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Vaccine Immunogenicity Versus Gastrointestinal Microbiome Status: Implications For Poultry Production, Chrysta N. Beck, Jiangchao Zhao, Gisela F. Erf

Poultry Science Faculty Publications and Presentations

At the turn of the 21st century, the importance of maintaining a balanced microbiome was brought to the forefront of the microbiology, immunology, and physiology research fields. Exploring the complex interactions between vaccine administration, mucosal microbiome, oral tolerance, and enteric inflammation in health and disease is challenging since environmental factors (such as diet and sanitation) have major influences on gut microbiota composition. High enteric pathogen load has been shown to contribute to dampened cell-mediated and humoral immune responses to vaccines in human case studies, either through elevated enteric inflammation or increased tolerance to environmental microbes. Although antibiotic and probiotic interventions …

Antimicrobial Tolerance In Salmonella: Contributions To Survival And Persistence In Processing Environments, Tomi Obe, Aaron S. Kiess, Ramakrishna Nannapaneni

Poultry Science Faculty Publications and Presentations

Salmonella remains a top bacterial pathogen implicated in several food-borne outbreaks, despite the use of antimicrobials and sanitizers during production and processing. While these chemicals have been effective, Salmonella has shown the ability to survive and persist in poultry processing environments. This can be credited to its microbial ability to adapt and develop/acquire tolerance and/or resistance to different antimicrobial agents including oxidizers, acids (organic and inorganic), phenols, and surfactants. Moreover, there are several factors in processing environments that can limit the efficacy of these antimicrobials, thus allowing survival and persistence. This mini-review examines the antimicrobial activity of common disinfectants/sanitizers used …

Effects Of Environmental Enrichments On Welfare And Hepatic Metabolic Regulation Of Broiler Chickens, Seong W. Kang, Karen D. Christensen, Michael T. Kidd, Sara K. Orlowski

Poultry Science Faculty Publications and Presentations

The aims of this study were to find suitable environmental enrichment (EE) and evaluate the combined effect of two EEs, variable light intensity (VL) lighting program and EH, on mental health and hepatic metabolic regulation in commercial broilers. To find the advantageous EEs for broilers, three different EEs (board, hut, and ramp) were tested in trial 1. EEs were placed and the engagement of birds to EEs, dustbathing behavior, and daily physical activity were observed. Birds treated with huts showed higher engagement than the board- or ramp-treated birds (p < 0.05). The results of dustbathing behavior and daily physical activity indicated that the environmental hut (EH) is the most favorable enrichment for broilers. In the second trial, to test the effect of EHs on mental health and hepatic metabolic conditions, the brain and liver were sampled from the four treatment birds (20 lx_Con, 20 lx_Hut, VL_Con and VL_Hut) on day 42. The lower expression of TPH2 (tryptophan hydroxylase 2) of VL_Hut birds than those of VL_Con and 20 lx_Hut treated birds suggests the combining effect of EHs with the VL lighting program on the central serotonergic homeostasis of broilers. Reduced expressions of TH (tyrosine hydroxylase), GR (glucocorticoid receptor), BDNF (brain-derived neurotrophic factor) of VL_Hut treated birds compared to those of VL_Con and 20 lx_Hut birds suggest lower stress, stress susceptibility, and chronic social stress in VL_Hut treated birds. The expression of CPT1A (carnitine palmitoyl transferase 1) increased over three-fold in the liver of VL_Con birds compared to 20 lx_Con birds (p < 0.05). EHs treatment in VL birds (VL_Hut) significantly decreased CPT1A but not in 20 lx birds (20 lx_Hut). The expression of ACCα (acetyl-CoA carboxylase alpha) was significantly decreased in VL_Con birds compared to 20 lx_Con birds. There was no significant difference in the hepatic FBPase (fructose-1,6-bisphosphatase), GR, and 11β-HSD1 (11 β-hydroxysteroid dehydrogenease-1) expression between 20 lx_Con and VL_Con birds, but EHs significantly stimulated GR in 20 lx_Hut birds, and stimulated FBPase and 11β-HSD1 expression in the VL_Hut birds compared to 20 lx_Con birds, suggesting that the VL lighting program reduced fatty acid synthesis and increased fatty acid β-oxidation in the broilers’ liver and VL_Hut improved the hepatic de novo glucose production. Taken together, the results suggest that the stimulated voluntary activity by EHs in the light-enriched broiler house improved mental health and hepatic metabolic function of broilers and may indicate that the improved hepatic metabolic function contributes to efficient nutritional support for broilers.

