Morphogenesis underlying the development of the everted teleost telencephalon

Background: Although the mechanisms underlying brain patterning and regionalization are very much conserved, the morphology of different brain regions is extraordinarily variable across vertebrate phylogeny. This is especially manifest in the telencephalon, where the most dramatic variation is seen between ray-finned fish, which have an everted telencephalon, and all other vertebrates, which have an evaginated telencephalon. The mechanisms that generate these distinct morphologies are not well understood. Results: Here we study the morphogenesis of the zebrafish telencephalon from 12 hours post fertilization (hpf) to 5 days post fertilization (dpf) by analyzing forebrain ventricle formation, evolving patterns of gene and transgene expression, neuronal organization, and fate mapping. Our results highlight two key events in telencephalon morphogenesis. First, the formation of a deep ventricular recess between telencephalon and diencephalon, the anterior intraencephalic sulcus (AIS), effectively creates a posterior ventricular wall to the telencephalic lobes. This process displaces the most posterior neuroepithelial territory of the telencephalon laterally. Second, as telencephalic growth and neurogenesis proceed between days 2 and 5 of development, the pallial region of the posterior ventricular wall of the telencephalon bulges into the dorsal aspect of the AIS. This brings the ventricular zone (VZ) into close apposition with the roof of the AIS to generate a narrow ventricular space and the thin tela choroidea (tc). As the pallial VZ expands, the tc also expands over the upper surface of the telencephalon. During this period, the major axis of growth and extension of the pallial VZ is along the anteroposterior axis. This second step effectively generates an everted telencephalon by 5 dpf. Conclusion: Our description of telencephalic morphogenesis challenges the conventional model that eversion is simply due to a laterally directed outfolding of the telencephalic neuroepithelium. This may have significant bearing on understanding the eventual organization of the adult fish telencephalon

Characteristics of Kepler Planetary Candidates Based on the First Data Set: The Majority are Found to be Neptune-Size and Smaller

In the spring of 2009, the Kepler Mission commenced high-precision photometry on nearly 156,000 stars to determine the frequency and characteristics of small exoplanets, conduct a guest observer program, and obtain asteroseismic data on a wide variety of stars. On 15 June 2010 the Kepler Mission released data from the first quarter of observations. At the time of this publication, 706 stars from this first data set have exoplanet candidates with sizes from as small as that of the Earth to larger than that of Jupiter. Here we give the identity and characteristics of 306 released stars with planetary candidates. Data for the remaining 400 stars with planetary candidates will be released in February 2011. Over half the candidates on the released list have radii less than half that of Jupiter. The released stars include five possible multi-planet systems. One of these has two Neptune-size (2.3 and 2.5 Earth-radius) candidates with near-resonant periods.Comment: Paper to accompany Kepler's June 15, 2010 data release; submitted to Astrophysical Journal Figures 1,2,& 3 revised. Improved labeling on all figures. Slight changes to planet frequencies in result

Human settlement of East Polynesia earlier, incremental, and coincident with prolonged South Pacific drought

The timing of human colonization of East Polynesia, a vast area lying between Hawai‘i, Rapa Nui, and New Zealand, is much debated and the underlying causes of this great migration have been enigmatic. Our study generates evidence for human dispersal into eastern Polynesia from islands to the west from around AD 900 and contemporaneous paleoclimate data from the likely source region. Lake cores from Atiu, Southern Cook Islands (SCIs) register evidence of pig and/or human occupation on a virgin landscape at this time, followed by changes in lake carbon around AD 1000 and significant anthropogenic disturbance from c. AD 1100. The broader paleoclimate context of these early voyages of exploration are derived from the Atiu lake core and complemented by additional lake cores from Samoa (directly west) and Vanuatu (southwest) and published hydroclimate proxies from the Society Islands (northeast) and Kiribati (north). Algal lipid and leaf wax biomarkers allow for comparisons of changing hydroclimate conditions across the region before, during, and after human arrival in the SCIs. The evidence indicates a prolonged drought in the likely western source region for these colonists, lasting c. 200 to 400 y, contemporaneous with the phasing of human dispersal into the Pacific. We propose that drying climate, coupled with documented social pressures and societal developments, instigated initial eastward exploration, resulting in SCI landfall(s) and return voyaging, with colonization a century or two later. This incremental settlement process likely involved the accumulation of critical maritime knowledge over several generations

