Digital Commons Network^™

Structure Of Adenylyl Cyclase 5 In Complex With Gβγ Offers Insights Into Adcy5-Related Dyskinesia, Yu-Chen Yen, Yong Li, Chun-Liang Chen, Thomas Klose, Val J Watts, Carmen W Dessauer, John J G Tesmer

Faculty, Staff and Student Publications

The nine different membrane-anchored adenylyl cyclase isoforms (AC1-9) in mammals are stimulated by the heterotrimeric G protein, Gαs, but their response to Gβγ regulation is isoform specific. In the present study, we report cryo-electron microscope structures of ligand-free AC5 in complex with Gβγ and a dimeric form of AC5 that could be involved in its regulation. Gβγ binds to a coiled-coil domain that links the AC transmembrane region to its catalytic core as well as to a region (C1b) that is known to be a hub for isoform-specific regulation. We confirmed the Gβγ interaction with both purified proteins and cell-based …

Parkinson’S Disease Variant Detection And Disclosure: Pd Generation, A North American Study, Lola Cook, Jennifer Verbrugge, Tae-Hwi Schwantes-An, Jeanine Schulze, Tatiana Foroud, Anne Hall, Karen S Marder, Ignacio F Mata, Niccolò E Mencacci, Martha A Nance, Michael A Schwarzschild, Tanya Simuni, Susan Bressman, Anne-Marie Wills, Hubert H Fernandez, Irene Litvan, Kelly E Lyons, Holly A Shill, Carlos Singer, Thomas F Tropea, Nora Vanegas Arroyave, Janfreisy Carbonell, Rossy Cruz Vicioso, Linn Katus, Joseph F Quinn, Priscila D Hodges, Yan Meng, Samuel P Strom, Cornelis Blauwendraat, Katja Lohmann, Cynthia Casaceli, Shilpa C Rao, Kamalini Ghosh Galvelis, Anna Naito, James C Beck, Roy N Alcalay

Faculty, Staff and Students Publications

Variants in seven genes (LRRK2, GBA1, PRKN, SNCA, PINK1, PARK7 and VPS35) have been formally adjudicated as causal contributors to Parkinson's disease; however, individuals with Parkinson's disease are often unaware of their genetic status since clinical testing is infrequently offered. As a result, genetic information is not incorporated into clinical care, and variant-targeted precision medicine trials struggle to enrol people with Parkinson's disease. Understanding the yield of genetic testing using an established gene panel in a large, geographically diverse North American population would help patients, clinicians, clinical researchers, laboratories and insurers better understand the importance of genetics in approaching Parkinson's …

Fetal Malrotation With Midgut Volvulus: Prenatal Diagnosis And Planning, Jai Sidpra, Sniya Sudhakar, Asthik Biswas, Flavia Massey, Valentina Turchetti, Tracy Lau, Edward Cook, Javeria Raza Alvi, Hasnaa M Elbendary, Jerry L Jewell, Antonella Riva, Alessandro Orsini, Aglaia Vignoli, Zara Federico, Jessica Rosenblum, An-Sofie Schoonjans, Matthias De Wachter, Ignacio Delgado Alvarez, Ana Felipe-Rucián, Nourelhoda A Haridy, Shahzad Haider, Mashaya Zaman, Selina Banu, Najwa Anwaar, Fatima Rahman, Shazia Maqbool, Rashmi Yadav, Vincenzo Salpietro, Reza Maroofian, Rajan Patel, Rupa Radhakrishnan, Sanjay P Prabhu, Klaske Lichtenbelt, Helen Stewart, Yoshiko Murakami, Ulrike Löbel, Felice D'Arco, Emma Wakeling, Wendy Jones, Eleanor Hay, Sanjay Bhate, Thomas S Jacques, David M Mirsky, Matthew T Whitehead, Maha S Zaki, Tipu Sultan, Pasquale Striano, Anna C Jansen, Maarten Lequin, Linda S De Vries, Mariasavina Severino, Andrew C Edmondson, Lara Menzies, Philippe M Campeau, Henry Houlden, Amy Mctague, Stephanie Efthymiou, Kshitij Mankad

