Differential recognition of the Multiple Banded Antigen isoforms across Ureaplasma parvum and Ureaplasma urealyticum species by monoclonal antibodies

Two separate species of Ureaplasma have been identified that infect humans: Ureaplasma parvum and Ureaplasma urealyticum. Most notably, these bacteria lack a cell wall and are the leading infectious organism associated with infection-related induction of preterm birth. Fourteen separate representative prototype bacterial strains, called serovars, are largely differentiated by the sequence of repeating units in the C-terminus of the major surface protein: multiple-banded antigen (MBA). Monoclonal antibodies that recognise single or small groups of serovars have been previously reported, but these reagents remain sequestered in individual research laboratories. Here we characterise a panel of commercially available monoclonal antibodies raised against the MBA and describe the first monoclonal antibody that cross-reacts by immunoblot with all serovars of U. parvum and U. urealyticum species. We also describe a recombinant MBA expressed by Escherichia coli which facilitated further characterisation by immunoblot and demonstrate immunohistochemistry of paraffin-embedded antigens. Immunoblot reactivity was validated against well characterised previously published monoclonal antibodies and individual commercial antibodies were found to recognise all U. parvum strains, only serovars 3 and 14 or only serovars 1 and 6, or all strains belonging to U. parvum and U. urealyticum. MBA mass was highly variable between strains, consistent with variation in the number of C-terminal repeats between strains. Antibody characterisation will enable future investigations to correlate severity of pathogenicity to MBA isoform number or mass, in addition to development of antibody-based diagnostics that will detect infection by all Ureaplasma species or alternately be able to differentiate between U. parvum, U. urealyticum or mixed infections

Variant calling on the GRCh38 assembly with the data from phase three of the 1000 Genomes Project

We present biallelic SNVs called from 2,548 samples across 26 populationsfrom the 1000 Genomes Project, called directly on GRCh38. We believethis will be a useful reference resource for those using GRCh38,representing an improvement over the “lift-overs” of the 1000 GenomesProject data that have been available to date and providing a resourcenecessary for the full adoption of GRCh38 by the community. Here, wedescribe how the call set was created and provide benchmarking datadescribing how our call set compares to that produced by the final phase ofthe 1000 Genomes Project on GRCh37

CLASH: The enhanced lensing efficiency of the highly elongated merging cluster MACS J0416.1-2403

We perform a strong-lensing analysis of the merging galaxy cluster MACS J0416.1-2403 (M0416; z=0.42) in recent CLASH/HST observations. We identify 70 new multiple images and candidates of 23 background sources in the range 0.7<z_{phot}<6.14 including two probable high-redshift dropouts, revealing a highly elongated lens with axis ratio ~5:1, and a major axis of ~100\arcsec (z_{s}~2). Compared to other well-studied clusters, M0416 shows an enhanced lensing efficiency. Although the critical area is not particularly large (~0.6 \square\arcmin; z_{s}~2), the number of multiple images, per critical area, is anomalously high. We calculate that the observed elongation boosts the number of multiple images, \emph{per critical area}, by a factor of ~2.5\times, due to the increased ratio of the caustic area relative to the critical area. Additionally, we find that the observed separation between the two main mass components enlarges the critical area by a factor of ~2. These geometrical effects can account for the high number (density) of multiple images observed. We find in numerical simulations, that only ~4% of the clusters (with M_{vir}>6 x 10^{14} h^{-1}M_{\odot}) exhibit as elongated critical curves as M0416.Comment: 7 pages, 4 figures, 1 table. V2: accepted to ApJ Letters; minor changes and updates; in Fig.3 labeling error corrected. Mass models available online: ftp://wise-ftp.tau.ac.il/pub/adiz/M0416

CLASH: A Census of Magnified Star-Forming Galaxies at z ~ 6-8

We utilize 16 band Hubble Space Telescope (HST) observations of 18 lensing clusters obtained as part of the Cluster Lensing And Supernova survey with Hubble (CLASH) Multi-Cycle Treasury program to search for $z\sim6-8$ galaxies. We report the discovery of 204, 45, and 13 Lyman-break galaxy candidates at $z\sim6$, $z\sim7$, and $z\sim8$, respectively, identified from purely photometric redshift selections. This large sample, representing nearly an order of magnitude increase in the number of magnified star-forming galaxies at $z\sim 6-8$ presented to date, is unique in that we have observations in four WFC3/UVIS UV, seven ACS/WFC optical, and all five WFC3/IR broadband filters, which enable very accurate photometric redshift selections. We construct detailed lensing models for 17 of the 18 clusters to estimate object magnifications and to identify two new multiply lensed $z \gtrsim 6$ candidates. The median magnifications over the 17 clusters are 4, 4, and 5 for the $z\sim6$, $z\sim7$, and $z\sim8$ samples, respectively, over an average area of 4.5 arcmin$^2$ per cluster. We compare our observed number counts with expectations based on convolving "blank" field UV luminosity functions through our cluster lens models and find rough agreement down to $\sim27$ mag, where we begin to suffer significant incompleteness. In all three redshift bins, we find a higher number density at brighter observed magnitudes than the field predictions, empirically demonstrating for the first time the enhanced efficiency of lensing clusters over field surveys. Our number counts also are in general agreement with the lensed expectations from the cluster models, especially at $z\sim6$, where we have the best statistics.Comment: Accepted for publication in the Astrophysical Journal, 25 pages, 13 figures, 7 table

