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Molecular And Therapeutic Implications Of Notch1 Signaling In Pediatric T-Cell Acute Lymphoblastic Leukemia, Amanda Larson Gedman Jan 2010

Molecular And Therapeutic Implications Of Notch1 Signaling In Pediatric T-Cell Acute Lymphoblastic Leukemia, Amanda Larson Gedman

Wayne State University Dissertations

T-cell acute lymphoblastic leukemia (T-ALL) accounts for 15% of pediatric ALL cases and is associated with early relapse and inferior outcome. The poorer prognosis of T-ALL compared to B-precursor ALL may in part reflect the lack of unique features on which to base therapy. NOTCH1 mutations are of particular interest since these were reported in 37-71% of T-ALLs. The prognostic value of NOTCH1 mutations remains controversial as both favorable and unfavorable associations were reported, whereas in other studies, there were no associations between NOTCH1 mutations and treatment outcome. We explored the impact of mutations in NOTCH1, FBW7 and PTEN on …


Impact Of Static Stretch And Muscular Contractions On Force Production Within The Human Triceps Surae Muscle-Tendon Complex, Anthony D. Kay Jan 2010

Impact Of Static Stretch And Muscular Contractions On Force Production Within The Human Triceps Surae Muscle-Tendon Complex, Anthony D. Kay

Theses: Doctorates and Masters

Pre-performance routines commonly include stretching and intense muscular contractions in an attempt to optimise muscular performance and reduce injury risk. However, the isolated and combined effects of stretching and muscle contractions on neuromuscular performance are not well described. The aims of this research were to examine the effects of acute static stretch and intense muscular contractions on force production of the human plantarflexors and to examine possible mechanical and neuromuscular mechanisms underpinning any changes. Techniques including isokinetic dynamometry, electromyography (EMG), sonography and motion analysis were used in three studies on recreationally active human volunteers (n=20). In the first study, three …


Subacute Neural Stem Cell Therapy For Traumatic Brain Injury, Mikhail Bogdanov, Philip N Heacock, William Dowhan Jan 2010

Subacute Neural Stem Cell Therapy For Traumatic Brain Injury, Mikhail Bogdanov, Philip N Heacock, William Dowhan

Faculty, Staff and Student Publications

A protocol is described using lipid mutants and thiol-specific chemical reagents to study lipid-dependent and host-specific membrane protein topogenesis by the substituted-cysteine accessibility method as applied to transmembrane domains (SCAM). SCAM is adapted to follow changes in membrane protein topology as a function of changes in membrane lipid composition. The strategy described can be adapted to any membrane system.


Imaging Spontaneous Mmtvneu Transgenic Murine Mammary Tumors: Targeting Metabolic Activity Versus Genetic Products., Mathew L Thakur, Devakumar Devadhas, Kaijun Zhang, Richard G Pestell, Chenguang Wang, Peter Mccue, Eric Wickstrom Jan 2010

Imaging Spontaneous Mmtvneu Transgenic Murine Mammary Tumors: Targeting Metabolic Activity Versus Genetic Products., Mathew L Thakur, Devakumar Devadhas, Kaijun Zhang, Richard G Pestell, Chenguang Wang, Peter Mccue, Eric Wickstrom

Department of Radiology Faculty Papers

INTRODUCTION: Despite the great strides made in imaging breast cancer (BC) in humans, the current imaging modalities miss up to 30% of BC, do not distinguish malignant lesions from benign ones, and require histologic examinations for which invasive biopsy must be performed. Annually in the United States, approximately 5.6 million biopsies find benign lesions. More than 50% of human BCs overexpress cyclin D1, and all BCs exhibit VPAC1 oncogene products. Together, these gene products may provide an excellent biomarker for the early and accurate detection of BC. We have evaluated 4 biologically active peptide analogs that have high affinity for …


When You Hear Hoof Beats, It Might Be A Zebra: Lupus Patient With Fever And Leukopenia, Erica Peart Do, James Ross Md, Facp Jan 2010

When You Hear Hoof Beats, It Might Be A Zebra: Lupus Patient With Fever And Leukopenia, Erica Peart Do, James Ross Md, Facp

Department of Medicine

No abstract provided.


