An investigation of the interaction between isoniazid and the contraceptive steroid norethindrone in vivo

Summary Isonicotinic acid hydrazide (isoniazid) was shown to react readily with 17-ethinyl-17-hydroxyestr-4-en-3-one (norethindrone) to form the isonicotinyl hydrazone of the steroid under conditions likely to exist in the stomach. The hydrazone was detected in guinea-pig, but not rat, plasma following its oral administration. Rat liver tissue metabolized the compound more rapidly than guinea-pig liver in vitro which probably accounts for the failure to detect the hydrazone in rat plasma.     

仓鼠妊娠期瘦素分泌及其调节机制

对妊娠期瘦素的分泌及其调节机制进行探讨. 将100只3月龄雌性金黄仓鼠分成16组, 每组6~7只, 每天采血样用于测定其妊娠期的瘦素分泌. 实验结果表明, 瘦素于妊娠第9天开始显著升高, 于妊娠第12天达到高峰. 为验证不同生殖阶段的血清是否对瘦素分泌有不同影响, 将不同生殖阶段抽提与未抽提类固醇激素的血清加入培养液中进行培养, 发现动情期及妊娠期的血清均可刺激体外培养的脂肪细胞瘦素分泌, 动情期抽提与未抽提类固醇激素的血清对脂肪细胞瘦素分泌的刺激作用没有显著差异(P > 0.05). 与动情期血清相比, 妊娠中后期未抽提类固醇激素的血清显著刺激脂肪细胞瘦素分泌(P < 0.01). 但妊娠中后期的血清在抽提类固醇激素后对瘦素分泌的刺激作用显著下降, 与动情期的血清对瘦素分泌的刺激作用已没有显著差异(P > 0.05). 妊娠不同阶段未抽提类固醇激素的血清对瘦素分泌的刺激作用有很大差异, 妊娠第15天的血清对瘦素分泌的刺激作用显著高于妊娠第8天(P < 0.0001)和妊娠第12天(P < 0.001)的血清. 体外研究进一步表明, 肾上腺皮质素、孕酮以及胰岛素均能刺激瘦素分泌, 而雌激素却能抑制体外瘦素分泌. 研究结果提示, 妊娠期血液类固醇激素水平的上升是引起妊娠期瘦素峰出现的重要因素.     

Growth ages of ferromanganese crusts from the western and central Pacific： Comparison between nannofossil analysis and ^10Be dating

Based on results of nannofossil analysis and 10Be dating in ferromanganese crusts M1-1 and A1-1 (no nannofossils were found in it),from the western and central Pacific respectively,it is found that the crust growth ages from nannofossil biostrati-graphy agree well with those based on 10Be isotope analysis. Both crusts have three growth layers,and the oldest layer was deposited in Miocene at about 12.80 Ma. The maximum,minimum,and average growth rates of crust A1-1 (from the central Pacific) are 8.11,1.92 and 3.47 mm/Ma,and those of crust M1-1 (from the western Pacific) are 2.93,0.47,and 0.94 mm/Ma.     

Regulation of IgA production by naturally occurring TNF/iNOS-producing dendritic cells

Immunoglobulin-A has an irreplaceable role in the mucosal defence against infectious microbes. In human and mouse, IgA-producing plasma cells comprise approximately 20% of total plasma cells of peripheral lymphoid tissues, whereas more than 80% of plasma cells produce IgA in mucosa-associated lymphoid tissues (MALT). One of the most biologically important and long-standing questions in immunology is why this 'biased' IgA synthesis takes place in the MALT but not other lymphoid organs. Here we show that IgA class-switch recombination (CSR) is impaired in inducible-nitric-oxide-synthase-deficient (iNOS-/-; gene also called Nos2) mice. iNOS regulates the T-cell-dependent IgA CSR through expression of transforming growth factor-beta receptor, and the T-cell-independent IgA CSR through production of a proliferation-inducing ligand (APRIL, also called Tnfsf13) and a B-cell-activating factor of the tumour necrosis factor (TNF) family (BAFF, also called Tnfsf13b). Notably, iNOS is preferentially expressed in MALT dendritic cells in response to the recognition of commensal bacteria by toll-like receptor. Furthermore, adoptive transfer of iNOS+ dendritic cells rescues IgA production in iNOS-/- mice. Further analysis revealed that the MALT dendritic cells are a TNF-alpha/iNOS-producing dendritic-cell subset, originally identified in mice infected with Listeria monocytogenes. The presence of a naturally occurring TNF-alpha/iNOS-producing dendritic-cell subset may explain the predominance of IgA production in the MALT, critical for gut homeostasis.     

