College of Sciences
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Browsing College of Sciences by Department "Neuroscience, Developmental and Regenerative Biology"
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Item A De Novo Sequence Variant in Barrier-to-Autointegration Factor Is Associated with Dominant Motor Neuronopathy(2023-03-09) Marcelot, Agathe; Rodriguez-Tirado, Felipe; Cuniasse, Philippe; Joiner, Mei-ling; Miron, Simona; Soshnev, Alexey A.; Fang, Mimi; Pufall, Miles A.; Mathews, Katherine D.; Moore, Steven A.; Zinn-Justin, Sophie; Geyer, Pamela K.Barrier-to-autointegration factor (BAF) is an essential component of the nuclear lamina. Encoded by BANF1, this DNA binding protein contributes to the regulation of gene expression, cell cycle progression, and nuclear integrity. A rare recessive BAF variant, Ala12Thr, causes the premature aging syndrome, Néstor–Guillermo progeria syndrome (NGPS). Here, we report the first dominant pathogenic BAF variant, Gly16Arg, identified in a patient presenting with progressive neuromuscular weakness. Although disease variants carry nearby amino acid substitutions, cellular and biochemical properties are distinct. In contrast to NGPS, Gly16Arg patient fibroblasts show modest changes in nuclear lamina structure and increases in repressive marks associated with heterochromatin. Structural studies reveal that the Gly16Arg substitution introduces a salt bridge between BAF monomers, reducing the conformation ensemble available to BAF. We show that this structural change increases the double-stranded DNA binding affinity of BAF Gly16Arg. Together, our findings suggest that BAF Gly16Arg has an increased chromatin occupancy that leads to epigenetic changes and impacts nuclear functions. These observations provide a new example of how a missense mutation can change a protein conformational equilibrium to cause a dominant disease and extend our understanding of mechanisms by which BAF function impacts human health.Item A bacterial two-hybrid system that utilizes Gateway cloning for rapid screening of protein-protein interactions(Future Science Group, 2010-11) Karna, S. L. Rajasekhar; Zogaj, Xhavit; Barker, Jeffrey R.; Seshu, Janakiram; Dove, Simon L.; Klose, Karl E.Comprehensive clone sets representing the entire genome now exist for a large number of organisms. The Gateway entry clone sets are a particularly useful means to study gene function, given the ease of introduction into any Gateway-suitable destination vector. We have adapted a bacterial two-hybrid system for use with Gateway entry clone sets, such that potential interactions between proteins encoded within these clone sets can be determined by new destination vectors. We show that utilizing the Gateway clone sets for Francisella tularensis and Vibrio cholerae, known interactions between F. tularensis IglA and IglB and V. cholerae VipA and VipB could be confirmed with these destination vectors. Moreover, the introduction of unique tags into each vector allowed for visualization of the expressed hybrid proteins via Western immunoblot. This Gateway-suitable bacterial two-hybrid system provides a new tool for rapid screening of protein-protein interactions.Item Biophotons and Emergence of Quantum Coherence—A Diffusion Entropy Analysis(MDPI, 2021-04-29) Benfatto, Maurizio; Pace, Elisabetta; Curceanu, Catalina; Scordo, Alessandro; Clozza, Alberto; Davoli, Ivan; Lucci, Massiliano; Francini, Roberto; De Matteis, Fabio; Grandi, Maurizio; Tuladhar, Rohisha; Grigolini, PaoloWe study the emission of photons from germinating seeds using an experimental technique designed to detect light of extremely small intensity. We analyze the dark count signal without germinating seeds as well as the photon emission during the germination process. The technique of analysis adopted here, called diffusion entropy analysis (DEA) and originally designed to measure the temporal complexity of astrophysical, sociological and physiological processes, rests on Kolmogorov complexity. The updated version of DEA used in this paper is designed to determine if the signal complexity is generated either by non-ergodic crucial events with a non-stationary correlation function or by the infinite memory of a stationary but non-integrable correlation function or by a mixture of both processes. We find that dark count yields the ordinary scaling, thereby showing that no complexity of either kinds may occur