Medical Neurobiology Commons^™

Apigenin Alleviates Autistic-Like Stereotyped Repetitive Behaviors And Mitigates Brain Oxidative Stress In Mice, Petrilla Jayaprakash, Dmytro Isaev, Keun-Hang Susan Yang, Rami Beiram, Murat Oz, Bassem Sadek

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Studying the involvement of nicotinic acetylcholine receptors (nAChRs), specifically α7-nAChRs, in neuropsychiatric brain disorders such as autism spectrum disorder (ASD) has gained a growing interest. The flavonoid apigenin (APG) has been confirmed in its pharmacological action as a positive allosteric modulator of α7-nAChRs. However, there is no research describing the pharmacological potential of APG in ASD. The aim of this study was to evaluate the effects of the subchronic systemic treatment of APG (10–30 mg/kg) on ASD-like repetitive and compulsive-like behaviors and oxidative stress status in the hippocampus and cerebellum in BTBR mice, utilizing the reference drug aripiprazole (ARP, 1 …

The Feigned Annoyance And Frustration Test To Activate The Sympathoadrenal Medullary System, Ted W. Gehrig Iii, Lee S. Berk, Robert I. Dudley, Jo A. Smith, Lida Gharibvand, Everett B. Lohman Iii

Physical Therapy Faculty Articles and Research

When perceived as threatening, social interactions have been shown to trigger the sympathoadrenal medullary system as well as the hypothalamic-pituitary-adrenal axis resulting in a physiologic stress response. The allostatic load placed on human health and physiology in the context of acute and chronic stress can have profound health consequences. The purpose of this study was to develop a protocol for a lab-based stress stimulus using social-evaluative threat. While several valid, stress-stimulating protocols exist, we sought to develop one that triggered a physiologic response, did not require significant lab resources, and could be completed in around 10 min. We included 53 …

Neuromodulation Of Mouse Auditory Cortex Using Focused Ultrasound, Jacob Hehir

NYMC Student Theses and Dissertations

Neurological diseases impose a large health and financial burden for nations worldwide. Current treatments for many conditions are limited to pharmacological or invasive surgical approaches. Neuromodulation is an alternative therapy wherein electrical currents, magnetic fields, or electromagnetic waves are used to noninvasively modify brain function. Focused ultrasound (FUS) has been shown to alter neural activity, theoretically with much higher spatial resolution than other neuromodulation techniques. However, these predictions assume that neuromodulatory effects are constrained to the acoustic focus. Given that the architecture of neural circuitry in the cerebral cortex supports delicately balanced lateral processing on spatial scales that may exceed …

The Impact Of Neurological Diseases In Kisumu, Kenya: Case Studies At Jootrh And Kcrh, Jack F. Dunham

Independent Study Project (ISP) Collection

Introduction: The burden that neurological diseases put on health systems is high, and growing across the globe, especially in Low- and Middle-Income Countries (LMICs) like Kenya. For this reason, our study sought out to study the burden and impact of neurological diseases at Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH) and Kisumu County Referral Hospital (KCRH), which are in Western Kenya.

Methods: Utilizing data from handwritten patient records spanning 23 months, our study collected said data and analyzed the prevalence, incidence, distribution, and outcomes of different neurological diseases as they impact the Kisumu community.

Results/Discussion: Comparing …

Exploring Neuroplasticity Changes In Neurotoxin-Induced Parkinson’S Disease: A Preliminary Analysis Using Transcranial Magnetic Stimulation, Tomas Gomez Jr., Daniel Salinas, Kelsey Potter-Baker, Nawaz Hack, Ramu Vadukapuram

Research Symposium

Background: Parkinson’s disease (PD) is a neurodegenerative condition that affects movement, cognition, gait, and significantly impacts one's quality of life. Studies have suggested that neurotoxin pre-exposure is related to PD pathology and progressive motor/non-motor deficits, though it remains unclear how neurotoxin exposure affects neuroplasticity. The present study aimed to examine neurotoxin–induced PD-associated neuroplasticity changes in relationship to mental acuity and PD motor functionalities.

