Digital Commons Network^™

Robust Rnai-Based Resistance To Mixed Infection Of Three Viruses In Soybean Plants Expressing Separate Short Hairpins From A Single Transgene, Xiuchun Zhang, Shirley Sato, Xiaohong Ye, Anne E. Dorrance, Thomas Jack Morris, Thomas E. Clemente, Feng Qu

Nebraska Center for Virology: Faculty Publications

Transgenic plants expressing double-stranded RNA (dsRNA) of virus

origin have been previously shown to confer resistance to virus infections

through the highly conserved RNA-targeting process termed RNA silencing

or RNA interference (RNAi). In this study we applied this strategy to

soybean plants and achieved robust resistance to multiple viruses with a

single dsRNA-expressing transgene. Unlike previous reports that relied

on the expression of one long inverted repeat (IR) combining sequences

of several viruses, our improved strategy utilized a transgene designed to

express several shorter IRs. Each of these short IRs contains highly conserved

sequences of one virus, forming dsRNA of …

Kaposi Sarcoma-Associated Herpesvirus Degrades Cellular Toll-Interleukin-1 Receptor Domain-Containing Adaptor-Inducing Β-Interferon (Trif), Humera Ahmad, Rachel Gubbels, Florencia Meyer, Thomas Waterbury, Rongtuan Lin, Luwen Zhang

Nebraska Center for Virology: Faculty Publications

Kaposi sarcoma-associated herpesvirus (KSHV) is a human ƴ - herpesvirus associated with several human malignancies. The replication and transcription activator (RTA) is necessary and sufficient for the switch from KSHV latency to lytic replication. Toll-interleukin-1 receptor (TIR) domain-containing adaptorinducing β-interferon (TRIF, also called TIR-domain-containing adaptor molecule-1 (TICAM-1)) is a signaling adaptor molecule that is critically involved in the Toll-like receptor 3 (TLR-3) and TLR-4 signaling pathways for type I interferon (IFN) production, a key component of innate immunity against microbial infection. In this report, we find a new mechanism by which RTA blocks innate immunity by targeting cellular TRIF. RTA …

Human Papillomavirus 16 Variants From Zambian Women With Normal Pap Smears, Yan Jun Lei, Kgomotso Makhaola, Daraporn Pittayakhajonwut, Charles Wood, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

Human papillomavirus (HPV) type 16 is the most prevalent high-risk viral genotype associated with cervical cancer. Six distinct phylogenetic clusters of HPVs have been identified and are distributed differently across five continents. HPV16 DNA was extracted from cervico-lavage samples from women with normal pap smears. The LCR regions were amplified in triplicate, cloned, sequenced, and analyzed from a total of 11 recovered HPV16 positive samples [Ng’andwe et al. (2007): BMC Infect Dis 7:77] were analyzed for sequence variation. The HPV16 LCR variants were assessed for promoter activity by use of a luciferase reporter gene. Six novel HPV16 variants with nucleotide …

Hiv-1 Clade B And C Isolates Exhibit Differential Replication: Relevance To Macrophage-Mediated Neurotoxicity, Agnes A. Constantino, Yunlong Huang, Hong Zhang, Charles Wood, Jialin C. Zheng

Nebraska Center for Virology: Faculty Publications

HIV-associated neurocognitive disorders (HAND) continue to be a consequence of HIV-1 infection among clade B-infected individuals. In contrast, the incidence of severe neurological impairment is lower among clade C-infected patients in regions of Sub-Saharan Africa and India. Biological aspects such as replication, cytopathicity, inflammatory response, and neurotoxicity unique to each clade influence neuropathogenicity and ultimately affect the clinical outcome of the disease. We hypothesize that productive infection by clade C isolates leads to macrophagemediated neurotoxicity, although to a lesser extent than clade B isolates. Using a panel of primary isolates of clades B and C we demonstrated that clade B …

The Zambia Children's Ks-Hhv8 Study: Rationale, Study Design, And Study Methods, Veenu Minhas, Kay L. Crabtree, Ann Chao, Janet M. Wojcicki, Adrian M. Sifuniso, Catherine Nkonde, Chipepo Kankasa, Charles D. Mitchell, Charles Wood

