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Articles 1 - 30 of 3160
Full-Text Articles in Biochemistry
Waste Streams From Next Generation Molten Salt Reactors: The Challenge Of Creating An Insoluble Ceramic For Chloride Salt Waste, Alevtina A. Maksimova, Jake W. Amoroso, Matthew Page, Gregory Morrison, Hans Conrad Zur Loye
Waste Streams From Next Generation Molten Salt Reactors: The Challenge Of Creating An Insoluble Ceramic For Chloride Salt Waste, Alevtina A. Maksimova, Jake W. Amoroso, Matthew Page, Gregory Morrison, Hans Conrad Zur Loye
Faculty Publications
Molten salt reactors (MSRs) design development is of interest to many research groups and companies. Waste management for MSRs is one of the most important issues that needs to be resolved due to its impact on environmental safety, primarily via the dissolution of radionuclides in water. Furthermore, the waste treatment strategy will have a significant influence on the operating cost of MSRs, which is why a reliable process for the immobilization, transportation, storage and disposal of MSR waste must be addressed. This work presents a new approach for the immobilization of chloride salts from molten salt reactors in stable oxyhalide …
Characterization Of Mettl3/14-Mediated M6a Modification In Human Transcriptome Using Nanopore Direct Rna Sequencing, Emily Kurtyan, Andrew J. Stein, Kelly J. Abdalla, Zhangerjiao Yuan, Miten Jain, Fadia Ibrahim
Characterization Of Mettl3/14-Mediated M6a Modification In Human Transcriptome Using Nanopore Direct Rna Sequencing, Emily Kurtyan, Andrew J. Stein, Kelly J. Abdalla, Zhangerjiao Yuan, Miten Jain, Fadia Ibrahim
Department of Biochemistry and Molecular Biology Faculty Papers
Post-transcriptional RNA modifications modulate diverse aspects of RNA metabolism. N6-methyladenosine (m6A), one of the most abundant internal RNA modifications, is deposited by the core methyltransferase complex, METTL3 and METTL14. Oxford Nanopore Technologies (ONT) platform permits direct, single RNA molecule sequencing while preserving native modifications. However, without rigorous benchmarking, the accuracy and reproducibility of modification detection remain uncertain. Here, we leveraged ONT to comprehensively profile bona fide m6A modifications in cellular RNAs at single-nucleotide resolution by integrating two direct RNA sequencing chemistries (RNA002 and RNA004) with the m6Anet and Dorado modification-detection models. We independently depleted METTL3 and METTL14 in human cells …
Instruction Guide, Mark C. Hall
Instruction Guide, Mark C. Hall
Analytical Biochemistry: A Practical Handbook for Undergraduates
The instruction guide provides useful information for setting up and running the lab activities each week and assessing student preparation, performance, and comprehension.
A Comprehensive In-Silico Pipeline For The Discovery Of Non-Toxic, Stable Antimicrobial Peptides From Databases For Targeting Multi-Drug Resistant K. Pneumoniae, Pranab D. Sharma, Abdullah A. Noman, Al Hafiz
A Comprehensive In-Silico Pipeline For The Discovery Of Non-Toxic, Stable Antimicrobial Peptides From Databases For Targeting Multi-Drug Resistant K. Pneumoniae, Pranab D. Sharma, Abdullah A. Noman, Al Hafiz
Faculty Articles
The rapid emergence of multidrug-resistant Klebsiella pneumoniae has significantly reduced the effectiveness of conventional antibiotics, highlighting the need for alternative therapeutic strategies. This study employed a comprehensive in silico pipeline to identify antimicrobial peptides (AMPs) targeting the essential DNA replication initiator protein DnaA. A total of 28,361 peptide sequences were collected from publicly available AMP databases and sequentially filtered based on peptide length, net charge, GRAVY score, instability index, antimicrobial activity, toxicity, hemolytic potential, aggregation propensity, sequence similarity and favorable amphipathic properties. Four peptides satisfied all selection criteria and were subjected to structural prediction, membrane-binding analysis, protein–DNA docking, protein–peptide docking, …
