Digital Commons Network^™

A Study On The Function Of 14-3-3sigma In Regulating Cancer Energy Metabolism, Liem M. Phan, Liem M. Phan

Dissertations and Theses (Open Access)

Metabolic reprogramming has been shown to be a major cancer hallmark providing tumor cells with significant advantages for survival, proliferation, growth, metastasis and resistance against anti-cancer therapies. Glycolysis, glutaminolysis and mitochondrial biogenesis are among the most essential cancer metabolic alterations because these pathways provide cancer cells with not only energy but also crucial metabolites to support large-scale biosynthesis, rapid proliferation and tumorigenesis. In this study, we find that 14-3-3σ suppresses all these three metabolic processes by promoting the degradation of their main driver, c-Myc. In fact, 14-3-3s significantly enhances c-Myc poly-ubiquitination and subsequent degradation, reduces c-Myc transcriptional activity, and down-regulates …

The Role Of Hsc-70 In Very Low Density Lipoprotein Tranport Vesicle Golgi Fusion Complex Formation, Erika Nafi Valencia

HIM 1990-2015

Excess production and secretion of very low-density lipoprotein (VLDL) by the liver into the circulatory system is directly related to atherosclerosis, a chronic cardiovascular disease that threatens the lives of many worldwide and continues to be a leading cause of death in the United States. The rate-limiting step in VLDL secretion is its transport from the site of biogenesis, the hepatic endoplasmic reticulum to the cis-Golgi. This step is mediated by a specialized ER- derived vesicle, the VLDL transport vesicle (VTV). Upon exit of the ER the VTV targets, fuses and delivers VLDL into the lumen of the Golgi. The …

Characterization Of Beryllium As A Novel Agent To Study Cell Cycle Arrest And Cellular Senescence, Priyatham Gorjala

UNLV Theses, Dissertations, Professional Papers, and Capstones

Cancer cells evade senescence, apoptosis, and other constraints on proliferation, often via mutation of the p53 tumor suppressor gene (TP53). Normal human lung fibroblasts have been shown to enter premature senescence upon exposure to beryllium. In these cells, BeSO₄ stabilizes p53 protein, increases p21 gene expression, induces senescence-associated β-galactosidase activity and causes cell proliferation arrest. In the present study, we have investigated whether BeSO₄ is able to induce similar effects in cancer cells that have wildtype p53. We have demonstrated that beryllium salt at low concentration can induce molecular changes in the p53 signaling pathway leading to cell …

Anti-Germinants As A New Strategy To Prevent Clostridium Difficile Infections, Amber Janece Howerton

UNLV Theses, Dissertations, Professional Papers, and Capstones

Clostridium difficileinfections (CDI) have emerged as a leading cause of hospital-associated complications. CDI is the major cause of antibiotic-related cases of diarrhea and nearly all cases of pseudomembranous colitis. The infective form of C. difficileis the spore, a dormant and hardy structure that forms under stress. Germination of C. difficile spores into toxin producing bacteria in the GI tract of susceptible patients is the first step in CDI establishment. Patient susceptibility occurs with a disruption of the natural gut microbiota by broad-spectrum antibiotics. Antibiotic treatments usually resolve CDI but refractory cases are on the rise. Of great concern is the …

The Role Of Centromeric Chromatin And Kinetochore-Associated Factors In Chromosome Segregation, Wesley Williamson

Graduate Theses and Dissertations

Previous work in our lab has identified a point mutation in HTA1, one of the genes encoding histone H2A, which causes an increase-in-ploidy phenotype in Saccharomyces cerevisiae. This histone mutant strain was used to carry out a transposon insertion screen to identify suppressors of the increase-in-ploidy phenotype. This screen identified all three subunits of the Hda histone deacetylase complex, HDA1, HDA2, and HDA3. This study aims to elucidate the function of the Hda complex in chromosome segregation by exploring interactions among the members of the complex, as well as interactions between Hda complex and kinetochore components. …

Functional Analysis Of Drosophila Integrator Complex In Snrna 3' End Processing, Jiandong Chen

Dissertations and Theses (Open Access)

Uridine-rich small nuclear RNAs (U snRNAs) play essential roles in eukaryotic gene expression by facilitating the removal of introns from mRNA precursors and the processing of the replication-dependent histone pre-mRNAs. Formation of the 3’ end of these snRNAs is carried out by a poorly characterized, twelve-membered protein complex named Integrator Complex.

