Neotabrizicola shimadae gen. nov., sp. nov., an aerobic anoxygenic phototrophic bacterium harbouring photosynthetic genes in the family Rhodobacteraceae,isolated from a terrestrial hot spring

A bacteriochlorophyll-containing bacterium, designated as strain N10^T, was isolated from a terrestrial hot spring in Nagano Prefecture, Japan. Gram-stain-negative, oxidase- and catalase-positive and ovoid to rod-shaped cells showed the features of aerobic anoxygenic phototrophic bacteria, i.e., strain N10^T synthesised bacteriochlorophylls under aerobic conditions and could not grow anaerobically even under illumination. Genome analysis found genes for bacteriochlorophyll and carotenoid biosynthesis, light-harvesting complexes and type-2 photosynthetic reaction centre in the chromosome. Phylogenetic analyses based on the 16S rRNA gene sequence and 92 core proteins revealed that strain N10^T was located in a distinct lineage near the type species of the genera Tabrizicola and Xinfangfangia and some species in the genus Rhodobacter (e.g., Rhodobacter blasticus). Strain N10^T shared?<?97.1% 16S rRNA gene sequence identity with those species in the family Rhodobacteraceae. The digital DNA–DNA hybridisation, average nucleotide identity and average amino acid identity values with the relatives, Tabrizicola aquatica RCRI19^T (an aerobic anoxygenic phototrophic bacterium), Xinfangfangia soli ZQBW^T and R. blasticus ATCC 33485^T were 19.9–20.7%, 78.2–79.1% and 69.1–70.1%, respectively. Based on the phenotypic features, major fatty acid and polar lipid compositions, genome sequence and phylogenetic position, a novel genus and species are proposed for strain N10^T, to be named Neotabrizicola shimadae (=?JCM 34381^T?=?DSM 112087T). Strain N10^T which is phylogenetically located among aerobic anoxygenic phototrophic bacteria (Tabrizicola), bacteriochlorophyll-deficient bacteria (Xinfangfangia) and anaerobic anoxygenic phototrophic bacteria (Rhodobacter) has great potential to promote studies on the evolution of photosynthesis in Rhodobacteraceae.

     

Abundance estimation of riverine macrophyte Egeria densa using environmental DNA: effects of sampling season and location

Invasive macrophytes can have a variety of effects on aquatic ecosystems. The early detection and abundance estimation of an invasive species is important to effectively control it and minimize the ecosystem impacts. It is imperative to develop more efficient sampling methods for the abundance quantification of aquatic plants in large riverine systems. We examined (1) relationships between the environmental DNA (eDNA) concentrations of the invasive macrophyte, Egeria densa, and the upstream coverage area on the multiple life-history stages (dormant, growing, and senescence seasons) in a large riverine system in Japan and (2) if the relationships between the eDNA concentrations and coverage area could vary with the lateral sampling locations (left bank, middle, and right bank). The eDNA concentrations had significant positive relationships with the upstream coverage area of E. densa at multiple spatial scales for the dormant and senescence seasons. These results suggest that the eDNA analysis could be useful to quantify the relative abundance of this aquatic macrophyte in the riverine system; however, the selection of the eDNA sampling season could be important to accurately estimate abundance. Our results also showed that the eDNA concentrations of E. densa did not significantly differ from the lateral sampling location, suggesting that the eDNA samples could reflect the relative abundance of E. densa upstream of the study sites regardless of the lateral sampling location.

     

Sleep Apnea Syndrome (SAS) Clinical Practice Guidelines 2020

Sleep and Biological Rhythms - The prevalence of sleep-disordered breathing (SDB) is reportedly very high. Among SDBs, the incidence of obstructive sleep apnea (OSA) is higher than previously...     

Discovery of NR2B-selective antagonists via scaffold hopping and pharmacokinetic profile optimization

Selective N-methyl-d-aspartate receptor subunit 2B (NR2B) antagonists show potential as analgesic drugs, and do not cause side effects associated with non-selective N-methyl-d-aspartate (NMDA) antagonists. Using a scaffold-hopping approach, we previously identified isoxazole derivative 4 as a potent selective NR2B antagonist. In this study, further scaffold hopping of isoxazole derivative 4 and optimization of its pharmacokinetic profile led to the discovery of the orally bioavailable compound 6v. In a rat study of analgesia, 6v demonstrated analgesic effects against neuropathic pain.     

Pyrrolinone derivatives as a new class of P2X3 receptor antagonists Part 2: Discovery of orally bioavailable compounds

Some P2X3 receptor antagonists have been developed as new therapeutic drugs for pain. We discovered a novel chemotype of P2X3 receptor antagonists with a pyrrolinone skeleton. Because of SAR studies to improve bioavailability of lead compound 2, compound (R)-24 was identified, which showed an analgesic effect against neuropathic pain by oral administration. We constructed a human P2X3 homology model as a template for the zebrafish P2X4 receptor, which agreed with SAR studies of pyrrolinone derivatives.     

