from PHENOMENAL

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A spontaneous increase in intracellular Ca2+ in metaphase II human oocytes in vitro can be prevented by drugs targeting ATP-sensitive K+ channels

STUDY QUESTION: Could drugs targeting ATP-sensitive K+ (KATP) channels prevent any spontaneous increase in intracellular Ca2+ that may occur in human metaphase II (MII) oocytes under in vitro conditions? SUMMARY ANSWER: Pinacidil, a KATP channel opener, and glibenclamide, a KATP channel blocker, prevent a spontaneous increase in intracellular Ca2+ in human MII oocytes. WHAT IS KNOWN ALREADY: The quality of the oocyte and maintenance of this quality during in vitro processing in the assisted reproductive technology (ART) laboratory is of critical importance to successful embryo development and a healthy live birth. Maintenance of Ca2+ homeostasis is crucial for cell wellbeing and increased intracellular Ca2+ levels is a well-established indicator of cell stress. STUDY DESIGN, SIZE, DURATION: Supernumerary human oocytes (n = 102) collected during IVF/ICSI treatment that failed to fertilize were used from October 2013 to July 2015. All experiments were performed on mature (MII) oocytes. Dynamics of intracellular Ca2+ levels were monitored in oocytes in the following experimental groups: (i) Control, (ii) Dimethyl sulfoxide (DMSO; used to dissolve pinacidil, glibenclamide and 2,4-Dinitrophenol (DNP)), (iii) Pinacidil, (iv) Glibenclamide, (v) DNP: an inhibitor of oxidative phosphorylation, (vi) Pinacidil and DNP and (vii) Glibenclamide and DNP. PARTICIPANTS/MATERIALS/SETTINGS/METHODS: Oocytes were collected under sedation as part of routine treatment at an assisted conception unit from healthy women (mean ± SD) age 34.1 ± 0.6 years, n = 41. Those surplus to clinical use were donated for research. Oocytes were loaded with Fluo-3 Ca2+-sensitive dye, and monitored by laser confocal microscopy for 2 h at 10 min intervals. Time between oocyte collection and start of Ca2+ monitoring was 80.4 ± 2.1 h. MAIN RESULTS AND THE ROLE OF CHANCE: Intracellular levels of Ca2+ increased under in vitro conditions with no deliberate challenge, as shown by Fluo-3 fluorescence increasing from 61.0 ± 11.8 AU (AU = arbitrary units; n = 23) to 91.8 ± 14.0 AU (n = 19; P <0.001) after 2 h of monitoring. Pinacidil (100 µM) inhibited this increase in Ca2+ (85.3 ± 12.3 AU at the beginning of the experiment, 81.7 ± 11.0 AU at the end of the experiment; n = 13; P = 0.616). Glibenclamide (100 µM) also inhibited the increase in Ca2+ (74.7 ± 10.6 AU at the beginning and 71.8 ± 10.9 AU at the end of the experiment; n = 13; P = 0.851. DNP (100 mM) induced an increase in intracellular Ca2+ that was inhibited by glibenclamide (100 µM; n = 9) but not by pinacidil (100 µM; n = 5). LIMITATIONS, REASONS FOR CAUTION: Owing to clinical and ethical considerations, it was not possible to monitor Ca2+ in MII oocytes immediately after retrieval. MII oocytes were available for our experimentation only after unsuccessful IVF or ICSI, which was, on average, 80.4 ± 2.1 h (n = 102 oocytes) after the moment of retrieval. As the MII oocytes used here were those that were not successfully fertilized, it is possible that they may have been abnormal with impaired Ca2+ homeostasis and, furthermore, the altered Ca2+ homeostasis might have been associated solely with the protracted incubation. WIDER IMPLICATIONS OF THE FINDINGS: These results show that maintenance of oocytes under in vitro conditions is associated with intracellular increase in Ca2+, which can be counteracted by drugs targeting KATP channels. As Ca2+ homeostasis is crucial for contributing to a successful outcome of ART, these results suggest that KATP channel openers and blockers should be tested as drugs for improving success rates of ART

