Medicine and Health Sciences Commons^™

Formation Of Complex And Unstable Chromosomal Translocations In Yeast, Kristina H. Schmidt, Emilie Viebranz, Lillian Doerfler, Christina Lester, Aaron Rubenstein

Molecular Biosciences Faculty Publications

Genome instability, associated with chromosome breakage syndromes and most human cancers, is still poorly understood. In the yeast Saccharomyces cerevisiae, numerous genes with roles in the preservation of genome integrity have been identified. DNA-damage-checkpoint-deficient yeast cells that lack Sgs1, a RecQ-like DNA helicase related to the human Bloom's-syndrome-associated helicase BLM, show an increased rate of genome instability, and we have previously shown that they accumulate recurring chromosomal translocations between three similar genes, CAN1, LYP1 and ALP1. Here, the chromosomal location, copy number and sequence similarity of the translocation targets ALP1 and LYP1 were altered to gain insight into the …

Serious Mental Illness In Florida Nursing Homes: A Study Of Resident, Facility And Cost Characteristics, Marion Becker, Shabnam Mehra

Mental Health Law & Policy Faculty Publications

No abstract provided.

Epistatic Relationships Between Sara And Agr In Staphylococcus Aureus Biofilm Formation, Karen E. Beenken, Lara N. Mrak, Linda M. Griffin, Agnieszka K. Zielinska, Lindsey N. Shaw, Kelly C. Rice, Alexander R. Horswill, Kenneth W. Bayles, Mark S. Smeltzer

Molecular Biosciences Faculty Publications

Background: The accessory gene regulator (agr) and staphylococcal accessory regulator (sarA) play opposing roles in Staphylococcus aureus biofilm formation. There is mounting evidence to suggest that these opposing roles are therapeutically relevant in that mutation of agr results in increased biofilm formation and decreased antibiotic susceptibility while mutation of sarA has the opposite effect. To the extent that induction of agr or inhibition of sarA could potentially be used to limit biofilm formation, this makes it important to understand the epistatic relationships between these two loci.

Methodology/Principal Findings: We generated isogenic sarA and agr mutants in clinical isolates of S. …

Archaic Chaos: Intrinsically Disordered Proteins In Archaea, Bin Xue, Robert W. Williams, Christopher J. Oldfield, A. Keith Dunker, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Background: Many proteins or their regions known as intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) lack unique 3D structure in their native states under physiological conditions yet fulfill key biological functions. Earlier bioinformatics studies showed that IDPs and IDRs are highly abundant in different proteomes and carry out mostly regulatory functions related to molecular recognition and signal transduction. Archaea belong to an intriguing domain of life whose members, being microbes, are characterized by a unique mosaic-like combination of bacterial and eukaryotic properties and include inhabitants of some of the most extreme environments on the planet. With the expansion …

Leiomyosarcoma Arising In The Pancreatic Duct: A Case Report And Review Of The Current Literature, Nicole D. Riddle, Brian C. Quigley, Irwin Browarsky, Marilyn M. Bui

Pathology and Cell Biology Faculty Publications

Context. Leiomyosarcomas are rare malignant smooth muscle tumors that may arise in any organ or tissue that contains smooth muscle, commonly within the gastrointestinal tract. They are most often found in the stomach, large and small intestines, and retroperitoneum. Primary pancreatic leiomyosarcoma is extremely rare, and to the best of our knowledge only 30 cases have been reported in the world literature since 1951. Our case represents the first to have a clear origin from the main pancreatic duct. Case Report. This case was diagnosed in a large, tertiary care center in Tampa, Florida. Pertinent information was obtained …

Radical Nephrectomy With Ivc Thrombectomy (Level-Iii) Conducted On Veno-Veno Bypass, Tariq S. Hakky, Lucas R. Wiegand, Devannand Mangar, Angel Alsina, Philippe E. Spiess

Urology Faculty Publications

Introduction: We report a 43 year old man who was diagnosed with a level-I thrombus and was managed on oral sunitinib for two months by a community Urologist. The thrombus progressed to a level-III and he subsequently developed a pulmonary embolus, which required oral anticoagulation. He was then referred to our facility for definitive surgical care. A computed tomography scan demonstrated a 12 by 15 centimeter right renal mass and on magnetic resonance venography of the abdomen a tumor-thrombus extending into the infradiaphragmatic inferior vena cava was noted. Pre-operatively consults with hepatobiliary, vascular, and chest surgeons were obtained.

