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Min-Kyung Yeo, Yong-Moon Lee, In-Ock Seong, Song-Yi Choi, Kwang-Sun Suh, Kyu Sang Song, Choong-Sik Lee, Jin Man Kim, Kyung-Hee Kim
AIM: Cluster of differentiation 24 (CD24) is known to be a putative marker of stem cell and tumor metastasis. This study aimed to verify the clinicopathological value of CD24 expression in colorectal adenocarcinoma (CRAC). MATERIALS AND METHODS: A total of seven whole-tissue sections of malignant polyps including the sequence non-neoplastic colorectal tissue-adenoma-CRAC, 48 adenomas and 161 CRACs arranged as tissue microarray were examined by immunohistochemistry for CD24 protein expression...
December 2016: Anticancer Research
Nasser B Alsaleh, Indushekhar Persaud, Jared M Brown
Engineered nanomaterial (ENM)-mediated toxicity often involves triggering immune responses. Mast cells can regulate both innate and adaptive immune responses and are key effectors in allergic diseases and inflammation. Silver nanoparticles (AgNPs) are one of the most prevalent nanomaterials used in consumer products due to their antimicrobial properties. We have previously shown that AgNPs induce mast cell degranulation that was dependent on nanoparticle physicochemical properties. Furthermore, we identified a role for scavenger receptor B1 (SR-B1) in AgNP-mediated mast cell degranulation...
2016: PloS One
Mariarosaria Ferraro, Matteo Masetti, Maurizio Recanatini, Andrea Cavalli, Giovanni Bottegoni
Serotonin transporter (SERT) modulates serotonergic signaling via re-uptake of serotonin in pre-synaptic cells. The inclusion in cholesterol-enriched membrane domains is crucial for SERT activity, suggesting a cross-talk between the protein and the sterol. Here, we develop a protocol to identify potential cholesterol interaction sites coupling statistical analysis to multi-microsecond coarse-grained molecular dynamics simulations of SERT in a previously validated raft-like membrane model. Six putative sites were found, including a putative CRAC motif on TM4 and a CARC motif on TM10...
2016: PloS One
M Garibaldi, F Fattori, B Riva, C Labasse, G Brochier, P Ottaviani, S Sacconi, E Vizzaccaro, F Laschena, N B Romero, A Genazzani, E Bertini, G Antonini
We present three members of an Italian family affected by tubular aggregate myopathy (TAM) and congenital miosis harboring a novel missense mutation in ORAI1. All patients had a mild, late onset TAM revealed by asymptomatic creatine kinase (CK) elevation and congenital miosis consistent with a Stormorken-like Syndrome, in the absence of thrombocytopathy. Muscle biopsies showed classical histological findings but ultrastructural analysis revealed atypical tubular aggregates (TAs). The whole body muscle magnetic resonance imaging (MRI) showed a similar pattern of muscle involvement that correlated with clinical severity...
October 13, 2016: Clinical Genetics
N Chrimes
No abstract text is available yet for this article.
December 2016: Anaesthesia
Krishna Samanta, Anant B Parekh
Stimulation of cell-surface receptors that couple to phospholipase C to generate the second messenger inositol trisphosphate often evoke repetitive oscillations in cytosolic Ca(2+) . Signalling information is encoded in both the amplitude and frequency of the Ca(2+) spikes. Recent studies have revealed that the spatial profile of the oscillation also imparts signalling power; Ca(2+) microdomains near store-operated CRAC channels in the plasma membrane and inositol trisphosphate-gated channels in the endoplasmic reticulum both signal to distinct downstream targets...
November 17, 2016: Journal of Physiology
Sacha Beaumeunier, Jérôme Audoux, Anthony Boureux, Florence Ruffle, Thérèse Commes, Nicolas Philippe, Ronnie Alves
BACKGROUND: High-throughput sequencing technology and bioinformatics have identified chimeric RNAs (chRNAs), raising the possibility of chRNAs expressing particularly in diseases can be used as potential biomarkers in both diagnosis and prognosis. RESULTS: The task of discriminating true chRNAs from the false ones poses an interesting Machine Learning (ML) challenge. First of all, the sequencing data may contain false reads due to technical artifacts and during the analysis process, bioinformatics tools may generate false positives due to methodological biases...
2016: BioData Mining
Michelle Yen, Ludmila A Lokteva, Richard S Lewis
Store-operated Ca(2+) entry occurs through the binding of the endoplasmic reticulum (ER) Ca(2+) sensor STIM1 to Orai1, the pore-forming subunit of the Ca(2+) release-activated Ca(2+) (CRAC) channel. Although the essential steps leading to channel opening have been described, fundamental questions remain, including the functional stoichiometry of the CRAC channel. The crystal structure of Drosophila Orai indicates a hexameric stoichiometry, while studies of linked Orai1 concatemers and single-molecule photobleaching suggest that channels assemble as tetramers...
