Medicine and Health Sciences Commons^™

Sleep Disorders And Cardiac Consequences, Robert D. Vorona

Case Studies from Age in Action

Educational Objectives:

1. Review the clear relationship between obstructive sleep apnea and hypertension.

2. Discuss the cardiac consequences of sleep apnea, including coronary heart disease, heart failure, and different dysrhythmias.

3. Understand that sleep disorders beyond obstructive sleep apnea, such as insufficient sleep itself, may have an impact on the cardiovascular system.

4. Appreciate the potential benefits of identifying and treating sleep disorders for our health.

Bringing Comfort To People With Advanced Dementia, Ann Wyatt

Case Studies from Age in Action

Educational Objectives

1. Explain the purpose of looking at palliative care through a dementia lens.

2. Define dementia-capable palliative care.

3. Identify and provide examples of specific care practices that can bring comfort to people with advanced dementia.

4. Describe the process that staff use in identifying what brings comfort to individual residents.

Building Interprofessional Teams Through Evidence Based Practice Training In Falls Prevention, Constance L. Coogle, Edward F. Ansello, Patricia Slattum, Pamela L. Parsons

Case Studies from Age in Action

Objectives

1. Analyze an Evidence Based Practice (EBP) program on falls prevention as a vehicle for successful interprofessional team-building.

2. Examine ways that organizational characteristics can affect team functioning.

3. Compare interprofessional teambuilding in two sites.

4. Discuss elements of interprofessional teams that contributed to practice changes.

Pde5 Inhibitors Enhance Celecoxib Killing In Multiple Tumor Types, Laurence Booth, Jane L. Roberts, Nichola Cruickshanks, Seyedmehrad Tavallai, Timothy Webb, Peter Samuel, Adam Conley, Brittany Binion, Harold F. Young, Andrew Poklepovic, Sarah Spiegel, Paul Dent

Biochemistry and Molecular Biology Publications

The present studies determined whether clinically relevant phosphodiesterase 5 (PDE5) inhibitors interacted with a clinically relevant NSAID, celecoxib, to kill tumor cells. Celecoxib and PDE5 inhibitors interacted in a greater than additive fashion to kill multiple tumor cell types. Celecoxib and sildenafil killed ex vivo primary human glioma cells as well as their associated activated microglia. Knock down of PDE5 recapitulated the effects of PDE5 inhibitor treatment; the nitric oxide synthase inhibitor L-NAME suppressed drug combination toxicity. The effects of celecoxib were COX2 independent. Over-expression of c-FLIP-s or knock down of CD95/FADD significantly reduced killing by the drug combination. CD95 …

The Signal Transducer And Activator Of Transcription 1 (Stat1) Inhibits Mitochondrial Biogenesis In Liver And Fatty Acid Oxidation In Adipocytes, Jennifer D. Sisler, Magdalena Morgan, Vidisha Raje, Rebecca C. Grande, Marta Derecka, Jeremy Meier, Marc Cantwell, Karol Szczepanek, William J. Korzun, Edward J. Lesnefsky, Thurl E. Harris, Colleen M. Croniger, Andrew C. Larner

Biochemistry and Molecular Biology Publications

The transcription factor STAT1 plays a central role in orchestrating responses to various pathogens by activating the transcription of nuclear-encoded genes that mediate the antiviral, the antigrowth, and immune surveillance effects of interferons and other cytokines. In addition to regulating gene expression, we report that STAT1-/- mice display increased energy expenditure and paradoxically decreased release of triglycerides from white adipose tissue (WAT). Liver mitochondria from STAT1-/- mice show both defects in coupling of the electron transport chain (ETC) and increased numbers of mitochondria. Consistent with elevated numbers of mitochondria, STAT1-/- mice expressed increased amounts of PGC1α, a …

