Biochemistry Commons^™

Kegg_Pull: A Software Package For The Restful Access And Pulling From The Kyoto Encyclopedia Of Gene And Genomes, Erik D. Huckvale, Hunter N. B. Moseley

Markey Cancer Center Faculty Publications

Background: The Kyoto Encyclopedia of Genes and Genomes (KEGG) provides organized genomic, biomolecular, and metabolic information and knowledge that is reasonably current and highly useful for a wide range of analyses and modeling. KEGG follows the principles of data stewardship to be findable, accessible, interoperable, and reusable (FAIR) by providing RESTful access to their database entries via their web-accessible KEGG API. However, the overall FAIRness of KEGG is often limited by the library and software package support available in a given programming language. While R library support for KEGG is fairly strong, Python library support has been lacking. Moreover, there …

Attenuation Of Human Dmc1 Recombination Activities By Substitution Of A Conserved Residue, Melody Hayman

All Theses

Unrepaired DNA double strand breaks (DSB) are detrimental to the viability of the cell. The repair of DSBs can occur by a process called homologous recombination (HR). HR is used whenever the cell has a homologous template in the way of a homologous chromosome available. The process of HR during mitosis is different from meiotic HR. To initiate meiotic recombination, DSBs are formed and processed to allow proper chromosome segregation and ultimately genetic variation. Meiotic HR is mediated by the meiosis specific recombinase, DMC1. The DMC1 recombinase binds to the 3’ end of a newly resected DSB forming a nucleoprotein …

Editorial: Structure And Function Of Chloroplasts, Volume Iii, Hongbo Gao, Alistair J. Mccormick, Rebecca Roston, Yan Lu

Department of Biochemistry: Faculty Publications

Chloroplasts are endosymbiotic organelles derived from cyanobacteria. They have a double envelope membrane, including the outer envelope and the inner envelope. A complex membrane system, thylakoids, exists inside the chloroplast. It is the site of the light-dependent reactions of photosynthesis. The stroma is the main site of the carbon fixation reactions. Although photosynthesis is a very complicated process with many proteins involved, there are many other important processes that occur in chloroplasts, including the regulation of photosynthesis, the biogenesis and maintenance of the structures, carbohydrate, lipid, tetrapyrrole, amino acid, and isoprenoid metabolism, production of some phytohormones, production of specialized metabolites, …

Cholesterol In Class C Gpcrs: Role, Relevance, And Localization, Ugochi H. Isu, Shadi A. Badiee, Ehsaneh Khodadadi, Mahmoud Moradi

Chemistry & Biochemistry Faculty Publications and Presentations

G-protein coupled receptors (GPCRs), one of the largest superfamilies of cell-surface receptors, are heptahelical integral membrane proteins that play critical roles in virtually every organ system. G-protein-coupled receptors operate in membranes rich in cholesterol, with an imbalance in cholesterol level within the vicinity of GPCR transmembrane domains affecting the structure and/or function of many GPCRs, a phenomenon that has been linked to several diseases. These effects of cholesterol could result in indirect changes by altering the mechanical properties of the lipid environment or direct changes by binding to specific sites on the protein. There are a number of studies and …

Preparation And Characterization Of Salvia Triloba Extract And Evaluation Of Its Cytotoxic Effect On Bone Cancer Cell Line, Basma Hossam Abdelmonem

Theses and Dissertations

Background: Osteosarcoma is a tumor of mesenchymal origin characterized by uncontrolled production of immature osteoid tissue. It is more common in children and adults over the age of 65. Many studies reported the cytotoxic effect of many plant extracts, including Salvia triloba, on different cancer cell lines when used alone or in combination with other chemotherapeutic agents.

Methods: In our study, the methanolic extract obtained from the air-dried leaves of Salvia triloba leaves from Palestine was screened for its total phenolic and flavonoid contents. The major components of phenolics and flavonoids were detected using LC-QToF-MS technique. The two phenolics …

Probing Amyloid-Beta Protein Structure And Dynamics With A Selective Antibody, Shikha Grover

Dissertations

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. The AD brain is characterized by significant neuronal loss and accumulation of insoluble fibrillar amyloid-β protein (Aβ) plaques and tau protein neurofibrillary tangles in the brain. However, over the last decade, many studies have shown that the neurodegenerative effect of Aβ may in fact be caused by various soluble oligomeric forms as opposed to the insoluble fibrils. Furthermore, the data suggest that a pre-fibrillar aggregated form, termed protofibrils, mediates direct neurotoxicity, and triggers a robust neuroinflammatory response.

