Digital Commons Network^™

Trace Element Concentrations In Blood And Scute Tissues From Wild And Captive Hawaiian Green Sea Turtles (Chelonia Mydas), Katherine R Shaw, Jennifer M Lynch, George H Balazs, T Todd Jones, Jeff Pawloski, Marc R Rice, Amanda D French, Jing Liu, George P Cobb, David M Klein

Faculty, Staff and Students Publications

Sea turtles are exposed to trace elements through water, sediment, and food. Exposure to these elements has been shown to decrease immune function, impair growth, and decrease reproductive output in wildlife. This study compares trace element concentrations in green turtles in captivity at Sea Life Park Hawaii (n = 6) to wild green turtles in Kapoho Bay, HI (n = 5 to 7). Blood and scute samples were collected and analyzed for eleven elements via inductively coupled plasma-mass spectrometry (ICP-MS). Selenium was significantly greater (p < 0.05) in the blood of captive turtles compared to wild turtles, while V, Ni, and Pb were significantly greater in the blood of wild turtles. In scute, V, Cu, Se, and Cr were significantly greater in captive turtles, while As was significantly greater in wild turtles. Pelleted food fed to the captive turtles and representative samples of the wild turtle diet were analyzed via ICP-MS to calculate trophic transfer factors and daily intake values. Wild turtles had greater estimated daily intake than captive turtles for all elements except Cu and Se. Because captive turtles are fed a diet very different from their wild counterparts, captive turtles do not represent control or reference samples for chemical exposure studies in wild turtles. No toxic thresholds are known for sea turtles, but rehabilitation and managed care facilities should monitor sea turtle elemental concentrations to ensure the animals’ health.

Mucins, Gut Microbiota, And Postbiotics Role In Colorectal Cancer, Ramesh Pothuraju, Sanjib Chaudhary, Satyanarayana Rachagani, Sukhwinder Kaur, Hemant K Roy, Michael Bouvet, Surinder K Batra

Faculty, Staff and Students Publications

An imbalance in the crosstalk between the host and gut microbiota affects the intestinal barrier function, which results in inflammatory diseases and colorectal cancer. The colon epithelium protects itself from a harsh environment and various pathogenic organisms by forming a double mucus layer, primarily comprising mucins. Recent studies are focusing on how dietary patterns alter the gut microbiota composition, which in turn regulates mucin expression and maintains the intestinal layers. In addition, modulation of gut microbiota by microbiotic therapy (involving fecal microbiota transplantation) has emerged as a significant factor in the pathologies associated with dysbiosis. Therefore, proper communication between host …

A Developmental Stage-Specific Network Approach For Studying Dynamic Co-Regulation Of Transcription Factors And Micrornas During Craniofacial Development, Fangfang Yan, Peilin Jia, Hiroki Yoshioka, Akiko Suzuki, Junichi Iwata, Zhongming Zhao

Faculty, Staff and Student Publications

Craniofacial development is regulated through dynamic and complex mechanisms that involve various signaling cascades and gene regulations. Disruption of such regulations can result in craniofacial birth defects. Here, we propose the first developmental stage-specific network approach by integrating two crucial regulators, transcription factors (TFs) and microRNAs (miRNAs), to study their co-regulation during craniofacial development. Specifically, we used TFs, miRNAs and non-TF genes to form feed-forward loops (FFLs) using genomic data covering mouse embryonic days E10.5 to E14.5. We identified key novel regulators (TFs Foxm1, Hif1a, Zbtb16, Myog, Myod1 and Tcf7, and miRNAs miR-340-5p and miR-129-5p) and target genes (

The Cardiac Neural Crest Cells In Heart Development And Congenital Heart Defects, Eileen M Burd, Ahmed Babiker, Jessica K Fairley, Divya Bhamidipati, Laila E Woc-Colburn, Blaine A Mathison

Faculty, Staff and Student Publications

No abstract provided.