Nebraska Center for Virology: Faculty Publications

The epidemic of human immunodeficiency virus in Zambia has led to a dramatic rise in the incidence of human herpesvirus-8 (HHV-8)–associated Kaposi's sarcoma in both adults and children. However, there is a paucity of knowledge about the routes of HHV-8 transmission to young children. The Zambia Children's KS-HHV8 Study, a large, prospective cohort study in Lusaka, Zambia, was launched in 2004 to investigate the role of household members as a source of HHV-8 infection in young children and social behaviors that may modify the risk of HHV-8 acquisition. This cohort is distinct from other epidemiologic studies designed to investigate HHV-8 …

Prevalence Of Human Herpesvirus 8 (Hhv8) And Hepatitis C Virus (Hcv) In A Rural Community With High Risk For Blood Borne Infections In Central China, Tiejun Zhang, Na He, Yingying Ding, Kay L. Crabtree, Veenu Minhas, Charles Wood

Nebraska Center for Virology: Faculty Publications

Former illegal blood donation in the past decade has caused HIV outbreaks in some rural areas in China. Other HIV associated virus infections, such as human herpesvirus 8 (HHV8) in such areas are still not well defined. In order to explore HHV8 and HCV seroprevalence and potential risk factors in such areas, a cross-sectional study with 305 HIV positive and 315 HIV negative subjects recruited from a rural county in Shanxi province was conducted, where illegal blood collection was reported. Interview questionnaires and serum testing were carried out with these participants. HCV and HHV8 seroprevalence were found to be higher …

Comparison Of Adenoviruses As Oncolytics And Cancer Vaccines In An Immunocompetent B Cell Lymphoma Model, Eric A. Weaver, Christopher Y. Chen, Shannon M. May, Mary E. Barry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

We have screened human adenoviruses (Ads) for oncolytic activity against a variety of mouse and hamster cell lines and have found a number that are susceptible to a variety of Ad serotypes. A20 lymphoma is derived from BALB/c mice and is susceptible to infection and killing by a variety of human Ads. A20 is also a suitable cancer vaccine model, because these cells express a unique immunoglobulin variable region that can be targeted by vaccination. To compare Ads as cancer vaccines versus Ads as oncolytics, A20 tumors were initiated in im- munocompetent BALB/c mice. Mice immunized with first-generation Ad5 expressing …

Advances And Future Challenges In Adenoviral Vector Pharmacology And Targeting, Reeti Khare, Christopher Y. Chen, Eric A. Weaver, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Adenovirus is a robust vector for therapeutic applications, but its use is limited by our understanding of its complex in vivo pharmacology. In this review we describe the necessity of identifying its natural, widespread, and multi-faceted interactions with the host since this information will be crucial for efficiently redirecting virus into target cells. In the rational design of vectors, the notion of overcoming a sequence of viral “sinks” must be combined with re-targeting to target populations with capsid as well as shielding the vectors from pre-existing or toxic immune responses. It must also be noted that most known adenoviral pharmacology …

Species D Adenoviruses As Oncolytics Against B-Cell Cancers, Christopher Y. Chen, Julien S. Senac, Eric A. Weaver, Shannon M. May, Diane F. Jelinek, Philip Greipp, Thomas Witzig, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Purpose: Oncolytic viruses are self-amplifying anticancer agents that make use of the natural ability of viruses to kill cells. Adenovirus serotype 5 (Ad5) has been extensively tested against solid cancers, but less so against B-cell cancers because these cells do not generally express the coxsackie and adenoviral receptor (CAR). To determine whether other adenoviruses might have better potency, we "mined" the adenovirus virome of 55 serotypes for viruses that could kill B-cell cancers.

Experimental Design: Fifteen adenoviruses selected to represent Ad species B, C, D, E, and F were tested in vitro against cell lines and primary patient B-cell cancers …

Rosuvastatin Therapy Does Not Affect Serum Mmp-13 Or Timp-1 Levels In Hypercholesterolemic Patients, Cihan Cevik, Kenneth Nugent, Gary Meyerrose, Mohammad Otahbachi, Cemil Izgi, Mark Lyte, R David Fish

The Texas Heart Institute Journal

Matrix metalloproteinases degrade the collagen content of atherosclerotic plaque and reduce plaque stability. In tissue sections of atherosclerotic plaque, the expression of matrix metalloproteinases is increased. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) decrease the tissue expression of matrix metalloproteinases-1, -2, -3, and -9 in atheromatous plaque by attenuating the inflammatory process that leads to increased expression. However, it is not known whether statins decrease levels of matrix metalloproteinase-13—an enzyme crucial to the initiation of collagen degradation—as part of their plaque-stabilizing effect.