Can Dynamic Multidetector Computerized Tomography Detect Renal Cell Carcinoma Subtypes?, Ayhan Di̇ri̇m, Ni̇hal Tutar, Levent Peşki̇rci̇oğlu, Hüseyi̇n Çeli̇k, Mehmet İlteri̇ş Teki̇n, Hakan Özkardeş Jan 2010

Can Dynamic Multidetector Computerized Tomography Detect Renal Cell Carcinoma Subtypes?, Ayhan Di̇ri̇m, Ni̇hal Tutar, Levent Peşki̇rci̇oğlu, Hüseyi̇n Çeli̇k, Mehmet İlteri̇ş Teki̇n, Hakan Özkardeş

Turkish Journal of Medical Sciences

To evaluate the efficacy of the biphasic and triphasic dynamic multidedector computerized tomography (MDCT) in the preoperative prediction of histological subtypes of renal cell carcinoma (RCC). Materials and methods: The preoperative dynamic MDCT findings of 51 patients with renal mass who had undergone nephrectomy were reviewed retrospectively. Twenty-five of the patients had biphasic (portal and excretory) and 26 had triphasic (arterial, portal, and excretory) MDCT images. Tumor size, presence of calcification, tumor-aorta attenuation values in all phases and homogeneicity of the tumor were noted for every patient. In heterogeneous tumors, the minimum and maximum attenuation values were noted to determine …


Expression Of Ck-19, Cerbb2, Galectin-3, And P53 In Papillary Thyroid Carcinomas, Selda Seçki̇n, Ülker Karagece Jan 2010

Expression Of Ck-19, Cerbb2, Galectin-3, And P53 In Papillary Thyroid Carcinomas, Selda Seçki̇n, Ülker Karagece

Turkish Journal of Medical Sciences

To determine the immunohistochemical expression of CK-19, cErbB2, galectin-3, and p53 in papillary thyroid carcinomas (PTC). Materials and methods: In this study immunohistochemistry was performed on 23 papillary carcinomas (PCs) and 20 papillary microcarcinomas (PMCs). The extents of staining and intensity were scored semiquantitatively. Results: Of the PC cases 56.5% and of the PMC cases 15.0% were stained strongly by cErbB2. The extent of 2+ staining by galectin-3 was 47.8% in PC, whereas it was only 10.0% in PMC (P = 0.003). All PMC cases were stained by CK-19 and 21 cases of PC expressed positivity in varying extent of …


Effects Of Adenosine A1 Receptor Agonist Ccpa And Antagonist Dpcpx On Ischemia/Reperfusion-Induced Arrhythmias In Rats*, Ömer Bozdoğan, Ersöz Gonca, Nuran Ekerbi̇çer Jan 2010

Effects Of Adenosine A1 Receptor Agonist Ccpa And Antagonist Dpcpx On Ischemia/Reperfusion-Induced Arrhythmias In Rats*, Ömer Bozdoğan, Ersöz Gonca, Nuran Ekerbi̇çer

Turkish Journal of Medical Sciences

Adenosine has been commonly used to treat supraventricular tachycardia in clinics. However, there are only a few studies on the effects of adenosine on ischemia or reperfusion induced arrhythmia and they conflict with the results of the present study. During this study, we aimed to clarify the effect of adenosine on ischemia-reperfusion induced arrhythmia. Materials and methods: Left coronary artery was ligated for 6 min and it was released for 15 min to produce reperfusion. A1 adenosine agonist CCPA (2 Chloro - N6 - Cyclopentyl-adenosine), and A1 selective antagonist DPCPX (8 - Cyclopentyl - 1,3 -dipropylxanthine) in 5 µg/kg dose …


Anti-Diabetic Activity Of Tinospora Cordifolia (Willd.) In Streptozotocin Diabetic Rats; Does It Act Like Sulfonylureas?, Nagaraja Puranik, Kararashah Fakruddin Kammar, Sheela Devi Jan 2010

Anti-Diabetic Activity Of Tinospora Cordifolia (Willd.) In Streptozotocin Diabetic Rats; Does It Act Like Sulfonylureas?, Nagaraja Puranik, Kararashah Fakruddin Kammar, Sheela Devi

