Child Rearing Policies and Economic Growth

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Single-molecular real-time deep sequencing reveals the dynamics of multi-drug resistant haplotypes and structural variations in the hepatitis C virus genome

While direct-acting antivirals (DAAs) for hepatitis C virus (HCV) have dramatically progressed, patients still suffer from treatment failures. For the radical eradication of HCV, a deeper understanding of multiple resistance-associated substitutions (RASs) at the single-clone level is essential. To understand HCV quasispecies and their dynamics during DAA treatment, we applied single-molecule real-time (SMRT) deep sequencing on sera from 12 patients with genotype-1b HCV infections with DAA treatment failures, both pre- and post-treatment. We identified >3.2 kbp sequences between NS3 and NS5A genes of 187, 539 clones in total, classifying into haplotype codes based on the linkage of seven RAS loci. The number of haplotype codes during the treatment, per sample, significantly decreased from 14.67 ± 9.12 to 6.58 ± 7.1, while the number of nonsynonymous codons on the seven RAS loci, per clone, significantly increased from 1.50 ± 0.92 to 3.64 ± 0.75. In five cases, the minority multi-drug resistant haplotypes at pre-treatment were identical to the major haplotypes at relapse. Moreover, various structural variations (SVs) were detected and their dynamics analysed. These results suggest that SMRT deep sequencing is useful for detecting minority haplotypes and SVs, and to evaluate the dynamics of viral genomes at the single-clone level

Evolutional transition of HBV genome during the persistent infection determined by single-molecule real-time sequencing

BACKGROUND: Although HBV infection is a serious health issue worldwide, the landscape of HBV genome dynamics in the host has not yet been clarified. This study aimed to determine the continuous genome sequence of each HBV clone using a single-molecule real-time sequencing platform, and clarify the dynamics of structural abnormalities during persistent HBV infection without antiviral therapy. PATIENTS AND METHODS: Twenty-five serum specimens were collected from 10 untreated HBV-infected patients. Continuous whole-genome sequencing of each clone was performed using a PacBio Sequel sequencer; the relationship between genomic variations and clinical information was analyzed. The diversity and phylogeny of the viral clones with structural variations were also analyzed. RESULTS: The whole-genome sequences of 797, 352 HBV clones were determined. The deletion was the most common structural abnormality and concentrated in the preS/S and C regions. Hepatitis B e antibody (anti-HBe)-negative samples or samples with high alanine aminotransferase levels have significantly diverse deletions than anti-HBe-positive samples or samples with low alanine aminotransferase levels. Phylogenetic analysis demonstrated that various defective and full-length clones evolve independently and form diverse viral populations. CONCLUSIONS: Single-molecule real-time long-read sequencing revealed the dynamics of genomic quasispecies during the natural course of chronic HBV infections. Defective viral clones are prone to emerge under the condition of active hepatitis, and several types of defective variants can evolve independently of the viral clones with the full-length genome

Mutational spectrum of hepatitis C virus in patients with chronic hepatitis C determined by single molecule real-time sequencing

The emergence of hepatitis C virus (HCV) with resistance-associated substitution (RAS), produced by mutations in the HCV genome, is a major problem in direct acting antivirals (DAA) treatment. This study aimed to clarify the mutational spectrum in HCV-RNA and the substitution pattern for the emergence of RASs in patients with chronic HCV infection. HCV-RNA from two HCV replicon cell lines and the serum HCV-RNA of four non-liver transplant and four post-liver transplant patients with unsuccessful DAA treatment were analyzed using high-accuracy single-molecule real-time long-read sequencing. Transition substitutions, especially A>G and U>C, occurred prominently under DAAs in both non-transplant and post-transplant patients, with a mutational bias identical to that occurring in HCV replicon cell lines during 10-year culturing. These mutational biases were reproduced in natural courses after DAA treatment. RASs emerged via both transition and transversion substitutions. NS3-D168 and NS5A-L31 RASs resulted from transversion mutations, while NS5A-Y93 RASs was caused by transition substitutions. The fidelity of the RNA-dependent RNA polymerase, HCV-NS5B, produces mutational bias in the HCV genome, characterized by dominant transition mutations, notably A>G and U>C substitutions. However, RASs are acquired by both transition and transversion substitutions, and the RASs-positive HCV clones are selected and proliferated under DAA treatment pressure

Wide and Deep Exploration of Radio Galaxies with Subaru HSC (WERGS). III. Discovery of a z = 4.72 Radio Galaxy with Lyman Break Technique

We report a discovery of $z = 4.72$ radio galaxy, HSC J083913.17+011308.1, by using the Lyman break technique with the Hyper Suprime-Cam Subaru Strategic Survey (HSC-SSP) catalog for VLA FIRST radio sources. The number of known high-$z$ radio galaxies (HzRGs) at $z > 3$ is quite small to constrain the evolution of HzRGs so far. The deep and wide-area optical survey by HSC-SSP enables us to apply the Lyman break technique to a large search for HzRGs. For an HzRG candidate among pre-selected $r$-band dropouts with a radio detection, a follow-up optical spectroscopy with GMOS/Gemini has been performed. The obtained spectrum presents a clear Ly$\alpha$ emission line redshifted to $z=4.72$. The SED fitting analysis with the rest-frame UV and optical photometries suggests the massive nature of this HzRG with $\log{M_*/M_{\odot}} = 11.4$. The small equivalent width of Ly$\alpha$ and the moderately red UV colors indicate its dusty host galaxy, implying a chemically evolved and dusty system. The radio spectral index does not meet a criterion for an ultra-steep spectrum: $\alpha^{325}_{1400}$ of $-1.1$ and $\alpha^{150}_{1400}$ of $-0.9$, demonstrating that the HSC-SSP survey compensates for a sub-population of HzRGs which are missed in surveys focusing on an ultra-steep spectral index.Comment: 10 pages, 5 figures, accepted for publication in A

eROSITA Final Equatorial-Depth Survey (eFEDS): eFEDS X-ray view of WERGS Radio Galaxies selected by the Subaru/HSC and VLA/FIRST survey

