Digital Commons Network^™

Combating Hypertension Beyond Genome-Wide Association Studies: Microbiome And Artificial Intelligence As Opportunities For Precision Medicine, Sachin Aryal, Ishan Manandhar, Xue Mei, Beng S Yeoh, Ramakumar Tummala, Piu Saha, Islam Osman, Jasenka Zubcevic, David J Durgan, Matam Vijay-Kumar, Bina Joe

Faculty, Staff and Students Publications

The single largest contributor to human mortality is cardiovascular disease, the top risk factor for which is hypertension (HTN). The last two decades have placed much emphasis on the identification of genetic factors contributing to HTN. As a result, over 1,500 genetic alleles have been associated with human HTN. Mapping studies using genetic models of HTN have yielded hundreds of blood pressure (BP) loci but their individual effects on BP are minor, which limits opportunities to target them in the clinic. The value of collecting genome-wide association data is evident in ongoing research, which is beginning to utilize these data …

Open-Source, Highly Efficient, Post-Acquisition Synchronization For 4d Dual-Contrast Imaging Of The Mouse Embryonic Heart Over Development With Optical Coherence Tomography, Andre C Faubert, Irina V Larina, Shang Wang

Faculty, Staff and Students Publications

Dynamic imaging of the beating embryonic heart in 3D is critical for understanding cardiac development and defects. Optical coherence tomography (OCT) plays an important role in embryonic heart imaging with its unique imaging scale and label-free contrasts. In particular, 4D (3D + time) OCT imaging enabled biomechanical analysis of the developing heart in various animal models. While ultrafast OCT systems allow for direct volumetric imaging of the beating heart, the imaging speed remains limited, leading to an image quality inferior to that produced by post-acquisition synchronization. As OCT systems become increasingly available to a wide range of biomedical researchers, a …

Second Virtual International Symposium On Cellular And Organismal Stress Responses, September 8-9, 2022, Patricija Van Oosten-Hawle, Sarah J Backe, Anat Ben-Zvi, Dimitra Bourboulia, Mara Brancaccio, Jeff Brodsky, Melody Clark, Giorgio Colombo, Marc B Cox, Paolo De Los Rios, Frank Echtenkamp, Adrienne Edkins, Brian Freeman, Pierre Goloubinoff, Walid Houry, Jill Johnson, Paul Lapointe, Wei Li, Valerie Mezger, Len Neckers, Nadinath B Nillegoda, Veena Prahlad, Adam Reitzel, Ruth Scherz-Shouval, Lea Sistonen, Francis T F Tsai, Mark R Woodford, Mehdi Mollapour, Andrew W Truman

Faculty, Staff and Students Publications

The Second International Symposium on Cellular and Organismal Stress Responses took place virtually on September 8-9, 2022. This meeting was supported by the Cell Stress Society International (CSSI) and organized by Patricija Van Oosten-Hawle and Andrew Truman (University of North Carolina at Charlotte, USA) and Mehdi Mollapour (SUNY Upstate Medical University, USA). The goal of this symposium was to continue the theme from the initial meeting in 2020 by providing a platform for established researchers, new investigators, postdoctoral fellows, and students to present and exchange ideas on various topics on cellular stress and chaperones. We will summarize the highlights of …

A Guide To Naming Eukaryotic Circular Rnas, Ling-Ling Chen, Albrecht Bindereif, Irene Bozzoni, Howard Y Chang, A Gregory Matera, Myriam Gorospe, Thomas B Hansen, Jørgen Kjems, Xu-Kai Ma, Jun Wei Pek, Nikolaus Rajewsky, Julia Salzman, Jeremy E Wilusz, Li Yang, Fangqing Zhao

Faculty, Staff and Students Publications

Alternative splicing of eukaryotic transcripts often leads to production of multiple mature RNAs from a single gene locus. In addition to encoding linear RNAs, genes can produce stable circular RNAs (circRNAs) that are often co-expressed with their cognate linear RNAs. Multiple distinct circRNAs are frequently generated from a gene locus via back-splicing, with each mature transcript having a potentially unique function due to its distinct combination of exons and sometimes retained introns. However, names currently given to circRNAs are often ambiguous and lack consistency across studies. Here, we call on the community to embrace standards for naming circRNAs so that …