Turkish Journal of Medical Sciences

As an alternative medicine to treat diabetes mellitus, many herbal drugs are being studied throughout the world. In the present study, an attempt was made to investigate the anti-diabetic activity of Tinospora cordifolia (Willd.) (TC) stem extracts (both aqueous and alcoholic) in different dosages (200 and 400 mg/kg b.w.) in streptozotocin diabetic albino rats. The probable mechanism by which TC may act as an anti-hyperglycemic drug was also investigated. Materials and methods: The drug was administered orally for 10 days and 30 days in different groups of animal, with each group containing 6 animals. The efficacy of this drug was …


Trace Elements And Physical Activity In Children And Adolescents With Depression, M. Meti̇n Donma, Orki̇de Donma Jan 2010

Trace Elements And Physical Activity In Children And Adolescents With Depression, M. Meti̇n Donma, Orki̇de Donma

Turkish Journal of Medical Sciences

Depression is a common mental health problem among adolescents. Depressive symptoms are also important and may appear even during the preschool period. Physical activity, which may improve some mental health problems, is inversely associated with depression. Due to the presence of some clinical evidence about the relation between the use of antidepressants and suicide, there is a need for supportive agents during antidepressant therapy. Within this context, essential trace elements gain importance for further consideration. Protection of the developing brain from the negative effects of iron deficiency is important because of iron deficiency's association with poor mental development. Reactions between …


Caustic Esophageal Injury Decreases The Number Of Interstitial Cells Of Cajal In The Rat Esophagus, Tutku Soyer, Şebnem Ayva, Sali̇h Somuncu, Pinar Atasoy, Turan Kanmaz, Murat Çakmak Jan 2010

Caustic Esophageal Injury Decreases The Number Of Interstitial Cells Of Cajal In The Rat Esophagus, Tutku Soyer, Şebnem Ayva, Sali̇h Somuncu, Pinar Atasoy, Turan Kanmaz, Murat Çakmak

Turkish Journal of Medical Sciences

To evaluate the effect of caustic esophageal injury (CEI) on the number of interstitial cells of Cajal (ICC). Materials and methods: Wistar rats were divided into 3 groups: control, acid, and alkali induced CEI. CEI was performed by the injection of 1 mL of 10% hypochloric acid in the acid group, and 1 mL of 10% sodium hydroxide was injected into the alkali group. Distal esophageal segments were removed 24 h after injection. CEI was graded and the number of ICC were investigated (CD-117 staining). The number of ICC was compared in groups and correlated with CEI grades. Results: Typical …


The Prevalence Of Home Injuries Among Elderly People In Samsun, Turkey, And The Influencing Factors, Hülya Doğan, Sevgi̇ Canbaz, Berna Tander, Yildiz Pekşen, Ferhan Cantürk, Ni̇met Özal Oruç Jan 2010

The Prevalence Of Home Injuries Among Elderly People In Samsun, Turkey, And The Influencing Factors, Hülya Doğan, Sevgi̇ Canbaz, Berna Tander, Yildiz Pekşen, Ferhan Cantürk, Ni̇met Özal Oruç

Turkish Journal of Medical Sciences

Home injuries are a serious public health problem for the elderly. Our aim was to investigate the prevalence of home injuries among elderly people in Samsun, Turkey, and the influencing factors. Materials and methods: This cross-sectional study was conducted between 1 January and 28 February 2007. A questionnaire, the Home-Screen Scale (HSS), and the Geriatric Depression Scale (GDS) were administered to the elderly subjects. Results: Of all participants, 20.6% had experienced some kind of home injury. Seven participants living alone and 14 living with their families had suffered home injuries, suggesting a statistically significant difference between these 2 groups (P < 0.05). Eleven (14.7%) subjects living in secure housing and 10 (37.0%) living in unsecure housing had suffered home injuries, the difference again being statistically significant (P < 0.05). Conclusion: Home injuries are more common among people living alone and in unsecure housing according to the HSS.


