Digital Commons Network^™

The Association Of Race And Ethnicity With Severe Maternal Morbidity Among Individuals Diagnosed With Hypertensive Disorders Of Pregnancy, Ashok Krishnaswami, Michael W Rich, Min Ji Kwak, Parag Goyal, Daniel E Forman, Abdulla A Damluji, Matthew Solomon, Jamal S Rana, Deborah M Kado, Michelle C Odden

Faculty, Staff and Student Publications

AIMS: Randomized clinical trials of hypertension treatment intensity evaluate the effects on incident major adverse cardiovascular events (MACEs) and serious adverse events (SAEs). Occurrences after a non-fatal index event have not been rigorously evaluated. The aim of this study was to evaluate the association of intensive (<120 >mmHg) to standard (<140 >mmHg) blood pressure (BP) treatment with mortality mediated through a non-fatal MACE or non-fatal SAE in 9361 participants in the Systolic Blood Pressure Intervention Trial.

METHODS AND RESULTS: Logistic regression and causal mediation modelling to obtain direct and mediated effects of intensive BP treatment. Primary outcome was all-cause mortality …

Not All Cities Are The Same: Variation In Animal Phenotypes Across Cities Within Urban Ecology Studies, Javier Delbarco-Trillo, Breanna J. Putman

Faculty Publications – Biological Sciences

The sustained expansion of urban environments has been paralleled by an increase in the number of studies investigating the phenotypic changes of animals driven by urbanization. Most of these studies have been confined to only one urban center. However, as the types and strength of anthropogenic stressors differ across cities, a generalizable understanding of the effects of urbanization on urban-dwelling species can only be reached by comparing the responses of urban populations from the same species across more than one city. We conducted phylogenetic meta-analyses on data for animal species (including both invertebrates and vertebrates) for which measures about any …

The Lithium Industry And Its Human Rights Impacts: The Case Of The Lickanantay People In Chile, José Alywin, Marcel Didier, Oriana Mora

Wyoming Law Review

No abstract provided.

Variable Rates Of Hybridization Among Contact Zones Between A Pair Of Topminnow Species, Fundulus Notatus And F. Olivaceus, David D. Duvernell, Naznin S. Remex, Jeffrey T. Miller, Jacob F. Schaefer

Biological Sciences Faculty Research & Creative Works

Pairs of species that exhibit broadly overlapping distributions, and multiple geographically isolated contact zones, provide opportunities to investigate the mechanisms of reproductive isolation. Such naturally replicated systems have demonstrated that hybridization rates can vary substantially among populations, raising important questions about the genetic basis of reproductive isolation. The topminnows, Fundulus notatus and F. olivaceus, are reciprocally monophyletic, and co-occur in drainages throughout much of the central and southern United States. Hybridization rates vary substantially among populations in isolated drainage systems. We employed genome-wide sampling to investigate geographic variation in hybridization, and to assess the possible importance of chromosome fusions to …

Satellite-Based Shoreline Detection Along High-Energy Macrotidal Coasts And Influence Of Beach State, Aikaterini Konstantinou, Tim Scott, Gerd Masselink, Kit Stokes, Daniel Conley, Bruno Castelle

School of Biological and Marine Sciences

Earth observation coupled with novel image analysis techniques now present a unique and powerful tool for the historical study of shoreline change at local to global scale. However, satellite-derived shoreline (SDS) data is limited in certain areas and is associated with large uncertainties relating to environmental factors, tidal range, and wave action. We use 14 years of monthly topographic surveys at two macrotidal sites in the UK representing end members of beach type (reflective, dissipative) to investigate the influence of tidal elevation and wave action on SDS accuracy. We find that applying appropriate water level corrections can significantly improve SDS …

Biomimetic Aerosol Exposure System For In Vitro Human Airway Exposure Studies, Samantha Emma Sarles

