Genomic evidence for elevated mutation rates in highly expressed genes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102069/1/embr2012165.reviewer_comments.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102069/2/embr2012165-sup-0001.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102069/3/embr2012165.pd

Screening for type 2 diabetes is feasible, acceptable, but associated with increased short-term anxiety: A randomised controlled trial in British general practice

Background To assess the feasibility and uptake of a diabetes screening programme; to examine the effects of invitation to diabetes screening on anxiety, self-rated health and illness perceptions. Methods Randomised controlled trial in two general practices in Cambridgeshire. Individuals aged 40–69 without known diabetes were identified as being at high risk of having undiagnosed type 2 diabetes using patient records and a validated risk score (n = 1,280). 355 individuals were randomised in a 2 to 1 ratio into non-invited (n = 238) and invited (n = 116) groups. A stepwise screening programme confirmed the presence or absence of diabetes. Six weeks after the last contact (either test or invitation), a questionnaire was sent to all participants, including non-attenders and those who were not originally invited. Outcome measures included attendance, anxiety (short-form Spielberger State Anxiety Inventory-STAI), self-rated health and diabetes illness perceptions. Results 95 people (82% of those invited) attended for the initial capillary blood test. Six individuals were diagnosed with diabetes. Invited participants were more anxious than those not invited (37.6 vs. 34.1 STAI, p-value = 0.015), and those diagnosed with diabetes were considerably more anxious than those classified free of diabetes (46.7 vs. 37.0 STAI, p-value = 0.031). Non-attenders had a higher mean treatment control sub-scale (3.87 vs. 3.56, p-value = 0.016) and a lower mean emotional representation sub-scale (1.81 vs. 2.68, p-value = 0.001) than attenders. No differences in the other five illness perception sub-scales or self-rated health were found. Conclusion Screening for type 2 diabetes in primary care is feasible but may be associated with higher levels of short-term anxiety among invited compared with non-invited participants. Trial registration ISRCTN9917549

Gravel pits support waterbird diversity in an urban landscape

We assessed the benefit of 11 gravel pits for the settlement of waterbird communities in an urbanized area lacking natural wetlands. Gravel pits captured 57% of the regional species pool of aquatic birds. We identified 39 species, among which five were regionally rare. We used the Self Organizing Map algorithm to calculate the probabilities of presence of species, and to bring out habitat conditions that predict assemblage patterns. The age of the pits did not correlate with assemblage composition and species richness. There was a positive influence of macrophyte cover on waterbird species richness. Larger pits did not support more species, but species richness increased with connectivity. As alternative wetland habitats, gravel pits are attractive to waterbirds, when they act as stepping stones that ensure connectivity between larger natural and/or artificial wetlands separated in space

Shape-based peak identification for ChIP-Seq

We present a new algorithm for the identification of bound regions from ChIP-seq experiments. Our method for identifying statistically significant peaks from read coverage is inspired by the notion of persistence in topological data analysis and provides a non-parametric approach that is robust to noise in experiments. Specifically, our method reduces the peak calling problem to the study of tree-based statistics derived from the data. We demonstrate the accuracy of our method on existing datasets, and we show that it can discover previously missed regions and can more clearly discriminate between multiple binding events. The software T-PIC (Tree shape Peak Identification for ChIP-Seq) is available at http://math.berkeley.edu/~vhower/tpic.htmlComment: 12 pages, 6 figure

Molecular Valves for Controlling Gas Phase Transport Made from Discrete Angstrom-Sized Pores in Graphene

An ability to precisely regulate the quantity and location of molecular flux is of value in applications such as nanoscale 3D printing, catalysis, and sensor design. Barrier materials containing pores with molecular dimensions have previously been used to manipulate molecular compositions in the gas phase, but have so far been unable to offer controlled gas transport through individual pores. Here, we show that gas flux through discrete angstrom-sized pores in monolayer graphene can be detected and then controlled using nanometer-sized gold clusters, which are formed on the surface of the graphene and can migrate and partially block a pore. In samples without gold clusters, we observe stochastic switching of the magnitude of the gas permeance, which we attribute to molecular rearrangements of the pore. Our molecular valves could be used, for example, to develop unique approaches to molecular synthesis that are based on the controllable switching of a molecular gas flux, reminiscent of ion channels in biological cell membranes and solid state nanopores.Comment: to appear in Nature Nanotechnolog

