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Gonzalo Almanza, Jeffrey J Rodvold, Brian Tsui, Kristen Jepsen, Hannah Carter, Maurizio Zanetti
The successful implementation of miRNA (miR) therapies in humans will ultimately rely on the use of vehicles with improved cellular delivery capability. Here we tested a new system that leverages extracellular vesicles (EVs) laden with a tumor suppressor miRNA (miR-335) produced in B cells by plasmid DNA induction (iEVs). We demonstrate that iEVs-335 efficiently and durably restored the endogenous miR-335 pool in human triple negative breast cancer cells, downregulated the expression of the miR-335 target gene SOX4 transcription factor, and markedly inhibited tumor growth in vivo...
December 4, 2018: Scientific Reports
Brian G Vassallo, Hannah P Litwa, Mark F Haussmann, Ryan T Paitz
Vertebrates release glucocorticoids during stressful events. If stress occurs during reproduction, the resulting offspring can show altered phenotypes that are thought to arise from increased exposure to maternal glucocorticoids. Developing offspring can metabolize maternal glucocorticoids, which can alter the pattern of exposure they encounter. For egg laying vertebrates, we are just beginning to understand how embryonic steroid metabolism impacts embryonic exposure to maternal glucocorticoids. Here we injected three doses of radioactive corticosterone into Japanese quail (Coturnix japonica) eggs to determine the degree of embryonic exposure at days six and nine of development...
November 27, 2018: General and Comparative Endocrinology
So-Yoon Won, Kristin Hunt, Hannah Guak, Benedeta Hasaj, Nathalie Charland, Nathalie Landry, Brian J Ward, Connie M Krawczyk
Cell-mediated immunity is an important component of immediate and long-term anti-viral protection. Dendritic cells (DCs) are essential for the induction of cell-mediated immunity by instructing the activation and differentiation of antigen-specific T cell responses. Activated DCs that express co-stimulatory molecules and pro-inflammatory cytokines are necessary to promote the development of type 1 immune responses required for viral control. Here we report that plant-derived virus-like particles (VLPs) bearing influenza hemagglutinins (HA) directly stimulate mouse and human DCs...
November 14, 2018: Vaccine
Matthew A Jolley, Andras Lasso, Hannah H Nam, Patrick V Dinh, Adam B Scanlan, Alex V Nguyen, Anna Ilina, Brian Morray, Andrew C Glatz, Francis X McGowan, Kevin Whitehead, Yoav Dori, Joseph H Gorman, Robert C Gorman, Gabor Fichtinger, Matthew J Gillespie
BACKGROUND: Pulmonary insufficiency is a consequence of transannular patch repair in Tetralogy of Fallot (ToF) leading to late morbidity and mortality. Transcatheter native outflow tract pulmonary valve replacement has become a reality. However, predicting a secure, atraumatic implantation of a catheter-based device remains a significant challenge due to the complex and dynamic nature of the right ventricular outflow tract (RVOT). We sought to quantify the differences in compression and volume for actual implants, and those predicted by pre-implant modeling...
November 15, 2018: Catheterization and Cardiovascular Interventions
Hadj S Aoued, Soma Sannigrahi, Nandini Doshi, Filomene G Morrison, Hannah Linsenbaum, Sarah C Hunter, Hasse Walum, Justin Baman, Bing Yao, Peng Jin, Kerry J Ressler, Brian G Dias
BACKGROUND: Stressors affect populations exposed to them as well as offspring. Strategies preventing the intergenerational propagation of effects of stress would benefit public health. Olfactory cue-based fear conditioning provides a framework to address this issue. METHODS: We 1) exposed adult male mice to an odor, acetophenone (Ace) or Lyral (parental generation [F0]-Exposed), 2) trained mice to associate these odors with mild foot shocks (F0-Trained), and 3) trained mice to associate these odors with mild foot shocks and then extinguished their fear toward these odors with odor-only presentations (F0-Extinguished)...
