Genetics and Genomics Commons^™

Temperature And Polyunsaturated Fatty Acid’S Effect On Daphnia Magna Reproduction, Mark Albright

Electronic Theses and Dissertations

Organisms adapt to their environments by adjusting their biochemistry and physiology; such adaptation is limited by resource availability and physiological constraints. The freshwater crustacean Daphnia magna inhabits a wide range of environments and must survive and reproduce within a range of temperatures. One limit to low-temperature adaptation is thought to be the availability of unsaturated fatty acids necessary to maintain proper fluidity of cellular membranes. D. magna maintained at 10 ºC on a diet poor in unsaturated fatty acids have been observed to produce clutches that fail to develop. However, this has not been observed on a diet rich in …

Sip-428, A Sir2 Deacetylase Enzyme And Its Role In Biotic Stress Signaling Pathway, Bal Krishna Chand Thakuri

Electronic Theses and Dissertations

SABP2 (Salicylic Acid Binding Protein 2) plays a vital role in the salicylic acid signaling pathway of plants both regarding basal resistance and systemic acquired resistance against pathogen infection. SIP-428 (SABP2 Interacting Protein-428) is a Silent information regulator 2 (SIR2) like deacetylase enzyme that physically interacts with SABP2 in a yeast two-hybrid interaction and confirmed independently by a GST pull-down assay. We demonstrated that SIP- 428 is an NAD+ dependent SIR2 deacetylase enzyme. Transgenic tobacco plants silenced in SIP- 428 expression via RNAi showed enhanced basal resistance to microbial pathogens. Moreover, these SIP-428-silenced lines also exhibited a robust induction of …

Glucose Signaling Is Important For Nutrient Adaptation During Differentiation Of Pleomorphic African Trypanosomes, Yijian Qiu, Jillian E. Milanes, Jessica A. Jones, Rooksana E. Noorai, Vijay Shankar, James C. Morris

Publications

The African trypanosome has evolved mechanisms to adapt to changes in nutrient availability that occur during its life cycle. During transition from mammalian blood to insect vector gut, parasites experience a rapid reduction in environmental glucose. Here we describe how pleomorphic parasites respond to glucose depletion with a focus on parasite changes in energy metabolism and growth. Long slender bloodstream form parasites were rapidly killed as glucose concentrations fell, while short stumpy bloodstream form parasites persisted to differentiate into the insect-stage procyclic form parasite. The rate of differentiation was lower than that triggered by other cues but reached physiological rates …

Role Of Nucleotide Identity In Effective Crispr Target Escape Mutations, Tim Künne, Yifan Zhu, Fausia Da Silva, Nico Konstantinides, Rebecca E. Mckenzie, Ryan N. Jackson, Stan J.J. Brouns

Chemistry and Biochemistry Faculty Publications

Prokaryotes use primed CRISPR adaptation to update their memory bank of spacers against invading genetic elements that have escaped CRISPR interference through mutations in their protospacer target site. We previously observed a trend that nucleotide-dependent mismatches between crRNA and the protospacer strongly influence the efficiency of primed CRISPR adaptation. Here we show that guanine-substitutions in the target strand of the protospacer are highly detrimental to CRISPR interference and interference-dependent priming, while cytosine-substitutions are more readily tolerated. Furthermore, we show that this effect is based on strongly decreased binding affinity of the effector complex Cascade for guanine-mismatched targets, while cytosine-mismatched targets …

Rna-Seq Reveals Transcriptomic Program Associated With Stemness In Taxane Resistant Prostate Cancer, Christina K. Cajigas-Du Ross

Loma Linda University Electronic Theses, Dissertations & Projects

There is no cure for advanced prostate cancer (PCa), and taxane chemotherapy is the only treatment option once other therapies have failed. However, this is problematic since all patients eventually develop chemoresistance. Emerging treatments for advanced PCa have shown promise at the benchside, but clinical trials have not resulted in newly approved drugs due in part to redundant survival pathways utilized by prostate tumor cells to maintain therapy-resistance. Using RNAsequencing—an innovative approach for quantifying gene expression changes—this dissertation sought to elucidate chemoresistance-associated molecular pathways as a catalyst to develop new therapeutic targets. Results revealed a differential upregulation of stemness-associated genes …

The N-Terminal Methyltransferase Homologs Nrmt1 And Nrmt2 Exhibit Novel Regulation Of Activity Through Heterotrimer Formation., Jon David Faughn