In the effort to understand Integrator Complex function in the formation of the snRNA 3’ end, we performed a functional RNAi screen in Drosophila S2 cells to identify protein factors required for snRNA 3’ end formation. This screen was conducted by using a fluorescence-based reporter that elicits GFP expression …

Structure-Function Analysis Of A Protein Encoded By The Bhv-1 Latency Related Gene, Devis Sinani

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Bovine herpes virus 1 (BHV-1) is a significant viral pathogen in cattle that induces a myriad of clinical symptoms. These symptoms include: conjunctivitis, upper respiratory tract infections, genital disorders, and abortions. BHV-1 infection can also lead to transient immune-suppression, which predisposes cattle to secondary bacterial infection leading to life-threatening pneumonia referred to as bovine respiratory disease (BRD). Following acute infection, BHV-1 establishes latency in sensory neurons within trigeminal ganglia. Reactivation of the virus can occur periodically, resulting in virus transmission. The latency-related (LR) RNA is the only abundantly expressed transcript in latently infected sensory neurons and it encodes several proteins, …

Tumour Inflammasome-Derived Il-1b Recruits Neutrophils And Improves Local Recurrence-Free Survival In Ebv-Induced Nasopharyngeal Carcinoma, Lih-Chyang Chen, Li-Jie Wang, Nang-Ming Tsang, David M. Ojcius, Chia-Chen Chen, Chun-Nan Ouyang, Chuen Hsueh, Ying Liang, Kai-Ping Chang, Chiu-Chin Chen, Yu-Sun Chang

All Dugoni School of Dentistry Faculty Articles

Inflammasomes sense infection and cellular damage and are critical for triggering inflammation through IL-1β production. In carcinogenesis, inflammasomes may have contradictory roles through facilitating antitumour immunity and inducing oncogenic factors. Their function in cancer remains poorly characterized. Here we show that the NLRP3, AIM2 and RIG-I inflammasomes are overexpressed in Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), and expression levels correlate with patient survival. In tumour cells, AIM2 and RIG-I are required for IL-1β induction by EBV genomic DNA and EBV-encoded small RNAs, respectively, while NLRP3 responds to extracellular ATP and reactive oxygen species. Irradiation and chemotherapy can further activate AIM2 …

Reversible Inhibition Of Chlamydia Trachomatis Infection In Epithelial Cells Due To Stimulation Of P2x4 Receptors, Matthew A. Pettengill, Camila Marques-Da-Silva, Maria Luisa Avila, Verissa W. Lam, Ikechukwu Ollawa, Ali Abdul-Sater, Robson Coutinho-Silva, Georg Hacker, David M. Ojcius, Suellen D'Arc Dos Santos Oliveira

All Dugoni School of Dentistry Faculty Articles

Bacterial infections of the mucosal epithelium are a major cause of human disease. The prolonged presence of microbial pathogens stimulates inflammation of the local tissues, which leads to changes in the molecular composition of the extracellular milieu. A well-characterized molecule that is released to the extracellular milieu by stressed or infected cells is extracellular ATP and its ecto-enzymatic degradation products, which function as signaling molecules through ligation of purinergic receptors. There has been little information, however, on the effects of the extracellular metabolites on bacterial growth in inflamed tissues. Millimolar concentrations of ATP have been previously shown to inhibit irreversibly …

Glutaredoxin 2 (Grx2) Knockout Increases Sensitivity To Oxidative Stress In Mouse Lens Epithelial Cells, Hongli Wu, Liren Lin, Frank Giblin, Ye-Sheh Ho, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

Glutaredoxin belongs to the oxidoreductase family with cytosolic glutaredoxin 1 (Grx1) and mitochondrial gluraredoxin 2 (Grx2) isoforms. Of the two isozymes, the function of Grx2 is not well understood. This paper studied the effect of Grx2 deletion on cellular function using primary lens epithelial cell cultures isolated from Grx2 gene knockout (KO) and wild type (WT) mice. We found that both cell types showed similar growth patterns and morphology, and comparable mitochondrial glutathione pool and complex I activity. Cells with deleted Grx2 did not show affected Grx1 or thioredoxin (Trx) expression but exhibited high sensitivity to oxidative stress. Under treatment …

