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https://www.readbyqxmd.com/read/27926989/targeting-gm-csf-in-epithelial-and-vascular-remodeling-in-experimental-eosinophilic-esophagitis
#1
Eóin N McNamee, Kathryn A Biette, Juliet Hammer, Rachel Harris, Heather Miyazawa, James J Lee, Glenn T Furuta, Joanne C Masterson
BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic antigen-mediated clinicopathologic disease of the esophagus characterized by an eosinophil-predominant inflammatory infiltrate. A clinical hallmark is extensive tissue remodeling including basal zone hyperplasia, fibrosis and angiogenesis. However, the cellular mechanisms responsible for these processes are not fully defined. We hypothesized that targeting GM-CSF (an agonist cytokine linked with eosinophil survival and activation) would be protective in a pre-clinical model of EoE...
December 7, 2016: Allergy
https://www.readbyqxmd.com/read/27926931/microbial-translocation-and-inflammation-occur-in-hyperacute-immunodeficiency-virus-infection-and-compromise-host-control-of-virus-replication
#2
Adam J Ericsen, Michael Lauck, Mariel S Mohns, Sarah R DiNapoli, James P Mutschler, Justin M Greene, Jason T Weinfurter, Gabrielle Lehrer-Brey, Trent M Prall, Samantha M Gieger, Connor R Buechler, Kristin A Crosno, Eric J Peterson, Matthew R Reynolds, Roger W Wiseman, Benjamin J Burwitz, Jacob D Estes, Jonah B Sacha, Thomas C Friedrich, Jason M Brenchley, David H O'Connor
Within the first three weeks of human immunodeficiency virus (HIV) infection, virus replication peaks in peripheral blood. Despite the critical, causal role of virus replication in determining transmissibility and kinetics of progression to acquired immune deficiency syndrome (AIDS), there is limited understanding of the conditions required to transform the small localized transmitted founder virus population into a large and heterogeneous systemic infection. Here we show that during the hyperacute "pre-peak" phase of simian immunodeficiency virus (SIV) infection in macaques, high levels of microbial DNA transiently translocate into peripheral blood...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926496/the-therapeutic-potential-of-targeting-the-pi3k-pathway-in-pediatric-brain-tumors
#3
REVIEW
Hazel A Rogers, Jasper Estranero, Keshni Gudka, Richard G Grundy
Central nervous system tumors are the most common cancer type in children and the leading cause of cancer related deaths. There is therefore a need to develop novel treatments. Large scale profiling studies have begun to identify alterations that could be targeted therapeutically, including the phosphoinositide 3-kinase (PI3K) signaling pathway, which is one of the most commonly activated pathways in cancer with many inhibitors under clinical development. PI3K signaling has been shown to be aberrantly activated in many pediatric CNS neoplasms...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926445/rewarding-feedback-promotes-motor-skill-consolidation-via-striatal-activity
#4
M Widmer, N Ziegler, J Held, A Luft, K Lutz
Knowledge of performance can activate the striatum, a key region of the reward system and highly relevant for motivated behavior. Using functional magnetic resonance imaging, striatal activity linked to knowledge of performance was measured during the training of a repetitive arc-tracking task. Knowledge of performance was given after a random selection of trials or after good performance. The third group received knowledge of performance after good performance plus a monetary reward. Skill learning was measured from pre- to post- (acquisition) and from post- to 24h posttraining (consolidation)...
2016: Progress in Brain Research
https://www.readbyqxmd.com/read/27925848/hospitalizations-for-pneumococcal-diseases-in-tuscany-from-2002-to-2014-impact-of-universal-pediatric-vaccination-on-the-population
#5
Sara Boccalini, Ornella Varone, Martina Chellini, Luca Pieri, Antonino Sala, Cesare Berardi, Paolo Bonanni, Angela Bechini
Streptococcus pneumoniae is the main causative organism of acute media otitis in children and meningitis and bacterial pneumonia in the community. Since 2008 in Tuscany, central Italy, the pneumococcal conjugate vaccine (7-valent vaccine, switched in 13-valent vaccine in 2010) was actively offered free of charge to all newborns. Aim of the study is to evaluate the impact of pneumococcal paediatric vaccination on the Tuscan population on hospitalizations potentially caused by S. pneumoniae, during pre-vaccination (PVP, 2002-2007) and vaccination period (VP, 2009-2014)...