August 27, 2018: Biological Psychiatry
Michelle Dow, Rachel M Pyke, Brian Y Tsui, Ludmil B Alexandrov, Hayato Nakagawa, Koji Taniguchi, Ekihiro Seki, Olivier Harismendy, Shabnam Shalapour, Michael Karin, Hannah Carter, Joan Font-Burgada
Cancer genomics has enabled the exhaustive molecular characterization of tumors and exposed hepatocellular carcinoma (HCC) as among the most complex cancers. This complexity is paralleled by dozens of mouse models that generate histologically similar tumors but have not been systematically validated at the molecular level. Accurate models of the molecular pathogenesis of HCC are essential for biomedical progress; therefore we compared genomic and transcriptomic profiles of four separate mouse models [MUP transgenic, TAK1-knockout, carcinogen-driven diethylnitrosamine (DEN), and Stelic Animal Model (STAM)] with those of 987 HCC patients with distinct etiologies...
October 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
Clare Brennan, Hannah Whillis, Choy Man, Brian Wynne, Vani Vannappagari
Objective : Increased rates of suicidal ideation/behavior have been reported in individuals with human immunodeficiency virus infection/acquired immunodeficiency syndrome. The electronic Columbia-Suicidality Severity Rating Scale (eC-SSRS™) is a validated tool for assessment of suicidal risk. The objective of this study was to assess the site perspectives on implementation of the eC-SSRS used in Phase IIIb studies of dolutegravir. Methods : We developed and validated the ViiV eC-SSRS Metrics and Perspectives Site Questionnaire (VEQ)...
July 2018: Innovations in Clinical Neuroscience
Luke C Dutton, Jayesh Dudhia, Brian Catchpole, Hannah Hodgkiss-Geere, Dirk Werling, David J Connolly
Cardiosphere-derived cells (CDCs) are a cardiac progenitor cell population, which have been shown to possess cardiac regenerative properties and can improve heart function in a variety of cardiac diseases. Studies in large animal models have predominantly focussed on using autologous cells for safety, however allogeneic cell banks would allow for a practical, cost-effective and efficient use in a clinical setting. The aim of this work was to determine the immunomodulatory status of these cells using CDCs and lymphocytes from 5 dogs...
September 6, 2018: Scientific Reports
M Elise Graham, Brian D Westerberg, Jane Lea, Paul Hong, Simon Walling, David P Morris, Andrea L O Hebb, Rochelle Galleto, Emily Papsin, Maeve Mulroy, Hannah Foggin, Manohar Bance
BACKGROUND: Patients with vestibular schwannomas (VS) are faced with complex management decisions. Watchful waiting, surgical resection, and radiation are all viable options with associated risks and benefits. We sought to determine if patients with VS experience decisional conflict when deciding between surgery or non-surgical management, and factors influencing the degree of decisional conflict. METHODS: A prospective cohort study in two tertiary ambulatory skull-base clinics was performed...
September 3, 2018: Journal of Otolaryngology—Head & Neck Surgery
Alkistis N Mitropoulou, Holly Bowen, Tihomir S Dodev, Anna M Davies, Heather J Bax, Rebecca L Beavil, Andrew J Beavil, Hannah J Gould, Louisa K James, Brian J Sutton
Antibodies classically bind antigens via their complementarity-determining regions, but an alternative mode of interaction involving V-domain framework regions has been observed for some B cell "superantigens." We report the crystal structure of an antibody employing both modes of interaction simultaneously and binding two antigen molecules. This human antibody from an allergic individual binds to the grass pollen allergen Phl p 7. Not only are two allergen molecules bound to each antibody fragment (Fab) but also each allergen molecule is bound by two Fabs: One epitope is recognized classically, the other in a superantigen-like manner...
