Genetic Processes Commons^™

Differential Degeneration Of Neurons In A Mouse Model Of Canavan Disease, Vibha Chauhan, Quy Nguyen, Jeremy Francis, Paola Leone

Stratford Campus Research Day

Canavan disease (CD) is an inherited leukodystrophy caused by inactivating mutations to the glial enzyme aspartoacylase (ASPA). ASPA catabolizes neuronal N-acetylaspartate (NAA) into free acetate and aspartate and loss of this function results in the chronic elevation of non-catabolized NAA and the failure of developmental myelination. Elevated NAA is thought to cause damage to myelin and myelin-producing cells (oligodendrocytes, but the viability of neurons in CD is relatively unexplored. We compare here the progressive degeneration of neurons in two regions of the CD mouse brain, the thalamus and the cortex, distinguished by differing degrees of vacuolation, and show that the …

The Presence Of Childhood Obesity In Nebraska And The Physiological Repercussions Of The Disease, Madison R. Bezousek

Honors Theses, University of Nebraska-Lincoln

Childhood Obesity can cause lifelong repercussions in children and adults. There has been stigma around the causes of obesity and its relation to lifestyle choices, without consideration of the genetic and syndromic causes. In this literature review the causes of obesity were investigated, along with the effect on the physiological systems and the enviornmental factors that are continuing the obesity epidemic. Preventing and treating lifestyle obesity is something that is seen to have the greatest effect on youth, especially with intergenerational obesity. Nebraska schools have implemented programs to encourage healthy living, and ongoing research is being implemented to reduce the …

Meta-Narrative Review Of Possible Impacts Of Genetic Screening On Treatment Of Breast Cancer, Toqa Al Alawi, Sheza Khan, Ivey Knebel, Steven Luong, Vilma Sanchez, Kamilah Walker-Charles

Research Methods Poster Session 2023

Objective: To examine the impacts of genetic screening on the treatment of breast cancer, in relation to differences, outcomes and decisions in treatment plans or surgery in patients that performed genetic screening versus those that did not.

Background: Genetic screening technology has become commercially available, yet standard preventative care for breast cancer has no genetic screening involved. Genetic screening in breast cancer treatment is performed, but its usage is not standardized.

Methods: Findings were synthesized using the meta-narrative review style to examine articles retrieved from searches of digital databases PubMed and the M.D. Anderson Scholarly Library.

Discussion: Articles were selected …

Effects That The Methylenetetrahydrofolate Gene Mutation (Both The C677t And A1298c Polymorphisms) Have On Both Men And Women’S Fertility Abilities And Subsequent Fetal Development, As Well As What Nutritional Changes Can Possibly Do To Aid In Reversing These Supposed Negative Effects., Elizabeth Simkanin

Williams Honors College, Honors Research Projects

This study discusses the perceived negative effects of variants (C677T and A1298C) of the methylenetetrahydrofolate (MTHFR) gene on male and female fertility and fetal development, as well as the potential for nutrition changes to aid in reversing these negative effects. This research project was completed in order to discuss the possible association with and connection between nutrition and fertility in both male and female individuals who have either of the two most common MTHFR gene polymorphisms, 677C>T and 1298A>C. These two polymorphisms are of particular interest because they are associated with the most decreased activity of the MTHFR …

Investigation Of The Dyrk1a Regulation By Lzts2-Sipa1l1 Complex, Rebecca Gunnin, Austin Witt B.S., Larisa Litovchick M.D.,Ph.D.

Undergraduate Research Posters

A region on chromosome 21, the Down Syndrome critical region (DSCR), is associated with major defects found in Down Syndrome, such as craniofacial malformations. DYRK1A is a gene found on chromosome 21 within the DSCR that encodes an enzyme, dual specificity tyrosine-phosphorylation-regulated kinase 1A. DYRK1A is known to phosphorylate many substrate proteins and is thought to be involved in tumor suppression, neurological development, cell cycle regulation, and aging. Recently, the Litovchick lab and others reported that DYRK1A also plays a role in the double-strand break repair of DNA, which could lead to mutations and tumorigenesis, if deregulated.

