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2013

University of South Florida

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Full-Text Articles in Medicine and Health Sciences

Black Hispanic And Black Nonhispanic Breast Cancer Survival Data Analysis With Half-Normal Model Application, Hafiz Mohammad Rafiqullah Khan, Anshul Saxena, Veronica Vera, Faheema Abdool-Ghany, Kemesha Gabbidon, Nancy Perea Perea, Ts Stewart, Venkataraghavan Ramamoorthy Ramamoorthy Dec 2013

Black Hispanic And Black Nonhispanic Breast Cancer Survival Data Analysis With Half-Normal Model Application, Hafiz Mohammad Rafiqullah Khan, Anshul Saxena, Veronica Vera, Faheema Abdool-Ghany, Kemesha Gabbidon, Nancy Perea Perea, Ts Stewart, Venkataraghavan Ramamoorthy Ramamoorthy

USF St. Petersburg campus Faculty Publications

Background: Breast cancer is the second leading cause of cancer death for women in the United States. Differences in survival of breast cancer have been noted among racial and ethnic groups, but the reasons for these disparities remain unclear. This study presents the characteristics and the survival curve of two racial and ethnic groups and evaluates the effects of race on survival times by measuring the lifetime data-based half-normal model. Materials and Methods: The distributions among racial and ethnic groups are compared using female breast cancer patients from nine states in the country all taken from the National Cancer Institute’s …


Long-Term Upregulation Of Inflammation And Suppression Of Cell Proliferation In The Brain Of Adult Rats Exposed To Traumatic Brain Injury Using The Controlled Cortical Impact Model, Sandra A. Acosta, Naoki Tajiri, Kazutaka Shinozuka, Hiroto Ishikawa, Bethany Grimmig, David M. Diamond, Paul R. Sanberg, Paula C. Bickford, Yuji Kaneko, Cesario V. Borlongan Jan 2013

Long-Term Upregulation Of Inflammation And Suppression Of Cell Proliferation In The Brain Of Adult Rats Exposed To Traumatic Brain Injury Using The Controlled Cortical Impact Model, Sandra A. Acosta, Naoki Tajiri, Kazutaka Shinozuka, Hiroto Ishikawa, Bethany Grimmig, David M. Diamond, Paul R. Sanberg, Paula C. Bickford, Yuji Kaneko, Cesario V. Borlongan

Psychology Faculty Publications

The long-term consequences of traumatic brain injury (TBI), specifically the detrimental effects of inflammation on the neurogenic niches, are not very well understood. In the present in vivo study, we examined the prolonged pathological outcomes of experimental TBI in different parts of the rat brain with special emphasis on inflammation and neurogenesis. Sixty days after moderate controlled cortical impact injury, adult Sprague-Dawley male rats were euthanized and brain tissues harvested. Antibodies against the activated microglial marker, OX6, the cell cycle-regulating protein marker, Ki67, and the immature neuronal marker, doublecortin, DCX, were used to estimate microglial activation, cell proliferation, and neuronal …


Profile Of Alcohol And Drug Indicators For Hillsborough County, Florida, Kathleen A. Moore, M. Scott Young, Ellen Snelling Jan 2013

Profile Of Alcohol And Drug Indicators For Hillsborough County, Florida, Kathleen A. Moore, M. Scott Young, Ellen Snelling

Mental Health Law & Policy Faculty Publications

Alcohol has the highest prevalence of use of any substance in Hillsborough County and throughout the nation. In 2011, Hillsborough County ranked first among all counties in alcohol-related fatalities. Although Hillsborough County DUI arrests decreased in 2011, Hillsborough still had more DUI arrests than any other Florida county. To address these concerns, the Hillsborough County Anti Drug Alliance (HCADA) and the Tampa Alcohol Coalition (TAC) have continued to support: DUI law enforcement operations, The Hillsborough County Sheriff’s Alcohol Vendor Enforcement program (SAVE), DUI Counterattack, DUI media coverage, alcohol awareness programs, improved alcohol policies and community coalitions’ collaborative efforts to reduce …


Actinidia Drm1 - An Intrinsically Disordered Protein Whose Mrna Expression Is Inversely Correlated With Spring Budbreak In Kiwifruit, Marion Wood, Georgina M. Rae, Rong-Mei Wu, Eric F. Walton, Bin Xue, Roger P. Hellens, Vladimir N. Uversky Jan 2013

