Genetics and Genomics Commons^™

Tail-Tape-Fused Virion And Non-Virion Rna Polymerases Of A Thermophilic Virus With An Extremely Long Tail, Anastasiia Chaban, Leonid Minakhin, Ekaterina Goldobina, Brain Bae, Yue Hao, Sergei Borukhov, Leena Putzeys, Maarten Boon, Florian Kabinger, Rob Lavigne, Kira S Makarova, Eugene V Koonin, Satish K Nair, Shunsuke Tagami, Konstantin Severinov, Maria L Sokolova

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Thermus thermophilus bacteriophage P23-45 encodes a giant 5,002-residue tail tape measure protein (TMP) that defines the length of its extraordinarily long tail. Here, we show that the N-terminal portion of P23-45 TMP is an unusual RNA polymerase (RNAP) homologous to cellular RNAPs. The TMP-fused virion RNAP transcribes pre-early phage genes, including a gene that encodes another, non-virion RNAP, that transcribes early and some middle phage genes. We report the crystal structures of both P23-45 RNAPs. The non-virion RNAP has a crab-claw-like architecture. By contrast, the virion RNAP adopts a unique flat structure without a clamp. Structure and sequence comparisons of …

Contextualizing The Revised Patient Perception Of Patient-Centeredness (Pppc-R) Scale In Primary Healthcare Settings: A Validity And Reliability Evaluation Study, Yiyuan Cai, Pengfei Guo, Jiong Tu, Mengyao Hu, Lingrui Liu, Bridget L Ryan, Jing Liao, Rubee Dev, Yiran Li, Tianyu Huang, Ruilin Wang, Li Kuang, Ruonan Huang, Xinfang Li, Edmundo Roberto Melipillán, Shuaixiang Zhao, Wenjun He, Xiaohui Wang, Nan Zhang, Dong Roman Xu

Faculty, Staff and Student Publications

BACKGROUND: An English version of the Patient Perception of Patient-Centeredness (PPPC) scale was recently revised, and it is necessary to test this instrument in different primary care populations.

AIM: This study aimed to assess the validity and reliability of a Chinese version of the PPPC scale.

DESIGN: A mixed method was used in this study. The Delphi method was used to collect qualitative and quantitative data to address the content validity of the PPPC scale by calculating the Content Validity Index, Content Validity Ratio, the adjusted Kappa, and the Item Impact Score. Confirmatory factor analysis (CFA) and exploratory factor analysis …

Clinicalomicsdb: Exploring Molecular Associations Of Oncology Drug Responses In Clinical Trials, Chang In Moon, John Michael Elizarraras, Jonathan Thomas Lei, Byron Jia, Bing Zhang

Faculty, Staff and Students Publications

Matching patients to optimal treatment is challenging, in part due to the limited availability of real-world clinical datasets for predictive biomarker identification. The growing integration of omics profiling into clinical trials presents a new opportunity to tackle this challenge. Here, we introduce ClinicalOmicsDB, a web application for exploring molecular associations of oncology drug responses in clinical trials. This database includes transcriptomic data from 40 clinical trial studies, with 5913 patients spanning 11 cancer types. These studies include 67 treatment arms with a variety of chemotherapy, targeted therapy and immunotherapy drugs, and their combinations, which we organize based on an established …

Computational Analysis Of Cas Proteins Unlocks New Potential In Hiv-1 Targeted Gene Therapy, Will Dampier, Rachel Berman, Michael Nonnemacher, Brian Wigdahl

Kimmel Cancer Center Faculty Papers

Introduction: The human immunodeficiency virus type 1 (HIV-1) pandemic has been slowed with the advent of anti-retroviral therapy (ART). However, ART is not a cure and as such has pushed the disease into a chronic infection. One potential cure strategy that has shown promise is the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas gene editing system. It has recently been shown to successfully edit and/or excise the integrated provirus from infected cells and inhibit HIV-1 in vitro, ex vivo, and in vivo. These studies have primarily been conducted with SpCas9 or SaCas9. However, additional Cas proteins are …

Factors Associated With Blood Mercury Concentrations And Their Interactions With Three Glutathione S-Transferase Genes (Gstt1, Gstm1, And Gstp1): An Exposure Assessment Study Of Typically Developing Jamaican Children, Sheikh Farzana Zaman, Maureen Samms-Vaughan, Sepideh Saroukhani, Jan Bressler, Manouchehr Hessabi, Megan L Grove, Sydonnie Shakespeare Pellington, Katherine A Loveland, Mohammad H Rahbar

Faculty, Staff and Student Publications

BACKGROUND: Jamaican soil is abundant in heavy metals including mercury (Hg). Due to availability and ease of access, fish is a traditional dietary component in Jamaica and a significant source of Hg exposure. Mercury is a xenobiotic and known neuro-toxicant that affects children's neurodevelopment. Human glutathione S-transferase (GST) genes, including GSTT1, GSTM1, and GSTP1, affect Hg conjugation and elimination mechanisms.