Fancm And Faap24 Maintain Genomic Stability Through Cooperative And Unique Functions, Yucai Wang

Dissertations and Theses (Open Access)

Fanconi anemia (FA) is a rare recessive genetic disease with an array of clinical manifestations including multiple congenital abnormalities, progressive bone marrow failure and profound cancer susceptibility. A hallmark of cells derived from FA patients is hypersensitivity to DNA interstrand crosslinking agents such as mitomycin C (MMC) and cisplatin, suggesting that FA- and FA-associated proteins play important roles in protecting cells from DNA interstrand crosslink (ICL) damage. Two genes involved in the FA pathway, FANCM and FAAP24, are of particular interest because they contain DNA interacting domains. However, there are no definitive patient mutations for these two genes, and the …

Differential Activity Of The Kras Oncogene By Method Of Activation: Implications For Signaling And Therapeutic Intervention, Nathan Ihle

Dissertations and Theses (Open Access)

Despite having been identified over thirty years ago and definitively established as having a critical role in driving tumor growth and predicting for resistance to therapy, the KRAS oncogene remains a target in cancer for which there is no effective treatment. KRas is activated b y mutations at a few sites, primarily amino acid substitutions at codon 12 which promote a constitutively active state. I have found that different amino acid substitutions at codon 12 can activate different KRas downstream signaling pathways, determine clonogenic growth potential and determine patient response to molecularly targeted therapies. Computer modeling of the KRas structure …

The Role Of The Arched Helicases In Exosome-Mediated Function, A. Alejandra Klauer

Dissertations and Theses (Open Access)

RNA processing and degradation are two important functions that control gene expression and promote RNA fidelity in the cell. A major ribonuclease complex, called the exosome, is involved in both of these processes. The exosome is composed of ten essential proteins with only one catalytically active subunit, called Rrp44. While the same ten essential subunits make up both the nuclear and cytoplasmic exosome, there are nuclear and cytoplasmic exosome cofactors that promote specific exosome functions in each of the cell compartments. To date, it is unclear how the exosome distinguishes between RNA substrates. We hypothesize that compartment specific cofactors may …

Trim24-Regulated Estrogen Response Is Dependent On Specific Histone Modifications In Breast Cancer Cells, Teresa T. Yiu

Dissertations and Theses (Open Access)

In this dissertation, I discovered that function of TRIM24 as a co-activator

of ERα-mediated transcriptional activation is dependent on specific histone

modifications in tumorigenic human breast cancer-derived MCF7 cells. In the first

part, I proved that TRIM24-PHD finger domain, which recognizes unmethylated

histone H3 lysine K4 (H3K4me0), is critical for ERα-regulated transcription.

Therefore, when LSD1-mediated demethylation of H3K4 is inhibited, activation of

TRIM24-regulated ERα target genes is greatly impaired. Importantly, I

demonstrated that TRIM24 and LSD1 are cyclically recruited to estrogen

responsive elements (EREs) in a time-dependent manner upon estrogen

induction, and depletion of their expression exert corresponding time-dependent

effect …

Tet1: A Unique Dna Demethylase For Maintenance Of Dna Methylation Pattern, Chunlei Jin

Dissertations and Theses (Open Access)

DNA methylation at the C5 position of cytosine (5-methylcytosine, 5mC) is a crucial epigenetic modification of the genome and has been implicated in numerous cellular processes in mammals, including embryonic development, transcription, X chromosome inactivation, genomic imprinting and chromatin structure. Like histone modifications, DNA methylation is also dynamic and reversible. However, in contrast to well defined DNA methyltransferases, the enzymes responsible for erasing DNA methylation still remain to be studied. The ten-eleven translocation family proteins (TET1/2/3) were recently identified as Fe(II)/2-oxoglutarate (2OG)-dependent 5mC dioxygenases, which consecutively convert 5mC into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine and 5-carboxylcytosine both in vitro and in mammalian …

Gene Duplication And The Evolution Of Hemoglobin Isoform Differentiation In Birds, Michael T. Grispo