Possible Transmission Flow Of Sars-Cov-2 Based On Ace2 Features, Sk Sarif Hassan, Shinjini Ghosh, Diksha Attrish, Pabitra Pal Choudhury, Alaa A A Aljabali, Bruce D Uhal, Kenneth Lundstrom, Nima Rezaei, Vladimir N Uversky, Murat Seyran, Damiano Pizzol, Parise Adadi, Antonio Soares, Tarek Mohamed Abd El-Aziz, Ramesh Kandimalla, Murtaza M Tambuwala, Gajendra Kumar Azad, Samendra P Sherchan, Wagner Baetas-Da-Cruz, Kazuo Takayama, Ángel Serrano-Aroca, Gaurav Chauhan, Giorgio Palu, Adam M Brufsky

All publications

Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that is engendering the severe coronavirus disease 2019 (COVID-19) pandemic. The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 binds to the three sub-domains viz. amino acids (aa) 22-42, aa 79-84, and aa 330-393 of ACE2 on human cells to initiate entry. It was reported earlier that the receptor utilization capacity of ACE2 proteins from different species, such as cats, chimpanzees, dogs, and cattle, are different. A comprehensive analysis of ACE2 receptors of nineteen species was carried out in this study, and the …

Yap And Taz Maintain Prox1 Expression In The Developing Lymphatic And Lymphovenous Valves In Response To Vegf-C Signaling, Boksik Cha, Yen-Chun Ho, Xin Geng, Md Riaj Mahamud, Lijuan Chen, Yeunhee Kim, Dongwon Choi, Tae Hoon Kim, Gwendalyn J Randolph, Xinwei Cao, Hong Chen, R Sathish Srinivasan

Open Access Publications

Lymphatic vasculature is an integral part of digestive, immune and circulatory systems. The homeobox transcription factor PROX1 is necessary for the development of lymphatic vessels, lymphatic valves (LVs) and lymphovenous valves (LVVs). We and others previously reported a feedback loop between PROX1 and vascular endothelial growth factor-C (VEGF-C) signaling. PROX1 promotes the expression of the VEGF-C receptor VEGFR3 in lymphatic endothelial cells (LECs). In turn, VEGF-C signaling maintains PROX1 expression in LECs. However, the mechanisms of PROX1/VEGF-C feedback loop remain poorly understood. Whether VEGF-C signaling is necessary for LV and LVV development is also unknown. Here, we report for the …

Global Hypermethylation Of Intestinal Epithelial Cells Is A Hallmark Feature Of Neonatal Surgical Necrotizing Enterocolitis, Misty Good, Tianjiao Chu, Patricia Shaw, Lora Mcclain, Austin Chamberlain, Carlos Castro, Jamie M Rimer, Belgacem Mihi, Qingqing Gong, Lila S Nolan, Krista Cooksey, Laura Linneman, Pranjal Agrawal, David N Finegold, David Peters

2020-Current year OA Pubs

BACKGROUND: Necrotizing enterocolitis (NEC) remains one of the overall leading causes of death in premature infants, and the pathogenesis is unpredictable and not well characterized. The aim of our study was to determine the molecular phenotype of NEC via transcriptomic and epithelial cell-specific epigenomic analysis, with a specific focus on DNA methylation.

METHODS: Using laser capture microdissection, epithelial cell-specific methylation signatures were characterized by whole-genome bisulfite sequencing of ileal and colonic samples at the time of surgery for NEC and after NEC had healed at reanastomosis (n = 40). RNA sequencing was also performed to determine the transcriptomic profile of …

Functional Redundancy Of Type I And Type Ii Receptors In The Regulation Of Skeletal Muscle Growth By Myostatin And Activin A., Se-Jin Lee, Adam Lehar, Yewei Liu, Chi Hai Ly, Quynh-Mai Pham, Michael Michaud, Renata Rydzik, Daniel W Youngstrom, Michael M Shen, Vesa Kaartinen, Emily L Germain-Lee, Thomas A Rando