Transformations Between Rotational And Translational Invariants Formulated In Reciprocal Spaces, Philip R Baldwin

Faculty, Staff and Students Publications

Correlation functions play an important role in the theoretical underpinnings of many disparate areas of the physical sciences: in particular, scattering theory. More recently, they have become useful in the classification of objects in areas such as computer vision and our area of cryoEM. Our primary classification scheme in the cryoEM image processing system, EMAN2, is now based on third order invariants formulated in Fourier space. This allows a factor of 8 speed up in the two classification procedures inherent in our software pipeline, because it allows for classification without the need for computationally costly alignment procedures. In this work, …

Editorial: Biological Drivers Of Vector-Pathogen Interactions – Vol Ii, Ryan O M Rego, Job E Lopez, Alejandro Cabesas-Cruz

Faculty, Staff and Students Publications

No abstract provided.

Problems With Etiologic Diagnosis Of Community-Acquired Pneumonia Using Plasma Microbial Cell-Free Dna Sequencing, Daniel M Musher

Faculty, Staff and Students Publications

No abstract provided.

Editorial: Regeneration From Cells To Limbs: Past, Present, And Future, Pamela Imperadore, Kathryn Maxson Jones, Jennifer R Morgan, Fabio De Sio, Frank W Stahnisch

Faculty, Staff and Students Publications

No abstract provided.

Protocol Of Detection Of West Nile Virus In Clinical Samples, Hephzibah Nwanosike, Freedom M Green, Kristy O Murray, Jill E Weatherhead, Shannon E Ronca

Faculty, Staff and Students Publications

West Nile virus (WNV) is one of the leading causes of arboviral encephalitis in the United States but is often underdiagnosed. Despite the wide breadth of WNV-induced clinical disease syndromes, many of the symptoms associated with WNV are nonspecific at the time of presentation; thus, choosing the right diagnostic tool is essential to not only understand the true burden of disease but also provide pathogen-directed interventions for WNV-infected patients. In this chapter, we briefly discuss the three most common types of diagnostic methods for WNV in human clinical samples: nucleic acid detection, enzyme-linked immunoassay (ELISA), and plaque reduction neutralization test …

Safety Procedures To Work With West Nile Virus In Biosafety Level 3 Facilities, Freedom M Green, Shannon E Ronca

Faculty, Staff and Students Publications

West Nile virus (WNV) can cause severe and sometimes fatal disease, but we do not have treatments or therapeutics to manage these outcomes. Since its introduction to the USA in 1999, WNV has been handled in a biosafety level 3 laboratory to decrease risk to researchers, requiring strict safety protocols and important considerations with planning experiments. Recent changes in US guidelines suggest that WNV can be handled at a lower biosafety level due to its endemicity in the USA and generally minor symptoms, but some research still requires the use of the agent at biosafety level 3. This chapter will …

Coping During The Covid-19 Pandemic Among Young Adults Experiencing Homelessness And Unstable Housing: A Qualitative Study, Karen Divalerio Gibbs, Jennifer Torres Jones, Whitney Lamark, Sarah Abdulmooti, Lauren Bretz, Kelly D Kearney, Sarah Carter Narendorf, Diane M Santa Maria

Faculty, Staff and Students Publications

BACKGROUND: Young adults experiencing homelessness (YAEH) experience more stressors compared to housed peers, yet little is known about the impact of the COVID-19 pandemic on these youth. The purpose of this qualitative study was to explore how YAEH perceived the pandemic's impact on their well-being and coping.

METHODS: YAEH were recruited from those participating in an HIV prevention study. Semi-structured interviews were conducted and analysis was guided by Lazarus and Folkman's transactional theory of stress and coping.

