Temporal Regulation of Foregut Development by HTZ-1/H2A.Z and PHA-4/FoxA

The histone variant H2A.Z is evolutionarily conserved and plays an essential role in mice, Drosophila, and Tetrahymena. The essential function of H2A.Z is unknown, with some studies suggesting a role in transcriptional repression and others in activation. Here we show that Caenorhabditis elegans HTZ-1/H2A.Z and the remodeling complex MYS-1/ESA1–SSL-1/SWR1 synergize with the FoxA transcription factor PHA-4 to coordinate temporal gene expression during foregut development. We observe dramatic genetic interactions between pha-4 and htz-1, mys-1, and ssl-1. A survey of transcription factors reveals that this interaction is specific, and thus pha-4 is acutely sensitive to reductions in these three proteins. Using a nuclear spot assay to visualize HTZ-1 in living embryos as organogenesis proceeds, we show that HTZ-1 is recruited to foregut promoters at the time of transcriptional onset, and this recruitment requires PHA-4. Loss of htz-1 by RNAi is lethal and leads to delayed expression of a subset of foregut genes. Thus, the effects of PHA-4 on temporal regulation can be explained in part by recruitment of HTZ-1 to target promoters. We suggest PHA-4 and HTZ-1 coordinate temporal gene expression by modulating the chromatin environment

BL Lacertae objects beyond redshift 1.3 - UV-to-NIR photometry and photometric redshift for Fermi/LAT blazars

Observations of the gamma-ray sky with Fermi led to significant advances towards understanding blazars, the most extreme class of Active Galactic Nuclei. A large fraction of the population detected by Fermi is formed by BL Lacertae (BL Lac) objects, whose sample has always suffered from a severe redshift incompleteness due to the quasi-featureless optical spectra. Our goal is to provide a significant increase of the number of confirmed high-redshift BL Lac objects contained in the 2 LAC Fermi/LAT catalog. For 103 Fermi/LAT blazars, photometric redshifts using spectral energy distribution fitting have been obtained. The photometry includes 13 broad-band filters from the far ultraviolet to the near-IR observed with Swift/UVOT and the multi-channel imager GROND at the MPG/ESO 2.2m telescope. Data have been taken quasi-simultaneously and the remaining source-intrinsic variability has been corrected for. We release the UV-to-near-IR 13-band photometry for all 103 sources and provide redshift constraints for 75 sources without previously known redshift. Out of those, eight have reliable photometric redshifts at z>1.3, while for the other 67 sources we provide upper limits. Six of the former eight are BL Lac objects, which quadruples the sample of confirmed high-redshift BL Lac. This includes three sources with redshifts higher than the previous record for BL Lac, including CRATES J0402-2615 with the best-fit solution at z~1.9.Comment: Uploaded correct Fig 4. Changed counterpart name for 2FGLJ0537.7-5716 from PKS 0541-834 (different source) to SUMSS J053748-57182

Evidence for Supernova-Synthesised Dust from the Rising Afterglow of GRB 071025 at z~5

We present observations and analysis of the broadband afterglow of Swift GRB 071025. Using optical and infrared (RIYJHK) photometry, we derive a photometric redshift of 4.4 < z < 5.2; at this redshift our simultaneous multicolour observations begin at ~30 s after the GRB trigger in the host frame and during the initial rising phase of the afterglow. We associate the light curve peak at 580 s in the observer frame with the formation of the forward shock, giving an estimate of the initial Lorentz factor Gamma_0 ~ 200. The red spectral energy distribution (even in regions not affected by the Lyman-alpha break) provides secure evidence of a large dust column. However, the inferred extinction curve shows a prominent flat component between 2000-3000 Angstroms in the rest-frame, inconsistent with any locally observed template but well-fit by models of dust formed by supernovae. Time-dependent fits to the extinction profile reveal no evidence of dust destruction and limit the decrease in the extinction column to Delta A_3000 < 0.54 mag after t = 50 s in the rest frame. Our observations provide evidence of a transition in dust properties at z~5, in agreement with studies of high-z quasars, and suggest that SN-formed dust continues to dominate the opacity of typical galaxies at this redshift.Comment: Resubmitted to MNRAS following referee report. Contains additional figure and some extra analysis/discussio