without any seeds in the chamber. In the presence of seeds in the chamber anomalous scaling emerges, reminiscent of that found in neuro-physiological processes. However, this is a mixture of both processes and with the progress of germination the non-ergodic component tends to vanish and complexity becomes dominated by the stationary infinite memory. We illustrate some conjectures ranging from stress induced annihilation of crucial events to the emergence of quantum coherence.Item Challenges and Strategies of Successful Mentoring: The Perspective of LEADS Scholars and Mentors from Minority Serving Institutions(2021-06-07) Talbert, Patricia Y.; Perry, George; Ricks-Santi, Luisel; Soto de Laurido, Lourdes E.; Shaheen, Magda; Seto, Todd; Kumar, Deepak; Quarshie, Alexander; Thakar, Maya; Rubio, Doris M.Mentoring continues to be a salient conversation in academia among junior and senior faculty and administrators. Mentors provide guidance and structure to junior faculty so that they can meet their academic and professional goals. Mentors also convey skills in balancing life and academic pursuits. Therefore, the purpose of this descriptive study was to provide additional insight from a training program called Leading Emerging and Diverse Scientists to Success (LEADS) regarding successful strategies and challenges of mentoring relating to lessons learned from the scholars and mentees’ perspective. The LEADS program provided multiple training platforms to increase skills and knowledge regarding research to promote expertise in grant writing and submission for funding opportunities among diverse scientists. These findings reinforce the knowledge about the value of a mentor in helping define the research pathway of their mentee and underscoring the importance of mentoring.Item Community Engagement Practices at Research Centers in U.S. Minority Institutions: Priority Populations and Innovative Approaches to Advancing Health Disparities Research(2021-06-21) Henry Akintobi, Tabia; Sheikhattari, Payam; Shaffer, Emma; Evans, Christina L.; Braun, Kathryn L.; Sy, Angela U.; Mancera, Bibiana; Campa, Adriana; Miller, Stephania T.; Sarpong, Daniel; Holliday, Rhonda; Jimenez-Chavez, Julio; Khan, Shafiq; Hinton, Cimona; Sellars-Bates, Kimberly; Ajewole, Veronica; Teufel-Shone, Nicolette I.; McMullin, Juliet; Suther, Sandra; Kimbro, K. Sean; Taylor, Lorraine; Velez Vega, Carmen M.; Williams, Carla; Perry, George; Zuchner, Stephan; Marzan Rodriguez, Melissa; Tchounwou, Paul B.This paper details U.S. Research Centers in Minority Institutions (RCMI) Community Engagement Cores (CECs): (1) unique and cross-cutting components, focus areas, specific aims, and target populations; and (2) approaches utilized to build or sustain trust towards community participation in research. A mixed-method data collection approach was employed for this cross-sectional study of current or previously funded RCMIs. A total of 18 of the 25 institutions spanning 13 U.S. states and territories participated. CEC specific aims were to support community engaged research (94%); to translate and disseminate research findings (88%); to develop partnerships (82%); and to build capacity around community research (71%). Four open-ended questions, qualitative analysis, and comparison of the categories led to the emergence of two supporting themes: (1) establishing trust between the community-academic collaborators and within the community and (2) building collaborative relationships. An overarching theme, building community together through trust and meaningful collaborations, emerged from the supporting themes and subthemes. The RCMI institutions and their CECs serve as models to circumvent the historical and current challenges to research in communities disproportionately affected by health disparities. Lessons learned from these cores may help other institutions who want to build community trust in and capacities for research that addresses community-related health concerns.Item Conserved Transcriptome Features Define Prepubertal Primate Spermatogonial Stem Cells as Adark Spermatogonia and Identify Unique Regulators(2023-03-01) Singh, Anukriti; Hermann, Brian P.Antineoplastic treatments for cancer and other non-malignant disorders can result in long-term or permanent male infertility by ablating spermatogonial stem cells (SSCs). SSC transplantation using testicular tissue harvested before a sterilizing treatment is a promising