Other Biochemistry, Biophysics, and Structural Biology Commons^™

Hiv-Tat Exacerbates The Actions Of Atazanavir, Efavirenz, And Ritonavir On Cardiac Ryanodine Receptor (Ryr2), Imam Abdulrahman Bin Faisal University, Chengju Tian, Sean R. Bidasee, Zachary L. Venn, Evan Schroder, Nick Y. Palermo, Mohammad Alshabeeb, Benson J. Edagwa, Jason J. Payne, Keshoer R. Bidasee

Department of Biochemistry: Faculty Publications

The incidence of sudden cardiac death (SCD) in people living with HIV infection (PLWH), especially those with inadequate viral suppression, is high and the reasons for this remain incompletely characterized. The timely opening and closing of type 2 ryanodine receptor (RyR2) is critical for ensuring rhythmic cardiac contraction–relaxation cycles, and the disruption of these processes can elicit Ca²⁺ waves, ventricular arrhythmias, and SCD. Herein, we show that the HIV protein Tat (HIVTat: 0–52 ng/mL) and therapeutic levels of the antiretroviral drugs atazanavir (ATV: 0–25,344 ng/mL), efavirenz (EFV: 0–11,376 ng/mL), and ritonavir (RTV: 0–25,956 ng/mL) bind to and modulate the …

Insights Into The Biotechnology Potential Of Methanosarcina, Sean Carr, Nicole R. Buan

Department of Biochemistry: Faculty Publications

Methanogens are anaerobic archaea which conserve energy by producing methane. Found in nearly every anaerobic environment on earth, methanogens serve important roles in ecology as key organisms of the global carbon cycle, and in industry as a source of renewable biofuels. Environmentally, methanogenic archaea play an essential role in the reintroducing unavailable carbon to the carbon cycle by anaerobically converting low-energy, terminal metabolic degradation products such as one and two-carbon molecules into methane which then returns to the aerobic portion of the carbon cycle. In industry, methanogens are commonly used as an inexpensive source of renewable biofuels as well as …

A Review Of Radiation-Induced Alterations Of Multi-Omic Profiles, Radiation Injury Biomarkers, And Countermeasures, Sushil K. Shakyawar, Nitish K. Mishra, Neetha N. Vellichirammal, Lynnette Cary, Tomáš Helikar, Robert Powers, Rebecca E. Oberley-Deegan, David B. Berkowitz, Kenneth W. Bayles, Vijay K. Singh, Chittibabu Guda

Department of Biochemistry: Faculty Publications

Increasing utilization of nuclear power enhances the risks associated with industrial accidents, occupational hazards, and the threat of nuclear terrorism. Exposure to ionizing radiation interferes with genomic stability and gene expression resulting in the disruption of normal metabolic processes in cells and organs by inducing complex biological responses. Exposure to high-dose radiation causes acute radiation syndrome, which leads to hematopoietic, gastrointestinal, cerebrovascular, and many other organ-specific injuries. Altered genomic variations, gene expression, metabolite concentrations, and microbiota profiles in blood plasma or tissue samples reflect the whole-body radiation injuries. Hence, multi-omic profiles obtained from high-resolution omics platforms offer a holistic approach …

Reproducibility Of Protein X-Ray Diffuse Scattering And Potential Utility For Modeling Atomic Displacement Parameters, Zhen Su, Medhanjali Dasgupta, Frédéric Poitevin, Irimpan I. Mathews, Henry Van Den Bedem, Michael E. Wall, Chun Hong Yoon, Mark A. Wilson

Department of Biochemistry: Faculty Publications

Protein structure and dynamics can be probed using x-ray crystallography. Whereas the Bragg peaks are only sensitive to the average unit-cell electron density, the signal between the Bragg peaks—diffuse scattering—is sensitive to spatial correlations in electron-density variations. Although diffuse scattering contains valuable information about protein dynamics, the diffuse signal is more difficult to isolate from the background compared to the Bragg signal, and the reproducibility of diffuse signal is not yet well understood. We present a systematic study of the reproducibility of diffuse scattering from isocyanide hydratase in three different protein forms. Both replicate diffuse datasets and datasets obtained from …

Editorial: Function And Formation Of Mitochondrial Metalloproteome, Michał Wasilewski, Vishal M. Gohil, Oleh Khalimonchuk

Department of Biochemistry: Faculty Publications

No abstract provided.