Methods: The …

Access For Laparoendoscopic Single Site Surgery, Sharona B. Ross, C. Whalen Clark, Connor A. Morton, Alexander S. Rosemurgy

Surgery Faculty Publications

Laparoscopic surgery is the standard of care for many abdominal and pelvic operations and is widely applied today. LESS (Laparo-Endoscopic Single Site) surgery, originally attempted in the 1990s, is an advanced minimally invasive approach that allows laparoscopic operations to be undertaken through a small (<15 mm) incision in the umbilicus, a preexisting scar. The presence of a preexisting scar allows LESS surgery to be essentially scarless, which is the key benefit to LESS operations. Herein, we review our experience with over 500 LESS operations and discuss the key techniques to establishing access to the peritoneal cavity. We review the options for obtaining access, available instrumentation, common challenges and solutions for access. We conclude that LESS surgery is safe and provides outcomes with superior cosmesis relative to conventional laparoscopy. LESS surgery should be embraced, as patient demand is rapidly increasing.

Calbindin-D28k Acts As A Calcium-Dependent Chaperone Suppressing Α-Synuclein Fibrillation In Vitro, Wenbo Zhou, Chunmei Long, Anthony L. Fink, Vladimir N. Uversky

Molecular Medicine Faculty Publications

α-Synuclein, a natively unfolded protein aggregation which is implicated in the pathogenesis of Parkinson’s disease and several other neurodegenerative diseases, is known to interact with a great number of unrelated proteins. Some of these proteins, such as ß-synuclein and DJ-1, were shown to inhibit α-synuclein aggregation in vitro and in vivo therefore acting as chaperones. Since calbindin-D28K is co-localized with Ca2+ neuronal membrane pumps, and since α-synuclein is also found in the membrane proximity, these two proteins can potentially interact in vivo. Here we show that calbindin-D28K interacts with α-synuclein and inhibits its fibrillation in a calcium-dependent manner, therefore potentially …

N-Terminal Domains Of Della Proteins Are Intrinsically Unstructured In The Absence Of Interaction With Gid1/Gibberellic Acid Receptors, Xiaolin Sun, William T. Jones, Dawn Harvey, Patrick J. B. Edwards, Steven M. Pascale, Christopher Kirk, Thérèse Considine, David J. Sheerin, Jasna Rakonjac, Christopher J. Oldfield, Bin Xue, A. Keith Dunker, Vladimir N. Uversky

Molecular Medicine Faculty Publications

The plant growth-repressing DELLA proteins (DELLAs) are known to represent a convergence point in integration of multiple developmental and environmental signals in planta, one of which is hormone gibberellic acid (GA). Binding of the liganded GA receptor (GID1/GA) to the N-terminal domain of DELLAs is required for GA-induced degradation of DELLAs via the ubiquitin-proteasome pathway, thus derepressing plant growth. However, the conformational changes of DELLAs upon binding to GID1/GA, which are the key to understanding the precise mechanism of GID1/GA-mediated degradation of DELLAs, remain unclear. Using biophysical, biochemical, and bioinformatics approaches, we demonstrated for the first time that the …

Share On Role Of An Expanded Inositol Transporter Repertoire In Cryptococcus Neoformans Sexual Reproduction And Virulence, Chaoyang Xue, Tongbao Liu, Lydia Chen, Wenjun Li, Iris Liu, James W. Kronstad, Andreas Seyfang, Joseph Heitman

Molecular Medicine Faculty Publications

Cryptococcus neoformans and Cryptococcus gattii are globally distributed human fungal pathogens and the leading causes of fungal meningitis. Recent studies reveal that myo-inositol is an important factor for fungal sexual reproduction. That C. neoformans can utilize myo-inositol as a sole carbon source and the existence of abundant inositol in the human central nervous system suggest that inositol is important for Cryptococcus development and virulence. In accord with this central importance of inositol, an expanded myo-inositol transporter (ITR) gene family has been identified in Cryptococcus. This gene family contains two phylogenetically distinct groups, with a …

Fluorescence Quantum Yield Of Thioflavin T In Rigid Isotropic Solution And Incorporated Into The Amyloid Fibrils, Anna I. Sulatskaya, Alexander A. Maskevich, Irina M. Kuznetsova, Vladimir N. Uversky, Konstantin K. Turoverov