Antibodies targeting the various conformation of Aβ are important therapeutic agents to prevent the progression …

Endogenous L- To D-Amino Acid Residue Isomerization Modulates Selectivity Between Distinct Neuropeptide Receptor Family Members, Baba M. Yussif, Cole V. Blasing, James W. Checco

Department of Biochemistry: Faculty Publications

The L- to D-amino acid residue isomerization of neuropeptides is an understudied post-translational modification found in animals across several phyla. Despite its physiological importance, little information is available regarding the impact of endogenous peptide isomerization on receptor recognition and activation. As a result, the full roles peptide isomerization play in biology are not well understood. Here, we identify that the Aplysia allatotropin-related peptide (ATRP) signaling system utilizes L- to D-residue isomerization of one amino acid residue in the neuropeptide ligand to modulate selectivity between two distinct G protein-coupled receptors (GPCRs). We first identified a novel receptor for ATRP that is …

Gasdermin D Deficiency In Vascular Smooth Muscle Cells Ameliorates Abdominal Aortic Aneurysm Through Reducing Putrescine Synthesis, Jianing Gao, Yanghui Chen, Huiqing Wang, Xin Li, Ke Li, Yangkai Xu, Xianwei Xie, Yansong Guo, Nana Yang, Xinhua Zhang, Dong Ma, Hong S. Lu, Ying H. Shen, Yong Liu, Jifeng Zhang, Y. Eugene Chen, Alan Daugherty, Dao Wen Wang, Lemin Zheng

Saha Cardiovascular Research Center Faculty Publications

Abdominal aortic aneurysm (AAA) is a common vascular disease associated with significant phenotypic alterations in vascular smooth muscle cells (VSMCs). Gasdermin D (GSDMD) is a pore-forming effector of pyroptosis. In this study, the role of VSMC-specific GSDMD in the phenotypic alteration of VSMCs and AAA formation is determined. Single-cell transcriptome analyses reveal Gsdmd upregulation in aortic VSMCs in angiotensin (Ang) II-induced AAA. VSMC-specific Gsdmd deletion ameliorates Ang II-induced AAA in apolipoprotein E (ApoE)−/− mice. Using untargeted metabolomic analysis, it is found that putrescine is significantly reduced in the plasma and aortic tissues of VSMC-specific GSDMD deficient mice. High putrescine levels …

Leveraging Bio-Inspired Molecules For Cancer Theranostics, Douglas S. Macpherson

Dissertations, Theses, and Capstone Projects

A variety of molecules can be radiolabeled and delivered to a cancer site for the purposes of diagnostics and therapy. Among the most promising of tumor targeting molecules are peptides and antibodies. These bio-inspired molecules can be designed and synthesized to target and respond to cancer cells based on the properties of those cells. Matrix metalloproteinase (MMP) enzymes are over-expressed by some metastatic cancers, in which they are responsible for the degradation and remodeling of the extracellular matrix. In recent years, MMPs have emerged as promising targets for enzyme-responsive diagnostic probes because oligopeptides can be designed to be selectively hydrolyzed …

Bilirubin Nanoparticle Treatment In Obese Mice Inhibits Hepatic Ceramide Production And Remodels Liver Fat Content, Zachary A. Kipp, Genesee J. Martinez, Evelyn A. Bates, Agil B. Maharramov, Robert M. Flight, Hunter N. B. Moseley, Andrew J. Morris, David E. Stec, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Studies have indicated that increasing plasma bilirubin levels might be useful for preventing and treating hepatic lipid accumulation that occurs with metabolic diseases such as obesity and diabetes. We have previously demonstrated that mice with hyperbilirubinemia had significantly less lipid accumulation in a diet-induced non-alcoholic fatty liver disease (NAFLD) model. However, bilirubin’s effects on individual lipid species are currently unknown. Therefore, we used liquid chromatography-mass spectroscopy (LC-MS) to determine the hepatic lipid composition of obese mice with NAFLD treated with bilirubin nanoparticles or vehicle control. We placed the mice on a high-fat diet (HFD) for 24 weeks and then treated …

Clic And Membrane Wound Repair Pathways Enable Pandemic Norovirus Entry And Infection, B. Vijayalakshmi Ayyar, Khalil Ettayebi, Wilhelm Salmen, Umesh C. Karandikar, Frederick H. Neill, Victoria R. Tenge, Sue E. Crawford, Erhard Bieberich, B. V. Venkataram Prasad, Robert L. Atmar, Mary K. Estes