September 11, 2018: Proceedings of the National Academy of Sciences of the United States of America
Hannah E Wong, Joanna Hedley, Nadene Stapleton, Brian Murphy, Simon L Priestnall
Odontoameloblastomas (previously incorporated within ameloblastic odontomas) are matrix-producing odontogenic mixed tumors and are closely related in histologic appearance to the 2 other types of matrix-producing odontogenic mixed tumors: odontomas and ameloblastic fibro-odontomas. The presence or absence of intralesional, induced non-neoplastic tissue must be accounted for in the diagnosis. Herein we describe a naturally occurring odontoameloblastoma with extensive chondroid cementum deposition in a guinea pig ( Cavia porcellus)...
September 2018: Journal of Veterinary Diagnostic Investigation
Hannah R Shanks, Mingning Zhu, Amir H Milani, James Turton, Sarah Haigh, Nigel W Hodson, Daman Adlam, Judith Hoyland, Tony Freemont, Brian R Saunders
Polymer dots (PDs) are promising fluorescent probes for biomaterials applications. Here, novel cytocompatible composite PD particles have been synthesised with a core-shell-shell morphology. The particles show near-infrared emission, improved fluorescent brightness and enhanced colloidal stability compared to pure PDs. The particles also show non-radiative resonance energy transfer (NRET) with a model dye.
August 16, 2018: Chemical Communications: Chem Comm
Hannah E Ledvina, Katherine A Kelly, Aria Eshraghi, Rachael L Plemel, S Brook Peterson, Brian Lee, Shaun Steele, Marlen Adler, Thomas H Kawula, Alexey J Merz, Shawn J Skerrett, Jean Celli, Joseph D Mougous
Many pathogenic intracellular bacteria manipulate the host phago-endosomal system to establish and maintain a permissive niche. The fate and identity of these intracellular compartments is controlled by phosphoinositide lipids. By mechanisms that have remained undefined, a Francisella pathogenicity island-encoded secretion system allows phagosomal escape and replication of bacteria within host cell cytoplasm. Here we report the discovery that a substrate of this system, outside pathogenicity island A (OpiA), represents a family of wortmannin-resistant bacterial phosphatidylinositol (PI) 3-kinase enzymes with members found in a wide range of intracellular pathogens, including Rickettsia and Legionella spp...
August 8, 2018: Cell Host & Microbe
Matthew L Yuknis, Elizabeth Weinstein, Hannah Maxey, Lori Price, Sierra X Vaughn, Tom Arkins, Brian D Benneyworth
: media-1vid110.1542/5789654354001PEDS-VA_2017-3082 Video Abstract BACKGROUND: Management of pediatric emergencies is challenging for ambulatory providers because these rare events require preparation and planning tailored to the expected emergencies. The current recommendations for pediatric emergencies in ambulatory settings are based on 20-year-old survey data. We aimed to objectively identify the frequency and etiology of pediatric emergencies in ambulatory practices. METHODS: We examined pediatric emergency medical services (EMS) runs originating from ambulatory practices in the greater Indianapolis metropolitan area between January 1, 2012, and December 31, 2014...
August 2018: Pediatrics
Samantha M Harvey, Brian T Phelan, Daniel C Hannah, Kristen E Brown, Ryan M Young, Matthew S Kirschner, Michael R Wasielewski, Richard D Schaller
We report femtosecond stimulated Raman spectroscopy (FSRS) measurements on dispersions of CdSe semiconductor nanocrystals (NCs) as a function of particle size and pump fluence. Upon photoexcitation, we observe depletion of stimulated Raman gain corresponding to generation of longitudinal optical (LO) phonons followed by recovery on picosecond timescales. At higher fluences, production of multiple excitons slows recovery of FSRS signals, which we attribute to sustained increases of LO phonon populations due to multiexcitonic Auger heating...
