Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by developmental delay, impaired communication, motor deficits and ataxia, intellectual disabilities, microcephaly, and ...seizures. The genetic cause of AS is the loss of expression of UBE3A (ubiquitin protein ligase E6-AP) in the brain, typically due to a deletion of the maternal 15q11-q13 region. Previous studies have been performed using a mouse model with a deletion of a single exon of Ube3a. Since three splice variants of Ube3a exist, this has led to a lack of consistent reports and the theory that perhaps not all mouse studies were assessing the effects of an absence of all functional UBE3A. Herein, we report the generation and functional characterization of a novel model of Angelman syndrome by deleting the entire Ube3a gene in the rat. We validated that this resulted in the first comprehensive gene deletion rodent model. Ultrasonic vocalizations from newborn Ube3a
were reduced in the maternal inherited deletion group with no observable change in the Ube3a
paternal transmission cohort. We also discovered Ube3a
exhibited delayed reflex development, motor deficits in rearing and fine motor skills, aberrant social communication, and impaired touchscreen learning and memory in young adults. These behavioral deficits were large in effect size and easily apparent in the larger rodent species. Low social communication was detected using a playback task that is unique to rats. Structural imaging illustrated decreased brain volume in Ube3a
and a variety of intriguing neuroanatomical phenotypes while Ube3a
did not exhibit altered neuroanatomy. Our report identifies, for the first time, unique AS relevant functional phenotypes and anatomical markers as preclinical outcomes to test various strategies for gene and molecular therapies in AS.
► Dense core vesicles and KIF1A co-transport in a bidirectional manner in axons. ► Knockdown of KIF1A reduces bidirectional axonal transport of dense-core vesicles. ► Dense-core vesicles likely ...contain a coordinated motor complex.
Dense-core vesicles (DCVs) are responsible for transporting, processing, and secreting neuropeptide cargos that mediate a wide range of biological processes, including neuronal development, survival, and learning and memory. DCVs are synthesized in the cell body and are transported by kinesin motor proteins along microtubules to pre- and postsynaptic release sites. Due to the dependence on kinesin-based transport, we sought to determine if the kinesin-3 family member, KIF1A, transports DCVs in primary cultured hippocampal neurons, as has been described for invertebrate neurons. Two-color, live-cell imaging showed that the DCV markers, chromogranin A-RFP and BDNF-RFP, move together with KIF1A-GFP in both the anterograde and retrograde directions. To demonstrate a functional role for KIF1A in DCV transport, motor protein expression in neurons was reduced using RNA interference (shRNA). Fluorescently tagged DCV markers showed a significant reduction in organelle flux in cells expressing shRNA against KIF1A. The transport of cargo driven by motors other than KIF1A, including mitochondria and the transferrin receptor, was unaffected in KIF1A shRNA expressing cells. Taken together, these data support a primary role for KIF1A in the anterograde transport of DCVs in mammalian neurons, and also provide evidence that KIF1A remains associated with DCVs during retrograde DCV transport.
We study the observables of 158 relatively normal Type Ia supernovae (SNe Ia) by dividing them into two groups in terms of the expansion velocity inferred from the absorption minimum of the Si II ...lambda 6355 line in their spectra near B-band maximum brightness. One group ('Normal') consists of normal SNe Ia populating a narrow strip in the Si II velocity distribution, with an average expansion velocity v = 10, 600 - 400 km s-1 near B maximum; the other group ('HV') consists of objects with higher velocities, v 11, 800 km s-1. Compared with the Normal group, the HV one shows a narrower distribution in both the peak luminosity and the luminosity decline rate Delta m 15. In particular, their B-V colors at maximum brightness are found to be on average redder by ~ 0.1 mag, suggesting that they either are associated with dusty environments or have intrinsically red B-V colors. The HV SNe Ia are also found to prefer a lower extinction ratio RV 1.6 (versus ~ 2.4 for the Normal ones). Applying such an absorption-correction dichotomy to SNe Ia of these two groups remarkably reduces the dispersion in their peak luminosity from 0.178 mag to only 0.125 mag.
