A regulator of the protein phosphatase 2A (PP2A), α4, has been implicated in a variety of functions that regulate many cellular processes. To explore the role of α4 in human cell transformation and ...tumorigenesis, we show that α4 is highly expressed in human cells transformed by chemical carcinogens including benzo(a)pyrene, aflatoxin B(1), N-methyl-N'-nitro-N-nitrosoguanidine, nickel sulfate and in several hepatic and lung cancer cell lines. In addition, overexpression of α4 was detected in 87.5% (74/80) of primary hepatocellular carcinomas, 84.0% (21/25) of primary lung cancers and 81.8% (9/11) of primary breast cancers, indicating that α4 is ubiquitously highly expressed in human cancer. Functional studies revealed that elevated α4 expression results in an increase in cell proliferation, promotion of cell survival and decreased PP2A-attributable activity. Importantly, ectopic expression of α4 permits non-transformed human embryonic kidney cells (HEKTER) and L02R cells to form tumors in immunodeficient mice. Furthermore, we show that the highly expressed α4 in transformed cells or human tumors is not regulated by DNA hypomethylation. A microRNA, miR-34b, that suppresses the expression of α4 through specific binding to the 3'-untranslated region of α4 is downregulated in transformed or human lung tumors. Taken together, these observations identify that α4 possesses an oncogenic function. Reduction of PP2A activity due to an enhanced α4-PP2A interaction contributes directly to chemical carcinogen-induced tumorigenesis.
We present a three-dimensional (3D) extinction map of the southern sky. The map covers the SkyMapper Southern Survey (SMSS) area of ∼14,000 deg2 and has spatial resolutions between 6 9 and 27′. Based ...on the multi-band photometry of SMSS, the Two Micron All Sky Survey, the Wide-Field Infrared Survey Explorer Survey, and the Gaia mission, we have estimated values of the r-band extinction for ∼19 million stars with the spectral energy distribution analysis. Together with the distances calculated from the Gaia data release 2 (DR2) parallaxes, we have constructed a 3D extinction map of the southern sky. By combining our 3D extinction map with those from the literature, we present an all-sky 3D extinction map, and use it to explore the 3D distribution of the Galactic dust grains. We use two different models, one consisting of a single disk and another of two disks, to fit the 3D distribution of the Galactic dust grains. The data is better fitted by a two-disk model, yielding smaller values of the Bayesian Information Criterion. The best-fit model has scale heights of 73 and 225 pc for the "thin" and "thick" dust disks, respectively.
Background
Altered visceral sensation is common in irritable bowel syndrome (IBS) and nerve growth factor (NGF) participates in visceral pain development. Sodium butyrate (NaB) could induce colonic ...hypersensitivity via peripheral up‐regulation of NGF in animals. Enteric glial cells (EGCs) appear to be an important source of NGF. Whether butyrate could induce visceral hypersensitivity via increased EGC‐derived NGF is still unknown.
Methods
CRL‐2690 cells were used for transcriptome analyses after butyrate treatment. Rats received butyrate enemas to induce colonic hypersensitivity. Colorectal distention test was performed to assess visceral sensitivity. Immunofluorescence studies were used to evaluate the co‐expression of glial fibrillary acidic protein (GFAP) and NGF or growth associated protein 43 in animal model. NGF expression in rat colon was also investigated. In vitro, CRL‐2690 cells were stimulated with NaB or trichostatin A (TSA). NGF or GFAP expression was also examined.
Key Results
Transcriptome analyses showed that butyrate induced marked changes of genes expression related to neurotrophic signaling pathways. NaB‐treated rats showed increased visceral sensitivity. An improved NGF expression level was observed in NaB‐treated rats. Meanwhile, a 2.1‐fold increase in co‐expression of GFAP and NGF was also determined in rats received NaB enemas. In cultured cells, both NaB and TSA treatment could cause obvious NGF expression. Thus, butyrate might regulate EGC function via histone deacetylase inhibition.
Conclusions & Inferences
Butyrate‐EGC interplay may play a pivotal role in regulation of NGF expression and the development of colonic hypersensitivity in IBS‐like animal model.
Our study illustrated that butyrate promoted the secretion of NGF from enteric glial cells (EGCs) and contributed to visceral hypersensitivity in rats. The results clarified the potential unignorable source of NGF from EGC and highlighted the important role of EGC in pathogenesis of irritable bowel syndrome (IBS).
