Identification of ovarian cancer metastatic miRNAs

Serous epithelial ovarian cancer (EOC) patients often succumb to aggressive metastatic disease, yet little is known about the behavior and genetics of ovarian cancer metastasis. Here, we aim to understand how omental metastases differ from primary tumors and how these differences may influence chemotherapy. We analyzed the miRNA expression profiles of primary EOC tumors and their respective omental metastases from 9 patients using miRNA Taqman qPCR arrays. We find 17 miRNAs with differential expression in omental lesions compared to primary tumors. miR-21, miR-150, and miR-146a have low expression in most primary tumors with significantly increased expression in omental lesions, with concomitant decreased expression of predicted mRNA targets based on mRNA expression. We find that miR-150 and miR-146a mediate spheroid size. Both miR-146a and miR-150 increase the number of residual surviving cells by 2–4 fold when challenged with lethal cisplatin concentrations. These observations suggest that at least two of the miRNAs, miR-146a and miR-150, up-regulated in omental lesions, stimulate survival and increase drug tolerance. Our observations suggest that cancer cells in omental tumors express key miRNAs differently than primary tumors, and that at least some of these microRNAs may be critical regulators of the emergence of drug resistant disease.<br/

The CatWISE Preliminary Catalog: Motions from WISE{\it WISE} and NEOWISE{\it NEOWISE} Data

CatWISE is a program to catalog sources selected from combined ${\it WISE}$ and ${\it NEOWISE}$ all-sky survey data at 3.4 and 4.6 $\mu$m (W1 and W2). The CatWISE Preliminary Catalog consists of 900,849,014 sources measured in data collected from 2010 to 2016. This dataset represents four times as many exposures and spans over ten times as large a time baseline as that used for the AllWISE Catalog. CatWISE adapts AllWISE software to measure the sources in coadded images created from six-month subsets of these data, each representing one coverage of the inertial sky, or epoch. The catalog includes the measured motion of sources in 8 epochs over the 6.5 year span of the data. From comparison to ${\it Spitzer}$, the SNR=5 limits in magnitudes in the Vega system are W1=17.67 and W2=16.47, compared to W1=16.96 and W2=16.02 for AllWISE. From comparison to ${\it Gaia}$, CatWISE positions have typical accuracies of 50 mas for stars at W1=10 mag and 275 mas for stars at W1=15.5 mag. Proper motions have typical accuracies of 10 mas yr$^{-1}$ and 30 mas yr$^{-1}$ for stars with these brightnesses, an order of magnitude better than from AllWISE. The catalog is available in the WISE/NEOWISE Enhanced and Contributed Products area of the NASA/IPAC Infrared Science Archive.Comment: 53 pages, 20 figures, 5 tables. Accepted by ApJ

The CatWISE2020 Catalog

The CatWISE2020 Catalog consists of 1,890,715,640 sources over the entire sky selected from WISE and NEOWISE survey data at 3.4 and 4.6 $\mu$m (W1 and W2) collected from 2010 Jan. 7 to 2018 Dec. 13. This dataset adds two years to that used for the CatWISE Preliminary Catalog (Eisenhardt et al., 2020), bringing the total to six times as many exposures spanning over sixteen times as large a time baseline as the AllWISE catalog. The other major change from the CatWISE Preliminary Catalog is that the detection list for the CatWISE2020 Catalog was generated using ${\it crowdsource}$ (Schlafly et al. 2019), while the CatWISE Preliminary Catalog used the detection software used for AllWISE. These two factors result in roughly twice as many sources in the CatWISE2020 Catalog. The scatter with respect to ${\it Spitzer}$ photometry at faint magnitudes in the COSMOS field, which is out of the Galactic plane and at low ecliptic latitude (corresponding to lower WISE coverage depth) is similar to that for the CatWISE Preliminary Catalog. The 90% completeness depth for the CatWISE2020 Catalog is at W1=17.7 mag and W2=17.5 mag, 1.7 mag deeper than in the CatWISE Preliminary Catalog. From comparison to ${\it Gaia}$, CatWISE2020 motions are accurate at the 20 mas yr$^{-1}$ level for W1$\sim$15 mag sources, and at the $\sim100$ mas yr$^{-1}$ level for W1$\sim$17 mag sources. This level of precision represents a 12$\times$ improvement over AllWISE. The CatWISE catalogs are available in the WISE/NEOWISE Enhanced and Contributed Products area of the NASA/IPAC Infrared Science Archive.Comment: 27 pages, 24 figure, 2 tables. Accepted for publication in ApJS. arXiv admin note: text overlap with arXiv:1908.0890

JWST reveals a population of ultra-red, flattened disk galaxies at 2<z<6 previously missed by HST

