Digital Commons Network^™

P38 Mapk Regulates Cavitation And Tight Junction Function In The Mouse Blastocyst., Christine E Bell, Andrew J Watson

Obstetrics & Gynaecology Publications

UNLABELLED: Blastocyst formation is essential for implantation and maintenance of pregnancy and is dependent on the expression and coordinated function of a series of proteins involved in establishing and maintaining the trans-trophectoderm ion gradient that enables blastocyst expansion. These consist of Na/K-ATPase, adherens junctions, tight junctions (TJ) and aquaporins (AQP). While their role in supporting blastocyst formation is established, the intracellular signaling pathways that coordinate their function is unclear. The p38 MAPK pathway plays a role in regulating these proteins in other cell types and is required for embryo development at the 8-16 cell stage, but its role has not …

Mice With Deficient Bk Channel Function Show Impaired Prepulse Inhibition And Spatial Learning, But Normal Working And Spatial Reference Memory., Marei Typlt, Magdalena Mirkowski, Erin Azzopardi, Lukas Ruettiger, Peter Ruth, Susanne Schmid

Brain and Mind Institute Researchers' Publications

Genetic variations in the large-conductance, voltage- and calcium activated potassium channels (BK channels) have been recently implicated in mental retardation, autism and schizophrenia which all come along with severe cognitive impairments. In the present study we investigate the effects of functional BK channel deletion on cognition using a genetic mouse model with a knock-out of the gene for the pore forming α-subunit of the channel. We tested the F1 generation of a hybrid SV129/C57BL6 mouse line in which the slo1 gene was deleted in both parent strains. We first evaluated hearing and motor function to establish the suitability of this …

A Phase 1b Study Of Humanized Ks-Interleukin-2 (Huks-Il2) Immunocytokine With Cyclophosphamide In Patients With Epcam-Positive Advanced Solid Tumors, Joseph P. Connor, Mihaela C. Cristea, Nancy L. Lewis, Lionel D. Lewis

Dartmouth Scholarship

BackgroundHumanized KS-interleukin-2 (huKS-IL2), an immunocytokine with specificity for epithelial cell adhesion molecule (EpCAM), has demonstrated favorable tolerability and immunologic activity as a single agent.MethodsPhase 1b study in patients with EpCAM-positive advanced solid tumors to determine the maximum tolerated dose (MTD) and safety profile of huKS-IL2 in combination with low-dose cyclophosphamide. Treatment consisted of cyclophosphamide (300mg/m2 on day 1), and escalating doses of h

Loss Of Mef2d Expression Inhibits Differentiation And Contributes To Oncogenesis In Rhabdomyosarcoma Cells., Meiling Zhang, Jamie Truscott, Judith Davie

Articles

BACKGROUND: Rhabdomyosarcoma (RMS) is a highly malignant pediatric cancer that is the most common form of soft tissue tumors in children. RMS cells have many features of skeletal muscle cells, yet do not differentiate. Thus, our studies have focused on the defects present in these cells that block myogenesis.

METHODS: Protein and RNA analysis identified the loss of MEF2D in RMS cells. MEF2D was expressed in RD and RH30 cells by transient transfection and selection of stable cell lines, respectively, to demonstrate the rescue of muscle differentiation observed. A combination of techniques such as proliferation assays, scratch assays and soft …

Cattle-Related Injuries And Farm Management Practices On Kentucky Beef Cattle Farms, Steven R. Browning, Susan C. Westneat, Wayne T. Sanderson, Deborah B. Reed

Epidemiology and Environmental Health Faculty Publications

While working on farms with livestock increases the risk of injury among farm workers in comparison to other commodity farms, few studies have examined the role offarm management practices in association with the risk of cattle-related injury. We examined the farm management practices of Kentucky beef cattle farms in association with self-reported rates of cattle-related injuries among workers. We conducted a mail survey of a random sample of 2,500 members of the Kentucky Cattlemen's Association. Results from 1,149 farm operators who were currently raising beef cattle and provided complete survey response are reported. During the busy season, the principal operator …

