Other Biochemistry, Biophysics, and Structural Biology Commons^™

Methanogens: Pushing The Boundaries Of Biology, Nicole R. Buan

Department of Biochemistry: Faculty Publications

Methanogens are anaerobic archaea that grow by producing methane gas. These microbes and their exotic metabolism have inspired decades of microbial physiology research that continues to push the boundary of what we know about how microbes conserve energy to grow. The study of methanogens has helped to elucidate the thermodynamic and bioenergetics basis of life, contributed our understanding of evolution and biodiversity, and has garnered an appreciation for the societal utility of studying trophic interactions between environmental microbes, as methanogens are important in microbial conversion of biogenic carbon into methane, a high-energy fuel. This review discusses the theoretical basis for …

Methanogens: Pushing The Boundaries Of Biology, Nicole R. Buan

Department of Biochemistry: Faculty Publications

Methanogens are anaerobic archaea that grow by producing methane gas. These microbes and their exotic metabolism have inspired decades of microbial physiology research that continues to push the boundary of what we know about how microbes conserve energy to grow. The study of methanogens has helped to elucidate the thermodynamic and bioenergetics basis of life, contributed our understanding of evolution and biodiversity, and has garnered an appreciation for the societal utility of studying trophic interactions between environmental microbes, as methanogens are important in microbial conversion of biogenic carbon into methane, a high-energy fuel. This review discusses the theoretical basis for …

Molecular Fossils From Phytoplankton Reveal Secular Pco2 Trend Over The Phanerozoic, Caitlyn R. Witkowski, Johan W. H. Weijers, Brian S. Blais, Stefan Schouten, Jaap S. Sinninghe Damsté

Science and Technology Department Faculty Journal Articles

Past changes in the atmospheric concentration of carbon dioxide (PCO2) have had a major impact on earth system dynamics; yet, reconstructing secular trends of past PCO2 remains a prevalent challenge in paleoclimate studies. The current long-term PCO2reconstructions rely largely on the compilation of many different proxies, often with discrepancies among proxies, particularly for periods older than 100 million years (Ma). Here, we reconstructed Phanerozoic PCO2 from a single proxy: the stable carbon isotopic fractionation associated with photosynthesis (Ɛp) that increases as PCO2 increases. This concept has been widely applied to alkenones, but here, we …

Combining Mass Spectrometry And Nmr Improves Metabolite Detection And Annotation, Fatema Bhinderwala, Nishikant Wase, Concetta Dirusso, Robert Powers

Department of Biochemistry: Faculty Publications

Despite inherent complementarity, nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) are routinely separately employed to characterize metabolomics samples. More troubling is the erroneous view that metabolomics is better served by exclusively utilizing MS. Instead, we demonstrate the importance of combining NMR and MS for metabolomics by using small chemical compound-treatments of Chlamydomonas reinhardtii as an illustrative example. A total of 102 metabolites were detected (82 by GC-MS, 20 by NMR and 22 by both techniques). Out of these 47 metabolites of interest were identified, where 14 metabolites were uniquely identified by NMR and 16 metabolites were uniquely identified …

Mouse Genome-Wide Association Studies And Systems Genetics Uncover The Genetic Architecture Associated With Hepatic Pharmacokinetic And Pharmacodynamic Properties Of A Constrained Ethyl Antisense Oligonucleotide Targeting Malat1, Elaine Pirie, Shayoni Ray, Calvin Pan, Wuxia Fu, Andrew F. Powers, Danielle Polikoff, Colton M. Miller, Katrina M. Kudrna, Edward N. Harris, Aldons J. Lusis, Rosanne M. Crooke, Richard G. Lee