Crystal Structure Of New Polar Rare Earth Borates Na2.62Ln2.12(Bo3)3 (Ln = Pr, Nd, Sm) Containing Isolated Bo3 Groups, Alevtina A. Maksimova, Mark D. Smith, Hans Conrad Zur Loye
Crystal Structure Of New Polar Rare Earth Borates Na2.62Ln2.12(Bo3)3 (Ln = Pr, Nd, Sm) Containing Isolated Bo3 Groups, Alevtina A. Maksimova, Mark D. Smith, Hans Conrad Zur Loye
Faculty Publications
Three new rare earth borates, Na2.62Ln2.12(BO3)3 (Ln = Pr, Nd, Sm), were synthesized via a high-temperature solution reaction using a BaCO3–H3BO3–NaF flux and structurally characterized by single-crystal X-ray diffraction analysis. The compounds crystallize in the orthorhombic space group Amm2 with lattice parameters a = 5.0985(10) Å, b = 11.180(2) Å, c = 7.1483(14) Å, and a unit cell volume of 407.48(14) Å3 (Z = 2) for Na2.62Pr2.12(BO3)3, a = 5.0983(10) Å, b = 11.181(2) Å, c = 7.1491(14) Å, and a unit cell volume of 407.51(14) Å3 (Z = 2) for Na2.62Nd2.12(BO3)3, and a = 5.08630(10) Å, b …
Single Crystal Growth Of The Orthoborate Nabalu(Bo3)2 And Optical Investigation Of Eu3+ And Tb3+ Doped Nabalu(Bo3)2, Alevtina A. Maksimova, Mark D. Smith, Lakshani W. Masachchi, Hans Conrad Zur Loye
Single Crystal Growth Of The Orthoborate Nabalu(Bo3)2 And Optical Investigation Of Eu3+ And Tb3+ Doped Nabalu(Bo3)2, Alevtina A. Maksimova, Mark D. Smith, Lakshani W. Masachchi, Hans Conrad Zur Loye
Faculty Publications
Sodium barium lutetium borate NaBaLu(BO3)2 crystals were synthesized using a high-temperature solution method. The crystal structure of this layered orthoborate is described and corresponds to that of an extensive orthoborates family, NaBaR(BO3)2 (R = Sc, Y, Yb, Tb – Lu). NaBaLu(BO3)2 was doped by Eu3+ and Tb3+ to explore its performance as a host material and to investigate the luminescent properties of the Eu3+ and Tb3+ doped materials. The emission spectra of the NaBaLu(BO3)2:Ln (Ln = Eu, Tb) crystals are presented. The most …
Analysis Of The Atypical Temperature Dependence And Conformational Changes During Turnover Of A Lactobacillus Chlorogenic Acid Esterase, Nathaniel Carl, Yianni Tsigaris, Dan Ji, Nora K. Anpree, Kellie K. Omori, Cedric P. Owens
Analysis Of The Atypical Temperature Dependence And Conformational Changes During Turnover Of A Lactobacillus Chlorogenic Acid Esterase, Nathaniel Carl, Yianni Tsigaris, Dan Ji, Nora K. Anpree, Kellie K. Omori, Cedric P. Owens
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Many bacterial chlorogenic acid esterases (ChlEs) exhibit atypical temperature behavior, featuring activities that barely change with temperature and activity maxima that fall below the thermal denaturation point. This work focuses on a ChlE from Lactobacillus helveticus (Lh–ChlE), which has a flat temperature dependence. First, it was determined that conformational changes during Lh–ChlE turnover are not rate-limiting and that the overall rate depends on the chemical step at all temperatures. Next, Lh–ChlE’s temperature dependence was investigated using a conformational equilibrium model that assumes the existence of a temperature-dependent equilibrium between an active and an inactive conformation and an activation heat capacity …
Mechanistic Determination Of Host Environmental Impacts On Shigella Virulence, Nicholas E. Dickenson
Mechanistic Determination Of Host Environmental Impacts On Shigella Virulence, Nicholas E. Dickenson
Funded Research Records
No abstract provided.