Perceived Stress Levels, Chemotherapy, Radiation Treatment And Tumor Characteristics Are Associated With A Persistent Increased Frequency Of Somatic Chromosomal Instability In Women Diagnosed With Breast Cancer: A One Year Longitudinal Study, Noran Aboalela, Debra E. Lyon, R. K. Elswick Jr., Debra Lynch Kelly, Jenni Brumelle, Harry D. Bear, Colleen Jackson-Cook

Human and Molecular Genetics Publications

While advances in therapeutic approaches have resulted in improved survival rates for women diagnosed with breast cancer, subsets of these survivors develop persistent psychoneurological symptoms (fatigue, depression/anxiety, cognitive dysfunction) that compromise their quality of life. The biological basis for these persistent symptoms is unclear, but could reflect the acquisition of soma-wide chromosomal instability following the multiple biological/psychological exposures associated with the diagnosis/treatment of breast cancer. An essential first step toward testing this hypothesis is to determine if these cancer-related exposures are indeed associated with somatic chromosomal instability frequencies. Towards this end, we longitudinally studied 71 women (ages 23-71) with early-stage …

Differential Expression Analysis Of Rna Sequencing Data By Incorporating Non-Exonic Mapped Reads, Hung-I Harry Chen, Yuanhang Liu, Yi Zou, Zhao Lai, Devanand Sarkar, Yufei Huang, Yidong Chen

Human and Molecular Genetics Publications

Background

RNA sequencing (RNA-seq) is a powerful tool for genome-wide expression profiling of biological samples with the advantage of high-throughput and high resolution. There are many existing algorithms nowadays for quantifying expression levels and detecting differential gene expression, but none of them takes the misaligned reads that are mapped to non-exonic regions into account. We developed a novel algorithm, XBSeq, where a statistical model was established based on the assumption that observed signals are the convolution of true expression signals and sequencing noises. The mapped reads in non-exonic regions are considered as sequencing noises, which follows a Poisson distribution. Given …

Depletion Of The Chromatin Remodeler Chd4 Sensitizes Aml Blasts To Genotoxic Agents And Reduces Tumor Formation, Justin Sperlazza, Mohamed Rahmani, Jason Beckta, Mandy Aust, Elisa Hawkins, Shou Zhen Wang, Sheng Zu Zhu, Shreya Podder, Catherine Dumur, Kellie Archer, Steven Grant, Gordon D. Ginder

Human and Molecular Genetics Publications

Chromodomain helicase DNA-binding protein 4 (CHD4) is an ATPase that alters the phasing of nucleosomes on DNA and has recently been implicated in DNA double-stranded break (DSB) repair. Here, we show that depletion of CHD4 in acute myeloid leukemia (AML) blasts induces a global relaxation of chromatin that renders cells more susceptible to DSB formation, while concurrently impeding their repair. Furthermore, CHD4 depletion renders AML blasts more sensitive both in vitro and in vivo to genotoxic agents used in clinical therapy: daunorubicin (DNR) and cytarabine (ara-C). Sensitization to DNR and ara-C is mediated in part by activation of the ataxia-telangiectasia …

Knockdown Of Cdk2ap1 In Primary Human Fibroblasts Induces P53 Dependent Senescence, Khaled N. Alsayegh, Venkat S. Gadepalli, Shilpa Iyer, Raj R. Rao

Human and Molecular Genetics Publications

Cyclin Dependent Kinase-2 Associated Protein-1 (CDK2AP1) is known to be a tumor suppressor that plays a role in cell cycle regulation by sequestering monomeric CDK2, and targeting it for proteolysis. A reduction of CDK2AP1 expression is considered to be a negative prognostic indicator in patients with oral squamous cell carcinoma and also associated with increased invasion in human gastric cancer tissue. CDK2AP1 overexpression was shown to inhibit growth, reduce invasion and increase apoptosis in prostate cancer cell lines. In this study, we investigated the effect of CDK2AP1 downregulation in primary human dermal fibroblasts. Using a short-hairpin RNA to reduce its …

