Biochemistry, Biophysics, and Structural Biology Commons^™

Targeting The Cdk6 Dependence Of Ph+ Acute Lymphoblastic Leukemia, Patrizia Porazzi, Marco De Dominici, Joseph Salvino, Bruno Calabretta

Department of Cancer Biology Faculty Papers

Ph+ ALL is a poor-prognosis leukemia subtype driven by the BCR-ABL1 oncogene, either the p190-or the p210-BCR/ABL isoform in a 70:30 ratio. Tyrosine Kinase inhibitors (TKIs) are the drugs of choice in the therapy of Ph+ ALL. In combination with standard chemotherapy, TKIs have markedly improved the outcome of Ph+ ALL, in particular if this treatment is followed by bone marrow transplantation. However, resistance to TKIs develops with high frequency, causing leukemia relapse that results in

Effects Of Copper Oxide (Cuo) And Zinc Oxide (Zno) Nano And Bulk Forms To Soil Fungal Community [Research Note], Jonathan Jaime Guerrero, Teresita Dalisay, Nolissa Organo, Ireneo Pangga

The Philippine Agricultural Scientist

The effects of copper oxide (CuO) and zinc oxide (ZnO) in bulk and nano forms on soil fungal community was determined. Lipa clay loam soil collected from the University of the Philippines Los Baños were placed in polypropylene bags and amended with 300 mg/L of CuO or ZnO in either forms. Colony-forming units (CFU) as well as average well color development (AWCD), functional richness and stress index were determined on day 1, 8 and 15 via indirect viable plate count method and community – level physiological profiling (CLPP). Fungal isolates from the same soil samples were likewise identified and tested …

An Evaluation Of The Hargreaves-Samani Method For Estimating Evapotranspiration Under Semi-Arid Conditions, Yusuf Aydin

The Philippine Agricultural Scientist

It is suggested by the Food and Agriculture Organization of the United Nations (FAO) to use the FAO56-Penman-Monteith (FAO56-PM) model as the standard model in reference crop water consumption studies. However, the climate parameters required by the standard model cannot be fully and reliably obtained in under developed or developing countries. Hence, the Hargreaves-Samani (HS) equation is used as an alternative to the FAO56-PM model since it can be used for calculations with less climate data. In this study, ET_o-PM and ET_o-HS values calculated at 8 provinces in Southeastern Turkey using the IAM-ET_o software were evaluated and …

Complete Mitochondrial Genome Sequence Of The Gulf Coast Tick (Amblyomma Maculatum), Amanda E. Brenner, Rahul Raghavan

Biology Faculty Publications and Presentations

The complete circularized mitochondrial genome sequence of Amblyomma maculatum is 14,803 bp long. It encodes 13 protein coding genes, 2 rRNA genes, 22 tRNA genes, 2 tick box motifs, and 2 control regions. The gene arrangement and content are consistent with those of previously reported Metastriata tick mitochondrial genomes.

Machine Learning And Solvation Theory For Drug Discovery, Lieyang Chen

Dissertations, Theses, and Capstone Projects

Drug discovery is a notoriously expensive and time-consuming process; hence, developing computational methods to facilitate the discovery process and lower the associated costs is a long-sought goal of computational chemists. Protein-ligand binding, which provides the physical and chemical basis for the mechanism of action of most drugs, occurs in an aqueous environment, and binding affinity is determined not only by atomic interactions between the protein and ligand but also by changes in their interactions with surrounding water molecules that occur upon binding. Thus, a quantitative understanding of the roles water molecules play in the protein-ligand binding process is an essential …

Study Of The Gain-Of-Function Mutant P53 And Parp1 In Triple-Negative Breast Cancer, Devon Lundine

Dissertations, Theses, and Capstone Projects

Cancer cells often lose expression of the p53 protein or express mutant forms of p53. Some of these mutant p53 proteins, called gain-of-function mutant p53, have gained oncogenic functions. Previously, our group observed mutant p53 R273H interacts with replicating DNA and upregulates the chromatin localization of several DNA replication factors including PCNA, MCM2-7, and PARP1 (termed the mtp53-PARP-MCM axis). In this thesis, we explore the contribution of mutant p53 and PARP1 in castration-resistant prostate cancer (mutant p53 P223L and V274F) and triple-negative breast cancer (mutant p53 R273H). In the castration-resistant prostate cancer cell line DU145, we examine two mutant p53 …

