Medicine and Health Sciences Commons^™

N-Glycosylation Dictates Proper Processing Of Organic Anion Transporting Polypeptide 1b1, Juan Yao, Weifang Hong, Jiujiu Huang, Kai Zhan, Hong Huang, Mei Hong

School of Information Faculty Publications

Organic anion transporting polypeptides (OATPs) have been extensively recognized as key determinants of absorption, distribution, metabolism and excretion (ADME) of various drugs, xenobiotics and toxins. Putative N-glycosylation sites located in the extracellular loops 2 and 5 is considered a common feature of all OATPs and some members have been demonstrated to be glycosylated proteins. However, experimental evidence is still lacking on how such a post-translational modification affect the transport activity of OATPs and which of the putative glycosylation sites are utilized in these transporter proteins. In the present study, we substituted asparagine residues that are possibly involved in N-glycosylation with …

Missing Drivers With Dementia: Antecedents And Recovery, Meredeth Rowe, Catherine Greenblum, Marie Boltz, James E. Galvin

Nursing Faculty Publications

Objectives: To determine the circumstances under which persons with dementia become lost while driving, how missing drivers are found, and how Silver Alert notifications are instrumental in those discoveries.

Design: A retrospective, descriptive study.

Setting: Retrospective record review.

Participants: Conducted using 156 records from the Florida Silver Alert program for October 2008 through May 2010. These alerts were issued in Florida for missing drivers with dementia.

Measurements: Information derived from the reports on characteristics of the missing driver, antecedents to missing event, and discovery of a missing driver.

Results: The majority of missing drivers were men aged 58 to 94 …

Day-To-Day Variability In Nap Duration Predicts Medical Morbidity In Older Adults, Natalie D. Dautovich, Daniel B. Kay, Michael L. Perlis, Joseph M. Dzierzewski, Meredeth Rowe, Christina S. Mccrae

Nursing Faculty Publications

Objective: The objectives for the present study were to (a) examine within-person variability of nap duration and (b) assess how variability in nap duration is related to the number of health conditions in a sample of older adults. For highly variable behaviors such as sleep, it is important to consider fluctuations within the person instead of solely comparing averages of behaviors across persons. Method: Data were drawn from a previous study examining sleep in 103 community-dwelling older adults. Subjective estimates of napping behavior were obtained from sleep diaries and objective estimates of napping behavior were obtained using actigraphy. Both measures …

Housing And Housing Services Program Measure – Veterans Version (Hhspm-V), Colleen Clark, M. Scott Young, Sarah R. Moody, Gregory Teague, Rhonda Ort, James Winarski, Kathleen Moore, Minnie Norton, Blake Barrett

Mental Health Law & Policy Faculty Publications

No abstract provided.

Genome-Wide Patterns Of Arabidopsis Gene Expression In Nature, Christina L. Richards, Ulises Rosas, Joshua A. Banta, Naeha Bhambra, Michael D. Purugganan

Integrative Biology Faculty and Staff Publications

Organisms in the wild are subject to multiple, fluctuating environmental factors, and it is in complex natural environments that genetic regulatory networks actually function and evolve. We assessed genome-wide gene expression patterns in the wild in two natural accessions of the model plant Arabidopsis thaliana and examined the nature of transcriptional variation throughout its life cycle and gene expression correlations with natural environmental fluctuations. We grew plants in a natural field environment and measured genome-wide time-series gene expression from the plant shoot every three days, spanning the seedling to reproductive stages. We find that 15,352 genes were expressed in the …

Using Health Information Technology To Engage Communities In Health, Education, And Research, Lisa K. Marriott, David A. Nelson, Shauntice Allen, Karen Calhoun, Christina Eldredge, Kim S. Kimminau, Robert J. Lucero, Fernando Pineda-Reyes, Bernice B. Rumala, Arti P. Varanasi, June S. Wasser, Jackilen Shannon

School of Information Faculty Publications

The August 2011 Clinical and Translational Science Awards conference "Using IT to Improve Community Health: How Health Care Reform Supports Innovation" convened four "Think Tank" sessions. Thirty individuals, representing various perspectives on community engagement, attended the "Health information technology (HIT) as a resource to improve community health and education" session, which focused on using HIT to improve patient health, education, and research involvement. Participants discussed a range of topics using a semistructured format. This article describes themes and lessons that emerged from that session, with a particular focus on using HIT to engage communities to improve health and reduce health …

