Chemicals and Drugs Commons^™

Lrtm Left-Right Transition Matrices For Molecular Interaction Prediction, Kaitlin Zheng, Guihua Duan, Mengyun Yang, Wei Wu, Yao-Hang Li, Jianxin Wang

Computer Science Faculty Publications

Molecular interactions are central to most biological processes. The discovery and identification of potential associations between molecules can provide insights into biological exploration, diagnostic and therapeutic interventions, and drug development. So far many relevant computational methods have been proposed, but most of them are usually limited to specific domains and rely on complex preprocessing procedures, which restricts the models’ ability to be applied to other tasks. Therefore, it remains a challenge to explore a generalized approach to accurately predicting potential associations. In this study, We propose Left-Right Transition Matrices (LRTM) for molecular interaction prediction. From the perspective on the diffusion …

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 …

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 …

Exploring The Intersection Of Sexual Identity And Route Of Administration In Relation To Cannabis Use Among Young Adult Females, Sarah J. Ehlke, Samantha A. Fitzer, Jennifer L. Shipley, Abby L. Braitman

Psychology Faculty Publications

Background and Objective: Rates of cannabis use continue to increase with sexual minority women (SMW) reporting greater use than heterosexual women. Along with these increasing trends, the routes of administration (ROA) for cannabis are evolving. The current study examined associations between cannabis ROA and frequency of use, as well as differences across sexual identity (heterosexual vs. SMW).

Methods: Participants were 949 young adult (18–25 years old) women (29.8% SMW) who reported past month cannabis use and were recruited through Amazon Mechanical Turk. Number of cannabis use days and each ROA used (joint, pipe, blunt, bong, vape, edible, and ointment) in …

Quantification Of Antiviral Drug Tenofovir (Tfv) By Surface-Enhanced Raman Spectroscopy (Sers) Using Cumulative Distribution Functions (Cdfs), Marguerite R. Butler, Jana Hrncirova, Meredith Clark, Sucharita Dutta, John B. Cooper

Chemistry & Biochemistry Faculty Publications

Surface-enhanced Raman spectroscopy (SERS) is an ultrasensitive spectroscopic technique that generates signal-enhanced fingerprint vibrational spectra of small molecules. However, without rigorous control of SERS substrate active sites, geometry, surface area, or surface functionality, SERS is notoriously irreproducible, complicating the consistent quantitative analysis of small molecules. While evaporatively prepared samples yield significant SERS enhancement resulting in lower detection limits, the distribution of these enhancements along the SERS surface is inherently stochastic. Acquiring spatially resolved SERS spectra of these dried surfaces, we have shown that this enhancement is governed by a power law as a function of analyte concentration. Consequently, by definition, …

Exploration Of Potential Broad-Spectrum Antiviral Targets In The Enterovirus Replication Element: Identification Of Six Distinct 5' Cloverleaves, Morgan G. Daniels, Meagan E. Werner, Rockwell T. Li, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Enterovirus genomic replication initiates at a predicted RNA cloverleaf (5′CL) at the 5′ end of the RNA genome. The 5′CL contains one stem (SA) and three stem-loops (SLB, SLC, SLD). Here, we present an analysis of 5′CL conservation and divergence for 209 human health-related serotypes from the enterovirus genus, including enterovirus and rhinovirus species. Phylogenetic analysis indicates six distinct 5′CL serotypes that only partially correlate with the species definition. Additional findings include that 5′CL sequence conservation is higher between the EV species than between the RV species, the 5′CL of EVA and EVB are nearly identical, and RVC has the …

Host-Defense Piscidin Peptides As Antibiotic Adjuvants Against Clostridioides Difficile, Adenrele Oludiran, Areej Malik, Andriana C. Zourou, Yonghan Wu, Steven P. Gross, Albert Siryapon, Asia Poudel, Kwincy Alleyne, Savion Adams, David S. Courson, Myriam L. Cotten, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

