DISC1-dependent switch from progenitor proliferation to migration in the developing cortex

Regulatory mechanisms governing the sequence from progenitor cell proliferation to neuronal migration during corticogenesis are poorly understood. Here we report that phosphorylation of DISC1, a major susceptibility factor for several mental disorders, acts as a molecular switch from maintaining proliferation of mitotic progenitor cells to activating migration of postmitotic neurons in mice. Unphosphorylated DISC1 regulates canonical Wnt signalling via an interaction with GSK3β, whereas specific phosphorylation at serine 710 (S710) triggers the recruitment of Bardet-Biedl syndrome (BBS) proteins to the centrosome. In support of this model, loss of BBS1 leads to defects in migration, but not proliferation, whereas DISC1 knockdown leads to deficits in both. A phospho-dead mutant can only rescue proliferation, whereas a phospho-mimic mutant rescues exclusively migration defects. These data highlight a dual role for DISC1 in corticogenesis and indicate that phosphorylation of this protein at S710 activates a key developmental switch.     

Permanent El Niño during the Pliocene warm period not supported by coral evidence

The El Ni?o/Southern Oscillation (ENSO) system during the Pliocene warm period (PWP; 3-5 million years ago) may have existed in a permanent El Ni?o state with a sharply reduced zonal sea surface temperature (SST) gradient in the equatorial Pacific Ocean. This suggests that during the PWP, when global mean temperatures and atmospheric carbon dioxide concentrations were similar to those projected for near-term climate change, ENSO variability--and related global climate teleconnections-could have been radically different from that today. Yet, owing to a lack of observational evidence on seasonal and interannual SST variability from crucial low-latitude sites, this fundamental climate characteristic of the PWP remains controversial. Here we show that permanent El Ni?o conditions did not exist during the PWP. Our spectral analysis of the δ(18)O SST and salinity proxy, extracted from two 35-year, monthly resolved PWP Porites corals in the Philippines, reveals variability that is similar to present ENSO variation. Although our fossil corals cannot be directly compared with modern ENSO records, two lines of evidence suggest that Philippine corals are appropriate ENSO proxies. First, δ(18)O anomalies from a nearby live Porites coral are correlated with modern records of ENSO variability. Second, negative-δ(18)O events in the fossil corals closely resemble the decreases in δ(18)O seen in the live coral during El Ni?o events. Prior research advocating a permanent El Ni?o state may have been limited by the coarse resolution of many SST proxies, whereas our coral-based analysis identifies climate variability at the temporal scale required to resolve ENSO structure firmly.     

Fabrication, nanostructures and electronic properties of nanodiamond-based solar cells

Nanodiamond-based solar cells were fa bricated and the photovoltaic properties were investigated. Fullerene (C60) and fullerenol (C60(OH)10-12) were used as n-type semiconductors, and diamond nan oparticles and metal phthalocyanine derivative were used as p-type semiconductors. The nanostructures of the solar cel ls were investigated by transmission electron microscopy and X-ray diffracometry, and the electronic property was discussed.     

Human ES-cell-derived cardiomyocytes electrically couple and suppress arrhythmias in injured hearts

Transplantation studies in mice and rats have shown that human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) can improve the function of infarcted hearts, but two critical issues related to their electrophysiological behaviour in vivo remain unresolved. First, the risk of arrhythmias following hESC-CM transplantation in injured hearts has not been determined. Second, the electromechanical integration of hESC-CMs in injured hearts has not been demonstrated, so it is unclear whether these cells improve contractile function directly through addition of new force-generating units. Here we use a guinea-pig model to show that hESC-CM grafts in injured hearts protect against arrhythmias and can contract synchronously with host muscle. Injured hearts with hESC-CM grafts show improved mechanical function and a significantly reduced incidence of both spontaneous and induced ventricular tachycardia. To assess the activity of hESC-CM grafts in vivo, we transplanted hESC-CMs expressing the genetically encoded calcium sensor, GCaMP3 (refs 4, 5). By correlating the GCaMP3 fluorescent signal with the host ECG, we found that grafts in uninjured hearts have consistent 1:1 host–graft coupling. Grafts in injured hearts are more heterogeneous and typically include both coupled and uncoupled regions. Thus, human myocardial grafts meet physiological criteria for true heart regeneration, providing support for the continued development of hESC-based cardiac therapies for both mechanical and electrical repair.     

Ornithine decarboxylase is degraded by the 26S proteasome without ubiquitination.

Ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis, is the most rapidly turned over mammalian enzyme. We have shown that its degradation is accelerated by ODC antizyme, an inhibitory protein induced by polyamines. This is a new type of enzyme regulation and may be a model for selective protein degradation. Here we report the identification of the protease responsible for ODC degradation. Using a cell-free degradation system, we demonstrate that immunodepletion of proteasomes from cell extracts causes almost complete loss of ATP- and antizyme-dependent degradation of ODC. In addition, purified 26S proteasome complex, but not the 20S proteasome, catalyses ODC degradation in the absence of ubiquitin. These results strongly suggest that the 26S proteasome, widely viewed as specific for ubiquitin-conjugated proteins, is the main enzyme responsible for ODC degradation. The 26S proteasome may therefore have a second role in ubiquitin-independent proteolysis.     

Wetting of fibrin plate and apparent promotion of fibrinolysis by surfactin,a new bacterial peptidelipid surfactant

Zusammenfassung Aus Kulturen vonBacillus subtilis wurde Surfactin, eine neue Substanz, isoliert und aufgeklärt. Es handelt sich um ein Peptidlipid, welches netzende Eigenschaften besitzt und dadurch die Fibrinolyse beschleunigt.     

Structure in the early afterglow light curve of the gamma-ray burst of 29 March 2003

Gamma-ray bursts (GRBs) are energetic explosions that for 0.01-100 s are the brightest gamma-ray sources in the sky. Observations of the early evolution of afterglows are expected to provide clues about the nature of the bursts, but their rapid fading has hampered such studies; some recent rapid localizations of bursts have improved the situation. Here we report an early detection of the very bright afterglow of the burst of 29 March 2003 (GRB030329). Our data show that, even early in the afterglow phase, the light curve shows unexpectedly complicated structures superimposed on the fading background.     

乙酸-苯-三乙胺的液液相平衡

测定了在293.15K时乙酸、苯和三乙胺的液液二相平衡，并将实验数据和UNIQUAC缔合溶液模型的计算结果进行比较。模型假设乙酸以二聚形式存在，乙酸与三乙胺可以形成1：1、2：1、3：1和4：1型的化合物，并且假设在三元体系中不同分子之间没有其他的相互作用力。UNIQUAC缔合溶液模型成功地描述了乙酸、苯和三乙胺的液液二相平衡．