A search for the heaviest isotopes of fluorine, neon, and sodium was conducted by fragmentation of an intense ^{48}Ca beam at 345 MeV/nucleon with a 20-mm-thick beryllium target and identification ...of isotopes in the large-acceptance separator BigRIPS at the RIKEN Radioactive Isotope Beam Factory. No events were observed for ^{32,33}F, ^{35,36}Ne, and ^{38}Na and only one event for ^{39}Na after extensive running. Comparison with predicted yields excludes the existence of bound states of these unobserved isotopes with high confidence levels. The present work indicates that ^{31}F and ^{34}Ne are the heaviest bound isotopes of fluorine and neon, respectively. The neutron dripline has thus been experimentally confirmed up to neon for the first time since ^{24}O was confirmed to be the dripline nucleus nearly 20 years ago. These data provide new keys to understanding the nuclear stability at extremely neutron-rich conditions.
Gut microbiota is involved in the metabolism of uremic solutes. However, the precise influence of microbiota to the retention of uremic solutes in CKD is obscure. To clarify this, we compared ...adenine-induced renal failure and control mice under germ-free or specific pathogen-free (SPF) conditions, examining the metabolite profiles of plasma, feces, and urine using a capillary electrophoresis time-of-flight mass spectrometry–based approach. Mice with renal failure under germ-free conditions demonstrated significant changes in plasma metabolites. Among 183 detected solutes, plasma levels of 11 solutes, including major uremic toxins, were significantly lower in germ-free mice than in SPF mice with renal failure. These 11 solutes were considered microbiota-derived uremic solutes and included indoxyl sulfate, p-cresyl sulfate, phenyl sulfate, cholate, hippurate, dimethylglycine, γ-guanidinobutyrate, glutarate, 2-hydroxypentanoate, trimethylamine N-oxide, and phenaceturate. Metabolome profiling showed that these solutes were classified into three groups depending on their origins: completely derived from microbiota (indoxyl sulfate, p-cresyl sulfate), derived from both host and microbiota (dimethylglycine), and derived from both microbiota and dietary components (trimethylamine N-oxide). Additionally, germ-free renal failure conditions resulted in the disappearance of colonic short-chain fatty acids, decreased utilization of intestinal amino acids, and more severe renal damage compared with SPF mice with renal failure. Microbiota-derived short-chain fatty acids and efficient amino acid utilization may have a renoprotective effect, and loss of these factors may exacerbate renal damage in germ-free mice with renal failure. Thus, microbiota contributes substantially to the production of harmful uremic solutes, but conversely, growth without microbiota has harmful effects on CKD progression.
•In-flight particle identification of RI beams developed for BigRIPS separator.•Atomic number Z and mass-to-charge ratio A/Q are deduced by the TOF-Bρ-ΔE.•Precise determinations of Bρ and TOF with ...trajectory reconstruction and slew correction, respectively.•The achieved A/Q resolution is high enough to clearly identify the charge state.•Thorough removal of background events improves the reliability of identification.
We have developed a method for achieving excellent resolving power in in-flight particle identification of radioactive isotope (RI) beams at the BigRIPS fragment separator at the RIKEN Nishina Center RI Beam Factory (RIBF). In the BigRIPS separator, RI beams are identified by their atomic number Z and mass-to-charge ratio A/Q which are deduced from the measurements of time of flight (TOF), magnetic rigidity (Bρ) and energy loss (ΔE), and delivered as tagged RI beams to a variety of experiments including secondary reaction measurements. High A/Q resolution is an essential requirement for this scheme, because the charge state Q of RI beams has to be identified at RIBF energies such as 200–300MeV/nucleon. By precisely determining the Bρ and TOF values, we have achieved relative A/Q resolution as good as 0.034% (root-mean-square value). The achieved A/Q resolution is high enough to clearly identify the charge state Q in the Z versus A/Q particle identification plot, where fully-stripped and hydrogen-like peaks are very closely located. The precise Bρ determination is achieved by refined particle trajectory reconstruction, while a slew correction is performed to precisely determine the TOF value. Furthermore background events are thoroughly removed to improve reliability of the particle identification. In the present paper we present the details of the particle identification scheme in the BigRIPS separator. The isotope separation in the BigRIPS separator is also briefly introduced.
