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https://www.readbyqxmd.com/read/27933712/the-importance-of-mrna-structure-in-determining-the-pathogenicity-of-synonymous-and-non-synonymous-mutations-in-haemophilia
#1
N Hamasaki-Katagiri, B C Lin, J Simon, R C Hunt, T Schiller, E Russek-Cohen, A A Komar, H Bar, C Kimchi-Sarfaty
INTRODUCTION: Mutational analysis is commonly used to support the diagnosis and management of haemophilia. This has allowed for the generation of large mutation databases which provide unparalleled insight into genotype-phenotype relationships. Haemophilia is associated with inversions, deletions, insertions, nonsense and missense mutations. Both synonymous and non-synonymous mutations influence the base pairing of messenger RNA (mRNA), which can alter mRNA structure, cellular half-life and ribosome processivity/elongation...
December 9, 2016: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/27933701/ccr2-mediates-helicobacter-pylori-induced-immune-tolerance-and-contributes-to-mucosal-homeostasis
#2
Xia Sun, Min Zhang, Mohamad El-Zaatari, Gray B Huffnagle, John Y Kao
BACKGROUND: We previously demonstrated that H. pylori infection leads to increased induction of regulatory T cells in local and systemic immune compartments. Here, we investigate the role of CCR2 in the tolerogenic programing of dendritic cells in a mouse model of H. pylori infection. MATERIALS AND METHODS: CCR2 deficient (CCR2KO) mice and wild-type (Wt) mice infected with H. pylori SS1 strain were analyzed by qPCR and FACS analysis. In vitro, bone marrow-derived DC on day 6 from CCR2KO and Wt mice cocultured with or without H...
December 8, 2016: Helicobacter
https://www.readbyqxmd.com/read/27933650/up-regulation-of-microrna-133a-inhibits-the-mek-erk-signaling-pathway-to-promote-cell-apoptosis-and-enhance-radio-sensitivity-by-targeting-egfr-in-esophageal-cancer-in-vivo-and-in-vitro
#3
Qing-Shan Yang, Li-Peng Jiang, Chun-Yan He, Yu-Na Tong, Yuan-Yuan Liu
This study aims to explore how microRNA-133a (miR-133a) affects cell apoptosis and radio-sensitivity by targeting EGFR via regulating MEK/ERK pathway in esophageal cancer (EC). A total of 358 EC patients were selected and assigned into the resistant and sensitive groups. Human EC KYSE 150 cell line was assigned into the blank, negative control (NC), miR-133a mimic, miR-133a inhibitors, si-EGFR, miR-133a inhibitors + si-EGFR groups after transfection. MiR-133a and EGFR mRNA expressions were detected by qRT-PCR and EGFR, MEK/ERK pathway-related protein expressions were detected by Western blotting...
December 8, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27933547/anti-neuroinflammatory-effects-of-fucoxanthin-via-inhibition-of-akt-nf-%C3%AE%C2%BAb-and-mapks-ap-1-pathways-and-activation-of-pka-creb-pathway-in-lipopolysaccharide-activated-bv-2-microglial-cells
#4
Dong Zhao, Seung-Hwan Kwon, Yoon Sun Chun, Ming-Yao Gu, Hyun Ok Yang
Microglia play a critical role in controlling the homeostasis of the brain, but over-activated microglia secrete pro-inflammatory mediators and cytokines, which induce neuronal cell death. Fucoxanthin (Fx), a marine carotenoid, has demonstrated a variety of beneficial health effects. Despite accumulating evidence supporting the immune-modulating effects of Fx in vitro, the underlying signaling pathways remain unknown. In the present study, Fx dose-dependently inhibited the secretion of lipopolysaccharide (LPS)-induced pro-inflammatory mediators including interleukin (IL)-6, tumor necrosis factor (TNF)-α, reactive oxygen species (ROS), prostaglandin (PG) E2, and nitric oxide (NO) productions, and also suppressed the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 enzymes...
