Amino Acids, Peptides, and Proteins Commons^™

Her2 Alterations Across Solid Tumors: Implications For Comprehensive Testing, Ahmed Ismail, Chimay Jani, Nusrat Jahan, Malla Midhun, Arnab Basu, Garima Gupta, Bassel El-Rayes, Sejong Bae, Tyler Mattox, Cyntanna Hawkins, Rebecca C. Arend, Mehmet Akce, Yanis Boumber, Aakash Desai

Department of Medicine Faculty Publications

Purpose

ERBB2 (HER2) alterations (e.g., overexpression, amplification, and mutations) are known to drive tumor progression. These changes, particularly in non-breast and gastric/gastroesophageal cancers, remain poorly characterized. With pan-tumor approval of HER2-targeted therapies like Trastuzumab deruxetecan (T-DXd), understanding ERBB2 alterations across diverse cancers is crucial.

Methods

HER2 analysis was conducted on 653 solid tumor specimens at the University of Alabama, using immunohistochemistry (IHC), copy number (CN) variation (CNV) assessment, and mutational profiling. The correlation between CN amplification and IHC expression was evaluated using Somers' D ordinal association.

Results

Of the 653 cases, HER2 IHC scores were distributed as 3 + (3.1%), …

A Novel D-Peptide Modulates Dclk1 Gelsolin Interactions, Reducing Pdac Tumor Growth, Landon L. Moore, Dongfeng Qu, Parthasarathy Chandrekesan, Kamille Pitts, Randal May, Byron E. Anderson, Milton L. Brown, Courtney W. Houchen

Department of Medicine Faculty Publications

What drives inflammation-associated tumorigenesis and progression in pancreatic ductal adenocarcinoma (PDAC)? Doublecortin-like kinase 1 (DCLK1) is a central driver of inflammation-associated tumorigenesis, with elevated expression linked to worse clinical outcomes. Two isoforms of DCLK1 possess a unique extracellular domain (ECD). DCLK1 isoform 2 contains two microtubule-binding domains, while isoform 4, lacks the microtubule-binding domains but, plays a pivotal role in tumor progression. We identified novel D-peptides that selectively target this ECD, significantly suppressing PDAC cell proliferation in vitro and tumor growth in xenograft models without inducing cell death. In silico modeling and binding assays revealed DCLK1 isoform 4 interacts with …

Fibrinolysis For Apical Thrombus As A Bridge To Emergent Valve-In-Valve Transcatheter Aortic Valve Replacement, Nicholas J. Valle, Omar A. Saleh, Mani C. Akunuri, Parth K. Parikh, Joshua A. Cohen, Deepak R. Talreja, Matthew R. Summers

Department of Medicine Faculty Publications

Background

Left ventricular (LV) thrombus is traditionally a contraindication to transcatheter aortic valve replacement due to embolic risk. Consequently, management of valvular cardiogenic shock complicated by LV thrombus identifies unique challenges that require innovative strategies.

Case Summary

A 58-year-old woman with critical bioprosthetic aortic stenosis, cardiogenic shock, and large LV thrombus (2.8 × 2.6 cm) underwent successful valve-in-valve transcatheter aortic valve replacement after systemic fibrinolysis bridge therapy.

Why Beyond the Guidelines

Current guidelines contraindicate transcatheter aortic valve replacement in patients with LV thrombus. This case demonstrates the novel use of low-dose, slow infusion tissue plasminogen activator as a bridge therapy …

Automating The Amino Acid Identification In Elliptical Dichroism Spectrometer With Machine Learning, Ridhanya Sree Balamurugan, Yusuf Asad, Tommy Gao, Dharmakeerthi Nawarathna, Umamaheswara Rao Tida, Dali Sun

Electrical & Computer Engineering Faculty Publications

Amino acid identification is crucial across various scientific disciplines, including biochemistry, pharmaceutical research, and medical diagnostics. However, traditional methods such as mass spectrometry require extensive sample preparation and are time-consuming, complex and costly. Therefore, this study presents a pioneering Machine Learning (ML) approach for automatic amino acid identification by utilizing the unique absorption profiles from an Elliptical Dichroism (ED) spectrometer. Advanced data preprocessing techniques and ML algorithms to learn patterns from the absorption profiles that distinguish different amino acids were investigated to prove the feasibility of this approach. The results show that ML can potentially revolutionize the amino acid analysis …

