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2023

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Articles 31 - 60 of 451

Full-Text Articles in Neurosciences

Qa-Snare Syntaxin 18 Mediates Lipid Droplet Fusion With Snap23 And Sec22b, Yuhui Fu, Binbin Ding, Xiaoxia Liu, Shangang Zhao, Fang Chen, Linsen Li, Yi Zhu, Jingxuan Zhao, Zhen Yuan, Yafeng Shen, Chaofeng Yang, Mengle Shao, She Chen, Perry E Bickel, Qing Zhong Nov 2023

Qa-Snare Syntaxin 18 Mediates Lipid Droplet Fusion With Snap23 And Sec22b, Yuhui Fu, Binbin Ding, Xiaoxia Liu, Shangang Zhao, Fang Chen, Linsen Li, Yi Zhu, Jingxuan Zhao, Zhen Yuan, Yafeng Shen, Chaofeng Yang, Mengle Shao, She Chen, Perry E Bickel, Qing Zhong

Faculty, Staff and Students Publications

Lipid droplets (LDs) are dynamic lipid storage organelles that can sense and respond to changes in systemic energy balance. The size and number of LDs are controlled by complex and delicate mechanisms, among which, whether and which SNARE proteins mediate LD fusion, and the mechanisms governing this process remain poorly understood. Here we identified a SNARE complex, syntaxin 18 (STX18)-SNAP23-SEC22B, that is recruited to LDs to mediate LD fusion. STX18 targets LDs with its transmembrane domain spanning the phospholipid monolayer twice. STX18-SNAP23-SEC22B complex drives LD fusion in adiposome lipid mixing and content mixing in vitro assays. CIDEC/FSP27 directly binds STX18, …


Tert Immunohistochemistry As A Surrogate Marker For Tert Promoter Mutations In Infiltrating Gliomas, Gillian Gordon Perue, Hao Ying, Antonio Bustillo, Lili Zhou, Carolina M Gutierrez, Hannah E Gardener, Judith Krigman, Angus Jameson, Chuanhui Dong, Tatjana Rundek, David Z Rose, Jose G Romano, Ayham Alkhachroum, Ralph L Sacco, Negar Asdaghi, Sebastian Koch Nov 2023

Tert Immunohistochemistry As A Surrogate Marker For Tert Promoter Mutations In Infiltrating Gliomas, Gillian Gordon Perue, Hao Ying, Antonio Bustillo, Lili Zhou, Carolina M Gutierrez, Hannah E Gardener, Judith Krigman, Angus Jameson, Chuanhui Dong, Tatjana Rundek, David Z Rose, Jose G Romano, Ayham Alkhachroum, Ralph L Sacco, Negar Asdaghi, Sebastian Koch

Faculty, Staff and Student Publications

BACKGROUND: Guideline-based hypertension management is integral to the prevention of stroke. We examine trends in antihypertensive medications prescribed after stroke and assess how well a prescriber's blood pressure (BP) medication choice adheres to clinical practice guidelines (BP-guideline adherence).

METHODS AND RESULTS: The FSR (Florida Stroke Registry) uses statewide data prospectively collected for all acute stroke admissions. Based on established guidelines, we defined optimal BP-guideline adherence using the following hierarchy of rules: (1) use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker as first-line antihypertensive among diabetics; (2) use of thiazide-type diuretics or calcium channel blockers among Black patients; (3) …


A Two-Sample Mendelian Randomization Study Of Atherosclerosis And Dementia, Qiaoyun Zhang, Guangheng Wu, Xiaoyu Zhang, Sheng Wang, Youxin Wang Nov 2023

A Two-Sample Mendelian Randomization Study Of Atherosclerosis And Dementia, Qiaoyun Zhang, Guangheng Wu, Xiaoyu Zhang, Sheng Wang, Youxin Wang

Research outputs 2022 to 2026

The causality between atherosclerosis and dementia remains unclear. This study aimed to explore the causal effect of atherosclerosis related indicators on dementia risk based on two-sample Mendelian randomization (MR) using summary statistics of genome-wide association studies (GWASs). The inverse variance weighted (IVW) method was performed as the main analysis, supplemented by different sensitivity analyses. Suggestive evidence indicated that peripheral arterial disease (PAD) (odds ratio (OR): 0.864, 95% confidence interval (CI): 0.797–0.937), coronary atherosclerosis (CoAS) (OR: 0.927, 95% CI: 0.860–0.998) and atherosclerosis, excluding cerebral, coronary, and PAD (ATHSCLE) (OR: 0.812, 95% CI: 0.725–0.909) were inversely associated with the risk of AD. …


