Medicine and Health Sciences Commons^™

Solvent Properties Of Water In Aqueous Solutions Of Elastin-Like Polypeptide, Luisa A. Ferreira, James T. Cole, Christian Reichardt, Nolan B. Holland, Vladimir N. Uversky, Boris Y. Zaslavsky

Molecular Medicine Faculty Publications

The phase-transition temperatures of an elastin-like polypeptide (ELP) with the (GVGVP)₄₀ sequence and solvent dipolarity/polarizability, hydrogen-bond donor acidity, and hydrogen-bond acceptor basicity in its aqueous solutions were quantified in the absence and presence of different salts (Na₂SO₄, NaCl, NaClO₄, and NaSCN) and various osmolytes (sucrose, sorbitol, trehalose, and trimethylamine N-oxide (TMAO)). All osmolytes decreased the ELP phase-transition temperature, whereas NaCl and Na₂SO₄ decreased, and NaSCN and NaClO₄ increased it. The determined phase-transition temperatures may be described as a linear combination of the solvent’s dipolarity/polarizability and hydrogen-bond donor acidity. The …

Identification Of Proteins Associated With Amyloidosis By Polarity Index Method., Carlos Polanco, José Lino Samaniego, Vladimir N N. Uversky, Jorge Alberto Castañón-González, Thomas Buhse, Marili Leopold-Sordo, Alejandro Madero-Arteaga, Alicia Morales-Reyes, Lourdes Tavera-Sierra, Jesus A. González-Bernal, Miguel Arias-Estrada

Molecular Medicine Faculty Publications

There is a natural protein form, insoluble and resistant to proteolysis, adopted by many proteins independently of their amino acid sequences via specific misfolding-aggregation process. This dynamic process occurs in parallel with or as an alternative to physiologic folding, generating toxic protein aggregates that are deposited and accumulated in various organs and tissues. These proteinaceous deposits typically represent bundles of β-sheet-enriched fibrillar species known as the amyloid fibrils that are responsible for serious pathological conditions, including but not limited to neurodegenerative diseases, grouped under the term amyloidoses. The proteins that might adopt this fibrillar conformation are some globular proteins and …

Beyond The Excluded Volume Effects: Mechanistic Complexity Of The Crowded Milieu, Irina M. Kuznetsova, Boris Y. Zaslavsky, Leonid Breydo, Konstantin K. Turoverov, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Macromolecular crowding is known to affect protein folding, binding of small molecules, interaction with nucleic acids, enzymatic activity, protein-protein interactions, and protein aggregation. Although for a long time it was believed that the major mechanism of the action of crowded environments on structure, folding, thermodynamics, and function of a protein can be described in terms of the excluded volume effects, it is getting clear now that other factors originating from the presence of high concentrations of “inert” macromolecules in crowded solution should definitely be taken into account to draw a more complete picture of a protein in a crowded milieu. …

Identifying Similar Patterns Of Structural Flexibility In Proteins By Disorder Prediction And Dynamic Programming, Aidan Petrovich, Adam Borne, Vladimir N. Uversky, Bin Xue

Molecular Medicine Faculty Publications

Computational methods are prevailing in identifying protein intrinsic disorder. The results from predictors are often given as per-residue disorder scores. The scores describe the disorder propensity of amino acids of a protein and can be further represented as a disorder curve. Many proteins share similar patterns in their disorder curves. The similar patterns are often associated with similar functions and evolutionary origins. Therefore, finding and characterizing specific patterns of disorder curves provides a unique and attractive perspective of studying the function of intrinsically disordered proteins. In this study, we developed a new computational tool named IDalign using dynamic programming. This …

Intrinsically Disordered Proteins In The Nucleus Of Human Cells, Telma Frege, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Intrinsically disordered proteins are known to perform a variety of important functions such as macromolecular recognition, promiscuous binding, and signaling. They are crucial players in various cellular pathway and processes, where they often have key regulatory roles. Among vital cellular processes intimately linked to the intrinsically disordered proteins is transcription, an intricate biological performance predominantly developing inside the cell nucleus. With this work, we gathered information about proteins that exist in various compartments and sub-nuclear bodies of the nucleus of the human cells, with the goal of identifying which ones are highly disordered and which functions are ascribed to the …