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

The majority of bird species co-express two functionally distinct hemoglobin (Hb) isoforms in definitive erythrocytes: HbA (the major adult Hb isoform, with α-chain subunits encoded by the α^A-globin gene) and HbD (the minor adult Hb isoform, with α-chain subunits encoded by the α^D-globin gene). The α^D-globin gene originated via tandem duplication of an embryonic α-like globin gene in the stem lineage of tetrapod vertebrates, which suggests the possibility that functional differentiation between the HbA and HbD isoforms may be attributable to a retained ancestral character state in HbD that harkens back to a primordial, …

Characterization And Epidemiology Of Soybean Vein Necrosis Associated Virus, Jing Zhou

Graduate Theses and Dissertations

Soybean vein necrosis disease (SVND) is widespread in major soybean-producing areas in the U.S. The typical disease symptoms exhibit as vein clearing along the main vein, which turn into chlorosis or necrosis as season progresses. Double-stranded RNA isolation and shot gun cloning of symptomatic tissues revealed the presence of a new tospovirus, provisionally named as Soybean vein necrosis associated virus (SVNaV). The presence of the virus has been confirmed in 12 states: Arkansas, Illinois, Missouri, Kansas, Tennessee, Kentucky, Mississippi, Maryland, Delaware, Virginia and New York. Symptomatic samples collected from eight states (AR, IL, MO, MS, KS, TN, MD and DE), …

Regulation Of The Lipid Raft Localization Of The Gal/Galnac Lectin, An Adhesin On The Surface Of The Human Protozoan Parasite, Entamoeba Histolytica, Amanda Goldston

All Dissertations

Lipid rafts, sterol- and sphingolipid-rich membrane microdomains, have been shown to control virulence in a variety of parasites including Entamoeba histolytica, an intestinal parasite that causes dysentery and liver abscess. Parasite cell surface receptors, such as the Gal/GalNAc lectin, facilitate attachment to host cells and extracellular matrix. The Gal/GalNAc lectin binds to galactose or N-acetylgalactosamine residues on host components, and is composed of heavy (Hgl), intermediate (Igl), and light (Lgl) subunits. Although Igl is constitutively localized to lipid rafts, Hgl and Lgl transiently associate with this compartment in a cholesterol-dependent fashion. Exposure to bonafide Gal/GalNAc lectin ligands is associated with …

A Genetic, Transgenic, And Transcriptomic Analysis Of Larval Salivary Gland Physiology In Drosophila Melanogaster, Elana A. Paladino

UNLV Theses, Dissertations, Professional Papers, and Capstones

Cholesterol is the precursor to a unique class of lipophilic signaling molecules called steroid hormones that initiate the development of sexual characteristics, reactions to stress, and maintenance of metabolism, among many other functions. Although much progress has been made in understanding the function of these signaling hormones, we do not fully understand how a single steroid can cause many distinct, tissue-specific responses. Drosophila melanogaster is an effective model for understanding steroid hormone action because of its simplicity. The steroid molting hormone 20-hydroxyecdysone (hereafter, 20E) is the primary active steroid in Drosophila and mediates not only larval molts and the emergence …

Capillary And Microchip Electrophoresis For The Monitoring Of Disease Causing Amyloid Proteins, Elizabeth Nancy Pryor

Graduate Theses and Dissertations

The detection of oligomers and aggregates formed by two amyloid proteins, insulin and amyloid-beta (AB), is of particular importance due to the role which these species play in Diabetes and Alzheimer's disease, respectively. However, existing techniques are limited in the ability to detect insulin and AB; oligomers due to the fact that these early aggregates are transient, present at low concentrations, and difficult to isolate. Improvements must be made to existing techniques or alternative techniques must be explored in order to identify and quantify the size of these oligomeric and aggregate species without disrupting their structure.