Identification Of Cdk1, Pbk, And Chek1 As An Oncogenic Signature In Glioblastoma: A Bioinformatics Approach To Repurpose Dapagliflozin As A Therapeutic Agent, Harold A Chinyama, Li Wei, Ntlotlang Mokgautsi, Bashir Lawal, Alexander T H Wu, Hsu-Shan Huang Nov 2023

Identification Of Cdk1, Pbk, And Chek1 As An Oncogenic Signature In Glioblastoma: A Bioinformatics Approach To Repurpose Dapagliflozin As A Therapeutic Agent, Harold A Chinyama, Li Wei, Ntlotlang Mokgautsi, Bashir Lawal, Alexander T H Wu, Hsu-Shan Huang

Faculty, Staff and Student Publications

Glioblastoma multiforme (GBM) is the most aggressive and lethal primary brain tumor whose median survival is less than 15 months. The current treatment regimen comprising surgical resectioning, chemotherapy with Temozolomide (TMZ), and adjuvant radiotherapy does not achieve total patient cure. Stem cells' presence and GBM tumor heterogeneity increase their resistance to TMZ, hence the poor overall survival of patients. A dysregulated cell cycle in glioblastoma enhances the rapid progression of GBM by evading senescence or apoptosis through an over-expression of cyclin-dependent kinases and other protein kinases that are the cell cycle's main regulatory proteins. Herein, we identified and validated the …


Circulating Tumor Dna Monitoring On Chemo-Immunotherapy For Risk Stratification In Advanced Non-Small Cell Lung Cancer, Bruna Pellini, Russell W Madison, Merrida A Childress, Shoshana T Miller, Ole Gjoerup, Jason Cheng, Richard S P Huang, Michael Krainock, Pratyush Gupta, Wei Zou, David S Shames, Solomon Moshkevich, Marcus Ballinger, Minetta C Liu, Amanda Young, Minu K Srivastava, Geoffrey R Oxnard, Mark A Socinski Nov 2023

Circulating Tumor Dna Monitoring On Chemo-Immunotherapy For Risk Stratification In Advanced Non-Small Cell Lung Cancer, Bruna Pellini, Russell W Madison, Merrida A Childress, Shoshana T Miller, Ole Gjoerup, Jason Cheng, Richard S P Huang, Michael Krainock, Pratyush Gupta, Wei Zou, David S Shames, Solomon Moshkevich, Marcus Ballinger, Minetta C Liu, Amanda Young, Minu K Srivastava, Geoffrey R Oxnard, Mark A Socinski

Faculty, Staff and Student Publications

PURPOSE: Chemoimmunotherapy (chemoIO) is a prevalent first-line treatment for advanced driver-negative non-small cell lung cancer (NSCLC), with maintenance therapy given after induction. However, there is significant clinical variability in the duration, dosing, and timing of maintenance therapy after induction chemoIO. We used circulating tumor DNA (ctDNA) monitoring to inform outcomes in patients with advanced NSCLC receiving chemoIO.

EXPERIMENTAL DESIGN: This retrospective study included 221 patients from a phase III trial of atezolizumab+carboplatin+nab-paclitaxel versus carboplatin+nab-paclitaxel in squamous NSCLC (IMpower131). ctDNA monitoring used the FoundationOne Tracker involving comprehensive genomic profiling of pretreatment tumor tissue, variant selection using an algorithm to exclude nontumor …


Targeted Suppression Of Mtorc2 Reduces Seizures Across Models Of Epilepsy, James Okoh, Jacqunae Mays, Alexandre Bacq, Juan A Oses-Prieto, Stefka Tyanova, Chien-Ju Chen, Khalel Imanbeyev, Marion Doladilhe, Hongyi Zhou, Paymaan Jafar-Nejad, Alma Burlingame, Jeffrey Noebels, Stephanie Baulac, Mauro Costa-Mattioli Nov 2023

Targeted Suppression Of Mtorc2 Reduces Seizures Across Models Of Epilepsy, James Okoh, Jacqunae Mays, Alexandre Bacq, Juan A Oses-Prieto, Stefka Tyanova, Chien-Ju Chen, Khalel Imanbeyev, Marion Doladilhe, Hongyi Zhou, Paymaan Jafar-Nejad, Alma Burlingame, Jeffrey Noebels, Stephanie Baulac, Mauro Costa-Mattioli

Faculty, Staff and Students Publications

Epilepsy is a neurological disorder that poses a major threat to public health. Hyperactivation of mTOR complex 1 (mTORC1) is believed to lead to abnormal network rhythmicity associated with epilepsy, and its inhibition is proposed to provide some therapeutic benefit. However, mTOR complex 2 (mTORC2) is also activated in the epileptic brain, and little is known about its role in seizures. Here we discover that genetic deletion of mTORC2 from forebrain neurons is protective against kainic acid-induced behavioral and EEG seizures. Furthermore, inhibition of mTORC2 with a specific antisense oligonucleotide robustly suppresses seizures in several pharmacological and genetic mouse models …