December 7, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27925216/light-regulation-of-alternative-pre-mrna-splicing-in-plants
#6
Hangxiao Zhang, Chentao Lin, Lianfeng Gu
Alternative splicing (AS) is a major post-transcriptional mechanism to enhance the diversity of proteome in response to environmental signals. Among the numerous external signals perceived by plants, light is the most crucial one. Plants utilize complex photoreceptor signaling networks to sense different light conditions and adjust their growth and development accordingly. Although light-mediated gene expression has been widely investigated, little is known regarding the mechanism of light affecting AS to modulate mRNA at the post-transcriptional level...
December 7, 2016: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/27925188/a-human-3d-in-vitro-model-to-assess-the-relationship-between-osteoporosis-and-dissemination-to-bone-of-breast-cancer-tumour-cells
#7
F Salamanna, V Borsari, S Brogini, P Torricelli, S Cepollaro, M Cadossi, M Fini
Despite consistent improvements in diagnostic and therapeutic strategies for breast cancer, up to 40% of patients will develop bone metastases. To reduce the morbidity and complications related with bone metastases, it is imperative to reduce their etiological factors. Osteoporosis, being characterized by a sudden estrogen deficiency, may provide a favorable condition for bone metastasis. This work, using a humanized 3D in vitro model, aims at evaluating the relationship between osteoporosis and breast cancer-derived bone metastases...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27925020/susceptibility-of-phytomonas-serpens-to-calpain-inhibitors-in-vitro-interference-on-the-proliferation-ultrastructure-cysteine-peptidase-expression-and-interaction-with-the-invertebrate-host
#8
Simone Santiago Carvalho de Oliveira, Diego de Souza Gonçalves, Aline Dos Santos Garcia-Gomes, Inês Correa Gonçalves, Sergio Henrique Seabra, Rubem Figueiredo Menna-Barreto, Angela Hampshire de Carvalho Santos Lopes, Claudia Masini D'Avila-Levy, André Luis Souza Dos Santos, Marta Helena Branquinha
A pleiotropic response to the calpain inhibitor MDL28170 was detected in the tomato parasite Phytomonas serpens. Ultrastructural studies revealed that MDL28170 caused mitochondrial swelling, shortening of flagellum and disruption of trans Golgi network. This effect was correlated to the inhibition in processing of cruzipain-like molecules, which presented an increase in expression paralleled by decreased proteolytic activity. Concomitantly, a calcium-dependent cysteine peptidase was detected in the parasite extract, the activity of which was repressed by pre-incubation of parasites with MDL28170...
December 1, 2016: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/27924477/assessing-anti-mir-pharmacology-with-mirna-polysome-shift-assay
#9
John R Androsavich
Target engagement measurements are critical for evaluating developmental drug candidates and their pharmacological activity. microRNA (miRNA) Polysome Shift Assay enables measurement of anti-miR drug target engagement (i.e. extent of miRNA inhibition) without the need to pre-identify or pre-validate downstream miRNA-regulated genes. This makes it useful for assessing anti-miR activity in target tissues or cells where biology of the inhibited miRNAs may not be well understood. In addition, miRNA Polysome Shift Assay can be multiplexed to assess inhibition of multiple miRNAs by a single anti-miR, thus guiding drug optimization for enhancing or avoiding these activities as desired...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924070/modified-methods-for-isolation-of-pancreatic-stellate-cells-from-human-and-rodent-pancreas
#10
Liangtao Zhao, Baobao Cai, Zipeng Lu, Lei Tian, Song Guo, Pengfei Wu, Dong Qian, Qingcheng Xu, Kuirong Jiang, Yi Miao
Primary cultures of pancreatic stellate cells (PSCs) remain an important basis for in vitro study. However, effective methods for isolating abundant PSCs are currently lacking. We report on a novel approach to isolating PSCs from normal rat pancreases and human pancreatic ductal adenocarcinoma (PDAC) tissue. After anaesthesia and laparotomy of the rat, a blunt cannula was inserted into the pancreatic duct through the anti-mesentery side of the duodenum, and the pancreas was slowly infused with an enzyme solution until all lobules were fully dispersed...
