Biochemistry, Biophysics, and Structural Biology Commons^™

A Bioengineered Probiotic For The Oral Delivery Of A Peptide Kv13 Channel Blocker To Treat Rheumatoid Arthritis, Yuqing Wang, Duolong Zhu, Laura C Ortiz-Velez, Jacob L Perry, Michael W Pennington, Joseph M Hyser, Robert A Britton, Christine Beeton

Faculty, Staff and Students Publications

New therapeutics that combine efficacy with limited side effects and can be delivered noninvasively are needed to adequately treat patients with rheumatoid arthritis (RA) and other autoimmune diseases. Kv1.3 channel-expressing CCR7− effector memory T (TEM) lymphocytes are significant players in the pathogenesis of multiple autoimmune diseases, and blocking Kv1.3 reduces disease severity in rat models of RA and patients with plaque psoriasis. However, peptide therapeutics require repeated injections, reducing patient compliance. We used a bioengineered Lactobacillus reuteri as an oral delivery method of a Kv1.3 blocker for immunomodulation in rat models of atopic dermatitis and RA. This study demonstrates a …

Rbp Image Database: A Resource For The Systematic Characterization Of The Subcellular Distribution Properties Of Human Rna Binding Proteins, Louis Philip Benoit Bouvrette, Xiaofeng Wang, Jonathan Boulais, Jian Kong, Easin Uddin Syed, Steven M Blue, Lijun Zhan, Sara Olson, Rebecca Stanton, Xintao Wei, Brian Yee, Eric L Van Nostrand, Xiang-Dong Fu, Christopher B Burge, Brenton R Graveley, Gene W Yeo, Eric Lécuyer

Faculty, Staff and Students Publications

RNA binding proteins (RBPs) are central regulators of gene expression implicated in all facets of RNA metabolism. As such, they play key roles in cellular physiology and disease etiology. Since different steps of post-transcriptional gene expression tend to occur in specific regions of the cell, including nuclear or cytoplasmic locations, defining the subcellular distribution properties of RBPs is an important step in assessing their potential functions. Here, we present the RBP Image Database, a resource that details the subcellular localization features of 301 RBPs in the human HepG2 and HeLa cell lines, based on the results of systematic immuno-fluorescence studies …

A Low-Fat/Sucrose Diet Rich In Complex Carbohydrates Reverses High-Fat/Sucrose Diet-Induced Corneal Dysregulation, Prince K Akowuah, Carolina Lema, Rolando E Rumbaut, Alan R Burns

Faculty, Staff and Students Publications

High-fat/sucrose diet feeding in mice causes loss of corneal nerve function and impairs corneal wound healing. While changing to a diet with a low fat/sugar composition and enrichments in complex carbohydrates mitigates the reduction in nerve function, it remains to be determined if it has an effect on corneal wound healing. In this study, 6-week-old C57BL/6 male mice were fed either a normal diet or a high-fat/sucrose diet for 20 weeks. A third group (diet reversal) was placed on a high-fat/sucrose diet for 10 weeks followed by a normal diet for an additional 10 weeks. A central corneal epithelial abrasion …

Observing Ceramide Pathway With Ferroptosis Via Mia Paca-2 Cell Treatment With Rsl3, Tazrin Rahman

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Composed of sphingosine and a fatty acid, ceramides are lipid molecules that serve as key metabolic signaling molecules of a sphingolipid pathway. While it acts as a precursor of complex sphingolipids, inducing ceramide generation can cause cell stress leading to subsequent cell death via apoptosis, necrosis, and even mitophagy. With regards to cell death specifically, a novel form of regulated cell death, ferroptosis, has recently been recognized of necrotic nature. Its unique morphological features and distinct properties have been observed over the last several decades; however, the molecular features were not identifiable as pure evidence of cell death, until recently …

Identification Of Novel Biosynthetic Gene Clusters Encoding For Polyketide/Nrps-Producing Chemotherapeutic Compounds From Marine-Derived Streptomyces Hygroscopicus From A Marine Sanctuary, Hannah Ruth Flaherty

Honors Theses and Capstones

Nearly one out of six deaths in 2020, around ten million people, were caused by cancer, making it a leading cause of death worldwide (WHO, 2022). This major public health issue, in addition to the rise of multidrug-resistant (MDR) pathogens, provides a high demand for the discovery of new pharmaceutical drugs to be used clinically to treat these conditions. The Streptomyces genus accounts to produce 39% of all microbial metabolites currently approved for human health, indicating its potential as an important species to study for antimicrobial and anticancer agents. The long linear genome of Streptomyces contains specialized sequences known as …