Faculty, Staff and Students Publications

Inherited glycosylphosphatidylinositol deficiency disorders (IGDs) are a group of rare multisystem disorders arising from pathogenic variants in glycosylphosphatidylinositol anchor pathway (GPI-AP) genes. Despite associating 24 of at least 31 GPI-AP genes with human neurogenetic disease, prior reports are limited to single genes without consideration of the GPI-AP as a whole and with limited natural history data. In this multinational retrospective observational study, we systematically analyse the molecular spectrum, phenotypic characteristics and natural history of 83 individuals from 75 unique families with IGDs, including 70 newly reported individuals; the largest single cohort to date. Core clinical features were developmental delay or …

A Group 3 Medulloblastoma Stem Cell Program Is Maintained By Otx2-Mediated Alternative Splicing, Olivier Saulnier, Jamie Zagozewski, Lisa Liang, Liam D Hendrikse, Paul Layug, Victor Gordon, Kimberly A Aldinger, Parthiv Haldipur, Stephanie Borlase, Ludivine Coudière-Morrison, Ting Cai, Emma Martell, Naomi M Gonzales, Gareth Palidwor, Christopher J Porter, Stéphane Richard, Tanveer Sharif, Kathleen J Millen, Brad W Doble, Michael D Taylor, Tamra E Werbowetski-Ogilvie

Faculty, Staff and Students Publications

OTX2 is a transcription factor and known driver in medulloblastoma (MB), where it is amplified in a subset of tumours and overexpressed in most cases of group 3 and group 4 MB. Here we demonstrate a noncanonical role for OTX2 in group 3 MB alternative splicing. OTX2 associates with the large assembly of splicing regulators complex through protein-protein interactions and regulates a stem cell splicing program. OTX2 can directly or indirectly bind RNA and this may be partially independent of its DNA regulatory functions. OTX2 controls a pro-tumorigenic splicing program that is mirrored in human cerebellar rhombic lip origins. Among …

Bigh3 Mediates Apoptosis And Gap Junction Failure In Osteocytes During Renal Cell Carcinoma Bone Metastasis Progression, Tianhong Pan, Fengshuo Liu, Xiaoxin Hao, Shubo Wang, Murtaza Wasi, Jian H Song, Valerae O Lewis, Patrick P Lin, Bryan Moon, Justin E Bird, Theocharis Panaretakis, Sue-Hwa Lin, Danielle Wu, Mary C Farach-Carson, Liyun Wang, Ningyan Zhang, Zhiqiang An, Xiang H-F Zhang, Robert L Satcher

Faculty, Staff and Student Publications

Renal cell carcinoma (RCC) bone metastatis progression is driven by crosstalk between tumor cells and the bone microenvironment, which includes osteoblasts, osteoclasts, and osteocytes. RCC bone metastases (RCCBM) are predominantly osteolytic and resistant to antiresorptive therapy. The molecular mechanisms underlying pathologic osteolysis and disruption of bone homeostasis remain incompletely understood. We previously reported that BIGH3/TGFBI (transforming growth factor-beta-induced protein ig-h3, shortened to BIGH3 henceforth) secreted by colonizing RCC cells drives osteolysis by inhibiting osteoblast differentiation, impairing healing of osteolytic lesions, which is reversible with osteoanabolic agents. Here, we report that BIGH3 induces osteocyte apoptosis in both human RCCBM tissue specimens …

Detection Of Soil-Transmitted Helminths And Schistosoma Spp By Nucleic Acid Amplification Test: Results Of The First 5 Years Of The Only International External Quality Assessment Scheme, Annemiek H J Schutte, Rob Koelewijn, Sitara S R Ajjampur, Bruno Levecke, James S Mccarthy, Rojelio Mejia, Steven A Williams, Jaco J Verweij, Lisette Van Lieshout, Jaap J Van Hellemond

Faculty, Staff and Students Publications

BACKGROUND: Infections with soil-transmitted helminths (STH) and schistosomiasis (SCH) result in a significant global health burden, particularly in rural communities in low and middle-income countries. While microscopy remains the primary diagnostic method for STH and SCH in resource-limited settings, nucleic acid amplification tests (NAATs) are gaining prominence as tools for evaluation of public health control programs in endemic countries, and individual diagnosis in high-income countries. Despite the high sensitivity and specificity of NAATs, previous research has highlighted inter-laboratory variations, both in technical and clinical performance, justifying the need for continuous proficiency testing.

