Genetics and Genomics Commons^™

An Overview Of The Immune Modulatory Properties Of Long Non-Coding Rnas And Their Potential Use As Therapeutic Targets In Cancer, Moises Martinez-Castillo, Abdelrahman M Elsayed, Gabriel López-Berestein, Paola Amero, Cristian Rodríguez-Aguayo

Faculty, Staff and Student Publications

Long non-coding RNAs (lncRNAs) play pivotal roles in regulating immune responses, immune cell differentiation, activation, and inflammatory processes. In cancer, they are gaining prominence as potential therapeutic targets due to their ability to regulate immune checkpoint molecules and immune-related factors, suggesting avenues for bolstering anti-tumor immune responses. Here, we explore the mechanistic insights into lncRNA-mediated immune modulation, highlighting their impact on immunity. Additionally, we discuss their potential to enhance cancer immunotherapy, augmenting the effectiveness of immune checkpoint inhibitors and adoptive T cell therapies. LncRNAs as therapeutic targets hold the promise of revolutionizing cancer treatments, inspiring further research in this field …

Regulatory Mechanisms Of Epithelial Tube Formation During Drosophila Embryogenesis, Vishakha Vishwakarma

LSU Doctoral Dissertations

The formation of three-dimensional tubes by invagination from flat epithelial sheets is a fundamental process in forming organs, such as lungs and kidneys. Defects in tube formation can lead to many diseases, such as spina bifida and pulmonary agenesis. Therefore, determining the mechanisms underlying tube formation is essential to understanding many developmental processes and common human diseases. To investigate the regulatory mechanisms behind the formation of epithelial tubes, the Chung lab uses Drosophila melanogaster as a model system with simple and complex epithelial tubular organs such as the salivary gland (SG) and trachea. My work broadly aims to identify and …

Effect Of Ploidy On Salinity And Temperature Tolerance In Early Life Stages Of The Eastern Oyster (Crassostrea Virginica), Christian Boudreaux, Jessica Pruett, Alexz Carpenter, Kristie Willett, Deborah Gochfeld

Honors Theses

The U.S. Gulf of Mexico contains the largest remaining wild oyster fishery in the world, but populations have declined in recent decades. A growing interest in off-bottom aquaculture that relies on triploid eastern oysters (Crassostrea virginica) has emerged in the Gulf region, yet these faster growing oysters suffer high mortality as adults during low salinity events (< 5 ppt) in warmer summer months. The combined effects of salinity and temperature stressors on early life stages of triploid oysters are unknown. Early life stages are particularly crucial to understand because triploid oysters do not occur naturally and must be reared in hatchery settings, requiring appropriate water conditions to yield the greatest survival and growth. Thus, we tested the effects of different temperatures (28oC and 32oC) and salinities (5, 10, and 15 ppt) on diploid and triploid oysters at three critical production stages: veliger, pediveliger, and spat. Veliger survival was significantly lower for triploids relative to diploid oysters at all experimental conditions, but triploid veligers had faster growth than diploids at 32oC and 15 ppt. Pediveliger settlement was not affected by ploidy type and only reduced at high temperature (32oC) and the lowest salinity (5 ppt). Diploid spat showed highest survival at 28oC and 15 ppt, while triploids survived best at 32oC and 15 ppt. Triploid spat attained greater shell height compared to diploids in our 6-day exposures, but growth decreased for both ploidies at lower salinities. At the salinity and temperature levels examined, diploid early life stages performed best at 28oC and 15 ppt, whereas triploids were more successful at 32oC and 15 ppt. A broader understanding of the combined effects of environmental stressors will improve the success of hatchery production yields and the resulting economic and environmental benefits of the oyster industry.

The Typical Trna Co-Expresses Multiple 5' Trna Halves Whose Sequences And Abundances Depend On Isodecoder And Isoacceptor And Change With Tissue Type, Cell Type, And Disease, Robert Akins, Kayleigh Ostberg, Tess Cherlin, Nikolas Tsiouplis, Phillipe Loher, Isidore Rigoutsos

Computational Medicine Center Faculty Papers

Transfer RNA-derived fragments (tRFs) are noncoding RNAs that arise from either mature transfer RNAs (tRNAs) or their precursors. One important category of tRFs comprises the tRNA halves, which are generated through cleavage at the anticodon. A given tRNA typically gives rise to several co-expressed 5'-tRNA halves (5'-tRHs) that differ in the location of their 3' ends. These 5'-tRHs, even though distinct, have traditionally been treated as indistinguishable from one another due to their near-identical sequences and lengths. We focused on co-expressed 5'-tRHs that arise from the same tRNA and systematically examined their exact sequences and abundances across 10 different human …

