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2019

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Culpability And Social Commentary In Titus Andronicus And King Lear, Jay S. Looney Jan 2019

Culpability And Social Commentary In Titus Andronicus And King Lear, Jay S. Looney

USF St. Petersburg campus Master's Theses (Graduate)

In Shakespeare’s Titus Andronicus and King Lear, notions of identity, power, violence, madness, disability, transformation, and problematic masculinity are used to complicate culpability and comment on the societies within these plays and on Shakespeare’s own society. In both plays, the main characters’ identities ultimately break down as they attempt to rigidly conform to irreconcilably conflicting values. Additionally, the stage villains in both plays provide interesting insights into culpability and social commentary. I explore these themes individually in each play, and I also explore and argue for the connections between these themes in both plays. I argue that the social …


A Comparative Behavioral Analysis Of Time Budgets Of Sea Turtles At The Florida Aquarium Through The Application Of An Ethogram, Kate Rae Lowry Jan 2019

A Comparative Behavioral Analysis Of Time Budgets Of Sea Turtles At The Florida Aquarium Through The Application Of An Ethogram, Kate Rae Lowry

USF St. Petersburg campus Master's Theses (Graduate)

Sea turtles are a crucial component of many coastline habitats due to their roles as ecosystem engineers and their ability to raise awareness for conservation efforts. Despite the extensive amount of research conducted on nesting behaviors of wild sea turtles, there are few behavioral studies of turtles in managed care. Sea turtles were observed at The Florida Aquarium from February 2018 to May 2019 to examine possible variations among behavior for five Loggerhead (Caretta caretta), Green (Chelonia mydas), and Kemp’s Ridley turtles (Lepidochelys kempii). The first part of this study includes a baseline time budget for the five turtles using …


Pah Exposure In Red Snapper (Lutjanus Campechanus) Collected At Natural And Artificial Reef Systems In The Northwestern Gulf Of Mexico, Tiffany Jane Nicholson Jan 2019

Pah Exposure In Red Snapper (Lutjanus Campechanus) Collected At Natural And Artificial Reef Systems In The Northwestern Gulf Of Mexico, Tiffany Jane Nicholson

USF St. Petersburg campus Master's Theses (Graduate)

Red Snapper are commonly recognized as an important fishery across the bordering states of the Gulf of Mexico (GoM) and are found in abundance around oil and gas platforms. A small, yet toxic and environmentally persistent component, of crude oil known as polycyclic aromatic hydrocarbons (PAHs), are released into Gulf waters through both anthropogenic (e.g., oil and gas activities) and natural (e.g., hydrocarbon seeps) sources. These pollutants are associated with a variety of negative health effects in fish including cardio-toxicity, reproductive and developmental impairment, and external skin lesions. The objectives of this study were to measure and to compare PAH …


Connections Between Female Sexuality And Hell: Misogyny In Shakespeare’S Sonnets, Jordan Kohn-Foley Jan 2019

Connections Between Female Sexuality And Hell: Misogyny In Shakespeare’S Sonnets, Jordan Kohn-Foley

USF St. Petersburg campus Master's Theses (Graduate)

This paper explores the primary way misogyny is exhibited in Shakespeare’s Sonnets and finds that it is through a connection between the female body and sexuality with Hell. The link between the two continues a long-standing literary tradition which includes medieval Catholicism, and is also expressed by writers including Petrarch, Chaucer, and Boccaccio. Shakespeare continues this tradition in the Sonnets, and it becomes the primary way that women are presented in a misogynistic manner within them. This conflation of female genitalia with Hell furthers early modern anxieties regarding the control of women’s bodies, as well as the expression of lust …


A Survey And Comparison Of Plant Communities In Crescent Lake Park, An Urban Lake In St. Petersburg, Florida, Hunter Hajaistron Jan 2019

A Survey And Comparison Of Plant Communities In Crescent Lake Park, An Urban Lake In St. Petersburg, Florida, Hunter Hajaistron

USF St. Petersburg campus Master's Theses (Graduate)