Electronic Theses and Dissertations

Protein, DNA, and RNA methyltransferases have an ever-expanding list of novel substrates and catalytic activities. Even within families and between homologs, it is becoming clear the intricacies of methyltransferase specificity and regulation are far more diverse than originally thought. In addition to specific substrates and distinct methylation levels, methyltransferase activity can be altered through formation of complexes with close homologs. This work involves the N-terminal methyltransferase homologs NRMT1 and NRMT2. NRMT1 is a ubiquitously expressed distributive trimethylase. NRMT2 is a monomethylase expressed at low levels and in a tissue-specific manner. They are both nuclear methyltransferases with overlapping target consensus sequences …

Bayesian Analytical Approaches For Metabolomics : A Novel Method For Molecular Structure-Informed Metabolite Interaction Modeling, A Novel Diagnostic Model For Differentiating Myocardial Infarction Type, And Approaches For Compound Identification Given Mass Spectrometry Data., Patrick J. Trainor

Electronic Theses and Dissertations

Metabolomics, the study of small molecules in biological systems, has enjoyed great success in enabling researchers to examine disease-associated metabolic dysregulation and has been utilized for the discovery biomarkers of disease and phenotypic states. In spite of recent technological advances in the analytical platforms utilized in metabolomics and the proliferation of tools for the analysis of metabolomics data, significant challenges in metabolomics data analyses remain. In this dissertation, we present three of these challenges and Bayesian methodological solutions for each. In the first part we develop a new methodology to serve a basis for making higher order inferences in metabolomics, …

Quantitative Studies Of Amyloidogenic Protein Residue Interaction Networks And Abnormal Ammonia Metabolism In Neurotoxicity And Disease, Jeddidiah Griffin

Electronic Theses and Dissertations

Investigating similarities among neurological diseases can provide insight into disease processes. Two prominent commonalities of neurological diseases are the formation of amyloid deposits and altered ammonia and glutamate metabolism. Computational techniques were used to explore these processes in several neurological diseases. Residue interaction networks (RINs) abstract protein structure into a series of nodes (representing residues) and edges (representing connections between residues likely to interact). Analyzing the RINs of monomeric forms of amyloidogenic proteins for common network features revealed similarities not previously known. First, amyloidogenic variants of lysozyme were used to demonstrate the usefulness of RINs to the study of amyloidogenic …

Deciphering The Role Of Human Arylamine N-Acetyltransferase 1 (Nat1) In Breast Cancer Cell Metabolism Using A Systems Biology Approach., Samantha Marie Carlisle

Electronic Theses and Dissertations

Background: Human arylamine N-acetyltransferase 1 (NAT1) is a phase II xenobiotic metabolizing enzyme found in almost all tissues. NAT1 can additionally hydrolyze acetyl-coenzyme A (acetyl-CoA) in the absence of an arylamine substrate. NAT1 expression varies inter-individually and is elevated in several cancers including estrogen receptor positive (ER+) breast cancers. Additionally, multiple studies have shown the knockdown of NAT1, by both small molecule inhibition and siRNA methods, in breast cancer cells leads to decreased invasive ability and proliferation and decreased anchorage-independent colony formation. However, the exact mechanism by which NAT1 expression affects cancer risk and progression remains unclear. Additionally, consequences …

Transcriptomics Of Learning, Pablo Iturralde

Theses

Learning is a basic and important component of behavior yet we have very little empirical information about the interaction between mechanisms of learning and evolution. In our work, we are testing hypotheses about the neurogenetic mechanisms through which animal learning abilities evolve. We are able to test this directly by using experimentally evolved populations of flies, which differ in learning ability. These populations were previously evolved within the lab by creating worlds with different patterns of change following theoretically predicted effects on which enhanced learning will evolve. How has evolution acted to modulate genes and gene expression in the brain …

Defective Aba-Mediated Sugar Signalling Pathway In An Established Arabidopsis Thaliana Cell Suspension Culture Explains Its Stay-Green Phenotype At High Sugar Concentrations, Avery Mccarthy

Electronic Thesis and Dissertation Repository

An unusual sugar insensitive phenotype was identified in an established cell suspension culture of Arabidopsis thaliana. We characterized the physiology, biochemistry and genetics of the sugar insensitive cell culture, in order to identify factors contributing to the phenotype. Chlorophyll levels of the cell suspension culture were insensitive to high sucrose (6-15% w/v) and maintained a green phenotype. Immunoblotting indicated that levels of key photosynthetic proteins (PsaA, Lhcb2 and Rubisco) increased as a function of external sucrose concentration. The green cell culture was photosynthetically competent based on light-dependent, CO₂-saturated rates of O₂ evolution as well as Fv/Fm …