Department of Biochemistry: Faculty Publications

Antisense oligonucleotides (ASOs) have demonstrated variation of efficacy in patient populations. This has prompted our investigation into the contribution of genetic architecture to ASO pharmacokinetics (PK) and pharmacodynamics (PD). Genome wide association (GWA) and transcriptomic analysis in a hybrid mouse diversity panel (HMDP) were used to identify and validate novel genes involved in the uptake and efficacy of a single dose of a Malat1 constrained ethyl (cEt) modified ASO. The GWA of the HMDP identified two significant associations on chromosomes 4 and 10 with hepatic Malat1 ASO concentrations. Stabilin 2 (Stab2) and vesicle associated membrane protein 3 ( …

Induction Of Oil Accumulation By Heat Stress Is Metabolically Distinct From N Stress In The Green Microalgae Coccomyxa Subellipsoidea C169, James W. Allen, Rahul Tevatia, Yaşar Demirel, Concetta C. Dirusso, Paul N. Black

Department of Biochemistry: Faculty Publications

Algae are often promoted as feedstock organisms to produce a sustainable petroleum fossil fuel alternative. However, to induce lipid accumulation most often requires a severe stress that is difficult to induce in large batch cultures. The objective of this study is to analyze and mathematically model heat stress on growth, chlorophyll content, triacylglyceride, and starch synthesis in algae. We initially screened 30 algal species for the most pronounced induction of lipid droplets from heat stress using confocal microscopy and mass spectroscopy techniques. One species, Coccomyxa subellipsoidea C169, was selected and subjected to further biochemical analyses using a jacketed bioreactor amended …

Identification Of Biologically Essential Nodes Via Determinative Power In Logical Models Of Cellular Processes, Trevor Pentzien, Bhanwar L. Puniya, Tomas Helikar, Mihaela T. Matache

Department of Biochemistry: Faculty Publications

A variety of biological networks can bemodeled as logical or Boolean networks. However, a simplification of the reality to binary states of the nodes does not ease the difficulty of analyzing the dynamics of large, complex networks, such as signal transduction networks, due to the exponential dependence of the state space on the number of nodes. This paper considers a recently introduced method for finding a fairly small subnetwork, representing a collection of nodes that determine the states of most other nodes with a reasonable level of entropy. The subnetwork contains the most determinative nodes that yield the highest information …

Fars2 Mutations Presenting With Pure Spastic Paraplegia And Lesions Of The Dentate Nuclei, Supreet K. Sahai, Rebecca E. Steiner, Margaret G. Au, John M. Graham, Norikio Salamon, Michael Ibba, Tyler M. Pierson

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Mutations in FARS2, the gene encoding the mitochondrial phenylalanine‐tRNA synthetase (mtPheRS), have been linked to a range of phenotypes including epileptic encephalopathy, developmental delay, and motor dysfunction. We report a 9‐year‐old boy with novel compound heterozygous variants of FARS2, presenting with a pure spastic paraplegia syndrome associated with bilateral signal abnormalities in the dentate nuclei. Exome sequencing identified a paternal nonsense variant (Q216X) lacking the catalytic core and anticodon‐binding regions, and a maternal missense variant (P136H) possessing partial enzymatic activity. This case confirms and expands the phenotype related to FARS mutations with regards to clinical presentation and neuroimaging findings.

Lipid Transport Required To Make Lipids Of Photosynthetic Membranes, Evan Labrant, Allison C. Barnes, Rebecca Roston

Department of Biochemistry: Faculty Publications

Photosynthetic membranes provide much of the usable energy for life on earth. To produce photosynthetic membrane lipids, multiple transport steps are required, including fatty acid export from the chloroplast stroma to the endoplasmic reticulum, and lipid transport from the endoplasmic reticulum to the chloroplast envelope membranes. Transport of hydrophobic molecules through aqueous space is energetically unfavorable and must be catalyzed by dedicated enzymes, frequently on specialized membrane structures. Here, we review photosynthetic membrane lipid transport to the chloroplast in the context of photosynthetic membrane lipid synthesis. We independently consider the identity of transported lipids, the proteinaceous transport components, and membrane …

