Neurosciences Commons^™

Neurovascular Regulation In Diabetic Retinopathy And Emerging Therapies, Liyang Ji, Hong Tian, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

Diabetic retinopathy (DR) is the leading cause of vision loss in working adults in developed countries. The disease traditionally classified as a microvascular complication of diabetes is now widely recognized as a neurovascular disorder resulting from disruption of the retinal neurovascular unit (NVU). The NVU comprising retinal neurons, glia and vascular cells coordinately regulates blood flow, vascular density and permeability to maintain homeostasis. Disturbance of the NVU during DR can lead to vision-threatening clinical manifestations. A limited number of signaling pathways have been identified for intercellular communication within the NVU, including vascular endothelial growth factor (VEGF), the master switch for …

Deep Learning-Based Mixed-Dimensional Gaussian Mixture Model For Characterizing Variability In Cryo-Em, Muyuan Chen, Steven J Ludtke

Faculty, Staff and Students Publications

Structural flexibility and/or dynamic interactions with other molecules is a critical aspect of protein function. Cryogenic electron microscopy (cryo-EM) provides direct visualization of individual macromolecules sampling different conformational and compositional states. While numerous methods are available for computational classification of discrete states, characterization of continuous conformational changes or large numbers of discrete state without human supervision remains challenging. Here we present e2gmm, a machine learning algorithm to determine a conformational landscape for proteins or complexes using a three-dimensional Gaussian mixture model mapped onto two-dimensional particle images in known orientations. Using a deep neural network architecture, e2gmm can automatically resolve the …

Objective Physiological Measures Of Lingual And Jaw Function In Healthy Individuals And Individuals With Dysphagia Due To Neurodegenerative Diseases, Megan E. Cuellar, Elizabeth Oommen

Faculty Research, Scholarly, and Creative Activity

Swallowing is a neuromuscular process that involves a complex sequence of sensorimotor events, which are executed to efficiently and safely transport food and liquid from the mouth to the stomach. Safe oropharyngeal swallowing involves the activation, modulation, and coordination of oral, pharyngeal, laryngeal, and esophageal structures and musculature. Impaired or atypical patterns of swallowing are considered characteristic of a swallowing disorder, otherwise referred to as dysphagia, and affect the performance of all stages, i.e., oral preparatory, oral transit, pharyngeal, and esophageal. Lingual and jaw musculature play critical roles in mediating swallowing function, particularly during the oral preparatory and oral transit …

The Experience Of Off Periods In Parkinson’S Disease: Descriptions, Triggers, And Alleviating Factors, Sneha Mantri, Madeline Lepore, Briana Edison, Margaret Daeschler, Catherine Kopil, Connie Marras, Lana Chahine

Journal of Patient-Centered Research and Reviews

Purpose: Wearing off of Parkinson’s disease medication is common, but triggers and coping strategies for this transient phenomenon are poorly understood. We aimed to assess the lived experience of OFF periods for people with Parkinson’s disease.

Methods: Participants in the longitudinal Fox Insight study who endorsed OFF periods were invited to complete a survey consisting of both multiple-choice and free-text responses. Descriptive statistics were used to summarize multiple-choice responses, and free-text responses were classified into themes through iterative discussion by 3 movement disorders specialists.

Results: A total of 2110 participants (52.4% male) completed the survey. Tremor was the most common …

Elucidating The Structure And Functions Of Resolvin D6 Isomers On Nerve Regeneration With A Distinctive Trigeminal Transcriptome, Thang L. Pham, Azucena H. Kakazu, Jiucheng He, Robert Nshimiyimana, Nicos A. Petasis, Bokkyoo Jun, Nicolas G. Bazan, Haydee E.P. Bazan

School of Medicine Faculty Publications

Innervation sustains cornea integrity. Pigment epithelium-derived factor (PEDF) plus docosahexaenoic acid (DHA) regenerated damaged nerves by stimulating the synthesis of a new stereoisomer of Resolvin D6 (RvD6si). Here, we resolved the structure of this lipid isolated from mouse tears after injured corneas were treated with PEDF + DHA. RvD6si synthesis was inhibited by fluvoxamine, a cytochrome P450 inhibitor, but not by 15- or 5-LOX inhibitors, suggesting that the 4- and 17-hydroxy of DHA have an RR- or SR-configuration. The two compounds were chemically synthesized. Using chiral phase HPLC, four peaks of RvD6si1-4 from tears were resolved. The RR-RvD6 standard eluted …