Profiles Of Resting State Functional Connectivity In Temporal Lobe Epilepsy Associated With Post-Laser Interstitial Thermal Therapy Seizure Outcomes And Semiologies, Mashaal Syed, Jingya Miao, Anish Sathe, Kichang Kang, Arichena Manmatharayan, Michael Kogan, Caio M. Matias, Ashwini Sharan, Mahdi Alizadeh Nov 2023

Profiles Of Resting State Functional Connectivity In Temporal Lobe Epilepsy Associated With Post-Laser Interstitial Thermal Therapy Seizure Outcomes And Semiologies, Mashaal Syed, Jingya Miao, Anish Sathe, Kichang Kang, Arichena Manmatharayan, Michael Kogan, Caio M. Matias, Ashwini Sharan, Mahdi Alizadeh

Farber Institute for Neuroscience Staff Papers and Presentations

Introduction: It is now understood that in focal epilepsy, impacted neural regions are not limited to the epileptogenic zone. As such, further investigation into the underlying functional connectivity (FC) patterns in those enduring Temporal Lobe Epilepsy (TLE) with Mesial Temporal Sclerosis (MTS) is imperative to understanding the intricacies of the disease.

Methods: The rsfMRIs of 17 healthy participants, 10 left-sided TLE-MTS patients with a pre-operative history of focal impaired awareness seizures (FIA), and 13 left-sided TLE-MTS patients with a pre-operative history of focal aware seizures (FA) were compared to determine the existence of distinct FC patterns with respect to seizure …


Voltage- And Calcium-Gated Membrane Currents Tune The Plateau Potential Properties Of Multiple Neuron Types, Curtis L Neveu, Paul Smolen, Douglas A Baxter, John H Byrne Nov 2023

Voltage- And Calcium-Gated Membrane Currents Tune The Plateau Potential Properties Of Multiple Neuron Types, Curtis L Neveu, Paul Smolen, Douglas A Baxter, John H Byrne

Faculty, Staff and Student Publications

Many neurons exhibit regular firing that is limited to the duration and intensity of depolarizing stimuli. However, some neurons exhibit all-or-nothing plateau potentials that, once elicited, can lead to prolonged activity that is independent of stimulus intensity or duration. To better understand this diversity of information processing, we compared the voltage-gated and Ca2+-gated currents of three identified neurons from hermaphroditic Aplysia californica Two of these neurons, B51 and B64, generated plateau potentials and a third neuron, B8, exhibited regular firing and was incapable of generating a plateau potential. With the exception of the Ca2+-gated potassium current (I KCa), all …


Advances In Deep Brain Stimulation: From Mechanisms To Applications, Stephanie S Sandoval-Pistorius, Mallory L Hacker, Allison C Waters, Jing Wang, Nicole R Provenza, Coralie De Hemptinne, Kara A Johnson, Melanie A Morrison, Stephanie Cernera Nov 2023

Advances In Deep Brain Stimulation: From Mechanisms To Applications, Stephanie S Sandoval-Pistorius, Mallory L Hacker, Allison C Waters, Jing Wang, Nicole R Provenza, Coralie De Hemptinne, Kara A Johnson, Melanie A Morrison, Stephanie Cernera

Faculty, Staff and Students Publications

Deep brain stimulation (DBS) is an effective therapy for various neurologic and neuropsychiatric disorders, involving chronic implantation of electrodes into target brain regions for electrical stimulation delivery. Despite its safety and efficacy, DBS remains an underutilized therapy. Advances in the field of DBS, including in technology, mechanistic understanding, and applications have the potential to expand access and use of DBS, while also improving clinical outcomes. Developments in DBS technology, such as MRI compatibility and bidirectional DBS systems capable of sensing neural activity while providing therapeutic stimulation, have enabled advances in our understanding of DBS mechanisms and its application. In this …


The Functions Of Oligodendrocyte Lineage-Derived Laminins Under Homeostatic And Intracerebral Hemorrhagic Stroke Conditions, Minkyung Kang Nov 2023

The Functions Of Oligodendrocyte Lineage-Derived Laminins Under Homeostatic And Intracerebral Hemorrhagic Stroke Conditions, Minkyung Kang

USF Tampa Graduate Theses and Dissertations

Oligodendrocyte lineage is a glial cell population in the central nervous system. The lineage starts with oligodendrocyte precursor cells, which differentiate and mature into mature oligodendrocytes. Myelination, the major function of mature oligodendrocytes, plays a significant role for normal function of the central nervous system, and its dysfunction leads to many demyelinating diseases, such as multiple sclerosis. During the lineage progression, an extracellular matrix protein, laminin, actively regulates the cells' biology, including cell proliferation, differentiation, and myelination. However, the cellular sources of the laminin that controls oligodendrocyte lineage cells remain largely unknown. Interestingly, previous studies have shown that oligodendrocyte lineage …