Faculty Research 2020

Myostatin (MSTN) is a transforming growth factor-β (TGF-β) family member that normally acts to limit muscle growth. The function of MSTN is partially redundant with that of another TGF-β family member, activin A. MSTN and activin A are capable of signaling through a complex of type II and type I receptors. Here, we investigated the roles of two type II receptors (ACVR2 and ACVR2B) and two type I receptors (ALK4 and ALK5) in the regulation of muscle mass by these ligands by genetically targeting these receptors either alone or in combination specifically in myofibers in mice. We show that targeting …

A Steroid Receptor Coactivator Stimulator (Mcb-613) Attenuates Adverse Remodeling After Myocardial Infarction, Lisa K Mullany, Aarti D Rohira, John P Leach, Jong H Kim, Tanner O Monroe, Andrea R Ortiz, Brittany Stork, M Waleed Gaber, Poonam Sarkar, Andrew G Sikora, Todd K Rosengart, Brian York, Yongcheng Song, Clifford C Dacso, David M Lonard, James F Martin, Bert W O'Malley

Faculty, Staff and Students Publications

Progressive remodeling of the heart, resulting in cardiomyocyte (CM) loss and increased inflammation, fibrosis, and a progressive decrease in cardiac function, are hallmarks of myocardial infarction (MI)-induced heart failure. We show that MCB-613, a potent small molecule stimulator of steroid receptor coactivators (SRCs) attenuates pathological remodeling post-MI. MCB-613 decreases infarct size, apoptosis, hypertrophy, and fibrosis while maintaining significant cardiac function. MCB-613, when given within hours post MI, induces lasting protection from adverse remodeling concomitant with: 1) inhibition of macrophage inflammatory signaling and interleukin 1 (IL-1) signaling, which attenuates the acute inflammatory response, 2) attenuation of fibroblast differentiation, and 3) promotion …

Systematic Comparison Of Sea Urchin And Sea Star Developmental Gene Regulatory Networks Explains How Novelty Is Incorporated In Early Development., Gregory A Cary, Brenna S Mccauley, Olga Zueva, Joseph Pattinato, William J R Longabaugh, Veronica F Hinman

Articles, Abstracts, and Reports

The extensive array of morphological diversity among animal taxa represents the product of millions of years of evolution. Morphology is the output of development, therefore phenotypic evolution arises from changes to the topology of the gene regulatory networks (GRNs) that control the highly coordinated process of embryogenesis. A particular challenge in understanding the origins of animal diversity lies in determining how GRNs incorporate novelty while preserving the overall stability of the network, and hence, embryonic viability. Here we assemble a comprehensive GRN for endomesoderm specification in the sea star from zygote through gastrulation that corresponds to the GRN for sea …

Humoral Immune Responses Mediate The Development Of A Restrictive Phenotype Of Chronic Lung Allograft Dysfunction, Keizo Misumi, David S Wheeler, Yoshiro Aoki, Michael P Combs, Russell R Braeuer, Ryuji Higashikubo, Wenjun Li, Daniel Kreisel, Ragini Vittal, Jeffrey Myers, Amir Lagstein, Natalie M Walker, Carol F Farver, Vibha N Lama

Open Access Publications

Understanding the distinct pathogenic mechanisms that culminate in allograft fibrosis and chronic graft failure is key in improving outcomes after solid organ transplantation. Here, we describe an F1 → parent orthotopic lung transplant model of restrictive allograft syndrome (RAS), a particularly fulminant form of chronic lung allograft dysfunction (CLAD), and identify a requisite pathogenic role for humoral immune responses in development of RAS. B6D2F1/J (H2-b/d) donor lungs transplanted into the parent C57BL/6J (H2-b) recipients demonstrated a spectrum of histopathologic changes, ranging from lymphocytic infiltration, fibrinous exudates, and endothelialitis to peribronchial and pleuroparenchymal fibrosis, similar to those noted in the human …

Aging, But Not Sex And Genetic Diversity, Impacts The Pathobiology Of Bacterial Endophthalmitis, Pawan Kumar Singh, Sukhvinder Singh, Robert Emery Wright, Ramandeep Rattan, Ashok Kumar

Obstetrics, Gynecology and Women's Health Services Articles

Purpose: Age, sex, and genetics are important biological variables in determining an individual's susceptibility or response to infectious agents; however, their role has not been evaluated in intraocular infections. In this study, we comprehensively examined the impact of these host biological factors in the pathogenesis of experimental bacterial endophthalmitis.

