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Propagation of tau and α-synuclein in the brain: therapeutic potential of the glymphatic system

Translational Neurodegeneration 2022年第1期11卷 667-689页

作者： Douglas M.Lopes Sophie K.Llewellyn ian f.harrison Division of Medicine Department of ImagingCentre for Advanced Biomedical ImagingFaculty of Medical SciencesUniversity College LondonPaul O’Gorman Building72 Huntley StreetLondon WC1E 6DDUK

Many neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease, are characterised by the accumulation of misfolded protein deposits in the brain, leading to a progressive destabilisation of the neuronal network and neuronal death. Among the proteins that can abnormally accumulate are tau and α-synuclein, which can propagate in a prion-like manner and which upon aggregation, represent the most common intracellular proteinaceous lesions associated with neurodegeneration. for years it was thought that these intracellular proteins and their accumulation had no immediate relationship with extracellular homeostasis pathways such as the glymphatic clearance system;however, mounting evidence has now suggested that this is not the case. The involvement of the glymphatic system in neurodegenerative disease is yet to be fully defined;however, it is becoming increasingly clear that this pathway contributes to parenchymal solute clearance. Importantly, recent data show that proteins prone to intracellular accumulation are subject to glymphatic clearance, suggesting that this system plays a key role in many neurological disorders. In this review, we provide a background on the biology of tau and α-synuclein and discuss the latest findings on the cell-to-cell propagation mechanisms of these proteins. Importantly, we discuss recent data demonstrating that manipulation of the glymphatic system may have the potential to alleviate and reduce pathogenic accumulation of propagation-prone intracellular cytotoxic proteins. furthermore, we will allude to the latest potential therapeutic opportunities targeting the glymphatic system that might have an impact as disease modifiers in neurodegenerative diseases.

关键词： Glymphatic Propagation Tauopathy Synucleinopathy Clearance Aquaporin-4

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Reduced texaphyrin:A ratiometric optical sensor for heavy metals in aqueous solution

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frontiers of Chemical Science and Engineering 2020年第1期14卷 19-27页

作者： harrison D.Root Gregory Thiabaud Jonathan L.Sessler Department of Chemistry The University of Texas at AustinAustinTX 78712-1224USA

We report here a water-soluble metal cation sensor system based on the as-prepared or reduced form of an expanded porphyrin,*** metal complexation,a change in the redox state of the ligand occurs that is accompanied by a color change from red to *** long employed for synthesis in organic media,we have now found that this complexation-driven redox behavior may be used to achieve the naked eye detectable colorimetric sensing of several number of less-common metal ions in aqueous *** to In(Ⅲ),Hg(Ⅱ),Cd(Ⅱ),Mn(Ⅱ),Bi(Ⅲ),Co(Ⅱ),and Pb(Ⅱ)cations leads to a colorimetric response within 10 *** process is selective for Hg(Ⅱ)under conditions of competitive ***,among the subset of responseproducing cations,In(Ⅲ)proved unique in giving rise to a ratiometric change in the ligand-based fluorescence features,including an overall increase in *** cation selectivity observed in aqueous media stands in contrast to what is seen in organic solvents,where a wide range of texaphyrin metal complexes may be *** formation of metal cation complexes under the present aqueous conditions was confirmed by reversed phase highperformance liquid chromatography,ultra-violet-visible absorption and fluorescence spectroscopies,and highresolution mass spectrometry.

关键词： texaphyrin fluorescent sensor ion-sensing indium mercury

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Dead Space Breathing in Patients with Malignancies: Determination by Cardiopulmonary Exercise Testing

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Open Journal of Respiratory Diseases 2022年第1期12卷 15-36页

作者： harrison Ngue Maranda Ngue ian Lee Ching-fei Chang Ahmet Baydur Division of Pulmonary Critical Care and Sleep Medicine Keck School of Medicine University of Southern California Medical Center Los Angeles CA USA

