Über eine frühe lateinische Bearbeitung der Algebra al-Khwārizmīs in MS Lyell 52 der Bodleian Library Oxford

Ohne Zusammenfassung Vorgelegt von A. P. Youschkevitch Herrn Professor Dr. Kurt Vogel, München, in dankbarer Verehrung zum 95. Geburtstag     

Phenotyping transgenic embryos: a rapid 3-D screening method based on episcopic fluorescence image capturing.

We describe a technique suitable for routine three-dimensional (3-D) analysis of mouse embryos that is based on episcopic fluorescence images captured during serial sectioning of wax-embedded specimens. We have used this procedure to describe the cardiac phenotype and associated blood vessels of trisomic 16 (Ts16) and Cited2-null mutant mice, as well as the expression pattern of an Myf5 enhancer/beta-galactosidase transgene. The consistency of the images and their precise alignment are ideally suited for 3-D analysis using video animations, virtual resectioning or commercial 3-D reconstruction software packages. Episcopic fluorescence image capturing (EFIC) provides a simple and powerful tool for analyzing embryo and organ morphology in normal and transgenic embryos.     

Pyramidal classification based on incomplete dissimilarity data

Two algorithms for pyramidal classification — a generalization of hierarchical classification — are presented that can work with incomplete dissimilarity data. These approaches — a modification of the pyramidal ascending classification algorithm and a least squares based penalty method — are described and compared using two different types of complete dissimilarity data in which randomly chosen dissimilarities are assumed missing and the non-missing ones are subjected to random error. We also consider relationships between hierarchical classification and pyramidal classification solutions when both are based on incomplete dissimilarity data.     

中锰钢奥氏体逆相变的多相场模拟

Medium-Mn steels have attracted immense attention for automotive applications owing to their outstanding combination of high strength and superior ductility. This steel class is generally characterized by an ultrafine-grained duplex microstructure consisting of ferrite and a large amount of austenite. Such a unique microstructure is processed by intercritical annealing, where austenite reversion occurs in a fine martensitic matrix. In the present study, austenite reversion in a medium-Mn alloy was simulated by the multiphase-field approach using the commercial software MICRESS? coupled with the thermodynamic database TCFE8 and the kinetic database MOBFE2. In particular, a faceted anisotropy model was incorporated to replicate the lamellar morphology of reversed austenite. The simulated microstructural morphology and phase transformation kinetics (indicated by the amount of phase) concurred well with experimental observations by scanning electron microscopy and in situ synchrotron high-energy X-ray diffraction, respectively.     

大黄素对辣椒素诱导的TRPV1通道电流的抑制作用

本研究通过显微注射技术将TRPV1 cRNA(1ng/nL)注射至非洲爪蟾卵母细胞(20nL/个)体内,放置于G-ORi培养液中,并在(19±1)℃的恒温培养箱内表达.同时利用灌流技术将不同浓度梯度的大黄素、辣椒素按照设计顺序依次灌流进入流动腔,同时控制流速保证非洲爪蟾卵母细胞完全浸没于流动腔内.使用双电极电压钳技术记录0.1,1.0,10.0,50.0μmol/L浓度梯度的大黄素对500nmol/L浓度的辣椒素激活TRPV1电流的影响.得到大黄素作用辣椒素激活TRPV1通道的抑制作用表现出浓度依耐性和电压非依赖性,IC50=38μmol/L,Hill系数n=0.5.结果表明了大黄素对TRPV1位点的相互作用是负协同的,在天然药物里面是一类比较弱的拮抗剂,且大黄素在ORi溶液中开始析出沉淀的浓度在50~60μmol/L之间.我们首次发现了大黄素能够抑制TRPV1通道电流,这可能为开发新的镇痛药物提供理论基础.     