We prospectively examined the effect of statin therapy on serum levels of matrix metalloproteinase-13, tissue inhibitor of metalloproteinase-1, and …

The Effect Of Spiritualism On The Neuropsychological Function Of Memory, Carla Farcello

McNair Poster Presentations

The amount of physiological-neurological research performed over the past few years has dramatically increased due to our ability to view the structure and function of the brain in living human beings. The use of imaging tools has resulted in huge strides forward in unlocking some of the mysteries of the 3 pound universe-the human brain. One of the more unique neural processes being recently addressed is the affect of belief and spiritualism-the sense of being connected to something larger than oneself-on the human brain. This study hypothesized that better memory will be documented among the experimental group who report being …

Bacterial Vaginosis Is Associated With Uterine Cervical Human Papillomavirus Infection: A Meta-Analysis, Evy Gillet, Joris Fa Meys, Hans Verstraelen, Carolyne Bosire, Philippe De Sutter, Marleen Temmerman, Davy Vanden Broeck

Obstetrics and Gynaecology, East Africa

Background: Bacterial vaginosis (BV), an alteration of vaginal flora involving a decrease in Lactobacilli and predominance of anaerobic bacteria, is among the most common cause of vaginal complaints for women of childbearing age. It is well known that BV has an influence in acquisition of certain genital infections. However, association between BV and cervical human papillomavirus (HPV) infection has been inconsistent among studies. The objective of this meta-analysis of published studies is to clarify and summarize published literature on the extent to which BV is associated with cervical HPV infection.

Methods: Medline and Web of Science were systematically searched for …

Heart Disease And Hormones, Stephanie A Coulter

The Texas Heart Institute Journal

Results from more than 40 observational studies conducted in women over 3 decades have repeatedly indicated the cardioprotective effects of postmenopausal hormone replacement therapy (HRT). Women taking estrogen in these observational trials experienced a consistent 30% to 50% reduction in cardiovascular (CV) events. The biologic benefit of estrogen has been attributed to improvements in lipid profiles and endothelial function.

Prenatal Maternal Stress Programs Infant Stress Regulation, Elyssia Poggi Davis, Laura M. Glynn, Feizal Waffarn, Curt A. Sandman

Psychology Faculty Articles and Research

Objective: Prenatal exposure to inappropriate levels of glucocorticoids (GCs) and maternal stress are putative mechanisms for the fetal programming of later health outcomes. The current investigation examined the influence of prenatal maternal cortisol and maternal psychosocial stress on infant physiological and behavioral responses to stress.

Methods: The study sample comprised 116 women and their full term infants. Maternal plasma cortisol and report of stress, anxiety and depression were assessed at 15, 19, 25, 31 and 36 + weeks' gestational age. Infant cortisol and behavioral responses to the painful stress of a heel-stick blood draw were evaluated at 24 hours after …

Complete Genome Sequence Of Treponema Paraluiscuniculi, Strain Cuniculi A: The Loss Of Infectivity To Humans Is Associated With Genome Decay, David Smajs, Marie Zobaníková, Michal Strouhal, Darina Cejková, Shannon Dugan-Rocha, Petra Pospíšilová, Steven J Norris, Tom Albert, Xiang Qin, Kym Hallsworth-Pepin, Christian Buhay, Donna M Muzny, Lei Chen, Richard A Gibbs, George M Weinstock

Faculty, Staff and Student Publications

Treponema paraluiscuniculi is the causative agent of rabbit venereal spirochetosis. It is not infectious to humans, although its genome structure is very closely related to other pathogenic Treponema species including Treponema pallidum subspecies pallidum, the etiological agent of syphilis. In this study, the genome sequence of Treponema paraluiscuniculi, strain Cuniculi A, was determined by a combination of several high-throughput sequencing strategies. Whereas the overall size (1,133,390 bp), arrangement, and gene content of the Cuniculi A genome closely resembled those of the T. pallidum genome, the T. paraluiscuniculi genome contained a markedly higher number of pseudogenes and gene fragments (51). In …

Alterations In Content And Localization Of Defensins In Rat Ileum And Jejunum Following Ischemia-Reperfusion Specific Peptides, In Specific Places, For Specific Jobs?, Rosemary A Kozar, Rachel J Santora, Brian J Poindexter, Stephen M Milner, Roger J Bick