Theses

Tobacco use remains the number one cause of preventable death in the United States, disproportionately affecting residents of rural areas, people who are financially disadvantaged, and adults who identify as gay, lesbian, or bisexual. The impact that electronic cigarettes will have on public health is not yet fully understood. Combinations of electronic cigarette products, human airway geometries, and user behaviors create barriers to understanding products’ interaction with the human airway and their health effects. Current in vitro emissions systems, also called smoking robots, lack biomimicry, use unrealistic flow conditions, produce unrealistic aerosol dose, and provide inaccurate bio-mechanical cues to cell …

An Exploratory Examination Of The Cultural Understandings Of Communication Competence Among Nigerian Immigrant Adult Children, Fredous Gambo

Communication & Theatre Arts Theses

Although “communication competence” may be considered a trans-cultural concept, its unique meanings and practices across cultures have yet to be studied. Communication between parents and children in African households, for example, have often been associated with a restive and high level of control. Specifically in Nigerian households, a major critique of parenting communication styles is the necessity of continually seeking the permissions of a patriarchal and hierarchical family structure. When families immigrate, parents and children alike must navigate learning to communicate in the new culture while also seeking to preserve their culture of origin. Past research shows that adult immigrant …

Interpersonal Stress And Proinflammatory Activity In Emerging Adults With A History Of Suicide Risk: A Pilot Study, Annamarie B Defayette, Christianne Esposito-Smythers, Ian Cero, Katherine M Harris, Emma D Whitmyre, Roberto López

Faculty, Staff and Student Publications

Interpersonal stress during adolescence and young adulthood can threaten healthy developmental trajectories. A “primed” proinflammatory response to acute stress may serve as an underlying process that results in negative outcomes for youth. The present pilot study examined the relation between interpersonal stress and two proinflammatory cytokines in a sample of 42 university-recruited emerging adults with recent suicidal thoughts and behaviors. Participants completed self-report measures of mood, suicidal thoughts and behaviors, recent peer-related stressors, and interpersonal sensitivity. They also participated in an acute laboratory social stress task and provided three saliva samples to measure their proinflammatory responses (IL-6 and TNF-α) to …

Elucidating College Students’ Stressors: Photovoice As A Pedagogical Tool And Qualitative Methodology, Deanne Priddis, Heather L. Hundley

Journal of Communication Pedagogy

Traditional research examining student stress relies on surveys using pre-determined categories. This study diverts from that approach by adopting a Communication in Conflict class assignment over seven classes (N = 115) using photovoice to determine if results fluctuate by using a different methodology. Additionally, we sought to understand if the sources of stress vary by gender and semester. The data revealed seven categories as the main stressors of student conflict: 1) time management, 2) mental health, 3) finding oneself, 4) future uncertainty, 5) other, 6) financial, and 7) past mistakes. Regardless of participants’ sex/gender or semester in which the data …

Perceived Teacher Confirmation And The Online Classroom: Capturing Student Descriptions Of Experiences With Faculty Online, Ashley Jones-Bodie, Lindsey Anderson, Jennifer Hall

Journal of Communication Pedagogy

This study explored and examined students’ perceptions of teacher confirmation, those behaviors that teachers engage in that make students feel confirmed as valuable, significant individuals, as experienced in online courses. With over 450 students’ written descriptions of experiences in online classes across three different universities, this study provides an important initial examination of teaching practices in the online context. While prior research has situated study of students’ perceptions of teacher confirmation in the traditional in-person course experience, the current project extends understanding of teacher confirmation into the online setting. The study provides detailed descriptions, in students’ own words, of specific …

Adaptation Of Nirtrifiers And Heterotrophs To Low Dissolved Oxygen In An Activated Sludge Biological Nutrient Removal Pilot Plant, Shashank Khatiwada