Codon Usage Revisited: Lack Of Correlation Between Codon Usage And The Number Of Trna Genes In Enterobacteria, Joaquín Rojas, Gabriel Castillo, Lorenzo Eugenio Leiva, Sara Elgamal, Omar Orellana, Michael Ibba, Assaf Katz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

It is widely believed that if a high number of genes are found for any tRNA in a rapidly replicating bacteria, then the cytoplasmic levels of that tRNA will be high and an open reading frame containing a higher frequency of the complementary codon will be translated faster. This idea is based on correlations between the number of tRNA genes, tRNA concentration and the frequency of codon usage observed in a limited number of strains as well as from the fact that artificially changing the number of tRNA genes alters translation efficiency and consequently the amount of properly folded protein …

Structure And Mechanism Of Mycobacterial Topoisomerase I, Nan Cao

FIU Electronic Theses and Dissertations

The enzyme DNA topoisomerase I is an essential enzyme that plays an important role in eukaryotic and prokaryotic cellular processes such as DNA replication, transcription, recombination and repair. Mycobacterium tuberculosistopoisomerase I (MtTOP1) is a validated drug target for antituberculosis treatment. Mycobacterial topoisomerase I regulates the topological constraints in chromosomes and helps in maintaining the growth of mycobacteria. The N- terminal domain (NTD) of mycobacterial topoisomerase I contains conserved catalytic domains that along with the active site Tyrosine are involved in cleaving and rejoining a single strand of DNA. Magnesium is required in DNA cleavage activity of type IA topoisomerases. …

Reversible Heparin Molecules And Methods Of Making And Using The Same, Jian Liu, Yongmei Xu, Robert J. Linhardt, Edward Harris

Department of Biochemistry: Faculty Publications

Methods and systems for synthesizing heparin compounds are provided . The chemoenzymatic synthesis of structurally homogeneous low molecular weight heparins that have a reversible anticoagulant activity is provided . Also disclosed are heparin compounds having anticoagulant activity , including a binding affinity to antithrombin and an anti - Xa activity , but no detectable anti - lla activity . Additionally , provided are synthetic , low - molecular weight heparin com pounds with reversible anticoagulant activity , where the anticoagulant activity is reversible by protamine.

Ef-P Post-Translational Modification Has Variable Impact On Polyproline Translation In Bacillus Subtilis, Anne Witzky, Katherine R. Hummels, Rodney Tollerson Ii, Andrei Rajkovic, Lisa A. Jones, Daniel B. Kearns, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Elongation factor P (EF-P) is a ubiquitous translation factor that facilitates translation of polyproline motifs. In order to perform this function, EF-P generally requires posttranslational modification (PTM) on a conserved residue. Although the position of the modification is highly conserved, the structure can vary widely between organisms. In Bacillus subtilis, EF-P is modified at Lys³² with a 5-aminopentanol moiety. Here, we use a forward genetic screen to identify genes involved in 5-aminopentanolylation. Tandem mass spectrometry analysis of the PTM mutant strains indicated that ynbB, gsaB, and ymfI are required for modification and that yaaO, yfkA, and …

Intraperitoneal Nanotherapy For Metastatic Ovarian Cancer Based On Sirna-Mediated Suppression Of Dj-1 Protein Combined With A Low Dose Of Cisplatin, Canan Schumann, Stephanie Chan, Jess A. Miller, Yuliya Bortnyak, Katherine Carey, Alex Fedchyk, Leon Wong, Tetiana Korzun, Abraham S. Moses, Anna Lorenz, Delany Shea, Olena Taratula, Oleh Khalimonchuk, Oleh Taratula

Department of Biochemistry: Faculty Publications

Herein, we report an efficient combinatorial therapy for metastatic ovarian cancer based on siRNA-mediated suppression of DJ-1 protein combined with a low dose of cisplatin. DJ-1 protein modulates, either directly or indirectly, different oncogenic pathways that support and promote survival, growth, and invasion of ovarian cancer cells. To evaluate the potential of this novel therapy, we have engineered a cancer-targeted nanoplatform and validated that DJ-1 siRNA delivered by this nanoplatform after intraperitoneal injection efficiently downregulates the DJ-1 protein in metastatic ovarian cancer tumors and ascites. In vivo experiments revealed that DJ-1 siRNA monotherapy outperformed cisplatin alone by inhibiting tumor growth …

