Budding yeast ATM/ATR control meiotic double-strand break (DSB) levels by down-regulating Rec114, an essential component of the DSB-machinery

An essential feature of meiosis is Spo11 catalysis of programmed DNA double strand breaks (DSBs). Evidence suggests that the number of DSBs generated per meiosis is genetically determined and that this ability to maintain a pre-determined DSB level, or "DSB homeostasis", might be a property of the meiotic program. Here, we present direct evidence that Rec114, an evolutionarily conserved essential component of the meiotic DSB-machinery, interacts with DSB hotspot DNA, and that Tel1 and Mec1, the budding yeast ATM and ATR, respectively, down-regulate Rec114 upon meiotic DSB formation through phosphorylation. Mimicking constitutive phosphorylation reduces the interaction between Rec114 and DSB hotspot DNA, resulting in a reduction and/or delay in DSB formation. Conversely, a non-phosphorylatable rec114 allele confers a genome-wide increase in both DSB levels and in the interaction between Rec114 and the DSB hotspot DNA. These observations strongly suggest that Tel1 and/or Mec1 phosphorylation of Rec114 following Spo11 catalysis down-regulates DSB formation by limiting the interaction between Rec114 and DSB hotspots. We also present evidence that Ndt80, a meiosis specific transcription factor, contributes to Rec114 degradation, consistent with its requirement for complete cessation of DSB formation. Loss of Rec114 foci from chromatin is associated with homolog synapsis but independent of Ndt80 or Tel1/Mec1 phosphorylation. Taken together, we present evidence for three independent ways of regulating Rec114 activity, which likely contribute to meiotic DSBs-homeostasis in maintaining genetically determined levels of breaks

X-ray photoemission electron microscopy for the study of semiconductor materials

Photoemission Electron Microscopy (PEEM) using X-rays is a novel combination of two established materials analysis techniques--PEEM using UV light, and Near Edge X-ray Absorption Fine Structure (NEXAFS) spectroscopy. This combination allows the study of elemental composition and bonding structure of the sample by NEXAFS spectroscopy with a high spatial resolution given by the microscope. A simple, two lens, 10 kV operation voltage PEEM has been used at the Stanford Synchrotron Radiation Laboratory and at the Advanced Light Source (ALS) in Berkeley to study various problems including materials of interest for the semiconductor industry. In the present paper the authors give a short overview over the method and the instrument which was used, and describe in detail a number of applications. These applications include the study of the different phases of titanium disilicide, various phases of boron nitride, and the analysis of small particles. A brief outlook is given on possible new fields of application of the PEEM technique, and the development of new PEEM instruments

Ipl1/aurora kinase suppresses S-CDK-driven spindle formation during prophase I to ensure chromosome integrity during meiosis

Cells coordinate spindle formation with DNA repair and morphological modifications to chromosomes prior to their segregation to prevent cell division with damaged chromosomes. Here we uncover a novel and unexpected role for Aurora kinase in preventing the formation of spindles by Clb5-CDK (S-CDK) during meiotic prophase I and when the DDR is active in budding yeast. This is critical since S-CDK is essential for replication during premeiotic S-phase as well as double-strand break induction that facilitates meiotic recombination and, ultimately, chromosome segregation. Furthermore, we find that depletion of Cdc5 polo kinase activity delays spindle formation in DDR-arrested cells and that ectopic expression of Cdc5 in prophase I enhances spindle formation, when Ipl1 is depleted. Our findings establish a new paradigm for Aurora kinase function in both negative and positive regulation of spindle dynamics

Fabrication and characterization of a new high density Sc/Si multilayer sliced grating

State of the art soft x-ray spectroscopy techniques like Resonant Inelastic X-ray Scattering (RIXS) require diffraction gratings which can provide extremely high spectral resolution of 105-106. This problem may be addressed with a sliced multilayer grating with an ultra-high groove density (up to 50,000 mm-1) proposed in the recent publication [Voronov, D. L., Cambie, R., Feshchenko, R. M., Gullikson, E., Padmore, H. A., Vinogradov, A. V., Yashchuk, V. V., Proc. SPIE 6705, 67050E (2007)]. It has been suggested to fabricate such a grating by deposition of a soft x-ray multilayer on a substrate which is a blazed saw-tooth grating (echellette) with low groove density. Subsequent polishing applied to the coated grating removes part of the coating and forms an oblique-cut multiline structure that is a sliced multilayer grating. The resulting grating has a short-scale periodicity of lines (bilayers), which is defined by the multilayer period and the oblique-cut angle. We fabricated and tested a Sc/Si multilayer sliced grating suitable for EUV applications, which is a first prototype based on the suggested technique. In order to fabricate an echellette substrate, we used anisotropic KOH etching of a Si wafer. The etching regime was optimized to obtain smooth and flat echellette facets. A Sc/Si multilayer was deposited by dc-magnetron sputtering, and after that it was mechanically polished using a number of diamond pastes. The resulting sliced grating prototype with ~;;270 nm line period has demonstrated a dispersive ability in the 41-49 nm photon wavelength range with a diffraction efficiency of ~;;7percent for the optimized 38th order assigned to the echellette grating of 10 mu m period

Status of the LBNL normal-conducting CW VHF electron photo-gun

The fabrication and installation at the Lawrence Berkeley National Laboratory of a high-brightness high-repetition rate photo-gun, based on a normal conducting 187 MHz (VHF) RF cavity operating in CW mode, is in an advanced phase. The cavity will generate an electric field at the cathode plane of ∼ 20 MV/m to accelerate the electron bunches up to ∼ 750 keV, with peak current, energy spread and transverse emittance suitable for FEL and ERL applications. The gun vacuum system has been designed for achieving pressures compatible with the use of "delicate" high quantum efficiency semiconductor cathodes to generate up to a nC bunches at MHz repetition rate with present laser technology. Several photo-cathode/laser systems are under consideration, and in particular photo-cathodes based on K CsSb are being developed for the gun and have already achieved a QE of 8% at 532 nm wavelength, or close to 20% including the Schottky barrier lowering. The cathode will be operated by a μJ fiber laser in conjunction with refractive transverse beam shaping to create a flat top transverse profile, as well as a birefringent pulse stacker to create a flat top temporal profile. The present status and the plan for future activities are presented.

Ultra-high Resolution Optics for EUV and Soft X-ray Inelastic Scattering

Abstract. We describe a revolutionary new approach to high spectral resolution soft x-ray optics. Conventionally in the soft x-ray energy range, high spectral resolution is obtained by use of a relatively low line density grating operated in 1 st order with small slits. This severely limits throughput. This limitation can be removed by use of a grating either in very high order, or with very high line density, if one can maintain high diffraction efficiency. We have developed a new technology for achieving both of these goals which should allow high throughput spectroscopy, at resolving powers of up to 10 6 at 1 keV. Such optics should provide a revolutionary advance for high resolution lifetime free spectroscopy, such as RIXS, and for pulse compression of chirped beams. We report recent developmental fabrication and characterization of a prototype grating optimized for 14.2 nm EUV light. The prototype grating with a 200 nm period of the blazed grating substrate coated with 20 Mo/Si bilayers with a period of 7.1 nm demonstrates good dispersion in the third order (effective groove density of 15,000 lines per mm) with a diffraction efficiency of more than 33%

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Frequent and Efficient Use of the Sister Chromatid for DNA Double-Strand Break Repair during Budding Yeast Meiosis

Studies of DNA double-strand break repair during meiosis reveal that a substantial fraction of recombination occurs between sister chromatids