Role of the prolyl isomerase Pin1 in protecting against age-dependent neurodegeneration

The neuropathological hallmarks of Alzheimer's disease and other tauopathies include senile plaques and/or neurofibrillary tangles. Although mouse models have been created by overexpressing specific proteins including beta-amyloid precursor protein, presenilin and tau, no model has been generated by gene knockout. Phosphorylation of tau and other proteins on serine or threonine residues preceding proline seems to precede tangle formation and neurodegeneration in Alzheimer's disease. Notably, these phospho(Ser/Thr)-Pro motifs exist in two distinct conformations, whose conversion in some proteins is catalysed by the Pin1 prolyl isomerase. Pin1 activity can directly restore the conformation and function of phosphorylated tau or it can do so indirectly by promoting its dephosphorylation, which suggests that Pin1 is involved in neurodegeneration; however, genetic evidence is lacking. Here we show that Pin1 expression is inversely correlated with predicted neuronal vulnerability and actual neurofibrillary degeneration in Alzheimer's disease. Pin1 knockout in mice causes progressive age-dependent neuropathy characterized by motor and behavioural deficits, tau hyperphosphorylation, tau filament formation and neuronal degeneration. Thus, Pin1 is pivotal in protecting against age-dependent neurodegeneration, providing insight into the pathogenesis and treatment of Alzheimer's disease and other tauopathies.     

Methane emissions from wetlands on the Qinghai-Tibet Plateau

The areal extent of cold freshwater wetlands on the Qinghai-Tibet Plateau (QTP) is estimated at 0.133 × 10⁶ km², suggesting a significant methane potential. Methane fluxes from wet alpine meadows, peatlands,Hippuris vulgaris mires and secondary marshes were 43.18, 12.96, −0.28 and 45.90 mg · m⁻² · d⁻¹, respectively based on the transect flux studies at the Huashixia Permafrost Station (HPS) from July to August 1996. Average CH₄ fluxes in the thaw season were extrapolated at 5.68 g · m⁻² according to the areal percentage of wetland areas in the Huashixia region. The CH₄ fluxes at four fixed sites, representative of similar ecosystems, ranged from −19.384–347.15 mg · m⁻² · d⁻¹, and the average CH₄ fluxes varied from 6.54 to 71.97 mg · m⁻² · d⁻¹ at each site during the observation period from April to September 1997. The CH₄ emissions at each site during the entire thaw season was estimated from 1.21 to 10.65 g · m⁻², displaying strong spatial variations. Seasonal variations of CH₄ fluxes also were observed at four sites: CH₄ outbursts occurred upon the spring thaw in May and June, CH₄ fluxes increased afterwards with rising soil temperatures. Episodic fluxes were observed in summer, which influenced the average CH₄ fluxes considerably. Annual CH₄ emissions from cold wetlands on the QTP were estimated at about 0.7–0.9 Tg based on the distribution of wetlands, representative CH₄ fluxes, and number of thaw days. The centers of CH₄ releasing were located in the sources of the Yangtze and Yellow rivers, and Zoigê Peatlands.     

SHARPIN is a component of the NF-κB-activating linear ubiquitin chain assembly complex

Cpdm (chronic proliferative dermatitis) mice develop chronic dermatitis and an immunodeficiency with increased serum IgM, symptoms that resemble those of patients with X-linked hyper-IgM syndrome and hypohydrotic ectodermal dysplasia (XHM-ED), which is caused by mutations in NEMO (NF-κB essential modulator; also known as IKBKG). Spontaneous null mutations in the Sharpin (SHANK-associated RH domain interacting protein in postsynaptic density) gene are responsible for the cpdm phenotype in mice. SHARPIN shows significant similarity to HOIL-1L (also known as RBCK1), a component of linear ubiquitin chain assembly complex (LUBAC), which induces NF-κB activation through conjugation of linear polyubiquitin chains to NEMO. Here, we identify SHARPIN as an additional component of LUBAC. SHARPIN-containing complexes can linearly ubiquitinate NEMO and activated NF-κB. Thus, we re-define LUBAC as a complex containing SHARPIN, HOIL-1L, and HOIP (also known as RNF31). Deletion of SHARPIN drastically reduced the amount of LUBAC, which resulted in attenuated TNF-α- and CD40-mediated activation of NF-κB in mouse embryonic fibroblasts (MEFs) or B cells from cpdm mice. Considering the pleomorphic phenotype of cpdm mice, these results confirm the predicted role of LUBAC-mediated linear polyubiquitination in NF-κB activation induced by various stimuli, and strongly suggest the involvement of LUBAC-induced NF-κB activation in various disorders.     

Atomic-beam alignment of inorganic materials for liquid-crystal displays

The technique used to align liquid crystals-rubbing the surface of a substrate on which a liquid crystal is subsequently deposited-has been perfected by the multibillion-dollar liquid-crystal display industry. However, it is widely recognized that a non-contact alignment technique would be highly desirable for future generations of large, high-resolution liquid-crystal displays. A number of alternative alignment techniques have been reported, but none of these have so far been implemented in large-scale manufacturing. Here, we report a non-contact alignment process, which uses low-energy ion beams impinging at a glancing angle on amorphous inorganic films, such as diamond-like carbon. Using this approach, we have produced both laptop and desktop displays in pilot-line manufacturing, and found that displays of higher quality and reliability could be made at a lower cost than the rubbing technique. The mechanism of alignment is explained by adopting a random network model of atomic arrangement in the inorganic films. Order is induced by exposure to an ion beam because unfavourably oriented rings of atoms are selectively destroyed. The planes of the remaining rings are predominantly parallel to the direction of the ion beam.     