Methods: 7 voluntary participants experiencing early-stage PD symptoms with self-reported neurotoxin pre-exposure were enrolled in the longitudinal, repeated-measures clinical study; 2 sex-matched, age-matched, and occupation-matched healthy subjects were recruited for controlled comparative analysis (n=9). UTRGV’s Institute …

Cns-Associated Macrophages Contribute To Intracerebral Aneurysm Pathophysiology, Martina Glavan, Ana Jelic, Damien Levard, Juhana Frösen, Sara Keränen, Bart A A Franx, Ana-Rita Bras, Estelle R Louet, Ádám Dénes, Mario Merlini, Denis Vivien, Marina Rubio

Faculty, Staff and Student Publications

Simple Summary

Vestibular schwannoma (VS), benign cranial nerve sheath tumors of the vestibulocochlear nerve, lack efficacious systemic therapies, especially if they develop in a NF2-related schwannomatosis (NF2) background. They cause hearing loss, tinnitus and balance problems. Metastasis associated in colon cancer 1 (MACC1) is a key driver of metastasis. Although MACC1 expression is associated with highly malignant tumors and VS are considered benign, both are attached to the HGF/MET signaling pathway and MACC1 is a candidate gene localized at a hearing loss-related gene locus. Therefore, it was investigated whether MACC1 might be involved in VS pathogenesis. Surprisingly, MACC1 expression …

A Novel Spatiotemporal Graph Convolutional Network Framework For Functional Connectivity Biomarkers Identification Of Alzheimer’S Disease, Ying Zhang, Le Xue, Shuoyan Zhang, Jiacheng Yang, Qi Zhang, Min Wang, Luyao Wang, Mingkai Zhang, Jiehui Jiang, Yunxia Li

Faculty, Staff and Student Publications

BACKGROUND: Functional connectivity (FC) biomarkers play a crucial role in the early diagnosis and mechanistic study of Alzheimer's disease (AD). However, the identification of effective FC biomarkers remains challenging. In this study, we introduce a novel approach, the spatiotemporal graph convolutional network (ST-GCN) combined with the gradient-based class activation mapping (Grad-CAM) model (STGC-GCAM), to effectively identify FC biomarkers for AD.

METHODS: This multi-center cross-racial retrospective study involved 2,272 participants, including 1,105 cognitively normal (CN) subjects, 790 mild cognitive impairment (MCI) individuals, and 377 AD patients. All participants underwent functional magnetic resonance imaging (fMRI) and T1-weighted MRI scans. In this study, …

Antioxidant Responses And Phytochemical Accumulation In Raphanus Species Sprouts Through Elicitors And Predictive Models Under High Temperature Stress, María-Trinidad Toro, Roberto Fustos-Toribio, Jaime Ortiz, José Becerra, Nelson Zapata, María Dolores López-Belchí

Faculty, Staff and Students Publications

Crop production is being impacted by higher temperatures, which can decrease food yield and pose a threat to human nutrition. In the current study, edible and wild radish sprouts were exposed to elevated growth temperatures along with the exogenous application of various elicitors to activate defense mechanisms. Developmental traits, oxidative damage, glucosinolate and anthocyanin content, and antioxidant capacity were evaluated alongside the development of a predictive model. A combination of four elicitors (citric acid, methyl jasmonate—MeJa, chitosan, and K2SO4) and high temperatures were applied. The accumulation of bioactives was significantly enhanced through the application of two elicitors, K2SO4 and methyl …

Caldendrin Is A Repressor Of Piezo2 Channels And Touch Sensation In Mice, Josue A Lopez, Luis O Romero, Wai-Lin Kaung, J Wesley Maddox, Valeria Vásquez, Amy Lee

Faculty, Staff and Student Publications

The sense of touch is crucial for cognitive, emotional, and social development and relies on mechanically activated (MA) ion channels that transduce force into an electrical signal. Despite advances in the molecular characterization of these channels, the physiological factors that control their activity are poorly understood. Here, we used behavioral assays, electrophysiological recordings, and various mouse strains (males and females analyzed separately) to investigate the role of the calmodulin-like Ca2+ sensor, caldendrin, as a key regulator of MA channels and their roles in touch sensation. In mice lacking caldendrin (Cabp1 KO), heightened responses to tactile stimuli correlate with enlarged …

Neural Correlates Of Fear Extinction: Investing The Impact Of Puberty And Sex In Children And Adolescents Through Neuroimaging, Sneha Bhargava, Clara Zundel, Samantha Ely, Carmen Carpenter, Reem Tamimi, Leah Gowatch, Mackenna Shampine, Emilie-Clare O'Mara, Jovan Jande, Shravya Chanamolu, Ahmad Almaat, Hilary Marusak