Reversible Degradation Of Peptidoglycan By Lytic Transglycosylases, Aaron Devereaux

Theses and Dissertations (Comprehensive)

Antimicrobial resistance continues to be a burden on the global healthcare system with an estimated cost of billions of dollars and millions of deaths each year. Recently, there has been little to no development on new antibiotics to treat bacterial infection, and any that are developed become resisted to within a few years. Both Gram-positive and Gram-negative bacteria contain a mesh-like layer called peptidoglycan (PG) that surrounds their cells providing strength, cell shape, and protection from their environments. This layer is a polymer of N-acetylmuramic acid (MurNAc) and N-acetylglucosamine (GlcNAc) connected via a b-1,4-glycosidic bond, with each strand being cross-linked …

Cath-Ddg: Towards Robust Mutation Effect Prediction On Protein-Protein Interactions Out Of Cath Homologous Superfamily, Guanglei Yu, Xuehua Bi, Teng Ma, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

Motivation: Protein-protein interactions (PPIs) are fundamental aspects in understanding biological processes. Accurately predicting the effects of mutations on PPIs remains a critical requirement for drug design and disease mechanistic studies. Recently, deep learning models using protein 3D structures have become predominant for predicting mutation effects. However, significant challenges remain in practical applications, in part due to the considerable disparity in generalization capabilities between easy and hard mutations. Specifically, a hard mutation is defined as one with its maximum TM-score < 0.6 when compared to the training set. Additionally, compared to physics-based approaches, deep learning models may overestimate performance due to potential data leakage.

Results: We propose new training/test splits that mitigate data leakage according to the CATH homologous superfamily. Under the constraints of physical …

A Survey On Deep Learning For Drug-Target Binding Prediction: Models, Benchmarks, Evaluation, And Case Studies, Kusal Debnath, Pratip Rana, Preetam Ghosh

Computer Science Faculty Publications

Conventional drug discovery is expensive, time-consuming, and prone to failure. Artificial intelligence has become a potent substitute over the last decade, providing strong answers to challenging biological issues in this field. Among these difficulties, drug-target binding (DTB) is a key component of drug discovery techniques. In this context, drug-target affinity and drug–target interaction are complementary and essential frameworks that work together to improve our comprehension of DTB dynamics. In this work, we thoroughly analyze the most recent deep learning models, popular benchmark datasets, and assessment metrics for DTB prediction. We look at the paradigm shift in the development of drug …

Deepssetracer 2.0: Improved Deep Learning Model Performance For Protein Secondary Structure Segmentation From Cryo-Em Maps, Bryan Hawickhorst, Thu Nguyen, Willy Wriggers, Jiangwen Sun, Jing He

Computer Science Faculty Publications

DeepSSETracer is a method for segmenting protein secondary structure from medium-resolution (5-10Å) cryogenic electron microscopy (cryo-EM) density maps. We conducted experiments and ablation studies to examine the effects of normalization methods, max-pooling, activation functions, and loss calculation region on DeepSSETracer. By combining multiple technical improvements, the performance of the new version, DeepSSETracer 2.0, was significantly enhanced compared to DeepSSETracer 1.1. On a set of 77 test cases, the weighted average per-voxel F1 score increased from 62.1% to 70.3% for helix detection, and from 47.8% to 62.5% for β-sheet detection. While each of the five modifications in the network enhanced the …

The Complexity And Significance Of Fibroblast Growth Factor (Fgf) Signaling For Fgf-Targeted Cancer Therapies, Anh Nguyen, Caroline Facey, Bruce Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Fibroblast growth factors (FGFs) have diverse functions in the regulation of cell proliferation and differentiation in development, tissue maintenance, wound repair, and angiogenesis. The goal of this review paper is to (i) deliberate on the role of FGFs and FGF receptors (FGFRs) in different cancers, (ii) present advances in FGF-targeted cancer therapies, and (iii) explore cell signaling mechanisms that explain how FGF expression becomes dysregulated during cancer development. FGF is often mutated and overexpressed in cancer and the different FGF and FGFR isoforms have unique expression patterns and distinct roles in different cancers. Among the FGF members, the FGF 15/19 …