Understanding The Influence Of Zinc On Grain Cadmium Accumulation And Bioaccessibility In Rice, Michael A. Tavarez

Dissertations, Theses, and Capstone Projects

The effect of cadmium and zinc on mineral concentrations in three cultivars of rice

Interactions between the essential mineral zinc (Zn) and the toxic heavy metal cadmium (Cd) play an important role in regulating transport of both minerals to rice grains. Understanding these interactions is crucial for limiting cadmium and increasing zinc transfer to the food chain. Previous studies on the matter have had conflicting results suggesting synergistic and antagonistic relationships between the minerals. The goal of this work was to identify the effect of external cadmium and zinc on the uptake and translocation of both minerals from roots to …

The Structural And Functional Role Of Photosensing In Rgs-Lov Proteins, Zaynab Jaber

Dissertations, Theses, and Capstone Projects

Light provides organisms with energy and spatiotemporal information. To survive and adapt, organisms have developed the ability to sense light to drive biochemical effects that underlie vision, entrainment of circadian rhythm, stress response, virulence, and many other important molecularly driven responses. Blue-light sensing Light-Oxygen-Voltage (LOV) domains are ubiquitous across multiple kingdoms of life and modulate various physiological events via diverse effector domains. Using a small molecule flavin chromophore, the LOV domain undergoes light-dependent structural changes leading to activation or repression of these catalytic and non-catalytic effectors. In silico analyses of high-throughput genomic sequencing data has led to the marked expansion …

The Role Of Estrogen Receptor Alpha In Regulating Messenger Rna 3’ End Processing And Controlling Gene Expression In Breast Cancer Cells, Sophia Varriano

Dissertations, Theses, and Capstone Projects

Estrogen signaling regulates various physiological processes within the female reproductive, cardiovascular, immune, and central nervous systems and is predominantly mediated by estrogen receptors (ER), ERα and ERβ. Transcriptional regulation by ERs has been widely studied, where activated ERs bind either directly to target genes through binding to estrogen response elements or indirectly through interacting with other proteins, resulting in changes in gene expression. However, the potential role of factors involved in the estrogen signaling pathway in posttranscriptional regulation has not been extensively documented. As 70-80% of breast cancers (BCs) are identified as ER(+), studying how these factors, particularly ERα, regulates …

Conformation Of The Protein-Free Spliceosomal U2-U6 Snrna Complex And Remodeling By Mg2+ And Proteins, Huong Chu

Dissertations, Theses, and Capstone Projects

Splicing of precursor messenger RNA is an essential process in eukaryotes in which the non-coding regions (introns) are removed and coding regions (exons) ligated together to form a mature mRNA. This process is catalyzed by a multi-mega Dalton ribonucleoprotein complex called the spliceosome, which is assembled from five small nuclear ribonucleoproteins (snRNP) in the form of RNA-protein complexes (U1, U2, U4, U5 and U6) and hundreds of proteins. U2 and U6 small nuclear (sn)RNAs are the only snRNAs directly implicated in catalyzing the splicing of pre-mRNA, but assembly and rearrangement steps prior to catalysis require numerous proteins. Previous studies have …

Dual Control Of One Component Signaling: Mechanistic And Structural Insights Into El222 Active States, Uthama Phani R. Edupuganti

Dissertations, Theses, and Capstone Projects

Photoreceptors play a crucial role in signal transduction as specialized proteins which sense light as environmental stimuli and transduce the signal to control of downstream functions. Here we focus our attention on one class of these proteins, the Light-Oxygen-Voltage (LOV) domain, which is sensitive to blue light via an internally-bound flavin chromophore. Since their initial discovery in plant phototropins, many details of their photochemistry, chromophore interactions, and use with a diverse set of functional effectors have been described. However, several key details, especially a comprehensive understanding of signaling mechanism and its regulation, still remain elusive due in part to the …