Actinidia Drm1 - An Intrinsically Disordered Protein Whose Mrna Expression Is Inversely Correlated With Spring Budbreak In Kiwifruit, Marion Wood, Georgina M. Rae, Rong-Mei Wu, Eric F. Walton, Bin Xue, Roger P. Hellens, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Intrinsically disordered proteins (IDPs) are a relatively recently defined class of proteins which, under native conditions, lack a unique tertiary structure whilst maintaining essential biological functions. Functional classification of IDPs have implicated such proteins as being involved in various physiological processes including transcription and translation regulation, signal transduction and protein modification. Actinidia DRM1 (Ade DORMANCY ASSOCIATED GENE 1), represents a robust dormancy marker whose mRNA transcript expression exhibits a strong inverse correlation with the onset of growth following periods of physiological dormancy. Bioinformatic analyses suggest that DRM1 is plant specific and highly conserved at both the nucleotide and protein …


Ordered Disorder Of The Astrocytic Dystrophin-Associated Protein Complex In The Norm And Pathology, Insung Na, Derek Redmon, Markus Kopa, Yiru Qin, Bin Xue, Vladimir N. Uversky Jan 2013

Ordered Disorder Of The Astrocytic Dystrophin-Associated Protein Complex In The Norm And Pathology, Insung Na, Derek Redmon, Markus Kopa, Yiru Qin, Bin Xue, Vladimir N. Uversky

Molecular Medicine Faculty Publications

The abundance and potential functional roles of intrinsically disordered regions in aquaporin-4, Kir4.1, a dystrophin isoforms Dp71, α-1 syntrophin, and α-dystrobrevin; i.e., proteins constituting the functional core of the astrocytic dystrophin-associated protein complex (DAPC), are analyzed by a wealth of computational tools. The correlation between protein intrinsic disorder, single nucleotide polymorphisms (SNPs) and protein function is also studied together with the peculiarities of structural and functional conservation of these proteins. Our study revealed that the DAPC members are typical hybrid proteins that contain both ordered and intrinsically disordered regions. Both ordered and disordered regions are important for the stabilization of …


The Alphabet Of Intrinsic Disorder: I. Act Like A Pro: On The Abundance And Roles Of Proline Residues In Intrinsically Disordered Proteins, Francois-Xavier Theillet, Lajos Kalmar, Peter Tompa, Kyou-Hoon Han, Philipp Selenko, A. Keith Dunker, Gary W. Daughdrill, Vladimir N. Uversky Jan 2013

The Alphabet Of Intrinsic Disorder: I. Act Like A Pro: On The Abundance And Roles Of Proline Residues In Intrinsically Disordered Proteins, Francois-Xavier Theillet, Lajos Kalmar, Peter Tompa, Kyou-Hoon Han, Philipp Selenko, A. Keith Dunker, Gary W. Daughdrill, Vladimir N. Uversky

Molecular Medicine Faculty Publications

A significant fraction of every proteome is occupied by biologically active proteins that do not form unique three-dimensional structures. These intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) have essential biological functions and are characterized by extensive structural plasticity. Such structural and functional behavior is encoded in the amino acid sequences of IDPs/IDPRs, which are enriched in disorder-promoting residues and depleted in order-promoting residues. In fact, amino acid residues can be arranged according to their disorder-promoting tendency to form an alphabet of intrinsic disorder that defines the structural complexity and diversity of IDPs/IDPRs. This review is the first in a …


What’S In A Name? Why These Proteins Are Intrinsically Disordered, A. Keith Dunker, M. Madan Babu, Elisar Barbar, Martin Blackledge, Sarah E. Bondos, Zsuzsanna Dosztányi, H. Jane Dyson, Julie D. Forman-Kay, Monika Fuxreiter, Joerg Gsponer, Kyou-Hoon Han, David T. Jones, Sonia Longhi, Steven J. Metallo, Ken Nishikawa, Ruth Nussinov, Zoran Obradovic, Rohit V. Pappu, ,Burkhard Rost, Philipp Selenko, Vinod Subramaniam, Joel Sussman, Peter Tompa, Vladimir N. Uversky Jan 2013

