151 research outputs found

    Near-Infrared Spectroscopy of the Cool Brown Dwarf, SDSS 1624+00

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    Using the Subaru Telescope, we have obtained multiple near-infrared spectra of the cool brown dwarf, SDSS 1624+00, in search of spectral variability in an 80 minute time span. We have found the suspected variability of water vapor absorption throughout the observations, which requires confirmation by a longer time baseline. After coadding the spectra, we have obtained a high-quality spectrum covering 1.05 to 1.8 um. Three kinds of spectral indicators, the water vapor bands, methane band, and KI lines in J band, suggest that SDSS 1624+00 is warmer and dustier than Gl 229B.Comment: 6 figures, to appear in PAS

    Association of Thioautotrophic Bacteria with Deep-Sea Sponges

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    We investigated microorganisms associated with a deep-sea sponge, Characella sp. (Pachastrellidae) collected at a hydrothermal vent site (686 m depth) in the Sumisu Caldera, Ogasawara Island chain, Japan, and with two sponges, Pachastrella sp. (Pachastrellidae) and an unidentified Poecilosclerida sponge, collected at an oil seep (572 m depth) in the Gulf of Mexico, using polymerase chain reaction–denaturing gradient gel electrophoresis (PCR-DGGE) directed at bacterial 16S rRNA gene sequences. In the PCR-DGGE profiles, we detected a single clearly dominant band in each of the Characella sp. and the unidentified Poecilosclerida sponge. BLAST search of their sequences showed that they were most similar (>99% identity) to those of the gammaproteobacterial thioautotrophic symbionts of deep-sea bivalves from hydrothermal vents, Bathymodiolus spp. Phylogenetic analysis of the near-full length sequences of the 16S rRNA genes cloned from the unidentified Poecilosclerida sponge and Characella sp. confirmed that they were closely related to thioautotrophic symbionts. Although associations between sponges and methanotrophic bacteria have been reported previously, this is the first report of a possible stable association between sponges and thioautotrophic bacteria

    Spatiotemporal T790M Heterogeneity in Individual Patients with EGFR-Mutant Non–Small-Cell Lung Cancer after Acquired Resistance to EGFR-TKI

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    IntroductionEpidermal growth factor receptor (EGFR) mutation T790M accounts for approximately half of acquired resistances to EGFR-tyrosine kinase inhibitor (TKI). Because T790M is mediated by TKI exposure, its penetration and “on–off” may affect T790M status.MethodsWe retrospectively reviewed T790M status and clinical course of patients who had undergone multiple rebiopsies after acquired resistance to EGFR-TKI.ResultsOf 145 patients with EGFR-mutant NSCLC receiving rebiopsy after acquired resistance, 30 underwent multiple site rebiopsies, and 24 received repeated rebiopsies at the same lesion. In 22 patients who underwent rebiopsies from both central nervous system (CNS; 20 cerebrospinal fluids [CSF] and 2 brain tumoral tissues) and thoracic lesions (7 lung tissues, 14 pleural effusions, and 1 lymph node), 12 were thoracic-T790M-positive. Of these 12 patients, 10 were CNS-T790M-negative, despite exhibiting thoracic-T790M-positive. All 10 thoracic-T790M-negatives were CNS-T790M-negative. Three patients revealed a spatial heterogeneous T790M status among their thoracic lesions. In 24 patients receiving repeated rebiopsies at the same lesion (12 lung tissues, 6 CSFs, and 6 pleural effusions), T790M status of lung lesions varied in five patients after TKI-free interval. In all five patients whose T790M status changed from positive to negative, EGFR-TKI rechallenge was effective. In three of these five patients, after further TKI exposure, T790M status changed from negative to positive again. There was also a patient whose CSF T790M status changed from negative to positive after high-dose erlotinib therapy.ConclusionsT790M status in an individual patient can be spatiotemporally heterogeneous because of selective pressure from EGFR-TKI

    How Sensitive Are Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitors for Squamous Cell Carcinoma of the Lung Harboring EGFR Gene–Sensitive Mutations?

