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2008

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Articles 241 - 270 of 3703

Full-Text Articles in Medicine and Health Sciences

Ultrasound Diagnosis, Phiwipha Kamonrat Dec 2008

Ultrasound Diagnosis, Phiwipha Kamonrat

The Thai Journal of Veterinary Medicine

No abstract provided.


Role Of The Veterinarian On Animal Welfare, Achariya Sailasuta Dec 2008

Role Of The Veterinarian On Animal Welfare, Achariya Sailasuta

The Thai Journal of Veterinary Medicine

No abstract provided.


What Is Your Diagnosis?, Pranee Tuntivanich, Suwicha Chuthatep Dec 2008

What Is Your Diagnosis?, Pranee Tuntivanich, Suwicha Chuthatep

The Thai Journal of Veterinary Medicine

No abstract provided.


Comparative Effects Of Zinc Methionylglycinate And Zinc Sulfate On Hair Coat Characteristics And Zinc Concentration In Plasma, Hair, And Stool Of Dogs, Uttra Jamikorn, Thanisara Preedapattarapong Dec 2008

Comparative Effects Of Zinc Methionylglycinate And Zinc Sulfate On Hair Coat Characteristics And Zinc Concentration In Plasma, Hair, And Stool Of Dogs, Uttra Jamikorn, Thanisara Preedapattarapong

The Thai Journal of Veterinary Medicine

There are two form of Zn supplement used in commercial dog foods, organic and inorganic forms. These forms can influence Zn absorption and utilization of the animals. The goal of the current study was to evaluate the effects of zinc methionylglycinate (ZnMG) compared to zinc sulfate (ZnSO4) supplementations in commercial dog foods on haircoat characteristics, and Zn concentration in plasma, hair, and stool of the dogs. Eight mature female beagles were randomly divided into two groups of four dogs each. A Cross-over design was used for this study. The treatments composed of 120 ppm Zn supplement of either ZnMG or …


Impact Of Afghan Refugees On The Infectious Disease Profile Of Pakistan: Beyond Economy, Ali Jawaid, Abdul Mueed Zafar, Syed Faisal Mahmood Dec 2008

Impact Of Afghan Refugees On The Infectious Disease Profile Of Pakistan: Beyond Economy, Ali Jawaid, Abdul Mueed Zafar, Syed Faisal Mahmood

Department of Medicine

No abstract provided.


Increased Myocardial Susceptibility To Repetitive Ischemia With High-Fat–Diet-Induced Obesity, Geeta D Thakker, Nikolaos G Frangogiannis, Pawel T Zymek, Saumya Sharma, Joe L Raya, Philip M Barger, Heinrich Taegtmeyer, Mark L Entman, Christie M Ballantyne Dec 2008

Increased Myocardial Susceptibility To Repetitive Ischemia With High-Fat–Diet-Induced Obesity, Geeta D Thakker, Nikolaos G Frangogiannis, Pawel T Zymek, Saumya Sharma, Joe L Raya, Philip M Barger, Heinrich Taegtmeyer, Mark L Entman, Christie M Ballantyne

Faculty, Staff and Student Publications

Obesity and diabetes are frequently associated with cardiovascular disease. When a normal heart is subjected to brief/sublethal repetitive ischemia and reperfusion (I/R), adaptive responses are activated to preserve cardiac structure and function. These responses include but are not limited to alterations in cardiac metabolism, reduced calcium responsiveness, and induction of antioxidant enzymes. In a model of ischemic cardiomyopathy inducible by brief repetitive I/R, we hypothesized that dysregulation of these adaptive responses in diet-induced obese (DIO) mice would contribute to enhanced myocardial injury. DIO C57BL/6J mice were subjected to 15 min of daily repetitive I/R while under short-acting anesthesia, a protocol …