Evaluation Of Methyl-Binding Domain Based Enrichment Approaches Revisited, Karolina A. Aberg, Linying Xie, Robin F. Chan, Min Zhao, Ashutosh K. Pandey, Gaurav Kumar, Shaunna L. Clark, Edwin J. C. G. Van Den Oord

Human and Molecular Genetics Publications

Methyl-binding domain (MBD) enrichment followed by deep sequencing (MBD-seq), is a robust and cost efficient approach for methylome-wide association studies (MWAS). MBD-seq has been demonstrated to be capable of identifying differentially methylated regions, detecting previously reported robust associations and producing findings that replicate with other technologies such as targeted pyrosequencing of bisulfite converted DNA. There are several kits commercially available that can be used for MBD enrichment. Our previous work has involved MethylMiner (Life Technologies, Foster City, CA, USA) that we chose after careful investigation of its properties. However, in a recent evaluation of five commercially available MBD-enrichment kits the …

Tumor-Specific Expression And Detection Of A Cest Reporter Gene, Il Minn, Amnon Bar-Shir, Keerthi Yarlagadda, Jeff W. M. Bulte, Paul B. Fisher, Hao Wang, Assaf A. Gilad, Martin G. Pomper

Human and Molecular Genetics Publications

Purpose

To develop an imaging tool that enables the detection of malignant tissue with enhanced specificity using the exquisite spatial resolution of MRI.

Methods

Two mammalian gene expression vectors were created for the expression of the lysine-rich protein (LRP) under the control of the cytomegalovirus (CMV) promoter and the progression elevated gene-3 promoter (PEG-3 promoter) for constitutive and tumor-specific expression of LRP, respectively. Using those vectors, stable cell lines of rat 9L glioma, 9LCMV-LRP and 9LPEG-LRP, were established and tested for CEST contrast in vitro and in vivo.

Results

9LPEG-LRP cells showed increased CEST contrast compared with 9L cells …

Genetic Risks To Nicotine Dependence Predict Negative Mood And Affect In Current Non-Smokers, Xiangning Chen, Steven H. Aggen, Jingchun Chen, Lingxi Li, Kenneth S. Kendler, Melissa Blank, Thomas Eissenberg

Human and Molecular Genetics Publications

Nicotine is the psychoactive agent involved in nicotine dependence. However, nicotine as a drug, and its effects on human psychology are largely under-investigated in genetic studies. In this study, we recruited 208 current non-smokers to evaluate the effect of nicotine and its relationship to genetic risks to nicotine dependence. Exploratory and confirmatory factor analyses, as well as measurement invariance testing, were conducted to evaluate the latent factor structures of the POMS, PANAS and DEN questionnaires across 3 nicotine doses. Structural models were used to examine the effects of nicotine and their relationship to genetic risks of nicotine dependence. We found …

Tumor-Specific Expression And Detection Of A Cest Reporter Gene, Il Minn, Amnon Bar-Shir, Keerthi Yarlagadda, Jeff W. M. Bulte, Paul B. Fisher, Hao Wang, Assaf A. Gilad, Martin G. Pomper

Human and Molecular Genetics Publications

Purpose

To develop an imaging tool that enables the detection of malignant tissue with enhanced specificity using the exquisite spatial resolution of MRI.

Methods

Two mammalian gene expression vectors were created for the expression of the lysine-rich protein (LRP) under the control of the cytomegalovirus (CMV) promoter and the progression elevated gene-3 promoter (PEG-3 promoter) for constitutive and tumor-specific expression of LRP, respectively. Using those vectors, stable cell lines of rat 9L glioma, 9LCMV-LRP and 9LPEG-LRP, were established and tested for CEST contrast in vitro and in vivo.

