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Impaired glymphatic function in the early stages of disease in a TDP-43 mouse model of amyotrophic lateral sclerosis

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Translational Neurodegeneration 2022年第1期11卷 707-717页

作者： Akram Zamani Adam K.Walker Ben Rollo Katie l.Ayers Raysha Farah Terence J.O’Brien David K.Wright Department of Neuroscience Central Clinical SchoolMonash UniversityMelbourneVIC 3004Australia Queensland Brain Institute The University of QueenslandSt LuciaQLD 4072Australia The Murdoch Children’s Research Institute The Royal Children’s HospitalParkvilleVIC 3052Australia Department of Pediatrics The University of MelbourneParkvilleVIC 3052Australia Department of Medicine The Royal Melbourne HospitalThe University of MelbourneParkvilleVIC 3052Australia

Background: Multiple lines of evidence suggest possible impairment of the glymphatic system in amyotrophic lateral sclerosis (AlS). To investigate this, we used in vivo magnetic resonance imaging (MRI) to assess glymphatic func-tion early in the course of disease in a transgenic mouse with doxycycline (Dox)-controlled expression of cytoplasmic human TDP-43 (hTDP-43ΔNlS), mimicking the key pathology implicated in AlS. Methods: Adult TDP-43 transgenic and littermate monogenic control mice underwent longitudinal multimodal MRI one and three weeks after the cessation of Dox feed, together with weekly rotarod assessments of motor per-formance. Glymphatic function was assessed using dynamic contrast-enhanced MRI to track the clearance of an MR contrast agent injected into the cisterna magna. Results: Compared to their littermate controls, TDP-43 mice exhibited progressive neurodegeneration including that within the primary motor cortex, primary somatosensory cortex and corticospinal tract, significant weight loss includ-ing gastrocnemius atrophy, and shortened telomere length. Furthermore, in the presence of this AlS-like phenotype, these mice have significantly disrupted glymphatic function. Conclusions: Although the relationship between glymphatic clearance and AlS disease progression remains to be elucidated, these changes occurred very early in the disease course. This provides initial evidence to suggest that the glymphatic system might be a potential therapeutic target in the treatment of AlS.

关键词： Magnetic resonance imaging Diffusion-weighted imaging Neurodegeneration Cerebrospinal fluid Telomere

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万家灯火

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现代装饰（家居） 2014年第4期 70-75页

作者： Cecilie Manz Dan Yeffet d'Esposito & Gaillard Hans Sandgren Jakobsen Komplot Jake Phipps Jo Hammerborg Jordi lópez Aguiló Jorn Utzon lukas Dahln lucie Koldova Maija Puoskari Markus Johansson ross Gardam 伏平

乍暖还寒的三月，满眼绿意中花蕊还在悄悄地张望。这个夜晚，天空不见月亮，只是稀稀疏疏地散落着几颗星星。难得的清闲，我披了件外套漫步于街头，风从身边飘过，还带着几分丝丝的寒气。循着浓香四溢的咖啡香，不知不觉地走进灯光摇曳... 详细信息

乍暖还寒的三月，满眼绿意中花蕊还在悄悄地张望。这个夜晚，天空不见月亮，只是稀稀疏疏地散落着几颗星星。难得的清闲，我披了件外套漫步于街头，风从身边飘过，还带着几分丝丝的寒气。循着浓香四溢的咖啡香，不知不觉地走进灯光摇曳的星巴克。咖啡店里顾客不多，有年轻人在抱着笔记本上网，全神贯注；有情侣浓情软语相视而坐，温情而娴静。满屋漫溢着蓝调爵士的旋律……

关键词：灯光咖啡店星巴克笔记本年轻人

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Xylanase, protease and superdosing phytase interactions in broiler performance, carcass yield and digesta transit time

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Animal Nutrition 2017年第2期3卷 121-126页

作者： Tiago T.dos Santos Helen V.Masey O'Neill Gemma González-Ortiz Daniel Camacho-Fernández Carlos lópez-Coello AB Vista Facultad de Medicina Veteriaria y Zootecnia Universidad Nacional Autónoma de México

