Metazoan arrestins bind to seven-transmembrane (7TM) receptors to regulate function. Aspergillus nidulans PalF, a protein involved in the fungal ambient pH signaling pathway, contains arrestin ...N-terminal and C-terminal domains and binds strongly to two different regions within the C-terminal cytoplasmic tail of the 7TM, putative pH sensor PalH. Upon exposure to alkaline ambient pH, PalF is phosphorylated and, like mammalian β-arrestins, ubiquitinated in a signal-dependent and 7TM protein-dependent manner. Substitution in PalF of a highly conserved arrestin N-terminal domain Ser residue prevents PalF-PalH interaction and pH signaling in vivo. Thus, PalF is the first experimentally documented fungal arrestin-related protein, dispelling the notion that arrestins are restricted to animal proteomes. Epistasis analyses demonstrate that PalF posttranslational modification is partially dependent on the 4TM protein Pall but independent of the remaining pH signal transduction pathway proteins PalA, PalB, and PalC, yielding experimental evidence bearing on the order of participation of the six components of the pH signal transduction pathway. Our data strongly implicate PalH as an ambient pH sensor, possibly with the cooperation of PalI.
During bacteriophage morphogenesis DNA is translocated into a preformed prohead by the complex formed by the portal protein, or connector, plus the terminase, which are located at an especial prohead ...vertex. The terminase is a powerful motor that converts ATP hydrolysis into mechanical movement of the DNA. Here, we have determined the structure of the T7 large terminase by electron microscopy. The five terminase subunits assemble in a toroid that encloses a channel wide enough to accommodate dsDNA. The structure of the complete connector-terminase complex is also reported, revealing the coupling between the terminase and the connector forming a continuous channel. The structure of the terminase assembled into the complex showed a different conformation when compared with the isolated terminase pentamer. To understand in molecular terms the terminase morphological change, we generated the terminase atomic model based on the crystallographic structure of its phage T4 counterpart. The docking of the threaded model in both terminase conformations showed that the transition between the two states can be achieved by rigid body subunit rotation in the pentameric assembly. The existence of two terminase conformations and its possible relation to the sequential DNA translocation may shed light into the molecular bases of the packaging mechanism of bacteriophage T7.
Background: The complex formed by the terminase and the connector provides the structural framework and the chemical energy for DNA packaging during bacteriophage morphogenesis.
Results: The terminase builds a pentamer that presents two conformational topologies.
Conclusion: The conformational change of the terminase might be coupled to DNA packaging.
Significance: Terminase function might be based on concerted intersubunit movement within the connector-terminase complex.
The alkaline ambient pH signal transduction pathway component PalC has no assigned molecular role. Therefore we attempted a gene-specific mutational analysis and obtained 55 new palC loss-of-function ...alleles including 24 single residue substitutions. Refined similarity searches reveal conserved PalC regions including one with convincing similarity to the BRO1 domain, denoted PCBROH, where clustering of mutational changes, including PCBROH key residue substitutions, supports its structural and/or functional importance. Since the BRO1 domain occurs in the multivesicular body (MVB) pathway protein Bro1/Vps31 and also the pH signal transduction protein PalA (Rim20), both of which interact with MVB component (ESCRT-III protein) Vps32/Snf7, this might reflect a further link between the pH response and endocytosis.
Background. The combination of didanosine, lamivudine, and efavirenz (ddI/3TC/EFV) for the initial treatment of human immunodeficiency virus type 1 (HIV-1) infection has been insufficiently analyzed ...in clinical trials. Methods. We conducted an open-label, randomized study to compare the noninferiority of ddI/3TC/EFV with the lamivudine-zidovudine tablet and EFV (COM/EFV), both administered with food to improve tolerability and convenience. Patients were stratified by HIV-1 RNA level of <5.0 log10 or ⩾5.0 log10 copies/mL. The primary end point was the percentage of patients with an HIV-1 RNA level of <50 copies/mL at week 48, determined by intention-to-treat analysis. Results. Three hundred sixty-nine patients were randomized: 186 for ddI/3TC/EFV treatment and 183 for COM/EFV treatment. Both groups were well matched in terms of baseline characteristics; 19.3% of patients received a Centers for Disease Control and Prevention assessment of clinical category C, median HIV RNA level was 5.0 log10 copies/mL, and median CD4+ cell count was 208 cells/µL. At week 48, by intention-to-treat analysis, 70% of patients in the ddI/3TC/EFV group and 63% of patients in the COM/EFV group had an HIV-1 RNA level of <50 copies/mL (treatment difference, 7.1%; 95% confidence interval, −2.39% to 16.59%). Fourteen patients (8%) in the COM/EFV arm and 26 patients (14%) in the ddI/3TC/EFV arm discontinued the study medication because of adverse events (P=.046). One patient (1%) in the ddI/3TC/EFV arm and 11 patients (6%) in the COM/EFV arm discontinued medication because of hematological toxicity (P=.003). Conclusions. At week 48, ddI/3TC/EFV administered once per day with food did not have results inferior to those of COM/EFV treatment. A statistically significantly higher proportion of patients in the COM/EFV arm than in the ddI/3TC/EFV arm discontinued therapy because of adverse events, mainly because of hematological toxicity. Clinical trials registration. NCT00256828.