Determination Of The Kinetic Parameters Of Cholesterol Oxidation Using Cholesterol Oxidase From Streptomyces Sp., Meka Saima Perdani, Heri Hermansyah, Muhamad Sahlan, Dwini Normayulisa Putri, Teguh Pambudi, Anggi Khairina Hanum Hasibuan

Makara Journal of Technology

Cholesterol oxidase (CO) was successfully produced from Streptomyces sp. via the submerged fermentation method, and 69 U/mL enzyme activity was obtained. This study aimed to determine cholesterol oxidation kinetics and the production of CO as a catalyst. The enzyme was diluted to 0.15, 0.075, and 0.00375 U/mL for the oxidation reaction. The substrate was also prepared in three concentrations: 3.23, 6.46, and 12.93 mM. The optimization of conditions for enzymatic cholesterol oxidation was investigated through measurement of the effect of initial cholesterol and enzyme concentrations. Cholesterol concentration was rapidly measured via high-performance liquid chromatography (HPLC). The kinetics of CO were …

Assembly Of Ppsu-Oligomers, Mariam Nesterov

Student Theses and Dissertations

The development of nanostructures for delivering multiple proteins to targeted antibodies has become a promising avenue in biotechnology, driven by advancements in synthetic polymers like poly(propylene sulfone), PPSU. However, the PPSU polymer faces a major limitation - its high insolubility. To address this challenge, this study investigates whether PPSU oligomers can enhance both the solubility and stability of lysozyme, a model protein that is cost-effective and widely accessible. Using dimer, trimer, tetramer, and hexamer configurations, we analyzed the interactions between PPSU oligomer and lysozyme under varying conditions. Our results show that the dimer and trimer are water soluble (no aggregate …

Proteoglycan 4 (Lubricin) And Regulation Of Xanthine Oxidase In Synovial Macrophage As A Mechanism Of Controlling Synovitis, Khaled A. Elsaid, Ling X. Zhang, Thomas Zhao, Ava Marks, Derek Jenkins, Tannin A. Schmidt, Gregory D. Jay

Pharmacy Faculty Articles and Research

Background

Synovial macrophages (SMs) are important effectors of joint health and disease. A novel Cx3CR1 + TREM2 + SM population expressing the tight junction protein claudin-5, was recently discovered in synovial lining. Ablation of these SMs was associated with onset of arthritis. Proteoglycan 4 (PRG4) is a mucinous glycoprotein that fulfills lubricating and homeostatic roles in the joint. The aim of this work is to study the role of PRG4 in modulating synovitis in the context of SM homeostasis and assess the contribution of xanthine oxidase (XO)-hypoxia inducible factor alpha (HIF-1a) axis to this regulation.

Methods

We used Prg4FrtloxP/FrtloxP …

A Conjugate Of An Egfr-Binding Peptide And Doxorubicin Shows Selective Toxicity To Triple-Negative Breast Cancer Cells, Phi-Phung Than, Shih-Jing Yao, Emad Althagafi, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Selective targeting of cancer cells via overexpressed cell-surface receptors is a promising strategy to enhance chemotherapy efficacy and minimize off-target side effects. In this study, we designed peptide 31 (YHWYGYTPERVI) to target the overexpressed epidermal growth factor receptor (EGFR) in triple-negative breast cancer (TNBC) cells. Peptide 31 is internalized by TNBC cells through EGFR-mediated endocytosis and shares sequence and structural similarities with human EGF (hEGF), a natural EGFR ligand. Unlike hEGF, peptide 31 does not induce cell migration in TNBC cells. A novel conjugate of peptide 31 with doxorubicin (Dox) retains selectivity for TNBC cells and exhibits significant toxicity comparable …

Design, Synthesis, And Nmr-Guided Characterization Of A Targeted Covalent Inhibitor-Like Molecule Against Ivyp1 From P. Aeruginosa, Samuel Taylor Moore