Associations between bladder cancer risk and NAT2 and GSTM1 polymorphisms have emerged as some of the most consistent findings in the genetic epidemiology of common metabolic polymorphisms and ...cancer, but their interaction with tobacco use, intensity and duration remain unclear. In a New England population-based case-control study of urothelial carcinoma, we collected mouthwash samples from 1088 of 1171 cases (92.9%) and 1282 of 1418 controls (91.2%) for genotype analysis of GSTM1, GSTT1 and NAT2 polymorphisms. Odds ratios and 95% confidence intervals of bladder cancer among New England Bladder Cancer Study subjects with one or two inactive GSTM1 alleles (i.e. the 'null' genotype) were 1.26 (0.85-1.88) and 1.54 (1.05-2.25), respectively (P-trend = 0.008), compared with those with two active copies. GSTT1 inactive alleles were not associated with risk. NAT2 slow acetylation status was not associated with risk among never (1.04; 0.71-1.51), former (0.95; 0.75-1.20) or current smokers (1.33; 0.91-1.95); however, a relationship emerged when smoking intensity was evaluated. Among slow acetylators who ever smoked at least 40 cigarettes/day, risk was elevated among ever (1.82; 1.14-2.91, P-interaction = 0.07) and current heavy smokers (3.16; 1.22-8.19, P-interaction = 0.03) compared with rapid acetylators in each category; but was not observed at lower intensities. In contrast, the effect of GSTM1-null genotype was not greater among smokers, regardless of intensity. Meta-analysis of the NAT2 associations with bladder cancer showed a highly significant relationship. Findings from this large USA population-based study provided evidence that the NAT2 slow acetylation genotype interacts with tobacco smoking as a function of exposure intensity.
The ALPINE-ALMA [CII] survey Khusanova, Y.; Bethermin, M.; Le Fèvre, O. ...
Astronomy and astrophysics (Berlin),
05/2021, Letnik:
649
Journal Article
Recenzirano
Odprti dostop
Star formation rate (SFR) measurements at
z
> 4 have relied mostly on the rest-frame far-ultraviolet (FUV) observations. The corrections for dust attenuation based on the IRX-
β
relation are highly ...uncertain and are still debated in the literature. Hence, rest-frame far-infrared (FIR) observations are necessary to constrain the dust-obscured component of the SFR. In this paper, we exploit the rest-frame FIR continuum observations collected by the ALMA Large Program to INvestigate CII at Early times (ALPINE) to directly constrain the obscured SFR in galaxies at 4.4 <
z
< 5.9. We used stacks of continuum images to measure average infrared luminosities taking both detected and undetected sources into account. Based on these measurements, we measured the position of the main sequence of star-forming galaxies and the specific SFR (sSFR) at
z
∼ 4.5 and
z
∼ 5.5. We find that the main sequence and sSFR do not significantly evolve between
z
∼ 4.5 and
z
∼ 5.5, as opposed to lower redshifts. We developed a method to derive the obscured SFR density (SFRD) using the stellar masses or FUV-magnitudes as a proxy of FIR fluxes measured on the stacks and combining them with the galaxy stellar mass functions and FUV luminosity functions from the literature. We obtain consistent results independent of the chosen proxy. We find that the obscured fraction of SFRD is decreasing with increasing redshift, but even at
z
∼ 5.5 it constitutes around 61% of the total SFRD.
ABSTRACT Local starbursts have a higher efficiency of converting gas into stars, as compared to typical star-forming galaxies at a given stellar mass, possibly indicative of different modes of star ...formation. With the peak epoch of galaxy formation occurring at z > 1, it remains to be established whether such an efficient mode of star formation is occurring at high redshift. To address this issue, we measure the molecular gas content of seven high-redshift (z ∼ 1.6) starburst galaxies with the Atacama Large Millimeter/submillimeter Array and IRAM/Plateau de Bure Interferometer. Our targets are selected from the sample of Herschel far-infrared-detected galaxies having star formation rates (∼300-800 M yr−1) elevated ( 4×) above the star-forming main sequence (MS) and included in the FMOS-COSMOS near-infrared spectroscopic survey of star-forming galaxies at z ∼ 1.6 with Subaru. We detect CO emission in all cases at high levels of significance, indicative of high gas fractions (∼30%-50%). Even more compelling, we firmly establish with a clean and systematic selection that starbursts, identified as MS outliers, at high redshift generally have a lower ratio of CO to total infrared luminosity as compared to typical MS star-forming galaxies, although with a smaller offset than expected based on past studies of local starbursts. We put forward a hypothesis that there exists a continuous increase in star formation efficiency with elevation from the MS with galaxy mergers as a possible physical driver. Along with a heightened star formation efficiency, our high-redshift sample is similar in other respects to local starbursts, such as being metal rich and having a higher ionization state of the interstellar medium.