Diurnal And Developmental Differences In Gene Expression Between Adult Dispersing And Flightless Morphs Of The Wing Polymorphic Cricket, Gryllus Firmus: Implications For Life-History Evolution, Anthony J. Zera, Neetha Nanoth Vellichirammal, Jennifer A. Brisson

Anthony Zera Publications

The functional basis of life history adaptation is a key topic of research in life history evolution. Studies of wing polymorphism in the cricket Gryllus firmus have played a prominent role in this field. However, prior in-depth investigations of morph specialization have primarily focused on a single hormone, juvenile hormone, and a single aspect of intermediary metabolism, the fatty-acid biosynthetic component of lipid metabolism. Moreover, the role of diurnal variation in life history adaptation in G. firmus has been understudied, as is the case for organisms in general. Here, we identify genes whose expression differs consistently between the …

Structural Determinants For The Interactions Of Chemically Modified Nucleic Acids With The Stabilin‑2 Clearance Receptor, Hans Gaus, Colton M. Miller, Punit P. Seth, Edward N. Harris

Department of Biochemistry: Faculty Publications

The Stabilin receptors are systemic clearance receptors for some classes of chemically modified nucleic acid therapeutics. In this study, the recombinant human secreted ecto-domain of the small isoform of Stabilin-2 (s190) was purified from cell culture and evaluated for direct binding with a multitude of antisense oligonucleotides (ASOs) using a fluorescence polarizationbased assay. The tested ASOs varied in their backbone composition, modification of the ribose 2′ position, overall length of the oligo, and sequence of the nucleotide bases. A fully phosphorothioate (PS) ASO with a 5−10−5 pattern of flanking 2′-O-methoxyethyl modifications was then used to test the effects …

Curcumin Potentiates The Function Of Human Α7-Nicotinic Acetylcholine Receptors Expressed In Sh-Ep1 Cells, Eslam El Nebrisi, Lina T. Al Kury, Keun-Hang Susan Yang, Petrilla Jayaprakash, Frank Christopher Howarth, Nadine Kabbani, Murat Oz

Mathematics, Physics, and Computer Science Faculty Articles and Research

Effects of curcumin, a biologically active ingredient of turmeric, were tested on the Ca²⁺transients induced by the activation of α₇ subunit of the human nicotinic acetylcholine (α₇nACh) receptor expressed in SH-EP1 cells. Curcumin caused a significant potentiation of choline (1 mM)-induced Ca²⁺ transients with an EC₅₀ value of 133 nM. The potentiating effect of curcumin was not observed in Ca²⁺ transients induced by high K⁺ (60 mM) containing solutions or activation of α₄β₂ nACh receptors and the extent of curcumin potentiation was not altered in the presence of …

Dietary Omega-3 And Omega-6 Polyunsaturated Fatty Acids Modulate Hepatic Pathology, Saraswoti Khadge, J. Graham Sharp, Geoffrey M. Thiele, Timothy R. Mcguire, Lynell W. Klassen, Michael J. Duryee, Holly C. Britton, Jordan Beck, Paul N. Black, Concetta Dirusso, James Talmadge

Department of Biochemistry: Faculty Publications

Recent evidence has suggested that dietary polyunsaturated fatty acids (PUFAs) modulate inflammation; however, few studies have focused on the pathobiology of PUFA using isocaloric and isolipidic diets and it is unclear if the associated pathologies are due to dietary PUFA composition, lipid metabolism or obesity, as most studies compare diets fed ad libitum. Our studies used isocaloric and isolipidic liquid diets (35% of calories from fat), with differing compositions of omega (ω)-6 or long chain (Lc) ω-3 PUFA that were pair-fed and assessed hepatic pathology, inflammation and lipid metabolism. Consistent with an isocaloric, pair-fed model we observed no significant difference …