A Drosophila Model Relevant To Chemotherapy-Related Cognitive Impairment, Matthew Torre, Hassan Bukhari, Vanitha Nithianandam, Camila A Zanella, Douglas A Mata, Mel B Feany Nov 2023

A Drosophila Model Relevant To Chemotherapy-Related Cognitive Impairment, Matthew Torre, Hassan Bukhari, Vanitha Nithianandam, Camila A Zanella, Douglas A Mata, Mel B Feany

Duncan NRI Faculty and Staff Publications

Chemotherapy-related cognitive impairment (CRCI) is a common adverse effect of treatment and is characterized by deficits involving multiple cognitive domains including memory. Despite the significant morbidity of CRCI and the expected increase in cancer survivors over the coming decades, the pathophysiology of CRCI remains incompletely understood, highlighting the need for new model systems to study CRCI. Given the powerful array of genetic approaches and facile high throughput screening ability in Drosophila, our goal was to validate a Drosophila model relevant to CRCI. We administered the chemotherapeutic agents cisplatin, cyclophosphamide, and doxorubicin to adult Drosophila. Neurologic deficits were observed with all …


See Me, Hear Me, Know Me: Perspectives On Diet And Physical Activity Influences Among Teens Living In Rural Texas Communities, Debbe Thompson, Julie Miranda, Chishinga Callender, Jayna M Dave, Godlove Appiah, Salma M A Musaad Nov 2023

See Me, Hear Me, Know Me: Perspectives On Diet And Physical Activity Influences Among Teens Living In Rural Texas Communities, Debbe Thompson, Julie Miranda, Chishinga Callender, Jayna M Dave, Godlove Appiah, Salma M A Musaad

Faculty, Staff and Students Publications

Teens in rural communities are at greater risk of obesity than teens in urban areas. Diet and physical activity influence obesity risk. Understanding their perspectives is an important step in intervention design. This qualitative investigation explored teen perspectives on how living in a rural community influenced their diet and physical activity choices. Forty parent-teen pairs were recruited. Data collection included surveys and telephone interviews. This paper reports teen perspectives identified in the first interview. Thematic analysis was used to code and analyze the data. Findings revealed that the primary factor driving teens' diet and physical activity behaviors was the teens …


Tfeb And Tfe3 Control Glucose Homeostasis By Regulating Insulin Gene Expression, Adrien Pasquier, Nunzia Pastore, Luca D'Orsi, Rita Colonna, Alessandra Esposito, Veronica Maffia, Rossella De Cegli, Margherita Mutarelli, Susanna Ambrosio, Gennaro Tufano, Antonio Grimaldi, Marcella Cesana, Davide Cacchiarelli, Nathalie Delalleau, Gennaro Napolitano, Andrea Ballabio Nov 2023

Tfeb And Tfe3 Control Glucose Homeostasis By Regulating Insulin Gene Expression, Adrien Pasquier, Nunzia Pastore, Luca D'Orsi, Rita Colonna, Alessandra Esposito, Veronica Maffia, Rossella De Cegli, Margherita Mutarelli, Susanna Ambrosio, Gennaro Tufano, Antonio Grimaldi, Marcella Cesana, Davide Cacchiarelli, Nathalie Delalleau, Gennaro Napolitano, Andrea Ballabio

Duncan NRI Faculty and Staff Publications

To fulfill their function, pancreatic beta cells require precise nutrient-sensing mechanisms that control insulin production. Transcription factor EB (TFEB) and its homolog TFE3 have emerged as crucial regulators of the adaptive response of cell metabolism to environmental cues. Here, we show that TFEB and TFE3 regulate beta-cell function and insulin gene expression in response to variations in nutrient availability. We found that nutrient deprivation in beta cells promoted TFEB/TFE3 activation, which resulted in suppression of insulin gene expression. TFEB overexpression was sufficient to inhibit insulin transcription, whereas beta cells depleted of both TFEB and TFE3 failed to suppress insulin gene …


Importance Of Health Policy And Systems Research For Strengthening Rehabilitation In Health Systems: A Call To Action To Accelerate Progress, Walter R Frontera, Wouter Degroote, Abdul Ghaffar, Health Policy & Systems Research For Rehabilitation Group Nov 2023

Importance Of Health Policy And Systems Research For Strengthening Rehabilitation In Health Systems: A Call To Action To Accelerate Progress, Walter R Frontera, Wouter Degroote, Abdul Ghaffar, Health Policy & Systems Research For Rehabilitation Group

Faculty, Staff and Student Publications

No abstract provided.