The Correlation Between Metabolic Syndrome And Lower Urinary Tract Symptoms In Females, Cevdet Serkan Gökkaya, Cüneyt Özden, Bi̇nhan Kağan Aktaş, Hüseyi̇n Ci̇han Demi̇rel, Özer Güzel, Mehmet Karabakan, Aki̇f Ersoy Erkmen, Çeti̇n Volkan Özteki̇n, Ali̇ Memi̇ş

Turkish Journal of Medical Sciences

To evaluate the association between lower urinary tract symptoms (LUTS) and metabolic syndrome (MS) in women. Materials and methods: A total of 155 women with LUTS were included in the study. LUTS were evaluated using the International Prostate Symptom Score (IPSS) and the Bristol Female Lower Urinary Tract Symptoms (BFLUTS) questionnaire. Besides total IPSS, voiding and storage IPSS were calculated separately. Diagnosis of MS was made according to the consensus report of the International Diabetes Foundation. The patients were classified into 3 groups: those without MS (group 1), those with 3 risk factors of MS (group 2), and those with …

De Novo Orfs In Drosophila Are Important To Organismal Fitness And Evolved Rapidly From Previously Non-Coding Sequences, Josephine A. Reinhardt, Betty M. Wanjiru, Alicia T. Brant, Perot Saelao, David J. Begun, Corbin D. Jones

Biology

How non-coding DNA gives rise to new protein-coding genes (de novo genes) is not well understood. Recent work has revealed the origins and functions of a few de novo genes, but common principles governing the evolution or biological roles of these genes are unknown. To better define these principles, we performed a parallel analysis of the evolution and function of six putatively protein-coding de novo genes described in Drosophila melanogaster. Reconstruction of the transcriptional history of de novo genes shows that two de novo genes emerged from novel long non-coding RNAs that arose at least 5 MY prior to evolution …

Investigating The Expression And Functional Activities Of The Proteins That Are Involved In Uterine Fluid Ph Regulation At Different Stages Of The Oestrous Cycle And In Steroid Replaced Ovariectomized Rats / Khadijeh Gholami, Khadijeh Gholami

Student Works (2010-2019)

Precise control of the uterine luminal fluid pH is important for a number of key reproductive events. We hypothesized that sex-steroid could participate in this control via affecting the expression of H+ and HCO3- transporters as well as the enzyme that is involved in their generation. In view of this, we investigate the expressions and functional activities of few membrane transporters including CFTR, SLC26A6, NBC and NHE as well as CA enzyme in the uterus. Adult female WKY rats were divided into two main groups; (i) ovariectomized, steroid-replaced and (ii) intact rats at different phases of the oestrous cycle. The …

Investigating The Role For Il-21 In Rabies Virus Vaccine-Induced Immunity., Corin L Dorfmeier, Evgeni P Tzvetkov, Anthony Gatt, James P Mcgettigan

Department of Microbiology and Immunology Faculty Papers

Over two-thirds of the world's population lives in regions where rabies is endemic, resulting in over 15 million people receiving multi-dose post-exposure prophylaxis (PEP) and over 55,000 deaths per year globally. A major goal in rabies virus (RABV) research is to develop a single-dose PEP that would simplify vaccination protocols, reduce costs associated with RABV prevention, and save lives. Protection against RABV infections requires virus neutralizing antibodies; however, factors influencing the development of protective RABV-specific B cell responses remain to be elucidated. Here we used a mouse model of IL-21 receptor-deficiency (IL-21R-/-) to characterize the role for IL-21 in RABV …

A Phase 1b Study Of Humanized Ks-Interleukin-2 (Huks-Il2) Immunocytokine With Cyclophosphamide In Patients With Epcam-Positive Advanced Solid Tumors., Joseph P Connor, Mihaela C Cristea, Nancy L Lewis, Lionel D Lewis, Philip B Komarnitsky, Maria R Mattiacci, Mildred Felder, Sarah Stewart, Josephine Harter, Jean Henslee-Downey, Daniel Kramer, Roland Neugebauer, Roger Stupp

Kimmel Cancer Center Faculty Papers

BACKGROUND: Humanized KS-interleukin-2 (huKS-IL2), an immunocytokine with specificity for epithelial cell adhesion molecule (EpCAM), has demonstrated favorable tolerability and immunologic activity as a single agent.