The Effects Of 3-Benzoyl-1-Methyl-4-Phenyl-4 Piperidinolhydrochloride (C1), Indomethacin, Nimesulide And Rofecoxib On Cyclooxygenase Activities In Carrageenan-Induced Paw Edema Model, Yaşar Nuri̇ Şahi̇n, Berna Demi̇rcan, Hali̇s Süleyman, Hülya Aksoy, Hali̇se İnci̇ Gül Jan 2010

The Effects Of 3-Benzoyl-1-Methyl-4-Phenyl-4 Piperidinolhydrochloride (C1), Indomethacin, Nimesulide And Rofecoxib On Cyclooxygenase Activities In Carrageenan-Induced Paw Edema Model, Yaşar Nuri̇ Şahi̇n, Berna Demi̇rcan, Hali̇s Süleyman, Hülya Aksoy, Hali̇se İnci̇ Gül

Turkish Journal of Medical Sciences

The aim of this study was to investigate the effects of 3-benzoyl-1-methyl-4-phenyl-4-piperidinol-hydrochloride (C1), which is a structural and also non-classical isomer of bis Mannich base, bis (3-aryl-3-oxo-propyl) methylamine hydrochlorides (B1), on cyclooxygenase (COX) activities in 48 rats with inflammation by using carrageenan-induced paw edema, and to compare its effect with other non-steroidal anti-inflammatory drugs (NSAIDs). Materials and methods: Experimental animals were supplied by the Center of Experimental Research and Practice in Ataturk University. The animals were housed and fed in the laboratory (normal room temparature, food and water) under standard conditions. Rats were randomly assigned to eight groups (n = …


Adrenergic And Cholinergic Responses Of The Tracheal Smooth Muscle Is Enhanced During Estrus Phase In Rat, M. Kasim Çayci, Yasemi̇n Aydin, Kubi̇lay Uzuner Jan 2010

Adrenergic And Cholinergic Responses Of The Tracheal Smooth Muscle Is Enhanced During Estrus Phase In Rat, M. Kasim Çayci, Yasemi̇n Aydin, Kubi̇lay Uzuner

Turkish Journal of Medical Sciences

The aim of this study was to evaluate influences of hormonal changes during rat estrous cycle on airway responsiveness to bronchoconstrictor and bronchodilator agents. Materials and methods: The study was performed in 5 groups of rat tracheal smooth muscle obtained during proestrus, estrus, metestrus, and diestrus phases of the estrous cycle, as well as the ovariectomized group (n:8/group). Cumulative acetylcholine contractions ranging from 10^{-8} to 10^{-3} M bath doses and the cumulative isoproterenol relaxations ranging from 10^{-8} to 10^{-3} M precontracted with 10^{-5} M of acetylcholine were recorded on isolated tracheas placed in a computerized tissue bath system. Results: Acetylcholine-induced …


Investigation Of The Hla Class I Antigens In Patients With Primary Spontaneous Pneumothorax, Akin Eraslan Balci, Ebru Önalan, Muharrem Çakmak, Hali̇t Mohammed Elyas, Mehmet Oğuzhan Özyurtkan Jan 2010

Investigation Of The Hla Class I Antigens In Patients With Primary Spontaneous Pneumothorax, Akin Eraslan Balci, Ebru Önalan, Muharrem Çakmak, Hali̇t Mohammed Elyas, Mehmet Oğuzhan Özyurtkan

Turkish Journal of Medical Sciences

There is no report investigating the human leukocyte antigen system (HLA) class I alleles and haplotypes in the patients with primary spontaneous pneumothorax (PSP) without any familial history in the literature. We investigated the association of these alleles and haplotypes, and the occurrence of the PSP in Turkish patients. Materials and methods: The study group consisted of 20 patients diagnosed as PSP (without any familial history), and 20 healthy volunteers as control group. All the participants were Turkish male nonsmokers. Their genomic DNAs were extracted from venous samples, and the HLA class I alleles and haplotypes were analysed. Results: The …


The Effect Of Caffeic Acid Phenethyl Ester On Bacterial Translocation And Intestinal Damage After Intestinal Obstruction, Cengi̇z Ara, Abuzer Di̇ri̇can, Seli̇m Erdoğan, Burhan Ateş, Di̇nçer Özgör, Fai̇k Tatli, M. Sai̇t Tekerekoğlu, Vedat Kirimlioğlu Jan 2010