METHODOLOGY: Results from 5 rounds over a 5-year …

Circuit-Specific Deep Brain Stimulation Provides Insights Into Movement Control., Aryn H Gittis, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Deep brain stimulation (DBS), a method in which electrical stimulation is delivered to specific areas of the brain, is an effective treatment for managing symptoms of a number of neurological and neuropsychiatric disorders. Clinical access to neural circuits during DBS provides an opportunity to study the functional link between neural circuits and behavior. This review discusses how the use of DBS in Parkinson's disease and dystonia has provided insights into the brain networks and physiological mechanisms that underlie motor control. In parallel, insights from basic science about how patterns of electrical stimulation impact plasticity and communication within neural circuits are …

Preeclampsia In The Context Of Covid-19: Mechanisms, Pathophysiology, And Clinical Outcomes, Guilherme M Nobrega, Brittany R Jones, Indira U Mysorekar, Maria Laura Costa

Center on Aging Staff Publications

The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to the global COVID-19 pandemic, significantly impacting the health of pregnant women. Obstetric populations, already vulnerable, face increased morbidity and mortality related to COVID-19, aggravated by preexisting comorbidities. Recent studies have shed light on the potential correlation between COVID-19 and preeclampsia (PE), a leading cause of maternal and perinatal morbidity worldwide, emphasizing the significance of exploring the relationship between these two conditions. Here, we review the pathophysiological similarities that PE shares with COVID-19, with a particular focus on severe COVID-19 cases and in PE-like syndrome cases related with …

Community-Based Participatory Research And System Dynamics Modeling For Improving Retention In Hypertension Care, Jiancheng Ye, Ikechukwu A Orji, Michelle A Birkett, Lisa R Hirschhorn, Theresa L Walunas, Justin D Smith, Namratha R Kandula, Gabriel L Shedul, Mark D Huffman, Dike B Ojji

2020-Current year OA Pubs

IMPORTANCE: The high prevalence of hypertension calls for broad, multisector responses that foster prevention and care services, with the goal of leveraging high-quality treatment as a means of reducing hypertension incidence. Health care system improvements require stakeholder input from across the care continuum to identify gaps and inform interventions that improve hypertension care service, delivery, and retention; system dynamics modeling offers a participatory research approach through which stakeholders learn about system complexity and ways to model sustainable system-level improvements.

OBJECTIVE: To assess the association of simulated interventions with hypertension care retention rates in the Nigerian primary health care system using …

Advances In Blood Biomarkers For Alzheimer Disease (Ad): A Review, Araya Dimtsu Assfaw, Suzanne E Schindler, John C Morris

2020-Current year OA Pubs

Alzheimer disease (AD) and Alzheimer Disease and Related Dementias (AD/ADRD) are growing public health challenges globally affecting millions of older adults, necessitating concerted efforts to advance our understanding and management of these conditions. AD is a progressive neurodegenerative disorder characterized pathologically by amyloid plaques and tau neurofibrillary tangles that are the primary cause of dementia in older individuals. Early and accurate diagnosis of AD dementia is crucial for effective intervention and treatment but has proven challenging to accomplish. Although testing for AD brain pathology with cerebrospinal fluid (CSF) or positron emission tomography (PET) has been available for over 2 decades, …

Motives For And Consequences Of Deception In Romantic Relationships, Breanna De Leeuw

Graduate Theses and Dissertations

The goals of this study are twofold. First, I examined the influence of sex, relational intimacy, and face concerns on deploying deceptive communication within romantic relationships. Second, I investigated the impact of deceptive communication on relational commitment and relationship satisfaction. Two hundred twenty-two college-aged students completed self-report measures assessing the variables of interest. Results demonstrated that men and women deceive their romantic relationship partners at similar rates; however, deception is differentially motivated across the sexes. In addition, results indicated that relational intimacy was negatively associated with the frequency of deceit, although relational intimacy was not significantly associated with specific motives …