Methods: Endophthalmitis was induced by intravitreal injection of bacteria (Staphylococcus aureus) in the eyes of male and female C57BL/6 mice of different ages: group I (young, 6-8 weeks), group II (mid-age, 18-20 weeks), and group III (old, 1 year). Highly heterogeneous outbred J:DO mice were used for genetic diversity analysis. Eyes …

Trends In The Clinical Use Of Antibiotics In A Veterinary Hospital In Nigeria, 2013 –2017, Thelma Ebele Ihedioha, Isaac Uzoma Asuzu, John Anaelom Nwanta

The Thai Journal of Veterinary Medicine

This study was a retrospective survey that evaluated the trend of clinical use and misuse of antibiotics on animals presented for veterinary care at the Veterinary Teaching Hospital, Nsukka, Enugu State, Nigeria, from January 2013 to December 2017. A total of 4851 case files were evaluated and, overall, antibiotics were used in 2316 cases (47.74%). The most frequently used antibiotics were a penicillin-streptomycin combination (36.53%), oxytetracycline (32.08%), gentamicin (19.78%) and sulphadimidine (5.35%); the frequency of use of other antibiotics was each less than 5%. The overall use of antibiotics increased significantly (p<0.05) across the study period, from 35.25% in 2013 to 52.38% in2016. There was a significant (p<0.05) increase in the frequency of use of oxytetracycline (11.55% in 2013 to 40.31% in 2016) and sulphadimidine (0.8% in 2013 to 12.98% in 2017), but the frequency of penicillin-streptomycin use significantly (p<0.01) decreased from 74.5% in 2013 to 23.13% in 2017. The frequency of inappropriate use of antibiotics significantly (p<0.01) increased from 4.38% (2013) to 25.29% (2017), while that of non-compliance rose significantly (p<0.01) from 15.54% (2013) to 41.88% (2016).The frequency of use of antibiotics without definitive diagnosis/sensitivity testing was consistently high and did not significantly (p>0.05) vary across the study period (85.49% to …

Integrated Structural And Functional Analysis Of The Protective Effects Of Kinetin Against Oxidative Stress In Mammalian Cellular Systems, Muhammad Naseem, Eman M. Othman, Moustafa Fathy, Jibran Iqbal, Fares M. Howari, Fatima A. Alremeithi, Geema Kodandaraman, Helga Stopper, Elena Bencurova, Dimitrios Vlachakis, Thomas Dandekar

All Works

© 2020, The Author(s). Metabolism and signaling of cytokinins was first established in plants, followed by cytokinin discoveries in all kingdoms of life. However, understanding of their role in mammalian cells is still scarce. Kinetin is a cytokinin that mitigates the effects of oxidative stress in mammalian cells. The effective concentrations of exogenously applied kinetin in invoking various cellular responses are not well standardized. Likewise, the metabolism of kinetin and its cellular targets within the mammalian cells are still not well studied. Applying vitality tests as well as comet assays under normal and hyper-oxidative states, our analysis suggests that kinetin …

Depletion Of Essential Isoprenoids And Er Stress Induction Following Acute Liver-Specific Deletion Of Hmg-Coa Reductase, Marco De Giorgi, Kelsey E Jarrett, Jason C Burton, Alexandria M Doerfler, Ayrea Hurley, Ang Li, Rachel H Hsu, Mia Furgurson, Kalyani R Patel, Jun Han, Christoph H Borchers, William R Lagor