Loss Of Num1-Mediated Cortical Dynein Anchoring Negatively Impacts Respiratory Growth, Antoineen J. White, Clare S. Harper, Erica M. Rosario, Jonathan V. Dietz, Hannah G. Addis, Jennifer L. Fox, Oleh Khalimonchuk, Laura L. Lackner

Department of Biochemistry: Faculty Publications

Num1 is a multifunctional protein that both tethers mitochondria to the plasma membrane and anchors dynein to the cell cortex during nuclear inheritance. Previous work has examined the impact loss of Num1-based mitochondrial tethering has on dynein function in Saccharomyces cerevisiae; here, we elucidate its impact on mitochondrial function. We find that like mitochondria, Num1 is regulated by changes in metabolic state, with the protein levels and cortical distribution of Num1 differing between fermentative and respiratory growth conditions. In cells lacking Num1, we observe a reproducible respiratory growth defect, suggesting a role for Num1 in not only maintaining mitochondrial …

Ncoa4 Regulates Iron Recycling And Responds To Hepcidin Activity And Lipopolysaccharide In Macrophages, Cole A. Guggisberg, Juyoung Kim, Jaekwon Lee, Xiaoli Chen, Moon-Suhn Ryu

Department of Biochemistry: Faculty Publications

Macrophages, via erythrophagocytosis, recycle iron from effete erythrocytes to newly developing red blood cells. Conversion of potentially cytotoxic levels of iron from its heme into nonheme form during iron recycling is safely accomplished via coordinated regulations of cellular iron transport and homeostasis. Herein, we demonstrate the roles and regulation of NCOA4 (nuclear receptor coactivator 4)-mediated ferritinophagy in macrophages after erythrophagocytosis using the mouse macrophage cell line J774 cells. Ferritin in J774 cells increased with the rise of nonheme iron by erythrocyte ingestion and declined when total cellular iron contents subsequently decreased. NCOA4, a selective autophagic cargo receptor for ferritin, was …

Editorial: Mitochondria, Metabolism And Cardiovascular Diseases, Jun-Ichiro Koga, Xinghui Sun, Masuko Ushio-Fukai

Department of Biochemistry: Faculty Publications

No abstract provided.

Metabolite Damage And Damage Control In A Minimal Genome, Drago Haas, Antje M. Thamm, Jiayi Sun, Lili Huang, Lijie Sun, Guillaume A.W. Beaudoin, Kim S. Wise, Claudia Lerma-Ortiz, Steven D. Bruner, Marian Breuer, Zaida Luthey-Schulten, Jiusheng Lin, Mark A. Wilson, Greg Brown, Alexander F. Yakunin, Inna Kurilyak, Jacob Folz, Oliver Fiehn, John I. Glass, Andrew D. Hanson, Christopher S. Henry, Valérie De Crécy-Lagard

Department of Biochemistry: Faculty Publications

Analysis of the genes retained in the minimized Mycoplasma JCVI-Syn3A genome established that systems that repair or preempt metabolite damage are essential to life. Several genes known to have such functions were identified and experimentally validated, including 5-formyltetrahydrofolate cycloligase, coenzyme A (CoA) disulfide reductase, and certain hydrolases. Furthermore, we discovered that an enigmatic YqeK hydrolase domain fused to NadD has a novel proofreading function in NAD synthesis and could double as a MutT-like sanitizing enzyme for the nucleotide pool. Finally, we combined metabolomics and cheminformatics approaches to extend the core metabolic map of JCVI-Syn3A to include promiscuous enzymatic reactions and …

Variation On A Theme: The Structures And Biosynthesis Of Specialized Fatty Acid Natural Products In Plants, Samuel Scott, Edgar B. Cahoon, Lucas Busta