Capillary and microchip electrophoresis …

Sinusoidal Endothelial Dysfunction In Non-Alcoholic Fatty Liver Disease., Sandhya Lakshmi Gopalakrishnan

Department of Biochemistry: Dissertations, Theses, and Student Research

Non-alcoholic fatty liver disease (NAFLD) is an asymptomatic increasingly common disorder that affects liver metabolism and is often the precursor for liver pathologies such as fibrosis, cirrhosis and hepato-cellular carcinoma. The liver sinusoidal endothelial cells act as a liver sieve by allowing macromolecules and chylomicrons to traverse through their fenestrations (sieve plates) to hepatocytes. Since liver sinusoidal endothelial cells (LSEC) regulate serum derived macromolecular exposure to hepatocytes, we asked what role LSEC could play in the pathogenesis of NAFLD. To investigate the early events of NAFLD we used a rat model (Sprague-Dawley) in which animals were maintained on standard and …

Microfabrication, Characterization, And Application Of Carbon Nanotube Templated Thin Layer Chromatography Plates, And Functionalization Of Porous Graphitic Carbon, David S. Jensen

Theses and Dissertations

This dissertation contains the following sections. Chapter 1 contains a detailed description of the theory of thin layer chromatography (TLC). Chapter 2 describes the benefits and practical considerations of elevated temperatures in liquid chromatography (LC). The porous graphitic carbon (PGC) I modified as part of my work is often used in elevated temperature LC. Chapter 3 shows a thermodynamic analysis of chromatographic retention at elevated temperature, and Chapter 4 contains a closer look at the van 't Hoff equation in LC and how it can be used in retention modeling. In Chapter 5, I describe a new procedure for microfabricating …

Deposition And Characterization Of Hydrophobic Coatings, Vipul Gupta

Theses and Dissertations

Hydrophobic coatings find application in various sectors of the economy including to electronics, textiles, optical devices, and in scientific and commercial equipment. These different applications demand that different hydrophobic coatings posses a range of properties that may include smoothness or roughness, thicknesses on the order of a monolayer or a micron, robustness or the ability to dissolve quickly, transparency or opacity, water resistance or water permeability, electrical conductivity, oleophobicity, etc. However, whatever the final/desired properties, deposition via dry-deposition processes offers significant advantages, including greater reproducibility, increased environmental friendliness, and cost effectiveness on an industrial scale. Herein I explore the chemical …

Medicinal Plants: A Public Resource For Metabolomics And Hypothesis Development, Eve Syrkin Wurtele, Joe Chappell, A. Daniel Jones, Mary Dawn Celiz, Nick Ransom, Manhoi Hur, Ludmila Rizshsky, Matthew Crispin, Philip Dixon, Jia Liu, Mark P. Widrlechner, Basil J. Nikolau

Molecular and Cellular Biochemistry Faculty Publications

Specialized compounds from photosynthetic organisms serve as rich resources for drug development. From aspirin to atropine, plant-derived natural products have had a profound impact on human health. Technological advances provide new opportunities to access these natural products in a metabolic context. Here, we describe a database and platform for storing, visualizing and statistically analyzing metabolomics data from fourteen medicinal plant species. The metabolomes and associated transcriptomes (RNAseq) for each plant species, gathered from up to twenty tissue/organ samples that have experienced varied growth conditions and developmental histories, were analyzed in parallel. Three case studies illustrate different ways that the data …

Complex Of Myoglobin With Phenol Bound In A Proximal Cavity, Xiao Huang, Chunxue Wang, Lesa R. Celeste, Leslie L. Lovelace, Shengfang Sun, John H. Dawson, Lukasz Lebioda

Faculty Publications

Sperm whale myoglobin (Mb) has weak dehaloperoxidase activity and catalyzes the peroxidative dehalogenation of 2,4,6-trichlorophenol (TCP) to 2,6-dichloroquinone. Crystals of Mb and of its more active G65T variant were used to study the binding of TCP, 4-iodophenol (4-IP) and phenol. The structures of crystals soaked overnight in a 10 mM solution of phenol revealed that a phenol molecule binds in the proximal cavity, forming a hydrogen bond to the hydroxyl of Tyr146 and hydrophobic contacts which include interactions with C and C of the proximal histidine His93. The phenol position corresponds to the strongest xenon binding site, Xe1. It …

Proposed Coherent Trapping Of A Population Of Electrons In A C60 Molecule Induced By Laser Excitation, Thomas George, G.P. Zhang