November 2016: Journal of Biomedical Research
https://www.readbyqxmd.com/read/27923776/establishment-of-expression-in-the-shortroot-scarecrow-transcriptional-cascade-through-opposing-activities-of-both-activators-and-repressors
#11
Erin E Sparks, Colleen Drapek, Allison Gaudinier, Song Li, Mitra Ansariola, Ning Shen, Jessica H Hennacy, Jingyuan Zhang, Gina Turco, Jalean J Petricka, Jessica Foret, Alexander J Hartemink, Raluca Gordân, Molly Megraw, Siobhan M Brady, Philip N Benfey
Tissue-specific gene expression is often thought to arise from spatially restricted transcriptional cascades. However, it is unclear how expression is established at the top of these cascades in the absence of pre-existing specificity. We generated a transcriptional network to explore how transcription factor expression is established in the Arabidopsis thaliana root ground tissue. Regulators of the SHORTROOT-SCARECROW transcriptional cascade were validated in planta. At the top of this cascade, we identified both activators and repressors of SHORTROOT...
December 5, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27923758/evidence-for-use-of-teriparatide-in-spinal-fusion-surgery-in-osteoporotic-patients
#12
REVIEW
Navjot Chaudhary, Jennifer S Lee, Joy Y Wu, Suzanne Tharin
Osteoporosis is defined as a bone mineral density (BMD) less than 2.5 standard deviations below the mean BMD at peak bone mass, or the presence of a fragility fracture. In the setting of osteoporosis, early hardware loosening is thought to cause decreased spinal fusion rates. The two mainstays of osteoporosis treatment are bisphosphonates and Teriparatide. Teriparatide, a form of synthetic parathyroid hormone (PTH), is an anabolic agent that increases osteoblast activity and, thereby, bone mass. Preclinical studies in animal models show that Teriparatide increases spinal fusion rates...
December 3, 2016: World Neurosurgery
https://www.readbyqxmd.com/read/27923747/ibulocydine-sensitizes-human-hepatocellular-carcinoma-cells-to-trail-induced-apoptosis-via-calpain-mediated-bax-cleavage
#13
Seok Soon Park, Eunjin Jwa, Seol Hwa Shin, Eun Jin Ju, Intae Park, Jhang Ho Pak, Jung Jin Hwang, Dong-Hyung Cho, B Moon Kim, Sung-Bae Kim, Jung Shin Lee, Si Yeol Song, Seong-Yun Jeong, Eun Kyung Choi
Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) induces apoptosis selectively in cancer cells without affecting the majority of normal human cells. However, hepatocellular carcinoma (HCC) cells often display resistance to TRAIL-induced apoptosis. Ibulocydine (IB) is an isobutyrate ester pro-drug of a novel synthetic Cdk inhibitor that targets Cdk7 and Cdk9. In this study, we show that treatment with subtoxic doses of IB in combination with TRAIL displays potent cytotoxicity in TRAIL-resistant human HCC cells...
December 3, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27923111/evaluation-of-a-pilot-school-based-physical-activity-challenge-for-primary-students
#14
E Passmore, C Donato-Hunt, L Maher, R Havrlant, K Hennessey, A Milat, L Farrell
Issue addressed: Physical inactivity and sedentary behaviour among children are growing public health concerns. The Culture Health Communities Activity Challenge (hereafter known as the Challenge) is a school-based pedometer program in which classes compete to achieve the highest class average daily steps in an 8-week period. The Challenge aims to encourage physical activity in primary school students, with a focus on engaging Aboriginal students. The program was piloted in 15 classes in New South Wales in 2014...
December 2, 2016: Health Promotion Journal of Australia
https://www.readbyqxmd.com/read/27923043/clonal-evolutionary-analysis-during-her2-blockade-in-her2-positive-inflammatory-breast-cancer-a-phase-ii-open-label-clinical-trial-of-afatinib-vinorelbine
#15
Gerald Goh, Ramona Schmid, Kelly Guiver, Wichit Arpornwirat, Imjai Chitapanarux, Vinod Ganju, Seock-Ah Im, Sung-Bae Kim, Arunee Dechaphunkul, Jedzada Maneechavakajorn, Neil Spector, Thomas Yau, Mehdi Afrit, Slim Ben Ahmed, Stephen R Johnston, Neil Gibson, Martina Uttenreuther-Fischer, Javier Herrero, Charles Swanton
BACKGROUND: Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer associated with HER2 amplification, with high risk of metastasis and an estimated median survival of 2.9 y. We performed an open-label, single-arm phase II clinical trial (ClinicalTrials.gov NCT01325428) to investigate the efficacy and safety of afatinib, an irreversible ErbB family inhibitor, alone and in combination with vinorelbine in patients with HER2-positive IBC. This trial included prospectively planned exome analysis before and after afatinib monotherapy...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27923008/a-framework-for-health-communication-across-the-hiv-treatment-continuum
#16
Stella Babalola, Lynn M Van Lith, Elizabeth C Mallalieu, Zoe R Packman, Emily Myers, Kim Seifert Ahanda, Emily Harris, Tilly Gurman, Maria-Elena Figueroa
BACKGROUND: As test and treat rolls out, effective interventions are needed to address the determinants of outcomes across the HIV treatment continuum and ensure that people infected with HIV are promptly tested, initiate treatment early, adhere to treatment, and are virally suppressed. Communication approaches offer viable options for promoting relevant behaviors across the continuum. CONCEPTUAL FRAMEWORK: This article introduces a conceptual framework, which can guide the development of effective health communication interventions and activities that aim to impact behaviors across the HIV treatment continuum in low- and medium-income countries...