The Litovchick lab …

Modification Of The Tumor Microenvironment Enhances Anti-Pd-1 Immunotherapy In Metastatic Melanoma, Guilan Shi, Megan Scott, Cathryn G. Mangiamele, Richard Heller

Bioelectrics Publications

Resistance to checkpoint-blockade treatments is a challenge in the clinic. Both primary and acquired resistance have become major obstacles, greatly limiting the long-lasting effects and wide application of blockade therapy. Many patients with metastatic melanoma eventually require further therapy. The absence of T-cell infiltration to the tumor site is a well-accepted contributor limiting immune checkpoint inhibitor efficacy. In this study, we combined intratumoral injection of plasmid IL-12 with electrotransfer and anti-PD-1 in metastatic B16F10 melanoma tumor model to increase tumor-infiltrating lymphocytes and improve therapeutic efficacy. We showed that effective anti-tumor responses required a subset of tumor-infiltrating CD8⁺ and CD4 …

Sea-Phages Research Opportunity, Sarah Ballarin

Trick to the Treat of Internships and Research

Research opportunity targeted for freshmen and sophomores through the SEA-PHAGES program. The goal of the research is to discover new bacteriophages (viruses that infect bacteria) to help combat antibiotic resistance. Phage therapy is a promising alternative to conventional antibiotics. Phages have also been widely used in the food industry to prevent microbial growth on certain foods and are currently being explored as a method for bioremediation of oil spills and wastewater treatment.

Last year, my research team discovered two new bacteriophages: Genamy16 and NovaSharks that were able to infect the bacteria Gordonia rubripertincta. These phages can possibly be used for …

Full Issue, Winthrop Mcnair Research Bulletin

The Winthrop McNair Research Bulletin

Winthrop McNair Research Bulletin Volume 5, Full Issue

Locating Mutagen-Sensitivity Gene Mus109 In The Drosophila Melanogaster Genome Using Deficiency Mapping, Chandani Mitchell

The Winthrop McNair Research Bulletin

The complex processes involved in repairing damaged DNA are still being elucidated. Some genes that are known to have roles in the DNA repair process have been identified, such as the mutagen-sensitivity genes, or mus genes, in Drosophila melanogaster. However, the precise genomic location of some mus genes is still unknown, including mus109. It is known that mutations in mus109 cause chromosomal aberrations resulting in larval death, and previous research has mapped mus109 to a region of the X chromosome consisting of over 520,000 nucleotides and 41 genes. Therefore, this study aimed to locate mus109 using deficiency mapping. The mus109D2 …

Infection And Transmission Determinants Of Flea-Borne Rickettsioses, Hanna J. Laukaitis

Theses and Dissertations

The genus Rickettsia is comprised of Gram-negative, obligate intracellular bacteria that are spread by hematophagous arthropods. Elucidating the factors conferring rickettsial virulence has perplexed investigators for decades, complicated by the lack of efficient genetic tools necessary to uncover rickettsial- and vector-specific factors contributing to persistence. The advent of transposon mutagenesis has enabled the field to make vast developments in uncovering novel rickettsial mechanisms utilized in various host backgrounds. Thus, the aim of this study was to generate Rickettsia felis transposon mutants and characterize novel phenotypes associated with genetic disruption in an arthropod background. Distribution of rickettsiae is reliant on the …

Whole Genome Sequence Association Analysis Of Fasting Glucose And Fasting Insulin Levels In Diverse Cohorts From The Nhlbi Topmed Program, Daniel Dicorpo, Sheila M. Gaynor, Emily M. Russell, Kenneth E. Westerman, Laura M. Raffield, Marcio Almeida, Juan M. Peralta, John Blangero, Joanne E. Curran, Ravindranath Duggirala