Master's Theses

Multi-drug resistance poses a serious threat to future generations and historical antibiotic pipelines; consequently, the medical and economic burdens associated with treating multidrug-resistant bacteria are substantiated. In this context, P. aeruginosa (PA) emerges as one of the most significant healthcare challenges, being a leading cause of resistance-associated mortality worldwide. Despite modern efforts to combat these poor outcomes, drug-resistant cases continue to rise, and the need for novel antibiotic treatment is apparent. To this end, we investigated relevant resistance mechanisms and past antibiotic targets within PA, and in doing so, we identified relationships between peptidoglycan biology and a periplasmic protein, Inhibitor …

Induction Of Tier 2 Hiv-Neutralizing Iga Antibodies In Rhesus Macaques Vaccinated With Bg505.664 Sosip, Justin C. Smith, Prabhu S. Arunachalam, Traci H. Legere, Lisa A. Cavacini, Eric Hunter, Bali Pulendran, Rama R. Amara, Pamela A. Kozlowski

School of Graduate Studies Faculty Publications

BACKGROUND: A goal of mucosal human immunodeficiency virus type 1 (HIV-1) vaccines is to generate mucosal plasma cells producing polymeric IgA (pIgA)-neutralizing antibodies at sites of viral entry. However, vaccine immunogens capable of eliciting IgA neutralizing antibodies (nAbs) that recognize tier 2 viral isolates have not yet been identified. METHODS: To determine if stabilized native-like HIV-1 envelope (Env) trimers could generate IgA nAbs, we purified total IgA and IgG from the banked sera of six rhesus macaques that had been found in a previous study to develop serum nAbs after subcutaneous immunization with BG505.664 SOSIP and 3M-052 adjuvant, which is …

Evolving Treatment Strategies For Systemic Lupus Erythematosus In Clinical Practice: A Narrative Review, Alan D. Kaye, Joseph P. Tassin, William C. Upshaw, Chandni R. Patel, Alison M. Hawkins, Caroline R. Burroughs, Kristin Nicole Bembenick, Chizoba N. Mosieri, Shahab Ahmadzadeh, Adam M. Kaye, Sahar Shekoohi, Giustino Varrassi

School of Dentistry Faculty Publications

Systemic lupus erythematosus (SLE) is an autoimmune disease that more commonly affects African American people, although it is seen in people of all racial backgrounds. This condition is characterized by a dysregulated immune response resulting in widespread inflammation. Clinical manifestations caused by this inflammation include arthritis, anemia, cutaneous rashes, pleuritis, and nephritis. Treatment for SLE aims to reduce disease activity and maintain a state of low inflammation. In this regard, numerous treatments are used, such as hydroxychloroquine, glucocorticoids, and non-glucocorticoid immunosuppressants such as methotrexate. Related to these drugs resulting in significant adverse effects and being ineffective in controlling SLE symptoms …

Alphafold2-Based Characterization Of Apo And Holo Protein Structures And Conformational Ensembles Using Randomized Alanine Sequence Scanning Adaptation: Capturing Shared Signature Dynamics And Ligand-Induced Conformational Changes, Nishank Raisinghani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Proteins often exist in multiple conformational states, influenced by the binding of ligands or substrates. The study of these states, particularly the apo (unbound) and holo (ligand-bound) forms, is crucial for understanding protein function, dynamics, and interactions. In the current study, we use AlphaFold2, which combines randomized alanine sequence masking with shallow multiple sequence alignment subsampling to expand the conformational diversity of the predicted structural ensembles and capture conformational changes between apo and holo protein forms. Using several well-established datasets of structurally diverse apo-holo protein pairs, the proposed approach enables robust predictions of apo and holo structures and conformational ensembles, …

Nuclear Expression Of Dynamin 2 Is Associated With Tumor Aggressiveness In Bladder Cancer Patients: A Bioinformatics And Experimental Approach, Mahdieh Razmi, Leili Saeednejad Zanjani, Mandana Rahimi, Roya Sajed, Sadegh Safaei, Zahra Madjd, Roya Ghods

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Dynamin 2 (DNM2) is aberrantly expressed in different malignancies and exerts a function in tumor progression.

