gen. nov., sp. nov., an anaerobic, obligately syntrophic archaeon, the first isolate of the lineage 'Asgard' archaea, and proposal of the new archaeal phylum phyl. nov. and kingdom regn. nov.

An anaerobic, mesophilic, syntrophic, archaeon strain MK-D1, was isolated as a pure co-culture with sp. strain MK-MG from deep-sea methane seep sediment. This organism is, to our knowledge, the first cultured representative of 'Asgard' archaea, an archaeal group closely related to eukaryotes.

Characterization and cluster analyses of elderly asthma in comparison with nonelderly patients with asthma in Japan.

Background: Asthma is a heterogeneous disease with multiple phenotypes that are useful in precision medicine. As the population ages, the elderly asthma (EA, aged ≥ 65 years) population is growing, and EA is now a major health problem worldwide.

Objective: To characterize EA and identify its phenotypes.

Cultivation of previously uncultured microorganisms with a continuous-flow down-flow hanging sponge (DHS) bioreactor, using a syntrophic archaeon culture obtained from deep marine sediment as a case study.

In microbiology, cultivation is a central approach for uncovering novel physiology, ecology, and evolution of microorganisms, but conventional methods have left many microorganisms found in nature uncultured. To overcome the limitations of traditional methods and culture indigenous microorganisms, we applied a two-stage approach: enrichment/activation of indigenous organisms by using a continuous-flow down-flow hanging sponge bioreactor and subsequent selective batch cultivation. Here, we provide a protocol for this bioreactor-mediated technique using activation of deep marine sediment microorganisms and downstream isolation of a syntrophic co-culture containing an archaeon closely related to the eukaryote ancestor (Candidatus Promethearchaeum syntrophicum strain MK-D1) as an example.

Isolation of an archaeon at the prokaryote-eukaryote interface.

The origin of eukaryotes remains unclear. Current data suggest that eukaryotes may have emerged from an archaeal lineage known as 'Asgard' archaea. Despite the eukaryote-like genomic features that are found in these archaea, the evolutionary transition from archaea to eukaryotes remains unclear, owing to the lack of cultured representatives and corresponding physiological insights.

Methanofervidicoccus abyssi gen. nov., sp. nov., a hydrogenotrophic methanogen, isolated from a hydrothermal vent chimney in the Mid-Cayman Spreading Center, the Caribbean Sea.

A novel hydrogenotrophic methanogen, strain HHB, was isolated from a deep-sea hydrothermal vent chimney sample collected from Beebe Vent Field at the Mid-Cayman Spreading Center, Caribbean Sea. The cells were non-motile regular to irregular cocci possessing several flagella. The novel isolate grew at 60-80 °C, pH 5.

Aggregatilinea lenta gen. nov., sp. nov., a slow-growing, facultatively anaerobic bacterium isolated from subseafloor sediment, and proposal of the new order Aggregatilineales ord. nov. within the class Anaerolineae of the phylum Chloroflexi.

A novel slow-growing, facultatively anaerobic, filamentous bacterium, strain MO-CFX2, was isolated from a methanogenic microbial community in a continuous-flow bioreactor that was established from subseafloor sediment collected off the Shimokita Peninsula of Japan. Cells were multicellular filamentous, non-motile and Gram-stain-negative. The filaments were generally more than 20 µm (up to approximately 200 µm) long and 0.

Malignant hepatic epithelioid angiomyolipoma with recurrence in the lung 7 years after hepatectomy: a case report and literature review.

Angiomyolipoma (AML) arising in the liver is rare and usually benign, but it occasionally has malignant potential. A 58-year-old man with a liver tumor identified by a previous doctor with features suggestive of hepatocellular carcinoma on computed tomography (CT) underwent anterior segmentectomy of the liver in 2006. Microscopically, the tumor was composed of exclusively epithelioid cells that were scatteredly positive for human melanoma black 45 on immunohistochemistry.

Anti-Semaphorin 3A neutralization monoclonal antibody prevents sepsis development in lipopolysaccharide-treated mice.

Semaphorin 3A (Sema3A), originally identified as a potent growth cone collapsing factor in developing sensory neurons, is now recognized as a key player in immune, cardiovascular, bone metabolism and neurological systems. Here we established an anti-Sema3A monoclonal antibody that neutralizes the effects of Sema3A both in vitro and in vivo. The anti-Sema3A neutralization chick IgM antibodies were screened by combining an autonomously diversifying library selection system and an in vitro growth cone collapse assay.

Reductant-free colloidal synthesis of near-IR emitting germanium nanocrystals: role of primary amine.

High temperature colloidal synthesis without using hazardous reducing agent is demonstrated here to develop a straight forward pathway for synthesizing near-IR (NIR) light emitting germanium nanocrystals (Ge NCs). The NCs were prepared by heating a mixture of germanium (II) iodide and organoamine. This article presents an important role of the primary amine which serves as a reducing agent as well as an inhibitor against oxidation by comparing with the tertiary amine.