Molecular Genomic Analyses Of Enterococcus Cecorum From Sepsis Outbreaks In Broilers, Douglas D. Rhoads, Jeff Pummill, Adnan Ali Khalaf Alrubaye

Poultry Science Faculty Publications and Presentations

Extensive genomic analyses of Enterococcus cecorum isolates from sepsis outbreaks in broilers suggest a polyphyletic origin, likely arising from core genome mutations rather than gene acquisition. This species is a normal intestinal flora of avian species with particular isolates associated with osteomyelitis. More recently, this species has been associated with sepsis outbreaks affecting broilers during the first 3 weeks post-hatch. Understanding the genetic and management basis of this new phenotype is critical for developing strategies to mitigate this emerging problem. Phylogenomic analyses of 227 genomes suggest that sepsis isolates are polyphyletic and closely related to both commensal and osteomyelitis isolate …

Normative Impacts And Legitimacy Dimensions In The Intersection Of Trade And Agile Regulation Within Comprehensive Free Trade Agreements, Stefanie Schacherer

Research Collection Yong Pung How School Of Law

The article revisits the rationale of regulatory policy commitments in FTAs and assesses their normative impact considering the emerging paradigm of regulatory agility. It argues that commitments on best regulatory practices and regulatory cooperation can lead to more efficient, effective, and flexible regulations thereby preparing countries to implement future-proof and agile regulation to tackle current challenges stemming from technology and sustainability. Moreover, by promoting international regulatory cooperation activities, comprehensive FTAs further evolve into open-ended, living agreements, which are prone to establish dynamic bilateral or plurilateral regulatory relationships. However, the article also shows that the functionalist rationale perspective on the trade-(agile)regulation …

A Codified Liabilty Regime To Stimulate Greater Investment In Subpatentable Innovation, Ana Santos Rutschman, Jerome H. Reichman

Faculty Publications

The global intellectual property system rests on a distinction between exclusive property rights and free competition. Exclusive rights vary in strength and intensity, but the opposite of protection is almost always free competition. Distinctions of intensity are drawn in terms of the length of protection given to different subject matters plus variable lists of exceptions and limitations to exclusive rights. But the bottom line is that, when protection is not available under the existing system, free competition prevails, and vice-versa (i.e., where there is exclusivity, free competition is deferred for a specified period of time).

This Article departs from a …

Calorie Restriction Reduces Biomarkers Of Cellular Senescence In Humans, Zaira Aversa, Susan B Racette, Et Al.

2020-Current year OA Pubs

Calorie restriction (CR) with adequate nutrient intake is a potential geroprotective intervention. To advance this concept in humans, we tested the hypothesis that moderate CR in healthy young-to-middle-aged individuals would reduce circulating biomarkers of cellular senescence, a fundamental mechanism of aging and aging-related conditions. Using plasma specimens from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE™) phase 2 study, we found that CR significantly reduced the concentrations of several senescence biomarkers at 12 and 24 months compared to an ad libitum diet. Using machine learning, changes in biomarker concentrations emerged as important predictors of the change …

Multiomic Profiling Reveals Metabolic Alterations Mediating Aberrant Platelet Activity And Inflammation In Myeloproliferative Neoplasms, Fan He, Angelo Ba Laranjeira, Tim Kong, Shuyang Lin, Katrina J. Ashworth, Alice Liu, Nina M. Lasky, Daniel Ac Fisher, Maggie J. Cox, Mary C. Fulbright, Lilian Antunes-Heck, Layow Yu, Molly Brakhane, Bei Gao, Stephen M. Sykes, Angelo D'Alessandro, Jorge Di Paola, Stephen T. Oh

2020-Current year OA Pubs

Platelets from patients with myeloproliferative neoplasms (MPNs) exhibit a hyperreactive phenotype. Here, we found elevated P-selectin exposure and platelet-leukocyte aggregates indicating activation of platelets from essential thrombocythemia (ET) patients. Single-cell RNA-seq analysis of primary samples revealed significant enrichment of transcripts related to platelet activation, mTOR, and oxidative phosphorylation in ET patient platelets. These observations were validated via proteomic profiling. Platelet metabolomics revealed distinct metabolic phenotypes consisting of elevated ATP generation accompanied by increases in the levels of multiple intermediates of the tricarboxylic acid cycle, but lower α-ketoglutarate (α-KG) in MPN patients. Inhibition of PI3K/AKT/mTOR signaling significantly reduced metabolic responses and …