Investigation Into Molecular Bases Of Pregnancy-Associated Malaria, Nicole Pozo
Investigation Into Molecular Bases Of Pregnancy-Associated Malaria, Nicole Pozo
Biochemistry and Molecular Biology
Plasmodium falciparum causes the most severe and deadly form of malaria and remains a major global health problem, especially in sub-Saharan Africa (Milner, 2018). The parasite infects and multiplies inside red blood cells, leading to fever, anemia, organ damage, and death if untreated (Milner, 2018; Song et al., 2022). It is especially dangerous because it avoids the immune system by changing surface proteins called Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), which are encoded by more than 60 var genes. By switching between these genes, the parasite hides from immune detection and creates repeated waves of infection (Deitsch & Dzikowski, …
Personalizable Metabolic Models To Enable Immune Characterization And Drug Discovery, Joshua Loecker
Personalizable Metabolic Models To Enable Immune Characterization And Drug Discovery, Joshua Loecker
Department of Biochemistry: Dissertations, Theses, and Student Research
Cellular metabolism is reshaped by disease and physiological state, and genome-scale metabolic networks (GSMNs) offer a systematic way to interrogate this biology and identify therapeutic targets. Building a GSMN from expression data, however, requires a sequence of stages including read processing, normalization and gene-activity classification, multi-omic integration, model reconstruction, simulation, and biological interpretation. These are typically handled by disconnected tools spanning multiple programming languages, file formats, and databases. The resulting reliance on heterogeneous interfaces and manual steps threatens reproducibility. This work develops an ecosystem of computational tools that carry an analysis from raw sequencing reads to mechanistic biological interpretation. First, …
Rna G-Quadruplexes Function As A Tunable Switch Of Fus Phase Separation, Jenny L. Carey, Miyuki Hayashi, Emily A. Welebob, Laura R. Ganser, Huan Wang, Kerry Buckhaults, Jacquelyn A. Depierro, Zheng Shi, James Shorter, Sua Myong, Aaron R. Haeusler, Lin Guo
Rna G-Quadruplexes Function As A Tunable Switch Of Fus Phase Separation, Jenny L. Carey, Miyuki Hayashi, Emily A. Welebob, Laura R. Ganser, Huan Wang, Kerry Buckhaults, Jacquelyn A. Depierro, Zheng Shi, James Shorter, Sua Myong, Aaron R. Haeusler, Lin Guo
Department of Biochemistry and Molecular Biology Faculty Papers
Fused in sarcoma (FUS) undergoes liquid-liquid phase separation (LLPS) to support essential cellular functions, but aberrant phase transitions promote toxic aggregation in neurodegenerative disease. Short RNA oligonucleotides can reverse this behavior, yet the structural determinants that govern RNA activity remain poorly defined. Here, we identify RNA G-quadruplexes (rG4s) as tunable structural motifs that potently modulate FUS LLPS. rG4 activity depends on its concentration and is modulated by rG4 length and stability: increasing repeat number switches rG4s from inhibitor to nucleator of FUS assembly, whereas chemical modifications that stabilize rG4 enhance inhibitory function and render these activities resilient to ionic perturbation. …
Main-Chain Ion-Pair Polybenzimidazole Membranes Enabling Reduced-Temperature Ht-Pemfc Operation (Down To 120°C), Brian C. Benicewicz, Huina Lin
Main-Chain Ion-Pair Polybenzimidazole Membranes Enabling Reduced-Temperature Ht-Pemfc Operation (Down To 120°C), Brian C. Benicewicz, Huina Lin
Faculty Publications
Proton exchange membrane (PEM) fuel cells are promising for clean and efficient energy conversion across diverse applications. High-temperature PEM fuel cells (HT-PEMFCs) using phosphoric acid (PA)-doped polybenzimidazole (PBI) can operate up to 200°C, but at lower temperatures, water-induced PA loss often leads to performance degradation and reduced durability. In this work, we present a new class of main-chain ion-pair PBI membranes by integrating the imidazolium-biphosphate ion-pair units directly into the PBI backbone. This design results in membranes with high acid content, stronger acid-polymer interactions and stabilized acid retention. In single-cell tests, the Im+-PBI15-3 wt.% exhibits peak power densities of 0.79 …