Adenosine Has Two Faces: Regionally Dichotomous Adenosine Tone In A Model Of Epilepsy With Comorbid Sleep Disorders, Ted J. Warren, Timothy A. Simeone, D. David Smith, Ryan Grove, Jiri Adamec, Kaeli K. Samson, Harrison M. Roundtree, Deepak Madhavan, Kristina A. Simeone

Department of Biochemistry: Faculty Publications

Objective: Adenosine participates in maintaining the excitatory/inhibitory balance in neuronal circuits. Studies indicate that adenosine levels in the cortex and hippocampus increase and exert sleep pressure in sleep-deprived and control animals, whereas in epilepsy reduced adenosine tone promotes hyperexcitability. To date, the role of adenosine in pathological conditions that result in both seizures and sleep disorders is unknown. Here, we determined adenosine tone in sleep and seizure regulating brain regions of Kv1.1 knockout (KO) mice, a model of temporal epilepsy with comorbid sleep disorders.

Methods: 1) Reverse phase-high performance liquid chromatography (RP-HPLC) was performed on brain tissue to determine levels …

Total Mercury Determination In Muscle And Liver Tissue Samples From Brazilian Amazon Fish Using Slurry Sampling, João Vitor De Queiroz, José Cavalcante Souza Vieira, Izabela Da Cunha Bataglioli, Alis Correia Bittarello, Camila Pereira Braga, Grasieli De Oliveira, Cilene Do Carmo Federici Padilha, Pedro De Magalhães Padilha

Department of Biochemistry: Faculty Publications

This paper presents a slurry sampling method for total mercury determination by graphite furnace atomic absorption spectrometry (GFAAS) in tissue of fish from the Amazon. The tissue samples were lyophilized and macerated, and then the slurry samples were prepared by putting 20 mg of tissue, added to a solution containing Triton X-100, Suprapur HNO₃, and zirconium nitrate directly in sampling vials of a spectrometer. Mercury standard solutions were prepared under the same conditions as the slurry samples. The slurry samples and the mercury standard solutions were sonicated for 20 s. Twenty microliters of slurry samples were injected into …

Cancerdiscover: An Integrative Pipeline For Cancer Biomarker And Cancer Class Prediction From High-Throughput Sequencing Data, Akram Mohammed, Greyson Biegert, Jiri Adamec, Tomáš Helikar

Department of Biochemistry: Faculty Publications

Accurate identification of cancer biomarkers and classification of cancer type and subtype from High Throughput Sequencing (HTS) data is a challenging problem because it requires manual processing of raw HTS data from various sequencing platforms, quality control, and normalization, which are both tedious and timeconsuming. Machine learning techniques for cancer class prediction and biomarker discovery can hasten cancer detection and significantly improve prognosis. To date, great research efforts have been taken for cancer biomarker identification and cancer class prediction. However, currently available tools and pipelines lack flexibility in data preprocessing, running multiple feature selection methods and learning algorithms, therefore, developing …

The Colomoto Interactive Notebook: Accessible And Reproducible Computational Analyses For Qualitative Biological Networks, Aurelien Naldi, Celine Hernandez, Nicolas Levy, Gautier Stoll, Pedro T. Monteiro, Claudine Chaouiya, Tomáš Helikar, Andrei Zinovyev, Laurence Calzone, Sarah Cohen-Boulakia, Denis Thieffry, Loic Pauleve

Department of Biochemistry: Faculty Publications

Analysing models of biological networks typically relies on workflows in which different software tools with sensitive parameters are chained together,many times with additional manual steps. The accessibility and reproducibility of such workflows is challenging, as publications often overlook analysis details, and because some of these tools may be difficult to install, and/or have a steep learning curve. The CoLoMoTo Interactive Notebook provides a unified environment to edit, execute, share, and reproduce analyses of qualitative models of biological networks. This framework combines the power of different technologies to ensure repeatability and to reduce users’ learning curve of these technologies. The framework …