Civil & Environmental Engineering Theses & Dissertations

Low dissolved oxygen (DO) operation is one of the innovative technologies in biological nutrient removal (BNR) processes that is being investigated due to the potential to reduce aeration requirements, reduce a treatment plant’s carbon footprint, and to lower costs associated with chemical addition to promote denitrification. These benefits are achieved through development of micro-zones, within aerated basins where simultaneous nitrification and denitrification (SND) can occur. In this study, an activated sludge BNR pilot was run in an anerobic/aerobic (A/O) configuration at a controlled temperature and constant flow to observe microorganism-driven transformations of nitrogen and phosphorus at varying low DO conditions. …

Synthesis And Characterization Of Cobalt(Iii) Complexes And A Vanadium(Iv) Complex With Flavonoids As Ligands, Ethan Schroeder

Chemistry & Biochemistry Theses & Dissertations

For many years now, transition metal complexes have been used as favorable additional chemotherapeutic approaches to medicine that were previously unexplored in the literature. One well-known chemotherapeutic drug, cisplatin, has been applied, but is limited in use due to its toxicity to the cells and its undesirable side effects to humans. Newly developed cobalt-based complexes with ligands known as flavonoids are being used to fight cancer. Flavonoids, compounds mainly found in fruits and vegetables, are shown to have antioxidative and anticancer properties. Use of flavonoids as ligands in transition metal complexes, e.g., those with a Ru(II) metal center, have been …

Tidal Flooding In The Mid-Atlantic Region Of The Us: Water Quality Effects In The Lower Chesapeake Bay, Alfonso Macias Tapia

OES Theses and Dissertations

Many coastal areas around the globe suffer from nutrient pollution and its environmental, social, and economic consequences. Nutrient inputs can come from point (e.g., the end of a pipe) and nonpoint sources, from which the former are better constrained as sampling need only be conducted at a discharge point. Given the temporal and spatially extensive nature of tidal flooding events, they can represent another type of nonpoint source of nutrients to adjacent water bodies heretofore, unexamined and quantified. Most studies examining impacts of tidal flooding have focused on threats to resources on land, such as urban infrastructure and human health …

Physicochemical Properties Of Poly (Ε-Caprolactone) And Magnesium Oxide Incorporated Poly (Ε-Caprolactone) Nanofibers, Daisaku Gicheha

All Theses

Polymer nanofibers are used to develop materials that possess customized characteristics for diverse applications. The applications of nanofibers are influenced by their significant surface-to-volume ratio, the porosity of the nanofiber lattice, and distinctive physicochemical characteristics. The molecular orientation of electrospun nanofibers is a crucial and intricate feature that has a direct impact on the structures and properties of the nanofiber mat. The utilization of Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and X-Ray Diffractometry (XRD), facilitated the determination of the morphology, chemical structure, and thermal properties of nanofibers. The SEM analysis revealed that the …

Road Map Of Semiconductor Metal-Oxide-Based Sensors: A Review, Taposhree Dutta, Tanzila Noushin, Shawna Tabassum, Satyendra K. Mishra

Electrical Engineering Faculty Publications and Presentations

Identifying disease biomarkers and detecting hazardous, explosive, flammable, and polluting gases and chemicals with extremely sensitive and selective sensor devices remains a challenging and time-consuming research challenge. Due to their exceptional characteristics, semiconducting metal oxides (SMOxs) have received a lot of attention in terms of the development of various types of sensors in recent years. The key performance indicators of SMOx-based sensors are their sensitivity, selectivity, recovery time, and steady response over time. SMOx-based sensors are discussed in this review based on their different properties. Surface properties of the functional material, such as its (nano)structure, morphology, and crystallinity, greatly influence …

Sulfur Cycling Connects Microbiomes And Biogeochemistry In Deep-Sea Hydrothermal Plumes, Zhichao Zhou, Patricia Q. Tran, Alyssa M. Adams, Kristopher Kieft, John A. Breier, Caroline S. Fortunato, Cody S. Sheik, Julie A. Huber, Meng Li, Gregory J. Dick, Karthik Anantharaman