Markey Cancer Center Faculty Publications

Globally, most cases of gastroenteritis are caused by pandemic GII.4 human norovirus (HuNoV) strains with no approved therapies or vaccines available. The cellular pathways that these strains exploit for cell entry and internalization are unknown. Here, using nontransformed human jejunal enteroids (HIEs) that recapitulate the physiology of the gastrointestinal tract, we show that infectious GII.4 virions and virus-like particles are endocytosed using a unique combination of endosomal acidification-dependent clathrin-independent carriers (CLIC), acid sphingomyelinase (ASM)-mediated lysosomal exocytosis, and membrane wound repair pathways. We found that besides the known interaction of the viral capsid Protruding (P) domain with host glycans, the Shell …

Critical Role Of The Sulfiredoxin-Peroxiredoxin Iv Axis In Urethane-Induced Non-Small Cell Lung Cancer, Yanning Hao, Hong Jiang, Pratik Thapa, Na Ding, Aziza Alshahrani, Junichi Fujii, Michel B. Toledano, Qiou Wei

Markey Cancer Center Faculty Publications

Non-small cell lung cancer (NSCLC), the most common type of lung cancer, etiologically associates with tobacco smoking which mechanistically contributes to oxidative stress to facilitate the occurrence of mutations, oncogenic transformation and aberrantly activated signaling pathways. Our previous reports suggested an essential role of Sulfiredoxin (Srx) in promoting the development of lung cancer in humans, and was causally related to Peroxiredoxin IV (Prx4), the major downstream substrate and mediator of Srx-enhanced signaling. To further explore the role of the Srx-Prx4 axis in de novo lung tumorigenesis, we established Prx4−/− and Srx−/−/Prx4−/− mice in pure FVB/N background. Together with wild-type litter …

Engineered Plga Nanofibers For Drug Delivery, Andrew Mancuso

Dissertations, Theses, and Capstone Projects

Poly-lactic-co-glycolic acid (PLGA) polymers are rapidly gaining momentum as a platform for next-generation drug delivery systems due to their ease and low cost of synthesis, favorable biocompatibility and biodegradability, and lack of toxicity. In particular, the application of drug-loaded PLGA nanofibers directly to a target tissue may represent a promising alternative to traditional routes of drug administration (e.g., oral, injectable) as they offer the potential to greatly improve bioavailability, increase efficacy, and reduce off-target toxicity. Furthermore, the use of such a system may potentially allow for greater flexibility in clinical drug development, by enabling the use of compounds which have …

Supplementation Of Sulfide Or Acetate And 2-Mercaptoethane Sulfonate Restores Growth Of The Methanosarcina Acetivorans Δhdrabc Deletion Mutant During Methylotrophic Methanogenesis, Alicia M. Salvi, Niaz Bahar Chowdhury, Rajib Saha, Nicole R. Buan

Department of Biochemistry: Faculty Publications

Methanogenic archaea are important organisms in the global carbon cycle that grow by producing methane gas. Methanosarcina acetivorans is a methanogenic archaeum that can grow using methylated compounds, carbon monoxide, or acetate and produces renewable methane as a byproduct. However, there is limited knowledge of how combinations of substrates may affect metabolic fluxes in methanogens. Previous studies have shown that heterodisulfide reductase, the terminal oxidase in the electron transport system, is an essential enzyme in all methanogens. Deletion of genes encoding the nonessential methylotrophic heterodisulfide reductase enzyme (HdrABC) results in slower growth rate but increased metabolic efficiency. We hypothesized that …

Development Opportunities And Technical Challenges Of Industrialization For Hydrogen Production From Bio-Ethanol Reforming, Xue Han, Hong He, Guojun Yue, Hailong Lin, Jinsong Liu, Bin Yu

Bulletin of Chinese Academy of Sciences (Chinese Version)

Bio-ethanol reforming for hydrogen production, using renewable raw materials and adopting mature and efficient chemical processes, is an important source of green hydrogen supply to achieve the goals of carbon peaking and carbon neutrality. Bio-ethanol is a widely used substitute for fossil fuels. With the continuous progress of cellulosic ethanol technology in recent years, bio-ethanol will gradually break through the constraints of starch-based raw material supply. Based on the industrialization achievements of hydrogen production and bio-ethanol, bio-ethanol reforming can realize a rapid linkage with the existing hydrogen energy industry. However, the existence of a carbon-carbon signal bond in ethanol poses …

