Navigating heterochromatin

The condensed structure of heterochromatin differs significantly from euchromatin and DNA bound in heterochromatin is generally not transcriptionally active. Transcriptional silencing allows the control of gene expression and affords a novel mechanism of defense against genomic parasites. In addition, the physical structure of heterochromatin plays a direct role by contributing to centromere function in many eukaryotes. Mechanisms by which heterochromatin is established and maintained are only partly understood at this time. By studying the interaction of Ty5, a retrotransposon that integrates preferentially into heterochromatin-bound DNA, some of the basic biology of heterochromatin and the proteins that compose it were elucidated. The interaction between a portion of the Ty5 integrase and Sir4p, a component of yeast heterochromatin, was used to nucleate a heterochromatin complex. This complex was found to antagonize centromere-mediated plasmid segregation in a fashion similar to that reported between centromeres and other heterochromatin complexes. This antagonism was further found to be the result of double strand breaks in the plasmid DNA. The interaction between the Ty5 integrase and Sir4p was more fully mapped and four Sir4p amino acid residues were found to be required for the interaction. When mutations in these residues were introduced into the full-length SIR4 allele, the function of SIR4 in heterochromatic silencing was impaired. This is likely due to a decrease in Sir4p protein levels. The interaction between Sir4p and a short fragment of integrase required for targeting (LDSSPP), referred to as the targeting domain (TD) was also examined. This interaction was found to partially depend on other components of heterochromatin. Two-hybrid analysis of the integrase interacting portion of Sir4p identified three novel interacting proteins, Sum1p, Nma2p and Chd1p. Mutations in Sir4p required for the interaction between Sir4p and integrase were found to be required for the interaction between Sir4p and several other Sir4p interacting proteins. Expression of the targeting domain TD was also found to cause anti-silencing by lowering Sir4p levels. Genetic analysis identified the RING finger protein Ris1p as a required factor in the Sir4p turnover. These findings suggest that the previously identified role for Ris1p in gaining access to heterochromatin is likely mediated by Sir4p turnover

Is Energy Efficiency Priced in the Housing Market? Some Evidence from the United Kingdom.

This paper investigates whether energy performance ratings, as measured by mandatory Energy Performance Certificates (EPCs), are reflected in the sale prices of residential properties. This is the first large-scale empirical study of this topic in the UK involving approximately 400,000 dwellings in the period from 1995 to 2011. Applying hedonic regression and an augmented repeat sales regression, we find a positive relationship between the energy efficiency rating of a dwelling and the transaction price per square metre. The price effects of superior energy performance tend to be higher for terraced dwellings and flats compared to detached and semi-detached dwellings. The evidence is less clear-cut for house price growth rates but remains supportive of an overall positive association. Overall, the results of this study appear to support the hypothesis that energy efficiency levels are reflected in UK house prices, at least in recent years

Energy performance ratings and house prices in Wales: an empirical study

This paper investigates the effect of Energy Performance Certificate (EPC) ratings on residential prices in Wales. Drawing on a sample of approximately 192,000 transactions, the capitalisation of energy efficiency ratings into house prices is investigated using two approaches. The first adopts a cross-sectional framework to investigate the effect of EPC rating on price. The second approach applies a repeat-sales methodology to investigate the impact of EPC rating on house price appreciation. Statistically significant positive price premiums are estimated for dwellings in EPC bands A/B (12.8%) and C (3.5%) compared to houses in band D. For dwellings in band E (−3.6%) and F (−6.5%) there are statistically significant discounts. Such effects may not be the result of energy performance alone. In addition to energy cost differences, the price effect may be due to additional benefits of energy efficient features. An analysis of the private rental segment reveals that, in contrast to the general market, low-EPC rated dwellings were not traded at a significant discount. This suggests different implicit prices of potential energy savings for landlords and owner-occupiers

EXO 2030+375 Restarts in Reverse

The Be X-ray binary pulsar EXO 2030+375, first detected in 1985, has shown a significant detected X-ray outburst at nearly every periastron passage of its 46-day orbit for the past ~25 years, with one low state accompanied by a torque reversal in the 1990s. In early 2015 the outbursts progressively became fainter and less regular while the monotonic spin-up flattened. At the same time a decrease in the H$\alpha$ line equivalent width was reported, indicating a change in the disk surrounding the mass donor. In order to explore the source behaviour in the poorly explored low-flux state with a possible transition to a state of centrifugal inhibition of accretion we have undertaken an observing campaign with Swift/XRT, NuSTAR and the Nordic Optical Telescope (NOT). This conference contribution reports the preliminary results obtained from our campaign.Comment: 11th INTEGRAL Conference Gamma-Ray Astrophysics in Multi-Wavelength Perspective, 10-14 October 2016, Amsterdam, The Netherlands. 7 page