Development Of High-Throughput Methods For Screening Venom Peptides, Tanya Napolitano

Dissertations, Theses, and Capstone Projects

Bioactive venom peptides are increasingly being explored as drug leads in pharmaceutical research because of their immense therapeutic potential, however there is a need to more efficiently screen and characterize these peptides to discover medicinal leads more quickly.1,2 The Holford lab has leveraged recent technological achievements in genomics, transcriptomics, and proteomics to produce a leap in the discovery of venom peptides from previously hard to characterize small and neglected venomous animals such as Terebridae, an understudied lineage of the Conoidea Superfamily.4, 5–7 With the rise of -omic technologies the floodgates have opened and venom researchers are awash with large datasets …

Three Lc-Ms Plant Metabolomics Studies Of Hop (Humulus) Species: Wild H. Neomexicanus, Drought Stress, And Agricultural Terroir, Taylan Morcol

Dissertations, Theses, and Capstone Projects

The hop plant (Humulus L., Cannabaceae) is a dioecious, perennial, twining vine with a long history of human use. Nowadays, hop plants are generally grown for their inflorescences (“cones”), which are used in brewing for their phytochemical metabolites. Many of these metabolites are involved in plant stress response and communication. Genetics and environment are two major factors that affect plant metabolism. In three separate metabolomics studies, this project examined the effects of both genetic and environmental factors on hop phytochemistry.

In the first study, 23 hop genotypes were grown in two different locations in the Pacific Northwest region of …

Molecular Dynamics Simulations Of Self-Assemblies In Nature And Nanotechnology, Phu Khanh Tang

Dissertations, Theses, and Capstone Projects

Nature usually divides complex systems into smaller building blocks specializing in a few tasks since one entity cannot achieve everything. Therefore, self-assembly is a robust tool exploited by Nature to build hierarchical systems that accomplish unique functions. The cell membrane distinguishes itself as an example of Nature’s self-assembly, defining and protecting the cell. By mimicking Nature’s designs using synthetically designed self-assemblies, researchers with advanced nanotechnological comprehension can manipulate these synthetic self-assemblies to improve many aspects of modern medicine and materials science. Understanding the competing underlying molecular interactions in self-assembly is always of interest to the academic scientific community and industry. …

Tools And Strategies For The Patterning Of Bioactive Molecules And Macromolecules, Daniel J. Valles

Dissertations, Theses, and Capstone Projects

Hypersurface Photolithography (HP) is a printing method for fabricating structures and patterns composed of soft materials bound to solid surfaces and with ~1 micrometer resolution in the x, y, and z dimensions. This platform leverages benign, low intensity light to perform photochemical surface reactions with spatial and temporal control of irradiation, and, as a result, is particularly useful for patterning delicate organic and biological material. In particular, surface- initiated controlled radical polymerizations can be leveraged to create arbitrary polymer and block- copolymer brush patterns. Chapter 1 will review the advances in instrumentation architectures from our group that have made these …

Treatment Options For Managing Obesity In Chronic Kidney Disease, Vishnu P Parvathareddy, Krishiv M Ella, Maulin Shah, Sankar D Navaneethan

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Obesity is a risk factor for the development and progression of chronic kidney disease (CKD). In this review, we provide a comprehensive overview of various management options (lifestyle intervention, medications, and bariatric surgery) to address obesity in those with CKD.

RECENT FINDINGS: Few clinical trials have examined the benefits of lifestyle modifications in those with preexisting CKD and suggest potential renal and cardiovascular benefits in this population. Yet, superiority of different dietary regimen to facilitate weight loss in CKD is unclear. Although medications could offer short-term benefits and assist weight loss, their safety and long-term benefits warrant …