A Mechanistic Computational Model Reveals That Plasticity Of Cd4+ T Cell Differentiation Is A Function Of Cytokine Composition And Dosage, Bhanwar Lal Puniya, Robert G. Todd, Akram Mohammed, Deborah M. Brown, Matteo Barberis, Tomáš Helikar

Department of Biochemistry: Faculty Publications

CD4+ T cells provide cell-mediated immunity in response to various antigens. During an immune response, naïve CD4+ T cells differentiate into specialized effector T helper (Th1, Th2, and Th17) cells and induced regulatory (iTreg) cells based on a cytokine milieu. In recent studies, complex phenotypes resembling more than one classical T cell lineage have been experimentally observed. Herein, we sought to characterize the capacity of T cell differentiation in response to the complex extracellular environment. We constructed a comprehensive mechanistic (logical) computational model of the signal transduction that regulates T cell differentiation. The model’s dynamics were characterized and analyzed under …

Towards The Synthetic Design Of Camelina Oil Enriched In Tailored Acetyl-Triacylglycerols With Medium-Chain Fatty Acids, Sunil Bansal, Hae Jin Kim, Gunnam Na, Megan E. Hamilton, Edgar B. Cahoon, Chaofu Lu, Timothy P. Durrett

Department of Biochemistry: Faculty Publications

The ability to manipulate expression of key biosynthetic enzymes has allowed the development of genetically modified plants that synthesise unusual lipids that are useful for biofuel and industrial applications. By taking advantage of the unique activities of enzymes from different species, tailored lipids with a targeted structure can be conceived. In this study we demonstrate the successful implementation of such an approach by metabolically engineering the oilseed crop Camelina sativa to produce 3-acetyl-1,2-diacyl-sn-glycerols (acetyl-TAGs) with medium-chain fatty acids (MCFAs). Different transgenic camelina lines that had been genetically modified to produce MCFAs through the expression of MCFA-specific thioesterases and …

Single-Molecule Unbinding Forces Between The Polysaccharide Hyaluronan And Its Binding Proteins, Fouzia Bano, Markku I. Tammi, David W. Kang, Edward N. Harris, Ralf P. Richter

Department of Biochemistry: Faculty Publications

The extracellular polysaccharide hyaluronan (HA) is ubiquitous in all vertebrate tissues, where its various functions are encoded in the supramolecular complexes and matrices that it forms with HA-binding proteins (hyaladherins). In tissues, these supramolecular architectures are frequently subjected to mechanical stress, yet how this affects the intermolecular bonding is largely unknown. Here, we used a recently developed single-molecule force spectroscopy platform to analyze and compare the mechanical strength of bonds between HA and a panel of hyaladherins from the Link module superfamily, namely the complex of the proteoglycan aggrecan and cartilage link protein, the proteoglycan versican, the inflammation-associated protein TSG-6, …

Endosomal Escape Of Antisense Oligonucleotides Internalized By Stabilin Receptors Is Regulated By Rab5c And Eea1 During Endosomal Maturation, Colton M. Miller, W. Brad Wan, Punit P. Seth, Edward N. Harris

Department of Biochemistry: Faculty Publications

Second-generation (Gen 2) Antisense oligonucleotides (ASOs) show increased nuclease stability and affinity for their RNA targets, which has translated to improved potency and therapeutic index in the clinic. Gen 2 ASOs are typically modified using the phosphorothioate (PS) backbone modification, which enhances ASO interactions with plasma, cell surface, and intracellular proteins. This facilitates ASO distribution to peripheral tissues and also promotes cellular uptake after injection into animals. Previous work identified that Stabilin receptors specifically internalize PS-ASOs in the sinusoidal endothelial cells of the liver and the spleen. By modulating expression of specific proteins involved in the trafficking and maturation of …

3-O Sulfation Of Heparin Leads To Hepatotropism And Longer Circulatory Half-Life, Colton M. Miller, Yongmei Xu, Katrina M. Kudrna, Blake E. Hass, Brianna M. Kellar, Andrew W. Egger, Jian Liu, Edward N. Harris

Department of Biochemistry: Faculty Publications

Introduction: Heparins are common blood anticoagulants that are critical for many surgical and biomedical procedures used in modern medicine. In contrast to natural heparin derived from porcine gut mucosa, synthetic heparins are homogenous by mass, polymer length, and chemistry.

