Biochemistry, Biophysics, and Structural Biology Commons^™

Glutathione And Glutaredoxin In Redox Regulation And Cell Signaling Of The Lens, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

The ocular lens has a very high content of the antioxidant glutathione (GSH) and the enzymes that can recycle its oxidized form, glutathione disulfide (GSSG), for further use. It can be synthesized in the lens and, in part, transported from the neighboring anterior aqueous humor and posterior vitreous body. GSH is known to protect the thiols of the structural lens crystallin proteins from oxidation by reactive oxygen species (ROS) so the lens can maintain its transparency for proper visual function. Age-related lens opacity or senile cataract is the major visual impairment in the general population, and its cause is closely …

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.

Recent Emergence Of Bovine Coronavirus Variants With Mutations In The Hemagglutinin-Esterase Receptor Binding Domain In U.S. Cattle, Aspen M. Workman, Tara G. Mcdaneld, Gregory P. Harhay, Subha Das, John Dustin Loy, Benjamin M. Hause

School of Veterinary and Biomedical Sciences: Faculty Publications

Bovine coronavirus (BCoV) has spilled over to many species, including humans, where the host range variant coronavirus OC43 is endemic. The balance of the opposing activities of the surface spike (S) and hemagglutinin-esterase (HE) glycoproteins controls BCoV avidity, which is critical for interspecies transmission and host adaptation. Here, 78 genomes were sequenced directly from clinical samples collected between 2013 and 2022 from cattle in 12 states, primarily in the Midwestern U.S. Relatively little genetic diversity was observed, with genomes having >98% nucleotide identity. Eleven isolates collected between 2020 and 2022 from four states (Nebraska, Colorado, California, and Wisconsin) contained a …

Recent Emergence Of Bovine Coronavirus Variants With Mutations In The Hemagglutinin-Esterase Receptor Binding Domain In U.S. Cattle, Aspen M. Workman, Tara G. Mcdaneld, Gregory P. Harhay, Subha Das, John Dustin Loy, Benjamin M. Hause

School of Veterinary and Biomedical Sciences: Faculty Publications

Bovine coronavirus (BCoV) has spilled over to many species, including humans, where the host range variant coronavirus OC43 is endemic. The balance of the opposing activities of the surface spike (S) and hemagglutinin-esterase (HE) glycoproteins controls BCoV avidity, which is critical for interspecies transmission and host adaptation. Here, 78 genomes were sequenced directly from clinical samples collected between 2013 and 2022 from cattle in 12 states, primarily in the Midwestern U.S. Relatively little genetic diversity was observed, with genomes having >98% nucleotide identity. Eleven isolates collected between 2020 and 2022 from four states (Nebraska, Colorado, California, and Wisconsin) contained a …

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.

Co-Twin Relationship Quality As A Moderator Of Genetic And Environmental Factors On Urinary Cortisol Levels Among Adult Twins, Joseph A. Schwartz, Scott Jessick, Jessica L. Calvi, Douglas A. Granger

Athletic Performance Research

Previous research has indicated that genetic and environmental factors shape physiological activity. Cortisol levels, in particular, have received significant attention, with studies indicating substantive heritability estimates across various sampling techniques. A related line of research has indicated that genetic and environmental factors that explain variability in cortisol levels may vary across context and experiences by way of gene-environment interactions (G×Es). Despite these findings, a limited number of studies have examined the extent to which interpersonal relationships may operate as a moderator. The current study focused on co-twin relationship quality as a source of moderation, as twins are more likely to …

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 …

Methanogen Metabolic Flexibility, Sean R. Carr

School of Biological Sciences: Dissertations, Theses, and Student Research

Methanogens are obligately anaerobic archaea which produce methane as a byproduct of their respiration. They are found across a wide diversity of environments and play an important role in cycling carbon in anaerobic spaces and the removal of harmful fermentation byproducts which would otherwise inhibit other organisms. Methanogens subsist on low-energy substrates which requires them to utilize a highly efficient central metabolism which greatly favors respiratory byproducts over biomass. This metabolic strategy creates high substrate:product conversion ratios which is industrially relevant for the production of biomethane, but may also allow for the production of value-added commodities. Particularly of interest are …

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. …

Molecular-Level Control Over Ionic Conduction And Ionic Current Direction By Designing Macrocycle-Based Ionomers, Shyambo Chatterjee, Ehsan Zamani, Seefat Farzin, Iman Evazzade, Oghenetega Allen Obewhere, Tyler James Johnson, Vitaly Alexandrov, Shudipto Konika Dishari

Department of Chemical and Biomolecular Engineering: Faculty Publications

Poor ionic conductivity of the catalyst-binding, submicrometer- thick ionomer layers in energy conversion and storage devices is a huge challenge. However, ionomers are rarely designed keeping in mind the specific issues associated with nanoconfinement. Here, we designed nature-inspired ionomers (calix-2) having hollow, macrocyclic, calix[4]arene-based repeat units with precise, sub-nanometer diameter. In ≤100 nm-thick films, the in-plane proton conductivity of calix-2 was up to 8 times higher than the current benchmark ionomer Nafion at 85% relative humidity (RH), while it was 1−2 orders of magnitude higher than Nafion at 20−25% RH. Confocal laser scanning microscopy and other synthetic techniques allowed us …