Understanding Viral Transmission Behavior Via Protein Intrinsic Disorder Prediction: Coronaviruses, Gerard Kian-Meng Goh, A. Keith Dunker, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Besides being a common threat to farm animals and poultry, coronavirus (CoV) was responsible for the human severe acute respiratory syndrome (SARS) epidemic in 2002–4. However, many aspects of CoV behavior, including modes of its transmission, are yet to be fully understood. We show that the amount and the peculiarities of distribution of the protein intrinsic disorder in the viral shell can be used for the efficient analysis of the behavior and transmission modes of CoV. The proposed model allows categorization of the various CoVs by the peculiarities of disorder distribution in their membrane (M) and nucleocapsid (N). This categorization …

An Intrinsically Disordered Region Of The Acetyltransferase P300 With Similarity To Prion-Like Domains Plays A Role In Aggregation, Alexander Kirilyuk, Mika Shimoji, Jason Catania, Geetaram Sahu, Nagarajan Pattabiraman, Antonio Giordano, Christopher Albanese, Italo Mocchetti, Jeffrey A. Toretsky, Vladimir N. Uversky, Maria Laura Avantaggiati

Molecular Medicine Faculty Publications

Several human diseases including neurodegenerative disorders and cancer are associated with abnormal accumulation and aggregation of misfolded proteins. Proteins with high tendency to aggregate include the p53 gene product, TAU and alpha synuclein. The potential toxicity of aberrantly folded proteins is limited via their transport into intracellular sub-compartments, the aggresomes, where misfolded proteins are stored or cleared via autophagy. We have identified a region of the acetyltransferase p300 that is highly disordered and displays similarities with prion-like domains. We show that this region is encoded as an alternative spliced variant independently of the acetyltransferase domain, and provides an interaction interface …

Disease-Associated Mutations Disrupt Functionally Important Regions Of Intrinsic Protein Disorder, Vladimir Vacic, Phineus R. L. Markwick, Christopher J. Oldfield, Xiaoyue Zhao, Chad Haynes, Vladimir N. Uversky, Lilia M. Iakoucheva

Molecular Medicine Faculty Publications

The effects of disease mutations on protein structure and function have been extensively investigated, and many predictors of the functional impact of single amino acid substitutions are publicly available. The majority of these predictors are based on protein structure and evolutionary conservation, following the assumption that disease mutations predominantly affect folded and conserved protein regions. However, the prevalence of the intrinsically disordered proteins (IDPs) and regions (IDRs) in the human proteome together with their lack of fixed structure and low sequence conservation raise a question about the impact of disease mutations in IDRs. Here, we investigate annotated missense disease mutations …

Common Features At The Start Of The Neurodegeneration Cascade, Rubén Hervás, Javier Oroz, Albert Galera-Prat, Oscar Goñi, Alejandro Valbuena, Andrés M. Vera, Àngel Gómez-Sicilia, Fernando Losada-Urzáiz, Vladimir N. Uversky, Margarita Menéndez, Douglas V. Laurents, Marta Bruix, Mariano Carrión-Vázquez

Molecular Medicine Faculty Publications

Amyloidogenic neurodegenerative diseases are incurable conditions with high social impact that are typically caused by specific, largely disordered proteins. However, the underlying molecular mechanism remains elusive to established techniques. A favored hypothesis postulates that a critical conformational change in the monomer (an ideal therapeutic target) in these “neurotoxic proteins” triggers the pathogenic cascade. We use force spectroscopy and a novel methodology for unequivocal single-molecule identification to demonstrate a rich conformational polymorphism in the monomer of four representative neurotoxic proteins. This polymorphism strongly correlates with amyloidogenesis and neurotoxicity: it is absent in a fibrillization-incompetent mutant, favored by familial-disease mutations and diminished …

Morfpred, A Computational Tool For Sequence-Based Prediction And Characterization Of Short Disorder-To-Order Transitioning Binding Regions In Proteins, Fatemeh Miri Disfani, Wei-Lun Hsu, Marcin J. Mizianty, Christopher J. Oldfield, Bin Xue, A. Keith Dunker, Vladimir N. Uversky, Lukasz Kurgan

Molecular Medicine Faculty Publications

Motivation: Molecular recognition features (MoRFs) are short binding regions located within longer intrinsically disordered regions that bind to protein partners via disorder-to-order transitions. MoRFs are implicated in important processes including signaling and regulation. However, only a limited number of experimentally validated MoRFs is known, which motivates development of computational methods that predict MoRFs from protein chains.