Medical Student Research Symposium

Fear-based disorders, including anxiety and posttraumatic stress disorder, are more prevalent in females than males. Steroid hormones (e.g., estradiol) are involved in fear extinction learning and later recall—a process implicated in the pathophysiology of fear-based disorders. Fear-based disorders commonly emerge during the transition from childhood to adolescence, a period marked by the onset of puberty and a natural increase of steroid hormones. Here, we examined the effects of puberty, sex, and their interaction on extinction recall and underlying neural circuitry in youth. Eighty-five youth (6-17 years, 46% female) completed a two-day Pavlovian fear extinction paradigm while undergoing functional magnetic resonance …

The Emerging Importance Of Skull-Brain Interactions In Traumatic Brain Injury, Peixi Zhao, Rui Jin, Bin Zhao, Le Han, Wenjuan Chen, Nina Hao, Yi Cui, Ankit Madan, Joy Awosika, Shane Lloyd, Yili Zhang

Faculty, Staff and Student Publications

Background and Objective

Immune checkpoint inhibitors (ICIs) have been widely applied and studied in the treatment of gastrointestinal (GI) cancers, and have achieved good results. However, in clinical practice, it has been observed that only some patients respond well to ICIs, and some patients may experience various degrees of adverse reactions during the treatment. Timely evaluation of the potential therapeutic effects and adverse reactions of ICIs for patients has important clinical significance. This review aimed to summarize recent progress regarding efficacy-associated biomarkers for ICIs in GI cancer.

Methods

The literature on ICI treatment in GI cancers was searched in the …

Potential Value Of A Rapid Syndromic Multiplex Pcr For The Diagnosis Of Native And Prosthetic Joint Infections: A Real-World Evidence Study, Stéphanie Pascual, Brooklyn Noble, Nusreen Ahmad-Saeed, Catherine Aldridge, Simone Ambretti, Sharon Amit, Rachel Annett, Shaan Ashk O'Shea, Anna Maria Barbui, Gavin Barlow, Lucinda Barrett, Mario Berth, Alessandro Bondi, Nicola Boran, Sara E Boyd, Catarina Chaves, Martin Clauss, Peter Davies, Ileana T Dianzo-Delgado, Jaime Esteban, Stefan Fuchs, Lennart Friis-Hansen, Daniel Goldenberger, Andrej Golle, Juha O Groonroos, Ines Hoffmann, Tomer Hoffmann, Harriet Hughes, Marina Ivanova, Peter Jezek, Gwennan Jones, Zeynep Ceren Karahan, Cornelia Lass-Flörl, Frédéric Laurent, Laura Leach, Matilde Lee Horsbøll Pedersen, Caroline Loiez, Maureen Lynch, Robert J Maloney, Martin Marsh, Olivia Milburn, Shanine Mitchell, Luke S P Moore, Lynn Moffat, Marianna Murdjeva, Michael E Murphy, Deepa Nayar, Giacomo Nigrisoli, Fionnuala O'Sullivan, Büşra Öz, Teresa Peach, Christina Petridou, Mojgan Prinz, Mitja Rak, Niamh Reidy, Gian Maria Rossolini, Anne-Laure Roux, Patricia Ruiz-Garbajosa, Kordo Saeed, Llanos Salar-Vidal, Carlos Salas Venero, Mathyruban Selvaratnam, Eric Senneville, Peter Starzengruber, Ben Talbot, Vanessa Taylor, Rihard Trebše, Deborah Wearmouth, Birgit Willinger, Marjan Wouthuyzen-Bakker, Brianne Couturier, Florence Allantaz

Faculty, Staff and Student Publications

Introduction: The BIOFIRE Joint Infection (JI) Panel is a diagnostic tool that uses multiplex-PCR testing to detect microorganisms in synovial fluid specimens from patients suspected of having septic arthritis (SA) on native joints or prosthetic joint infections (PJIs). Methods: A study was conducted across 34 clinical sites in 19 European and Middle Eastern countries from March 2021 to June 2022 to assess the effectiveness of the BIOFIRE JI Panel. Results: A total of 1527 samples were collected from patients suspected of SA or PJI, with an overall agreement of 88.4 % and 85 % respectively between the …