RESULTS: Four major themes were identified from interviews with 40 youth: (1) ongoing harms, (2) COVID-19 as a stressor, (3) mental health impacts, …

Physiologic Profile Associated With Severe Multisystem Inflammatory Syndrome In Children: A Retrospective Study, Fabio Savorgnan, Alvaro Moreira, Axel Moreira, Ananth Annapragada, S Kristen Sexson Tejtel, Saul Flores, Craig G Rusin, Lara Shekerdemian, Sebastian Acosta

Faculty, Staff and Students Publications

OBJECTIVE: The purpose of this study was to describe the clinical presentation and physiologic profile of individuals with varying degrees of severity of multisystem inflammatory syndrome in children (MIS-C).

METHODS: We performed a retrospective study of children diagnosed with MIS-C admitted to a single quaternary children's hospital from May 2020 to April 2021. We created an MIS-C severity score using the following parameters: hospital admission status (e.g., floor vs intensive care unit), need for inotropic or vasoactive medications, and need for mechanical ventilation. Univariate and multivariate analyses were performed to associate risk factors corresponding to the MIS-C severity score.

RESULTS: …

The Many Faces Of Arrhythmogenic Cardiomyopathy: An Overview, Hanna J Tadros, Christina Y Miyake, Debra L Kearney, Jeffrey J Kim, Susan W Denfield

Faculty, Staff and Students Publications

Arrhythmogenic cardiomyopathy (AC) is a disease that involves electromechanical uncoupling of cardiomyocytes. This leads to characteristic histologic changes that ultimately lead to the arrhythmogenic clinical features of the disease. Initially thought to affect the right ventricle predominantly, more recent data show that it can affect both the ventricles or the left ventricle alone. Throughout the recent era, diagnostic modalities and criteria for AC have continued to evolve and our understanding of its clinical features in different age groups as well as the genotype to the phenotype correlations have improved. In this review, we set out to detail the epidemiology, etiologies, …

Semi-Automated Construction Of Patient-Specific Aortic Valves From Computed Tomography Images, Dan Lior, Charles Puelz, Colin Edwards, Silvana Molossi, Boyce E Griffith, Ravi K Birla, Craig G Rusin

Faculty, Staff and Students Publications

This paper presents a semi-automatic method for the construction of volumetric models of the aortic valve using computed tomography angiography images. Although the aortic valve typically cannot be segmented directly from a computed tomography angiography image, the method described herein uses manually selected samples of an aortic segmentation derived from this image to inform the construction. These samples capture certain physiologic landmarks and are used to construct a volumetric valve model. As a demonstration of the capabilities of this method, valve models for 25 pediatric patients are created. A selected valve anatomy is used to perform fluid-structure interaction simulations using …

Cerebrospinal Fluid Biomarkers Provide Evidence For Kidney-Brain Axis Involvement In Cerebral Malaria Pathogenesis, Andrea L Conroy, Dibyadyuti Datta, Robert O Opoka, Anthony Batte, Paul Bangirana, Adnan Gopinadhan, Kagan A Mellencamp, Ayse Akcan-Arikan, Richard Idro, Chandy C John

Faculty, Staff and Students Publications

INTRODUCTION: Cerebral malaria is one of the most severe manifestations of malaria and is a leading cause of acquired neurodisability in African children. Recent studies suggest acute kidney injury (AKI) is a risk factor for brain injury in cerebral malaria. The present study evaluates potential mechanisms of brain injury in cerebral malaria by evaluating changes in cerebrospinal fluid measures of brain injury with respect to severe malaria complications. Specifically, we attempt to delineate mechanisms of injury focusing on blood-brain-barrier integrity and acute metabolic changes that may underlie kidney-brain crosstalk in severe malaria.

METHODS: We evaluated 30 cerebrospinal fluid (CSF) markers …

Characterization Of Propofol Use For Non-Procedural Sedation In A Pediatric Intensive Care Unit, Jenna Wood Bartlett, Brooke N Curry, Matthew A Musick, Megan Mckee Moore

Faculty, Staff and Students Publications

OBJECTIVE: Given the limited literature describing propofol use in pediatric patients, this study aimed to describe the dosing and duration of propofol infusions for non-procedural sedation in the pediatric intensive care unit (PICU). The secondary objectives were to describe the change in concomitant sedative requirements from the 24-hour period before propofol initiation to the 24-hour period after discontinuation of propofol and to review the frequency of adverse events.

