An Examination of the Influences of an International Teaching Practicum on the Perspectives and Practices of Participating Teachers

This study examines the ways in which an international teaching practicum influenced participants’ perspectives about teaching, learning and schooling, and the ways that these new or changed perspectives materialized in the participants’ teaching practice over the course of twelve months. To understand these influences, participants were given pre- and post- surveys that aimed to examine their intercultural competence, and were interviewed at three points in time after the completion of the international practicum. Their TEP supervisors were also interviewed. Findings revealed the ways in which participants made sense of their experiences abroad, and how the program supported (and possibly hindered) their sensemaking. Sensemaking was connected to changes in the participants’ global awareness, critical consciousness, self-concept, and empathy. Participants felt that these personal impacts were related to corresponding changes in their teaching practices. They attempted to emulate their hosts, bring global awareness into their classrooms, and described culturally responsive practices and attitudes. Participants also reported that their international practicums influenced their professional marketability, goals, and decisions

Laser-scanning velocimetry: A confocal microscopy method for quantitative measurement of cardiovascular performance in zebrafish embryos and larvae

Abstract Background The zebrafish Danio rerio is an important model system for drug discovery and to study cardiovascular development. Using a laser-scanning confocal microscope, we have developed a non-invasive method of measuring cardiac performance in zebrafish embryos and larvae that obtains cardiovascular parameters similar to those obtained using Doppler echocardiography in mammals. A laser scan line placed parallel to the path of blood in the dorsal aorta measures blood cell velocity, from which cardiac output and indices of vascular resistance and contractility are calculated. Results This technique, called laser-scanning velocimetry, was used to quantify the effects of pharmacological, developmental, and genetic modifiers of cardiac function. Laser-scanning velocimetry was applied to analyze the cardiovascular effects of morpholino knockdown of osmosensing scaffold for MEKK3 (OSM), which when mutated causes the human vascular disease cerebral cavernous malformations. OSM-deficient embryos had a constricted aortic arch and markedly increased peak cell velocity, a characteristic indicator of aortic stenosis. Conclusion These data validate laser-scanning velocimetry as a quantitative tool to measure cardiovascular performance for pharmacological and genetic analysis in zebrafish, which requires no specialized equipment other than a laser-scanning confocal microscope

Fluid-membrane tethers: minimal surfaces and elastic boundary layers

Thin cylindrical tethers are common lipid bilayer membrane structures, arising in situations ranging from micromanipulation experiments on artificial vesicles to the dynamic structure of the Golgi apparatus. We study the shape and formation of a tether in terms of the classical soap-film problem, which is applied to the case of a membrane disk under tension subject to a point force. A tether forms from the elastic boundary layer near the point of application of the force, for sufficiently large displacement. Analytic results for various aspects of the membrane shape are given.Comment: 12 page

IL-14 and IL-16 are expressed in the thyroid of patients with either Graves' disease or Hashimoto's thyroiditis

OBJECTIVES: Cytokines have an important role in orchestrating the pathophysiology in autoimmune thyroid disease. The aim of the current study was to analyse the expression of interleukin (IL)-14 and IL-16 in the thyroid tissue of patients with Graves' disease (GD), Hashimoto's thyroiditis (HT) or multi-nodular goitre (MNG) and in that of normal individuals, in patients' intra-thyroidal CD4(+) and CD8(+) T cells, and in patient and normal cultured thyroid follicular cells. METHODS: The expression of IL-14 and IL-16 mRNA and protein was investigated using reverse transcription-polymerase chain reaction (RT-PCR) amplification, and western blotting and ELISAs, respectively. RESULTS: IL-14 mRNA expression was detected in thyroid tissue from 8/9 GD, 3/4 HT and 3/13 MNG patients and 1/6 normal individuals, and IL-16 mRNA expression in thyroid tissue from 9/9 GD, 4/4 HT and 9/13 MNG patients and 4/6 normal individuals. IL-14 mRNA expression was detected in intra-thyroidal CD4(+) and CD8(+) T cells from 2/2 GD and 2/2 HT patients, while IL-16 mRNA was detected in samples from 1/2 HT but not in those from either GD patients. IL-14 and IL-16 mRNA expression was found in thyroid follicular cells derived from 2/2 patients with GD and 1/1 normal individual. IL-14 protein was detected in thyroid tissue from 6/6 GD, 1/1 HT and 0/6 MNG patients and 0/6 normal individuals, and IL-16 protein in thyroid tissue from 6/6 GD, 1/1 HT and 1/6 MNG patients and 0/6 normal individuals. Expression of IL-14 protein was stimulated in thyroid follicular cells derived from two GD patients and one normal individual by peripheral blood mononuclear cell (PBMC)-conditioned medium. Treatment of thyrocytes from two GD patients and one normal individual with PBMC-conditioned medium and tumour necrosis factor (TNF)-α stimulated IL-16 protein expression. In normal thyrocytes, IL-16 protein synthesis was induced also by IL-1β, IL-17A, IL-4 and transforming growth factor (TGF)-β. CONCLUSIONS: The data provide evidence that the intra-thyroidal production of IL-14 and IL-16 is associated with the pathogenesis of autoimmune thyroid disease. Thyroid follicular cells display the ability to express IL-14 and IL-16 mRNA and can be stimulated to express IL-16 protein, by a panel of cytokines, and IL-14 protein, by as yet unidentified factors. This article is protected by copyright. All rights reserved

