Biochemistry, Biophysics, and Structural Biology Commons^™

Suppressing Hepatic Ugt1a1 Increases Plasma Bilirubin, Lowers Plasma Urobilin, Reorganizes Kinase Signaling Pathways And Lipid Species And Improves Fatty Liver Disease, Evelyn A. Bates, Zachary A. Kipp, Genesee J. Martinez, Olufunto O. Badmus, Mangala M. Soundarapandian, Donald Foster, Mei Xu, Justin F. Creeden, Jennifer R. Greer, Andrew J. Morris, David E. Stec, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Several population studies have observed lower serum bilirubin levels in patients with non-alcoholic fatty liver disease (NAFLD). Yet, treatments to target this metabolic phenotype have not been explored. Therefore, we designed an N-Acetylgalactosamine (GalNAc) labeled RNAi to target the enzyme that clears bilirubin from the blood, the UGT1A1 glucuronyl enzyme (GNUR). In this study, male C57BL/6J mice were fed a high-fat diet (HFD, 60%) for 30 weeks to induce NAFLD and were treated subcutaneously with GNUR or sham (CTRL) once weekly for six weeks while continuing the HFD. The results show that GNUR treatments significantly raised plasma bilirubin levels and …

The Link Between Intracellular Calcium Signaling And Exosomal Pd-L1 In Cancer Progression And Immunotherapy, Rakibul Alam, Mizanur Rahman, Zhiguo Li

Markey Cancer Center Faculty Publications

Exosomes are small membrane vesicles containing microRNA, RNA, DNA fragments, and proteins that are transferred from donor cells to recipient cells. Tumor cells release exo- somes to reprogram the factors associated with the tumor microenvironment (TME) causing tu- mor metastasis and immune escape. Emerging evidence revealed that cancer cell-derived exosomes carry immune inhibitory molecule program death ligand 1 (PD-L1) that binds with re- ceptor program death protein 1 (PD-1) and promote tumor progression by escaping immune response. Currently, some FDA-approved monoclonal antibodies are clinically used for cancer treatment by blocking PD-1/PD-L1 interaction. Despite notable treatment outcomes, some pa- tients show …

Mites [Of Dogs And Cats], Susan E. Little, Roberto Cortinas

School of Veterinary and Biomedical Sciences: Faculty Publications

Veterinary parasitology: 20,000-word article details recognition and treatments for mite infestations of dogs and cats. Mite species reviewed include:

Cheyletiella spp. (“Walking Dandruff”)

Demodex spp. (Hair Follicle Mites, Red Mange, Demodicosis, Demodectic Mange)

Sarcoptes scabiei (Itch Mite, Scabies, Sarcoptic Mange)

Notoedres cati (Feline Head and Neck Mange)

Otodectes cynotis (Ear Mites)

Pneumonyssoides caninum (Nasal Mite)

Lynxacarus radovskyi (Fur Mite, Hair Clasping Mite)

Trombiculid Mites (Chiggers, Red Bugs, Berry Bugs, Harvest Mites, Scrub Itch or Grass Itch Mites)

Discussions include Etiology and epidemiology, Pathogenesis, Clinical features, Diagnosis, Treatment and prognosis, Immunity, Prevention, and Public health aspects.

Complete with 209 references.

More People, More Cats, More Parasites: Human Population Density And Temperature Variation Predict Prevalence Of Toxoplasma Gondii Oocyst Shedding In Free-Ranging Domestic And Wild Felids, Sophie Zhu, Elizabeth Vanwormer, Karen Shapiro

School of Veterinary and Biomedical Sciences: Faculty Publications

Toxoplasma gondii is a ubiquitous zoonotic parasite that can infect warm-blooded vertebrates, including humans. Felids, the definitive hosts, drive T. gondii infections by shedding the environmentally resistant stage of the parasite (oocysts) in their feces. Few studies characterize the role of climate and anthropogenic factors in oocyst shedding among free-ranging felids, which are responsible for the majority of environmental contamination. We determined how climate and anthropogenic factors influence oocyst shedding in free-ranging domestic cats and wild felids using generalized linear mixed models. T. gondii oocyst shedding data from 47 studies were systematically reviewed and compiled for domestic cats and six …