Structure And Stability Of Recombinant Bovine Odorant-Binding Protein: Ii. Unfolding Of The Monomeric Forms, Olga V. Stepanenko, Denis O. Roginskii, Olesya V. Stepanenko, Irina M. Kuznetsova, Vladimir N. Uversky, Konstantin K. Turoverov

Molecular Medicine Faculty Publications

In a family of monomeric odorant-binding proteins (OBPs), bovine OBP (bOBP), that lacks conserved disulfide bond found in other OBPs, occupies unique niche because of its ability to form domain-swapped dimers. In this study, we analyzed conformational stabilities of the recombinant bOBP and its monomeric variants, the bOBP-Gly121+ mutant containing an additional glycine residue after the residue 121 of the bOBP, and the GCC-bOBP mutant obtained from the bOBP-Gly121+ form by introduction of the Trp64Cys/His155Cys double mutation to restore the canonical disulfide bond. We also analyzed the effect of the natural ligand binding on the conformational stabilities of these bOBP …

Brca1 185delag Mutation Enhances Interleukin-1Β Expression In Ovarian Surface Epithelial Cells, Kamisha T. Woolery, Mai Mohamed, Rebecca J. Linger, Kimberly P. Dobrinski, Jesse Roman, Patricia A. Kruk

Pathology and Cell Biology Faculty Publications

Familial history remains the strongest risk factor for developing ovarian cancer (OC) and is associated with germline BRCA1 mutations, such as the 185delAG founder mutation. We sought to determine whether normal human ovarian surface epithelial (OSE) cells expressing the BRCA1 185delAG mutant, BRAT, could promote an inflammatory phenotype by investigating its impact on expression of the proinflammatory cytokine, Interleukin-1β (IL-1β). Cultured OSE cells with and without BRAT were analyzed for differential target gene expression by real-time PCR, western blot, ELISA, luciferase reporter, and siRNA assays. We found that BRAT cells expressed increased cellular and secreted levels of …

Tp53 And Mdm2 Single Nucleotide Polymorphisms Influence Survival In Non-Del(5q) Myelodysplastic Syndromes, Kathy L. Mcgraw, Thomas Cluzeau, David A. Sallman, Ashley A. Basiorka, Brittany A. Irvine, Ling Zhang, P.K. Epling-Burnette, Dana E. Rollison, Mar Mallo, Lubomir Sokol, Francesc Solé, Jaroslaw Maciejewski, Alan F. List

Pathology and Cell Biology Faculty Publications

P53 is a key regulator of many cellular processes and is negatively regulated by the human homolog of murine double minute-2 (MDM2) E3 ubiquitin ligase. Single nucleotide polymorphisms (SNPs) of either gene alone, and in combination, are linked to cancer susceptibility, disease progression, and therapy response. We analyzed the interaction of TP53 R72P and MDM2 SNP309 SNPs in relationship to outcome in patients with myelodysplastic syndromes (MDS). Sanger sequencing was performed on DNA isolated from 208 MDS cases. Utilizing a novel functional SNP scoring system ranging from +2 to −2 based on predicted p53 activity, we found statistically significant differences …

Surface Electromyography Of The Forearm Musculature During The Windmill Softball Pitch, D. Trey Remaley, Bryce Fincham, Bryan Mccullough, Kirk Davis, Charles Nofsinger, Charles Armstrong, Julie M. Stausmire

Orthopaedics and Sports Medicine Faculty Publications

Background: Previous studies investigating the windmill softball pitch have focused primarily on shoulder musculature and function, collecting limited data on elbow and forearm musculature. Little information is available in the literature regarding the forearm. This study documents forearm muscle electromyographic (EMG) activity that has not been previously published.

Purpose: Elbow and upper extremity overuse injuries are on the rise in fast-pitch softball pitchers. This study attempts to describe forearm muscle activity in softball pitchers during the windmill softball pitch. Overuse injuries can be prevented if a better understanding of mechanics is defined.