The Effect Of Caffeic Acid Phenethyl Ester On Bacterial Translocation And Intestinal Damage After Intestinal Obstruction, Cengi̇z Ara, Abuzer Di̇ri̇can, Seli̇m Erdoğan, Burhan Ateş, Di̇nçer Özgör, Fai̇k Tatli, M. Sai̇t Tekerekoğlu, Vedat Kirimlioğlu

Turkish Journal of Medical Sciences

Intestinal obstruction (IO) induces bacterial translocation due to failure of the intestinal barrier function. Following bacterial overgrowth, its degradation products play a decisive role in the development of systemic septic complications. The aim of this study was to evaluate the effects of caffeic acid phenethyl ester (CAPE) on bacterial translocation and intestinal damage in an IO model in rats. Materials and methods: Complete IO was created in the distal ileum of rats by a single 4-0 silk suture. A total of 21 Wistar albino rats were randomized into 3 groups: Group 1, Sham (n = 7); Group 2, IO (n …


Structure Elucidation Of A Glycosylated Benzyl Ester Of Salicylic Acid From The North American Prairie Plant Oligoneuron Rigidum, Sarah Katherine Miesner Jan 2010

Structure Elucidation Of A Glycosylated Benzyl Ester Of Salicylic Acid From The North American Prairie Plant Oligoneuron Rigidum, Sarah Katherine Miesner

Honors Program Theses

The organic extract from Oligoneuron rigidum displayed anti-microbial activity, indicating a potential future use as a natural food preservative. Three novel compounds were isolated from the active extract. The skeletal structure of the three compounds was determined by spectral methods, and the final structural component that remained to be determined was the locations of the acetate groups. Neutral permethylations were performed on the compounds as the first step in determining the locations of the acetate groups; however, the permethylation technique proved to be ineffective, causing cleavage of the native compounds. The structure elucidation will be complete when a non-degradable method …


Autoimmunity In Transfusion Babesiosis: A Spectrum Of Clinical Presentations., Jay H Herman, Saleh Ayache, Danuta Olkowska Jan 2010

Autoimmunity In Transfusion Babesiosis: A Spectrum Of Clinical Presentations., Jay H Herman, Saleh Ayache, Danuta Olkowska

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Transfusion-acquired babesiosis can be an asymptomatic or self-limited febrile hemolytic illness in a healthy host. A persistent, relapsing, and/or fulminant course with the development of life-threatening complications may be seen in immunocompromised or splenectomized patients. As in malaria, erythrocyte parasitemia is often associated with nonimmune hemolysis, and can be treated with erythrocytapheresis. Just as warm autoantibodies have been reported in malaria infection, the development of autoantibody-mediated immune hemolysis has been reported in babesiosis. We treated a previously healthy male with multiple injuries from a motor vehicle accident necessitating massive transfusion. Late in the hospitalization, his blood smear revealed Babesia microti, …


Sustained Expression Of Tdp-43 And Fus In Motor Neurons In Rodent's Lifetime., Cao Huang, Pedro Yuxing Xia, Hongxia Zhou Jan 2010

Sustained Expression Of Tdp-43 And Fus In Motor Neurons In Rodent's Lifetime., Cao Huang, Pedro Yuxing Xia, Hongxia Zhou

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

TAR DNA-binding protein (TDP-43) and fused in sarcoma (FUS) are two highly conserved ribonucleoproteins. Pathogenic mutations of the TDP-43 or the FUS gene are all linked to amyotrophic lateral sclerosis (ALS) that is characterized by progressive degeneration of motor neurons. To better understand the correlation of ALS disease genes with the selectivity of chronic motor neuron degeneration, we examined the longitudinal expression of the TDP-43 and the FUS genes in C57BL6 mice and in Sprague-Dawley rats. TDP-43 and FUS were robustly and ubiquitously expressed in the postnatal mice and rats, but were markedly decreased in the adult rodents. In adulthood, …