Rationale: Patients with cancer commonly experience dyspnea originating from ventilatory, circulatory and musculoskeletal sources, and dyspnea is best determined by cardiopulmonary exercise testing (CPET). Objectives: In this retrospective pilot study, we evaluated patients with hematologic and solid malignancies by CPET to determine the primary source of their dyspnea. Methods: Subjects were exercised on a cycle ergometer with increasing workloads. Minute ventilation, heart rate, breathing reserve, oxygen uptake (V’O2), O2-pulse, ventilatory equivalents for carbon dioxide and oxygen (V’E/V’CO2 and V’E/V’O2, respectively) were measured at baseline and peak exercise. The slope and intercept for V’E/V’CO2 was computed for all subjects. Peak V’O2 4% predicted indicated a circulatory or ventilatory limitation. Results: Complete clinical and physiological data were available for 36 patients (M/f 20/16);32 (89%) exhibited ventilatory or circulatory limitation as shown by a reduced peak V’O2 and 10 subjects with normal physiologic data. The largest cohort comprised the pulmonary vascular group (n = 18) whose mean ± SD peak V’O2 was 61% ± 17% predicted. There were close associations between V’O2 and spirometric values. Peak V’E/V’O2 and V’E/V’CO2 were highest in the circulatory and ventilatory cohorts, consistent with increase in dead space breathing. The intercept of the V’E-V’CO2 relationship was lowest in patients with cardiovascular impairment. Conclusion: Dyspneic patients with malignancies exhibit dead space breathing, many exhibiting a circulatory source for exercise limitation with a prominent pulmonary vascular component. Potential factors include effects of chemo- and radiation therapy on cardiac function and pulmonary vascular endothelium.

关键词： Cardiopulmonary Exercise Testing Cardiovascular Limitation Dead Space Breathing Dyspnea Malignancies Oxygen Uptake Pulmonary Vascular Limitation Ventilatory Equivalents

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Ammonia and greenhouse gas emissions from a subtropical wheat field under different nitrogen fertilization strategies

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Journal of Environmental Sciences 2017年第7期29卷 196-210页

作者： Shuai Liu Jim J.Wang Zhou Tian Xudong Wang Stephen harrison College of Resources and Environment Northwest A & F University School of Plant Environmental and Soil SciencesLouisiana State University Agricultural Center

Minimizing soil ammonia（NH_3） and nitrous oxide（N_2O） emission factors（Efs） has significant implications in regional air quality and greenhouse gas（GHG） emissions besides nitrogen（N） nutrient *** aim of this study was to investigate the impacts of different N fertilizer treatments of conventional urea,polymer-coated urea,ammonia sulfate,urease inhibitor（NBPT,N-（n-butyl） thiophosphoric triamide）-treated urea,and nitrification inhibitor（DCD,dicyandiamide）-treated urea on emissions of NH_3 and GHGs from subtropical wheat cultivation.A field study was established in a Cancienne silt loam *** growth season,NH_3 emission following N fertilization was characterized using active chamber method whereas GHG emissions of N_2O,carbon dioxide（CO_2）,and methane（CH_4） were by passive chamber *** results showed that coated urea exhibited the largest reduction（49%） in the Ef of NH_3-N followed by NBPT-treated urea（39%） and DCD-treated urea（24%） over conventional urea,whereas DCD-treated urea had the greatest suppression on N_2O-N（87%） followed by coated urea（76%） and NBPT-treated urea（69%）.Split fertilization of ammonium sulfate-urea significantly lowered both NH_3-N and N_2O-N Ef values but split urea treatment had no impact over one-time application of *** NBPT and DCD-treated urea treatments lowered CO_2-C flux but had no effect on CH_4-C ***,application of coated urea or urea with NPBT or DCD could be used as a mitigation strategy for reducing NH_3 and N_2O emissions in subtropical wheat production in Southern USA.

关键词： Ammonia Nitrous oxide Carbon dioxide Methane Nitrogen fertilization

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Did maize domestication and early spread mediate the population genetics of corn leafhopper?

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Insect Science 2019年第3期26卷 569-586页

作者： Julio S. Bernal Amanda M. Davila-flores Raul f. Medina Yolanda H. Chen Kyle E. harrison Kimberly A. Berrier Department of Entomology Texas A&M University College Station Texas USA Department of Plant and Soil Sciences University of Vermont Burlington Vermont USA

