Site-Specific Cleavage by Topoisomerase 2: A Mark of the Core Centromere.

In addition to its roles in transcription and replication, topoisomerase 2 (topo 2) is crucial in shaping mitotic chromosomes and in ensuring the orderly separation of sister chromatids. As well as its recruitment throughout the length of the mitotic chromosome, topo 2 accumulates at the primary constriction. Here, following cohesin release, the enzymatic activity of topo 2 acts to remove residual sister catenations. Intriguingly, topo 2 does not bind and cleave all sites in the genome equally; one preferred site of cleavage is within the core centromere. Discrete topo 2-centromeric cleavage sites have been identified in α-satellite DNA arrays of active human centromeres and in the centromere regions of some protozoans. In this study, we show that topo 2 cleavage sites are also a feature of the centromere in Schizosaccharomyces pombe, the metazoan Drosophila melanogaster and in another vertebrate species, Gallus gallus (chicken). In vertebrates, we show that this site-specific cleavage is diminished by depletion of CENP-I, an essential constitutive centromere protein. The presence, within the core centromere of a wide range of eukaryotes, of precise sites hypersensitive to topo 2 cleavage suggests that these mark a fundamental and conserved aspect of this functional domain, such as a non-canonical secondary structure

Circulating LH/hCG receptor (LHCGR) may identify pre-treatment IVF patients at risk of OHSS and poor implantation

<p>Abstract</p> <p>Background</p> <p>Successful pregnancy via <it>in vitro </it>fertilization (IVF) depends on the recovery of an adequate number of healthy oocytes and on blastocyst implantation following uterine transfer. Two hormones, LH and hCG, utilize a common LH/hCG receptor (LHCGR), variations in which have profound implications in human reproduction. Soluble LHCGR (sLHCGR) is released from experimental cell lines and placental explants and it can be detected in the follicular fluid and serum.</p> <p>Methods</p> <p>To evaluate the impact of circulating soluble LHCGR (sLHCGR) in fertility treatment, we measured sLHCGR and LH-sLHCGR complex in serum from women seeking IVF using specifically developed quantitative enzyme-linked immunosorbent assays (ELISA). Following an IVF cycle of treatment, patients were grouped according to oocyte yield into low (lower than or equal to 7 oocytes), intermediate (8-14 oocytes) and high (greater than or equal to 15 oocytes) responders and pregnancy outcome noted.</p> <p>Results</p> <p>Pre-treatment sLHCGR identified many women at risk of ovarian hyperstimulation. Low levels of sLHCGR were associated with pregnancy in both high and low responders but sLHCGR did not significantly affect the treatment outcome of intermediate responders. Low responders who failed to become pregnant had high levels of circulating sLHCGR bound to LH (LH-sLHCGR).</p> <p>Conclusions</p> <p>Pre-treatment measurement of sLHCGR could be used to tailor individual fertility treatment programs and improve outcomes by avoiding ovarian hyperstimulation and poor embryo implantation.</p

Threats for Global Food Supply of Increasing Surface Ozone - Spatial Assessment of Impacts and Adaptation Options

Surface ozone (O3) is a potent phytotoxic air pollutant and significantly reduces the productivity of important agricultural crops. Growing use of fossil fuel and changes in climate are increasing the global background surface ozone concentrations to levels that threaten regional and global food supply. We performed an integrated modeling study, considering biophysical and crop management factors, to identify the spatial pattern of ozone damage in lands suitable for crop cultivation and to assess the potential for adaptation for four key crops (wheat, maize, rice and soybean) under current and future air quality legislation. Results indicate that China, India and the United States are by far the most affected countries, bearing more than half of all global losses and threatened areas. Short-erm adaptive measures at farm level, such as shifting crop calendars (by changing sowing dates or using crop cultivars with different cycle lengths) can reduce ozone damage regionally but have only limited impact at the global level. Considering these limited benefits of adaptation, mitigation of O3 precursors remains the main option to secure regional and global food production

Maternally and paternally silenced imprinted genes differ in their intron content.