approach for restoring male fertility in these cases, but a lack of exclusive biomarkers to unequivocally identify prepubertal SSCs limits their therapeutic potential. To address this, we performed single-cell RNA-seq on testis cells from immature baboons and macaques and compared these cells with published data from prepubertal human testis cells and functionally-defined mouse SSCs. While we found discrete groups of human spermatogonia, baboon and rhesus spermatogonia appeared less heterogenous. A cross-species analysis revealed cell types analogous to human SSCs in baboon and rhesus germ cells, but a comparison with mouse SSCs revealed significant differences with primate SSCs. Primate-specific SSC genes were enriched for components and regulators of the actin cytoskeleton and participate in cell-adhesion, which may explain why the culture conditions for rodent SSCs are not appropriate for primate SSCs. Furthermore, correlating the molecular definitions of human SSC, progenitor and differentiating spermatogonia with the histological definitions of A dark/A pale spermatogonia indicates that both SSCs and progenitor spermatogonia are A dark, while A pale spermatogonia appear biased towards differentiation. These results resolve the molecular identity of prepubertal human SSCs, define novel pathways that could be leveraged for advancing their selection and propagation in vitro, and confirm that the human SSC pool resides entirely within A dark spermatogonia.Item Construction of targeted insertion mutations in Francisella tularensis subsp. novicida(Future Science Group, 2007-10) Liu, Jirong; Zogaj, Xhavit; Barker, Jeffrey R.; Klose, Karl E.Francisella tularensis is one of the most deadly bacterial agents, yet most of the genetic determinants of pathogenesis are still unknown. We have developed an efficient targeted mutagenesis strategy in the model organism F. tularensis subsp. novicida by utilizing universal priming of optimized antibiotic resistance cassettes and splicing by overlap extension (SOE). This process enables fast and efficient construction of targeted insertion mutations in F. tularensis subsp. novicida that have characteristics of nonpolar mutations; optimized targeted mutagenesis strategies will promote the study of this mysterious bacterium and facilitate vaccine development against tularemia. Moreover, the general strategy of gene disruption by PCR-based antibiotic resistance cassette insertion is broadly applicable to many bacterial species.Item Correlated Oxidative Stress and Mitochondrial Abnormalities in Aging are Discontinuous with Alzheimer’s Disease(Office of the Vice President for Research, 2018) Nguyen, Richard Q.; Bach, Stephan H.; Phelix, Clyde F.; Perry, GeorgeOxidative stress and mitochondrial damage precede Alzheimer’s disease (AD) hallmark pathologies, neurofibrillarytangles (NFT), and senile plaques.Mitochondria’s exact role in oxidation of pyruvate and NADH play a critical role in oxidative damage. We conducted this study to identify the relationship of oxidized RNA, 8--OHG biomarker, and mtDNA accumulation in AD and aging individuals. Abnormalities were examined by using densitometry of hippocampal pyramidal neurons: mtDNA accumulation as a marker of mitophagy and oxidative damage by 8-OHG. Among aging individuals, 8-OHG and mtDNA accumulation were highly correlated (R2=0.87,p=0.0007). While both 8-OHG and mtDNA were at higher levels in AD individuals, they were uncorrelated (R2=0.4418,p=0.07).In AD individuals, 8-OHG was inversely correlated with amyloid-β, while in aging, there was no significant correlation. These results suggest the discontinuity of similarities between aging and AD. These findings also indicate that the onset of AD is marked by a pleotrophic change in oxidative stress, one characterized by a change from mitochondria degeneration to amyloid-β independency.Item Evasion of IFN-γ Signaling by Francisella novicida Is Dependent upon Francisella Outer Membrane Protein C(Public Library of Science, 2011-03-31) Nallaparaju, Kalyan C.; Yu, Jieh-Juen; Rodriguez, Stephen A.; Zogaj, Xhavit; Manam, Srikanth; Guentzel, M. Neal; Seshu, Janakiram; Murthy, Ashlesh K.; Chambers, James P.; Klose, Karl E.; Arulanandam, Bernard P.Background: Francisella tularensis is a Gram-negative facultative intracellular bacterium and the causative agent of the lethal disease tularemia. An outer membrane protein (FTT0918) of F. tularensis subsp. tularensis