The spore-forming intestinal pathogen Clostridioides difficile causes multidrug resistant infection with a high rate of recurrence after treatment. Piscidins 1 (p1) and 3 (p3), cationic host defense peptides with micromolar cytotoxicity against C. difficile, sensitize C. difficile to clinically relevant antibiotics tested at sublethal concentrations. Both peptides bind to Cu²⁺ using an amino terminal copper and nickel binding motif. Here, we investigate the two peptides in the apo and holo states as antibiotic adjuvants against an epidemic strain of C. difficile. We find that the presence of the peptides leads to lower doses of …

Synthesis Of Bis-Thioacid Derivatives Of Diarylethene And Their Photochromic Properties, Pramod Aryal, Jonathan Bietsch, Gowri Sankar Grandhi, Richard Chen, Surya B. Adhikari, Ephraiem S. Sarabamoun, Joshua J. Choi, Guijun Wang

Chemistry & Biochemistry Faculty Publications

Diarylethenes (DAEs) are an important class of photoswitchable compounds that typically undergo reversible photochemical conversions between the open and closed cyclized forms upon treatment with UV light or visible light. In this study, we introduced thioacid functional groups to several photochromic dithienylethene (DTE) derivatives and established a method that can be used to prepare these photoswitchable thioacids. Four thioacid-functionalized diarylethene derivatives were synthesized through the activation of carboxylic acids with N-hydroxysuccinimide, followed by reactions with sodium hydrosulfide with yields over 90%. These derivatives exhibited reversible photoswitching and photochromic properties upon treatment with ultraviolet (UV) and visible lights. The thioacid groups …

Quantification Of Antiretroviral Drug Emtricitabine In Human Plasma By Surface Enhanced Raman Spectroscopy, Marguerite R. Butler, Terry A. Jacot, Sucharita M. Dutta, Gustavo F. Doncel, John B. Cooper

Chemistry & Biochemistry Faculty Publications

In this study, reproducible label-free detection and quantification of the antiretroviral drug emtricitabine (FTC) down to 78 ng/mL in human plasma by surface enhanced Raman spectroscopy (SERS) is presented. A novel plasma sample pretreatment method using silver nitrate and silver colloidal nanoparticles (Ag CNPs) was used to prepare the plasma samples for analysis. The pretreated plasma samples were evaporated to dryness on an aluminum surface and a computer-controlled Raman scanning system was used to collect spatially resolved SERS spectra of the entire surface. Calibration curves of commercial human plasma samples containing FTC in a concentration range of 5000 to 78 …

Plasma Protein Signatures Of Adult Asthma, Gordon J. Smilnak, Yura Lee, Abhijnan Chattopadhyay, Annah B. Wyss, Julie D. White, Sinjini Sikdar, Jianping Jin, Andrew J. Grant, Alison A. Motsinger-Reif, Jian-Liang Li, Mikyeong Lee, Bing Yu, Stephanie J. London

Mathematics & Statistics Faculty Publications

Background: Adult asthma is complex and incompletely understood. Plasma proteomics is an evolving technique that can both generate biomarkers and provide insights into disease mechanisms. We aimed to identify plasma proteomic signatures of adult asthma.

Methods: Protein abundance in plasma was measured in individuals from the Agricultural Lung Health Study (ALHS) (761 asthma, 1095 non-case) and the Atherosclerosis Risk in Communities study (470 asthma, 10,669 non-case) using the SOMAScan 5K array. Associations with asthma were estimated using covariate adjusted logistic regression and meta-analyzed using inverse-variance weighting. Additionally, in ALHS, we examined phenotypes based on both asthma and seroatopy (asthma with …

A New Approach For Discriminating Spatially Acquired Sers Spectra Using Antiretroviral Drug Emtricitabine As A Test Sample, Jana Hrncirova, Marguerite R. Butler, Meredith R. Clark, Gustavo F. Doncel, John B. Cooper

Chemistry & Biochemistry Faculty Publications

In this study, an antiretroviral drug emtricitabine (also known as FTC or Emtriva) was detected and quantified down to 40 ng/ml by using surface-enhanced Raman spectroscopy (SERS). Its aqueous standards were tested with two types of silver nanoparticles (colloidal and dendritic) using a specially developed aluminum well plate. The SERS spectra were acquired using a Raman scanning device with 30-mu m spatial resolution. The spectral data were analyzed using a new approach for the discrimination of the spatially acquired spectra based on the Quality index (Qi). After the Qi is calculated, the spectral data are sorted based on the Qi. …

