Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Tumor-associated macrophages (TAMs) are alternatively activated cells induced by interleukin-4 (IL-4)-releasing CD4⁺T cells. TAMs promote breast cancer invasion and metastasis; however, the mechanisms underlying these interactions between macrophages and tumor cells that lead to cancer metastasis remain elusive. Previous studies have found microRNAs (miRNAs) circulating in the peripheral blood and have identified microvesicles, or exosomes, as mediators of cell-cell communication. Therefore, one alternative mechanism for the promotion of breast cancer cell invasion by TAMs may be through macrophage-secreted exosomes, which would deliver invasion-potentiating miRNAs to breast cancer cells.</p> <p>Results</p> <p>We utilized a co-culture system with IL-4-activated macrophages and breast cancer cells to verify that miRNAs are transported from macrophages to breast cancer cells. The shuttling of fluorescently-labeled exogenous miRNAs from IL-4-activated macrophages to co-cultivated breast cancer cells without direct cell-cell contact was observed. miR-223, a miRNA specific for IL-4-activated macrophages, was detected within the exosomes released by macrophages and was significantly elevated in the co-cultivated SKBR3 and MDA-MB-231 cells. The invasiveness of the co-cultivated breast cancer cells decreased when the IL-4-activated macrophages were treated with a miR-223 antisense oligonucleotide (ASO) that would inhibit miR-223 expression. Furthermore, results from a functional assay revealed that miR-223 promoted the invasion of breast cancer cells via the Mef2c-β-catenin pathway.</p> <p>Conclusions</p> <p>We conclude that macrophages regulate the invasiveness of breast cancer cells through exosome-mediated delivery of oncogenic miRNAs. Our data provide insight into the mechanisms underlying the metastasis-promoting interactions between macrophages and breast cancer cells.</p

A CRY-BIC negative-feedback circuitry regulating blue light sensitivity of Arabidopsis.

Cryptochromes are blue light receptors that regulate various light responses in plants. Arabidopsis cryptochrome 1 (CRY1) and cryptochrome 2 (CRY2) mediate blue light inhibition of hypocotyl elongation and long-day (LD) promotion of floral initiation. It has been reported recently that two negative regulators of Arabidopsis cryptochromes, Blue light Inhibitors of Cryptochromes 1 and 2 (BIC1 and BIC2), inhibit cryptochrome function by blocking blue light-dependent cryptochrome dimerization. However, it remained unclear how cryptochromes regulate the BIC gene activity. Here we show that cryptochromes mediate light activation of transcription of the BIC genes, by suppressing the activity of CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1), resulting in activation of the transcription activator ELONGATED HYPOCOTYL 5 (HY5) that is associated with chromatins of the BIC promoters. These results demonstrate a CRY-BIC negative-feedback circuitry that regulates the activity of each other. Surprisingly, phytochromes also mediate light activation of BIC transcription, suggesting a novel photoreceptor co-action mechanism to sustain blue light sensitivity of plants under the broad spectra of solar radiation in nature

Reconfigurable Meta-Radiator Based on Flexible Mechanically Controlled Current Distribution in Three-dimensional Space

In this paper, we provide an experimental proof-of-concept of this dynamic 3D current manipulation through a 3D-printed reconfigurable meta-radiator with periodically slotted current elements. By utilizing the working frequency and the mechanical configuration comprehensively, the radiation pattern can be switched among 12 states. Inspired by maximum likelihood method in digital communications, a robustness-analysis method is proposed to evaluate the potential error ratio between ideal cases and practice. Our work provides a previously unidentified model for next-generation information distribution and terahertz-infrared wireless communications

Research Progress on the Effects of Anthocyanidin Compounds on Physicochemical Properties of Starch

Anthocyanidin compounds include proanthocyanidins, anthocyanidins, anthocyanins, etc. Among them, proanthocyanidin is a kind of polyphenol compound, then anthocyanidin and anthocyanin belong to flavonoid compounds. When heated in an acidic medium, proanthocyanidins can produce anthocyanidins, which combine with sugars via glycosidic bonds to produce anthocyanins. Proanthocyanidins, anthocyanidins and anthocyanins are widely distributed in dark grains, berries and vegetables, all of them have various functional effects. Starch is low in price, rich in sources, and has a variety of functional properties. The sensory quality and nutritional value of starch-based foods are mainly determined by the changes of starch gelatinization properties, thermodynamic properties, rheological properties, aging properties and digestive properties. There have been many studies about the co-existence of starch and other compounds that can improve the original properties of starch. However, there is limited overview on the effects of anthocyanidin compounds on starch properties. Therefore, this paper reviews the latest research progress of anthocyanidin compounds and their effects on the gelatinization properties, thermodynamic properties, rheological properties, aging properties and digestive properties of starch through increasing the gelatinization temperature of starch and reducing its gelatinization enthalpy can affect its thermodynamic properties, as well as reduce its aging enthalpy and aging rate, additionally and the digestion rate of starch etc. These can provide guidance for the use of anthocyandin compounds to improve the processing properties, sensory and nutritional quality of starch-based foods