Medical Schools Ignore The Nature Of Consciousness At Great Cost, Anoop Kumar

Journal of Wellness

The essential question of the relationship between consciousness and matter is ignored in medical school curricula, leading to a machine-like view of the human being that contributes to physician burnout and intellectual dissatisfaction. The evidence suggesting that the brain may not be the seat of consciousness is generally ignored to preserve the worldview of the primacy of matter. By investigating new frameworks detailing the nature of consciousness at different levels of hierarchy, we can bring intellectual rigor to a once opaque subject that supports a fundamental reality about our experience: We are human beings, not only human bodies.

Therapeutic Efficacy Of A Potent Anti-Venezuelan Equine Encephalitis Virus Antibody Is Contingent On Fc Effector Function, Vanja Krneta-Stankic, Mark E Corkins, Adriana Paulucci-Holthauzen, Malgorzata Kloc, Andrew B Gladden, Rachel K Miller

Faculty, Staff and Student Publications

E-cadherin junctions facilitate assembly and disassembly of cell contacts that drive development and homeostasis of epithelial tissues. In this study, using Xenopus embryonic kidney and Madin-Darby canine kidney (MDCK) cells, we investigate the role of the Wnt/planar cell polarity (PCP) formin Daam1 (Dishevelled-associated activator of morphogenesis 1) in regulating E-cadherin-based intercellular adhesion. Using live imaging, we show that Daam1 localizes to newly formed cell contacts in the developing nephron. Furthermore, analyses of junctional filamentous actin (F-actin) upon Daam1 depletion indicate decreased microfilament localization and slowed turnover. We also show that Daam1 is necessary for efficient and timely localization of junctional …

Current State Of Preeclampsia Mouse Models: Approaches, Relevance, And Standardization, Christopher A. Waker, Melissa R. Kaufman, Thomas L. Brown

Neuroscience, Cell Biology & Physiology Faculty Publications

Preeclampsia (PE) is a multisystemic, pregnancy-specific disorder and a leading cause of maternal and fetal death. PE is also associated with an increased risk for chronic morbidities later in life for mother and offspring. Abnormal placentation or placental function has been well-established as central to the genesis of PE; yet much remains to be determined about the factors involved in the development of this condition. Despite decades of investigation and many clinical trials, the only definitive treatment is parturition. To better understand the condition and identify potential targets preclinically, many approaches to simulate PE in mice have been developed and …

A Novel Three-Choice Touchscreen Task To Examine Spatial Attention And Orienting Responses In Rodents, Faraj L. Haddad, Maryam Ghahremani, Cleusa De Oliveira, Ella E. Doornaert, Kevin D. Johnston, Stefan Everling, Susanne Schmid

Brain and Mind Institute Researchers' Publications

Mammalian orienting behavior consists of coordinated movements of the eyes, head, pinnae, vibrissae, or body to attend to an external stimulus. The present study aimed to develop a novel operant task using a touch-screen system to measure spatial attention. In this task, rats were trained to nose-poke a light stimulus presented in one of three locations. The stimulus was presented more frequently in the center location to develop spatial attention bias toward the center stimulus. Changes in orienting responses were detected by measuring the animals’ response accuracy and latency to stimuli at the lateral locations, following reversible unilateral chemogenetic inactivation …

Early Indicators Of Cognitive Dysfunction: The Role Of Mild Behavioral Impairment, Hillary J. Rouse

USF Tampa Graduate Theses and Dissertations

Older age is associated with an increased risk for cognitively impairing diseases such as dementia. Despite significant research to find ways to cure this disease, there has been little success. However, a critical need when an intervention is discovered is a need to find ways to identify people who are at the greatest risk of developing dementia earlier in the disease process so that interventions can be implemented at that time. This could potentially lessen their risk or delay when they are diagnosed. Using longitudinal data from the National Alzheimer’s Coordinating Center (NACC), the aims of this current dissertation were …

Smoking-Induced Sex Differences In Clinical Outcomes In Patients Undergoing Mechanical Thrombectomy For Stroke, Jacqueline A. Frank, Kara Jo Swafford, Jill M. Roberts, Amanda L. Trout, Ann M. Stowe, Douglas E. Lukins, Stephen Grupke, Keith R. Pennypacker, Justin F. Fraser

Neurology Faculty Publications

OBJECTIVE: Ischemic stroke is the fifth leading cause of death in the United States. Smoking accelerates the onset of stroke by 10 years. The effects of smoking status on percent change in National Institutes of Health Stroke Scale (NIHSS) score, infarct volume, and edema volume were examined following mechanical thrombectomy for large vessel occlusion in patients with acute ischemic stroke.