Results

9LPEG-LRP cells showed increased CEST contrast compared with 9L cells …

Perceived Stress Levels, Chemotherapy, Radiation Treatment And Tumor Characteristics Are Associated With A Persistent Increased Frequency Of Somatic Chromosomal Instability In Women Diagnosed With Breast Cancer: A One Year Longitudinal Study, Noran Aboalela, Debra E. Lyon, R. K. Elswick Jr., Debra Lynch Kelly, Jenni Brumelle, Harry D. Bear, Colleen Jackson-Cook

Human and Molecular Genetics Publications

While advances in therapeutic approaches have resulted in improved survival rates for women diagnosed with breast cancer, subsets of these survivors develop persistent psychoneurological symptoms (fatigue, depression/anxiety, cognitive dysfunction) that compromise their quality of life. The biological basis for these persistent symptoms is unclear, but could reflect the acquisition of soma-wide chromosomal instability following the multiple biological/psychological exposures associated with the diagnosis/treatment of breast cancer. An essential first step toward testing this hypothesis is to determine if these cancer-related exposures are indeed associated with somatic chromosomal instability frequencies. Towards this end, we longitudinally studied 71 women (ages 23-71) with early-stage …

Knockdown Of Cdk2ap1 In Primary Human Fibroblasts Induces P53 Dependent Senescence, Khaled N. Alsayegh, Venkat S. Gadepalli, Shilpa Iyer, Raj R. Rao

Human and Molecular Genetics Publications

Cyclin Dependent Kinase-2 Associated Protein-1 (CDK2AP1) is known to be a tumor suppressor that plays a role in cell cycle regulation by sequestering monomeric CDK2, and targeting it for proteolysis. A reduction of CDK2AP1 expression is considered to be a negative prognostic indicator in patients with oral squamous cell carcinoma and also associated with increased invasion in human gastric cancer tissue. CDK2AP1 overexpression was shown to inhibit growth, reduce invasion and increase apoptosis in prostate cancer cell lines. In this study, we investigated the effect of CDK2AP1 downregulation in primary human dermal fibroblasts. Using a short-hairpin RNA to reduce its …

Comparison Of Effects Of P53 Null And Gain-Of-Function Mutations On Salivary Tumors In Mmtv-Hras Transgenic Mice, Dadi Jiang, Catherine I. Dumur, H. Davis Massey, Viswanathan Ramakrishnan, Mark A. Subler, Jolene J. Windle

Human and Molecular Genetics Publications

p53 is an important tumor suppressor gene which is mutated in ~50% of all human cancers. Some of these mutants appear to have acquired novel functions beyond merely losing wild-type functions. To investigate these gain-of-function effects in vivo, we generated mice of three different genotypes: MMTV-Hras/p53+/+, MMTV-Hras/p53-/-, and MMTV-Hras/p53R172H/R172H. Salivary tumors from these mice were characterized with regard to age of tumor onset, tumor growth rates, cell cycle distribution, apoptotic levels, tumor histopathology, as well as response to doxorubicin treatment. Microarray analysis was also performed to profile gene expression. The MMTV-Hras/p53-/- and …

Psychosocial Factors Of Caregiver Burden In Child Caregivers: Results From The New National Study Of Caregiving, Steven A. Cohen, Sarah Cook, Lauren Kelley, Trisha Sando, Allison E. Bell

Family Medicine and Population Health Publications

Background

Over 50 million informal caregivers in the United States provide care to an aging adult, saving the economy hundreds of billions of dollars annually from costly hospitalization or institutionalization. Despite the benefits associated with caregiving, caregiver stress can lead to negative physical and mental health consequences, or “caregiver burden”. Given these potential negative consequences of caregiver burden, it is important not only to understand the multidimensional components of burden but to also understand the experience from the perspective of the caregiver themselves. Therefore, the objectives of our study are to use exploratory factor analysis to obtain a set of …

Source Of Care And Variation In Long Acting Reversible Contraception Use, Lauren Groskaufmanis, Saba W. Masho

Family Medicine and Population Health Publications

OBJECTIVE: To examine variation in long acting reversible contraception (LARC) use by source of birth control services.

DESIGN: Cross-sectional study.