Investigating The Detection And Transport Of Low Molecular Weight Species To Better Understand Their Impact On Disease Pathology And Treatment, Haley Michelle Duncan

Graduate Theses and Dissertations

Due to the drastic differences in the projects involved, this dissertation will be split into two sections: Alzheimer’s disease and chronic kidney disease. Each chapter will contain an introduction, materials and methods section, results and discussion, conclusions, and works cited section. The Alzheimer’s disease chapter will also have a supplemental figures section containing the polyacrylamide gels that were silver stained and quantified via ImageJ. The presence of elevated levels of amyloid beta oligomeric species in the brain has been related to the pathology of Alzheimer’s disease. As these oligomeric species are transient in nature, their kinetics pose a challenge to …

Quantifying Physical Function: Moving Towards A New Definition And Better Assessment, Anthony Campitelli

Graduate Theses and Dissertations

Though poor physical function (PF) and disability are two of the most impactful problems facing older adults today, the field of kinesiology has not yet devised a method of measuring PF, thus limiting investigations with the potential to lead to improved PF interventions and assessments. This dissertation aimed to develop a single, continuous measure of PF using a latent variable modeling approach, and then use the generated scores to evaluate the role of lower body muscular power in PF assessment and to construct an improved PF assessment battery for predicting overall PF. Each aim of this dissertation was addressed through …

Sex-Dependent Differences In Vulnerability To Early Risk Factors For Posttraumatic Stress Disorder: Results From The Aurora Study, Stephanie Haering, Stacey L House, Et Al.

2020-Current year OA Pubs

BACKGROUND: Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD.

METHODS: As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with …

Opportunities To Improve Antibiotic Prescribing For Adults With Acute Sinusitis, United States, 2016–2020, Axel A Vazquez Deida, Destani J Bizune, Christine Kim, John M Sahrmann, Guillermo V Sanchez, Adam L Hersh, Anne M Butler, Lauri A Hicks, Sarah Kabbani

2020-Current year OA Pubs

BACKGROUND: Better understanding differences associated with antibiotic prescribing for acute sinusitis can help inform antibiotic stewardship strategies. We characterized antibiotic prescribing patterns for acute sinusitis among commercially insured adults and explored differences by patient- and prescriber-level factors.

METHODS: Outpatient encounters among adults aged 18 to 64 years diagnosed with sinusitis between 2016 and 2020 were identified by national administrative claims data. We classified antibiotic agents-first-line (amoxicillin-clavulanate or amoxicillin) and second-line (doxycycline, levofloxacin, or moxifloxacin)-and ≤7-day durations as guideline concordant based on clinical practice guidelines. Modified Poisson regression was used to examine the association between patient- and prescriber-level factors and guideline-concordant …

Investigating The Applications Of Peps To The Measurement Of The Stabilities Of Staphylococcal Nuclease (Stw) And Human Acidic Fibroblast Growth Factor (Hfgf1), Motolani Omolade Matthew

Graduate Theses and Dissertations

This dissertation presents a detailed investigation into the applications of Protein Equilibrium Population Snapshot H/D Exchange Electrospray Ionization Mass Spectrometry (PEPS-H/D exchange or PEPS) method. This method is based on protein equilibrium unfolding, and its fundamental capability is to capture a "snapshot" of the protein's state, allowing us to monitor the ratio of the unfolded to folded populations at different chemical denaturant concentrations. First, to increase the accuracy of PEPS data analysis for assessing protein stability, the traditional linear extrapolation method (LEM) was replaced. Instead of using LEM, which calculates free energy change based on the peak ratio of unfolded …

Partial Immunity To Mycoplasma Gallisepticum After An Initial Infection Is Long-Lasting And Reduces Transmission In Flocks Of Canaries, Madeline Sudnick