METHODS: Phase 1b study in patients with EpCAM-positive advanced solid tumors to determine the maximum tolerated dose (MTD) and safety profile of huKS-IL2 in combination with low-dose cyclophosphamide. Treatment consisted of cyclophosphamide (300 mg/m2 on day 1), and escalating doses of huKS-IL2 (0.5-4.0 mg/m2 IV continuous infusion over 4 hours) on days 2, 3, and 4 of each 21-day cycle. Safety, pharmacokinetic profile, immunogenicity, anti-tumor and biologic activity were evaluated.

RESULTS: Twenty-seven patients were treated …

Eight Days In Oak Lake, Cyndi Eubanks

All ETDs from UAB

Eight Days in Oak Lake is an incomplete fictional novel about teenage Laine Reardon, who finds her life in turmoil after her family embarks on a trip to Oak Lake, Mississippi, for a family reunion. On the trip, Laine learns a disturbing secret about her father, and she is reunited with her childhood friend, Jake Donnelly. With sisters she often does not understand and parents who have their own problems, Laine seeks solace in the now-grown boy she grew up with. As she struggles to understand her feelings for Jake and deal with the revelation about her father, Laine is …

System Analysis Of Spatial Frequency Domain Imaging For Quantitative Mapping Of Surgically Resected Breast Tissues, Ashley M. Laughney, Venkataramanan Krishnaswamy, Tyler B. Rice, David J. Cuccia

Dartmouth Scholarship

No abstract provided.

The Ambiguity Of Panem: Capitalism, Nationalism, And Sexuality In Suzanne Collins' The Hunger Games Series, Megan Ann Peters

All Graduate Theses, Dissertations, and Other Capstone Projects

The publication of and the critical and public success of Suzanne Collins' The Hunger Games trilogy marks a significant departure from the norms of traditionally-popular young adult literature, particularly in its portrayal of a fiercely active female protagonist. This thesis argues that despite the noticeable progress these novels make in representing a strong female character, The Hunger Games series fails to adequately challenge other important aspects of oppression. I conduct a feminist literary analysis of The Hunger Games, Catching Fire, and Mockingjay, focusing specifically on representations of capitalism and commodification, national and district pride, and sexual objectification and sexual harassment …

Nitric Oxide Affects Short-Term Olfactory Memory In The Antennal Lobe Of Manduca Sexta, S. L. Gage, K. C. Daly, A. Nighorn

Faculty & Staff Scholarship

No abstract provided.

Ash2 Acts As An Ecdysone Receptor Coactivator By Stabilizing The Histone Methyltransferase Trr., Albert Carbonell, Alexander Mazo, Florenci Serras, Montserrat Corominas

Department of Biochemistry and Molecular Biology Faculty Papers

The molting hormone ecdysone triggers chromatin changes via histone modifications that are important for gene regulation. On hormone activation, the ecdysone receptor (EcR) binds to the SET domain-containing histone H3 methyltransferase trithorax-related protein (Trr). Methylation of histone H3 at lysine 4 (H3K4me), which is associated with transcriptional activation, requires several cofactors, including Ash2. We find that ash2 mutants have severe defects in pupariation and metamorphosis due to a lack of activation of ecdysone-responsive genes. This transcriptional defect is caused by the absence of the H3K4me3 marks set by Trr in these genes. We present evidence that Ash2 interacts with Trr …

Immune Response To Snake Envenoming And Treatment With Antivenom; Complement Activation, Cytokine Production And Mast Cell Degranulation, Shelley Stone, Geoffrey K. Isbister, Seyed Shahmy, Fahim Mohamed, Chandana Abeysinghe, Harendra Karunathilake, Ariaranee Ariaratnam, Tamara E. Jacoby-Alner, Claire L. Cotterell, Simon G A Brown

Research outputs 2013

Background:Snake bite is one of the most neglected public health issues in poor rural communities worldwide. In addition to the clinical effects of envenoming, treatment with antivenom frequently causes serious adverse reactions, including hypersensitivity reactions (including anaphylaxis) and pyrogenic reactions. We aimed to investigate the immune responses to Sri Lankan snake envenoming (predominantly by Russell's viper) and antivenom treatment.Methodology/Principal Findings:Plasma concentrations of Interleukin (IL)-6, IL-10, tumor necrosis factor α (TNFα), soluble TNF receptor I (sTNFRI), anaphylatoxins (C3a, C4a, C5a; markers of complement activation), mast cell tryptase (MCT), and histamine were measured in 120 Sri Lankan snakebite victims, both before and …