School of Earth, Environmental, & Marine Sciences Faculty Publications

In globally distributed deep-sea hydrothermal vent plumes, microbiomes are shaped by the redox energy landscapes created by reduced hydrothermal vent fluids mixing with oxidized seawater. Plumes can disperse over thousands of kilometers and their characteristics are determined by geochemical sources from vents, e.g., hydrothermal inputs, nutrients, and trace metals. However, the impacts of plume biogeochemistry on the oceans are poorly constrained due to a lack of integrated understanding of microbiomes, population genetics, and geochemistry. Here, we use microbial genomes to understand links between biogeography, evolution, and metabolic connectivity, and elucidate their impacts on biogeochemical cycling in the deep sea. Using …

Effects Of Cathepsin S Inhibition In The Age-Related Dry Eye Phenotype, Jeremias G Galletti, Kaitlin K Scholand, Claudia M Trujillo-Vargas, Wolfgang Haap, Tiago Santos-Ferreira, Christoph Ullmer, Zhiyuan Yu, Cintia S De Paiva

Faculty, Staff and Students Publications

PURPOSE: Aged C57BL/6J (B6) mice have increased levels of cathepsin S, and aged cathepsin S (Ctss-/-) knockout mice are resistant to age-related dry eye. This study investigated the effects of cathepsin S inhibition on age-related dry eye disease.

METHODS: Female B6 mice aged 15.5 to 17 months were randomized to receive a medicated diet formulated by mixing the RO5461111 cathepsin S inhibitor or a standard diet for at least 12 weeks. Cornea mechanosensitivity was measured with a Cochet-Bonnet esthesiometer. Ocular draining lymph nodes and lacrimal glands (LGs) were excised and prepared for histology or assayed by flow cytometry to quantify …

Machine Learning Driven Index Of Tumor Multinucleation Correlates With Survival And Suppressed Anti-Tumor Immunity In Head And Neck Squamous Cell Carcinoma Patients, Can F Koyuncu, Mitchell J Frederick, Lester D R Thompson, Germán Corredor, Sirvan Khalighi, Zelin Zhang, Bolin Song, Cheng Lu, Reetoja Nag, Vidya Sankar Viswanathan, Michael Gilkey, Kailin Yang, Shlomo A Koyfman, Deborah J Chute, Patricia Castro, James S Lewis, Anant Madabhushi, Vlad C Sandulache

Faculty, Staff and Students Publications

OBJECTIVES: Matching treatment intensity to tumor biology is critical to precision oncology for head and neck squamous cell carcinoma (HNSCC) patients. We sought to identify biological features of tumor cell multinucleation, previously shown by us to correlate with survival in oropharyngeal (OP) SCC using a machine learning approach.

MATERIALS AND METHODS: Hematoxylin and eosin images from an institutional OPSCC cohort formed the training set (D

RESULTS: MuNI correlated with overall survival. A multivariable nomogram that included MuNI, age, race, sex, T/N stage, and smoking status yielded a C-index of 0.65, and MuNI was prognostic of overall survival (2.25, 1.07-4.71, 0.03), …

Deployment Of Cisplatin In Veterans With Oropharyngeal Cancer: Toxicity And Impact On Oncologic Outcomes, Ola Soliman, David C Wilde, Jan O Kemnade, Anita L Sabichi, George Chen, Albert Chen, Samantha N Little, Andrew T Huang, David J Hernandez, Vlad C Sandulache

Faculty, Staff and Students Publications

OBJECTIVE: Cisplatin forms the backbone of systemic chemotherapy treatment for oropharyngeal squamous cell carcinoma (OPSCC). The ideal cisplatin dosing regimen remains yet to be fully defined for achieving optimal efficacy and toxicity profiles in patients with comorbidity.

