Life Sciences Commons^™

Apigenin Alleviates Autistic-Like Stereotyped Repetitive Behaviors And Mitigates Brain Oxidative Stress In Mice, Petrilla Jayaprakash, Dmytro Isaev, Keun-Hang Susan Yang, Rami Beiram, Murat Oz, Bassem Sadek

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Studying the involvement of nicotinic acetylcholine receptors (nAChRs), specifically α7-nAChRs, in neuropsychiatric brain disorders such as autism spectrum disorder (ASD) has gained a growing interest. The flavonoid apigenin (APG) has been confirmed in its pharmacological action as a positive allosteric modulator of α7-nAChRs. However, there is no research describing the pharmacological potential of APG in ASD. The aim of this study was to evaluate the effects of the subchronic systemic treatment of APG (10–30 mg/kg) on ASD-like repetitive and compulsive-like behaviors and oxidative stress status in the hippocampus and cerebellum in BTBR mice, utilizing the reference drug aripiprazole (ARP, 1 …

Methionyl-Trna Synthetase Synthetic And Proofreading Activities Are Determinants Of Antibiotic Persistence, Whitney N. Wood, Miguel Angel Rubio, Lorenzo Eugenio Leiva, Gregory J. Phillips, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Bacterial antibiotic persistence is a phenomenon where bacteria are exposed to an antibiotic and the majority of the population dies while a small subset enters a low metabolic, persistent, state and are able to survive. Once the antibiotic is removed the persistent population can resuscitate and continue growing. Several different molecular mechanisms and pathways have been implicated in this phenomenon. A common mechanism that may underly bacterial antibiotic persistence is perturbations in protein synthesis. To investigate this mechanism, we characterized four distinct metG mutants for their ability to increase antibiotic persistence. Two metG mutants encode changes near the catalytic site …

Β-Sheets Mediate The Conformational Change And Allosteric Signal Transmission Between The Aslov2 Termini, Sian Xiao, Mayar Terek Ibrahim, Gennady M. Verkhivker, Brian D. Zoltowski, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

Avena sativa phototropin 1 light-oxygen-voltage 2 domain (AsLOV2) is a model protein of Per-Arnt-Sim (PAS) superfamily, characterized by conformational changes in response to external environmental stimuli. This conformational change begins with the unfolding of the N-terminal A'α helix in the dark state followed by the unfolding of the C-terminal Jα helix. The light state is characterized by the unfolded termini and the subsequent modifications in hydrogen bond patterns. In this photoreceptor, β-sheets are identified as crucial components for mediating allosteric signal transmission between the two termini. Through combined experimental and computational investigations, the Hβ …

Toward A Coordinated Understanding Of Hydro-Biogeochemical Root Functions In Tropical Forests For Application In Vegetation Models, Daniela F. Cusack, Bradley Christoffersen, Chris M. Smith-Martin, Kelly M. Andersen, Amanda L. Cordeiro, Katrin Fleischer, S. Joseph Wright, Nathaly R. Guerrero-Ramírez, Laynara F. Lugli, Lindsay A. Mcculloch, Mareli Sanchez-Julia, Sarah A. Batterman, Caroline Dallstream, Claire Fortunel, Laura Toro, Lucia Fuchslueger, Michelle Y. Wong, Daniela Yaffar, Joshua B. Fisher, Marie Arnaud, Lee H. Dietterich, Shalom D. Addo-Danso, Oscar J. Valverde-Barrantes, Monique Weemstra, Jing Cheng Ng, Richard J. Norby

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Tropical forest root characteristics and resource acquisition strategies are underrepresented in vegetation and global models, hampering the prediction of forest–climate feedbacks for these carbon-rich ecosystems. Lowland tropical forests often have globally unique combinations of high taxonomic and functional biodiversity, rainfall seasonality, and strongly weathered infertile soils, giving rise to distinct patterns in root traits and functions compared with higher latitude ecosystems. We provide a roadmap for integrating recent advances in our understanding of tropical forest belowground function into vegetation models, focusing on water and nutrient acquisition. We offer comparisons of recent advances in empirical and model understanding of root characteristics …