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 …

Investigation Of The Role Of Overexpression Of Psbs Under Stress Inducible And Constitutive Promoters To Improve Water Use Efficiency., Annie Nelson

Honors Program: Senior Projects (Public)

As climate change continues to impact environmental growth conditions, it has become increasingly more important to identify potential mechanisms of crop development to resist these changes. Previous studies have identified the role of PsbS in the non-photochemical quenching (NPQ) mechanism in the plant by identifying its direct effect on the rate in which excitation energy absorbed by photosystem II is dissipated as heat. It was identified also that PsbS via NPQ oxidizes chloroplastic quinone A (QA) which is a signal for stomatal opening in response to light. By identifying this relationship between PsbS and the signal for stomatal opening in …

Als-Associated Kif5a Mutations Abolish Autoinhibition Resulting In A Toxic Gain Of Function, Desiree M. Barron, Adam R. Fenton, Sara Saez-Atienzar, Anthony Giampetruzzi, Aparna Sreeram, Shankaracharya, Pamela J. Keagle, Victoria R. Doocy, Nathan J. Smith, Eric W. Danielson, Megan Andresano, Mary C. Mccormack, Jaqueline Garcia, Valérie Bercier, Ludo Van Den Bosch, Jonathan R. Brent, Claudia Fallini, Brian J. Traynor, Erica L.F. Holzbaur, John E. Landers

Biochemistry -- Faculty Publications

Understandingthepathogenicmechanismsof diseasemutations is critical toadvancingtreatments.ALS-associated mutations in the gene encoding the microtubulemotor KIF5A result in skipping of exon 27 (KIF5ADExon27) and the encoding of a protein with a novel 39 amino acid residue C-terminal sequence. Here, we report that expression of ALS-linked mutant KIF5A results in dysregulated motor activity, cellular mislocalization, altered axonal transport, and decreased neuronal survival. Single-molecule analysis revealed that the altered C terminus of mutant KIF5A results in a constitutively active state. Furthermore,mutant KIF5A possesses altered protein and RNA interactions and its expression results in altered gene expression/splicing. Taken together, our data support the hypothesis that causative …

Assessment Of Diversity Of Antimicrobial Resistance Phenotypes And Genotypes Of Mannheimia Haemolytica Isolates From Bovine Nasopharyngeal Swabs, Hannah F. Carter, Robert W. Wills, Matthew A. Scott, Alexis C. Thompson, Randall S. Singer, John Dustin Loy, Brandi B. Karisch, William B. Epperson, Amelia R. Woolums

School of Veterinary and Biomedical Sciences: Faculty Publications

The threat of bovine respiratory disease (BRD) for cattle operations is exacerbated by increasing prevalence of antimicrobial resistance (AMR) in Mannheimia haemolytica, a leading cause of BRD. Characterization of AMR in M. haemolytica by culture and susceptibility testing is complicated by uncertainty regarding the number of colonies that must be selected to accurately characterize AMR phenotypes (antibiograms) and genotypes in a culture. The study objective was to assess phenotypic and genotypic diversity of M. haemolytica isolates on nasopharyngeal swabs (NPS) from 28 cattle at risk for BRD or with BRD. NPS were swabbed onto five consecutive blood agar plates; …

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 …

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 …

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 …

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 …

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 …

Vaccinia Virus Arrests And Shifts The Cell Cycle, Caroline K. Martin, Jerzy Samolej, Annabel T. Olson, Cosetta Bertoli, Matthew S. Wiebe, Robertus A. M. De Bruin, Jason Mercer

School of Veterinary and Biomedical Sciences: Faculty Publications

Modulation of the host cell cycle is a common strategy used by viruses to create a proreplicative environment. To facilitate viral genome replication, vaccinia virus (VACV) has been reported to alter cell cycle regulation and trigger the host cell DNA damage response. However, the cellular factors and viral effectors that mediate these changes remain unknown. Here, we set out to investigate the effect of VACV infection on cell proliferation and host cell cycle progression. Using a subset of VACV mutants, we characterise the stage of infection required for inhibition of cell proliferation and define the viral effectors required to dysregulate …

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 …

Evaluation Of Bioactive Properties Of Lipophilic Fractions Of Edible And Non-Edible Parts Of Nasturtium Officinale (Watercress) In A Model Of Human Malignant Melanoma Cells, Sotiris Kyriakou, Venetia Tragkola, Heba Alghol, Ioannis Anestopoulos, Tom Amery, Kyle Stewart, Paul G. Winyard, Dimitrios T. Trafalis, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidis

School of Veterinary and Biomedical Sciences: Faculty Publications

Watercress is an enriched source of phenethyl isothiocyanate (PEITC), among other phytochemicals, with an antioxidant capacity. The aim of this study was to (i) chemically characterize and (ii) biologically evaluate the profile of the main health-promoting compounds contained in edible (i.e., mixture of leaves and lateral buds) and non-edible (i.e., stems) parts of watercress in an in vitro model of malignant melanoma consisting of human malignant melanoma (A375), non-melanoma (A431) and keratinocyte (HaCaT) cells. The extraction of the main constituents of watercress was performed by subjecting the freeze-dried edible and non-edible samples through different extraction protocols, whereas their concentration was …