A Fimh Inhibitor Prevents Acute Bladder Infection And Treats Chronic Cystitis Caused By Multidrug-Resistant Uropathogenic Escherichia Coli St131., Makrina Totsika, Maria Kostakioti, Thomas J. Hannan, Mathew Upton, Scott A. Beatson, James W. Janetka, Scott J. Hultgren, Mark A. Schembri

School of Biomedical Sciences

BACKGROUND: Escherichia coli O25b:H4-ST131 represents a predominant clone of multidrug-resistant uropathogens currently circulating worldwide in hospitals and the community. Urinary tract infections (UTIs) caused by E. coli ST131 are typically associated with limited treatment options and are often recurrent. METHODS: Using established mouse models of acute and chronic UTI, we mapped the pathogenic trajectory of the reference E. coli ST131 UTI isolate, strain EC958. RESULTS: We demonstrated that E. coli EC958 can invade bladder epithelial cells and form intracellular bacterial communities early during acute UTI. Moreover, E. coli EC958 persisted in the bladder and established chronic UTI. Prophylactic antibiotic administration …

Preventing Sudden Cardiac Death In Athletes: In Search Of Evidence-Based, Cost-Effective Screening, Paolo Angelini, Mladen I Vidovich, Christine E Lawless, Macarthur A Elayda, J Alberto Lopez, Dwayne Wolf, James T Willerson

The Texas Heart Institute Journal

Sudden cardiac death in athletes is a recurrent phenomenon at sporting events and during training. Recent studies have associated sudden cardiac death with such cardiovascular conditions as coronary artery anomalies, cardiomyopathies, and electrocardiographic abnormalities, most of which are screenable with modern imaging techniques. We recently inaugurated the Center for Coronary Artery Anomalies at the Texas Heart Institute, which is dedicated to preventing sudden cardiac death in the young and investigating coronary artery anomalies. There, we are conducting 2 cross-sectional studies intended to firmly establish and quantify, in a large group of individuals from a general population, risk factors for sudden …

Low Serum Triglyceride Levels As Predictors Of Cardiac Death In Heart Failure Patients, Guliz Kozdag, Gokhan Ertas, Ender Emre, Yasar Akay, Umut Celikyurt, Tayfun Sahin, Gozde Gorur, Kurtulus Karauzum, Irem Yilmaz, Dilek Ural, Mira Sarsekeyeva

The Texas Heart Institute Journal

Understanding the influence of sex differences on predictors of cardiac mortality rates in chronic heart failure might enable us to lengthen lifetimes and to improve lives. This study describes the influence of sex on cardiovascular mortality rates among chronic heart failure patients.

From January 2003 through December 2009, we evaluated 637 consecutive patients (409 men and 228 women) with chronic heart failure, who ranged in age from 18 through 94 years (mean age, 64 ± 13 yr) and ranged in New York Heart Association (NYHA) functional class from II through IV. The mean follow-up period was 38 ± 15 months, …

Stab Wound Of The Heart With Unusual Sequelae, Peter I Praeger, Jonathan Praeger, Ahmed M Abdel-Razek, Elie M Elmann

The Texas Heart Institute Journal

A 31-year-old woman was admitted to the emergency department with a stab wound to the heart. She was initially stable but rapidly developed hypotension. While the operating room and staff were in preparation, she underwent pericardiocentesis. She was then rushed to the operating room by the general surgical trauma team, who performed a bilateral anterior thoracotomy to control the bleeding. In the recovery room, the patient was still hypotensive, so cardiothoracic surgery was consulted.