SETTING: Not applicable.

PATIENT(S): Sexually active women who received contraceptive services in the past 12 months, who were neither pregnant nor trying to become pregnant and who were not sterilized and nor were their partners sterilized.

INTERVENTION(S): Three multinomial logistic regression models assessed the relationship between source of services and LARC use, controlling for covariates. The odds of LARC use were compared with LARC nonuse, high-efficacy use, and low-efficacy use.

MAIN OUTCOME MEASURE(S): Reported …

Spatiotemporal Discordance In Five Common Measures Of Rurality For Us Counties And Applications For Health Disparities Research In Older Adults, Steven A. Cohen, Lauren Kelley, Alison E. Bell

Family Medicine and Population Health Publications

Introduction

Rural populations face numerous barriers to health, including poorer health care infrastructure, access to care, and other sociodemographic factors largely associated with rurality. Multiple measures of rurality used in the biomedical and public health literature can help assess rural–urban health disparities and may impact the observed associations between rurality and health. Furthermore, understanding what makes a place truly “rural” versus “urban” may vary from region to region in the US.

Purpose

The objectives of this study are to compare and contrast five common measures of rurality and determine how well-correlated these measures are at the national, regional, and divisional …

Supporting Practices To Adopt Registry-Based Care (Sparc): Protocol For A Randomized Controlled Trial, Rebecca S. Etz, Rosalind E. Keith, Anna M. Maternick, Karen L. Stein, Roy T. Sabo, Melissa S. Hayes, Purvi Sevak, John Holland, Jesse C. Crosson

Family Medicine and Population Health Publications

Background

Diabetes is predicted to increase in incidence by 42% from 1995 to 2025. Although most adults with diabetes seek care from primary care practices, adherence to treatment guidelines in these settings is not optimal. Many practices lack the infrastructure to monitor patient adherence to recommended treatment and are slow to implement changes critical for effective management of patients with chronic conditions. Supporting Practices to Adopt Registry-Based Care (SPARC) will evaluate effectiveness and sustainability of a low-cost intervention designed to support work process change in primary care practices and enhance focus on population-based care through implementation of a diabetes registry. …

Sex And Sexual Orientation Disparities In Adverse Childhood Experiences And Early Age At Sexual Debut In The United States: Results From A Nationally Representative Sample, Monique J. Brown, Saba W. Masho, Robert A. Perera, Briana Mezuk, Steven A. Cohen

Family Medicine and Population Health Publications

Adverse childhood experiences (ACEs) have been linked to early sexual debut, which has been found to be associated with multiple adverse health outcomes. Sexual minorities and men tend to have earlier sexual debut compared to heterosexual populations and women, respectively. However, studies examining the association between ACEs and early sexual debut among men and sexual minorities are lacking. The aim of this study was to examine the sex and sexual orientation disparities in the association between ACEs and age at sexual debut. Data were obtained from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. Logistic and …

Suicide Risk In Nursing Homes And Assisted Living Facilities: 2003–2011, Brianna Mezuk, Matthew Lohman, Marc Leslie, Virginia Powell

Family Medicine and Population Health Publications

Objectives

We investigated the epidemiology of suicide among adults aged 50 years and older in nursing homes and assisted living facilities and whether anticipating transitioning into long-term care (LTC) is a risk factor for suicide.

Methods

Data come from the Virginia Violent Death Reporting System (2003–2011). We matched locations of suicides (n = 3453) against publicly available resource registries of nursing homes (n = 285) and assisted living facilities (n = 548). We examined individual and organizational correlates of suicide by logistic regression. We identified decedents anticipating entry into LTC through qualitative text analysis.

