The CREB Coactivator CRTC2 Is a Lymphoma Tumor Suppressor that Preserves Genome Integrity through Transcription of DNA Mismatch Repair Genes

The CREB-regulated transcription coactivator CRTC2 stimulates CREB target gene expression and has a well-established role in modulating glucose and lipid metabolism. Here, we find, unexpectedly, that loss of CRTC2, as well as CREB1 and its coactivator CREB-binding protein (CBP), results in a deficiency in DNA mismatch repair (MMR) and a resultant increased mutation frequency. We show that CRTC2, CREB1, and CBP are transcriptional activators of well-established MMR genes, including EXO1, MSH6, PMS1, and POLD2. Mining of expression profiling databases and analysis of patient samples reveal that CRTC2 and its target MMR genes are downregulated in specific T cell lymphoma subtypes, which are microsatellite unstable. The levels of acetylated histone H3 on the CRTC2 promoter are significantly reduced in lymphoma in comparison to normal tissue, explaining the decreased CRTC2 expression. Our results establish a role for CRTC2 as a lymphoma tumor suppressor gene that preserves genome integrity by stimulating transcription of MMR genes

Magnetic micro-structural uniformity of die-upset Nd-Fe-B magnets

Die-upset Nd13.62Fe75.70Co4.45B5.76Ga0.47 magnets have been prepared with height reduction (h) in the range of 60 to 88%. The energy product as high as 50.4 MGOe was obtained in the sample with h~70%. The magnetic domains of the samples are revealed by using magnetic force microscopy (MFM). The average domain widths of the die-upset samples with surface normal parallel (//) and perpendicular (\) to the loading direction are in the range of w//: 0.4-0.6lm; w\: 0.9-3.8 μm, respectively. These interaction domains are formed due to the strong inter-granular exchange interaction and magnetostatic interaction between grains. It was found that the ratio of ϕrms// to ϕrms\ is a good indicator for the quality of the magnet, where the ϕrms// and ϕrms\ are defined as the root-mean-square values of phase shift for the MFM images. The microstructures have been investigated by scanning electron microscopy (SEM), MFM and SEM results indicate the magnetic and crystalline microstructures are uniform for the sample with h~70%, giving rise to the highest magnetic performance among these samples

The Effects of Packaging on Collision Energy Absorption of Automotive Seat Headrest

The automotive seat headrest plays an important role in the passenger protection during car crashes, and its structure parameters and performance have direct influence on the seat crashworthiness. In this paper, according to relevant regulations of GB11550-2009, collision simulation analyses of the seat headrest structure were carried out by Ls-dyna code. The law of different headrest packaging parameters on collision energy absorption was investigated to provide guidance for the headrest structure optimization design and improvement. The research results show that, with the increase of packaging of the headrest, the maximum acceleration and high acceleration duration time of head gradually decreases

The Effects of Packaging on Collision Energy Absorption of Automotive Seat Headrest

The automotive seat headrest plays an important role in the passenger protection during car crashes, and its structure parameters and performance have direct influence on the seat crashworthiness. In this paper, according to relevant regulations of GB11550-2009, collision simulation analyses of the seat headrest structure were carried out by Ls-dyna code. The law of different headrest packaging parameters on collision energy absorption was investigated to provide guidance for the headrest structure optimization design and improvement. The research results show that, with the increase of packaging of the headrest, the maximum acceleration and high acceleration duration time of head gradually decreases

Tanshinone IIA Promotes Pulmonary Artery Smooth Muscle Cell Apoptosis in Vitro

Background: Tanshinone IIA inhibits the proliferation of pulmonary artery smooth muscle cells (PASMCs), but the potential mechanisms of its effects on PASMCs apoptosis remain unclear. Methods: Rat were subjected to hypoxia for 9 days with or without Tanshinone IIA treatment. PASMCs were exposed to the conditions of 2% O2 and 93% N2 for 24 h in vitro. Hematoxylin and eosin (HE) staining was used to evaluate vascular remodeling. The Cell viability was determined using cell fluorescence staining and MTT assays, and apoptosis was assessed using flow cytometry. Protein expression was quantified by Western blotting. Results: Our results showed that Tanshinone IIA treatment reduced pulmonary artery media thickening in hypoxic rats. Tanshinone IIA reduced PASMC viability in a dose-dependent manner. Additionally, Tanshinone IIA promoted PASMC apoptosis, lowered Hsp60 levels, and upregulated caspase-3 expressions under hypoxic conditions. This pro-apoptotic effect of Tanshinone IIA might be due to the reduction of the phosphorylation of JAK2/STAT3 signaling markers and the increase in the levels of the downstream target, Cx43 in PASMCs. Conclusion: These data suggest that Tanshinone IIA promotes PASMC apoptosis during hypoxia and reverses vascular remodeling. This effect is mediated by modulating the expression of Hsp60, caspase-3, and Cx43 via the JAK2/STAT3 signaling pathway. These results might provide a new therapeutic target to explore a novel strategy for hypoxia-induced vessel remodeling

Investigation of interaction mechanisms in nanocomposite PtCo permanent magnetic alloy

The effect of the atomic disorder-order transformation on the interaction mechanisms in isotropic PtCo alloys has been studied by isothermal annealing at 953 K, well below the transformation temperature, for 5-30 min after quenching from 1273 K. The transmission electron microscopy (TEM) testing showed that the ordered regions grew with prolonging heat treatment time. Investigation of the interaction mechanisms in PtCo alloys has been made using analysis of the delta M(H) plot. The results of the delta M(H) plot and TEM indicate that the interaction mechanisms are changed by the size of the magnetically soft and hard phases. The Kneller-Hawig model was used to explain the continuously changing degree of exchange coupling between the magnetically soft and hard phases. (c) 2011 American Institute of Physics. [doi:10.1063/1.3565996