Study Design: Descriptive laboratory study.

Methods: Surface EMG …

Controlled Laboratory Comparison Study Of Motion With Football Equipment In A Destabilized Cervical Spine: Three Spine-Board Transfer Techniques, Mark L. Prasarn, Marybeth Horodyski, Matthew J. Dipaola, Christian P. Dipaola, Gianluca Del Rossi, Bryan P. Conrad, Glenn R. Rechtine Ii

Orthopaedics and Sports Medicine Faculty Publications

Background: Numerous studies have shown that there are better alternatives to log rolling patients with unstable spinal injuries, although this method is still commonly used for placing patients onto a spine board. No previous studies have examined transfer maneuvers involving an injured football player with equipment in place onto a spine board.

Purpose: To test 3 different transfer maneuvers of an injured football player onto a spine board to determine which method most effectively minimizes spinal motion in an injured cervical spine model.

Study Design: Controlled laboratory study.

Methods: Five whole, lightly embalmed cadavers were fitted with shoulder pads and …

Expandable Total Humeral Replacement In A Child With Osteosarcoma, Eric R. Henderson, Jidi Gao, John Groundland, Odion Binitie, G. Douglas Letson

Orthopaedics and Sports Medicine Faculty Publications

Case. A right-handed 8-year-old female patient presented with a conventional, high-grade osteosarcoma involving her right humerus; through-shoulder amputation was recommended. After consultation, total humerus resection with expandable, total humeral endoprosthesis reconstruction was performed with a sleeve to encourage soft-tissue ingrowth. At three-year follow-up she has received one lengthening procedure and her functional scores are excellent. Conclusion. Total humeral resection and replacement in the pediatric population are rare and although early reports of expandable total humeral endoprosthesis outcomes demonstrate high failure rates, this patient’s success indicates that expandable total humeral replacement is a viable option.

Effect Of Utilization Of Veno-Venous Bypass Vs. Cardiopulmonary Bypass On Complications For High Level Inferior Vena Cava Tumor Thrombectomy And Concomitant Radical Nephrectomy, Ross M. Simon, Timothy Kim, Patrick Espiritu, Tony Kurian, Wade J. Sexton, Julio M. Pow-Sang, Einar Sverrisson, Philippe E. Spiess

Urology Faculty Publications

Purpose: To determine if patients with renal cell carcinoma (RCC) with levels III and IV tumor thrombi are receive any reduction in complication rate utilizing veno-venous bypass (VVB) over cardiopulmonary bypass (CPB) for high level (III/IV) inferior vena cava (IVC) tumor thrombectomy and concomitant radical nephrectomy.

Materials and Methods: From May 1990 to August 2011, we reviewed 21 patients that had been treated for RCC with radical nephrectomy and concomitant IVC thrombectomy employing either CPB (n =16) or VVB (n=5). We retrospectively reviewed our study population for complication rates and perioperative characteristics.

Results: Our results are reported using the validated …

Partial Priapism Treated With Pentoxifylline, Meghan A. Cooper, Rafael E. Carrion, Christopher Yang

Urology Faculty Publications

Main findings: A 26-year-old man suffering from partial priapism was successfully treated with a regimen including pentoxifylline, a nonspecific phosphodiesterase inhibitor that is often used to conservatively treat Peyronie's disease.

Case hypothesis: Partial priapism is an extremely rare urological condition that is characterized by thrombosis within the proximal segment of a single corpus cavernosum. There have only been 36 reported cases to date. Although several factors have been associated with this unusual disorder, such as trauma or bicycle riding, the etiology is still not completely understood. Treatment is usually conservative and consists of a non-steroidal anti-inflammatory and anti-thrombotic.

Promising future …

Reduction Corporoplasty, Tariq S. Hakky, Daniel Martinez, Christopher Yang, Rafael E. Carrion

Urology Faculty Publications

Objective: Here we present the first video demonstration of reduction corporoplasty in the management of phallic disfigurement in a 17 year old man with a history sickle cell disease and priapism.