The Development, Content And Response Process Validation Of A Caregiver-Reported Severity Measure For Cdkl5 Deficiency Disorder, Sonja I Ziniel, Alexandra Mackie, Jacinta Saldaris, Helen Leonard, Peter Jacoby, Eric D Marsh, Bernhard Suter, Elia Pestana-Knight, Heather E Olson, Dana Price, Judith Weisenberg, Rajsekar Rajaraman, Gina Vanderveen, Tim A Benke, Jenny Downs, Scott Demarest Nov 2023

The Development, Content And Response Process Validation Of A Caregiver-Reported Severity Measure For Cdkl5 Deficiency Disorder, Sonja I Ziniel, Alexandra Mackie, Jacinta Saldaris, Helen Leonard, Peter Jacoby, Eric D Marsh, Bernhard Suter, Elia Pestana-Knight, Heather E Olson, Dana Price, Judith Weisenberg, Rajsekar Rajaraman, Gina Vanderveen, Tim A Benke, Jenny Downs, Scott Demarest

Faculty, Staff and Students Publications

BACKGROUND: CDKL5 Deficiency Disorder (CDD) is a severe X-linked developmental and epileptic encephalopathy. Existing developmental outcome measures have floor effects and cannot capture incremental changes in symptoms. We modified the caregiver portion of a CDD clinical severity assessment (CCSA) and assessed content and response-process validity.

METHODS: We conducted cognitive interviews with 15 parent caregivers of 1-39-year-old children with CDD. Caregivers discussed their understanding and concerns regarding appropriateness of both questions and answer options. Item wording and questionnaire structure were adjusted iteratively to ensure questions were understood as intended.

RESULTS: The CCSA was refined during three rounds of cognitive interviews into …


Untargeted Metabolomic Analysis Investigating Links Between Unprocessed Red Meat Intake And Markers Of Inflammation, Alexis C Wood, Goncalo Graca, Meghana Gadgil, Mackenzie K Senn, Matthew A Allison, Ioanna Tzoulaki, Philip Greenland, Timothy Ebbels, Paul Elliott, Mark O Goodarzi, Russell Tracy, Jerome I Rotter, David Herrington Nov 2023

Untargeted Metabolomic Analysis Investigating Links Between Unprocessed Red Meat Intake And Markers Of Inflammation, Alexis C Wood, Goncalo Graca, Meghana Gadgil, Mackenzie K Senn, Matthew A Allison, Ioanna Tzoulaki, Philip Greenland, Timothy Ebbels, Paul Elliott, Mark O Goodarzi, Russell Tracy, Jerome I Rotter, David Herrington

Faculty, Staff and Students Publications

BACKGROUND: Whether red meat consumption is associated with higher inflammation or confounded by increased adiposity remains unclear. Plasma metabolites capture the effects of diet after food is processed, digested, and absorbed, and correlate with markers of inflammation, so they can help clarify diet-health relationships.

OBJECTIVE: To identify whether any metabolites associated with red meat intake are also associated with inflammation.

METHODS: A cross-sectional analysis of observational data from older adults (52.84% women, mean age 63 ± 0.3 y) participating in the Multi-Ethnic Study of Atherosclerosis (MESA). Dietary intake was assessed by food-frequency questionnaire, alongside C-reactive protein (CRP), interleukin-2, interleukin-6, fibrinogen, …


Therapeutic Implications Of Impaired Nuclear Receptor Function And Dysregulated Metabolism In Wilson’S Disease, Clavia Ruth Wooton-Kee Nov 2023

Therapeutic Implications Of Impaired Nuclear Receptor Function And Dysregulated Metabolism In Wilson’S Disease, Clavia Ruth Wooton-Kee

Faculty, Staff and Students Publications

Copper is an essential trace element that is required for the activity of many enzymes and cellular processes, including energy homeostasis and neurotransmitter biosynthesis; however, excess copper accumulation results in significant cellular toxicity. The liver is the major organ for maintaining copper homeostasis. Inactivating mutations of the copper-transporting P-type ATPase, ATP7B, result in Wilson’s disease, an autosomal recessive disorder that requires life-long medicinal therapy or liver transplantation. Current treatment protocols are limited to either sequestration of copper via chelation or reduction of copper absorption in the gut (zinc therapy). The goal of these strategies is to reduce free copper, redox …


The Atoh1-Cre Knock-In Allele Ectopically Labels A Subpopulation Of Amacrine Cells And Bipolar Cells In Mouse Retina, Sih-Rong Wu, Huda Y Zoghbi Nov 2023

The Atoh1-Cre Knock-In Allele Ectopically Labels A Subpopulation Of Amacrine Cells And Bipolar Cells In Mouse Retina, Sih-Rong Wu, Huda Y Zoghbi