We construct the eROSITA X-ray catalog of radio galaxies discovered by the WERGS survey that is made by the cross-matching of the wide-area Subaru/HSC optical survey and VLA/FIRST 1.4 GHz radio survey. We find 393 eROSITA detected radio galaxies in the 0.5--2 keV band in the eFEDS field covering 140~deg$^2$. Thanks to the wide and medium depth eFEDS X-ray survey, the sample contains the rare and most X-ray luminous radio galaxies above the knee of the X-ray luminosity function, spanning 44<log L(0.5-2keV,abs)<46.5 at $1<z<4$. Based on the X-ray properties obtained by the spectral fitting, 37 sources show obscured AGN signature with $\log (N_\mathrm{H}/\mathrm{cm}^{-2})>22$. Those obscured and radio AGN reside in $0.4<z<3.2$, indicating that they are obscured counterparts of the radio-loud quasar, which are missed in the previous optical quasar surveys. By combining radio and X-ray luminosities, the jet production efficiency $\eta_\mathrm{jet}$ is investigated, and we find 14 sources with extremely high jet production efficiency at $\eta_\mathrm{jet}\approx1$. This high $\eta_\mathrm{jet}$ value might be a result of 1) the decreased radiation efficiency of $\eta_\mathrm{rad}<0.1$ due to the low accretion rate for those sources and/or 2) the boosting due to the decline of $L_\mathrm{bol}$ by a factor of 10--100 by keeping $P_\mathrm{jet}$ constant in the previous Myr, indicating the experience of the AGN feedback. Finally, inferring the BH masses from the stellar-mass, we find that X-ray luminous sources show the excess of the radio emission with respect to the value estimated from the fundamental plane. Such radio emission excess cannot be explained by the Doppler booming alone, and therefore disk-jet connection of X-ray luminous eFEDS-WERGS is fundamentally different from the conventional fundamental plane which mainly covers low accretion regime.Comment: 20 pages, 11 figures, accepted for publication in A&

The population of merging compact binaries inferred using gravitational waves through GWTC-3

We report on the population properties of 76 compact binary mergers detected with gravitational waves below a false alarm rate of 1 per year through GWTC-3. The catalog contains three classes of binary mergers: BBH, BNS, and NSBH mergers. We infer the BNS merger rate to be between 10 $\rm{Gpc^{-3} yr^{-1}}$ and 1700 $\rm{Gpc^{-3} yr^{-1}}$ and the NSBH merger rate to be between 7.8 $\rm{Gpc^{-3}\, yr^{-1}}$ and 140 $\rm{Gpc^{-3} yr^{-1}}$ , assuming a constant rate density versus comoving volume and taking the union of 90% credible intervals for methods used in this work. Accounting for the BBH merger rate to evolve with redshift, we find the BBH merger rate to be between 17.9 $\rm{Gpc^{-3}\, yr^{-1}}$ and 44 $\rm{Gpc^{-3}\, yr^{-1}}$ at a fiducial redshift (z=0.2). We obtain a broad neutron star mass distribution extending from $1.2^{+0.1}_{-0.2} M_\odot$ to $2.0^{+0.3}_{-0.3} M_\odot$. We can confidently identify a rapid decrease in merger rate versus component mass between neutron star-like masses and black-hole-like masses, but there is no evidence that the merger rate increases again before 10 $M_\odot$. We also find the BBH mass distribution has localized over- and under-densities relative to a power law distribution. While we continue to find the mass distribution of a binary's more massive component strongly decreases as a function of primary mass, we observe no evidence of a strongly suppressed merger rate above $\sim 60 M_\odot$. The rate of BBH mergers is observed to increase with redshift at a rate proportional to $(1+z)^{\kappa}$ with $\kappa = 2.9^{+1.7}_{-1.8}$ for $z\lesssim 1$. Observed black hole spins are small, with half of spin magnitudes below $\chi_i \simeq 0.25$. We observe evidence of negative aligned spins in the population, and an increase in spin magnitude for systems with more unequal mass ratio

Diving below the spin-down limit:constraints on gravitational waves from the energetic young pulsar PSR J0537-6910

We present a search for continuous gravitational-wave signals from the young, energetic X-ray pulsar PSR J0537-6910 using data from the second and third observing runs of LIGO and Virgo. The search is enabled by a contemporaneous timing ephemeris obtained using NICER data. The NICER ephemeris has also been extended through 2020 October and includes three new glitches. PSR J0537-6910 has the largest spin-down luminosity of any pulsar and is highly active with regards to glitches. Analyses of its long-term and inter-glitch braking indices provided intriguing evidence that its spin-down energy budget may include gravitational-wave emission from a time-varying mass quadrupole moment. Its 62 Hz rotation frequency also puts its possible gravitational-wave emission in the most sensitive band of LIGO/Virgo detectors. Motivated by these considerations, we search for gravitational-wave emission at both once and twice the rotation frequency. We find no signal, however, and report our upper limits. Assuming a rigidly rotating triaxial star, our constraints reach below the gravitational-wave spin-down limit for this star for the first time by more than a factor of two and limit gravitational waves from the l = m = 2 mode to account for less than 14% of the spin-down energy budget. The fiducial equatorial ellipticity is limited to less than about 3 x 10⁻⁵, which is the third best constraint for any young pulsar