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https://www.readbyqxmd.com/read/28550686/microrna-186-suppresses-cell-proliferation-and-metastasis-through-targeting-sentrin-specific-protease-1-in-renal-cell-carcinoma
#1
Dan Jiao, Man Wu, Lei Ji, Feng Liu, Yingying Liu
Recent evidence suggests that dysregulation of microRNAs are associated with the development of multiple malignancies.miR-186 has been reported as a critical cancer regulator in several types of cancers. However, its functional significance and molecular mechanism underlying renal cell carcinoma (RCC) remains unknown. In this study, our results showed that miR-186 expression was dramatically downregulated in RCC tissues and cell lines compared to that in adjacent normal tissues and cell lines. Overexpression of miR-186 significantly inhibited cell growth, colony formation, cell invasion, caused cell cycle arrest at G0/G1 phase, and induced cell apoptosis as detected by MTT, colony formation, Transwell assay, and flow cytometry assays in RCC cells...
May 21, 2017: Oncology Research
https://www.readbyqxmd.com/read/28550425/cpg-oligonucleotide-mediated-co-stimulation-of-mouse-invariant-natural-killer-t-cells-negatively-regulates-their-activation-status
#2
Raveendra R Kulkarni, Alexander Ian Villanueva, Leah R Read, Jennifer T Brisbin, Siddhartha Kumar Bhaumik, Jonathan LaMarre, Kaja Murali-Krishna, Shayan Sharif
Invariant natural killer T (iNKT) cells play important roles in antimicrobial defense and immune-regulation. We have previously shown that iNKT cells express certain toll-like receptors (TLR), and that TLR co-stimulation of iNKT cells in the presence of suboptimal concentrations of T cell receptor (TCR) agonists enhances cellular activation. In the present study, we investigated the regulatory effects of CpG oligonucleotides in mouse primary hepatic and splenic iNKT cells and in DN32.D3 iNKT cells. We show that CpG treatment of iNKT cells in the presence of higher concentrations of TCR agonists (α-GalCer or anti-CD3 mAb) results in the up-regulation of TLR9 in iNKT cells with a concurrent reduction in their cellular activation, as assessed by their production of IL-2, IL-4 and IFN-γ compared with controls...
May 27, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28550395/a-critical-role-for-il-21-receptor-signaling-in-the-coxsackievirus-b3-induced-myocarditis
#3
Fan Yang, Xiao-Mou Wei, Wen-Wu Liang, Wen-Hong Mo, Bao-Ping Tan, Hong Wang
To determine whether IL-21 receptor signaling plays a significant role in promoting Tfh cell-mediated cardiac injury in viral myocarditis (VMC), we compared IL-21R-deficient mice for some parameters of VMC. Balb/c and IL-21R(-/-) mice were infected with CVB3. Frequencies of splenic Tfh cells were determined by flow cytometric analysis, and productions of anti-adenine nucleotide translocator (ANT) autoantibodies were detected by enzyme-linked immunosorbent assay. To determine the effects of IL-21R signal on the proliferation of B cells, lymphocytes from spleens of the IL-21R(-/-) and Balb/c mice infected by CVB3 were tagged with carboxyfluorescein succinimidyl ester (CFSE) and then were stimulated with lipopolysaccharides plus IL-21 or anti-IL-21 neutralizing antibody for 3 days...
May 26, 2017: Inflammation
https://www.readbyqxmd.com/read/28550302/antigenicity-of-bovine-pericardium-determined-by-a-novel-immunoproteomic-approach
#4
Katherine V Gates, Ailsa J Dalgliesh, Leigh G Griffiths
Despite bovine pericardium (BP) being the primary biomaterial used in heart valve bioprostheses, recipient graft-specific immune responses remain a significant cause of graft failure. Consequently, tissue antigenicity remains the principal barrier for expanding use of such biomaterials in clinical practice. We hypothesize that our understanding of BP antigenicity can be improved by application of a combined affinity chromatography shotgun immunoproteomic approach to identify antigens that have previously been overlooked...
May 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28550288/infants-learn-better-from-left-to-right-a-directional-bias-in-infants-sequence-learning
#5
Hermann Bulf, Maria Dolores de Hevia, Valeria Gariboldi, Viola Macchi Cassia
A wealth of studies show that human adults map ordered information onto a directional spatial continuum. We asked whether mapping ordinal information into a directional space constitutes an early predisposition, already functional prior to the acquisition of symbolic knowledge and language. While it is known that preverbal infants represent numerical order along a left-to-right spatial continuum, no studies have investigated yet whether infants, like adults, organize any kind of ordinal information onto a directional space...