Graduate Theses and Dissertations

Pathology during a second infection can be influenced by immunity and an increase in resistance or tolerance of individuals. Population-level differences in the ability to maintain immunity can lead to contrasting survival outcomes between groups and determine how future outbreaks will spread. However, long term wildlife disease surveillance can be challenging due to lack of infrastructure and host-pathogen specific tests. Calculating disease transmission likelihood requires understanding individual-level heterogeneity in pathology and behavior, and there is limited knowledge in understanding how populations in different stages of an epidemic will transmit disease. In Chapter I, we aim to help fill a gap …

Milk Exosome-Glow Nanosystem For Cancer Cellular And Tissue Bioimaging, Nycol Cotto, Neeraj Chauhan, Benilde Adriano, Deepak S. Chauhan, Marco A. Cabrera, Subhash Chauhan, Murali Yallapu

School of Medicine Publications

Milk-derived exosomes are widely used for diagnosis, delivery, imaging, and theranostic applications. Near-Infrared (NIR) based fluorescence bioimaging is an attractive and safer technique that is used for clinical applications. However, almost all NIR imaging agents tend to have poor photostability, short half-life, nonspecific protein binding, and concentration-dependent aggregation(s). Therefore, there is an unmet clinical need to develop newer and safer modalities to package and deliver NIR imaging agents. Bovine milk exosomes are natural, biocompatible, safe, and efficient nanocarriers that facilitate the delivery of micro- and macromolecules. Herein, we developed an exosome-based NIR dye loaded nanoimaging formulation that offers improved solubility …

Pathways To Parenthood Among Transgender Men And Gender Diverse People Assigned Female Or Intersex At Birth In The United States: Analysis Of A Cross-Sectional 2019 Survey, Shalmali Sunil Bane, Juno Obedin-Maliver, Sachiko Ragosta, Jen Hastings, Mitchell R. Lunn, Annesa Flentje, Matthew R. Capriotti, Micah E. Lubensky, Diana M. Tordoff, Heidi Moseson

Faculty Research, Scholarly, and Creative Activity

Objective: To assess pathways to parenthood, pregnancy outcomes, future pregnancy desire, and fertility counseling experiences among a cross-sectional sample of transgender men and gender diverse individuals assigned female or intersex at birth in the United States Methods: Participants were recruited from The Population Research in Identity and Disparities for Equality (PRIDE) Study and the general public. Eligible participants for this analysis were able to read and understand English, assigned female or intersex at birth, US residents, 18+ years old, and identified as transgender, nonbinary, or gender diverse. We analyzed responses to close-ended survey questions, overall and stratified by gender identity, …

Ultrathin Boron Growth Onto Nanodiamond Surfaces Via Electrophilic Boron Precursors, Krishna Govindaraju, Tyanna Supreme, Daniel N. Labunsky, Nicole Martin, Juan Miguel Del Rosario, Alana Washington, Ezhioghode O. Uwadiale, Solomon Adjei, Sandra Ladjadj, Cynthia V. Melendrez, Sang Jun Lee, Maria V. Altoe, Avery Green, Sebastian Riano, Sami Sainio, Dennis Nordlund, Abraham Wolcott

Faculty Research, Scholarly, and Creative Activity

Diamond as a templating substrate is largely unexplored, and the unique properties of diamond, including its large bandgap, thermal conductance, and lack of cytotoxicity, makes it versatile in emergent technologies in medicine and quantum sensing. Surface termination of an inert diamond substrate and its chemical reactivity are key in generating new bonds for nucleation and growth of an overlayer material. Oxidized high-pressure high temperature (HPHT) nanodiamonds (NDs) are largely terminated by alcohols that act as nucleophiles to initiate covalent bond formation when an electrophilic reactant is available. In this work, we demonstrate a templated synthesis of ultrathin boron on ND …

Tai Chi Expertise Classification In Older Adults Using Wrist Wearables And Machine Learning, Yang Hu, Mengyue Huang, Jonathan Cerna, Rachneet Kaur, Manuel E. Hernandez

Faculty Research, Scholarly, and Creative Activity

Tai Chi is a Chinese martial art that provides an adaptive and accessible exercise for older adults with varying functional capacity. While Tai Chi is widely recommended for its physical benefits, wider adoption in at-home practice presents challenges for practitioners, as limited feedback may hamper learning. This study examined the feasibility of using a wearable sensor, combined with machine learning (ML) approaches, to automatically and objectively classify Tai Chi expertise. We hypothesized that the combination of wrist acceleration profiles with ML approaches would be able to accurately classify practitioners’ Tai Chi expertise levels. Twelve older active Tai Chi practitioners were …