Zfta-Rela Dictates Oncogenic Transcriptional Programs To Drive Aggressive Supratentorial Ependymoma, Amir Arabzade, Yanhua Zhao, Srinidhi Varadharajan, Hsiao-Chi Chen, Selin Jessa, Bryan Rivas, Austin J Stuckert, Minerva Solis, Alisha Kardian, Dana Tlais, Brian J Golbourn, Ann-Catherine J Stanton, Yuen San Chan, Calla Olson, Kristen L Karlin, Kathleen Kong, Robert Kupp, Baoli Hu, Sarah G Injac, Madeline Ngo, Peter R Wang, Luz A De León, Felix Sahm, Daisuke Kawauchi, Stefan M Pfister, Charles Y Lin, H Courtney Hodges, Irtisha Singh, Thomas F Westbrook, Murali M Chintagumpala, Susan M Blaney, Donald W Parsons, Kristian W Pajtler, Sameer Agnihotri, Richard J Gilbertson, Joanna Yi, Nada Jabado, Claudia L Kleinman, Kelsey C Bertrand, Benjamin Deneen, Stephen C Mack

Faculty, Staff and Students Publications

Over 60% of supratentorial (ST) ependymomas harbor a ZFTA-RELA (ZRfus) gene fusion (formerly C11orf95-RELA). To study the biology of ZRfus, we developed an autochthonous mouse tumor model using in utero electroporation (IUE) of the embryonic mouse brain. Integrative epigenomic and transcriptomic mapping was performed on IUE driven ZRfus tumors by CUT&RUN, ChIP, ATAC, and RNA sequencing and compared to human ZRfus driven ependymoma. In addition to direct canonical NF-κB pathway activation, ZRfus dictates a neoplastic transcriptional program and binds to thousands of unique sites across the genome that are enriched with Plagl family transcription factor (TF) motifs. ZRfus activates …

Structure And Dynamics Of Photoreceptor Sensory Cilia, Theodore G Wensel, Valencia L Potter, Abigail Moye, Zhixian Zhang, Michael A Robichaux

Faculty, Staff and Students Publications

The rod and cone photoreceptor cells of the vertebrate retina have highly specialized structures that enable them to carry out their function of light detection over a broad range of illumination intensities with optimized spatial and temporal resolution. Most prominent are their unusually large sensory cilia, consisting of outer segments packed with photosensitive disc membranes, a connecting cilium with many features reminiscent of the primary cilium transition zone, and a pair of centrioles forming a basal body which serves as the platform upon which the ciliary axoneme is assembled. These structures form a highway through which an enormous flux of …

Oxydifficidin-Producing Bacillus Presents Novel Antimicrobial Activity Against Neisseria Gonorrhoeae Involving The Deda Protein, Jingbo Kan

Dissertations, Theses, and Capstone Projects

Bacterial human pathogens cause severe infectious diseases which are the second most common cause of death next to cancer and cardiovascular diseases in the world, especially in developing countries. Gonorrhea particularly, is the second most common sexually transmitted infection (STI) which is caused by the microorganism Neisseria gonorrhoeae (GC). Centers for Disease Control and Prevention (CDC) estimates that more than 1.6 million new gonorrhea cases emerged in USA in 2018 (“Detailed STD Facts - Gonorrhea” n.d.). Also, the WHO (World Health Organization) shows that gonorrhea is the most antibiotic resistant STI (“PAHO/WHO | Gonorrhea” n.d.), highlighting the shortage of efficient …

Don't Sell Them Short, There's More To Bacterial Natural Products Than Antibiotics, Alison Clare Domzalski

Dissertations, Theses, and Capstone Projects

Recent genomic studies of microbiomes have revealed an overwhelming number of biosynthetic genes of unknown function. Most of these “cryptic” biosynthetic genes are not expressed in laboratory monocultures of individual microbes. Thus, there remains tremendous untapped potential for natural products discovery. Here we employ mixed microbial culture (MMC) as a simple yet powerful approach to awaken cryptic biosynthetic gene clusters. Our preliminary studies demonstrated that arrays of metabolites could be induced in MMCs upon environmental cues, such as surface adhesion. Using this system, we have screened, identified, and isolated bioactive bacterial metabolites, which were characterized structurally and biologically. Of the …

Hemodynamic Outcomes After Valve-In-Valve Transcatheter Aortic Valve Replacement: A Single-Center Experience, R Yazan Kherallah, Srikanth Koneru, Zvonimir Krajcer, Ourania Preventza, Kathryn G Dougherty, Melissa L Mccormack, Briana T Costello, Stephanie Coulter, Neil E Strickman, Juan Carlos Plana Gomez, Ali Mortazavi, Jose G Díez, James J Livesay, Joseph S Coselli, Guilherme V Silva

Faculty, Staff and Students Publications

BACKGROUND: Valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) has emerged as a safe, effective alternative to redo aortic valve surgery in high-risk patients with degenerated surgical bioprosthetic valves. However, ViV-TAVR has been associated high postprocedural valvular gradients, compared with TAVR for native-valve aortic stenosis.