December 8, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27933533/systems-genetics-as-a-tool-to-identify-master-genetic-regulators-in-complex-disease
#5
Aida Moreno-Moral, Francesco Pesce, Jacques Behmoaras, Enrico Petretto
Systems genetics stems from systems biology and similarly employs integrative modeling approaches to describe the perturbations and phenotypic effects observed in a complex system. However, in the case of systems genetics the main source of perturbation is naturally occurring genetic variation, which can be analyzed at the systems-level to explain the observed variation in phenotypic traits. In contrast with conventional single-variant association approaches, the success of systems genetics has been in the identification of gene networks and molecular pathways that underlie complex disease...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27933513/effect-of-yiqi-tongyang-decoction-on-blood-t-cell-subsets-in-patients-with-chronic-immune-thrombocytopenia
#6
Xiu-Peng Yang, Rou Ma, Xiao-Hong Yang, Hui-Lan Zhu, Yong-Gang Xu
OBJECTIVE: To measure the proportions of blood T cell subsets, Th1, Th2, Th17, Th22, and Treg cells, and other parameters in patients with chronic immune thrombocytopenia (CITP) before and after treatment with Yiqi Tongyang Decoction (, YTD) to explore T cell status of patients with CITP, and to define the mechanism of action of YTD. METHODS: The changes in peripheral blood T lymphocyte subsets, and those of Th1, Th2, Th17, Th22, and Treg cells in 30 patients with CITP (22 females and 8 males) were analyzed using multiparametric flow cytometry before and after treatment with YTD for 6 months, and 26 healthy volunteers (14 males and 12 females) acted as a control...
December 9, 2016: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/27933466/microrna-145-modulates-epithelial-mesenchymal-transition-and-suppresses-proliferation-migration-and-invasion-by-targeting-sip1-in-human-cervical-cancer-cells
#7
Anusha Sathyanarayanan, Karthik Subramanian Chandrasekaran, Devarajan Karunagaran
PURPOSE: Previously, it has been reported that microRNA-145 (miR-145) is lowly expressed in human cervical cancers and that its putative tumour suppressive role may be attributed to epithelial-mesenchymal transition (EMT) regulation. Here, we aimed to assess whether miR-145 may affect EMT-associated markers/genes and suppress cervical cancer growth and motility, and to provide a mechanistic basis for these phenomena. METHODS: The identification of the SMAD-interacting protein 1 (SIP1) mRNA as putative miR-145 target was investigated using a 3' untranslated region (3'UTR) luciferase assay and Western blotting, respectively...
December 8, 2016: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/27933341/intragenic-variations-in-btla-gene-influence-mrna-expression-of-btla-gene-in-chronic-lymphocytic-leukemia-patients-and-confer-susceptibility-to-chronic-lymphocytic-leukemia
#8
Lidia Karabon, Anna Partyka, Monika Jasek, Ewa Lech-Maranda, Olga Grzybowska-Izydorczyk, Agnieszka Bojarska-Junak, Edyta Pawlak-Adamska, Anna Tomkiewicz, Tadeusz Robak, Jacek Rolinski, Irena Frydecka
The aim of this study was to determine the association between polymorphisms in gene encoding B- and T-lymphocyte attenuator (BTLA) and susceptibility to chronic lymphocytic leukemia (CLL) and their influence on mRNA expression of BTLA gene in T and B cells from CLL patients (pts.). The following BTLA single-nucleotide polymorphisms (SNPs): rs2705511, rs1982809, rs9288952, rs76844316, rs16859633, rs9288953, rs2705535, rs1844089, rs2705565, rs2633580 were genotyped with use of TaqMan probes in 321 CLL pts. and in 470 controls...
December 8, 2016: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/27933306/significant-changes-in-endogenous-retinal-gene-expression-assessed-1-year-after-a-single-intraocular-injection-of-aav-cntf-or-aav-bdnf
#9
Chrisna J LeVaillant, Anil Sharma, Jill Muhling, Lachlan Pg Wheeler, Greg S Cozens, Mats Hellström, Jennifer Rodger, Alan R Harvey
Use of viral vectors to deliver therapeutic genes to the central nervous system holds promise for the treatment of neurodegenerative diseases and neurotrauma. Adeno-associated viral (AAV) vectors encoding brain-derived neurotrophic factor (BDNF) or ciliary derived neurotrophic factor (CNTF) promote the viability and regeneration of injured adult rat retinal ganglion cells. However, these growth-inducing transgenes are driven by a constitutively active promoter, thus we examined whether long-term AAV-mediated secretion of BDNF or CNTF affected endogenous retinal gene expression...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27933271/functional-significance-of-aurora-kinases-p53-protein-family-interactions-in-cancer
#10
REVIEW
Kaori Sasai, Warapen Treekitkarnmongkol, Kazuharu Kai, Hiroshi Katayama, Subrata Sen
Aurora kinases play critical roles in regulating spindle assembly, chromosome segregation, and cytokinesis to ensure faithful segregation of chromosomes during mitotic cell division cycle. Molecular and cell biological studies have revealed that Aurora kinases, at physiological levels, orchestrate complex sequential cellular processes at distinct subcellular locations through functional interactions with its various substrates. Aberrant expression of Aurora kinases, on the other hand, cause defects in mitotic spindle assembly, checkpoint response activation, and chromosome segregation leading to chromosomal instability...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27933176/pancreatic-%C3%AE-cell-hyperplasia-and-hyperglucagonemia-due-to-a-glucagon-receptor-splice-mutation
#11
Etienne Larger, Nicolai J Wewer Albrechtsen, Lars H Hansen, Richard W Gelling, Jacqueline Capeau, Carolyn F Deacon, Ole D Madsen, Fumiatsu Yakushiji, Pierre De Meyts, Jens J Holst, Erica Nishimura
: Glucagon stimulates hepatic glucose production by activating specific glucagon receptors in the liver, which in turn increase hepatic glycogenolysis as well as gluconeogenesis and ureagenesis from amino acids. Conversely, glucagon secretion is regulated by concentrations of glucose and amino acids. Disruption of glucagon signaling in rodents results in grossly elevated circulating glucagon levels but no hypoglycemia. Here, we describe a patient carrying a homozygous G to A substitution in the invariant AG dinucleotide found in a 3' mRNA splice junction of the glucagon receptor gene...