Evidence Of Direct Interaction Between Cisplatin And The Caspase-Cleaved Prostate Apoptosis Response-4 Tumor Suppressor, Krishna K. Raut, Samjhana Pandey, Gyanendra Kharel, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Prostate apoptosis response-4 (Par-4) tumor suppressor protein has gained attention as a potential therapeutic target owing to its unique ability to selectively induce apoptosis in cancer cells, sensitize them to chemotherapy and radiotherapy, and mitigate drug resistance. It has recently been reported that Par-4 interacts synergistically with cisplatin, a widely used anticancer drug. However, the mechanistic details underlying this relationship remain elusive. In this investigation, we employed an array of biophysical techniques, including circular dichroism spectroscopy, dynamic light scattering, and UV–vis absorption spectroscopy, to characterize the interaction between the active caspase-cleaved Par-4 (cl-Par-4) fragment and cisplatin. Additionally, elemental analysis was …

Polarizable Amoeba Force Field Predicts Thin And Dense Hydration Layer Around Monosaccharides, Luke A. Newman, Mackenzie G. Patton, Breyanna A. Rodriguez, Ethan W. Summer, Valerie Vaissier Welbourn

Chemistry & Biochemistry Faculty Publications

Polarizable force fields crucially enhance the modeling of macromolecules in polar media. Here, we present new parameters to model six common monosaccharides with the polarizable AMOEBA force field. These parameters yield a thinner, but denser, hydration layer than that previously reported. This denser hydration layer results in eliminating non-physical aggregation of glucose in water-an issue that has plagued molecular dynamics simulations of carbohydrates for decades.

A Novel Non-Rodent Animal Model Of Hydrochloric Acid-Induced Acute And Chronic Lung Injury, Pavel A. Solopov, Ruben Manuel Luciano Biancatelli, Tierney Day, Christiana Dimitropoulou, John D. Catravas

Bioelectrics Publications

Hydrochloric acid is one of the most prevalent and hazardous chemicals. Accidental spills occur in industrial plants or during transportation. Exposure to HCl can induce severe health impairment, including acute and chronic pulmonary diseases. We have previously described the molecular, structural, and functional aspects of the development of chronic lung injury and pulmonary fibrosis caused by intratracheal instillation of HCl in mice. Although mouse models of human disease have many advantages, rodents are evolutionary far from human and exhibit significant anatomical and physiological differences. Genetic and anatomic similarities between rabbits and humans are significantly higher. Rabbit models of HCl-induced lung …

Cumulative Distribution Function And Spatially Resolved Surface-Enhanced Raman Spectroscopy For The Quantitative Analysis Of Emtricitabine, Jana Hrncirova, Marguerite R. Butler, Sucharita Dutta, Meredith R. Clark, John B. Cooper

Chemistry & Biochemistry Faculty Publications

Surface-enhanced Raman spectroscopy (SERS) has exceptional analytical sensitivity and selectivity. However, SERS irreproducibility presents an obstacle when using it for precise quantitative measurements. In this study, colloidal nanoparticles evaporated to dryness are used as a SERS active surface for the detection of the HIV drug emtricitabine (FTC; trade name Emtriva). Despite the irreproducibility of the SERS resulting from the stochastic process of evaporation, using a SERS scanning instrument, the SERS enhancement factors of spatially resolved spectra have a well-defined distribution of signals for a given analyte concentration. This distribution follows a power law function ranging from weak (very abundant signals) …

Fat-Free Mass Is Positively Associated With Urine Specific Gravity In Athletes And Active Adults: A Quantitative Review, Patrick B. Wilson, Ian P. Winter

Exercise Science Faculty Publications

Background: Urine specific gravity (USG) is a commonly used assessment method to estimate the prevalence of hypohydration, typically based on a common threshold of ≥ 1.020. Some research has shown that USG can vary based on body size and composition, but the evidence to date is limited. This review examined whether an association between fat-free mass (FFM), a component of body composition, and USG could be detected among published articles that have reported these variables in athletes and physically active individuals.

