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排序方式: 共有246条查询结果,搜索用时 15 毫秒
31.
32.
Jian-kang Jiang Xiuli Huang Khalida Shamim Paresma R. Patel Arthur Lee Amy Q. Wang Kimloan Nguyen Gregory Tawa Gregory D. Cuny Paul B. Yu Wei Zheng Xin Xu Philip Sanderson Wenwei Huang 《Bioorganic & medicinal chemistry letters》2018,28(20):3356-3362
The pyrazolo[1,5-a]pyrimidine LDN-193189 is a potent inhibitor of activin receptor-like kinase 2 (ALK2) but is nonselective for highly homologous ALK3 and shows only modest kinome selectivity. Herein, we describe the discovery of a novel series of potent and selective ALK2 inhibitors by replacing the quinolinyl with a 4-(sulfamoyl)naphthyl, yielding ALK2 inhibitors that exhibit not only excellent discrimination versus ALK3 but also high kinome selectivity. In addition, the optimized compound 23 demonstrates good ADME and in vivo pharmacokinetic properties. 相似文献
33.
The genetic differentiation of teak meta-population in India was investigated in relation to geographical and climatic variations employing dominant ISSR markers followed by Bayesian statistical analysis to understand adaptability of the species. The analysis based on 290 teak genotypes representing 29 locations of its natural distribution and 43 ISSR loci exhibited an insignificant structure and low 2.76% LD (≥?0.1 R2 values, p?<?0.001) in teak meta-population. The genetic and geographical variables despite acting independently with each other resulted in three sub-population clusters in the meta-population. The geographical barrier played a significant role in direction/restriction of gene flow. The integration of spatial/climatic variables altered the clustering pattern of the teak meta-population with signature of the adaptation to the temperature and longitudinal gradients that was also verified by the similar adaptation pattern of meta-population towards predicted global climate modeling for year 2050. The findings can help tackle the sustainable management and conservation of the species and its survival quotient in threat of changing climatic conditions. 相似文献
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35.
Distribution of amiloride-sensitive sodium channels in the oral cavity of the hamster 总被引:3,自引:3,他引:0
The distribution of amiloride-sensitive sodium channels (ASSCs) in taste
buds isolated from the oral cavity of hamsters was assessed by patch clamp
recording. In contrast to the case for rats, taste cells from the
fungiform, foliate and vallate papillae and from the soft palate all
contain functional ASSCs. The differential distribution of ASSCs between
the hamster and the rat may be important for understanding the physiology
underlying the differing behavioral responses of these species to sodium
salts.
相似文献
36.
Victor Mukherjee D. Vijayalaksmi Jagadeesh Gulipalli R. Premalatha Shamim A. Sufi Athithan Velan Kotteazeth Srikumar 《Molecular biology reports》2016,43(10):1049-1058
Understanding the influence of ubiquitously present plant steroids on mammalian cell biology is currently of interest. Feedback inhibition of HMGCoA reductase (HMGCR) catalytic activity in the transformation of HMG-CoA to mevalonate is a significant regulatory step in sterol biosynthetic pathway. To assess the role of dietary steroids in this biochemical transformation, the phytosteroid isoform 28-homobrassinolide (28-HB), 90 % pure, obtained from Godrej Agrovet (India) was used to determine its effect on mammalian HMG-CoA reductase. Photometric assay of pure human and select rat tissue HMGCR post 28-HB oral feed, PCR-HMGCR gene expression, and in silico docking of 28-HB and HMGCoA on HMGCR protein template were carried out. Using an oral feed regimen of pure 28-HB, we noted a decrease of 16 % in liver, 17.1 % in kidney and 9.3 % in testicular HMGCR enzyme activity, 25 % in HMGCR gene expression and 44 % in the activity of pure human HMGCR due to this plant oxysterol. In silico docking studies yielded binding metrics for 28-HB-HMGCR lower than for HMGCoA-HMGCR, indicating stronger binding of HMGCR by this ligand. 28-HB exerts differential effects on rat tissue HMGCR, down regulates liver HMGCR gene expression and significantly inhibits HMGCR activity. 相似文献
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38.