Comparative Analysis Of Swine Antibody Responses Following Vaccination With Live-Attenuated And Killed African Swine Fever Virus Vaccines, Hung Q. Luong, Huong T. L. Lai, Lam Q. Truong, The N. Nguyen, Hanh D. Vu, Hoa T. Nguyen, Lan T. Nguyen, Trang H. Pham, David Scott Mcvey, Hiep Vu

Nebraska Center for Virology: Faculty Publications

African swine fever virus (ASFV) is circulating in many swine-producing countries, causing significant economic losses. It is observed that pigs experimentally vaccinated with a live-attenuated virus (LAV) but not a killed virus (KV) vaccine develop solid homologous protective immunity. The objective of this study was to comparatively analyze antibody profiles between pigs vaccinated with an LAV vaccine and those vaccinated with a KV vaccine to identify potential markers of vaccineinduced protection. Thirty ASFV seronegative pigs were divided into three groups: Group 1 received a single dose of an experimental LAV, Group 2 received two doses of an experimental KV vaccine, …

Identification Of Circulating Proteins Associated With General Cognitive Function Among Middle-Aged And Older Adults, Adrienne Tin, Alison E Fohner, Qiong Yang, Jennifer A Brody, Gail Davies, Jie Yao, Dan Liu, Ilana Caro, Joni V Lindbohm, Michael R Duggan, Osorio Meirelles, Sarah E Harris, Valborg Gudmundsdottir, Adele M Taylor, Albert Henry, Alexa S Beiser, Ali Shojaie, Annabell Coors, Annette L Fitzpatrick, Claudia Langenberg, Claudia L Satizabal, Colleen M Sitlani, Eleanor Wheeler, Elliot M Tucker-Drob, Jan Bressler, Josef Coresh, Joshua C Bis, Julián Candia, Lori L Jennings, Maik Pietzner, Mark Lathrop, Oscar L Lopez, Paul Redmond, Robert E Gerszten, Stephen S Rich, Susan R Heckbert, Thomas R Austin, Timothy M Hughes, Toshiko Tanaka, Valur Emilsson, Ramachandran S Vasan, Xiuqing Guo, Yineng Zhu, Christophe Tzourio, Jerome I Rotter, Keenan A Walker, Luigi Ferrucci, Mika Kivimäki, Monique M B Breteler, Simon R Cox, Stephanie Debette, Thomas H Mosley, Vilmundur G Gudnason, Lenore J Launer, Bruce M Psaty, Sudha Seshadri, Myriam Fornage

Faculty, Staff and Student Publications

Identifying circulating proteins associated with cognitive function may point to biomarkers and molecular process of cognitive impairment. Few studies have investigated the association between circulating proteins and cognitive function. We identify 246 protein measures quantified by the SomaScan assay as associated with cognitive function (p < 4.9E-5, n up to 7289). Of these, 45 were replicated using SomaScan data, and three were replicated using Olink data at Bonferroni-corrected significance. Enrichment analysis linked the proteins associated with general cognitive function to cell signaling pathways and synapse architecture. Mendelian randomization analysis implicated higher levels of NECTIN2, a protein mediating viral entry into neuronal cells, with higher Alzheimer's disease (AD) risk (p = 2.5E-26). Levels of 14 other protein measures were implicated as consequences of AD susceptibility (p < 2.0E-4). Proteins implicated as causes or consequences of AD susceptibility may provide new insight into the potential relationship between immunity and AD susceptibility as well as potential therapeutic targets.

Phenotypic Correlations Between Enteric Methane Emissions And Feeding Behaviour Traits In Beef Cattle, Sean Crowley

ORBioM (Open Research BioSciences Meeting)

Background

Animal breeding for methane mitigation offers the unique potential to make cumulative and permanent improvements, setting it apart from nutritional or management strategies that require ongoing investment. Internationally multiple phenotypes for enteric methane emissions have been defined, however the complexity of the relationship between methane and feed intake and ultimately animal performance, has meant there has been little consensus on which methane definition should be used in breeding goals.

Aims

Previous enteric methane research focused on traditional methane metrics like yield, intensity and residual emissions, leaving a gap in understanding how alternative traits, such as feeding behaviour, impact methane …

Development Of A Protocol For The Extraction Of Genomic Material From Fecal Matter For Metagenome And Virome Sequencing, Keith Coughlan

ORBioM (Open Research BioSciences Meeting)

With the advent of increasingly more accurate and reliable sequencing methods, the requirement for extraction methods yielding large volumes of high-quality genomic material has become progressively more significant. While the analysis of genomic material through bioinformatics can offer some methods of “cleaning” and standardizing data, it is essential that the “wet lab” aspects of data produce abundant amounts of high-quality genetic material. Therefore, the purpose of this project is to develop an optimized method of DNA extraction for fecal material sequencing in microbiome and virome investigations. The samples used for the optimized protocol are infant fecal samples collected and stored …

Characterisation Of Sex Chromosome Aneuploidy In Female Cattle Using Genotype Information, Cliona Ryan

ORBioM (Open Research BioSciences Meeting)

Background

Aneuploidy is a genetic condition characterized by the loss (monosomy) or gain (trisomy) of one or more chromosomes. Aneuploidy affecting the sex chromosomes often leads to infertility. The objective of this study was to estimate the prevalence of sex chromosome aneuploidy in a large juvenile population using routinely available genotype intensity information.