Shewanella Phage Encoding A Putative Anti-Crispr-Like Gene Represents A Novel Potential Viral Family, Hongmin Wang, Kaiyang Zheng, Min Wang, Keran Ma, Linyi Ren, Ruizhe Guo, Lina Ma, Hong Zhang, Yundan Liu, Yao Xiong, Miaolan Wu, Hongbing Shao, Yeong Yik Sung, Wen Jye Mok, Li Lian Wong, Andrew Mcminn, Yantao Liang

Faculty, Staff and Student Publications

Shewanella is a prevalent bacterial genus in deep-sea environments including marine sediments, exhibiting diverse metabolic capabilities that indicate its significant contributions to the marine biogeochemical cycles. However, only a few Shewanella phages were isolated and deposited in the NCBI database. In this study, we report the isolation and characterization of a novel Shewanella phage, vB_SbaS_Y11, that infects Shewanella KR11 and was isolated from the sewage in Qingdao, China. Transmission electron microscopy revealed that vB_SbaS_Y11 has an icosahedral head and a long tail. The genome of vB_SbaS_Y11 is a linear, double-stranded DNA with a length of 62,799 bp and a G+C …

Insights Of Clinical Significance From 109 695 Solid Tumor Tissue-Based Comprehensive Genomic Profiles, Andreas M Heilmann, Jonathan W Riess, Margaret Mclaughlin-Drubin, Richard S P Huang, Meghann Hjulstrom, James Creeden, Brian M Alexander, Rachel L Erlich

Faculty, Staff and Student Publications

BACKGROUND: FoundationOneCDx is approved in the US and Japan as a companion diagnostic test to identify patients with cancer who may benefit from treatment with 30 drug therapies in the US and 23 in Japan. Tumor profiling with FoundationOneCDx also detects genomic findings with evidence of clinical significance that may inform clinical care decisions beyond companion diagnostic claims. This observational study reports the breadth and impact of clinical decision insights from FoundationOneCDx solid tumor profiles.

MATERIALS AND METHODS: Consecutive test result reports for patients with solid tumor diagnoses (n = 109 695) were retrospectively analyzed for clinically significant predictive, prognostic, …

Sarin-Induced Neuroinflammation In Mouse Brain Is Attenuated By The Caspase Inhibitor Q-Vd-Oph, Ekta J. Shah, William C. Grunwald Jr., Teresa L. Garrett, Thomas L. Brown, David R. Cool

Neuroscience, Cell Biology & Physiology Faculty Publications

Organophosphates cause hyperstimulation of the central nervous system, leading to extended seizures, convulsions, and brain damage. Sarin is a highly toxic organophosphate nerve agent that has been employed in several terrorist attacks. The prolonged toxicity of sarin may be enhanced by the neuroinflammatory response initiated by the inflammasome, caspase involvement, and generation/release of proinflammatory cytokines. Since neurodegeneration and neuroinflammation are prevalent in sarin-exposed animals, we were interested in evaluating the capacity of quinolyl-valyl-O-methylaspartyl-[-2,6-difluorophenoxy]-methyl ketone (Q-VD-OPh), a pan caspase inhibitor to attenuate neuroinflammation following sarin exposure. To test this hypothesis, sarin-exposed C57BL/6 mice were treated with Q-VD-OPh or negative control quinolyl-valyl-O-methylglutamyl-[-2,6-difluorophenoxy]-methyl …

Boosting The Electron Beam Transmittance Of Field Emission Cathode Using A Self-Charging Gate, Dongyang Xiao, Huanhuan Du, Leimeng Sun, Xiaochen Suo, Yurong Wang, Yili Zhang, Shaolin Zhang, Shuangyang Kuang, Fangjing Hu, Liangcheng Tu, Daren Yu, Peiyi Song

Faculty, Staff and Student Publications

The gate-type carbon nanotubes cathodes exhibit advantages in long-term stable emission owing to the uniformity of electrical field on the carbon nanotubes, but the gate inevitably reduces the transmittance of electron beam, posing challenges for system stabilities. In this work, we introduce electron beam focusing technique using the self-charging SiN_x/Au/Si gate. The potential of SiN_x is measured to be approximately −60 V quickly after the cathode turning on, the negative potential can be maintained as the emission goes on. The charged surface generates rebounding electrostatic forces on the following electrons, significantly focusing the electron beam on the …

