N-Glycolylneuraminic acid (NeuGc) is abundantly expressed in most mammals, but it is not detectable in humans. The expression of NeuGc is controlled by cytidine monophospho-N-acetylneuraminic acid (CMPNeuAc) hydroxylase activity. We previously cloned a cDNA for mouse CMP-NeuAc hydroxylase and found that the human genome contains a homologue. We report here the molecular basis for the absence of NeuGc in humans. We cloned a cDNA for human CMP-NeuAc hydroxylase from a HeLa cell cDNA library. The cDNA encodes a 486-amino acid protein, and its deduced amino acid sequence lacks a domain corresponding to the N-terminal 104 amino acids of the mouse CMPNeuAc hydroxylase protein, although the human protein is highly identical (93%) to the rest of the mouse hydroxylase protein. The N-terminal truncation of the human hydroxylase is caused by deletion of a 92-base pair-long exon in human genomic DNA. The human hydroxylase expressed in COS-7 cells exhibited no enzymatic activity, and a mouse hydroxylase mutant, which lacks the N-terminal domain, was also inactive. A chimera composed of the human hydroxylase and the Nterminal domain of the mouse hydroxylase displayed the enzyme activity. These results indicate that the human homologue of CMP-NeuAc hydroxylase is inactive because it lacks an N-terminal domain that is essential for enzyme activity. The absence of NeuGc in human glycoconjugates is due to a partial deletion in the gene that encodes CMP-NeuAc hydroxylase.Sialic acids are components of the carbohydrate chains of glycoconjugates and are involved in cell-cell recognition (1, 2) and cell-pathogen interactions (3, 4). Sialic acid is a generic designation used for N-acylneuraminic acids and their derivatives (5, 6). N-Acetylneuraminic acid (NeuAc) 1 and N-glycolylneuraminic acid (NeuGc) are two of the most abundant derivatives. Previous studies suggest that some adhesion molecules recognize glycoconjugates containing NeuGc and NeuAc with different affinities. Sialoadhesin, a cell adhesion molecule of marginal zone macrophages, recognizes NeuAc␣2-3Gal but not NeuGc␣2-3Gal (7). On the other hand, mouse CD22, a B cellrestricted adhesion molecule, binds more strongly to NeuGc␣2-6Gal than to NeuAc␣2-6Gal (7). Influenza hemagglutinins recognize glycoconjugates that contain NeuAc and NeuGc with different affinities (8). These studies suggest that the diversity of sialic acids is biologically important in recognition events mediated by glycoconjugates. Although NeuGc-containing glycoconjugates are found in most mammals (5, 6), NeuGc is not detectable in normal human tissues. Glycoconjugates containing NeuGc are immunogenic in human, and an antibody against NeuGc, which is known as Hanganutziu-Deicher antibody, is produced by patients who receive therapeutic injections of animal antisera (9, 10).NeuGc is assumed to be produced from NeuAc through enzymatic hydroxylation of the N-acetyl residue of free NeuAc, CMP-NeuAc, or glycoconjugate-linked NeuAc (11,12). Previous studies showed that the major mechanism for biosynthesis of N...

Sialic acid (Sia) is a family of acidic nine-carbon sugars that occupies the nonreducing terminus of glycan chains. Diversity of Sia is achieved by variation in the linkage to the underlying sugar and modification of the Sia molecule. Here we identified Sia-dependent epitope specificity for GL7, a rat monoclonal antibody, to probe germinal centers upon T cell-dependent immunity. GL7 recognizes sialylated glycan(s), the ␣2,6-linked N-acetylneuraminic acid (Neu5Ac) on a lactosamine glycan chain(s), in both Sia modification-and Sia linkage-dependent manners. In mouse germinal center B cells, the expression of the GL7 epitope was upregulated due to the in situ repression of CMP-Neu5Ac hydroxylase (Cmah), the enzyme responsible for Sia modification of Neu5Ac to Neu5Gc. Such Cmah repression caused activation-dependent dynamic reduction of CD22 ligand expression without losing ␣2,6-linked sialylation in germinal centers. The in vivo function of Cmah was analyzed using gene-disrupted mice. Phenotypic analyses showed that Neu5Gc glycan functions as a negative regulator for B-cell activation in assays of T-cell-independent immunization response and splenic B-cell proliferation. Thus, Neu5Gc is required for optimal negative regulation, and the reaction is specifically suppressed in activated B cells, i.e., germinal center B cells.