Coordinated Changes In Mrna Turnover, Translation, And Rna Processing Bodies In Bronchial Epithelial Cells Following Inflammatory Stimulation, Yuxin Zhai, Zhenping Zhong, Chyi-Ying A Chen, Zhenfang Xia, Ling Song, Michael R Blackburn, Ann-Bin Shyu Dec 2008

Coordinated Changes In Mrna Turnover, Translation, And Rna Processing Bodies In Bronchial Epithelial Cells Following Inflammatory Stimulation, Yuxin Zhai, Zhenping Zhong, Chyi-Ying A Chen, Zhenfang Xia, Ling Song, Michael R Blackburn, Ann-Bin Shyu

Faculty, Staff and Student Publications

Bronchial epithelial cells play a pivotal role in airway inflammation, but little is known about posttranscriptional regulation of mediator gene expression during the inflammatory response in these cells. Here, we show that activation of human bronchial epithelial BEAS-2B cells by proinflammatory cytokines interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-alpha) leads to an increase in the mRNA stability of the key chemokines monocyte chemotactic protein 1 and IL-8, an elevation of the global translation rate, an increase in the levels of several proteins critical for translation, and a reduction of microRNA-mediated translational repression. Moreover, using the BEAS-2B cell system and …


Knowledge And Practices Regarding Cigarette Smoking Among Adult Women In A Rural District Of Sindh, Pakistan, Sajid Ali, Naseem Ara, Arif Ali, Beena Ali, Muhammad Masood Kadir Dec 2008

Knowledge And Practices Regarding Cigarette Smoking Among Adult Women In A Rural District Of Sindh, Pakistan, Sajid Ali, Naseem Ara, Arif Ali, Beena Ali, Muhammad Masood Kadir

Community Health Sciences

OBJECTIVE: To determine the prevalence of cigarette smoking and to obtain information on socio-demographic factors and attitude regarding cigarette smoking among adult women in a rural district of Sindh Province, Pakistan.

METHODS: A cross sectional community based survey was done in a rural district of Sindh province of Pakistan using a two stage cluster sampling design. A pre tested questionnaire was used to interview 502 adult women (aged 18- 60 years) from the study site. The study was approved by the ethical research committee and informed consent was taken from participants.

RESULTS: A total of 502 women were interviewed for …


Pathological Sub-Types, Risk Factors And Outcome Of Stroke At The Nairobi Hospital, Kenya, James Jowi, Peter Mativo Dec 2008

Pathological Sub-Types, Risk Factors And Outcome Of Stroke At The Nairobi Hospital, Kenya, James Jowi, Peter Mativo

Internal Medicine, East Africa

Background: Stroke is one of the most common causes of morbidity and mortality the world over. Established risk factors such as arterial hypertension, diabetes mellitus, cigarette smoking, hyper-lipidaemia, micro-vascular rupture, male gender, age and observed co-morbities such as sickle cell disease, HIV/AIDS infection and cerebral malaria are increasingly being encountered in the tropics.

Objectives: To determine pathological sub-types, risk factors, in-hospital period prevalence and in-hospital outcome of stroke.

Design: Hospital-based retrospective study.

Setting: The Nairobi Hospital, Nairobi, Kenya.

Subjects: Patients with recorded diagnosis of stroke/cerebral vascular accident; as per WHO criteria for diagnosis of stroke, …


Confessions Of An Angry Insomniac, Gayle Greene Nov 2008

Confessions Of An Angry Insomniac, Gayle Greene

Scripps Faculty Publications and Research

The first thing to go is your sense of humour. Then it's the desire to do the things you used to do, and then the desire to do anything at all. Parts of your body ache that you don't even know the names of, and your eyes forget how to focus. Words you once knew aren't there any more, and there's less and less to say. People you once cared about fall by the wayside and you let them go, too.


