DNA methylation epigenetically silences crossover hot spots and controls chromosomal domains of meiotic recombination in Arabidopsis.

During meiosis, homologous chromosomes undergo crossover recombination, which is typically concentrated in narrow hot spots that are controlled by genetic and epigenetic information. Arabidopsis chromosomes are highly DNA methylated in the repetitive centromeres, which are also crossover-suppressed. Here we demonstrate that RNA-directed DNA methylation is sufficient to locally silence Arabidopsis euchromatic crossover hot spots and is associated with increased nucleosome density and H3K9me2. However, loss of CG DNA methylation maintenance in met1 triggers epigenetic crossover remodeling at the chromosome scale, with pericentromeric decreases and euchromatic increases in recombination. We used recombination mutants that alter interfering and noninterfering crossover repair pathways (fancm and zip4) to demonstrate that remodeling primarily involves redistribution of interfering crossovers. Using whole-genome bisulfite sequencing, we show that crossover remodeling is driven by loss of CG methylation within the centromeric regions. Using cytogenetics, we profiled meiotic DNA double-strand break (DSB) foci in met1 and found them unchanged relative to wild type. We propose that met1 chromosome structure is altered, causing centromere-proximal DSBs to be inhibited from maturation into interfering crossovers. These data demonstrate that DNA methylation is sufficient to silence crossover hot spots and plays a key role in establishing domains of meiotic recombination along chromosomes.We thank Korbinian Schneeberger and Beth Rowan for advice implementing TIGER and Ler polymorphism data, Donna Bond for pJawohl-Act2, Quentin Gouil for the bisulfite sequencing protocol, Simon Andrews and Felix Krueger for advice using SeqMonk, Gregory Copenhaver and Avi Levy for fluorescent lines, Raphael Mercier for zip4-2 fancm-1, Chris Franklin for the ASY1 antibody, and the Gurdon Institute Imaging Facility for access to microscopes. Research was supported by a Broodbank Fellowship (to N.E.Y.), a Royal Society University Research Fellowship (to I.R.H.), grant GAT2962 from the Gatsby Charitable Foundation (to I.R.H.), and Biotechnology and Biological Sciences Research Council grant BB/L006847/1 (to I.R.H.).This is the final version of the article. It first appeared from Cold Spring Habour Laboratory Press via http://dx.doi.org/10.1101/gad.270876.11

WebCSD: the online portal to the Cambridge Structural Database

The new web-based application WebCSD is introduced, which provides a range of facilities for searching the Cambridge Structural Database within a standard web browser. Search options within WebCSD include two-dimensional substructure, molecular similarity, text/numeric and reduced cell searching

Spectral Analysis of the September 2017 Solar Energetic Particle Events

An interval of exceptional solar activity was registered in early September 2017, late in the decay phase of solar cycle 24, involving the complex Active Region 12673 as it rotated across the western hemisphere with respect to Earth. A large number of eruptions occurred between 4 and 10 September, including four associated with Xclass flares. The X9.3 flare on 6 September and the X8.2 flare on 10 September are currently the two largest during cycle 24. Both were accompanied by fast coronal mass ejections and gave rise to solar energetic particle (SEP) events measured by nearEarth spacecraft. In particular, the partially occulted solar event on 10 September triggered a groundlevel enhancement (GLE), the second GLE of cycle 24. A further, much less energetic SEP event was recorded on 4 September. In this work we analyze observations by the Advanced Composition Explorer (ACE) and the Geostationary Operational Environmental Satellites (GOES), estimating the SEP eventintegrated spectra above 300 keV and carrying out a detailed study of the spectral shape temporal evolution. Derived spectra are characterized by a lowenergy break at few/tens of MeV; the 10 September event spectrum, extending up to 1 GeV, exhibits an additional rollover at several hundred MeV. We discuss the spectral interpretation in the scenario of shock acceleration and in terms of other important external influences related to interplanetary transport and magnetic connectivity, taking advantage of multipoint observations from the Solar Terrestrial Relations Observatory. Spectral results are also compared with those obtained for the 17 May 2012 GLE event

Guidance for laboratories performing molecular pathology for cancer patients

Molecular testing is becoming an important part of the diagnosis of any patient with cancer. The challenge to laboratories is to meet this need, using reliable methods and processes to ensure that patients receive a timely and accurate report on which their treatment will be based. The aim of this paper is to provide minimum requirements for the management of molecular pathology laboratories. This general guidance should be augmented by the specific guidance available for different tumour types and tests. Preanalytical considerations are important, and careful consideration of the way in which specimens are obtained and reach the laboratory is necessary. Sample receipt and handling follow standard operating procedures, but some alterations may be necessary if molecular testing is to be performed, for instance to control tissue fixation. DNA and RNA extraction can be standardised and should be checked for quality and quantity of output on a regular basis. The choice of analytical method(s) depends on clinical requirements, desired turnaround time, and expertise available. Internal quality control, regular internal audit of the whole testing process, laboratory accreditation, and continual participation in external quality assessment schemes are prerequisites for delivery of a reliable service. A molecular pathology report should accurately convey the information the clinician needs to treat the patient with sufficient information to allow for correct interpretation of the result. Molecular pathology is developing rapidly, and further detailed evidence-based recommendations are required for many of the topics covered here

Wide Distribution of a High-Virulence Borrelia burgdorferi Clone in Europe and North America

We found substantial population differentiation and recent trans-Atlantic dispersal of a high-virulence B. burgdorferi clone