Structure-Based Discovery Of Malate Dehydrogenase Inhibitors With Efficacy Against C. Parvum Oocysts, Ankita Bharatbhai Kheni
Structure-Based Discovery Of Malate Dehydrogenase Inhibitors With Efficacy Against C. Parvum Oocysts, Ankita Bharatbhai Kheni
Biochemistry and Molecular Biology
Cryptosporidium parvum, the etiological agent of Cryptosporidiosis (diarrheal illness) represents a significant global health burden, particularly affecting immunodeficient and pediatric populations. Since the parasite has a highly reduced mitochondrion and relies on glycolysis, enzymes such as C. parvum malate dehydrogenase (CpMDH), which are believed to be indispensable for parasite viability due to their pivotal roles in NAD⁺ regeneration and redox balance, remain largely unexplored as therapeutic targets. The present study employed a multifaceted experimental and computational strategy to evaluate the inhibitory activity of two lead-like and drug-like small molecules, referred to as compound 1.8 and compound 1.5, against the cofactor …
Chromatin Insulators Homie And Nhomie Can Interact With Distant Copies Either Together Or Separately, With Distinct Outcomes For Enhancer-Promoter Interactions, Miki Fujioka, Wenfan Ke, Paul Schedl, James B. Jaynes
Chromatin Insulators Homie And Nhomie Can Interact With Distant Copies Either Together Or Separately, With Distinct Outcomes For Enhancer-Promoter Interactions, Miki Fujioka, Wenfan Ke, Paul Schedl, James B. Jaynes
Department of Biochemistry and Molecular Biology Faculty Papers
Chromatin insulators, a.k.a. boundary elements, separate regions of the chromosome with distinct chromatin characteristics, including distinct histone modifications. This activity affects gene expression by allowing chromatin domains to be stably regulated and maintained. Insulators also block enhancer-promoter interactions and, somewhat paradoxically, facilitate other interactions, particularly when they stitch together distant regions of the chromosome by pairing with specific partners. Here we explore how long-range interactions facilitated by insulator pairing are affected by the presence of two potentially competing partners. Our results show that when two partners are present, they can reduce each other's effects on distant gene expression, suggesting that …
Hydroxamate Formation In The Lipopeptide Containing Siderophore Taiwachelin, Aaron J. Gringer, Kernen P. Agwaza, Isabel Da Fonseca, Pablo Sobrado
Hydroxamate Formation In The Lipopeptide Containing Siderophore Taiwachelin, Aaron J. Gringer, Kernen P. Agwaza, Isabel Da Fonseca, Pablo Sobrado
Chemistry Faculty Research & Creative Works
Cupriavidus taiwanensis is a nitrogen-fixing bacterium found in root nodules of the invasive tropical weed Mimosa pudica . C. taiwanensis has been shown to grow in environments contaminated with heavy metals such as Pb, Cu, and Cd. Taiwachelin, a recently identified siderophore produced by C. taiwanensis , is an iron chelator that contains a hydroxamate functional group for metal binding. In its biosynthesis, a flavin-dependent N-monooxygenase (NMO) was predicted to hydroxylate l -ornithine, leading to formation of the metal binding hydroxamate moiety. Here, we report the cloning, expression, and biochemical characterization of this enzyme, herein referred to as CtNMO. CtNMO …
Structure Of Ergosteryl-Aspartate Synthase Reveals How An Entrapped Trna Is Used Like A Prosthetic Swinging Arm In The Synthesis Of Aminoacylated Sterols, Hanako Murayama, Nathaniel Yakobov, Nassira Mahmoudi, Sasha Legrosdidier, Nicolas Fournier, Solène Zuttion, Kanata Matsumoto, Michihiro Nishimura, Jingwei Ji, Bruno Senger, Laurence Huck, Howard Gamper, Yoshiaki Kise, Ralph Kleiner, Mathieu Frechin, Ya-Ming Hou, Hubert Becker, Yuzuru Itoh, Frédéric Fischer, Osamu Nureki
Structure Of Ergosteryl-Aspartate Synthase Reveals How An Entrapped Trna Is Used Like A Prosthetic Swinging Arm In The Synthesis Of Aminoacylated Sterols, Hanako Murayama, Nathaniel Yakobov, Nassira Mahmoudi, Sasha Legrosdidier, Nicolas Fournier, Solène Zuttion, Kanata Matsumoto, Michihiro Nishimura, Jingwei Ji, Bruno Senger, Laurence Huck, Howard Gamper, Yoshiaki Kise, Ralph Kleiner, Mathieu Frechin, Ya-Ming Hou, Hubert Becker, Yuzuru Itoh, Frédéric Fischer, Osamu Nureki