November 1, 2016: Biophysical Journal
Sher Ali, Tao Xu, Xiaolan Xu
Ca(2+) release-activated Ca(2+) (CRAC) channels play an essential role in the immune system. The pore-forming subunit, Orai1, is an important pharmacological target. Here, we summarize the recent discoveries on the structure-function relationship of Orai1, as well as its interaction with the native channel opener STIM1 and chemical modulator 2-aminoethoxydiphenyl borate (2-APB). We first introduce the critical structural elements of Orai1, which include a Ca(2+) accumulating region, ion selectivity filter, hydrophobic centre, basic region, extended transmembrane Orai1 N-terminal (ETON) region, transmembrane (TM) regions 2 and 3, P245 bend, (263) SHK(265) hinge linker and L273-L276 hydrophobic patch...
October 18, 2016: Journal of Physiology
Axel R Concepcion, Martin Vaeth, Larry E Wagner, Miriam Eckstein, Lee Hecht, Jun Yang, David Crottes, Maximilian Seidl, Hyosup P Shin, Carl Weidinger, Scott Cameron, Stuart E Turvey, Thomas Issekutz, Isabelle Meyts, Rodrigo S Lacruz, Mario Cuk, David I Yule, Stefan Feske
Eccrine sweat glands are essential for sweating and thermoregulation in humans. Loss-of-function mutations in the Ca2+ release-activated Ca2+ (CRAC) channel genes ORAI1 and STIM1 abolish store-operated Ca2+ entry (SOCE), and patients with these CRAC channel mutations suffer from anhidrosis and hyperthermia at high ambient temperatures. Here we have shown that CRAC channel-deficient patients and mice with ectodermal tissue-specific deletion of Orai1 (Orai1K14Cre) or Stim1 and Stim2 (Stim1/2K14Cre) failed to sweat despite normal sweat gland development...
November 1, 2016: Journal of Clinical Investigation
Amit Jairaman, Chelsea H Maguire, Robert P Schleimer, Murali Prakriya
Aberrant immune responses to environmental allergens including insect allergens from house dust mites and cockroaches contribute to allergic inflammatory diseases such as asthma in susceptible individuals. Airway epithelial cells (AECs) play a critical role in this process by sensing the proteolytic activity of allergens via protease-activated receptors (PAR2) to initiate inflammatory and immune responses in the airway. Elevation of cytosolic Ca(2+) is an important signaling event in this process, yet the fundamental mechanism by which allergens induce Ca(2+) elevations in AECs remains poorly understood...
September 8, 2016: Scientific Reports
Bin Jia, Yanzi Song, Min Wu, Baicheng Lin, Kang Xiao, Zhangli Hu, Ying Huang
BACKGROUND: Microalgae biofuel has become the most promising renewable energy over the past few years. But limitations still exist because of its high cost. Although, efforts have been made in enhancement of lipid productivity, the major cost problem in harvesting and oil extraction is still intractable. Thus, the idea of fatty acids (FAs) secretion which can massively facilitate algae harvesting and oil extraction was investigated here. RESULTS: The cDNAs of two long-chain acyl-CoA synthetases (LACSs) genes were cloned from Chlamydomonas reinhardtii and named as cracs1 and cracs2...
2016: Biotechnology for Biofuels
Catherine A Rivet, Ariel S Kniss-James, Margaret A Gran, Anish Potnis, Abby Hill, Hang Lu, Melissa L Kemp
T cells reach a state of replicative senescence characterized by a decreased ability to proliferate and respond to foreign antigens. Calcium release associated with TCR engagement is widely used as a surrogate measure of T cell response. Using an ex vivo culture model that partially replicates features of organismal aging, we observe that while the amplitude of Ca2+ signaling does not change with time in culture, older T cells exhibit faster Ca2+ rise and a faster decay. Gene expression analysis of Ca2+ channels and pumps expressed in T cells by RT-qPCR identified overexpression of the plasma membrane CRAC channel subunit ORAI1 and PMCA in older T cells...
2016: PloS One
Evan Koufos, En Hyung Chang, Elnaz S Rasti, Eric Krueger, Angela C Brown
Recognition of and binding to cholesterol on the host cell membrane is an initial step in the mechanism of numerous pathogens, including viruses, bacteria, and bacterial toxins; however, a viable method of inhibiting this interaction has not yet been uncovered. Here, we describe the mechanism by which a cholesterol recognition amino acid consensus peptide interacts with cholesterol and inhibits the activity of a cholesterol-binding bacterial leukotoxin (LtxA). Using a series of biophysical techniques, we have shown that the peptide recognizes the hydroxyl group of cholesterol with nanomolar affinity and does not disrupt membrane packing, suggesting that it sits primarily near the membrane surface...