Faculty, Staff and Student Publications

Objective: To determine alterations in quantities and distributions of natural antimicrobials following ischemia-reperfusion injury. We hypothesized that these compounds would be upregulated in areas of small intestine where changes in permeability and cellular disruption were likely and where protective mechanisms would be initiated. Methods: Rats with ischemia-reperfusion underwent superior mesenteric artery clamping and reperfusion. Shams were subjected to laparotomy but no clamping. Ileum and jejunum were harvested and sectioned, and subjected to fluorescence deconvolution microscopy for determinations of content and localization of rat beta defensins, 1, 2, 3; rat neutrophil protein-1; and cathelicidin LL-37. Modeling was performed to determine cellular …

Association Of Retinoic Acid Receptor Genes With Meningomyelocele, Phong X Tran, Kit Sing Au, Alanna C Morrison, Jack M Fletcher, Kathryn K Ostermaier, Gayle H Tyerman, Hope Northrup

Faculty, Staff and Student Publications

BACKGROUND: Neural tube defects (NTDs) occur in as many as 0.5-2 per 1000 live births in the United States. One of the most common and severe neural tube defects is meningomyelocele (MM) resulting from failed closure of the caudal end of the neural tube. MM has been induced by retinoic acid teratogenicity in rodent models. We hypothesized that genetic variants influencing retinoic acid (RA) induction via retinoic acid receptors (RARs) may be associated with risk for MM.

METHODS: We analyzed 47 single nucleotide polymorphisms (SNPs) that span across the three retinoic acid receptor genes using the SNPlex genotyping platform. Our …

Immunopathology Of Postprimary Tuberculosis: Increased T-Regulatory Cells And Dec-205-Positive Foamy Macrophages In Cavitary Lesions, Kerry J Welsh, Semyon A Risin, Jeffrey K Actor, Robert L Hunter

Faculty, Staff and Student Publications

Postprimary tuberculosis occurs in immunocompetent people infected with Mycobacterium tuberculosis. It is restricted to the lung and accounts for 80% of cases and nearly 100% of transmission. Little is known about the immunopathology of postprimary tuberculosis due to limited availability of specimens. Tissues from 30 autopsy cases of pulmonary tuberculosis were located. Sections of characteristic lesions of caseating granulomas, lipid pneumonia, and cavitary stages of postprimary disease were selected for immunohistochemical studies of macrophages, lymphocytes, endothelial cells, and mycobacterial antigens. A higher percentage of cells in lipid pneumonia (36.1%) and cavitary lesions (27.8%) were positive for the dendritic cell marker …

Labrad : Vol 36, Issue 1 - January 2011, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• Routine and Special Liver Function Tests
• Management of Coagulopathy Associated with Liver Disease
• Significance of Clinical and Laboratory Scoring System in Diagnosis of Disseminated Intravascular Coagulation in Chronic Liver Disease
• Laboratory Diagnosis of Hydatid Disease
• Laboratory Diagnosis of Amoebiasis
• Improvement of Bacteriological Yield of Liver Abscess by use of Anaerobic Chambers
• Radiofrequency Ablation of Liver Tumours
• HER2 in Breast Cancer: Frequently Asked Questions
• Clinical Laboratory Continuing Medical Education (CME) Seminar
• World Blood Donor Day at Aga Khan University Blood Bank

Plasmodium Falciparum Population Dynamics During The Early Phase Of Anti-Malarial Drug Treatment In Tanzanian Children With Acute Uncomplicated Malaria, A.M. Carlsson, B.E. Ngasala, S. Dahlstrom, C. Membi, I.M. Veiga, L. Rombo, S. Abdulla, Zul Premji, J.P. Gil, A. Bjorkman, A. Martensson

Pathology, East Africa

Background: This study aimed to explore Plasmodium falciparum population dynamics during the early phase of anti-malarial drug treatment with artemisinin-based combination therapy in children with clinical malaria in a high transmission area in Africa.

