The inflammatory mediator leukotriene D4 induces beta-catenin signaling and its association with antiapoptotic Bcl-2 in intestinal epithelial cells.
AuthorsMezhybovska M, Wikström K, Ohd JF, Sjölander A
JournalJ Biol Chem
PubMed ID16407243
'Increased levels of the inflammatory mediator leukotriene D4 (LTD4) are present at sites of inflammatory bowel disease, and such areas also exhibit an increased risk for subsequent cancer development. It is known that LTD4 affects the expression of many proteins that influence survival and proliferation of intestinal epithelial cells. We ... More
ATP-dependent interaction of the cytosolic domains of the inwardly rectifying K+ channel Kir6.2 revealed by fluorescence resonance energy transfer.
AuthorsTsuboi T, Lippiat JD, Ashcroft FM, Rutter GA
JournalProc Natl Acad Sci U S A
PubMed ID14681552
'ATP-sensitive K(+) (K(ATP)) channels play important roles in the regulation of membrane excitability in many cell types. ATP inhibits channel activity by binding to a specific site formed by the N and C termini of the pore-forming subunit, Kir6.2, but the structural changes associated with this interaction remain unclear. Here, ... More
Nucleic acid binding agents exert local toxic effects on neurites via a non-nuclear mechanism.
AuthorsPin S, Chen H, Lein PJ, Wang MM
JournalJ Neurochem
PubMed ID16441515
'The mechanism by which drugs that target nucleic acids cause neurotoxicity is not well described. We characterized the neurotoxicity of Hoechst 33342 (bis-benzimide), a common cell permeable nuclear dye, in primary neuronal cultures. The mechanism of cell death was not apoptotic, as death is rapid, not accompanied by typical nuclear ... More
Real-time multiple particle tracking of gene nanocarriers in complex biological environments.
AuthorsLai SK, Hanes J,
JournalMethods Mol Biol
PubMed ID18470640
'Complex biological fluids, such as the vast and molecularly crowded cell cytoplasm and the highly viscoelastic mucus that protects many entry ways to the body, pose significant barriers to efficient gene delivery. Understanding the dynamics of gene carriers in such environments allows insight that leads to rational improvements in gene ... More
Isolation, structure elucidation and cytotoxic evaluation of endiandrin B from the Australian rainforest plant Endiandra anthropophagorum.
Chemical investigations of the DCM extract from the roots of Endiandra anthropophagorum resulted in the isolation of a new cyclobutane lignan endiandrin B (1), together with the known natural products, endiandrin A (2), and (-)-dihydroguaiaretic acid (3). The structure of 1 was determined by extensive spectroscopic analyses, and confirmed by ... More
High content screening of cortical neurons identifies novel regulators of axon growth.
AuthorsBlackmore MG, Moore DL, Smith RP, Goldberg JL, Bixby JL, Lemmon VP,
JournalMol Cell Neurosci
PubMed ID20159039
Neurons in the central nervous system lose their intrinsic capacity for axon regeneration as they mature, and it is widely hypothesized that changes in gene expression are responsible. Testing this hypothesis and identifying the relevant genes has been challenging because hundreds to thousands of genes are developmentally regulated in CNS ... More
Tuning of synapse number, structure and function in the cochlea.
Cochlear inner hair cells (IHCs) transmit acoustic information to spiral ganglion neurons through ribbon synapses. Here we have used morphological and physiological techniques to ask whether synaptic mechanisms differ along the tonotopic axis and within IHCs in the mouse cochlea. We show that the number of ribbon synapses per IHC ... More
Vertical silicon nanowires as a universal platform for delivering biomolecules into living cells.
AuthorsShalek AK, Robinson JT, Karp ES, Lee JS, Ahn DR, Yoon MH, Sutton A, Jorgolli M, Gertner RS, Gujral TS, Macbeath G, Yang EG, Park H,
JournalProc Natl Acad Sci U S A
PubMed ID20080678
A generalized platform for introducing a diverse range of biomolecules into living cells in high-throughput could transform how complex cellular processes are probed and analyzed. Here, we demonstrate spatially localized, efficient, and universal delivery of biomolecules into immortalized and primary mammalian cells using surface-modified vertical silicon nanowires. The method relies ... More
Violet laser diodes as light sources for cytometry.