Methods

Genotype and genotype intensity data was available on 145,476 female dairy and beef cattle below 15 months of age at the time of genotyping, with no recorded progeny. Genotype intensity data included the LogR Ratio (LRR), R-value (the sum of X and Y SNP probe intensities), …

Impact Of Breeding For Dairy Traits On Beef Production, Shauna Mulhall

ORBioM (Open Research BioSciences Meeting)

Background

In recent years, there has been a large expansion in the dairy herd, accompanied by a reduction in the beef herd. Consequently, there has been a growing proportion of beef originating from the dairy herd. This study aims to investigate the impact of the current dairy cow breeding program on beef merit.

Methods

Following data edits, this study analysed 53,358 records of cow live weights and body condition scores, as well as slaughter records for 58,151 cows and 156,522 prime animals. Covariance components were estimated between various cow traits (BCS, live weight, carcass weight, conformation and fat score). Additionally, …

The Detection Of Putative Recessive Lethal Haplotypes In Irish Sheep Populations, Rory Mcauley

ORBioM (Open Research BioSciences Meeting)

In livestock populations, recessive lethal alleles are a known contributor to poor reproductive performance due to embryonic death in homozygous individuals. Despite their lethal effect in the recessive form, these alleles may be maintained at high frequencies among carrier animals because of their positive pleiotropic effects on economically important traits. Although several such recessive alleles have been identified in cattle and pig populations, limited studies have been completed in sheep, and none within Irish sheep populations. Genotype data for 69,034 animals from five major Irish sheep breeds genotyped on a variety of panels was available for this study. Only animals …

Genetic Evaluation Of Enteric Methane For Sustainable Irish Beef Cattle, Clodagh Ryan

ORBioM (Open Research BioSciences Meeting)

Background:

Globally, livestock agriculture significantly contributes to human-induced greenhouse gas emissions, particularly through methane production. A potential approach to effectively, durably, and progressively reduce enteric methane emissions at a reasonable cost is through animal breeding.

Methods:

Individual animal methane records were available from 1,508 multi-breed growing beef cattle using GreenFeed Emission Monitoring systems. The objective of this study was to derive genetic parameters for a series of definitions of enteric methane, carbon dioxide, and dry matter intake (DMI). Estimated breeding values (EBVs) were generated for nine alternative definitions of enteric methane and EBVs were validated against phenotypic performance (adjusted for …

Estimating Heritability Explained By Local Ancestry And Evaluating Stratification Bias In Admixture Mapping From Summary Statistics, Tsz Fung Chan, Xinyue Rui, David V Conti, Myriam Fornage, Mariaelisa Graff, Jeffrey Haessler, Christopher Haiman, Heather M Highland, Su Yon Jung, Eimear E Kenny, Charles Kooperberg, Loic Le Marchand, Kari E North, Ran Tao, Genevieve Wojcik, Christopher R Gignoux, Charleston W K Chiang, Nicholas Mancuso

Faculty, Staff and Student Publications

The heritability explained by local ancestry markers in an admixed population (h

Comparison Of Dna Extraction Methods For The Detection Of Canned Tuna Species With Dna Mini-Barcoding, Aubrey J. Emmi, Biola Fatusin, Rosalee S. Hellberg

Food Science Faculty Articles and Research

Tuna is susceptible to species mislabeling due to its high demand, quick rate of production, and wide range of price points. DNA barcoding, a sequencing-based technique, allows for the detection of species mislabeling by targeting a standardized region of DNA. A mitochondrial control region (CR) DNA barcode has been found to be capable of species discrimination for tuna, but it is challenging to recover the entire DNA fragment from canned tuna. While a short fragment of CR, referred to as a “mini-barcode,” has shown some success with canned tuna species identification, more research is needed to improve identification rates. The …

Identification Of Significant Gene Expression Changes Incorporating Heterogeneity In Perturbation Experiments, Katharine Cross

