement *** addition,NETs can act as a scaffold for thrombus formation during *** crosstalk between the coagulation and complement systems has been previously described,NETosis appears to be a third important player in this consortium to protect the host against *** review summarizes our current knowledge on the mutual interactions between NETosis,the complement system and the coagulation system,with an emerging description of their complex triangular relationship.

关键词： coagulation complement NETosis neutrophils thrombosis

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A pretargeting nanoplatform for imaging and enhancing anti-inflammatory drug delivery

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Bioactive materials 2020年第4期5卷 1102-1112页

作者： min Kyung Khang Jun Zhou cynthia m.Co Shuxin Li Liping Tang Department of Chemistry and Biochemistry University of Texas at Arlington700 Planetarium PlaceChemistry Physics Building Room 130ArlingtonTX76019-0065USA Department of Bioengineering University of Texas at ArlingtonEngineering Research BuildingRoom 226Box 19138ArlingtonTX76010USA

This work details a newly developed“sandwich”nanoplatform via neutravidin-biotin system for the detection and treatment of ***,biotinylated-and folate-conjugated optical imaging micelles targeted activated macrophages via folate/folate receptor ***,multivalent neutravidin proteins in an optimal concentration accumulated on the biotinylated ***,biotinylated anti-inflammatory drug-loaded micelles delivered drugs effectively at the inflammatory sites via a highly specific neutravidin-biotin *** in vitro and in vivo studies have shown that the“sandwich”pretargeting platform was able to diagnose inflammation by targeting activated macrophages as well as improve the therapeutic efficacy by amplifying the drug delivery to the inflamed *** overall results support that our new pretargeting platform has the potential for inflammatory disease diagnosis and treatment.

关键词： Polymeric micelles Neutravidin/biotin system Pretargeting macrophages Dexamethasone Inflammatory responses

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Socio-cultural determinants of timely and delayed treatment of Buruli ulcer: implications for disease control

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Infectious Diseases of Poverty 2012年第1期1卷 48-60页

作者： mercy m Ackumey margaret Gyapong matilda Pappoe cynthia Kwakye maclean mitchell G Weiss School of Public Health College of Health SciencesUniversity of GhanaAccraGhana Swiss Tropical and Public Health Institute BaselSwitzerland University of Basel BaselSwitzerland Dodowa Health Research Centre Ghana Health ServiceDodowaGhana Amasaman Hospital Ghana Health ServiceAccraGhana

Introduction:Public health programmes recommend timely medical treatment for Buruli ulcer(BU)infection to prevent pre-ulcer conditions from progressing to ulcers,to minimise surgery,disabilities and the socio-economic impact of *** the role of socio-cultural determinants of timely medical treatment may assist in guiding public health programmes to improve treatment *** study clarified the role of socio-cultural determinants and health system factors affecting timely medical treatment for BU in an endemic area in ***:A semi-structured explanatory model interview based on the explanatory model interview catalogue(EmIC)was administered to 178 BU-affected *** on research evidence,respondents were classified as timely treatment(use of medical treatment 3 months from awareness of disease)and delayed treatment(medical treatment 3 months after onset of disease and failure to use medical treatment).The outcome variable,timely treatment was analysed with cultural epidemiological variables for categories of distress,perceived causes of BU,outside-help and reasons for medical treatment in logistic regression *** median time for the onset of symptoms to treatment was computed in *** phenomenological analysis of respondents’narratives clarified the meaning,context and dynamic features of the relationship of explanatory variables with timely medical ***:The median time for initiating treatment was 25 days for pre-ulcers,and 204 days for *** loss and use of herbalists showed significantly negative associations with timely ***’use of herbalists was often motivated by the desire for quick recovery in order to continue with work and because herbalists were relatives and easily ***,drinking unclean water was significantly associated with timely treatment and access to health services encouraged timely treatment(OR 8.5,p=0.012).Findings show that health system factors of

关键词： services lists clarified

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Click chemistry-based pre-targeting cell delivery for cartilage regeneration

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Regenerative Biomaterials 2021年第3期8卷 11-21页

作者： cynthia m.Co Samira Izuagbe Jun Zhou Ning Zhou Xiankai Sun Joseph Borrelli Liping Tang Department of Bioengineering University of Texas at ArlingtonPO Box 19138ArlingtonTX 76019USA Department of Radiology University of Texas Southwestern MedicalDallasTX 75390USA