Department of Biochemistry: Faculty Publications

Plants are able to construct lineage-specific natural products from a wide array of their core metabolic pathways. Considerable progress has been made toward documenting and understanding, for example, phenylpropanoid natural products derived from phosphoenolpyruvate via the shikimate pathway, terpenoid compounds built using isopentyl pyrophosphate, and alkaloids generated by the extensive modification of amino acids. By comparison, natural products derived from fatty acids have received little attention, except for unusual fatty acids in seed oils and jasmonate-like oxylipins. However, scattered but numerous reports show that plants are able to generate many structurally diverse compounds from fatty acids, including some with highly …

Dj-1 Is Not A Deglycase And Makes A Modest Contribution To Cellular Defense Against Methylglyoxal Damage In Neurons, Melissa Conti Mazza, Sarah C. Shuck, Jiusheng Lin, Michael Moxley, John Termini, Mark R. Cookson, Mark A. Wilson

Department of Biochemistry: Faculty Publications

Human DJ-1 is a cytoprotective protein whose absence causes Parkinson's disease and is also associated with other diseases. DJ-1 has an established role as a redox-regulated protein that defends against oxidative stress and mitochondrial dysfunction. Multiple studies have suggested that DJ-1 is also a protein/nucleic acid deglycase that plays a key role in the repair of glycation damage caused by methylglyoxal (MG), a reactive α-keto aldehyde formed by central metabolism. Contradictory reports suggest that DJ-1 is a glyoxalase but not a deglycase and does not play a major role in glycation defense. Resolving this issue is important for understanding how …

Altered Collective Mitochondrial Dynamics In The Arabidopsis Msh1 Mutant Compromising Organelle Dna Maintenance, Joanna M. Chustecki, Ross D. Etherington, Daniel J. Gibbs, Iain G. Johnston

Department of Biochemistry: Faculty Publications

Mitochondria form highly dynamic populations in the cells of plants (and almost all eukaryotes). The characteristics and benefits of this collective behaviour, and how it is influenced by nuclear features, remain to be fully elucidated. Here, we use a recently developed quantitative approach to reveal and analyse the physical and collective ‘social’ dynamics of mitochondria in an Arabidopsis msh1 mutant where the organelle DNA maintenance machinery is compromised. We use a newly created line combining the msh1 mutant with mitochondrially targeted green fluorescent protein (GFP), and characterize mitochondrial dynamics with a combination of single-cell time-lapse microscopy, computational tracking, and network …

In Silico Identification Of Potential Inhibitors Of The Sars‑Cov‑2 Nucleocapsid Through Molecular Docking‑Based Drug Repurposing, Rukhsar Afreen, Saleem Iqbal, Ab Rauf Shah, Heena Afreen, Maitreyi College, Mohd. Shkir

Department of Biochemistry: Faculty Publications

SARS-CoV-2 is the virus responsible for the COVID-19 pandemic, and its effects on people worldwide continue to grow. Protein-targeted therapeutics are currently unavailable for this virus. As with other coronaviruses, the nucleocapsid (N) protein is the most conserved RNA-binding structural protein of SARS-CoV-2. The N protein is an appealing target because of its functional role in viral transcription and replication. Therefore, molecular docking method for structure-based drug design was used to investigate the binding energy and binding modes of various anti-N inhibitors in depth. The inhibitors selected were originally developed to target stress granules and other molecules involved in RNA …

Guard-Cell-Targeted Overexpression Of Arabidopsis Hexokinase 1 Can Improve Water Use Efficiency In Field-Grown Tobacco Plants, Liana G. Acevedo-Siaca, Katarzyna Glowacka, Steven M. Driever, Coralie E. Salesse-Smith, Nitsan Lugassi, David Granot, Stephen P. Long, Johannes Kromdijk

Department of Biochemistry: Faculty Publications

Water deficit currently acts as one of the largest limiting factors for agricultural productivity worldwide. Additionally, limitation by water scarcity is projected to continue in the future with the further onset of effects of global climate change. As a result, it is critical to develop or breed for crops that have increased water use efficiency and that are more capable of coping with water scarce conditions. However, increased intrinsic water use efficiency (iWUE) typically brings a trade-off with CO₂ assimilation as all gas exchange is mediated by stomata, through which CO₂ enters the leaf while water vapor exits. …

