Trigonometric distance and proper motions of H2O maser bowshocks in AFGL 5142

We present the results of multi-epoch VLBI observations of water masers in the AGFL 5142 massive star forming region. We measure an annual parallax of $\pi=0.467 \pm 0.010$ mas, corresponding to a source distance of $D=2.14^{+0.051}_{-0.049}$ kpc. Proper motion and line of sight velocities reveal the 3D kinematics of masers in this region, most of which associate with millimeter sources from the literature. In particular we find remarkable bipolar bowshocks expanding from the most massive member, AFGL 5142 MM1, which are used to investigate the physical properties of its protostellar jet. We attempt to link the known outflows in this region to possible progenitors by considering a precessing jet scenario and we discuss the episodic nature of ejections in AFGL 5142

Missense Mutation in the Alternative Splice Region of the PAX6 Gene in Eye Anomalies

SummaryThe PAX6 gene is involved in ocular morphogenesis, and PAX6 mutations have been detected in various types of ocular anomalies, including aniridia, Peters anomaly, corneal dystrophy, congenital cataract, and foveal hypoplasia. The gene encodes a transcriptional regulator that recognizes target genes through its paired-type DNA-binding domain. The paired domain is composed of two distinct DNA-binding subdomains, the N-terminal subdomain (NTS) and the C-terminal subdomain (CTS), which bind respective consensus DNA sequences. The human PAX6 gene produces two alternative splice isoforms that have the distinct structure of the paired domain. The insertion, into the NTS, of 14 additional amino acids encoded by exon 5a abolishes the DNA-binding activity of the NTS and unmasks the DNA-binding ability of the CTS. Thus, exon 5a appears to function as a molecular switch that specifies target genes. We ascertained a novel missense mutation in four pedigrees with Peters anomaly, congenital cataract, Axenfeldt anomaly, and/or foveal hypoplasia, which, to our knowledge, is the first mutation identified in the splice-variant region. A T→A transition at the 20th nucleotide position of exon 5a results in a Val→Asp (GTC→GAC) substitution at the 7th codon of the alternative splice region. Functional analyses demonstrated that the V54D mutation slightly increased NTS binding and decreased CTS transactivation activity to almost half

DSIF contributes to transcriptional activation by DNA-binding activators by preventing pausing during transcription elongation

The transcription elongation factor 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole (DRB) sensitivity-inducing factor (DSIF) regulates RNA polymerase II (RNAPII) processivity by promoting, in concert with negative elongation factor (NELF), promoter-proximal pausing of RNAPII. DSIF is also reportedly involved in transcriptional activation. However, the role of DSIF in transcriptional activation by DNA-binding activators is unclear. Here we show that DSIF acts cooperatively with a DNA-binding activator, Gal4-VP16, to promote transcriptional activation. In the absence of DSIF, Gal4-VP16-activated transcription resulted in frequent pausing of RNAPII during elongation in vitro. The presence of DSIF reduced pausing, thereby supporting Gal4-VP16-mediated activation. We found that DSIF exerts its positive effects within a short time-frame from initiation to elongation, and that NELF does not affect the positive regulatory function of DSIF. Knockdown of the gene encoding the large subunit of DSIF, human Spt5 (hSpt5), in HeLa cells reduced Gal4-VP16-mediated activation of a reporter gene, but had no effect on expression in the absence of activator. Together, these results provide evidence that higher-level transcription has a stronger requirement for DSIF, and that DSIF contributes to efficient transcriptional activation by preventing RNAPII pausing during transcription elongation

Synthesis, Crystal Structures, Electronic Spectra, and Magnetic Properties of Thiolato-Bridged Trinuclear Cobalt(II) Complexes with N, N, S-Tridentate Thiolate Ligands

New trinuclear CoII complexes, [{Co(apaet)2}2Co]X2 (apaet– = 2-[(3-aminopropyl)amino]ethanethiolato; X = SCN (1), ClO4 (2), NO3 (3), Cl (4), Br (5), I (6)) and [{Co(apampt)2}2Co]X2 (apampt– = 1-[(3-aminopropyl)amino]-2-methylpropane-2-thiolato; X = NO3(7), ClO4 (8), Cl (9), Br (10), I (11)), and mononuclear CoIII complexes, [Co(apaet)2]X (X = ClO4 (12), NO3 (13)), were synthesized. Single-crystal X-ray crystallography of 1 and 7 confirmed that the trinuclear complexes have a linear arrangement of octahedral CoIIS2N4-tetrahedral CoIIS4-octahedral CoIIS2N4 chromophores where two thiolate ligands are coordinated to each terminal Co atom in a mer coordination mode and the two thiolato S atoms are further bound to the central Co atom, which is consistent with the electronic spectra and antiferromagnetic propertie

Bofutsushosan, an Oriental Herbal Medicine, Attenuates the Weight Gain of White Adipose Tissue and the Increased Size of Adipocytes Associated with the Increase in Their Expression of Uncoupling Protein 1 in High-Fat Diet-Fed Male KK/Ta mice