What’S In A Name? Why These Proteins Are Intrinsically Disordered, A. Keith Dunker, M. Madan Babu, Elisar Barbar, Martin Blackledge, Sarah E. Bondos, Zsuzsanna Dosztányi, H. Jane Dyson, Julie D. Forman-Kay, Monika Fuxreiter, Joerg Gsponer, Kyou-Hoon Han, David T. Jones, Sonia Longhi, Steven J. Metallo, Ken Nishikawa, Ruth Nussinov, Zoran Obradovic, Rohit V. Pappu, ,Burkhard Rost, Philipp Selenko, Vinod Subramaniam, Joel Sussman, Peter Tompa, Vladimir N. Uversky

Molecular Medicine Faculty Publications

“What’s in a name? That which we call a rose By any other name would smell as sweet.” From “Romeo and Juliet”, William Shakespeare (1594)

This article opens a series of publications on disambiguation of the basic terms used in the field of intrinsically disordered proteins. We start from the beginning, namely from the explanation of what the expression “intrinsically disordered protein” actually means and why this particular term has been chosen as the common denominator for this class of proteins characterized by broad structural, dynamic and functional characteristics.


Modulating The Intrinsic Disorder In The Cytoplasmic Domain Alters The Biological Activity Of The N-Methyl-D-Spartate-Sensitive Glutamate Receptor, Ucheor B. Choi, Rashek Kazi, Natalie Stenzoski, Lonnie P. Wollmuth, Vladimir N. Uversky, Mark E. Bowen Jan 2013

Modulating The Intrinsic Disorder In The Cytoplasmic Domain Alters The Biological Activity Of The N-Methyl-D-Spartate-Sensitive Glutamate Receptor, Ucheor B. Choi, Rashek Kazi, Natalie Stenzoski, Lonnie P. Wollmuth, Vladimir N. Uversky, Mark E. Bowen

Molecular Medicine Faculty Publications

The NMDA-sensitive glutamate receptor is a ligand-gated ion channel that mediates excitatory synaptic transmission in the nervous system. Extracellular zinc allosterically regulates the NMDA receptor by binding to the extracellular N-terminal domain, which inhibits channel gating. Phosphorylation of the intrinsically disordered intracellular C-terminal domain alleviates inhibition by extracellular zinc. The mechanism for this functional effect is largely unknown. Proline is a hallmark of intrinsic disorder, so we used proline mutagenesis to modulate disorder in the cytoplasmic domain. Proline depletion selectively uncoupled zinc inhibition with little effect on receptor biogenesis, surface trafficking, or ligand-activated gating. Proline depletion also reduced the affinity …


Alpha 1-Antichymotrypsin, An Inflammatory Protein Overexpressed In The Brains Of Patients With Alzheimer’S Disease, Induces Tau Hyperphosphorylation Through C-Jun N-Terminal Kinase Activation, Ethika Tyagi, Tina Fiorelli, Michelle Norden, Jaya Padmanabhan Jan 2013

Alpha 1-Antichymotrypsin, An Inflammatory Protein Overexpressed In The Brains Of Patients With Alzheimer’S Disease, Induces Tau Hyperphosphorylation Through C-Jun N-Terminal Kinase Activation, Ethika Tyagi, Tina Fiorelli, Michelle Norden, Jaya Padmanabhan

Molecular Medicine Faculty Publications

The association of inflammatory proteins with neuritic plaques in the brains of Alzheimer’s disease (AD) patients has led to the hypothesis that inflammation plays a pivotal role in the development of pathology in AD. Earlier studies have shown that alpha 1-antichymotrypsin (ACT) enhances amyloid beta fibrillization and accelerated plaque formation in APP transgenic mice. Later studies from our laboratory have shown that purified ACT induces tau hyperphosphorylation and degeneration in neurons. In order to understand the mechanisms by which inflammatory proteins enhance tau hyperphosphorylation, we injected interleukin-1β (IL-1β) intracerebroventricularly into mice expressing human ACT, human tau, or …


Dysregulated Alternative Splicing Pattern Of Pkc During Differentiation Of Human Preadipocytes Represents Distinct Differences Between Lean And Obese Adipocytes, Gay Carter, André Apostolatos, Rekha Patel, Abhishek Mathur, Denise Cooper, Michel Murr, Niketa A. Patel Jan 2013

Dysregulated Alternative Splicing Pattern Of Pkc During Differentiation Of Human Preadipocytes Represents Distinct Differences Between Lean And Obese Adipocytes, Gay Carter, André Apostolatos, Rekha Patel, Abhishek Mathur, Denise Cooper, Michel Murr, Niketa A. Patel