Chemical Characterization And Biological Evaluation Of Epilobium Parviflorum Extracts In An In Vitro Model Of Human Malignant Melanoma, Sotiris Kyriakou, Venetia Tragkola, Ioannis Paraskevaidis, Mihalis Plioukas, Dimitrios T. Trafalis, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidi

School of Veterinary and Biomedical Sciences: Faculty Publications

Malignant melanoma is an aggressive type of skin cancer characterised by high metastatic capacity and mortality rate. On the other hand, Epilobium parviflorum is known for its medicinal properties, including its anticancer potency. In this context, we aimed to (i) isolate various extracts of E. parviflorum, (ii) characterize their phytochemical content, and (iii) determine their cytotoxic potential in an in vitro model of human malignant melanoma. To these ends, we utilized various spectrophotometric and chromatographic (UPLC-MS/MS) approaches to document the higher content of the methanolic extract in polyphenols, soluble sugars, proteins, condensed tannins, and chlorophylls -a and -b as …

Does Swab Type Matter? Comparing Methods For Mannheimia Haemolytica Recovery And Upper Respiratory Microbiome Characterization In Feedlot Cattle, William B. Crosby, Lee Pinnell, John T. Richeson, Cory Wolfe, Jake Castle, John Dustin Loy, Sheryl P. Gow, Keun Seok Seo, Sarah F. Capik, Amelia R. Woolums, Paul S. Morley

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: Bovine respiratory disease (BRD) is caused by interactions among host, environment, and pathogens. One standard method for antemortem pathogen identification in cattle with BRD is deep-guarded nasopharyngeal swabbing, which is challenging, costly, and waste generating. The objective was to compare the ability to recover Mannheimia haemolytica and compare microbial community structure using 29.5 inch (74.9 cm) deep-guarded nasopharyngeal swabs, 16 inch (40.6 cm) unguarded proctology swabs, or 6 inch (15.2 cm) unguarded nasal swabs when characterized using culture, real time-qPCR, and 16S rRNA gene sequencing. Samples for aerobic culture, qPCR, and 16S rRNA gene sequencing were collected from the …

Detection Of Mannheimia Haemolytica-Specific Igg, Igm And Iga In Sera And Their Relationship To Respiratory Disease In Cattle, Korakrit Poonsuk, Carita Kordik, Matthew M. Hille, Ting-Yu Cheng, William B. Crosby, Amelia R. Woolums, Michael L. Clawson, Carol G. Chitko-Mckown, Bruce Brodersen, John Dustin Loy

School of Veterinary and Biomedical Sciences: Faculty Publications

Mannheimia haemolytica is one of the major causes of bovine respiratory disease in cattle. The organism is the primary bacterium isolated from calves and young cattle affected with enzootic pneumonia. Novel indirect ELISAs were developed and evaluated to enable quantification of antibody responses to whole cell antigens using M. haemolytica A1 strain P1148. In this study, the ELISAs were initially developed using sera from both M. haemolytica-culture-free and clinically infected cattle, then the final prototypes were tested in the validation phase using a larger set of known-status M. haemolytica sera (n = 145) collected from feedlot cattle. The test …

First Gene-Edited Calf With Reduced Susceptibility To A Major Viral Pathogen, Aspen M. Workman, Michael P. Heaton, Brian L. Vander Ley, Dennis A. Webster, Luke Sherry, Jonathan R. Bostrom, Sabrina Larson, Theodore S. Kalbfleisch, Gregory P. Harhay, Erin E. Jobman, Daniel F. Carlson, Tad S. Sonstegard

