Digital Commons Network^™

The Genome Evolution And Domestication Of Tropical Fruit Mango, Peng Wang, Yingfeng Luo, Jianfeng Huang, Shenghan Gao, Guopeng Zhu, Zhiguo Dang, Jiangtao Gai, Meng Yang, Min Zhu, Huangkai Zhang, Xiuxu Ye, Aiping Gao, Xinyu Tan, Sen Wang, Shuangyang Wu, Edgar B. Cahoon, Beibei Bai, Zhichang Zhao, Qian Li, Junya Wei, Huarui Chen, Ruixiong Luo, Deyong Gong, Kexuan Tang, Bing Zhang, Zhangguang Ni, Guodi Huang, Songnian Hu, Yeyuan Chen

Department of Biochemistry: Faculty Publications

Background: Mango is one of the world’s most important tropical fruits. It belongs to the family Anacardiaceae, which includes several other economically important species, notably cashew, sumac and pistachio from other genera. Many species in this family produce family-specific urushiols and related phenols, which can induce contact dermatitis.

Results: We generate a chromosome-scale genome assembly of mango, providing a reference genome for the Anacardiaceae family. Our results indicate the occurrence of a recent whole-genome duplication (WGD) event in mango. Duplicated genes preferentially retained include photosynthetic, photorespiration, and lipid metabolic genes that may have provided adaptive advantages to sharp historical decreases …

From Synthesis To Utilization: The Ins And Outs Of Mitochondrial Heme, Samantha A. Swenson, Courtney M. Moore, Jason R. Marcero, Amy E. Medlock, Amit R. Reddi, Oleh Khalimonchuk

Department of Biochemistry: Faculty Publications

Heme is a ubiquitous and essential iron containing metallo-organic cofactor required for virtually all aerobic life. Heme synthesis is initiated and completed in mitochondria, followed by certain covalent modifications and/or its delivery to apo-hemoproteins residing throughout the cell. While the biochemical aspects of heme biosynthetic reactions are well understood, the trafficking of newly synthesized heme—a highly reactive and inherently toxic compound—and its subsequent delivery to target proteins remain far from clear. In this review, we summarize current knowledge about heme biosynthesis and trafficking within and outside of the mitochondria.

Connecting Theory To Practice: Using Self-Determination Theory To Better Understand Inclusion In Stem, Michael E. Moore, Dulce M. Vega, Katie M. Wiens, Natalia Caporale

Department of Biochemistry: Faculty Publications

In the United States, persistence for women and ethnic minorities in science, technology, engineering, and math (STEM) careers is strongly impacted by affective factors such as science identity, agency, and sense of belonging. Policies aimed at increasing the diversity of the national STEM student population and workforce have recently focused on fostering inclusive learning environments that can positively impact the experi-ences of underrepresented minorities (URMs) in STEM, thus increasing their retention. While research on inclusion in STEM in higher education is relatively new, inclusion research has a rich history in several other disciplines. These fields have developed theoretical frameworks and …

Systematic Age-, Organ-, And Diet-Associated Ionome Remodeling And The Development Of Ionomic Aging Clocks, Bohan Zhang, Dmitriy I. Podolskiy, Marco Mariotti, Javier Seravalli, Vadim N. Gladyshev

Department of Biochemistry: Faculty Publications

Aging involves coordinated yet distinct changes in organs and systems throughout life, including changes in essential trace elements. However, how aging affects tissue element composition (ionome) and how these changes lead to dysfunction and dis-ease remain unclear. Here, we quantified changes in the ionome across eight organs and 16 age groups of mice. This global profiling revealed novel interactions between elements at the level of tissue, age, and diet, and allowed us to achieve a broader, organismal view of the aging process. We found that while the entire ionome stead-ily transitions along the young-to-old trajectory, individual organs are characterized by …