The origin of domestication genes in goats

Goat domestication was critical for agriculture and civilization, but its underlying genetic changes and selection regimes remain unclear. Here, we analyze the genomes of worldwide domestic goats, wild caprid species, and historical remains, providing evidence of an ancient introgression event from a West Caucasian tur-like species to the ancestor of domestic goats. One introgressed locus with a strong signature of selection harbors the MUC6 gene, which encodes a gastrointestinally secreted mucin. Experiments revealed that the nearly fixed introgressed haplotype confers enhanced immune resistance to gastrointestinal pathogens. Another locus with a strong signal of selection may be related to behavior. The selected alleles at these two loci emerged in domestic goats at least 7200 and 8100 years ago, respectively, and increased to high frequencies concurrent with the expansion of the ubiquitous modern mitochondrial haplogroup A. Tracking these archaeologically

The ALMA Frontier Fields Survey. II. Multiwavelength Photometric analysis of 1.1 mm continuum sources in Abell 2744, MACSJ0416.1-2403 and MACSJ1149.5+2223

CONTEXT: The Hubble and Spitzer Space Telescope surveys of the Frontier Fields provide extremely deep images around six massive, strong-lensing clusters of galaxies. The ALMA Frontier Fields survey aims to cover the same fields at 1.1 mm, with maps reaching (unlensed) sensitivities of <70 μJy, in order to explore the properties of background dusty star-forming galaxies. AIMS: We report on the multi-wavelength photometric analysis of all 12 significantly detected (>5σ) sources in the first three Frontier Fields clusters observed by ALMA, based on data from Hubble and Spitzer, the Very Large Telescope and the Herschel Space Observatory. METHODS: We measure the total photometry in all available bands and determine the photometric redshifts and the physical properties of the counterparts via SED-fitting. In particular, we carefully estimate the far-infrared (FIR) photometry using 1.1 mm priors to limit the misidentification of blended FIR counterparts, which strongly affect some flux estimates in previous FIR catalogs. Due to the extremely red nature of these objects, we used a large range of parameters (e.g. 0.0 <Av< 20.0) and templates (including AGNs and ULIRGs models). RESULTS: We identify robust near-infrared (NIR) counterparts for all 11 sources with Ks detection, the majority of which are quite red, with eight having F814W − Ks ≳ 4 and five having F160W − [ 4.5 ] ≳ 3. From the FIR point of view, all our objects have zphot ~ 1–3, whereas based on the optical SED one object prefers a high-z solution (z ≥ 7). Five objects among our sample have spectroscopic redshifts from the GLASS survey for which we can reproduce their SEDs with existing templates. This verification confirms the validity of our photometric redshift methodology. The mean redshift of our sample is zphot = 1.99 ± 0.27. All 1.1 mm selected objects are massive (10.0 < log  [ M⋆(M⊙) ] < 11.5), with high star formation rates (⟨ log [ SFR(M⊙/ yr) ] ⟩ ≈ 1.6) and high dust contents (8.1 < log  [ Mdust(M⊙) ] < 8.8), consistent with previous ALMA surveys

A Potent Lead Induces Apoptosis in Pancreatic Cancer Cells

Pancreatic cancer is considered a lethal and treatment-refractory disease. To obtain a potent anticancer drug, the cytotoxic effect of 2-(benzo[d]oxazol-3(2H)-ylmethyl)- 5-((cyclohexylamino)methyl)benzene-1,4-diol, dihydrochloride (NSC48693) on human pancreatic cancer cells CFPAC-1, MiaPaCa-2, and BxPC-3 was assessed in vitro. The proliferation of CFPAC-1, MiaPaCa-2, and BxPC-3 is inhibited with IC50 value of 12.9±0.2, 20.6±0.3, and 6.2±0.6 µM at 48 h, respectively. This discovery is followed with additional analysis to demonstrate that NSC48693 inhibition is due to induction of apoptosis, including Annexin V staining, chromatins staining, and colony forming assays. It is further revealed that NSC48693 induces the release of cytochrome c, reduces mitochondrial membrane potential, generates reactive oxygen species, and activates caspase. These results collectively indicate that NSC48693 mainly induces apoptosis of CFPAC-1, MiaPaCa-2, and BxPC-3 cells by the mitochondrial-mediated apoptotic pathway. Excitingly, the study highlights an encouraging inhibition effect that human embryonic kidney (HEK-293) and liver (HL-7702) cells are more resistant to the antigrowth effect of NSC48693 compared to the three cancer cell lines. From this perspective, NSC48693 should help to open up a new opportunity for the treatment of patients with pancreatic cancer