Presumptive Hepatogenous Photosensitization In Beef Cattle Winter Grazing A Cover Crop Containing Brassica Spp. Turnips, Matthew M. Hille, Scott A. Fritz, Breanna C. Brown

School of Veterinary and Biomedical Sciences: Faculty Publications

Over a period of ~2 wk, 5 adult beef cows developed severe necrotizing skin lesions on the face and neck shortly after being moved to a field with a cover crop of Brassica spp. turnips. We describe here the clinical signs, hematology, and serum chemistry results, as well as gross and histopathologic findings, from this outbreak. We made a presumptive diagnosis of Brassica-associated liver disease (BALD) based on the similarities in the history and diagnostic findings observed with previously reported cases of BALD from elsewhere in the world. BALD has not been reported previously in cattle in North America, …

Detection Of Sars-Cov-2 Neutralizing Antibodies In Retropharyngeal Lymph Node Exudates Of White-Tailed Deer (Odocoileus Virginianus) From Nebraska, Usa, Korakrit Poonsuk, Duan S. Loy, Rachael Birn, Bryan Buss, Matthew Donahue, Todd Nordeen, Kylie Sinclair, Luke Meduna, Bruce Brodersen, John Dustin Loy

School of Veterinary and Biomedical Sciences: Faculty Publications

Disease surveillance testing for emerging zoonotic pathogens in wildlife is a key component in understanding the epidemiology of these agents and potential risk to human populations. Recent emergence of SARS-CoV-2 in humans, and subsequent detection of this virus in wildlife, highlights the need for developing new One Health surveillance strategies. We used lymph node exudate, a sample type that is routinely collected in hunter-harvested white-tailed deer (WTD, Odocoileus virginianus) for surveillance of chronic wasting disease, to assess anti-SARS-CoV-2 neutralizing antibodies. A total of 132 pairs of retropharyngeal lymph nodes collected from Nebraska WTD harvested in Nebraska, US, in 2019 …

Characterizing Cellular Injury And Inflammation With Aldob-/-Mouse Model Of Mafld, Andy Rashid

All Master's Theses

Metabolic-associated fatty liver disease (MAFLD) affects 1 in 3 people in the US and is a healthcare burden on the order of billions of dollars. MAFLD is characterized by pathological lipid accumulation in the liver, excess production of triglycerides and cholesterol, and export of LDL particles that raise serum lipid levels. These metabolic perturbations can lead to the development of liver fibrosis, chronic inflammation, and insulin resistance. Diagnosing MAFLD prior to fibrosis is crucial for successful intervention and prevention of advanced liver disease and other metabolic complications. Fructose-1Phospahte (F1P) accumulation from fructose overconsumption can drive hepatic lipogenesis and MAFLD progression. …

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 …

A Novel Interaction Between Extracellular Vimentin And Fibrinogen In Fibrin Formation, Marina Martinez-Vargas, Adrian Cebula, Lisa S Brubaker, Nitin Seshadri, Fong W Lam, Michele Loor, Todd K Rosengart, Andrew Yee, Rolando E Rumbaut, Miguel A Cruz

Faculty, Staff and Students Publications

INTRODUCTION: Thrombosis is frequently manifested in critically ill patients with systemic inflammation, including sepsis and COVID-19. The coagulopathy in systemic inflammation is often associated with increased levels of fibrinogen and D-dimer. Because elevated levels of vimentin have been detected in sepsis, we sought to investigate the relationship between vimentin and the increased fibrin formation potential observed in these patients.

MATERIALS AND METHODS: This hypothesis was examined by using recombinant human vimentin, anti-vimentin antibodies, plasma derived from healthy and critically ill patients, confocal microscopy, co-immunoprecipitation assays, and size exclusion chromatography.

RESULTS: The level of vimentin in plasma derived from critically ill …

A Rare Case Of Pancreatic Actinomyces, Marguerite Poche, Kyle Liu, Codey Pham, Shilpa Jain, Robert Sealock

Faculty, Staff and Students Publications

Actinomyces israelii is a filamentous, gram-positive anaerobic bacterium commonly found in the upper gastrointestinal tract, colon, and female genital tract. Rarely, actinomycosis can infect the pancreas most commonly after pancreatic instrumentation, often mimicking malignancy. We describe a case of a 26-year-old woman who presented with epigastric abdominal pain and nausea without prior pancreatic instrumentation. Abdominal imaging demonstrated a mass in the pancreatic head with fine-needle biopsy revealing Actinomyces. The patient was successfully treated with long-term antibiotic therapy resulting in resolution of the mass. Our case emphasizes the importance of considering nonmalignant etiologies in the differential diagnosis of pancreatic masses.

