Subnanosecond spectral diffusion measurement using photon correlation

Spectral diffusion is a result of random spectral jumps of a narrow line as a result of a fluctuating environment. It is an important issue in spectroscopy, because the observed spectral broadening prevents access to the intrinsic line properties. However, its characteristic parameters provide local information on the environment of a light emitter embedded in a solid matrix, or moving within a fluid, leading to numerous applications in physics and biology. We present a new experimental technique for measuring spectral diffusion based on photon correlations within a spectral line. Autocorrelation on half of the line and cross-correlation between the two halves give a quantitative value of the spectral diffusion time, with a resolution only limited by the correlation set-up. We have measured spectral diffusion of the photoluminescence of a single light emitter with a time resolution of 90 ps, exceeding by four orders of magnitude the best resolution reported to date

Identification of Genetic and Epigenetic Variations in a Rat Model for Neurodevelopmental Disorders

A combination of genetic variations, epimutations and environmental factors may be involved in the etiology of complex neurodevelopmental disorders like schizophrenia. To study such disorders, we use apomorphine-unsusceptible (APO-UNSUS) Wistar rats and their phenotypic counterpart apomorphine-susceptible (APO-SUS) rats that display a complex phenotype remarkably similar to that of schizophrenic patients. As the molecular basis of the APO-SUS/UNSUS rat model, we recently identified a genomic rearrangement of the Aph-1b gene. Here, we discovered between the two rat lines differences other than the Aph-1b gene defect, including a remarkable cluster of genetic variations, two variants corresponding to topoisomerase II-based recombination hot spots and an epigenetic (DNA methylation) difference in cerebellum and (hypo)thalamic but not hippocampal genomic DNA. Furthermore, genetic variations were found to correlate with the degree of apomorphine susceptibility in unselected Wistar rats. Together, the results show that a number of genetic and epigenetic differences exist between the APO-SUS and -UNSUS rat genomes, raising the possibility that in addition to the Aph-1b gene defect the newly identified variations may also contribute to the complex APO-SUS phenotype

Settling Decisions and Heterospecific Social Information Use in Shrikes

Animals often settle near competitors, a behavior known as social attraction, which belies standard habitat selection theory. Two hypotheses account for these observations: individuals obtain Allee benefits mediated by the physical presence of a competitor, or they use successfully settled individual as a source of information indicating the location of high quality habitat. We evaluated these hypotheses experimentally in two species of shrikes. These passerine birds with a raptor-like mode of life impale prey to create larders that serve as an indicator of male/habitat quality. Thus, two forms of indirect information are available in our system: a successfully settled shrike and its larder. Typically these two cues are associated with each other, however, our experimental treatment created an unnatural situation by disassociating them. We manipulated the presence of larders of great grey shrikes and examined the settling decisions of red-backed shrikes within and outside the great grey shrike territories. Male red-backed shrikes did not settle sooner on plots with great grey shrikes compared to plots that only contained artificial larders indicating that red-backed shrikes do not use the physical presence of a great grey shrike when making settling decisions which is inconsistent with the Allee effect hypothesis. In contrast, for all plots without great grey shrikes, red-backed shrikes settled, paired and laid clutches sooner on plots with larders compared to plots without larders. We conclude that red-backed shrikes use larders of great grey shrikes as a cue to rapidly assess habitat quality

Epigenetic reprogramming at estrogen-receptor binding sites alters 3D chromatin landscape in endocrine-resistant breast cancer

Endocrine therapy resistance frequently develops in estrogen receptor positive (ER+) breast cancer, but the underlying molecular mechanisms are largely unknown. Here, we show that 3-dimensional (3D) chromatin interactions both within and between topologically associating domains (TADs) frequently change in ER+ endocrine-resistant breast cancer cells and that the differential interactions are enriched for resistance-associated genetic variants at CTCF-bound anchors. Ectopic chromatin interactions are preferentially enriched at active enhancers and promoters and ER binding sites, and are associated with altered expression of ER-regulated genes, consistent with dynamic remodelling of ER pathways accompanying the development of endocrine resistance. We observe that loss of 3D chromatin interactions often occurs coincidently with hypermethylation and loss of ER binding. Alterations in active A and inactive B chromosomal compartments are also associated with decreased ER binding and atypical interactions and gene expression. Together, our results suggest that 3D epigenome remodelling is a key mechanism underlying endocrine resistance in ER+ breast cancer