Pycallingcards: An Integrated Environment For Visualizing, Analyzing, And Interpreting Calling Cards Data, Juanru Guo, Wenjin Zhang, Xuhua Chen, Allen Yen, Lucy Chen, Christian A Shively, Daofeng Li, Ting Wang, Joseph D Dougherty, Robi D Mitra

2020-Current year OA Pubs

MOTIVATION: Unraveling the transcriptional programs that control how cells divide, differentiate, and respond to their environments requires a precise understanding of transcription factors' (TFs) DNA-binding activities. Calling cards (CC) technology uses transposons to capture transient TF binding events at one instant in time and then read them out at a later time. This methodology can also be used to simultaneously measure TF binding and mRNA expression from single-cell CC and to record and integrate TF binding events across time in any cell type of interest without the need for purification. Despite these advantages, there has been a lack of dedicated …

Mousevuer: Video Based Open-Source System For Laboratory Mouse Home-Cage Monitoring, Ghadi Salem, Niall Cope, Marcial Garmendia, Alex Pu, Abhishek Somenhalli, Jonathan Krynitsky, Noah Cubert, Thomas Jones, George Dold, Anthony Fletcher, Alexxai Kravitz, Thomas Pohida, John Dennis

2020-Current year OA Pubs

Video monitoring of mice in the home-cage reveals behavior profiles without the disruptions caused by specialized test setups and makes it possible to quantify changes in behavior patterns continually over long time frames. Several commercial home-cage monitoring systems are available with varying costs and capabilities; however there are currently no open-source systems for home-cage monitoring. We present an open-source system for top-down video monitoring of research mice in a slightly modified home-cage. The system is designed for integration with Allentown NexGen ventilated racks and allows unobstructed view of up to three mice, but can also be operated outside the rack. …

Spatial And Amplitude Dynamics Of Neurostimulation: Insights From The Acute Intrahippocampal Kainate Seizure Mouse Model, Thomas J Foutz, Nicholas Rensing, Lirong Han, Dominique M Durand, Michael Wong

2020-Current year OA Pubs

OBJECTIVE: Neurostimulation is an emerging treatment for patients with drug-resistant epilepsy, which is used to suppress, prevent, and terminate seizure activity. Unfortunately, after implantation and despite best clinical practice, most patients continue to have persistent seizures even after years of empirical optimization. The objective of this study is to determine optimal spatial and amplitude properties of neurostimulation in inhibiting epileptiform activity in an acute hippocampal seizure model.

METHODS: We performed high-throughput testing of high-frequency focal brain stimulation in the acute intrahippocampal kainic acid mouse model of status epilepticus. We evaluated combinations of six anatomic targets and three stimulus amplitudes.

RESULTS: …

Zf Automotive V. Luxshare: The Supreme Court’S New Gloss On 28 U.S. Code § 1782 And What It Means For International Commercial Arbitration, Madina Lokova

Journal of Dispute Resolution

The federal statute 28 U.S.C. § 1782 (“Section 1782”) allows litigants in foreign proceedings to obtain discovery in the United States, under the broad US discovery rules, for use in such proceedings. Although Section 1782’s use by parties to foreign proceedings has been expanding, there was a split in authority regarding whether the statute was broad enough to permit United States’ courts to authorize discovery for use in private arbitration proceedings overseas.

Divergent Responses Of Highly Migratory Species To Climate Change In The California Current, Nerea Lezama-Ochoa, Stephanie Brodie, Heather Welch, Michael G. Jacox, Mercedes Pozo Buil, Jerome Fiechter, Megan Cimino, Barbara Muhling, Heidi Dewar, Elizabeth A. Becker, Karin A. Forney, Daniel Costa, Scott R. Benson, Nima Farchadi, Camrin Braun, Rebecca Lewison, Steven Bograd, Elliott L. Hazen

