PGL-III, a Rare Intermediate of <i>Mycobacterium leprae</i> Phenolic Glycolipid Biosynthesis, Is a Potent Mincle Ligand

Although leprosy (Hansen's disease) is one of the oldest known diseases, the pathogenicity of Mycobacterium leprae (M. leprae) remains enigmatic. Indeed, the cell wall components responsible for the immune response against M. leprae are as yet largely unidentified. We reveal here phenolic glycolipid-III (PGL-III) as an M. leprae-specific ligand for the immune receptor Mincle. PGL-III is a scarcely present trisaccharide intermediate in the biosynthetic pathway to PGL-I, an abundant and characteristic M. leprae glycolipid. Using activity-based purification, we identified PGL-III as a Mincle ligand that is more potent than the well-known M. tuberculosis trehalose dimycolate. The cocrystal structure of Mincle and a synthetic PGL-III analogue revealed a unique recognition mode, implying that it can engage multiple Mincle molecules. In Mincle-deficient mice infected with M. leprae, increased bacterial burden with gross pathologies were observed. These results show that PGL-III is a noncanonical ligand recognized by Mincle, triggering protective immunity. </p

The globular cluster VVV CL002 falling down to the hazardous Galactic centre

© 2024 The Author(s). Published by EDP Sciences. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Context. The Galactic centre is hazardous for stellar clusters because of the strong tidal force in action there. It is believed that many clusters were destroyed there and contributed stars to the crowded stellar field of the bulge and the nuclear stellar cluster. However, the development of a realistic model to predict the long-term evolution of the complex inner Galaxy has proven difficult, and observations of surviving clusters in the central region would provide crucial insights into destruction processes. Aims: Among the known Galactic globular clusters, VVV CL002 is the closest to the centre, at 0.4 kpc, but has a very high transverse velocity of 400 km s−1. The nature of this cluster and its impact on Galactic astronomy need to be addressed with spectroscopic follow up. Methods: Here we report the first measurements of its radial velocity and chemical abundance based on near-infrared high-resolution spectroscopy. Results: We find that this cluster has a counter-rotating orbit constrained within 1.0 kpc of the centre, and as close as 0.2 kpc at the perigalacticon, confirming that the cluster is not a passerby from the halo but a genuine survivor enduring the harsh conditions of the tidal forces of the Galactic mill. In addition, its metallicity and α abundance ([α/Fe] ≃ +0.4 and [Fe/H] = −0.54) are similar to those of some globular clusters in the bulge. Recent studies suggest that stars with such α-enhanced stars were more common at 3-6 kpc from the centre around 10 Gyr ago. Conclusions: We infer that VVV CL002 was formed outside but is currently falling down to the centre, showcasing a real-time event that must have occurred to many clusters a long time ago.Peer reviewe

男性膀胱癌患者に対する自然排尿型尿路再建術の臨床経験

自然排尿型尿路再建術を施行した23例の男子膀胱癌患者の手術成績を検討した.術式はhemi-Kock法8例, Hautmann法12例, Reddy法3例で, 平均経過観察期間は36ヵ月である.手術関連死はなかった.早期合併症は7例にみられ, パウチからの尿瘻4例, 創感染3例, 腎盂腎炎2例であった.昼間尿禁制は22例で得られたが, 夜間尿失禁は7例にみられ, Reddy法では3例全てにみられた.排尿困難は4例にみられ, うち1例は尿閉となった.晩期合併症としては, 尿道狭窄2例, 創ヘルニア 2例, パウチ内結石1例, 胆石症1例であったBetween 1988 and 1996, 23 male patients with bladder cancer underwent bladder substitution after cystectomy, using either the hemi-Kock, Hautmann, and Reddy procedures. The mean postoperative follow-up period was 36 months, with a range of 3 to 85 months. There were no perioperative deaths, and early postoperative complications occurred in 7 patients (30%); transient urine leak from the pouch in 4, wound infection in 3 and pyelonephritis in 2 patients. Twenty-two of the 23 patients (96%) were continent during the day, while 7 (30%) had nocturnal incontinence. All 3 patients with the Reddy procedure had nocturnal incontinence. Complete continence was preserved in 70% of the patients. Dysuria was seen in 4 patients, including retention in 1 patient. Late complications included urethral stricture in 3, wound hernia in 2, metabolic acidosis in 1, stone in the pouch in 1, and gallbladder stone in 1 patient. However, reoperation was necessary in 1 patient for internal urethrotomy and 1 patient for removal of a stone in the neobladder. Mild degree of hydronephrosis and unilateral reflux were seen in 3 patients each, and followed up conservatively. No urethral recurrence has occurred and only 1 patient died of cancer. The need for reoperation was very low and the high reservoir capacity resulted in continence from the beginning in most patients. We considered the neobladder useful as an alternative form of urinary diversion in selected cases