Hepatoma Cells Up-Regulate Expression Of Programmed Cell Death-1 On T Cells, Ji Chen, Gui-Qiang Wang Nov 2008

Hepatoma Cells Up-Regulate Expression Of Programmed Cell Death-1 On T Cells, Ji Chen, Gui-Qiang Wang

Pharmacology and Toxicology Faculty Publications

AIM: To investigate the effect of hepatoma cells on up-regulation of programmed cell death-1 (PD-1), and the function of PD-1 on T cells. METHODS: HepG2 or HepG2.2.1.5 cells were co-cultured with a lymphoma cell line-Jurkat cells. PD-1 expression was detected by flow cytometry. IL-2, INF-γ and IL-10 in culture supernatant were detected by enzyme-linked immunosorbent assay (ELISA). Cytotoxic action of T cells was determined by MTT reduction assay-direct mononuclear cell cytotoxicity assay. RESULTS: The PD-1 expression on Jurkat cells increased by 16.17% ± 2.5% and 17.43% ± 2.2% after HepG2 or HepG2.2.1.5 cells were co-cultured for 48 h. The levels …


Genetic Counselling And Testing For Inherited Gene Mutations In Newly Diagnosed Patients With Breast Cancer: A Review Of The Existing Literature And A Proposed Research Agenda, Bettina Meiser, Kathy Tucker, Michael Friedlander, Kristine Barlow-Stewart, Elizabeth Lobb, Christobel Saunders, Gillian Mitchell Nov 2008

Genetic Counselling And Testing For Inherited Gene Mutations In Newly Diagnosed Patients With Breast Cancer: A Review Of The Existing Literature And A Proposed Research Agenda, Bettina Meiser, Kathy Tucker, Michael Friedlander, Kristine Barlow-Stewart, Elizabeth Lobb, Christobel Saunders, Gillian Mitchell

Research outputs pre 2011

Many women newly diagnosed with breast cancer and with a strong family history of breast cancer are referred to a family cancer service for genetic counselling and for consideration of genetic testing for germline mutations in cancer predisposition genes following completion of their cancer treatment. However, there is growing evidence that mutation status may influence treatment recommendations, and that there may be benefits in having 'treatment-focused genetic counselling and testing' available shortly after cancer diagnosis. This article reviews the literature that could inform the development of treatment-focused genetic counselling and testing, including: the rationale for genetic testing to aid with …


Stromal Gene Signatures In Large-B-Cell Lymphomas., G Lenz, G Wright, S S Dave, W Xiao, J Powell, H Zhao, W Xu, B Tan, N Goldschmidt, Javeed Iqbal, Julie M. Vose, M Bast, Kai Fu, D D. Weisenburger, T C Greiner, James O. Armitage, A Kyle, L May, R D Gascoyne, J M Connors, G Troen, H Holte, S Kvaloy, D Dierickx, G Verhoef, J Delabie, E B Smeland, P Jares, A Martinez, A Lopez-Guillermo, E Montserrat, E Campo, R M Braziel, T P Miller, L M Rimsza, J R Cook, B Pohlman, J Sweetenham, R R Tubbs, R I Fisher, E Hartmann, A Rosenwald, G Ott, H-K Muller-Hermelink, D Wrench, T A Lister, E S Jaffe, W H Wilson, W C. Chan, L M Staudt Nov 2008

Stromal Gene Signatures In Large-B-Cell Lymphomas., G Lenz, G Wright, S S Dave, W Xiao, J Powell, H Zhao, W Xu, B Tan, N Goldschmidt, Javeed Iqbal, Julie M. Vose, M Bast, Kai Fu, D D. Weisenburger, T C Greiner, James O. Armitage, A Kyle, L May, R D Gascoyne, J M Connors, G Troen, H Holte, S Kvaloy, D Dierickx, G Verhoef, J Delabie, E B Smeland, P Jares, A Martinez, A Lopez-Guillermo, E Montserrat, E Campo, R M Braziel, T P Miller, L M Rimsza, J R Cook, B Pohlman, J Sweetenham, R R Tubbs, R I Fisher, E Hartmann, A Rosenwald, G Ott, H-K Muller-Hermelink, D Wrench, T A Lister, E S Jaffe, W H Wilson, W C. Chan, L M Staudt

Journal Articles: Pathology and Microbiology

BACKGROUND: The addition of rituximab to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), or R-CHOP, has significantly improved the survival of patients with diffuse large-B-cell lymphoma. Whether gene-expression signatures correlate with survival after treatment of diffuse large-B-cell lymphoma is unclear.