Training Population Optimization For Genomic Selection In Miscanthus, Marcus O. Olatoye, Lindsay V. Clark, Nicholas R. Labonte, Hongxu Dong, Maria S. Dwiyanti, Kossonou G. Anzoua, Joe E. Brummer, Bimal K. Ghimire, Elena Dzyubenko, Nikolay Dzyubenko, Larisa Bagmet, Andrey Sabitov, Pavel Chebukin, Katarzyna Głowacka, Kweon Heo, Xiaoli Jin, Hironori Nagano, Junhua Peng, Chang Y. Yu, Ji H. Yoo, Hua Zhao, Stephen P. Long, Toshihiko Yamada, Erik J. Sacks, Alexander E. Lipka

Department of Biochemistry: Faculty Publications

Miscanthus is a perennial grass with potential for lignocellulosic ethanol production. To ensure its utility for this purpose, breeding efforts should focus on increasing genetic diversity of the nothospecies Miscanthus x giganteus (M·g) beyond the single clone used in many programs. Germplasm from the corresponding parental speciesM. sinensis (Msi) and M. sacchariflorus (Msa) could theoretically be used as training sets for genomic prediction of M·g clones with optimal genomic estimated breeding values for biofuel traits. To this end, we first showed that subpopulation structure makes a substantial contribution to the genomic selection (GS) prediction accuracies within a 538-member diversity panel …

Differences In Blood-Derived Francisella Tularensis Type B Strains From Clinical Cases Of Tularemia, Marilyn A. Larson, Baha Abdalhamid, Bhanwar Lal Puniya, Tomáš Helikar, David W. Kelley, Peter C. Iwen

Department of Biochemistry: Faculty Publications

Francisella tularensis can cause the zoonotic disease tularemia and is partitioned into subspecies due to differences in chromosomal organization and virulence. The subspecies holarctica (type B) is generally considered more clonal than the other subpopulations with moderate virulence compared to the hypervirulent A.I clade. We performed whole genome sequencing (WGS) on six type B strains isolated from the blood of patients with tularemia within a one-year period from the same United States region, to better understand the associated pathogenicity. The WGS data were compared to the prototype strain for this subspecies, specifically FSC200, which was isolated from a patient with …

Metabolic Feedback Inhibition Influences Metabolite Secretion By The Human Gut Symbiont Bacteroides Thetaiotaomicron, Jennie L. Catlett, Jonathan Catazaro, Mikaela Cashman, Sean Carr, Robert Powers, Myra B. Cohen, Nicole R. Buan

Department of Biochemistry: Faculty Publications

Microbial metabolism and trophic interactions between microbes give rise to complex multispecies communities in microbe-host systems. Bacteroides thetaiotaomicron (B. theta) is a human gut symbiont thought to play an important role in maintaining host health. Untargeted nuclear magnetic resonance metabolomics revealed B. theta secretes specific organic acids and amino acids in defined minimal medium. Physiological concentrations of acetate and formate found in the human intestinal tract were shown to cause dose-dependent changes in secretion of metabolites known to play roles in host nutrition and pathogenesis. While secretion fluxes varied, biomass yield was unchanged, suggesting feedback inhibition does not affect metabolic …

Amphiphiliccyclobutenes And Cylobutanes, Wantanee Sittiwong, Patrick H. Dussault, Raul Barletta, Robert Power

Department of Biochemistry: Faculty Publications

This disclosure relates to amphiphilic compounds containing a cyclobutene or cyclobutane moiety. In some embodiments, the compounds are useful for treating infection by Mycobacterium such as Mycobacterium tuberculosis. Cyclobutene containing compounds are also useful as monomers in the preparation of amphiphilic polymers.

Reactive Oxygen Species (Ros) Mediated Degradation Of Organophosphate T Pesticides By The Green Microalgae Coccomyxa Subellipsoidea☆, Timothy J Nicodemus, Concetta C. Dirusso, Mark A. Wilson, Paul N. Black

Department of Biochemistry: Faculty Publications

The aim of this study was to define the mechanism allowing the green alga Coccomyxa subellipsoidea to break down organophosphates from agricultural run-off. This study found that metabolically active cultures of the microalga C. subellipsoidea breakdown organophosphates (paraoxon, malathion and diazinon) with differing structural conformations in freshwater through a mechanism that requires the formation of reactive oxygen species (ROS) with little to no toxic effects on the algae. Under these conditions, organophosphate levels were reduced to 0.1 mg/mL or less over the 8–10 day experimental period. These findings demonstrate a biological- based system can be tailored for the remediation of …