Dust-enshrouded, starbursting, submillimeter galaxies (SMGs) at z ≥ 3 have been proposed as progenitors of z ≥ 2 compact quiescent galaxies (cQGs). To test this connection, we present a detailed ...spatially resolved study of the stars, dust, and stellar mass in a sample of six submillimeter-bright starburst galaxies at z ∼ 4.5. The stellar UV emission probed by HST is extended and irregular and shows evidence of multiple components. Informed by HST, we deblend Spitzer/IRAC data at rest-frame optical, finding that the systems are undergoing minor mergers with a typical stellar mass ratio of 1:6.5. The FIR dust continuum emission traced by ALMA locates the bulk of star formation in extremely compact regions (median re = 0.70 0.29 kpc), and it is in all cases associated with the most massive component of the mergers (median ). We compare spatially resolved UV slope (β) maps with the FIR dust continuum to study the infrared excess (IRX = LIR/LUV)-β relation. The SMGs display systematically higher IRX values than expected from the nominal trend, demonstrating that the FIR and UV emissions are spatially disconnected. Finally, we show that the SMGs fall on the mass-size plane at smaller stellar masses and sizes than the cQGs at z = 2. Taking into account the expected evolution in stellar mass and size between z = 4.5 and z = 2 due to the ongoing starburst and mergers with minor companions, this is in agreement with a direct evolutionary connection between the two populations.
We present the results of a program to acquire high-quality optical spectra of X-ray sources detected in the Extended-Chandra Deep Field-South (E-CDF-S) and its central 2 Ms area. New spectroscopic ...redshifts, up to z = 4, are measured for 283 counterparts to Chandra sources with deep exposures (t ~ 2-9 hr per pointing) using multi-slit facilities on both VLT (VIMOS) and Keck (DEIMOS), thus bringing the total number of spectroscopically identified X-ray sources to over 500 in this survey field. Since our new spectroscopic identifications are mainly associated with X-ray sources in the shallower 250 ks coverage, we provide a comprehensive catalog of X-ray sources detected in the E-CDF-S including the optical and near-infrared counterparts, determined by a likelihood routine, and redshifts (both spectroscopic and photometric), that incorporate published spectroscopic catalogs, thus resulting in a final sample with a high fraction (80%) of X-ray sources having secure identifications. We demonstrate the remarkable coverage of the luminosity-redshift plane now accessible from our data while emphasizing the detection of active galactic nuclei (AGNs) that contribute to the faint end of the luminosity function (L 0.5-8 keV ~ 1043-1044 erg s--1) at 1.5 z 3 including those with and without broad emission lines. Our redshift catalog includes 17 type-2 QSOs at 1 z 3.5 that significantly increases such samples (2X). Based on our deepest (9 hr) VLT/VIMOS observation, we identify 'elusive' optically faint galaxies (R mag ~ 25) at z ~ 2-3 based upon the detection of interstellar absorption lines (e.g., O II+Si IV, C II, C IV); we highlight one such case, an absorption-line galaxy at z = 3.208 having no obvious signs of an AGN in its optical spectrum. In addition, we determine accurate distances to eight galaxy groups with extended X-ray emission detected both by Chandra and XMM-Newton. Finally, we measure the physical extent of known large-scale structures (z ~ 0.7) evident in the CDF-S. While a thick sheet (a radial size of 67.7 Mpc) at z ~ 0.67 extends over the full field, the z ~ 0.73 structure is thin (18.8 Mpc) and filamentary as traced by both AGNs and galaxy groups. In the Appendix, we provide spectroscopic redshifts for 49 counterparts to fainter X-ray sources detected only in the 1 and 2 Ms catalogs, and 48 Very Large Array radio sources not detected in X-rays.