Department of Biochemistry and Molecular Biology Faculty Papers
Ergosteryl-3β-O-L-aspartate synthase (ErdS) catalyzes tRNA-dependent aspartylation of ergosterol, a lipid essential for fungal cell membrane integrity. However, the functional significance of ergosteryl-aspartate and the molecular mechanisms underlying its synthesis remain unclear. Here, we show that ErdS localization is highly dynamic and that Erg-Asp is required for proper hyphal growth, sporulation, and spore germination, and likely influences stress tolerance. The cryo-electron microscopy structure of ErdS revealed an unprecedented sterol-binding pocket. In addition, the structures in complex with a non-hydrolyzable Asp-N-tRNAAsp show a tRNA-guided intramolecular aminoacyl transfer mechanism between two functional domains of the enzyme. The CCA end of tRNAAsp undergoes a …
Crystal Structure Of Mouse Dxo In Complex With The Udp-N-Acetylglucosamine Cap And Molecular Mechanism For The Decapping Reactions, Najeeb Ullah, Selom K. Doamekpor, Liang Tong
Crystal Structure Of Mouse Dxo In Complex With The Udp-N-Acetylglucosamine Cap And Molecular Mechanism For The Decapping Reactions, Najeeb Ullah, Selom K. Doamekpor, Liang Tong
Department of Biochemistry and Molecular Biology Faculty Papers
Noncanonical metabolite 5' caps have recently been identified on RNAs, and the DXO/Rai1 family of enzymes can remove these caps in eukaryotes. While the binding modes of NAD, FAD and dephospho-CoA (dpCoA) caps in the active site of mouse DXO have been determined, how DXO recognizes the UDP-glucose (UDP-Glc) and UDP-N-acetylglucosamine (UDP-GlcNAc) caps is not known. In addition, the molecular mechanism by which DXO catalyzes the decapping reactions is still poorly understood, especially the location of the water/hydroxide that attacks the scissile phosphate to initiate the decapping. Here we report the crystal structure of mouse DXO in complex with UDP-GlcNAc …
Bioinformatic Resolution Of Candidate Stress-Response Homologs In Cryptosporidium Parvum: P53-Family Vs Sestrin Identity, Freeman Tobechukwu Ezeala Mr.
Bioinformatic Resolution Of Candidate Stress-Response Homologs In Cryptosporidium Parvum: P53-Family Vs Sestrin Identity, Freeman Tobechukwu Ezeala Mr.
Biochemistry and Molecular Biology
Cryptosporidium parvum is an apicomplexan protozoan of major public-health importance, but accurate genome annotation in this organism remains difficult because of its compact genome, deep protein divergence, and the presence of compositionally biased or low-complexity regions that can mislead similarity-based analysis.
In this thesis, I examined one such annotation problem involving a conserved Cryptosporidium stress-response candidate protein, CPATCC_0028580_t1 (833 aa). The central question was whether this protein is better interpreted as a member of the p53 family, based on similarity to p53-like DNA-binding domains (PF00870), or as a member of the Sestrin family associated with the PA26 domain.
I explored …
Sequence Determinants Of Rna G-Quadruplex Unfolding By Arg-Rich Regions, Naiduwadura Ivon Upekala De Silva, Puspa Kunwar, Md Ibnul Rifat Rahman, Joanna Koryo Kwao, Nathan Lehman, Zihan Zhang, Trenton Paul, Claire Cheng, Nicholas Truex, Hui-Ting Lee, Jun Zhang
Sequence Determinants Of Rna G-Quadruplex Unfolding By Arg-Rich Regions, Naiduwadura Ivon Upekala De Silva, Puspa Kunwar, Md Ibnul Rifat Rahman, Joanna Koryo Kwao, Nathan Lehman, Zihan Zhang, Trenton Paul, Claire Cheng, Nicholas Truex, Hui-Ting Lee, Jun Zhang
Faculty Publications
RNA sequences with the potential to form G-quadruplexes (rGQs) are widespread but largely unfolded in cells by unknown mechanisms. rGQ folding status is a critical regulator of RNA splicing and translation. We show that rGQs can be unfolded by SR proteins, SR-related proteins, and other Arg-rich proteins, including SRSF1, SRSF3, SRSF9, U1-70K, and U2AF1. The length and composition of Arg-rich regions are key determinants of this activity: Arg residues are the primary drivers, while acidic residues attenuate the unfolding activity. To unfold ARPC2 rGQ, at least 13 Arg residues are required. Our findings identify Arg-rich proteins as previously unrecognized, helicase-independent …