Duncan NRI Faculty and Staff Publications

The retina has diverse neuronal cell types derived from a common pool of retinal progenitors. Many molecular drivers, mostly transcription factors, have been identified to promote different cell fates. In Drosophila, atonal is required for specifying photoreceptors. In mice, there are two closely related atonal homologs, Atoh1 and Atoh7. While Atoh7 is known to promote the genesis of retinal ganglion cells, there is no study on the function of Atoh1 in retinal development. Here, we crossed Atoh1Cre/+ mice to mice carrying a Cre-dependent TdTomato reporter to track potential Atoh1-lineage neurons in retinas. We characterized a heterogeneous …


Vertebro-Vertebral Fistula Occlusion Using A Woven Endobridgetm-Device, Rasmus Holmboe Dahl, Mohammad Ghasemi-Rad, Vagn Eskesen, Susanne Christiansen Frevert, Christine Sølling, Goetz Benndorf Nov 2023

Vertebro-Vertebral Fistula Occlusion Using A Woven Endobridgetm-Device, Rasmus Holmboe Dahl, Mohammad Ghasemi-Rad, Vagn Eskesen, Susanne Christiansen Frevert, Christine Sølling, Goetz Benndorf

Faculty, Staff and Students Publications

Vertebro-vertebral fistulas (VVFs) are vascular lesions that may develop after trauma or spontaneously in association with connective tissue disorders. We present a rare case of a post-traumatic VVF in a young patient presenting with a painless swelling and a bruit in her left upper neck. Digital subtraction angiography showed an arteriovenous fistula between the left vertebral artery (VA) and the vertebral venous plexus with significant steal phenomenon. Endovascular therapy was performed using a Woven EndoBridgeTM (WEB)-device combined with coils that allowed preservation of the VA. The patient fully recovered from her symptoms and follow-up imaging showed stable occlusion. In conclusion, …


Dicarboxylic Acylcarnitine Biomarkers In Peroxisome Biogenesis Disorders, Michael F Wangler, Barbara Lesko, Rejwi Dahal, Sharayu Jangam, Pradnya Bhadane, Theodore E Wilson, Molly Mcpheron, Marcus J Miller Nov 2023

Dicarboxylic Acylcarnitine Biomarkers In Peroxisome Biogenesis Disorders, Michael F Wangler, Barbara Lesko, Rejwi Dahal, Sharayu Jangam, Pradnya Bhadane, Theodore E Wilson, Molly Mcpheron, Marcus J Miller

Duncan NRI Faculty and Staff Publications

The peroxisome is an essential eukaryotic organelle with diverse metabolic functions. Inherited peroxisomal disorders are associated with a wide spectrum of clinical outcomes and are broadly divided into two classes, those impacting peroxisome biogenesis (PBD) and those impacting specific peroxisomal factors. Prior studies have indicated a role for acylcarnitine testing in the diagnosis of some peroxisomal diseases through the detection of long chain dicarboxylic acylcarnitine abnormalities (C16-DC and C18-DC). However, there remains limited independent corroboration of these initial findings and acylcarnitine testing for peroxisomal diseases has not been widely adopted in clinical laboratories. To explore the utility of acylcarnitine testing …


Effects Of Jaw Clenching And Mental Stress On Persistent Inward Currents Estimated By Two Different Methods, Ricardo N. O. Mesquita, Janet L. Taylor, Gabriel S. Trajano, Aleš Holobar, Basílio A. M. Gonçalves, Anthony J. Blazevich Nov 2023

Effects Of Jaw Clenching And Mental Stress On Persistent Inward Currents Estimated By Two Different Methods, Ricardo N. O. Mesquita, Janet L. Taylor, Gabriel S. Trajano, Aleš Holobar, Basílio A. M. Gonçalves, Anthony J. Blazevich

Research outputs 2022 to 2026

Spinal motoneuron firing depends greatly on persistent inward currents (PICs), which in turn are facilitated by the neuromodulators serotonin and noradrenaline. The aim of this study was to determine whether jaw clenching (JC) and mental stress (MS), which may increase neuromodulator release, facilitate PICs in human motoneurons. The paired motor unit (MU) technique was used to estimate PIC contribution to motoneuron firing. Surface electromyograms were collected using a 32-channel matrix on gastrocnemius medialis (GM) during voluntary, ramp, plantar flexor contractions. MU discharges were identified, and delta frequency ( F), a measure of recruitment–derecruitment hysteresis, was calculated. Additionally, another technique was …


Prevalent Distribution Of Conscious Processes On Either Side Of The Brain, Sohail Adnan, Mubasher Shah, Muhammad Fateen Rashed, Sadaf Nawab Oct 2023

Prevalent Distribution Of Conscious Processes On Either Side Of The Brain, Sohail Adnan, Mubasher Shah, Muhammad Fateen Rashed, Sadaf Nawab