Sestrins Are Evolutionarily Conserved Mediators Of Exercise Benefits, Myungjin Kim, Alyson Sujkowski, Sim Namkoong, Bondong Gu, Tyler Cobb, Boyoung Kim, Allison H. Kowalsky, Chun-Seok Cho, Ian Semple, Seung-Hyun Ro, Carol Davis, Susan V. Brooks, Michael Karin, Robert J. Wessells, Jun Hee Lee

Department of Biochemistry: Faculty Publications

Exercise is among the most effective interventions for age-associated mobility decline and metabolic dysregulation. Although long-term endurance exercise promotes insulin sensitivity and expands respiratory capacity, genetic components and pathways mediating the meta- bolic benefits of exercise have remained elusive. Here, we show that Sestrins, a family of evolutionarily conserved exercise-inducible proteins, are critical mediators of exercise ben- efits. In both fly and mouse models, genetic ablation of Sestrins prevents organisms from acquiring metabolic benefits of exercise and improving their endurance through training. Conversely, Sestrin upregulation mimics both molecular and physiological effects of exercise, suggesting that it could be a major …

Automated Inference Of Boolean Models From Molecular Interaction Maps Using Casq, Sara Sadat Aghamiri, Vidisha Singh, Aurelien Naldi, Tomáš Helikar, Sylvain Soliman, Anna Niarakis

Department of Biochemistry: Faculty Publications

Motivation: Molecular interaction maps have emerged as a meaningful way of representing biological mechanisms in a comprehensive and systematic manner. However, their static nature provides limited insights to the emerging behaviour of the described biological system under different conditions. Computational modelling provides the means to study dynamic properties through in silico simulations and perturbations. We aim to bridge the gap be- tween static and dynamic representations of biological systems with CaSQ, a software tool that infers Boolean rules based on the topology and semantics of molecular interaction maps built with CellDesigner.

Results: We developed CaSQ by defining conversion rules and …

Sbml Level 3: An Extensible Format For The Exchange And Reuse Of Biological Models, Sarah M. Keating, Dagmar Waltemath, Tomáš Helikar, Michael Hucka, 50 Additional Co-Authors

Department of Biochemistry: Faculty Publications

Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction-based models and packages that extend the core with features suited to other model types including constraintbased models, reaction-diffusion models, logical network models, and rule-based models. The format leverages …

Photosynthetic Efficiency And Mesophyll Conductance Are Unaffected In Arabidopsis Thaliana Aquaporin Knock-Out Lines, Johannes Kromdijk, Katarzyna Głowacka, Stephen P. Long

Department of Biochemistry: Faculty Publications

Improving photosynthetic efficiency is widely regarded as a major route to achieving much-needed yield gains in crop plants. In plants with C₃ photosynthesis, increasing the diffusion conductance for CO₂ transfer from substomatal cavity to chloroplast stroma (g_m) could help to improve the efficiencies of CO₂ assimilation and photosynthetic water use in parallel. The diffusion pathway from substomatal cavity to chloroplast traverses cell wall, plasma membrane, cytosol, chloroplast envelope membranes, and chloroplast stroma. Specific membrane intrinsic proteins of the aquaporin family can facilitate CO₂ diffusion across membranes. Some of these aquaporins, such as PIP1;2 …

Serotonin 5-Ht2a And 5-Ht2c Receptors Regulate Rat Maternal Behavior Through Distinct Behavioral And Neural Mechanisms, Jun Gao, Lina Nie, Yu Li, Ming Li