CDK-dependent phosphorylation of Sld2 and Sld3 initiates DNA replication in budding yeast

In eukaryotic cells, cyclin-dependent kinases (CDKs) have an important involvement at various points in the cell cycle. At the onset of S phase, active CDK is essential for chromosomal DNA replication, although its precise role is unknown. In budding yeast (Saccharomyces cerevisiae), the replication protein Sld2 (ref. 2) is an essential CDK substrate, but its phospho-mimetic form (Sld2-11D) alone neither affects cell growth nor promotes DNA replication in the absence of CDK activity, suggesting that other essential CDK substrates promote DNA replication. Here we show that both an allele of CDC45 (JET1) and high-copy DPB11, in combination with Sld2-11D, separately confer CDK-independent DNA replication. Although Cdc45 is not an essential CDK substrate, CDK-dependent phosphorylation of Sld3, which associates with Cdc45 (ref. 5), is essential and generates a binding site for Dpb11. Both the JET1 mutation and high-copy DPB11 by-pass the requirement for Sld3 phosphorylation in DNA replication. Because phosphorylated Sld2 binds to the carboxy-terminal pair of BRCT domains in Dpb11 (ref. 4), we propose that Dpb11 connects phosphorylated Sld2 and Sld3 to facilitate interactions between replication proteins, such as Cdc45 and GINS. Our results demonstrate that CDKs regulate interactions between BRCT-domain-containing replication proteins and other phosphorylated proteins for the initiation of chromosomal DNA replication; similar regulation may take place in higher eukaryotes.     

The medaka draft genome and insights into vertebrate genome evolution

Teleosts comprise more than half of all vertebrate species and have adapted to a variety of marine and freshwater habitats. Their genome evolution and diversification are important subjects for the understanding of vertebrate evolution. Although draft genome sequences of two pufferfishes have been published, analysis of more fish genomes is desirable. Here we report a high-quality draft genome sequence of a small egg-laying freshwater teleost, medaka (Oryzias latipes). Medaka is native to East Asia and an excellent model system for a wide range of biology, including ecotoxicology, carcinogenesis, sex determination and developmental genetics. In the assembled medaka genome (700 megabases), which is less than half of the zebrafish genome, we predicted 20,141 genes, including approximately 2,900 new genes, using 5'-end serial analysis of gene expression tag information. We found single nucleotide polymorphisms (SNPs) at an average rate of 3.42% between the two inbred strains derived from two regional populations; this is the highest SNP rate seen in any vertebrate species. Analyses based on the dense SNP information show a strict genetic separation of 4 million years (Myr) between the two populations, and suggest that differential selective pressures acted on specific gene categories. Four-way comparisons with the human, pufferfish (Tetraodon), zebrafish and medaka genomes revealed that eight major interchromosomal rearrangements took place in a remarkably short period of approximately 50 Myr after the whole-genome duplication event in the teleost ancestor and afterwards, intriguingly, the medaka genome preserved its ancestral karyotype for more than 300 Myr.     

A high-resolution environmental change record since 19 cal ka BP in Pumoyum Co,southern Tibet

A 380-cm-long sediment core was acquired from the deep water area of Pumoyum Co, southern Tibet. Twenty-five plant residue samples were selected, and organic carbon stable isotopes were obtained using the AMS ¹⁴C chronological method. The ¹⁴C age and carbon reservoir effect were calibrated with surface sedimentation rate measurements using ²¹⁰Pb dating. Results showed that the core sediment deposited over 19 cal ka BP. Based on a multi-proxy analysis of TOC and IC contents, grain size and pollen assemblage data, the palaeoclimatic evolution of Pumoyum Co was reconstructed since the last glacial. Pumoyum Co was a shallow lake prior to 16.2 cal ka BP; although the glacier around the lake began to melt due to increasing temperatures, climate was still cold and dry. In the interval of 16.2–11.8 cal ka BP, the sedimentary environment fluctuated drastically and frequently. Two cold-events occurred at 14.2 and 11.8 cal ka BP, and these may correspond to the Older Dryas and the Younger Dryas events, respectively. After 11.8 cal ka BP, Pumoyun Co developed into the deep lake as it is now. The lake water temperature was relatively lower at that time because of influx of cold water from glacial meltwater entering the lake. As a result, the multi-proxy indicators showed no sign of warm conditions. Comparisons between the sedimentary record of Pumoyum Co with that of other lakes of the same age in southern Tibet indicate a warmer climate following the last deglaciation influenced the southeastern Tibetan Plateau. These results imply that the southwest Asian monsoon gradually became stronger since the deglaciation during its expansion to the inner plateau. The glacial-supplied water of the lake responded sensitively to cold-events. The entire southern Tibet region was dominantly influenced climatically by the southwest Asian monsoon during the Holocene.     

Performance of Ion-gel Actuator Containing Ionic Liquids

1 Results Electroactive polymers (EAPs) driven by transducing electric energy into mechanical energy have been the subjects of recent interest[1].“Ionic liquids“,consisting entirely of cation and anion,have characteristic features such as negligible volatility,non-flammability,thermal and chemical stability,and high ionic conductivity.We proposed an EAP actuator utilizing ion-gels[2-3],which consist of ionic liquids and polymers,sandwiching with two carbon material sheets as shown in Fig.1.This electrol...