Molecular Medicine Faculty Publications

Obesity and its comorbidities affect millions of people. Here, we demonstrate that human preadipocytes are susceptible to programmed cell death (apoptosis) while mature adipocytes are resistant to apoptosis. The molecular mechanisms underlying the phenotype of apoptosis-resistant adipocytes are lesser known. To study the role of apoptosis and define molecular differences in the developmental process of adipogenesis, human preadipocytes were differentiated in vitro to mature adipocytes. Many genes in the apoptosis pathway are alternatively spliced. Our data demonstrates that during differentiation PKCδ, Bclx, and Caspase9 switch to their prosurvival splice variants along with an increase in Bcl2 expression when …


Persistent Human Herpesvirus-6 Infection In Patients With An Inherited Form Of The Virus, Shara N. Pantry, Maria M. Medveczky, Jesse H. Arbuckle, Janos Luka, Jose G. Montoya, Jianhong Hu, Rolf Renne, Daniel Peterson, Joshua C. Pritchett, Dharam V. Ablashi, Peter G. Medveczky Jan 2013

Persistent Human Herpesvirus-6 Infection In Patients With An Inherited Form Of The Virus, Shara N. Pantry, Maria M. Medveczky, Jesse H. Arbuckle, Janos Luka, Jose G. Montoya, Jianhong Hu, Rolf Renne, Daniel Peterson, Joshua C. Pritchett, Dharam V. Ablashi, Peter G. Medveczky

Molecular Medicine Faculty Publications

Human herpesvirus-6 (HHV-6)A and 6B are ubiquitous betaherpesviruses viruses with lymphotropic and neurotropic potential. As reported earlier, these viruses establish latency by integration into the telomeres of host chromosomes. Chromosomally integrated HHV-6 (CIHHV-6) can be transmitted vertically from parent to child. Some CIHHV-6 patients are suffering from neurological symptoms, while others remain asymptomatic. Four patients with CIHHV-6 and CNS dysfunction were treated with valganciclovir or foscarnet. HHV-6 replication was detected by reverse transcriptase polymerase chain reaction amplification of a late envelope glycoprotein. In this study we also compared the inherited and persistent HHV-6 viruses by DNA sequencing. The prevalence of …


Understanding The Molecular Mechanisms Underlying Complex Cancer Genome Rearrangements, Robert Hedlund, Vladimir N. Uversky Jan 2013

Understanding The Molecular Mechanisms Underlying Complex Cancer Genome Rearrangements, Robert Hedlund, Vladimir N. Uversky

Molecular Medicine Faculty Publications

In their recent paper, Malhotra et al. performed a comprehensive analysis of the structural variation breakpoints in 64 cancer genomes from 7 tumor types to find the prevalence and origins of complex genomic rearrangements.1 Since this work represents a breakthrough in understanding of the molecular mechanisms underlying complex cancer genome rearrangements, we provide a brief overview of this outstanding study.


Interplay Between Estrogen Receptor And Akt In Estradiol-Induced Alternative Splicing, Poornima Bhat-Nakshatri, Eun-Kyung Song, Nikail R. Collins, Vladimir N. Uversky, A. Keith Dunker, Bert W. O'Malley, Tim R. Geistlinger, Jason S. Carroll, Myles Brown, Harikrishna Nakshatri Jan 2013

Interplay Between Estrogen Receptor And Akt In Estradiol-Induced Alternative Splicing, Poornima Bhat-Nakshatri, Eun-Kyung Song, Nikail R. Collins, Vladimir N. Uversky, A. Keith Dunker, Bert W. O'Malley, Tim R. Geistlinger, Jason S. Carroll, Myles Brown, Harikrishna Nakshatri

Molecular Medicine Faculty Publications

Background: Alternative splicing is critical for generating complex proteomes in response to extracellular signals. Nuclear receptors including estrogen receptor alpha (ERα) and their ligands promote alternative splicing. The endogenous targets of ERα:estradiol (E2)-mediated alternative splicing and the influence of extracellular kinases that phosphorylate ERα on E2-induced splicing are unknown.
Methods: MCF-7 and its anti-estrogen derivatives were used for the majority of the assays. CD44 mini gene was used to measure the effect of E2 and AKT on alternative splicing. ExonHit array analysis was performed to identify E2 and AKT-regulated endogenous alternatively spliced apoptosis-related genes. Quantitative reverse transcription polymerase chain reaction …


