Aneuploidy and cancer

In contrast to normal cells, aneuploidy--alterations in the number of chromosomes--is consistently observed in virtually all cancers. A growing body of evidence suggests that aneuploidy is often caused by a particular type of genetic instability, called chromosomal instability, which may reflect defects in mitotic segregation in cancer cells. A better understanding of the molecular mechanisms leading to aneuploidy holds promise for the development of cancer drugs that target this process.     

Mutations in CLCN2 encoding a voltage-gated chloride channel are associated with idiopathic generalized epilepsies

Idiopathic generalized epilepsy (IGE) is an inherited neurological disorder affecting about 0.4% of the world's population. Mutations in ten genes causing distinct forms of idiopathic epilepsy have been identified so far, but the genetic basis of many IGE subtypes is still unknown. Here we report a gene associated with the four most common IGE subtypes: childhood and juvenile absence epilepsy (CAE and JAE), juvenile myoclonic epilepsy (JME), and epilepsy with grand mal seizures on awakening (EGMA; ref. 8). We identified three different heterozygous mutations in the chloride-channel gene CLCN2 in three unrelated families with IGE. These mutations result in (i) a premature stop codon (M200fsX231), (ii) an atypical splicing (del74-117) and (iii) a single amino-acid substitution (G715E). All mutations produce functional alterations that provide distinct explanations for their pathogenic phenotypes. M200fsX231 and del74-117 cause a loss of function of ClC-2 channels and are expected to lower the transmembrane chloride gradient essential for GABAergic inhibition. G715E alters voltage-dependent gating, which may cause membrane depolarization and hyperexcitability.     

Implementation of the Deutsch-Jozsa algorithm on an ion-trap quantum computer

Determining classically whether a coin is fair (head on one side, tail on the other) or fake (heads or tails on both sides) requires an examination of each side. However, the analogous quantum procedure (the Deutsch-Jozsa algorithm) requires just one examination step. The Deutsch-Jozsa algorithm has been realized experimentally using bulk nuclear magnetic resonance techniques, employing nuclear spins as quantum bits (qubits). In contrast, the ion trap processor utilises motional and electronic quantum states of individual atoms as qubits, and in principle is easier to scale to many qubits. Experimental advances in the latter area include the realization of a two-qubit quantum gate, the entanglement of four ions, quantum state engineering and entanglement-enhanced phase estimation. Here we exploit techniques developed for nuclear magnetic resonance to implement the Deutsch-Jozsa algorithm on an ion-trap quantum processor, using as qubits the electronic and motional states of a single calcium ion. Our ion-based implementation of a full quantum algorithm serves to demonstrate experimental procedures with the quality and precision required for complex computations, confirming the potential of trapped ions for quantum computation.     

The evolutionary origin of complex features

A long-standing challenge to evolutionary theory has been whether it can explain the origin of complex organismal features. We examined this issue using digital organisms--computer programs that self-replicate, mutate, compete and evolve. Populations of digital organisms often evolved the ability to perform complex logic functions requiring the coordinated execution of many genomic instructions. Complex functions evolved by building on simpler functions that had evolved earlier, provided that these were also selectively favoured. However, no particular intermediate stage was essential for evolving complex functions. The first genotypes able to perform complex functions differed from their non-performing parents by only one or two mutations, but differed from the ancestor by many mutations that were also crucial to the new functions. In some cases, mutations that were deleterious when they appeared served as stepping-stones in the evolution of complex features. These findings show how complex functions can originate by random mutation and natural selection.     

Evolution of the polarization of the optical afterglow of the gamma-ray burst GRB030329

The association of a supernova with GRB030329 strongly supports the 'collapsar' model of gamma-ray bursts, where a relativistic jet forms after the progenitor star collapses. Such jets cannot be spatially resolved because gamma-ray bursts lie at cosmological distances; their existence is instead inferred from 'breaks' in the light curves of the afterglows, and from the theoretical desire to reduce the estimated total energy of the burst by proposing that most of it comes out in narrow beams. Temporal evolution of the polarization of the afterglows may provide independent evidence for the jet structure of the relativistic outflow. Small-level polarization ( approximately 1-3 per cent) has been reported for a few bursts, but its temporal evolution has yet to be established. Here we report polarimetric observations of the afterglow of GRB030329. We establish the polarization light curve, detect sustained polarization at the per cent level, and find significant variability. The data imply that the afterglow magnetic field has a small coherence length and is mostly random, probably generated by turbulence, in contrast with the picture arising from the high polarization detected in the prompt gamma-rays from GRB021206 (ref. 18).     