Methods: A total of 50 children aged 1-10 years with acute uncomplicated P. falciparum malaria in Bagamoyo District, Tanzania, were enrolled. Participants were hospitalized and received supervised standard treatment with artemether-lumefantrine according to body weight in six doses over 3 days. Blood samples were collected 11 times, i.e. at time of diagnosis (-2 h) and 0, 2, 4, 8, 16, 24, 36, 48, 60 and 72 …

Measuring The Symptom Burden Of Lung Cancer: The Validity And Utility Of The Lung Cancer Module Of The M D Anderson Symptom Inventory, Tito R Mendoza, Xin Shelley Wang, Charles Lu, Guadalupe R Palos, Zhongxing Liao, Gary M Mobley, Shitij Kapoor, Charles S Cleeland

Faculty, Staff and Student Publications

We conducted a study to establish the psychometric properties of a module of the M. D. Anderson Symptom Inventory (MDASI) developed specifically for patients with lung cancer (MDASI-LC). The MDASI measures 13 common "core" symptoms of cancer and its treatment. The MDASI-LC includes the 13 core MDASI symptom items and three lung cancer-specific items: coughing, constipation, and sore throat. MDASI-LC items were administered to three cohorts of patients with lung cancer undergoing either chemotherapy or chemoradiotherapy. Known-group validity and criterion (concurrent) validity of the MDASI-LC were evaluated using the Eastern Cooperative Oncology Group performance status and the 12-item Short-Form Health …

Ventral Hernia Repairs: 10 Year Single Institution Review At Thomas Jefferson University Hospital, Frederick C. Sailes, Md, Jason Walls, Md, Daria Guelig, Md, Mike Mirzabeigi, Ma, William D. Long, Ms, Albert Crawford, Phd, John H. Moore Jr, Md, Facs, Steven E. Copit, Md, Gary A. Tuma, M.D, James Fox, Md

Department of Surgery Faculty Papers

Abstract

Background Definitive repair of recurrent ventral hernias using abdominal wall reconstruction techniques is an essential tool in the armentarium for general and plastic surgeons. Ramirez 1 et al describes the “component separation” technique to mobilize the rectus-abdominus internal oblique and external oblique flap to correct the defect. The recurrence rate of incisional hernias increases to 20% after gastric bypass or extensive weight loss.2 The incidence of ventral hernias after failed recurrent hernia repair increases to 40%.3 It has been reported that utilizing the sliding myofascial flap repair technique, the recurrence rate was reduced to 8.5%.4

Materials and Methods This …

Cathepsin B: A Potential Prognostic Marker For Inflammatory Breast Cancer, Mohamed A. Nouh, Mona M. Mohamed, Mohamed El-Shinawi, Mohamed A. Shaalan, Dora Cavallo-Medved, Hussein M. Khaled, Bonnie F. Sloane

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. In non-IBC, the cysteine protease cathepsin B (CTSB) is known to be involved in cancer progression and invasion; however, very little is known about its role in IBC.

Methods

In this study, we enrolled 23 IBC and 27 non-IBC patients. All patient tissues used for analysis were from untreated patients. Using immunohistochemistry and immunoblotting, we assessed the levels of expression of CTSB in IBC versus non-IBC patient tissues. Previously, we found that CTSB is localized to caveolar membrane microdomains in cancer cell lines including IBC, and …

Inhibition Of Cathepsin B Activity Attenuates Extracellular Matrix Degradation And Inflammatory Breast Cancer Invasion, Bernadette C. Victor, Arulselvi Anbalagan, Mona M. Mohamed, Bonnie F. Sloane, Dora Cavallo-Medved

Wayne State University Associated BioMed Central Scholarship

Abstract

Introduction

Inflammatory breast cancer (IBC) is an aggressive, metastatic and highly angiogenic form of locally advanced breast cancer with a relatively poor three-year survival rate. Breast cancer invasion has been linked to proteolytic activity at the tumor cell surface. Here we explored a role for active cathepsin B on the cell surface in the invasiveness of IBC.

Methods

We examined expression of the cysteine protease cathepsin B and the serine protease urokinase plasminogen activator (uPA), its receptor uPAR and caveolin-1 in two IBC cell lines: SUM149 and SUM190. We utilized a live cell proteolysis assay to localize in real …

The Potential Role Of Innate Immunity In The Pathogenesis Of Post-Operative Adhesions, Jennell White

Wayne State University Dissertations

Post-operative adhesion development occurs in the vast majority of patients following abdominal surgery and is a natural occurrence of peritoneal-wound healing. These fibrous bands may form within the first 5-7 days post-surgery and have the ability to cause a distortion in the normal anatomical positioning of abdominal organs. Consequently, adhesions are major contributors to small bowel obstruction, infertility, and severe pelvic and abdominal pain. Physiological processes responsible for adhesion formation remain obscure though it is believed to involve cell migration, proliferation, and differentiation of several cell types including mesothelial cells, fibroblasts, and inflammatory and immune cells. Substances released from these …