Kinome and Transcriptome Profiling Reveal Broad and Distinct Activities of Erlotinib, Sunitinib, and Sorafenib in the Mouse Heart and Suggest Cardiotoxicity From Combined Signal Transducer and Activator of Transcription and Epidermal Growth Factor Receptor Inhibition

BACKGROUND: Most novel cancer therapeutics target kinases that are essential to tumor survival. Some of these kinase inhibitors are associated with cardiotoxicity, whereas others appear to be cardiosafe. The basis for this distinction is unclear, as are the molecular effects of kinase inhibitors in the heart. METHODS AND RESULTS: We administered clinically relevant doses of sorafenib, sunitinib (cardiotoxic multitargeted kinase inhibitors), or erlotinib (a cardiosafe epidermal growth factor receptor inhibitor) to mice daily for 2 weeks. We then compared the effects of these 3 kinase inhibitors on the cardiac transcriptome using RNAseq and the cardiac kinome using multiplexed inhibitor beads coupled with mass spectrometry. We found unexpectedly broad molecular effects of all 3 kinase inhibitors, suggesting that target kinase selectivity does not define either the molecular response or the potential for cardiotoxicity. Using in vivo drug administration and primary cardiomyocyte culture, we also show that the cardiosafety of erlotinib treatment may result from upregulation of the cardioprotective signal transducer and activator of transcription 3 pathway, as co-treatment with erlotinib and a signal transducer and activator of transcription inhibitor decreases cardiac contractile function and cardiomyocyte fatty acid oxidation. CONCLUSIONS: Collectively our findings indicate that preclinical kinome and transcriptome profiling may predict the cardiotoxicity of novel kinase inhibitors, and suggest caution for the proposed therapeutic strategy of combined signal transducer and activator of transcription/epidermal growth factor receptor inhibition for cancer treatment

Small fetal thymus and adverse obstetrical outcome: a systematic review and a meta-analysis.

INTRODUCTION: To explore the association between small fetal thymus on ultrasound and adverse obstetrical outcome. MATERIAL AND METHODS: Medline, Embase, Cochrane and Web of Science databases were searched. Primary outcome was the risk of preterm birth before 37 and 34 weeks in fetuses with compared to those without a small thymus on ultrasound. SECONDARY OUTCOMES: occurrence of chorioamnionitis, intra-uterine growth restriction, neonatal sepsis, gestational age at birth, birthweight, neonatal morbidity and pre-eclampsia. RESULTS: Twelve studies including 1744 fetuses who had ultrasound assessment of thymus during pregnancy were included. Women with preterm premature rupture of the membranes (PPROM) or with preterm labour with a small fetal thymus were at higher risk of preterm birth <37 (p= 0.01), <34 (12.5 (p<0.001) weeks in fetuses with compared to those without small thymus, and the risk of chorioamnionitis was higher when the thymus was small (p<0.001). Fetuses with small thymus were not at higher risk of intra-uterine growth restriction (p= 0.3). A small thymus increased the risk of neonatal sepsis (p= 0.007) and morbidity (p= 0.003), but not the risk of pre-eclampsia (p= 0.9). CONCLUSIONS: A small fetal thymus is associated with a higher risk of preterm birth, chorioamnionitis, neonatal sepsis and morbidity, but not with intra-uterine growth restriction and pre-eclampsia. This article is protected by copyright. All rights reserved

PDMP Blocks Brefeldin A–induced Retrograde Membrane Transport from Golgi to ER: Evidence for Involvement of Calcium Homeostasis and Dissociation from Sphingolipid Metabolism

In this study, we show that an inhibitor of sphingolipid biosynthesis, d,l-threo-1-phenyl-2- decanoylamino-3-morpholino-1-propanol (PDMP), inhibits brefeldin A (BFA)-induced retrograde membrane transport from Golgi to endoplasmic reticulum (ER). If BFA treatment was combined with or preceded by PDMP administration to cells, disappearance of discrete Golgi structures did not occur. However, when BFA was allowed to exert its effect before PDMP addition, PDMP could not “rescue” the Golgi compartment

PRESTO-Tango as an open-source resource for interrogation of the druggable human GPCRome

G protein-coupled receptors (GPCRs) are essential mediators of cellular signaling and important targets of drug action. Of the approximately 350 non-olfactory human GPCRs, more than 100 are still considered “orphans” as their endogenous ligand(s) remain unknown. Here, we describe a unique open-source resource that provides the capacity to interrogate the druggable human GPCR-ome via a G protein-independent β-arrestin recruitment assay. We validate this unique platform at more than 120 non-orphan human GPCR targets, demonstrate its utility for discovering new ligands for orphan human GPCRs, and describe a method (PRESTO-TANGO; Parallel Receptor-ome Expression and Screening via Transcriptional Output - TANGO) for the simultaneous and parallel interrogation of the entire human GPCR-ome