Faculty, Staff and Students Publications

HMG-CoA reductase (Hmgcr) is the rate-limiting enzyme in the mevalonate pathway and is inhibited by statins. In addition to cholesterol, Hmgcr activity is also required for synthesizing nonsterol isoprenoids, such as dolichol, ubiquinone, and farnesylated and geranylgeranylated proteins. Here, we investigated the effects of Hmgcr inhibition on nonsterol isoprenoids in the liver. We have generated new genetic models to acutely delete genes in the mevalonate pathway in the liver using AAV-mediated delivery of Cre-recombinase (AAV-Cre) or CRISPR/Cas9 (AAV-CRISPR). The genetic deletion of Hmgcr by AAV-Cre resulted in extensive hepatocyte apoptosis and compensatory liver regeneration. At the biochemical …

Sequence Analysis In Bos Taurus Reveals Pervasiveness Of X-Y Arms Races In Mammalian Lineages, Jennifer F Hughes, Colin Kremitzki, Catrina Fronick, Tina A Graves-Lindsay, Lucinda Fulton, Wesley C Warren, Richard K Wilson, Et Al.

2020-Current year OA Pubs

Studies of Y Chromosome evolution have focused primarily on gene decay, a consequence of suppression of crossing-over with the X Chromosome. Here, we provide evidence that suppression of X-Y crossing-over unleashed a second dynamic: selfish X-Y arms races that reshaped the sex chromosomes in mammals as different as cattle, mice, and men. Using super-resolution sequencing, we explore the Y Chromosome of

Stat1 Dissociates Adipose Tissue Inflammation From Insulin Sensitivity In Obesity, Aaron R Cox, Natasha Chernis, David A Bader, Pradip K Saha, Peter M Masschelin, Jessica B Felix, Robert Sharp, Zeqin Lian, Vasanta Putluri, Kimal Rajapakshe, Kang Ho Kim, Dennis T Villareal, Reina Armamento-Villareal, Huaizhu Wu, Cristian Coarfa, Nagireddy Putluri, Sean M Hartig

Faculty, Staff and Students Publications

Obesity fosters low-grade inflammation in white adipose tissue (WAT) that may contribute to the insulin resistance that characterizes type 2 diabetes. However, the causal relationship of these events remains unclear. The established dominance of STAT1 function in the immune response suggests an obligate link between inflammation and the comorbidities of obesity. To this end, we sought to determine how STAT1 activity in white adipocytes affects insulin sensitivity. STAT1 expression in WAT inversely correlated with fasting plasma glucose in both obese mice and humans. Metabolomic and gene expression profiling established STAT1 deletion in adipocytes (STAT1a-KO) enhanced mitochondrial function …

Mouse Models To Study The Pathophysiology Of Combined Methylmalonic Acidemia And Homocystinuria, Cblc Type, Tiffany Chern, Annita Achilleos, Xuefei Tong, Chih-Wei Hsu, Leeyean Wong, Ross A Poché

Faculty, Staff and Students Publications

Combined methylmalonic acidemia and homocystinuria, cblC type, is the most common inherited disorder of cobalamin metabolism and is characterized by severe fetal developmental defects primarily impacting the central nervous system, hematopoietic system, and heart. CblC was previously shown to be due to mutations in the MMACHC gene, which encodes a protein thought to function in intracellular cobalamin trafficking and biosynthesis of adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). These coenzymes are required for the production of succinyl-CoA and methionine, respectively. However, it is currently unclear whether additional roles for MMACHC exist outside of cobalamin metabolism. Furthermore, due to a lack of sufficient …

Role Of Metabolism In Bone Development And Homeostasis, Akiko Suzuki, Mina Minamide, Chihiro Iwaya, Kenichi Ogata, Junichi Iwata

