Estrogen receptor alpha (ESR1) gene amplification is frequent in breast cancer

Using an Affymetrix 10K SNP array to screen for gene copy number changes in breast cancer, we detected a single-gene amplification of the ESR1 gene, which encodes estrogen receptor alpha, at 6q25. A subsequent tissue microarray analysis of more than 2,000 clinical breast cancer samples showed ESR1 amplification in 20.6% of breast cancers. Ninety-nine percent of tumors with ESR1 amplification showed estrogen receptor protein overexpression, compared with 66.6% cancers without ESR1 amplification (P < 0.0001). In 175 women who had received adjuvant tamoxifen monotherapy, survival was significantly longer for women with cancer with ESR1 amplification than for women with estrogen receptor-expressing cancers without ESR1 amplification (P = 0.023). Notably, we also found ESR1 amplification in benign and precancerous breast diseases, suggesting that ESR1 amplification may be a common mechanism in proliferative breast disease and a very early genetic alteration in a large subset of breast cancers.     

Voltage-dependent electrogenic chloride/proton exchange by endosomal CLC proteins

Eukaryotic members of the CLC gene family function as plasma membrane chloride channels, or may provide neutralizing anion currents for V-type H(+)-ATPases that acidify compartments of the endosomal/lysosomal pathway. Loss-of-function mutations in the endosomal protein ClC-5 impair renal endocytosis and lead to kidney stones, whereas loss of function of the endosomal/lysosomal protein ClC-7 entails osteopetrosis and lysosomal storage disease. Vesicular CLCs have been thought to be Cl- channels, in particular because ClC-4 and ClC-5 mediate plasma membrane Cl- currents upon heterologous expression. Here we show that these two mainly endosomal CLC proteins instead function as electrogenic Cl-/H+ exchangers (also called antiporters), resembling the transport activity of the bacterial protein ClC-e1, the crystal structure of which has already been determined. Neutralization of a critical glutamate residue not only abolished the steep voltage-dependence of transport, but also eliminated the coupling of anion flux to proton counter-transport. ClC-4 and ClC-5 may still compensate the charge accumulation by endosomal proton pumps, but are expected to couple directly vesicular pH gradients to Cl- gradients.     

Induction of an illusory shadow person

Stimulation of a site on the brain's left hemisphere prompts the creepy feeling that somebody is close by. The strange sensation that somebody is nearby when no one is actually present has been described by psychiatric and neurological patients, as well as by healthy subjects, but it is not understood how the illusion is triggered by the brain. Here we describe the repeated induction of this sensation in a patient who was undergoing presurgical evaluation for epilepsy treatment, as a result of focal electrical stimulation of the left temporoparietal junction: the illusory person closely 'shadowed' changes in the patient's body position and posture. These perceptions may have been due to a disturbance in the multisensory processing of body and self at the temporoparietal junction.     

Is the valid species Synchaeta monopus Plate, 1889 (Rotifera: Monogononta) a product of preparation artefacts?

The morphology of soft-bodied rotifers, including those of Synchaeta spp, can be strongly affected by preparation artefacts including contraction and deformation. The long-standing, valid species Synchaeta monopus is known exclusively from ethanol- or formaldehyde-preserved material and no live specimens of it have ever been described. Although this alone is cause for concern, we could also reproduce unique characteristics diagnostic for this species (e.g. the swollen body and the rudimental foot) by subjecting specimens of Synchaeta pectinata to the preservation conditions under which it was first described. This proxy experiment and comparisons to other Synchaeta species indicate that literature occurrences of S. monopus likely represent preserved and deformed specimens of Synchaeta cecilia or other marine species of Synchaeta, thereby highlighting the importance of thorough morphological investigations of the habitus using live specimens and of features that are unaffected by preservation (e.g. the trophi). We therefore recommend that S. monopus be listed as a species inquirenda until topotypes are examined. Furthermore, in ecological studies including rotifers, where the examination of preserved material is often unavoidable, we stress that light-microscopical images of the habitus and trophi of the specimens minimally be included to facilitate independent verification of the species assignments.     

Maternal signals for progeny prevention against allergy and asthma

Allergy and asthma are chronic inflammatory diseases which result from complex gene–environment interactions. Recent evidence indicates the importance of prenatal and postnatal developmental processes in terms of maturation of balanced immune responses. According to the current view, gene–environment interactions during a restricted time frame are responsible for programming of the immune system in favor of allergic immune mechanisms later in life. The interaction between genes and environment is complex and only partially understood; however, heritable epigenetic modifications including chemical additions in and alternative packaging of the DNA have been shown to play a crucial role in this context. Novel data indicate that epigenetic mechanisms contribute to the development of T-helper cell function. Environmental factors, including diesel exhaust particles (DEP), vitamins and tobacco smoke, operate through such mechanisms. Furthermore, the role of environmental microbes provides another and maybe even more important group of exogenous exposures which operates in this critical time frame.     