In Florida, urban lakes are challenged. Pollution from surrounding urban ecosystems is detrimental to the ecological health of these lakes. Planting and restoring native wetlands along the littoral zone of these lakes will reduce the effects of pollution. Crescent Lake is an urban lake in Pinellas County, Florida, USA, that has recently begun to restore its wetlands system. This study surveys and evaluates the plant species in the wetland, shoreline, and parkland habitats of Crescent Lake to determine the effectiveness of management. Transects and quadrats were used to determine the diversity and structure of native and non-native plant species. 58 …


Becoming Lincoln: His Changing Legacy From Savior Of The Union To The Great Emancipator, 1865 - 1965, Nicki Hannum Jan 2019

Becoming Lincoln: His Changing Legacy From Savior Of The Union To The Great Emancipator, 1865 - 1965, Nicki Hannum

USF St. Petersburg campus Master's Theses (Graduate)

The aim of this project is to demonstrate the relationship between scholarly treatments of Abraham Lincoln since his death and popular conceptions of the man and his legacy in the United States. Lincoln is an integral figure in American identity and central to collective national narratives of exceptionalism and racial progress. As such, Lincoln manifests in scholarly discourse and popular American culture with regularity. For this thesis, I analyzed the connections between academic and popular representations of Lincoln, illustrating the evolution of his legacy in American memory. I drew upon academic journal articles and long-form publications for an understanding of …


Efficient Identification Of Function: A Comparison Of Different Implementers During Functional Analyses, Katelyn E. Nicklow Jan 2019

Efficient Identification Of Function: A Comparison Of Different Implementers During Functional Analyses, Katelyn E. Nicklow

Theses and Dissertations--Early Childhood, Special Education, and Counselor Education

Functional analyses (FAs) are a common tool used in the assessment and treatment of severe problem behaviors and often occur in the context of clinical settings with unfamiliar, trained staff. Previous research suggests that inconsistent outcomes can emerge when caregivers with an existing history of seeing their child’s challenging behavior are trained to implement the assessment in place of clinical staff. The purpose of the current study was to expand on existing literature by comparing FA implemented by clinical staff and caregivers in the context of a clinical setting. Results demonstrate that efficient identification of function and differentiated rates of …


Full Issue Jan 2019

Full Issue

Swiss American Historical Society Review

No abstract provided.


At The Intersection Of Health And Justice: How The Health Of American Indians And Alaska Natives Is Disproportionately Affected By Disparities In The Criminal Justice System, Bette Jacobs, Mehgan Gallagher, Nicole Heydt Jan 2019

At The Intersection Of Health And Justice: How The Health Of American Indians And Alaska Natives Is Disproportionately Affected By Disparities In The Criminal Justice System, Bette Jacobs, Mehgan Gallagher, Nicole Heydt

Belmont Law Review

American Indian and Alaska Natives (AI/AN) are a neglected population in the United States. Their health and welfare needs are often swept aside and, because of historical treaty agreements with the United States government, they suffer disparities in the justice system and, consequently, poor health. A deep look into everyday life for an AI/AN tells a story of poverty and relatively low life expectancy, proportionately high incidences of disease, high rates of incarceration, and prolific alcohol and substance abuse. AI/ANs are incarcerated at a higher rate proportionately than their white counterparts. They experience harsher sentences, due in part to jurisdictional …


Psychological Factors Related To Resilience And Vulnerability Among Youth With Hiv In An Integrated Care Setting., Tiffany Chenneville, Kemesha Gabbidon, Courtney Lynn, Carina Rodriguez Jan 2019

Psychological Factors Related To Resilience And Vulnerability Among Youth With Hiv In An Integrated Care Setting., Tiffany Chenneville, Kemesha Gabbidon, Courtney Lynn, Carina Rodriguez

USF St. Petersburg Campus Faculty Publications

Approximately 22% of HIV diagnoses in 2015 occurred among youth aged 13–24. Much is known about the risk factors and psychopathology present in youth living with HIV (YLWH), however, relatively little is known about resiliency in this population. The current study sought to assess factors related to resilience and vulnerability among YLWH as well as the impact of psychosocial factors on these constructs using existing clinical data from an integrated care clinic serving YLWH in the southeastern United States. Data included findings from mental health screeners administered as part of the standard protocol of care for youth aged 13–24 including …


Exploring Data Literacy Via A Librarian-Faculty Learning Community: A Case Study, Theresa G. Burress, Emily Z. Mann, Tina Neville Jan 2019