Optimal pre-hospital care for out-of-hospital cardiac arrest (OHCA) caused by respiratory disease may differ from that for OHCA associated with other aetiologies, especially with respect to ...respiratory management. We aimed to investigate whether pre-hospital advanced airway management (AAM) was associated with favourable outcomes after OHCA caused by intrinsic respiratory disease. This nationwide, population-based, propensity score-matched study of adult patients in Japan with OHCA due to respiratory disease from 1 January 2005 to 31 December 2012 compared patients with and without pre-hospital AAM. The primary outcome was neurologically favourable survival at one month after the OHCA. Of 49,534 eligible patients, 20,458 received pre-hospital AAM and 29,076 did not. In a propensity score-matched cohort (18,483 versus 18,483 patients), the odds of neurologically favourable survival were significantly lower for patients receiving pre-hospital AAM (0.6% versus 1.5%; odds ratio OR 0.42 95% confidence interval {CI} 0.34 to 0.52). The results from multivariable logistic regression analysis also showed that pre-hospital AAM was significantly associated with a decreased chance of neurologically favourable survival (adjusted OR 0.43 95% CI 0.35 to 0.52). Similar findings were observed for one-month survival and pre-hospital return of spontaneous circulation. In subgroup analyses, pre-hospital AAM was associated with poor neurological outcomes, regardless of the type of airway device used (laryngeal mask airway, adjusted OR 0.35 95% CI 0.19 to 0.57; oesophageal obturator airway, adjusted OR 0.44 95% CI 0.35 to 0.55; and endotracheal tube, adjusted OR 0.47 95% CI 0.30 to 0.69). In conclusion, pre-hospital AAM was associated with poor neurological outcome among patients with OHCA caused by intrinsic respiratory disease.
Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides (O-glycans) having terminal α1,4-linked N-acetylglucosamine residues (αGlcNAc). ...Previously, we identified human α1,4-N-acetylglucosaminyltransferase (α4GnT), which is responsible for the O-glycan biosynthesis and characterized αGlcNAc function in suppressing Helicobacter pylori in vitro. In the present study, we engineered A4gnt(-/-) mice to better understand its role in vivo. A4gnt(-/-) mice showed complete lack of αGlcNAc expression in gastric gland mucin. Surprisingly, all the mutant mice developed gastric adenocarcinoma through a hyperplasia-dysplasia-carcinoma sequence in the absence of H. pylori infection. Microarray and quantitative RT-PCR analysis revealed upregulation of genes encoding inflammatory chemokine ligands, proinflammatory cytokines, and growth factors, such as Ccl2, Il-11, and Hgf in the gastric mucosa of A4gnt(-/-) mice. Further supporting an important role for this O-glycan in cancer progression, we also observed significantly reduced αGlcNAc in human gastric adenocarcinoma and adenoma. Our results demonstrate that the absence of αGlcNAc triggers gastric tumorigenesis through inflammation-associated pathways in vivo. Thus, αGlcNAc-terminated gastric mucin plays dual roles in preventing gastric cancer by inhibiting H. pylori infection and also suppressing tumor-promoting inflammation.
This study reported the development of an advanced shaft furnace, which improved the conventional waste gasification system, and evaluated its performance using operation data and gasification ...criteria such as cold gas efficiency, carbon conversion ratio, lower heating value, emissions, slag quality, and heavy metal distributions. The coke consumption of the Advance Shaft Furnace was 15.2 kg/t-MSW, which was approximately 1/4 that of the conventional system. The carbon conversion ratio of the Advance Shaft Furnace was 90.7%. Because of higher carbon conversion, the air pollution control residue was reduced from 39.8 kg-t-MSW to 25.3 kg/t-MSW. With the equivalence ratio increasing, carbon monoxide concentration in the syngas decreased and the syngas temperature increased. The other gasification criteria of the advanced shaft furnace were also comparable to the conventional system. The PCDD/DFs emissions from the stack of the advance shaft furnace were 0.0088 ng-TEQ/m
3
N
, which were comparable to that of the conventional system. The total emissions of the PCDD/DFs from the developed system were 3.9 μg-TEQ/t-MSW, indicating that the developed system can contribute to the reduction of the environmental impact. The Advance Shaft Furnace also has the possibility of recovering materials efficiently. Most of the lead, zinc, and chlorine were distributed in the air pollution control residue at rates of 94.9%, 80.4%, and 97.7%, respectively. Most high-boiling-point heavy metals, such as iron and copper, are distributed in metal. These results indicate that the development of the Advance Shaft Furnace can overcome the disadvantages of the conventional system while keeping the advantages, reducing the environmental impact. Furthermore, the application of biomass coke to the advanced shaft furnace can contribute to the decarbonization and carbon neutrality.