Introduction: Surgical management of aneurysmal dilation of the corpora has yet to be defined in the literature. Materials and Methods: We preformed bilateral elliptical incisions over the lateral corpora as management of aneurysmal dilation of the corpora to correct phallic disfigurement.

Results: The patient tolerated the procedure well and has resolution of his corporal disfigurement.

Conclusions: Reduction corporoplasty using bilateral lateral elliptical incisions in the management of aneurysmal dilation …

A Novel Approach For The Treatment Of Radiation-Induced Hemorrhagic Cystitis With The Greenlight™ Xps Laser, Daniel Roberto Martinez, Cesar E. Ercole, Juan Gabriel Lopez, Justin Parker, Mary K. Hall

Urology Faculty Publications

Introduction: The treatment of pelvic malignancies with radiotherapy can develop severe sequelae, especially radiation-induced hemorrhagic cystitis. It is a progressive disease that can lead to the need for blood transfusion, hospitalizations, and surgical interventions. This tends to affect the quality of life of these patients, and management can at times be difficult. We have evaluated the GreenLight Xcelerated Performance System (XPS) with TruCoag, although primarily used for management of benign prostatic hypertrophy (BPH), for the treatment of radiation-induced hemorrhagic cystitis.

Materials and Methods: After International Review Board (IRB) approval, a retrospective chart review was performed in addition to a literature …

Distal Spermatic Cord Peritoneal Stripping: An Adjunct Technique During Inguinal Orchiopexy, Hubert S. Swana, Rikin Patel, Mark A. Rich

Urology Faculty Publications

No abstract provided.

Bilateral Ureteral-Iliac Artery Fistula In A Patient With Chronic Indwelling Ureteral Stents: A Case Report And Review, Arash Rafiei, Timothy A. Weber, Michael Kongnyuy, Raul Ordorica

Urology Faculty Publications

Ureteral-arterial fistula (UAF) is an exceedingly rare but life-threatening condition warranting emergent intervention. Prompt recognition and management of UAF in suspect patients presenting with gross hematuria are required for a successful outcome. We report a rare subset of UAF involving the bilateral common iliac arteries. The patient underwent successful endovascular stent-grafting to correct the arterial defect and delayed open repair of the ureteral strictures. Timely management has benefited from the collaboration of the involved medical teams, which included emergency medicine, urology, and interventional radiology.

A Rare Case Of A Renal Cell Carcinoma Confined To The Isthmus Of A Horseshoe Kidney, Michael Kongnyuy, Daniel Martinez, Anthony Park, Barrett Mccormick, Justin Parker, Mary Hall

Urology Faculty Publications

Horseshoe kidney (HSK) is the most common renal anomaly. Reports of the incidence of renal cell carcinoma (RCC) in HSK are conflicting. Very few cases of isthmus-located RCC have been reported in the literature. We report a unique case of an isthmus-located RCC. Proper vascular and tumor imaging prior to surgery is key to successful tumor removal.

Frataxin Levels In Peripheral Tissue In Friedreich Ataxia, Michael Lazaropoulos, Yina Dong, Elisia Clark, Nathaniel R. Greeley, Lauren A. Seyer, Karlla W. Brigatti, Carlton Christie, Susan L. Perlman, George R. Wilmot, Christoper M. Gomez, Katherine D. Mathews, Grace Yoon, Theresa Zesiewicz, Chad Hoyle, Sub H. Subramony, Alicia F. Brocht, Jennifer M. Farmer, Robert B. Wilson, Eric C. Deutsch, David R. Lynch

Neurology Faculty Publications

No abstract provided.