Cytidine monophospho-N-acetylneuraminic acid (CMP-NeuAc) hydroxylase, which is the key enzyme for the synthesis of N-glycolylneuraminic acid (NeuGc), has been purified from the cytosolic fraction of mouse liver, as described in our previous paper. The amino acid sequences of the purified CMP-NeuAc hydroxylase, and peptides obtained by lysylendopeptidase digestion, were used to synthesize specific oligonucleotide primers. A mouse cDNA clone of the enzyme was obtained by a combination of the polymerase chain reaction and rapid amplification of cDNA ends. The sequence of the clone contained an open reading frame coding for a protein of 577 amino acids with a predicted molecular mass of 66 kDa. The deduced sequence included the amino acid sequences obtained for the purified enzyme and peptides, and a complete match was obtained for 159 residues. The enzyme has neither a signal peptide sequence nor a membrane spanning domain, which is consistent with localization of the enzyme in the cytosol. Transfection of a cDNA construct to COS-1 cells increased the enzyme activity and the amount of NeuGc. Comparison of the sequence with GenBank data indicated that no similar sequence has been reported so far. Northern blot analysis of various mouse tissues with the enzyme cDNA as a probe indicated that expression of NeuGc is related to the level of CMP-NeuAc hydroxylase mRNA. On Southern blot analysis with the same probe, cross-hybridizing bands were detected in the human and fish genomes.

We report the discovery of a quasar at z = 7.07, which was selected from the deep multi-band imaging data collected by the Hyper Suprime-Cam (HSC) Subaru Strategic Program survey. This quasar, HSC J124353.93+010038.5, has an order of magnitude lower luminosity than do the other known quasars at z > 7. The rest-frame ultraviolet absolute magnitude is M 1450 = −24.13 ± 0.08 mag and the bolometric luminosity is erg s−1. Its spectrum in the optical to near-infrared shows strong emission lines, and shows evidence for a fast gas outflow, as the C iv line is blueshifted and there is indication of broad absorption lines. The Mg ii-based black hole mass is , thus indicating a moderate mass accretion rate with an Eddington ratio . It is the first z > 7 quasar with sub-Eddington accretion, besides being the third most distant quasar known to date. The luminosity and black hole mass are comparable to, or even lower than, those measured for the majority of low-z quasars discovered by the Sloan Digital Sky Survey, and thus this quasar likely represents a z > 7 counterpart to quasars commonly observed in the low-z universe.

We report the discovery of 28 quasars and 7 luminous galaxies at 5.7 ≤ z ≤ 7.0. This is the tenth in a series of papers from the Subaru High-z Exploration of Low-Luminosity Quasars (SHELLQs) project, which exploits the deep multi-band imaging data produced by the Hyper Suprime-Cam (HSC) Subaru Strategic Program survey. The total number of spectroscopically identified objects in SHELLQs has now grown to 93 high-z quasars, 31 high-z luminous galaxies, 16 [O III] emitters at z ∼ 0.8, and 65 Galactic cool dwarfs (low-mass stars and brown dwarfs). These objects were found over 900 deg 2 , surveyed by HSC between 2014 March and 2018 January. The full quasar sample includes 18 objects with very strong and narrow Lyα emission, whose stacked spectrum is clearly different from that of other quasars or galaxies. While the stacked spectrum shows N V λ1240 emission and resembles that Corresponding author: Yoshiki Matsuoka yk.matsuoka@cosmos.ehime-u.ac.jp of lower-z narrow-line quasars, the small Lyα width may suggest a significant contribution from the host galaxies. Thus these objects may be composites of quasars and star-forming galaxies.