Methods: By searching Google Scholar, the authors identified a large number of published articles (n = 161) reporting anthropometrics …

The Impact Of Aging And Storage Conditions On The Performance Of Universal Adhesives: A Systematic Review, Maryam Ghamgosar, Mehrsima Ghavami-Lahiji, Sanaz Mihandoust, Enayatollah Homaie Rad, Hassan Salehipour Masooleh, Lobat Tayebi

Electrical & Computer Engineering Faculty Publications

Objective: This systematic review evaluated how different storage times and conditions affect universal adhesives' bond strength and degree of conversion (DC).

Methods: A literature search was conducted in PubMed, Scopus, Web of Science, and Google Scholar databases for articles published from January 1st, 2000, until May 15th, 2022. The researchers comprehensively evaluated the articles using a multi-step process to identify articles relevant to the topic of interest. Quality assessment was performed through the ROBDEMAT tool. Due to the high heterogeneity in the preliminary data, performing a meta-analysis was not feasible.

Results: A total of 3169 records were obtained, and after …

Mesoporous Silica Administration As A New Strategy In The Management Of Warfarin Toxicity: An In-Vitro And In-Vivo Study, Fatemeh Farjadian, Fatemeh Parsi, Reza Heidari, Khatereh Zarkesh, Hamid Reza Mohammadi, Soliman Mohammadi-Samani, Lobat Tayebi

Electrical & Computer Engineering Faculty Publications

Purpose: Warfarin is one of the most widely used anticoagulants that functions by inhibiting vitamin K epoxide reductase. Warfarin overdose, whether intentional or unintentional, can cause life-threatening bleeding. Here, we present a novel warfarin adsorbent based on mesoporous silica that could serve as an antidote to warfarin toxicity.

Method: Amino-functionalized mesoporous silica (MS-NH₂) was synthesized based on the cocondensation method through a soft template technique followed by template removal. The prepared structure and functional group were studied by Fourier transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) checked the morphology. The …

Hsp70 Is A Critical Regulator Of Hsp90 Inhibitor's Effectiveness In Preventing Hcl-Induced Chronic Lung Injury And Pulmonary Fibrosis, Ruben M. L. Colunga Biancatelli, Pavel A. Solopov, Tierney Day, Betsy Gregory, Michael Osei-Nkansah, Christiana Dimitropoulou, John D. Catravas

Bioelectrics Publications

Exposure to hydrochloric acid (HCl) can provoke acute and chronic lung injury. Because of its extensive production for industrial use, frequent accidental exposures occur, making HCl one of the top five chemicals causing inhalation injuries. There are no Food and Drug Administration (FDA)-approved treatments for HCl exposure. Heat shock protein 90 (HSP90) inhibitors modulate transforming growth factor-β (TGF-β) signaling and the development of chemical-induced pulmonary fibrosis. However, little is known on the role of Heat Shock Protein 70 (HSP70) during injury and treatment with HSP90 inhibitors. We hypothesized that administration of geranylgeranyl-acetone (GGA), an HSP70 inducer, or gefitinib (GFT), an …

Synthesis And Structure-Activity Relationship Of Boronic Acid Bioisosteres Of Combretastatin A-4 As Anticancer Agents, Yali Kong, Michael C. Edler, Ernest Hamel, Asa R. Britton-Jenkins, Omar Gillan, Susan L. Mooberry, David Mu, Milton L. Brown

Department of Biomedical and Translational Sciences Faculty Publications

The boronic acid group plays an important role in drug discovery. Following our discovery of a boronic acid analog of combretastatin A-4 (CA-4), a series of analogs featuring a boronic acid group on the C phenyl ring of CA-4 was synthesized and evaluated for cytotoxicity, as well as for their ability to inhibit tubulin polymerization, inhibit the binding of [³H]colchicine to tubulin and cause depolymerization of cellular microtubules. Modifications on the C ring of CA-4, either eliminating the methoxy group or replacing the C phenyl ring with a pyridine ring, resulted in a reduced potency for inhibiting tubulin polymerization, colchicine …

Radiation Induced Skin Fibrosis (Risf): Opportunity For Angiotensin Ii-Dependent Intervention, Patricia F. Boothe, Vidya P. Kumar, Yali Kong, Kan Wang, Howard Levinson, David Mu, Milton L. Brown

