Psoriasis is associated with increased beta-defensin genomic copy number

Psoriasis is a common inflammatory skin disease with a strong genetic component. We analyzed the genomic copy number polymorphism of the beta-defensin region on human chromosome 8 in 179 Dutch individuals with psoriasis and 272 controls and in 319 German individuals with psoriasis and 305 controls. Comparisons in both cohorts showed a significant association between higher genomic copy number for beta-defensin genes and risk of psoriasis.     

Consensus supertrees: The synthesis of rooted trees containing overlapping sets of labeled leaves

Given two dendrograms (rooted tree diagrams) which have some but not all of their base points in common, a supertree is a dendrogram from which each of the original trees can be regarded as samples The distinction is made between inconsistent and consistent sample trees, defined by whether or not the samples provide contradictory information about the supertree An algorithm for obtaining the strict consensus supertree of two consistent sample trees is presented, as are procedures for merging two inconsistent sample trees Some suggestions for future work are made     

De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes

Megalencephaly-capillary malformation (MCAP) and megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndromes are sporadic overgrowth disorders associated with markedly enlarged brain size and other recognizable features. We performed exome sequencing in 3 families with MCAP or MPPH, and our initial observations were confirmed in exomes from 7 individuals with MCAP and 174 control individuals, as well as in 40 additional subjects with megalencephaly, using a combination of Sanger sequencing, restriction enzyme assays and targeted deep sequencing. We identified de novo germline or postzygotic mutations in three core components of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway. These include 2 mutations in AKT3, 1 recurrent mutation in PIK3R2 in 11 unrelated families with MPPH and 15 mostly postzygotic mutations in PIK3CA in 23 individuals with MCAP and 1 with MPPH. Our data highlight the central role of PI3K-AKT signaling in vascular, limb and brain development and emphasize the power of massively parallel sequencing in a challenging context of phenotypic and genetic heterogeneity combined with postzygotic mosaicism.     

Cooling a nanomechanical resonator with quantum back-action

Quantum mechanics demands that the act of measurement must affect the measured object. When a linear amplifier is used to continuously monitor the position of an object, the Heisenberg uncertainty relationship requires that the object be driven by force impulses, called back-action. Here we measure the back-action of a superconducting single-electron transistor (SSET) on a radio-frequency nanomechanical resonator. The conductance of the SSET, which is capacitively coupled to the resonator, provides a sensitive probe of the latter's position; back-action effects manifest themselves as an effective thermal bath, the properties of which depend sensitively on SSET bias conditions. Surprisingly, when the SSET is biased near a transport resonance, we observe cooling of the nanomechanical mode from 550 mK to 300 mK--an effect that is analogous to laser cooling in atomic physics. Our measurements have implications for nanomechanical readout of quantum information devices and the limits of ultrasensitive force microscopy (such as single-nuclear-spin magnetic resonance force microscopy). Furthermore, we anticipate the use of these back-action effects to prepare ultracold and quantum states of mechanical structures, which would not be accessible with existing technology.