Functional Studies Of The E. Coli Proc And A Putative Ortholog Mrub_1345, Maureen Azar, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses the bioinformatics tools associated with the Guiding Education through Novel Investigation –Annotation Collaboration Toolkit (GENI-ACT) to predict gene function. We investigated the biological function of Escherichia coli and Meiothermus ruber proC genes using the complementation assay. In this research project, mutants of varying severity to the functional state of the protein were developed. The results showed that two or more amino acid deletions reduced or eliminated ProC function. Amino acid substitutions, on the other hand, were not severe enough to impact ProC function. Double and triple mutants …

Regulation Of The Tubulin Homolog Ftsz In Escherichia Coli, Monika S. Buczek

Dissertations, Theses, and Capstone Projects

Escherichia coli is a well-known pathogen, and importantly, a widely used model organism in all fields of biological sciences for cloning, protein purification, and as a model for Gram-negative bacterial species. And yet, researchers do not fully understand how this bacterium replicates and divides. Every year additional division proteins are discovered, which adds complexity to how we understand E. coli undergoes cell division. Due to their specific roles in cytokinesis, some of these proteins may be potential targets for development of antibacterials or bacteriostatics, which are much needed for fighting the current global antibacterial deficit. My thesis work focuses on …

Genetic Testing And A Real World Case Of Lynch Syndrome, Paige Montanaro

Senior Honors Projects

In recent years, advancements in genetic testing methods have revolutionized the medical field by enhancing the ability to identify persons with an inherited predisposition to cancer. According to the American Society for Clinical Oncology, individuals should undergo genetic testing when he or she meets the following criteria: the individual demonstrates familial history that indicates a predisposition to certain cancers, the test can be adequately interpreted, and the results will aid in the diagnosis, treatment, or management of the patient or additional family members at risk. Genetic testing can be done on samples of hair, skin, blood, amniotic fluid, or other …

Optimizing Genetic Manipulation Of Methanogens Through Faster Cloning Techniques, Merrisa Jennings

Biological and Agricultural Engineering Undergraduate Honors Theses

Methanogenesis is the biological production of methane. Only anaerobic archaea known as methanogens are capable of such a metabolic feat. They have strict living conditions and substrate sources which determine their rate of metabolism. This is of particular importance from a greenhouse gas reduction perspective or biogas capturing perspective. One of the best ways to optimize methanogen methane production is via genetic manipulation. The current procedures are timely though, therefore a faster cloning processes should be developed. The objective of this study was to optimize a premade genetic transformation kit known as the Gibson Kit. The Gibson Kit was supposed …

Functional Similarity Of Prd-Containing Virulence Regulators In Bacillus Anthracis, Malik Raynor

Dissertations & Theses (Open Access)

Bacillus anthracis produces three regulators, AtxA, AcpA, and AcpB, that control virulence gene expression and are members of an emerging class of regulators termed “PCVRs” (Phosphoenolpyruvate-dependent phosphotransferase regulation Domain-Containing Virulence Regulators). AtxA controls expression of the toxin genes; lef, cya, and pag, and is the master virulence regulator and archetype PCVR. AcpA and AcpB are less well studied. AcpA and AcpB independently positively control transcription of the capsule biosynthetic operon capBCADE, and culture conditions that enhance AtxA activity result in capBCADE transcription in strains lacking acpA and acpB. RNA-Seq was used to assess the regulons of the …

Functional And Structural Impact Of The Loss Of The Leucine-Rich Repeat Protein Lrit1 In The Mouse Retina., Catherine Ann Cobb

Electronic Theses and Dissertations

Mutations in genes encoding the leucine-rich repeat (LRR) proteins nyctalopin and LRIT3 lead to complete congenital stationary night blindness because they are critical to depolarizing bipolar cell function in the retina. LRIT3 has two closely related family members, LRIT1 and LRIT2. In silico analyses of publicly available RNA-Seq data showed that Lrit1 was highly expressed in the retina. Here I describe the expression pattern and impact of loss of LRIT1 on retinal function. To enable these studies, we used CRISPR/Cas9 technology to create an Lrit1^-/- mouse line. Retinal morphology and morphometry analyses showed no gross changes in retinal structure …

Investigation For Novel Anti-Apoptotic Factors In The Neurons Of Drosophila Melanogaster, Haylie Rachel Lam

Chancellor’s Honors Program Projects

No abstract provided.