The interaction of xylanase, protease and superdosing(1,500 FTU/kg) phytase in a 2×2×2 factorial arrangement was studied in broilers fed sorghum-based diets. A total of 2,800 one-day-old unsexed ross308 chicks were housed in 56 pens with 50 birds per pen, with or without inclusion of xylanase, protease and phytase, totaling 8 treatments and 7 replicates per treatment. Body weight(BW) and feed intake(FI)were measured at 21 and 42 days of age, and mortality corrected feed conversion ratio(FCR) was calculated for each period and cumulatively. Tibia ash and carcass yield were determined in 2 birds per replicate at 21 and 42 days of age, respectively. Digesta transit time was determined at 21, 28, 35 and 42 days of age using 5 birds per replicate. Results showed that superdosing phytase increased BW and FI at42 days of age(P lanase improved FCR(P lanase and phytase also positively influenced carcass yield and breast weight, respectively. Overall, inclusion of superdosing phytase increased transit time when included in a diet containing xylanase, and no change with protease inclusion. In conclusion, the beneficial effects of xylanase, protease and superdosing phytase in broiler performance were not additive. This limitation is likely not related to the lack of efficacy of any one of the individual enzymes but to a limitation of the bird to respond additively to successive additions of enzymes.

关键词： Sorghum Tibia ash Sub-additivity Exogenous enzyme

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编码人生长激素的DNA序列在大肠杆菌中的直接表达

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中国生物工程杂志 1984年第3期 13-20页

作者： David V.Goeddel ,Herbert l.Heyneker ,Toyohara Hozumi ,Rene Arentzen ,Keiichi Itakura ,Daniel H.Yansura ,Michael J.ross ,Giuseppe Miozzari ,Roberto Crea ,Peter H.Seeburg ,寇蔻

编码人生长激素的DNA通过用化学合成的DNA与酶促制备的CDNA连接而建立。这一“杂化物”基因在乳糖操纵子控制下在大肠杆菌中表达,产生的肽在大小和免疫学性质上具有成熟的人的生长激素的特性。人生长激素(HGH)是垂体前叶合成的具有191... 详细信息

编码人生长激素的DNA通过用化学合成的DNA与酶促制备的CDNA连接而建立。这一“杂化物”基因在乳糖操纵子控制下在大肠杆菌中表达,产生的肽在大小和免疫学性质上具有成熟的人的生长激素的特性。人生长激素(HGH)是垂体前叶合成的具有191个氨基酸的蛋白质。垂体机能减退的侏儒因HGH缺陷而身材矮小,在儿童期使用人生长激素可以治疗这一缺陷症。另外,HGH在治疗各种创伤疾病如骨折、皮肤烧伤、溃疡等被证实是有效的。由于生长激素具种属专一性,人的尸体成为HGH的唯一来源。生长激素mRNA的初级翻译产物是一个蛋白前体,含有与生长激素N末端相接的一段信号肽。这种信号或“前”序列是分泌蛋白的特征。对于大鼠生长激素(RGH),已经鉴定了由RGH mRNA制备的CDNA序列中前序列的26个氨基酸残基。由人生长激素cDNA序列获得的信息,我们设计并建立了一个细菌质粒,它可以在微生物细胞中指导合成大量的成熟HGH。

关键词： DNA 氨基酸化学合成氨基羧酸核糖体结合位点生长激素基因载体质粒序列大肠埃希氏菌埃希氏杆菌属大肠杆菌

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Superior growth performance in broiler chicks fed chelated compared to inorganic zinc in presence of elevated dietary copper

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Journal of Animal Science and Biotechnology 2016年第4期7卷 561-569页

作者： Junmei Zhao Robert B. Shirley Julia J. Dibner Karen J. Wedekind Frances Yan Paula Fisher Thomas R. Hampton Joseph l. Evans Mercedes Vazquez-Anon research and development novus international20 Research Park DriveSaint CharlesMO 63304USA current affiliation:poultry technical services adisseo usaAlpharettaGA 30022USA