May 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28550268/improving-reproducibility-of-phenotypic-assessments-in-the-dyw-mouse-model-of-laminin-%C3%AE-2-related-congenital-muscular-dystrophy
#6
Raffaella Willmann, Heather Gordish-Dressman, Sarina Meinen, Markus A Rüegg, Qing Yu, Kanneboyina Nagaraju, Ayar Kumar, Mahasweta Girgenrath, Caroline B M Coffey, Vivian Cruz, Pam M Van Ry, Laurent Bogdanik, Cathleen Lutz, Anne Rutkowski, Dean J Burkin
Laminin-α2 related Congenital Muscular Dystrophy (LAMA2-CMD) is a progressive muscle disease caused by partial or complete deficiency of laminin-211, a skeletal muscle extracellular matrix protein. In the last decade, basic science research has queried underlying disease mechanisms in existing LAMA2-CMD murine models and identified possible clinical targets and pharmacological interventions. Experimental rigor in preclinical studies is critical to efficiently and accurately quantify both negative and positive results, degree of efficiency of potential therapeutics and determine whether to move a compound forward for additional preclinical testing...
May 24, 2017: Journal of Neuromuscular Diseases
https://www.readbyqxmd.com/read/28550247/two-novel-mutations-in-the-first-transmembrane-domain-of-presenilin1-cause-young-onset-alzheimer-s-disease
#7
Collin Y Liu, Yu Ohki, Taisuke Tomita, Satoko Osawa, Bruce R Reed, William Jagust, Victoria Van Berlo, Lee-Way Jin, Helena C Chui, Giovanni Coppola, John M Ringman
BACKGROUND: The presenilin-1 protein (PS1) is the catalytic unit of γ-secretase implicated in the production of abnormally long forms of amyloid-β (Aβ), including Aβ42, proteins thought critical in the pathogenesis of Alzheimer's disease (AD). In AD of autosomal dominant inheritance, the majority of pathogenic mutations have been found in the PSEN1 gene within which the location of the mutation can provide clues as to the mechanism of pathogenesis. OBJECTIVE: To describe clinical features of two novel mutations in the transmembrane portion 1 (TMD-1) of PSEN1 as well as biochemical features in one and neuropathological findings in the other...
May 25, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28550239/clinical-conditions-responsible-for-hyperviscosity-and-skin-ulcers-complications
#8
Gregorio Caimi, Baldassare Canino, Rosalia Lo Presti, Caterina Urso, Eugenia Hopps
In this brief review, we have examined some clinical conditions that result to be associated to an altered hemorheological profile and at times accompanied by skin ulcers. This skin condition may be observed in patients with the following condtions, such as primary polycythemic hyperviscosity (polycythemia, thrombocytemia) treated with hydroxyurea, primary plasma hyperviscosity (multiple myeloma, cryoglobulinemia, cryofibrinogenemia, dysfibrinogenemia, and connective tissue diseases), primary sclerocythemic hyperviscosity (hereditary spherocytosis, thalassemia, and sickle cell disease)...
May 19, 2017: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/28550207/atx3-atx4-and-atx5-encode-putative-h3k4-methyltransferases-and-are-critical-for-plant-development
#9
Liqun Chen, Jinhong Luo, Zhenhai Cui, Ming Xue, Li Wang, Xiaoyu Zhang, Wojtek P Pawlowski, Yan He
Methylation of lysine residues in the tail of the H3 histone is a key regulator of chromatin state and gene expression, conferred by a large family of enzymes containing an evolutionarily-conserved SET domain. One of the main types of SET domain proteins are those controlling H3K4 di- and trimethylation. The genome of Arabidopsis encodes 12 such proteins, including five ARABIDOPSIS TRITHORAX (ATX) proteins and seven ATX-Related (ATXR) proteins. Here we examined three until-now-unexplored ATX proteins, ATX3, ATX4, and ATX5...