Synthesis Of Nanoparticles And Their Applications In Power Module Packaging And Organic Electronics, Xinsong Zhang

Graduate Theses and Dissertations

Nanoparticles can greatly change the properties of regular materials due to their special structures. In this research nanoparticles, such as silver nanowires, silver nanospheres and expanded graphite, are used in interconnection materials for power module packaging, and in conductive films for organic electronics. Silver nanowires synthesized by polyol synthesis, are used as fillers in micron silver paste. The electrical and mechanical properties of the sintered hybrid silver paste are investigated and compared with those of micron silver paste. The composites of silver nanospheres and expanded graphite are mixed with PEDOT:PSS solutions in 5 different weight ratio. The electrical and optical …

Neural Interactions In Bottom-Up Communication, Prashant Chama Raju

Graduate Theses and Dissertations

The visual system’s remarkable ability to process vast amounts of sensory information rapidly and accurately is fundamental to cognitive neuroscience. This study investigates a key aspect of this capability: the compartmentalization of information into feature-specific subspaces during bottom-up communication. My primary question was: does Canonical Correlation Analysis (CCA) reveal a subspace that encodes color and direction of moving dot stimuli? I found that the first canonical component (CC1) does an excellent job decoding the stimuli, despite being one-dimensional while the stimuli were drawn from a two-dimensional space (red-green and up-down plane). I demonstrate that motion features are processed within distinct …

Identifying New Potential Breeding Pond Sites For The Dusky Gopher Frog In Southern Mississippi, Shelbie Kellum

Master's Theses

The main objective of this thesis was to identify potential new pond sites across southern Mississippi for the critically endangered dusky gopher frog (DGF). Ephemeral ponds are the preferred breeding habitat for the species, but they are quite rare in the region due to the diminishment of the longleaf pine ecosystem. This research addresses gaps in the current literature by providing a broad overview of dusky gopher frog breeding habitat identification. LiDAR derived datasets as well as tools within ArcGIS Pro were utilized in order to perform spatial analysis on sites of interest in south Mississippi. By using this methodology …

Development Of A Flow Cytometry Method For The Identification And Enumeration Of Enterococcus Faecalis, Riza Magbitang

Master's Theses

A multi-color flow cytometry method coupled with fluorescent staining was developed to detect and quantify E. faecalis concentrations in coastal waters as an alternative to the traditional membrane filtration method. The developed method was used to characterize E. faecalis during batch growth and yielded consistent results across the various physiological states of the cells. Additionally, the application of propidium iodide (i.e., a viability stain), afforded the method the ability to differentiate between cells with intact and compromised cell membranes, which raises the potential of quantifying cells that are in viable-but-non-culturable (VBNC) state. Initial field test using natural seawater samples spiked …

Investigating The Response Of The Eastern Oyster (Crassostrea Virginica) To Low Dissolved Oxygen Conditions, Abiola Obafemi

Master's Theses

The Eastern oyster (Crassostrea virginica) requires dissolved oxygen (DO) of about 4 mg/L to support proper physiological function. Hypoxia and/or microxia occur when DO decreases to ≤ 2 mg/L. Salinity and temperature changes resulting from large-scale freshwater influx have been identified as key factors influencing the oyster populations in the Mississippi Sound. It is important to investigate the impacts of DO conditions on oyster mortality, biomass, size, and condition during these freshening events. Under controlled laboratory experiments, this thesis investigated 1) the response of oysters to microxic, hypoxic, and normoxic conditions 2) the response of oysters to combined hypoxia and …