METHODS: We profiled gene expression in pretreatment biopsy specimens from 181 patients with diffuse large-B-cell lymphoma who received CHOP and 233 patients with this disease who received R-CHOP. A multivariate gene-expression-based survival-predictor model derived from a training group was tested in a validation group.

RESULTS: A multivariate model created from three gene-expression signatures--termed "germinal-center B-cell," "stromal-1," and "stromal-2"--predicted …


Hemispheric Differences In The Recognition Of Environmental Sounds, Julio Gonza´Lez, Conor T. Mclennan Nov 2008

Hemispheric Differences In The Recognition Of Environmental Sounds, Julio Gonza´Lez, Conor T. Mclennan

Psychology Faculty Publications

In the visual domain, Marsolek and colleagues have found support for two dissociable and parallel neural subsystems underlying object and shape recognition: an abstract category subsystem that operates more effectively in the left cerebral hemisphere (LH), and a specific-exemplar subsystem that operates more effectively in the right cerebral hemisphere (RH). Evidence of this asymmetry has been observed for linguistic (words, pseudo-word forms) and non-linguistic (objects) stimuli. In the auditory domain, the authors previously found hemispheric asymmetries in priming effects when linguistic stimuli (spoken words) were used. In the present study, hemispheric asymmetries were investigated for non-linguistic stimuli (environmental sounds) by …


Androgen-Independent Prostate Cancer Cells Acquire The Complete Steroidogenic Potential Of Synthesizing Testosterone From Cholesterol., Paulette R. Dillard, Ming-Fong Lin, Shafiq A. Khan Nov 2008

Androgen-Independent Prostate Cancer Cells Acquire The Complete Steroidogenic Potential Of Synthesizing Testosterone From Cholesterol., Paulette R. Dillard, Ming-Fong Lin, Shafiq A. Khan

Journal Articles: Biochemistry & Molecular Biology

The proliferation and differentiation of normal prostate epithelial cells depends upon the action of androgens produced by the testis. Prostate cancers retain the ability to respond to androgens in the initial stages of cancer development, but progressively become independent of exogenous androgens in advanced stages of the disease while maintaining the expression of functional androgen receptor (AR). In the present study, we have determined the potential of prostate cancer cells to synthesize androgens from cholesterol which may be involved in intracrine regulation of AR in advanced stages of the disease. Established androgen-independent prostate cancer cell lines, PC3 and DU145 cells, …


In Vitro Models For Inhaled Corticosteroid (Ics) Aerosols: A Study Of Their Biopharmaceutics And Pharmacology, Deepika Arora Nov 2008

In Vitro Models For Inhaled Corticosteroid (Ics) Aerosols: A Study Of Their Biopharmaceutics And Pharmacology, Deepika Arora

Theses and Dissertations

Lung cellular disposition and anti-inflammatory pharmacology of inhaled corticosteroids (ICSs) is complex, comprised of a cascade of aerosol deposition and dissolution, followed by cellular uptake for local pharmacological action. This project hypothesized that the kinetics of dissolution for certain ICS aerosols generated from inhaler products were kinetically rate-determined for their cellular uptake and local pharmacological action. A novel dissolution testing system was developed to determine the dissolution kinetics for the ICS aerosols. A total of 5 ICSs aerosols generated from 6 inhaler products were collected in 2.1-3.3 or 4.7-5.8 µm of aerodynamic diameters at 0.7-19.8 µg on filter membranes by …