Exploring Data Literacy Via A Librarian-Faculty Learning Community: A Case Study, Theresa G. Burress, Emily Z. Mann, Tina Neville

USF St. Petersburg Campus Faculty Publications

Faculty learning communities (FLCs) are year-long professional development opportunities available at many higher education institutions in the United States. While the literature reflects some librarian engagement with FLCs, it seems limited primarily to areas of traditional librarian expertise such as information literacy and outreach. This article describes a case study of a librarian-facilitated FLC focused on data literacy, which resulted in the development of a teaching toolkit, library-led data literacy instruction, and ongoing collaborations between librarians and faculty. The FLC structure proved to be a valuable framework that facilitated collaborative learning in topics relevant to both disciplinary faculty and librarians. …


Novel Habitat Causes A Shift To Diurnal Activity In A Nocturnal Species, J. Sean Doody, Colin R. Mchenry, David Rhind, Simon Clulow Jan 2019

Novel Habitat Causes A Shift To Diurnal Activity In A Nocturnal Species, J. Sean Doody, Colin R. Mchenry, David Rhind, Simon Clulow

USF St. Petersburg Campus Faculty Publications

Plastic responses may allow individuals to survive and reproduce in novel environments, and can facilitate the establishment of viable populations. But can novel environments reveal plasticity by causing a shift in a behavior as fundamental and conspicuous as daily activity? We studied daily activity times near the invasion front of the cane toad (Rhinella marina), an invasive species that has colonized much of northern Australia. Cane toads in Australia are nocturnal, probably because diurnal activity would subject them to intolerably hot and dry conditions in the tropical savannah during the dry season. Our study can demonstrate, however, that upon reaching …


Lipophagy And Alcohol-Induced Fatty Liver, Li Yang, Changqing Yang, Paul G. Thomes, Kusum K. Kharbanda, Carol A. Casey, Mark A. Mcniven, Terrence M. Donohue Jan 2019

Lipophagy And Alcohol-Induced Fatty Liver, Li Yang, Changqing Yang, Paul G. Thomes, Kusum K. Kharbanda, Carol A. Casey, Mark A. Mcniven, Terrence M. Donohue

Journal Articles: Internal Medicine

This review describes the influence of ethanol consumption on hepatic lipophagy, a selective form of autophagy during which fat-storing organelles known as lipid droplets (LDs) are degraded in lysosomes. During classical autophagy, also known as macroautophagy, all forms of macromolecules and organelles are sequestered in autophagosomes, which, with their cargo, fuse with lysosomes, forming autolysosomes in which the cargo is degraded. It is well established that excessive drinking accelerates intrahepatic lipid biosynthesis, enhances uptake of fatty acids by the liver from the plasma and impairs hepatic secretion of lipoproteins. All the latter contribute to alcohol-induced fatty liver (steatosis). Here, our …


Stress Response And Performance Changes Of Law Enforcement Officers’ Marksmanship Under Varied Levels Of Stress, Brandon Michael Male Jan 2019

Stress Response And Performance Changes Of Law Enforcement Officers’ Marksmanship Under Varied Levels Of Stress, Brandon Michael Male

Graduate Research Theses & Dissertations

Objective: To investigate changes in physiological stress response and shooting performance of law enforcement officers under varying levels of stress. More specifically, the purpose of this study was to determine how increasing levels of stress from operating a firearm on static targets changes when law enforcement officers are subjected to a simulated life-threatening or dangerous situation.

Background: Performance changes associated with high levels of stress have been well documented in disciplines such as sports psychology, medicine, and military/law enforcement fields. However, little work has been done to draw comparisons between firearm training methods and qualification procedures which closely mimic armed …


Usft Services Assessment Dss Annual Report 2018-2019fy, Usf Libraries Jan 2019

Usft Services Assessment Dss Annual Report 2018-2019fy, Usf Libraries

All Assessment Data

No abstract provided.