DSCAM promotes axon fasciculation and growth in the developing optic pathway

Acknowledgments We thank Drs. Robert Burgess, Carol Mason, and Eloisa Herrera for helpful discussions; Dr. Thomas Theil for his invaluable advice on the slice culture methods; Francesca Lamb and Emma Smith for technical assistance; and the Institute of Medical Sciences Microscopy and Imaging Facility for assistance with confocal microscopy. This work was supported by a Biotechnology and Biological Sciences Research Council (BBSRC) doctoral training award studentship and a BBSRC project grant (BB/J00815X/1). Freely available online through the PNAS open access option.Peer reviewedPublisher PD

Accreting on the edge: a luminosity-dependent cyclotron line in the Be/X-ray Binary 2S 1553-542 accompanied by accretion regimes transition

Accreting X-ray pulsars (XRPs) undergo luminous X-ray outbursts during which the luminosity-dependent spectral and timing features of the neutron star's emission can be analyzed in detail, thus shedding light on the accretion regime at work. We took advantage of a monitoring campaign performed with NuSTAR, Swift/XRT, AstroSat and NICER, to follow the Be/X-ray Binary 2S 1553-542 along one of its rare outbursts and trace its spectral and timing evolution. We report the discovery of a luminosity-dependent cyclotron line energy for the first time in this source. The pulse profiles and pulsed fraction also show variability along the outburst, consistently with the interpretation that the source transitions from the sub-critical to the super-critical accretion regime, separated by a critical luminosity of L$_{crit}\approx4\times10^{37}$ erg/s.Comment: Accepted on ApJ. 11 pages, 7 figures, 3 table

The Nuclear Spectroscopic Telescope Array (NuSTAR) High-energy X-Ray Mission

The Nuclear Spectroscopic Telescope Array (NuSTAR) mission, launched on 2012 June 13, is the first focusing high-energy X-ray telescope in orbit. NuSTAR operates in the band from 3 to 79 keV, extending the sensitivity of focusing far beyond the ~10 keV high-energy cutoff achieved by all previous X-ray satellites. The inherently low background associated with concentrating the X-ray light enables NuSTAR to probe the hard X-ray sky with a more than 100-fold improvement in sensitivity over the collimated or coded mask instruments that have operated in this bandpass. Using its unprecedented combination of sensitivity and spatial and spectral resolution, NuSTAR will pursue five primary scientific objectives: (1) probe obscured active galactic nucleus (AGN) activity out to the peak epoch of galaxy assembly in the universe (at z ≾ 2) by surveying selected regions of the sky; (2) study the population of hard X-ray-emitting compact objects in the Galaxy by mapping the central regions of the Milky Way; (3) study the non-thermal radiation in young supernova remnants, both the hard X-ray continuum and the emission from the radioactive element ^(44)Ti; (4) observe blazars contemporaneously with ground-based radio, optical, and TeV telescopes, as well as with Fermi and Swift, to constrain the structure of AGN jets; and (5) observe line and continuum emission from core-collapse supernovae in the Local Group, and from nearby Type Ia events, to constrain explosion models. During its baseline two-year mission, NuSTAR will also undertake a broad program of targeted observations. The observatory consists of two co-aligned grazing-incidence X-ray telescopes pointed at celestial targets by a three-axis stabilized spacecraft. Deployed into a 600 km, near-circular, 6° inclination orbit, the observatory has now completed commissioning, and is performing consistent with pre-launch expectations. NuSTAR is now executing its primary science mission, and with an expected orbit lifetime of 10 yr, we anticipate proposing a guest investigator program, to begin in late 2014

Phylum Verrucomicrobia representatives share a compartmentalized cell plan with members of bacterial phylum Planctomycetes