Efficient Dual-Modal NIR-to-NIR Emission of Rare Earth Ions Co-doped Nanocrystals for Biological Fluorescence Imaging.

A novel approach has been developed for the realization of efficient near-infrared to near-infrared (NIR-to-NIR) upconversion and down-shifting emission in nanophosphors. The efficient dual-modal NIR-to-NIR emission is realized in a β-NaGdF4/Nd(3+)@NaGdF4/Tm(3+)-Yb(3+) core-shell nanocrystal by careful control of the identity and concentration of the doped rare earth (RE) ion species and by manipulation of the spatial distributions of these RE ions. The photoluminescence results reveal that the emission efficiency increases at least 2-fold when comparing the materials synthesized in this study with those synthesized through traditional approaches.

A novel method for determining vitamin B1 in a wide variety of foodstuffs with or without polyphenols.

Certain foodstuffs exhibit matrix interference effects on the vitamin B(1) analysis prescribed in the official methods of the European Union, AOAC International, and Japan. In this study, we demonstrated that one of the problematic polyphenols in green tea or cocoa was tannin. For these matrices, thiamine was found to interact with tannin in the extraction step and was thus removed by filtration as a residue.

Restoration of the behavioral rates and lifespan in clk-1 mutant nematodes in response to exogenous coenzyme Q(10).

The clk-1 gene encodes demethoxyubiquinone mono-oxygenase that is necessary for the biosynthesis of coenzyme Q (CoQ), which is an electron transporter in the respiratory chain of mitochondria. Therefore, clk-1 mutant nematodes that have loss-of-function mutations in the clk-1 gene lack endogenous CoQ(9) and exhibit slowed behavioral rates and an extended lifespan compared with wild-type animals when they are fed standard bacteria containing endogenous CoQ(8). This finding suggests that clk-1 regulates behavioral rates and the lifespan through CoQ in nematodes; however, the effects of exogenous CoQ on the regulation of these biological processes have been incompletely evaluated.

Lifespan and glucose metabolism in insulin receptor mutant mice.

Insulin/insulin-like growth factor type 1 signaling regulates lifespan and resistance to oxidative stress in worms, flies, and mammals. In a previous study, we revealed that insulin receptor (IR) mutant mice, which carry a homologous mutation found in the long-lived daf-2 mutant of Caenorhabditis elegans, showed enhanced resistance to oxidative stress cooperatively modulated by sex hormones and dietary signals (Baba et al., (2005)).

Semaphorin3A signaling mediated by Fyn-dependent tyrosine phosphorylation of collapsin response mediator protein 2 at tyrosine 32.

Collapsin response mediator protein 2 (CRMP2) is an intracellular protein that mediates signaling of Semaphorin3A (Sema3A), a repulsive axon guidance molecule. Fyn, a Src-type tyrosine kinase, is involved in the Sema3A signaling. However, the relationship between CRMP2 and Fyn in this signaling pathway is still unknown.

Cell surface N-glycans mediated isolation of mouse neural stem cells.

The isolation of neural stem cells (NSCs) from the brain has been hampered by the lack of valid cell surface markers and the requirement for long-term in vitro cultivation that may lead to phenotype deterioration. However, few suitable specific cell surface antigens are available on NSCs that could be used for their prospective isolation. The present study demonstrated that the expression of complex type asparagine-linked oligosaccharide (N-glycans) was detected on brain cells dissociated from embryonic and adult brain using Phaseolus vulgaris erythroagglutinating lectin (E-PHA) which binds to biantennary complex type N-glycans, and demonstrated that E-PHA bound preferentially to purified NSCs, but not to neurons, microglia, or oligodendrocyte precursor cells.

Vinorelbine plus gemcitabine followed by docetaxel versus carboplatin plus paclitaxel in patients with advanced non-small-cell lung cancer: a randomised, open-label, phase III study.

Background: Platinum-containing two-drug combinations improve survival and cancer-related symptoms in patients with advanced non-small-cell lung cancer (NSCLC). However, survival benefit is modest and platinum-containing regimens cause substantial toxic effects. We did a prospective randomised open-label phase III study to compare an experimental platinum-free, triplet, sequential regimen of vinorelbine plus gemcitabine followed by docetaxel with the standard platinum-containing, doublet regimen paclitaxel plus carboplatin in patients with advanced NSCLC.

Characterization of preexisting humoral immunity specific for two cancer-testis antigens overexpressed at the mRNA level in non-small cell lung cancer.

In order to establish a rationale for immunotherapy for lung cancer, we have investigated immunological characteristics of tumor-associated antigens (TAAs) discovered through molecular approaches. Preexisting Abs specific to these predicted TAAs were examined using specimens of lung pleural effusions (LPEs) and sera in non-small cell lung cancer (NSCLC) patients. The novel cancer-testis (CT) antigens L514S and L552S were highly expressed in approximately half of the NSCLC tissues and established cell lines examined.

