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891.
Ghosh AK Schiltz G Perali RS Leshchenko S Kay S Walters DE Koh Y Maeda K Mitsuya H 《Bioorganic & medicinal chemistry letters》2006,16(7):1869-1873
A series of novel oxyindole-derived HIV-1 protease inhibitors were designed and synthesized based upon our X-ray crystal structure of inhibitor 2 (TMC-114) bound to HIV-1 protease. The effects of substituents, spirocyclic rings, and ring sizes have been investigated. A number of inhibitors exhibited low nanomolar inhibitory potencies against HIV protease. 相似文献
892.
Androstenediol (Adiol, androst-5-ene-3beta,17beta-diol) is suspected of being an endogenous proliferation agent of prostate cancer (PCa) even after androgen deprivation therapy (ADT). A liquid chromatography-electron capture atmospheric pressure chemical ionization-mass spectrometric (LC-ECAPCI-MS) method for the determination of Adiol in prostatic tissue was developed and validated for evaluating the influence of ADT on the prostatic Adiol level. After derivatization of Adiol with 4-nitrobenzoyl chloride, the detection response of the derivative was increased 150 times more than that of intact Adiol. The LC-MS method was specific and reliable for the measurement of a trace amount of Adiol in 30 mg of tissue. The clinical study using the developed method showed that the prostatic Adiol level was not changed by ADT. That is, the prostatic Adiol levels of PCa patients with ADT (n = 12), benign prostate hypertrophy patients without ADT (n = 8) and bladder cancer patients (without prostatic disease) (n = 6) were 0.83 +/- 0.28, 0.62 +/- 0.31 and 0.71 +/- 0.28 ng g(-1)tissue, respectively, and there was no significant difference between these groups. 相似文献
893.
Maeng JY Won YJ Piao R Cho YI Jiang W Chin JH Koh HJ 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2006,112(8):1429-1433
Cleistogamy is the self-pollination within closed spikelets and is expected to be a useful genetic tool for prevention of possible gene transfer in transgenic crops, for maintenance of genetic purity in autogamous crops, and for increased tolerance to biotic and abiotic stresses. Mapping of the gene ld(t), which is responsible for lack of lodicules inside spikelets and causes cleistogamy, was carried out using F2 and F3 populations derived from a cleistogamous (CL) mutant CL-SNU × Milyang 23 cross. A number of STS markers along chromosomes were developed and bulked segregant analysis was adopted for preliminary mapping. The results showed that the ld(t) was located at the end region of chromosome 1L, flanked by S01178b (an STS marker developed for the locus at 178 cM based on the rice genetic map reported by Japanese Rice Genome Project) at 0.8 cM and co-segregated with S01181a and S01181b (an STS marker developed for the locus at 181 cM). 相似文献
894.
895.
S Han S Hong D Lee MH Lee JS Choi MJ Koh W Sun H Kim HW Lee 《Biochemical and biophysical research communications》2012,425(4):880-885
Contextual fear memory processing requires coordinated changes in neuronal activity and molecular networks within brain. A large number of fear memory-related genes, however, still remain to be identified. Synaptotagmin 13 (Syt13), an atypical member of synaptotagmin family, is highly expressed in brain, but its functional roles within brain have not yet been clarified. Here, we report that the expression of Syt13 mRNA in adult mouse brain was altered following contextual fear conditioning. C57BL/6 mice were exposed to a novel context and stimulated by strong electrical footshock according to a contextual fear conditioning protocol. After 24h, the mice were re-exposed to the context without electrical footshock for the retrieval of contextual fear memory. To investigate the relationship between Syt13 and contextual fear memory, we carried out in situ hybridization and analyzed gene expression patterns for Syt13 at four groups representing temporal changes in brain activity during contextual fear memory formation. Contextual fear conditioning test induced significant changes in mRNA levels for Syt13 within various brain regions, including lateral amygdala, somatosensory cortex, piriform cortex, habenula, thalamus, and hypothalamus, during both acquisition and retrieval sessions. Our data suggest that Syt13 may be involved in the process of contextual fear memory. 相似文献
896.
Koh H Kim H Kim MJ Park J Lee HJ Chung J 《The Journal of biological chemistry》2012,287(16):12750-12758
PTEN-induced kinase 1 (PINK1), which is associated with early onset Parkinson disease, encodes a serine-threonine kinase that is critical for maintaining mitochondrial function. Moreover, another Parkinson disease-linked gene, parkin, functions downstream of PINK1 in protecting mitochondria and dopaminergic (DA) neuron. In our fly genetic screening, knockdown of Sir2 blocked PINK1 overexpression-induced phenotypes. Consistently, ectopic expression of Sir2 successfully rescued mitochondrial defects in PINK1 null mutants, but unexpectedly, failed in parkin mutants. In further genetic analyses, deletion of FOXO nullified the Sir2-induced mitochondrial restoration in PINK1 null mutants. Moreover, overexpression of FOXO or its downstream target gene such as SOD2 or Thor markedly ameliorated PINK1 loss-of-function defects, suggesting that FOXO mediates the mitochondrial protecting signal induced by Sir2. Consistent with its mitochondria-protecting role, Sir2 expression prevented the DA neuron loss of PINK1 null mutants in a FOXO-dependent manner. Loss of Sir2 or FOXO induced DA neuron degeneration, which is very similar to that of PINK1 null mutants. Furthermore, PINK1 deletion had no deleterious effect on the DA neuron loss in Sir2 or FOXO mutants, supporting the idea that Sir2, FOXO, and PINK1 protect DA neuron in a common pathway. Overall, these results strongly support the role of Sir2 and FOXO in preventing mitochondrial dysfunction and DA neuron loss, further suggesting that Sir2 and FOXO function downstream of PINK1 and independently of Parkin. 相似文献
897.
