Microtubule organization within mitotic spindles revealed by serial block face scanning electron microscopy and image analysis

Serial block face scanning electron microscopy (SBF-SEM) is a powerful method to analyze cells in 3D. Here, working at the resolution limit of the method, we describe a correlative light-SBF-SEM workflow to resolve microtubules of the mitotic spindle in human cells. We present four examples of uses for this workflow that are not practical by light microscopy and/or transmission electron microscopy. First, distinguishing closely associated microtubules within K-fibers; second, resolving bridging fibers in the mitotic spindle; third, visualizing membranes in mitotic cells, relative to the spindle apparatus; and fourth, volumetric analysis of kinetochores. Our workflow also includes new computational tools for exploring the spatial arrangement of microtubules within the mitotic spindle. We use these tools to show that microtubule order in mitotic spindles is sensitive to the level of TACC3 on the spindle

The host galaxies and explosion sites of long-duration gamma-ray bursts: Hubble Space Telescope near-infrared imaging

We present the results of a Hubble Space Telescope WFC3/F160WSnapshot survey of the host galaxies of 39 long-duration gamma-ray bursts (LGRBs) at z < 3. We have non-detections of hosts at the locations of four bursts. Sufficient accuracy to astrometrically align optical afterglowimages and determine the location of the LGRB within its hostwas possible for 31/35 detected hosts. In agreement with other work, we find the luminosity distribution of LGRB hosts is significantly fainter than that of a star formation rate-weighted field galaxy sample over the same redshift range, indicating LGRBs are not unbiasedly tracing the star formation rate. Morphologically, the sample of LGRB hosts is dominated by spiral-like or irregular galaxies. We find evidence for evolution of the population of LGRB hosts towards lower luminosity, higher concentrated hosts at lower redshifts. Their half-light radii are consistent with other LGRB host samples where measurements were made on rest-frame UV observations. In agreement with recent work, we find their 80 per cent enclosed flux radii distribution to be more extended than previously thought, making them intermediate between core-collapse supernova (CCSN) and superluminous supernova (SLSN) hosts. The galactocentric projectedoffset distribution confirms LGRBs as centrally concentrated, much more so than CCSNe and similar to SLSNe. LGRBs are strongly biased towards the brighter regions in their host light distributions, regardless of their offset. We find a correlation between the luminosity of the LGRB explosion site and the intrinsic column density, NH, towards the burst. © 2017 The Authors

Detailed afterglow modelling and host galaxy properties of the dark GRB 111215A

Gamma-ray burst (GRB) 111215A was bright at X-ray and radio frequencies, but not detected in the optical or near-infrared (nIR) down to deep limits. We have observed the GRB afterglow with the Westerbork Synthesis Radio Telescope and Arcminute Microkelvin Imager at radio frequencies, with the William Herschel Telescope and Nordic Optical Telescope in the nIR/optical, and with the Chandra X-ray Observatory. We have combined our data with the Swift X-Ray Telescope monitoring, and radio and millimetre observations from the literature to perform broad-band modelling, and determined the macro- and microphysical parameters of the GRB blast wave. By combining the broad-band modelling results with our nIR upper limits we have put constraints on the extinction in the host galaxy. This is consistent with the optical extinction we have derived from the excess X-ray absorption, and higher than in other dark bursts for which similar modelling work has been performed.We also present deep imaging of the host galaxy with the Keck I telescope, Spitzer Space Telescope, and Hubble Space Telescope (HST), which resulted in a well-constrained photometric redshift, giving credence to the tentative spectroscopic redshift we obtained with the Keck II telescope, and estimates for the stellar mass and star formation rate of the host. Finally, our high-resolution HST images of the host galaxy show that the GRB afterglow position is offset from the brightest regions of the host galaxy, in contrast to studies of optically bright GRBs. © 2014 The Authors

Detailed multiwavelength modelling of the dark GRB 140713A and its host galaxy

We investigate the afterglow of GRB 140713A, a gamma-ray burst (GRB) that was detected and relatively well sampled at X-ray and radio wavelengths, but was not present at optical and near-infrared wavelengths, despite searches to deep limits. We present the emission spectrum of the likely host galaxy at z = 0.935 ruling out a high-redshift explanation for the absence of the optical flux detection. Modelling the GRB multiwavelength afterglow using the radiative transfer hydrodynamics code boxfit provides constraints on physical parameters of the GRB jet and its environment, for instance a relatively wide jet opening angle and an electron energy distribution slope p below 2. Most importantly, the model predicts an optical flux about two orders of magnitude above the observed limits. We calculated that the required host extinction to explain the observed limits in the r, i, and z bands was A rm host-V gt 3.2 mag, equivalent to E(B ' V) host > 1.0 mag. From the X-ray absorption we derive that the GRB host extinction is A rm host-V = 11.6 +7.5-5.3 mag, equivalent to E(B-V) rm host = 3.7 +2.4-1.7 mag, which is consistent with the extinction required from our boxfit derived fluxes. We conclude that the origin of the optical darkness is a high level of extinction in the line of sight to the GRB, most likely within the GRB host galaxy. © 2019 The Author(s) Published by Oxford University Press on behalf of the Royal Astronomical Society

Short GRB 160821B: A Reverse Shock, a Refreshed Shock, and a Well-sampled Kilonova