Johnny Appleseed: Citizenship Transmission Laws And A White Heteropatriarchal Property Right In Philandering, Sexual Exploitation, And Rape (The Whp) Or Johnny And The Whp, Blanche Cook Jan 2019

Johnny Appleseed: Citizenship Transmission Laws And A White Heteropatriarchal Property Right In Philandering, Sexual Exploitation, And Rape (The Whp) Or Johnny And The Whp, Blanche Cook

Law Faculty Scholarly Articles

Title 8, United States Code, Section 1409-one of this country's

citizenship transmission laws-creates a white heteropatriarchal property right

in philandering, sexual exploitation, and rape (the "WHP"). Section 1409

governs the transmission of citizenship from United States citizens to their

children, where the child is born abroad, outside of marriage, and one parent is a

citizen and the other is not. Section 1409, however, draws a distinct gender

distinction between women and men: An unwed female American citizen who

births a child outside the United States, fathered by a foreign man, automatically

transmits citizenship to her child. An unwed male American …


Silent Takeover! Invasive Plants In Florida, Katherine Harris, Linda Walters, Samantha Yuan Jan 2019

Silent Takeover! Invasive Plants In Florida, Katherine Harris, Linda Walters, Samantha Yuan

CEELAB Children's Books

Native plants in Florida create the beautiful, wild world around us. But they are in danger! Hundreds of invasive plant species are silently taking over Florida's natural environment. These unwelcome plants grow aggressively and can overgrow native plants and animals in many different habitats. Invasive plants are so widespread that there may even be some growing in your backyard. Look inside to learn about Florida's invasive plant problem. Find out about some of the most harmful invasive plants, the problems they cause to natural ecosystems, and how you can help to manage invasive plants to help keep Florida native and …


Carbon Cycling In The North American Coastal Ocean: A Synthesis, Katja Fennel, Simone Alin, Leticia Barbero, Wiley Evans, Timothée Bourgeois, Sarah Cooley, Frank E. Muller-Karger, Lisa Robbins Jan 2019

Carbon Cycling In The North American Coastal Ocean: A Synthesis, Katja Fennel, Simone Alin, Leticia Barbero, Wiley Evans, Timothée Bourgeois, Sarah Cooley, Frank E. Muller-Karger, Lisa Robbins

Marine Science Faculty Publications

A quantification of carbon fluxes in the coastal ocean and across its boundaries with the atmosphere, land, and the open ocean is important for assessing the current state and projecting future trends in ocean carbon uptake and coastal ocean acidification, but this is currently a missing component of global carbon budgeting. This synthesis reviews recent progress in characterizing these carbon fluxes for the North American coastal ocean. Several observing networks and high-resolution regional models are now available. Recent efforts have focused primarily on quantifying the net air–sea exchange of carbon dioxide (CO2). Some studies have estimated other key …


Minimum Information About An Uncultivated Virus Genome (Miuvig), Simon Roux, Evelien Adriaenssens, Bas Dutilh, Eugene Koonin, Andrew Kropinski, Mart Krupovic, Mya Breitbart, Karyna Rosario Jan 2019

Minimum Information About An Uncultivated Virus Genome (Miuvig), Simon Roux, Evelien Adriaenssens, Bas Dutilh, Eugene Koonin, Andrew Kropinski, Mart Krupovic, Mya Breitbart, Karyna Rosario

Marine Science Faculty Publications

We present an extension of the Minimum Information about any (x) Sequence (MIxS) standard for reporting sequences of uncultivated virus genomes. Minimum Information about an Uncultivated Virus Genome (MIUViG) standards were developed within the Genomic Standards Consortium framework and include virus origin, genome quality, genome annotation, taxonomic classification, biogeographic distribution and in silico host prediction. Community-wide adoption of MIUViG standards, which complement the Minimum Information about a Single Amplified Genome (MISAG) and Metagenome-Assembled Genome (MIMAG) standards for uncultivated bacteria and archaea, will improve the reporting of uncultivated virus genomes in public databases. In turn, this should enable more robust comparative …


Pepper Mild Mottle Virus: Agricultural Menace Turned Effective Tool For Microbial Water Quality Monitoring And Assessing (Waste)Water Treatment Technologies, Erin Symonds, Karyna Rosario, Mya Breitbart Jan 2019

Pepper Mild Mottle Virus: Agricultural Menace Turned Effective Tool For Microbial Water Quality Monitoring And Assessing (Waste)Water Treatment Technologies, Erin Symonds, Karyna Rosario, Mya Breitbart

Marine Science Faculty Publications

No abstract provided.