January 1, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/27922598/epha3-as-a-target-for-antibody-immunotherapy-in-acute-lymphoblastic-leukemia
#17
S Charmsaz, F Al-Ejeh, T Yeadon, K J Miller, F Smith, B Stringer, A S Moore, F-T Lee, L T Cooper, C Stylianou, G T Yarranton, J Woronicz, A M Scott, M Lackmann, A W Boyd
The human EphA3 gene was discovered in a pre-B acute lymphoblastic leukemia (pre-B ALL) using the EphA3-specific monoclonal antibody (mAb), IIIA4, which binds and activates both human and mouse EphA3. We use two models of human pre-B ALL to examine EphA3 function, demonstrating effects on pre-B cell receptor signaling. In therapeutic targeting studies we demonstrated anti-tumor effects of the IIIA4 mAb in EphA3-expressing leukemic xenografts and no anti-tumor effect in the xenografts with no EphA3 expression providing evidence that EphA3 is a functional therapeutic target in pre-B ALL...
December 6, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27922180/going-domestic-importing-the-study-abroad-experience-the-development-of-a-multicultural-new-york-city-study-away-program
#18
Susan Hayes Lane, Carolyn Huffman, Dana E Brackney, Alyssa Cuddy
PROBLEM: Significant off-campus domestic study away experiences have been shown to be a transformative active learning environment for students and achieve similar learning outcomes as study abroad programs. METHODS: This manuscript describes the conception, development, and pedagogical approach of a faculty-led domestic study away experience in New York City for pre-licensure and post-licensure nursing students as an active learning strategy for developing cultural competence...
December 6, 2016: Nursing Forum
https://www.readbyqxmd.com/read/27922056/identification-and-functional-analysis-of-long-intergenic-noncoding-rna-genes-in-porcine-pre-implantation-embryonic-development
#19
Jingyu Li, Zhengling Gao, Xingyu Wang, Hongbo Liu, Yan Zhang, Zhonghua Liu
Genome-wide transcriptome studies have identified thousands of long intergenic noncoding RNAs (lincRNAs), some of which play important roles in pre-implantation embryonic development (PED). Pig is an ideal model for reproduction, however, porcine lincRNAs are still poorly characterized and it is unknown if they are associated with porcine PED. Here we reconstructed 195,531 transcripts in 122,007 loci, and identified 7,618 novel lincRNAs from 4,776 loci based on published RNA-seq data. These lincRNAs show low exon number, short length, low expression level, tissue-specific expression and cis-acting, which is consistent with previous reports in other species...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27922004/annually-resolved-north-atlantic-marine-climate-over-the-last-millennium
#20
D J Reynolds, J D Scourse, P R Halloran, A J Nederbragt, A D Wanamaker, P G Butler, C A Richardson, J Heinemeier, J Eiríksson, K L Knudsen, I R Hall
Owing to the lack of absolutely dated oceanographic information before the modern instrumental period, there is currently significant debate as to the role played by North Atlantic Ocean dynamics in previous climate transitions (for example, Medieval Climate Anomaly-Little Ice Age, MCA-LIA). Here we present analyses of a millennial-length, annually resolved and absolutely dated marine δ(18)O archive. We interpret our record of oxygen isotope ratios from the shells of the long-lived marine bivalve Arctica islandica (δ(18)O-shell), from the North Icelandic shelf, in relation to seawater density variability and demonstrate that solar and volcanic forcing coupled with ocean circulation dynamics are key drivers of climate variability over the last millennium...
December 6, 2016: Nature Communications
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