has been identified as a virulence factor. We generated a F. novicida (F. tularensis subsp. novicida) FTN_0444 (homolog of FTT0918) fopC mutant to study the virulence-associated mechanism(s) of FTT0918. Methods and Findings: The ΔfopC strain phenotype was characterized using immunological and biochemical assays. Attenuated virulence via the pulmonary route in wildtype C57BL/6 and BALB/c mice, as well as in knockout (KO) mice, including MHC I, MHC II, and µmT (B cell deficient), but not in IFN-γ or IFN-γR KO mice was observed. Primary bone marrow derived macrophages (BMDM) prepared from C57BL/6 mice treated with rIFN-γ exhibited greater inhibition of intracellular ΔfopC than wildtype U112 strain replication; whereas, IFN-γR KO macrophages showed no IFN-γ-dependent inhibition of ΔfopC replication. Moreover, phosphorylation of STAT1 was downregulated by the wildtype strain, but not the fopC mutant, in rIFN-γ treated macrophages. Addition of NG-monomethyl-L-arginine, an NOS inhibitor, led to an increase of ΔfopC replication to that seen in the BMDM unstimulated with rIFN-γ. Enzymatic screening of ΔfopC revealed aberrant acid phosphatase activity and localization. Furthermore, a greater abundance of different proteins in the culture supernatants of ΔfopC than that in the wildtype U112 strain was observed. Conclusions: F. novicida FopC protein facilitates evasion of IFN-γ-mediated immune defense(s) by down-regulation of STAT1 phosphorylation and nitric oxide production, thereby promoting virulence. Additionally, the FopC protein also may play a role in maintaining outer membrane stability (integrity) facilitating the activity and localization of acid phosphatases and other F. novicida cell components.Item Exploring Molecular Targets for Mitochondrial Therapies in Neurodegenerative Diseases(2023-08-06) Plascencia-Villa, Germán; Perry, GeorgeThe progressive deterioration of function and structure of brain cells in neurodegenerative diseases is accompanied by mitochondrial dysfunction, affecting cellular metabolism, intracellular signaling, cell differentiation, morphogenesis, and the activation of programmed cell death. However, most of the efforts to develop therapies for Alzheimer's and Parkinson's disease have focused on restoring or maintaining the neurotransmitters in affected neurons, removing abnormal protein aggregates through immunotherapies, or simply treating symptomatology. However, none of these approaches to treating neurodegeneration can stop or reverse the disease other than by helping to maintain mental function and manage behavioral symptoms. Here, we discuss alternative molecular targets for neurodegeneration treatments that focus on mitochondrial functions, including regulation of calcium ion (Ca2+) transport, protein modification, regulation of glucose metabolism, antioxidants, metal chelators, vitamin supplementation, and mitochondrial transference to compromised neurons. After pre-clinical evaluation and studies in animal models, some of these therapeutic compounds have advanced to clinical trials and are expected to have positive outcomes in subjects with neurodegeneration. These mitochondria-targeted therapeutic agents are an alternative to established or conventional molecular targets that have shown limited effectiveness in treating neurodegenerative diseases.Item Fetal brain vulnerability to SARS-CoV-2 infection(Elsevier, 2023-08) McMahon, Courtney L.; Castro, Joshua; Silvas, Jesus; Muniz Perez, Aranis; Estrada, Manuel; Carrion, Ricardo Jr.; Hsieh, JennyWhether or not SARS-CoV-2 can cross from mother to fetus during a prenatal infection has been controversial; however, recent evidence such as viral RNA detection in umbilical cord blood and amniotic fluid, as well as the discovery of additional entry receptors in fetal tissues suggests a potential for viral transmission to and infection of the fetus. Furthermore, neonates exposed to maternal COVID-19 during later development have displayed neurodevelopmental and motor skill deficiencies, suggesting the potential for consequential neurological infection or inflammation in utero. Thus, we investigated transmission potential of SARS-CoV-2 and the consequences of infection on the developing brain using human ACE2 knock-in mice. In this model, we found that viral transmission to the fetal tissues, including the brain, occurred at later developmental stages, and that infection primarily targeted male