Molecular Medicine Faculty Publications

In this work, the fluorescence of thioflavin T (ThT) was studied in a wide range of viscosity and temperature. It was shown that ThT fluorescence quantum yield varies from 0.0001 in water at room temperature to 0.28 in rigid isotropic solution (T/η→0). The deviation of the fluorescence quantum yield from unity in rigid isotropic solution suggests that fluorescence quantum yield depends not only on the ultra-fast oscillation of ThT fragments relative to each other in an excited state as was suggested earlier, but also depends on the molecular configuration in the ground state. This means that the fluorescence …

Retro-Morfs: Identifying Protein Binding Sites By Normal And Reverse Alignment And Intrinsic Disorder Prediction, Bin Xue, A. Keith Dunker, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Many cell functions in all living organisms rely on protein-based molecular recognition involving disorder-to-order transitions upon binding by molecular recognition features (MoRFs). A well accepted computational tool for identifying likely protein-protein interactions is sequence alignment. In this paper, we propose the combination of sequence alignment and disorder prediction as a tool to improve the confidence of identifying MoRF-based protein-protein interactions. The method of reverse sequence alignment is also rationalized here as a novel approach for finding additional interaction regions, leading to the concept of a retro-MoRF, which has the reversed sequence of an identified MoRF. The set of retro-MoRF binding …

A Bimodal Distribution Of Two Distinct Categories Of Intrinsically Disordered Structures With Separate Functions In Fg Nucleoporins, Justin Yamada, Joshua L. Philips, Samir Patel, Gabriel Goldfien, Alison Calestagne-Morelli, Hans Huang, Ryan Reza, Justin Acheson, Viswanathan V. Krishnan, Shawn Newsam, Ajay Gopinathan, Edmond Y. Lau, Michael E. Colvin, Vladimir N. Uversky, Michael F. Rexach

Molecular Medicine Faculty Publications

Nuclear pore complexes (NPCs) gate the only conduits for nucleocytoplasmic transport in eukaryotes. Their gate is formed by nucleoporins containing large intrinsically disordered domains with multiple phenylalanine-glycine repeats (FG domains). In combination, these are hypothesized to form a structurally and chemically homogeneous network of random coils at the NPC center, which sorts macromolecules by size and hydrophobicity. Instead, we found that FG domains are structurally and chemically heterogeneous. They adopt distinct categories of intrinsically disordered structures in non-random distributions. Some adopt globular, collapsed coil configurations and are characterized by a low charge content. Others are highly charged and adopt more …

3, 4-Dihydroxyphenylacetic Acid (Dopac) Impairs Α-Synuclein Interaction With Lipids, Wenbo Zhou, Chunmei Long, Anthony L. Fink, Vladimir N. Uversky

Molecular Medicine Faculty Publications

α-Synuclein (α-Syn) is a small intrinsically disordered presynaptic protein known to form insoluble filamentous inclusions in Parkinson’s disease (PD) and other neurodegenerative disorders. Various catecholamines can inhibit the α-Syn fibrillation in vitro. Recently, non-covalent binding of DOPAC (3,4-dihydroxyphenylacetic acid), a normal product of the dopamine metabolism, was shown to inhibit the fibrillation of α-Syn due to the DOPAC-induced stabilization of the normally transient oligomers thus preventing them from subsequent fibril formation (Zhou, et al. J. Mol. Biol. 2009, 388 (3), 597-610). We are showing here that the interaction of DOPAC with α-Syn decreases the binding affinity of α- Syn to …

Effects Of Various Flavonoids On The Α-Synuclein Fibrillation Process, Xiaoyun Meng, Larissa A. Munishkina, Anthony L. Fink, Vladimir N. Uversky

Molecular Medicine Faculty Publications

α-Synuclein aggregation and fibrillation are closely associated with the formation of Lewy bodies in neurons and are implicated in the causative pathogenesis of Parkinson's disease and other synucleinopathies. Currently, there is no approved therapeutic agent directed toward preventing the protein aggregation, which has been recently shown to have a key role in the cytotoxic nature of amyloidogenic proteins. Flavonoids, known as plant pigments, belong to a broad family of polyphenolic compounds. Over 4,000 flavonoids have been identified from various plants and foodstuffs derived from plants and have been demonstrated as potential neuroprotective agents. In this study 48 flavonoids belonging to …