Mutational Analysis Of The Nitrogenase Carbon Monoxide Protective Protein Cown Reveals That A Conserved C‑Terminal Glutamic Acid Residue Is Necessary For Its Activity, Dustin L. Willard, Joshuah J. Arellano, Mitch Underdahl, Terrence M. Lee, Avinash S. Ramaswamy, Gabriella Fumes, Agatha Kliman, Emily Y. Wong, Cedric P. Owens

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Nitrogenase is the only enzyme that catalyzes the reduction of nitrogen gas into ammonia. Nitrogenase is tightly inhibited by the environmental gas carbon monoxide (CO). Many nitrogen fixing bacteria protect nitrogenase from CO inhibition using the protective protein CowN. This work demonstrates that a conserved glutamic acid residue near the C-terminus of Gluconacetobacter diazotrophicus CowN is necessary for its function. Mutation of the glutamic acid residue abolishes both CowN’s protection against CO inhibition and the ability of CowN to bind to nitrogenase. In contrast, a conserved C-terminal cysteine residue is not important for CO protection by CowN. Overall, this work …

Volcanic Diffuse Volatile Emissions Tracked By Plant Responses Detectable From Space, Robert R. Bogue, Peter M. J. Douglas, Joshua B. Fisher, John Stix

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Volcanic volatile emissions provide information about volcanic unrest but are difficult to detect with satellites. Volcanic degassing affects plants by elevating local CO2 and H2O concentrations, which may increase photosynthesis. Satellites can detect plant health, or a reaction to photosynthesis, through a Normalized Difference Vegetation Index (NDVI). This can act as a potential proxy for detecting changes in volcanic volatile emissions from space. We tested this method by analyzing 185 Landsat 5 and 8 images of the Tern Lake thermal area (TLTA) in northeast Yellowstone caldera from 1984 to 2022. We compared the NDVI values of the thermal area with …

Additive Effects Of Cyclic Peptide [R4w4] When Added Alongside Azithromycin And Rifampicin Against Mycobacterium Avium Infection, Melissa Kelley, Kayvan Sasaninia, Arbi Abnousian, Ali Badaoui, James Owens, Abrianna Beever, Nala Kachour, Rakesh Kumar Tiwari, Vishwanath Venketaraman

Pharmacy Faculty Articles and Research

Mycobacterium avium (M. avium), a type of nontuberculous mycobacteria (NTM), poses a risk for pulmonary infections and disseminated infections in immunocompromised individuals. Conventional treatment consists of a 12-month regimen of the first-line antibiotics rifampicin and azithromycin. However, the treatment duration and low antibiotic tolerability present challenges in the treatment of M. avium infection. Furthermore, the emergence of multidrug-resistant mycobacterium strains prompts a need for novel treatments against M. avium infection. This study aims to test the efficacy of a novel antimicrobial peptide, cyclic [R4W4], alongside the first-line antibiotics azithromycin and rifampicin in reducing M. avium survival. Colony-forming unit (CFU) …

Symbiotic Ucyn-A Strains Co-Occurred With El Niño, Relaxed Upwelling, And Varied Eukaryotes Over 10 Years Off Southern California, Colette Fletcher-Hoppe, Yi-Chun Yeh, Yubin Raut, J. L. Weissman, Jed A. Fuhrman

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Biological nitrogen fixation, the conversion of N₂ gas into a bioavailable form, is vital to sustaining marine primary production. Studies have shifted beyond traditionally studied tropical diazotrophs. Candidatus Atelocyanobacterium thalassa (or UCYN-A) has emerged as a focal point due to its streamlined metabolism, intimate partnership with a haptophyte host, and broad distribution. Here, we explore the environmental parameters that govern UCYN-A’s presence at the San Pedro Ocean Time-series (SPOT), its host specificity, and statistically significant interactions with non-host eukaryotes from 2008-2018. 16S and 18S rRNA gene sequences were amplified by “universal primers” from monthly samples and resolved into Amplicon …