AuthorsShapiro HM, Perlmutter NG
JournalCytometry
PubMed ID11378864
BACKGROUND: Violet laser diodes have recently become commercially available. These devices emit 5-25 mW in the range of 395-415 nm, and are available in systems that incorporate the diodes with collimating optics and regulated power supplies in housing incorporating thermoelectric coolers, which are necessary to maintain stable output. Such systems ... More
Two-photon molecular excitation imaging of Ca2+ transients in Langendorff-perfused mouse hearts.
AuthorsRubart M, Wang E, Dunn KW, Field LJ
JournalAm J Physiol Cell Physiol
PubMed ID12584115
The ability to image calcium signals at subcellular levels within the intact depolarizing heart could provide valuable information toward a more integrated understanding of cardiac function. Accordingly, a system combining two-photon excitation with laser-scanning microscopy was developed to monitor electrically evoked [Ca(2+)](i) transients in individual cardiomyocytes within noncontracting Langendorff-perfused mouse ... More
Analysis of Organelle Positioning Using Patterned Microdevices.
AuthorsCapmany A, Latgé B, Schauer K
JournalCurr Protoc Cell Biol
PubMed ID30431237
'The consequences of alterations in the distribution of intracellular organelles, observed in many diseases, are often not clear. Intracellular organelles alter their morphology and positioning to regulate cell homeostasis and function. We outline how organelle positioning can be studied employing a density-based analysis of 3D images applied to cells that ... More
Robust Classification of Small-Molecule Mechanism of Action Using a Minimalist High-Content Microscopy Screen and Multidimensional Phenotypic Trajectory Analysis.
AuthorsTwarog NR, Low JA, Currier DG, Miller G, Chen T, Shelat AA
JournalPLoS One
PubMed ID26886014
'Phenotypic screening through high-content automated microscopy is a powerful tool for evaluating the mechanism of action of candidate therapeutics. Despite more than a decade of development, however, high content assays have yielded mixed results, identifying robust phenotypes in only a small subset of compound classes. This has led to a ... More
Phospholipase A2 is involved in galactosylsphingosine-induced astrocyte toxicity, neuronal damage and demyelination.
AuthorsMisslin C, Velasco-Estevez M, Albert M, O'Sullivan SA, Dev KK
JournalPLoS One
PubMed ID29095858
'Krabbe disease is a fatal rare inherited lipid storage disorder affecting 1:100,000 births. This illness is caused by mutations in the galc gene encoding for the enzyme galactosylceramidase (GALC). Dysfunction of GALC has been linked to the toxic build-up of the galactolipid, galactosylsphingosine (psychosine), which induces cell death of oligodendrocytes. ... More
Normal murine respiratory tract has its mucus concentrated in clouds based on the Muc5b mucin.
AuthorsFakih D, Rodriguez-Piñeiro AM, Trillo-Muyo S, Evans CM, Ermund A, Hansson GC
JournalAm J Physiol Lung Cell Mol Physiol
PubMed ID32348677
'The organization of the normal airway mucus system differs in small experimental animals from that in humans and large mammals. To address normal murine airway mucociliary clearance, Alcian blue-stained mucus transport was measured ex vivo on tracheal tissues of naïve C57BL/6,' ... More
Chemovirotherapy of Lung Squamous Cell Carcinoma by Combining Oncolytic Adenovirus With Gemcitabine.
AuthorsLiu X, Yang Z, Li Y, Zhu Y, Li W, Li S, Wang J, Cui Y, Shang C, Liu Z, Song G, Li C, Li X, Shao G, Jin N
JournalFront Oncol
PubMed ID32158698
'Oncolytic virotherapy is emerging as an important agent in cancer treatment. In a previous study, we designed and constructed Ad-Apoptin-hTERTp-E1a (Ad-VT), a dual cancer-selective anti-tumor recombinant adenovirus. In this study, crystal violet staining and WST-1 assays showed that Ad-VT has a significant tumor killing effect in a time and dose ... More
Overexpression of collagen XIII in extraocular fat affected by active thyroid-associated ophthalmopathy: A crucial piece of the puzzle?
