Constitutive activation of JAK–STAT3 signaling by BRCA1 in human prostate cancer cells

AbstractGerm-line mutations of the breast cancer susceptibility gene 1 (BRCA1) confer a high risk for breast and ovarian cancer in women and prostate cancer in men. The BRCA1 protein contributes to cell proliferation, cell cycle regulation, DNA repair and apoptosis; however, the mechanisms underlying these functions of BRCA1 remain largely unknown. Here, we showed that, in Du-145 human prostate cancer cells, enhanced expression of BRCA1 resulted in constitutive activation of signal transducer and activator transcription factor 3 (STAT3) tyrosine and serine phosphorylation. Moreover, Janus kinase 1 (JAK1) and JAK2, the upstream activators of STAT3, were also activated by BRCA1. Immunoprecipitation assay showed that BRCA1 interacted with JAK1 and JAK2. Blocking STAT3 activation using antisense oligonucleotides significantly inhibited cell proliferation and triggered apoptosis in Du-145 cells with enhanced expression of BRCA1. These findings indicate that BRCA1 interacts with the components of the JAK–STAT signaling cascade and modulates its activation, which may provide a new critical survival signal for the growth of breast, ovarian and prostate cancers in the presence of normal BRCA1

Targeted insertion of regulatory elements enables translational enhancement in rice

In-locus editing of agronomically-important genes to optimize their spatiotemporal expression is becoming an important breeding approach. Compared to intensive studies on mRNA transcription, manipulating protein translation by genome editing has not been well exploited. Here, we found that precise knock-in of a regulating element into the 5’UTR of a target gene could efficiently increase its protein abundance in rice. We firstly screened a translational enhancer (AMVE) from alfalfa mosaic virus using protoplast-based luciferase assays with an 8.5-folds enhancement. Then the chemically modified donor of AMVE was synthesized and targeted inserted into the 5’UTRs of two genes (WRKY71 and SKC1) using CRISPR/Cas9. Following the in-locus AMVE knock-in, we observed up to a 2.8-fold increase in the amount of WRKY71 protein. Notably, editing of SKC1, a sodium transporter, significantly increased salt tolerance in T2 seedlings, indicating the expected regulation of AMVE knock-in. These data demonstrated the feasibility of such in-locus editing to enhance protein expression, providing a new approach to manipulating protein translation for crop breeding

MeV Astrophysical Spectroscopic Surveyor (MASS): A Compton Telescope Mission Concept

We propose a future mission concept, the MeV Astrophysical Spectroscopic Surveyor (MASS), which is a large area Compton telescope using 3D position sensitive cadmium zinc telluride (CZT) detectors optimized for emission line detection. The payload consists of two layers of CZT detectors in a misaligned chessboard layout, with a total geometric area of 4096 cm$^2$ for on-axis observations. The detectors can be operated at room-temperature with an energy resolution of 0.6\% at 0.662 MeV. The in-orbit background is estimated with a mass model. At energies around 1 MeV, a line sensitivity of about $10^{-5}$ photons cm$^{-2}$ s$^{-1}$ can be obtained with a 1 Ms observation. The main science objectives of MASS include nucleosynthesis in astrophysics and high energy astrophysics related to compact objects and transient sources. The payload CZT detectors weigh roughly 40 kg, suggesting that it can be integrated into a micro- or mini-satellite. We have constructed a pathfinder, named as MASS-Cube, to have a direct test of the technique with 4 detector units in space in the near future.Comment: accepted for publication in Experimental Astronom

Mouse RC/BTB2, a Member of the RCC1 Superfamily, Localizes to Spermatid Acrosomal Vesicles