ABSTRACT
We present a simulated cosmology analysis using the second and third moments of the weak lensing mass (convergence) maps. The second moment, or variances, of the convergence as a function of ...smoothing scale contains information similar to standard shear two-point statistics. The third moment, or the skewness, contains additional non-Gaussian information. The analysis is geared towards the third year (Y3) data from the Dark Energy Survey (DES), but the methodology can be applied to other weak lensing data sets. We present the formalism for obtaining the convergence maps from the measured shear and for obtaining the second and third moments of these maps given partial sky coverage. We estimate the covariance matrix from a large suite of numerical simulations. We test our pipeline through a simulated likelihood analyses varying 5 cosmological parameters and 10 nuisance parameters and identify the scales where systematic or modelling uncertainties are not expected to affect the cosmological analysis. Our simulated likelihood analysis shows that the combination of second and third moments provides a 1.5 per cent constraint on S8 ≡ σ8(Ωm/0.3)0.5 for DES Year 3 data. This is 20 per cent better than an analysis using a simulated DES Y3 shear two-point statistics, owing to the non-Gaussian information captured by the inclusion of higher order statistics. This paper validates our methodology for constraining cosmology with DES Year 3 data, which will be presented in a subsequent paper.
ABSTRACT
We present morphological classifications of ∼27 million galaxies from the Dark Energy Survey (DES) Data Release 1 (DR1) using a supervised deep learning algorithm. The classification scheme ...separates: (a) early-type galaxies (ETGs) from late-type galaxies (LTGs); and (b) face-on galaxies from edge-on. Our convolutional neural networks (CNNs) are trained on a small subset of DES objects with previously known classifications. These typically have mr ≲ 17.7 mag; we model fainter objects to mr < 21.5 mag by simulating what the brighter objects with well-determined classifications would look like if they were at higher redshifts. The CNNs reach 97 per cent accuracy to mr < 21.5 on their training sets, suggesting that they are able to recover features more accurately than the human eye. We then used the trained CNNs to classify the vast majority of the other DES images. The final catalogue comprises five independent CNN predictions for each classification scheme, helping to determine if the CNN predictions are robust or not. We obtain secure classifications for ∼87 per cent and 73 per cent of the catalogue for the ETG versus LTG and edge-on versus face-on models, respectively. Combining the two classifications (a) and (b) helps to increase the purity of the ETG sample and to identify edge-on lenticular galaxies (as ETGs with high ellipticity). Where a comparison is possible, our classifications correlate very well with Sérsic index (n), ellipticity (ϵ), and spectral type, even for the fainter galaxies. This is the largest multiband catalogue of automated galaxy morphologies to date.
ABSTRACT
Cosmological information from weak lensing surveys is maximized by sorting source galaxies into tomographic redshift subsamples. Any uncertainties on these redshift distributions must be ...correctly propagated into the cosmological results. We present hyperrank, a new method for marginalizing over redshift distribution uncertainties, using discrete samples from the space of all possible redshift distributions, improving over simple parametrized models. In hyperrank, the set of proposed redshift distributions is ranked according to a small (between one and four) number of summary values, which are then sampled, along with other nuisance parameters and cosmological parameters in the Monte Carlo chain used for inference. This approach can be regarded as a general method for marginalizing over discrete realizations of data vector variation with nuisance parameters, which can consequently be sampled separately from the main parameters of interest, allowing for increased computational efficiency. We focus on the case of weak lensing cosmic shear analyses and demonstrate our method using simulations made for the Dark Energy Survey (DES). We show that the method can correctly and efficiently marginalize over a wide range of models for the redshift distribution uncertainty. Finally, we compare hyperrank to the common mean-shifting method of marginalizing over redshift uncertainty, validating that this simpler model is sufficient for use in the DES Year 3 cosmology results presented in companion papers.
ABSTRACT
Determining the distribution of redshifts of galaxies observed by wide-field photometric experiments like the Dark Energy Survey (DES) is an essential component to mapping the matter density ...field with gravitational lensing. In this work we describe the methods used to assign individual weak lensing source galaxies from the DES Year 3 Weak Lensing Source Catalogue to four tomographic bins and to estimate the redshift distributions in these bins. As the first application of these methods to data, we validate that the assumptions made apply to the DES Y3 weak lensing source galaxies and develop a full treatment of systematic uncertainties. Our method consists of combining information from three independent likelihood functions: self-organizing map p(z) (sompz), a method for constraining redshifts from galaxy photometry; clustering redshifts (WZ), constraints on redshifts from cross-correlations of galaxy density functions; and shear ratios (SRs), which provide constraints on redshifts from the ratios of the galaxy-shear correlation functions at small scales. Finally, we describe how these independent probes are combined to yield an ensemble of redshift distributions encapsulating our full uncertainty. We calibrate redshifts with combined effective uncertainties of σ〈z〉 ∼ 0.01 on the mean redshift in each tomographic bin.
ABSTRACT
We present DES14X2fna, a high-luminosity, fast-declining Type IIb supernova (SN IIb) at redshift z = 0.0453, detected by the Dark Energy Survey (DES). DES14X2fna is an unusual member of its ...class, with a light curve showing a broad, luminous peak reaching Mr ≃ −19.3 mag 20 d after explosion. This object does not show a linear decline tail in the light curve until ≃60 d after explosion, after which it declines very rapidly (4.30 ± 0.10 mag 100 d−1 in the r band). By fitting semi-analytic models to the photometry of DES14X2fna, we find that its light curve cannot be explained by a standard 56Ni decay model as this is unable to fit the peak and fast tail decline observed. Inclusion of either interaction with surrounding circumstellar material or a rapidly-rotating neutron star (magnetar) significantly increases the quality of the model fit. We also investigate the possibility for an object similar to DES14X2fna to act as a contaminant in photometric samples of SNe Ia for cosmology, finding that a similar simulated object is misclassified by a recurrent neural network (RNN)-based photometric classifier as an SN Ia in ∼1.1–2.4 per cent of cases in DES, depending on the probability threshold used for a positive classification.
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