Mississippi River And Campeche Bank (Gulf Of Mexico) Episodes Of Cross-Shelf Export Of Coastal Waters Observed With Satellites, Daniel Otis, Matthieu Le Hénaff, Vassiliki H. Kourafalou, Lucas Mceachron, Frank Muller-Karger Jan 2019

Mississippi River And Campeche Bank (Gulf Of Mexico) Episodes Of Cross-Shelf Export Of Coastal Waters Observed With Satellites, Daniel Otis, Matthieu Le Hénaff, Vassiliki H. Kourafalou, Lucas Mceachron, Frank Muller-Karger

Marine Science Faculty Publications

The cross-shelf advection of coastal waters into the deep Gulf of Mexico is important for the transport of nutrients or potential pollutants. Twenty years of ocean color satellite imagery document such cross-shelf transport events via three export pathways in the Gulf of Mexico: from the Campeche Bank toward the central Gulf, from the Campeche Bank toward the Florida Straits, and from the Mississippi Delta to the Florida Straits. A catalog of these events was created based on the visual examination of 7280 daily satellite images. Water transport from the Campeche Bank to the central Gulf occurred frequently and with no …


Developing High Resolution Baseline Coast Resource Maps Using World View 2 Imagery For A Coastal Village In Fiji, Ashneel Ajay Singh, Anish Maharaj, Michelle Kumar, Priyatma Singh, Sanjay Singh, Frank Muller-Karger, Matthew James Mccarthy, Lionel Joseph, Herve Damlamian, Zulfikar Begg Jan 2019

Developing High Resolution Baseline Coast Resource Maps Using World View 2 Imagery For A Coastal Village In Fiji, Ashneel Ajay Singh, Anish Maharaj, Michelle Kumar, Priyatma Singh, Sanjay Singh, Frank Muller-Karger, Matthew James Mccarthy, Lionel Joseph, Herve Damlamian, Zulfikar Begg

Marine Science Faculty Publications

In Fiji, like most Pacific Island countries, there have been numerous reports of degradation of coastal resources, including adverse changes in abundance and stock distribution of numerous aquatic species associated with the coastal habitat. To develop effective management plans, assessment of existing coastal resources is pertinent. High spatial resolution satellite imagery, combined with geographic information systems allow for efficient and synoptic mapping of coastal resources to provide a baseline for developing effective and improved management plans. The purpose of this study was to develop a baseline habitat map of the intertidal benthic cover in Komave Village, Coral Coast, Sigatoka, Fiji. …


Bioinformatics Haracterisation Of The (Mutated) Proteins Related To Andersen–Tawil Syndrome, Carlos Polanco, Vladimir N. Uversky, Manlio F. Márquez, Thomas Buhse, Miguel Arias Estrada, Alberto Huberman Jan 2019

Bioinformatics Haracterisation Of The (Mutated) Proteins Related To Andersen–Tawil Syndrome, Carlos Polanco, Vladimir N. Uversky, Manlio F. Márquez, Thomas Buhse, Miguel Arias Estrada, Alberto Huberman

Molecular Medicine Faculty Publications

In the last two decades, a group of proteins whose mutations are associated with a disease manifested by episodes of muscle weakness (periodic paralysis), changes in heart rhythm (arrhythmia), and developmental abnormalities has been under constant study. This malady is known as Andersen–Tawil syndrome, with ~60% of cases of this syndrome being caused by 16 mutations in the KCNJ2 gene [UniProt ID: P63252-01—P63252-17]. In this work, we present a computational study designed to obtain a fingerprint of Andersen–Tawil mutated proteins and differentiate them from mutated proteins associated with Brugada syndrome and from functional groups of proteins belonging to APD3, UniProt, …


On The Need To Develop Guidelines For Characterizing And Reporting Intrinsic Disorder In Proteins, Michael Vincent, Vladimir N. Uversky, Santiago Schnell Jan 2019

On The Need To Develop Guidelines For Characterizing And Reporting Intrinsic Disorder In Proteins, Michael Vincent, Vladimir N. Uversky, Santiago Schnell