Results: We introduce a new MoRF predictor, MoRFpred, which identifies all MoRF types (α, β, coil and complex). We develop a comprehensive dataset of annotated MoRFs to build and empirically compare our method. MoRFpred utilizes a novel design in which annotations generated by sequence …

Understanding Viral Transmission Behavior Via Protein Intrinsic Disorder Prediction: Coronaviruses, Gerard Kian-Meng Goh, A. Keith Dunker, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Besides being a common threat to farm animals and poultry, coronavirus (CoV) was responsible for the human severe acute respiratory syndrome (SARS) epidemic in 2002–4. However, many aspects of CoV behavior, including modes of its transmission, are yet to be fully understood. We show that the amount and the peculiarities of distribution of the protein intrinsic disorder in the viral shell can be used for the efficient analysis of the behavior and transmission modes of CoV. The proposed model allows categorization of the various CoVs by the peculiarities of disorder distribution in their membrane (M) and nucleocapsid (N). This categorization …

Apolipoprotein E: Essential Catalyst Of The Alzheimer Amyloid Cascade, Huntington Potter, Thomas Wisniewski

Molecular Medicine Faculty Publications

The amyloid cascade hypothesis remains a robust model of AD neurodegeneration. However, amyloid deposits contain proteins besides Aβ, such as apolipoprotein E (apoE). Inheritance of the apoE4 allele is the strongest genetic risk factor for late-onset AD. However, there is no consensus on how different apoE isotypes contribute to AD pathogenesis. It has been hypothesized that apoE and apoE4 in particular is an amyloid catalyst or “pathological chaperone”. Alternatively it has been posited that apoE regulates Aβ clearance, with apoE4 been worse at this function compared to apoE3. These views seem fundamentally opposed. The former would indicate …

Free Cysteine Modulates The Conformation Of Human C/Ebp Homologous Protein, Vinay K. Singh, Mona M. Rahman, Kim Munro, Vladimir N. Uversky, Steven P. Smith, Zongchao Jia

Molecular Medicine Faculty Publications

The C/EBP Homologous Protein (CHOP) is a nuclear protein that is integral to the unfolded protein response culminating from endoplasmic reticulum stress. Previously, CHOP was shown to comprise extensive disordered regions and to self-associate in solution. In the current study, the intrinsically disordered nature of this protein was characterized further by comprehensive in silico analyses. Using circular dichroism, differential scanning calorimetry and nuclear magnetic resonance, we investigated the global conformation and secondary structure of CHOP and demonstrated, for the first time, that conformational changes in this protein can be induced by the free amino acid l-cysteine. Addition of l-cysteine caused …

Analyzing Thioflavin T Binding To Amyloid Fibrils By An Equilibrium Microdialysis-Based Technique, Irina M. Kuznetsova, Anna I. Sulatskaya, Vladimir N. Uversky, Konstantin K. Turoverov

Molecular Medicine Faculty Publications

A new approach for the determination of the amyloid fibril - thioflavin T (ThT) binding parameters (the number of binding modes, stoichiometry, and binding constants of each mode) is proposed. This approach is based on the absorption spectroscopy determination of the concentration of free and bound to fibril dye in solutions, which are prepared by equilibrium microdialysis. Furthermore, the proposed approach allowed us, for the first time, to determine the absorption spectrum, molar extinction coefficient, and fluorescence quantum yield of the ThT bound to fibril by each binding modes. This approach is universal and can be used for determining the …