2016: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/27933063/aire-downregulation-is-associated-with-changes-in-the-posttranscriptional-control-of-peripheral-tissue-antigens-in-medullary-thymic-epithelial-cells
#12
Ernna H Oliveira, Claudia Macedo, Cristhianna V Collares, Ana Carolina Freitas, Paula Barbim Donate, Elza T Sakamoto-Hojo, Eduardo A Donadi, Geraldo A Passos
Autoimmune regulator (Aire) is a transcriptional regulator of peripheral tissue antigens (PTAs) and microRNAs (miRNAs) in medullary thymic epithelial cells (mTECs). In this study, we tested the hypothesis that Aire also played a role as an upstream posttranscriptional controller in these cells and that variation in its expression might be associated with changes in the interactions between miRNAs and the mRNAs encoding PTAs. We demonstrated that downregulation of Aire in vivo in the thymuses of BALB/c mice imbalanced the large-scale expression of these two RNA species and consequently their interactions...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27933061/ncr1-expression-identifies-canine-natural-killer-cell-subsets-with-phenotypic-similarity-to-human-natural-killer-cells
#13
Jennifer A Foltz, Srinivas S Somanchi, Yanwen Yang, Arianexys Aquino-Lopez, Erin E Bishop, Dean A Lee
Canines spontaneously develop many cancers similar to humans - including osteosarcoma, leukemia, and lymphoma - offering the opportunity to study immune therapies in a genetically heterogeneous and immunocompetent environment. However, a lack of antibodies recognizing canine NK cell markers has resulted in suboptimal characterization and unknown purity of NK cell products, hindering the development of canine models of NK cell adoptive immunotherapy. To this end, we generated a novel antibody to canine NCR1 (NKp46), the putative species-wide marker of NK cells, enabling purification of NK cells for further characterization...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27933059/formation-of-neutrophil-extracellular-traps-under-low-oxygen-level
#14
Katja Branitzki-Heinemann, Helene Möllerherm, Lena Völlger, Diab M Husein, Nicole de Buhr, Stefanie Blodkamp, Friederike Reuner, Graham Brogden, Hassan Y Naim, Maren von Köckritz-Blickwede
Since their discovery, neutrophil extracellular traps (NETs) have been characterized as a fundamental host innate immune defense mechanism. Conversely, excessive NET-release may have a variety of detrimental consequences for the host. A fine balance between NET formation and elimination is necessary to sustain a protective effect during an infectious challenge. Our own recently published data revealed that stabilization of hypoxia-inducible factor 1α (HIF-1α) by the iron chelating HIF-1α-agonist desferoxamine or AKB-4924 enhanced the release of phagocyte extracellular traps...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27932994/comparative-mrna-and-microrna-profiling-during-acute-myocardial-infarction-induced-by-coronary-occlusion-and-ablation-radio-frequency-currents
#15
Eduardo T Santana, Regiane Dos Santos Feliciano, Andrey J Serra, Eduardo Brigidio, Ednei L Antonio, Paulo J F Tucci, Lubov Nathanson, Mariana Morris, José A Silva
The ligation of the left anterior descending coronary artery is the most commonly used experimental model to induce myocardial infarction (MI) in rodents. A high mortality in the acute phase and the heterogeneity of the size of the MI obtained are drawbacks recognized in this model. In an attempt to solve the problem, our group recently developed a new MI experimental model which is based on application of myocardial ablation radio-frequency currents (AB-RF) that yielded MI with homogeneous sizes and significantly reduce acute mortality...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27932980/tnf-%C3%AE-induced-cpla2-expression-via-nadph-oxidase-reactive-oxygen-species-dependent-nf-%C3%AE%C2%BAb-cascade-on-human-pulmonary-alveolar-epithelial-cells
#16
Chih-Chung Lin, Wei-Ning Lin, Rou-Ling Cho, Chen-Yu Wang, Li-Der Hsiao, Chuen-Mao Yang