Increased Cysteinyl-Trna Synthetase Drives Neuroinflammation In Alzheimer’S Disease, Xiu-Hong Qi, Peng Chen, Yue-Ju Wang, Zhe-Ping Zhou, Xue-Chun Liu, Hui Fang, Chen-Wei Wang, Ji Liu, Rong-Yu Liu, Han-Kui Liu, Zhen-Xin Zhang, Jiang-Ning Zhou

Faculty, Staff and Student Publications

Background

Microglia-mediated neuroinflammation in Alzheimer’s disease (AD) is not only a response to pathophysiological events, but also plays a causative role in neurodegeneration. Cytoplasmic cysteinyl-tRNA synthetase (CARS) is considered to be a stimulant for immune responses to diseases; however, it remains unknown whether CARS is involved in the pathogenesis of AD.

Methods

Postmortem human temporal cortical tissues at different Braak stages and AD patient-derived serum samples were used to investigate the changes of CARS levels in AD by immunocytochemical staining, real-time PCR, western blotting and ELISA. After that, C57BL/6J and APP/PS1 transgenic mice and BV-2 cell line were used to …

Blood And Mri Biomarkers Of Mild Traumatic Brain Injury In Non-Concussed Collegiate Football Players, Eunhan Cho, Joshua Granger, Bailey Theall, Nathan Lemoine, Derek Calvert, Jack Marucci, Shelly Mullenix, Hollis O’Neal, Tomas Jacome, Brian A. Irving, Neil M. Johannsen, Owen Carmichael, Guillaume Spielmann

School of Medicine Faculty Publications

Football has one of the highest incidence rates of mild traumatic brain injury (mTBI) among contact sports; however, the effects of repeated sub-concussive head impacts on brain structure and function remain under-studied. We assessed the association between biomarkers of mTBI and structural and functional MRI scans over an entire season among non-concussed NCAA Division I linemen and non-linemen. Concentrations of S100B, GFAP, BDNF, NFL, and NSE were assessed in 48 collegiate football players (32 linemen; 16 non-linemen) before the start of pre-season training (pre-camp), at the end of pre-season training (pre-season), and at the end of the competitive season (post-season). …

Preclinical Repurposing Of Sitagliptin As A Drug Candidate For Colorectal Cancer By Targeting Cd24/Ctnnb1/Sox4-Centered Signaling Hub, Jing-Wen Shih, Alexander T H Wu, Ntlotlang Mokgautsi, Po-Li Wei, Yan-Jiun Huang

Faculty, Staff and Student Publications

Despite significant advances in treatment modalities, colorectal cancer (CRC) remains a poorly understood and highly lethal malignancy worldwide. Cancer stem cells (CSCs) and the tumor microenvironment (TME) have been shown to play critical roles in initiating and promoting CRC progression, metastasis, and treatment resistance. Therefore, a better understanding of the underlying mechanisms contributing to the generation and maintenance of CSCs is crucial to developing CSC-specific therapeutics and improving the current standard of care for CRC patients. To this end, we used a bioinformatics approach to identify increased CD24/SOX4 expression in CRC samples associated with poor prognosis. We also …

Vibrio Cyclitrophicus Phage Encoding Gene Transfer Agent Fragment, Representing A Novel Viral Family, Yao Xiong, Keran Ma, Xiao Zou, Yantao Liang, Kaiyang Zheng, Tiancong Wang, Hong Zhang, Yue Dong, Ziyue Wang, Yundan Liu, Hongbing Shao, Andrew Mcminn, Min Wang

Faculty, Staff and Student Publications

Vibrio is a prevalent bacterial genus in aquatic environments and exhibits diverse metabolic capabilities, playing a vital role in marine biogeochemical cycles. This study isolated a novel virus infecting Vibrio cyclitrophicus, vB_VviC_ZQ26, from coastal waters near Qingdao, China. The vB_VviC_ZQ26 comprises a linear double-stranded DNA genome with a length of 42,982 bp and a G + C content of 43.21 %, encoding 72 putative open reading frames (ORFs). Transmission electron microscope characterization indicates a siphoviral-morphology of vB_VviC_ZQ26. Nucleic-acids-wide analysis indicates a tetranucleotide frequency deviation for genomic segments encoding putative gene transfer agent protein (GTA) and coil-containing protein, implying divergent …