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    Introduction:Epidermal growth factor receptor (EGFR) mutations are found mostly in adenocarcinoma, and rarely in squamous cell carcinoma (SQC). Little is known about SQC harboring EGFR mutations.Methods:Between April 2006 and October 2010, we investigated the incidence of EGFR activating mutations in SQC of the lung using the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method. The efficacy of EGFR-tyrosine kinase inhibitors (TKIs) was retrospectively evaluated in patients with EGFR-mutated SQC. Further pathologic analyses were performed using immunohistochemistry.Results:Thirty-three of 249 patients with SQC (13.3%) had EGFR mutations, including exon 19 deletion (19 of 33 patients, 58%), L858R point mutation in exon 21 (12 of 33, 36%), and G719S point mutation in exon 18 (2 of 33, 6%). Twenty of these 33 patients received EGFR-TKI therapy, and five of these 20 responded to EGFR-TKIs with a response rate of 25.0% (95% confidence interval [CI], 8.7%–49.1%). The patients’ median progression-free survival and median overall survival were 1.4 months (95% CI, 0.7–5.8 months) and 14.6 months (95% CI, 2.9–undeterminable months), respectively. Approximately one third of the EGFR-mutated SQC patients achieved progression-free survival for longer than 6 months. Some of these patients had high carcinoembryonic antigen levels or a history of never smoking, or were positive for thyroid transcription factor-1.Conclusions:Although EGFR-TKIs seem to be generally less effective in EGFR-mutated SQC than in EGFR-mutated adenocarcinoma, some EGFR-mutated SQC patients can obtain clinical benefit from EGFR-TKIs. To better identify these patients, not only EGFR mutation status, but also clinical factors and pathologic findings should be taken into consideration

    Heart Disease, Other Circulatory Diseases, and Onset of Major Depression among Community Residents in Japan: Results of the World Mental Health Survey Japan 2002-2004

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    We examined whether selected circulatory diseases (heart disease, stroke, diabetes and hypertension) were associated with an increased risk of major depression in the Japanese community population. Face-to-face household surveys were carried out in 7 areas, and a total of 2,436 persons participated (overall response rate: 58.4%) from 2002 to 2004. The WHO Composite International Diagnostic Interview 3.0 was used to diagnose major depression according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and additional interviews assessed the presence of circulatory diseases. Using data from a random subsample of the respondents (n=832), we conducted Cox proportional hazards models to calculate hazard ratios for the onset of major depression with comorbid circulatory diseases as a time-dependent covariate. Heart attack was significantly associated with the onset of major depression (hazard ratio [HR], 7.51 [95%Confidential Interval (CI), 1.36-41.45]) after adjusting for sex, birth cohort, smoking, alcohol intake, and education. Heart disease (HR, 2.12 [95% CI, 0.79-5.70]), diabetes (HR, 2.36 [95% CI, 0.42-13.34]) and hypertension (HR, 0.97 [95% CI, 0.37, 2.50]) were not significantly associated. There were no subjects who developed major depression after stroke. These results suggest that heart attack, and maybe also heart disease and diabetes, affect the onset of major depression.</p

    Circadian protection against bacterial skin infection by epidermal CXCL14-mediated innate immunity

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    体内時計は夜間に自然免疫を発動 --皮膚ケモカインによる自然免疫機構--. 京都大学プレスリリース. 2022-06-16.Biological clocks set for skin immunity. 京都大学プレスリリース. 2022-06-21.The epidermis is the outermost layer of the skin and the body’s primary barrier to external pathogens; however, the early epidermal immune response remains to be mechanistically understood. We show that the chemokine CXCL14, produced by epidermal keratinocytes, exhibits robust circadian fluctuations and initiates innate immunity. Clearance of the skin pathogen Staphylococcus aureus in nocturnal mice was associated with CXCL14 expression, which was high during subjective daytime and low at night. In contrast, in marmosets, a diurnal primate, circadian CXCL14 expression was reversed. Rhythmically expressed CXCL14 binds to S. aureus DNA and induces inflammatory cytokine production by activating Toll-like receptor (TLR)9-dependent innate pathways in dendritic cells and macrophages underneath the epidermis. CXCL14 also promoted phagocytosis by macrophages in a TLR9-independent manner. These data indicate that circadian production of the epidermal chemokine CXCL14 rhythmically suppresses skin bacterial proliferation in mammals by activating the innate immune system
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