Investigating how crop domestication and early farming mediated crop attributes, distributions, and interactions with antagonists may shed light on today's agricultural pest problems. Crop domestication generally involved artificial selection for traits desirable to early farmers, for example, in creased productivity or yield, and enhanced qualities, though invariably it altered the interactions between crops and insects, and expanded the geographical ranges of crops. Thus, some studies suggest that with crop domestication and spread, insect populations on wild crop ancestors gave rise to pestiferous insect populations on crops. Here, we addressed whether the emergence of corn leafhopper (Dalbulus ma id is) as an agricultural pest may be associated with domestication and early spread of maize (Zea mays mays). We used AfLP markers and mitochondrial COI sequences to assess population genetic structuring and haplotype relationships among corn leafhopper samples from maize and its wild relative Zea diploperennis from multiple locations in Mexico and Argentina. We uncovered seven corn leafhopper haplotypes contained within two haplogroups, one haplogroup containing haplotypes associated with maize and the other containing haplotypes associated with Z. diploperennis in a mountainous habitat. Within the first haplogroup, one haplotype was predominant across Mexican locations, and another across Argentinean locations;both were considered pestiferous. We suggested that the divergence times of the maize-associated haplogroup and of the "pestiferous" haplotypes are correlated with the chronology of maize spread following its domestication. Overall, our results support a hypothesis positing that maize domestication favored corn leafhopper genotypes preadapted for exploiting maize so that they became pestiferous, and that with the geographical expansi on of maize farming, corn leafhopper colonized Z. diploperennis, a host exclusive to secluded habitats that serves as a refuge fo

关键词： Dalbulus maidis haplotype network analysis perennial teosinte population genetic structuring Zea diploperennis Zea mays mays

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Mapping QTL associated with Verticillium dahliae resistance in the cultivated strawberry(fragaria×ananassa)

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Horticulture Research 2015年第1期2卷 272-279页

作者： L Antanaviciute NŠurbanovski N harrison K J McLeary D W Simpson f Wilson D J Sargent R J harrison East Malling Research New RoadEast MallingKent ME196BJUK Research and Innovation Centre Fondazione Edmund MachVia E.Mach 138010 San Michele all’Adige(TN)Italy

A biparental cross of octoploid strawberry segregating for resistance to Verticillium dahliae,the causative agent of Verticillium wilt,was screened under field conditions for three *** wilt scores were significantly associated with multiple QTL,which were mostly significant across all *** significantly associated with the traits were used to screen material with known wilt resistance and susceptibility phenotypes.A clear and statistically significant relationship was observed between resistant,tolerant and susceptible material and the total number of markers present in the different resistance *** field situations resistance QTL appear to behave in an additive *** markers are abundant in the cultivated strawberry germplasm indicating that,despite the large number of markers,clear genetic gain is possible through marker-assisted breeding.

关键词： straw fragaria resistance

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Prescription of intermittent preventive therapy (IPTp) among doctors practicing in an army hospital in Lagos, Nigeria

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Open Journal of Preventive Medicine 2013年第2期3卷 258-261页

作者： Nkechinyere E. harrison Tolulope f. Olufunlayo Nkiru N. Odunukwe Clinical Divisions Nigerian Institute of Medical Research Yaba Lagos Lagos Nigeria Department of Community Health and Primary Care College of Medicine University of Lagos Idi-Araba Lagos Nigeria Department of Medicine 68 Nigerian Army Reference Hospital Yaba Lagos Lagos Nigeria

Background: Malaria infestation in pregnancy is a major public health concern and ranks amongst the commonest complications of pregnancy in Nigeria. Approximately 50,000 Nigerian women die each year from largely preventable pregnancy related complications. Intermittent preventive therapy for malaria in pregnancy (IPTp) is a key recommendation in the National guideline for malaria treatment in Nigeria. This study assessed the prescription pattern of intermittent preventive therapy with Sulphadoxine-Pyrimethamine for pregnant women among doctors practicing in 68 Nigerian Army Reference Hospital, Yaba, Lagos, Nigeria. Methods: This was a retrospective study using case notes of pregnant women seen at antenatal clinic of 68 Nigerian Army Reference Hospital, Yaba, Lagos, Nigeria from January, 2008 to December, 2008. A total of 336 case notes were reviewed. The findings were precoded, data entry and analysis was done using EPI INfO 2002. Results: A good proportion of the women (82.9%) booked for antenatal clinic within the first and second trimesters of pregnancy. Most commonly prescribed by doctors was the weekly pyrimethamine (daraprim) for malaria prophylaxis in pregnancy (100.0%). Very few doctors prescribed intermittent preventive therapy with sulfadoxine-pyrimethamine, and the few who did prescribed just one dose. Conclusion: The study showed a very low level of prescription of IPTp among doctors practicing at 68 Nigerian Army Reference Hospital, Yaba, Lagos, Nigeria. There is a great need for training of these doctors and other health professionals on the recommendations of the current National Antimalarial Treatment Guidelines.

