Genomic analysis of the function of the transcription factor gata3 during development of the Mammalian inner ear

We have studied the function of the zinc finger transcription factor gata3 in auditory system development by analysing temporal profiles of gene expression during differentiation of conditionally immortal cell lines derived to model specific auditory cell types and developmental stages. We tested and applied a novel probabilistic method called the gamma Model for Oligonucleotide Signals to analyse hybridization signals from Affymetrix oligonucleotide arrays. Expression levels estimated by this method correlated closely (p<0.0001) across a 10-fold range with those measured by quantitative RT-PCR for a sample of 61 different genes. In an unbiased list of 26 genes whose temporal profiles clustered most closely with that of gata3 in all cell lines, 10 were linked to Insulin-like Growth Factor signalling, including the serine/threonine kinase Akt/PKB. Knock-down of gata3 in vitro was associated with a decrease in expression of genes linked to IGF-signalling, including IGF1, IGF2 and several IGF-binding proteins. It also led to a small decrease in protein levels of the serine-threonine kinase Akt2/PKB beta, a dramatic increase in Akt1/PKB alpha protein and relocation of Akt1/PKB alpha from the nucleus to the cytoplasm. The cyclin-dependent kinase inhibitor p27(kip1), a known target of PKB/Akt, simultaneously decreased. In heterozygous gata3 null mice the expression of gata3 correlated with high levels of activated Akt/PKB. This functional relationship could explain the diverse function of gata3 during development, the hearing loss associated with gata3 heterozygous null mice and the broader symptoms of human patients with Hearing-Deafness-Renal anomaly syndrome

The rise and fall of an extraordinary Ca-rich transient: The discovery of ATLAS19dqr/SN 2019bkc

This work presents the observations and analysis of ATLAS19dqr/SN 2019bkc, an extraordinary rapidly evolving transient event located in an isolated environment, tens of kiloparsecs from any likely host. Its light curves rise to maximum light in 5-6 d and then display a decline of Δm15 ∼ 5 mag. With such a pronounced decay, it has one of the most rapidly evolving light curves known for a stellar explosion. The early spectra show similarities to normal and "ultra-stripped" type Ic SNe, but the early nebular phase spectra, which were reached just over two weeks after explosion, display prominent calcium lines, marking SN 2019bkc as a Ca-rich transient. The Ca emission lines at this phase show an unprecedented and unexplained blueshift of 10 000-12 000 km s-1. Modelling of the light curve and the early spectra suggests that the transient had a low ejecta mass of 0.2-0.4 M⊙ and a low kinetic energy of (2-4) × 1050 erg, giving a specific kinetic energy Ek/Mej ∼ 1 [1051 erg]/M⊙. The origin of this event cannot be unambiguously defined. While the abundance distribution used to model the spectra marginally favours a progenitor of white dwarf origin through the tentative identification of Ar II, the specific kinetic energy, which is defined by the explosion mechanism, is found to be more similar to an ultra-stripped core-collapse events. SN 2019bkc adds to the diverse range of physical properties shown by Ca-rich events. © ESO 2020

Superluminous supernovae from PESSTO

We present optical spectra and light curves for three hydrogen-poor superluminous supernovae followed by the Public ESO Spectroscopic Survey of Transient Objects (PESSTO). Time series spectroscopy from a fewdays aftermaximum light to 100 d later shows them to be fairly typical of this class, with spectra dominated by Ca II, MgII, FeII, and Si II, which evolve slowly over most of the post-peak photospheric phase. We determine bolometric light curves and apply simple fitting tools, based on the diffusion of energy input by magnetar spin-down, Ni-56 decay, and collision of the ejecta with an opaque circumstellar shell. We investigate how the heterogeneous light curves of our sample (combined with others from the literature) can help to constrain the possible mechanisms behind these events. We have followed these events to beyond 100-200 d after peak, to disentangle host galaxy light from fading supernova flux and to differentiate between the models, which predict diverse behaviour at this phase. Models powered by radioactivity require unrealistic parameters to reproduce the observed light curves, as found by previous studies. Both magnetar heating and circumstellar interaction still appear to be viable candidates. A large diversity is emerging in observed tail-phase luminosities, with magnetar models failing in some cases to predict the rapid drop in flux. This would suggest either that magnetars are not responsible, or that the X-ray flux from the magnetar wind is not fully trapped. The light curve of one object shows a distinct rebrightening at around 100 d after maximum light. We argue that this could result either from multiple shells of circumstellar material, or from a magnetar ionization front breaking out of the ejecta.</p