GWAS for discovery and replication of genetic loci associated with sudden cardiac arrest in patients with coronary artery disease

<p>Abstract</p> <p>Background</p> <p>Epidemiologic evidence suggests a heritable component to risk for sudden cardiac arrest independent of risk for myocardial infarction. Recent candidate gene association studies for community sudden cardiac arrests have focused on a limited number of biological pathways and yielded conflicting results. We sought to identify novel gene associations for sudden cardiac arrest in patients with coronary artery disease by performing a genome-wide association study.</p> <p>Methods</p> <p>Tagging SNPs (n = 338,328) spanning the genome were typed in a case-control study comparing 89 patients with coronary artery disease and sudden cardiac arrest due to ventricular tachycardia or ventricular fibrillation to 520 healthy controls.</p> <p>Results</p> <p>Fourteen SNPs including 7 SNPs among 7 genes (ACYP2, AP1G2, ESR1, DGES2, GRIA1, KCTD1, ZNF385B) were associated with sudden cardiac arrest (all p < 1.30 × 10^-7), following Bonferroni correction and adjustment for population substructure, age, and sex; genetic variation in ESR1 (p = 2.62 × 10^-8; Odds Ratio [OR] = 1.43, 95% confidence interval [CI]:1.277, 1.596) has previously been established as a risk factor for cardiovascular disease. In tandem, the role of 9 genes for monogenic long QT syndrome (LQT1-9) was assessed, yielding evidence of association with CACNA1C (LQT8; p = 3.09 × 10^-4; OR = 1.18, 95% CI:1.079, 1.290). We also assessed 4 recently published gene associations for sudden cardiac arrest, validating NOS1AP (p = 4.50 × 10^-2, OR = 1.15, 95% CI:1.003, 1.326), CSMD2 (p = 6.6 × 10^-3, OR = 2.27, 95% CI:1.681, 2.859), and AGTR1 (p = 3.00 × 10^-3, OR = 1.13, 95% CI:1.042, 1.215).</p> <p>Conclusion</p> <p>We demonstrate 11 gene associations for sudden cardiac arrest due to ventricular tachycardia/ventricular fibrillation in patients with coronary artery disease. Validation studies in independent cohorts and functional studies are required to confirm these associations.</p

MACSE: Multiple Alignment of Coding SEquences Accounting for Frameshifts and Stop Codons

Until now the most efficient solution to align nucleotide sequences containing open reading frames was to use indirect procedures that align amino acid translation before reporting the inferred gap positions at the codon level. There are two important pitfalls with this approach. Firstly, any premature stop codon impedes using such a strategy. Secondly, each sequence is translated with the same reading frame from beginning to end, so that the presence of a single additional nucleotide leads to both aberrant translation and alignment

The Berkeley sample of Type II supernovae: BVRI light curves and spectroscopy of 55 SNe II

In this work, BVRI light curves of 55 Type II supernovae (SNe II) from the Lick Observatory Supernova Search programme obtained with the Katzman Automatic Imaging Telescope and the 1 m Nickel telescope from 2006 to 2018 are presented. Additionally, more than 150 spectra gathered with the 3 m Shane telescope are published. We conduct an analyse of the peak absolute magnitudes, decline rates, and time durations of different phases of the light and colour curves. Typically, our light curves are sampled with a median cadence of 5.5 d for a total of 5093 photometric points. In average, V-band plateau declines with a rate of 1.29 mag (100 d)−1, which is consistent with previously published samples. For each band, the plateau slope correlates with the plateau length and the absolute peak magnitude: SNe II with steeper decline have shorter plateau duration and are brighter. A time-evolution analysis of spectral lines in term of velocities and pseudo-equivalent widths is also presented in this paper. Our spectroscopic sample ranges between 1 and 200 d post-explosion and has a median ejecta expansion velocity at 50 d post-explosion of 6500 km s−1 (H α line) and a standard dispersion of 2000 km s−1. Nebular spectra are in good agreement with theoretical models using a progenitor star having a mass <16M⊙. All the data are available to the community and will help to understand SN II diversity better, and therefore to improve their utility as cosmological distance indicators