fetuses. In the brain, SARS-CoV-2 infection largely occurred within the vasculature, but also within other cells such as neurons, glia, and choroid plexus cells; however, viral replication and increased cell death were not observed in fetal tissues. Interestingly, early gross developmental differences were observed between infected and mock-infected offspring, and high levels of gliosis were seen in the infected brains 7 days post initial infection despite viral clearance at this time point. In the pregnant mice, we also observed more severe COVID-19 infections, with greater weight loss and viral dissemination to the brain, compared to non-pregnant mice. Surprisingly, we did not observe an increase in maternal inflammation or the antiviral IFN response in these infected mice, despite showing clinical signs of disease. Overall, these findings have concerning implications regarding neurodevelopment and pregnancy complications of the mother following prenatal COVID-19 exposure.Item Fractional Lotka-Volterra-Type Cooperation Models: Impulsive Control on Their Stability Behavior(2020-08-31) Tuladhar, Rohisha; Santamaria, Fidel; Stamova, IvankaWe present a biological fractional n-species delayed cooperation model of Lotka-Volterra type. The considered fractional derivatives are in the Caputo sense. Impulsive control strategies are applied for several stability properties of the states, namely Mittag-Leffler stability, practical stability and stability with respect to sets. The proposed results extend the existing stability results for integer-order n−species delayed Lotka-Volterra cooperation models to the fractional-order case under impulsive control.Item Natural Product Co-Metabolism and the Microbiota–Gut–Brain Axis in Age-Related Diseases(2022-12-23) Obrenovich, Mark; Singh, Sandeep Kumar; Li, Yi; Perry, George; Siddiqui, Bushra; Haq, Waqas; Reddy, V. PrakashComplementary alternative medicine approaches are growing treatments of diseases to standard medicine practice. Many of these concepts are being adopted into standard practice and orthomolecular medicine. Age-related diseases, in particular neurodegenerative disorders, are particularly difficult to treat and a cure is likely a distant expectation for many of them. Shifting attention from pharmaceuticals to phytoceuticals and "bugs as drugs" represents a paradigm shift and novel approaches to intervention and management of age-related diseases and downstream effects of aging. Although they have their own unique pathologies, a growing body of evidence suggests Alzheimer's disease (AD) and vascular dementia (VaD) share common pathology and features. Moreover, normal metabolic processes contribute to detrimental aging and age-related diseases such as AD. Recognizing the role that the cerebral and cardiovascular pathways play in AD and age-related diseases represents a common denominator in their pathobiology. Understanding how prosaic foods and medications are co-metabolized with the gut microbiota (GMB) would advance personalized medicine and represents a paradigm shift in our view of human physiology and biochemistry. Extending that advance to include a new physiology for the advanced age-related diseases would provide new treatment targets for mild cognitive impairment, dementia, and neurodegeneration and may speed up medical advancements for these particularly devastating and debilitating diseases. Here, we explore selected foods and their derivatives and suggest new dementia treatment approaches for age-related diseases that focus on reexamining the role of the GMB.Item Oxidative Stress Signaling in Blast TBI-Induced Tau Phosphorylation(2021-06-15) Wang, Chunyu; Shao, Changjuan; Zhang, Li; Siedlak, Sandra L.; Meabon, James S.; Peskind, Elaine R.; Lu, Yubing; Wang, Wenzhang; Perry, George; Cook, David G.; Zhu, XiongweiTraumatic brain injury caused by blast is associated with long-term neuropathological changes including tau phosphorylation and pathology. In this study, we aimed to determine changes in initial tau phosphorylation after exposure to a single mild blast and the potential contribution of oxidative stress response pathways. C57BL/6 mice were exposed to a single blast overpressure (BOP) generated by a compressed gas-driven shock tube that recapitulates battlefield-relevant openfield BOP, and cortical tissues were harvested at different time points up to 24 h after blast for Western blot analysis. We found that