Journal of Mind and Medical Sciences

Objectives. The brain has an intrinsic tendency for the lateralization of its functions. For instance, the left hemisphere assists in the comprehension and motor expression of language. What remains uncertain is whether conscious processes are also more prevalent in one hemisphere of the brain than the other. The epistemic goal of this research was to address this particular issue. Materials and Methods. We observed the rare pathological event of proximal occlusion of the middle cerebral artery (MCA), which halts blood flow to the central two-thirds of a hemisphere, and examined its effects on consciousness. We aggregated individual scores for eyes-opening …


Grammatical Parallelism In Aphasia: A Lesion-Symptom Mapping Study, William Matchin, Dirk B. Den Ouden, Alexandra Basilakos, Brielle Caserta Stark, Julius Fridriksson, Gregory Hickok Oct 2023

Grammatical Parallelism In Aphasia: A Lesion-Symptom Mapping Study, William Matchin, Dirk B. Den Ouden, Alexandra Basilakos, Brielle Caserta Stark, Julius Fridriksson, Gregory Hickok

Communication Sciences and Disorders Faculty Articles and Research

Sentence structure, or syntax, is potentially a uniquely creative aspect of the human mind. Neuropsychological experiments in the 1970s suggested parallel syntactic production and comprehension deficits in agrammatic Broca’s aphasia, thought to result from damage to syntactic mechanisms in Broca’s area in the left frontal lobe. This hypothesis was sometimes termed overarching agrammatism, converging with developments in linguistic theory concerning central syntactic mechanisms supporting language production and comprehension. However, the evidence supporting an association among receptive syntactic deficits, expressive agrammatism, and damage to frontal cortex is equivocal. In addition, the relationship among a distinct grammatical production deficit in aphasia, …


Anthocyanins: Molecular Aspects On Their Neuroprotective Activity, César A Zaa, Álvaro J Marcelo, Zhiqiang An, José L Medina-Franco, Marco A Velasco-Velázquez Oct 2023

Anthocyanins: Molecular Aspects On Their Neuroprotective Activity, César A Zaa, Álvaro J Marcelo, Zhiqiang An, José L Medina-Franco, Marco A Velasco-Velázquez

Faculty, Staff and Student Publications

Anthocyanins are a type of flavonoids that give plants and fruits their vibrant colors. They are known for their potent antioxidant properties and have been linked to various health benefits. Upon consumption, anthocyanins are quickly absorbed and can penetrate the blood-brain barrier (BBB). Research based on population studies suggests that including anthocyanin-rich sources in the diet lower the risk of neurodegenerative diseases. Anthocyanins exhibit neuroprotective effects that could potentially alleviate symptoms associated with such diseases. In this review, we compiled and discussed a large body of evidence supporting the neuroprotective role of anthocyanins. Our examination encompasses human studies, animal models, …


Rna-Based Translation Activators For Targeted Gene Upregulation, Yang Cao, Huachun Liu, Shannon S Lu, Krysten A Jones, Anitha P Govind, Okunola Jeyifous, Christine Q Simmons, Negar Tabatabaei, William N Green, Jimmy L Holder, Soroush Tahmasebi, Alfred L George, Bryan C Dickinson Oct 2023

Rna-Based Translation Activators For Targeted Gene Upregulation, Yang Cao, Huachun Liu, Shannon S Lu, Krysten A Jones, Anitha P Govind, Okunola Jeyifous, Christine Q Simmons, Negar Tabatabaei, William N Green, Jimmy L Holder, Soroush Tahmasebi, Alfred L George, Bryan C Dickinson

Duncan NRI Faculty and Staff Publications

Technologies capable of programmable translation activation offer strategies to develop therapeutics for diseases caused by insufficient gene expression. Here, we present "translation-activating RNAs" (taRNAs), a bifunctional RNA-based molecular technology that binds to a specific mRNA of interest and directly upregulates its translation. taRNAs are constructed from a variety of viral or mammalian RNA internal ribosome entry sites (IRESs) and upregulate translation for a suite of target mRNAs. We minimize the taRNA scaffold to 94 nucleotides, identify two translation initiation factor proteins responsible for taRNA activity, and validate the technology by amplifying SYNGAP1 expression, a haploinsufficiency disease target, in patient-derived cells. …


Methyl-Branched Liposomes As A Depot For Sustained Drug Delivery, Yang Li, Rachelle Shao, Claire A Ostertag-Hill, Matthew Torre, Ran Yan, Daniel S Kohane Oct 2023

Methyl-Branched Liposomes As A Depot For Sustained Drug Delivery, Yang Li, Rachelle Shao, Claire A Ostertag-Hill, Matthew Torre, Ran Yan, Daniel S Kohane