Monster in the Dark: The Ultraluminous GRB 080607 and its Dusty Environment

We present early-time optical through infrared photometry of the bright gamma-ray burst GRB 080607, starting only 6 s following the initial trigger in the rest frame. Complemented by our previously published spectroscopy, this high-quality photometric dataset allows us to solve for the extinction properties of the redshift 3.036 sightline, giving perhaps the most detailed information on the ultraviolet continuum absorption properties of any sightline outside our Local Group to date. The extinction properties are not adequately modeled by any ordinary extinction template (including the average Milky Way, Large Magellanic Cloud, and Small Magellanic Cloud curves), partially because the 2175 A feature (while present) is weaker by about a factor of two than when seen under similar cir-cumstances locally. However, the spectral energy distribution is exquisitely fitted by the more general Fitzpatrick & Massa (1990) parameterization of Local-Group extinction, putting it in the same family as some peculiar Milky Way extinction curves. After correcting for this (considerable, AV = 3.3±0.4 mag) extinction, GRB 080607 is revealed to have been among the most optically luminous events ever observed, comparable to the naked-eye burst GRB 080319B. Its early peak time (trest \u3c 6 s) indicates a high initial Lorentz factor (T \u3e 600), while the extreme luminosity may be explained in part by a large circumburst density. Only because of its early high luminosity could the afterglow of GRB 080607 be studied in such detail in spite of the large attenuation and great distance, making this burst an excellent prototype for the understanding of other highly obscured extragalactic objects, and of the class of “dark” GRBs in particular

On the nature of the extremely fast optical rebrightening of the afterglow of GRB 081029

Context. After the launch of the Swift satellite, the Gamma-Ray Burst (GRB) optical light-curve smoothness paradigm has been questioned thanks to the faster and better sampled optical follow-up, which has unveiled a very complex behaviour. This complexity is triggering the interest of the whole GRB community. The GROND multi-channel imager is used to study optical and near-infrared (NIR) afterglows of GRBs with unprecedented optical and near-infrared temporal and spectral resolution. The GRB 081029 has a very prominent optical rebrightening event and is an outstanding example of the application of the multi-channel imager to GRB afterglows. Aims. Here we exploit the rich GROND multi-colour follow-up of GRB 081029 combined with XRT observations to study the nature of late-time rebrightenings that appear in the optical-NIR light-curves of some GRB afterglows. Methods. We analyse the optical and NIR observations obtained with the seven-channel Gamma-Ray burst Optical and Near-infrared Detector (GROND) at the 2.2 m MPI/ESO telescope and the X-ray data obtained with the XRT telescope on board the Swift observatory. The multi-wavelength temporal and spectral evolution is discussed in the framework of different physical models. Results. The extremely steep optical and NIR rebrightening observed in GRB 081029 cannot be explained in the framework of the standard forward shock afterglow model. The absence of a contemporaneous X-ray rebrightening and the evidence of a strong spectral evolution in the optical-NIR bands during the rise suggest two separate components that dominate in the early and late-time lightcurves, respectively. The steepness of the optical rise cannot be explained even in the framework of the alternative scenarios proposed in the literature unless a late-time activity of the central engine is assumed.Comment: 9 pages, 7 figures, accepted for publication in Astronomy and Astrophysic

The Rapidly Flaring Afterglow of the Very Bright and Energetic GRB 070125

We report on multi-wavelength observations, ranging from the X-ray to radio wave bands, of the IPN-localized gamma-ray burst GRB 070125. Spectroscopic observations reveal the presence of absorption lines due to O I, Si II, and C IV, implying a likely redshift of z = 1.547. The well-sampled light curves, in particular from 0.5 to 4 days after the burst, suggest a jet break at 3.7 days, corresponding to a jet opening angle of ~7.0 degrees, and implying an intrinsic GRB energy in the 1 - 10,000 keV band of around E = (6.3 - 6.9)x 10^(51) erg (based on the fluences measured by the gamma-ray detectors of the IPN network). GRB 070125 is among the brightest afterglows observed to date. The spectral energy distribution implies a host extinction of Av < 0.9 mag. Two rebrightening episodes are observed, one with excellent time coverage, showing an increase in flux of 56% in ~8000 seconds. The evolution of the afterglow light curve is achromatic at all times. Late-time observations of the afterglow do not show evidence for emission from an underlying host galaxy or supernova. Any host galaxy would be subluminous, consistent with current GRB host-galaxy samples. Evidence for strong Mg II absorption features is not found, which is perhaps surprising in view of the relatively high redshift of this burst and the high likelihood for such features along GRB-selected lines of sight.Comment: 50 pages, 9 figures, 5 tables Accepted to the Astrophysical Journa