BOP caused elevated tau phosphorylation at Ser202/Thr205 detected by the AT8 antibody at 1 h post-blast followed by tau phosphorylation at additional sites (Ser262 and Ser396/Ser404 detected by PHF1 antibody) and conformational changes detected by Alz50 antibody. BOP also induced acute oxidative damage at 1 h post-blast and gradually declined overtime. Interestingly, Extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) were acutely activated in a similar temporal pattern as the rise and fall in oxidative stress after blast, with p38 showing a similar trend. However, glycogen synthase kinase-3 β (GSK3β) was inhibited at 1 h and remained inhibited for 24 h post blast. These results suggested that mitogenactivated protein kinases (MAPKs) but not GSK3β are likely involved in mediating the effects of oxidative stress on the initial increase of tau phosphorylation following a single mild blast.Item Polyphenols in Alzheimer's Disease and in the Gut–Brain Axis(2020-01-31) Reddy, V. Prakash; Aryal, Puspa; Robinson, Sara; Rafiu, Raheemat; Obrenovich, Mark; Perry, GeorgePolyphenolic antioxidants, including dietary plant lignans, modulate the gut–brain axis, which involves transformation of these polyphenolic compounds into physiologically active and neuroprotector compounds (called human lignans) through gut bacterial metabolism. These gut bacterial metabolites exert their neuroprotective effects in various neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), and also have protective effects against other diseases, such as cardiovascular diseases, cancer, and diabetes. For example, enterolactone and enterodiol, the therapeutically relevant polyphenols, are formed as the secondary gut bacterial metabolites of lignans, the non-flavonoid polyphenolic compounds found in plant-based foods. These compounds are also acetylcholinesterase inhibitors, and thereby have potential applications as therapeutics in AD and other neurological diseases. Polyphenols are also advanced glycation end product (AGE) inhibitors (antiglycating agents), and thereby exert neuroprotective effects in cases of AD. Thus, gut bacterial metabolism of lignans and other dietary polyphenolic compounds results in the formation of neuroprotective polyphenols—some of which have enhanced blood–brain barrier permeability. It is hypothesized that gut bacterial metabolism-derived polyphenols, when combined with the nanoparticle-based blood–brain barrier (BBB)-targeted drug delivery, may prove to be effective therapeutics for various neurological disorders, including traumatic brain injury (TBI), AD, and PD. This mini-review addresses the role of polyphenolic compounds in the gut–brain axis, focusing on AD.Item Promise from the Sea(2016-10-09) Perry, GeorgeThe twenty-first century's greatest medical challenge is degenerative disease. [...]Item Reevaluating the Language of Learning Advantage in Bilingual Arithmetic: An ERP Study on Spoken Multiplication Verification(2022-04-21) Cerda, Vanessa R.; Montufar Soria, Paola; Wicha, Nicole Y.Many studies of bilingual arithmetic report better performance when verifying arithmetic facts in the language of learning (LA+) over the other language (LA−). This could be due to language-specific memory representations, processes established during learning, or to language and task factors not related to math. The current study builds on a small number of event-related potential (ERP) studies to test this question while controlling language proficiency and eliminating potential task confounds. Adults proficient in two languages verified single-digit multiplications presented as spoken number words in LA+ and LA−, separately. ERPs and correctness judgments were measured from solution onset. Equivalent P300 effects, with larger positive amplitude for correct than incorrect solutions, were observed in both languages (Experiment 1A), even when stimuli presentation rate was shortened to increase difficulty (Experiment 1B). This effect paralleled the arithmetic correctness effect for trials presented as all digits (e.g., 2 4 8 versus 2 4 10), reflecting efficient categorization of the solutions, and was distinct from an N400 generated in a word–picture matching task, reflecting meaning processing (Experiment 2). The findings reveal that the language effects on arithmetic are likely driven by language and task factors rather than differences in memory representation in each language.Item