Evaluation Of Current Methods To Detect Cellular Leucine-Rich Repeat Kinase 2 (Lrrk2) Kinase Activity, Belén Fernández, Vinita G. Chittoor-Vinod, Jillian H. Kluss, Kaela Kelly, Nicole Bryant, An Phu Tran Nguyen, Syed A. Bukhari, Nathan J. Smith, Antonio Jesús Lara Ordóñez, Elena Fdez, Marie-Christine Chartier-Harlin, Thomas J. Montine, Mark A. Wilson, Darren J. Moore, Andrew B. West, Mark R. Cookson, R. Jeremy Nichols, Sabine Hilfiker

Department of Biochemistry: Faculty Publications

Background: Coding variation in the Leucine rich repeat kinase 2 gene linked to Parkinson’s disease (PD) promotes enhanced activity of the encoded LRRK2 kinase, particularly with respect to autophosphorylation at S1292 and/or phosphorylation of the heterologous substrate RAB10.

Objective: To determine the inter-laboratory reliability of measurements of cellular LRRK2 kinase activity in the context of wildtype or mutant LRRK2 expression using published protocols.

Methods: Benchmark western blot assessments of phospho-LRRK2 and phospho-RAB10 were performed in parallel with in situ immunological approaches in HEK293T, mouse embryonic fibroblasts, and lymphoblastoid cell lines. Rat brain tissue, with or without adenovirus-mediated …

Reduction Of Stabilin-2 Contributes To A Protection Against Atherosclerosis, Yukako Kayashima, Connor A. Clanton, Amanda M. Lewis, Xinghui Sun, Sylvia Hiller, Phillip Huynh, Jennifer Wilder, John Hagaman, Feng Li, Nobuyo Maeda-Smithies, Ed Harris

Department of Biochemistry: Faculty Publications

We have previously identified a novel atherosclerosis quantitative trait locus (QTL), Arch atherosclerosis 5 (Aath5), on mouse chromosome 10 by three-way QTL analyses between Apoe^−/− mice on a DBA/2J, 129S6 and C57BL/6J background. The DBA/2J haplotype at the Aath5 locus was associated with smaller plaque size. One of the candidate genes underlying Aath5 was Stabilin-2 (Stab2), which encodes a clearance receptor for hyaluronan (HA) predominantly expressed in liver sinusoidal endothelial cells (LSECs). However, the role of Stab2 in atherosclerosis is unknown. A congenic line of Apoe^−/− mice carrying Aath5 covering the Stab2 …

Reduction Of Stabilin-2 Contributes To A Protection Against Atherosclerosisstabilin, Yukako Kayashima1*,, Conner A. Clanton, Amanda M. Lewis, Xinghui Sun, Sylvia Hiller, Phillip Huynh, Jennifer Wilder, John Hagaman, Feng Li, Nobuyo Maeda-Smithies, Edward N. Harris

Department of Biochemistry: Faculty Publications

We have previously identified a novel atherosclerosis quantitative trait locus (QTL), Arch atherosclerosis 5 (Aath5), on mouse chromosome 10 by three-way QTL analyses between Apoe^−/− mice on a DBA/2J, 129S6 and C57BL/6J background. The DBA/2J haplotype at the Aath5 locus was associated with smaller plaque size. One of the candidate genes underlying Aath5 was Stabilin-2 (Stab2), which encodes a clearance receptor for hyaluronan (HA) predominantly expressed in liver sinusoidal endothelial cells (LSECs). However, the role of Stab2 in atherosclerosis is unknown. A congenic line of Apoe^−/− mice carrying Aath5 covering the Stab2^DBA allele …

Disruption Of Claudin-Made Tight Junction Barriers By Clostridium Perfringens Enterotoxin: Insights From Structural Biology, Chinemerem P. Ogbu, Sourav Roy, Alex J. Vecchio