We report our identification of the optical afterglow and host galaxy of the short-duration gamma-ray burst sGRB 160821B. The spectroscopic redshift of the host is z = 0.162, making it one of the lowest redshift short-duration gamma-ray bursts (sGRBs) identified by Swift. Our intensive follow-up campaign using a range of ground-based facilities as well as Hubble Space Telescope, XMM-Newton, and Swift, shows evidence for a late-time excess of optical and near-infrared emission in addition to a complex afterglow. The afterglow light curve at X-ray frequencies reveals a narrow jet, ${\theta }_{j}\sim {1.9}_{-0.03}^{+0.10}$ deg, that is refreshed at >1 day post-burst by a slower outflow with significantly more energy than the initial outflow that produced the main GRB. Observations of the 5 GHz radio afterglow shows a reverse shock into a mildly magnetized shell. The optical and near-infrared excess is fainter than AT2017gfo associated with GW170817, and is well explained by a kilonova with dynamic ejecta mass M dyn = (1.0 ± 0.6) × 10−3 M ⊙ and a secular (post-merger) ejecta mass with M pm = (1.0 ± 0.6) × 10−2 M ⊙, consistent with a binary neutron star merger resulting in a short-lived massive neutron star. This optical and near-infrared data set provides the best-sampled kilonova light curve without a gravitational wave trigger to date

A series of Fas receptor agonist antibodies that demonstrate an inverse correlation between affinity and potency

Receptor agonism remains poorly understood at the molecular and mechanistic level. In this study, we identified a fully human anti-Fas antibody that could efficiently trigger apoptosis and therefore function as a potent agonist. Protein engineering and crystallography were used to mechanistically understand the agonistic activity of the antibody. The crystal structure of the complex was determined at 1.9 Å resolution and provided insights into epitope recognition and comparisons with the natural ligand FasL (Fas ligand). When we affinity-matured the agonist antibody, we observed that, surprisingly, the higher-affinity antibodies demonstrated a significant reduction, rather than an increase, in agonist activity at the Fas receptor. We propose and experimentally demonstrate a model to explain this non-intuitive impact of affinity on agonist antibody signalling and explore the implications for the discovery of therapeutic agonists in general

Introduced Mammalian Predators Induce Behavioural Changes in Parental Care in an Endemic New Zealand Bird

The introduction of predatory mammals to oceanic islands has led to the extinction of many endemic birds. Although introduced predators should favour changes that reduce predation risk in surviving bird species, the ability of island birds to respond to such novel changes remains unstudied. We tested whether novel predation risk imposed by introduced mammalian predators has altered the parental behaviour of the endemic New Zealand bellbird (Anthornis melanura). We examined parental behaviour of bellbirds at three woodland sites in New Zealand that differed in predation risk: 1) a mainland site with exotic predators present (high predation risk), 2) a mainland site with exotic predators experimentally removed (low risk recently) and, 3) an off-shore island where exotic predators were never introduced (low risk always). We also compared parental behaviour of bellbirds with two closely related Tasmanian honeyeaters (Phylidonyris spp.) that evolved with native nest predators (high risk always). Increased nest predation risk has been postulated to favour reduced parental activity, and we tested whether island bellbirds responded to variation in predation risk. We found that females spent more time on the nest per incubating bout with increased risk of predation, a strategy that minimised activity at the nest during incubation. Parental activity during the nestling period, measured as number of feeding visits/hr, also decreased with increasing nest predation risk across sites, and was lowest among the honeyeaters in Tasmania that evolved with native predators. These results demonstrate that some island birds are able to respond to increased risk of predation by novel predators in ways that appear adaptive. We suggest that conservation efforts may be more effective if they take advantage of the ability of island birds to respond to novel predators, especially when the elimination of exotic predators is not possible

The unpolarized macronova associated with the gravitational wave event GW 170817

The merger of two dense stellar remnants including at least one neutron star (NS) is predicted to produce gravitational waves (GWs) and short duration gamma ray bursts (GRBs). In the process, neutron-rich material is ejected from the system and heavy elements are synthesized by r-process nucleosynthesis. The radioactive decay of these heavy elements produces additional transient radiation termed "kilonova" or "macronova". We report the detection of linear optical polarization P = (0.50 +/- 0.07)% at 1.46 days after detection of the GWs from GW170817, a double neutron star merger associated with an optical macronova counterpart and a short GRB. The optical emission from a macronova is expected to be characterized by a blue, rapidly decaying, component and a red, more slowly evolving, component due to material rich of heavy elements, the lanthanides. The polarization measurement was made when the macronova was still in its blue phase, during which there is an important contribution from a lanthanide-free outflow. The low degree of polarization is consistent with intrinsically unpolarized emission scattered by Galactic dust, suggesting a symmetric geometry of the emitting region and low inclination of the merger system. Stringent upper limits to the polarization degree from 2.45 - 9.48 days post-burst are consistent with the lanthanides-rich macronova interpretation.Comment: 18 pages, 1 figure, 2 tables, Nature Astronomy, in pres

Treatment options in end-stage heart failure: where to go from here?

Chronic heart failure is a major healthcare problem associated with high morbidity and mortality. Despite significant progress in treatment strategies, the prognosis of heart failure patients remains poor. The golden standard treatment for heart failure is heart transplantation after failure of medical therapy, surgery and/or cardiac resynchronisation therapy. In order to improve patients’ outcome and quality of life, new emerging treatment modalities are currently being investigated, including mechanical cardiac support devices, of which the left ventricular assist device is the most promising treatment option. Structured care for heart failure patients according to the most recent international heart failure guidelines may further contribute to optimal decision-making. This article will review the conventional and novel treatment modalities of heart failure