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Understanding the nature of high-redshift dusty galaxies requires a comprehensive view of their interstellar medium (ISM) and molecular complexity. However, the molecular ISM at high redshifts is commonly studied using only a few species beyond¹²C¹⁶O, limiting our understanding. In this paper, we present the results of deep 3 mm spectral line surveys using the NOrthern Extended Millimeter Array (NOEMA) targeting two strongly lensed dusty galaxies observed when the Universe was less than 1.8 Gyr old: APM 08279+5255, a quasar at redshiftz= 3.911, and NCv1.143 (H-ATLAS J125632.7+233625), az= 3.565 starburst galaxy. The spectral line surveys cover rest-frame frequencies from about 330 to 550 GHz for both galaxies. We report the detection of 38 and 25 emission lines in APM 08279+5255 and NCv1.143, respectively. These lines originate from 17 species, namely CO,¹³CO, C¹⁸O, CN, CCH, HCN, HCO⁺, HNC, CS, C³⁴S, H₂O, H₃O⁺, NO, N₂H⁺, CH, c-C₃H₂, and the vibrationally excited HCN and neutral carbon. The spectra reveal the chemical richness and the complexity of the physical properties of the ISM. By comparing the spectra of the two sources and combining the analysis of the molecular gas excitation, we find that the physical properties and the chemical imprints of the ISM are different: the molecular gas is more excited in APM 08279+5255, which exhibits higher molecular gas temperatures and densities compared to NCv1.143; the molecular abundances in APM 08279+5255 are akin to the values of local active galactic nuclei (AGN), showing boosted relative abundances of the dense gas tracers that might be related to high-temperature chemistry and/or the X-ray-dominated regions, while NCv1.143 more closely resembles local starburst galaxies. The most significant differences between the two sources are found in H₂O: the 448 GHz ortho-H₂O(4₂₃ − 3₃₀) line is significantly brighter in APM 08279+5255, which is likely linked to the intense far-infrared radiation from the dust powered by AGN. Our astrochemical model suggests that, at such high column densities, far-ultraviolet radiation is less important in regulating the ISM, while cosmic rays (and/or X-rays and shocks) are the key players in shaping the molecular abundances and the initial conditions of star formation. Both our observed CO isotopologs line ratios and the derived extreme ISM conditions (high gas temperatures, densities, and cosmic-ray ionization rates) suggest the presence of a top-heavy stellar initial mass function. From the ∼330–550 GHz continuum, we also find evidence of nonthermal millimeter flux excess in APM 08279+5255 that might be related to the central supermassive black hole. Such deep spectral line surveys open a new window into the physics and chemistry of the ISM and the radiation field of galaxies in the early Universe. 

Abstract BackgroundThe Nile rat (Avicanthis niloticus) is an important animal model because of its robust diurnal rhythm, a cone-rich retina, and a propensity to develop diet-induced diabetes without chemical or genetic modifications. A closer similarity to humans in these aspects, compared to the widely usedMus musculusandRattus norvegicusmodels, holds the promise of better translation of research findings to the clinic. ResultsWe report a 2.5 Gb, chromosome-level reference genome assembly with fully resolved parental haplotypes, generated with the Vertebrate Genomes Project (VGP). The assembly is highly contiguous, with contig N50 of 11.1 Mb, scaffold N50 of 83 Mb, and 95.2% of the sequence assigned to chromosomes. We used a novel workflow to identify 3613 segmental duplications and quantify duplicated genes. Comparative analyses revealed unique genomic features of the Nile rat, including some that affect genes associated with type 2 diabetes and metabolic dysfunctions. We discuss 14 genes that are heterozygous in the Nile rat or highly diverged from the house mouse. ConclusionsOur findings reflect the exceptional level of genomic resolution present in this assembly, which will greatly expand the potential of the Nile rat as a model organism. 

Abstract The current human reference genome, GRCh38, represents over 20 years of effort to generate a high-quality assembly, which has benefitted society 1,2 . However, it still has many gaps and errors, and does not represent a biological genome as it is a blend of multiple individuals 3,4 . Recently, a high-quality telomere-to-telomere reference, CHM13, was generated with the latest long-read technologies, but it was derived from a hydatidiform mole cell line with a nearly homozygous genome 5 . To address these limitations, the Human Pangenome Reference Consortium formed with the goal of creating high-quality, cost-effective, diploid genome assemblies for a pangenome reference that represents human genetic diversity 6 . Here, in our first scientific report, we determined which combination of current genome sequencing and assembly approaches yield the most complete and accurate diploid genome assembly with minimal manual curation. Approaches that used highly accurate long reads and parent–child data with graph-based haplotype phasing during assembly outperformed those that did not. Developing a combination of the top-performing methods, we generated our first high-quality diploid reference assembly, containing only approximately four gaps per chromosome on average, with most chromosomes within ±1% of the length of CHM13. Nearly 48% of protein-coding genes have non-synonymous amino acid changes between haplotypes, and centromeric regions showed the highest diversity. Our findings serve as a foundation for assembling near-complete diploid human genomes at scale for a pangenome reference to capture global genetic variation from single nucleotides to structural rearrangements.