Results

Incidence of suicide was 14.16 …

Widely Used Herpes Simplex Virus 1 Icp0 Deletion Mutant Strain Dl1403 And Its Derivative Viruses Do Not Express Glycoprotein C Due To A Secondary Mutation In The Gc Gene, Cristina W. Cunha, Kathryne E. Taylor, Suzanne M. Pritchard, Mark G. Delboy, Tri Komala Sari, Hector C. Aguilar, Karen L. Mossman, Anthony V. Nicola

Microbiology and Immunology Publications

Herpes simplex virus 1 (HSV-1) ICP0 is a multi-functional phosphoprotein expressed with immediate early kinetics. An ICP0 deletion mutant, HSV-1 dl1403, has been widely used to study the roles of ICP0 in the HSV-1 replication cycle including gene expression, latency, entry and assembly. We show that HSV-1 dl1403 virions lack detectable levels of envelope protein gC, and that gC is not synthesized in infected cells. Sequencing of the gC gene from HSV-1dl1403 revealed a single amino acid deletion that results in a frameshift mutation. The HSV-1dl1403 gC gene is predicted to encode a polypeptide …

Turning Over A New Leaf: Cannabinoid And Endocannabinoid Modulation Of Immune Function, Guy A. Cabral, Thomas J. Rogers, Aron H. Lichtman

Microbiology and Immunology Publications

Cannabis is a complex substance that harbors terpenoid-like compounds referred to as phytocannabinoids. The major psychoactive phytocannabinoid found in cannabis ∆9-tetrahydrocannabinol (THC) produces the majority of its pharmacological effects through two cannabinoid receptors, termed CB1 and CB2. The discovery of these receptors as linked functionally to distinct biological effects of THC, and the subsequent development of synthetic cannabinoids, precipitated discovery of the endogenous cannabinoid (or endocannabinoid) system. This system consists of the endogenous lipid ligands N- arachidonoylethanolamine (anandamide; AEA) and 2-arachidonylglycerol (2-AG), their biosynthetic and degradative enzymes, and the CB1 and CB2 receptors that they activate. Endocannabinoids have been …

Hiv Protease Inhibitors Sensitize Human Head And Neck Squamous Carcinoma Cells To Radiation By Activating Endoplasmic Reticulum Stress, Runping Liu, Luyong Zhang, Jing Yang, Xiaoxuan Zhang, Ross B. Mikkelsen, Shiyu Song, Huiping Zhou

Microbiology and Immunology Publications

Background

Human head and neck squamous cell carcinoma (HNSCC) is the sixth most malignant cancer worldwide. Despite significant advances in the delivery of treatment and surgical reconstruction, there is no significant improvement of mortality rates for this disease in the past decades. Radiotherapy is the core component of the clinical combinational therapies for HNSCC. However, the tumor cells have a tendency to develop radiation resistance, which is a major barrier to effective treatment. HIV protease inhibitors (HIV PIs) have been reported with radiosensitizing activities in HNSCC cells, but the underlying cellular/molecular mechanisms remain unclear. Our previous study has shown that …

Widely Used Herpes Simplex Virus 1 Icp0 Deletion Mutant Strain Dl1403 And Its Derivative Viruses Do Not Express Glycoprotein C Due To A Secondary Mutation In The Gc Gene, Cristina W. Cunha, Kathryne E. Taylor, Suzanne M. Pritchard, Mark Delboy, Tri Komala Sari, Hector C. Aguilar, Karen L. Mossman, Anthony V. Nicola

Microbiology and Immunology Publications

Herpes simplex virus 1 (HSV-1) ICP0 is a multi-functional phosphoprotein expressed with immediate early kinetics. An ICP0 deletion mutant, HSV-1 dl1403, has been widely used to study the roles of ICP0 in the HSV-1 replication cycle including gene expression, latency, entry and assembly. We show that HSV-1dl1403 virions lack detectable levels of envelope protein gC, and that gC is not synthesized in infected cells. Sequencing of the gC gene from HSV-1 dl1403 revealed a single amino acid deletion that results in a frameshift mutation. The HSV-1 dl1403 gC gene is predicted to encode a polypeptide …