关键词： Prescription Intermittent Preventive Therapy for Malaria Army Hospital

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Utilization of the current national antimalarial treatment guidelines among doctors in army hospitals in Lagos, Nigeria

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Open Journal of Preventive Medicine 2012年第3期2卷 390-393页

作者： Nkechinyere E. harrison Tolulope f. Olufunlayo Chimere O. Agomo Department of Community Health and Primary Care College of Medicine University of Lagos Idi-Araba Lagos Nigeria Department of Medicine 68 Nigerian Army Reference Hospital Yaba Lagos Nigeria Malaria Research Laboratory Department of Biochemistry Nigerian Institute of Medical Research Yaba Lagos Nigeria

Introduction: Human malaria infection remains a problem of public health importance in many regions of the world. The infection continues to spread particularly in sub-Saharan Africa. In Nigeria, malaria and its treatment have been affected by factors like wrong diagnosis, wrong attitude of the people, unavailability of drugs, fake and substandard drugs, attitude and practices of medical and paramedical personnel. Nigeria’s national standard for malaria treatment was recently changed to artemisinin combination therapy. Methods: A descriptive study using a structured questionnaire was administered to all doctors (123) practicing in the three Army hospitals in Lagos. The study was done between March, 2009 and April, 2009. The findings were precoded;data entry and analysis was done using EPI INfO version 3.5.1 statistical software. Results: Presumptive/clinical diagnosis was still a common practice for diagnosing malaria among doctors, as well as the use of microscopy. None of the doctors had the facility for diagnosing malaria with rapid diagnostic test in their hospitals. fifty one percent of the doctors stated that they utilized the current National antimalarial treatment guidelines. Significant proportion of the doctors used Artemisinin-based Combination Therapy (ACTs) as first line treatment of uncomplicated malaria in adults and children. Chloroquine was the commonest drug for first line treatment of uncomplicated malaria in pregnancy. Only 45.5% of the doctors had correct knowledge of Intermittent Preventive Treatment in pregnancy (IPTp), while 33.3% knew the stage of pregnancy in which a pregnant woman should receive IPTp with sulphadoxine-pyrimethamine. Awareness and the content of knowledge of the current National antimalarial treatment guideline were not affected by the category or current position of the doctors. Thirteen percent of the respondents had attended training/update workshop organized by the federal Ministry of Health (fMOH) Roll Back Malaria pro

关键词： National Antimalarial Treatment Guidelines Antimalarial Treatment Army Hospitals

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Invading from the garden？ A comparison of leaf herbivory for exotic and native plants in natural and ornamental settings

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Insect Science 2012年第6期19卷 677-682页

作者： Stephen f. Matter Jessica R.Brzyski Christopher J. harrison Sara Hyams Clement Loo Jessica Loomis Hannah R. Lubbers Leeann Seastrum Trevor I. Stamper Adam M. Stein Richard Stokes Brandy S. Wilkerson Department of Biological Sciences University of Cincinnati Cincinnati USA

The enemies release hypothesis proposes that exotic species can become in- vasive by escaping from predators and parasites in their novel environment. Agrawal et al. （Enemy release？ An experiment with congeneric plant pairs and diverse above- and below-ground enemies. Ecology, 86, 2979-2989） proposed that areas or times in which damage to introduced species is low provide opportunities for the invasion of native habitat. We tested whether ornamental settings may provide areas with low levels of herbivory for trees and shrubs, potentially facilitating invasion success. first, we compared levels of leaf herbivory among native and exotic species in ornamental and natural settings in Cincinnati, Ohio, United States. In the second study, we compared levels of herbivory for invasive and noninvasive exotic species between natural and ornamental settings. We found lower levels of leaf damage for exotic species than for native species; however, we found no differences in the amount of leaf damage suffered in ornamental or natural settings. Our results do not provide any evidence that ornamental settings afford additional release from herbivory for exotic plant species.

关键词： enemies release hypothesis forest herbivory host plant suburban urban

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土壤有机磷——文献述评

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土壤学进展 1990年第4期18卷 11-19,5页

作者： A.f.harrison 何念祖

本文引用了世界各国820篇文献,对土壤有机磷作了系统述评,内容包括土壤有机磷的含量、形态、剖面中的分布、与土壤组成的结合、矿化速率、提取测定方法等方面;文中还用多元回归方程表示土壤有机磷含量与土壤特性、耕作管理措施之间的相... 详细信息

本文引用了世界各国820篇文献,对土壤有机磷作了系统述评,内容包括土壤有机磷的含量、形态、剖面中的分布、与土壤组成的结合、矿化速率、提取测定方法等方面;文中还用多元回归方程表示土壤有机磷含量与土壤特性、耕作管理措施之间的相互关系。

关键词：土壤有机磷文献述评

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