Cross Talk Between Serum Kisspeptin-Leptin During Assisted Reproduction Techniques, Rehana Rehman, Zehra Jamil, Aqsa Khalid, Syeda Sadia Fatima

Department of Biological & Biomedical Sciences

Background & Objective: Leptin facilitates onset of puberty by impact on hypothalamic Kisspeptin, gonadotropin releasing hormone, follicle stimulating and luteinizing hormone. The link of peripheral Leptin-Kisspeptin in regulating the ovarian and endometrial tissue in relation to adiposity is unknown. Therefore, we wanted to identify Kisspeptin-Leptin association with body mass index (BMI) and success of assisted reproductive treatments (ART) in infertile females.
Methods: A cross sectional study was carried from August 2014 till May 2016 after receiving ethical approval at Australian Concept Infertility Medical Centre, and Aga Khan University. The study group comprised of females with an age range …

Prediction Of Lncrna-Disease Associations Based On Inductive Matrix Completion, Chengqian Lu, Mengyun Yang, Feng Luo, Fang-Xiang Wu, Min Li, Yi Pan, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

Motivation: Accumulating evidences indicate that long non-coding RNAs (lncRNAs) play pivotal roles in various biological processes. Mutations and dysregulations of lncRNAs are implicated in miscellaneous human diseases. Predicting lncRNA–disease associations is beneficial to disease diagnosis as well as treatment. Although many computational methods have been developed, precisely identifying lncRNA–disease associations, especially for novel lncRNAs, remains challenging.

Results: In this study, we propose a method (named SIMCLDA) for predicting potential lncRNA– disease associations based on inductive matrix completion. We compute Gaussian interaction profile kernel of lncRNAs from known lncRNA–disease interactions and functional similarity of diseases based on disease–gene and gene–gene onotology …

Self-Oligomerization Regulates Stability Of Survival Motor Neuron Protein Isoforms By Sequestering An ScfSlmb Degron, Kelsey M. Gray, Kevin A. Kaifer, David Baillat, Ying Wen, Thomas R. Bonacci, Allison D. Ebert, Amanda C. Raimer, Ashlyn M. Spring, Sara Ten Have, Jacqueline J. Glascock, Kushol Gupta, Gregory D. Van Duyne, Michael J. Emanuele, Angus I. Lamond, Eric J. Wagner, Christian L. Lorson, A. Gregory Matera

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Spinal muscular atrophy (SMA) is caused by homozygous mutations in human SMN1. Expression of a duplicate gene (SMN2) primarily results in skipping of exon 7 and production of an unstable protein isoform, SMNΔ7. Although SMN2 exon skipping is the principal contributor to SMA severity, mechanisms governing stability of survival motor neuron (SMN) isoforms are poorly understood. We used a Drosophila model system and label-free proteomics to identify the SCF^Slmb ubiquitin E3 ligase complex as a novel SMN binding partner. SCF^Slmb interacts with a phosphor degron embedded within the human and fruitfly SMN YG-box oligomerization domains. …

Killi-Data News (Winter), Tyrone Genade

Killifish Research Review

Valued readers, it is with a heavy heart that I inform you that this is the last issue of Killi-Data News. The good news is that we will be back as Killifish Research Review. The dissolution of Killi-Data International created a prob- lem: how can the newsletter of a defunct organization live on without that organization? But other additional problems were building in the background. The first issue numbered 15 pages. The previous issue was 28 pages. The number of killifish related papers is increasing while time on our end (the editorial team) is running out. It takes a lot …

Killi-Data News (Fall), Tyrone Genade

Killifish Research Review

Many interesting papers have been published over the last three months. The large volume of papers coupled with the start of the new college semester (and the workload it brings) delayed this issue of Killi-Data News. But better late than never—or so I hope! In this issue Richard van der Laan provides an insightful review of the recent Aphanius papers as to their taxonomic implications and questions. The systematic issues he raises show the importance of the Molecular project: we need to get more samples of the various cyprinodontiforme families to resolve unsettled systematic and taxonomic issues. In the Next …

Killi-Data News (Summer), Tyrone Genade

Killifish Research Review

Over the last three months several interesting and exciting pa- pers have been published. By now most of you have heard the Nothobranchius fish poo news emanating from the Valenzano lab. That paper is reviewed and certainly has repercussions for the health of our captive fish. Polaçik et al have published interesting data with ramifications as to how we breed and incubate annual killifish. The big news in this issue is the paper from the Reznick lab which Jean Huber reviews. The contents of that paper goes to the heart of the question of just what a killifish is. The …