Duncan NRI Faculty and Staff Publications

Inadequate drug loading and control of payload leakage limit the duration of the effect of liposomal drug carriers and may cause toxicity. Here, we report a liposome system as a depot for sustained drug delivery whose design is inspired by the low permeability of Archaeal membranes to protons and solutes. Incorporating methyl-branched phospholipids into lipid bilayers decreased payload diffusion across liposomal membranes, thereby enhancing the drug load capacity by 10-16% and reducing the release of small molecules in the first 24 h by 40-48%. The in vivo impact of this approach was demonstrated by injection at the sciatic nerve. Methyl-branched …


Tyramine And Its Amtyr1 Receptor Modulate Attention In Honey Bees (Apis Mellifera), Joseph S. Latshaw, Reece E. Mazade, Mary Petersen, Julie A. Mustard, Irina Sinakevitch, Lothar Wissler, Xiaojiao Guo, Chelsea Cook, Hong Lei, Brian Smith Oct 2023

Tyramine And Its Amtyr1 Receptor Modulate Attention In Honey Bees (Apis Mellifera), Joseph S. Latshaw, Reece E. Mazade, Mary Petersen, Julie A. Mustard, Irina Sinakevitch, Lothar Wissler, Xiaojiao Guo, Chelsea Cook, Hong Lei, Brian Smith

School of Integrative Biological & Chemical Sciences Faculty Publications

Animals must learn to ignore stimuli that are irrelevant to survival and attend to ones that enhance survival. When a stimulus regularly fails to be associated with an important consequence, subsequent excitatory learning about that stimulus can be delayed, which is a form of nonassociative conditioning called ‘latent inhibition’. Honey bees show latent inhibition toward an odor they have experienced without association with food reinforcement. Moreover, individual honey bees from the same colony differ in the degree to which they show latent inhibition, and these individual differences have a genetic basis. To investigate the mechanisms that underly individual differences in …


Neuromyelitis Optica Spectrum Disorder: Redefining An Old Disease Present And Future Challenges, Victor M Rivera Oct 2023

Neuromyelitis Optica Spectrum Disorder: Redefining An Old Disease Present And Future Challenges, Victor M Rivera

Faculty, Staff and Students Publications

No abstract provided.


Top Caregiver Concerns In Rett Syndrome And Related Disorders: Data From The Us Natural History Study, Jeffrey L Neul, Timothy A Benke, Eric D Marsh, Bernhard Suter, Lori Silveira, Cary Fu, Sarika U Peters, Alan K Percy Oct 2023

Top Caregiver Concerns In Rett Syndrome And Related Disorders: Data From The Us Natural History Study, Jeffrey L Neul, Timothy A Benke, Eric D Marsh, Bernhard Suter, Lori Silveira, Cary Fu, Sarika U Peters, Alan K Percy

Faculty, Staff and Students Publications

OBJECTIVE: Recent advances in the understanding of neurodevelopmental disorders such as Rett syndrome (RTT) have enabled the discovery of novel therapeutic approaches that require formal clinical evaluation of efficacy. Clinical trial success depends on outcome measures that assess clinical features that are most impactful for affected individuals. To determine the top concerns in RTT and RTT-related disorders we asked caregivers to list the top caregiver concerns to guide the development and selection of appropriate clinical trial outcome measures for these disorders.

METHODS: Caregivers of participants enrolled in the US Natural History Study of RTT and RTT-related disorders (n = 925) …


Maxsim: Multi-Angle-Crossing Structured Illumination Microscopy With Height-Controlled Mirror For 3d Topological Mapping Of Live Cells, Pedro Felipe Gardeazabal Rodriguez, Yigal Lilach, Abhijit Ambegaonkar, Teresa Vitali, Haani Jafri, Hae Won Sohn, Matthew B. Dalva, Susan Pierce, Inhee Chung Oct 2023

Maxsim: Multi-Angle-Crossing Structured Illumination Microscopy With Height-Controlled Mirror For 3d Topological Mapping Of Live Cells, Pedro Felipe Gardeazabal Rodriguez, Yigal Lilach, Abhijit Ambegaonkar, Teresa Vitali, Haani Jafri, Hae Won Sohn, Matthew B. Dalva, Susan Pierce, Inhee Chung

Department of Neuroscience Faculty Papers

Mapping 3D plasma membrane topology in live cells can bring unprecedented insights into cell biology. Widefield-based super-resolution methods such as 3D-structured illumination microscopy (3D-SIM) can achieve twice the axial ( ~ 300 nm) and lateral ( ~ 100 nm) resolution of widefield microscopy in real time in live cells. However, twice-resolution enhancement cannot sufficiently visualize nanoscale fine structures of the plasma membrane. Axial interferometry methods including fluorescence light interference contrast microscopy and its derivatives (e.g., scanning angle interference microscopy) can determine nanoscale axial locations of proteins on and near the plasma membrane. Thus, by combining super-resolution lateral imaging of 2D-SIM …