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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 …

Life In Phases: Intra- And Inter- Molecular Phase Transitions In Protein Solutions, Vladimir N. Uversky, Alexey V. Finkelstein

Molecular Medicine Faculty Publications

Proteins, these evolutionarily-edited biological polymers, are able to undergo intramolecular and intermolecular phase transitions. Spontaneous intramolecular phase transitions define the folding of globular proteins, whereas binding-induced, intra- and inter- molecular phase transitions play a crucial role in the functionality of many intrinsically-disordered proteins. On the other hand, intermolecular phase transitions are the behind-the-scenes players in a diverse set of macrosystemic phenomena taking place in protein solutions, such as new phase nucleation in bulk, on the interface, and on the impurities, protein crystallization, protein aggregation, the formation of amyloid fibrils, and intermolecular liquid–liquid or liquid–gel phase transitions associated with the biogenesis …

Structural And Dynamical Order Of A Disordered Protein: Molecular Insights Into Conformational Switching Of Page4 At The Systems Level, Xingcheng Lin, Prakash Kulkarni, Federico Bocci, Nicholas P. Schafer, Susmita Roy, Min-Yeh Tsai, Yanan He, Yihong Chen, Krithika Rajagopalan, Steven M. Mooney, Yu Zeng, Keith Weninger, Alex Grishaev, José N. Onuchic, Herbet Levine, Peter G. Wolynes, Ravi Salgia, Govindan Rangarajan, Vladimir N. Uversky, John Orban, Mohit Kumar Jolly

Molecular Medicine Faculty Publications

Folded proteins show a high degree of structural order and undergo (fairly constrained) collective motions related to their functions. On the other hand, intrinsically disordered proteins (IDPs), while lacking a well-defined three-dimensional structure, do exhibit some structural and dynamical ordering, but are less constrained in their motions than folded proteins. The larger structural plasticity of IDPs emphasizes the importance of entropically driven motions. Many IDPs undergo function-related disorder-to-order transitions driven by their interaction with specific binding partners. As experimental techniques become more sensitive and become better integrated with computational simulations, we are beginning to see how the modest structural ordering …

Intrinsic Disorder Of The Baf Complex: Roles In Chromatin Remodeling And Disease Development, Nashwa El Hadidy, Vladimir N. Uversky

Molecular Medicine Faculty Publications

The two-meter-long DNA is compressed into chromatin in the nucleus of every cell, which serves as a significant barrier to transcription. Therefore, for processes such as replication and transcription to occur, the highly compacted chromatin must be relaxed, and the processes required for chromatin reorganization for the aim of replication or transcription are controlled by ATP-dependent nucleosome remodelers. One of the most highly studied remodelers of this kind is the BRG1- or BRM-associated factor complex (BAF complex, also known as SWItch/sucrose non-fermentable (SWI/SNF) complex), which is crucial for the regulation of gene expression and differentiation in eukaryotes. Chromatin remodeling complex …

Experimental Insight Into The Structural And Functional Roles Of The ‘Black’ And ‘Gray’ Clusters In Recoverin, A Calcium Binding Protein With Four Ef-Hand Motifs, Sergei E. Permyakov, Alisa S. Vologzhannikova, Ekaterina L. Nemashkalova, Alexei S. Kazakov, Alexander I. Denesyuk, Konstantin Denessiouk, Viktoriia E. Baksheeva, Andrey A. Zamyatnin Jr., Eugene Yu. Zernii, Vladimir N. Uversky, Eugene A. Permyakov

Molecular Medicine Faculty Publications

Recently, we have found that calcium binding proteins of the EF-hand superfamily (i.e., a large family of proteins containing helix-loop-helix calcium binding motif or EF-hand) contain two types of conserved clusters called cluster I (‘black’ cluster) and cluster II (‘grey’ cluster), which provide a supporting scaffold for the Ca2+ binding loops and contribute to the hydrophobic core of the EF-hand domains. Cluster I is more conservative and mostly incorporates aromatic amino acids, whereas cluster II includes a mix of aromatic, hydrophobic, and polar amino acids of different sizes. Recoverin is EF-hand Ca2+-binding protein containing two ‘black’ clusters comprised of F35, …

Many-To-One Binding By Intrinsically Disordered Protein Regions, Wei-Lun Alterovitz, Eshel Faraggi, Christopher J. Oldfield, Jingwei Meng, Bin Xue, Fei Huang, Pedro Romero, Andrzej Kloczkowski, Vladimir N. Uversky, A. Keith Dunker