Planet Occurrence within 0.25 AU of Solar-type Stars from Kepler

We report the distribution of planets as a function of planet radius (R_p), orbital period (P), and stellar effective temperature (Teff) for P < 50 day orbits around GK stars. These results are based on the 1,235 planets (formally "planet candidates") from the Kepler mission that include a nearly complete set of detected planets as small as 2 Earth radii (Re). For each of the 156,000 target stars we assess the detectability of planets as a function of R_p and P. We also correct for the geometric probability of transit, R*/a. We consider first stars within the "solar subset" having Teff = 4100-6100 K, logg = 4.0-4.9, and Kepler magnitude Kp < 15 mag. We include only those stars having noise low enough to permit detection of planets down to 2 Re. We count planets in small domains of R_p and P and divide by the included target stars to calculate planet occurrence in each domain. Occurrence of planets varies by more than three orders of magnitude and increases substantially down to the smallest radius (2 Re) and out to the longest orbital period (50 days, ~0.25 AU) in our study. For P < 50 days, the radius distribution is given by a power law, df/dlogR= k R^\alpha. This rapid increase in planet occurrence with decreasing planet size agrees with core-accretion, but disagrees with population synthesis models. We fit occurrence as a function of P to a power law model with an exponential cutoff below a critical period P_0. For smaller planets, P_0 has larger values, suggesting that the "parking distance" for migrating planets moves outward with decreasing planet size. We also measured planet occurrence over Teff = 3600-7100 K, spanning M0 to F2 dwarfs. The occurrence of 2-4 Re planets in the Kepler field increases with decreasing Teff, making these small planets seven times more abundant around cool stars than the hottest stars in our sample. [abridged]Comment: Submitted to ApJ, 22 pages, 10 figure

Planetary Candidates Observed by Kepler, III: Analysis of the First 16 Months of Data

New transiting planet candidates are identified in sixteen months (May 2009 - September 2010) of data from the Kepler spacecraft. Nearly five thousand periodic transit-like signals are vetted against astrophysical and instrumental false positives yielding 1,091 viable new planet candidates, bringing the total count up to over 2,300. Improved vetting metrics are employed, contributing to higher catalog reliability. Most notable is the noise-weighted robust averaging of multi-quarter photo-center offsets derived from difference image analysis which identifies likely background eclipsing binaries. Twenty-two months of photometry are used for the purpose of characterizing each of the new candidates. Ephemerides (transit epoch, T_0, and orbital period, P) are tabulated as well as the products of light curve modeling: reduced radius (Rp/R*), reduced semi-major axis (d/R*), and impact parameter (b). The largest fractional increases are seen for the smallest planet candidates (197% for candidates smaller than 2Re compared to 52% for candidates larger than 2Re) and those at longer orbital periods (123% for candidates outside of 50-day orbits versus 85% for candidates inside of 50-day orbits). The gains are larger than expected from increasing the observing window from thirteen months (Quarter 1-- Quarter 5) to sixteen months (Quarter 1 -- Quarter 6). This demonstrates the benefit of continued development of pipeline analysis software. The fraction of all host stars with multiple candidates has grown from 17% to 20%, and the paucity of short-period giant planets in multiple systems is still evident. The progression toward smaller planets at longer orbital periods with each new catalog release suggests that Earth-size planets in the Habitable Zone are forthcoming if, indeed, such planets are abundant.Comment: Submitted to ApJS. Machine-readable tables are available at http://kepler.nasa.gov, http://archive.stsci.edu/kepler/results.html, and the NASA Exoplanet Archiv

Jupiter’s auroras during the Juno approach phase as observed by the Hubble Space Telescope

We present movies of the Hubble Space Telescope (HST) observations of Jupiter’s FUV auroras observed during the Juno approach phase and first capture orbit, and compare with Juno observations of the interplanetary medium near Jupiter and inside the magnetosphere. Jupiter’s FUV auroras indicate the nature of the dynamic processes occurring in Jupiter’s magnetosphere, and the approach phase provided a unique opportunity to obtain a full set of interplanetary data near to Jupiter at the time of a program of HST observations, along with the first simultaneous with Juno observations inside the magnetosphere. The overall goal was to determine the nature of the solar wind effect on Jupiter’s magnetosphere. HST observations were obtained with typically 1 orbit per day over three intervals: 16 May – 7 June, 22-30 June and 11-18 July, i.e. while Juno was in the solar wind, around the bow shock and magnetosphere crossings, and in the mid-latitude middle-outer magnetospheres. We show that these intervals are characterised by particularly dynamic polar auroras, and significant variations in the auroral power output caused by e.g. dawn storms, intense main emission and poleward forms. We compare the variation of these features with Juno observations of interplanetary compression regions and the magnetospheric environment during the intervals of these observations

Jupiter's X-ray Emission 2007 Part 2:Comparisons with UV and Radio Emissions and In-Situ Solar Wind Measurements

