76 research outputs found
Imaging Electronic Excitation of NO by Ultrafast Laser Tunneling Ionization
Tunneling-ionization imaging of photoexcitation of NO has been demonstrated by using few-cycle near-infrared intense laser pulses (8 fs, 800 nm, 1.1×1014 W/cm2). The ion image of N+ fragment ions produced by dissociative ionization of NO in the ground state, NO (X2Π,2π)→NO++e−→N++O+e−, exhibits a characteristic momentum distribution peaked at 45° with respect to the laser polarization direction. On the other hand, a broad distribution centered at ∼0° appears when the A2Σ+ (3sσ) excited state is prepared as the initial state by deep-UV photoexcitation. The observed angular distributions are in good agreement with the corresponding theoretical tunneling ionization yields, showing that the fragment anisotropy reflects changes of the highest-occupied molecular orbital by photoexcitation.journal articl
A Report on the Workshop of Teaching Portfolio in 2011
大阪府立大学工業高等専門学校は,2009年1月に全国の高等教育機関で初めて学内でティーチング・ポ ートフォリオ作成ワークショップを開催した.その後,2010年1月には第2回,8月には第3回,2011年 1月には第4回となるティーチング・ポートフォリオ作成ワークショップを開催し,現在常勤教員76名中 39名(51%)がティーチング・ポートフォリオを作成している.本稿では,2011年度に開催したワークショ ップの概要について説明した後,ワークショップ参加者の感想を報告する.departmental bulletin pape
Advantages of Tandem LC−MS for the Rapid Assessment of Tissue-Specific Metabolic Complexity Using a Pentafluorophenylpropyl Stationary Phase
In this study, a tandem LC-MS (Waters Xevo TQ) MRM-based MS method was developed for rapid, broad profiling of hydrophilic metabolites from biological samples, in either positive or negative ion modes without the need for an ion pairing reagent, using a reversed-phase pentafluorophenylpropyl (PFPP) column. The developed method was successfully applied to analyze various biological samples from C57BL/6 mice, including urine, duodenum, liver, plasma, kidney, heart, and skeletal muscle. As result, a total 112 of hydrophilic metabolites were detected within 8 min of running time to obtain a metabolite profile of the biological samples. The analysis of this number of hydrophilic metabolites is significantly faster than previous studies. Classification separation for metabolites from different tissues was globally analyzed by PCA, PLS-DA and HCA biostatistical methods. Overall, most of the hydrophilic metabolites were found to have a “fingerprint” characteristic of tissue dependency. In general, a higher level of most metabolites was found in urine, duodenum, and kidney. Altogether, these results suggest that this method has potential application for targeted metabolomic analyzes of hydrophilic metabolites in a wide ranges of biological samples
Optimization of Antitumor Modulators of Pre-mRNA Splicing
The
spliceosome regulates pre-mRNA splicing, which is a critical
process in normal mammalian cells. Recently, recurrent mutations in
numerous spliceosomal proteins have been associated with a number
of cancers. Previously, natural product antitumor agents have been
shown to interact with one of the proteins that is subject to recurrent
mutations (SF3B1). We report the optimization of a class of tumor-selective
spliceosome modulators that demonstrate significant in vivo antitumor
activity. This optimization culminated in the discovery of sudemycin
D6, which shows potent cytotoxic activity in the melanoma line SK-MEL-2
(IC<sub>50</sub> = 39 nM) and other tumor cell lines, including JeKo-1
(IC<sub>50</sub> = 22 nM), HeLa (IC<sub>50</sub> = 50 nM), and SK-N-AS
(IC<sub>50</sub> = 81 nM). We also report improved processes for the
synthesis of these compounds. Our work supports the idea that sudemycin
D6 is worthy of further investigation as a novel preclinical anticancer
agent with application in the treatment of numerous human cancers
Pre-mRNA Splicing-Modulatory Pharmacophores: The Total Synthesis of Herboxidiene, a Pladienolide–Herboxidiene Hybrid Analog and Related Derivatives
Herboxidiene
is a natural product that has previously been shown
to exhibit antitumor activity by targeting the spliceosome. This activity
makes herboxidiene a valuable starting point for the development of
anticancer drugs. Here, we report an improved enantioselective synthesis
of herboxidiene and the first report of its biologically active totally
synthetic analog: 6-norherboxidiene. The synthesis of the tetrahydropyran
moiety utilizes the novel application of inverse electron-demand Diels–Alder
chemistry and the Ferrier-type rearrangement as key steps. We report,
for the first time, cytotoxicity IC<sub>50</sub>s for synthetic herboxidiene
and analogs in human tumor cell lines. We have also demonstrated that
synthetic herboxidiene and its analogs can potently modulate the alternate
splicing of MDM-2 pre-mRNA
High Diversity of Rabies Viruses Associated with Insectivorous Bats in Argentina: Presence of Several Independent Enzootics
<div><h3>Background</h3><p>Rabies is a fatal infection of the central nervous system primarily transmitted by rabid animal bites. Rabies virus (RABV) circulates through two different epidemiological cycles: terrestrial and aerial, where dogs, foxes or skunks and bats, respectively, act as the most relevant reservoirs and/or vectors. It is widely accepted that insectivorous bats are not important vectors of RABV in Argentina despite the great diversity of bat species and the extensive Argentinean territory.</p> <h3>Methods</h3><p>We studied the positivity rate of RABV detection in different areas of the country, and the antigenic and genetic diversity of 99 rabies virus (RABV) strains obtained from 14 species of insectivorous bats collected in Argentina between 1991 and 2008.</p> <h3>Results</h3><p>Based on the analysis of bats received for RABV analysis by the National Rabies system of surveillance, the positivity rate of RABV in insectivorous bats ranged from 3.1 to 5.4%, depending on the geographic location. The findings were distributed among an extensive area of the Argentinean territory. The 99 strains of insectivorous bat-related sequences were divided into six distinct lineages associated with <em>Tadarida brasiliensis</em>, <em>Myotis spp</em>, <em>Eptesicus spp</em>, <em>Histiotus montanus</em>, <em>Lasiurus blosseviilli</em> and <em>Lasiurus cinereus</em>. Comparison with RABV sequences obtained from insectivorous bats of the Americas revealed co-circulation of similar genetic variants in several countries. Finally, inter-species transmission, mostly related with <em>Lasiurus</em> species, was demonstrated in 11.8% of the samples.</p> <h3>Conclusions</h3><p>This study demonstrates the presence of several independent enzootics of rabies in insectivorous bats of Argentina. This information is relevant to identify potential areas at risk for human and animal infection.</p> </div
Phylogenetic tree of insectivorous bats rabies from Americas.
<p>Tree was generated of N-J method (Kimura two-parameter model) of a portion of the N gene coding sequence (264 nt). Bold font indicates RABV samples from Argentinean bats analyzed in this study. The geographical origins of comparator group sequences are included in the name of each sample. Sample numbers appeared as GenBank database.</p
Consensus amino acid sequences of bat rabies viruses from Argentina.
<p>The last 88 amino acids encoded by the rabies virus nucleoprotein gene at the carboxy terminus are shown.</p
Assessment of glycerol-driven hepatic glucose production in fasted wild type (WT, black circles or black bars) and FynKO (open circles or open bars) mice.
<p>(A) intraperitoneal glycerol tolerance test (n=5 animals for each strain), (B) glucose production from [U<sup>13</sup>C] glycerol. *<i>p<0</i>.<i>05</i>. n=4 WT, n=4 FynKO. </p
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