Hossein MS Jeong YW Kim S Kim JJ Park SW Jeong CS Hyun SH Hwang WS 《Cloning and stem cells》2008,10(3):403-408
The collection of in vivo matured canine oocytes relies on the accurate prediction of ovulation. The present study was designed to develop a protocol for the recovery of in vivo matured canine oocytes based on once daily measurements of serum progesterone (P(4)) concentrations. Blood samples (2 mL) were collected every day at 0900 h, and P(4) concentrations were analyzed using a DSL-3900 ACTIVE((R)) Progesterone Coated-Tube Radioimmunoassay Kit. The average number of oocytes at the metaphase II (M II) stage was significantly higher at or after 72 h (6.7 to 7.5) compared to 56 h (1.7) following ovulation. The highest numbers of corpora lutea, and therefore the highest numbers of oocytes, were recovered from bitches with initial ovulatory P(4) concentrations ranging from 6.0 to 8.0 ng/ mL (12.2 and 11.4, respectively) compared to from 4.0 to 4.9 ng/ mL (9.6 and 8.8, respectively; p < 0.05). The average number of M II oocytes recovered at 84 h from bitches with initial ovulatory P(4) levels of 5.0 to 5.9 ng/mL (7.7) was higher compared to bitches with P(4) levels of 4.0 to 4.9 ng/ mL (3.5) and 6.0 to 8.0 ng/ mL (4.8; p < 0.05). When oocyte recovery time was adjusted for initial ovulatory P(4) concentration, no significant difference in recovery rates or oocyte quality were observed. In conclusion, once daily measurements of P(4) can be used to predict ovulation in bitches, and oocyte recovery time should be adjusted for initial ovulatory serum P(4) concentrations. 相似文献
39.
Ranjeet R. Kumar Suneha Goswami Mohammad Shamim Kavita Dubey Khushboo Singh Shweta Singh Yugal K. Kala Ravi R.K. Niraj Akshay Sakhrey Gyanendra P. Singh Monendra Grover Bhupinder Singh Gyanendra K. Rai Anil K. Rai Viswanathan Chinnusamy Shelly Praveen 《Functional & integrative genomics》2017,17(6):621-640
40.
Yusuke Suenaga S. M. Rafiqul Islam Jennifer Alagu Yoshiki Kaneko Mamoru Kato Yukichi Tanaka Hidetada Kawana Shamim Hossain Daisuke Matsumoto Mami Yamamoto Wataru Shoji Makiko Itami Tatsuhiro Shibata Yohko Nakamura Miki Ohira Seiki Haraguchi Atsushi Takatori Akira Nakagawara 《PLoS genetics》2014,10(1)
The rearrangement of pre-existing genes has long been thought of as the major mode of new gene generation. Recently, de novo gene birth from non-genic DNA was found to be an alternative mechanism to generate novel protein-coding genes. However, its functional role in human disease remains largely unknown. Here we show that NCYM, a cis-antisense gene of the MYCN oncogene, initially thought to be a large non-coding RNA, encodes a de novo evolved protein regulating the pathogenesis of human cancers, particularly neuroblastoma. The NCYM gene is evolutionally conserved only in the taxonomic group containing humans and chimpanzees. In primary human neuroblastomas, NCYM is 100% co-amplified and co-expressed with MYCN, and NCYM mRNA expression is associated with poor clinical outcome. MYCN directly transactivates both NCYM and MYCN mRNA, whereas NCYM stabilizes MYCN protein by inhibiting the activity of GSK3β, a kinase that promotes MYCN degradation. In contrast to MYCN transgenic mice, neuroblastomas in MYCN/NCYM double transgenic mice were frequently accompanied by distant metastases, behavior reminiscent of human neuroblastomas with MYCN amplification. The NCYM protein also interacts with GSK3β, thereby stabilizing the MYCN protein in the tumors of the MYCN/NCYM double transgenic mice. Thus, these results suggest that GSK3β inhibition by NCYM stabilizes the MYCN protein both in vitro and in vivo. Furthermore, the survival of MYCN transgenic mice bearing neuroblastoma was improved by treatment with NVP-BEZ235, a dual PI3K/mTOR inhibitor shown to destabilize MYCN via GSK3β activation. In contrast, tumors caused in MYCN/NCYM double transgenic mice showed chemo-resistance to the drug. Collectively, our results show that NCYM is the first de novo evolved protein known to act as an oncopromoting factor in human cancer, and suggest that de novo evolved proteins may functionally characterize human disease. 相似文献