Department of Biochemistry: Faculty Publications

Claudins are a family of integral membrane proteins that enable epithelial cell/cell interactions by localizing to and driving the formation of tight junctions. Via claudin self-assembly within the membranes of adjoining cells, their extracellular domains interact, forming barriers to the paracellular transport of small molecules and ions. The bacterium Clostridium perfringens causes prevalent gastrointestinal disorders in mammals by employing an enterotoxin (CpE) that targets claudins. CpE binds to claudins at or near tight junctions in the gut and disrupts their barrier function, potentially by disabling their assembly or via cell signaling means—the mechanism(s) remain unclear. CpE ultimately destroys claudin-expressing cells …

A Glass Bead Semi‑Hydroponic System For Intact Maize Root Exudate Analysis And Phenotyping, Martha G. Lopez-Guerrero, Peng Wang, Felicia Phares4, Daniel P. Schachtman, Sophie Alvarez, Karin Van Dijk

Department of Biochemistry: Faculty Publications

Background: Although there have been numerous studies describing plant growth systems for root exudate collection, a common limitation is that these systems require disruption of the plant root system to facilitate exudate collection. Here, we present a newly designed semi-hydroponic system that uses glass beads as solid support to simulate soil impedance, which combined with drip irrigation, facilitates growth of healthy maize plants, collection and analysis of root exudates, and phenotyping of the roots with minimal growth disturbance or root damage.

Results: This system was used to collect root exudates from seven maize genotypes using water or 1 mM CaCl …

Sesamum Indicum Diet Prevents Hyperlipidemia In Experimental Rats, Muinat M. Adeyanju, Idris A. Saheed, Oluwaseun I. Oyelekan, Taiwo A. Dele-Osibanjo, Ayodeji A. Adelegan, Adekunle J. Raimi, Samuel O. Olalekan, Olugbenga S. Alabi, Khadijat M. Alli

Department of Biochemistry: Faculty Publications

Cardiovascular diseases and metabolic complications caused by hyperlipidemia are the leading cause of death globally. In this study, the hypolipidemic potency of Sesamum indicum (SI) seeds was investigated. Of the thirty-five (35) male rats used in the study, five (5) were randomly selected for baseline measurements and thirty (30) were fed high fat diet (HFD) for four (4) weeks before random assignment into three (3) groups. The experimental group was treated with 50% SI seed, the positive control group was given a hypolipidemic drug, atorvastatin (5 mg/kg/day) while the untreated group served as the negative control. With SI administration, the …

Role Of Specialized Pro-Resolving Mediators In Reducing Neuroinflammation In Neurodegenerative Disorders, Jana Ponce, Arzu Ulu, Corrine Hanson, Erin Cameron-Smith, Jenna Wuebker, John Bertoni, Alfred Fisher, Ka-Chun Siu, Vivien Marmelat, Jiri Adamec, Danish Bhatti

Department of Biochemistry: Faculty Publications

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are neurodegenerative disorders that affect millions of individuals worldwide. As incidence of these conditions increases with age, there will undoubtedly be an increased prevalence of cases in the near future. Neuroinflammation is a hallmark in the development and progression of neurodegenerative diseases and prevention or resolution of chronic neuroinflammation may represent a novel approach to treatment. The present review highlights the potential of the anti-inflammatory and pro-resolving effects of polyunsaturated fatty acid (PUFA)- derived mediators (Specialized Pro-resolving Mediators—SPM) in neurodegenerative disorders. PUFA-derived SPM are biosynthesized in response to chemicals produced from acute inflammatory …

Two Heads Are Better Than One: Current Landscape Of Integrating Qsp And Machine Learning, Tongli Zhang, Ioannis P. Androulakis, Peter Bonate, Limei Cheng, Tomáš Helikar, Jaimit Parikh, Christopher Rackauckas, Kalyanasundaram Subramanian, Carolyn R. Cho