May 26, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28550197/viral-rna-unprimed-rig-i-restrains-stat3-activation-in-the-modulation-of-regulatory-t-cell-th17-cell-balance
#10
Hui Yang, He-Zhou Guo, Xian-Yang Li, Jian Lin, Wu Zhang, Jun-Mei Zhao, Hong-Xin Zhang, Sai-Juan Chen, Zhu Chen, Jiang Zhu
Innate immunity activation by viral RNA-primed retinoid acid inducible gene-I (Rig-I) in CD4(+) T cells antagonizes TGFβ signaling to suppress the differentiation of regulatory T cells (Tregs). However, how viral RNA-unliganded Rig-I (apo-Rig-I) modulates Treg generation remains unclear. In this article, we show that, in the absence of viral infection, Treg differentiation of Rig-I(-/-) CD4(+) T cells was compromised, in the presence of increased generation of Th17 cells and overactivation of Stat3, a critical regulator tilting the Treg/Th17 cell balance...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28550179/cyp2c44-gene-disruption-is-associated-with-increased-hematopoietic-stem-cells-implication-in-chronic-hypoxia-induced-pulmonary-hypertension
#11
Ryota Hashimoto, Sachindra Raj Joshi, Houli Jiang, Jorge H Capdevila, Ivan F McMurtry, Michal Laniado Schwartzman, Sachin A Gupte
We have recently demonstrated that disruption of the murine cytochrome P450 2c44 gene exacerbates chronic hypoxia-induced pulmonary artery remodeling and hypertension in mice. Subsequently, we serendipitously found that Cyp2c44 gene disruption also increases hematopoietic stem cell (HSC) number in bone marrow and blood. Therefore, the objective of this study was to investigate whether Cyp2c44 disruption regulates HSC phenotype and whether increases in differentiated HSCs contribute to chronic hypoxia-induced remodeling of pulmonary arteries...
May 26, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28550177/role-of-thiosulfate-in-hydrogen-sulfide-dependent-redox-signaling-in-endothelial-cells
#12
Anna Leskova, Siblile Pardue, John D Glawe, Christopher G Kevil, Xinggui Shen
Recent reports have revealed that hydrogen sulfide (H2S) exerts critical actions to promote cardiovascular homeostasis and health. Thiosulfate (S2O3(2-)) is one of the products formed during oxidative H2S metabolism, and thiosulfate has been used extensively and safely to treat calcific uremic arteriopathy in dialysis patients. Yet despite its significance, fundamental questions regarding how thiosulfate and H2S interact during redox signaling remain unanswered. In this study, we examined the effect of exogenous thiosulfate on hypoxia-induced H2S metabolite bioavailability in human umbilical vein endothelial cells (HUVECs)...
May 26, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28550169/the-gliotransmitter-d-serine-promotes-synapse-maturation-and-axonal-stabilization-in-vivo
#13
Marion R Van Horn, Arielle Strasser, Lois S Miraucourt, Loredano Pollegioni, Edward S Ruthazer
The N-methyl-D-aspartate receptor (NMDAR) is thought to play a key role in the refinement of connectivity in developing neural circuits. Pharmacological blockade or genetic loss-of-function manipulations that prevent NMDAR function during development result in the disorganization of topographic axonal projections. However, because NMDARs contribute to overall glutamatergic neurotransmission, such loss-of-function experiments fail to adequately distinguish between the roles played by NMDARs and neural activity in general...
May 26, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28550161/lymphoid-differentiation-of-hematopoietic-stem-cells-requires-efficient-cxcr4-desensitization
#14
Christelle Freitas, Monika Wittner, Julie Nguyen, Vincent Rondeau, Vincent Biajoux, Marie-Laure Aknin, Françoise Gaudin, Sarah Beaussant-Cohen, Yves Bertrand, Christine Bellanné-Chantelot, Jean Donadieu, Françoise Bachelerie, Marion Espéli, Ali Dalloul, Fawzia Louache, Karl Balabanian
The CXCL12/CXCR4 signaling exerts a dominant role in promoting hematopoietic stem and progenitor cell (HSPC) retention and quiescence in bone marrow. Gain-of-function CXCR4 mutations that affect homologous desensitization of the receptor have been reported in the WHIM Syndrome (WS), a rare immunodeficiency characterized by lymphopenia. The mechanisms underpinning this remain obscure. Using a mouse model with a naturally occurring WS-linked gain-of-function Cxcr4 mutation, we explored the possibility that the lymphopenia in WS arises from defects at the HSPC level...
May 26, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28550149/the-jasmonate-activated-transcription-factor-mdmyc2-regulates-ethylene-response-factor-and-ethylene-biosynthetic-genes-to-promote-ethylene-biosynthesis-during-apple-fruit-ripening
#15
Tong Li, Yaxiu Xu, Lichao Zhang, Yinglin Ji, Dongmei Tan, Hui Yuan, Aide Wang
The plant hormone ethylene is critical for ripening in climacteric fruits, including apple (Malus domestica). Jasmonate (JA) promotes ethylene biosynthesis in apple fruit, but the underlying molecular mechanism is unclear. Here we found that JA-induced ethylene production in apple fruit is dependent on the expression of MdACS1, an ACC synthase gene involved in ethylene biosynthesis. The expression of MdMYC2, encoding a transcription factor involved in the JA signaling pathway, was enhanced by MeJA treatment in apple fruits, and MdMYC2 directly bound to the promoters of both MdACS1 and the ACC oxidase gene MdACO1 and enhanced their transcription...