An echocardiogram revealed severe hypokinesis of both ventricles. The cardiothoracic surgeons returned her to the operating room and discovered that the anterior pericardium had been completely …

Multiple Subject Barycentric Discriminant Analysis (Musubada): How To Assign Scans To Categories Without Using Spatial Normalization, Hervé Abdi, Lynne J. Williams, Andrew C. Connolly, M. Ida Gobbini

Dartmouth Scholarship

We present a new discriminant analysis (DA) method called Multiple Subject Barycentric Discriminant Analysis (MUSUBADA) suited for analyzing fMRI data because it handles datasets with multiple participants that each provides different number of variables (i.e., voxels) that are themselves grouped into regions of interest (ROIs). Like DA, MUSUBADA (1) assigns observations to predefined categories, (2) gives factorial maps displaying observations and categories, and (3) optimally assigns observations to categories. MUSUBADA handles cases with more variables than observations and can project portions of the data table (e.g., subtables, which can represent participants or ROIs) on the factorial maps. Therefore MUSUBADA can …

The Demographic And Clinical Characteristics Of Female Veterans Who Engage In Complementary And Alternative Medicine, Heather W. Gladstone

Theses, Dissertations, and Projects

Prior research has demonstrated that specific types of complementary and alternative medicine (CAM) are beneficial in decreasing mental health symptoms. Despite this, rates of CAM use are relatively low among veterans, and data about CAM use among female veterans is non-existent. Thus, the purpose of this study is to examine the demographic and clinical characteristics of female veterans that engage in CAM. Female Operation Enduring Freedom and Operation Iraqi Freedom Veterans (n=365) in Veterans Affairs (VA) care participated in a web-based survey that was one component of a larger VA study. Results indicated that slightly more than one third of …

Rapid Synaptic Vesicle Endocytosis In Cone Photoreceptors Of Salamander Retina., Matthew J. Van Hook, Wallace B. Thoreson

Journal Articles: Ophthalmology

Following synaptic vesicle exocytosis, neurons retrieve the fused membrane by a process of endocytosis to provide a supply of vesicles for subsequent release and maintain the presynaptic active zone. Rod and cone photoreceptors use a specialized structure called the synaptic ribbon that enables them to sustain high rates of neurotransmitter release. They must also employ mechanisms of synaptic vesicle endocytosis capable of keeping up with release. While much is known about endocytosis at another retinal ribbon synapse, that of the goldfish Mb1 bipolar cell, less is known about endocytosis in photoreceptors. We used capacitance recording techniques to measure vesicle membrane …

Reactive Oxygen Species Production And Brugia Pahangi Survivorship In Aedes Polynesiensis With Artificial Wolbachia Infection Types, Elizabeth S. Andrews, Philip R. Crain, Yuqing Fu, Daniel K. Howe, Stephen L. Dobson

Entomology Faculty Publications

Heterologous transinfection with the endosymbiotic bacterium Wolbachia has been shown previously to induce pathogen interference phenotypes in mosquito hosts. Here we examine an artificially infected strain of Aedes polynesiensis, the primary vector of Wuchereria bancrofti, which is the causative agent of Lymphatic filariasis (LF) throughout much of the South Pacific. Embryonic microinjection was used to transfer the wAlbB infection from Aedes albopictus into an aposymbiotic strain of Ae. polynesiensis. The resulting strain (designated "MTB") experiences a stable artificial infection with high maternal inheritance. Reciprocal crosses of MTB with naturally infected wild-type Ae. polynesiensis demonstrate strong bidirectional incompatibility. Levels of reactive …

Evaluation Of Very High- And Very Low-Dose Intravitreal Aflibercept In Patients With Neovascular Age-Related Macular Degeneration., Quan Dong Nguyen, Peter A. Campochiaro, Syed Mahmood Shah, David J. Browning, Henry L. Hudson, Peter L. Sonkin, Seenu M. Hariprasad, Peter K. Kaiser, Jason Slakter, Julia A. Haller, Diana V. Do, William Mieler, Karen Chu, Avner Ingerman, Robert Vitti, Alyson J. Berliner, Jesse Cedarbaum, Clear-It 1 Investigators

Journal Articles: Ophthalmology

PURPOSE: To determine bioactivity and duration of effect of intravitreal aflibercept injection (also known as vascular endothelial growth factor Trap-Eye) for neovascular age-related macular degeneration (AMD).

