Fine mapping of variants associated with endometriosis in the WNT4 region on chromosome 1p36

Genome-wide association studies show strong evidence of association with endometriosis for markers on chromosome 1p36 spanning the potential candidate genes WNT4, CDC42 and LINC00339. WNT4 is involved in development of the uterus, and the expression of CDC42 and LINC00339 are altered in women with endometriosis. We conducted fine mapping to examine the role of coding variants in WNT4 and CDC42 and determine the key SNPs with strongest evidence of association in this region. We identified rare coding variants in WNT4 and CDC42 present only in endometriosis cases. The frequencies were low and cannot account for the common signal associated with increased risk of endometriosis. Genotypes for five common SNPs in the region of chromosome 1p36 show stronger association signals when compared with rs7521902 reported in published genome scans. Of these, three SNPs rs12404660, rs3820282, and rs55938609 were located in DNA sequences with potential functional roles including overlap with transcription factor binding sites for FOXA1, FOXA2, ESR1, and ESR2. Functional studies will be required to identify the gene or genes implicated in endometriosis risk

Ink-Jetting of Polymers and Biomaterials

Inkjet printing is a very common and largely developed technology in desktop printers. A wide range of diverse technologies, with different principles of drop generation, fall into the inkjet printing category. Inkjet technology, particularly the drop-on-demand mode for drop generation, is widely applicable in micro/nano electromechanical systems (MEMS/NEMS) and is promising for further developments in this domain. We are investigating the potentials of inkjet printing for the fabrication of MEMS and NEMS as well as life-science applications. We utilise inkjet as a direct-patterning and non-contact method to dispense different polymers, with viscosities ranging from 1-60 mPas with droplet diameters ranging from 30-100 um. In our contribution, we describe applications of ink-jetting of polymers in combination with micro-moulding and on pre-structured substrates. Surface biotechnology is another application range where inkjet is a promising tool for rapid micro-arraying or cell sorting. In our contribution we present the use of inkjet as a tool for chemical dosing of biomaterials, and for transporting and sampling cells. Early results have shown almost no cell damage compared to the control, with printed cells remaining viable

Seasonal Effects on Gene Expression

<div><p>Many health conditions, ranging from psychiatric disorders to cardiovascular disease, display notable seasonal variation in severity and onset. In order to understand the molecular processes underlying this phenomenon, we have examined seasonal variation in the transcriptome of 606 healthy individuals. We show that 74 transcripts associated with a 12-month seasonal cycle were enriched for processes involved in DNA repair and binding. An additional 94 transcripts demonstrated significant seasonal variability that was largely influenced by blood cell count levels. These transcripts were enriched for immune function, protein production, and specific cellular markers for lymphocytes. Accordingly, cell counts for erythrocytes, platelets, neutrophils, monocytes, and CD19 cells demonstrated significant association with a 12-month seasonal cycle. These results demonstrate that seasonal variation is an important environmental regulator of gene expression and blood cell composition. Notable changes in leukocyte counts and genes involved in immune function indicate that immune cell physiology varies throughout the year in healthy individuals.</p></div

Seasonal variation in cell count.

<p>The seasonal variation of five cells that demonstrate significant seasonal variation. The black lines represent the fitted values in a cosinor regression. The red lines represent the actual cell values. From these figures it is evident that the cells follow complex repeating patterns of peaks and troughs throughout the year. However, it can be observed that they show a consistent seasonal trend following one clear peak and trough per year. These values were collected over a three year period and are plotted in sequential order. The year of collection is labeled in the axis as a number (5–8) after the month. This corresponds to the years 2005, 2006, 2007 and 2008 respectively.</p

Gene list enrichment analysis for blood cells.

<p>Enrichment for blood cell signature was found using the userListEnrichment function in the WGCNA R package.</p><p>Gene list enrichment analysis for blood cells.</p

Nanocapsules, Nanocages and Metal-Organic Frameworks from Enantiomerically Pure Benzocyclotrimers

Replying to A. R. Wood et al. 514, http://dx.doi.org/10.1038/nature13691 (2014).We thank Wood et al. for their interesting observations and although their proposed mechanism does not explain all our reported results, we acknowledge that alternative mechanisms could be behind the observation of epistatic signals. Although we replicate our results in large, independent samples, 19/30 of our reported interactions (Table 1 in ref. 2), Wood et al. do not replicate in the InCHIANTI data set (n = 450) at a type-I error rate of 0.05/30 = 0.002, including none of our reported cis-trans interactions. Having insufficient data to replicate the discovery interactions makes it problematic to draw firm conclusions on the reported cis-trans effects