The Earth: Plasma Sources, Losses, and Transport Processes

This paper reviews the state of knowledge concerning the source of magnetospheric plasma at Earth. Source of plasma, its acceleration and transport throughout the system, its consequences on system dynamics, and its loss are all discussed. Both observational and modeling advances since the last time this subject was covered in detail (Hultqvist et al., Magnetospheric Plasma Sources and Losses, 1999) are addressed

Matrine induced G0 /G1 arrest and apoptosis in human acute T-cell lymphoblastic leukemia (T-ALL) cells

PubMed ID: 29045804Matrine, a natural product extracted from the root of Sophora flavescens, is a promising alternative drug in different types of cancer. Here, we aimed to investigate the therapeutic effects and underlying molecular mechanisms of matrine on human acute lymphoblastic leukemia (ALL) cell line, CCRF-CEM. Cell viability and IC50 values were determined by WST-1 cell cytotoxicity assay. Cell cycle distribution and apoptosis rates were analyzed by flow cytometry. Expression patterns of 44 selected miRNAs and 44 RNAs were analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) using the Applied Biosystems 7500 Fast Real-Time PCR System. Matrine inhibited cell viability and induced apoptosis of CCRF-CEM cells in a dose-dependent manner. Cell cycle analysis demonstrated that matrine-treated CCRF-CEM cells significantly accumulated in the G0 /G1 phase compared with the untreated control cells. hsa-miR-376b-3p (-37.09 fold, p = 0.008) and hsa-miR-106b-3p (-16.67 fold, p = 0.028) expressions were decreased, whereas IL6 (95.47 fold, p = 0.000011) and CDKN1A (140.03 fold, p = 0.000159) expressions were increased after matrine treatment. Our results suggest that the downregulation of hsa-miR-106b-3p leads to the upregulation of target p21 gene, CDKN1A, and plays a critical role in the cell cycle progression by arresting matrine-treated cells in the G0 /G1 phase. © 2018 ABMSFBIH

TET2, ASXL1, IDH1, and IDH2 single nucleotide polymorphisms in turkish patients with chronic myeloproliferative neoplasms [Kronik miyeloproliferatif neoplazi tanılı Türk Hastalarda TET2, ASXL1, IDH1 ve IDH2 tek nükleotid polimorfizmleri]

PubMed ID: 28218607We aimed to determine the genotype distribution, allele frequency, and prognostic impact of IDH1/2, TET2, and ASXL1 single nucleotide polymorphisms (SNPs) in myeloproliferative neoplasms (MPNs). TET2 (rs763480), ASXL1 (rs2208131), and IDH1 (rs11554137) variant homozygous genotype frequencies were found at rates of 1.5%, 9.2%, and 2.3%, respectively. No IDH2 SNP was identified. IDH1 and TET2 frequencies were 5% in essential thrombocythemia (ET) and 1.7% in ET and 5% in primary myelofibrosis (PMF), respectively. ASXL1 frequencies were 8.3%-10% in MPN subgroups. The TET2 mutant allele T and ASXL1 mutant allele G had the highest frequencies with 0.272 in the PMF and 0.322 in the polycythemia vera (PV) group, respectively. There was no impact of the SNPs on prognosis. IDH1 frequency in MPNs was found similar to the literature. ASXL1 frequencies were similar between ET, PV, and PMF patients. The ASXL1 and TET2 allele frequencies of the Turkish population are similar to those of the European population. The role of SNPs in MPNs might be further evaluated in larger multicenter studies. © 2017 by Turkish Society of Hematology

Effects of flavopiridol on critical regulation pathways of CD133high/CD44high lung cancer stem cells