The CDEX-1 1 kg Point-Contact Germanium Detector for Low Mass Dark Matter Searches

The CDEX Collaboration has been established for direct detection of light dark matter particles, using ultra-low energy threshold p-type point-contact germanium detectors, in China JinPing underground Laboratory (CJPL). The first 1 kg point-contact germanium detector with a sub-keV energy threshold has been tested in a passive shielding system located in CJPL. The outputs from both the point-contact p+ electrode and the outside n+ electrode make it possible to scan the lower energy range of less than 1 keV and at the same time to detect the higher energy range up to 3 MeV. The outputs from both p+ and n+ electrode may also provide a more powerful method for signal discrimination for dark matter experiment. Some key parameters, including energy resolution, dead time, decay times of internal X-rays, and system stability, have been tested and measured. The results show that the 1 kg point-contact germanium detector, together with its shielding system and electronics, can run smoothly with good performances. This detector system will be deployed for dark matter search experiments.Comment: 6 pages, 8 figure

Bioinformatic analysis of the human DHRS4 gene cluster and a proposed mechanism for its transcriptional regulation

<p>Abstract</p> <p>Background</p> <p>The human <it>DHRS4 </it>gene cluster consists of three genes, <it>DHRS4</it>, <it>DHRS4L2 </it>and <it>DHRS4L1</it>. Among them, <it>DHRS4 </it>encodes NADP(H)-dependent retinol dehydrogenase/reductase. In a previous study, we investigated the alternative splicing of <it>DHRS4 </it>and <it>DHRS4L2</it>. <it>DHRS4L1 </it>was added to the gene cluster recently, but little is known about its structure and expression. To reveal the regulatory mechanism of the <it>DHRS4 </it>gene cluster expression, we studied the structure and transcription of <it>DHRS4L1 </it>in the context of the transcriptional behaviors of the human <it>DHRS4 </it>gene cluster. Based on the results of bioinformatics analysis, we propose a possible mechanism for the transcriptional regulation of the human <it>DHRS4 </it>gene cluster.</p> <p>Results</p> <p>The homologous comparison analysis suggests that <it>DHRS4</it>, <it>DHRS4L2 </it>and <it>DHRS4L1 </it>are three homologous genes in human. <it>DHRS4L1 </it>and <it>DHRS4L2 </it>are paralogues of <it>DHRS4</it>, and <it>DHRS4L2 </it>is the most recent member of the <it>DHRS4 </it>gene cluster. In the minus strand of the human <it>DHRS4 </it>gene cluster, a gene transcribed in an antisense direction was found containing a 5' sequence overlapping the region of exon 1 and promoter of <it>DHRS4</it>. By cloning the full length of RNA variants through 5'RACE and 3'RACE, we identified two transcription start sites, within exon <it>a2 </it>and exon 1, of this newly named gene <it>DHRS4L1 </it>using neuroblastoma cell line BE(2)-M17. Analysis of exon composition in the transcripts of <it>DHRS4 </it>gene cluster revealed that exon 1 was absent in all the transcripts initiated from exon <it>a1 </it>of <it>DHRS4L2 </it>and exon <it>a2 </it>of <it>DHRS4L1</it>.</p> <p>Conclusions</p> <p>Alternatively spliced RNA variants are prevalent in the human <it>DHRS4 </it>gene cluster. Based on the analysis of gene transcripts and bioinformatic prediction, we propose here that antisense transcription may be involved in the transcriptional initiation regulation of <it>DHRS4 </it>and in the posttranscriptional splicing of <it>DHRS4L2 </it>and <it>DRHS4L1 </it>for the homologous identity of <it>DHRS4 </it>gene cluster. Beside the alternative transcriptional start sites, the antisense RNA is novel possible factor serving to remove exon 1 from the transcripts initiated from exon <it>a1 </it>and exon <it>a2</it>.</p