Genome‑Wide Investigation Of Snrk2 Gene Family In Two Jute Species: Corchorus Olitorius And Corchorus Capsularis, Borhan Ahmed, Fakhrul Hasan, Anika Tabassum, Rasel Ahmed, Rajnee Hassan, Ruhul Amin, Mobashwer Alam

Department of Biochemistry: Faculty Publications

Background Sucrose non-fermenting-1 (SNF1)-related protein kinase 2 (SnRK2), a plant-specific serine/threonine kinase family, is associated with metabolic responses, including abscisic acid signaling under biotic and abiotic stresses. So far, no information on a genome-wide investigation and stress-mediated expression profiling of jute SnRK2 is available. Recent whole-genome sequencing of two Corchorus species prompted to identify and characterize this SnRK2 gene family.

Result We identified seven SnRK2 genes of each of Corchorus olitorius (Co) and C. capsularis (Cc) genomes, with similar physico-molecular properties and sub-group patterns of other models and related crops. In both species, the SnRK2 …

Methylene Blue Inhibits Cromakalim-Activated K+ Currents In Follicle-Enclosed Oocytes, Dmytro Isaev, Keun-Hang Susan Yang, Georg Petroianu, Dietrich Ernst Lorke, Murat Oz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The effects of methylene blue (MB) on cromakalim-induced K⁺ currents were investigated in follicle-enclosed Xenopus oocytes. In concentrations ranging from 3–300 μM, MB inhibited K⁺ currents (IC₅₀: 22.4 μM) activated by cromakalim, which activates K_ATP channels. MB inhibited cromakalim-activated K⁺ currents in a noncompetitive and voltage-independent manner. The respective EC₅₀ and slope values for cromakalim-activation of K⁺ currents were 194 ± 21 µM and 0.91 for controls, and 206 ± 24 µM and 0.87 in the presence of 30 μM MB. The inhibition of cromakalim-induced K⁺ currents by MB was not …

Bitumen Aging—Laboratory Simulation Methods Used In Practice And Selected Directions Of Research On New Methods, Paweł Czajkowski, Andrzej Przyjazny, Grzegorz Boczkaj

Natural Sciences Publications

Changes in the properties of bitumen binders that occur as a result of aging have a huge impact on the durability of products produced from them. In particular, asphalt pavements, which constitute the most common use of petroleum bitumen, are susceptible to damage resulting from the increasing stiffness of the bitumen during its life cycle. Increased stiffness of asphalt pavements reduces the pavement resistance to low-temperature cracks and fatigue cracks, ultimately leading to the loss of their functional properties and the need for road repair. The rate of changes in bitumen properties is influenced by many factors, the most important …

Comparison Of Serum Albu-Min Levels In The Breast Milk Of Breastfeeding Infants Aged 1-3 Months And 4-6 Months, Ninik Mudjihartini

Indonesian Journal of Medical Chemistry and Bioinformatics

Abstract: Background: Serum albumin is the most abundant plasma protein in the blood, contributing to maintaining colloid osmotic pressure and binding substances that are poorly soluble in plasma so that they can be distributed throughout the body. Serum albumin levels in breast milk can vary, influenced by various factors such as the lactation phase (age of the baby), number of parities, age and body mass index (BMI) of the mother. This study aims to determine the comparison of serum albumin levels in breast milk of mothers who breastfeed infants aged 1-3 months and 4-6 months and to find the relationship …

Functional Impact Of A Cancer-Related Variant In Human Δ1‑Pyrroline-5-Carboxylate Reductase 1, Oseeyi I. Daudu, Kaylen R. Meeks, Lu Zhang, Javier Seravalli, John J. Tanner, Donald F. Becker

Department of Biochemistry: Faculty Publications

Pyrroline-5-carboxylate reductase (PYCR) is a proline biosynthetic enzyme that catalyzes the NAD(P)H-dependent reduction of Δ¹-pyrroline-5-carboxylate (P5C) to proline. Humans have three PYCR isoforms, with PYCR1 often upregulated in different types of cancers. Here, we studied the biochemical and structural properties of the Thr171Met variant of PYCR1, which is found in patients with malignant melanoma and lung adenocarcinoma. Although PYCR1 is strongly associated with cancer progression, characterization of a PYCR1 variant in cancer patients has not yet been reported. Thr171 is conserved in all three PYCR isozymes and is located near the P5C substrate binding site. We found that …