METHODS: We retrospectively reviewed oncologic and toxicity data for patients with OPSCC treated at the Michael E. DeBakey Veterans Affairs Medical Center between 2000 and 2020 who initiated curative intent, definitive chemo-radiation with one of three single agent regimens: high dose (HD) cisplatin, low dose (LD) cisplatin or cetuximab.

RESULTS: Patients with HPV-associated tumors and nonsmokers demonstrated improved overall and disease-free survival along …

Deconvolution Of Cancer Cell States By The Xdec-Sm Method, Oscar D Murillo, Varduhi Petrosyan, Emily L Laplante, Lacey E Dobrolecki, Michael T Lewis, Aleksandar Milosavljevic

Faculty, Staff and Students Publications

Proper characterization of cancer cell states within the tumor microenvironment is a key to accurately identifying matching experimental models and the development of precision therapies. To reconstruct this information from bulk RNA-seq profiles, we developed the XDec Simplex Mapping (XDec-SM) reference-optional deconvolution method that maps tumors and the states of constituent cells onto a biologically interpretable low-dimensional space. The method identifies gene sets informative for deconvolution from relevant single-cell profiling data when such profiles are available. When applied to breast tumors in The Cancer Genome Atlas (TCGA), XDec-SM infers the identity of constituent cell types and their proportions. XDec-SM also …

Chromatin Architectural Factor Ctcf Is Essential For Progesterone-Dependent Uterine Maturation, Sylvia C Hewitt, Artiom Gruzdev, Cynthia J Willson, San-Pin Wu, John P Lydon, Niels Galjart, Francesco J Demayo

Faculty, Staff and Students Publications

Receptors for estrogen and progesterone frequently interact, via Cohesin/CTCF loop extrusion, at enhancers distal from regulated genes. Loss-of-function CTCF mutation in >20% of human endometrial tumors indicates its importance in uterine homeostasis. To better understand how CTCF-mediated enhancer-gene interactions impact endometrial development and function, the Ctcf gene was selectively deleted in female reproductive tissues of mice. Prepubertal Ctcf

Trim28 Modulates Nuclear Receptor Signaling To Regulate Uterine Function, Rong Li, Tianyuan Wang, Ryan M Marquardt, John P Lydon, San-Pin Wu, Francesco J Demayo

Faculty, Staff and Students Publications

Estrogen and progesterone, acting through their cognate receptors the estrogen receptor α (ERα) and the progesterone receptor (PR) respectively, regulate uterine biology. Using rapid immunoprecipitation and mass spectrometry (RIME) and co-immunoprecipitation, we identified TRIM28 (Tripartite motif containing 28) as a protein which complexes with ERα and PR in the regulation of uterine function. Impairment of TRIM28 expression results in the inability of the uterus to support early pregnancy through altered PR and ERα action in the uterine epithelium and stroma by suppressing PR and ERα chromatin binding. Furthermore, TRIM28 ablation in PR-expressing uterine cells results in the enrichment of a …

Spatial Mapping Of The Dna Adducts In Cancer, Kimiko L Krieger, Elise K Mann, Kevin J Lee, Elyse Bolterstein, Deborah Jebakumar, Michael M Ittmann, Valeria L Dal Zotto, Mohamed Shaban, Arun Sreekumar, Natalie R Gassman

Faculty, Staff and Students Publications

DNA adducts and strand breaks are induced by various exogenous and endogenous agents. Accumulation of DNA damage is implicated in many disease processes, including cancer, aging, and neurodegeneration. The continuous acquisition of DNA damage from exogenous and endogenous stressors coupled with defects in DNA repair pathways contribute to the accumulation of DNA damage within the genome and genomic instability. While mutational burden offers some insight into the level of DNA damage a cell may have experienced and subsequently repaired, it does not quantify DNA adducts and strand breaks. Mutational burden also infers the identity of the DNA damage. With advances …

