Circadian oscillations of cytosolic free calcium regulate the Arabidopsis circadian clock

In the last decade, the view of circadian oscillators has expanded from transcriptional feedback to incorporate post-transcriptional, post-translational, metabolic processes and ionic signalling. In plants and animals, there are circadian oscillations in the concentration of cytosolic-free Ca2+ ([Ca2+]cyt), though their purpose has not been fully characterised. We investigated whether circadian oscillations of [Ca2+] cyt regulate the circadian oscillator of Arabidopsis thaliana. We report that in Arabidopsis, [Ca2+]cyt circadian oscillations can regulate circadian clock function through the Ca2+-dependent action of CALMODULIN-LIKE24 (CML24). Genetic analyses demonstrate a linkage between CML24 and the circadian oscillator, through pathways involving the circadian oscillator gene TIMING OF CAB2 EXPRESSION1 (TOC1).Supported by BBSRC UK research grants BBSRC BB/D010381/1 (A.N.D.), BB/D017904/1 (F.R.) BB/M00113X/1 (H.J.H.) awarded to (A.A.R.W.), Research Studentship (K.H.) and BBSRC Industrial Case (T.H.). A Swiss Science Foundation Award (PBZHP3-123289) and the Isaac Newton Trust Cambridge (M.C.M.R. and S.A.), 678 the National Science Foundation under Grant No. MCB 0817976 (Y-C.T. and J.B.), a Royal Society Grant RG081257 and Corpus Christi College, Cambridge Junior Research Fellowship (M.J.G.), a Cordenadoria de Apoio ao Ensino Superior Brazil 25681 studentship (C.T.H.), IEF Marrie Curie (Project No. 272186) (M.C.M.R.), a Broodbank Fellowship (M.C.M.R.), a Malaysian Government Studentship (N.I.M-H.)

Standards for plant synthetic biology: A common syntax for exchange of DNA parts

© 2015 New Phytologist Trust. Inventors in the field of mechanical and electronic engineering can access multitudes of components and, thanks to standardization, parts from different manufacturers can be used in combination with each other. The introduction of BioBrick standards for the assembly of characterized DNA sequences was a landmark in microbial engineering, shaping the field of synthetic biology. Here, we describe a standard for Type IIS restriction endonuclease-mediated assembly, defining a common syntax of 12 fusion sites to enable the facile assembly of eukaryotic transcriptional units. This standard has been developed and agreed by representatives and leaders of the international plant science and synthetic biology communities, including inventors, developers and adopters of Type IIS cloning methods. Our vision is of an extensive catalogue of standardized, characterized DNA parts that will accelerate plant bioengineering

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

Circadian and Diurnal Calcium Oscillations Encode Photoperiodic Information in Arabidopsis

We have tested the hypothesis that circadian oscillations in the concentration of cytosolic free calcium ([Ca(2+)](cyt)) can encode information. We imaged oscillations of [Ca(2+)](cyt) in the cotyledons and leaves of Arabidopsis (Arabidopsis thaliana) that have a 24-h period in light/dark cycles and also constant light. The amplitude, phase, and shape of the oscillations of [Ca(2+)](cyt) and [Ca(2+)](cyt) at critical daily time points were controlled by the light/dark regimes in which the plants were grown. These data provide evidence that 24-h oscillations in [Ca(2+)](cyt) encode information concerning daylength and light intensity, which are two major regulators of plant growth and development

Sensors Make Sense of Signaling

Signaling between and within cells involves reversible changes in the activity of chemicals, ions, metabolites and proteins. In this Special Focus Issue we have collected new articles investigating the function of biological sensors that detect these changes that occur during signaling. The Editors were keen also to seek the contribution of articles describing the development and use of man-made sensors to measure the in vivo dynamic changes in metabolites and second messengers. Sensors are components that detect, through binding, alterations in the environment, and transduce those alterations to an output. Endogenous cellular sensors that evoke biological responses and man-made sensors used by the experimentalist to measure signaling events should be capable of quantitative measurement of dynamic changes that can occur in milliseconds and could last for several hours. These sensors must be able to respond to the large fold changes in the concentration of hormones, second messengers, ions and metabolites that can occur in the apoplast and the symplast. The endogenous and man-made sensors also need to be capable of responding to and reporting spatially delimited signaling processes that might be restricted to specific organs, tissues, organelles or a subregion of the cytosol. Spatially delimited sensing can be achieved by cell type expression of endogenous and man-made sensors and subcellular targeting of proteins. Endogenous sensors are often restricted to specific regions of the cytosol by tethering to membranes or other signaling components. Man-made sensors are often based on fluorescent proteins to maintain the spatial fidelity of the reported output of the signal. There are strong parallels in the study of the endogenous sensors honed by evolution and those made by man as tools for the experimentalist because the nature of the signal transduced by the plant, or that detected by the experimentalist, will depend on both the pattern of the signal and the properties of the sensor. This is exemplified by a simple thought experiment in which a cellular gradient of a signal (e.g. second messenger or metabolite; Fig. 1A) is detected by a sensor (e.g. a protein receptor or a fluorescent indicator of biological activity; Fig. 1B). The sensor provides an output dependent on the sensor’s binding affinity for the signal (Fig. 1). The same is true for the measurement of temporal dynamics of changes in signals (Fig. 2A). The full dynamic pattern and temporal extent of the signal might not be accurately reflected by the reporter, depending on the sensor properties (Fig. 2B). Thus, the output from a signaling pathway or experimental analysis will depend on both the dynamics of the signal and the properties of the sensor. This presents challenges for the experimentalist, because one might not be certain of the true concentration and dynamic range of a signal. Experimentalists will have a better chance of correctly interpreting the temporal and spatial dynamics of the signal if they have access to a suite of sensors with a variety of properties. We are pleased that this issue contains reports of several new in vivo man-made sensor technologies. (c) The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists.1