Probing The Mechanical Properties Of Tnf-A Stimulated Endothelial Cell With Atomic Force Microscopy, Sei-Young Lee, Ana-Maria Zaske, Tommaso Novellino, Delia Danila, Mauro Ferrari, Jodie Conyers, Paolo Decuzzi

Faculty, Staff and Student Publications

TNF-α (tumor necrosis factor-α) is a potent pro-inflammatory cytokine that regulates the permeability of blood and lymphatic vessels. The plasma concentration of TNF-α is elevated (> 1 pg/mL) in several pathologies, including rheumatoid arthritis, atherosclerosis, cancer, pre-eclampsia; in obese individuals; and in trauma patients. To test whether circulating TNF-α could induce similar alterations in different districts along the vascular system, three endothelial cell lines, namely HUVEC, HPMEC, and HCAEC, were characterized in terms of 1) mechanical properties, employing atomic force microscopy; 2) cytoskeletal organization, through fluorescence microscopy; and 3) membrane overexpression of adhesion molecules, employing ELISA and immunostaining. Upon stimulation …

Addressing The Fertility Needs Of Hiv-Seropositive Males, Brian A. Levine, Sahadat K. Nurudeen, Jennifer T. Gosselin, Mark V. Sauer

Psychology Faculty Publications

An increasing number of serodiscordant couples are utilizing advanced reproductive technologies to address their reproductive needs. Recent literature has demonstrated that it is not only technically possible but also safe to utilize sperm-washing techniques to allow for the creation of embryos, thereby preventing both horizontal and vertical transmission of HIV. This article addresses the strengths and weakness of various reproductive techniques and discusses our experience at Columbia University (NY, USA), the location of the largest HIV-focused fertility program in the USA.

Transition Experiences Of Adolescent Survivors Of Childhood Cancer: A Qualitative Investigation, Alana Delores Lopez

USF Tampa Graduate Theses and Dissertations

Adolescent survivors of childhood cancer are a growing population with unique needs as they face a combination of challenges associated with normal development and returning to life after treatment completion (Wakefield et al., 2010). One specific need identified in the research literature includes the effective delivery of transitional care and planning (Hewitt, Greenfield, & Stovall, 2005). It has been suggested that the provision of transition care and planning can help facilitate the shift from one phase of care to another and promote positive transition experiences (National Cancer Institute, 2008). The shift from off-treatment to post-treatment and school reintegration have been …

Inhibition Of P53 Dna Binding Function By The Mdm2 Acidic Domain, Brittany Lynne Cross

USF Tampa Graduate Theses and Dissertations

MDM2 regulates p53 predominantly by promoting p53 ubiquitination. However, ubiquitination-independent mechanisms of MDM2 have also been implicated. Here we show that MDM2 inhibits p53 DNA binding activity in vitro and in vivo. MDM2 binding promotes p53 to adopt a mutant-like conformation, losing reactivity to antibody Pab1620, while exposing the Pab240 epitope. The acidic domain of MDM2 is required to induce p53 conformational change and inhibit p53 DNA binding. ARF binding to the MDM2 acidic domain restores p53 wild type conformation and rescues DNA binding activity. Furthermore, histone methyl transferase SUV39H1 binding to the MDM2 acidic domain also restores p53 wild …

The Roles Of Conserved And Nonconserved Cysteinyl Residues In The Oligomerization And Function Of Mammalian Prestin, Benjamin Currall, Danielle Rossino, Heather Jensen Smith, Richard Hallworth

Journal Articles: Eppley Institute

The creation of several prestin knockout and knockin mouse lines has demonstrated the importance of the intrinsic outer hair cell membrane protein prestin to mammalian hearing. However, the structure of prestin remains largely unknown, with even its major features in dispute. Several studies have suggested that prestin forms homo-oligomers that may be stabilized by disulfide bonds. Our phylogenetic analysis of prestin sequences across chordate classes suggested that the cysteinyl residues could be divided into three groups, depending on the extent of their conservation between prestin orthologs and paralogs or homologs. An alanine scan functional analysis was performed of all nine …