Germline Stem Cell Gene PIWIL2 Mediates DNA Repair through Relaxation of Chromatin

DNA damage response (DDR) is an intrinsic barrier of cell to tumorigenesis initiated by genotoxic agents. However, the mechanisms underlying the DDR are not completely understood despite of extensive investigation. Recently, we have reported that ectopic expression of germline stem cell gene PIWIL2 is associated with tumor stem cell development, although the underlying mechanisms are largely unknown. Here we show that PIWIL2 is required for the repair of DNA-damage induced by various types of genotoxic agents. Upon ultraviolet (UV) irradiation, silenced PIWIL2 gene in normal human fibroblasts was transiently activated after treatment with UV light. This activation was associated with DNA repair, because Piwil2-deficienct mouse embryonic fibroblasts (mili-/- MEFs) were defective in cyclobutane pyrimidine dimers (CPD) repair after UV treatment. As a result, the UV-treated mili-/- MEFs were more susceptible to apoptosis, as characterized by increased levels of DNA damage-associated apoptotic proteins, such as active caspase-3, cleaved Poly (ADP-ribose) polymerase (PARP) and Bik. The impaired DNA repair in the mili-/- MEFs was associated with the reductions of histone H3 acetylation and chromatin relaxation, although the DDR pathway downstream chromatin relaxation appeared not to be directly affected by Piwil2. Moreover, guanine–guanine (Pt-[GG]) and double strand break (DSB) repair were also defective in the mili-/- MEFs treated by genotoxic chemicals Cisplatin and ionizing radiation (IR), respectively. The results indicate that Piwil2 can mediate DNA repair through an axis of Piwil2 → histone acetylation → chromatin relaxation upstream DDR pathways. The findings reveal a new role for Piwil2 in DNA repair and suggest that Piwil2 may act as a gatekeeper against DNA damage-mediated tumorigenesis

A Comprehensive Expression Profile of MicroRNAs in Porcine Pituitary

MicroRNAs (miRNAs) are an abundant class of small RNAs that regulate expressions of most genes. miRNAs play important roles in the pituitary, the “master” endocrine organ.However, we still don't know which role miRNAs play in the development of pituitary tissue or how much they contribute to the pituitary function. By applying a combination of microarray analysis and Solexa sequencing, we detected a total of 450 miRNAs in the porcine pituitary. Verification with RT-PCR showed a high degree of confidence for the obtained data. According to the current miRBase release17.0, the detected miRNAs included 169 known porcine miRNAs, 163 conserved miRNAs not yet identified in the pig, and 12 potentially new miRNAs not yet identified in any species, three of which were revealed using Northern blot. The pituitary might contain about 80.17% miRNA types belonging to the animal. Analysis of 10 highly expressed miRNAs with the Kyoto Encyclopedia of Genes and Genomes (KEGG) indicated that the enriched miRNAs were involved not only in the development of the organ but also in a variety of inter-cell and inner cell processes or pathways that are involved in the function of the organ

Asymmetric Airfoil Morphing via Deep Reinforcement Learning

Morphing aircraft are capable of modifying their geometry configurations according to different flight conditions to improve their performance, such as by increasing the lift-to-drag ratio or reducing their fuel consumption. In this article, we focus on the airfoil morphing of wings and propose a novel morphing control method for an asymmetric deformable airfoil based on deep reinforcement learning approaches. Firstly, we develop an asymmetric airfoil shaped using piece-wise Bézier curves and modeled by shape memory alloys. Resistive heating is adopted to actuate the shape memory alloys and realize the airfoil morphing. With regard to the hysteresis characteristics exhibited in the phase transformation of shape memory alloys, we construct a second-order Markov decision process for the morphing procedure to formulate a reinforcement learning environment with hysteresis properties explicitly considered. Subsequently, we learn the morphing policy based on deep reinforcement learning techniques where the accurate information of the system model is unavailable. Lastly, we conduct simulations to demonstrate the benefits brought by our learning implementations and validate the morphing performance of the proposed method. The simulation results show that the proposed method provides an average 29.8% performance improvement over traditional methods