A fraction of the OA patient population is affected by post-traumatic osteoarthritis(PTOA)following acute joint *** or reversing the progression of PTOA following joint injury could improve long-term functional outcomes,reduced disability,and medical *** more effectively treat articular cartilage injury,we have developed a novel cell-based therapy that involves the pretargeting of apoptotic chondrocytes and the delivery of healthy,metabolically active chondrocytes using click ***,a pre-targeting agent was prepared via conjugating apoptotic binding peptide(ApoPep-1)and trans-cyclooctene(TCO)onto polyethylene glycol(PEG)polymer *** pre-targeting agent would be introduced to injured areas of articular cartilage,leading to the accumulation of TCO groups on the injured areas from actively binding to apoptotic ***,methyltetrazine(Tz)-bearing chondrocytes would be immobilized on the surface of TCO-coated injured cartilage via Tz-TCO click chemistry *** an ex vivo human cartilage explant PTOA model,the effectiveness of this new approach was *** studies show that this novel approach(Tz-TCO click chemistry)significantly enhanced the immobilization of healthy and metabolically active chondrocytes to the areas of apoptotic *** analyses demonstrated that this treatment regimen would significantly reduce the area of cartilage degeneration and enhance ECm *** results support that Tz-TCO click chemistry-mediated cell delivery approach has great potential in clinical applications for targeting and treatment of cartilage injury.

关键词： chondrocyte cartilage regeneration cell therapy click chemistry

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Intracrine androgen biosynthesis and drug resistance

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Cancer Drug Resistance 2020年第4期3卷 912-929页

作者： Trevor m.Penning Irfan A.Asangani cynthia Sprenger Stephen Plymate Department of Systems Pharmacology&Translational Therapeutics Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Department Cancer Biology Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Division of Gerontology&Geriatric medicine Department of MedicineUniversity of WashingtonSeattleWA 98109USA Geriatric Research Education and Clinical Center(GRECC) VA Puget Sound Health Care SystemSeattleWA 98108USA

Castration-resistant prostate cancer is the lethal form of prostate cancer and most commonly remains dependent on androgen receptor(AR)*** therapies use AR signaling inhibitors(ARSI)exemplified by abiraterone acetate,a P450c17 inhibitor,and enzalutamide,a potent AR ***,drug resistance to these agents occurs within 12-18 months and they only prolong overall survival by 3-4 *** mechanisms can contribute to ARSI drug *** mechanisms can include but are not limited to germline mutations in the AR,post-transcriptional alterations in AR structure,and adaptive expression of genes involved in the intracrine biosynthesis and metabolism of androgens within the *** review focuses on intracrine androgen biosynthesis,how this can contribute to ARSI drug resistance,and therapeutic strategies that can be used to surmount these resistance mechanisms.

关键词： Prostate cancer abiraterone acetate enzalutamide aldo-keto reductase 1C3 androgen biosynthesis

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Halogen-specific total organic halogen analysis： Assessment by recovery of total bromine

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Journal of Environmental Sciences 2017年第8期29卷 340-348页

作者： markus Langsa Sebastien Allard Ina Kristiana Anna Heitz cynthia A.Joll Curtin Water Quality Research Centre Department of Chemistry Curtin University Perth Western Australia 6102 Australia Department of Civil Engineering Curtin University Perth Western Australia 6102 Australia Jurusan Kimia Fakultas Matematika dan Ilmu Pengetahuan AlamUniversitas PapuaManokwaripapua Barat 98314Indonesia

Determination of halogen-specific total organic halogen（TOX） is vital for studies of disinfection of waters containing bromide, since total organic bromine（TOBr） is likely to be more problematic than total organic chlorine. Here, we present further halogen-specific TOX method optimisation and validation, focusing on measurement of TOBr. The optimised halogen-specific TOX method was validated based on the recovery of model compounds covering different classes of disinfection by-products（haloacetic acids, haloacetonitriles,halophenols and halogenated benzenes） and the recovery of total bromine（mass balance of TOBr and bromide concentrations） during disinfection of waters containing dissolved organic matter and bromide. The validation of a halogen-specific TOX method based on the mass balance of total bromine has not previously been reported. Very good recoveries of organic halogen from all model compounds were obtained, indicating high or complete conversion of all organic halogen in the model compound solution through to halide in the absorber solution for ion chromatography analysis. The method was also successfully applied to monitor conversion of bromide to TOBr in a groundwater treatment plant. An excellent recovery（101%）of total bromine was observed from the raw water to the post-chlorination stage. Excellent recoveries of total bromine（92%–95%） were also obtained from chlorination of a synthetic water containing dissolved organic matter and bromide, demonstrating the validity of the halogen-specific TOX method for TOBr measurement. The halogen-specific TOX method is an important tool to monitor and better understand the formation of halogenated organic compounds, in particular brominated organic compounds, in drinking water systems.