School of Veterinary and Biomedical Sciences: Faculty Publications

Bovine viral diarrhea virus (BVDV) is one of the most important viruses affecting the health and well-being of bovine species throughout the world. Here, we used CRISPR-mediated homology-directed repair and somatic cell nuclear transfer to produce a live calf with a six amino acid substitution in the BVDV binding domain of bovine CD46. The result was a gene-edited calf with dramatically reduced susceptibility to infection as measured by reduced clinical signs and the lack of viral infection in white blood cells. The edited calf has no off-target edits and appears normal and healthy at 20 months of age without obvious …

Aerobic Exercise And Scaffolds With Hierarchical Porosity Synergistically Promote Functional Recovery Post Volumetric Muscle Loss, Christina Zhu, Karina Skylar, Yori Endo, Mohamadmahdi Samandari,, Mehran Karvar, Azadeh Mostafavi, Jacob Quint, Chiara Rioldi, Wojciech Swieszkowski, Joshua Mauney, Shailesh Agarwal, Ali Tamayol, Indranil Sinha

School of Veterinary and Biomedical Sciences: Faculty Publications

Volumetric muscle loss (VML) is a composite loss of skeletal muscle tissue (greater than 20%) that heals with minimal muscle regeneration, substantial fibrosis, and subsequent functional deficits. Standard treatment, involving free functional muscle transfer and physical therapy, cannot restore full muscle function following VML. Tissue engineered scaffolds, 3D structural templates that mimic native extracellular matrix, are promising to enhance functional muscle formation and recovery. Bioprinted 3D scaffolds are engineered using bioinks, created from scaffolding material, cells, and growth factors, to replicate skeletal muscle architecture with precise control over their spatial deposition. METHODS: The present study evaluates a 3D-printed foam-like scaffold …

Host-Genetic-Based Outcome Of Co-Infection By Pcv2b And Prrsv In Pigs, Christian W. Eaton, Hiep Vu, Arabella L. Hodges, Seth P. Harris, Stephen D. Kachman, Daniel C. Ciobanu

School of Veterinary and Biomedical Sciences: Faculty Publications

Replication of porcine circovirus type 2 (PCV2), an important worldwide swine pathogen, has been demonstrated to be influenced by host genotype. Specifically, a missense DNA polymorphism (SYNGR2 p.Arg63Cys) within the SYNGR2 gene was demonstrated to contribute to variation in PCV2b viral load and subsequent immune response following infection. PCV2 is known to induce immunosuppression leading to an increase in susceptibility to subsequent infections with other viral pathogens such as porcine reproductive and respiratory syndrome virus (PRRSV). In order to assess the role of SYNGR2 p.Arg63Cys in co-infections, pigs homozygous for the favorable SYNGR2 p.63Cys (N = 30) …

Infection Of Feral Phenotype Swine With Japanese Encephalitis Virus, So Lee Park, Yan-Jang S. Huang, Amy C. Lyons, Victoria B. Ayers, Susan M. Hettenbach, D. Scott Mcvey, Leela E. Noronha, Kenneth R. Burton, Stephen Higgs, Dana L. Vanlandingham

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic flavivirus and the leading cause of pediatric encephalitis in the Asian Pacific region. The transmission cycle primarily involves Culex spp. mosquitoes and Ardeid birds, with domestic pigs (Sus scrofa domestica) being the source of infectious viruses for the spillover of JEV from the natural endemic transmission cycle into the human population. Although many studies have concluded that domestic pigs play an important role in the transmission cycle of JEV, and infection of humans, the role of feral pigs in the transmission of JEV remains unclear. Since domestic and …

Genome-Wide Investigation Of Snrk2 Gene Family In Two Jute Species: Corchorus Olitorius And Corchorus Capsularis, Borhan Ahmed, Fakhrul Hasan, Anika Tabassum, Rasel Ahmed, Rajnee Hassan, Ruhul Amin, Mobashwer Alam

Department of Biochemistry: Faculty Publications

Background Sucrose non-fermenting-1 (SNF1)-related protein kinase 2 (SnRK2), a plant-specifc serine/threonine kinase family, is associated with metabolic responses, including abscisic acid signaling under biotic and abiotic stresses. So far, no information on a genome-wide investigation and stress-mediated expression profling of jute SnRK2 is available. Recent whole-genome sequencing of two Corchorus species prompted to identify and characterize this SnRK2 gene family.