Faculty Research, Scholarly, and Creative Activity

Aim: Marine biodiversity faces unprecedented threats from anthropogenic climate change. Ecosystem responses to climate change have exhibited substantial variability in the direction and magnitude of redistribution, posing challenges for developing effective climate-adaptive marine management strategies. Location: The California Current Ecosystem (CCE), USA. Methods: We project suitable habitat for 10 highly migratory species in the California Current System using an ensemble of three high-resolution (~10 km) downscaled ocean projections under the Representative Concentration Pathway 8.5 (RCP8.5). Spanning the period from 1980 to 2100, our analysis focuses on assessing the direction and distance of distributional shifts, as well as changes in core …

Clostridium Butyricum And Carbohydrate Active Enzymes Contribute To The Reduced Fat Deposition In Pigs, Lingyan Ma, Shiyu Tao, Tongxing Song, Wentao Lyu, Ying Li, Wen Wang, Qicheng Shen, Yan Ni, Jiang Zhu, Jiangchao Zhao, Hua Yang, Yingping Xiao

Animal Science Faculty Publications and Presentations

Pig gastrointestinal tracts harbor a heterogeneous and dynamic ecosystem populated with trillions of microbes, enhancing the ability of the host to harvest energy from dietary carbohydrates and contributing to host adipogenesis and fatness. However, the microbial community structure and related mechanisms responsible for the differences between the fatty phenotypes and the lean phenotypes of the pigs remained to be comprehensively elucidated. Herein, we first found significant differences in microbial composition and potential functional capacity among different gut locations in Jinhua pigs with distinct fatness phenotypes. Second, we identified that Jinhua pigs with lower fatness exhibited higher levels of short-chain fatty …

Conditional Hepatocyte Ablation Of Pdia1 Uncovers Indispensable Roles In Both Apob And Mttp Folding To Support Vldl Secretion, Zhouji Chen, Shiyu Wang, Anita Pottekat, Alec Duffey, Insook Jang, Benny H Chang, Jaehyung Cho, Brian N Finck, Nicholas O Davidson, Randal J Kaufman

2020-Current year OA Pubs

OBJECTIVES: The assembly and secretion of hepatic very low-density lipoprotein (VLDL) plays pivotal roles in hepatic and plasma lipid homeostasis. Protein disulfide isomerase A1 (PDIA1/P4HB) is a molecular chaperone whose functions are essential for protein folding in the endoplasmic reticulum. Here we investigated the physiological requirement in vivo for PDIA1 in maintaining VLDL assembly and secretion.

METHODS: Pdia1/P4hb was conditionally deleted in adult mouse hepatocytes and the phenotypes characterized. Mechanistic analyses in primary hepatocytes determined how PDIA1 ablation alters MTTP synthesis and degradation as well as altering synthesis and secretion of Apolipoprotein B (APOB), along with complementary expression of intact …

Stem Cell Modeling Of Nervous System Tumors, Frank B Furnari, Corina Anastasaki, Shan Bian, Howard A Fine, Tomoyuki Koga, Lu Q Le, Fausto J Rodriguez, David H Gutmann

2020-Current year OA Pubs

Nervous system tumors, particularly brain tumors, represent the most common tumors in children and one of the most lethal tumors in adults. Despite decades of research, there are few effective therapies for these cancers. Although human nervous system tumor cells and genetically engineered mouse models have served as excellent platforms for drug discovery and preclinical testing, they have limitations with respect to accurately recapitulating important aspects of the pathobiology of spontaneously arising human tumors. For this reason, attention has turned to the deployment of human stem cell engineering involving human embryonic or induced pluripotent stem cells, in which genetic alterations …

Functional Network Disorganization And Cognitive Decline Following Fractionated Whole-Brain Radiation In Mice, Benjamin A. Seitzman, Francisco J. Reynoso, Timothy J. Mitchell, Annie R. Bice, Anmol Jarang, Xiaodan Wang, Cedric Mpoy, Lori Strong, Buck E. Rogers, Carla M. Yuede, Joshua B. Rubin, Stephanie M. Perkins, Adam Q. Bauer

2020-Current year OA Pubs

Cognitive dysfunction following radiotherapy (RT) is one of the most common complications associated with RT delivered to the brain, but the precise mechanisms behind this dysfunction are not well understood, and to date, there are no preventative measures or effective treatments. To improve patient outcomes, a better understanding of the effects of radiation on the brain's functional systems is required. Functional magnetic resonance imaging (fMRI) has shown promise in this regard, however, compared to neural activity, hemodynamic measures of brain function are slow and indirect. Understanding how RT acutely and chronically affects functional brain organization requires more direct examination of …

