103 research outputs found
Pediatric thioridazine poisoning as a result of a pharmacy compounding error
The adverse effects or overdose of thioridazine including sudden death, fatal arrhythmia, or retinopathy, in addition to the neurological signs have been reported. A three-year-old boy with bronchitis was prescribed erythromycin by a local clinic, but he started to complain of severe drowsiness and became unconscious. It was decided that this was a result of a compounding error of thioridazine instead of erythromycin owing to their similar commercial names. The thioridazine concentration in the child's serum on admission was two to three times higher than the Cmax for adults with the same dosage. The concentration of the lavage saline on admission was only 0.3% of the ingested amount, indicating that the lavage was not effective in our case. Pharmacokinetic analysis revealed the parameters as Tmax, 1.5 hr; Cmax, 1700 ng/mL; Ka, 2.01 L/hr; Vd, 3.6 L/kg; and T1/2, 6.8 hr. Further investigations on clinical cases with a pharmacokinetic analysis should be done to confirm the pharmacokinetic evidence obtained here and to give specific therapeutic guidelines for overdose management especially in children
Activation of ADF/cofilin by phosphorylation-regulated Slingshot phosphatase is required for the meiotic spindle assembly in Xenopus laevis oocytes
We identify Xenopus ADF/cofilin (XAC) and its activator, Slingshot phosphatase (XSSH), as key regulators of actin dynamics essential for spindle microtubule assembly during Xenopus oocyte maturation. Phosphorylation of XSSH at multiple sites within the tail domain occurs just after germinal vesicle breakdown (GVBD) and is accompanied by dephosphorylation of XAC, which was mostly phosphorylated in immature oocytes. This XAC dephosphorylation after GVBD is completely suppressed by latrunculin B, an actin monomer-sequestering drug. On the other hand, jasplakinolide, an F-actin-stabilizing drug, induces dephosphorylation of XAC. Effects of latrunculin B and jasplakinolide are reconstituted in cytostatic factor-arrested extracts (CSF extracts), and XAC dephosphorylation is abolished by depletion of XSSH from CSF extracts, suggesting that XSSH functions as an actin filament sensor to facilitate actin filament dynamics via XAC activation. Injection of anti-XSSH antibody, which blocks full phosphorylation of XSSH after GVBD, inhibits both meiotic spindle formation and XAC dephosphorylation. Coinjection of constitutively active XAC with the antibody suppresses this phenotype. Treatment of oocytes with jasplakinolide also impairs spindle formation. These results strongly suggest that elevation of actin dynamics by XAC activation through XSSH phosphorylation is required for meiotic spindle assembly in Xenopus laevis
Life-Detection Technologies for the Next Two Decades
Since its inception six decades ago, astrobiology has diversified immensely
to encompass several scientific questions including the origin and evolution of
Terran life, the organic chemical composition of extraterrestrial objects, and
the concept of habitability, among others. The detection of life beyond Earth
forms the main goal of astrobiology, and a significant one for space
exploration in general. This goal has galvanized and connected with other
critical areas of investigation such as the analysis of meteorites and early
Earth geological and biological systems, materials gathered by sample-return
space missions, laboratory and computer simulations of extraterrestrial and
early Earth environmental chemistry, astronomical remote sensing, and in-situ
space exploration missions. Lately, scattered efforts are being undertaken
towards the R&D of the novel and as-yet-space-unproven life-detection
technologies capable of obtaining unambiguous evidence of extraterrestrial
life, even if it is significantly different from Terran life. As the suite of
space-proven payloads improves in breadth and sensitivity, this is an apt time
to examine the progress and future of life-detection technologies.Comment: 6 pages, the white paper was submitted to and cited by the National
Academy of Sciences in support of the Astrobiology Science Strategy for the
Search for Life in the Univers
Polycomb-Mediated Loss of miR-31 Activates NIK-Dependent NF-κB Pathway in Adult T Cell Leukemia and Other Cancers