Characterization of the complete chloroplast genome of the medicinal herb Veronica polita Fr. 1819 (Lamiales: Plantaginaceae)

Veronica polita Fr. 1819 (synonym: Veronica didyma Ten. 1981) is a species of annual herb with high medicinal value. It is originally from Southwest Asia, but has been naturalized widely in many regions of the world. In this study, the complete chloroplast genome of V. polita was determined to be 150,191 bp long with a typical quadripartite structure, comprising two inverted repeat regions (IRa and IRb, 25,465 bp each), a large single-copy (LSC) region (81,847 bp) and a small single-copy (SSC) region (17,414 bp). It encodes a panel of 114 genes (including 79 protein-coding, 31 tRNA, and four rRNA genes) with 18 of them being completely or partially duplicated and 19 of them possessing one or two introns. Phylogenetic analysis supported the tribal-level taxonomy of the family Plantaginaceae, and revealed that V. polita was most closely related to the congener Veronica persica Poir. 1808

Insulin resistance enhances the mitogen-activated protein kinase signaling pathway in ovarian granulosa cells.

The ovary is the main regulator of female fertility. Granulosa cell dysfunction may be involved in various reproductive endocrine disorders. Here we investigated the effect of insulin resistance on the metabolism and function of ovarian granulosa cells, and dissected the functional status of the mitogen-activated protein kinase signaling pathway in these cells. Our data showed that dexamethasone-induced insulin resistance in mouse granulosa cells reduced insulin sensitivity, accompanied with an increase in phosphorylation of p44/42 mitogen-activated protein kinase. Furthermore, up-regulation of cytochrome P450 subfamily 17 and testosterone and down-regulation of progesterone were observed in insulin-resistant mouse granulosa cells. Inhibition of p44/42 mitogen-activated protein kinase after induction of insulin resistance in mouse granulosa cells decreased phosphorylation of p44/42 mitogen-activated protein kinase, downregulated cytochrome P450 subfamily 17 and lowered progesterone production. This insulin resistance cell model can successfully demonstrate certain mechanisms such as hyperandrogenism, which may inspire a new strategy for treating reproductive endocrine disorders by regulating cell signaling pathways

DataSheet1_Discovery of pyrrole derivatives as acetylcholinesterase-sparing butyrylcholinesterase inhibitor.pdf

Inspired by the crucial roles of (hetero)aryl rings in cholinesterase inhibitors and the pyrrole ring in new drug discovery, we synthesized 19 pyrrole derivatives and investigated their cholinesterase inhibitory activity. As a result, compounds 3o, 3p, and 3s with a 1,3-diaryl-pyrrole skeleton showed high selectivity toward BChE over AChE with a best IC50 value of 1.71 ± 0.087 µM, which were comparable to donepezil. The pharmaceutical potential of these structures was further predicted and compounds 3o and 3p were proved to meet well with the Lipinsky’s five rules. In combination of the inhibition kinetic studies with the results of molecular docking, we concluded that compound 3p inhibited BChE in a mixed competitive mode. This research has proved the potential of the 1,3-diaryl-pyrrole skeleton as a kind of selective BChE inhibitor.</p

Mitogen-activated protein kinase (MAPK) and phosphor-p44/42 MAPK (P-MAPK) protein expression in GCs.

<p>GCs were incubated in the absence (Con) or presence of Dex for 48 h (GD) or Dex for 48 h with PD98059 added 4 h before the end of the incubation (GDP). Relative density ratios were calculated by setting the control group value as one. Data are expressed as the mean + SEM. All data presented are representative of at least three separate experiments. *p < 0.05, ***p < 0.001.</p

Cytochrome P450 subfamily 17 (CYP17) and aromatase protein expression in GCs.

<p>GCs were incubated in the absence (Con) or presence of Dex for 48 h (GD) or Dex for 48 h with PD98059 added 4 h before the end of the incubation (GDP). Relative density ratios were calculated by setting the control group value as one. Data are expressed as the mean + SEM. All data presented are representative examples of at least three separate experiments. *p < 0.05.</p