Ubiquitous Filter Feeders Shape Open Ocean Microbial Community Structure And Function, Anne W. Thompson, Györgyi Nyerges, Kylee M. Brevick, Kelly Sutherland

Biology Faculty Publications and Presentations

The mechanism of mortality plays a large role in how microorganisms in the open ocean contribute to global energy and nutrient cycling. Salps are ubiquitous pelagic tunicates that are a well-known mortality source for large phototrophic microorganisms in coastal and high-latitude systems, but their impact on the immense populations of smaller prokaryotes in the tropical and subtropical open ocean gyres is not well quantified. We used robustly quantitative techniques to measure salp clearance and enrichment of specific microbial functional groups in the North Pacific Subtropical Gyre, one of the largest ecosystems on Earth. We discovered that salps are a previously …

Sirt1 Safeguards Adipogenic Differentiation By Orchestrating Anti-Oxidative Responses And Suppressing Cellular Senescence, An Yu, Ruofan Yu, Haiying Liu, Chenliang Ge, Weiwei Dang

Faculty, Staff and Students Publications

Adipose tissue is an important endocrine organ that regulates metabolism, immune response and aging in mammals. Healthy adipocytes promote tissue homeostasis and longevity. SIRT1, a conserved NAD⁺-dependent deacetylase, negatively regulates adipogenic differentiation by deacetylating and inhibiting PPAR-γ. However, knocking out SIRT1 in mesenchymal stem cells (MSCs) in mice not only causes defects in osteogenesis, but also results in the loss of adipose tissues, suggesting that SIRT1 is also important for adipogenic differentiation.

Here, we report that severe impairment of SIRT1 function in MSCs caused significant defects and cellular senescence during adipogenic differentiation. These were observed only when inhibiting …

Delays Starting Postoperative Radiotherapy Among Head And Neck Cancer Patients: A Systematic Review And Meta-Analysis, Kelsey A Duckett, Mohamed Faisal Kassir, Shaun A Nguyen, Emily A Brennan, Bhishamjit S Chera, Katherine R Sterba, Chanita Hughes Halbert, Elizabeth G Hill, Jessica Mccay, Sidharth V Puram, Vlad C Sandulache, Russel Kahmke, Salma Ramadan, Brian Nussenbaum, Anthony J Alberg, Evan M Graboyes

Faculty, Staff and Students Publications

OBJECTIVE: Initiating postoperative radiotherapy (PORT) within 6 weeks (42 days) of surgery is the first and only Commission on Cancer (CoC) approved quality metric for head and neck squamous cell carcinoma (HNSCC). No study has systematically reviewed nor synthesized the literature to establish national benchmarks for delays in starting PORT.

DATA SOURCES: Following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we performed a systematic review of PubMed, Scopus, and CINAHL.

REVIEW METHODS: Studies that described time-to-PORT or PORT delays in patients with HNSCC treated in the United States after 2003 were included. Meta-analysis of proportions and continuous measures …

Cocaine Use And Head And Neck Cancer Risk: A Pooled Analysis In The International Head And Neck Cancer Epidemiology Consortium, Mingyan Zhang, Chu Chen, Guojun Li, Alzina Koric, Yuan-Chin Amy Lee, Hal Morgenstern, Stephen M Schwartz, Erich M Sturgis, Paolo Boffetta, Mia Hashibe, Zuo-Feng Zhang

Faculty, Staff and Students Publications

BACKGROUND: Cocaine is an illegal recreational drug used worldwide, yet little is known about whether cocaine inhalation (smoking/snorting) increases the risk of head and neck cancer (HNC).

METHODS: The analyses were conducted by pooling data from three case-control studies with 1639 cases and 2506 controls from the International Head and Neck Cancer Epidemiology Consortium. Epidemiologic data, including cocaine use histories, were obtained in face-to-face interviews. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using hierarchical logistic regression models.