Inactivated Whole Virus Particle Influenza Vaccine Induces Anti-Neuraminidase Antibodies That May Contribute to Cross-Protection against Heterologous Virus Infection

Despite the use of vaccines, seasonal influenza remains a risk to public health. We previously proposed the inactivated whole virus particle vaccine (WPV) as an alternative to the widely used split vaccine (SV) for the control of seasonal and pandemic influenza based on the superior priming potency of WPV to that of SV. In this study, we further examined and compared the immunological potency of monovalent WPV and SV of A/California/7/2009 (X-179A) (H1N1) pdm09 (CA/09) to generate immune responses against heterologous viruses, A/Singapore/GP1908/2015 (IVR-180) (H1N1) pdm09 (SG/15), and A/duck/Hokkaido/Vac-3/2007 (H5N1) (DH/07) in mice. Following challenge with a lethal dose of heterologous SG/15, lower virus titer in the lungs and milder weight loss were observed in WPV-vaccinated mice than in SV-vaccinated ones. To investigate the factors responsible for the differences in the protective effect against SG/15, the sera of vaccinated mice were analyzed by hemagglutination-inhibition (HI) and neuraminidase-inhibition (NI) assays to evaluate the antibodies induced against viral hemagglutinin (HA) and neuraminidase (NA), respectively. While the two vaccines induced similar levels of HI antibodies against SG/15 after the second vaccination, only WPV-vaccinated mice induced significantly higher titers of NI antibodies against the strain. Furthermore, given the significant elevation of NI antibody titers against DH/07, an H5N1 avian influenza virus, WPV was also demonstrated to induce NA-inhibiting antibodies that recognize NA of divergent strains. This could be explained by the higher conservation of epitopes of NA among strains than for HA. Taking these findings together, NA-specific antibodies induced by WPV may have contributed to better protection from infection with heterologous influenza virus SG/15, compared with SV. The present results indicate that WPV is an effective vaccine for inducing antibodies against both HA and NA of heterologous viruses and may be a useful vaccine to conquer vaccine strain mismatch

Metallicities of Classical Cepheids in the Inner Galactic Disk

Metallicity gradients refer to the sloped radial profiles of the metallicities of gas and stars and are commonly seen in disk galaxies. A well-defined metallicity gradient of the Galactic disk is observed particularly well with classical Cepheids, which are good stellar tracers thanks to their period–luminosity relation, allowing precise distance estimation and other advantages. However, the measurement of the inner-disk gradient has been impeded by the incompleteness of previous samples of Cepheids and the limitations of optical spectroscopy in observing highly reddened objects. Here we report the metallicities of 16 Cepheids measured with high-resolution spectra in the near-infrared YJ bands. These Cepheids are located at 3–5.6 kpc in Galactocentric distance, R _GC , and reveal the metallicity gradient in this range for the first time. Their metallicities are mostly between 0.1 and 0.3 dex in [Fe/H] and more or less follow the extrapolation of the metallicity gradient found in the outer part, R _GC > 6.5 kpc. The gradient in the inner disk may be shallower or even flat, but the small sample does not allow the determination of the slope precisely. More extensive spectroscopic observations would also be necessary for studying minor populations, if any, with higher or lower metallicities that were reported in previous literature. In addition, the 3D velocities of our inner-disk Cepheids show a kinematic pattern that indicates noncircular orbits caused by the Galactic bar, which is consistent with the patterns reported in recent studies on high-mass star-forming regions and red giant branch stars