AIMS: This study, for the first time, aimed to evaluate the clinical and prognostic value of DNM2 in the pathophysiology of bladder cancer using bioinformatics analysis and experimental evaluation.

METHODS AND RESULTS: We analyzed gene expression of DNM2 in bladder tumor by GEPIA2 and GENT2 platforms. Cluster subnetworks were recognized from the protein-protein interaction (PPI) network using the MCODE plugin to screen the key genes. Subsequently, the pathway enrichment analysis was evaluated. Then, the immunohistochemical examination was conducted on 209 paraffin-embedded bladder cancer …

The Life And Discoveries Of Yellapragada Subbarow, Nikhil R, Varuni Pragya, Subramanian Ramaswamy, Shiva Prasad B N, Mahabaleshwar Mamadapur

Digital Journal of Clinical Medicine

Dr. Yellapragada Subbarow was a researcher, teacher, and a wizard of wonder drugs who constantly made efforts in the discoveries/ inventions such as vitamins, anti-vitamins, antibiotics, and many more by disentangling the mysteries of nature for the betterment of the people. He inspired the youngsters to take up the challenges and to stand up above mediocrity. The reward for his achievement was delayed. The article describes a true humanist's journey, discoveries, and his achievements that are largely unknown to date.

Opa1 And Disease-Causing Mutants Perturb Mitochondrial Nucleoid Distribution, J. Macuada, I. Molina-Riquelme, G. Vidal, N. Pérez-Bravo, C. Vásquez-Trincado, G. Aedo, D. Lagos, P. Yu-Wai-Man, R. Horvath, T. J. Rudge, B. Cartes-Saavedra, V. Eisner

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Optic atrophy protein 1 (OPA1) mediates inner mitochondrial membrane (IMM) fusion and cristae organization. Mutations in OPA1 cause autosomal dominant optic atrophy (ADOA), a leading cause of blindness. Cells from ADOA patients show impaired mitochondrial fusion, cristae structure, bioenergetic function, and mitochondrial DNA (mtDNA) integrity. The mtDNA encodes electron transport chain subunits and is packaged into nucleoids spread within the mitochondrial population. Nucleoids interact with the IMM, and their distribution is tightly linked to mitochondrial fusion and cristae shaping. Yet, little is known about the physio-pathological relevance of nucleoid distribution. We studied the effect of OPA1 and ADOA-associated mutants on …

Role Of Myeloid Cell-Specific Adenylyl Cyclase Type 7 In Lipopolysaccharide- And Alcohol-Induced Immune Responses, Yawen Hu, Sonika Patial, Yogesh Saini, Masami Yoshimura

School of Graduate Studies Faculty Publications

Clinical and experimental evidence indicates that alcohol use causes various abnormalities in the immune system and compromises immune functions. However, the mechanistic understanding of ethanol’s effects on the immune system remains limited. Cyclic AMP (cAMP) regulates multiple processes, including immune responses. Earlier research indicated that type 7 adenylyl cyclase (AC7) regulates the immune system and is highly responsive to ethanol. Therefore, we hypothesized that AC7 is a central player in regulating the effects of alcohol on innate immune responses. To test this hypothesis, we utilized a myeloid lineage-specific AC7 KO mouse model and compared the effects of acute and chronic …

Functions Of Tam Receptors And Ligands Protein S And Gas6 In Atherosclerosis And Cardiovascular Disease, Teagan Prouse, Samarpan Majumder, Rinku Majumder

School of Medicine Faculty Publications

Atherosclerosis and cardiovascular disease are associated with high morbidity and mortality in industrialized nations. The Tyro3, Axl, and Mer (TAM) family of receptor tyrosine kinases is involved in the amplification or resolution of atherosclerosis pathology and other cardiovascular pathology. The ligands of these receptors, Protein S (PS) and growth arrest specific protein 6 (Gas6), are essential for TAM receptor functions in the amplification and resolution of atherosclerosis. The Axl-Gas6 interaction has various effects on cardiovascular disease. Mer and PS dampen inflammation, thereby protecting against atherosclerosis progression. Tyro3, the least studied TAM receptor in cardiovascular disease, appears to protect against fibrosis …