Updating The Dual C And O Isotope—Gas-Exchange Model: A Concept To Understand Plant Responses To The Environment And Its Implications For Tree Rings, Rolf T. W. Siegwolf, Marco M. Lehmann, Gregory R. Goldsmith, Olga V. Churakova (Sidorova), Cathleen Mirande-Ney, Galina Timoveeva, Rosmarie B. Weigt, Matthias Saurer

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The combined study of carbon (C) and oxygen (O) isotopes in plant organic matter has emerged as a powerful tool for understanding plant functional responses to environmental change. The approach relies on established relationships between leaf gas exchange and isotopic fractionation to derive a series of model scenarios that can be used to infer changes in photosynthetic assimilation and stomatal conductance driven by changes in environmental parameters (CO₂, water availability, air humidity, temperature, nutrients). We review the mechanistic basis for a conceptual model, in light of recently published research, and discuss where isotopic observations do not match our …

Arginine Methylation Of The Pgc-1Α C‑Terminus Is Temperature- Dependent, Meryl Mendoz, Mariel Mendoza, Tiffany Lubrino, Sidney Briski, Immaculeta Osuji, Janielle Cuala, Brendan Ly, Ivan Ocegueda, Harvey Peralta, Benjamin A. Garcia, Cecilia Zurita-Lopez

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

We set out to determine whether the C-terminus (amino acids 481–798) of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α, UniProt Q9UBK2), a regulatory metabolic protein involved in mitochondrial biogenesis, and respiration, is an arginine methyltransferase substrate. Arginine methylation by protein arginine methyltransferases (PRMTs) alters protein function and thus contributes to various cellular processes. In addition to confirming methylation of the C-terminus by PRMT1 as described in the literature, we have identified methylation by another member of the PRMT family, PRMT7. We performed in vitro methylation reactions using recombinant mammalian PRMT7 and PRMT1 at 37, 30, 21, 18, and 4 °C. …

Technical Note: On Uncertainties In Plant Water Isotopic Composition Following Extraction By Cryogenic Vacuum Distillation, Haoyu Diao, Philipp Schuler, Gregory R. Goldsmith, Rolf T. W. Siegwolf, Matthias Saurer, Marco M. Lehmann

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Recent studies have challenged the interpretation of plant water isotopes obtained through cryogenic vacuum distillation (CVD) based on observations of a large 2H fractionation. These studies have hypothesized the existence of an H-atom exchange between water and organic tissue during CVD extraction with the magnitude of H exchange related to relative water content of the sample; however, clear evidence is lacking. Here, we systematically tested the uncertainties in the isotopic composition of CVD-extracted water by conducting a series of incubation and rehydration experiments using isotopically depleted water, water at natural isotope abundance, woody materials with exchangeable H, and organic materials …

Subtype-Selective Positive Modulation Of KCa2.3 Channels Increases Cilia Length, Young-Woo Nam, Rajasekharreddy Pala, Naglaa Salem El-Sayed, Denisse Laren-Henriquez, Farideh Amirrad, Grace Yang, Mohammad Asikur Rahman, Razan Orfali, Myles Downey, Keykavous Parang, Surya M. Nauli, Miao Zhang

Pharmacy Faculty Articles and Research

Small-conductance Ca²⁺-activated potassium (K_Ca2.x) channels are gated exclusively by intracellular Ca²⁺. The activation of K_Ca2.3 channels induces hyperpolarization, which augments Ca²⁺ signaling in endothelial cells. Cilia are specialized Ca²⁺ signaling compartments. Here, we identified compound 4 that potentiates human K_Ca2.3 channels selectively. The subtype selectivity of compound 4 for human K_Ca2.3 over rat K_Ca2.2a channels relies on an isoleucine residue in the HA/HB helices. Positive modulation of K_Ca2.3 channels by compound 4 increased flow-induced Ca²⁺ signaling and cilia length, while negative …