α-Dystroglycan (α-DG) represents a highly glycosylated cell surface molecule that is expressed in the epithelial cell-basement membrane (BM) interface and plays an essential role in epithelium ...development and tissue organization. The α-DG-mediated epithelial cell-BM interaction is often impaired in invasive carcinomas, yet roles and underlying mechanisms of such an impaired interaction in tumor progression remain unclear. We report here a suppressor function of laminin-binding glycans on α-DG in tumor progression. In aggressive prostate and breast carcinoma cell lines, laminin-binding glycans are dramatically decreased, although the amount of α-DG and β-dystroglycan is maintained. The decrease of laminin-binding glycans and consequent increased cell migration were associated with the decreased expression of β3-N-acetylglucosaminyltransferase-1 (β3GnT1). Forced expression of β3GnT1 in aggressive cancer cells restored the laminin-binding glycans and decreased tumor formation. β3GnT1 was found to be required for laminin-binding glycan synthesis through formation of a complex with LARGE, thus regulating the function of LARGE. Interaction of the laminin-binding glycans with laminin and other adhesive molecules in BM attenuates tumor cell migratory potential by antagonizing ERK/AKT phosphorylation induced by the components in the ECM. These results identify a previously undescribed role of carbohydrate-dependent cell-BM interaction in tumor suppression and its control by β3GnT1 and LARGE.
Androgen receptor (AR) functions as a ligand-dependent transcription factor to regulate its downstream signaling for prostate cancer progression. AR complex formation by multiple transcription ...factors is important for enhancer activity and transcriptional regulation. However, the significance of such collaborative transcription factors has not been fully understood. In this study, we show that Oct1, an AR collaborative factor, coordinates genome-wide AR signaling for prostate cancer growth. Using global analysis by chromatin immunoprecipitation sequencing (ChIP-seq), we found that Oct1 is recruited to AR-binding enhancer/promoter regions and facilitates androgen signaling. Moreover, a major target of AR/Oct1 complex, acyl-CoA synthetase 3 (ACSL3), contributes to tumor growth in nude mice, and its high expression is associated with poor prognosis in prostate cancer patients. Next, we examined the therapeutic effects of pyrrole-imidazole polyamides that target the Oct1-binding sequence identified in the center of the ACSL3 AR-binding site. We observed that treatment with Oct1 polyamide severely blocked the Oct1 binding at the ACSL3 enhancer responsible for its transcriptional activity and ACSL3 induction. In addition, Oct1 polyamides suppressed castration-resistant tumor growth and specifically repressed global Oct1 chromatin association and androgen signaling in prostate cancer cells, with few nonspecific effects on basal promoter activity. Thus, targeting Oct1 binding could be a novel therapeutic strategy for AR-activated castration-resistant prostate cancer.
Phage display technology is an emerging drug discovery tool. Using that approach, short peptides that mimic part of a carbohydrate's conformation are selected by screening a peptide-displaying phage ...library with anti-carbohydrate antibodies. Chemically synthesized peptides with an identified sequence have been used as an alternative ligand to carbohydrate-binding proteins. These peptides represent research tools useful to assay the activities of glycosyltransferases and/or sulfotransferases or to inhibit the carbohydrate-dependent binding of proteins in vitro and in vivo. Peptides can also serve as immunogens to raise anti-carbohydrate antibodies in vivo in animals. Phage display has also been used in single-chain antibody technology by inserting an immunoglobulin's variable region sequence into the phage. A single-chain antibody library can then be screened with a carbohydrate antigen as the target, resulting in a recombinant anti-carbohydrate antibody with high affinity to the antigen. This review provides examples of successful applications of peptide-displaying phage technology to glycobiology. Such an approach should benefit translational research by supplying carbohydrate-mimetic peptides and carbohydrate-binding polypeptides.
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