RESULTS: Controlling for cumulative tobacco and alcohol use, we observed a weak positive association between cocaine use and HNC …

Pulsatile Leucine Administration During Continuous Enteral Feeding Enhances Skeletal Muscle Mechanistic Target Of Rapamycin Complex 1 Signaling And Protein Synthesis In A Preterm Piglet Model, Marko Rudar, Agus Suryawan, Hanh V Nguyen, Shaji K Chacko, Caitlin Vonderohe, Barbara Stoll, Douglas G Burrin, Marta L Fiorotto, Teresa A Davis

Faculty, Staff and Students Publications

BACKGROUND: Continuous feeding does not elicit an optimal anabolic response in skeletal muscle but is required for some preterm infants. We reported previously that intermittent intravenous pulses of leucine (Leu; 800 μmol Leu·kg–1·h–1 every 4 h) to continuously fed pigs born at term promoted mechanistic target of rapamycin complex 1 (mTORC1) activation and protein synthesis in skeletal muscle.

OBJECTIVES: The aim was to determine the extent to which intravenous Leu pulses activate mTORC1 and enhance protein synthesis in the skeletal muscle of continuously fed pigs born preterm.

METHODS: Pigs delivered 10 d preterm was advanced to full oral feeding >4 …

Adverse Metabolic Phenotypes In Parenterally Fed Neonatal Pigs Do Not Persist Into Adolescence, Sarah K Elefson, Barbara Stoll, Teresa A Davis, Marta L Fiorotto, Samer W El-Kadi, Kenneth Genovese, Thomas Thymann, Per T Sangild, Douglas G Burrin

Faculty, Staff and Students Publications

BACKGROUND: Nutrition during fetal and neonatal life is an important determinant for the risk of adult-onset diseases, especially type 2 diabetes and obesity.

OBJECTIVES: We aimed to determine whether total parenteral nutrition (TPN) compared with enteral formula feeding [enteral nutrition (EN)] in term piglets during the first 2 wk after birth would increase the long-term (5-mo) development of metabolic syndrome phenotypes with adverse glucose homeostasis, fatty liver disease, and obesity.

METHODS: Neonatal female pigs were administered TPN (n = 12) or fed enterally with a liquid enteral milk-replacer formula (EN, n = 12) for 14 d. After transitioning TPN pigs …

Circadian Dysfunction Induces Nafld-Related Human Liver Cancer In A Mouse Model, Jennifer Padilla, Noha M Osman, Beatrice Bissig-Choisat, Sandra L Grimm, Xuan Qin, Angela M Major, Li Yang, Dolores Lopez-Terrada, Cristian Coarfa, Feng Li, Karl-Dimiter Bissig, David D Moore, Loning Fu

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Chronic circadian dysfunction increases the risk of non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC), but the underlying mechanisms and direct relevance to human HCC have not been established. In this study, we aimed to determine whether chronic circadian dysregulation can drive NAFLD-related carcinogenesis from human hepatocytes and human HCC progression.

METHODS: Chronic jet lag of mice with humanized livers induces spontaneous NAFLD-related HCCs from human hepatocytes. The clinical relevance of this model was analysed by biomarker, pathological/histological, genetic, RNA sequencing, metabolomic, and integrated bioinformatic analyses.

RESULTS: Circadian dysfunction induces glucose intolerance, NAFLD-associated human HCCs, and human …

Genome-Wide P63-Target Gene Analyses Reveal Tap63/Nrf2-Dependent Oxidative Stress Responses, Marco Napoli, Avani A Deshpande, Deepavali Chakravarti, Kimal Rajapakshe, Preethi H Gunaratne, Cristian Coarfa, Elsa R Flores

Faculty, Staff and Students Publications

The p53 family member TP63 encodes two sets of N-terminal isoforms, TAp63 and ΔNp63 isoforms. They each regulate diverse biological functions in epidermal morphogenesis and in cancer. In the skin, where their activities have been extensively characterized, TAp63 prevents premature aging by regulating the quiescence and genomic stability of stem cells required for wound healing and hair regeneration, while ΔNp63 controls maintenance and terminal differentiation of epidermal basal cells. This functional diversity is surprising given that these isoforms share a high degree of similarity, including an identical sequence for a DNA-binding domain. To understand the mechanisms of the transcriptional programs …

Risk Factors For Childhood Brain Tumours: A Systematic Review And Meta-Analysis Of Observational Studies From 1976 To 2022, Felix M Onyije, Roya Dolatkhah, Ann Olsson, Liacine Bouaoun, Isabelle Deltour, Friederike Erdmann, Audrey Bonaventure, Michael E Scheurer, Jacqueline Clavel, Joachim Schüz

Center for Medical Ethics and Health Policy Staff Publications

BACKGROUND: Childhood brain tumours (CBTs) are the leading cause of cancer death in children under the age of 20 years globally. Though the aetiology of CBT remains poorly understood, it is thought to be multifactorial. We aimed to synthesize potential risk factors for CBT to inform primary prevention.