Delayed Skeletal Development And Igf-1 Deficiency In A Mouse Model Of Lysinuric Protein Intolerance, Bridget M Stroup, Xiaohui Li, Sara Ho, Haonan Zhouyao, Yuqing Chen, Safa Ani, Brian Dawson, Zixue Jin, Ronit Marom, Ming-Ming Jiang, Isabel Lorenzo, Daniel Rosen, Denise Lanza, Nathalie Aceves, Sara Koh, John R Seavitt, Jason D Heaney, Brendan Lee, Lindsay C Burrage

Faculty, Staff and Students Publications

SLC7A7 deficiency, or lysinuric protein intolerance (LPI), causes loss of function of the y+LAT1 transporter critical for efflux of arginine, lysine and ornithine in certain cells. LPI is characterized by urea cycle dysfunction, renal disease, immune dysregulation, growth failure, delayed bone age and osteoporosis. We previously reported that Slc7a7 knockout mice (C57BL/6×129/SvEv F2) recapitulate LPI phenotypes, including growth failure. Our main objective in this study was to characterize the skeletal phenotype in these mice. Compared to wild-type littermates, juvenile Slc7a7 knockout mice demonstrated 70% lower body weights, 87% lower plasma IGF-1 concentrations and delayed skeletal development. Because poor survival prevents …

Why Animal Experiments Are Still Indispensable In Bone Research: A Statement By The European Calcified Tissue Society, Merle Stein, Florent Elefteriou, Björn Busse, Imke Ak Fiedler, Ronald Young Kwon, Eric Farrell, Mubashir Ahmad, Anita Ignatius, Liam Grover, Liesbet Geris, Jan Tuckermann

Faculty, Staff and Students Publications

Major achievements in bone research have always relied on animal models and in vitro systems derived from patient and animal material. However, the use of animals in research has drawn intense ethical debate and the complete abolition of animal experimentation is demanded by fractions of the population. This phenomenon is enhanced by the reproducibility crisis in science and the advance of in vitro and in silico techniques. 3D culture, organ-on-a-chip, and computer models have improved enormously over the last years. Nevertheless, the overall complexity of bone tissue-cross talk and the systemic and local regulation of bone physiology can often only …

Prdm16 Deletion Is Associated With Sex-Dependent Cardiomyopathy And Cardiac Mortality: A Translational, Multi-Institutional Cohort Study, Ryan J Kramer, Amir Nima Fatahian, Alice Chan, Jeffery Mortenson, Jennifer Osher, Bo Sun, Lauren E Parker, Michael B Rosamilia, Kyra B Potter, Kaila Moore, Sage L Atkins, Jill A Rosenfeld, Alona Birjiniuk, Edward Jones, Taylor S Howard, Jeffrey J Kim, Daryl A Scott, Seema Lalani, Omid M T Rouzbehani, Samantha Kaplan, Marissa A Hathaway, Jennifer L Cohen, S Yukiko Asaki, Hugo R Martinez, Sihem Boudina, Andrew P Landstrom

Faculty, Staff and Students Publications

BACKGROUND: 1p36 deletion syndrome can predispose to pediatric-onset cardiomyopathy. Deletion breakpoints are variable and may delete the transcription factor

METHODS: This retrospective cohort included subjects with 1p36 deletion syndrome from 4 hospitals. Prevalence of cardiomyopathy and freedom from death, cardiac transplantation, or ventricular assist device were analyzed. A systematic review cohort was derived for further analysis. A cardiac-specific

RESULTS: The retrospective cohort included 71 patients. Among individuals with

CONCLUSIONS:

Shinybioheat: An Interactive Shiny App To Identify Phenotype Driver Genes In Ecoli And Bsubtilis, Chen Wang, Harikumar Govindarajan, Panagiotis Katsonis, Olivier Lichtarge