Materials & methods: Stable cell lines expressing the human and mouse Stabilin receptors were used to evaluate endocytosis of natural and synthetic heparin. We chemoenzymatically produced synthetic heparin consisting of 12 sugars (dodecamers) containing 14 sulfate groups resulting in a non-3-O sulfated structure (n12mer). Half of the n12mer was modified with a 3-O sulfate on a single GlcNS sugar producing the …

Reactive Oxygen Species In Chronic Obstructive Pulmonary Disease, Samia Boukhenouna, Mark A. Wilson, Karim Bahmed, Beata Kosmider

Department of Biochemistry: Faculty Publications

Chronic obstructive pulmonary disease (COPD) includes chronic bronchitis and emphysema. Environmental exposure, primarily cigarette smoking, can cause high oxidative stress and is the main factor of COPD development. Cigarette smoke also contributes to the imbalance of oxidant/antioxidant due to exogenous reactive oxygen species (ROS). Moreover, endogenously released ROS during the inflammatory process and mitochondrial dysfunction may contribute to this disease progression. ROS and reactive nitrogen species (RNS) can oxidize different biomolecules such as DNA, proteins, and lipids leading to epithelial cell injury and death. Various detoxifying enzymes and antioxidant defense systems can be involved in ROS removal. In this review, …

Characterization Of A Recurrent Missense Mutation In The Forkhead Dna-Binding Domain Of Foxp1, Tyler B. Johnson, Keegan Mechels, Ruth Ellen Anderson, Jacob T. Cain, David A. Sturdevant, Stephen Braddock, Hailey Pinz, Mark A. Wilson, Megan Landsverk, Kyle J. Roux, Jill M. Weimer

Department of Biochemistry: Faculty Publications

Haploinsufficiency of Forkhead box protein P1 (FOXP1), a highly conserved transcription factor, leads to developmental delay, intellectual disability, autism spectrum disorder, speech delay, and dysmorphic features. Most of the reported FOXP1 mutations occur on the C-terminus of the protein and cluster around to the forkhead domain. All reported FOXP1 pathogenic variants result in abnormal cellular localization and loss of transcriptional repression activity of the protein product. Here we present three patients with the same FOXP1 mutation, c.1574G>A (p.R525Q), that results in the characteristic loss of transcription repression activity. This mutation, however, represents the first reported FOXP1 mutation that does …

Identification Of Genes Encoding Enzymes Catalyzing The Early Steps Of Carrot Polyacetylene Biosynthesis, Lucas Busta, Won Cheol Yim, Evan William Labrant, Peng Wang, Lindsey Grimes, Kiah Malyszka, John C. Cushman, Patricia Santos, Dylan K. Kosma, Edgar B. Cahoon

Department of Biochemistry: Faculty Publications

Polyacetylenic lipids accumulate in various Apiaceae species after pathogen attack, suggesting that these compounds are naturally occurring pesticides and potentially valuable resources for crop improvement. These compounds also promote human health and slow tumor growth. Even though polyacetylenic lipids were discovered decades ago, the biosynthetic pathway underlying their production is largely unknown. To begin filling this gap and ultimately enable polyacetylene engineering, we studied polyacetylenes and their biosynthesis in the major Apiaceae crop carrot (Daucus carota subsp. sativus). Using gas chromatography and mass spectrometry, we identified three known polyacetylenes and assigned provisional structures to two novel polyacetylenes. We …