School of Medicine Publications and Presentations

The genetic determinants of fasting glucose (FG) and fasting insulin (FI) have been studied mostly through genome arrays, resulting in over 100 associated variants. We extended this work with high-coverage whole genome sequencing analyses from fifteen cohorts in NHLBI’s Trans-Omics for Precision Medicine (TOPMed) program. Over 23,000 non-diabetic individuals from five race-ethnicities/populations (African, Asian, European, Hispanic and Samoan) were included. Eight variants were significantly associated with FG or FI across previously identified regions MTNR1B, G6PC2, GCK, GCKR and FOXA2. We additionally characterize suggestive associations with FG or FI near previously identified SLC30A8, TCF7L2, and ADCY5 regions as well …

Structural Basis For The Simultaneous Recognition Of Nemo And Acceptor Ubiquitin By The Hoip Nzf1 Domain, Simin Rahighi, Mamta Iyer, Hamid Oveisi, Sammy Nasser, Vincent Duong

Pharmacy Faculty Articles and Research

Ubiquitination of NEMO by the linear ubiquitin chain assembly complex (LUBAC) is essential for activating the canonical NF-κB signaling pathway. While the NZF1 domain of the HOIP subunit of LUBAC recognizes the NEMO substrate, it is unclear how it cooperates with the catalytic domains in the ubiquitination process. Here, we report a crystal structure of NEMO in complex with HOIP NZF1 and linear diubiquitin chains, in which the two proteins bind to distinct sites on NEMO. Moreover, the NZF1 domain simultaneously interacts with NEMO and Ile44 surface of a proximal ubiquitin from a linear diubiquitin chain, where the C-term tail …

Synthesis And Evaluation Of Anti-Hiv Activity Of Mono- And Di-Substituted Phosphonamidate Conjugates Of Tenofovir, Aaminat Qureshi, Louise A. Ouattara, Naglaa Salem El-Sayed, Amita Verma, Gustavo F. Doncel, Muhammad Iqbal Choudhary, Hina Siddiqui, Keykavous Parang

Pharmacy Faculty Articles and Research

The activity of nucleoside and nucleotide analogs as antiviral agents requires phosphorylation by endogenous enzymes. Phosphate-substituted analogs have low bioavailability due to the presence of ionizable negatively-charged groups. To circumvent these limitations, several prodrug approaches have been proposed. Herein, we hypothesized that the conjugation or combination of the lipophilic amide bond with nucleotide-based tenofovir (TFV) (1) could improve the anti-HIV activity. During the current study, the hydroxyl group of phosphonates in TFV was conjugated with the amino group of L-alanine, L-leucine, L-valine, and glycine amino acids and other long fatty ester hydrocarbon chains to synthesize 43 derivatives. Several …

Non-Alcoholic Fatty Liver Disease And Depression: Evidence For Genotype × Environment Interaction In Mexican Americans, Eron G. Manusov, Vincent P. Diego, Khalid Sheikh, Sandra Laston, John Blangero, Sarah Williams-Blangero

School of Medicine Publications and Presentations

This study examines the impact of G × E interaction effects on non-alcoholic fatty liver disease (NAFLD) among Mexican Americans in the Rio Grande Valley (RGV) of South Texas. We examined potential G × E interaction using variance components models and likelihood-based statistical inference in the phenotypic expression of NAFLD, including hepatic steatosis and hepatic fibrosis (identified using vibration controlled transient elastography and controlled attenuation parameter measured by the FibroScan Device). We screened for depression using the Beck Depression Inventory-II (BDI-II). We identified significant G × E interactions for hepatic fibrosis × BDI-II. These findings provide evidence that genetic factors …

Identification Of Healthspan-Promoting Genes In Caenorhabditis Elegans Based On A Human Gwas Study, Nadine Saul, Ineke Dhondt, Mikko Kuokkanen, Markus Perola, Clara Verschuuren, Brecht Wouters, Henrik Von Chrzanowski, Winnok H. De Vos, Liesbet Temmerman, Walter Luyten