Plac1 Expression Decreases In Chorionic Villi In Response To Labor, Yahdira M. Rodriguez-Prado, Xiaoyuan Kong, Michael E. Fant Jan 2013

Plac1 Expression Decreases In Chorionic Villi In Response To Labor, Yahdira M. Rodriguez-Prado, Xiaoyuan Kong, Michael E. Fant

Pediatrics Faculty Publications

PLAC1 (Placenta-Specific 1) is a recently described, trophoblast-expressed gene essential for normal placental development. The protein localizes to the microvillus membrane surface of the syncytiotrophoblast in direct proximity to the maternal compartment. Although its role has not been defined, increased circulating levels of human PLAC1 mRNA in maternal blood are associated with preeclampsia. Furthermore, PLAC1-null mice exhibit decreased viability in the peripartum period suggesting a role in pregnancy maintenance late in gestation. We examined PLAC1 gene expression in the human placenta during normal pregnancy and pregnancies associated with maternal diabetes and preeclampsia using quantitative, real time PCR (q-RT-PCR). Although …


Surgical Management Of A Locally Advanced Symptomatic Recurrence Of Penile Sarcoma Secondary To Prostate Brachytherapy, Tariq S. Hakky, Patrick Espiritu, Alejandro R. Rodriguez, Nicholas Gould, Philippe E. Spiess Jan 2013

Surgical Management Of A Locally Advanced Symptomatic Recurrence Of Penile Sarcoma Secondary To Prostate Brachytherapy, Tariq S. Hakky, Patrick Espiritu, Alejandro R. Rodriguez, Nicholas Gould, Philippe E. Spiess

Urology Faculty Publications

Background: The surgical management of patients with symptomatic metastatic or locally advanced recurrences involving the penis remains poorly characterized. The aim of the present abstract and video is to detail our experience in the surgical management of a specific patient with a locally advanced symptomatic recurrence of penile sarcoma secondary to prostate cancer treated with primary brachytherapy.

Materials and Methods: A 70 year old male patient initially treated for localized prostate cancer with interstitial brachytherapy at an outside facility developed an unfortunate secondary malignancy consisting of a locally advanced penile sarcoma involving as well the prostate and base of the …


Hippocampal Neurogenesis And The Brain Repair Response To Brief Stereotaxic Insertion Of A Microneedle, Shijie Song, Shuojing Song, Chuanhai Cao, Xiaoyang Lin, Kunyu Li, Vasyl Sava, Juan Sanchez-Ramos Jan 2013

Hippocampal Neurogenesis And The Brain Repair Response To Brief Stereotaxic Insertion Of A Microneedle, Shijie Song, Shuojing Song, Chuanhai Cao, Xiaoyang Lin, Kunyu Li, Vasyl Sava, Juan Sanchez-Ramos

Neurology Faculty Publications

We tested the hypothesis that transient microinjury to the brain elicits cellular and humoral responses that stimulate hippocampal neurogenesis. Brief stereotaxic insertion and removal of a microneedle into the right hippocampus resulted in (a) significantly increased expression of granulocyte-colony stimulating factor (G-CSF), the chemokine MIP-1a, and the proinflammatory cytokine IL12p40; (b) pronounced activation of microglia and astrocytes; and (c) increase in hippocampal neurogenesis. This study describes immediate and early humoral and cellular mechanisms of the brain’s response to microinjury that will be useful for the investigation of potential neuroprotective and deleterious effects of deep brain stimulation in various neuropsychiatric disorders.


Lateral Access Surgery For The Thoracolumbar Spine, Luiz Pimenta, William Smith, William Taylor, Juan Uribe Jan 2013

Lateral Access Surgery For The Thoracolumbar Spine, Luiz Pimenta, William Smith, William Taylor, Juan Uribe

Neurosurgery and Brain Repair Faculty Publications

No abstract provided.