Brevicoryne brassicae aphids interfere with transcriptome responses of Arabidopsis thaliana to feeding by Plutella xylostella caterpillars in a density‑dependent manner

Plants are commonly attacked by multiple herbivorous species. Yet, little is known about transcriptional patterns underlying plant responses to multiple insect attackers feeding simultaneously. Here, we assessed= transcriptomic responses of Arabidopsis thaliana plants to simultaneous feeding by Plutella xylostella caterpillars and Brevicoryne brassicae aphids in comparison to plants infested by P. xylostella caterpillars alone, using microarray analysis. We particularly investigated how aphid feeding interferes with the transcriptomic response to P. xylostella caterpillars and whether this interference is dependent on aphid density and time since aphid attack. Various JA-responsive genes were up-regulated in response to feeding by P. xylostella caterpillars. The additional presence of aphids, both at low and high densities, clearly affected the transcriptional plant response to caterpillars. Interestingly, some important modulators of plant defense signalling, including WRKY transcription factor genes and ABA-dependent genes, were differentially induced in response to simultaneous aphid feeding at low or high density compared with responses to P. xylostella caterpillars feeding alone. Furthermore, aphids affected the P. xylostella-induced transcriptomic response in a density dependent manner, which caused an acceleration in plant response against dual insect attack at high aphid density compared to dual insect attack at low aphid density. In conclusion, our study provides evidence that aphids influence the caterpillar-induced transcriptional response of A. thaliana in a density-dependent manner. It highlights the importance of addressing insect density to understand how plant responses to single attackers interfere with responses to other attackers and thus underlines the importance of the dynamics of transcriptional plant responses to multiple herbivory

Differential methylation relative to breast cancer subtype and matched normal tissue reveals distinct patterns

Due to the heterogeneous nature of breast cancer and the widespread use of single-gene studies, there is limited knowledge of multi-gene, locus-specific DNA methylation patterns in relation to molecular subtype and clinical features. We, therefore, quantified DNA methylation of 70 candidate gene loci in 140 breast tumors and matched normal tissues and determined associations with gene expression and tumor subtype. Using Sequenom’s EpiTYPER platform, approximately 1,200CpGs were interrogated and revealed six DNA methylation patterns in breast tumors relative to matched normal tissue. Differential methylation of several gene loci was observed within all molecular subtypes, while other patterns were subtype-dependent. Methylation of numerous gene loci was inversely correlated with gene expression, and in some cases, this correlation was only observed within specific breast tumor subtypes. Our findings were validated on a larger set of tumors and matched adjacent normal tissue from The Cancer Genome Atlas dataset, which utilized methylation data derived from both Illumina Infinium 27 and 450k arrays. These findings highlight the need to control for subtype when interpreting DNA methylation results, and the importance of interrogating multiple CpGs across varied gene regions.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-013-2738-0) contains supplementary material, which is available to authorized users

Estrogen-induced chromatin decondensation and nuclear re-organization linked to regional epigenetic regulation in breast cancer

BACKGROUND: Epigenetic changes are being increasingly recognized as a prominent feature of cancer. This occurs not only at individual genes, but also over larger chromosomal domains. To investigate this, we set out to identify large chromosomal domains of epigenetic dysregulation in breast cancers. RESULTS: We identify large regions of coordinate down-regulation of gene expression, and other regions of coordinate activation, in breast cancers and show that these regions are linked to tumor subtype. In particular we show that a group of coordinately regulated regions are expressed in luminal, estrogen-receptor positive breast tumors and cell lines. For one of these regions of coordinate gene activation, we show that regional epigenetic regulation is accompanied by visible unfolding of large-scale chromatin structure and a repositioning of the region within the nucleus. In MCF7 cells, we show that this depends on the presence of estrogen. CONCLUSIONS: Our data suggest that the liganded estrogen receptor is linked to long-range changes in higher-order chromatin organization and epigenetic dysregulation in cancer. This may suggest that as well as drugs targeting histone modifications, it will be valuable to investigate the inhibition of protein complexes involved in chromatin folding in cancer cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-015-0719-9) contains supplementary material, which is available to authorized users