Faculty, Staff and Student Publications

Carbohydrates, fats, and proteins are the underlying energy sources for animals and are catabolized through specific biochemical cascades involving numerous enzymes. The catabolites and metabolites in these metabolic pathways are crucial for many cellular functions; therefore, an imbalance and/or dysregulation of these pathways causes cellular dysfunction, resulting in various metabolic diseases. Bone, a highly mineralized organ that serves as a skeleton of the body, undergoes continuous active turnover, which is required for the maintenance of healthy bony components through the deposition and resorption of bone matrix and minerals. This highly coordinated event is regulated throughout life by bone cells such …

Differences In Gynecologic Tumor Development In Amhr2-Cre Mice With Krasg12d Or Krasg12v Mutations, Eucharist H S Kun, Yvonne T M Tsang, Sophia Lin, Sophia Pan, Tejas Medapalli, Anais Malpica, Joanne S Richards, David M Gershenson, Kwong-Kwok Wong

Faculty, Staff and Students Publications

How different KRAS variants impact tumor initiation and progression in vivo has not been thoroughly examined. We hypothesize that the ability of either KRASG12D or KRASG12V mutations to initiate tumor formation is context dependent. Amhr2-Cre mice express Cre recombinase in tissues that develop into the fallopian tubes, uterus, and ovaries. We used these mice to conditionally express either the KRASG12V/+ or KRASG12D/+ mutation. Mice with the genotype Amhr2-Cre Pten(fl/fl) KrasG12D/+(G12D mice) had abnormal follicle structures and developed low-grade serous ovarian carcinomas with 100% penetrance within 18 weeks. In contrast, mice with …

A Review Of Volatile Organic Compound Contamination In Post-Industrial Urban Centers: Reproductive Health Implications Using A Detroit Lens, Carol J. Miller, Melissa Runge-Morris, Andrea E. Cassidy-Bushrow, Jennifer K. Straughen, Timothy M. Dittrich, Tracie R. Baker, Michael C. Petriello, Gil Mor, Douglas M. Ruden, Brendan F. O'Leary, Sadaf Teimoori, Chandra M. Tummala, Samantha Heldman, Manisha Agarwal, Katherine Roth, Zhao Yang, Bridget B. Baker

Public Health Sciences Articles

Volatile organic compounds (VOCs) are a group of aromatic or chlorinated organic chemicals commonly found in manufactured products that have high vapor pressure, and thus vaporize readily at room temperature. While airshed VOCs are well studied and have provided insights into public health issues, we suggest that belowground VOCs and the related vapor intrusion process could be equally or even more relevant to public health. The persistence, movement, remediation, and human health implications of subsurface VOCs in urban landscapes remain relatively understudied despite evidence of widespread contamination. This review explores the state of the science of subsurface movement and remediation …

Altered Capicua Expression Drives Regional Purkinje Neuron Vulnerability Through Ion Channel Gene Dysregulation In Spinocerebellar Ataxia Type 1, Ravi Chopra, David D Bushart, John P Cooper, Dhananjay Yellajoshyula, Logan M Morrison, Haoran Huang, Hillary P Handler, Luke J Man, Warunee Dansithong, Daniel R Scoles, Stefan M Pulst, Harry T Orr, Vikram G Shakkottai

2020-Current year OA Pubs

Selective neuronal vulnerability in neurodegenerative disease is poorly understood. Using the ATXN1[82Q] model of spinocerebellar ataxia type 1 (SCA1), we explored the hypothesis that regional differences in Purkinje neuron degeneration could provide novel insights into selective vulnerability. ATXN1[82Q] Purkinje neurons from the anterior cerebellum were found to degenerate earlier than those from the nodular zone, and this early degeneration was associated with selective dysregulation of ion channel transcripts and altered Purkinje neuron spiking. Efforts to understand the basis for selective dysregulation of channel transcripts revealed modestly increased expression of the ATXN1 co-repressor Capicua (Cic) in anterior cerebellar Purkinje neurons. Importantly, …

Central Nervous System Pathology In Preclinical Mps Iiib Dogs Reveals Progressive Changes In Clinically Relevant Brain Regions, Martin T Egeland, Marta M Tarczyluk-Wells, Melissa M Asmar, Evan G Adintori, Roger Lawrence, Elizabeth M Snella, Jackie K Jens, Brett E Crawford, Jill C M Wait, Emma Mccullagh, Jason Pinkstaff, Jonathan D Cooper, N Matthew Ellinwood