Supernova remnant S147 and its associated neutron star(s)

The supernova remnant S147 harbors the pulsar PSR J0538+2817 whose characteristic age is more than an order of magnitude greater than the kinematic age of the system (inferred from the angular offset of the pulsar from the geometric center of the supernova remnant and the pulsar proper motion). To reconcile this discrepancy we propose that PSR J0538+2817 could be the stellar remnant of the first supernova explosion in a massive binary system and therefore could be as old as its characteristic age. Our proposal implies that S147 is the diffuse remnant of the second supernova explosion (that disrupted the binary system) and that a much younger second neutron star (not necessarily manifesting itself as a radio pulsar) should be associated with S147. We use the existing observational data on the system to suggest that the progenitor of the supernova that formed S147 was a Wolf-Rayet star (so that the supernova explosion occurred within a wind bubble surrounded by a massive shell) and to constrain the parameters of the binary system. We also restrict the magnitude and direction of the kick velocity received by the young neutron star at birth and find that the kick vector should not strongly deviate from the orbital plane of the binary system.Comment: 9 pages, 5 figures, revised version accepted for publication in A&

O stars with weak winds: the Galactic case

We study the stellar and wind properties of a sample of Galactic O dwarfs to track the conditions under which weak winds (i.e mass loss rates lower than ~ 1e-8 Msol/yr) appear. The sample is composed of low and high luminosity dwarfs including Vz stars and stars known to display qualitatively weak winds. Atmosphere models including non-LTE treatment, spherical expansion and line blanketing are computed with the code CMFGEN. Both UV and Ha lines are used to derive wind properties while optical H and He lines give the stellar parameters. Mass loss rates of all stars are found to be lower than expected from the hydrodynamical predictions of Vink et al. (2001). For stars with log L/Lsol > 5.2, the reduction is by less than a factor 5 and is mainly due to the inclusion of clumping in the models. For stars with log L/Lsol < 5.2 the reduction can be as high as a factor 100. The inclusion of X-ray emission in models with low density is crucial to derive accurate mass loss rates from UV lines. The modified wind momentum - luminosity relation shows a significant change of slope around this transition luminosity. Terminal velocities of low luminosity stars are also found to be low. The physical reason for such weak winds is still not clear although the finding of weak winds in Galactic stars excludes the role of a reduced metallicity. X-rays, through the change in the ionisation structure they imply, may be at the origin of a reduction of the radiative acceleration, leading to lower mass loss rates. A better understanding of the origin of X-rays is of crucial importance for the study of the physics of weak winds.Comment: 31 pages, 42 figures. A&A accepted. A version of the paper with full resolution figures is available at http://www.mpe.mpg.de/~martins/publications.htm

The binary fraction of planetary nebula central stars - III. the promise of VPHAS+

This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society ©: 2017 The Author(s). Published by Oxford University Press on behalf of the Royal Astronomical Society. Content in the UH Research Archive is made available for personal research, educational, and non-commercial purposes only. Unless otherwise stated, all content is protected by copyright, and in the absence of an open license, permissions for further re-use should be sought from the publisher, the author, or other copyright holder.The majority of planetary nebulae (PNe) are not spherical, and current single-star models cannot adequately explain all the morphologies we observe. This has led to the Binary Hypothesis, which states that PNe are preferentially formed by binary systems. This hypothesis can be corroborated or disproved by comparing the estimated binary fraction of all PNe central stars (CS) to that of the supposed progenitor population. One way to quantify the rate of CS binarity is to detect near infra-red (IR) excess indicative of a low-mass main sequence companion. In this paper, a sample of known PNe within data release 2 of the ongoing VPHAS+ are investigated. We give details of the method used to calibrate VPHAS+ photometry, and present the expected colours of CS and main sequence stars within the survey. Objects were scrutinized to remove PN mimics from our sample and identify true CS. Within our final sample of 7 CS, 6 had previously either not been identified or confirmed. We detected an $i$ band excess indicative of a low-mass companion star in 3 CS, including one known binary, leading us to to conclude that VPHAS+ provides the precise photometry required for the IR excess method presented here, and will likely improve as the survey completes and the calibration process finalised. Given the promising results from this trial sample, the entire VPHAS+ catalogue should be used to study PNe and extend the IR excess-tested CS sample.Peer reviewedFinal Published versio