Photomechanics: directed bending of a polymer film by light

Polymer solutions and solids that contain light-sensitive molecules can undergo photo-contraction, whereby light energy is converted into mechanical energy. Here we show that a single film of a liquid-crystal network containing an azobenzene chromophore can be repeatedly and precisely bent along any chosen direction by using linearly polarized light. This striking photomechanical effect results from a photoselective volume contraction and may be useful in the development of high-speed actuators for microscale or nanoscale applications, for example in microrobots in medicine or optical microtweezers.     

In situ backscattered electron imaging study of the effect of annealing on the deformation behaviors of Ni electroformed from additive-free and saccharin-containing sulfamate solutions

The Ni samples were electroformed from additive-free(AF) and saccharin-containing(SC) sulfamate solutions, respectively. In situ backscattered electron(BSE) imaging, electron backscatter diffraction(EBSD), and electron-probe microanalysis(EPMA) were used to investigate the effect of annealing on the deformation behaviors of the AF and SC samples. The results indicate that columnar grains of the as-deposited AF sample had an approximated average width of 3 μm and an approximated aspect ratio of 8. The average width of columnar grains of the as-deposited SC sample was reduced to approximately 400 nm by the addition of saccharin to the electrolyte. A few very-large grains distributed in the matrix of the SC sample after annealing. No direct evidence indicated that S segregated at the grain boundaries before or after annealing. The average value of the total elongations of the SC samples decreased from 16% to 6% after annealing, whereas that of the AF samples increased from 18% to 50%. The dislocation recovery in grain-boundary areas of the annealed AF sample was reduced, which contributed to the appearance of microvoids at the triple junctions. The incompatibility deformation between very-large grains and fine grains contributed to the brittle fracture behavior of the annealed SC Ni.     

A genome-wide association study identifies three new risk loci for Kawasaki disease

We performed a genome-wide association study (GWAS) of Kawasaki disease in Japanese subjects using data from 428 individuals with Kawasaki disease (cases) and 3,379 controls genotyped at 473,803 SNPs. We validated the association results in two independent replication panels totaling 754 cases and 947 controls. We observed significant associations in the FAM167A-BLK region at 8p22-23 (rs2254546, P = 8.2 × 10(-21)), in the human leukocyte antigen (HLA) region at 6p21.3 (rs2857151, P = 4.6 × 10(-11)) and in the CD40 region at 20q13 (rs4813003, P = 4.8 × 10(-8)). We also replicated the association of a functional SNP of FCGR2A (rs1801274, P = 1.6 × 10(-6)) identified in a recently reported GWAS of Kawasaki disease. Our findings provide new insights into the pathogenesis and pathophysiology of Kawasaki disease.     

Fabrication of silicon nitride／boron nitride nanocomposite powder

Si3N4/BN nanocomposite powders with the microstructure of the micro-sized α-Si3N4 particles coated with nano-sized BN particles were synthesized via the chemical reaction boric acid,urea,and α- Si3N4 powder in a hydrogen gas.The results of XRD,TEM,and selected area electron diffraction showed that amorphous BN and a little amount of turbostratic BN(t-BN) were coated on Si3N4 particles as the second phase after reaction at 1100℃.After re-heating the composite powders at 1450℃ in a nitrogen gas,the amorphous and turbostratic BN is transformed into h-BN.These nanocomposite powders can be used to prepare Si3N4/BN ceramic composites by hot-pressing at 1800℃,which have perfect machinability and can be drilled with normal metal tools.     

Sexual behavior mutants revisited: molecular and cellular basis of Drosophila mating

The study of Drosophila melanogaster by a combination of forward genetics with specific mutants, and reverse genetics, in which a given gene is expressed in an appropriate brain area to test its effect on behavior, provides a unique opportunity to explore the causal relationship between a particular gene, its function in the cell and the behavioral outcome at the organismic level. Enhanced male-to-male courtship has been shown to occur as a result of mutations in several different genes. For example, the Voila mutant exhibits intense GAL4 reporter expression in the tarsal gustatory sensilla, suggesting the importance of tapping by a male on the female abdomen with his forelegs. Feminization of parts of the antennal lobe and mushroom body by targeted expression of a female-determining gene transformer ⁺ (tra ⁺) drives the male to court other males. Mutations in the tra target gene fruitless (fru), which is expressed in the antennal lobe as well as the suboesophageal ganglion (the gustatory inputs are processed here), also induce homosexual courtship in males. These results suggest that sensory inputs mediated and/or processed by the tarsal receptors, suboesophageal ganglion, antennal lobe and mushroom body contribute to the regulation of male–female courtship. Mosaic analysis localized the neural center for male courtship behavior to the posterior dorsal brain, in which the sensory information processed by the aforementioned neural structures may be integrated. Another mosaic study mapped the neural center for female sexual behavior, as measured by her receptiveness to copulation, to the anterior dorsal brain. The issue as to how the mutations that reduce female sexual receptiveness, e.g. dissatisfaction (dsf), spinster (spin) and chaste (cht), affect the structure and/or function of this neural center deserves to be addressed urgently. Received 27 April 1999; received after revision 21 June 1999; accepted 8 July 1999