2020-Current year OA Pubs

Mucopolysaccharidosis type IIIB (MPS IIIB; Sanfilippo syndrome B) is an autosomal recessive lysosomal storage disorder caused by the deficiency of alpha-N-acetylglucosaminidase activity, leading to increased levels of nondegraded heparan sulfate (HS). A mouse model has been useful to evaluate novel treatments for MPS IIIB, but has limitations. In this study, we evaluated the naturally occurring canine model of MPS IIIB for the onset and progression of biochemical and neuropathological changes during the preclinical stages (onset approximately 24-30 months of age) of canine MPS IIIB disease. Even by 1 month of age, MPS IIIB dogs had elevated HS levels in brain …

Role For Carbohydrate Response Element-Binding Protein (Chrebp) In High Glucose-Mediated Repression Of Long Noncoding Rna Tug1, Jianyin Long, Daniel L Galvan, Koki Mise, Yashpal S Kanwar, Li Li, Naravat Poungavrin, Paul A Overbeek, Benny H Chang, Farhad R Danesh

Faculty, Staff and Students Publications

Long noncoding RNAs (lncRNAs) have been shown to play key roles in a variety of biological activities of the cell. However, less is known about how lncRNAs respond to environmental cues and what transcriptional mechanisms regulate their expression. Studies from our laboratory have shown that the lncRNA Tug1 (taurine upregulated gene 1) is crucial for the progression of diabetic kidney disease, a major microvascular complication of diabetes. Using a combination of proximity labeling with the engineered soybean ascorbate peroxidase (APEX2), ChIP-qPCR, biotin-labeled oligonucleotide pulldown, and classical promoter luciferase assays in kidney podocytes, we extend our initial observations in the current …

Social And Leisure Activities Predict Transitions In Cognitive Functioning In Older Mexican Adults: A Latent Transition Analysis Of The Mexican Health And Aging Study, Heather Mary Brown, Stephen A Murray, Hope Northrup, Kit Sing Au, Lee A Niswander

Faculty, Staff and Student Publications

Disruptions in neural tube (NT) closure result in neural tube defects (NTDs). To understand the molecular processes required for mammalian NT closure, we investigated the role of Snx3, a sorting nexin gene. Snx3−/− mutant mouse embryos display a fully-penetrant cranial NTD. In vivo, we observed decreased canonical WNT target gene expression in the cranial neural epithelium of the Snx3−/− embryos and a defect in convergent extension of the neural epithelium. Snx3−/− cells show decreased WNT secretion, and live cell imaging reveals aberrant recycling of the WNT ligand-binding protein WLS and mis-trafficking to the lysosome for degradation. The importance …

Ryanodine Receptor 1-Related Disorders: An Historical Perspective And Proposal For A Unified Nomenclature, Tokunbor A Lawal, Joshua J Todd, Jessica W Witherspoon, Carsten G Bönnemann, James J Dowling, Susan L Hamilton, Katherine G Meilleur, Robert T Dirksen

Faculty, Staff and Students Publications

The RYR1 gene, which encodes the sarcoplasmic reticulum calcium release channel or type 1 ryanodine receptor (RyR1) of skeletal muscle, was sequenced in 1988 and RYR1 variations that impair calcium homeostasis and increase susceptibility to malignant hyperthermia were first identified in 1991. Since then, RYR1-related myopathies (RYR1-RM) have been described as rare, histopathologically and clinically heterogeneous, and slowly progressive neuromuscular disorders. RYR1 variants can lead to dysfunctional RyR1-mediated calcium release, malignant hyperthermia susceptibility, elevated oxidative stress, deleterious post-translational modifications, and decreased RyR1 expression. RYR1-RM-affected individuals can present with delayed motor milestones, contractures, scoliosis, ophthalmoplegia, and respiratory insufficiency.Historically, RYR1-RM-affected individuals were …