A deep search for the host galaxies of GRBs with no detected optical afterglow

Gamma-Ray Bursts can provide information about star formation at high redshifts. Even in the absence of a optical/near-infrared/radio afterglow, the high detection rate of X-ray afterglows by swift/XRT and its localization precision of 2-3 arcsec facilitates the identification and study of GRB host galaxies. We focus on the search for the host galaxies of a sample of 17 bursts with XRT error circles but no detected long-wavelength afterglow. Three of these events can also be classified as truly dark bursts: the observed upper limit on the optical flux of the afterglow was less than expected based on the X-ray flux. Our study is based on deep R and K-band observations performed with ESO/VLT instruments, supported by GROND and NEWFIRM. To be conservative, we searched for host galaxies in an area with a radius twice the 90% swift/XRT error circle. For 15 of the 17 bursts we find at least one galaxy inside the doubled XRT error circle. In seven cases we discover extremely red objects in the error circles. The most remarkable case is the host of GRB 080207 which as a colour of R-K~4.7 mag (AB), one of the reddest galaxies ever associated with a GRB. As a by-product of our study we identify the optical afterglow of GRB 070517A. Optically dim afterglows result from cosmological Lyman drop out and dust extinction, but the former process is only equired for a minority of cases (<1/3). Extinction by dust in the host galaxies might explain all other events. Thereby, a seemingly non-negligible fraction of these hosts are globally dust-enshrouded, extremely red galaxies. This suggests that bursts with optically dim afterglows trace a subpopulation of massive starburst galaxies, which are markedly different from the main body of the GRB host galaxy population, namely the blue, subluminous, compact galaxies.Comment: 29 pages, 31 figures, accepted for publication in A&

Measuring routine childhood vaccination coverage in 204 countries and territories, 1980–2019 : a systematic analysis for the Global Burden of Disease Study 2020, Release 1

Background: Measuring routine childhood vaccination is crucial to inform global vaccine policies and programme implementation, and to track progress towards targets set by the Global Vaccine Action Plan (GVAP) and Immunization Agenda 2030. Robust estimates of routine vaccine coverage are needed to identify past successes and persistent vulnerabilities. Drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020, Release 1, we did a systematic analysis of global, regional, and national vaccine coverage trends using a statistical framework, by vaccine and over time. Methods: For this analysis we collated 55 326 country-specific, cohort-specific, year-specific, vaccine-specific, and dose-specific observations of routine childhood vaccination coverage between 1980 and 2019. Using spatiotemporal Gaussian process regression, we produced location-specific and year-specific estimates of 11 routine childhood vaccine coverage indicators for 204 countries and territories from 1980 to 2019, adjusting for biases in country-reported data and reflecting reported stockouts and supply disruptions. We analysed global and regional trends in coverage and numbers of zero-dose children (defined as those who never received a diphtheria-tetanus-pertussis [DTP] vaccine dose), progress towards GVAP targets, and the relationship between vaccine coverage and sociodemographic development. Findings: By 2019, global coverage of third-dose DTP (DTP3; 81·6% [95% uncertainty interval 80·4–82·7]) more than doubled from levels estimated in 1980 (39·9% [37·5–42·1]), as did global coverage of the first-dose measles-containing vaccine (MCV1; from 38·5% [35·4–41·3] in 1980 to 83·6% [82·3–84·8] in 2019). Third-dose polio vaccine (Pol3) coverage also increased, from 42·6% (41·4–44·1) in 1980 to 79·8% (78·4–81·1) in 2019, and global coverage of newer vaccines increased rapidly between 2000 and 2019. The global number of zero-dose children fell by nearly 75% between 1980 and 2019, from 56·8 million (52·6–60·9) to 14·5 million (13·4–15·9). However, over the past decade, global vaccine coverage broadly plateaued; 94 countries and territories recorded decreasing DTP3 coverage since 2010. Only 11 countries and territories were estimated to have reached the national GVAP target of at least 90% coverage for all assessed vaccines in 2019. Interpretation: After achieving large gains in childhood vaccine coverage worldwide, in much of the world this progress was stalled or reversed from 2010 to 2019. These findings underscore the importance of revisiting routine immunisation strategies and programmatic approaches, recentring service delivery around equity and underserved populations. Strengthening vaccine data and monitoring systems is crucial to these pursuits, now and through to 2030, to ensure that all children have access to, and can benefit from, lifesaving vaccines