Evaluation Of Flt3 Inhibition With Quizartinib During Busulfan Conditioning For Hematopoietic Stem Cell Transplantation, Catherine Jankovic
Evaluation Of Flt3 Inhibition With Quizartinib During Busulfan Conditioning For Hematopoietic Stem Cell Transplantation, Catherine Jankovic
Biochemistry and Molecular Biology
Hematopoietic stem cell transplantation (HSCT) is one of the only curative therapy options for many hematologic malignancies. HSCT relies on effective conditioning regimens to deplete host hematopoietic cells and enable donor engraftment. The alkylating agent Busulfan is widely used in myeloablative conditioning strategies due to its potent cytotoxic effects on hematopoietic cells and ability to clear the bone marrow. However, optimization of conditioning strategies remains an important area of investigation to improve transplant outcomes and reduce toxicity. Preliminary studies have shown that the FLT3 inhibitor Quizartinib synergizes with some chemotherapeutic agents, suggesting that targeted inhibitors may enhance conventional conditioning regimens. …
Understanding Tlr3 Immune Response Activation In Cryptosporidium Parvum And Cryspovirus Pathogenesis, Surayya Hudayberganova
Understanding Tlr3 Immune Response Activation In Cryptosporidium Parvum And Cryspovirus Pathogenesis, Surayya Hudayberganova
Biochemistry and Molecular Biology
Cryptosporidiosis is a serious gastrointestinal illness caused by a protozoan parasite known as Cryptosporidium. It is particularly dangerous for malnourished children and those with compromised immune systems. My research focuses on the Toll-like receptor 3 (TLR3) response to the Cryptosporidium parvum infection, specifically in the presence of the parasite’s viral mutualist named cryspovirus (CSpV1). Results using research methodologies like ELISA and RT-qPCR have indicated that TLR3 expression increases during the infection process of Cryptosporidium parvum (C. parvum). Furthermore, one intriguing observation concluded during this study suggests that administering the TLR3-specific inhibitor CU-CPT4a to infected cells drastically decreased this activation. This …
Mechanistic Insights Into Enterolactone-Mediated Glut4-Dependent Glucose Uptake, Merritt Smith
Mechanistic Insights Into Enterolactone-Mediated Glut4-Dependent Glucose Uptake, Merritt Smith
Senior Honors Theses
Type 2 diabetes mellitus (T2D) is one of the leading causes of morbidity and mortality in the United States, with approximately 25% of healthcare expenditures directed toward its management and associated metabolic complications. In response to the urgent need for novel therapeutic strategies, recent research has focused on bioactive compounds derived from dietary sources. In light of that, we identified the plant lignan matairesinol (MA) and its gut-derived metabolite, enterolactone (ENL), as agents capable of enhancing glucose uptake in 3T3-L1 differentiated adipocytes. These results suggest that enterolactone may represent a promising dietary supplement for improving glycemic control in patients with …
Mitochondrial Dna Replication Is Regulated By Endoplasmic Reticulum-Mitochondrial Contact Sites, The Mitochondrial Calcium Uniporter, And Manganese, Amaia Lopez De Arbina, Angelica Zamudio-Ochoa, Mikel Muñoz-Oreja, Diego Perez-Rodriguez, Laura Mosqueira-Martín, Rebecca Lasalandra, Marina Villar-Fernandez, Uxoa Fernandez-Pelayo, Laura Rodriguez-Gomez, Seungtae Lee, Francisco Gil-Bea, Nerea Osinalde, Ainara Vallejo-Illaramendi, Dmitry Temiakov, Antonella Spinazzola, Ian Holt
Mitochondrial Dna Replication Is Regulated By Endoplasmic Reticulum-Mitochondrial Contact Sites, The Mitochondrial Calcium Uniporter, And Manganese, Amaia Lopez De Arbina, Angelica Zamudio-Ochoa, Mikel Muñoz-Oreja, Diego Perez-Rodriguez, Laura Mosqueira-Martín, Rebecca Lasalandra, Marina Villar-Fernandez, Uxoa Fernandez-Pelayo, Laura Rodriguez-Gomez, Seungtae Lee, Francisco Gil-Bea, Nerea Osinalde, Ainara Vallejo-Illaramendi, Dmitry Temiakov, Antonella Spinazzola, Ian Holt
Department of Biochemistry and Molecular Biology Faculty Papers