Result We identifed seven SnRK2 genes of each of Corchorus olitorius (Co) and C. capsularis (Cc) genomes, with similar physico-molecular properties and sub-group patterns of other models and related crops. In both species, the SnRK2 gene …

Oligogalactolipid Production During Cold Challenge Is Conserved In Early Diverging Lineages, Allison C. Barnes, Jennifer L. Myers, Samantha M. Surber, Zhikai Liang, Jeffrey P. Mower, James Schnable, Rebecca Roston

Department of Biochemistry: Faculty Publications

Oligogalactolipid production is a response to severe cold in many land plant lineages. It occurs during times of membrane damage and can be reproduced in multiple species by cytosolic acidification.

Severe cold, defined as a damaging cold beyond acclimation temperatures, has unique responses, but the signaling and evolution of these responses are not well understood. Production of oligogalactolipids, which is triggered by cytosolic acidification in Arabidopsis (Arabidopsis thaliana), contributes to survival in severe cold. Here, we investigated oligogalactolipid production in species from bryophytes to angiosperms. Production of oligogalactolipids differed within each clade, suggesting multiple evolutionary origins of severe …

A Facile Strategy For The Fabrication Of Cell-Laden Porous Alginate Hydrogels Based On Two-Phase Aqueous Emulsions, Wen Xue, Donghee Lee, Yunfan Kong, Mitchell Kuss, Ying Huang, Taesung Kim, Soonkyu Chung, Andrew T. Dudley, Seung-Hyun Ro, Bin Duan

Department of Biochemistry: Faculty Publications

Porous alginate (Alg) hydrogels possess many advantages as cell carriers. However, current pore generation methods require either complex or harsh fabrication processes, toxic components, or extra purification steps, limiting the feasibility and affecting the cellular survival and function. In this study, a simple and cell-friendly approach to generate highly porous cell-laden Alg hydrogels based on two-phase aqueous emulsions is reported. The pre-gel solutions, which contain two immiscible aqueous phases of Alg and caseinate (Cas), are cross-linked by calcium ions. The porous structure of the hydrogel construct is formed by subsequently removing the Cas phase from the ion-cross-linked Alg hydrogel. Those …

Structural Basis Of Dna Binding By The Whib-Like Transcription Factor Whib3 In Mycobacterium Tuberculosis, Tao Wan, Magdaléna Horová, Vimmy Khetrapal, Shanren Li, Camden Jones, Andrew Schacht, Xinghui Sun, Limei Zhang

Department of Biochemistry: Faculty Publications

Mycobacterium tuberculosis (Mtb) WhiB3 is an iron–sulfur cluster-containing transcription factor belonging to a subclass of the WhiB-Like (Wbl) family that is widely distributed in the phylum Actinobacteria. WhiB3 plays a crucial role in the survival and pathogenesis of Mtb. It binds to the conserved region 4 of the principal sigma factor (σ^A₄) in the RNA polymerase holoenzyme to regulate gene expression like other known Wbl proteins in Mtb. However, the structural basis of how WhiB3 coordinates with σ^A₄ to bind DNA and regulate transcription is unclear. Here we determined crystal structures …

Akkermansia Muciniphila And Its Membrane Protein Ameliorates Intestinal Inflammatory Stress And Promotes Epithelial Wound Healing Via Crebh And Mir‑143/145, Henry Wade, Kaichao Pan, Qihua Duan, Szczepan Kaluzny, Ekta Pandey, Linda Fatumoju, Viswanathan Saraswathi, Rongxue Wu, Edward N. Harris, Qiaozhu Su

Department of Biochemistry: Faculty Publications

Background The intestinal epithelial barrier is the interface for interaction between gut microbiota and host metabolic systems. Akkermansia muciniphila (A. muciniphila) is a key player in the colonic microbiota that resides in the mucus layer, whose abundance is selectively decreased in the faecal microbiota of inflammatory bowel disease (IBD) patients. This study aims to investigate the regulatory mechanism among A. muciniphila, a transcription factor cAMPresponsive element-binding protein H (CREBH), and microRNA-143/145 (miR-143/145) in intestinal inflammatory stress, gut barrier integrity and epithelial regeneration.