Department of Biochemistry: Faculty Publications

Quantitative systems pharmacology (QSP) modeling is applied to address essential questions in drug development, such as the mechanism of action of a therapeutic agent and the progression of disease. Meanwhile, machine learning (ML) approaches also contribute to answering these questions via the analysis of multi-layer ‘omics’ data such as gene expression, proteomics, metabolomics, and high-throughput imaging. Furthermore, ML approaches can also be applied to aspects of QSP modeling. Both approaches are powerful tools and there is considerable interest in integrating QSP modeling and ML. So far, a few successful implementations have been carried out from which we have learned about …

Functional Foods: Promising Therapeutics For Nigerian Children With Sickle Cell Diseases, Oladeji John Alabi, Fikayo Noah Adegboyega, Dolapo Samuel Olawoyin, Oluwakemi Arinola Babatunde

Department of Biochemistry: Faculty Publications

Sickle cell disease (SCD), also known as sickle cell anemia (SCA) is one of the structural hemoglobinopathies that occurs due to a single nucleotide mutation from GAG to GTG, which changes the amino acid of a β-globin chain of hemoglobin (Hb) from glutamate to valine. This singular mutation results to disorderliness in red blood cells (RBCs) with advent of changes in RBC morphology and other pathological conditions. In the 1980s, intermittent red blood cell transfusions, opioids, and penicillin prophylaxis were the only available therapy for SCA and were commonly reserved for acute, life threatening complications. So far, the US Food …

Development, Structure, And Mechanism Of Synthetic Antibodies That Target Claudin And Clostridium Perfringens Enterotoxin Complexes, Benjamin J. Orlando, Pawel K. Dominik, Sourav Roy, Chinemerem P. Ogbu, Satchal K. Erramilli, Anthony A. Kossiakoff, Alex J. Vecchio

Department of Biochemistry: Faculty Publications

Strains of Clostridium perfringens produce a two-domain enterotoxin (CpE) that afflicts humans and domesticated animals, causing prevalent gastrointestinal illnesses. CpE’s C-terminal domain (cCpE) binds cell surface receptors, followed by a restructuring of its N-terminal domain to form a membranepenetrating β-barrel pore, which is toxic to epithelial cells of the gut. The claudin family of membrane proteins are known receptors for CpE and also control the architecture and function of cell-cell contacts (tight junctions) that create barriers to intercellular molecular transport. CpE binding and assembly disables claudin barrier function and induces cytotoxicity via β-pore formation, disrupting gut homeostasis; however, a structural …

Metabolic Synergy Between Human Symbionts Bacteroides And Methanobrevibacter, Jennie L. Catlett, Sean Carr, Mikaela Cashman, Megan D. Smith, Mary Walter, Zahmeeth Sakkaff, Christine A. Kelley, Massimiliano Pierobon, Myra B. Cohen, Nicole R. Buan

Department of Biochemistry: Faculty Publications

ABSTRACT Trophic interactions between microbes are postulated to determine whether a host microbiome is healthy or causes predisposition to disease. Two abundant taxa, the Gram-negative heterotrophic bacterium Bacteroides thetaiotaomicron and the methanogenic archaeon Methanobrevibacter smithii, are proposed to have a synergistic metabolic relationship. Both organisms play vital roles in human gut health; B. thetaiotaomicron assists the host by fermenting dietary polysaccharides, whereas M. smithii consumes end-stage fermentation products and is hypothesized to relieve feedback inhibition of upstream microbes such as B. thetaiotaomicron. To study their metabolic interactions, we defined and optimized a coculture system and used software testing …

The Follicular Lymphoma Epigenome Regulates Its Microenvironment, Rada Amin, Mounia S. Braza

Department of Biochemistry: Faculty Publications

Follicular lymphoma (FL) is a B-cell non-Hodgkin lymphoma of germinal center (GC) origin with a distinctive tumor microenvironment (TME) and a unique spectrum of mutations. Despite the important therapeutic advances, FL is still incurable. During B-cell development, the GC reaction is a complex multistep process in which epigenetic regulators dynamically induce or suppress transcriptional programs. In FL, epigenetic gene mutations perturb the regulation of these programs, changing GC B-cell function and skewing differentiation towards tumor cells and altering the microenvironment interactions. FL pathogenesis and malignant transformation are promoted by epigenetic reprogramming of GC B cells that alters the immunological synapse …