Climatic Influences On Summer Use Of Winter Precipitation By Trees, Gregory R. Goldsmith, Scott T. Allen, Sabine Braun, Rolf T. W. Siegwolf, James W. Kirchner

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Trees in seasonal climates may use water originating from both winter and summer precipitation. However, the seasonal origins of water used by trees have not been systematically studied. We used stable isotopes of water to compare the seasonal origins of water found in three common tree species across 24 Swiss forest sites sampled in two different years. Water from winter precipitation was observed in trees at most sites, even at the peak of summer, although the relative representation of seasonal sources differed by species. However, the representation of winter precipitation in trees decreased with site mean annual precipitation in both …

Evaluating Alternative Ebullition Models For Predicting Peatland Methane Emission And Its Pathways Via Data–Model Fusion, Shuang Ma, Lifen Jiang, Rachel M. Wilson, Jeff P. Chanton, Scott Bridgham, Shuli Niu, Colleen M. Iversen, Avni Malhotra, Jiang Jiang, Xingjie Lu, Yuanyuan Huang, Jason Keller, Xiaofeng Xu, Daniel M. Ricciuto, Paul J. Hanson, Yiqi Luo

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Understanding the dynamics of peatland methane (CH4) emissions and quantifying sources of uncertainty in estimating peatland CH4 emissions are critical for mitigating climate change. The relative contributions of CH4 emission pathways through ebullition, plant-mediated transport, and diffusion, together with their different transport rates and vulnerability to oxidation, determine the quantity of CH4 to be oxidized before leaving the soil. Notwithstanding their importance, the relative contributions of the emission pathways are highly uncertain. In particular, the ebullition process is more uncertain and can lead to large uncertainties in modeled CH4 emissions. To improve model simulations of CH4 emission and its pathways, …

1st Place Contest Entry: Designing Hollow Nanogels For Drug Delivery Applications, Mo Hijazi

Kevin and Tam Ross Undergraduate Research Prize

This is Mo Hijazi's submission for the 2022 Kevin and Tam Ross Undergraduate Research Prize, which won first place. It contains their essay on using library resources, their bibliography, and a summary of their research project on hollow-core nanogels.

Mo is a second-year student at Chapman University, majoring in Biological Sciences. Their faculty mentor is Dr. Molla Islam.

Structural And Computational Studies Of The Sars-Cov-2 Spike Protein Binding Mechanisms With Nanobodies: From Structure And Dynamics To Avidity-Driven Nanobody Engineering, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Nanobodies provide important advantages over traditional antibodies, including their smaller size and robust biochemical properties such as high thermal stability, high solubility, and the ability to be bioengineered into novel multivalent, multi-specific, and high-affinity molecules, making them a class of emerging powerful therapies against SARS-CoV-2. Recent research efforts on the design, protein engineering, and structure-functional characterization of nanobodies and their binding with SARS-CoV-2 S proteins reflected a growing realization that nanobody combinations can exploit distinct binding epitopes and leverage the intrinsic plasticity of the conformational landscape for the SARS-CoV-2 S protein to produce efficient neutralizing and mutation resistant characteristics. Structural …

Allosteric Determinants Of The Sars-Cov-2 Spike Protein Binding With Nanobodies: Examining Mechanisms Of Mutational Escape And Sensitivity Of The Omicron Variant, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Structural and biochemical studies have recently revealed a range of rationally engineered nanobodies with efficient neutralizing capacity against the SARS-CoV-2 virus and resilience against mutational escape. In this study, we performed a comprehensive computational analysis of the SARS-CoV-2 spike trimer complexes with single nanobodies Nb6, VHH E, and complex with VHH E/VHH V nanobody combination. We combined coarse-grained and all-atom molecular simulations and collective dynamics analysis with binding free energy scanning, perturbation-response scanning, and network centrality analysis to examine mechanisms of nanobody-induced allosteric modulation and cooperativity in the SARS-CoV-2 spike trimer complexes with these nanobodies. By quantifying energetic and allosteric …