Department of Biomedical and Translational Sciences Faculty Publications

Medical procedures, such as radiation therapy, are a vital element in treating many cancers, significantly contributing to improved survival rates. However, a common long-term complication of such exposure is radiation-induced skin fibrosis (RISF), a complex condition that poses substantial physical and psychological challenges. Notably, about 50% of patients undergoing radiation therapy may achieve long-term remission, resulting in a significant number of survivors managing the aftereffects of their treatment. This article delves into the intricate relationship between RISF, reactive oxygen species (ROS), and angiotensin II (Ang II) signaling. It proposes the underlying mechanisms and examines potential treatments for mitigating skin fibrosis. …

Listeria Adhesion Protein Orchestrates Caveolae-Mediated Apical Junctional Remodeling Of Epithelial Barrier For Listeria Monocytogenes Translocation, Rishi Drolia, Donald B. Bryant, Shivendra Tenguria, Zuri A. Jules-Culver, Jessie Thind, Breanna Amelunke, Donqi Liu, Nicholas L. F. Gallina, Krishna K. Mishra, Manalee Samaddar, Manoj R. Sawale, Dharmendra K. Mishra, Abigail D. Cox, Arun K. Bhunia

Biological Sciences Faculty Publications

The cellular junctional architecture remodeling by Listeria adhesion protein-heat shock protein 60 (LAP-Hsp60) interaction for Listeria monocytogenes (Lm) passage through the epithelial barrier is incompletely understood. Here, using the gerbil model, permissive to internalin (Inl) A/B-mediated pathways like in humans, we demonstrate that Lm crosses the intestinal villi at 48 h post-infection. In contrast, the single isogenic (lap− or ΔinlA) or double (lap−ΔinlA) mutant strains show significant defects. LAP promotes Lm translocation via endocytosis of cell-cell junctional complex in enterocytes that do not display luminal E-cadherin. In comparison, InlA facilitates …

Receptor-Targeted Next-Generation Probiotics Ameliorate Mammalian Colitis, Nicholas L. F. Gallina, Vignesh Nathan, Akshay Krishnakumar, Dongqi Liu, Rishi Drolia, Nicole Irrizary Tardi, Yang Fu, Manalee Samadar, Shivendra Tenguria, Alvin Cai, Ruth Eunice Centeno-Martinez, Timothy A. Johnson, Abigail Cox, Lavanya Reddivari, Bruce Applegate, Xingjian Bai, Luping Xu, Deepti Tanjore, Ramesh Vemulapalli, Rahim Rahimi, Arun K. Bhunia

Biological Sciences Faculty Publications

Introduction: a loss of intestinal barrier function, inflammation, and an elevated expression of epithelial heat shock protein 60 (Hsp60) are features of an inflamed bowel. Probiotics have been used to alleviate colitis-induced pathologies, but offer poor adhesion and adaptation to the diseased gut. We hypothesize that enhancing probiotic adhesion in the inflamed bowel may ameliorate such pathologies. Listeria adhesion protein (LAP; 94-kDa acetaldehyde alcohol dehydrogenase) aids Listeria attachment to the epithelial cells by interacting with the mammalian receptor Hsp60. Bioengineered Lactobacillus casei probiotics (BLPs) expressing LAP showed strong interaction with epithelial Hsp60, a high immunomodulatory response, and sustained epithelial barrier …

Electrophysiological And Clinical Fundamentals Of Qtc Prolongation Induced By Antipsychotic Medications, Zaid Naseer, Minaal Khan, Najeeb Manalai, Allison Foroobar, Patricia Harrison, Charles Scercy, Beth Yanoff, Partam Manalai

Department Surgery Faculty Publications

Patients with psychiatric disorders undergoing antipsychotic treatment are at an elevated risk for adverse cardiovascular events, including arrhythmias and sudden cardiac death. While the precise mechanisms linking cardiovascular diseases and psychiatric conditions remain unclear, QTc prolongation is suspected to be a contributing factor. The human ether-à-go-go-related gene (hERG, or KCNH2), which affects potassium channels, is implicated in the cardiotoxicity of various medications, including antipsychotics. This gene plays a critical role in determining whether a drug will be approved for market use. This paper elucidates the electrophysiological basis of QTc prolongation and reviews the evidence concerning which antipsychotics may exacerbate QTc …