Department of Psychology: Faculty Publications

Serotonin 5-HT_2A and 5-HT_2C receptors play important yet distinctive roles in the regulation of rat maternal behavior. The present study investigated their neural substrates and explored the possible behavioral mechanisms (i.e., behavioral organization or maternal motivation). Sprague-Dawley postpartum females were microinjected with either a selective 5-HT_2A agonist (TCB-2, 0.4 or 4.0 μg/side) or a 5-HT_2C agonist (MK212, 2.5 or 5.0 μg/side) into the medial prefrontal cortex (mPFC) or ventral tegmental area (VTA). Ten and 60 min later, their maternal activities were observed in the home cage; and their motivational responses towards pups were examined in a …

The Balancing Act Of Cytokinin In Environmental Stress Tolerance, Sumudu Sandeepani Karunadasa

Theses and Dissertations--Plant and Soil Sciences

Cytokinin, long known as a phytohormone that regulates plant growth and development, has been recently recognized as an important regulator of stress responses. However, our current knowledge about the mechanisms by which cytokinin regulates stress responses is fragmentary, as many of the studies in this field yielded conflicting results. Most of the work described here has focused on analyses of the molecular mechanisms of cytokinin-dependent regulation of growth and development under stress conditions, with an emphasis on the role of cytokinin-dependent regulation of protein synthesis in development and stress tolerance.

One of the important contributions of this study is the …

Size-Dependent Interactions Of Lipid-Coated Gold Nanoparticles: Developing A Better Mechanistic Understanding Through Model Cell Membranes And In Vivo Toxicity, Arek M. Engstrom, Ryan A. Faase, Joe E. Baio, Marilyn R. Mackiewicz, Stacey L. Harper

Chemistry Faculty Publications and Presentations

Introduction: Humans are intentionally exposed to gold nanoparticles (AuNPs) where they are used in variety of biomedical applications as imaging and drug delivery agents as well as diagnostic and therapeutic agents currently in clinic and in a variety of upcoming clinical trials. Consequently, it is critical that we gain a better understanding of how physiochemical properties such as size, shape, and surface chemistry drive cellular uptake and AuNP toxicity in vivo. Understanding and being able to manipulate these physiochemical properties will allow for the production of safer and more efficacious use of AuNPs in biomedical applications.
Methods and Materials: Here, …

Effect Of Mptp On Α-Synuclein Spreading, Accumulation And Toxicity In Mice With Intrastriatal Innoculation Of Human Α-Synuclein Preformed Fibril, Madiha Mohieldin Merghani

Theses

Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder, characterized by abnormal accumulation of interneuronal inclusions of α-synuclein (α-syn) known as Lewy bodies (LBs) and Lewy neurites (LNs), and significant loss of dopamine neurons in the substantia nigra pars compacta (SNc) region of the brain. Recent evidence suggests that intrastriatal inoculation of α-syn Preformed Fibril (PFF) into mice induces PD-like LBs and LNs pathology formed by aggregated α-syn in anatomically interconnected brain regions which needs several months of incubation to develop the pathology. In the present study, we have evaluated the effect of different doses of 1-methyl, 4-phenyl, …

Fggy Carbohydrate Kinase Domain Containing Is Induced During Skeletal Muscle Atrophy And Modulates Map Kinase And Akt Signaling, Anastasia L. Smith

UNF Graduate Theses and Dissertations

Skeletal muscle atrophy can result from a range of physiological conditions, including denervation, immobilization, hindlimb unweighting, and aging. To better characterize the molecular genetic events of atrophy, a microarray was performed using skeletal muscle isolated from mice after 3 and 14 days of denervation and compared to control muscle to identify novel atrophy-induced genes. The microarray revealed that FGGY carbohydrate kinase domain containing (Fggy) is expressed in skeletal muscle and is induced in response to denervation. Bioinformatic analysis of the Fggy gene locus revealed two validated alternative isoforms, that we have termed Fggy-L-552 and Fggy-S-387, which have distinct transcription initiation …

Special Issue On The Third Workshop On Biological Mentality, Kenneth A. Augustyn

Michigan Tech Publications, Part 1

The Third Workshop on Biological Mentality was held from September 23, 2019 to March 2, 2020 as a series of twenty-one Monday online conferencing sessions, each consisting of a talk followed by a Q&A discussion. Like the two previous workshops [1, 2], the objective of this workshop was to seek a deeper level of understanding the physical foundations of biological mentality (whether conscious or nonconscious).