Escherichia Coli Alanyl-Trna Synthetase Maintains Proofreading Activity And Translational Accuracy Under Oxidative Stress, Arundhati Kavoor, Paul Kelly, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Aminoacyl-tRNA synthetases (aaRSs) are enzymes that synthesize aminoacyl-tRNAs to facilitate translation of the genetic code. Quality control by aaRS proofreading and other mechanisms maintains translational accuracy, which promotes cellular viability. Systematic disruption of proofreading, as recently demonstrated for alanyl-tRNA synthetase (AlaRS), leads to dysregulation of the proteome and reduced viability. Recent studies showed that environmental challenges such as exposure to reactive oxygen species can also alter aaRS synthetic and proofreading functions, prompting us to investigate if oxidation might positively or negatively affect AlaRS activity. We found that while oxidation leads to modification of several residues in Escherichia coli AlaRS, unlike …

Evaluation Of The Trunarc Handheld Narcotics Analyzer As A Pre-Analysis Screening Device For The Orange County Crime Lab, Sarah Yang, D. Bauer, C. Woltz, S. Soto, Michael Ibba

Student Scholar Symposium Abstracts and Posters

Forensic analysis of suspected narcotics is often dangerous as the substances’ composition is unknown. Many techniques for drug identification require handling of the substance outside of its packaging, which can expose the analyst to potentially harmful chemicals. The TruNarc Handheld Narcotics Analyzer is a portable Raman spectroscopy device that is non-destructive of evidence and can be used to screen drugs through simple packaging to minimize the risk of exposure. The Orange County Crime Lab (OCCL) is testing the limits of this device to determine if it can be used to screen new evidence within the Seized Drugs Lab. The OCCL …

Oxidation Alters The Architecture Of The Phenylalanyl-Trna Synthetase Editing Domain To Confer Hyperaccuracy, Pooja Srinivas, Rebecca E. Steiner, Ian J. Pavelich, Ricardo Guerrera-Ferreira, Puneet Juneja, Michael Ibba, Christine M. Dunham

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

High fidelity during protein synthesis is accomplished by aminoacyl-tRNA synthetases (aaRSs). These enzymes ligate an amino acid to a cognate tRNA and have proofreading and editing capabilities that ensure high fidelity. Phenylalanyl-tRNA synthetase (PheRS) preferentially ligates a phenylalanine to a tRNA^Phe over the chemically similar tyrosine, which differs from phenylalanine by a single hydroxyl group. In bacteria that undergo exposure to oxidative stress such as Salmonella enterica serovar Typhimurium, tyrosine isomer levels increase due to phenylalanine oxidation. Several residues are oxidized in PheRS and contribute to hyperactive editing, including against mischarged Tyr-tRNA^Phe, despite these oxidized residues not …

Automated Parsing Of Flexible Molecular Systems Using Principal Component Analysis And K-Means Clustering Techniques, Matthew J. Nwerem

Computational and Data Sciences (MS) Theses

Computational investigation of molecular structures and reactions of biological and pharmaceutical interests remains a grand scientific challenge due to the size and conformational flexibility of these systems. The work requires parsing and analyzing thousands of conformations in each molecular state for meaningful chemical information and subjecting the ensemble to costly quantum chemical calculations. The current status quo typically involves a manual process where the investigator must look at each conformation, separating each into structural families. This process is time-intensive and tedious, making this process infeasible in some cases, and limiting the ability of theoreticians to study these systems. However, the …

A Bacterial Inflammation Sensor Regulates C-Di-Gmp Signaling, Adhesion, And Biofilm Formation, Arden Perkins, Dan A. Tudorica, Raphael D. Teixeira, Tilman Schirmer, Lindsay Zumwalt, O. Maduka Ogba, C. Keith Cassidy, Phillip J. Stansfeld, Karen Guillemin