METHODS: We performed a retrospective study of all patients who underwent ViV-TAVR for a degenerated aortic valve bioprosthesis between January 1, 2013 and March 31, 2019 at our center. The primary outcome was postprocedural mean aortic valve gradient. Outcomes were compared across surgical valve type (stented versus stentless), surgical valve internal diameter (≤19 versus >19 mm), and …

A Narrative Review Of Interstitial Lung Disease In Anti-Synthetase Syndrome: A Clinical Approach, Naina Sawal, Sanjay Mukhopadhyay, Sheetal Rayancha, Alastair Moore, Puneet Garcha, Anupam Kumar, Viren Kaul

Faculty, Staff and Students Publications

Anti-synthetase syndrome (AS) is a rare autoimmune disorder characterized by the presence of aminoacyl-transfer RNA synthetase antibodies in conjunction with clinical features such as interstitial lung disease (ILD), Raynaud's phenomenon, nonerosive arthritis, and myopathy. AS distinguishes itself from other inflammatory myopathies by its significant lung involvement and rapidly progressive interstitial lung disease (AS-ILD), therefore the management of AS-ILD requires careful clinical, serologic and radiologic assessment. Glucocorticoids are considered the mainstay of therapy; however, additional immunosuppressive agents are often required to achieve disease control. Patient prognosis is highly dependent on early diagnosis and symptom recognition as the antibody profile is thought …

The Veiled Lady Fungus, Nick Parbhoo

Symposium of Student Scholars

This semester I studied the Stinkhorn mushroom Phallus Indusiatus. The plan of this research is to develop a protocol for growing this fungus and using it in collaboration with research on it’s web-like properties of the unique veil produced by the fruiting body. This will be distributed to teams of engineers as well as NASA for Dr. Penick’s research. Due to logistics of receiving spores from across the world, we still have not been able to begin growing these mushrooms. However, I have described a protocol that we will follow in order to grow. The protocol contains detailed descriptions …

Conserved Regions Mediate Interactions Between Canonical Nox Domains, Akua Acheampong

Symposium of Student Scholars

NAPDH oxidase (NOXes) are membrane-bound enzymes that generate reactive oxygen species (ROS) that play a role in immune response and signaling. Misregulation of NOXes is implicated in various human pathologies. NOXes contain a catalytic core comprised of a heme-containing transmembrane (TM) domain and a cytoplasmic dehydrogenase (DH) domain that binds FAD and NADPH. Several conserved regions at the interface of the TM and DH domains in eukaryotic NOXes have been suggested to mediate enzyme function and activity. In 2017, researchers successfully purified SpNox, a bona fide NOX homolog from Streptococcus pneumoniae and verified its NOX properties. SpNox’s robust activity in …

Nutritional Composition, Sensory Profile And Consumer Acceptability Of Wheat-Jackfruit Seed Composite Buns, Sarah S Ngwere, Richard J Mongi

Tanzania Journal of Science

Jackfruit seeds flour is very rich in nutrients and may be incorporated into wheat flour to develop nutrient dense baked products. Consumption of these products may improve the nutrition status of the people, hence fulfill sustainable development goal number two. In this study, nutritional composition, sensory profile, and consumer acceptability of wheat-jackfruit seeds composite buns (Mandazi) were investigated. Jackfruit seeds flour (JSF) was developed and incorporated into wheat flour (WF) at 10, 20, and 30% to produce composite flour used for bun preparation. Flours and buns were subjected to proximate, mineral, and sensory analyses with WF serving as a control …

Preparation Of Meta-Nitrobenzoylhydrazone Ferrocenoylacetone And Synthesis On Its Basis, Zilola Abduraxmonovna Sulaymonova, Bako Bafayevich Umarov Doctor Chemical Science, Professor