Epigenetic Modifications Of The Pgc-1Α Promoter During Exercise Induced Expression In Mice, Timothy L. Lochmann, Ravindar R. Thomas, James P. Bennett Jr., Shirley M. Taylor

Microbiology and Immunology Publications

The transcriptional coactivator, PGC-1α, is known for its role in mitochondrial biogenesis. Although originally thought to exist as a single protein isoform, recent studies have identified additional promoters which produce multiple mRNA transcripts. One of these promoters (promoter B), approximately 13.7kb upstream of the canonical PGC-1α promoter (promoter A), yields alternative transcripts present at levels much lower than the canonical PGC-1α mRNA transcript. In skeletal muscle, exercise resulted in a substantial, rapid increase of mRNA of these alternative PGC-1α transcripts. Although the β2-adrenergic receptor was identified as a signaling pathway that activates transcription from PGC-1α promoter B, it is not …

Essential Domains Of Anaplasma Phagocytophilum Invasins Utilized To Infect Mammalian Host Cells, David Seidman, Kathryn S. Hebert, Hilary K. Truchan, Daniel P. Miller, Brittney K. Tegels, Richard T. Marconi, Jason A. Carlyon

Microbiology and Immunology Publications

Anaplasma phagocytophilum causes granulocytic anaplasmosis, an emerging disease of humans and domestic animals. The obligate intracellular bacterium uses its invasins OmpA, Asp14, and AipA to infect myeloid and non-phagocytic cells. Identifying the domains of these proteins that mediate binding and entry, and determining the molecular basis of their interactions with host cell receptors would significantly advance understanding of A. phagocytophilum infection. Here, we identified the OmpA binding domain as residues 59 to 74. Polyclonal antibody generated against a peptide spanning OmpA residues 59 to 74 inhibited A. phagocytophilum infection of host cells and binding to its receptor, sialyl Lewis x …

Intracellular Uropathogenic E. Coli Exploits Host Rab35 For Iron Acquisition And Survival Within Urinary Bladder Cells, Neha Dikshit, Pradeep Bist, Shannon N. Fenlon, Niyas Kudukkil Pulloor, Christelle En Lin Chua, Marci A. Scidmore, Jason A. Carlyon, Bor Luen Tang, Swaine L. Chen, Bindu Sukumaran

Microbiology and Immunology Publications

Recurrent urinary tract infections (UTIs) caused by uropathogenic E. coli (UPEC) are common and morbid infections with limited therapeutic options. Previous studies have demonstrated that persistent intracellular infection of bladder epithelial cells (BEC) by UPEC contributes to recurrent UTI in mouse models of infection. However, the mechanisms employed by UPEC to survive within BEC are incompletely understood. In this study we aimed to understand the role of host vesicular trafficking proteins in the intracellular survival of UPEC. Using a cell culture model of intracellular UPEC infection, we found that the small GTPase Rab35 facilitates UPEC survival in UPEC-containing vacuoles …

Intracellular Uropathogenic E. Coli Exploits Host Rab35 For Iron Acquisition And Survival Within Urinary Bladder Cells, Neha Dikshit, Pradeep Bist, Shannon N. Fenlon, Niyas Kudukkil Pulloor, Christelle En Lin Chua, Marci A. Scidmore, Jason A. Carlyon, Bor Len Tang, Swaine L. Chen, Bindu Sukumaran

Microbiology and Immunology Publications

Recurrent urinary tract infections (UTIs) caused by uropathogenic E. coli (UPEC) are common and morbid infections with limited therapeutic options. Previous studies have demonstrated that persistent intracellular infection of bladder epithelial cells (BEC) by UPEC contributes to recurrent UTI in mouse models of infection. However, the mechanisms employed by UPEC to survive within BEC are incompletely understood. In this study we aimed to understand the role of host vesicular trafficking proteins in the intracellular survival of UPEC. Using a cell culture model of intracellular UPEC infection, we found that the small GTPase Rab35 facilitates UPEC survival in UPEC-containing vacuoles …