Background： The goal of this study was to compare the antagonism of elevated dietary Cu （250 mg/kg） from CuS04 on three different Zn sources （ZnS04. H20; [Zn bis（-2-hydroxy-4-（methylthio）butanoic acid）], Zn（HMTBa）2 a chelated Zn methionine hydroxy analogue; and Zn-Methionine）, as measured using multiple indices of animal performance in ross 308 broilers. Methods： Three experiments were conducted in broiler chicks fed a semi-purified diet. All birds were fed a Zn-deficient diet （8.5 mg/kg diet） for 1 wk, and then provided with the experimental diets for 2 wks. Results： Experiment 1 was a 2 x 2 factorial design with two levels of Cu （8 vs. 250 mg/kg diet from CuSO4） and two Zn sources at 30 mg/kg [ZnSO4. H20 vs. Zn（HMTBa）2]. Elevated Cu impaired growth performance only in birds fed ZnSO4. Compared to ZnSO4. H20, Zn（HMTBa）2 improved feed intake （12 %; P 〈 0.001） and weight gain （12 %, P 〈 0.001） and the benefits were more pronounced in the presence of 250 mg/kg diet Cu. Experiment 2 was a dose titration of ZnSO4- H20 and Zn（HMTBa）2 at 30, 4,5, 60, and 75 mg/kg diet in the presence of 250 mg/kg CuSO4. Feed：gain was decreased and tibia Zn was increased with increasing Zn levels from 30 to 75 mg/kg. Birds fed Zn（HMTBa）2 consumed more food and gained more weight compared to birds fed ZnSO4, especially at lower supplementation levels （30 and 45 mg/kg; interaction P 〈 0,05）. Experiment 3 compared two organic Zn sources （Zn（HMTBa）2 vs. Zn-Methionine） at 30 mg/kg with or without 250 mg/kg CuSO4. No interactions were observed between Zn sources and Cu levels on performance or tissue mineral concentrations. High dietary Cu decreased weight gain （P 〈 0.01）. Tibia Cu and liver Cu were significantly increased with 250 mg/kg dietary Cu supplementation （P 〈 0.01）. No difference was observed between the two Zn sources. Conclusions： Dietary 250 mg/kg Cu significantly impaired feed intake and weight gain in birds fed ZnSO4. H20, but had less impact in birds fed Zn（HMTBa）2. No difference

关键词： Antagonism Broilers Chelates Growth Minerals Organic Performance

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Effect of feeding broilers diets differing in susceptible phytate content

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Animal Nutrition 2016年第1期2卷 33-39页

作者： Natalie K.Morgan Carrie l.Walk Michael R.Bedford Dawn V.Scholey Emily J.Burton School of Animal Rural and Environmental Science Nottingham Trent University AB Vista Feed Ingredients

Measurements of total phytate phosphorus content of diets may be deceptive as they do not indicate substrate availability for phytase; it may be that measurements of phytate susceptible to phytase effects are a more accurate measure of phosphorus(P) availability to the bird. To verify this hypothesis, an experiment was conducted to compare diets formulated to contain either high or low susceptible phytate, supplemented with either 0 or 500 FTU/kg phytase. Susceptible phytate was determined by exposing the feed samples to conditions that mimicked the average pH of the proximal gastrointestinal tract(pH 4.5) and the optimum temperature for phytase activity(37℃) and then measuring phytate dissolved. ross 308 birds(n = 240) were fed one of 4 dietary treatments in a 2 x 2 factorial design; 2 diets with high(8.54 g/kg, 57.90% of total phytate) or low(5.77 g/kg, 46.33% of total phytate) susceptible phytate, containing 0 or 500 FTU/kg phytase. Diets were fed to broilers(12 replicate pens of 5 birds per pen) from d 0 to 28 post hatch. Birds fed diets high in susceptible phytate had greater phytate hydrolysis in the gizzard(P leum(P lting greater body weight gain(BWG)(P = 0.015) and lower FCR(P = 0.003) than birds fed the low susceptible phytate diets,irrespective of phytase presence. Birds fed the high susceptible diets also had greater P solubility in the gizzard and Ca and P solubility in the jejunum and ileum(P lting greater tibia and femur Ca and P(P low susceptible diets. All the susceptible phytate was fully degraded in the tract in the absence of added phytase, suggesting the assay used in this study was able to successfully estimate the amount of total dietary phytate that was susceptible to the effects of phytase when used at standard levels. No interactions were observed between susceptible phytate and phytase on phytate hydrolysis. Hydrolysis of phytate was greate

关键词： Broiler Phytate Digestibility Phytase Phosphorus

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院校研究的理想实践宣言

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山东高等教育 2017年第3期5卷 1-6页

作者：兰迪.斯温莉娅.尤因.罗丝雷洪德黄敏美国院校研究会华中科技大学教育科学研究院湖北武汉430074

院校研究需要一种新模式,让数据在决策中得到更广泛的使用,让学生获得更大的成功。院校研究办公室需要与高校其它部门及单位合作,在全校范围内履行院校研究功能。这一愿景的关键是,从广义上来理解"决策者",把学生也看作院校研究的决策... 详细信息