METHODS: This retrospective descriptive cohort study evaluated children 1 month to less than 18 years old who received a continuous infusion of propofol for non-procedural sedation in the PICU between May 2018 …

Transcriptomic Profiles Of Multiple Organ Dysfunction Syndrome Phenotypes In Pediatric Critical Influenza, Tanya Novak, Jeremy Chase Crawford, Georg Hahn, Mark W Hall, Simone A Thair, Margaret M Newhams, Janet Chou, Peter M Mourani, Keiko M Tarquinio, Barry Markovitz, Laura L Loftis, Scott L Weiss, Renee Higgerson, Adam J Schwarz, Neethi P Pinto, Neal J Thomas, Rainer G Gedeit, Ronald C Sanders, Sidharth Mahapatra, Bria M Coates, Natalie Z Cvijanovich, Kate G Ackerman, David W Tellez, Patrick Mcquillen, Stephen C Kurachek, Steven L Shein, Christoph Lange, Paul G Thomas, Adrienne G Randolph

Faculty, Staff and Students Publications

BACKGROUND: Influenza virus is responsible for a large global burden of disease, especially in children. Multiple Organ Dysfunction Syndrome (MODS) is a life-threatening and fatal complication of severe influenza infection.

METHODS: We measured RNA expression of 469 biologically plausible candidate genes in children admitted to North American pediatric intensive care units with severe influenza virus infection with and without MODS. Whole blood samples from 191 influenza-infected children (median age 6.4 years, IQR: 2.2, 11) were collected a median of 27 hours following admission; for 45 children a second blood sample was collected approximately seven days later. Extracted RNA was hybridized …

Case Report: Selexipag In Pediatric Pulmonary Hypertension: Initiation, Transition, And Titration, Jenna M Faircloth, Neelam D Bhatt, Corey A Chartan, Ryan D Coleman, Natalie Villafranco, Fadel E Ruiz, Raysa Morales-Demori, Elise Whalen, Erin Ely, Rozmeen Fombin, Nidhy P Varghese

Faculty, Staff and Students Publications

Selexipag, a selective prostacyclin receptor agonist, is approved for treating pulmonary arterial hypertension in WHO Group 1 adult patients. Compared to parenteral prostacyclin formulations, selexipag offers a significant improvement in patient’s and caregiver’s quality of life because of its oral formulation, frequency of administration, and mechanism of action. Although experience in the pediatric population is limited and selexipag is not FDA-approved for use in the pediatric pulmonary hypertension population, many US pediatric centers are expanding the use of this therapy to this younger population. We report our institution's experience in the use of selexipag to treat pulmonary hypertension in children …

Pediatric Traumatic Hemorrhagic Shock Consensus Conference Recommendations, Robert T Russell, Joseph R Esparaz, Michael A Beckwith, Peter J Abraham, Melania M Bembea, Matthew A Borgman, Randall S Burd, Barbara A Gaines, Mubeen Jafri, Cassandra D Josephson, Christine Leeper, Julie C Leonard, Jennifer A Muszynski, Kathleen K Nicol, Daniel K Nishijima, Paul A Stricker, Adam M Vogel, Trisha E Wong, Philip C Spinella

Faculty, Staff and Students Publications

Hemorrhagic shock in pediatric trauma patients remains a challenging yet preventable cause of death. There is little high-quality evidence available to guide specific aspects of hemorrhage control and specific resuscitation practices in this population. We sought to generate clinical recommendations, expert consensus, and good practice statements to aid providers in care for these difficult patients.The Pediatric Traumatic Hemorrhagic Shock Consensus Conference process included systematic reviews related to six subtopics and one consensus meeting. A panel of 16 consensus multidisciplinary committee members evaluated the literature related to 6 specific topics: (1) blood products and fluid resuscitation for hemostatic resuscitation, (2) utilization …