METHODS: We conducted a systematic review and meta-analysis of epidemiological studies indexed in the PubMed, Web of Science, and Embase databases from the start of those resources through 27 July 2023. We included data from case-control or cohort studies that reported effect estimates for each risk factor around the time of conception, …

A Zika Virus Protein Expression Screen In Drosophila To Investigate Targeted Host Pathways During Development, Nichole Link, J Michael Harnish, Brooke Hull, Shelley Gibson, Miranda Dietze, Uchechukwu E Mgbike, Silvia Medina-Balcazar, Priya S Shah, Shinya Yamamoto

Faculty, Staff and Students Publications

In the past decade, Zika virus (ZIKV) emerged as a global public health concern. Although adult infections are typically mild, maternal infection can lead to adverse fetal outcomes. Understanding how ZIKV proteins disrupt development can provide insights into the molecular mechanisms of disease caused by this virus, which includes microcephaly. In this study, we generated a toolkit to ectopically express ZIKV proteins in vivo in Drosophila melanogaster in a tissue-specific manner using the GAL4/UAS system. We used this toolkit to identify phenotypes and potential host pathways targeted by the virus. Our work identified that expression of most ZIKV proteins caused …

Study Design And Methods: Us Study To Protect Brain Health Through Lifestyle Intervention To Reduce Risk (Us Pointer), Laura D Baker, Heather M Snyder, Mark A Espeland, Rachel A Whitmer, Miia Kivipelto, Nancy Woolard, Jeffrey Katula, Kathryn V Papp, Jennifer Ventrelle, Sarah Graef, Marcus A Hill, Scott Rushing, Julia Spell, Laura Lovato, Deborah Felton, Benjamin J Williams, Mina Ghadimi Nouran, Rema Raman, Tiia Ngandu, Alina Solomon, Sharon Wilmoth, Maryjo L Cleveland, Jeff D Williamson, Katherine L Lambert, Sarah Tomaszewski Farias, Claire E Day, Christy C Tangney, Darren R Gitelman, Olivia Matongo, Terrianne Reynolds, Valory N Pavlik, Melissa M Yu, Ashley S Alexander, Richard Elbein, Ann Marie Mcdonald, Stephen Salloway, Rena R Wing, Susan Antkowiak, Martha Clare Morris, Maria C Carrillo

Faculty, Staff and Students Publications

INTRODUCTION: The U.S. study to protect brain health through lifestyle intervention to reduce risk (U.S. POINTER) is conducted to confirm and expand the results of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) in Americans.

METHODS: U.S. POINTER was planned as a 2-year randomized controlled trial of two lifestyle interventions in 2000 older adults at risk for dementia due to well-established factors. The primary outcome is a global cognition composite that permits harmonization with FINGER.

RESULTS: U.S. POINTER is centrally coordinated and conducted at five clinical sites (ClinicalTrials.gov: NCT03688126). Outcomes assessments are completed at baseline and …

Distribution Of P2y And P2x Purinergic Receptor Expression Within The Intestine, Kristen A Engevik, Francesca J Scribano, J Thomas Gebert, Jacob L Perry, Sue E Crawford, Joseph M Hyser

Faculty, Staff and Students Publications

Nucleotides are potent extracellular signaling molecules during homeostasis, infection, and injury due to their ability to activate purinergic receptors. The nucleotide ATP activates P2X receptors (P2RXs), whereas the nucleotides ADP, ATP, UTP, and UDP-glucose selectively activate different P2Y receptors (P2RYs). Several studies have established crucial roles for P2 receptors during intestinal inflammatory and infectious diseases, yet the most extensive characterization of purinergic signaling has focused on immune cells and the central and enteric nervous systems. As epithelial cells serve as the first barrier against irritants and infection, we hypothesized that the gut epithelium may express multiple purinergic receptors that respond …

Dapagliflozin For Atrial Fibrillation, Na Li, Mihail G Chelu, Yochai Birnbaum

Faculty, Staff and Students Publications

No abstract provided.