Logarithmic Corrections to Schwarzschild and Other Non-extremal Black Hole Entropy in Different Dimensions

Euclidean gravity method has been successful in computing logarithmic corrections to extremal black hole entropy in terms of low energy data, and gives results in perfect agreement with the microscopic results in string theory. Motivated by this success we apply Euclidean gravity to compute logarithmic corrections to the entropy of various non-extremal black holes in different dimensions, taking special care of integration over the zero modes and keeping track of the ensemble in which the computation is done. These results provide strong constraint on any ultraviolet completion of the theory if the latter is able to give an independent computation of the entropy of non-extremal black holes from microscopic description. For Schwarzschild black holes in four space-time dimensions the macroscopic result seems to disagree with the existing result in loop quantum gravity.Comment: LaTeX, 40 pages; corrected small typos and added reference

In an in vitro model of human tuberculosis, monocyte-microglial networks regulate matrix metalloproteinase-1 and -3 gene expression and secretion via a p38 mitogen activated protein kinase-dependent pathway.

BACKGROUND: Tuberculosis (TB) of the central nervous system (CNS) is characterized by extensive tissue inflammation, driven by molecules that cleave extracellular matrix such as matrix metalloproteinase (MMP)-1 and MMP-3. However, relatively little is known about the regulation of these MMPs in the CNS. METHODS: Using a cellular model of CNS TB, we stimulated a human microglial cell line (CHME3) with conditioned medium from Mycobacterium tuberculosis-infected primary human monocytes (CoMTb). MMP-1 and MMP-3 secretion was detected using ELISAs confirmed with casein zymography or western blotting. Key results of a phospho-array profile that detects a wide range of kinase activity were confirmed with phospho-Western blotting. Chemical inhibition (SB203580) of microglial cells allowed investigation of expression and secretion of MMP-1 and MMP-3. Finally we used promoter reporter assays employing full length and MMP-3 promoter deletion constructs. Student's t-test was used for comparison of continuous variables and multiple intervention experiments were compared by one-way ANOVA with Tukey's correction for multiple pairwise comparisons. RESULTS: CoMTb up-regulated microglial MMP-1 and MMP-3 secretion in a dose- and time-dependent manner. The phospho-array profiling showed that the major increase in kinase activity due to CoMTb stimulation was in p38 mitogen activated protein kinase (MAPK), principally the α and γ subunits. p38 phosphorylation was detected at 15 minutes, with a second peak of activity at 120 minutes. High basal extracellular signal-regulated kinase activity was further increased by CoMTb. Secretion and expression of MMP-1 and MMP-3 were both p38 dependent. CoMTb stimulation of full length and MMP-3 promoter deletion constructs demonstrated up-regulation of activity in the wild type but a suppression site between -2183 and -1612 bp. CONCLUSIONS: Monocyte-microglial network-dependent MMP-1 and MMP-3 gene expression and secretion are dependent upon p38 MAPK in tuberculosis. p38 is therefore a potential target for adjuvant therapy in CNS TB

Spectroscopic analysis of finite size effects around a Kondo quantum dot

We consider a simple setup in which a small quantum dot is strongly connected to a finite size box. This box can be either a metallic box or a finite size quantum wire.The formation of the Kondo screening cloud in the box strongly depends on the ratio between the Kondo temperature and the box level spacing. By weakly connecting two metallic reservoirs to the quantum dot, a detailed spectroscopic analysis can be performed. Since the transport channels and the screening channels are almost decoupled, such a setup allows an easier access to the measure of finite-size effects associated with the finite extension of the Kondo cloud.Comment: contribution to Les Houches proceeding, ``Quantum magnetism'' 200