We present point-source catalogs for the sim2 Ms exposure of the Chandra Deep Field-South (CDF-S); this is one of the two most sensitive X-ray surveys ever performed. The survey covers an area of ...sim436 arcmin super(2) and reaches on-axis sensitivity limits of simimage and simimage ergs cm super(-2) s super(-1) for the 0.5-2.0 and 2-8 keV bands, respectively. Four hundred and sixty-two X-ray point sources are detected in at least one of three X-ray bands that were searched; 135 of these sources are new compared to the previous sim1 Ms CDF-S detections. Source positions are determined using centroid and matched-filter techniques; the median positional uncertainty is sim0.36 super(image ). The X-ray-to-optical flux ratios of the newly detected sources indicate a variety of source types; sim55% of them appear to be active galactic nuclei, while sim45% appear to be starburst and normal galaxies. In addition to the main Chandra catalog, we provide a supplementary catalog of 86 X-ray sources in the sim2 Ms CDF-S footprint that was created by merging the sim250 ks Extended Chandra Deep Field-South with the CDF-S; this approach provides additional sensitivity in the outer portions of the CDF-S. A second supplementary catalog that contains 30 X-ray sources was constructed by matching lower significance X-ray sources to bright optical counterparts; the majority of these sources appear to be starburst and normal galaxies. The total number of sources in the main and supplementary catalogs is 578. Optical R-band counterparts and basic optical and infrared photometry are provided for the X-ray sources in the main and supplementary catalogs. We also include existing spectroscopic redshifts for 224 of the X-ray sources. The average backgrounds in the 0.5-2.0 and 2-8 keV bands are 0.066 and 0.167 counts Ms super(-1) pixel super(-1), respectively, and the background counts follow Poisson distributions. The effective exposure times and sensitivity limits of the CDF-S are now comparable to those of the sim2 Ms Chandra Deep Field-North (CDF-N). We also present cumulative number counts for the main catalog and compare the results to those for the CDF-N. The soft-band number counts for these two fields agree well with each other at fluxes higher than simimage ergs cm super(-2) s super(-1), while the CDF-S number counts are up to sim25% smaller than those for the CDF-N at fluxes below simimage ergs cm super(-2) s super(-1) in the soft band and simimage ergs cm super(-2) s super(-1) in the hard band, suggesting small field-to-field variations.
We report on the discovery of a merger-driven starburst at z = 1.52, PACS-787, based on high signal-to-noise ALMA observations. CO(5-4) and continuum emission (850 m) at a spatial resolution of 0 3 ...reveal two compact (r1/2 ∼ 1 kpc) and interacting molecular gas disks at a separation of 8.6 kpc, indicative of an early stage in a merger. With an SFR of 991 M yr−1, this starburst event should occur closer to final coalescence, as is usually seen in hydrodynamical simulations. From the CO size, inclination, and velocity profile for both disks, the dynamical mass is calculated through a novel method that incorporates a calibration using simulations of galaxy mergers. Based on the dynamical mass, we measure (1) the molecular gas mass, independent from the CO luminosity, (2) the ratio of the total gas mass and the CO(1-0) luminosity ( ), and (3) the gas-to-dust ratio, with the latter two being lower than typically assumed. We find that the high star formation triggered in both galaxies is caused by a set of optimal conditions: a high gas mass/fraction, a short depletion time (τdepl = 85 and 67 Myr) to convert gas into stars, and the interaction of likely counter-rotating molecular disks that may accelerate the loss of angular momentum. The state of interaction is further established by the detection of diffuse CO and continuum emission, tidal debris that bridges the two nuclei and is associated with stellar emission seen by HST/WFC3. This observation demonstrates the power of ALMA to study the dynamics of galaxy mergers at high redshift.