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Bacteria that colonize animals must overcome, or coexist, with the reactive oxygen species products of inflammation, a front-line defense of innate immunity. Among these is the neutrophilic oxidant bleach, hypochlorous acid (HOCl), a potent antimicrobial that plays a primary role in killing bacteria through nonspecific oxidation of proteins, lipids, and DNA. Here, we report that in response to increasing HOCl levels, Escherichia coli regulates biofilm production via activation of the diguanylate cyclase DgcZ. We identify the mechanism of DgcZ sensing of HOCl to be direct oxidation of its regulatory chemoreceptor zinc-binding (CZB) domain. Dissection of CZB signal transduction reveals that …

Cown Sustains Nitrogenase Turnover In The Presence Of The Inhibitor Carbon Monoxide, Michael S. Medina, Kevin O. Bretzing, Richard A. Aviles, Kiersten M. Chong, Alejandro Espinoza, Chloe Nicole G. Garcia, Benjamin B. Katz, Ruchita N. Kharwa, Andrea Hernandez, Justin L. Lee, Terrence M. Lee, Christine Lo Verde, Max W. Strul, Emily Y. Wong, Cedric P. Owens

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Nitrogenase is the only enzyme capable of catalyzing nitrogen fixation, the reduction of dinitrogen gas (N₂) to ammonia (NH₃). Nitrogenase is tightly inhibited by the environmental gas carbon monoxide (CO). Nitrogen-fixing bacteria rely on the protein CowN to grow in the presence of CO. However, the mechanism by which CowN operates is unknown. Here, we present the biochemical characterization of CowN and examine how CowN protects nitrogenase from CO. We determine that CowN interacts directly with nitrogenase and that CowN protection observes hyperbolic kinetics with respect to CowN concentration. At a CO concentration of 0.001 atm, …

Capsaicin Is A Negative Allosteric Modulator Of The 5-Ht3 Receptor, Eslam El Nebrisi, Tatiana Prytkova, Dietrich Ernst Lorke, Luke Howarth, Asma Hassan Alzaabi, Keun-Hang Susan Yang, Frank Christopher Howarth, Murat Oz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

In this study, effects of capsaicin, an active ingredient of the capsicum plant, were investigated on human 5-hydroxytryptamine type 3 (5-HT₃) receptors. Capsaicin reversibly inhibited serotonin (5-HT)-induced currents recorded by two-electrode voltage clamp method in Xenopus oocytes. The inhibition was time- and concentration-dependent with an IC₅₀ = 62 μM. The effect of capsaicin was not altered in the presence of capsazepine, and by intracellular BAPTA injections or trans-membrane potential changes. In radio-ligand binding studies, capsaicin did not change the specific binding of the 5-HT₃ antagonist [³H]GR65630, indicating that it is a noncompetitive inhibitor of …

Allosteric Regulation At The Crossroads Of New Technologies: Multiscale Modeling, Networks, And Machine Learning, Gennady M. Verkhivker, Steve Agajanian, Guang Hu, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

Allosteric regulation is a common mechanism employed by complex biomolecular systems for regulation of activity and adaptability in the cellular environment, serving as an effective molecular tool for cellular communication. As an intrinsic but elusive property, allostery is a ubiquitous phenomenon where binding or disturbing of a distal site in a protein can functionally control its activity and is considered as the “second secret of life.” The fundamental biological importance and complexity of these processes require a multi-faceted platform of synergistically integrated approaches for prediction and characterization of allosteric functional states, atomistic reconstruction of allosteric regulatory mechanisms and discovery of …

Leaf Traits Can Be Used To Predict Rates Of Litter Decomposition, Marc Rosenfield, Jennifer L. Funk, Jason K. Keller, Catrina Clausen, Kimberlee Cyphers

