Heterozygous deletion of the linked genes ZIC1 and ZIC4 is involved in Dandy-Walker malformation

Dandy-Walker malformation (DWM; OMIM #220200) is a common but poorly understood congenital cerebellar malformation in humans. Through physical mapping of 3q2 interstitial deletions in several individuals with DWM, we defined the first critical region associated with DWM, encompassing two adjacent Zinc finger in cerebellum genes, ZIC1 and ZIC4. Mice with a heterozygous deletion of these two linked genes have a phenotype that closely resembles DWM, providing a mouse model for this malformation.     

Development of City Transport System and Two-wheel Vehicles

Based on the study on the city transport systems of some typical cities worldwide, this paper put forward that each city transport system has its own development mode, which is influenced by the city development plan, economic development level, traveling vehicle composition etc.. When some problems occur, such as the congestions caused by contradiction between the road capacity and vehicle composition, the city transport system may come into temporary maturity period. If the improvement for road system is limited meanwhile, optimized structure of vehicle composition should be an effective solution in this case. With the development of economy-internationalization, the development speed of city transport modernization is rapid. When traveling easiness is conflicting with efficiency, the advantages of public transport system become more obvious. Correspondingly, the superiority of two-wheel vehicles will reappear. Though the important function of two-wheel vehicles for alleviating city traffic problems i     

Event-horizon-scale structure in the supermassive black hole candidate at the Galactic Centre

The cores of most galaxies are thought to harbour supermassive black holes, which power galactic nuclei by converting the gravitational energy of accreting matter into radiation. Sagittarius A* (Sgr A*), the compact source of radio, infrared and X-ray emission at the centre of the Milky Way, is the closest example of this phenomenon, with an estimated black hole mass that is 4,000,000 times that of the Sun. A long-standing astronomical goal is to resolve structures in the innermost accretion flow surrounding Sgr A*, where strong gravitational fields will distort the appearance of radiation emitted near the black hole. Radio observations at wavelengths of 3.5 mm and 7 mm have detected intrinsic structure in Sgr A*, but the spatial resolution of observations at these wavelengths is limited by interstellar scattering. Here we report observations at a wavelength of 1.3 mm that set a size of 37(+16)(-10) microarcseconds on the intrinsic diameter of Sgr A*. This is less than the expected apparent size of the event horizon of the presumed black hole, suggesting that the bulk of Sgr A* emission may not be centred on the black hole, but arises in the surrounding accretion flow.     

Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protect against malaria

Haemoglobin C, which carries a glutamate-to-lysine mutation in the beta-globin chain, protects West African children against Plasmodium falciparum malaria. Mechanisms of protection are not established for the heterozygous (haemoglobin AC) or homozygous (haemoglobin CC) states. Here we report a marked effect of haemoglobin C on the cell-surface properties of P. falciparum-infected erythrocytes involved in pathogenesis. Relative to parasite-infected normal erythrocytes (haemoglobin AA), parasitized AC and CC erythrocytes show reduced adhesion to endothelial monolayers expressing CD36 and intercellular adhesion molecule-1 (ICAM-1). They also show impaired rosetting interactions with non-parasitized erythrocytes, and reduced agglutination in the presence of pooled sera from malaria-immune adults. Abnormal cell-surface display of the main variable cytoadherence ligand, PfEMP-1 (P. falciparum erythrocyte membrane protein-1), correlates with these findings. The abnormalities in PfEMP-1 display are associated with markers of erythrocyte senescence, and are greater in CC than in AC erythrocytes. Haemoglobin C might protect against malaria by reducing PfEMP-1-mediated adherence of parasitized erythrocytes, thereby mitigating the effects of their sequestration in the microvasculature.     

An empirical test of the mutational landscape model of adaptation using a single-stranded DNA virus

The primary impediment to formulating a general theory for adaptive evolution has been the unknown distribution of fitness effects for new beneficial mutations. By applying extreme value theory, Gillespie circumvented this issue in his mutational landscape model for the adaptation of DNA sequences, and Orr recently extended Gillespie's model, generating testable predictions regarding the course of adaptive evolution. Here we provide the first empirical examination of this model, using a single-stranded DNA bacteriophage related to phiX174, and find that our data are consistent with Orr's predictions, provided that the model is adjusted to incorporate mutation bias. Orr's work suggests that there may be generalities in adaptive molecular evolution that transcend the biological details of a system, but we show that for the model to be useful as a predictive or inferential tool, some adjustments for the biology of the system will be necessary.     

Rapid Manufacturing of Non-Assembly Complex Micro-Devices by Microstereolithography

This paper introduces a non-assembly manufacturing case with microstereolithography technology. The design and manufacturing process of a pneumatic thrust bearing is described, and a special tessellation method is developed to further improve the capability of the manufacturing system thus bigger products can also be easily manufactured. Implemented in a layer-by-layer fashion, stereolithography has been used for the rapid manufacturing of complex devices, and it avoids the expensive assembly process in the traditional manufacturing. This paper presents that microstereolithography can produce high-resolution products with intricate details, small openings, and smooth surfaces. The potential of the microstereolithograhy technique is explored for the rapid manufacturing of small and complex objects.     

Oncogenic pathway signatures in human cancers as a guide to targeted therapies

The development of an oncogenic state is a complex process involving the accumulation of multiple independent mutations that lead to deregulation of cell signalling pathways central to the control of cell growth and cell fate. The ability to define cancer subtypes, recurrence of disease and response to specific therapies using DNA microarray-based gene expression signatures has been demonstrated in multiple studies. Various studies have also demonstrated the potential for using gene expression profiles for the analysis of oncogenic pathways. Here we show that gene expression signatures can be identified that reflect the activation status of several oncogenic pathways. When evaluated in several large collections of human cancers, these gene expression signatures identify patterns of pathway deregulation in tumours and clinically relevant associations with disease outcomes. Combining signature-based predictions across several pathways identifies coordinated patterns of pathway deregulation that distinguish between specific cancers and tumour subtypes. Clustering tumours based on pathway signatures further defines prognosis in respective patient subsets, demonstrating that patterns of oncogenic pathway deregulation underlie the development of the oncogenic phenotype and reflect the biology and outcome of specific cancers. Predictions of pathway deregulation in cancer cell lines are also shown to predict the sensitivity to therapeutic agents that target components of the pathway. Linking pathway deregulation with sensitivity to therapeutics that target components of the pathway provides an opportunity to make use of these oncogenic pathway signatures to guide the use of targeted therapeutics.