Faculty, Staff and Students Publications

SUMMARY: In any population under selective pressure, a central challenge is to distinguish the genes that drive adaptation from others which, subject to population variation, harbor many neutral mutations de novo. We recently showed that such genes could be identified by supplementing information on mutational frequency with an evolutionary analysis of the likely functional impact of coding variants. This approach improved the discovery of driver genes in both lab-evolved and environmental Escherichia coli strains. To facilitate general adoption, we now developed ShinyBioHEAT, an R Shiny web-based application that enables identification of phenotype driving gene in two commonly used model bacteria, …

The Clinical And Genetic Spectrum Of Autosomal-Recessive Tor1a-Related Disorders, Afshin Saffari, Tracy Lau, Homa Tajsharghi, Ehsan Ghayoor Karimiani, Ariana Kariminejad, Stephanie Efthymiou, Giovanni Zifarelli, Tipu Sultan, Mehran Beiraghi Toosi, Sahar Sedighzadeh, Victoria Mok Siu, Juan Darío Ortigoza-Escobar, Aisha M Alshamsi, Shahnaz Ibrahim, Nouriya Abbas Al-Sannaa, Walla Al-Hertani, Whalen Sandra, Mark Tarnopolsky, Shahryar Alavi, Chumei Li, Debra-Lynn Day-Salvatore, Maria Jesús Martínez-González, Kristin M Levandoski, Emma Bedoukian, Suneeta Madan-Khetarpal, Michaela J Idleburg, Minal Juliet Menezes, Aishwarya Siddharth, Konrad Platzer, Henry Oppermann, Martin Smitka, Felicity Collins, Monkol Lek, Mohmmad Shahrooei, Maryam Ghavideldarestani, Isabella Herman, John Rendu, Julien Faure, Janice Baker, Vikas Bhambhani, Laurel Calderwood, Javad Akhondian, Shima Imannezhad, Hanieh Sadat Mirzadeh, Narges Hashemi, Mohammad Doosti, Mojtaba Safi, Najmeh Ahangari, Paria Najarzadeh Torbati, Soheila Abedini, Vincenzo Salpietro, Elif Yilmaz Gulec, Safieh Eshaghian, Mohammadreza Ghazavi, Michael T Pascher, Marina Vogel, Angela Abicht, Sébastien Moutton, Ange-Line Bruel, Claudine Rieubland, Sabina Gallati, Tim M Strom, Hanns Lochmüller, Mohammad Hasan Mohammadi, Javeria Raza Alvi, Elaine H Zackai, Beth A Keena, Cara M Skraban, Seth I Berger, Erin H Andrew, Elham Rahimian, Michelle M Morrow, Ingrid M Wentzensen, Francisca Millan, Lindsay B Henderson, Hormos Salimi Dafsari, Heinz Jungbluth, Natalia Gomez-Ospina, Anne Mcrae, Merlene Peter, Danai Veltra, Nikolaos M Marinakis, Christalena Sofocleous, Farah Ashrafzadeh, Davut Pehlivan, Johannes R Lemke, Judith Melki, Audrey Benezit, Peter Bauer, Denisa Weis, James R Lupski, Jan Senderek, John Christodoulou, Wendy K Chung, Rose Goodchild, Amaka C Offiah, Andres Moreno-De-Luca, Mohnish Suri, Darius Ebrahimi-Fakhari, Henry Houlden, Reza Maroofian

Faculty, Staff and Students Publications

In the field of rare diseases, progress in molecular diagnostics led to the recognition that variants linked to autosomal-dominant neurodegenerative diseases of later onset can, in the context of biallelic inheritance, cause devastating neurodevelopmental disorders and infantile or childhood-onset neurodegeneration. TOR1A-associated arthrogryposis multiplex congenita 5 (AMC5) is a rare neurodevelopmental disorder arising from biallelic variants in TOR1A, a gene that in the heterozygous state is associated with torsion dystonia-1 (DYT1 or DYT-TOR1A), an early-onset dystonia with reduced penetrance. While 15 individuals with AMC5-TOR1A have been reported (less than 10 in detail), a systematic investigation of …