Anti-Nmda Receptor Encephalitis In A Patient With Previous Psychosis And Neurological Abnormalities: A Diagnostic Challenge, R. David Heekin, Maria C. Catalano, Alfred T. Frontera, Glenn Catalano

Neurology Faculty Publications

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an autoimmune disorder characterized by IgG autoantibodies directed against the NR1 subunit of the NMDA glutamate receptor. Psychiatric symptoms are common and include psychosis, mania, depressed mood, aggression, and speech abnormalities. Neurological symptoms such as seizures, decreased responsiveness, dyskinesias, and other movement abnormalities and/or autonomic instability are frequently seen as well. We present the case of a woman who was followed up at our facility for over 14 years for the treatment of multiple neuropsychiatric symptoms. Initially, she presented with paresthesias, memory loss, and manic symptoms. Nine years later, she presented to our facility again, …

Mobile Stroke Unit (Msu): The Future Of Acute Stroke Treatment, Waldo R. Guerrero

Neurosurgery and Brain Repair Faculty Publications

No abstract provided.

Dendritic And Langerhans Cells Respond To Aβ Peptides Differently: Implication For Ad Immunotherapy, Jiang Cheng, Xiaoyang Lin, David Morgan, Marcia Gordon, Xi Chen, Zhen-Hai Wang, Hai-Ning Li, Lan-Jie He, Shu-Feng Zhou, Chuanhai Cao

Molecular Pharmacology & Physiology Faculty Publications

Both wild-type and mutated beta-amyloid (Aβ) peptides can elicit an immune response when delivered subcutaneously. However, only mutated forms of Aβ can sensitize dendritic cells when administered intravenously or intraperitoneally. To understand the role of mutation and delivery routes in creating immune responses, and the function of dendritic cells as therapeutic agents, we used fluorescent-conjugated WT Aβ1-40 (WT40) and artificially mutated Aβ1-40 (22W40) peptides to treat dendritic and Langerhans cells from young and/or old mice at different time points. The cell types were analyzed by flow cytometry and confocal microscopy to identify differences in function and antigen presentation, and Luminex …

Craniopharyngioma Causing Bilateral Vision Loss 4 Months After Unremarkable Magnetic Resonance Imaging Of The Brain, Rainy Betts, Curtis E. Margo, Mitchell Drucker

Ophthalmology Faculty Publications

A 65-year-old man developed bilateral vision loss 4 months after magnetic resonance imaging demonstrated no lesion in the vicinity of the optic chiasm, hypothalamus, and suprasellar tissues. Repeat computed tomography 3 months later showed a predominantly cystic mass of the suprasellar cistern with extension into the anterior third ventricle, which histologically was a craniopharyngioma. The clinical course of this case fuels the controversy whether craniopharyngiomas arise from embryonic rests or can be acquired. From a clinical perspective, it raises questions about when to obtain imaging studies dedicated to the chiasm and the appropriate interval in which a scan should be …

Visual Electrodiagnostic Testing In Birdshot Chorioretinopathy, Radouil Tzekov, Brian Madow

Ophthalmology Faculty Publications

Birdshot chorioretinopathy (BSCR) is a rare form of autoimmune posterior uveitis that can affect the visual function and, if left untreated, can lead to sight-threatening complications and loss of central vision. We performed a systematic search of the literature focused on visual electrophysiology studies, including electroretinography (ERG), electrooculography (EOG), and visual evoked potentials (VEP), used to monitor the progression of BSCR and estimate treatment efficacy. Many reports were identified, including using a variety of methodologies and patient populations, which makes a direct comparison of the results difficult, especially with some of the earlier studies using nonstandardized methodology. Several different electrophysiological …

Itraq-Based Proteomic Analysis Of Visual Cycle-Associated Proteins In Rpe Of Rd12 Mice Before And After Rpe65 Gene Delivery, Qinxiang Zheng, Yueping Ren, Radouil Tzekov, Shanshan Hua, Minghan Li, Jijing Pang, Jia Qu, Wensheng Li

Ophthalmology Faculty Publications

Purpose. To investigate the iTRAQ-based proteomic changes of visual cycle-associated proteins in RPE of rd12 mice before and after RPE65 gene delivery. Mehtods. The right eyes of rd12 mice underwent RPE65 gene delivery by subretinal injection at P14, leaving the left eyes as control. C57BL/6J mice were served as a wide-type control group. ERGs were recorded at P42, and RPE-choroid-sclera complex was collected to evaluate the proteomic changes in visual cycle-associated proteins by iTRAQ-based analysis. Western blot was used to confirm the changes in the differentially expressed proteins of interest. Results. ERG parameters improved dramatically at P42 after …