May 26, 2017: Plant Cell
https://www.readbyqxmd.com/read/28550123/essential-role-for-histone-deacetylase-11-hdac11-in-neutrophil-biology
#16
Eva Sahakian, Jie Chen, John J Powers, Xianghong Chen, Kamira Maharaj, Susan L Deng, Maritza Lienlaf, Hong Wei Wang, Fengdong Cheng, Andressa L Sodré, Allison Distler, Limin Xing, Patricio Perez-Villarroel, Sheng Wei, Alejandro Villagra, Ed Seto, Eduardo M Sotomayor, Pedro Horna, Javier Pinilla-Ibarz
Epigenetic changes in chromatin structure have been recently associated with the deregulated expression of critical genes in normal and malignant processes. HDAC11, the newest member of the HDAC family of enzymes, functions as a negative regulator of IL-10 expression in APCs, as previously described by our lab. However, at the present time, its role in other hematopoietic cells, specifically in neutrophils, has not been fully explored. In this report, for the first time, we present a novel physiologic role for HDAC11 as a multifaceted regulator of neutrophils...
May 26, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28550110/trpm8-inhibits-endothelial-cell-migration-via-a-non-channel-function-by-trapping-the-small-gtpase-rap1
#17
Tullio Genova, Guillaume P Grolez, Chiara Camillo, Michela Bernardini, Alexandre Bokhobza, Elodie Richard, Marco Scianna, Loic Lemonnier, Donatella Valdembri, Luca Munaron, Mark R Philips, Virginie Mattot, Guido Serini, Natalia Prevarskaya, Dimitra Gkika, Alessandra Fiorio Pla
Endothelial cell adhesion and migration are critical steps of the angiogenic process, whose dysfunction is associated with tumor growth and metastasis. The TRPM8 channel has recently been proposed to play a protective role in prostate cancer by impairing cell motility. However, the mechanisms by which it could influence vascular behavior are unknown. Here, we reveal a novel non-channel function for TRPM8 that unexpectedly acts as a Rap1 GTPase inhibitor, thereby inhibiting endothelial cell motility, independently of pore function...
May 26, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28550088/cardiac-telomere-length-in-heart-development-function-and-disease
#18
Scott A Booth, Fadi J Charchar
Telomeres are repetitive nucleoprotein structures at chromosome ends and a decrease in the number of these repeats, known as a reduction in telomere length (TL), triggers cellular senescence and apoptosis. Heart disease, the worldwide leading cause of death, often results from the loss of cardiac cells which could be explained by decreases in TL. Due to the cell-specific regulation of TL, this review focuses on studies that have measured telomeres in heart cells and critically assesses the relationship between cardiac TL and heart function...
May 26, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28550086/the-iron-dependent-mitochondrial-superoxide-dismutase-soda-promotes-leishmania-virulence
#19
Bidyottam Mittra, Maria Fernanda Laranjeira-Silva, Danilo Ciccone Miguel, Juliana Perrone Bezerra de Menezes, Norma W Andrews
Leishmaniasis is one of the leading global neglected diseases, affecting millions of people worldwide. Leishmania infection depends on the ability of insect-transmitted metacyclic promastigotes to invade mammalian hosts, differentiate into amastigotes and replicate inside macrophages. To counter the hostile oxidative environment inside macrophages, these protozoans contain anti-oxidant systems that include iron-dependent superoxide dismutases (SODs) in mitochondria and glycosomes. Increasing evidence suggests that in addition to this protective role, Leishmania mitochondrial SOD may also initiate H2O2-mediated redox signaling that regulates gene expression and metabolic changes associated with differentiation into virulent forms...
May 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28550060/surface-sensing-for-flagellar-gene-expression-on-solid-media-in-paenibacillus-sp-naist15-1
#20
Kazuo Kobayashi, Yu Kanesaki, Hirofumi Yoshikawa
A rhizosphere Gram-positive bacterial isolate, Paenibacillus sp. NAIST15-1, exhibits intriguing motility behavior on hard agar media. Paenibacillus sp. shows increased transcription of flagellar genes and hyperflagellation when transferred from liquid to solid media. Hyperflagellated cells form wandering colonies that are capable of moving around on the surface of media containing ≥1.5% agar. Transposon mutagenesis was used to identify genes critical for motility. In addition to flagellar genes, this mutagenesis identified five non-flagellar structural genes that were important for motility...
May 26, 2017: Applied and Environmental Microbiology
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