Successful Management Of Spontaneous Unilateral Twin Ectopic Pregnancy With Two-Step Dose Of Methotrexate, Lauren A. Forbes, Navya Nuthivana, Renee Morales

Department of Obstetrics & Gynecology Faculty Publications

The incidence of unilateral tubal twin pregnancy is 1/20,000–1/250,000 with about 100 reported cases. Four of the six cases that were medically managed were successful. A 24-year-old female presented to the emergency department (ED) with vaginal bleeding and abdominal cramping. She was hemodynamically stable without signs of an acute abdomen. Laboratory evaluation revealed she was pregnant with a serum beta-human chorionic gonadotropin (b-hCG) of 798 mIU/mL. Transvaginal ultrasound (TVUS) revealed a single left tubal pregnancy with a yolk sac. The patient elected medical management with body surface area (BSA)–based intramuscular (IM) methotrexate (MTX). On Day 4, the patient returned to …

Gene Expression Of Tight Junctions In Foreskin Is Not Affected By Hiv Pre-Exposure Prophylaxis, Emily L. Webb, Stefan Petkov, Heejin Yun, Laura Else, Limakatso Lebina, Jennifer Serwanga, Azure-Dee A.P. Pillay, Thabiso B. Seiphetlo, Susan Mugaba, Patricia Namubiru, Geoffrey Odoch, Daniel Opoka, Andrew S. Ssemata, Pontiano Kaleebu, Saye Khoo, Neil Martinson, Julie Fox, Clive M. Gray, Carolina Herrera, Francesca Chiodi

Department of Obstetrics & Gynecology Faculty Publications

Introduction: Tight junctions (TJs) serve as permeability filters between the internal and external cellular environment. A large number of proteins have been identified to be localized at the TJs. Due to limitations in tissue collection, TJs in the male genital tract have been understudied.

Methods: We analysed the transcriptomics of 132 TJ genes in foreskin tissue of men requesting voluntary medical male circumcision (VMMC) and enrolled in the Combined HIV Adolescent Prevention Study (CHAPS) trial conducted in South Africa and Uganda (NCT03986970). The trial evaluated the dose requirements for event-driven HIV pre-exposure prophylaxis (PrEP) with emtricitabine-tenofovir (FTC-TDF) or emtricitabine-tenofovir alafenamide …

Flexible Fitting Of Alphafold2-Predicted Models To Cryo-Em Density Maps Using Elastic Network Models: A Methodological Affirmation, Maytha Alshammari, Jing He, Willy Wriggers

Computer Science Faculty Publications

Motivation: This study investigates the flexible refinement of AlphaFold2 models against corresponding cryo-electron microscopy (cryo-EM) maps using normal modes derived from elastic network models (ENMs) as basis functions for displacement. AlphaFold2 generally predicts highly accurate structures, but 18 of the 137 models of isolated chains exhibit a TM-score below 0.80. We achieved a significant improvement in four of these deviating structures and used them to systematically optimize the parameters of the ENM motion model.

Results: We successfully refined four AlphaFold2 models with notable discrepancies: lipid-preserved respiratory supercomplex (TM-score increased from 0.52 to 0.69), flagellar L-ring protein (TM-score increased from 0.53 …

Enhancement Of Deep Learning Protein Structure Prediction, Ruoming Shen

Modeling, Simulation and Visualization Student Capstone Conference

Protein modeling is a rapidly expanding field with valuable applications in the pharmaceutical industry. Accurate protein structure prediction facilitates drug design, as extensive knowledge about the atomic structure of a given protein enables scientists to target that protein in the human body. However, protein structure identification in certain types of protein images remains challenging, with medium resolution cryogenic electron microscopy (cryo-EM) protein density maps particularly difficult to analyze. Recent advancements in computational methods, namely deep learning, have improved protein modeling. To maximize its accuracy, a deep learning model requires copious amounts of up-to-date training data.

This project explores DeepSSETracer, a …