“In-Plant” Nmr: Analysis Of The Intact Plant Vesicularia Dubyana By High Resolution Nmr Spectroscopy, Viktor P. Kutyshenko, Peter Beskaravayny, Vladimir N. Uversky

Molecular Medicine Faculty Publications

We present here the concept of “in-plant” NMR and show that high-resolution NMR spectroscopy is suitable for the analysis of intact plants and can be used to follow the changes in the intraorganismal molecular composition over long time periods. The NMR-based analysis of the effect of different concentrations of heavy water on the aquatic plant Vesicularia dubyana revealed that due to the presence of specific adaptive mechanisms this plant can sustain the presence of up to 85% of D₂O. However, it dies in 100% heavy water.

Fendiline Inhibits Proliferation And Invasion Of Pancreatic Cancer Cells By Interfering With Adam10 Activation And Β-Catenin Signaling, Neha Woods, Jose Trevino, Domenico Coppola, Srikumar Chellappan, Shengyu Yang, Jaya Padmanabhan

Molecular Medicine Faculty Publications

ADAM10 (A Disintegrin and Metalloprotease Domain 10) affects the pathophysiology of various cancers, and we had shown that inhibition of ADAM10 sensitizes pancreatic cancer cells to gemcitabine. ADAM10 is activated in response to calcium influx, and here we examined if calcium channel blockers (CCB) would impede ADAM10 activation and affect biology of pancreatic cancer cells. We find that the CCB, fendiline, significantly reduces proliferation, migration, invasion, and anchorage independent growth of pancreatic cancer cells. This was associated with ADAM10 inhibition and its localization at the actin-rich membrane protrusions. Further, fendiline-treated cells formed cadherin-catenin positive tight adherens junctions and elicited defective …

Does Intrinsically Disordered Caldesmon Bind Calmodulin Via The “Buttons On A String” Mechanism?, Sergei E. Permyakov, Eugene A. Permyakov, Vladimir N. Uversky

Molecular Medicine Faculty Publications

We show here that chicken gizzard caldesmon (CaD) and its C-terminal domain (residues 636-771, CaD136) are intrinsically disordered proteins. The computational and experimental analyses of the wild type CaD136 and series of its single tryptophan mutants (W674A, W707A, and W737A) and a double tryptophan mutant (W674A/W707A) suggested that although the interaction of CaD136 with calmodulin (CaM) can be driven by the non-specific electrostatic attraction between these oppositely charged molecules, the specificity of CaD136-CaM binding is likely to be determined by the specific packing of important CaD136 tryptophan residues at the CaD136-CaM interface. It is suggested that this interaction can be …

Does Intrinsically Disordered Caldesmon Bind Calmodulin Via The “Buttons On A String” Mechanism?, Sergei E. Permyakov, Eugene A. Permyakov, Vladimir N. Uversky

Molecular Medicine Faculty Publications

We show here that chicken gizzard caldesmon (CaD) and its C-terminal domain (residues 636-771, CaD136) are intrinsically disordered proteins. The computational and experimental analyses of the wild type CaD136 and series of its single tryptophan mutants (W674A, W707A, and W737A) and a double tryptophan mutant (W674A/W707A) suggested that although the interaction of CaD136 with calmodulin (CaM) can be driven by the non-specific electrostatic attraction between these oppositely charged molecules, the specificity of CaD136-CaM binding is likely to be determined by the specific packing of important CaD136 tryptophan residues at the CaD136-CaM interface. It is suggested that this interaction can be …

Basic Epidemiology, Center For Leadership In Public Health Practice

Preparedness and Emergency Response Learning Center

Basic Epidemiology, a training course from the USF Center for Leadership in Public Health Practice, develops the awareness and knowledge of public health workers who may be deployed on Field Epidemiology strike teams. It is designed to help them assist local, regional, state, and national epidemiology staff in disease investigations during surge capacity. Basic Epidemiology is a required prerequisite for the IFIRST and IFIRST-2 programs.