The Expression And Function Of Phosphacan/Rptpβ In Adaptive Synaptogenesis After Traumatic Brain Injury, Janna Harris Nov 2008

The Expression And Function Of Phosphacan/Rptpβ In Adaptive Synaptogenesis After Traumatic Brain Injury, Janna Harris

Theses and Dissertations

Traumatic brain injury (TBI) affects 1.5 million Americans annually and is a major health concern. Increasing evidence suggests that the brain extracellular environment regulates plasticity and synaptic recovery following TBI. Here we have focused on phosphacan/RPTPβ, an alternatively spliced group of chondroitin sulfate proteoglycans which are prominent within the mature brain extracellular matrix (ECM). Previous studies show that phosphacan/RPTPβ influences neuronal migration, adhesion, neurite outgrowth, and morphogenesis. However, our understanding of how these important ECM components are involved in recovery from brain trauma remains unclear. In the present study, we used unilateral entorhinal cortex lesion (UEC), a model which induces …


Neuroimaging And Recovery Of Language In Aphasia, Cynthia K. Thompson, Dirk B. Den Ouden Nov 2008

Neuroimaging And Recovery Of Language In Aphasia, Cynthia K. Thompson, Dirk B. Den Ouden

Communication Sciences and Disorders Faculty Articles and Research

The use of functional neuroimaging techniques has advanced what is known about the neural mechanisms used to support language processing in aphasia resulting from brain damage. This paper highlights recent findings derived from neuroimaging studies focused on neuroplasticity of language networks, the role of the left and right hemispheres in this process, and studies examining how treatment affects the neurobiology of recovery. We point out variability across studies as well as factors related to this variability, and we emphasize challenges that remain for research.


How Much Is Enough: The Intensity Evidence In Language Intervention, Teresa Ukrainetz, Kerry Proctor-Williams, James Baumann, Melissa Allen, Lavae M. Hoffman, Laura Justice Nov 2008

How Much Is Enough: The Intensity Evidence In Language Intervention, Teresa Ukrainetz, Kerry Proctor-Williams, James Baumann, Melissa Allen, Lavae M. Hoffman, Laura Justice

ETSU Faculty Works

No abstract provided.


In Vivo Trafficking Of Endogenous Opioid Receptors, Yulin Wang, Elisabeth J. Van Bockstaele, Lee-Yuan Liu-Chen Nov 2008

In Vivo Trafficking Of Endogenous Opioid Receptors, Yulin Wang, Elisabeth J. Van Bockstaele, Lee-Yuan Liu-Chen

Department of Neurosurgery Faculty Papers

Studies on trafficking of endogenous opioid receptors in vivo are subject of the present review. In many of the in vivo studies, the use of semi-quantitative immuno-electron microscopy is the approach of choice. Endogenous opioid receptors display differential subcellular distributions with μ opioid receptor (MOPR) being mostly present on the plasma membrane and δ- and κ-opioid receptors (DOPR and KOPR, respectively) having a significant intracellular pool. Etorphine and DAMGO cause endocytosis of the MOPR, but morphine does not, except in some dendrites. Interestingly, chronic inflammatory pain and morphine treatment promote trafficking of intracellular DOPR to the cell surface which may …


A Novel Gβγ-Subunit Inhibitor Selectively Modulates Μ-Opioid- Dependent Antinociception And Attenuates Acute Morphine-Induced Antinociceptive Tolerance And Dependence, Jennifer L. Mathews, Alan V. Smrcka, Jean M. Bidlack Nov 2008

A Novel Gβγ-Subunit Inhibitor Selectively Modulates Μ-Opioid- Dependent Antinociception And Attenuates Acute Morphine-Induced Antinociceptive Tolerance And Dependence, Jennifer L. Mathews, Alan V. Smrcka, Jean M. Bidlack

Pharmacy Faculty/Staff Publications

No abstract provided.