Methods A novel mouse model with increased colonization of A muciniphila in the intestine of CREBH knockout …

Factors Influencing Instructors’ Adoption And Continued Use Of Computing Science Technologies: A Case Study In The Context Of Cell Collective, Changsoo Song, Resa M. Helikar, Wendy M. Smith, Tomáš Helikar

Department of Biochemistry: Faculty Publications

Acquiring computational modeling and simulation skills has become ever more critical for students in life sciences courses at the secondary and tertiary levels. Many modeling and simulation tools have been created to help instructors nurture those skills in their classrooms. Understanding the factors that may motivate instructors to use such tools is crucial to improve students’ learning, especially for having authentic modeling and simulation learning experiences. This study designed and tested a decomposed technology acceptance model in which the perceived usefulness and perceived ease of use constructs are split between the teaching and learning sides of the technology to examine …

Conformal Electrodeposition Of Antimicrobial Hydrogels Formed By Self-Assembled Peptide Amphiphiles, Gervasio Zaldivar, Jiachen Feng, Leonardo Lizarraga, Yafan Yu, Luana De Campos, Kelly Mari Pires De Oliveira, Kurt Piepenbrink, Martin Conda-Sheridan, Mario Tagliazucchi

Department of Biochemistry: Faculty Publications

The colonization of biomedical surfaces by bacterial biofilms is concerning because these microorganisms display higher antimicrobial resistance in biofilms than in liquid cultures. Developing antimicrobial coatings that can be easily applied to medically-relevant complex-shaped objects, such as implants and surgical instruments, is an important and challenging research direction. This work reports the preparation of antibacterial surfaces via the electrodeposition of a conformal hydrogel of self-assembling cationic peptide-amphiphiles (PAs). Hydrogels of three PAs are electrodeposited: C₁₆K₂, C₁₆K₃, and C₁₈K₂, where C_n is an alkyl chain of n methylene …

Genetic Control Of Photoprotection And Photosystem Ii Operating Efficiency In Plants, Seema Sahay, Marcin Grzybowski, James Schnable, Katarzyna Głowacka

Department of Biochemistry: Faculty Publications

• Photoprotection against excess light via nonphotochemical quenching (NPQ) is indispensable for plant survival. However, slow NPQ relaxation under low light conditions can decrease yield of field-grown crops up to 40%.

• Using semi-high-throughput assay, we quantified the kinetics of NPQ and photosystem II operating efficiency (ΦPSII) in a replicated field trial of more than 700 maize (Zea mays) genotypes across 2 yr. Parametrized kinetics data were used to conduct genome-wide association studies.

• For six candidate genes involved in NPQ and ΦPSII kinetics in maize the loss of function alleles of orthologous genes in Arabidopsis (Arabidopsis thaliana) …

Advancements In Computational Modelling Of Biological Systems: Seventh Annual Sysmod Meeting, Bhanwar Lal Puniya, Andreas Dräger

Department of Biochemistry: Faculty Publications

The Computational Modelling of Systems Biology (SysMod) Community of Special Interest (COSI) convenes annually at the Intelligent Systems for Molecular Biology (ISMB) conference to facilitate knowledge dissemination and exchange of research findings on systems modelling from interdisciplinary domains. The SysMod meeting 2022 was held in a hybrid mode in Madison, Wisconsin, spanning a 1-day duration centred on modelling techniques, applications, and single-cell technology implementations. The meeting showcased innovative approaches to modelling biological systems using cell-specific and multiscale modelling, multiomics data integration, and novel tools to develop systems models using single-cell and multiomics technology. The meeting also recognized outstanding research by …