Development of 99mTc radiolabeled A85380 derivatives targeting cerebral nicotinic acetylcholine receptor: Novel radiopharmaceutical ligand 99mTc-A-YN-IDA-C4

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that have been implicated in higher brain functions. To elucidate the functional mechanisms underlying nAChRs and contribute significantly to development of drugs targeting neurological and neuropsychiatric diseases, non-invasive nuclear medical imaging can be used for evaluation. In addition, technetium-99m (^99mTc) is a versatile radionuclide used clinically as a tracer in single-photon emission computed tomography. Because A85380 is known as a potent α4β2-nAChR agonist, we prepared A85380 derivatives labeled with ^99mTc using a bifunctional chelate system. A computational scientific approach was used to design the probe efficiently. We used non-radioactive rhenium (Re) for a ^99mTc analog and found that one of the derivatives, Re-A-YN-IDA-C4, exhibited high binding affinity at α4β2-nAChR in both the docking simulation (?19.3 kcal/mol) and binding assay (Ki = 0.4 ± 0.04 nM). Further, ^99mTc-A-YN-IDA-C4 was synthesized using microwaves, and its properties were examined. Consequently, we found that ^99mTc-A-YN-IDA-C4, with a structure optimized by using computational chemistry techniques, maintained affinity and selectivity for nAChR in vitro and possessed efficient characteristics as a nuclear medicine molecular imaging probe, demonstrated usefulness of computational scientific approach for molecular improvement strategy.     

Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche

Maintenance of hematopoietic stem cells (HSCs) depends on interaction with their niche. Here we show that the long-term (LT)-HSCs expressing the thrombopoietin (THPO) receptor, MPL, are a quiescent population in adult bone marrow (BM) and are closely associated with THPO-producing osteoblastic cells. THPO/MPL signaling upregulated beta1-integrin and cyclin-dependent kinase inhibitors in HSCs. Furthermore, inhibition and stimulation of THPO/MPL pathway by treatments with anti-MPL neutralizing antibody, AMM2, and with THPO showed reciprocal regulation of quiescence of LT-HSC. AMM2 treatment reduced the number of quiescent LT-HSCs and allowed exogenous HSC engraftment without irradiation. By contrast, exogenous THPO transiently increased quiescent HSC population and subsequently induced HSC proliferation in vivo. Altogether, these observations suggest that THPO/MPL signaling plays a critical role of LT-HSC regulation in the osteoblastic niche.     

Constitutive autophagy in plant root cells

In previous studies, using a membrane-permeable protease inhibitor, E-64d, we showed that autophagy occurs constitutively in the root cells of barley and Arabidopsis. In the present study, a fusion protein composed of the autophagy-related protein AtAtg8 and green fluorescent protein (GFP) was expressed in Arabidopsis to visualize autophagosomes. We first confirmed the presence of autophagosomes with GFP fluorescence in the root cells of seedlings grown on a nutrient-sufficient medium. The number of autophagosomes changed as the root cells grew and differentiated. In cells near the apical meristem, autophagosomes were scarcely found. However, a small but significant number of autophagosomes existed in the elongation zone. More autophagosomes were found in the differentiation zone where cell growth ceases but the cells start to form root hair. In addition, we confirmed that autophagy is activated under starvation conditions in Arabidopsis root cells. When the root tips were cultured in a sucrose-free medium, the number of autophagosomes increased in the elongation and differentiation zones, and a significant number of autophagosomes appeared in cells near the apical meristem. The results suggest that autophagy in plant root cells is involved not only in nutrient recycling under nutrient-limiting conditions but also in cell growth and root hair formation.     

Intra- and extra-familial adverse childhood experiences and a history of childhood psychosomatic disorders among Japanese university students

Many patients with somatoform disorders are frequently encountered in psychosomatic clinics as well as in primary care clinics. To assess such patients objectively, the concept of somatosensory amplification may be useful. Somatosensory amplification refers to the tendency to experience a somatic sensation as intense, noxious, and disturbing. It may have a role in a variety of medical conditions characterized by somatic symptoms that are disproportionate to demonstrable organ pathology. It may also explain some of the variability in somatic symptomatology found among different patients with the same serious medical disorder. It has been assessed with a self-report questionnaire, the Somatosensory Amplification Scale. This instrument was developed in a clinical setting in the U.S., and the reliability and validity of the Japanese and Turkish versions have been confirmed as well.