Extended Kalman Filter For Estimation Of Parameters In Nonlinear State-Space Models Of Biochemical Networks, Xiaodian Sun, Li Jin, Momiao Xiong Nov 2008

Extended Kalman Filter For Estimation Of Parameters In Nonlinear State-Space Models Of Biochemical Networks, Xiaodian Sun, Li Jin, Momiao Xiong

Faculty, Staff and Student Publications

It is system dynamics that determines the function of cells, tissues and organisms. to develop mathematical models and estimate their parameters are an essential issue for studying dynamic behaviors of biological systems which include metabolic networks, genetic regulatory networks and signal transduction pathways, under perturbation of external stimuli. In general, biological dynamic systems are partially observed. Therefore, a natural way to model dynamic biological systems is to employ nonlinear state-space equations. Although statistical methods for parameter estimation of linear models in biological dynamic systems have been developed intensively in the recent years, the estimation of both states and parameters of …


Wood, Rhonda (Fa 327), Manuscripts & Folklife Archives Nov 2008

Wood, Rhonda (Fa 327), Manuscripts & Folklife Archives

Folklife Archives Finding Aids

Finding aid and full-text scan of paper (Click on “Additional Files” below) for Folklife Archives Project FA 327. Paper: "Remedies & Cures of Muhlenberg County Folks" written by Rhonda Wood for a Western Kentucky University folk studies class.


Utilitaires Informatiques Pour La Gestion Des Contraintes Thermiques (Document Archivé), Daniel Drolet, Pierre C. Dessureault Nov 2008

Utilitaires Informatiques Pour La Gestion Des Contraintes Thermiques (Document Archivé), Daniel Drolet, Pierre C. Dessureault

Rapports de recherche scientifique

Pendant les périodes très chaudes, les travailleurs qui exercent leur métier à l’extérieur peuvent être sujets à des malaises allant parfois jusqu’au coup de chaleur. Le Règlement sur la santé et la sécurité du travail (RSST) prévoit des valeurs d’exposition admissibles (VEA) à la chaleur basées sur la Wet Bulb and Globe Temperature (WBGT). L’application de cette mesure exige toutefois des moyens techniques dont les milieux de travail ne disposent pas toujours. C’est pourquoi la CSST propose depuis plusieurs années le Guide de prévention des coups de chaleur qui utilise le paramètre nommé démarche de la température d’air corrigée (TAC), …


Ada News - 11/17/2008, American Dental Association, Publishing Division Nov 2008

Ada News - 11/17/2008, American Dental Association, Publishing Division

ADA News

Established in 1970 as the official newspaper of the American Dental Association, the ADA News serves practicing dentists and others allied to the dental profession in the U.S. and internationally. It is the No. 1 source of news and information about the many benefits and services the ADA delivers to members daily as well as timely information on scientific, social, political and economic developments affecting dentistry and health care.


Today - November 17, 2008, Loma Linda University Nov 2008

Today - November 17, 2008, Loma Linda University

TODAY

Inside this issue:

-- Spiritual life and wholeness banquet recognizes institutional employees for faith and passion
-- Compassion in Action opens with feature on Afghanistan
-- SPH addresses reform at American Health Care Congress
-- ‘Space aliens’ invade Loma Linda University Children’s Hospital
-- School of Dentistry releases fall quarter dean’s list
-- LLU student take on AHI hospital as mission project
-- LLU trains environmental health professionals from 13 states during Oklahoma conference
-- Thanksgiving road trip features Big Sur, Carmel, and San Francisco
-- Summer research program inspires Inland Empire students to pursue health careers
-- A crisis …


Argument Structure Effects In Action Verb Naming In Static And Dynamic Conditions, Dirk B. Den Ouden, Steve Fix, Todd B. Parrish, Cynthia K. Thompson Nov 2008