Neuromyelitis Optica In Child: Diagnostic And Therapeutic Challenges, Karolina Dembinski, Maria Gieron-Korthals, Carlos R. Martinez, Lisa Rodriguez Jan 2013

Neuromyelitis Optica In Child: Diagnostic And Therapeutic Challenges, Karolina Dembinski, Maria Gieron-Korthals, Carlos R. Martinez, Lisa Rodriguez

Pediatrics Faculty Publications

Neuromyelitis optica (NMO) is a rare syndrome of severe inflammatory demyelination of the central nervous system, causing attacks of optic neuritis and transverse myelitis. Although uncommon, attention should be given to the proper identification and management of the affected patients. We present a case of a 13-year-old girl with severe neuromyelitis optica. The patient’s initial presentation consisted of encephalopathy and optic neuritis. Approximately 2 months later, coinciding with the weaning of steroid treatment, she presented with ascending paralysis and respiratory failure. She was seropositive for NMO-IgG. Treatment included intravenous immune globulin, steroids, plasmapheresis, and rituximab and was complemented with proper …


Complex Cytogenetic Rearrangements At The Durs1 Locus In Syndromic Duane Retraction Syndrome, Hagit N. Baris, Wai-Man Chan, Caroline Andrews, Doron M. Behar, Diana J. Donovan, Cynthia C. Morton, Judith Ranells, Tuya Pal, Azra H. Ligon, Elizabeth C. Engle Jan 2013

Complex Cytogenetic Rearrangements At The Durs1 Locus In Syndromic Duane Retraction Syndrome, Hagit N. Baris, Wai-Man Chan, Caroline Andrews, Doron M. Behar, Diana J. Donovan, Cynthia C. Morton, Judith Ranells, Tuya Pal, Azra H. Ligon, Elizabeth C. Engle

Pediatrics Faculty Publications

No abstract provided.


Fishing-Injury-Related Flexor Tenosynovitis Of The Hand: A Case Report And Review, Danny A. Young-Afat, Deniz Dayicioglu, John C. Oeltjen, Audene P. Garrison Jan 2013

Fishing-Injury-Related Flexor Tenosynovitis Of The Hand: A Case Report And Review, Danny A. Young-Afat, Deniz Dayicioglu, John C. Oeltjen, Audene P. Garrison

Surgery Faculty Publications

Hand infections occurring after fishing and other marine-related activities may involve uncommon bacteria that are not susceptible to the conventional or empiric antibiotic therapy used to treat soft tissue infections. Therefore appropriate treatment is often delayed and could lead to severe hand damage. An illustrative case of fishing-related injury leading to complicated tenosynovitis and horseshoe abscess caused by Mycobacterium marinum and its treatment course is outlined. Laceration of the skin during boating is fairly common. Because of the rarity of some of the bacteria, referrals to the appropriate specialist including hand surgeons and infectious disease specialists should occur in early …


Open Tracheostomy After Aborted Percutaneous Approach Due To Tracheoscopy Revealing Occult Tracheal Wall Ulcer, John Schweiger, Collin Sprenker, Devanand Mangar, Rachel Karlnoski, Naga Pullakhandam, Enrico M. Camporesi Jan 2013

Open Tracheostomy After Aborted Percutaneous Approach Due To Tracheoscopy Revealing Occult Tracheal Wall Ulcer, John Schweiger, Collin Sprenker, Devanand Mangar, Rachel Karlnoski, Naga Pullakhandam, Enrico M. Camporesi

Surgery Faculty Publications

Tracheostomy is a common procedure for intensive care patients requiring prolonged mechanical ventilation. In this case report, we describe a 78-year-old female patient admitted for an aneurysm of the cerebral anterior communicating artery. Following immediate endovascular coiling, she remained ventilated and was transferred to the neurological intensive care unit. On postoperative day ten, a percutaneous tracheostomy (PCT) was requested; however, a large ulcer or possible tracheoesophageal fistula was identified on the posterior tracheal wall following bronchoscopic assessment of the trachea. Therefore, the requested PCT procedure was aborted. An open tracheostomy in the operating room was completed; however, due to the …


The Role Of Lumbar Puncture And Pressure.Lowering Therapy For Transverse Dural Sinus Thrombosis, Joshua Grant, Andrew Carey, Curtis Margo, Murtagh Reed, Mitchell Drucker Jan 2013

The Role Of Lumbar Puncture And Pressure.Lowering Therapy For Transverse Dural Sinus Thrombosis, Joshua Grant, Andrew Carey, Curtis Margo, Murtagh Reed, Mitchell Drucker

Ophthalmology Faculty Publications

Transverse (lateral) sinus thrombosis is a well-known complication of acute otitis media and mastoiditis in the pediatric and adult population. Thrombosis involving the transverse sinus can ultimately cause elevation of intracranial pressure (ICP) as a result of decreased cerebrospinal fluid absorption. If treatment to lower ICP is not undertaken, it can lead to ophthalmological complications including irreversible vision loss. The following case report describes an 11-year-old girl who was diagnosed with AOM by her pediatrician and subsequently presented to the emergency department complaining of nausea, vomiting, headache, and diplopia.