Mouse RC/BTB2 is an unstudied protein of the RCC1 (Regulator of Chromosome Condensation) superfamily. Because of the significant remodeling of chromatin that occurs during spermiogenesis, we characterized the expression and localization of mouse RC/BTB2 in the testis and male germ cells. The Rc/btb2 gene yields two major transcripts: 2.3 kb Rc/btb2-s, present in most somatic tissues examined; and 2.5 kb Rc/btb2-t, which contains a unique non-translated exon in its 5′-UTR that is only detected in the testis. During the first wave of spermatogenesis, Rc/btb2-t mRNA is expressed from day 8 after birth, reaching highest levels of expression at day 30 after birth. The full-length protein contains three RCC1 domains in the N-terminus, and a BTB domain in the C-terminus. In the testis, the protein is detectable from day 12, but is progressively up-regulated to day 30 and day 42 after birth. In spermatids, some of the protein co-localizes with acrosomal markers sp56 and peanut lectin, indicating that it is an acrosomal protein. A GFP-tagged RCC1 domain is present throughout the cytoplasm of transfected CHO cells. However, both GFP-tagged, full-length RC/BTB2 and a GFP-tagged BTB domain localize to vesicles in close proximity to the nuclear membrane, suggesting that the BTB domain might play a role in mediating full-length RC/BTB2 localization. Since RCC1 domains associate with Ran, a small GTPase that regulates molecular trafficking, it is possible that RC/BTB2 plays a role in transporting proteins during acrosome formation

The wheat LLM-domain-containing transcription factor TaGATA1 positively modulates host immune response to Rhizoctonia cerealis

Wheat (Triticumaestivum) is essential for global food security. Rhizoctonia cerealis is the causal pathogen of sharp eyespot, an important disease of wheat. GATA proteins in model plants have been implicated in growth and development; however, little is known about their roles in immunity. Here, we reported a defence role of a wheat LLM-domain-containing B-GATA transcription factor, TaGATA1, against R. cerealis infection and explored the underlying mechanism. Through transcriptomic analysis, TaGATA1 was identified to be more highly expressed in resistant wheat genotypes than in susceptible wheat genotypes. TaGATA1 was located on chromosome 3B and had two homoeologous genes on chromosomes 3A and 3D. TaGATA1 was demonstrated to localize in the nucleus, possess transcriptional-activation activity, and bind to GATA-core cis-elements. TaGATA1 overexpression significantly enhanced resistance of transgenic wheat to R. cerealis, whereas silencing of TaGATA1 suppressed the resistance. RT-qPCR and chromatin immunoprecipitation-qPCR results indicated that TaGATA1 directly bound to and activated certain defence genes in host immune response to R. cerealis. Collectively, TaGATA1 positively regulates immune responses to R. cerealis through activating expression of defence genes in wheat. This study reveals a new function of plant GATAs in immunity and provides a candidate gene for improving crop resistance to R. cerealis

Provoking the Adversary by Detecting Eavesdropping and Jamming Attacks: A Game-Theoretical Framework

This paper investigates the secrecy and reliability of a communication where the user is assisting an Intrusion Detection System (IDS) in detecting the adversary’s attack. The adversary is assumed to be sophisticated such that it can conduct eavesdropping and jamming attacks. The IDS is equipped with the capability of detecting both of those attacks. Two scenarios were considered; the first scenario is that the user is trying to detect the adversary by assisting the IDS, and the second scenario is that the user is equipped with a silent time slot in its communication protocol besides assisting the IDS, in order to provoke the adversary into jamming the channel, thus detecting it with a higher probability. Interestingly, adding the capability of detecting eavesdropping attacks pushed the adversary into conducting jamming attacks much more, thus aiding in detecting the adversary earlier. All of that was modeled by means of stochastic game theory, in order to analyze and study the behavior and the interactions between the user and the adversary. Results show a major improvement in the first scenario by 188% and an improvement by 294% in the second scenario in the game value when the probability of detecting eavesdropping attacks was 0.3, which represents the payoff that the user gains in terms of secrecy and reliability

Multi-skeleton model for top-down design of complex products

Generally, there are two alternative design approaches available to engineers: bottom-up and top-down. Considering the sharp increase in the complexity of most mechanical products, the top-down design approach is more widely adopted in the development of complex products. However, in traditional top-down design process, design parameters are communicated through single-skeleton models, and design units are strongly coupled due to the multi-dimensional complexity of products. Toward this end, a new top-down design approach based on multi-skeleton model is proposed in this article. First, in accordance with different kinds of design parameters, three major skeleton models are defined, including location skeleton model, published skeleton model, and design skeleton model. And the characteristics of multi-skeleton models are also described. Then, the top-down design process based on the multi-skeleton model is explored, especially in the multi-skeleton modeling phase. It is also illustrated in detail that how to realize design parameter transmission and design unit reuse. Subsequently, it elaborates the communicating way and structure optimization of design parameters to support parameters controlled publishing and design units reuse. Finally, a meteorological satellite and a crawler crane design cases are implemented to expound the feasibility and effectiveness of the proposed framework