August 16, 2018: Journal of Physical Chemistry Letters
Caigang Zhu, Hannah L Martin, Brian T Crouch, Amy F Martinez, Martin Li, Gregory M Palmer, Mark W Dewhirst, Nimmi Ramanujam
The shifting metabolic landscape of aggressive tumors, with fluctuating oxygenation conditions and temporal changes in glycolysis and mitochondrial metabolism, is a critical phenomenon to study in order to understand negative treatment outcomes. Recently, we have demonstrated near-simultaneous optical imaging of mitochondrial membrane potential (MMP) and glucose uptake in non-tumor window chambers, using the fluorescent probes tetramethylrhodamine ethyl ester (TMRE) and 2-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG)...
July 1, 2018: Biomedical Optics Express
Nicole K Campbell, Hannah K Fitzgerald, Anna Malara, Roisin Hambly, Cheryl M Sweeney, Brian Kirby, Jean M Fletcher, Aisling Dunne
Psoriasis is a chronic autoimmune disease mediated by dysregulated immune responses in dendritic cells (DC) and T cells. The stress-response enzyme heme oxygenase-1 (HO-1) has been described as protective in animal models of psoriasis, however, implementation of HO-1-based therapies is hindered by the lack of clinically-suitable HO-1 inducers. The plant-derived polyphenols, carnosol and curcumin, have been identified as candidate HO-1 inducers however there has been little investigation into their effects on human immune cells...
July 6, 2018: Scientific Reports
Joseph Geiger, Bridget A Morton, Elton Jose Rosas Vasconcelos, Maryam Tngrian, Malika Kachani, Eduardo A Barrón, Cesar M Gavidia, Robert H Gilman, Noelia P Angulo, Richard Lerner, Tamerin Scott, N Hannah Mirrashed, Brian Oakley, Pedro Paulo V P Diniz
Ehrlichia spp. are emerging infectious pathogens, especially in the Americas. Although Ehrlichia canis is primarily a parasite of dogs, polymerase chain reaction-confirmed human infections have been reported from Mexico, Venezuela, and Costa Rica. This study reports the presence of E. canis DNA in 13.7% of 205 dogs from urban areas in Peru and of those, five were analyzed for phylogenetic variation using the Tandem Repeat Protein 36 (TRP36) gene. The use of the TRP36 gene for such analysis was validated against 16S rRNA and heat shock protein genes using Shannon's entropy bioinformatic approach...
August 2018: American Journal of Tropical Medicine and Hygiene
Zihan Yan, Zeenat A Shyr, Manuela Fortunato, Alecia Welscher, Mariana Alisio, Michael Martino, Brian N Finck, Hannah Conway, Maria S Remedi
AIMS: To examine the effects of a high-fat-diet (HFD) on monogenic neonatal diabetes, without the confounding effects of compensatory hyperinsulinaemia. METHODS: Mice expressing KATP channel gain-of-function (KATP -GOF) mutations, which models human neonatal diabetes, were fed an HFD. RESULTS: Surprisingly, KATP -GOF mice exhibited resistance to HFD-induced obesity, accompanied by markedly divergent blood glucose control, with some KATP -GOF mice showing persistent diabetes (KATP -GOF-non-remitter [NR] mice) and others showing remission of diabetes (KATP -GOF-remitter [R] mice)...
November 2018: Diabetes, Obesity & Metabolism
Gurjot S Walia, Jeffrey Aston, Ricardo Bello, Gina A Mackert, Rachel A Pedreira, Brian H Cho, Hannah M Carl, Erin M Rada, Gedge D Rosson, Justin M Sacks
Background: Traditionally, tissue expanders (TEs) for breast reconstruction have been placed beneath the pectoralis major muscle with or without acellular dermal matrix. More recently, full acellular dermal matrix coverage has been described for prepectoral TE placement. Our study aims to explore differences in clinical and quality-of-life (QOL) outcomes for prepectoral versus subpectoral TE breast reconstruction. Methods: We identified patients who underwent postmastectomy breast reconstruction with prepectoral or subpectoral TE placement between 2011 and 2015 and completed QOL surveys...
April 2018: Plastic and Reconstructive Surgery. Global Open
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