Polo inhibits progenitor self-renewal and regulates Numb asymmetry by phosphorylating Pon

Self-renewal and differentiation are cardinal features of stem cells. Asymmetric cell division provides one fundamental mechanism by which stem cell self-renewal and differentiation are balanced. A failure of this balance could lead to diseases such as cancer. During asymmetric division of stem cells, factors controlling their self-renewal and differentiation are unequally segregated between daughter cells. Numb is one such factor that is segregated to the differentiating daughter cell during the stem-cell-like neuroblast divisions in Drosophila melanogaster, where it inhibits self-renewal. The localization and function of Numb is cell-cycle-dependent. Here we show that Polo (ref. 13), a key cell cycle regulator, the mammalian counterparts of which have been implicated as oncogenes as well as tumour suppressors, acts as a tumour suppressor in the larval brain. Supernumerary neuroblasts are produced at the expense of neurons in polo mutants. Polo directly phosphorylates Partner of Numb (Pon, ref. 16), an adaptor protein for Numb, and this phosphorylation event is important for Pon to localize Numb. In polo mutants, the asymmetric localization of Pon, Numb and atypical protein kinase C are disrupted, whereas other polarity markers are largely unaffected. Overexpression of Numb suppresses neuroblast overproliferation caused by polo mutations, suggesting that Numb has a major role in mediating this effect of Polo. Our results reveal a biochemical link between the cell cycle and the asymmetric protein localization machinery, and indicate that Polo can inhibit progenitor self-renewal by regulating the localization and function of Numb.     

Maize HapMap2 identifies extant variation from a genome in flux

Whereas breeders have exploited diversity in maize for yield improvements, there has been limited progress in using beneficial alleles in undomesticated varieties. Characterizing standing variation in this complex genome has been challenging, with only a small fraction of it described to date. Using a population genetics scoring model, we identified 55 million SNPs in 103 lines across pre-domestication and domesticated Zea mays varieties, including a representative from the sister genus Tripsacum. We find that structural variations are pervasive in the Z. mays genome and are enriched at loci associated with important traits. By investigating the drivers of genome size variation, we find that the larger Tripsacum genome can be explained by transposable element abundance rather than an allopolyploid origin. In contrast, intraspecies genome size variation seems to be controlled by chromosomal knob content. There is tremendous overlap in key gene content in maize and Tripsacum, suggesting that adaptations from Tripsacum (for example, perennialism and frost and drought tolerance) can likely be integrated into maize.     

Spontaneous excision of a large composite transposable element of Drosophila melanogaster

The TE1 family of transposable elements (TEs) of Drosophila consists of unusually large transposons, cytologically visible in larval polytene chromosomes as one or more bands. They are composite elements, as their termini consist of foldback (FB) sequences which are themselves transposable. The location of FB elements at the termini of transposable elements suggests that these sequences have a direct role in the genetic instability of TEs. To investigate the structural and phenotypic consequence of TE excision, we have cloned genomic DNA required for the expression of the no-ocelli (noc) gene of Drosophila; this gene has been mutated by the insertion of TE146, a member of the TE1 family carrying six polytene chromosome bands including functional copies of the white (w+) and roughest (rst+) genes. As reported here, our experiments indicate that the spontaneous excision of TE146, which results in the loss of the w+ and rst+ markers, can occur either as a single-step event or following a partial internal deletion. In either case, the end product is an imprecise excision in which a residual portion of the element, varying in size from 3 to 10 kilobases (kb), is left at the insertion site. These residual sequences share homology with the FB family. Furthermore, despite their imprecise nature, all these spontaneous excisions restore a wild-type noc+ phenotype.     

Site-directed mutagenesis reveals role of mobile arginine residue in lactate dehydrogenase catalysis

The binding of substrates to lactate dehydrogenases induces a marked rearrangement of the protein structure in which a 'loop' of polypeptide (residues 98-110) closes over the active site of the enzyme. In this rearrangement, arginine 109 (a basic residue conserved in all known lactate dehydrogenase sequences and in the homologous malate dehydrogenases) moves 0.8 nm from a position in the solvent to one in the active site where its guanidinium group resides within hydrogen bonding distance of both the reactive carbonyl of pyruvate and imidazole ring of the catalytic histidine 195 (see Fig. 1). Whilst this feature of the enzyme has been commented upon previously, the function of this mobile arginine residue during catalysis has not been tested experimentally. The advent of protein engineering has now enabled us to define the role of this basic residue by substituting it with the neutral glutamine. Transient kinetic and equilibrium studies of the mutant enzyme indicate that arginine 109 enhances the polarization of the pyruvate carbonyl group in the ground state and stabilizes the transition state. The gross active-site structure of the enzyme is not altered by the mutation since an alternative catalytic function of the enzyme (rate of addition of sulphite to NAD+), which does not require hydride transfer, is insensitive to the arginine----glutamine substitution.     

Regulation of self-renewal and differentiation by the intestinal stem cell niche

The gastrointestinal epithelium is a highly organised tissue that is constantly being renewed. In order to maintain homeostasis, the balance between intestinal stem cell (ISC) self-renewal and differentiation must be carefully regulated. In this review, we describe how the intestinal stem cell niche provides a unique environment to regulate self-renewal and differentiation of ISCs. It has traditionally been believed that the mesenchymal myofibroblasts play an important role in the crosstalk between ISCs and the niche. However, recent evidence in Drosophila and in vertebrates suggests that epithelial cells also contribute to the niche. We discuss the multiple signalling pathways that are utilised to regulate stemness within the niche, including members of the Wnt, BMP and Hedgehog pathways, and how aberrations in these signals lead to disruption of the normal crypt–villus axis. Finally, we also discuss how CDX1 and inhibition of the Notch pathway are important in specifying enterocyte and goblet cell differentiation respectively.     

Global Spiral Patterns in Galaxies : A Review of the Density Wave Theory from the Theoretical Perspective

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一种新型双层电磁带隙结构及其在微波电路中的应用

提出了一种新型双层电磁带隙结构, 并分别用数值和实验的方法对这种结构的特性进行了分析. 在对这种结构单元的电磁特性分析的基础上, 给出了其集总参数等效电路, 并且讨论了这种结构的几何参数对电磁特性和等效参数的影响. 与已有的EBG结构相比, 该结构具有小型化及背向辐射小的特点. 基于单元结构的特性和等效电路, 设计了一种紧凑型转弯线带阻滤波器, 以及带阻型天线双工器. 理论和测量结果显示, 这种结构在微波和射频系统中具有潜在的应用价值.     

Random walk hypothesis in exchange rate reconsidered

An econometric model for exchange rate based on the behavior of dynamic international asset allocation is considered. The capital movement intensity index is constructed from the adjustment of a fully hedged international portfolio. Including this index as an additional explanatory variable helps to explain the fluctuation of the exchange rate and predict better than the competing random walk model. Supporting empirical evidence is found in Germany–USA, Japan–USA, Singapore–USA and Taiwan–USA exchange markets. Copyright © 2006 John Wiley & Sons, Ltd.     

Peristaltic constrictions in fertilized barnacle eggs (Pollicipes polymerus)

Résumés La vitesse et l'amplitude des resserrements péristaltiques dans les ufs fertilisés de balane (Pollicipes polymerus) dépend de l'âge de l'embryon et de la position du resserrement dans celui-ci. Les resserrements péristaltiques sont probablement réglés par des microfilaments et non par des microtubules et il se peut que la synthèse de protéine soit nécessaire, mais la phosphorylation oxydative ne l'est pas. Le rapport possible entre les resserrements et les événements morphogénétiques des ufs fertilisés est discuté.