Molecular Medicine Faculty Publications

Since the early 2000s, numerous computational tools have been created and used to predict intrinsic disorder in proteins. At present, the output from these algorithms is difficult to interpret in the absence of standards or references for comparison. There are many reasons to establish a set of standard-based guidelines to evaluate computational protein disorder predictions. This viewpoint explores a handful of these reasons, including standardizing nomenclature to improve communication, rigor and reproducibility, and making it easier for newcomers to enter the field. An approach for reporting predicted disorder in single proteins with respect to whole proteomes is discussed. The suggestions …


Cyclized Ndga Modifies Dynamic Α-Synuclein Monomers Preventing Aggregation And Toxicity, Malcolm J. Daniels, J. Brucker Nourse, Hanna Kim, Valerio Sainati, Marco Schiavina, Maria Grazia Murrali, Buyan Pan, John J. Ferrie, Conor M. Haney, Rani Moons, Neal S. Gould, Antonino Natalello, Rita Grandori, Frank Sobott, E. James Petersson, Elizabeth Rhoades, Roberta Pierattelli, Isabella Felli, Vladimir N. Uversky, Kim A. Caldwell, Guy A. Caldwell, Edward S. Krol, Harry Ischiropoulos Jan 2019

Cyclized Ndga Modifies Dynamic Α-Synuclein Monomers Preventing Aggregation And Toxicity, Malcolm J. Daniels, J. Brucker Nourse, Hanna Kim, Valerio Sainati, Marco Schiavina, Maria Grazia Murrali, Buyan Pan, John J. Ferrie, Conor M. Haney, Rani Moons, Neal S. Gould, Antonino Natalello, Rita Grandori, Frank Sobott, E. James Petersson, Elizabeth Rhoades, Roberta Pierattelli, Isabella Felli, Vladimir N. Uversky, Kim A. Caldwell, Guy A. Caldwell, Edward S. Krol, Harry Ischiropoulos

Molecular Medicine Faculty Publications

Growing evidence implicates α-synuclein aggregation as a key driver of neurodegeneration in Parkinson’s disease (PD) and other neurodegenerative disorders. Herein, the molecular and structural mechanisms of inhibiting α-synuclein aggregation by novel analogs of nordihydroguaiaretic acid (NDGA), a phenolic dibenzenediol lignan, were explored using an array of biochemical and biophysical methodologies. NDGA analogs induced modest, progressive compaction of monomeric α-synuclein, preventing aggregation into amyloid-like fibrils. This conformational remodeling preserved the dynamic adoption of α-helical conformations, which are essential for physiological membrane interactions. Oxidation-dependent NDGA cyclization was required for the interaction with monomeric α-synuclein. NDGA analog-pretreated α-synuclein did not aggregate even without …


Small Heat Shock Proteins, Big Impact On Protein Aggregation In Neurodegenerative Disease, Jack M. Webster, April L. Darling, Vladimir N. Uversky, Laura J. Blair Jan 2019

Small Heat Shock Proteins, Big Impact On Protein Aggregation In Neurodegenerative Disease, Jack M. Webster, April L. Darling, Vladimir N. Uversky, Laura J. Blair

Molecular Medicine Faculty Publications

Misfolding, aggregation, and aberrant accumulation of proteins are central components in the progression of neurodegenerative disease. Cellular molecular chaperone systems modulate proteostasis, and, therefore, are primed to influence aberrant protein-induced neurotoxicity and disease progression. Molecular chaperones have a wide range of functions from facilitating proper nascent folding and refolding to degradation or sequestration of misfolded substrates. In disease states, molecular chaperones can display protective or aberrant effects, including the promotion and stabilization of toxic protein aggregates. This seems to be dependent on the aggregating protein and discrete chaperone interaction. Small heat shock proteins (sHsps) are a class of molecular chaperones …


Intrinsically Disordered Proteins And Their “Mysterious” (Meta)Physics, Vladimir N. Uversky Jan 2019

Intrinsically Disordered Proteins And Their “Mysterious” (Meta)Physics, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Recognition of the natural abundance and functional importance of intrinsically disordered proteins (IDPs), and protein hybrids that contain both intrinsically disordered protein regions (IDPRs) and ordered regions, is changing protein science. IDPs and IDPRs, i.e., functional proteins and protein regions without unique structures, can often be found in all organisms, and typically play vital roles in various biological processes. Disorder-based functionality complements the functions of ordered proteins and domains. However, by virtue of their existence, IDPs/IDPRs, which are characterized by remarkable conformational flexibility and structural plasticity, break multiple rules established over the years to explain structure, folding, and functionality of …