SummaryConstitutive NF-κB activation has causative roles in adult T cell leukemia (ATL) caused by HTLV-1 and other cancers. Here, we report a pathway involving Polycomb-mediated miRNA silencing and NF-κB activation. We determine the miRNA signatures and reveal miR-31 loss in primary ATL cells. MiR-31 negatively regulates the noncanonical NF-κB pathway by targeting NF-κB inducing kinase (NIK). Loss of miR-31 therefore triggers oncogenic signaling. In ATL cells, miR-31 level is epigenetically regulated, and aberrant upregulation of Polycomb proteins contribute to miR-31 downregulation in an epigenetic fashion, leading to activation of NF-κB and apoptosis resistance. Furthermore, this emerging circuit operates in other cancers and receptor-initiated NF-κB cascade. Our findings provide a perspective involving the epigenetic program, inflammatory responses, and oncogenic signaling
Expression and function of ephrin-B1 and its cognate receptor EphB2 in human abdominal aortic aneurysm
We examined the expression of ephrin-B1 and its cognate receptor EphB2, key regulators of angiogenesis and embryogenesis, in human abdominal aortic aneurysm (AAA) and analyzed their functional roles in cell migration. From 10 patients (9 males and 1 female; age, 68.5 ± 2.4) who underwent vascular surgery for AAA, we obtained AAA and adjacent control tissues. Using real-time RT-PCR, we analyzed expression of ephrin-B1 and EphB2. We also histologically localized these molecules in AAA tissues. Finally, effects of ephrin-B1 and EphB2 on inflammatory cell chemotaxis were examined by cell migration assay. Expression levels of ephrin-B1 (0.410 ± 0.046 versus 1.198 ± 0.252, P = 0.027) and EphB2 (0.764 ± 0.212 versus 1.272 ± 0.137, P = 0.594) were higher in AAA than normal control. Both ephrin-B1 and EphB2 were expressed in macrophages, T lymphocytes, and endothelial cells within AAA. In chemotaxis assay, ephrin-B1 and EphB2 inhibited mononuclear-cell chemotaxis induced by stromal derived factor-1 down to 54.7 ± 12.7 (P = 0.01) and 50.7 ± 13.1 (P = 0.01), respectively. These data suggest that ephrin-B1 and EphB2 might be functional in human adult inflammatory cells and involved in the pathogenesis of AAA, although specific roles of these molecules should further be sought. © 2012 Aiji Sakamoto et al
Expression and function of ephrin-B1 and its cognate receptor EphB2 in human abdominal aortic aneurysm
We examined the expression of ephrin-B1 and its cognate receptor EphB2, key regulators of angiogenesis and embryogenesis, in human abdominal aortic aneurysm (AAA) and analyzed their functional roles in cell migration. From 10 patients (9 males and 1 female; age, 68.5 ± 2.4) who underwent vascular surgery for AAA, we obtained AAA and adjacent control tissues. Using real-time RT-PCR, we analyzed expression of ephrin-B1 and EphB2. We also histologically localized these molecules in AAA tissues. Finally, effects of ephrin-B1 and EphB2 on inflammatory cell chemotaxis were examined by cell migration assay. Expression levels of ephrin-B1 (0.410 ± 0.046 versus 1.198 ± 0.252, P = 0.027) and EphB2 (0.764 ± 0.212 versus 1.272 ± 0.137, P = 0.594) were higher in AAA than normal control. Both ephrin-B1 and EphB2 were expressed in macrophages, T lymphocytes, and endothelial cells within AAA. In chemotaxis assay, ephrin-B1 and EphB2 inhibited mononuclear-cell chemotaxis induced by stromal derived factor-1 down to 54.7 ± 12.7 (P = 0.01) and 50.7 ± 13.1 (P = 0.01), respectively. These data suggest that ephrin-B1 and EphB2 might be functional in human adult inflammatory cells and involved in the pathogenesis of AAA, although specific roles of these molecules should further be sought. © 2012 Aiji Sakamoto et al
This white paper is a part of the National Academy of Sciences Astrobiology Science Strategy for the Search for Life in the Universe report assembled by a the world's foremost astrobiology experts, chaired by the University of Toronto's Barbara Sherwood Lollar. Here are links to the report and articles that discuss the paper and the report"http://sites.nationalacademies.org/SSB/CurrentProjects/SSB_180812https://amp.space.com/42086-whats-next-for-astrobiology-at-nasa.htmlhttps://qz.com/1418576/us-scientists-lay-out-plan-to-search-for-life-in-universe/amp/
4fce auroral roar: New aspects pertaining to MF/HF auroral radio emissions observed at ground level
第3回極域科学シンポジウム/第36回極域宙空圏シンポジウム 11月27日(火) 国立極地研究所 2階大会議
Current status of Iceland-Syowa conjugate observation in 2019
The Tenth Symposium on Polar Science/Ordinary sessions: [OS] Space and upper atmospheric sciences, Wed. 4 Dec. / Institute of Statistics and Mathematics (ISM) Seminar room 2 (D304) (3rd floor
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