Mitochondrial DNA replication occurs at contact sites between the endoplasmic reticulum (ER) and mitochondria (ERMCS). Beyond the known role of the tubular ER protein RTN4, the factors regulating this process are poorly defined. Here, we show that repressing the ER protein ERLIN2 in human fibroblasts depletes ER-mitochondrial contact sites and inhibits mitochondrial DNA replication, as does silencing RTN4 or the ER-mitochondrial tether GRP75. GRP75 or RTN4 scarcity also decreases the level of the mitochondrial calcium uniporter (MCU), whose inhibition blocks mitochondrial DNA synthesis. Because ERMCS depletion did not diminish mitochondrial calcium, and MCU complex can transport manganese, we tested whether …
Mechanistic Insights Into E. Coli Recovery From Growth Arrest, Ahmed H. Hassan, Yuko Nakano, Howard Gamper, Isao Masuda, Ludmila Vesela, Matyas Pinkas, Sathya Narayanan Nagarajan, Jonathan Dworkin, Gregor Blaha, Ya-Ming Hou, Gabriel Demo
Mechanistic Insights Into E. Coli Recovery From Growth Arrest, Ahmed H. Hassan, Yuko Nakano, Howard Gamper, Isao Masuda, Ludmila Vesela, Matyas Pinkas, Sathya Narayanan Nagarajan, Jonathan Dworkin, Gregor Blaha, Ya-Ming Hou, Gabriel Demo
Department of Biochemistry and Molecular Biology Faculty Papers
Bacteria survive hostile conditions by shutting down protein synthesis, but how they restart growth remains poorly understood. Here, we use an E. coli ΔrimM strain, which exhibits a prolonged growth arrest, as a model to investigate how bacteria recover from this state and restore protein synthesis. RimM is a conserved ribosome maturation factor for the 3'-major (head) domain of the 16S rRNA within the bacterial 30S subunit. The loss of RimM causes a longer delay in recovery than other 30S maturation factors, including RbfA. Cryo-EM analysis of ΔrimM ribosomes suggests a delayed recruitment of ribosomal proteins to the 30S head …
Dendrimer Nanogels With Built-In Free Radical Scavenging Enable Efficient Topical Delivery Of A Hydrophilic Antioxidant To Restore Lens Redox Balance For Cataract Treatment, Lin Qi, Huari Kou, Anna Chernatynskaya, Da Huang, Vimalin Jeyalatha Mani, Humeyra Karacal, Nuran Ercal, Hu Yang
Dendrimer Nanogels With Built-In Free Radical Scavenging Enable Efficient Topical Delivery Of A Hydrophilic Antioxidant To Restore Lens Redox Balance For Cataract Treatment, Lin Qi, Huari Kou, Anna Chernatynskaya, Da Huang, Vimalin Jeyalatha Mani, Humeyra Karacal, Nuran Ercal, Hu Yang
Chemistry Faculty Research & Creative Works
Cataract is a leading cause of vision impairment worldwide and are primarily caused by oxidative stress that damages and aggregates lens proteins, leading to lens opacification. However, the eye's anatomical barriers limit the penetration and bioavailability of antioxidant therapies. To address this challenge, a dendrimer-based nanogel with a built-in reactive oxygen species (ROS)-scavenging capability developed by us was employed to deliver the antioxidant N-acetylcysteine (NAC) to the lens. NAC was loaded into a generation-5 PEGylated poly(amidoamine) dendrimer (G5-PEG-TK, termed the GPT) nanogel. The resulting NAC-GPT was characterized for its ROS-scavenging activity, bioavailability, and corneal permeability. The efficacy of NAC-GPT was …
Synthesis Of Copper-Phenanthroline Complexes: A Solvothermal-Compatible Approach For The Exploration Of Metal Complexes, Yunping Zhoujin, Michael Anim Safo, Navindra Keerthisinghe, Mark D. Smith, Sophya Garashchuk, Hans Conrad Zur Loye
Synthesis Of Copper-Phenanthroline Complexes: A Solvothermal-Compatible Approach For The Exploration Of Metal Complexes, Yunping Zhoujin, Michael Anim Safo, Navindra Keerthisinghe, Mark D. Smith, Sophya Garashchuk, Hans Conrad Zur Loye
Faculty Publications
Inorganic–organic hybrid materials have been widely investigated for their applications in catalysis, optics, magnetism, and biomedicine. Copper halide complexes are of particular interest due to their structural diversity and physicochemical properties. Conventional crystal growth approaches, such as slow evaporation and hydro(solvo)thermal synthesis, typically require extended reaction times and often favor thermodynamically stable phases. In this study, we prepared ten copper-phenanthroline halide (X = Cl, Br, and I) complexes using both traditional hydrothermal reactions and microwave-assisted hydrothermal methods and obtained [CuI(C12H8N2)2][I3], [C12H9N2][CuI2]·(H2 …