METHODS: In this exposure assessment study we used data from 375 typically developing (TD) 2-8-year-old Jamaican children to explore the association between environmental Hg exposure, GST genes, and their interaction effects on blood Hg concentrations (BHgCs). We used multivariable general …

A Syndromic Neurodevelopmental Disorder Caused By Rare Variants In Ppfia3, Maimuna S Paul, Sydney L Michener, Hongling Pan, Hiuling Chan, Jessica M Pfliger, Jill A Rosenfeld, Vanesa C Lerma, Alyssa Tran, Megan A Longley, Richard A Lewis, Monika Weisz-Hubshman, Mir Reza Bekheirnia, Nasim Bekheirnia, Lauren Massingham, Michael Zech, Matias Wagner, Hartmut Engels, Kirsten Cremer, Elisabeth Mangold, Sophia Peters, Jessica Trautmann, Jessica L Mester, Maria J Guillen Sacoto, Richard Person, Pamela P Mcdonnell, Stacey R Cohen, Laina Lusk, Ana S A Cohen, Jean-Baptiste Le Pichon, Tomi Pastinen, Dihong Zhou, Kendra Engleman, Caroline Racine, Laurence Faivre, Sébastien Moutton, Anne-Sophie Denommé-Pichon, Hyun Yong Koh, Annapurna Poduri, Jeffrey Bolton, Cordula Knopp, Dong Sun Julia Suh, Andrea Maier, Mehran Beiraghi Toosi, Ehsan Ghayoor Karimiani, Reza Maroofian, Gerald Bradley Schaefer, Vijayalakshmi Ramakumaran, Pradeep Vasudevan, Chitra Prasad, Matthew Osmond, Sarah Schuhmann, Georgia Vasileiou, Sophie Russ-Hall, Ingrid E Scheffer, Gemma L Carvill, Heather Mefford, Undiagnosed Diseases Network, Carlos A Bacino, Brendan H Lee, Hsiao-Tuan Chao

Faculty, Staff and Students Publications

PPFIA3 encodes the protein-tyrosine phosphatase, receptor-type, F-polypeptide-interacting-protein-alpha-3 (PPFIA3), which is a member of the LAR-protein-tyrosine phosphatase-interacting-protein (liprin) family involved in synapse formation and function, synaptic vesicle transport, and presynaptic active zone assembly. The protein structure and function are evolutionarily well conserved, but human diseases related to PPFIA3 dysfunction are not yet reported in OMIM. Here, we report 20 individuals with rare PPFIA3 variants (19 heterozygous and 1 compound heterozygous) presenting with developmental delay, intellectual disability, hypotonia, dysmorphisms, microcephaly or macrocephaly, autistic features, and epilepsy with reduced penetrance. Seventeen unique PPFIA3 variants were detected in 18 families. To determine the pathogenicity …

An Evolutionary Perspective On Complex Neuropsychiatric Disease, Jon M Mcclellan, Anthony W Zoghbi, Joseph D Buxbaum, Carolina Cappi, James J Crowley, Jonathan Flint, Dorothy E Grice, Suleyman Gulsuner, Conrad Iyegbe, Sanjeev Jain, Po-Hsiu Kuo, Maria Claudia Lattig, Maria Rita Passos-Bueno, Meera Purushottam, Dan J Stein, Anna B Sunshine, Ezra S Susser, Christopher A Walsh, Olivia Wootton, Mary-Claire King

Faculty, Staff and Students Publications

The forces of evolution-mutation, selection, migration, and genetic drift-shape the genetic architecture of human traits, including the genetic architecture of complex neuropsychiatric illnesses. Studying these illnesses in populations that are diverse in genetic ancestry, historical demography, and cultural history can reveal how evolutionary forces have guided adaptation over time and place. A fundamental truth of shared human biology is that an allele responsible for a disease in anyone, anywhere, reveals a gene critical to the normal biology underlying that condition in everyone, everywhere. Understanding the genetic causes of neuropsychiatric disease in the widest possible range of human populations thus yields …