Roles of Oxidative Stress in Synaptic Dysfunction and Neuronal Cell Death in Alzheimer's Disease(2023-08-17) Plascencia-Villa, Germán; Perry, GeorgeAlzheimer’s disease (AD) is a brain disorder that progressively undermines memory and thinking skills by affecting the hippocampus and entorhinal cortex. The main histopathological hallmarks of AD are the presence of abnormal protein aggregates (Aβ and tau), synaptic dysfunction, aberrant proteostasis, cytoskeletal abnormalities, altered energy homeostasis, DNA and RNA defects, inflammation, and neuronal cell death. However, oxidative stress or oxidative damage is also evident and commonly overlooked or considered a consequence of the advancement of dementia symptoms. The control or onset of oxidative stress is linked to the activity of the amyloid-β peptide, which may serve as both antioxidant and pro-oxidant molecules. Furthermore, oxidative stress is correlated with oxidative damage to proteins, nucleic acids, and lipids in vulnerable cell populations, which ultimately lead to neuronal death through different molecular mechanisms. By recognizing oxidative stress as an integral feature of AD, alternative therapeutic or preventive interventions are developed and tested as potential or complementary therapies for this devastating neurodegenerative disease.Item The Effect of Code-Switching Experience on the Neural Response Elicited to a Sentential Code Switch(2022-07-11) Blackburn, Angélique M.; Wicha, Nicole Y. Y.Switching between languages, or codeswitching, is a cognitive ability that multilinguals can perform with ease. This study investigates whether codeswitching during sentence reading affects early access to meaning, as indexed by the robust brain response called the N400. We hypothesize that the brain prioritizes the meaning of the word during comprehension with codeswitching costs emerging at a different stage of processing. Event-related potentials (ERPs) were recorded while Spanish–English balanced bilinguals (n = 24) read Spanish sentences containing a target noun that could create a semantic violation, codeswitch or both. Self-reported frequency of daily codeswitching was used as a regressor to determine if the cost of reading a switch is modulated by codeswitching experience. A robust N400 to semantic violations was followed by a late positive component (LPC). Codeswitches modulated the left anterior negativity (LAN) and LPC, but not the N400, with codeswitched semantic violations resulting in a sub-additive interaction. Codeswitching experience modulated the LPC, but not the N400. The results suggest that early access to semantic memory during comprehension happens independent of the language in which the words are presented. Codeswitching affects a separate stage of comprehension with switching experience modulating the brain's response to experiencing a language switch.Item The Interrelation of Neurological and Psychological Symptoms of COVID-19: Risks and Remedies(2020-08-13) Nami, Mohammad; Gadad, Bharathi S.; Chong, Li; Ghumman, Usman; Misra, Amogh; Gadad, Shrikanth S.; Kumar, Dharmendra; Perry, George; Abraham, Samuel J. K.; Rao, K. S.COVID-19 has catastrophically affected the world's panoramic view of human well-being in terms of healthcare and management. With the increase in the number of cases worldwide, neurological symptoms and psychological illnesses from COVID-19 have increasingly upsurged. Mental health illness and affective disorders, including depression, obsessive-compulsive disorder, anxiety, phobia, and panic disorders, are highly impacted due to social distress. The COVID-19 pandemic not only affected people with pre-existing mental and affective illnesses, but also healthy individuals with anxiety, worrying, and panic symptoms, and fear conditioning. In addditon, the novel coronavirus is known to impact the central nervous system in the brain, resulting in severe and certain long-lasting neurological issues. Owing to the significance of neurological and psychological events, the present perspective has been an attempt to disseminate the impact of COVID-19 on neural injury through inflammation, and its interrelation with psychological symptoms. In this current review, we synthesize the literature to highlight the critical associations between SARS-CoV-2 infection and the nervous system, and mental health illness, and discuss potential mechanisms of neural injury through psycho-neuroimmunity.