METHODS: Subjects (N = 90; >18 years old) were divided into 3 groups based on smoking status: current smokers, previous smokers (defined as having quit >6 months before the ischemic event), and nonsmokers. Percent change in NIHSS score was …

Effects Of Genetics And Sex On Hippocampal Gene Expression And Adolescent Behaviors Following Neonatal Ethanol Exposure In Bxd Recombinant Inbred Mice, Jessica A. Baker

Theses and Dissertations (ETD)

Fetal alcohol spectrum disorders (FASD) are the leading preventable neurodevelopmental disorders in the western world. A hallmark symptom of FASD is cognitive and learning deficits that present in early childhood and continue throughout adulthood. Teratogenic effects of alcohol include increased cell death in the hippocampus, a brain region critically important in learning and memory. Genetics have been shown to have a role in the severity of alcohol’s teratogenic effect on the developing brain. Previous work in our lab identified differential vulnerability to ethanol-induced call death in the hippocampus using fourteen BXD strains and the two parental strains. The goal of …

Intermittent Hypoxia And Effects On Early Learning/Memory: Exploring The Hippocampal Cellular Effects Of Pediatric Obstructive Sleep Apnea, Arvind Chandrakantan, Adam C Adler, Mehmet Tohsun, Farrah Kheradamand, Russell S Ray, Steven Roth

Faculty, Staff and Students Publications

This review provides an update on the neurocognitive phenotype of pediatric obstructive sleep apnea (OSA). Pediatric OSA is associated with neurocognitive deficits involving memory, learning, and executive functioning. Adenotonsillectomy (AT) is presently accepted as the first-line surgical treatment for pediatric OSA, but the executive function deficits do not resolve postsurgery, and the timeline for recovery remains unknown. This finding suggests that pediatric OSA potentially causes irreversible damage to multiple areas of the brain. The focus of this review is the hippocampus, 1 of the 2 major sites of postnatal neurogenesis, where new neurons are formed and integrated into existing circuitry …

Taste Learning In Insular Cortex: Plasticity Is Influenced By Experience Type, Stephanie Marie Staszko

Theses and Dissertations (ETD)

The gustatory cortex (GC) has long been studied as the main cortical area encoding taste stimuli and likely integrates sensory, visceral, and emotional information to guide taste-related behaviors. However, our understanding of cortical taste coding on a single-cell level has only become clear in recent years. The anatomical location of GC on the lateral and ventral surface of the brain makes it difficult to target with traditional imaging methods. Thus, much of what we know about cortical taste coding and cortical taste plasticity has been derived either from multiunit electrode recordings or anesthetized imaging experiments, techniques which lack the ability …

Relationship Between Cognitive Performance, Physical Activity, And Socio-Demographic/ Individual Characteristics Among Aging Americans, Imtiaz Masfique Dowllah

Theses and Dissertations

Despite the attenuation of association following adjustments for covariates, participants who engaged in 3–6 hr/wk of vigorous- and > 1 hr/wk of moderate-intensity PA scored significantly higher in tests that assessed executive function and processing speed domains of cognition compared to inactive peers (η2 = 0.005 & 0.007 respectively, p < 0.05). Also, after adjustment, the effects of 1–3 hr/wk of vigorous-intensity PA became trivial for the delayed recall memory domain test scores (β = 0.33; 95% CI: –0.01, 0.67; η2 = 0.002; p = 0.56). There was no clear dose-response relationship between the cognitive test scores and weekly moderate-intensity PA. Interestingly, higher handgrip strength and higher late-life body-mass-index were associated with a higher performance across all cognitive domains. Observed associations provide evidence linking habitual PA with superior cognition health among older adults. Furthermore, increased muscle strength and higher late-life adiposity may …