Foot and ankle injuries during the Athens 2004 Olympic Games

<p>Abstract</p> <p>Background</p> <p>Major, rare and complex incidents can occur at any mass-gathering sporting event and team medical staff should be appropriately prepared for these. One such event, the Athens Olympic Games in 2004, presented a significant sporting and medical challenge. This study concerns an epidemiological analysis of foot and ankle injuries during the Games.</p> <p>Methods</p> <p>An observational, epidemiological survey was used to analyse injuries in all sport tournaments (men's and women's) over the period of the Games.</p> <p>Results</p> <p>A total of 624 injuries (525 soft tissue injuries and 99 bony injuries) were reported. The most frequent diagnoses were contusions, sprains, fractures, dislocations and lacerations. Significantly more injuries in male (58%) versus female athletes (42%) were recorded. The incidence, diagnosis and cause of injuries differed substantially between the team sports.</p> <p>Conclusion</p> <p>Our experience from the Athens Olympic Games will inform the development of public health surveillance systems for future Olympic Games, as well as other similar mass events.</p

Complexity in the light curves and spectra of slow-evolving superluminous supernovae

A small group of the newly discovered superluminous supernovae show broad and slow-evolving light curves. Here we present extensive observational data for the slow-evolving superluminous supernova LSQ14an, which brings this group of transients to four in total in the low-redshift Universe ($z$ < 0.2; SN 2007bi, PTF12dam, SN 2015bn). We particularly focus on the optical and near-infrared evolution during the period from 50 d up to 400 d from peak, showing that they are all fairly similar in their light curve and spectral evolution. LSQ14an shows broad, blueshifted [O $\small{III}$] λλ4959, 5007 lines, as well as a blueshifted [O $\small{II}$] λλ7320, 7330 and [Ca $\small{II}$] λλ7291, 7323. Furthermore, the sample of these four objects shows common features. Semi-forbidden and forbidden emission lines appear surprisingly early at 50–70 d and remain visible with almost no variation up to 400 d. The spectra remain blue out to 400 d. There are small, but discernible light-curve fluctuations in all of them. The light curve of each shows a faster decline than $^{56}$Co after 150 d and it further steepens after 300 d. We also expand our analysis presenting X-ray limits for LSQ14an and SN 2015bn and discuss their diagnostic power. These features are quite distinct from the faster evolving superluminous supernovae and are not easily explained in terms of only a variation in ejecta mass. While a central engine is still the most likely luminosity source, it appears that the ejecta structure is complex, with multiple emitting zones and $\textit{at least}$ some interaction between the expanding ejecta and surrounding material.This work is based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere, Chile as part of PESSTO (the Public ESO Spectroscopic Survey for Transient Objects Survey) ESO programme 188.D-3003, 191.D-0935, 197.D-1075 and the X-Shooter programmes 093.D-0229, 092.D-0555. The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC Grant agreement no [291222]. SJS acknowledges funding from STFC grants ST/I001123/1 and ST/L000709/1. This research was supported by the Munich Institute for Astro- and Particle Physics (MIAPP) of the DFG cluster of excellence ‘Origin and Structure of the Universe’. MF acknowledges the support of a Royal Society – Science Foundation Ireland University Research Fellowship. KM acknowledges support from the STFC through an Ernest Rutherford Fellowship. TWC and TK acknowledge the support through the Sofia Kovalevskaja Award to P. Schady from the Alexander von Humboldt Foundation of Germany. The Liverpool Telescope is operated on the island of La Palma by Liverpool John Moores University in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisica de Canarias with financial support from the UK Science and Technology Facilities Council. The Pan-STARRS1 Surveys (PS1) have been made possible through contributions of the Institute for Astronomy, the University of Hawaii, the Pan-STARRS Project Office, the Max Planck Society and its participating institutes, the Max Planck Institute for Astronomy, Heidelberg and the Max Planck Institute for Extraterrestrial Physics, Garching, the Johns Hopkins University, Durham University, the University of Edinburgh, Queen’s University Belfast, the Harvard-Smithsonian Center for Astrophysics, the Las Cumbres Observatory Global Telescope Network Incorporated, the National Central University of Taiwan, the Space Telescope Science Institute, the National Aeronautics and Space Administration under Grant No. NNX08AR22G issued through the Planetary Science Division of the NASA Science Mission Directorate, the National Science Foundation under Grant No. AST-1238877, the University of Maryland, and Eotvos Lorand University (ELTE) and the Los Alamos National Laboratory

An outflow powers the optical rise of the nearby, fast-evolving tidal disruption event AT2019qiz

