Differential regulation of Ota and Otb, two primary glycine betaine transporters in the methanogenic archaeon Methanosarcina mazei go1

Methanogenic archaea accumulate glycine betaine in response to hypersalinity, but the regulation of proteins involved, their mechanism of activation and regulation of the corresponding genes are largely unknown. Methanosarcina mazei differs from most other methanoarchaea in having two gene clusters both encoding a potential glycine betaine transporter, Ota and Otb. Western blot as well as quantitative real-time PCR revealed that Otb is not regulated by osmolarity. On the other hand, cellular levels of Ota increased with increasing salt concentrations. A maximum was reached at 300-500 m M NaCl. Ota concentrations reached a maximum 4 h after an osmotic upshock. Hyperosmolarity also caused an increase in cellular Ota concentrations. In addition to osmolarity Ota expression was regulated by the growth phase. Expression of Ota as well as transport of betaine was downregulated in the presence of glycine betaine. Copyright (c) 2007 S. Karger AG, Basel

The Expression and Localization of N-Myc Downstream-Regulated Gene 1 in Human Trophoblasts

The protein N-Myc downstream-regulated gene 1 (NDRG1) is implicated in the regulation of cell proliferation, differentiation, and cellular stress response. NDRG1 is expressed in primary human trophoblasts, where it promotes cell viability and resistance to hypoxic injury. The mechanism of action of NDRG1 remains unknown. To gain further insight into the intracellular action of NDRG1, we analyzed the expression pattern and cellular localization of endogenous NDRG1 and transfected Myc-tagged NDRG1 in human trophoblasts exposed to diverse injuries. In standard conditions, NDRG1 was diffusely expressed in the cytoplasm at a low level. Hypoxia or the hypoxia mimetic cobalt chloride, but not serum deprivation, ultraviolet (UV) light, or ionizing radiation, induced the expression of NDRG1 in human trophoblasts and the redistribution of NDRG1 into the nucleus and cytoplasmic membranes associated with the endoplasmic reticulum (ER) and microtubules. Mutation of the phosphopantetheine attachment site (PPAS) within NDRG1 abrogated this pattern of redistribution. Our results shed new light on the impact of cell injury on NDRG1 expression patterns, and suggest that the PPAS domain plays a key role in NDRG1's subcellular distribution. © 2013 Shi et al

Identification of Candidate Growth Promoting Genes in Ovarian Cancer through Integrated Copy Number and Expression Analysis

Ovarian cancer is a disease characterised by complex genomic rearrangements but the majority of the genes that are the target of these alterations remain unidentified. Cataloguing these target genes will provide useful insights into the disease etiology and may provide an opportunity to develop novel diagnostic and therapeutic interventions. High resolution genome wide copy number and matching expression data from 68 primary epithelial ovarian carcinomas of various histotypes was integrated to identify genes in regions of most frequent amplification with the strongest correlation with expression and copy number. Regions on chromosomes 3, 7, 8, and 20 were most frequently increased in copy number (>40% of samples). Within these regions, 703/1370 (51%) unique gene expression probesets were differentially expressed when samples with gain were compared to samples without gain. 30% of these differentially expressed probesets also showed a strong positive correlation (r≥0.6) between expression and copy number. We also identified 21 regions of high amplitude copy number gain, in which 32 known protein coding genes showed a strong positive correlation between expression and copy number. Overall, our data validates previously known ovarian cancer genes, such as ERBB2, and also identified novel potential drivers such as MYNN, PUF60 and TPX2

Insights into organic-Aerosol sources via a novel laser-desorption/ionization mass spectrometry technique applied to one year of PM10 samples from nine sites in central Europe

We assess the benefits of offline laser-desorption/ionization mass spectrometry in understanding ambient particulate matter (PM) sources. The technique was optimized for measuring PM collected on quartz-fiber filters using silver nitrate as an internal standard for m\uc4\u9d\ue2\u80\ua2z calibration. This is the first application of this technique to samples collected at nine sites in central Europe throughout the entire year of 2013 (819 samples). Different PM sources were identified by positive matrix factorization (PMF) including also concomitant measurements (such as NOx, levoglucosan, and temperature). By comparison to reference mass spectral signatures from laboratory wood burning experiments as well as samples from a traffic tunnel, three biomass burning factors and two traffic factors were identified. The wood burning factors could be linked to the burning conditions; the factors related to inefficient burns had a larger impact on air quality in southern Alpine valleys than in northern Switzerland. The traffic factors were identified as primary tailpipe exhaust and most possibly aged/secondary traffic emissions. The latter attribution was supported by radiocarbon analyses of both the organic and elemental carbon. Besides these sources, factors related to secondary organic aerosol were also separated. The contribution of the wood burning emissions based on LDI-PMF (laser-desorption/ionization PMF) correlates well with that based on AMS-PMF (aerosol mass spectrometer PMF) analyses, while the comparison between the two techniques for other components is more complex

Identification of Nine Novel Loci Associated with White Blood Cell Subtypes in a Japanese Population

White blood cells (WBCs) mediate immune systems and consist of various subtypes with distinct roles. Elucidation of the mechanism that regulates the counts of the WBC subtypes would provide useful insights into both the etiology of the immune system and disease pathogenesis. In this study, we report results of genome-wide association studies (GWAS) and a replication study for the counts of the 5 main WBC subtypes (neutrophils, lymphocytes, monocytes, basophils, and eosinophils) using 14,792 Japanese subjects enrolled in the BioBank Japan Project. We identified 12 significantly associated loci that satisfied the genome-wide significance threshold of P<5.0×10−8, of which 9 loci were novel (the CDK6 locus for the neutrophil count; the ITGA4, MLZE, STXBP6 loci, and the MHC region for the monocyte count; the SLC45A3-NUCKS1, GATA2, NAALAD2, ERG loci for the basophil count). We further evaluated associations in the identified loci using 15,600 subjects from Caucasian populations. These WBC subtype-related loci demonstrated a variety of patterns of pleiotropic associations within the WBC subtypes, or with total WBC count, platelet count, or red blood cell-related traits (n = 30,454), which suggests unique and common functional roles of these loci in the processes of hematopoiesis. This study should contribute to the understanding of the genetic backgrounds of the WBC subtypes and hematological traits