Disordered Competitive Recruiter: Fast And Foldable, Vladimir N. Uversky

Molecular Medicine Faculty Publications

We report the crystal structure of the Escherichia coli TolB-Pal complex, a protein−protein complex involved in maintaining the integrity of the outer membrane (OM) in all Gram-negative bacteria that is parasitized by colicins (protein antibiotics) to expedite their entry into cells. Nuclease colicins competitively recruit TolB using their natively disordered regions (NDRs) to disrupt its complex with Pal, which is thought to trigger translocation of the toxin across a locally destabilized OM. The structure shows induced-fit binding of peptidoglycan-associated lipoprotein (Pal) to the β-propeller domain of TolB causing the N-terminus of one of its α-helices to unwind and several residues …

Development Of A Communication Intervention To Assist Hospitalized Suddenly Speechless Patients, Carmen S. Rodriguez, Meredeth A. Rowe, Brent Koeppel, Loris A. Thomas, Michelle S. Troche, Glenna Paguio

Nursing Faculty Publications

Healthcare staff face significant challenges while caring for hospitalized patients experiencing sudden inability to verbalize their needs (sudden speechlessness). Familiar methods of communication such as non-verbal strategies are limited and often fail to assist suddenly speechless patients (SS) communicate their needs. Consequently, strategies tailored to the needs of hospitalized speechless patients are necessary, and must consider factors intrinsic to the patients and the complexities of the acute care environment. The feasibility and usability of a multi-functional prototype communication system (speech-generating device) tailored to the needs of hospitalized SS patients was evaluated in this pilot study. Adult SS patients admitted to …

Treatment Choices Based On Oncotypedx In The Breast Oncology Care Setting, Teri L. Malo, Isaac Lipkus, Tobi Wilson, Hyo S. Han, Geza Acs, Susan T. Vadaparampil

Pathology and Cell Biology Faculty Publications

Introduction. This study aimed to evaluate whether OncotypeDx test results predict receipt of adjuvant chemotherapy in breast cancer patients who received an OncotypeDx recurrence score (RS). Materials and Methods. Pathology records were used to identify breast cancer patients who had OncotypeDx testing between December 2004 and January 2009 (𝑛 = 1 1 8). Patient sociodemographic information, tumor characteristics, RS, and treatment-specific data were collected via chart review. RS was classified as follows: low (R S ≤ 1 7), intermediate (RS = 18–30), or high (R S ≥ 3 1). Bivariate analyses were …

Primary Uterine Cervix Schwannoma: A Case Report And Review Of The Literature, Maryam Tahmasbi, Johnny Nguyen, Masoumeh Ghayouri, Yuan Shan, Ardeshir Hakam

Pathology and Cell Biology Faculty Publications

Schwannoma (neurilemmoma) is a benign peripheral nerve sheath tumor that occurs in a wide variety of locations; however, its finding in the uterine cervix is extremely rare. We report a case of an incidental primary benign cervical schwannoma in a 48-year-old woman. In the English literature, a few cases of primary schwannoma of the cervix have been reported, which include seven cases of primary malignant cervical schwannoma and only two that are benign. These cases are reviewed in the following discussion.

Homeostatic Imbalance In Epithelial Ducts And Its Role In Carcinogenesis, Katarzyna A. Rejniak

Oncologic Sciences Faculty Publications

An epithelial duct is a well-defined multicellular structure composed of tightly packed cells separating and protecting body compartments that are used for enzyme secretion and its transport across the internal. The structural and functional integrity (homeostasis) of such ducts is vital in carrying many life functions (breathing, lactation, production of hormones). However, the processes involved in maintaining the homeostatic balance are not yet fully understood. On the other hand, the loss of epithelial tissue architecture, such as filled lumens or ductal disorganization, are among the first symptoms of the emerging epithelial tumors (carcinomas). Using the previously developed biomechanical model of …

Receptor Antagonism And Dyskinesia In Parkinson’S Disease, Micaela Morelli, Fabio Blandini, Nicola Simola, Robert A. Hauser