At 66 Mpc, AT2019qiz is the closest optical tidal disruption event (TDE) to date, with a luminosity intermediate between the bulk of the population and the faint-and-fast event iPTF16fnl. Its proximity allowed a very early detection and triggering of multiwavelength and spectroscopic follow-up well before maximum light. The velocity dispersion of the host galaxy and fits to the TDE light curve indicate a black hole mass ≈106 M, disrupting a star of ≈1 M. By analysing our comprehensive UV, optical, and X-ray data, we show that the early optical emission is dominated by an outflow, with a luminosity evolution L ∝ t 2, consistent with a photosphere expanding at constant velocity (2000 km s−1), and a line-forming region producing initially blueshifted H and He II profiles with v = 3000–10 000 km s−1. The fastest optical ejecta approach the velocity inferred from radio detections (modelled in a forthcoming companion paper from K. D. Alexander et al.), thus the same outflow may be responsible for both the fast optical rise and the radio emission – the first time this connection has been observed in a TDE. The light-curve rise begins 29 ± 2 d before maximum light, peaking when the photosphere reaches the radius where optical photons can escape. The photosphere then undergoes a sudden transition, first cooling at constant radius then contracting at constant temperature. At the same time, the blueshifts disappear from the spectrum and Bowen fluorescence lines (N III) become prominent, implying a source of far-UV photons, while the X-ray light curve peaks at ≈1041 erg s−1. Assuming that these X-rays are from prompt accretion, the size and mass of the outflow are consistent with the reprocessing layer needed to explain the large optical to X-ray ratio in this and other optical TDEs, possibly favouring accretion-powered over collision-powered outflow models

Pan-STARRS and PESSTO search for an optical counterpart to the LIGO gravitational-wave source GW150914

This is the author accepted manuscript. The final version is available from Oxford University Press via http://dx.doi.org/10.1093/mnras/stw1893We searched for an optical counterpart to the first gravitational wave source discovered by LIGO (GW150914), using a combination of the Pan-STARRS1 wide-field telescope and the PESSTO spectroscopic follow-up programme. As the final LIGO sky maps changed during analysis, the total probability of the source being spatially coincident with our fields was finally only 4.2 per cent. Therefore we discuss our results primarily as a demonstration of the survey capability of Pan-STARRS and spectroscopic capability of PESSTO. We mapped out 442 square degrees of the northern sky region of the initial map. We discovered 56 astrophysical transients over a period of 41 days from the discovery of the source. Of these, 19 were spectroscopically classified and a further 13 have host galaxy redshifts. All transients appear to be fairly normal supernovae and AGN variability and none is obviously linked with GW150914. We illustrate the sensitivity of our survey by defining parameterised lightcurves with timescales of 4, 20 and 40 days and use the sensitivity of the Pan-STARRS1 images to set limits on the luminosities of possible sources. The Pan-STARRS1 images reach limiting magnitudes of $\textit{i}$$_{P\rceil}$ = 19.2, 20.0 and 20.8 respectively for the three timescales. For long timescale parameterised lightcurves (with FWHM≃40d) we set upper limits of $\textit{M}$$_{i}$ ≤ −17.2$^{−0.9}_{+1.4}$ if the distance to GW150914 is $\textit{D}_{\lfloor}$ = 400 ± 200 Mpc. The number of type Ia SN we find in the survey is similar to that expected from the cosmic SN rate, indicating a reasonably complete efficiency in recovering supernova like transients out to $\textit{D}_{\lfloor}$ = 400 ± 200 Mpc.Pan-STARRS is supported by the University of Hawaii and the National Aeronautics and Space Administration's Planetary Defense Office under Grant No. NNX14AM74G. The Pan-STARRS-LIGO effort is in collaboration with the LIGO Consortium and supported by Queen's University Belfast. The Pan-STARRS1 Sky Surveys have been made possible through contributions by the Institute for Astronomy, the University of Hawaii, the Pan-STARRS Project Office, the Max Planck Society and its participating institutes, the Max Planck Institute for Astronomy, Heidelberg and the Max Planck Institute for Extraterrestrial Physics, Garching, The Johns Hopkins University, Durham University, the University of Edinburgh, the Queen's University Belfast, the Harvard-Smithsonian Center for Astrophysics, the Las Cumbres Observatory Global Telescope Network Incorporated, the National Central University of Taiwan, the Space Telescope Science Institute, and the National Aeronautics and Space Administration under Grant No. NNX08AR22G issued through the Planetary Science Division of the NASA Science Mission Directorate, the National Science Foundation Grant No. AST-1238877, the University of Maryland, Eotvos Lorand University (ELTE), and the Los Alamos National Laboratory. This work is based (in part) on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere, Chile as part of PESSTO, (the Public ESO Spectroscopic Survey for Transient Objects Survey) ESO programs 188.D-3003, 191.D-0935. Some of the data presented herein were obtained at the Palomar Observatory, California Institute of Technology. SJS acknowledges funding from the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013)/ERC Grant agreement no [291222] and STFC grants ST/I001123/1 and ST/L000709/1. MF is supported by the European Union FP7 programme through ERC grant number 320360. KM acknowledges support from the STFC through an Ernest Rutherford Fellowship FOE acknowledges support from FONDECYT through postdoctoral grant 3140326. This research has made use of the NASA/IPAC Extragalactic Database (NED) which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration and data products from the Two Micron All Sky Survey, which is a joint project of the University of Massachusetts and the Infrared Processing and Analysis Center/California Institute of Technology, funded by the National Aeronautics and Space Administration and the National Science Foundation