Killi-Data News (Spring), Tyrone Genade

Killifish Research Review

This is the start of Killi-Data News’ second year. In this first issue of the year we have the usual review of research pub- lications as well as input from Martin Reichard on his lab’s Nothobranchius research. Martin is responding to my reviews of his lab’s work in the previous edition. I am serious about making sure the content in this newsletter is reliable but I erred in the previous edition and Martin has written extensively to correct my mistake in the section “Erratum”. This reply is welcomed and owed to readers. I must confess that I don’t know everything …

Killi-Data News (Winter), Tyrone Genade

Killifish Research Review

This is the fourth edition, and concluding issue of the first volume, of Killi-Data News and I am happy that it has been well received by readers. At 25 pages this issue is a bit thin- ner than the last but this is because we agreed to make the cut-off for submissions the 1 st of December so we could get this edition out by the New Year. This is an exciting edition full of new species descrip- tions and analyses that will keep taxonomists busy for years to come. Costa has given us two molecular phylogenies on Melanorivulus as …

Killi-Data News (Spring), Tyrone Genade

Killifish Research Review

This is the start of Killi-Data News’ second year. In this first issue of the year we have the usual review of research pub- lications as well as input from Martin Reichard on his lab’s Nothobranchius research. Martin is responding to my reviews of his lab’s work in the previous edition. I am serious about making sure the content in this newsletter is reliable but I erred in the previous edition and Martin has written extensively to correct my mistake in the section “Erratum”. This reply is welcomed and owed to readers. I must confess that I don’t know everything …

Analysis For Science Librarians Of The 2017 Nobel Prize In Physiology Or Medicine: The Life And Work Of Jeffrey C. Hall, Michael Rosbash, And Michael W. Young, Neyda V. Gilman

Library Scholarship

Jeffrey C. Hall, Michael Rosbash, and Michael W. Young are the 2017 Nobel Prize in Physiology or Medicine Laureates, having earned the award for their “discoveries of molecular mechanisms controlling the circadian rhythm.” They identified the genes involved in the circadian rhythm mechanism and explained how all of the different pieces of the mechanism work together. These discoveries explain how the biological cycles of Earth’s organisms correspond to the rotation of the planet, acting as an inner clock. Their research also provides further opportunities to continue learning about the role of circadian rhythm and its relationship to human health (Nobelprize.org …

Examination Of Orthologous Genes (Mrub_2518 And B3728, Mrub_2519 And B3727, Mrub_2520 And B3726, Mrub_2521 And B3725) Responsible For Abc Phosphate Transporters In Two Species M. Ruber And E. Coli, Margaret Meyer, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

In this project we investigated the biological function of the genes b3725, b3726, b3727, b3728 and Mrub_2518, Mrub_2519, Mrub_2520 and Mrub_2521 (KEGG map number 02010). We predict that these genes encode the components of a Phosphate ABC transporter: Orthologous genes Mrub_2518 (DNA coordinates 2565359..2566438) and b3728 encodes the periplasmic phosphate binding component; Orthologous genes Mrub_2519 (DNA coordinates 2566499..2567485) and b3727, and Mrub_2520 (DNA coordinates 2567496..2568326) and b3726 encode for the two transmembrane proteins; Orthologous genes Mrub_2521 (DNA coordinates 2568338..2569159) and b3725 encode for the ATP binding protein within the cytoplasm. Within the two species, M. ruber and E. coli, …

Mrub_1325, Mrub_1326, Mrub_1327, And Mrub_1328 Are Orthologs Of B_3454, B_3455, B_3457, B_3458, Respectively Found In Escherichia Coli Coding For A Branched Chain Amino Acid Atp Binding Cassette (Abc) Transporter System, Bennett Tomlin, Adam Buric, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

In this project we investigated the biological function of the genes Mrub_1325, Mrub_1326, Mrub_1327, and Mrub_1328 (KEGG map number 02010). We predict these genes encode components of a Branched Chain Amino Acid ATP Binding Cassette (ABC) transporter: 1) Mrub_1325 (DNA coordinates 1357399-1358130 on the reverse strand) encodes the ATP binding domain; 2) Mrub_1326 (DNA coordinates 1358127-1359899 on the reverse strand) encodes the ATP-binding domain and permease domain; 3) Mrub_1327 (DNA coordinates 1359899-1360930 on the reverse strand) encodes a permease domain; and 4)Mrub_1328 (DNA coordinates 1711022-1712185 on the reverse strand) encodes the substrate binding domain. This system is not predicted to …