Molecular Medicine Faculty Publications

Disordered binding regions (DBRs), which are embedded within intrinsically disordered proteins or regions (IDPs or IDRs), enable IDPs or IDRs to mediate multiple protein-protein interactions. DBR-protein complexes were collected from the Protein Data Bank for which two or more DBRs having different amino acid sequences bind to the same (100% sequence identical) globular protein partner, a type of interaction herein called many-to-one binding. Two distinct binding profiles were identified: independent and overlapping. For the overlapping binding profiles, the distinct DBRs interact by means of almost identical binding sites (herein called “similar”), or the binding sites contain both common and divergent …

Hiv Vaccine Mystery And Viral Shell Disorder, Gerard Kian-Meng Goh, A. Keith Dunker, James A. Foster, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Hundreds of billions of dollars have been spent for over three decades in the search for an effective human immunodeficiency virus (HIV) vaccine with no success. There are also at least two other sexually transmitted viruses, for which no vaccine is available, the herpes simplex virus (HSV) and the hepatitis C virus (HCV). Traditional textbook explanatory paradigm of rapid mutation of retroviruses cannot adequately address the unavailability of vaccine for many sexually transmissible viruses, since HSV and HCV are DNA and non-retroviral RNA viruses, respectively, whereas effective vaccine for the horsefly-transmitted retroviral cousin of HIV, equine infectious anemia virus (EIAV), …

Intrinsically Disordered Proteins In Chronic Diseases, Prakash Kulkarni, Vladimir N. Uversky

Molecular Medicine Faculty Publications

No abstract provided.

Towards Comprehensive Observing And Modeling Systems For Monitoring And Predicting Regional To Coastal Sea Level, Rui M. Ponte, Mark Carson, Mauro Cirano, Catia M. Domingues, Svetlana Jevrejeva, Marta Marcos, Gary Mitchum, De Wal, Van De Wal, Philip L. Woodworth, Michaël Ablain, Fabrice Ardhuin, Valérie Ballu, Mélanie Becker, Jérôme Benveniste, Florence Birol, Elizabeth Bradshaw, Anny Cazenave, Mey-Frémaux, P. De Mey-Frémaux, Fabien Durand, Tal Ezer, Lee-Lueng Fu, Ichiro Fukumori, Kathy Gordon, Médéric Gravelle, Stephen M. Griffies, Weiqing Han, Angela Hibbert, Chris W. Hughes, Déborah Idier, Villy H. Kourafalou, Christopher M. Little, Andrew Matthews, Angélique Melet, Mark Merrifield, Benoit Meyssignac, Shoshiro Minobe, Thierry Penduff, Nicolas Picot, Christopher Piecuch, Richard D. Ray, Lesley Rickards, Alvaro Santamaría-Gómez, Detlef Stammer, Joanna Staneva, Laurent Testut, Keith Thompson, Philip Thompson, Stefano Vignudelli, Joanne Williams, Simon D. Williams, Guy Wöppelmann, Laure Zanna, Xuebin Zhang

Marine Science Faculty Publications

A major challenge for managing impacts and implementing effective mitigation measures and adaptation strategies for coastal zones affected by future sea level (SL) rise is our limited capacity to predict SL change at the coast on relevant spatial and temporal scales. Predicting coastal SL requires the ability to monitor and simulate a multitude of physical processes affecting SL, from local effects of wind waves and river runoff to remote influences of the large-scale ocean circulation on the coast. Here we assess our current understanding of the causes of coastal SL variability on monthly to multi-decadal timescales, including geodetic, oceanographic and …

2019 Accountability Plan Sarasota-Manatee, Usf

USF Accountability Reports

No abstract provided.

2019 Accountability Plan System, Usf

USF Accountability Reports

No abstract provided.

Usfh Library Survey Cop Pharm Ed 2019, Usf Libraries

All Assessment Data

No abstract provided.