An Atypical Form Of 60s Ribosomal Subunit In Diamond-Blackfan Anemia Linked To Rpl17 Variants., Florence Fellmann, Carol J. Saunders, Marie-Françoise O'Donohue, David W. Reid, Kelsey A. Mcfadden, Nathalie Montel-Lehry, Cong Yu, Mingyan Fang, Jianguo Zhang, Beryl Royer-Bertrand, Pietro Farinelli, Narjesse Karboul, Jason R. Willer, Lorraine Fievet, Zahurul Alam Bhuiyan, Alissa Lw Kleinhenz, Julie Jadeau, Joy M. Fulbright, Carlo Rivolta, Raffaele Renella, Nicholas Katsanis, Jacques S. Beckmann, Christopher V. Nicchitta, Lydie Da Costa, Erica E. Davis, Pierre-Emmanuel Gleizes

Manuscripts, Articles, Book Chapters and Other Papers

Diamond-Blackfan anemia syndrome (DBA) is a ribosomopathy associated with loss-of-function variants in more than 20 ribosomal protein (RP) genes. Here, we report the genetic, functional, and biochemical dissection of 2 multigenerational pedigrees with variants in RPL17, a large ribosomal subunit protein-encoding gene. Affected individuals had clinical features and erythroid proliferation defects consistent with DBA. Further, RPL17/uL22 depletion resulted in anemia and micrognathia in zebrafish larvae, and in vivo complementation studies indicated that RPL17 variants were pathogenic. Lymphoblastoid cell lines (LCLs) derived from patients displayed a ribosomal RNA maturation defect reflecting haploinsufficiency of RPL17. The proteins encoded by RPL17 variants were …

Translational Approaches To The Neurobiological Study Of Conditional Discrimination And Inhibition: Implications For Psychiatric Disease, Susan Sangha, Jacklynn M. Fitzgerald

Psychology Faculty Research and Publications

There is a growing number of studies investigating discriminatory fear conditioning and conditioned inhibition of fear to assess safety learning, in addition to extinction of cued fear. Despite all of these paradigms resulting in a reduction in fear expression, there are nuanced differences among them, which could be mediated through distinct behavioral and neural mechanisms. These differences could impact how we approach potential treatment options in clinical disorders with dysregulated fear responses. The objective of this review is to give an overview of the conditional discrimination and inhibition findings reported in both animal models and human neuropsychiatric disorders. Both behavioral …

Racial Discrimination Increases The Risk For Nonremitting Posttraumatic Stress Disorder Symptoms In Traumatically Injured Black Individuals Living In The United States, Lucas Torres, Timothy J. Geier, Carissa W. Tomas, Claire M. Bird, Sydney Clare Timmer-Murillo, Christine L. Larson, Terri A. Deroon-Cassini

Psychology Faculty Research and Publications

Traumatic, life-threatening events are experienced commonly among the general U.S. population, yet Black individuals in the United States (i.e., Black Americans) exhibit higher prevalence rates of posttraumatic stress disorder (PTSD) and more severe symptoms than other populations. Although empirical research has noted a range of symptom patterns that follow traumatic injury, minimal work has examined the role of racial discrimination in relation to PTSD symptom trajectories. The current study assessed racial discrimination and PTSD symptom trajectories at 6 months postinjury across two separate samples of traumatically injured Black Americans (i.e. emergency department (ED)–discharged and hospitalized). Identified PTSD symptom trajectories largely …

Neurocognitive Functioning In Adults With Trichotillomania: Predictors Of Treatment Response And Symptom Severity In A Randomized Control Trial, Kathryn E. Barber, Douglas W. Woods, Thilo Deckersbach, Christopher C. Bauer, Scott N. Compton, Michael P. Twohig, Emily J. Ricketts, Jordan Robinson, Stephen M. Saunders, Martin E. Franklin

Psychology Faculty Research and Publications

Trichotillomania (TTM) is associated with impairments in response inhibition and cognitive flexibility, but it is unclear how such impairments relate to treatment outcome. The present study examined pre-treatment response inhibition and cognitive flexibility as predictors of treatment outcome, change in these domains from pre-to post-treatment, and associations with TTM severity. Participants were drawn from a randomized controlled trial comparing acceptance-enhanced behavior therapy (AEBT) to psychoeducation and supportive therapy (PST) for TTM. Adults completed assessments at pre-treatment (n = 88) and following 12 weeks of treatment (n = 68). Response inhibition and cognitive flexibility were assessed using the Stop …