BACKGROUND: The phylum Verrucomicrobia is a divergent phylum within domain Bacteria including members of the microbial communities of soil and fresh and marine waters; recently extremely acidophilic members from hot springs have been found to oxidize methane. At least one genus, Prosthecobacter, includes species with genes homologous to those encoding eukaryotic tubulins. A significant superphylum relationship of Verrucomicrobia with members of phylum Planctomycetes possessing a unique compartmentalized cell plan, and members of the phylum Chlamydiae including human pathogens with a complex intracellular life cycle, has been proposed. Based on the postulated superphylum relationship, we hypothesized that members of the two separate phyla Planctomycetes and Verrucomicrobia might share a similar ultrastructure plan differing from classical prokaryote organization. RESULTS: The ultrastructure of cells of four members of phylum Verrucomicrobia – Verrucomicrobium spinosum, Prosthecobacter dejongeii, Chthoniobacter flavus, and strain Ellin514 – was examined using electron microscopy incorporating high-pressure freezing and cryosubstitution. These four members of phylum Verrucomicrobia, representing 3 class-level subdivisions within the phylum, were found to possess a compartmentalized cell plan analogous to that found in phylum Planctomycetes. Like all planctomycetes investigated, they possess a major pirellulosome compartment containing a condensed nucleoid and ribosomes surrounded by an intracytoplasmic membrane (ICM), as well as a ribosome-free paryphoplasm compartment between the ICM and cytoplasmic membrane. CONCLUSION: A unique compartmentalized cell plan so far found among Domain Bacteria only within phylum Planctomycetes, and challenging our concept of prokaryote cell plans, has now been found in a second phylum of the Domain Bacteria, in members of phylum Verrucomicrobia. The planctomycete cell plan thus occurs in at least two distinct phyla of the Bacteria, phyla which have been suggested from other evidence to be related phylogenetically in the proposed PVC (Planctomycetes-Verrucomicrobia-Chlamydiae) superphylum. This planctomycete cell plan is present in at least 3 of 6 subdivisions of Verrucomicrobia, suggesting that the common ancestor of the verrucomicrobial phylum was also compartmentalized and possessed such a plan. The presence of this compartmentalized cell plan in both phylum Planctomycetes and phylum Verrucomicrobia suggest that the last common ancestor of these phyla was also compartmentalized

Role of Pelvic Lymph Node Resection in Vulvar Squamous Cell Cancer:A Subset Analysis of the AGO-CaRE-1 Study

Background: As the population at risk for pelvic nodal involvement remains poorly described, the role of pelvic lymphadenectomy (LAE) in vulvar squamous cell cancer (VSCC) has been a matter of discussion for decades. Methods: In the AGO-CaRE-1 study, 1618 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB or higher primary VSCC treated at 29 centers in Germany between 1998 and 2008 were documented. In this analysis, only patients with pelvic LAE (n = 70) were analyzed with regard to prognosis and correlation between inguinal and pelvic lymph node involvement. Results: The majority of patients had T1b/T2 tumors (n = 47; 67.1%), with a median diameter of 40 mm (2–240 mm); 54/70 patients (77.1%) who received pelvic LAE had positive groin nodes. For 42 of these 54 patients, the number of affected groin nodes had been documented as a median of 3; 14/42 (33.3%) of these patients had histologically confirmed pelvic nodal metastases (median number of affected pelvic nodes 3 [1–12]). In these 14 patients, the median number of affected groin nodes was 7 (1–30), with a groin metastases median maximum diameter of 42.5 mm (12–50). Receiver operating characteristic analysis showed an area under the curve of 0.85, with 83.3% sensitivity and 92.6% specificity for the prediction of pelvic involvement in cases of six or more positive groin nodes. No cases of pelvic nodal involvement without groin metastases were observed. Prognosis in cases of pelvic metastasis was poor, with a median progression-free survival of only 12.5 months. Conclusion: For the majority of node-positive patients with VSCC, pelvic nodal staging appears unnecessary since a relevant risk for pelvic nodal involvement only seems to be present in highly node-positive disease

Adjuvant radiotherapy and local recurrence in vulvar cancer:a subset analysis of the AGO-CaRE-1 study

Background: The impact of adjuvant radiotherapy (RT) to the vulva with regard to prognosis and local recurrence in patients with vulvar squamous cell cancer (VSCC) is poorly described. Patients and methods: In the AGO-CaRE-1 study 1618 patients with primary VSCC FIGO stage ≥ IB, treated between 1998-2008, were documented. In this retrospective subanalysis, 360 patients were included based on the following criteria: nodal involvement (pN+), known RT treatment and known radiation fields. Results: The majority had pT1b/pT2 tumors (n=299; 83.1%). In 76.7%, R0 resection was achieved. 57/360 (15.8%) N+ patients were treated with adjuvant RT to the groins/pelvis and 146/360 (40.5%) received adjuvant RT to the vulva and groins/pelvis. 157/360 (43.6%) patients did not receive any adjuvant RT. HPV status was available in 162/360 patients (45.0%), 75/162 tumors were HPV+(46.3%), 87/162 (53.7%) HPV-. During a median follow-up of 17.2 months, recurrence at the vulva only occurred in 25.5% of patients without adjuvant RT, in 22.8% of patients with adjuvant RT to groins/pelvis and in 15.8% of patients with adjuvant RT to the vulva and groins/pelvis respectively. The risk reducing effect of local RT was independent of the resection margin status. 50% disease free survival time (50% DFST) indicated a stronger impact of adjuvant RT to the vulva in HPV+ compared to HPV- patients (50% DFST 20.7 months vs. 17.8 months). Conclusion: Adjuvant RT to the vulva was associated with a lower risk for local recurrence in N+ VSCC independent of the resection margin status. This observation was more pronounced in patients with HPV+ tumors in comparison to HPV– tumors