Gbdr Regulates Pseudomonas Aeruginosa Plch And Pchp Transcription In Response To Choline Catabolites, Matthew J. Wargo, Tiffany C. Ho, Maegan J. Gross, Laurie A. Whittaker, Deborah A. Hogan Dec 2009

Gbdr Regulates Pseudomonas Aeruginosa Plch And Pchp Transcription In Response To Choline Catabolites, Matthew J. Wargo, Tiffany C. Ho, Maegan J. Gross, Laurie A. Whittaker, Deborah A. Hogan

Dartmouth Scholarship

Pseudomonas aeruginosa hemolytic phospholipase C, PlcH, can degrade phosphatidylcholine (PC) and sphingomyelin in eukaryotic cell membranes and extracellular PC in lung surfactant. Numerous studies implicate PlcH in P. aeruginosa virulence. The phosphorylcholine released by PlcH activity on phospholipids is hydrolyzed by a periplasmic phosphorylcholine phosphatase, PchP. Both plcH gene expression and PchP enzyme activity are positively regulated by phosphorylcholine degradation products, including glycine betaine. Here we report that the induction of plcH and pchP transcription by glycine betaine is mediated by GbdR, an AraC family transcription factor. Mutants that lack gbdR are unable to induce plcH and pchP in media …


T Cell Receptor Cross-Reactivity Directed By Antigen-Dependent Tuning Of Peptide-Mhc Molecular Flexibility, Oleg Y. Borbulevych, Kurt H. Piepenbrink, Brian E. Gloor, Daniel R. Scott, Ruth F. Sommese, David K. Cole, Andrew K. Sewell, Brian M. Baker Dec 2009

T Cell Receptor Cross-Reactivity Directed By Antigen-Dependent Tuning Of Peptide-Mhc Molecular Flexibility, Oleg Y. Borbulevych, Kurt H. Piepenbrink, Brian E. Gloor, Daniel R. Scott, Ruth F. Sommese, David K. Cole, Andrew K. Sewell, Brian M. Baker

Food for Health: Publications

Tell mediated immunity requires T cell receptor (TCR) cross-reactivity, the mechanisms behind which remain incompletely elucidated. The αβ TCR A6 recognizes both the Tax (LLFGYPVYV) and Tel1p (MLWGYLQYV) peptides presented by the human class I MHC molecule HLA-A2. Here we found that although the two ligands are ideal structural mimics, they form substantially different interfaces with A6, with conformational differences in the peptide, the TCR, and unexpectedly, the MHC molecule. The differences between the Tax and Tel1p ternary complexes could not be predicted from the free peptide-MHC structures and are inconsistent with a traditional induced-fit mechanism. Instead, the differences were …


The Danger Signal Adenosine Induces Persistence Of Chlamydial Infection Through Stimulation Of A2b Receptors, Matthew A. Pettengill, Verissa W. Lam, David M. Ojcius Dec 2009

The Danger Signal Adenosine Induces Persistence Of Chlamydial Infection Through Stimulation Of A2b Receptors, Matthew A. Pettengill, Verissa W. Lam, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

Infections with intracellular bacteria such as chlamydiae affect the majority of the world population. Infected tissue inflammation and granuloma formation help contain the short-term expansion of the invading pathogen, leading also to local tissue damage and hypoxia. However, the effects of key aspects of damaged inflamed tissues and hypoxia on continued infection with intracellular bacteria remain unknown. We find that development of Chlamydia trachomatis is reversibly retarded by prolonged exposure of infected cells to extracellular adenosine, a hallmark of hypoxia and advanced inflammation. In epithelial cells, this effect was mediated by the A2b adenosine receptor, unique in the adenosine receptor …


Gamma Motor Neurons Express Distinct Genetic Markers At Birth And Require Muscle Spindle-Derived Gdnf For Postnatal Survival, Neil A. Shneider, Meghan N. Brown, Courtney A. Smith, James Pickel, Francisco J. Alvarez Dec 2009

Gamma Motor Neurons Express Distinct Genetic Markers At Birth And Require Muscle Spindle-Derived Gdnf For Postnatal Survival, Neil A. Shneider, Meghan N. Brown, Courtney A. Smith, James Pickel, Francisco J. Alvarez

