Mutations in axonemal dynein assembly factor DNAAF3 cause primary ciliary dyskinesia

Primary ciliary dyskinesia most often arises from loss of the dynein motors that power ciliary beating. Here we show that DNAAF3 (also known as PF22), a previously uncharacterized protein, is essential for the preassembly of dyneins into complexes before their transport into cilia. We identified loss-of-function mutations in the human DNAAF3 gene in individuals from families with situs inversus and defects in the assembly of inner and outer dynein arms. Knockdown of dnaaf3 in zebrafish likewise disrupts dynein arm assembly and ciliary motility, causing primary ciliary dyskinesia phenotypes that include hydrocephalus and laterality malformations. Chlamydomonas reinhardtii PF22 is exclusively cytoplasmic, and a PF22-null mutant cannot assemble any outer and some inner dynein arms. Altered abundance of dynein subunits in mutant cytoplasm suggests that DNAAF3 (PF22) acts at a similar stage as other preassembly proteins, for example, DNAAF2 (also known as PF13 or KTU) and DNAAF1 (also known as ODA7 or LRRC50), in the dynein preassembly pathway. These results support the existence of a conserved, multistep pathway for the cytoplasmic formation of assembly competent ciliary dynein complexes.     

菜籽粕发酵脱毒的一些影响因素

报告了菜籽饼粕发酵脱毒的菌种复壮方法及脱毒辅助剂．应用芥子甙的酶分解产物异硫氰酸酯类，通过产物耐受性筛选法，获得提高了脱毒率的曲霉（Ａｓｐｅｒｇｉｌｕｓｓｐ．）菌株．从饲料添加剂中寻找到一种可增强发酵脱毒效果的脱毒助剂，并试验了影响发酵脱毒的各种因子．     

Selective antiproliferative effects of thymidine

A substance with antiproliferative bioactivity in an aqueous extract ofCordyline terminalis was purified and identified by mass spectrometry to be the natural nucleoside, thymidine. 10^–5M Thymidine inhibited EL4 cell replication and decreased cell viability after 12–24 h. The effect was highly specific for this nucleoside. Treated cell cultures showed a significant increase in S phase cells and a corresponding decrease in G₁ phase cells. Nitrobenzylthioinosine (which prevented facilitated entry of thymidine) protected cells from the antiproliferative action of thymidine. A human breast cancer cell line (MCF7) was also growth-inhibited by 10^–5M thymidine but a murine lymphoma cell line (K36) was not. Thus, submillimolar thymidine has effects on cell proliferation which are selective both with respect to specificity for the compound and for different tumour cell lines.     

Cellular and molecular action of the putative GABA-mimetic,gabapentin

Gabapentin was originally designed as an anti-convulsant gamma-aminobutyric acid (GABA) mimetic capable of crossing the blood-brain barrier. In the present review we show that although gabapentin is not a GABA mimetic, it has great utility as an add-on therapy for epilepsy and as a first-line treatment for neuropathic pain. We summarise the studies that have been performed which demonstrate that gabapentin appears to interact with a novel binding site expressed at high density within the central nervous system (CNS), namely the alpha2delta voltage-dependent calcium channel subunit. The review continues by examining the effects of gabapentin on calcium channel function and neurotransmitter release before, in the latter part of the review, summarising the more recently discovered actions of gabapentin in relation to intracellular signalling.     

An electronic Mach-Zehnder interferometer

Double-slit electron interferometers fabricated in high mobility two-dimensional electron gases are powerful tools for studying coherent wave-like phenomena in mesoscopic systems. However, they suffer from low visibility of the interference patterns due to the many channels present in each slit, and from poor sensitivity to small currents due to their open geometry. Moreover, these interferometers do not function in high magnetic fields--such as those required to enter the quantum Hall effect regime--as the field destroys the symmetry between left and right slits. Here we report the fabrication and operation of a single-channel, two-path electron interferometer that functions in a high magnetic field. This device is the first electronic analogue of the optical Mach-Zehnder interferometer, and opens the way to measuring interference of quasiparticles with fractional charges. On the basis of measurements of single edge state and closed geometry transport in the quantum Hall effect regime, we find that the interferometer is highly sensitive and exhibits very high visibility (62%). However, the interference pattern decays precipitously with increasing electron temperature or energy. Although the origin of this dephasing is unclear, we show, via shot-noise measurements, that it is not a decoherence process that results from inelastic scattering events.     

Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan

In diverse organisms, calorie restriction slows the pace of ageing and increases maximum lifespan. In the budding yeast Saccharomyces cerevisiae, calorie restriction extends lifespan by increasing the activity of Sir2 (ref. 1), a member of the conserved sirtuin family of NAD(+)-dependent protein deacetylases. Included in this family are SIR-2.1, a Caenorhabditis elegans enzyme that regulates lifespan, and SIRT1, a human deacetylase that promotes cell survival by negatively regulating the p53 tumour suppressor. Here we report the discovery of three classes of small molecules that activate sirtuins. We show that the potent activator resveratrol, a polyphenol found in red wine, lowers the Michaelis constant of SIRT1 for both the acetylated substrate and NAD(+), and increases cell survival by stimulating SIRT1-dependent deacetylation of p53. In yeast, resveratrol mimics calorie restriction by stimulating Sir2, increasing DNA stability and extending lifespan by 70%. We discuss possible evolutionary origins of this phenomenon and suggest new lines of research into the therapeutic use of sirtuin activators.     

Origin of two differentiation trends in the Emeishan flood basalts

Both the Bowen and Fenner differentiation trends have been recognized in the Emeishan flood basalts.While the Longzhoushan laveas in Panxi paleorift evolved on a trend of silica enrichment (Bowen trend),the lavas from Guizhou evoled along the Fenner trend leading to the magmas with high Fe2O3 (23%) and low SiO2(44%) contents,This provides evidence for the existence of Fe-rich and Si-poor magmas in nature ,Such contrasting differentiation trends,marked by different timing of crystallization of Fe-Ti oxides,are correlated with the extent of crustal contamination of the magmas ,Linited crustal contamination in the Guizhou lavas is coupled with the low oxygen fugacity which delayed the onset of magnetite crystallization .In contrast,significant involvement of crustal components in the Long-Zhoushan lavas increased fo2 which in turn triggered early crystallization of magnetite.The close spatial association between the Longzhoushan lavs and the synchronous V-Fe-Ti deposit-bearing layered intrusions suggests a potential relationship between them.     

An improved R-tree based on childnode''''s probability

R Tree is a good structure for spatial searching. But in this indexing structure, either the sequence of nodes in the same level or sequence of traveling these nodes when queries are made is random. Since the possibility that the object appears in different MBR which have the same parents node is different, if we make the subnode who has the most possibility be traveled first, the time cost will be decreased in most of the cases. In some case, the possibility of a point belong to a rectangle will shows direct proportion with the size of the rectangle. But this conclusion is based on an assumption that the objects are symmetrically distributing in the area and this assumption is not always coming into existence. Now we found a more direct parameter to scale the possibility and made a little change on the structure of R tree, to increase the possibility of founding the satisfying answer in the front sub trees. We names this structure probability based arranged R tree (PBAR tree).     

Discovery of Middle Jurassic palaeontinids from Inner Mongolia, China (Homoptera: Palaeontinidae)

A new genus and three new species of fossil Palaeontinidae, Papilioncossus conchatus sp. nov., P. giganteus sp. nov. and P. pteroideus sp. nov., are described. All of them were collected from Middle Jurassic Jiulongshan Formation in Inner Mongolia, China. Based on distal part of forewing broader and longer than basal and Sc usually with branches, the new taxa are attributed to Palaeontinidae of Homoptera and compared with genus Pseudocossus. A key to species of Papilioncossus gen. nov. is provided. All type specimens are deposited in the Capital Normal University.     

Rapamycin selectively inhibits interleukin-2 activation of p70 S6 kinase.

The macrolide rapamycin induces cell cycle G1 arrest in yeast and in mammalian cells, which suggests that an evolutionarily conserved, rapamycin-sensitive pathway may regulate entry into S phase. In mammals, rapamycin inhibits interleukin-2 receptor-induced S phase entry and subsequent T-cell proliferation, resulting in immunosuppression. Here we show that interleukin-2 selectively stimulates the phosphorylation and activation of p70 S6 kinase but not the erk-encoded MAP kinases and rsk-encoded S6 kinases. Rapamycin completely and rapidly inhibits interleukin-2-induced phosphorylation and activation of p70 S6 kinase at concentrations comparable to those blocking S phase entry of T cells (0.05-0.2 nM). The structurally related macrolide FK506 competitively antagonizes the actions of rapamycin, indicating that these effects are mediated by FKBP, which binds the transition-state mimic structure common to both rapamycin and FK506 (refs 4, 6, 9-11). The selective blockade of the p70 S6 kinase activation cascade by the rapamycin-FKBP complex implicates this signalling pathway in the regulation of T cell entry into S phase.