METHODS: In this double-masked, phase 1 study, 28 patients with lesions ≤12 disc areas, ≥50% active choroidal neovascularization (CNV), and best corrected visual acuity (BCVA) ≤20/40 were randomized 1:1 to a single intravitreal injection of aflibercept 0.15 or 4 mg. The primary end point was the change from baseline in central retinal/lesion thickness (CR/LT) at week-8. Secondary outcomes were the change from baseline BCVA, the change in CNV lesion size and area of leakage, …

Necrostatin-1 Analogues: Critical Issues On The Specificity, Activity And In Vivo Use In Experimental Disease Models., N Takahashi, L Duprez, S Grootjans, A Cauwels, W Nerinckx, J B Duhadaway, V Goossens, R Roelandt, F Van Hauwermeiren, C Libert, W Declercq, N Callewaert, G C Prendergast, A Degterev, J Yuan, P Vandenabeele

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Necrostatin-1 (Nec-1) is widely used in disease models to examine the contribution of receptor-interacting protein kinase (RIPK) 1 in cell death and inflammation. We studied three Nec-1 analogs: Nec-1, the active inhibitor of RIPK1, Nec-1 inactive (Nec-1i), its inactive variant, and Nec-1 stable (Nec-1s), its more stable variant. We report that Nec-1 is identical to methyl-thiohydantoin-tryptophan, an inhibitor of the potent immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO). Both Nec-1 and Nec-1i inhibited human IDO, but Nec-1s did not, as predicted by molecular modeling. Therefore, Nec-1s is a more specific RIPK1 inhibitor lacking the IDO-targeting effect. Next, although Nec-1i was ∼100 × …

Frequent Arousals From Winter Torpor In Rafinesque's Big-Eared Bat (Corynorhinus Rafinesquii), Joseph S. Johnson, Michael J. Lacki, Steven C. Thomas, John F. Grider

Forestry and Natural Resources Faculty Publications

Extensive use of torpor is a common winter survival strategy among bats; however, data comparing various torpor behaviors among species are scarce. Winter torpor behaviors are likely to vary among species with different physiologies and species inhabiting different regional climates. Understanding these differences may be important in identifying differing susceptibilities of species to white-nose syndrome (WNS) in North America. We fitted 24 Rafinesque’s big-eared bats (Corynorhinus rafinesquii) with temperature-sensitive radio-transmitters, and monitored 128 PIT-tagged big-eared bats, during the winter months of 2010 to 2012. We tested the hypothesis that Rafinesque’s big-eared bats use torpor less often than values …

Open Release Of Male Mosquitoes Infected With A Wolbachia Biopesticide: Field Performance And Infection Containment, Linda O'Connor, Catherine Plichart, Ayo Cheong Sang, Corey L. Brelsfoard, Hervé C. Bossin, Stephen L. Dobson

Entomology Faculty Publications

BACKGROUND: Lymphatic filariasis (LF) is a globally significant disease, with 1.3 billion persons in 83 countries at risk. A coordinated effort of administering annual macrofilaricidal prophylactics to the entire at-risk population has succeeded in impacting and eliminating LF transmission in multiple regions. However, some areas in the South Pacific are predicted to persist as transmission sites, due in part to the biology of the mosquito vector, which has led to a call for additional tools to augment drug treatments. Autocidal strategies against mosquitoes are resurging in the effort against invasive mosquitoes and vector borne disease, with examples that include field …

Escherichia Coli-Mediated Impairment Of Ureteric Contractility Is Uropathogenic E. Coli Specific., Rachel V. Floyd, Mathew Upton, Scott J. Hultgren, Susan Wray, Theodor V. Burdyga, Craig Winstanley

School of Biomedical Sciences

BACKGROUND: Ureters are fundamental for keeping kidneys free from uropathogenic Escherichia coli (UPEC), but we have shown that 2 strains (J96 and 536) can subvert this role and reduce ureteric contractility. To determine whether this is (1) a widespread feature of UPEC, (2) exhibited only by UPEC, and (3) dependent upon type 1 fimbriae, we analyzed strains representing epidemiologically important multilocus sequence types ST131, ST73, and ST95 and non-UPEC E. coli. METHODS: Contractility and calcium transients in intact rat ureters were compared between strains. Mannose and fim mutants were used to investigate the role of type 1 fimbriae. RESULTS: Non-UPEC …

When Will Black Women Lawyers Slay The Two-Headed Dragon: Racism And Gender Bias, Wilma Williams Pinder

Pepperdine Law Review

No abstract provided.