Chemical Technology, Control and Management

β-diketone-ferrocenoylacetone was obtained by Claisen condensation. Meta-nitrobenzoylhydrazone of ferrocenoylacetone (H₂L) was synthesized by the interaction of meta-nitrobenzoic acid hydrazide with ferrocenoylacetone. On its basis, complexes with copper(II) and nickel(II) ions were synthesized. The obtained compounds were characterized by the methods of elemental analysis, IR-, ¹H NMR andelectronic spectroscopy. The research results showed that H₂L in solution exists in the form of a tautomeric mixture: hydrazone, α-hydroxyazine, and cyclic 5-hydroxypyrazoline forms. According to the results of IR and ¹H NMR spectra, the complexes were assigned a planar-square structure, and in them the doubly deprotonated …

High-Throughput Phenotyping Of Rice Grains Subjected To High Nighttime Temperature Stress, Shannon Shareice Cunningham

Student Theses and Dissertations

Rice grain size is affected by high nighttime temperature stress (HNT). Although studied in small subsets, the Rice Diversity Panel 1 has not been extensively studied to determine HNT effects on grain size. Accessions have been identified as tolerant and sensitive to HNT under greenhouse conditions (Dhatt et al., 2020). A high throughput phenotyping (HTPP) method and a PlantCV2 workflow were implemented in this work to determine grain dimensions. Seed area was found to be a good indicator of HNT tolerance with a coefficient of variation being 15%. Among tolerant accessions, seed area increased by an average of 1.57 mm2 …

Effects Of Osmotic Stress Induced By Polyethylene Glycol (Peg) 6000 And Mannitol On Seed Germination And Seedling Growth Of Durum Wheat, Ratiba Bousba, Rabah Bounar, Narimene Sedrati, Randa Lakhal, Chourouk Hamla, Malika Rached-Kanouni

Journal of Bioresource Management

Seed germination is generally the critical step in seed establishment and thus the determination of successful crop production. This study was focused at examination of the biochemical and germination parameters effected by low water potential which was generated by polyethylene glycol (PEG) 6000 and mannitol, related to drought stress and growth of Waha durum wheat genotype. Two tests were carried out in a growth chamber; the first comprises seed germination into Petri dishes in the presence of different concentrations of the two osmoticums (0, 5, 10, 15 and 20 % of PEG6000 and mannitol). The second test was carried out …

Insights Into Halophilic Microbial Adaptation: Analysis Of Integrons And Associated Genomic Structures And Characterization Of A Nitrilase In Hypersaline Environments, Sarah Sonbol

Theses and Dissertations

Hypersaline environments are extreme habitats that can be exploited as biotechnological resources. Here, we characterized a nitrilase (NitraS-ATII) isolated from Atlantis II Deep brine pool. It showed higher thermal stability and heavy metal tolerance compared to a closely related nitrilase.

We also studied integrons in halophiles and hypersaline environments. Integrons are genetic platforms in which an integron integrase (IntI) mediates the excision and integration of gene cassettes at specific recombination sites. In order to search for integrons in halophiles and hypersaline metagenomes, we used a PCR-based approach, in addition to different bioinformatics tools, mainly IntegronFinder.

We found that integrons and …

Down The Iron Path: Mitochondrial Iron Homeostasis And Beyond, Jonathan Dietz, Jennifer L. Fox, Oleh Khalimonchuk

Department of Biochemistry: Faculty Publications

Cellular iron homeostasis and mitochondrial iron homeostasis are interdependent. Mitochondria must import iron to form iron–sulfur clusters and heme, and to incorporate these cofactors along with iron ions into mitochondrial proteins that support essential functions, including cellular respiration. In turn, mitochondria supply the cell with heme and enable the biogenesis of cytosolic and nuclear proteins containing iron–sulfur clusters. Impairment in cellular or mitochondrial iron homeostasis is deleterious and can result in numerous human diseases. Due to its reactivity, iron is stored and trafficked through the body, intracellularly, and within mitochondria via carefully orchestrated processes. Here, we focus on describing the …