Vasa-Like DEAD-Box RNA Helicases of Schistosoma mansoni

Genome sequences are available for the human blood flukes, Schistosoma japonicum, S. mansoni and S. haematobium. Functional genomic approaches could aid in identifying the role and importance of these newly described schistosome genes. Transgenesis is established for functional genomics in model species, which can lead to gain- or loss-of-functions, facilitate vector-based RNA interference, and represents an effective forward genetics tool for insertional mutagenesis screens. Progress toward routine transgenesis in schistosomes might be expedited if germ cells could be reliably localized in cultured schistosomes. Vasa, a member of the ATP-dependent DEAD-box RNA helicase family, is a prototypic marker of primordial germ cells and the germ line in the Metazoa. Using bioinformatics, 33 putative DEAD-box RNA helicases exhibiting conserved motifs that characterize helicases of this family were identified in the S. mansoni genome. Moreover, three of the helicases exhibited vasa-like sequences; phylogenetic analysis confirmed the three vasa-like genes—termed Smvlg1, Smvlg2, and Smvlg3—were members of the Vasa/PL10 DEAD-box subfamily. Transcripts encoding Smvlg1, Smvlg2, and Smvlg3 were cloned from cDNAs from mixed sex adult worms, and quantitative real time PCR revealed their presence in developmental stages of S. mansoni with elevated expression in sporocysts, adult females, eggs, and miracidia, with strikingly high expression in the undeveloped egg. Whole mount in situ hybridization (WISH) analysis revealed that Smvlg1, Smvlg2 and Smvlg3 were transcribed in the posterior ovary where the oocytes mature. Germ cell specific expression of schistosome vasa-like genes should provide an informative landmark for germ line transgenesis of schistosomes, etiologic agents of major neglected tropical diseases

The Genomic Distribution and Function of Histone Variant HTZ-1 during C. elegans Embryogenesis

In all eukaryotes, histone variants are incorporated into a subset of nucleosomes to create functionally specialized regions of chromatin. One such variant, H2A.Z, replaces histone H2A and is required for development and viability in all animals tested to date. However, the function of H2A.Z in development remains unclear. Here, we use ChIP-chip, genetic mutation, RNAi, and immunofluorescence microscopy to interrogate the function of H2A.Z (HTZ-1) during embryogenesis in Caenorhabditis elegans, a key model of metazoan development. We find that HTZ-1 is expressed in every cell of the developing embryo and is essential for normal development. The sites of HTZ-1 incorporation during embryogenesis reveal a genome wrought by developmental processes. HTZ-1 is incorporated upstream of 23% of C. elegans genes. While these genes tend to be required for development and occupied by RNA polymerase II, HTZ-1 incorporation does not specify a stereotypic transcription program. The data also provide evidence for unexpectedly widespread independent regulation of genes within operons during development; in 37% of operons, HTZ-1 is incorporated upstream of internally encoded genes. Fewer sites of HTZ-1 incorporation occur on the X chromosome relative to autosomes, which our data suggest is due to a paucity of developmentally important genes on X, rather than a direct function for HTZ-1 in dosage compensation. Our experiments indicate that HTZ-1 functions in establishing or maintaining an essential chromatin state at promoters regulated dynamically during C. elegans embryogenesis