With just a month of data, JWST is already transforming our view of the Universe, revealing and resolving starlight in unprecedented populations of galaxies. Although ``HST-dark" galaxies have previously been detected at long wavelengths, these observations generally suffer from a lack of spatial resolution which limits our ability to characterize their sizes and morphologies. Here we report on a first view of starlight from a subset of the HST-dark population that are bright with JWST/NIRCam (4.4$\mu$m<24.5mag) and very faint or even invisible with HST ($<$1.6$\mu$m). In this Letter we focus on a dramatic and unanticipated population of physically extended galaxies ($\gtrsim$0.17''). These 12 galaxies have photometric redshifts $2<z<6$, high stellar masses $M_{\star}\gtrsim 10^{10}~M_{\odot}$, and significant dust-attenuated star formation. Surprisingly, the galaxies have elongated projected axis ratios at 4.4$\mu$m, suggesting that the population is disk-dominated or prolate. Most of the galaxies appear red at all radii, suggesting significant dust attenuation throughout. We refer to these red, disky, HST-dark galaxies as Ultra-red Flattened Objects (UFOs). With $r_e$(F444W)$\sim1-2$~kpc, the galaxies are similar in size to compact massive galaxies at $z\sim2$ and the cores of massive galaxies and S0s at $z\sim0$. The stellar masses, sizes, and morphologies of the sample suggest that some could be progenitors of lenticular or fast-rotating galaxies in the local Universe. The existence of this population suggests that our previous censuses of the universe may have missed massive, dusty edge-on disks, in addition to dust-obscured starbursts

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Phase-locking of bursting neuronal firing to dominant LFP frequency components

Neuronal firing in the hippocampal formation relative to the phase of local field potentials (LFP) has a key role in memory processing and spatial navigation. Firing can be in either tonic or burst mode. Although bursting neurons are common in the hippocampal formation, the characteristics of their locking to LFP phase are not completely understood. We investigated phase-locking properties of bursting neurons using simulations generated by a dual compartmental model of a pyramidal neuron adapted to match the bursting activity in the subiculum of a rat. The model was driven with stochastic input signals containing a power spectral profile consistent with physiologically relevant frequencies observed in LFP. The single spikes and spike bursts fired by the model were locked to a preferred phase of the predominant frequency band where there was a peak in the power of the driving signal. Moreover, the preferred phase of locking shifted with increasing burst size, providing evidence that LFP phase can be encoded by burst size. We also provide initial support for the model results by analysing example data of spontaneous LFP and spiking activity recorded from the subiculum of a single urethane-anaesthetised rat. Subicular neurons fired single spikes, two-spike bursts and larger bursts that locked to a preferred phase of either dominant slow oscillations or theta rhythms within the LFP, according to the model prediction. Both power-modulated phase-locking and gradual shift in the preferred phase of locking as a function of burst size suggest that neurons can use bursts to encode timing information contained in LFP phase into a spike-count code

JWST-TST DREAMS: Quartz Clouds in the Atmosphere of WASP-17b

Clouds are prevalent in many of the exoplanet atmospheres that have been observed to date. For transiting exoplanets, we know if clouds are present because they mute spectral features and cause wavelength-dependent scattering. While the exact composition of these clouds is largely unknown, this information is vital to understanding the chemistry and energy budget of planetary atmospheres. In this work, we observe one transit of the hot Jupiter WASP-17b with JWST's MIRI LRS and generate a transmission spectrum from 5-12 $\rm{\mu}$m. These wavelengths allow us to probe absorption due to the vibrational modes of various predicted cloud species. Our transmission spectrum shows additional opacity centered at 8.6 $\rm{\mu}$m, and detailed atmospheric modeling and retrievals identify this feature as SiO$_2$(s) (quartz) clouds. The SiO$_2$(s) clouds model is preferred at 3.5-4.2$\sigma$ versus a cloud-free model and at 2.6$\sigma$ versus a generic aerosol prescription. We find the SiO$_2$(s) clouds are comprised of small ${\sim}0.01$ $\rm{\mu}$m particles, which extend to high altitudes in the atmosphere. The atmosphere also shows a depletion of H$_2$O, a finding consistent with the formation of high-temperature aerosols from oxygen-rich species. This work is part of a series of studies by our JWST Telescope Scientist Team (JWST-TST), in which we will use Guaranteed Time Observations to perform Deep Reconnaissance of Exoplanet Atmospheres through Multi-instrument Spectroscopy (DREAMS).Comment: 19 pages, 7 figures, accepted for publication in ApJ

CWISEP J193518.59–154620.3: An Extremely Cold Brown Dwarf in the Solar Neighborhood Discovered with CatWISE

We present the discovery of an extremely cold, nearby brown dwarf in the solar neighborhood, found in the CatWISE catalog. Photometric follow-up with Spitzer reveals that the object, CWISEP J193518.59–154620.3, has ch1–ch2 = 3.24 ± 0.31 mag, making it one of the reddest brown dwarfs known. Using the Spitzer photometry and the polynomial relations from Kirkpatrick et al. we estimate an effective temperature in the ~270–360 K range, and a distance estimate in the 5.6–10.9 pc range. We combined the WISE, NEOWISE, and Spitzer data to measure a proper motion of μ_α cos δ = 337±69 mas yr^(−1), μ_δ = −50 ± 97 mas yr^(−1), which implies a relatively low tangential velocity in the range 7–22 km s^(−1)

American Gut: an Open Platform for Citizen Science Microbiome Research

McDonald D, Hyde E, Debelius JW, et al. American Gut: an Open Platform for Citizen Science Microbiome Research. mSystems. 2018;3(3):e00031-18

Implementation of corticosteroids in treating COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK:prospective observational cohort study

BACKGROUND: Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care. METHODS: We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260. FINDINGS: Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70–0·89], p=0·0001, for 70–79 years; 0·52 [0·46–0·58], p80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75–80% in January, 2021. INTERPRETATION: Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered. FUNDING: UK National Institute for Health Research and UK Medical Research Council