Absolute Lymphocyte Count Recovery Following Initial Acute Myelogenous Leukemia Therapy: Implications For Adoptive Cell Therapy, John C Molina, Yimei Li, William R Otto, Tamara P Miller, Kelly D Getz, Carly Mccoubrey, Mark Ramos, Edward Krause, Lusha Cao, M Monica Gramatges, Karen Rabin, Michael Scheurer, Caitlin W Elgarten, Regina M Myers, Alix E Seif, Brian T Fisher, Nirali N Shah, Richard Aplenc

Faculty, Staff and Students Publications

Background: An adequate absolute lymphocyte count (ALC) is an essential first step in autologous chimeric antigen receptor (CAR) T-cell manufacturing. For patients with acute myelogenous leukemia (AML), the intensity of chemotherapy received may affect adequate ALC recovery required for CAR T-cell production. We sought to analyze ALC following each course of upfront therapy as one metric for CAR T-cell manufacturing feasibility in children and young adults with AML.

Procedure: ALC data were collected from an observational study of patients with newly diagnosed AML between the ages of 1 month and 21 years who received treatment between the years of 2006 …

Human Papillomavirus Dose Reminder Preferences Among Parents From A Diverse Clinical Sample: A Qualitative Study, Jacqueline M Hirth, Kayla A Eboreime, Leslie E Cofie, Richard E Rupp, Abbey B Berenson

Faculty, Staff and Students Publications

Reminders are an important method for encouraging patients to return for follow-up visits, such as for successive doses of the human papillomavirus (HPV) vaccine. However, patients may have preferences for different types of reminders. This study examined which reminder methods parents of pediatric patients found most useful and their thoughts on how the reminders helped them to complete their children's HPV vaccine series. This qualitative study was conducted on a purposively sampled group of parents who participated in a multi-level intervention intended to improve uptake and completion of the HPV vaccine series. Parents who agreed to participate were interviewed by …

Kdm6b Variants May Contribute To The Pathophysiology Of Human Cerebral Folate Deficiency, Xiao Han, Xuanye Cao, Robert M Cabrera, Paula Andrea Pimienta Ramirez, Cuilian Zhang, Vincent T Ramaekers, Richard H Finnell, Yunping Lei

Faculty, Staff and Students Publications

(1) Background: The genetic etiology of most patients with cerebral folate deficiency (CFD) remains poorly understood. KDM6B variants were reported to cause neurodevelopmental diseases; however, the association between KDM6B and CFD is unknown; (2) Methods: Exome sequencing (ES) was performed on 48 isolated CFD cases. The effect of KDM6B variants on KDM6B protein expression, Histone H3 lysine 27 epigenetic modification and FOLR1 expression were examined in vitro. For each patient, serum FOLR1 autoantibodies were measured; (3) Results: Six KDM6B variants were identified in five CFD patients, which accounts for 10% of our CFD cohort cases. Functional experiments indicated that these …

Measurement Of Force And Intramuscular Pressure Changes Related To Thrust Spinal Manipulation In An In Vivo Animal Model, William R Reed, Carla R Lima, Michael A K Liebschner, Christopher P Hurt, Peng Li, Maruti R Gudavalli

Faculty, Staff and Students Publications

Simple Summary

Spinal manipulation is recommended by clinical guidelines to treat low back pain. However, our understanding of how spinal manipulation alleviates pain and knowledge of the role that viscoelastic tissue properties play in the dampening of applied spinal manipulation forces in vivo is limited. Superficial and deep intramuscular pressures and applied forces were measured using miniature pressure catheters and a force transducer during low back spinal manipulation using a clinically available spinal manipulation device (Activator V) or a feedback motor in a deeply anesthetized animal model. Viscoelastic properties of muscle and other soft tissues greatly diminished applied spinal manipulative …