AuthorsMorris OC, Schebitz Walter K, Telemo E, Hintschich C
JournalOrbit
PubMed ID27245701
Thyroid-associated ophthalmopathy (TAO) causes irreversible increase in extraocular fat volume that contributes to the risk of exophthalmos and compressive optic neuropathy. Collagen XIII is implicated in uncontrolled cell growth in some tumours, but we are not aware of any studies of collagen XIII in TAO-affected solid tissue to date. We ... More
Constitutively low expression of collagen XIII alpha 1 may help explain the vulnerability of the inferior rectus muscle to thyroid-associated ophthalmopathy.
AuthorsMorris OC, Schebitz Walter K, Telemo E, Hintschich C
JournalOrbit
PubMed ID27580012
Thyroid-associated ophthalmopathy (TAO) has a predilection for inferior rectus muscle that has never been explained. We conducted immunohistochemical staining for the soluble cleaved form of collagen XIII alpha 1 (COL13A1) and found constitutively low expression of COL13A1 in normal human inferior rectus muscles and moderate expression of COL13A1 in normal ... More
EBI2 receptor regulates myelin development and inhibits LPC-induced demyelination.
AuthorsRutkowska A, Sailer AW, Dev KK
JournalJ Neuroinflammation
PubMed ID29246262
The G protein-coupled receptor EBI2 (Epstein-Barr virus-induced gene 2) is activated by 7a, 25-dihydroxycholesterol (7a25HC) and plays a role in T cell-dependant antibody response and B cell migration. Abnormal EBI2 signaling is implicated in a range of autoimmune disorders; however, its role in the CNS remains poorly understood. ... More
Automated Tracking of Root for Confocal Time-lapse Imaging of Cellular Processes.
AuthorsDoumane M, Lionnet C, Bayle V, Jaillais Y, Caillaud MC
JournalBio Protoc
PubMed ID28459086
Here we describe a protocol that enables to automatically perform time-lapse imaging of growing root tips for several hours. Plants roots expressing fluorescent proteins or stained with dyes are imaged while they grow using automatic movement of the microscope stage that compensates for root growth and allows to follow a ... More
A Promising New Approach for the Treatment of Inflammatory Pain: Transfer of Stem Cell-Derived Tyrosine Hydroxylase-Positive Cells.
AuthorsEbbinghaus M, Jenei-Lanzl Z, Segond von Banchet G, Stangl H, Gajda M, Straub RH, Schaible HG
JournalNeuroimmunomodulation
PubMed ID30566959
The appearance of endogenous tyrosine hydroxylase-positive cells (TH+ cells) in collagen-induced arthritis was associated with an anti-inflammatory effect. Here we investigated putative anti-inflammatory and antinociceptive effects of the transfer of induced, bone marrow stem cell-derived TH+ cells (iTH+ cells) on murine antigen-induced arthritis (AIA). ... More
EBI2 regulates pro-inflammatory signalling and cytokine release in astrocytes.
AuthorsRutkowska A, Shimshek DR, Sailer AW, Dev KK
JournalNeuropharmacology
PubMed ID29374507
The endogenous oxysterol 7a, 25-dihydroxycholesterol (7a25HC) ligand activates the G protein-coupled receptor EBI2 to regulate T cell-dependant antibody response and B cell migration. We have demonstrated that EBI2 is expressed in human and mouse astrocytes, that 7a25HC induces intracellular signalling and astrocyte migration, and that EBI2 plays a role in ... More
Sphingosine 1-phosphate receptors regulate TLR4-induced CXCL5 release from astrocytes and microglia.
AuthorsO'Sullivan SA, O'Sullivan C, Healy LM, Dev KK, Sheridan GK
JournalJ Neurochem
PubMed ID29377126
Sphingosine 1-phosphate receptors (S1PR) are G protein-coupled and compose a family with five subtypes, S1P1R-S1P5R. The drug Gilenya
A Novel Three-Dimensional Glioma Blood-Brain Barrier Model for High-Throughput Testing of Tumoricidal Capability.
AuthorsSherman H, Rossi AE,
JournalFront Oncol
PubMed ID31131260
The blood-brain barrier (BBB) limits passage of substances between general circulation and the brain extracellular fluid, maintaining homeostasis in neural tissues and providing a defense against potential toxins. However, the protection provided by the BBB often prevents conventional chemotherapeutics from reaching brain tumors which makes brain cancers one of the ... More