The Ap 2-1 nebula and the surrounding molecular cloud G35.2-0.74: an active star forming region

Using data from large-scale surveys: 2MASS, GLIMPSE, MIPSGAL, VGPS, GRS, and IPHAS, we performed a multiwavelength study of the ISM in a region of about 20' x 20' towards the molecular cloud G35.2-0.74. Additionally, the Ap 2-1 nebula, that is seen in projection over the molecular cloud, was studied using optical data obtained with the 2.15 m telescope at CASLEO, Argentina. From the HI absorption study we estimate a distance of ~2 kpc for Ap 2-1 confirming that the nebula is embedded in the south portion of the molecular cloud G35.2-0.74. Performing a photometric study and analysing the spectral energy distributions of the sources likely embedded in the cloud, we confirm that this region is very active in star formation, mainly towards the north, where we discover a cluster of young stellar objects. From the H_alpha and [NII] lines we obtain a radial velocity of v_LSR ~ 31 km/s for the Ap 2-1 nebula, in coincidence with the velocity of the molecular cloud. Finally, we conclude that Ap 2-1 is an HII region probably excited by an early B-type star.Comment: 9 pages, 10 figures, accepted to be published in MNRAS (July 5, 2010

Exploratory genome-wide interaction analysis of non-steroidal anti-inflammatory drugs and predicted gene expression on colorectal cancer risk

Background: Regular use of nonsteroidal anti-inflammatory drugs (NSAID) is associated with lower risk of colorectal cancer. Genome-wide interaction analysis on single variants (G × E) has identified several SNPs that may interact with NSAIDs to confer colorectal cancer risk, but variations in gene expression levels may also modify the effect of NSAID use. Therefore, we tested interactions between NSAID use and predicted gene expression levels in relation to colorectal cancer risk. Methods: Genetically predicted gene expressions were tested for interaction with NSAID use on colorectal cancer risk among 19,258 colorectal cancer cases and 18,597 controls from 21 observational studies. A Mixed Score Test for Interactions (MiSTi) approach was used to jointly assess G × E effects which are modeled via fixed interaction effects of the weighted burden within each gene set (burden) and residual G × E effects (variance). A false discovery rate (FDR) at 0.2 was applied to correct for multiple testing. Results: Among the 4,840 genes tested, genetically predicted expression levels of four genes modified the effect of any NSAID use on colorectal cancer risk, including DPP10 (PG×E = 1.96 × 10-4), KRT16 (PG×E = 2.3 × 10-4), CD14 (PG×E = 9.38 × 10-4), and CYP27A1 (PG×E = 1.44 × 10-3). There was a significant interaction between expression level of RP11-89N17 and regular use of aspirin only on colorectal cancer risk (PG×E = 3.23 × 10-5). No interactions were observed between predicted gene expression and nonaspirin NSAID use at FDR < 0.2. Conclusions: By incorporating functional information, we discovered several novel genes that interacted with NSAID use

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Notes on "Lichen"

Abstract: ‘Notes on “Lichen”’ develops a lichenised homage to Susan Sontag’s ‘Notes on “Camp”’, rewilding Sontag’s essay to suggest a poetics of Lichen, a poetics associated symbiotically with the manifestos of Donna Haraway. This Lichen poetics engages with questions of symbiosis and solidarity, mutualism and collective voicing, sketching the turn away from humanist poetics as a critical characteristic of contemporary ecopoetics. From Conceptual Art to contemporary pop, lichen perspectives are gleaned. The attempt is made to rewild earlier conceptual formations, to recycle and repurpose shifts in contemporary taste and their associated politics. New faultlines in contemporary biopolitics are outlined. A chorus of micro-political shifts and transpositions are sketched, revealing emergent and potential turning-points in the rewilding of textual practice