PubMed ID: 27787370Background: Flavopiridol a semisynthetic flavone that inhibits cyclin-dependent kinases (CDKs) and has growth-inhibitory activity and induces a blockade of cell-cycle progression at G1-phase and apoptosis in numerous human tumor cell lines and is currently under investigation in phase II clinical trials. Cancer stem cells (CSCs) are comprised of subpopulation of cells in tumors that have been proposed to be responsible for recurrence and resistance to chemotherapy. The aim of the present study was to investigate the effects of flavopiridol in cancer stem cell cytoskeleton, cell adhesion, and epithelial to mesenchymal transition in CSCs. Methods:The cells were treated with flavopiridol to determine the inhibitory effect. Cell viability and proliferation were determined by using the WST-1 assay. Caspase activity and immunofluorescence analyses were performed for the evaluation of apoptosis, cell cytoskeleton, and epithelial-mesenchymal transition (EMT) markers. The effects of flavopiridol on the cell cycle were also evaluated. Flow cytometric analysis was used to detect the percentages of CSCs subpopulation. We analyzed the gene expression patterns to predict cell cycle and cell cytoskeleton in CSCs by RT-PCR. Results: Flavopiridol-induced cytotoxicity and apoptosis at the IC50 dose, resulting in a significant increase expression of caspases activity. Cell cycle analyses revealed that flavopiridol induces G1 phase cell cycle arrest. Flavopiridol significantly decreased the mRNA expressions of the genes that regulate the cell cytoskeleton and cell cycle components and cell motility in CSCs. Conclusion: Our results suggest that Flavopiridol has activity against lung CSCs and may be effective chemotherapeutic molecule for lung cancer treatment. © Copyright 2016 the Author(s). Published by Wolters Kluwer Health, Inc. All rights reserved

Revealing genome-wide mRNA and microRNA expression patterns in leukemic cells highlighted “hsa-miR-2278” as a tumor suppressor for regain of chemotherapeutic imatinib response due to targeting STAT5A

PubMed ID: 25953263BCR-ABL oncoprotein stimulates cell proliferation and inhibits apoptosis in chronic myeloid leukemia (CML). For cure, imatinib is a widely used tyrosine kinase inhibitor, but developing chemotherapeutic resistance has to be overcome. In this study, we aimed to determine differing genome-wide microRNA (miRNA) and messenger RNA (mRNA) expression profiles in imatinib resistant (K562/IMA-3 µM) and parental cells by targeting STAT5A via small interfering RNA (siRNA) applications. After determining possible therapeutic miRNAs, we aimed to check their effects upon cell viability and proliferation, apoptosis, and find a possible miRN

Molecular evaluation of t(14;18)(bcl-2/IgH) translocation in follicular lymphoma at diagnosis using paraffin-embedded tissue sections [Foliküler lenfoma Tani{dotless}si{dotless}nda Parafine-Gömülü Dokular kullani{dotless}larak t(14;18)(bcl-2/IgH) translokasyonun moleküler yöntemler ile Degerlendirilmesi]

Objective: Follicular lymphoma (FL) is one of the most common lymphomas, and is characterized by t(14;18) (q32;q21) in more than 80% of patients. The aim of this study was to determine the rate of t(14;18) positivity based on the detection of mbr or mcr in paraffin-embedded tissue samples. Material and Methods: The study included 32 paraffin-embedded tissue samples collected from 32 consecutive FL patients that were diagnosed and followed-up at our hospital between 1999 and 2006. The MBR breakpoint was identified based on real-time PCR using a LightCycler v.2.0 t(14;18) Quantification Kit (MBR), multiplex PCR, and seminested PCR. To identify the mcr breakpoint, real-time PCR was performed using specific primers and the FastStart DNA Master SYBR Green I Kit. To detect t(14;18) via fluorescence in situ hybridization (FISH) nuclei from paraffin-embedded tissue sections were extracted and used together with LSI IgH (immunoglobulin heavy chain) (spectrum green)/bcl-2 (B-cell leukemia-lymphoma 2) (spectrum orange) probes. Results: The DNA and nuclei isolation success rate for B5 formalin-fixed, paraffin-embedded tissue sections (n = 12) was 42% and 33%, respectively, versus 95% and 60%, respectively, for 20 tissue sections fixed in formalin only. In all, 24 paraffin-embedded tissue sections were analyzed and mbr positivity was observed in the DNA of 82.14% via seminested PCR, in 53.57% via multiplex PCR, and in 28.57% via real-time PCR. We did not detect mcr rearrangement in any of the samples. In all, 15 of 16 patients (93.75%) whose nuclei were successfully isolated were observed to be t(14;18) positive via the FISH method. Conclusion: Semi-nested PCR and FISH facilitated the genetic characterization of FL tumors. As such, FISH and PCR complement each other and are both essential for detecting t(14;18) translocation

The Earth: Plasma Sources, Losses, and Transport Processes

International audienceThis paper reviews the state of knowledge concerning the source of magnetospheric plasma at Earth. Source of plasma, its acceleration and transport throughout the system, its consequences on system dynamics, and its loss are all discussed. Both observational and modeling advances since the last time this subject was covered in detail (Hultqvist et al., Magnetospheric Plasma Sources and Losses, 1999) are addressed