Assembling A Global Database Of Child Pneumonia Studies To Inform Who Pneumonia Management Algorithm: Methodology And Applications, Helena Martin, Jennifer Falconer, Emmanuel Addo-Yobo, Satinder Aneja, Luis Martinez Arroyo, Rai Asghar, Shally Awasthi, Salem Banajeh, Abdul Bari, Sudha Basnet, Ashish Bavdekar, Nita Bhandari, Shinjini Bhatnagar, Zulfiqar A Bhutta, Abdullah Brooks, Mandeep Chadha, Noel Chisaka, Monidarin Chou, Alexey W Clara, Tim Colbourn, Clare Cutland, Valérie D'Acremont, Marcela Echavarria, Angela Gentile, Brad Gessner, Christopher J Gregory, Tabish Hazir, Patricia L Hibberd, Siddhivinayak Hirve, Shubhada Hooli, Imran Iqbal, Prakash Jeena, Cissy B Kartasasmita, Carina King, Romina Libster, Rakesh Lodha, Juan M Lozano, Marilla Lucero, Norman Lufesi, William B Macleod, Shabir Ahmed Madhi, Joseph L Mathew, Irene Maulen-Radovan, Eric D Mccollum, Greta Mino, Charles Mwansambo, Mark I Neuman, Ngoc Tuong Vy Nguyen, Marta C Nunes, Pagbajabyn Nymadawa, Kerry-Ann F O'Grady, Jean-William Pape, Glaucia Paranhos-Baccala, Archana Patel, Valentina Sanchez Picot, Mala Rakoto-Andrianarivelo, Zeba Rasmussen, Vanessa Rouzier, Graciela Russomando, Raul O Ruvinsky, Salim Sadruddin, Samir K Saha, Mathuram Santosham, Sunit Singhi, Sajid Soofi, Tor A Strand, Mariam Sylla, Somsak Thamthitiwat, Donald M Thea, Claudia Turner, Philippe Vanhems, Nitya Wadhwa, Jianwei Wang, Syed Ma Zaman, Harry Campbell, Harish Nair, Shamim Ahmad Qazi, Yasir Bin Nisar, World Health Organization Pneumonia Research Partnership To Assess Who Recommendation (Prepare) Study Group

Faculty, Staff and Students Publications

BACKGROUND: The existing World Health Organization (WHO) pneumonia case management guidelines rely on clinical symptoms and signs for identifying, classifying, and treating pneumonia in children up to 5 years old. We aimed to collate an individual patient-level data set from large, high-quality pre-existing studies on pneumonia in children to identify a set of signs and symptoms with greater validity in the diagnosis, prognosis, and possible treatment of childhood pneumonia for the improvement of current pneumonia case management guidelines.

METHODS: Using data from a published systematic review and expert knowledge, we identified studies meeting our eligibility criteria and invited investigators to …

Feasibility And Effectiveness Of A Worksite-Weight-Loss Program For Cancer Prevention Among School-District Employees With Overweight And Obesity, Che Young Lee, Michael C Robertson, Hannah Johnston, Thuan Le, Margaret Raber, Ruth Rechis, Katherine Oestman, Alise Neff, Amber Macneish, Karen M Basen-Engquist

Faculty, Staff and Students Publications

The effects of Vibrant Lives, a 6-month worksite-weight-loss program, were examined in a cohort of school-district employees with overweight or obesity. The VL Basic (VLB) participants received materials and tailored text messages, the VL Plus (VLP) participants additionally received WIFI-enabled activity monitors and scales and participated in health challenges throughout the school year, and the VL Plus with Support (VLP + S) participants additionally received coaching support. The levels of program satisfaction and retention and changes in weight, physical activity (PA), and diet were compared across groups using Pearson chi-square tests, repeated-measure mixed models, and logistic regression. After the program, …

Xatlas: Scalable Small Variant Calling Across Heterogeneous Next-Generation Sequencing Experiments, Jesse Farek, Daniel Hughes, William Salerno, Yiming Zhu, Aishwarya Pisupati, Adam Mansfield, Olga Krasheninina, Adam C English, Ginger Metcalf, Eric Boerwinkle, Donna M Muzny, Richard Gibbs, Ziad Khan, Fritz J Sedlazeck

Faculty, Staff and Students Publications

Background: The growing volume and heterogeneity of next-generation sequencing (NGS) data complicate the further optimization of identifying DNA variation, especially considering that curated high-confidence variant call sets frequently used to validate these methods are generally developed from the analysis of comparatively small and homogeneous sample sets.