Consciousness As A Factor In Evolution, Kenneth A. Augustyn

Michigan Tech Publications, Part 1

What I call the mind began as a non-conscious robotic biochemical process control system in the very earliest forms of life. As life evolved, problems in control became more difficult and exceeded the computational capabilities of the organisms. Nature discovered a means of transcending computable physical processes resulting in non-computational subjective mental capabilities that, while still not conscious, had a degree of genuine autonomy from the physical world. These autonomous subjective wants and goals now affected the course of (but not the mechanism of) evolution. The integrated amalgam of robotic and transrobotic unconscious capabilities eventually gave rise to consciousness, which …

A Eukaryotic Signature Based Method For Identification Of Saliva, Feces, And Urine, Alyssa Daniels

Master of Science in Forensic Science Directed Research Projects

The conception of the Human Microbiome Project advanced the understanding of microbial communities in the human body and previous research has established that unique microbial signatures can help distinguish each body fluid. While these signatures have been developed for the prokaryotic microbiome, the next step is the examination of the eukaryotic microbiome. Eukaryotic signatures could provide a greater specificity and statistical weight when discerning between body fluids. These microbial markers can be implemented to develop a confirmatory assay for body fluid identification that works in tandem with other DNA based methods in the forensic workflow. Using a VCU approved IRB …

Engineering Ph-Dependent Antibody Interactions Through Linked Protonation Events In Interdomain Interfaces, Hyeyoung Eom

Graduate Research Theses & Dissertations

Engineered antibodies are frequently used in life science applications, such as therapeutics and clinical diagnostics. These customized antibodies typically possess enhanced binding affinity and/or specificity, yet these interactions are only one-way binding events that cannot be easily controlled without extreme changes in conditions, such as pH, denaturant, and/or temperature that likely irreversible damage the antibody and antigen. Here, we explore the design of proton-linked binding events in the context of both antibody/hapten (i.e., a low molecular weight ligand target) and antibody/antigen complexes. Specifically, this work looks to overcome the challenges of engineering pH-dependent small ligand/protein interactions, as well as develop …

Investigation Of Glutamate Carboxypeptidase Ii Roles In The Folate Cycle Dependent Reproduction And Development Of Caenorhabditis Elegans, Jessica M. Derham

Masters Theses

Glutamate Carboxypeptidase II (GCPII) is a transmembrane, zinc metallopeptidase that is expressed in a wide range of organisms, including roundworms, mice, and humans. In humans, GCPII is primarily expressed in the prostate, kidneys, small intestine, and central nervous system. Within the small intestine, the expected function of GCPII is to aid in the absorption of dietary folate from the intestinal lumen. GCPII cleaves excess glutamates from folate to yield monoglutamated folate which is then readily transported into the enterocyte. Folate can then be used through the one carbon metabolic cycle for the synthesis of nucleotides, conversion of homocysteine to methionine, …

Reprograming Neuronal Cells By Overexpression Of Fibroblast-Specific Transcription Factors, Abdulmohsen Alanazi

Masters Theses

In mammals, a complex system of regulatory signals distinguishes tissues, structures and functions. Combinations of transcription factors and co-factors regulate activation and repression of genes that result in cellular differentiation. Whole genome arrays allow the monitoring of genomic expression in specific tissues. Fibroblast microarray studies have shown candidate genes that may be involved in fibroblast identification, including genes that express transcription factors Prrx1, Snai2 and Twist1. A previous study showed that the Prrx1 and Snai2 could reactivate a fibroblast phenotype in hybrid cells that had lost fibroblast identity. Furthermore, overexpression of these factors in liver-derived cells strongly repressed liver gene …

A Kinesin Adapter Directly Mediates Dendritic Mrna Localization During Neural Development In Mice, Hao Wu, Jing Zhou, Tianhui Zhu, Ivan Cohen, Jason Dictenberg