School of Medicine Publications and Presentations

To find drivers of healthy ageing, a genome-wide association study (GWAS) was performed in healthy and unhealthy older individuals. Healthy individuals were defined as free from cardiovascular disease, stroke, heart failure, major adverse cardiovascular event, diabetes, dementia, cancer, chronic obstructive pulmonary disease (COPD), asthma, rheumatism, Crohn’s disease, malabsorption or kidney disease. Six single nucleotide polymorphisms (SNPs) with unknown function associated with ten human genes were identified as candidate healthspan markers. Thirteen homologous or closely related genes were selected in the model organism C. elegans for evaluating healthspan after targeted RNAi-mediated knockdown using pathogen resistance, muscle integrity, chemotaxis index and the …

Leveraging Single Cell Technologies For The Characterization And Treatment Of Refractory Pancreatic Cancer, Maria Monberg

Dissertations and Theses (Open Access)

Heterogeneity is a hallmark of cancer, and the advent of multimodal single-cell technologies has helped uncover heterogeneity in a high-throughput manner in different cancers across varied contexts at an unprecedented resolution. In an effort to improve precision medicine approaches in pancreatic ductal adenocarcinoma (PDAC), a highly lethal malignancy with a mere 11% 5-year survival rate, this dissertation focuses on first questioning the assumptions of the most basic models used to study PDAC via multimodal single-cell characterization methods at multiple levels of biological organization (scCNVseq and snATACseq for DNA assays, scRNAseq for transcriptomics, and paired protein assays such as multiplexed immunofluorescence …

How Environmental Change Will Impact Mosquito-Borne Diseases, Arsal Khan

Master's Projects and Capstones

Mosquitos, the most lethal species throughout human history, are the most prevalent source of vector-borne diseases and therefore a major global health burden. Mosquito-borne disease incidence is expected to shift with environmental change. These changes can be predicted using species distribution models. With the wide variety of methods used for models, consensus for improving accuracy and comparability is needed. A comparative analysis of three recent modeling approaches revealed that integrating modeling techniques compensates for trade-offs associated with a singular approach. An area that represents a critical gap in our ability to predict mosquito behavior in response to changing climate factors, …

Genetic Origins Of Polycystic Ovarian Syndrome (Pcos): An Analysis Of The Genetic Correlation Between Pcos And Insulin Receptor Mutations, Lauren Henry

Undergraduate Theses

Polycystic Ovarian Syndrome (PCOS) remains an extremely common, yet understudied syndrome experienced by 6-12% of females of reproductive age. Not only does it cause painful side effects manifesting both physically and mentally, but it also poses a threat to the fertility of those affected. For this reason, a more in-depth analysis to better understand how to detect this condition early and prevent fertility complications later is certainly warranted. PCOS is suspected to be primarily genetic due to correlations among immediate female family members. Based on previous research, a good starting point for analysis is the INSR gene. Various mutations within …

The Use Of Embark In Teaching About Genetic Relatedness, Anna Bonvillain, Tori Trammel

Honors Theses

Because of the increasing importance of precision medicine, it is vital that future healthcare providers master concepts related to genetic variation taught during their undergraduate classes. However, studies have shown that physicians often lack an adequate understanding of genetics, which serves as a hindrance to effectively caring for their patients. To address this issue, we created a collaborative active-learning protocol to improve pre-health students' comprehension of key concepts such as genetic relatedness and the source of genetic variation between siblings. Our worksheet guides students to compare the genetic profiles of two canine siblings using the Embark DNA genotyping platform. Embark …

Modeling The Role Of Cyclin C In Connecting Stress-Induced Mitochondrial Fission To Apoptosis, Steven J. Doyle, Randy Strich

Stratford Campus Research Day

For normal cell function, exogenous signals must be correctly interpreted, and the proper response executed. The mitochondria are key regulatory nodes of cellular fate. For example, mitochondria undergo fission and fusion cycles depending on the energetic needs of the cell. Additionally, regulated cell death pathways also function at the mitochondria. Cyclin C is a transcriptional regulator of stress response and growth control genes. Following stress, a portion of cyclin C translocates to the cytoplasm, where it interacts with both the mitochondrial fission and apoptotic machinery. Based on these findings, we hypothesize that Cyclin C represents a key mediator linking transcription …