Clinical And Functional Heterogeneity Associated With The Disruption Of Retinoic Acid Receptor Beta, Véronique Caron, Nicolas Chassaing, Nicola Ragge, Felix Boschann, Angelina My-Hoa Ngu, Elisabeth Meloche, Sarah Chorfi, Saquib A Lakhani, Weizhen Ji, Laurie Steiner, Julien Marcadier, Philip R Jansen, Laura A Van De Pol, Johanna M Van Hagen, Alvaro Serrano Russi, Gwenaël Le Guyader, Magnus Nordenskjöld, Ann Nordgren, Britt-Marie Anderlid, Julie Plaisancié, Corinna Stoltenburg, Denise Horn, Anne Drenckhahn, Fadi F Hamdan, Mathilde Lefebvre, Tania Attie-Bitach, Peggy Forey, Vasily Smirnov, Françoise Ernould, Marie-Line Jacquemont, Sarah Grotto, Alberto Alcantud, Alicia Coret, Rosario Ferrer-Avargues, Siddharth Srivastava, Catherine Vincent-Delorme, Shelby Romoser, Nicole Safina, Dimah Saade, James R Lupski, Daniel G Calame, David Geneviève, Nicolas Chatron, Caroline Schluth-Bolard, Kenneth A Myers, William B Dobyns, Patrick Calvas, Ddd Study, Caroline Salmon, Richard Holt, Frances Elmslie, Marc Allaire, Daniil M Prigozhin, André Tremblay, Jacques L Michaud

Faculty, Staff and Students Publications

PURPOSE: Dominant variants in the retinoic acid receptor beta (RARB) gene underlie a syndromic form of microphthalmia, known as MCOPS12, which is associated with other birth anomalies and global developmental delay with spasticity and/or dystonia. Here, we report 25 affected individuals with 17 novel pathogenic or likely pathogenic variants in RARB. This study aims to characterize the functional impact of these variants and describe the clinical spectrum of MCOPS12.

METHODS: We used in vitro transcriptional assays and in silico structural analysis to assess the functional relevance of RARB variants in affecting the normal response to retinoids.

RESULTS: We found that …

Broadening The Phenotypic And Molecular Spectrum Of Finca Syndrome: Biallelic Nhlrc2 Variants In 15 Novel Individuals, Henrike L Sczakiel, Max Zhao, Brigitte Wollert-Wulf, Magdalena Danyel, Nadja Ehmke, Corinna Stoltenburg, Nadirah Damseh, Motee Al-Ashhab, Tugce B Balci, Matthew Osmond, Andrea Andrade, Jens Schallner, Joseph Porrmann, Kimberly Mcdonald, Mingjuan Liao, Henry Oppermann, Konrad Platzer, Nadine Dierksen, Majid Mojarrad, Atieh Eslahi, Behnaz Bakaeean, Daniel G Calame, James R Lupski, Zahra Firoozfar, Seyed Mohammad Seyedhassani, Seyed Ahmad Mohammadi, Najwa Anwaar, Fatima Rahman, Dominik Seelow, Martin Janz, Denise Horn, Reza Maroofian, Felix Boschann

Faculty, Staff and Students Publications

FINCA syndrome [MIM: 618278] is an autosomal recessive multisystem disorder characterized by fibrosis, neurodegeneration and cerebral angiomatosis. To date, 13 patients from nine families with biallelic NHLRC2 variants have been published. In all of them, the recurrent missense variant p.(Asp148Tyr) was detected on at least one allele. Common manifestations included lung or muscle fibrosis, respiratory distress, developmental delay, neuromuscular symptoms and seizures often followed by early death due to rapid disease progression.

Here, we present 15 individuals from 12 families with an overlapping phenotype associated with nine novel NHLRC2 variants identified by exome analysis. All patients described here presented with …