Publications and Research

Motor protein-based active transport is essential for mRNA localization and local translation in animal cells, yet how mRNA granules interact with motor proteins remains poorly understood. Using an unbiased yeast two–hybrid screen for interactions between murine RNA-binding proteins (RBPs) and motor proteins, here we identified protein interaction with APP tail-1 (PAT1) as a potential direct adapter between zipcode-binding protein 1 (ZBP1, a β-actin RBP) and the kinesin-I motor complex. The amino acid sequence of mouse PAT1 is similar to that of the kinesin light chain (KLC), and we found that PAT1 binds to KLC directly. Studying PAT1 in mouse …

A Biophysical Investigation Of Stability, Ligand Binding, And Iron State Of Cyp102a1, Catherine A. Denning-Jannace

Theses and Dissertations--Chemistry

Cytochrome P450s (CYPs) are cysteine ligated Fe-heme monooxygenases that are found in all domains of life. In mammals, they have a role in xenobiotic metabolism and steroid synthesis, making them a fundamental requirement for survival. In addition, their ability to perform a variety of chemical reactions on an array of substrates makes CYPs highly sought for biotechnical applications such as wastewater remediation, production of potential drug candidates, and creation of drug metabolites. By mutating specific amino acids, these enzymes can be engineered to change their substrate binding profiles and achieve stereo- and regio-specific chemistry. While these mutations are essential to …

New Single Molecule In Vivo And Ex Vivo Methods To Understand The Physiological Effects Of Nicotine Use, Xu Fu

Theses and Dissertations--Chemistry

The consumption of tobacco products leads to several health risks, including respiratory diseases, cardiovascular diseases, and many different cancers. Nicotine, the primary addictive compound in tobacco, acts on the cholinergic system through nicotinic acetylcholine receptors (nAChRs), which is believed to be an essential component of addiction. However, the lack of a complete understanding of the neurobiological mechanisms of nicotine abuse is one of the primary barriers to finding potent therapeutics for smoking cessation. Single-molecule imaging is an ideal tool to study molecular mechanisms of protein and physiological changes both in vitro and in vivo. In this dissertation, our research …

Deconvolution Tools For Extracting Insight From Challenging Two-Flavin Systems, Dallas Michael Bell

Theses and Dissertations--Chemistry

Flavoproteins have long been explored for their ubiquity among a number of metabolic and energetic reactions. The flavin cofactor has the inherent benefit of distinct spectral changes associated with redox transitions; however, the double-edged sword is incurred as these distinct signatures overlap and take up much of the UV-vis spectral range. Therefore, it is crucial to create a method to demarcate the expressed redox transitions for studying these systems. The first portion of these studies discusses the creation of a program that deduces spectra for redox transitions in a single-flavin containing model protein: flavodoxin. The latter portions discuss the application …

Single-Domain Vhh Antibodies As Protein Stabilization Modules, Nourhan Mohamed Disouky Mostafa

Graduate Research Theses & Dissertations

VHH domains are the antigen-binding units found in heavy-chain-only antibodies from the Camelidae family (e.g., camels and llamas). They are considered a unique minimalist antibody scaffold due to the lack of a variable light chain domain. Despite having half the antigen-binding interface of conventional antibodies, these VHH antibodies bind their target antigens with affinities comparable to conventional antibodies. This project explored how flexible linkers connecting an anti-GFP VHH (αGFP VHH) domain to its antigen (EGFP) enhanced antigen stability and influenced oligomeric assembly. It was hypothesized that linking the anti-GFP VHH antibody to its target antigen (EGFP) will increase the local …

A Bioinformatic Approach To Exploring Land Plant Evolution, Lauren Margaret Orton

Graduate Research Theses & Dissertations

Today, researchers are inundated with an overwhelming amount of data due to advances in DNA sequencing technologies. This has benefited the fields of both bioinformatics and phylogenomics substantially. With the ability to increase sampling at both the taxonomic and molecular levels, we are now able to produce robust phylogenomic reconstructions and better discern relationships between taxa.

The goals of this dissertation are in two distinct parts: 1) to advance the understanding of land plant terrestrialization and evolution through examination of the closest relative to the land plant lineage, a species of green algae; and 2) to explore evolution among a …