August 30, 2016: Biochemistry
Masato Mashimo, Yukako Yurie, Koichiro Kawashima, Takeshi Fujii
AIMS: T lymphocytes express muscarinic acetylcholine receptors (mAChRs) involved in regulating their proliferation, differentiation and cytokine release. Activation of M1, M3 or M5 mAChRs increases the intracellular Ca(2+) concentration ([Ca(2+)]i) through inositol-1,4,5-phosphate (IP3)-mediated Ca(2+) release from endoplasmic reticulum Ca(2+) stores. In addition, T lymphocytes express Ca(2+)-release activated Ca(2+) (CRAC) channels to induce Ca(2+) influx and to regulate diverse immune functions...
September 15, 2016: Life Sciences
Ilaria Maccari, Renping Zhao, Martin Peglow, Karsten Schwarz, Ivan Hornak, Mathias Pasche, Ariel Quintana, Markus Hoth, Bin Qu, Heiko Rieger
Ca(2+) microdomains and spatially resolved Ca(2+) signals are highly relevant for cell function. In T cells, local Ca(2+) signaling at the immunological synapse (IS) is required for downstream effector functions. We present experimental evidence that the relocation of the MTOC towards the IS during polarization drags mitochondria along with the microtubule network. From time-lapse fluorescence microscopy we conclude that mitochondria rotate together with the cytoskeleton towards the IS. We hypothesize that this movement of mitochondria towards the IS together with their functionality of absorption and spatial redistribution of Ca(2+) is sufficient to significantly increase the cytosolic Ca(2+) concentration...
July 7, 2016: Cell Calcium
Ahmad Almilaji, Jing Yan, Zohreh Hosseinzadeh, Evi Schmid, Meinrad Gawaz, Florian Lang
BACKGROUND: Blood platelets are activated by increase of cytosolic Ca2+ activity ([Ca2+]i). Ca2+ entry is accomplished in part by store operated Ca2+ entry (SOCE) involving Ca2+ release activated Ca2+-channel (CRAC) moiety Orai1 and its regulator STIM1, which are stimulated by depletion of intracellular Ca2+ stores. An increase of [Ca2+]i is terminated by Na+/Ca2+-exchange. The expression of both, Orai1 and STIM1 in megakaryocytes is up-regulated by tumor growth factor TGFβ1, a powerful regulator of megakaryocyte differentiation...
2016: Cellular Physiology and Biochemistry
Catherine A Hartzell, Katarzyna I Jankowska, Janis K Burkhardt, Richard S Lewis
T cell receptor (TCR) engagement opens Ca(2+) release-activated Ca(2+) (CRAC) channels and triggers formation of an immune synapse between T cells and antigen-presenting cells. At the synapse, actin reorganizes into a concentric lamellipod and lamella with retrograde actin flow that helps regulate the intensity and duration of TCR signaling. We find that Ca(2+) influx is required to drive actin organization and dynamics at the synapse. Calcium acts by promoting actin depolymerization and localizing actin polymerization and the actin nucleation promotion factor WAVE2 to the periphery of the lamellipod while suppressing polymerization elsewhere...
2016: ELife
Renshan Sun, Yongqiang Yang, Xinze Ran, Tao Yang
Using the systematic evolution of ligands by exponential enrichment (SELEX) method, we identified oligonucleotides that bind to the first extracellular domain of the Orai1 protein with high affinities and high specificities. These ligands were isolated from a random single-strand DNA (ssDNA) library with 40 randomized sequence positions, using synthesized peptides with amino acid sequences identical to the first extracellular domain of the Orai1 protein as the targets for SELEX selection. Seven aptamers were obtained after 12 rounds of SELEX...
2016: PloS One
Xiaolan Xu, Sher Ali, Yufeng Li, Haijie Yu, Mingshu Zhang, Jingze Lu, Tao Xu
2-Aminoethoxydiphenyl borate (2-APB) elicits potentiation current (Ip) on Ca(2+) release-activated Ca(2+) (CRAC) channels. An accurate investigation into this modulation mechanism would reveal how STIM1-dependent channel gating is enhanced, and benefit the future immune enhancer development. Here, we directly probed the pore diameter of CRAC channels and found that 2-APB enlarged the pore size of STIM1-activated Orai1 from 3.8 to 4.6 Å. We demonstrated that ions with small sizes, i.e., Ca(2+) and Na(+), mediated prominent 2-APB-induced Ip on the wildtype (WT) Orai1 channels of narrow pore sizes, while conducted decreased or no Ip on Orai1-V102C/A/G mutant channels with enlarged pore diameters...
2016: Scientific Reports
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