Tumor necrosis factor-α (TNF-α) triggers activation of cytosolic phospholipase A2 (cPLA2) and then enhancing the synthesis of prostaglandin (PG) in inflammatory diseases. However, the detailed mechanisms of TNF-α induced cPLA2 expression were not fully defined in human pulmonary alveolar epithelial cells (HPAEpiCs). We found that TNF-α-stimulated increases in cPLA2 mRNA (5.2 folds) and protein (3.9 folds) expression, promoter activity (4.3 folds), and PGE2 secretion (4.7 folds) in HPAEpiCs, determined by Western blot, real-time PCR, promoter activity assay and PGE2 ELISA kit...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27932973/decline-in-proliferation-and-immature-neuron-markers-in-the-human-subependymal-zone-during-aging-relationship-to-egf-and-fgf-related-transcripts
#17
Christin Weissleder, Samantha J Fung, Matthew W Wong, Guy Barry, Kay L Double, Glenda M Halliday, Maree J Webster, Cynthia Shannon Weickert
Neuroblasts exist within the human subependymal zone (SEZ); however, it is debated to what extent neurogenesis changes during normal aging. It is also unknown how precursor proliferation may correlate with the generation of neuronal and glial cells or how expression of growth factors and receptors may change throughout the adult lifespan. We found evidence of dividing cells in the human SEZ (n D 50) in conjunction with a dramatic age-related decline (21-103 years) of mRNAs indicative of proliferating cells (Ki67) and immature neurons (doublecortin)...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/27932956/hypothalamic-vasopressinergic-projections-innervate-central-amygdala-gabaergic-neurons-implications-for-anxiety-and-stress-coping
#18
Vito S Hernández, Oscar R Hernández, Miguel Perez de la Mora, María J Gómora, Kjell Fuxe, Lee E Eiden, Limei Zhang
The arginine-vasopressin (AVP)-containing hypothalamic magnocellular neurosecretory neurons (VPMNNs) are known for their role in hydro-electrolytic balance control via their projections to the neurohypophysis. Recently, projections from these same neurons to hippocampus, habenula and other brain regions in which vasopressin infusion modulates contingent social and emotionally-affected behaviors, have been reported. Here, we present evidence that VPMNN collaterals also project to the amygdaloid complex, and establish synaptic connections with neurons in central amygdala (CeA)...
2016: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/27932954/neuronal-release-of-cytokine-il-3-triggered-by-mechanosensitive-autostimulation-of-the-p2x7-receptor-is-neuroprotective
#19
Jason C Lim, Wennan Lu, Jonathan M Beckel, Claire H Mitchell
Mechanical strain due to increased pressure or swelling activates inflammatory responses in many neural systems. As cytokines and chemokine messengers lead to both pro-inflammatory and neuroprotective actions, understanding the signaling patterns triggered by mechanical stress may help improve overall outcomes. While cytokine signaling in neural systems is often associated with glial cells like astrocytes and microglia, the contribution of neurons themselves to the cytokine response is underappreciated and has bearing on any balanced response...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27932951/high-pressure-induced-mtdna-alterations-in-retinal-ganglion-cells-and-subsequent-apoptosis
#20
Sheng-Hai Zhang, Feng-Juan Gao, Zhong-Mou Sun, Ping Xu, Jun-Yi Chen, Xing-Huai Sun, Ji-Hong Wu
Purpose: Our previous study indicated that mitochondrial DNA (mtDNA) damage and mutations are crucial to the progressive loss of retinal ganglion cells (RGCs) in a glaucomatous rat model. In this study, we examined whether high pressure could directly cause mtDNA alterations and whether the latter could lead to mitochondrial dysfunction and RGC death. Methods: Primary cultured rat RGCs were exposed to 30 mm Hg of hydrostatic pressure (HP) for 12, 24, 48, 72, 96 and 120 h. mtDNA alterations and mtDNA repair/replication enzymes OGG1, MYH and polymerase gamma (POLG) expressions were also analyzed...
2016: Frontiers in Cellular Neuroscience
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