Unravelling The Erythropoietin Heterodimeric Complex: In Silico Analysis Of Complex Assembly And Binding Interface, Atiya Habib, Urooj Qureshi, Mohammad Nur-E-Alam, Aftab Ahmed, Zaheer Ul-Haq

Pharmacy Faculty Articles and Research

Erythropoietin (Epo), a glycosylated protein categorized as a member of the cytokine family, is responsible for the modulation of erythrogenesis. Besides this, the nonhaematopoietic effects of Epo are associated with tissue-protective activity via an antiapoptotic pathway. This function of Epo is linked with its heterodimeric form, i.e. EpoR/βcR belonging to the cytokine family as well. Both receptors are dissected into three domains: extracellular (also known as ligand-binding domain), transmembrane and cytoplasmic domain. The transmembrane and cytoplasmic domains are assumed to play a paramount role in dimerization and tissue protection. However, the tertiary structure of cytoplasmic domains of both …

Acute Stress Activates Basolateral Amygdala Neurons Expressing Corticotropin-Releasing Hormone Receptor Type 1 (Crhr1): Topographical Distribution And Projection-Specific Activation In Male And Female Rats, Robert J. Aukema, Gavin N. Petrie, Samantha L. Baglot, Nicholas W. Gilpin, Matthew N. Hill

School of Medicine Faculty Publications

Although the basolateral amygdala (BLA) and corticotropin releasing hormone receptor type I (CRHR1) signaling are both central to the stress response, the spatial and circuit-specific distribution of CRHR1 have not been identified in the BLA at a high resolution. We used transgenic male and female CRHR1-Cre-tdTomato rats to topographically map the distribution of BLA neurons and identify whether they are activated by acute stress. Additionally, we used the BLA circuits projecting to the central amygdala (CeA) and nucleus accumbens (NAc) as a model to test circuit-specific expression of CRHR1 in the BLA. We established several key findings. First, CRHR1 had …

Meca In Streptococcus Mutans Is A Multi-Functional Protein, Kassapa Ellepola, Robert C. Shields, Jessica K. Kajfasz, Hua Zhang, Jose A. Lemos, Hui Wu, Zezhang T. Wen

School of Dentistry Faculty Publications

UNLABELLED: Our recent studies have shown that deficiency of MecA in Streptococcus mutans significantly affects cell division, growth, and biofilm formation. In this study, an in vitro mixed-species model, proteomics, and affinity pull-down assays were used to further characterize the MecA-mediated regulation in S. mutans. The results showed that compared with the wild type, UA159, the mecA mutant significantly reduced its production of glucans and weakened its ability to facilitate mixed-species biofilm formation. Relative to the wild type, the mecA mutant also displayed unique characteristics, including colony morphology, growth rate, and biofilm formation that did not fully resemble any of …

Synthesis And Evaluation Of Cyclic Peptide-Dasatinib Conjugates As Anti-Melanoma Agents, Shaban Darwish, Dorna Davani-Davari, Shirley Tong, Rakesh Kumar Tiwari, Sun Yang, Keykavous Parang

Pharmacy Faculty Articles and Research

Herein, we synthesized two amphiphilic cyclic peptides, incorporating tryptophan and arginine residues, linked to dasatinib via a Cathepsin B-sensitive tetrapeptide (Gly-Phe-Leu-Gly). To mitigate steric hindrance and optimize drug release, we integrated two different linkers, succinate and glutarate, between the drug and peptide. The synthesis involved solid-phase techniques for the assembly of the peptide, followed by the coupling of the peptide on-resin with the linker, mild cleavage, and solution-phase cyclization. Conjugation of the peptide-attached linker with dasatinib was conducted in the presence of N-methylmorpholine and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), generating the novel prodrugs. The synthesized compounds were characterized by high-resolution mass …