We compare Chandra and XMM‐Newton X‐ray observations of Jupiter during 2007 with a rich multi‐instrument dataset including: upstream in‐situ solar wind measurements from the New Horizons spacecraft, radio emissions from the Nançay Decametric Array and Wind/Waves, and UV observations from the Hubble Space Telescope. New Horizons data revealed two corotating interaction regions (CIRs) impacted Jupiter during these observations. Non‐Io decametric bursts and UV emissions brightened together and varied in phase with the CIRs. We characterise 3 types of X‐ray aurorae: hard X‐ray bremsstrahlung main emission, pulsed/flared soft X‐ray emissions and a newly identified dim flickering (varying on short‐timescales, but quasi‐continuously present) aurora. For most observations, the X‐ray aurorae were dominated by pulsed/flaring emissions, with ion spectral lines that were best fit by Iogenic plasma. However, the brightest X‐ray aurora was coincident with a magnetosphere expansion. For this observation, the aurorae were produced by both flickering emission and erratic pulses/flares. Auroral spectral models for this observation required the addition of solar wind ions to attain good fits, suggesting solar wind entry into the outer magnetosphere or directly into the pole for this particularly bright observation. X‐ray bremsstrahlung from high energy electrons was only bright for one observation, which was during a forward shock. This bremsstrahlung was spatially coincident with bright UV main emission (power> 1TW) and X‐ray ion spectral line dusk emission, suggesting closening of upward and downward current systems during the shock. Otherwise, the bremsstrahlung was dim and UV main emission power was also lower(<700 GW), suggesting their power scaled together

Genome-wide association study identifies 30 loci associated with bipolar disorder.

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P &lt; 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P &lt; 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder

Transdermal oestradiol for androgen suppression in prostate cancer: long-term cardiovascular outcomes from the randomised Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme

Background Androgen suppression is a central component of prostate cancer management but causes substantial long-term toxicity. Transdermal administration of oestradiol (tE2) circumvents first-pass hepatic metabolism and, therefore, should avoid the cardiovascular toxicity seen with oral oestrogen and the oestrogen-depletion effects seen with luteinising hormone releasing hormone agonists (LHRHa). We present long-term cardiovascular follow-up data from the Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme. Methods PATCH is a seamless phase 2/3, randomised, multicentre trial programme at 52 study sites in the UK. Men with locally advanced or metastatic prostate cancer were randomly allocated (1:2 from August, 2007 then 1:1 from February, 2011) to either LHRHa according to local practice or tE2 patches (four 100 μg patches per 24 h, changed twice weekly, reducing to three patches twice weekly if castrate at 4 weeks [defined as testosterone ≤1·7 nmol/L]). Randomisation was done using a computer-based minimisation algorithm and was stratified by several factors, including disease stage, age, smoking status, and family history of cardiac disease. The primary outcome of this analysis was cardiovascular morbidity and mortality. Cardiovascular events, including heart failure, acute coronary syndrome, thromboembolic stroke, and other thromboembolic events, were confirmed using predefined criteria and source data. Sudden or unexpected deaths were attributed to a cardiovascular category if a confirmatory post-mortem report was available and as other relevant events if no post-mortem report was available. PATCH is registered with the ISRCTN registry, ISRCTN70406718; the study is ongoing and adaptive. Findings Between Aug 14, 2007, and July 30, 2019, 1694 men were randomly allocated either LHRHa (n=790) or tE2 patches (n=904). Overall, median follow-up was 3·9 (IQR 2·4–7·0) years. Respective castration rates at 1 month and 3 months were 65% and 93% among patients assigned LHRHa and 83% and 93% among those allocated tE2. 157 events from 145 men met predefined cardiovascular criteria, with a further ten sudden deaths with no post-mortem report (total 167 events in 153 men). 26 (2%) of 1694 patients had fatal cardiovascular events, 15 (2%) of 790 assigned LHRHa and 11 (1%) of 904 allocated tE2. The time to first cardiovascular event did not differ between treatments (hazard ratio 1·11, 95% CI 0·80–1·53; p=0·54 [including sudden deaths without post-mortem report]; 1·20, 0·86–1·68; p=0·29 [confirmed group only]). 30 (34%) of 89 cardiovascular events in patients assigned tE2 occurred more than 3 months after tE2 was stopped or changed to LHRHa. The most frequent adverse events were gynaecomastia (all grades), with 279 (38%) events in 730 patients who received LHRHa versus 690 (86%) in 807 patients who received tE2 (p<0·0001) and hot flushes (all grades) in 628 (86%) of those who received LHRHa versus 280 (35%) who received tE2 (p<0·0001). Interpretation Long-term data comparing tE2 patches with LHRHa show no evidence of a difference between treatments in cardiovascular mortality or morbidity. Oestrogens administered transdermally should be reconsidered for androgen suppression in the management of prostate cancer. Funding Cancer Research UK, and Medical Research Council Clinical Trials Unit at University College London