Using a sample of nearly 140,000 primary red-clump stars selected from the LAMOST and Gaia surveys, we have identified a large sample of "young" /Fe-enhanced stars with stellar ages younger than 6.0 ...Gyr and /Fe ratios greater than 0.15 dex. The stellar ages and /Fe ratios are measured from LAMOST spectra, using a machine-learning method trained with common stars in the LAMOST-APOGEE fields (for /Fe) and in the LAMOST-Kepler fields (for stellar age). The existence of these "young" /Fe-enhanced stars is not expected from the classical Galactic chemical evolution models. To explore their possible origins, we have analyzed the spatial distribution, and the chemical and kinematic properties of those stars and compared the results with those of the chemically thin and thick disk populations. We find that those "young" /Fe-enhanced stars have distributions in number density, metallicity, C/N abundance ratio, velocity dispersion, and orbital eccentricity that are essentially the same as those of the chemically thick disk population. Our results clearly show those so-called "young" /Fe-enhanced stars are not really young but genuinely old. Although other alternative explanations can not be fully ruled out, our results suggest that the most possible origin of these old stars is the result of stellar mergers or mass transfer.
Summary
Background
Vitiligo is an autoimmune chronic depigmentation disorder caused by melanocyte loss. Previous studies found that CD4+CD25+ regulatory T‐cell (Treg) dysfunction was involved in the ...pathogenesis of vitiligo and that gene polymorphisms in forkhead box P3 (FOXP3) – a master regulator of Treg development and function – were associated with susceptibility to some autoimmune disorders. Therefore, we hypothesized that functional polymorphisms of the FOXP3 gene might be associated with vitiligo via dysregulation of Treg cells.
Objectives
To evaluate whether FOXP3 polymorphisms are associated with vitiligo risk.
Material and methods
In this hospital‐based case–control study of 682 patients with vitiligo and 682 vitiligo‐free age‐ and sex‐matched controls, we genotyped three single nucleotide polymorphisms (SNPs) of the FOXP3 gene – rs2232365, rs3761548 and rs5902434 – by performing polymerase chain reaction with sequence‐specific primers (PCR‐SSP).
Results
Significantly increased vitiligo risk was associated with the rs2232365 GG odds ratio (OR) 1·68, 95% confidence interval (CI) 1·17–2·39, P = 0·004 and rs3761548 AA (OR 1·82, 95% CI 1·10–3·01, P = 0·033) genotypes compared with the rs2232365 AA and rs3761548 CC genotypes. On combined analysis of these three variant alleles, we found that individuals carrying 2–6 variant alleles had significantly increased vitiligo risk (OR 1·34, 95% CI 1·08–1·66). This risk was more pronounced in the following subgroups: age > 20 years, male sex, active vitiligo, nonsegmental vitiligo and other accompanying autoimmune diseases.
Conclusions
FOXP3 gene polymorphisms contributed to vitiligo risk in a Han Chinese population.
What's already known about this topic?
Previous findings have suggested that forkhead box P3 (FOXP3) is a master regulator of regulatory T cells (Tregs) for maintaining immune tolerance and abrogating autoimmune diseases.
Dysfunction of Tregs is involved in the autoimmune mechanism of vitiligo.
FOXP3 polymorphisms negatively affect the expression and functions of FOXP3 as well as of its target genes.
What does this study add?
Our study suggests an association between FOXP3 gene polymorphisms and vitiligo susceptibility.
Using a sample of nearly 140,000 red clump stars selected from the LAMOST and Gaia Galactic surveys, we have mapped mean vertical velocity in the X-Y plane for a large volume of the Galactic disk (6 ...< R < 16 kpc; −20 < φ < 50°; kpc). A clear signature where increases with R is detected for the chemically thin disk. The signature for the thick disk, however, is not significant, in line with the hot nature of this disk component. For the thin disk, the warp signature shows significant variations in both the radial and azimuthal directions, in excellent agreement with the previous results of star counts. Fitting the two-dimensional distribution of with a simple long-lived static warp model yields a line-of-node angle for this kinematic warp of about 12 5, again consistent with the previous results.
As a major component of the LAMOST Galactic surveys, the LAMOST Spectroscopic Survey of the Galactic Anticentre (LSS-GAC) aims to survey a significant volume of the Galactic thin/thick discs and halo ...for a contiguous sky area of over 3400 deg2 centred on the Galactic anticentre (|b| ≤ 30°, 150 ≤ l ≤ 210°), and obtain λλ3700–9000 low-resolution (R ∼ 1800) spectra for a statistically complete sample of ∼3 M stars of all colours down to a limiting magnitude of r ∼ 17.8 mag (to 18.5 mag for limited fields). Together with Gaia, the LSS-GAC will yield a unique data set to advance our understanding of the structure and assemblage history of the Galaxy, in particular its disc(s). In addition to the main survey, the LSS-GAC will also target hundreds of thousands objects in the vicinity fields of M 31 and M 33 and survey a significant fraction (over a million) of randomly selected very bright stars (r ≤ 14 mag) in the Northern hemisphere. During the Pilot and the first year Regular Surveys of LAMOST, a total of 1042 586 750 867 spectra of a signal-to-noise ratio S/N(7450 Å) ≥ 10 S/N(4650 Å) ≥ 10 have been collected. In this paper, we present a detailed description of the target selection algorithm, survey design, observations and the first data release of value-added catalogues (including radial velocities, effective temperatures, surface gravities, metallicities, values of interstellar extinction, distances, proper motions and orbital parameters) of the LSS-GAC.