The Use Of Cardiac Magnetic Resonance In Hypertrophic Cardiomyopathy Over The Past 10 Years [2013-2023]: A Citespace-Based Bibliometric Analysis, Mengyao Hu, Yu Shen, Yipei Song, Shuhao Li, Pei Yang, Ao Kan, Qiming Fang, Yun Peng, Haibo Ren, Yajing Zhang, Lianggeng Gong

Faculty, Staff and Student Publications

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a common genetic cardiac disorder characterized by the hypertrophy of a segment of the myocardium. Cardiac magnetic resonance (CMR) has been widely used in the assessment of HCM. However, no bibliometric assessment has been conducted on the progress of research in this field. This study thus aimed to examine the current state of research into the application of CMR in HCM and the hotspots and trends that have emerged in this field over the past decade.

METHODS: A systematic search was conducted on the Web of Science regarding CMR in the assessment of HCM. The …

Fused In Sarcoma Regulates Glutamate Signaling And Oxidative Stress Response, Chiong-Hee Wong, Abu Rahat, Howard C Chang

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Mutations in fused in sarcoma (fust-1) are linked to ALS. However, how these ALS causative mutations alter physiological processes and lead to the onset of ALS remains largely unknown. By obtaining humanized fust-1 ALS mutations via CRISPR-CAS9, we generated a C. elegans ALS model. Homozygous fust-1 ALS mutant and fust-1 deletion animals are viable in C. elegans. This allows us to better characterize the molecular mechanisms of fust-1-dependent responses. We found FUST-1 plays a role in regulating superoxide dismutase, glutamate signaling, and oxidative stress. FUST-1 suppresses SOD-1 and VGLUT/EAT-4 in the nervous system. FUST-1 also regulates synaptic AMPA-type glutamate receptor …

Whole Genome Sequencing For The Millipede Cherokia Georgiana, Elena Cruz, Will Wittstock, Daniel Hastings, Arnab Sengupta, Bruce A. Snyder

Graduate Research Showcase

Out of thousands of known millipede species, only five sequenced genomes of species (in four of sixteen orders) are publicly available. No whole genomes and limited genetic information are available for incredibly diverse families such as Xystodesmidae. Our research goal is to sequence the whole genome of the millipede Cherokia georgiana. A de novo sequence of the complete genome of a North American species will facilitate future research in understanding gene expression under a variety of conditions. Many interesting biological processes in millipedes are poorly described, such as the production of a defensive hydrogen cyanide secretion found in the …

Lipid Genetics In Pregnant Women: Maneuvering The Challenges Of Using Degraded Samples, Kylee Meece

Mahurin Honors College Capstone Experience/Thesis Projects

The results of this project will explore a novel approach to lipid metabolism in pregnant women by exploring the relationship between maternal gene expression of genes critical for fat metabolism, protein expression, and maternal and neonatal outcomes. The study will also examine gene expression in lean pregnant women compared to obese pregnant women, shedding light into the adverse pathology of obesity during pregnancy. These findings may uncover a mechanism related to gene-expression that connects unfavorable maternal fat metabolism to inflammation and/or insulin resistance, which may help to uncover future targets for interventions.

The analysis of lipid gene expression requires the …

Development Of A Novel Edna Sampling Method For Macroinvertebrate Species Of Greatest Conservation Need (Sgcn) In Texas, James York

Biology Theses

Environmental DNA (eDNA) sampling is a new sampling technique that allows for non-invasive sampling of target species or the characterization of entire communities based on barcoding genes. The goal of this study was to sequence common barcoding genes such as 28S rRNA and Cytochrome C Oxidase I (COI), and then develop species-specific primers for eight macroinvertebrates listed as Species of Greatest Conservation Need (SGCN) in Texas. After sampling for the target species, five were not found, all of which were in the Order Trichoptera (caddisflies). A sixth target species, Isoperla sagittata, was found to have only one gap and …

Precommentary: Animal Personality Needs Animal Sentience, Ralph Adolphs, Yue Xu

Animal Sentience

We are grateful to Owens, Bryja & Bekoff (2024) for their important discussion of individual differences in animals, emphasizing the role of personality in conservation, wildlife research, and wellbeing. But their emphasis also raises new challenges: How should we conceive of personality in nonhuman species? what modern tools could be leveraged to best measure it? and, perhaps most important of all: how can we ensure that the conscious experience of animals — their capacity for wellbeing and for suffering — is not forgotten along the way? We touch on each of these challenges in this invited Precommentary in the hope …

Individuality Matters But Its Cause Has Consequences, Daniel T. Blumstein

Animal Sentience

I discuss the relationship between individuality and heritability and note that the mechanism driving individual differences matters for conservation and management outcomes.