The Balance Of Excitation And Inhibition And Its Influence On Cortical States And Rett Syndrome, Jingwen Li

Graduate Theses and Dissertations

Our brain consists of billions of neurons, properly coordinating to process information and realize brain functions. Among them, there are two types of neurons: excitatory neurons and inhibitory neurons. The firing of excitatory neurons increases the membrane potential of downstream neurons, and thus excites other neurons to fire. The firing of inhibitory neurons, in contrast, decreases the membrane potential of downstream neurons, and thus inhibits other neurons to fire. The interplay of excitatory and inhibitory neurons shape the spiking activity in the population. Thus, the `balance of excitation and inhibition' plays an important role in cortical processing and brain functions. …

What Internal Variables Affect Sensorimotor Rhythm Brain-Computer Interface (Smr-Bci) Performance?, Alex J. Horowitz, Christoph Guger, Milena Korostenskaja

HCA Healthcare Journal of Medicine

In this review article, we aimed to create a summary of the effects of internal variables on the performance of sensorimotor rhythm-based brain computer interfaces (SMR-BCIs). SMR-BCIs can be potentially used for interfacing between the brain and devices, bypassing usual central nervous system output, such as muscle activity. The careful consideration of internal factors, affecting SMR-BCI performance, can maximize BCI application in both healthy and disabled people. Internal variables may be generalized as descriptors of the processes mainly dependent on the BCI user and/or originating within the user. The current review aimed to critically evaluate and summarize the currently accumulated …

What External Variables Affect Sensorimotor Rhythm Brain-Computer Interface (Smr-Bci) Performance?, Alex J. Horowitz, Christoph Guger, Milena Korostenskaja

HCA Healthcare Journal of Medicine

Sensorimotor rhythm-based brain-computer interfaces (SMR-BCIs) are used for the acquisition and translation of motor imagery-related brain signals into machine control commands, bypassing the usual central nervous system output. The selection of optimal external variable configuration can maximize SMR-BCI performance in both healthy and disabled people. This performance is especially important now when the BCI is targeted for everyday use in the environment beyond strictly regulated laboratory settings. In this review article, we summarize and critically evaluate the current body of knowledge pertaining to the effect of the external variables on SMR-BCI performance. When assessing the relationship between SMR-BCI performance and …

The Role Of Action Potential Waveform In Failure Of Excitation Contraction Coupling, Xueyong Wang, Murad Nawaz, Steve R.A. Burke, Roger Bannister, Brent D. Foy, Andrew A. Voss, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

Excitation contraction coupling (ECC) is the process by which electrical excitation of muscle is converted into force generation. Depolarization of skeletal muscle resting potential contributes to failure of ECC in diseases such as periodic paralysis, ICU acquired weakness and possibly fatigue of muscle during vigorous exercise. When extracellular K+ is raised to depolarize the resting potential, failure of ECC occurs suddenly, over a range of several mV of resting potential. While some studies have hypothesized the sudden failure of ECC is due to all-or-none failure of excitation, other studies suggest failure of excitation is graded. Intracellular recordings of action potentials …

Reduced Mitochondrial Dna And Oxphos Protein Content In Skeletal Muscle Of Children With Cerebral Palsy, Ferdinand Von Walden, Ivan J. Vechetti Jr., Davis A. Englund, Vandré C. Figueiredo, Rodrigo Fernandez-Gonzalo, Kevin A. Murach, Jessica Pingel, John J. Mccarthy, Per Stål, Eva Pontén

Physiology Faculty Publications

AIM: To provide a detailed gene and protein expression analysis related to mitochondrial biogenesis and assess mitochondrial content in skeletal muscle of children with cerebral palsy (CP).

METHOD: Biceps brachii muscle samples were collected from 19 children with CP (mean [SD] age 15y 4mo [2y 6mo], range 9-18y, 16 males, three females) and 10 typically developing comparison children (mean [SD] age 15y [4y], range 7-21y, eight males, two females). Gene expression (quantitative reverse transcription polymerase chain reaction [PCR]), mitochondrial DNA (mtDNA) to genomic DNA ratio (quantitative PCR), and protein abundance (western blotting) were analyzed. Microarray data sets (CP/aging/bed rest) were …