Feedlot Diets Containing Different Starch Levels And Additives Change The Cecal Proteome Involved In Cattle’S Energy Metabolism And Inflammatory Response, Leone Campos Rocha, Andrey Sávio De Almeida Assunção, Renata Aparecida Martins, Victor Valério De Carvalho, Alexandre Perdigão2, Marília Afonso Rabelo Buzalaf, Jiri Adamec, Camila Pereira Braga, Danilo Domingues Millen, José Cavalcante Souza Vieira, Pedro De Magalhães Padilha

Department of Biochemistry: Faculty Publications

Diets for feedlot cattle must be a higher energy density, entailing high fermentable carbohydrate content. Feed additives are needed to reduce possible metabolic disorders. This study aimed to analyze the post-rumen effects of different levels of starch (25%, 35%, and 45%) and additives (monensin or a blend of essential oils and exogenous α-amylase) in diets for Nellore feedlot cattle. The cecum tissue proteome was analyzed via two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and then differentially expressed protein spots were identified with liquid chromatography–tandem mass spectrometry (LC–MS/MS). The use of blends of essential oils associated with α-amylase as a feed additive promoted …

Recognition Of Extracellular Dna By Type Iv Pili Promotes Biofilm Formation By Clostridioides Difficile, Leslie A. Ronish, Ben Sidner, Yafan Yu, Kurt H. Piepenbrink

Department of Biochemistry: Faculty Publications

Clostridioides difficile is a Gram-positive bacillus, which is a frequent cause of gastrointestinal infections triggered by the depletion of the gut microbiome. Because of the frequent recurrence of these infections after antibiotic treatment, mechanisms of C. difficile persistence and recurrence, including biofilm formation, are of increasing interest. Previously, our group and others found that type IV pili, filamentous helical appendages polymerized from protein subunits, promoted microcolony and biofilm formation in C. difficile. In Gram-negative bacteria, the ability of type IV pili to mediate bacterial self-association has been explained through interactions between the pili of adjacent cells, but type …

Arginine Catabolism And Polyamine Biosynthesis Pathway Disparities Within Francisella Tularensis Subpopulations, Yinshi Yue, Bhanwar Lal Puniya, Tomáš Helikar, Benjamin Girardo, Steven H. Hinrichs, Marilyn A. Larson

Department of Biochemistry: Faculty Publications

Francisella tularensis is a highly infectious zoonotic pathogen with as few as 10 organisms causing tularemia, a disease that is fatal if untreated. Although F. tularensis subspecies tularensis (type A) and subspecies holarctica (type B) share over 99.5% average nucleotide identity, notable differences exist in genomic organization and pathogenicity. The type A clade has been further divided into subtypes A.I and A.II, with A.I strains being recognized as some of the most virulent bacterial pathogens known. In this study, we report on major disparities that exist between the F. tularensis subpopulations in arginine catabolism and subsequent polyamine biosynthesis. The genes …

Addressing Barriers In Comprehensiveness, Accessibility, Reusability, Interoperability And Reproducibility Of Computational Models In Systems Biology, Anna Niarakis, Dagmar Waltemath, James Glazier, Falk Schreiber, Sarah M. Keating, David Nickerson, Claudine Chaouiya, Anne Siegel, Vincent Noël, Henning Hermjakob, Tomáš Helikar, Sylvain Soliman, Laurence Calzone

Department of Biochemistry: Faculty Publications

Computational models are often employed in systems biology to study the dynamic behaviours of complex systems. With the rise in the number of computational models, finding ways to improve the reusability of these models and their ability to reproduce virtual experiments becomes critical. Correct and effective model annotation in community-supported and standardised formats is necessary for this improvement. Here,we present recent efforts toward a common framework for annotated, accessible, reproducible and interoperable computational models in biology, and discuss key challenges of the field.

Scientists from different systems biology fields have long been developing community-driven guidelines and best practices for annotation, …