A role for cell-cycle-regulated histone H3 lysine 56 acetylation in the DNA damage response

DNA breaks are extremely harmful lesions that need to be repaired efficiently throughout the genome. However, the packaging of DNA into nucleosomes is a significant barrier to DNA repair, and the mechanisms of repair in the context of chromatin are poorly understood. Here we show that lysine 56 (K56) acetylation is an abundant modification of newly synthesized histone H3 molecules that are incorporated into chromosomes during S phase. Defects in the acetylation of K56 in histone H3 result in sensitivity to genotoxic agents that cause DNA strand breaks during replication. In the absence of DNA damage, the acetylation of histone H3 K56 largely disappears in G2. In contrast, cells with DNA breaks maintain high levels of acetylation, and the persistence of the modification is dependent on DNA damage checkpoint proteins. We suggest that the acetylation of histone H3 K56 creates a favourable chromatin environment for DNA repair and that a key component of the DNA damage response is to preserve this acetylation.     

Direct observation of Anderson localization of matter waves in a controlled disorder

In 1958, Anderson predicted the localization of electronic wavefunctions in disordered crystals and the resulting absence of diffusion. It is now recognized that Anderson localization is ubiquitous in wave physics because it originates from the interference between multiple scattering paths. Experimentally, localization has been reported for light waves, microwaves, sound waves and electron gases. However, there has been no direct observation of exponential spatial localization of matter waves of any type. Here we observe exponential localization of a Bose-Einstein condensate released into a one-dimensional waveguide in the presence of a controlled disorder created by laser speckle. We operate in a regime of pure Anderson localization, that is, with weak disorder-such that localization results from many quantum reflections of low amplitude-and an atomic density low enough to render interactions negligible. We directly image the atomic density profiles as a function of time, and find that weak disorder can stop the expansion and lead to the formation of a stationary, exponentially localized wavefunction-a direct signature of Anderson localization. We extract the localization length by fitting the exponential wings of the profiles, and compare it to theoretical calculations. The power spectrum of the one-dimensional speckle potentials has a high spatial frequency cutoff, causing exponential localization to occur only when the de Broglie wavelengths of the atoms in the expanding condensate are greater than an effective mobility edge corresponding to that cutoff. In the opposite case, we find that the density profiles decay algebraically, as predicted in ref. 13. The method presented here can be extended to localization of atomic quantum gases in higher dimensions, and with controlled interactions.     

Spink5-deficient mice mimic Netherton syndrome through degradation of desmoglein 1 by epidermal protease hyperactivity

Mutations in SPINK5, encoding the serine protease inhibitor LEKTI, cause Netherton syndrome, a severe autosomal recessive genodermatosis. Spink5(-/-) mice faithfully replicate key features of Netherton syndrome, including altered desquamation, impaired keratinization, hair malformation and a skin barrier defect. LEKTI deficiency causes abnormal desmosome cleavage in the upper granular layer through degradation of desmoglein 1 due to stratum corneum tryptic enzyme and stratum corneum chymotryptic enzyme-like hyperactivity. This leads to defective stratum corneum adhesion and resultant loss of skin barrier function. Profilaggrin processing is increased and implicates LEKTI in the cornification process. This work identifies LEKTI as a key regulator of epidermal protease activity and degradation of desmoglein 1 as the primary pathogenic event in Netherton syndrome.     

MODELING COMMERCIAL PROCESSES AND CUSTOMER BEHAVIORS TO ESTIMATE THE DIFFUSION RATE OF NEW PRODUCTS

1. Introduction In his famous seminal book (Rogers 1962), Rogers introduced and popularized a generic framework for analyzing and describing how the mechanism of diffusion of innovations works inside a given population. In this general approach, “innovation” can of course be understood in a large way: it may indeed referto various contexts such as the learning of a new practice, the use of a new tool, the launch of a new product, etc. The strength of Rogers' point of view comes from the fac…     

The auroral footprint of Enceladus on Saturn

Although there are substantial differences between the magnetospheres of Jupiter and Saturn, it has been suggested that cryovolcanic activity at Enceladus could lead to electrodynamic coupling between Enceladus and Saturn like that which links Jupiter with Io, Europa and Ganymede. Powerful field-aligned electron beams associated with the Io-Jupiter coupling, for example, create an auroral footprint in Jupiter's ionosphere. Auroral ultraviolet emission associated with Enceladus-Saturn coupling is anticipated to be just a few tenths of a kilorayleigh (ref. 12), about an order of magnitude dimmer than Io's footprint and below the observable threshold, consistent with its non-detection. Here we report the detection of magnetic-field-aligned ion and electron beams (offset several moon radii downstream from Enceladus) with sufficient power to stimulate detectable aurora, and the subsequent discovery of Enceladus-associated aurora in a few per cent of the scans of the moon's footprint. The footprint varies in emission magnitude more than can plausibly be explained by changes in magnetospheric parameters--and as such is probably indicative of variable plume activity.