Myosight-Semi-Automated Image Analysis Of Skeletal Muscle Cross Sections, Lyle W Babcock, Amy D Hanna, Nadia H Agha, Susan L Hamilton

Faculty, Staff and Students Publications

BACKGROUND: Manual analysis of cross-sectional area, fiber-type distribution, and total and centralized nuclei in skeletal muscle cross sections is tedious and time consuming, necessitating an accurate, automated method of analysis. While several excellent programs are available, our analyses of skeletal muscle disease models suggest the need for additional features and flexibility to adequately describe disease pathology. We introduce a new semi-automated analysis program, MyoSight, which is designed to facilitate image analysis of skeletal muscle cross sections and provide additional flexibility in the analyses.

RESULTS: We describe staining and imaging methods that generate high-quality images of immunofluorescent-labelled cross sections from mouse …

Evolution Of Brain-Wide Activity In The Awake Behaving Mouse After Acute Fear By Longitudinal Manganese-Enhanced Mri, Taylor W. Uselman, Daniel R. Barto, Russell E. Jacobs, Elaine L. Bearer

Pathology Research and Scholarship

Life threatening fear after a single exposure evolves in a subset of vulnerable individuals to anxiety, which may persist for their lifetime. Yet neither the whole brain's response to innate acute fear nor how brain activity evolves over time is known. Sustained neuronal activity may be a factor in the development of a persistent fear response. We couple two experimental protocols to provoke acute fear leading to prolonged fear: Predator stress (PS), a naturalistic approach to induce fear in rodents; and Serotonin transporter knockout mouse (SERT-KO) that responds to PS with sustained defensive behavior. Behavior was monitored before, during and …

A Praziquantel Treatment Study Of Immune And Transcriptome Profiles In Schistosoma Haematobium-Infected Gabonese Schoolchildren, Lucja A Labuda, Ayola A Adegnika, Bruce A Rosa, John Martin, Ulysse Ateba-Ngoa, Abena Serwaa Amoah, Honorine Mbenkep Lima, Lynn Meurs, Moustapha Mbow, Mikhael D Manurung, Jeannot F Zinsou, Hermelijn H Smits, Peter G Kremsner, Makedonka Mitreva, Maria Yazdanbakhsh

2020-Current year OA Pubs

BACKGROUND: Although Schistosoma haematobium infection has been reported to be associated with alterations in immune function, in particular immune hyporesponsiveness, there have been only few studies that have used the approach of removing infection by drug treatment to establish this and to understand the underlying molecular mechanisms.

METHODS: Schistosoma haematobium-infected schoolchildren were studied before and after praziquantel treatment and compared with uninfected controls. Cellular responses were characterized by cytokine production and flow cytometry, and in a subset of children RNA sequencing (RNA-Seq) transcriptome profiling was performed.

RESULTS: Removal of S haematobium infection resulted in increased schistosome-specific cytokine responses that were …

Structural Basis Of Ion Transport And Inhibition In Ferroportin, Yaping Pan, Zhenning Ren, Shuai Gao, Jiemin Shen, Lie Wang, Zhichun Xu, Ye Yu, Preetham Bachina, Hanzhi Zhang, Xiao Fan, Arthur Laganowsky, Nieng Yan, Ming Zhou

Faculty, Staff and Students Publications

Ferroportin is an iron exporter essential for releasing cellular iron into circulation. Ferroportin is inhibited by a peptide hormone, hepcidin. In humans, mutations in ferroportin lead to ferroportin diseases that are often associated with accumulation of iron in macrophages and symptoms of iron deficiency anemia. Here we present the structures of the ferroportin from the primate Philippine tarsier (TsFpn) in the presence and absence of hepcidin solved by cryo-electron microscopy. TsFpn is composed of two domains resembling a clamshell and the structure defines two metal ion binding sites, one in each domain. Both structures are in an outward-facing conformation, and …