Effect Of Novel Antimicrobial Compounds On Fungal And Bacterial Pathogens, Megan Wilderman
Effect Of Novel Antimicrobial Compounds On Fungal And Bacterial Pathogens, Megan Wilderman
Honors Program: Senior Projects (Public)
Antimicrobial resistance is a growing concern in medicine1 leading to a need for the development of novel compounds. Two compounds were tested in this study, 2-hydroxyethylhydrazine (HEH) and para-nitrophenyl-isocyanide (NPIC). HEH targets phosphatidylcholine (PC) production2, and NPIC targets mitochondrial function3. Choline (Cho) is a compound that bypasses the inhibition of HEH through the Kennedy pathway.2 Two-fold serial dilutions were conducted in 96-well plates to test the sensitivity of different bacteria to HEH and fungi to HEH and NPIC in different media types. A choline condition was also included in the HEH dilutions to test …
Interview With Orca Award Winner David Hage, Unl Chemistry; Drug-Protein Interactions, Mark Griep, David Hage
Interview With Orca Award Winner David Hage, Unl Chemistry; Drug-Protein Interactions, Mark Griep, David Hage
UNL ORCA Interview Series
Prof. David Hage was awarded the ORCA in 2018. He was born in La Crosse, Wisconsin, and earned a bachelor’s in chemistry at the University of Wisconsin in La Crosse. Next, he earned a doctorate from Iowa State University and did postdoctoral work at the Mayo Clinic in Rochester, Minnesota. In 1989, he joined UNL as an assistant professor of chemistry and quickly rose through the ranks. He has won many awards and, for the past 13 years, has been the James Hewet University Professor of Chemistry. Allow me to share some remarkable facts about Dave before we get into …
Role Of Wadsley Defects And Cation Disorder To Enhance Monb12O33 Diffusion, Cj Sturgill, Manish Kumar, Nima Karimitari, Iva Millisavljevic, Coby S. Collins, Aaron Hegler, Hsin-Yun Joy Chao, Santosh Kiran Balijepalli, Scott T. Misture, Christopher Sutton, Morgan Stefik
Role Of Wadsley Defects And Cation Disorder To Enhance Monb12O33 Diffusion, Cj Sturgill, Manish Kumar, Nima Karimitari, Iva Millisavljevic, Coby S. Collins, Aaron Hegler, Hsin-Yun Joy Chao, Santosh Kiran Balijepalli, Scott T. Misture, Christopher Sutton, Morgan Stefik
Faculty Publications
Wadsley-Roth (WR) niobates have emerged as high-rate anode materials that can combine rapid ionic diffusion with good electronic conductivity. WR compounds have been defect-enhanced by limited annealing, however, such materials often contain multiple types of defects. In particular, both Wadsley defects (variable block size) and transition metal disorder have the potential to modify transport rates, however the corresponding effects are not well understood mechanistically. Here, MoNb12O33 (MNO) was calcined at two different temperatures to compare a defect-rich condition (MNO-800) with a proximal order-rich condition (MNO-900) as assessed through XRD, XANES, EXAFS, and STEM characterizations. Galvanostatically cycled lithium half cells of …
Tlr3 Mediated Type I Interferon Response In Mammalian Cell Defense Against Cryptosporidium Parvum Infection., Anjelica Matias
Tlr3 Mediated Type I Interferon Response In Mammalian Cell Defense Against Cryptosporidium Parvum Infection., Anjelica Matias
Biochemistry and Molecular Biology
Cryptosporidium parvum is a major cause of a diarrheal disease which affects many children in the USA as well as the rest of the world, yet the contribution of its double stranded RNA (dsRNA) viral symbiont, Cryspovirus (CSpV1) to host innate immunity remains unclear. This study investigated whether CSpV1 activates Toll Like Receptor 3 (TLR3) signaling pathways and downstream Interferon type I (IFN I) responses in mammalian intestinal epithelial cells. Confluent Human Ileocecal Colorectal Adenocarcinoma cells (HCT8) were exposed to CSpV1, and the expression levels of Tumor Necrosis Factor Receptor-Associated Factor 3 (TRAF3), Nuclear Factor-𝜅-light chain enhancer of activated B-cells …