Living planktonic foraminifera from the northwestern Pacific Ocean: SSU rDNA sequences and their paleoceanographic significance

Living planktonic foraminifera (PF) samples from the Okinawa Trough of the northwestern Pacific Ocean were taken for DNA analysis. The SSU rDNA sequences of two PF species, Globigerina sp. and Pulleniatina obliquiloculata collected at Station WP01, were obtained and compared with those from the southwestern Pacific Ocean. Only small differences (<0.7%—1.2% for P. obliquiloculata, and 0.3% for Globigerina sp.) were found between samples from the north- and south-western Pacific Ocean areas and this molecular evidence supported that these micropaleontological species are the same species, which implies that the West Pacific Ocean circulation system influences the planktonic foraminiferal gene communication.     

Linear ubiquitination prevents inflammation and regulates immune signalling

Members of the tumour necrosis factor (TNF) receptor superfamily have important functions in immunity and inflammation. Recently linear ubiquitin chains assembled by a complex containing HOIL-1 and HOIP (also known as RBCK1 and RNF31, respectively) were implicated in TNF signalling, yet their relevance in vivo remained uncertain. Here we identify SHARPIN as a third component of the linear ubiquitin chain assembly complex, recruited to the CD40 and TNF receptor signalling complexes together with its other constituents, HOIL-1 and HOIP. Mass spectrometry of TNF signalling complexes revealed RIP1 (also known as RIPK1) and NEMO (also known as IKKγ or IKBKG) to be linearly ubiquitinated. Mutation of the Sharpin gene (Sharpin(cpdm/cpdm)) causes chronic proliferative dermatitis (cpdm) characterized by inflammatory skin lesions and defective lymphoid organogenesis. Gene induction by TNF, CD40 ligand and interleukin-1β was attenuated in cpdm-derived cells which were rendered sensitive to TNF-induced death. Importantly, Tnf gene deficiency prevented skin lesions in cpdm mice. We conclude that by enabling linear ubiquitination in the TNF receptor signalling complex, SHARPIN interferes with TNF-induced cell death and, thereby, prevents inflammation. Our results provide evidence for the relevance of linear ubiquitination in vivo in preventing inflammation and regulating immune signalling.     

Genetic variegation of clonal architecture and propagating cells in leukaemia

Little is known of the genetic architecture of cancer at the subclonal and single-cell level or in the cells responsible for cancer clone maintenance and propagation. Here we have examined this issue in childhood acute lymphoblastic leukaemia in which the ETV6-RUNX1 gene fusion is an early or initiating genetic lesion followed by a modest number of recurrent or 'driver' copy number alterations. By multiplexing fluorescence in situ hybridization probes for these mutations, up to eight genetic abnormalities can be detected in single cells, a genetic signature of subclones identified and a composite picture of subclonal architecture and putative ancestral trees assembled. Subclones in acute lymphoblastic leukaemia have variegated genetics and complex, nonlinear or branching evolutionary histories. Copy number alterations are independently and reiteratively acquired in subclones of individual patients, and in no preferential order. Clonal architecture is dynamic and is subject to change in the lead-up to a diagnosis and in relapse. Leukaemia propagating cells, assayed by serial transplantation in NOD/SCID IL2Rγ(null) mice, are also genetically variegated, mirroring subclonal patterns, and vary in competitive regenerative capacity in vivo. These data have implications for cancer genomics and for the targeted therapy of cancer.     

维也纳应用科技大学ENERGYbase大楼简析——奥地利首个绿色生态示范办公建筑

通过欧亚太平洋大学联盟国际合作研究项目,对奥地利首个绿色生态示范办公建筑一维也纳ENERGYbase大楼设计理念、可再生能源的利用方式、生态技术设计手段进行了介绍,以使国内建筑师对欧洲生态节能建筑有一个全面的了解．     

Land-atmosphere coupling and climate change in Europe

Increasing greenhouse gas concentrations are expected to enhance the interannual variability of summer climate in Europe and other mid-latitude regions, potentially causing more frequent heatwaves. Climate models consistently predict an increase in the variability of summer temperatures in these areas, but the underlying mechanisms responsible for this increase remain uncertain. Here we explore these mechanisms using regional simulations of recent and future climatic conditions with and without land-atmosphere interactions. Our results indicate that the increase in summer temperature variability predicted in central and eastern Europe is mainly due to feedbacks between the land surface and the atmosphere. Furthermore, they suggest that land-atmosphere interactions increase climate variability in this region because climatic regimes in Europe shift northwards in response to increasing greenhouse gas concentrations, creating a new transitional climate zone with strong land-atmosphere coupling in central and eastern Europe. These findings emphasize the importance of soil-moisture-temperature feedbacks (in addition to soil-moisture-precipitation feedbacks) in influencing summer climate variability and the potential migration of climate zones with strong land-atmosphere coupling as a consequence of global warming. This highlights the crucial role of land-atmosphere interactions in future climate change.