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Strong relationships exist between litter chemistry traits and rates of litter decomposition. However, leaf traits are more commonly found in online trait databases than litter traits and fewer studies have examined how well leaf traits predict litter decomposition rates. Furthermore, while bulk leaf nitrogen (N) content is known to regulate litter decomposition, few studies have explored the importance of N biochemistry fractions, such as protein and amino acid concentration. Here, we decomposed green leaves and naturally senesced leaf litter of nine species representing a wide range of leaf functional traits. We evaluated the ability of traits associated with leaf and …

Integration Of Random Forest Classifiers And Deep Convolutional Neural Networks For Classification And Biomolecular Modeling Of Cancer Driver Mutations, Steve Agajanian, Odeyemi Oluyemi, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Development of machine learning solutions for prediction of functional and clinical significance of cancer driver genes and mutations are paramount in modern biomedical research and have gained a significant momentum in a recent decade. In this work, we integrate different machine learning approaches, including tree based methods, random forest and gradient boosted tree (GBT) classifiers along with deep convolutional neural networks (CNN) for prediction of cancer driver mutations in the genomic datasets. The feasibility of CNN in using raw nucleotide sequences for classification of cancer driver mutations was initially explored by employing label encoding, one hot encoding, and embedding to …

Purification And Characterization Of A Nonspecific Lipid Transfer Protein 1 (Nsltp1) From Ajwain (Trachyspermum Ammi) Seeds, Meshal Nazeer, Humera Waheed, Maria Saeed, Saman Yousuf Ali, M. Iqbal Choudhary, Zaheer Ul-Haq, Aftab Ahmed

Pharmacy Faculty Articles and Research

Ajwain (Trachyspermum ammi) belongs to the family Umbelliferae, is commonly used in traditional, and folk medicine due to its carminative, stimulant, antiseptic, diuretic, antihypertensive, and hepatoprotective activities. Non-specific lipid transfer proteins (nsLTPs) reported from various plants are known to be involved in transferring lipids between membranes and in plants defense response. Here, we describe the complete primary structure of a monomeric non-specific lipid transfer protein 1 (nsLTP1), with molecular weight of 9.66 kDa, from ajwain seeds. The nsLTP1 has been purified by combination of chromatographic techniques, and further characterized by mass spectrometry, and Edman degradation. The ajwain nsLTP1 …

Seasonal Origins Of Soil Water Used By Trees, Scott T. Allen, James W. Kirchner, Sabine Braun, Rolf T. W. Siegwolf, Gregory R. Goldsmith

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Rain recharges soil water storages and either percolates downward into aquifers and streams or is returned to the atmosphere through evapotranspiration. Although it is commonly assumed that summer rainfall recharges plant-available water during the growing season, the seasonal origins of water used by plants have not been systematically explored. We characterize the seasonal origins of waters in soils and trees by comparing their midsummer isotopic signatures (δ2H) to seasonal isotopic cycles in precipitation, using a new seasonal origin index. Across 182 Swiss forest sites, xylem water isotopic signatures show that summer rain was not the predominant water source …

Ferrocenylchalcone-Uracil Conjugates: Synthesis And Cytotoxic Evaluation, Amandeep Singh, Vishu Mehra, Neda Sadeghiani, Saghar Mozaffari, Keykavous Parang, Vipan Kumar

Pharmacy Faculty Articles and Research

Huisgen’s azide-alkyne cycloaddition reaction was employed to synthesize a series of 1H-1,2,3-triazole-tethered uracil-ferrocenyl chalcone conjugates with the aim of evaluating their in vitro anti-proliferative efficacy on human leukemia (CCRF-CEM) and human breast adenocarcinoma (MDA-MB-468) cell lines. Cytotoxic evaluation studies identified a number of synthesized conjugates that inhibited the proliferation of leukemia cancer cells by ~70% after 72 h. The selected synthesized conjugates were found to be significantly less cytotoxic against normal kidney cell line (LLC-PK1) when compared with CCRF-CEM cancer cells.