We present the molecular gas mass fraction (f H2 ) and star-formation efficiency (SFE) of local galaxies on the basis of our new CO(J = 1 − 0) observations with the Nobeyama 45m radio telescope, combined with the COLDGASS galaxy catalog, as a function of galaxy environment defined as the local number density of galaxies measured with SDSS DR7 spectroscopic data. Our sample covers a wide range in the stellar mass and SFR, and covers wide environmental range over two orders of magnitude. This allows us to conduct the first, systematic study of environmental dependence of molecular gas properties in galaxies from the lowest-to the highest-density environments in the local universe. We confirm that both f H2 and SFE have strong positive correlations with the SFR offset from the star-forming main sequence (∆MS), and most importantly, we find that these correlations are universal across all environments. Our result demonstrates that star-formation activity within individual galaxies is primarily controlled by their molecular gas content, regardless of their global environment. Therefore, we claim that one always needs to be careful about the ∆MS distribution of the sample when investigating the environmental effects on the H 2 gas content in galaxies.

We investigate the cold-gas properties of massive Virgo galaxies (>109 M ⊙) at <3R 200 (R 200 is the radius where the mean interior density is 200 times the critical density) on the projected phase-space diagram with the largest archival data set to date to understand the environmental effects on galaxy evolution in the Virgo cluster. We find lower H i and H2 mass fractions and higher star formation efficiencies (SFEs) from H i and H2 in the Virgo galaxies than in the field galaxies for matched stellar masses; the Virgo galaxies generally follow the field relationships between the offset from the main sequence of the star-forming galaxies [Δ(MS)] and the gas fractions and SFEs, to the slight offset to lower gas fractions or higher SFEs compared to field galaxies at Δ(MS) < 0; lower gas fractions in galaxies with smaller clustocentric distance and velocity; and lower gas fractions in the galaxies in the W cloud, a substructure of the Virgo cluster. Our results suggest the cold-gas properties of some Virgo galaxies are affected by their environment at least at 3R 200 maybe via strangulation and/or preprocesses, and H i and H2 in some galaxies are removed by ram pressure at <1.5R 200. Our data cannot rule out the possibility of other processes such as strangulation and galaxy harassment accounting for gas reduction in some galaxies at <1.5R 200. Future dedicated observations of a mass-limited complete sample are required for definitive conclusions.

Context. An essential part of the paradigm describing active galactic nuclei is the alignment between the radio jet and the associated rotation axis of the sub-pc sized accretion disks. Because of the small linear and angular scales involved, this alignment has not yet been checked in a sufficient number of Low Luminosity Active Galactic Nuclei (LLAGNs). Aims. The project intends to examine the validity of this paradigm by measuring the radio continuum on the same physical scale as the accretion disks, to investigate any possible connection between these disks and the radio continuum. Methods. We observed a sample of 18 LLAGNs in the 4.8 GHz (6 cm) radio continuum using the Very Long Baseline Array (VLBA) with 3.3 to 6.5 milliarcseconds resolution. The sources were selected to show both an edge-on accretion disk revealed by 22 GHz H 2 O megamaser emission and signatures of a radio jet. Furthermore, the sources were previously detected in 33 GHz radio continuum observations made with the Very Large Array. Results. Five out of 18 galaxies observed were detected at 8 σ or higher levels (Mrk 0001, Mrk 1210, Mrk 1419, NGC 2273. While all these sources are known to have maser disks, four of these five sources exhibit a maser disk with known orientation. For all four sources, the radio continuum is misaligned relative to the rotation axis of the maser disk, but with a 99.1% confidence level, the orientations are not random and are confined to a cone within 32 • of the maser disk's normal. Among the four sources the misalignment of the radio continuum with respect to the normal vector to the maser disk is smaller when the inner radius of the maser disk is larger. Furthermore, a correlation is observed between the 5 GHz VLBA radio continuum and the [OIII] luminosity and also with the H 2 O maser disk's inner radius.