The Ube2e Proteins As Conjugating Dispersers: Extending Function With Extended Extensions, Vladimir N. Uversky Jan 2013

The Ube2e Proteins As Conjugating Dispersers: Extending Function With Extended Extensions, Vladimir N. Uversky

Molecular Medicine Faculty Publications

No abstract provided.


Malleable Ribonucleoprotein Machine: Protein Intrinsic Disorder In The Saccharomyces Cerevisiae Spliceosome, Maria De Lourdes Coelho Ribeiro, Julio Espinosa, Sameen Islam, Osvaldo Martinez, Jayesh Jamnadas Thanki, Stephanie Mazariegos, Tam Nguyen, Maya Larina, Bin Xue, Vladimir N. Uversky Jan 2013

Malleable Ribonucleoprotein Machine: Protein Intrinsic Disorder In The Saccharomyces Cerevisiae Spliceosome, Maria De Lourdes Coelho Ribeiro, Julio Espinosa, Sameen Islam, Osvaldo Martinez, Jayesh Jamnadas Thanki, Stephanie Mazariegos, Tam Nguyen, Maya Larina, Bin Xue, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Recent studies revealed that a significant fraction of any given proteome is presented by proteins that do not have unique 3D structures as a whole or in significant parts. These intrinsically disordered proteins possess dramatic structural and functional variability, being especially enriched in signaling and regulatory functions since their lack of fixed structure defines their ability to be involved in interaction with several proteins and allows them to be re-used in multiple pathways. Among recognized disorder-based protein functions are interactions with nucleic acids and multi-target binding; i.e., the functions ascribed to many spliceosomal proteins. Therefore, the spliceosome, a multimegadalton ribonucleoprotein …


Structural Characterizations Of Phosphorylatable Residues In Transmembrane Proteins From Arabidopsis Thaliana, Bin Xue, Vladimir N. Uversky Jan 2013

Structural Characterizations Of Phosphorylatable Residues In Transmembrane Proteins From Arabidopsis Thaliana, Bin Xue, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Phosphorylation is a common post-translational modification that plays important roles in a wide range of biochemical and cellular processes. Many enzymes and receptors can be switched “on” or “off” by conformational changes induced by phosphorylation. The phosphorylation process is mediated by a family of enzymes called kinase. Currently, more than 1,000 different kinases have been identified in Arabidopsis thaliana proteome. Kinases interact with each other and with many regulatory proteins forming phosphorylation networks. These phosphorylation networks modulate the signaling processes and control the functions of cells. Normally, kinases phosphorylate serines, threonines, and tyrosines. However, in many proteins, not all of …


Distribution And Cluster Analysis Of Predicted Intrinsically Disordered Protein Pfam Domains, Robert W. Williams, Bin Xue, Vladimir N. Uversky, A. Keith Dunker Jan 2013

Distribution And Cluster Analysis Of Predicted Intrinsically Disordered Protein Pfam Domains, Robert W. Williams, Bin Xue, Vladimir N. Uversky, A. Keith Dunker

Molecular Medicine Faculty Publications

The Pfam database groups regions of proteins by how well hidden Markov models (HMMs) can be trained to recognize similarities among them. Conservation pressure is probably in play here. The Pfam seed training set includes sequence and structure information, being drawn largely from the PDB. A long standing hypothesis among intrinsically disordered protein (IDP) investigators has held that conservation pressures are also at play in the evolution of different kinds of intrinsic disorder, but we find that predicted intrinsic disorder (PID) is not always conserved across Pfam domains. Here we analyze distributions and clusters of PID regions in 193024 members …


Intrinsic Disorder In Pten And Its Interactome Confers Structural Plasticity And Functional Versatility, Prerna Malaney, Ravi Ramesh Pathak, Bin Xue, Vladimir N. Uversky, Vrushank Davé Jan 2013

Intrinsic Disorder In Pten And Its Interactome Confers Structural Plasticity And Functional Versatility, Prerna Malaney, Ravi Ramesh Pathak, Bin Xue, Vladimir N. Uversky, Vrushank Davé