Hormone Replacement Therapy Attenuates Hearing Loss: Mechanisms Involving Estrogen And The Igf-1 Pathway, Tanika T. Williamson, Bo Ding, Xiaoxia Zhu, Robert D. Frisina

Chemical, Biological and Materials Engineering Faculty Publications

Estradiol (E) is a multitasking hormone that plays a prominent role in the reproductive system, and also contributes to physiological and growth mechanisms throughout the body. Frisina and colleagues have previously demonstrated the beneficial effects of this hormone, with E-treated subjects maintaining low auditory brainstem response (ABR) thresholds relative to control subjects (Proceedings of the National Academy of Sciences of the United States of America, 2006;103:14246; Hearing Research, 2009;252:29). In the present study, we evaluated the functionality of the peripheral and central auditory systems in female CBA/CaJ middle-aged mice during and after long-term hormone replacement therapy (HRT) via …

P53 Phosphomimetics Preserve Transient Secondary Structure But Reduce Binding To Mdm2 And Mdmx, Robin Levy, Emily Gregory, Wade Borcherds, Gary W. Daughdrill

Molecular Biosciences Faculty Publications

The disordered p53 transactivation domain (p53TAD) contains specific levels of transient helical secondary structure that are necessary for its binding to the negative regulators, mouse double minute 2 (Mdm2) and MdmX. The interactions of p53 with Mdm2 and MdmX are also modulated by posttranslational modifications (PTMs) of p53TAD including phosphorylation at S15, T18 and S20 that inhibits p53-Mdm2 binding. It is unclear whether the levels of transient secondary structure in p53TAD are changed by phosphorylation or other PTMs. We used phosphomimetic mutants to determine if adding a negative charge at positions 15 and 18 has any effect on the transient …

Relationships Between The Diabetes Awareness And Clinical Indices/Nutrient Intakes In Korean Adults: Based On The 2012–2013 Korea National Health And Nutrition Examination Survey Data, Seul Lee, Haeryun Park, Youngmi Lee, Onjeong Choi, Jiwon Kim, Heewon L. Gray, Kyunghee Song

Community and Family Health Faculty Publications

Background/Objectives: Diabetes is diagnosed after an average of 10–12 years of diabetic development. Strict glycemic control in diabetic patients promotes the normalization of blood glucose and reduces cardiovascular diseases (CVDs) and diabetic complications. Therefore, early diagnosis in non-aware individuals is very important.

Subjects/Methods: Clinical indices and nutrient intakes in Korean diabetic adults aged 19–64 years were examined according to the awareness of diabetes, using 2012 and 2013 Korea National Health and Nutrition Examination Survey (KNHANES) data. The aware group was defined as individuals who were aware of having diabetes from diagnosis by physician before the survey and the non-aware group …

The Caricomp Network Of Caribbean Marine Laboratories (1985–2007): History, Key Findings, And Lessons Learned, Jorge Cortes, Hazel A. Oxenford, Brigitta I. Van Tussenbroek, Eric Jordan-Dahlgren, Aldo Croquer, Carolina Bastidas, John C. Ogden

Integrative Biology Faculty and Staff Publications

Caribbean Coastal Marine Productivity (CARICOMP) was a basin-wide cooperative, international network of marine laboratories established in 1985. Recognizing major trends of change in coastal ecosystems and the importance of the linkages among them, our goal was to monitor synoptically with standardized methods the physical environment and to document trends in measures of the structure and functioning of coral reefs, seagrasses and mangroves. Between 1985 and 1993, the CARICOMP Steering Committee established a data management center and wrote a methods manual. Marine laboratories joined the program by appointing a Site Director and signing an agreement specifying the cost sharing and responsibilities …

Prophylactic Treatment Of Hyperbaric Oxygen Treatment Mitigates Inflammatory Response Via Mitochondria Transfer, Trenton Lippert, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

No abstract provided.

Concise Review: Stem Cell Therapy For Stroke Patients: Are We There Yet?, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

Four decades of preclinical research demonstrating survival, functional integration, and behavioral effects of transplanted stem cells in experimental stroke models have provided ample scientific basis for initiating limited clinical trials of stem cell therapy in stroke patients. Although safety of the grafted cells has been overwhelmingly documented, efficacy has not been forthcoming. Two recently concluded stroke clinical trials on mesenchymal stem cells (MSCs) highlight the importance of strict adherence to the basic science findings of optimal transplant regimen of cell dose, timing, and route of delivery in enhancing the functional outcomes of cell therapy. Echoing the Stem Cell Therapeutics as …

Microrna-133a And Myocardial Infarction, Yi Xiao, Jiling Zhao, Julian P. Tuazon, Cesar V. Borlongan, Guolong Yu

Neurosurgery and Brain Repair Faculty Publications

Myocardial infarction (MI) is the leading cause of morbidity and mortality in the world. The infarcted heart displays typical cell death cascades characterized by a loss of cells and fibrotic scarring in the myocardium. Cardiac hypertrophy and fibrosis largely contribute to ventricular wall thickening and stiffening, altogether defining an adverse cardiac remodeling that ultimately leads to impaired cardiac function and subsequent heart failure. Finding a strategy to promote therapeutic, instead of detrimental, cardiac remodeling may pose as a potent MI treatment. Accumulating evidence shows that microRNAs (miRNAs) may play an essential role in cardiovascular diseases. In particular, microRNA-133a (miR-133a) is …