院校研究需要一种新模式,让数据在决策中得到更广泛的使用,让学生获得更大的成功。院校研究办公室需要与高校其它部门及单位合作,在全校范围内履行院校研究功能。这一愿景的关键是,从广义上来理解"决策者",把学生也看作院校研究的决策支持对象,激发学生基于数据做出明智决策;有目的地建立有利于提高数据能力的组织结构与领导,在决策支持中采用"以学生为中心"的范式。

关键词：院校研究学生成功决策支持理想愿景

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Patients’Participation on Their On-Site Review of Doctors’Notes:Physicians’OpenNotes Experiences in a Pain Clinic

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Psychology Research 2018年第12期8卷 603-613页

作者： Christopher Gilligan Ashish Bhandari Edgar l.ross Victor C.Wang Ji Hong lee Aimaiti Bomaliyamu Andrew Pisansky Divya Chirumamilla Alan Sheydwasser Manasi Parikh Brigham and Women’s Hospital MassachusettsUSA Memorial Hermann Hospital TexasUSA Beth Israel Deaconess Medical Center(BIDMC) MassachusettsUSA Boston University MassachusettsUSA

Inviting patients with chronic pain to read their doctors’visit notes via secure electronic portals may empower them and improve their understanding of their health ***,sharing the clinician’s perspective on the psychosocial contributors to a patient’s pain via transparent medical records could potentially lead to conflicts between patients and *** the OpenNotes study,we investigate and describe here the effects of increased clinic visit note transparency on physician experience in a large outpatient pain medicine *** analyzed pre-and post-intervention questionnaire data from nine chronic pain medicine physicians over a six-month *** this period,patients were given full access to their clinic visit notes that were not previously available to *** this study,we found that previous concerns of the potential risks and workload concerns of OpenNotes were not realized to the degree that the pain medicine providers had predicted but were more prevalent when compared to data from primary care physicians.

关键词： OpenNotes chronic pain pain clinic intervention physician’s perception

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laser-direct-drive program: Promise, challenge, and path forward

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Matter and Radiation at Extremes 2017年第2期2卷 37-54页

作者： E.M.Campbell V.N.Goncharov T.C.Sangster S.P.Regan P.B.Radha R.Betti J.F.Myatt D.H.Froula M.J.Rosenberg I.V.Igumenshchev W.Seka A.A.Solodov A.V.Maximov J.A.Marozas T.J.B.Collins D.Turnbull F.J.Marshall A.Shvydky J.P.Knauer R.l.McCrory A.B.Sefkow M.Hohenberger P.A.Michel T.Chapman l.Masse C.Goyon S.ross J.W.Bates M. Karasik J.Oh J.Weaver A.J.Schmitt K.Obenschain S.P.Obenschain S.Reyes B.Van Wonterghem laboratory for laser Energetics University of RochesterRochesterNYUSA lawrence livermore National laboratory LivermoreCAUSA Naval Research laboratory WashingtonDCUSA

Along with laser-indirect(X-ray)-drive and magnetic-drive target concepts,laser direct drive is a viable approach to achieving ignition and gain with inertial confinement *** the United States,a national program has been established to demonstrate and understand the physics of laser direct *** program utilizes the Omega laser Facility to conduct implosion and coupling physics at the nominally 30-kJ scale and lasereplasma interaction and coupling physics at the MJ scale at the National Ignition *** article will discuss the motivation and challenges for laser direct drive and the broad-based program presently underway in the United States.

关键词： Inertial fusion Direct drive laser interactions Hydrodynamics Omega National ignition facility

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挪威人葡糖脑苷脂酶基因突变与帕金森病之间的关系

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世界核心医学期刊文摘（神经病学分册） 2006年第9期2卷 7-7页

作者： Toft M. Pielsticker l. ross O.A. 牛亚利 Department of Neuroscience Norwegian University of Science and Technology N-7489 Trondheim Norway Dr.

An association between mutations in the glucocerebrosidase (GBA) gene and Parkinson disease (PD) was recently reported in Ashkenazi Jews. The authors screened a series of 311 Norwegian patients with PD and 474 controls for 2 common functional mutations of the GBA protein, N370S and l444P. Seven patients (2.3%) and 8 controls (1.7%) carried a mutant GBA allele (p = 0.58). This study does not indicate increased susceptibility to PD in GBA mutations carriers in Norway.

关键词：酶基因突变葡糖脑苷脂酶帕金森病挪威等位基因突变犹太人功能性 A蛋白

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