Native Bk Polyomavirus Nephropathy In An Orthotopic Heart Transplant Patient, Zachary M Thompson, George Ajene, Prathit A Kulkarni, Nidhi Aggarwal, Savitri Fedson, Maulin K Shah

Faculty, Staff and Students Publications

BK polyomavirus nephropathy (BKVN) is a common cause of nephropathy in kidney transplant patients and is typically seen within the first year after transplantation. BK polyomavirus nephropathy can occur in the native kidneys of patients with nonrenal solid-organ transplants (NRSOT). However, this is rare, especially outside the early post-transplant period, and BKVN is not usually considered in the differential diagnosis for acute kidney injury in NRSOT patients. We present a case of a 75-year-old man who had undergone orthotopic heart transplant 13 years prior with stable allograft function who developed progressive renal dysfunction in the setting of recent unilateral obstructive …

Impact Of Gastrointestinal Polymerase Chain Reaction Panels On Antibiotic Utilization In Hospitalized Adult Patients, Gillean A Kelly, Roumen Iordanov, Alex Franklin, Amna Ahmed, Krithika Srinivasan, Jesica Hayon, Todd Lasco, Rosie Amini, Sabra Shay, Prathit A Kulkarni, Mayar Al Mohajer

Faculty, Staff and Students Publications

Multiplex stool polymerase chain reaction (PCR) panels offer rapid comprehensive testing for patients with infectious diarrhea. We compared antibiotic utilization among hospitalized patients with suspected infectious diarrhea who underwent diagnostic testing with either a stool culture or stool PCR panel. No significant differences in antibiotic utilization were identified.

Second Virtual International Symposium On Cellular And Organismal Stress Responses, September 8-9, 2022, Patricija Van Oosten-Hawle, Sarah J Backe, Anat Ben-Zvi, Dimitra Bourboulia, Mara Brancaccio, Jeff Brodsky, Melody Clark, Giorgio Colombo, Marc B Cox, Paolo De Los Rios, Frank Echtenkamp, Adrienne Edkins, Brian Freeman, Pierre Goloubinoff, Walid Houry, Jill Johnson, Paul Lapointe, Wei Li, Valerie Mezger, Len Neckers, Nadinath B Nillegoda, Veena Prahlad, Adam Reitzel, Ruth Scherz-Shouval, Lea Sistonen, Francis T F Tsai, Mark R Woodford, Mehdi Mollapour, Andrew W Truman

Faculty, Staff and Students Publications

The Second International Symposium on Cellular and Organismal Stress Responses took place virtually on September 8-9, 2022. This meeting was supported by the Cell Stress Society International (CSSI) and organized by Patricija Van Oosten-Hawle and Andrew Truman (University of North Carolina at Charlotte, USA) and Mehdi Mollapour (SUNY Upstate Medical University, USA). The goal of this symposium was to continue the theme from the initial meeting in 2020 by providing a platform for established researchers, new investigators, postdoctoral fellows, and students to present and exchange ideas on various topics on cellular stress and chaperones. We will summarize the highlights of …

Targeting Hiv-1 Reservoirs In T Cell Subsets, Min Li, Marietta M Budai, Min Chen, Jin Wang

Faculty, Staff and Students Publications

The HIV-1 reservoirs harbor the latent proviruses that are integrated into the host genome. It is a challenging task to eradicate the proviruses in order to achieve an HIV cure. We have described a strategy for the clearance of HIV-1 infection through selective elimination of host cells harboring replication-competent HIV (SECH), by inhibition of autophagy and promotion of apoptosis during viral re-activation. HIV-1 can infect various CD4+ T cell subsets, but it is not known whether the SECH approach is equally effective in targeting HIV-1 reservoirs in these different subsets in vivo. In a humanized mouse model, we found …

Mortality Difference From Klebsiella Aerogenes Vs Enterobacter Cloacae Bloodstream Infections, Andrew Chou, Richard Sucgang, Richard J Hamill, Lynn Zechiedrich, Barbara W Trautner

Faculty, Staff and Students Publications

Members of the order Enterobacterales, including Escherichia coli , Klebsiella species and Enterobacter species, are important pathogens in healthcare-associated infections. Higher mortality has been reported from infections due to Klebsiella pneumoniae than from E. coli , but prior studies comparing Enterobacter aerogenes (recently renamed Klebsiella aerogenes ) bacteraemia and Enterobacter cloacae complex bacteraemia have yielded conflicting results regarding whether clinical outcomes differ. We found bacteraemia with K. aerogenes was independently associated with greater risk of 30-day mortality than bacteraemia with Enterobacter cloacae complex.