Neurology Faculty Publications

Dyskinesia, a major complication of treatment of Parkinson’s disease (PD), involves two phases: induction, which is responsible for dyskinesia onset, and expression, which underlies its clinical manifestation. The unique cellular and regional distribution of adenosine receptors in basal ganglia areas that are richly innervated by dopamine, and their antagonistic role towards dopamine receptor stimulation, have positioned receptor antagonists as an attractive nondopaminergic target to improve the motor deficits that characterize PD. In this paper, we describe the biochemical characteristics of receptors and the effects of adenosine antagonists in rodent and primate models of PD on L-DOPA-induced dyskinesia, together with relevant …

Peripheral Nerve Repair With Cultured Schwann Cells: Getting Closer To The Clinics, Maria Carolina O. Rodrigues, Antonio Antunes Rodrigues, Loren E. Glover, Julio Voltarelli, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

Peripheral nerve injuries are a frequent and disabling condition, which affects 13 to 23 per 100.000 persons each year. Severe cases, with structural disruption of the nerve, are associated with poor functional recovery. The experimental treatment using nerve grafts to replace damaged or shortened axons is limited by technical difficulties, invasiveness, and mediocre results. Other therapeutic choices include the adjunctive application of cultured Schwann cells and nerve conduits to guide axonal growth. The bone marrow is a rich source of mesenchymal cells, which can be differentiated in vitro into Schwann cells and subsequently engrafted into the damaged nerve. Alternatively, undifferentiated …

Early Outcomes Of Minimally Invasive Anterior Longitudinal Ligament Release For Correction Of Sagittal Imbalance In Patients With Adult Spinal Deformity, Armen R. Deukmedjian, Elias Dakwar, Amir Ahmadian, Donald A. Smith, Juan S. Uribe

Neurosurgery and Brain Repair Faculty Publications

The object of this study was to evaluate a novel surgical technique in the treatment of adult degenerative scoliosis and present our early experience with the minimally invasive lateral approach for anterior longitudinal ligament release to provide lumbar lordosis and examine its impact on sagittal balance. Methods. All patients with adult spinal deformity (ASD) treated with the minimally invasive lateral retroperitoneal transpsoas interbody fusion (MIS LIF) for release of the anterior longitudinal ligament were examined. Patient demographics, clinical data, spinopelvic parameters, and outcome measures were recorded. Results. Seven patients underwent release of the anterior longitudinal ligament (ALR) to …

The Effect Of The Retroperitoneal Transpsoas Minimally Invasive Lateral Interbody Fusion On Segmental And Regional Lumbar Lordosis, Tien V. Le, Andrew C. Vivas, Elias Dakwar, Ali A. Baaj, Juan S. Uribe

Neurosurgery and Brain Repair Faculty Publications

Background. The minimally invasive lateral interbody fusion (MIS LIF) in the lumbar spine can correct coronal Cobb angles, but the effect on sagittal plane correction is unclear. Methods. A retrospective review of thirty-five patients with lumbar degenerative disease who underwent MIS LIF without supplemental posterior instrumentation was undertaken to study the radiographic effect on the restoration of segmental and regional lumbar lordosis using the Cobb angles on pre- and postoperative radiographs. Mean disc height changes were also measured. Results. The mean follow-up period was 13.3 months. Fifty total levels were fused with a mean of 1.42 levels …

Methicillin-Resistant Staphylococcus Aureus Infections In Human Immunodeficiency Virus-Infected Children And Adolescents, George K. Siberry, Toni Frederick, Patricia Emmanuel, Mary E. Paul, Beverly Bohannon, Travis Wheeling, Theresa Barton, Mobeen H. Rathore, Kenneth L. Dominguez

Pediatrics Faculty Publications

Background. Methicillin-resistant Staphylococcus aureus (MRSA) infection incidence has increased in healthy US children. Our objective was to evaluate MRSA incidence and correlates in HIV-infected youth. Methods. The CDC-sponsored LEGACY study is a US multicenter chart abstraction study of HIV-infected youth. We identified MRSA infections among participants with ≥1 visit during 2006. We used bivariate and multivariable analyses to compare sociodemographic and HIV clinical factors between MRSA cases and noncases. Results. Fourteen MRSA infections (1 invasive, 12 soft tissue, 1 indeterminate) occurred among 1,813 subjects (11.1 infections/1,000 patient-years (PY), 95% CI: 11.06–11.14). Most (86%) isolates were clindamycin susceptible. …