Long-term relationships between ecological stability and biodiversity in Phanerozoic reefs

High biodiversity has been shown to enhance ecological stability on small spatial scales and over intervals of weeks to decades. It remains unclear, however, whether this diversity-stability relationship can be scaled up to regional scales, or to longer timescales. Without empirical validation at larger scales, the implications of the diversity-stability relationship for both ecology and long-term conservation strategies cannot readily be resolved. Here I show that in biogenic reefs, ecological stability is related to taxonomic diversity on million-year timescales. The higher the mean reef diversity in a particular time interval, the smaller the change in skeletal density, style of reef building and biotic reef types in the subsequent time interval. Because the relationships apply to a wide spectrum of disturbance regimes and reef types, these results support the hypothesis that species richness itself promotes ecological stability. Carbonate production by reefs, while closely correlated with reef diversity without temporal lag, is not stabilized by reef diversity over these long timescales. This suggests that ecological stability and productivity may be decoupled in natural ecosystems.     

Regulation of HP1-chromatin binding by histone H3 methylation and phosphorylation

Tri-methylation of histone H3 lysine 9 is important for recruiting heterochromatin protein 1 (HP1) to discrete regions of the genome, thereby regulating gene expression, chromatin packaging and heterochromatin formation. Here we show that HP1alpha, -beta, and -gamma are released from chromatin during the M phase of the cell cycle, even though tri-methylation levels of histone H3 lysine 9 remain unchanged. However, the additional, transient modification of histone H3 by phosphorylation of serine 10 next to the more stable methyl-lysine 9 mark is sufficient to eject HP1 proteins from their binding sites. Inhibition or depletion of the mitotic kinase Aurora B, which phosphorylates serine 10 on histone H3, causes retention of HP1 proteins on mitotic chromosomes, suggesting that H3 serine 10 phosphorylation is necessary for the dissociation of HP1 from chromatin in M phase. These findings establish a regulatory mechanism of protein-protein interactions, through a combinatorial readout of two adjacent post-translational modifications: a stable methylation and a dynamic phosphorylation mark.     

Variants of ENPP1 are associated with childhood and adult obesity and increase the risk of glucose intolerance and type 2 diabetes

We identified a locus on chromosome 6q16.3-q24.2 (ref. 1) associated with childhood obesity that includes 2.4 Mb common to eight genome scans for type 2 diabetes (T2D) or obesity. Analysis of the gene ENPP1 (also called PC-1), a candidate for insulin resistance, in 6,147 subjects showed association between a three-allele risk haplotype (K121Q, IVS20delT-11 and A-->G+1044TGA; QdelTG) and childhood obesity (odds ratio (OR) = 1.69, P = 0.0006), morbid or moderate obesity in adults (OR = 1.50, P = 0.006 or OR = 1.37, P = 0.02, respectively) and T2D (OR = 1.56, P = 0.00002). The Genotype IBD Sharing Test suggested that this obesity-associated ENPP1 risk haplotype contributes to the observed chromosome 6q linkage with childhood obesity. The haplotype confers a higher risk of glucose intolerance and T2D to obese children and their parents and associates with increased serum levels of soluble ENPP1 protein in children. Expression of a long ENPP1 mRNA isoform, which includes the obesity-associated A-->G+1044TGA SNP, was specific for pancreatic islet beta cells, adipocytes and liver. These findings suggest that several variants of ENPP1 have a primary role in mediating insulin resistance and in the development of both obesity and T2D, suggesting that an underlying molecular mechanism is common to both conditions.     

Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways

Cystic renal diseases are caused by mutations of proteins that share a unique subcellular localization: the primary cilium of tubular epithelial cells. Mutations of the ciliary protein inversin cause nephronophthisis type II, an autosomal recessive cystic kidney disease characterized by extensive renal cysts, situs inversus and renal failure. Here we report that inversin acts as a molecular switch between different Wnt signaling cascades. Inversin inhibits the canonical Wnt pathway by targeting cytoplasmic dishevelled (Dsh or Dvl1) for degradation; concomitantly, it is required for convergent extension movements in gastrulating Xenopus laevis embryos and elongation of animal cap explants, both regulated by noncanonical Wnt signaling. In zebrafish, the structurally related switch molecule diversin ameliorates renal cysts caused by the depletion of inversin, implying that an inhibition of canonical Wnt signaling is required for normal renal development. Fluid flow increases inversin levels in ciliated tubular epithelial cells and seems to regulate this crucial switch between Wnt signaling pathways during renal development.