Imprinted genes exhibit silencing of one of the parental alleles during embryonic development. In a previous study imprinted genes were found to have reduced intron content relative to a non-imprinted control set (Hurst et al., 1996). However, due to the small sample size, it was not possible to analyse the source of this effect. Here, we re-investigate this observation using larger datasets of imprinted and control (non-imprinted) genes that allow us to consider mouse and human, and maternally and paternally silenced, imprinted genes separately. We find that, in the human and mouse, there is reduced intron content in the maternally silenced imprinted genes relative to a non-imprinted control set. Among imprinted genes, a strong bias is also observed in the distribution of intronless genes, which are found exclusively in the maternally silenced dataset. The paternally silenced dataset in the human is not different to the control set; however, the mouse paternally silenced dataset has more introns than the control group. A direct comparison of mouse maternally and paternally silenced imprinted gene datasets shows that they differ significantly with respect to a variety of intron-related parameters. We discuss a variety of possible explanations for our observations.Peer Reviewe

Clustered Star Formation in the Center of NGC 253 Contributes to Driving the Ionized Nuclear Wind

We present new 3 mm observations of the ionized gas toward the nuclear starburst in the nearby (D similar to 3.5 Mpc) galaxy NGC 253. With ALMA, we detect emission from the H40 alpha and He40 alpha lines in the central 200 pc of this galaxy on spatial scales of similar to 4 pc. The recombination line emission primarily originates from a population of approximately a dozen embedded super star clusters in the early stages of formation. We find that emission from these clusters is characterized by electron temperatures ranging from 7000 to 10,000 K and measures an average singly ionized helium abundance Y (+) = 0.25 +/- 0.06, both of which are consistent with values measured for H ii regions in the center of the Milky Way. We also report the discovery of unusually broad line width recombination line emission originating from seven of the embedded clusters. We suggest that these clusters contribute to the launching of the large-scale hot wind observed to emanate from the central starburst. Finally, we use the measured recombination line fluxes to improve the characterization of overall embedded cluster properties, including the distribution of cluster masses and the fractional contribution of the clustered star formation to the total starburst, which we estimate is at least 50%.Peer reviewe

Knowledge, Perceptions and Information about Hormone Therapy (HT) among Menopausal Women: A Systematic Review and Meta-Synthesis

BACKGROUND: The use of hormone therapy (HT) by menopausal women has declined since the Women's Health Initiative randomized trial (WHI) in 2002 demonstrated important harms associated with long-term use. However, how this information has influenced women's knowledge and attitudes is uncertain. We aimed to evaluate the attitudes and perceptions towards HT use, as well as specific concerns and information sources on HT since the WHI trial. METHOD/RESULTS: We did a systematic review to assess the attitudes and knowledge towards HT in women, and estimate the magnitude of the issue by pooling across the studies. Using meta-synthesis methods, we reviewed qualitative studies and surveys and performed content analysis on the study reports. We pooled quantitative studies using a random-effects meta-analysis. We analyzed 11 qualitative studies (n = 566) and 27 quantitative studies (n = 39251). Positive views on HT included climacteric symptom control, prevention of osteoporosis and a perceived improvement in quality of life. Negative factors reported included concerns about potential harmful effects, particularly cancer risks. Sources of information included health providers, media, and social contact. By applying a meta-synthesis approach we demonstrate that these findings are broadly applicable across large groups of patients. CONCLUSIONS: Although there are clear hazards associated with long-term HT use, many women view HT favorably for climacteric symptom relief. Media, as a source of information, is often valued as equivalent to health providers

RC J0311+0507: A Candidate for Superpowerful Radio Galaxies in the Early Universe at Redshift z=4.514

A strong emission line at 6703A has been detected in the optical spectrum for the host galaxy (R=23.1) of the radio source RC J0311+0507 (4C+04.11). This radio galaxy, with a spectral index of 1.31 in the frequency range 365-4850 MHz, is one of the ultrasteep spectrum objects from the deep survey of a sky strip conducted with RATAN-600 in 1980-1981. We present arguments in favor of the identification of this line with Ly\alpha at redshift z=4.514. In this case, the object belongs to the group of extremely distant radio galaxies of ultrahigh radio luminosity (P_{1400}=1.3 x 10^{29}W Hz^{-1}). Such power can be provided only by a fairly massive black hole (~10^9M_\sun}) that formed in a time less than the age of the Universe at the observed z(1.3 Gyr) or had a primordial origin.Comment: 8 pages, 3 figure

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Measurement of the ttbar Production Cross Section in ppbar Collisions at sqrt(s) = 1.96 TeV

We present a measurement of the top quark pair production cross section in ppbar collisions at sqrt(s)=1.96 TeV using 318 pb^{-1} of data collected with the Collider Detector at Fermilab. We select ttbar decays into the final states e nu + jets and mu nu + jets, in which at least one b quark from the t-quark decays is identified using a secondary vertex-finding algorithm. Assuming a top quark mass of 178 GeV/c^2, we measure a cross section of 8.7 +-0.9 (stat) +1.1-0.9 (syst) pb. We also report the first observation of ttbar with significance greater than 5 sigma in the subsample in which both b quarks are identified, corresponding to a cross section of 10.1 +1.6-1.4(stat)+2.0-1.3 (syst) pb.Comment: Accepted for publication in Physics Review Letters, 7 page