Rational Discovery Of Antimetastatic Agents Targeting The Intrinsically Disordered Region Of Mbd2, Min Young Kim, Insung Na, Ji Sook Kim, Seung Han Son, Sungwoo Choi, Seol Eui Lee, Ji-Hun Kim, Kiseok Jang, Gil Alterovitz, Yu Chen, Arjant Van Der Vaar, Hyung-Sik Won, Vladimir N. Uversky, Chul Geun Kim Jan 2019

Rational Discovery Of Antimetastatic Agents Targeting The Intrinsically Disordered Region Of Mbd2, Min Young Kim, Insung Na, Ji Sook Kim, Seung Han Son, Sungwoo Choi, Seol Eui Lee, Ji-Hun Kim, Kiseok Jang, Gil Alterovitz, Yu Chen, Arjant Van Der Vaar, Hyung-Sik Won, Vladimir N. Uversky, Chul Geun Kim

Molecular Medicine Faculty Publications

Although intrinsically disordered protein regions (IDPRs) are commonly engaged in promiscuous protein-protein interactions (PPIs), using them as drug targets is challenging due to their extreme structural flexibility. We report a rational discovery of inhibitors targeting an IDPR of MBD2 that undergoes disorder-to-order transition upon PPI and is critical for the regulation of the Mi-2/NuRD chromatin remodeling complex (CRC). Computational biology was essential for identifying target site, searching for promising leads, and assessing their binding feasibility and off-target probability. Molecular action of selected leads inhibiting the targeted PPI of MBD2 was validated in vitro and in cell, followed by confirming their …


Intrinsic Disorder-Based Emergence In Cellular Biology: Physiological And Pathological Liquid-Liquid Phase Transitions In Cells, April L. Darling, Boris Zaslavsky, Vladimir N. Uversky Jan 2019

Intrinsic Disorder-Based Emergence In Cellular Biology: Physiological And Pathological Liquid-Liquid Phase Transitions In Cells, April L. Darling, Boris Zaslavsky, Vladimir N. Uversky

Molecular Medicine Faculty Publications

The visible outcome of liquid-liquid phase transitions (LLPTs) in cells is the formation and disintegration of various proteinaceous membrane-less organelles (PMLOs). Although LLPTs and related PMLOs have been observed in living cells for over 200 years, the physiological functions of these transitions (also known as liquid-liquid phase separation, LLPS) are just starting to be understood. While unveiling the functionality of these transitions is important, they have come into light more recently due to the association of abnormal LLPTs with various pathological conditions. In fact, several maladies, such as various cancers, different neurodegenerative diseases, and cardiovascular diseases, are known to be …


Evolutionary Analyses Of Sequence And Structure Space Unravel The Structural Facets Of Sod1, Sourav Chowdury, Dwipanjan Sanyal, Sagnik Sen, Vladimir N. Uversky, Ujjwal Maulik, Krishnananda Chattopadhyay Jan 2019

Evolutionary Analyses Of Sequence And Structure Space Unravel The Structural Facets Of Sod1, Sourav Chowdury, Dwipanjan Sanyal, Sagnik Sen, Vladimir N. Uversky, Ujjwal Maulik, Krishnananda Chattopadhyay

Molecular Medicine Faculty Publications

Superoxide dismutase (SOD) is the primary enzyme of the cellular antioxidant defense cascade. Misfolding, concomitant oligomerization, and higher order aggregation of human cytosolic SOD are linked to amyotrophic lateral sclerosis (ALS). Although, with two metal ion cofactors SOD1 is extremely robust, the de-metallated apo form is intrinsically disordered. Since the rise of oxygen-based metabolism and antioxidant defense systems are evolutionary coupled, SOD is an interesting protein with a deep evolutionary history. We deployed statistical analysis of sequence space to decode evolutionarily co-varying residues in this protein. These were validated by applying graph theoretical modelling to understand the impact of the …