Oral Gauze For Bleeding Control In Perioral And Perinasal Dermatologic Surgery, Riyad N H Seervai, Jose A Cervantes, Ikue Shimizu, Ida F Orengo

Faculty, Staff and Students Publications

The use of oral gauze is a quick, cheap, and effective method of preventing bleeding into the patient's mouth during dermatologic surgery. We recommend this technique combined with appropriate positioning for lesions in the perioral and perinasal regions. Similar approaches may be applied for the prevention of bleeding into the ear canal during facial/periauricular surgery.

Adeno-Associated Virus 8 Delivers An Immunomodulatory Peptide To Mouse Liver More Efficiently Than To Rat Liver, Yuqing Wang, Ayrea Hurley, Marco De Giorgi, Mark R Tanner, Rong-Chi Hu, Michael W Pennington, William R Lagor, Christine Beeton

Faculty, Staff and Students Publications

Targeting the Kv1.3 potassium channel has proven effective in reducing obesity and the severity of animal models of autoimmune disease. Stichodactyla toxin (ShK), isolated from the sea anemone Stichodactyla helianthus, is a potent blocker of Kv1.3. Several of its analogs are some of the most potent and selective blockers of this channel. However, like most biologics, ShK and its analogs require injections for their delivery, and repeated injections reduce patient compliance during the treatment of chronic diseases. We hypothesized that inducing the expression of an ShK analog by hepatocytes would remove the requirement for frequent injections and lead to a …

Quantitative Measurement Of Protac Intracellular Accumulation, Xin Yu, Jin Wang

Faculty, Staff and Students Publications

In recent years, Proteolysis Targeting Chimera (PROTAC) technology has emerged as one of the most promising approaches to remove disease-associated proteins by utilizing cells' own destruction machinery. To achieve successful degradation of a protein of interest (POI), the heterobifunctional PROTAC molecules must penetrate into the cells first, followed by target engagement and formation of the POI-PROTAC-E3 ligase complex. Based on this understanding, the assessment of cell permeability and in cell target engagement are of great importance to evaluate the efficacy of PROTAC candidates. PROTAC molecules can be classified as non-covalent and covalent, and covalent PROTACs can be further divided into …

A Guide To Naming Eukaryotic Circular Rnas, Ling-Ling Chen, Albrecht Bindereif, Irene Bozzoni, Howard Y Chang, A Gregory Matera, Myriam Gorospe, Thomas B Hansen, Jørgen Kjems, Xu-Kai Ma, Jun Wei Pek, Nikolaus Rajewsky, Julia Salzman, Jeremy E Wilusz, Li Yang, Fangqing Zhao

Faculty, Staff and Students Publications

Alternative splicing of eukaryotic transcripts often leads to production of multiple mature RNAs from a single gene locus. In addition to encoding linear RNAs, genes can produce stable circular RNAs (circRNAs) that are often co-expressed with their cognate linear RNAs. Multiple distinct circRNAs are frequently generated from a gene locus via back-splicing, with each mature transcript having a potentially unique function due to its distinct combination of exons and sometimes retained introns. However, names currently given to circRNAs are often ambiguous and lack consistency across studies. Here, we call on the community to embrace standards for naming circRNAs so that …

Heat Shock Protein 90 (Hsp90) System In Health And Disease., Daniella Munezero

Graduate Theses, Dissertations, and Problem Reports (ETD)

Cells rely on heat shock proteins (HSP) to facilitate and regulate the folding of the substrate proteins into their native state, and degradation if misfolding cannot be prevented. HSP90, a member of the HSP family, is a potential target for treatment of cancer and neurodegenerative diseases. Unfortunately, several clinical trials for cancer treatment have been discontinued due to cell toxicity accompanying HSP90 inhibition. HSP90 has four distinct but structurally similar paralogs. HSP90 inhibitors target all the paralogs despite increasing proof of functional differences among the paralogs. Understanding the in vivo function of HSP90 and the role played by each paralog …