Molecular Medicine Faculty Publications

IDPs, while structurally poor, are functionally rich by virtue of their flexibility and modularity. However, how mutations in IDPs elicit diseases, remain elusive. Herein, we have identified tumor suppressor PTEN as an intrinsically disordered protein (IDP) and elucidated the molecular principles by which its intrinsically disordered region (IDR) at the carboxyl-terminus (C-tail) executes its functions. Post-translational modifications, conserved eukaryotic linear motifs and molecular recognition features present in the C-tail IDR enhance PTEN's protein-protein interactions that are required for its myriad cellular functions. PTEN primary and secondary interactomes are also enriched in IDPs, most being cancer related, revealing that PTEN functions …


D2P2: Database Of Disordered Protein Predictions, Matt E. Oates, Pedro R. Romero, Takashi Ishida, Mohamed Ghalwash, Marcin J. Mizianty, Bin Xue, Zsuzsanna Dosztányi, Vladimir N. Uversky, Zoran Obradovic, Lukasz Kurgan, A. Keith Dunker, Julian Gough Jan 2013

D2P2: Database Of Disordered Protein Predictions, Matt E. Oates, Pedro R. Romero, Takashi Ishida, Mohamed Ghalwash, Marcin J. Mizianty, Bin Xue, Zsuzsanna Dosztányi, Vladimir N. Uversky, Zoran Obradovic, Lukasz Kurgan, A. Keith Dunker, Julian Gough

Molecular Medicine Faculty Publications

We present the Database of Disordered Protein Prediction (D2P2), available at http://d2p2.pro (including website source code). A battery of disorder predictors and their variants, VL-XT, VSL2b, PrDOS, PV2, Espritz and IUPred, were run on all protein sequences from 1765 complete proteomes (to be updated as more genomes are completed). Integrated with these results are all of the predicted (mostly structured) SCOP domains using the SUPERFAMILY predictor. These disorder/structure annotations together enable comparison of the disorder predictors with each other and examination of the overlap between disordered predictions and SCOP domains on a large scale. D2P2 will increase our understanding of …


Extracting Structural Information From Charge-State Distributions Of Intrinsically Disordered Proteins By Non-Denaturing Electrospray-Ionization Mass Spectrometry, Lorenzo Testa, Stefania Brocca, Carlo Santambrogio, Annalisa D'Urzo, Johnny Habchi, Sonia Longhi, Vladimir N. Uversky, Rita Grandori Jan 2013

Extracting Structural Information From Charge-State Distributions Of Intrinsically Disordered Proteins By Non-Denaturing Electrospray-Ionization Mass Spectrometry, Lorenzo Testa, Stefania Brocca, Carlo Santambrogio, Annalisa D'Urzo, Johnny Habchi, Sonia Longhi, Vladimir N. Uversky, Rita Grandori

Molecular Medicine Faculty Publications

Intrinsically disordered proteins (IDPs) exert key biological functions but tend to escape identification and characterization due to their high structural dynamics and heterogeneity. The possibility to dissect conformational ensembles by electrospray-ionization mass spectrometry (ESI-MS) offers an attracting possibility to develop a signature for this class of proteins based on their peculiar ionization behavior. This review summarizes available data on charge-state distributions (CSDs) obtained for IDPs by non-denaturing ESI-MS, with reference to globular or chemically denatured proteins. The results illustrate the contributions that direct ESI-MS analysis can give to the identification of new putative IDPs and to their conformational investigation.


Looking At Microbial Metabolism By High-Resolution (2)H-Nmr Spectroscopy, Victor P. Kutyshenko, Peter M. Beskaravayny, Maxim V. Molchanov, Svetlana I. Paskevich, Dmitry A. Prokhorov, Vladimir N. Uversky Jan 2013

Looking At Microbial Metabolism By High-Resolution (2)H-Nmr Spectroscopy, Victor P. Kutyshenko, Peter M. Beskaravayny, Maxim V. Molchanov, Svetlana I. Paskevich, Dmitry A. Prokhorov, Vladimir N. Uversky

Molecular Medicine Faculty Publications

We analyzed the applicability of high-resolution (2)H-HMR spectroscopy for the analysis of microbe metabolism in samples of mitochondrion isolated from rat liver and from aqueous extracts of homogenates of rat liver and other organs and tissues in the presence of high D2O contents. Such analysis is possible due to the fast microbe adaptation to life in the heavy water. It is also shown that some enzymatic processes typical for the intact cells are preserved in the homogenized tissue preparations. The microbial and cellular metabolic processes can be differentiated via the strategic use of cell poisons and antibiotics.