Cataract-Causing Defect of a Mutant γ-Crystallin Proceeds through an Aggregation Pathway Which Bypasses Recognition by the α-Crystallin Chaperone

Background: The transparency of the eye lens depends upon maintenance of the native state of the γ- and β-crystallins, which is aided by the abundant chaperones αA- and αB-crystallin. Mature onset cataract, the leading cause of blindness worldwide, involves the polymerization of covalently damaged or partially unfolded crystallins into light-scattering aggregates. A number of single amino acid substitutions and truncations of γ-crystallins result in congenital cataract in both humans and mice, though in many cases the coupling between the protein alterations and the accumulation of aggregates is poorly defined. Methodology/Principal Findings: We have studied the aggregation properties and chaperone interactions of human γD-crystallin carrying substitutions of two buried core mutants, I90F and V75D, which cause congenital cataract in mice. The in vitro aggregation pathway competing with productive refolding was not altered by either substitution. Furthermore, this aggregation pathway for both mutant proteins–originating from a partially folded intermediate–was efficiently suppressed by αB-crystallin. Thus the cataract pathology was unlikely to be associated with a direct folding defect. The native state of wild-type human γD-crystallin exhibited no tendency to aggregate under physiological conditions. However both I90F and V75D native-like proteins exhibited slow (days) aggregation to high molecular weight aggregates under physiological conditions. The perturbed conformation of I90F was recognized and bound by both αA and αB chaperones. In contrast, the aggregation derived from the perturbed state of V75D was not suppressed by either chaperone, and the aggregating species were not bound by the chaperone. Conclusions/Significance: The cataract phenotype of I90F in mice may be due to premature saturation of the finite α- crystallin pool. The V75D aggregation pathway and its escape from chaperone surveillance and aggregation suppression can account for the congenital cataract pathology of this mutant. Failure of chaperone recognition may be an important source of pathology for many other protein folding defects.National Eye Institute (Grant no. EY015834 )National Institutes of Health (U.S.) (Grant no. GM17980

Inequalities in health: a comparative study between ethnic Norwegians and Pakistanis in Oslo, Norway

BACKGROUND: The objective of the study was to observe the inequality in health from the perspective of socio-economic factors in relation to ethnic Pakistanis and ethnic Norwegians in Oslo, Norway. METHOD: Data was collected by using an open and structured questionnaire, as a part of the Oslo Health Study 2000–2001. Accordingly 13581 ethnic Norwegians (45% of the eligible) participated as against 339 ethnic Pakistanis (38% of the eligible). RESULTS: The ethnic Pakistanis reported a higher prevalence of poor self-rated health 54.7% as opposed to 22.1% (p < 0.001) in ethnic Norwegians, 14% vs. 2.6% (p < 0.001) in diabetes, and 22.0% vs. 9.9% (p < 0.001) in psychological distress. The socio-economic conditions were inversely related to self- rated health, diabetes and distress for the ethnic Norwegians. However, this was surprisingly not the case for the ethnic Pakistanis. Odd ratios did not interfere with the occurrence of diabetes, even after adjusting all the markers of socio-economic status in the multivariate model, while self-reported health and distress showed moderate reduction in the risk estimation. CONCLUSION: There is a large diversity of self-rated health, prevalence of diabetes and distress among the ethnic Pakistanis and Norwegians. Socio-economic status may partly explain the observed inequalities in health. Uncontrolled variables like genetics, lifestyle factors and psychosocial factors related to migration such as social support, community participation, discrimination, and integration may have contributed to the observed phenomenon. This may underline the importance of a multidisciplinary approach in future studies