A Hallmark Clinical Study Of Cord Blood Therapy In Adults With Ischemic Stroke, Paul R. Sanberg, Jared Ehrhart

Neurosurgery and Brain Repair Faculty Publications

The therapeutic application of human umbilical cord blood cells has been an area of great interest for at least the last 25 years. Currently, cord blood cells are approved for reconstitution of the bone marrow following myeloablation in both young and old patients with myeloid malignancies and other blood cancers. Translational studies investigating alternative uses of cord blood have also shown that these cells not only stimulate neurogenesis in the aged brain but are also potentially therapeutic in the treatment of adult neurodegenerative disorders including amyotrophic lateral sclerosis, Alzheimer’s disease, ischemic stroke, traumatic brain injury, and Parkinson’s disease. Recent advances …

Immunomodulation With Human Umbilical Cord Blood Stem Cells Ameliorates Ischemic Brain Injury – A Brain Transcriptome Profiling Analysis, Maple L. Shiao, Ce Yuan, Andrew T. Crane, Joseph P. Voth, Mario Juliano, Laura L. Hocum Stone, Zhenghong Nan, Ying Zhang, Nicole Kuzmin-Nichols, Paul R. Sanberg, Andrew W. Grande, Walter C. Low

Neurosurgery and Brain Repair Faculty Publications

Our group previously demonstrated that administration of a CD34-negative fraction of human non- hematopoietic umbilical cord blood stem cells (UCBSC) 48 h after ischemic injury could reduce infarct volume by 50% as well as significantly ameliorate neurological deficits. In the present study, we explored possible mechanisms of action using next generation RNA sequencing to analyze the brain transcriptome profiles in rats with ischemic brain injury following UCBSC therapy. Two days after ischemic injury, rats were treated with UCBSC. Five days after administration, total brain mRNA was then extracted for RNAseq analysis using Illumina Hiseq 2000. We found 275 genes that …

Central Pain Mimicking Trigeminal Neuralgia As A Result Of Lateral Medullary Ischemic Stroke, Abinayaa Ravichandran, Kareem S. Elsayed, Hussam A. Yacoub

Neurology Faculty Publications

Background. Central pain mimicking trigeminal neuralgia (TN) as a result of lateral medullary infarction or Wallenberg syndrome has been rarely reported. Case Report. We discuss a patient who presented with a lateral medullary infarct and shortly after developed facial pain mimicking TN. We also elaborate on the anatomical pathway of the trigeminal nerve explaining facial pain as a result of a lateral medullary lesion. Discussion. Clinicians should be aware of this typical complication of lateral medullary infarct in order to attain proper management and work-up.

A Case Report Of Extensive Cerebral Venous Sinus Thrombosis As A Presenting Sign Of Relapsing Nephrotic Syndrome, Janet K. Lee, Kathleen Murray, Swetha Renati

Neurology Faculty Publications

Nephrotic syndrome is defined by three characteristic features including proteinuria of >3 g in 24 hours, hypoalbuminemia of less than 3 g/dL, and peripheral edema. Multiple nephropathies can result in nephrotic syndrome. Most commonly, minimal change disease is seen in children under the age of 10, while adults are more commonly found to have membranous nephropathy. Hypercoagulability and thrombotic sequela can be seen in nephrotic syndrome, regardless of underlying etiology, and thrombosis is most commonly seen in deep veins of the lower extremities and renal veins. Our case identifies an adult with previously diagnosed and treated for minimal change disease …

Lamotrigine Odt-Induced Seizure In A 3-Year-Old Child After Accidental Ingestion, Ashley Griswold, Briana Tully, Kenneth Katz, Gillian Beauchamp, Matthew Cook, Robert Cannon

Pediatrics Faculty Publications

Lamotrigine is a new generation antiepileptic which blocks sodium channels and can cause significant toxicity in overdose. A case of a three-year-old child who suffered a seizure and required endotracheal intubation after accidental lamotrigine ingestion is presented. The lamotrigine concentration measured 23.2 mcg/mL which is the highest reported after accidental pediatric exposure. A review of the literature regarding pediatric lamotrigine poisoning is also included.