Honors Projects in Biological and Biomedical Sciences

Machine learning methods have been widely applied to the field of genomics and bioinformatics. Specifically utilizing novel machine learning algorithms to study gene-drug interactions has the potential to make a major positive impact on new drug discovery. It is possible that heterogeneity may exist within Vorinostat drug perturbation experiments due to the effects of the perturbations on the gene expressions. Thus, the challenge is to identify the most important genes in a high-dimensional setting while first identifying subpopulations to address population heterogeneity. In this work, clustering techniques are applied to first identify group sub-population structures in the gene expression changes …

Association Of Elevated Serum Aldosterone Concentrations In Pregnancy With Hypertension, Robin C. Shoemaker, Marko Poglitsch, Dolph Lewis Davis Iii, Hong Huang, Aric Schadler, Neil Patel, Katherine Vignes, Aarthi Srinivasan, Cynthia Cockerham-Morris, John Anthony Bauer, John M. O’Brien

UK CARES Faculty Publications

Emerging evidence indicates a previously unrecognized, clinically relevant spectrum of abnormal aldosterone secretion associated with hypertension severity. It is not known whether excess aldosterone secretion contributes to hypertension during pregnancy. We quantified aldosterone concentrations and angiotensin peptides in serum (using liquid chromatography with tandem mass spectrometry) in a cohort of 128 pregnant women recruited from a high-risk obstetrics clinic and followed prospectively for the development of gestational hypertension, pre-eclampsia, superimposed pre-eclampsia, chronic hypertension, or remaining normotensive. The cohort was grouped by quartile of aldosterone concentration in serum measured in the first trimester, and blood pressure, angiotensin peptides, and hypertension outcomes …

Motif-Cluster: A Spatial Clustering Package For Repetitive Motif Binding Patterns, Mengyuan Zhou

School of Computing: Dissertations, Theses, and Student Research

Previous efforts in using genome-wide analysis of transcription factor binding sites (TFBSs) have overlooked the importance of ranking potential significant regulatory regions, especially those with repetitive binding within a local region. Identifying these homogenous binding sites is critical because they have the potential to amplify the binding affinity and regulation activity of transcription factors, impacting gene expression and cellular functions. To address this issue, we developed an open-source tool Motif-Cluster that prioritizes and visualizes transcription factor regulatory regions by incorporating the idea of local motif clusters. Motif-Cluster can rank the significant transcription factor regulatory regions without the need for experimental …

Tracing Evolution Of Gene Transfer Agents Using Comparative Genomics, Roman Kogay

Dartmouth College Ph.D Dissertations

The accumulating evidence suggest that viruses and their components can be domesticated by their hosts, equipping them with convenient molecular toolkits for various functions. One of such domesticated system is Gene Transfer Agents (GTAs) that are produced by some bacteria and archaea. GTAs morphologically resemble small phage-like particles and contain random fragments of their host genome. They are produced only by a small fraction of the microbial population and are released through a lysis of the host cell. Bioinformatic analyses suggest that GTAs are especially abundant in the taxonomic class of Alphaproteobacteria, where they are vertically inherited and evolve …

Multi-Omics Analysis Of Circulating Exosomes In Adherent Long-Term Treated Osa Patients, Abdelnaby Khalyfa, Jose M. Marin, David Sanz-Rubio, Zhen Lyu, Trupti Joshi, David Gozal

Biomedical Sciences

Obstructive sleep apnea (OSA) is a highly prevalent chronic disease affecting nearly a billion people globally and increasing the risk of multi-organ morbidity and overall mortality. However, the mechanisms underlying such adverse outcomes remain incompletely delineated. Extracellular vesicles (exosomes) are secreted by most cells, are involved in both proximal and long-distance intercellular communication, and contribute toward homeostasis under physiological conditions. A multi-omics integrative assessment of plasma-derived exosomes from adult OSA patients prior to and after 1-year adherent CPAP treatment is lacking. We conducted multi-omic integrative assessments of plasma-derived exosomes from adult OSA patients prior to and following 1-year adherent CPAP …

Human Schwann Cells In Vitro I. Nerve Tissue Processing, Pre-Degeneration, Isolation, And Culturing Of Primary Cells, Gabriela I. Aparicio, Paula V. Monje

Markey Cancer Center Faculty Publications

This paper presents versatile protocols to prepare primary human Schwann cell (hSC) cultures from mature peripheral nervous system tissues, including fascicles from long spinal nerves, nerve roots, and ganglia. This protocol starts with a description of nerve tissue procurement, handling, and dissection to obtain tissue sections suitable for hSC isolation and culturing. A description follows on how to disintegrate the nerve tissue by delayed enzymatic dissociation, plate the initial cell suspensions on a two-dimensional substrate, and culture the primary hSCs. Each section contains detailed procedures, technical notes, and background information to aid investigators in understanding and managing all steps. Some …