Epigenetics And Character Virtue Development, David S. Moore

Pitzer Faculty Publications and Research

Current understandings of epigenetics offer some insights into the developmental origins of character virtues. Research on epigenetics has demonstrated that phenotypes depend on both genomic and non-genomic information for their development, and such is true for the development of character virtues as well. This conclusion offers significant support for the Developmental Systems perspective. Although researchers have not yet studied the role of molecular epigenetic factors in the development of character, the field of behavioral epigenetics has revealed how such factors contribute to psychological and other behavioral phenotypes in general. In particular, behavioral epigenetics research can highlight the plasticity of human …

Understanding The Origin Of Parthenogenesis Via Crossing And Crispr Gene Editing In Daphnia Pulex, Thinh Pham

Biology Dissertations - Archive

Daphnia has been used as a key model system for studying ecological changes, evolution, and genomics for the past few decades due to its rapid turnover time in reproduction. The organism possesses two fascinating modes of reproduction: obligate parthenogenesis and cyclical parthenogenesis. This dissertation delves into the intricate reproductive strategies of Daphnia pulex, focusing on hybrid F1s from different reproductive modes. The first aim is to investigate 31 hybrid F1s generated from obligate parthenogenesis (OP) and cyclical parthenogenesis (CP) parental lines. Transcriptomic analysis reveals misexpression patterns and regulatory divergences, highlighting meiosis-related genes like CDC6 as potential parthenogenesis regulators. The …

Managing Stress: A Study Of Stress Response Mechanisms In Mycobacteria, Augusto C. Hunt Serracin

Biology Dissertations - Archive

Mycobacteria encompass many pathogenic species known to cause severe disease in humans. A well-known example is Mycobacterium tuberculosis (Mtb), the causative agent of the lung disease tuberculosis, which kills millions of humans worldwide yearly. Pathogenic mycobacteria like Mtb are challenging to treat because of their innate ability to adapt to environmental stress. Their unique cell physiology and conserved stress responses allow them to combat biological insults, regulate growth, and regulate genes involved in stress; all these responses increase tolerance to antibiotics. The current therapies to treat mycobacterial infections are lengthy and, at times, unsuccessful, partly due to antibiotic tolerance. A …

Carbaryl-Induced Leaf Necrosis In Vitis Rupestris B-38, Courtney Nicole Duncan

Graduate Theses/Dissertations

Agricultural insecticides are formulated to target insects while minimizing harm to the intended crop. In rare instances, however, insecticides induce harmful physiological reactions in certain plant genomes, inflicting severe tissue damage. This project investigated the genetic basis of such a reaction observed in the grape genotype Vitis rupestris B38 following exposure to the insecticide carbaryl, which manifests as interveinal leaf necrosis. Through analysis of an F1 hybrid progeny of this grapevine, I mapped this phenotype to a QTL on chromosome 16. The carbaryl-sensitive trait was repeatedly mapped to the same locus using phenotype data from two different field locations and …

Assessing The Utility Of Breast Cancer Polygenic Risk Scores And Association With Clinical Factors In A Population Of Breast Cancer Patients, John L. Slunecka

Dissertations and Theses

INTRODUCTION: Breast cancer (BC) is the most common cancer among women and is classified as a complex disease. Advances in population genomics have led to the development of polygenic risk scores (PRSs) with the potential to enhance current risk models, but replication is often limited. OBJECTIVE: We sought to assess the predictive capabilities of two high-powered BC PRSs in a sample population selected for breast cancer. In addition, the capacity of the PRSs to predict clinical variables that could improve BC screening and treatments was explored. METHODS: Two published PRS algorithms (313 vs 3820) were used to score female subjects …

Multi-Cancer Early Detection Testing (Mced), Ora K Gordon, Brad Bott, Nanor Parseghian, Paul Psychogios, Kimberly K Childers, Sandra Brown

Articles, Abstracts, and Reports

No abstract provided.