Plasma Proteome Alterations Of Laying Hens Subjected To Heat Stress And Fed A Diet Supplemented With Pequi Oil (Caryocar Brasiliense Camb.): New Insights In The Identification Of Heat Stress Biomarkers, Joyce Da Silva, Luane Andrade, Paola Rodrigues, Laís Cordeiro, Gabrieli Lima, Júlia Lopes, Elis Castillo, Renata Martins, Andrey Assunção, José Vieira, Marília Busalaf, Jiri Adamec, José Sartori, Pedro Padilha

School of Medicine Faculty Publications

Heat stress can disrupt the balance between the heat poultry release into the environment and the heat they generate. Pequi oil has antioxidant properties, which may mitigate the heat stress effects. This study aimed to investigate the response of laying hens to pequi oil supplementation under heat stress using a proteomic approach. A total of 96 Lohmann White laying hens with 26 weeks old were housed in a completely randomized design with a 2 × 2 factorial arrangement. They were housed in two climate chambers, thermal comfort temperature ± 24.04 °C with the relative humidity ± 66.35 and heat stress …

Metallomic Approach To Mercury And Selenium In The Liver Tissue Of Psectrogaster Amazonica And Raphiodon Vulpinus From The Brazilian Amazon, Izabela Bataglioli, José Vieira, Joyce Da Siva, Luane Andrade, Victor Faria, Rebeca Corcoba, Ronaldo De Almeida, Luiz Zara, Marília Buzalaf, Jiri Adamec, Pedro Padilha

School of Medicine Faculty Publications

This paper reports the results of a mercury (Hg) and selenium (Se) metallomic study in the liver tissues of Psectrogaster amazonica and Raphiodon vulpinus from the Brazilian Amazon. Two-dimensional electrophoresis, graphite furnace atomic absorption spectrometry, and liquid chromatography-tandem mass spectrometry were performed. Hg and Se determinations allowed the calculation of Hg:Se and Se:Hg molar ratio and Se values for health benefits (Se HBVs). The Se:Hg values were >1 for both fish species, whereas the Se HBVs were >5 for P. amazonica and >10 for R. vulpinus, indicating that both possess Se reserves to control Hg toxicity. The metallomic data allowed …

Identification Of The N-Terminal Residues Responsible For The Differential Microdomain Localization Of Cyp1a1 And Cyp1a2, Robert M. Fuchs, James R. Reed, J. Patrick Connick, Markéta Paloncýová, Martin Šrejber, Petra Čechová, Michal Otyepka, Marilyn K. Eyer, Wayne L. Backes

School of Graduate Studies Faculty Publications

The endoplasmic reticulum is organized into ordered regions enriched in cholesterol and sphingomyelin, and disordered microdomains characterized by more fluidity. Rabbit CYP1A1 and CYP1A2 localize into disordered and ordered microdomains, respectively. Previously, a CYP1A2 chimera containing the first 109 amino acids of CYP1A1 showed altered microdomain localization. The goal of this study was to identify specific residues responsible for CYP1A microdomain localization. Thus, CYP1A2 chimeras containing substitutions from homologous regions of CYP1A1 were expressed in HEK 293T/17 cells, and the localization was examined after solubilization with Brij 98. A CYP1A2 mutant with the three amino acids from CYP1A1 (VAG) at …

Identification Of New Leads Against Ubiquitin Specific Protease-7 (Usp7): A Step Towards The Potential Treatment Of Cancers, Sumaira Javaid, Seema Zadi, Muhammad Awais, Atai-Tul Wahab, Humaira Zafar, Innokentiy Maslennikov, M. Iqbal Choudhary

Pharmacy Faculty Articles and Research

Ubiquitin-specific protease-7 (USP7) is an important drug target as it regulates multiple proteins and genes (such as MDM2 and p53) with roles in cancer progression. Its inhibition can hinder the function of oncogenes, increase tumor suppression, and enhance immune response. The current study was designed to express USP7 in a prokaryotic system, followed by screening of small molecules against it using biophysical methods, primarily STD-NMR technique. Among them, 12 compounds showed interaction with USP7 as inferred from NMR-based screening. These compounds further caused destabilization of USP7 by reducing its melting temperature (T_m) up to 6 °C in …