Argument Structure Effects In Action Verb Naming In Static And Dynamic Conditions, Dirk B. Den Ouden, Steve Fix, Todd B. Parrish, Cynthia K. Thompson

Communication Sciences and Disorders Faculty Articles and Research

Argument structure, as in the participant roles entailed within the lexical representation of verbs, affects verb processing. Recent neuroimaging studies show that when verbs are heard or read, the posterior temporoparietal region shows increased activation for verbs with greater versus lesser argument structure complexity, usually bilaterally. In addition, patients with agrammatic aphasia show verb production deficits, graded based on argument structure complexity. In the present study, we used fMRI to examine the neural correlates of verb production in overt action naming conditions. In addition, we tested the differential effects of naming when verbs were presented dynamically in video segments versus …


The Role Of The Environment In Poverty Alleviation, Paolo Galizzi, Alena Herklotz Nov 2008

The Role Of The Environment In Poverty Alleviation, Paolo Galizzi, Alena Herklotz

Environment

The new millennium raised hopes for a better future for humanity through a new spirit of international cooperation. Participants at the United Nations Millennium Summit agreed on an ambitious agenda for international cooperation that singled out, among other issues, environmental protection and development as key objectives.

The increasing degradation of our planet continues to emphasize the need to conserve and preserve natural resources. Yet with more than half of the global population still living on $2 dollars a day or less, there is also a glaring need for development initiatives to combat poverty.

This book draws on contributions to the …


The Effect Of Knowledge And Attitudes Of Emergency Contraception On Its Use In Undergraduate Students, Amanda Marie Waldrup Nov 2008

The Effect Of Knowledge And Attitudes Of Emergency Contraception On Its Use In Undergraduate Students, Amanda Marie Waldrup

Master's Theses and Doctoral Dissertations

A web-based cross sectional analysis utilizing the Spearman Coefficient was used to examine the relationship between 341 college students’ knowledge and attitudes toward emergency contraception. Personal characteristics and background factors such as age, race, gender, past and current use of contraception, past unintended pregnancies, and type of sex education in high school were compared to current knowledge levels and attitudes as related to use among college students. Results indicated that general knowledge is high, but detailed knowledge is lacking. Confusion between emergency contraception and RU-486 exist, which could lead to concerned attitudes ultimately effecting use. Most high schools that offer …


The Parkinson's Disease Protein Α-Synuclein Disrupts Cellular Rab Homeostasis, Aaron D. Gitler, Brooke J. Bevis, James Shorter, Katherine E. Strathearn, Shusei Hamamichi, Linhui Julie Su, Kim A. Caldwell, Guy A. Caldwell, Jean-Christophe Rochet, J. Michael Mccaffrey, Charles Barlowe, Susan Lindquist Nov 2008

The Parkinson's Disease Protein Α-Synuclein Disrupts Cellular Rab Homeostasis, Aaron D. Gitler, Brooke J. Bevis, James Shorter, Katherine E. Strathearn, Shusei Hamamichi, Linhui Julie Su, Kim A. Caldwell, Guy A. Caldwell, Jean-Christophe Rochet, J. Michael Mccaffrey, Charles Barlowe, Susan Lindquist

Dartmouth Scholarship

α-Synuclein (α-syn), a protein of unknown function, is the most abundant protein in Lewy bodies, the histological hallmark of Parkinson's disease (PD). In yeast α-syn inhibits endoplasmic reticulum (ER)-to-Golgi (ER→Golgi) vesicle trafficking, which is rescued by overexpression of a Rab GTPase that regulates ER→Golgi trafficking. The homologous Rab1 rescues α-syn toxicity in dopaminergic neuronal models of PD. Here we investigate this conserved feature of α-syn pathobiology. In a cell-free system with purified transport factors α-syn inhibited ER→Golgi trafficking in an α-syn dose-dependent manner. Vesicles budded efficiently from the ER, but their docking or fusion to Golgi membranes was inhibited. Thus, …