Findings: We have developed xAtlas, a single-sample variant caller for single-nucleotide variants (SNVs) and small insertions and deletions (indels) in NGS data. xAtlas features rapid runtimes, support for CRAM and gVCF file formats, and retraining capabilities. xAtlas reports SNVs with 99.11% recall and 98.43% precision across a reference HG002 sample at 60× whole-genome coverage …

The Effect Of Zinc Supplementation On The Course Of Covid-19 – A Systematic Review And Meta-Analysis, Monika Olczak-Pruc, Lukasz Szarpak, Alla Navolokina, Jaroslaw Chmielewski, Lech Panasiuk, Raúl Juárez-Vela, Michal Pruc, Damian Swieczkowski, Ryszard Majer, Zubaid Rafique, Frank William Peacock

Faculty, Staff and Students Publications

Introduction and objective: Zinc is a trace element that plays a role in stimulating innate and acquired immunity. The aim of the study was to determine the antiviral effect of the administration of zinc in COVID-19 patients.

Material and methods: A literature search was performed in P Web of Science, PubMed, Scopus and Cochrane databases from 1 January 2020 - 22 August 2022. In addition, reference lists of the included articles and their related citations in PubMed were also reviewed for additional pertinent studies.

Results: A total of 9 eligible studies were identified. In-hospital mortality in zinc supplementation patients, and …

Truvari: Refined Structural Variant Comparison Preserves Allelic Diversity, Adam C English, Vipin K Menon, Richard A Gibbs, Ginger A Metcalf, Fritz J Sedlazeck

Faculty, Staff and Students Publications

The fundamental challenge of multi-sample structural variant (SV) analysis such as merging and benchmarking is identifying when two SVs are the same. Common approaches for comparing SVs were developed alongside technologies which produce ill-defined boundaries. As SV detection becomes more exact, algorithms to preserve this refined signal are needed. Here, we present Truvari-an SV comparison, annotation, and analysis toolkit-and demonstrate the effect of SV comparison choices by building population-level VCFs from 36 haplotype-resolved long-read assemblies. We observe over-merging from other SV merging approaches which cause up to a 2.2× inflation of allele frequency, relative to Truvari.

Proximity-Dependent Biotin Labeling In Testicular Germ Cells Identified Tesmin-Associated Proteins, Seiya Oura, Akinori Ninomiya, Fuminori Sugihara, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

Characterization of protein-protein interactions (PPI) is a key to understanding the functions of proteins of interest. Recently developed proximity-dependent biotin identification (BioID) has been actively investigated as an alternative PPI mapping method because of its usefulness in uncovering transient PPI. Here, as an example of proximity labeling proteomics application in the testis, we generated two transgenic mouse lines expressing two biotin ligases (BioID2 or TurboID) fused with TESMIN, which translocates from the cytosol to the nucleus during meiotic progression and is required for reproduction. The BioID2 transgene, albeit not the TurboID transgene, rescued fertility defects of the Tesmin KO male …

Rare Diseases And Space Health: Optimizing Synergies From Scientific Questions To Care, Maria Puscas, Gabrielle Martineau, Gurjot Bhella, Penelope E Bonnen, Phil Carr, Robyn Lim, John Mitchell, Matthew Osmond, Emmanuel Urquieta, Jaime Flamenbaum, Giuseppe Iaria, Yann Joly, Étienne Richer, Joan Saary, David Saint-Jacques, Nicole Buckley, Etienne Low-Decarie

Faculty, Staff and Students Publications

Knowledge transfer among research disciplines can lead to substantial research progress. At first glance, astronaut health and rare diseases may be seen as having little common ground for such an exchange. However, deleterious health conditions linked to human space exploration may well be considered as a narrow sub-category of rare diseases. Here, we compare and contrast research and healthcare in the contexts of rare diseases and space health and identify common barriers and avenues of improvement. The prevalent genetic basis of most rare disorders contrasts sharply with the occupational considerations required to sustain human health in space. Nevertheless small sample …