Alpha-internexin as a corneal autoantigen in spontaneous autoimmune keratitis mouse model.

Purpose: The purpose of this study was to identify target antigens of autoimmune keratitis with a disease-prone mouse model.

Methods: BALB/c nude mice grafted with embryonic rat thymi (TG nude mice) develop various organ-localized autoimmune lesions, including keratitis. A hybridoma producing a monoclonal antibody (OT-20), specific for corneal epithelium was established by using spleen cells from this model mouse of keratitis, and the target of OT-20 was identified by immunoblot analysis.

Estrogen, insulin, and dietary signals cooperatively regulate longevity signals to enhance resistance to oxidative stress in mice.

To investigate the biological significance of a longevity mutation found in daf-2 of Caenorhabditis elegans, we generated a homologous murine model by replacing Pro-1195 of insulin receptors with Leu using a targeted knock-in strategy. Homozygous mice died in the neonatal stage from diabetic ketoacidosis, whereas heterozygous mice showed the suppressed kinase activity of the insulin receptor but grew normally without spontaneously developing diabetes during adulthood. We examined heterozygous insulin receptor mutant mice for longevity phenotypes.

[Lung toxicity of trimodality chemoradiotherapy with mitomycin C, vindesine, and cisplatin followed by surgery for locally advanced non-small cell lung cancer].

To evaluate lung toxicity of mitomycin C containing chemotherapy regimen combined with thoracic radiotherapy, a retrospective study was carried out in patients with locally advanced non-small cell lung cancer who were enrolled in a randomized trial for chemoradiotherapy. Postoperative complications and pathological pulmonary toxicity were investigated in 7 surgical patients out of 306 enrolled patients who were treated with MVP combination chemotherapy and concurrent or sequential thoracic radiotherapy of 56 Gy. The 7 patients were 45-66 years old (median 50 years old), with 4 of stage IIIA, 3 of stage IIIB, 4 with adenocarcinoma, 2 with squamous cell carcinoma, and 1 with large cell carcinoma.

Phase II study of weekly irinotecan and carboplatin for refractory or relapsed small-cell lung cancer.

We designed a phase II study of weekly irinotecan (CPT-11) and carboplatin for refractory or relapsed small cell lung cancer (SCLC) and assessed the response rate, survival, and toxicity. Twenty-nine patients with refractory or relapsed SCLC were entered onto the trial. The median time off chemotherapy was 3.

Adenoviral expression of protein-L-isoaspartyl methyltransferase (PIMT) partially attenuates the biochemical changes in PIMT-deficient mice.

Protein-L-isoaspartyl methyltransferase (PIMT) is a putative protein repair enzyme, which methylates the alpha-carboxyl group of atypical L-isoaspartyl residues in aged proteins and converts them to normal L-aspartyl residues. Two splicing variants, PIMT-I and PIMT-II, have been reported, although their biological functions and specific subcellular substrates are still to be defined. We and another group have previously showed that PIMT-deficient mice succumbed to fatal epileptic seizures associated with an abnormal accumulation of isoaspartate (IsoAsp) in the brain.

Transgenic expression of the protein-L-isoaspartyl methyltransferase (PIMT) gene in the brain rescues mice from the fatal epilepsy of PIMT deficiency.

Protein-L-isoaspartyl methyltransfearase (PIMT) plays a physiological role in the repair of damaged proteins containing isoaspartyl residues. In previous studies, we showed that PIMT-deficient mice developed a fatal epileptic seizure associated with the accumulation of damaged proteins in the brain. The mutant mice also showed a neurodegenerative pathology in hippocampi and impaired spatial memory.

A feasibility study of paclitaxel 225 mg/m(2) and carboplatin AUC = 6 in untreated advanced non-small cell lung cancer patients in Japan.

Background: The combination of paclitaxel (225 mg/m(2), 3 h infusion) and carboplatin [area under the curve (AUC) 6 mg/ml x min] is used widely for non-small cell lung cancer in the USA and is one of the standard regimens in the Southwest Oncology Group. In Japan, however, the upper limit of the approved dose for single-use paclitaxel is 210 mg/m(2) and the optimum dose of this agent in combination with carboplatin has not yet been established. This study was designated to determine whether the paclitaxel dose of 225 mg/m(2 ) plus carboplatin (AUC = 6) is tolerable for Japanese patients with untreated advanced non-small cell lung cancer.

A phase II study of continuous concurrent thoracic radiotherapy in combination with mitomycin, vindesine and cisplatin in unresectable stage III non-small cell lung cancer.

The split-course concurrent thoracic radiation therapy (TRT) and full-dose chemotherapy for unresectable stage III non-small cell lung cancer (NSCLC) has produced promising results by comparison with the sequential approach. Instead of split-course radiation, we conducted a phase II study to investigate the feasibility of continuous concurrent TRT and chemotherapy. Twenty-two patients with unresectable NSCLC were enrolled onto a phase II study of continuous concurrent radiotherapy and chemotherapy.