Bofutsushosan (BOF), an oriental herbal medicine, has been used as an anti-obesity drug in overweight patients. In the present study, to evaluate the anti-obesity and anti-diabetic effects of BOF, we investigated the effects of BOF on the white adipose tissue (WAT) weight, the size of adipocytes, adiponectin expression, and oral glucose tolerance test results in high-fat diet-fed male KK/Ta mice. In addition, the mRNA expression levels of uncoupling protein 1 (UCP1) and UCP2 mRNA in WAT and brown adipose tissue (BAT) were measured. 6-week-old KK/Ta mice were divided into four groups and fed a purified powdered basal diet (the BD group), a purified high-fat (HF) powdered diet containing suet powder at 37.5 g/100 g diet (the HF group), a high-fat diet plus 1.0% bofutsushosan (BOF) treatment (the HF + BOF group), or a high-fat diet plus 1.0% daisaikoto (DAI) treatment (the HF + DAI group) for 4 weeks. The weight of WAT and the size of adipocytes were increased in the HF group compared with those in the BD group, and these increases in the HF group were significantly inhibited in the HF + BOF group, but not affected in the HF + DAI group. There were no statistically significant differences in plasma levels and tissue mRNA levels of adiponectin among the four groups. There were no significant differences in UCP1 mRNA expression of BAT among the four groups. The expression of UCP1 mRNA in WAT was found in the HF + BOF group, but little expression was seen in the WAT of the BD, HF, or HF + DAI groups. The elevated plasma glucose levels and responses after the glucose loading in the HF group tended to decrease in the HF + BOF group. These results suggest that BOF decreases the weight and size gains of WAT along with up-regulating UCP1 mRNA in WAT in high-fat diet-fed mice

A Mouse Model of Metabolic Syndrome; Increase in Visceral Adipose Tissue Precedes the Development of Fatty Liver and Insulin Resistance in High-Fat Diet-Fed Male KK/Ta Mice

To determine the relative contribution of obesity and visceral white adipose tissue (WAT) to metabolic syndrome, we developed a model that is susceptible to high-fat diet-induced obesity and insulin resistance using male KK/Ta mice. The ratio of WAT weight to body weight was greater in the high-fat diet group compared with the control group in 10-, 14-, and 22-week-old mice. The increase in visceral WAT preceded development of fatty liver and insulin resistance. Adiponectin mRNA expression in WAT was markedly decreased before the decrease in its plasma levels or the development of insulin resistance. Insulin resistance appeared in association with fatty infiltration and TNF-α expression in the liver in 22-week-old mice. These data indicate that our mouse model would be useful for future studies that investigate the role of visceral WAT and its products in the development of metabolic syndrome

Molecular characterization of Drosophila NELF

NELF and DSIF act together to inhibit transcription elongation in vitro, and are implicated in causing promoter proximal pausing on the hsp70 gene in Drosophila. Here, further characterization of Drosophila NELF is provided. Drosophila NELF has four subunits similar to subunits of human NELF. The amino acid sequences of NELF-B and NELF-D are highly conserved throughout their lengths, while NELF-A and NELF-E contain nonconserved regions inserted between conserved N- and C-terminal regions. Immunodepletion of NELF or DSIF from a nuclear extract desensitizes transcription in vitro to DRB. Immunodepletion of NELF also impairs promoter proximal pausing on the hsp70 promoter in vitro without affecting initiation. Chromatin immunoprecipitation analyses detect NELF at the promoters of the hsp70 and β1-tubulin genes where promoter proximal pausing has been previously detected. Heat shock induction of hsp70 results in a marked decrease in NELF at the hsp70 promoter. Immunofluorescence analysis of polytene chromosomes shows extensive colocalization of the NELF-B and NELF-D subunits at hundreds of interbands. Neither subunit appears to be recruited to puffs. These results provide a foundation for genetic and biochemical analysis of NELF in Drosophila

Comparison of Efficacy and Safety between Mosapride and Acotiamide for Japanese patients with Functional Dyspepsia

　Background: 5-HT4 agonists (mosapride) and acetylcholine esterase inhibitor (acotiamide) are prokinetics used to treat functional dyspepsia (FD). However, to date, there has been no direct comparative study between them. The aim of this study was to compare the drugs’ efficacy and safety and to determine their predictive biomarkers.　Methods: The present study was a prospective, randomized, open-labeled, and crossover trial in Japanese FD patients. FD was diagnosed using Rome IV. We performed upper gastrointestinal (GI) endoscopy, GI symptom rating scale, and 8-item Short-Form Health Survey to evaluate the presence of GI disorders, GI symptoms, and quality of life (QOL), respectively. Responders were defined when reporting at least a 40% improvement of the GSRS scores from their baseline.　Results: In total, 60 Japanese FD patients were randomly assigned to the acotiamide preceding group (n = 30) or mosapride preceding group (n = 30), and 51 patients were finally analyzed. Following treatment with both mosapride and acotiamide, GI symptoms and QOL scores improved significantly. The responder rates of mosapride and acotiamide were 37% and 33%, respectively. No severe adverse clinical event developed. The prevalence of H. pylori eradication history was significantly lower in the mosapride responder group than in the nonresponder group (45.9% vs. 14.2%, p = 0.03).　Discussion: Mosapride and acotiamide had similar effects on GI symptoms in FD patients in the absence of severe adverse events. H. pylori infection might impact in the pathogenesis of functional dyspepsia. Further investigation is needed to clarify the difference between mosapride and acotiamide