Neuroscience, Cell Biology & Physiology Faculty Publications

Background: Gamma motor neurons (γ-MNs) selectively innervate muscle spindle intrafusal fibers and regulate their sensitivity to stretch. They constitute a distinct subpopulation that differs in morphology, physiology and connectivity from α-MNs, which innervate extrafusal muscle fibers and exert force. The mechanisms that control the differentiation of functionally distinct fusimotor neurons are unknown. Progress on this question has been limited by the absence of molecular markers to specifically distinguish and manipulate γ-MNs. Recently, it was reported that early embryonic γ-MN precursors are dependent on GDNF. Using this knowledge we characterized genetic strategies to label developing γ-MNs based on GDNF receptor expression, …


Structural Characterization Of The C-Terminus Of The Cochlear Motor Protein Prestin: Intrinsic Disorder Linked To Voltage Sensor Function, Michael S. Podgorski Dec 2009

Structural Characterization Of The C-Terminus Of The Cochlear Motor Protein Prestin: Intrinsic Disorder Linked To Voltage Sensor Function, Michael S. Podgorski

Theses and Dissertations (ETD)

The sensitivity of mammalian hearing relies upon the ability to amplify sound. Outer hair cells (OHCs) in the cochlea have motile properties that support this function. The motor protein called prestin resides in the lateral wall of the OHCs. Prestin undergoes voltage-dependent conformational changes, which correlates to the movement of charge through the membrane or non-linear capacitance (NLC). This property underlies OHC electromotility. A mechanistic understanding of prestin’s function remains unknown. Previous research has tied prestin’s C-terminus (residues 499-799) to the voltage-dependent events that occur in the membrane. The folding and biochemical properties of prestin’s C-terminus were characterized. This information …


Altered Regulation Of Contraction-Induced Akt/Mtor/P70s6k Pathway Signaling In Skeletal Muscle Of The Obese Zucker Rat, Anjaiah Katta, Sunil K. Kakarla, Miaozong Wu, Satyanarayana Paturi, Murali K. Gadde, Ravi K. Arvapalli, Madhukar Babu Kolli, Kevin M. Rice, Eric R. Blough Dec 2009

Altered Regulation Of Contraction-Induced Akt/Mtor/P70s6k Pathway Signaling In Skeletal Muscle Of The Obese Zucker Rat, Anjaiah Katta, Sunil K. Kakarla, Miaozong Wu, Satyanarayana Paturi, Murali K. Gadde, Ravi K. Arvapalli, Madhukar Babu Kolli, Kevin M. Rice, Eric R. Blough

MIIR Faculty Research

Increased muscle loading results in the phosphorylation of the 70 kDa ribosomal S6 kinase (p70S6k), and this event is strongly correlated with the degree of muscle adaptation following resistance exercise. Whether insulin resistance or the comorbidities associated with this disorder may affect the ability of skeletal muscle to activate p70S6k signaling following an exercise stimulus remains unclear. Here, we compare the contraction-induced activation of p70S6k signaling in the plantaris muscles of lean and insulin resistant obese Zucker rats following a single bout of increased contractile loading. Compared to lean animals, the basal phosphorylation of p70S6k (Thr389; 37.2% and Thr421/Ser424; 101.4%), …


Inactivation Of The Fliy Gene Encoding A Flagellar Motor Switch Protein Attenuates Mobility And Virulence Of Leptospira Interrogans Strain Lai, Sumei Liao, Ai-Hua Sun, David M. Ojcius, Senlin Wu, Jinfang Zhao, Jie Yan Dec 2009

Inactivation Of The Fliy Gene Encoding A Flagellar Motor Switch Protein Attenuates Mobility And Virulence Of Leptospira Interrogans Strain Lai, Sumei Liao, Ai-Hua Sun, David M. Ojcius, Senlin Wu, Jinfang Zhao, Jie Yan

All Dugoni School of Dentistry Faculty Articles

Background: Pathogenic Leptospira species cause leptospirosis, a zoonotic disease of global importance. The spirochete displays active rotative mobility which may contribute to invasion and diffusion of the pathogen in hosts. FliY is a flagellar motor switch protein that controls flagellar motor direction in other microbes, but its role in Leptospira, and paricularly in pathogenicity remains unknown.