Insights from the genome of the biotrophic fungal plant pathogen Ustilago maydis

Ustilago maydis is a ubiquitous pathogen of maize and a well-established model organism for the study of plant-microbe interactions. This basidiomycete fungus does not use aggressive virulence strategies to kill its host. U. maydis belongs to the group of biotrophic parasites (the smuts) that depend on living tissue for proliferation and development. Here we report the genome sequence for a member of this economically important group of biotrophic fungi. The 20.5-million-base U. maydis genome assembly contains 6,902 predicted protein-encoding genes and lacks pathogenicity signatures found in the genomes of aggressive pathogenic fungi, for example a battery of cell-wall-degrading enzymes. However, we detected unexpected genomic features responsible for the pathogenicity of this organism. Specifically, we found 12 clusters of genes encoding small secreted proteins with unknown function. A significant fraction of these genes exists in small gene families. Expression analysis showed that most of the genes contained in these clusters are regulated together and induced in infected tissue. Deletion of individual clusters altered the virulence of U. maydis in five cases, ranging from a complete lack of symptoms to hypervirulence. Despite years of research into the mechanism of pathogenicity in U. maydis, no 'true' virulence factors had been previously identified. Thus, the discovery of the secreted protein gene clusters and the functional demonstration of their decisive role in the infection process illuminate previously unknown mechanisms of pathogenicity operating in biotrophic fungi. Genomic analysis is, similarly, likely to open up new avenues for the discovery of virulence determinants in other pathogens.     

Tonks-Girardeau gas of ultracold atoms in an optical lattice

Strongly correlated quantum systems are among the most intriguing and fundamental systems in physics. One such example is the Tonks-Girardeau gas, proposed about 40 years ago, but until now lacking experimental realization; in such a gas, the repulsive interactions between bosonic particles confined to one dimension dominate the physics of the system. In order to minimize their mutual repulsion, the bosons are prevented from occupying the same position in space. This mimics the Pauli exclusion principle for fermions, causing the bosonic particles to exhibit fermionic properties. However, such bosons do not exhibit completely ideal fermionic (or bosonic) quantum behaviour; for example, this is reflected in their characteristic momentum distribution. Here we report the preparation of a Tonks-Girardeau gas of ultracold rubidium atoms held in a two-dimensional optical lattice formed by two orthogonal standing waves. The addition of a third, shallower lattice potential along the long axis of the quantum gases allows us to enter the Tonks-Girardeau regime by increasing the atoms' effective mass and thereby enhancing the role of interactions. We make a theoretical prediction of the momentum distribution based on an approach in which trapped bosons acquire fermionic properties, finding that it agrees closely with the measured distribution.     

Architecture and material properties of diatom shells provide effective mechanical protection

Diatoms are the major contributors to phytoplankton blooms in lakes and in the sea and hence are central in aquatic ecosystems and the global carbon cycle. All free-living diatoms differ from other phytoplankton groups in having silicified cell walls in the form of two 'shells' (the frustule) of manifold shape and intricate architecture whose function and role, if any, in contributing to the evolutionary success of diatoms is under debate. We explored the defence potential of the frustules as armour against predators by measuring their strength. Real and virtual loading tests (using calibrated glass microneedles and finite element analysis) were performed on centric and pennate diatom cells. Here we show that the frustules are remarkably strong by virtue of their architecture and the material properties of the diatom silica. We conclude that diatom frustules have evolved as mechanical protection for the cells because exceptional force is required to break them. The evolutionary arms race between diatoms and their specialized predators will have had considerable influence in structuring pelagic food webs and biogeochemical cycles.     

Spatial quantum noise interferometry in expanding ultracold atom clouds

In a pioneering experiment, Hanbury Brown and Twiss (HBT) demonstrated that noise correlations could be used to probe the properties of a (bosonic) particle source through quantum statistics; the effect relies on quantum interference between possible detection paths for two indistinguishable particles. HBT correlations--together with their fermionic counterparts--find numerous applications, ranging from quantum optics to nuclear and elementary particle physics. Spatial HBT interferometry has been suggested as a means to probe hidden order in strongly correlated phases of ultracold atoms. Here we report such a measurement on the Mott insulator phase of a rubidium Bose gas as it is released from an optical lattice trap. We show that strong periodic quantum correlations exist between density fluctuations in the expanding atom cloud. These spatial correlations reflect the underlying ordering in the lattice, and find a natural interpretation in terms of a multiple-wave HBT interference effect. The method should provide a useful tool for identifying complex quantum phases of ultracold bosonic and fermionic atoms.