Chemistry & Biochemistry Faculty Works

This Letter demonstrates the possibility of generating coherent population trapping in C60. Similar to a three-level Λ system, C60 has a forbidden transition between the highest occupied molecular orbital (HOMO) (|a⟩) and the lowest unoccupied molecular orbital (LUMO) (|c⟩), but a dipole-allowed transition between HOMO and LUMO+1 (|b⟩) and between |b⟩ and |c⟩. We employ two cw laser fields, one coupling and one probe. The strong coupling field is switched on first to resonantly excite the transition between |b⟩ and |c⟩. After a delay, the probe is switched on; the coherent interaction between the coupling and probe fields traps the …

P21-Activated Kinase-1 Signaling Regulates Transcription Of Tissue Factor And Tissue Factor Pathway Inhibitor., Beatriz Sanchez-Solana, Mona Motwani, Da-Qiang Li, Jeyanthy Eswaran, Rakesh Kumar

Biochemistry and Molecular Medicine Faculty Publications

Tissue factor (TF) is a cell-surface glycoprotein responsible for initiating the coagulation cascade. Besides its role in homeostasis, studies have shown the implication of TF in embryonic development, cancer related events, and inflammation via coagulation-dependent and -independent (signaling) mechanisms. Tissue factor pathway inhibitor (TFPI) plays an important role in regulating TF-initiated blood coagulation. Therefore, transcriptional regulation of TF expression and its physiologic inhibitor TFPI, would allow us to understand the critical step that control many different processes. From a gene profiling study aimed to identify differentially regulated genes between wild type (WT) and p21-activated kinase 1-null (PAK1-KO) mouse embryonic fibroblasts …

Controls Of Nucleosome Positioning In The Human Genome, Daniel J. Gaffney, Graham Mcvicker, Athma A. Pai, Yvonne N. Fondufe-Mittendorf, Noah Lewellen, Katelyn Michelini, Jonathan Widom, Yoav Gilad, Jonathan K. Pritchard

Molecular and Cellular Biochemistry Faculty Publications

Nucleosomes are important for gene regulation because their arrangement on the genome can control which proteins bind to DNA. Currently, few human nucleosomes are thought to be consistently positioned across cells; however, this has been difficult to assess due to the limited resolution of existing data. We performed paired-end sequencing of micrococcal nuclease-digested chromatin (MNase-seq) from seven lymphoblastoid cell lines and mapped over 3.6 billion MNase-seq fragments to the human genome to create the highest-resolution map of nucleosome occupancy to date in a human cell type. In contrast to previous results, we find that most nucleosomes have more consistent positioning …

Targeting Astrocytes Ameliorates Neurologic Changes In A Mouse Model Of Alzheimer's Disease, Jennifer L. Furman, Diana M. Sama, John C. Gant, Tina L. Beckett, M. Paul Murphy, Adam D. Bachstetter, Linda J. Van Eldik, Christopher M. Norris

Pharmacology and Nutritional Sciences Faculty Publications

Astrocytes are the most abundant cell type in the brain and play a critical role in maintaining healthy nervous tissue. In Alzheimer's disease (AD) and most other neurodegenerative disorders, many astrocytes convert to a chronically "activated" phenotype characterized by morphologic and biochemical changes that appear to compromise protective properties and/or promote harmful neuroinflammatory processes. Activated astrocytes emerge early in the course of AD and become increasingly prominent as clinical and pathological symptoms progress, but few studies have tested the potential of astrocyte-targeted therapeutics in an intact animal model of AD. Here, we used adeno-associated virus (AAV) vectors containing the astrocyte-specific …

Mechanism Of Selective Vegf-A Binding By Neuropilin-1 Reveals A Basis For Specific Ligand Inhibition, Matthew W. Parker, Ping Xu, Hou-Fu Guo, Craig W. Vander Kooi

Molecular and Cellular Biochemistry Faculty Publications

Neuropilin (Nrp) receptors function as essential cell surface receptors for the Vascular Endothelial Growth Factor (VEGF) family of proangiogenic cytokines and the semaphorin 3 (Sema3) family of axon guidance molecules. There are two Nrp homologues, Nrp1 and Nrp2, which bind to both overlapping and distinct members of the VEGF and Sema3 family of molecules. Nrp1 specifically binds the VEGF-A_164/5 isoform, which is essential for developmental angiogenesis. We demonstrate that VEGF-A specific binding is governed by Nrp1 residues in the b1 coagulation factor domain surrounding the invariant Nrp C-terminal arginine binding pocket. Further, we show that Sema3F does not display …