A sub‐population of chemoresistant cells exhibits biological properties similar to cancer stem cells (CSCs), and these cells are believed to be a main cause for tumor relapse and metastasis. In our ...study, we explored the role of SOX8 and its molecular mechanism in the regulation of the stemness properties and the epithelial mesenchymal transition (EMT) of cisplatin‐resistant tongue squamous cell carcinoma (TSCC) cells. We found that SOX8 was upregulated in cisplatin‐resistant TSCC cells, which displayed CSC‐like properties and exhibited EMT. SOX8 was also overexpressed in chemoresistant patients with TSCC and was associated with higher lymph node metastasis, advanced tumor stage and shorter overall survival. Stable knockdown of SOX8 in cisplatin‐resistant TSCC cells inhibited chemoresistance, tumorsphere formation, and EMT. The Wnt/β‐catenin pathway mediated the cancer stem‐like properties in cisplatin‐resistant TSCC cells. Further studies showed that the transfection of active β‐catenin in SOX8 stable‐knockdown cells partly rescued the SOX8 silencing‐induced repression of stem‐like features and chemoresistance. Through chromatin immunoprecipitation and luciferase assays, we observed that SOX8 bound to the promoter region of Frizzled‐7 (FZD7) and induced the FZD7‐mediated activation of the Wnt/β‐catenin pathway. In summary, SOX8 confers chemoresistance and stemness properties and mediates EMT processes in chemoresistant TSCC via the FZD7‐mediated Wnt/β‐catenin pathway.
What's new?
Tongue cancer frequently spreads to the lymph nodes, and while chemotherapy with cisplatin has improved 5‐year survival rates, all too often the cancer becomes resistant to chemotherapy and returns. Here, the authors show that tongue squamous cell carcinoma (TSCC) cells that have acquired cisplatin resistance express more SOX‐8 mRNA than their parent TSCC cells. Getting rid of SOX‐8, they showed, hampered the cells' chemoresistance as well as the epithelial to mesenchymal transition. Adding active beta‐catenin to the cells lacking SOX‐8 partially restored these properties, showing that SOX‐8 acts through the Wnt/beta‐catenin pathway.
Abstract
We present the second release of value-added catalogues of the LAMOST Spectroscopic Survey of the Galactic Anticentre (LSS-GAC DR2). The catalogues present values of radial velocity Vr, ...atmospheric parameters – effective temperature Teff, surface gravity log g, metallicity Fe/H, α-element to iron (metal) abundance ratio α/Fe (α/M), elemental abundances C/H and N/H and absolute magnitudes MV and $M_{K_{\rm s}}$ deduced from 1.8 million spectra of 1.4 million unique stars targeted by the LSS-GAC since 2011 September until 2014 June. The catalogues also give values of interstellar reddening, distance and orbital parameters determined with a variety of techniques, as well as proper motions and multiband photometry from the far-UV to the mid-IR collected from the literature and various surveys. Accuracies of radial velocities reach 5 km s−1 for the late-type stars, and those of distance estimates range between 10 and 30 per cent, depending on the spectral signal-to-noise ratios. Precisions of Fe/H, C/H and N/H estimates reach 0.1 dex, and those of α/Fe and α/M reach 0.05 dex. The large number of stars, the contiguous sky coverage, the simple yet non-trivial target selection function and the robust estimates of stellar radial velocities and atmospheric parameters, distances and elemental abundances make the catalogues a valuable data set to study the structure and evolution of the Galaxy, especially the solar-neighbourhood and the outer disc.
The worm Caenorhabditis elegans is a model system for studying many aspects of biology, including host responses to bacterial pathogens, but it is not known to support replication of any virus. ...Plants and insects encode multiple Dicer enzymes that recognize distinct precursors of small RNAs and may act cooperatively. However, it is not known whether the single Dicer of worms and mammals is able to initiate the small RNA-guided RNA interference (RNAi) antiviral immunity as occurs in plants and insects. Here we show complete replication of the Flock house virus (FHV) bipartite, plus-strand RNA genome in C. elegans. We show that FHV replication in C. elegans triggers potent antiviral silencing that requires RDE-1, an Argonaute protein essential for RNAi mediated by small interfering RNAs (siRNAs) but not by microRNAs. This immunity system is capable of rapid virus clearance in the absence of FHV B2 protein, which acts as a broad-spectrum RNAi inhibitor upstream of rde-1 by targeting the siRNA precursor. This work establishes a C. elegans model for genetic studies of animal virus-host interactions and indicates that mammals might use a siRNA pathway as an antiviral response.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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