Shunsuke Imai Masanori Osawa Kenichiro Mita Shou Toyonaga Asako Machiyama Takumi Ueda Koh Takeuchi Shigetoshi Oiki Ichio Shimada 《The Journal of biological chemistry》2012,287(47):39634-39641
KcsA is a tetrameric K+ channel that is activated by acidic pH. Under open conditions of the helix bundle crossing, the selectivity filter undergoes an equilibrium between permeable and impermeable conformations. Here we report that the population of the permeable conformation (pperm) positively correlates with the tetrameric stability and that the population in reconstituted high density lipoprotein, where KcsA is surrounded by the lipid bilayer, is lower than that in detergent micelles, indicating that dynamic properties of KcsA are different in these two media. Perturbation of the membrane environment by the addition of 1–3% 2,2,2-trifluoroethanol increases pperm and the open probability, revealed by NMR and single-channel recording analyses. These results demonstrate that KcsA inactivation is determined not only by the protein itself but also by the surrounding membrane environments. 相似文献
898.
899.
Outer Membrane Vesicles Derived from Escherichia coli Induce Systemic Inflammatory Response Syndrome
Kyong-Su Park Kyoung-Ho Choi You-Sun Kim Bok Sil Hong Oh Youn Kim Ji Hyun Kim Chang Min Yoon Gou-Young Koh Yoon-Keun Kim Yong Song Gho 《PloS one》2010,5(6)
Sepsis, characterized by a systemic inflammatory state that is usually related to Gram-negative bacterial infection, is a leading cause of death worldwide. Although the annual incidence of sepsis is still rising, the exact cause of Gram-negative bacteria-associated sepsis is not clear. Outer membrane vesicles (OMVs), constitutively secreted from Gram-negative bacteria, are nano-sized spherical bilayered proteolipids. Using a mouse model, we showed that intraperitoneal injection of OMVs derived from intestinal Escherichia coli induced lethality. Furthermore, OMVs induced host responses which resemble a clinically relevant condition like sepsis that was characterized by piloerection, eye exudates, hypothermia, tachypnea, leukopenia, disseminated intravascular coagulation, dysfunction of the lungs, hypotension, and systemic induction of tumor necrosis factor-α and interleukin-6. Our study revealed a previously unidentified causative microbial signal in the pathogenesis of sepsis, suggesting OMVs as a new therapeutic target to prevent and/or treat severe sepsis caused by Gram-negative bacterial infection. 相似文献
900.
Styrkarsdottir U Halldorsson BV Gudbjartsson DF Tang NL Koh JM Xiao SM Kwok TC Kim GS Chan JC Cherny S Lee SH Kwok A Ho S Gretarsdottir S Kostic JP Palsson ST Sigurdsson G Sham PC Kim BJ Kung AW Kim SY Woo J Leung PC Kong A Thorsteinsdottir U Stefansson K 《PloS one》2010,5(10):e13217
Most genome-wide association (GWA) studies have focused on populations of European ancestry with limited assessment of the influence of the sequence variants on populations of other ethnicities. To determine whether markers that we have recently shown to associate with Bone Mineral Density (BMD) in Europeans also associate with BMD in East-Asians we analysed 50 markers from 23 genomic loci in samples from Korea (n = 1,397) and two Chinese Hong Kong sample sets (n = 3,869 and n = 785). Through this effort we identified fourteen loci that associated with BMD in East-Asian samples using a false discovery rate (FDR) of 0.05; 1p36 (ZBTB40, P = 4.3×10−9), 1p31 (GPR177, P = 0.00012), 3p22 (CTNNB1, P = 0.00013), 4q22 (MEPE, P = 0.0026), 5q14 (MEF2C, P = 1.3×10−5), 6q25 (ESR1, P = 0.0011), 7p14 (STARD3NL, P = 0.00025), 7q21 (FLJ42280, P = 0.00017), 8q24 (TNFRSF11B, P = 3.4×10−5), 11p15 (SOX6, P = 0.00033), 11q13 (LRP5, P = 0.0033), 13q14 (TNFSF11, P = 7.5×10−5), 16q24 (FOXL1, P = 0.0010) and 17q21 (SOST, P = 0.015). Our study marks an early effort towards the challenge of cataloguing bone density variants shared by many ethnicities by testing BMD variants that have been established in Europeans, in East-Asians. 相似文献