关键词： Total organic bromine Dissolved organic matter Bromide Chlorination Drinking water Health effects

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Genotypic diversity of a dominant C_(4) grass across a long-term fire frequency gradient

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Journal of Plant Ecology 2013年第6期6卷 448-458页

作者： cynthia C.Chang melinda D.Smith Department of Ecology and Evolutionary Biology Yale UniversityNew HavenCT 06511USA Department of Biology University of WashingtonSeattleWA 98195USA Department of Biology Colorado State UniversityFort CollinsCO 80523USA

Aims and methods Diversity-disturbance research has focused on community diversity,but disturbance frequency could impact diversity within species as well,with important consequences for community diversity and ecosystem *** examined patterns of genetic diversity of a dominant grass species,Andropogon gerardii,in native North American tallgrass prairie sites located in eastern Kansas that have been subjected to a gradient of fire frequency treatments(burned every 1,2,4 or 20 years)since the *** addition,we were able to assess the relationships between genetic diversity of ***,species diversity and productivity across this range of fire *** Findings We found no significant relationships between genetic diversity of *** at the local scale(1 m^(2) plot level)and disturbance frequency(burned 2 to 32 times over a 38-year period).However,at the site level(*** all plots sampled within a site,~100 m^(2))there were differences in genotype richness and composition,as well as genomic dissimilarity among individuals of *** richness was greatest for the site burned at an intermediate(4-year)frequency and lowest for the infrequently(20-year)burned *** addition,genotypes found in the frequently burned sites were more similar from each other than expected by random chance than those found in the infrequently burned *** composition of *** was not significantly different between the frequently burned sites(annual vs.2 year)but did differ between frequently burned and infrequently burned sites(1 and 2 year vs.4 and 20 year,etc.).Together,these results suggest site-level ecological sorting of genotypes in intact prairie across a broad gradient of disturbance frequencies,likely driven by alterations in environmental *** fire promotes the abundance of dominant grass species,reduces plant community diversity and impacts ecosystem processes such as *** study suggests that

关键词： Andropogon gerardii disturbance frequency genetic relatedness genetic-species diversity relationship genotype richness intermediate disturbance hypothesis productivity tallgrass prairie

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Comparison of gastrointestinal parasite communities in vervet monkeys

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Integrative Zoology 2017年第6期12卷 512-520页

作者： Kim VALENTA Dennis TWINOmUGISHA Kathleen GODFREY cynthia LIU Valérie A.m.SCHOOF Tony L.GOLDBERG Colin A.CHAPmAN mcGill School of Environment McGill UniversityMontrealQuebecCanada makerere University Biological Field Station KampalaUganda Bilingual Biology Program Department of Multidisciplinary StudiesGlendon CampusYork UniversityTorontoOntarioCanada Department of Pathobiological Sciences School of Veterinary MedicineUniversity of Wisconsin-MadisonMadisonWisconsinUSA Wildlife Conservation Society BronxNew YorkUSA

Globally,habitat degradation is accelerating,especially in the *** to interface habitats can increase environmental overlap among nonhuman primates,people,and domestic animals and change stress levels in wildlife,leading to changes in their risk of parasite ***,the direction and consequences of these changes are unclear,since animals may benefit by exploiting human resources(e.g.,improving nutritional health by eating nutritious crops)and decreasing susceptibility to infection,or interactions with humans may lead to chronic stress and increased susceptibility to *** monkeys are an excellent model to understand parasitic disease transmission because of their tolerance to anthropogenic *** we quantify the gastrointestinal parasites of a group of vervet monkeys(Chlorocebus aethiops)near Lake Nabugabo,Uganda,that frequently overlaps with people in their use of a highly modified *** compare the parasites found in this population to seven other sites where vervet monkey gastrointestinal parasites have been identi*** vervets of Lake Nabugabo have the greatest richness of parasites documented to *** discuss how this may reflect differences in sampling intensity or differences in the types of habitat where vervet parasites have been sampled.

关键词： anthropogenic disturbance disease gastrointestinal parasite habitat degradation Nabugabo vervet zoonotic disease

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