Tumor suppressor C-RASSF proteins

Human genome has ten genes that are collectedly called Ras association domain family (RASSF). RASSF is composed of two subclasses, C-RASSF and N-RASSF. Both N-RASSF and C-RASSF encode Ras association domain-containing proteins and are frequently suppressed by DNA hypermethylation in human cancers. However, C-RASSF and N-RASSF are quite different. Six C-RASSF proteins (RASSF1–6) are characterized by a C-terminal coiled-coil motif named Salvador/RASSF/Hippo domain, while four N-RASSF proteins (RASSF7–10) lack it. C-RASSF proteins interact with mammalian Ste20-like kinases—the core kinases of the tumor suppressor Hippo pathway—and cross-talk with this pathway. Some of them share the same interacting molecules such as MDM2 and exert the tumor suppressor role in similar manners. Nevertheless, each C-RASSF protein has distinct characters. In this review, we summarize our current knowledge of how C-RASSF proteins play tumor suppressor roles and discuss the similarities and differences among C-RASSF proteins.     

Susceptibility loci for intracranial aneurysm in European and Japanese populations

Stroke is the world's third leading cause of death. One cause of stroke, intracranial aneurysm, affects approximately 2% of the population and accounts for 500,000 hemorrhagic strokes annually in mid-life (median age 50), most often resulting in death or severe neurological impairment. The pathogenesis of intracranial aneurysm is unknown, and because catastrophic hemorrhage is commonly the first sign of disease, early identification is essential. We carried out a multistage genome-wide association study (GWAS) of Finnish, Dutch and Japanese cohorts including over 2,100 intracranial aneurysm cases and 8,000 controls. Genome-wide genotyping of the European cohorts and replication studies in the Japanese cohort identified common SNPs on chromosomes 2q, 8q and 9p that show significant association with intracranial aneurysm with odds ratios 1.24-1.36. The loci on 2q and 8q are new, whereas the 9p locus was previously found to be associated with arterial diseases, including intracranial aneurysm. Associated SNPs on 8q likely act via SOX17, which is required for formation and maintenance of endothelial cells, suggesting a role in development and repair of the vasculature; CDKN2A at 9p may have a similar role. These findings have implications for the pathophysiology, diagnosis and therapy of intracranial aneurysm.     

Novel Megalo-capacitance Capacitor Using Graphitic Carbons

1 Results During the past years,EDLC (electric double layer capacitors) using activated carbon (AC) as polarizable electrodes have receive great attention in the electric energy storage community because of the advantages of high power density,long cycle life and benignity towards environment,etc..However,one disadvantage must be solved before its further applications.That is the low energy density.Many attempts have been tried to increasing the surface area between 1 000-2 000 m2/g using alkaline or wa...     

Two-photon laser spectroscopy of antiprotonic helium and the antiproton-to-electron mass ratio

Physical laws are believed to be invariant under the combined transformations of charge, parity and time reversal (CPT symmetry). This implies that an antimatter particle has exactly the same mass and absolute value of charge as its particle counterpart. Metastable antiprotonic helium (pHe(+)) is a three-body atom consisting of a normal helium nucleus, an electron in its ground state and an antiproton (p) occupying a Rydberg state with high principal and angular momentum quantum numbers, respectively n and l, such that n?≈?l?+?1?≈?38. These atoms are amenable to precision laser spectroscopy, the results of which can in principle be used to determine the antiproton-to-electron mass ratio and to constrain the equality between the antiproton and proton charges and masses. Here we report two-photon spectroscopy of antiprotonic helium, in which p(3)He(+) and p(4)He(+) isotopes are irradiated by two counter-propagating laser beams. This excites nonlinear, two-photon transitions of the antiproton of the type (n, l)?→?(n?-?2, l?-?2) at deep-ultraviolet wavelengths (λ = 139.8, 193.0 and 197.0?nm), which partly cancel the Doppler broadening of the laser resonance caused by the thermal motion of the atoms. The resulting narrow spectral lines allowed us to measure three transition frequencies with fractional precisions of 2.3-5 parts in 10(9). By comparing the results with three-body quantum electrodynamics calculations, we derived an antiproton-to-electron mass ratio of 1,836.1526736(23), where the parenthetical error represents one standard deviation. This agrees with the proton-to-electron value known to a similar precision.     

Id3启动子/荧光素酶基因载体的构建及其在WEHI-231细胞中的活性表达

用PCR法从WEHI-231细胞基因组DNA扩增小鼠Id3(mId3)基因5’端含启动子序列的不同长度的DNA片段(mId3-pf)亚克隆至荧光素酶(Luc)报道基因载体PGV-B2,构建由mId3基因启动子片段控制的Luc报道基因重组载体mId3-pf/PGV-B2.用电穿孔术将mId3-pf/PGV-B2导入培养的WEHI-231细胞,用抗小鼠IgM抗体刺激转染后的WEHI-231细胞,24 h后测定胞内Luc活性.结果表明,4种Luc报道基因重组载体转染细胞均表现较高的mId3启动子活性,与空载体转染细胞相比,启动子活性分别升高25~60倍.抗IgM抗体刺激细胞后,Id3启动子活性较未刺激细胞均呈明显增高趋势,增高幅度可达2倍左右.表明抗IgM抗体诱导WEHI-231细胞Id3的上调表达与Id3转录活性的升高有关.     

Germline gain-of-function mutations in RAF1 cause Noonan syndrome

Noonan syndrome is characterized by short stature, facial dysmorphia and a wide spectrum of congenital heart defects. Mutations of PTPN11, KRAS and SOS1 in the RAS-MAPK pathway cause approximately 60% of cases of Noonan syndrome. However, the gene(s) responsible for the remainder are unknown. We have identified five different mutations in RAF1 in ten individuals with Noonan syndrome; those with any of four mutations causing changes in the CR2 domain of RAF1 had hypertrophic cardiomyopathy (HCM), whereas affected individuals with mutations leading to changes in the CR3 domain did not. Cells transfected with constructs containing Noonan syndrome-associated RAF1 mutations showed increased in vitro kinase and ERK activation, and zebrafish embryos with morpholino knockdown of raf1 demonstrated the need for raf1 for the development of normal myocardial structure and function. Thus, our findings implicate RAF1 gain-of-function mutations as a causative agent of a human developmental disorder, representing a new genetic mechanism for the activation of the MAPK pathway.     

Alpha-synuclein elicits glucose uptake and utilization in adipocytes through the Gab1/PI3K/Akt transduction pathway

Insulin is the main glucoregulator that promotes the uptake of glucose by tissues and the subsequent utilization of glucose as an energy source. In this paper, we describe a novel glucoregulator, the alpha-synuclein (SNCA) protein, that has previously been linked to Parkinson’s disease. Treatment with recombinant SNCA promotes glucose uptake in vitro in preadipocytes and in vivo in the adipose tissues and skeletal muscles of mice through the LPAR2/Gab1/PI3K/Akt pathway; these effects occur independently of the insulin receptor. This function of SNCA represents a new mechanistic insight that creates novel avenues of research with respect to the process of glucose regulation.