Results: A suicide plasmid for the fliY gene of Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai strain Lai that was disrupted by inserting the ampicillin resistance gene (bla) was constructed, and the inactivation of fliY gene in a mutant (fliY-) was confirmed by PCR and …


Discovery And Validation Of New Regulatory Rna Elements In Chlamydia Trachomatis, Yasser Mohammed Elsayed Metwally Abdelrahman Dec 2009

Discovery And Validation Of New Regulatory Rna Elements In Chlamydia Trachomatis, Yasser Mohammed Elsayed Metwally Abdelrahman

Theses and Dissertations (ETD)

Chlamydia trachomatis is an obligate intracellular bacterium that exhibits a unique biphasic developmental cycle that can be disrupted by growth in the presence of IFN-g and b-lactams, giving rise to an abnormal growth state termed persistence. Relatively little is known about the regulatory mechanisms that control temporal gene expression during the developmental cycle or the control of persistence and reactivation. Here we have examined the expression of a newly defined family of non-coding RNAs (ncRNAs) that are differentially expressed during the developmental cycle and the induction of persistence and reactivation (Using IFNγ and Carbenicillin). Non-coding RNAs were initially identified using …


Identification Of The Downstream Effector Genes Involved In Hoxb4-Induced Expansion Of Hematopoietic Progenitor Cells, Jie Jiang Dec 2009

Identification Of The Downstream Effector Genes Involved In Hoxb4-Induced Expansion Of Hematopoietic Progenitor Cells, Jie Jiang

Theses and Dissertations (ETD)

Overexpression of HOXB4, a member of Homeobox transcription factor family, promotes expansion of hematopoietic stem and progenitor cells bothin vivo and in vitro. However, the molecular mechanisms underlying this effect are not well understood. In order to identify direct target genes of HOXB4 in primary murine hematopoietice progenitor cells, we induced HOXB4 function in lineage-negative, murine bone marrow cells, using a tamoxifen-inducibleHOXB4-ERT2fusion protein. Seventy seven genes with differentially changed expression in early response to HOXB4 have been identified as candidate target genes. Among them, we show that Hemogen (Hemgn), encoding a nuclear protein specifically …


Pandemic Potential Of Reassortant Swine Influenza A Viruses, Christy Brockwell Staats Dec 2009

Pandemic Potential Of Reassortant Swine Influenza A Viruses, Christy Brockwell Staats

Theses and Dissertations (ETD)

Influenza A viruses are capable of causing disease in several species, including birds, humans and swine. Host specificity of the viruses is not absolute, and is influenced by a range of factors. Swine play a pivotal role in the interspecies transmission of influenza A viruses, as they are susceptible to infection with both human and avian strains and have been implicated as a “mixing vessel” for the reassortment of influenza A viruses from different species. The reassortment of influenza A viruses of human and avian origin led to human influenza pandemics in 1957 and 1968.

The dynamics of swine influenza …


Fluorescent Protein Markers To Tag Collagenous Proteins: The Paradigm Of Procollagen Vii, Hye J. Chung, Andrzej Steplewski, Jouni Uitto, Andrzej Fertala Dec 2009

Fluorescent Protein Markers To Tag Collagenous Proteins: The Paradigm Of Procollagen Vii, Hye J. Chung, Andrzej Steplewski, Jouni Uitto, Andrzej Fertala

Department of Dermatology and Cutaneous Biology Faculty Papers

Fluorescent proteins are powerful markers allowing tracking expression, intracellular localization, and translocation of tagged proteins but their effects on the structure and assembly of complex extracellular matrix proteins has not been investigated. Here, we analyzed the utility of fluorescent proteins as markers for procollagen VII, a triple-helical protein critical for the integrity of dermal-epidermal junction. DNA constructs encoding a red fluorescent protein-tagged wild type mini-procollagen VII α chain and green fluorescent protein-tagged α chains harboring selected mutations were genetically engineered. These DNA constructs were co-expressed in HEK-293 cells and the assembly of heterogeneous triple-helical mini-procollagen VII molecules was analyzed. Immunoprecipitation …