Development And Characterization Of Anti-Nitr9 Antibodies, Radhika N. Shah, Ivan Rodriguez-Nunez, Donna D. Eason, Robert N. Haire, Julien Y. Bertrand, Valērie Wittamer, David Traver, Shila K. Nordone

Pediatrics Faculty Publications

The novel immune-type receptors (NITRs), which have been described in numerous bony fish species, are encoded by multigene families of inhibitory and activating receptors and are predicted to be functional orthologs to the mammalian natural killer cell receptors (NKRs). Within the zebrafish NITR family, nitr9 is the only gene predicted to encode an activating receptor. However, alternative RNA splicing generates three distinct nitr9 transcripts, each of which encodes a different isoform. Although nitr9 transcripts have been detected in zebrafish lymphocytes, the specific hematopoietic lineage(s) that expresses Nitr9 remains to be determined. In an effort to better understand the role of …

The Florida Melanoma Trial I: A Prospective Multicenter Phase I/Ii Trial Of Postoperative Hypofractionated Adjuvant Radiotherapy With Concurrent Interferon-Alfa-2b In The Treatment Of Advanced Stage Iii Melanoma With Long-Term Toxicity Follow-Up, Steven E. Finkelstein, Andy Trotti, Nikhil Rao, Douglas Reintgen, Wayne Cruse, Lynn Feun, Vernon Sondak, Daohai Yu, Weiwei Zhu, Clement Gwede, Ronald Deconti

Surgery Faculty Publications

Radiotherapy (RT) and interferon-alfa-2b (IFN α-2b) have individually been used for adjuvant therapy stage III melanoma with high-risk pathologic features. We hypothesized that concurrent adjuvant RT and IFN α-2b may decrease the risk of regional recurrence following surgery with acceptable toxicity. A prospective multicenter phase I/II study was conducted to evaluate hypofractionated RT with concurrent IFN. Induction IFN α-2b, 20 MU/m2/d, was administered IV ×5 consecutive days every week for 4 weeks. Next, RT 30 Gy in 5 fractions was given with concurrent IFN α-2b, 10 MU/m2 SQ 3 times per week on days alternating with …

Penile Enhancement Procedures With Simultaneous Penile Prosthesis Placement, Tariq S. Hakky, Jessica Suber, Gerard Henry, David Smith, Paul Bradley, Daniel Martinez, Rafael E. Carrion

Surgery Faculty Publications

Here we present an overview of various techniques performed concomitantly during penile prosthesis surgery to enhance penile length and girth. We report on the technique of ventral phalloplasty and its outcomes along with augmentation corporoplasty, suprapubic lipectomy, suspensory ligament release, and girth enhancement procedures. For the serious implanter, outcomes can be improved by combining the use of techniques for each scar incision. These adjuvant procedures are a key addition in the armamentarium for the serious implant surgeon

Retroperitoneal Lymph Node Dissection With Concomitant Ivc Thrombectomy, Caval Wall Resection, And Grafting For Metastatic Nsgt, Tariq Hakky, Timothy Kim, Alejandro R. Rodriguez, Paul Armstrong, Devanand Mangar, Philippe E. Spiess

Obstetrics & Gynecology Faculty Publications

INTRODUCTION: The management of a post-chemotherapy retroperitoneal mass secondary to testicular cancer can present a surgical challenge when involving adjacent organs or major vascular structures. We present the first video of a retroperitoneal lymph node dissection (RPLND) with IVC (inferior vena cava) thrombectomy, caval wall resection resulting from metastatic non-seminomatous germ cell testis (NSGCT) cancer.

METHODS: In this surgical video, we highlight important surgical considerations in the management of a post-chemotherapy retroperitoneal mass with direct IVC wall invasion and level 2 thrombus in such a patient.

RESULTS: A 34 year old man underwent a right inguinal orchiectomy for a mixed …

The Role Of Epigenetics In Evolution: The Extended Synthesis, Aaron W. Schrey, Christina L. Richards, Victoria Meller, Vincent Sollars, Douglas M. Ruden

Integrative Biology Faculty and Staff Publications

No abstract provided.