Wire Guided Cannulation Facilitates Endoscopic Management Of Buried Bumper Syndrome: A Novel Technique, Jacquelin Peck, Kaitlin Sapp, Alexander Wilsey, Michael Wilsey

Pediatrics Faculty Publications

Buried bumper syndrome is a rare but potentially severe complication of percutaneous endoscopic gastrostomy tube insertion. Though this complication is uncommon, it may lead to pressure necrosis, bleeding, perforation, peritonitis, sepsis, or death. Each case of buried bumper syndrome is unique in terms of patient comorbidities and anatomic positioning of the buried bumper. For this reason, many approaches have been described in the management of buried bumper syndrome. In this case report, we describe the case of an adolescent Caucasian female who developed buried bumper syndrome three years after undergoing percutaneous endoscopic gastrostomy insertion. We review diagnosis and management of …

Cognitive And Functional Status Of Persons Newly Enrolled At Dementia-Specific Adult Day Centers And Burden Of Their Caregivers, David A. Chiriboga, Nan S. Park, Karen Gilbert, Victor A. Molinari, Mary Barnes

Child and Family Studies Faculty Publications

Background and Objectives: Recognizing the important role that dementia-specific adult day centers have in maintaining persons with a neurocognitive disorder in their home, this article examines three critical indicators at the time when people first enroll in such a center: cognitive and functional impairment of the enrollee, and burden reported by their family caregivers. We also considered variations in these 3 indicators by race/ethnicity and by the relationship of caregiver to the new enrollee.

Research Design and Methods: We conducted a secondary analysis of data collected by a nonprofit organization operating 11 dementia-specific adult day centers located on the east …

Psychological And Social Factors Associated With Sleep Health Across Adulthood, Soomi Lee, Orfeu M. Buxton

Aging Studies Faculty Publications

Sleep is associated with all-cause mortality, cardiovascular disease, cognitive impairment, as well as daily social interactions and productivity. Studies often have focused on sleep duration only, lacking the ability to comprehensively understand the importance of age-related changes in varied facets of sleep health. Moreover, psychological and social factors that may be associated with sleep health in adulthood are still poorly understood. This symposium showcases contemporary endeavors towards understanding how diverse indicators of sleep health relate to psychological and social factors across adulthood. Paper 1 uses perceived job discrimination as a social stressor to test associations between perceived job discrimination and …

The Examination Of Determinants And Barriers To End-Of-Life Decision Making And Planning, Brittany E. Gaines, Debra J. Dobbs

Aging Studies Faculty Publications

As individuals are living longer, in many cases with chronic diseases, there is an increased focus on end-of-life (EOL) planning and decision making. This includes a broad spectrum of choices including advance care planning (ACP) and turning to palliative care or hospice care. Although there has been an increase in palliative and hospice care enrollment and ACP engagement over the past decade, participation remains low for certain subgroups of the population. The purpose of this symposium is to offer insight into reasons for these varying rates of engagement by exploring determinants and barriers to EOL decision making and planning and …

Personality And Self-Reported And Actigraphy-Measured Sleep Health In Adulthood, Nasreen A. Sadeq, Soomi Lee, Alyssa Gamaldo, David M. Almeida

Aging Studies Faculty Publications

Personality may be associated with sleep health, however, the majority of existing studies rely on self-reported measures of sleep (often focusing on sleep duration). The purpose of this study is to examine the associations between Big Five personality traits and self-reported and actigraphy measured sleep. This study included 3928 participants and a subsample of 441 participants from the Midlife in the United States study. Linear regressions were used to analyze the relationships between personality traits and sleep. Neuroticism was associated with more frequent actigraphy-measured waking after sleep onset, and several self-reported measures of sleep quality, including shorter sleep duration, longer …

Is Ghana Ready To Attain Sustainable Development Goal (Sdg) Number 7?—A Comprehensive Assessment Of Its Renewable Energy Potential And Pitfalls, Michael Acheampong, Qiuyan Yu, Funda C. Ertem, Lucy E.D. Enomah, Shakhawat H. Tanim, Michael Eduful, Mehrdad Vaziri, Erick Ananga

School of Geosciences Student Publications

Ghana has declared support for the UN Sustainable Development Goal (SDG) number seven which most importantly target ensuring universal access to affordable, reliable and modern energy services. This target presents a formidable challenge to Ghana because the country still relies mainly on traditional biomass as its primary source of energy coupled with a chronically fragile hydropower sector. In this study, we assess Ghana’s potential in achieving sustainable goal number seven. Specifically, we comprehensively review the breakthroughs and impediments Ghana has experienced in its efforts towards improving its renewable energy potential. We note that while Ghana has made significant stride toward …