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排序方式: 共有363条查询结果,搜索用时 156 毫秒
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2.
Meghann Ryan Peter Kochunov Laura M. Rowland Braxton D. Mitchell S. Andrea Wijtenburg Els Fieremans Jelle Veraart Dmitry S. Novikov Xiaoming Du Bhim Adhikari Feven Fisseha Heather Bruce Joshua Chiappelli Hemalatha Sampath Seth Ament Jeffrey O'Connell Alan R. Shuldiner L. Elliot Hong 《Obesity (Silver Spring, Md.)》2017,25(11):1876-1880
3.
Birong Zhang James R. Kiefer Robert A. Blake Jae H. Chang Steven Hartman Ellen Rei Ingalla Tracy Kleinheinz Vidhi Mody Michelle Nannini Daniel F. Ortwine Yingqing Ran Amy Sambrone Deepak Sampath Maia Vinogradova Yu Zhong Jerome C. Nwachukwu Kendall W. Nettles Tommy Lai Jun Liang 《Bioorganic & medicinal chemistry letters》2019,29(7):905-911
Despite tremendous progress made in the understanding of the ERα signaling pathway and the approval of many therapeutic agents, ER+?breast cancer continues to be a leading cause of cancer death in women. We set out to discover compounds with a dual mechanism of action in which they not only compete with estradiol for binding with ERα, but also can induce the degradation of the ERα protein itself. We were attracted to the constrained chromenes containing a tetracyclic benzopyranobenzoxepine scaffold, which were reported as potent selective estrogen receptor modulators (SERMs). Incorporation of a fluoromethyl azetidine side chain yielded highly potent and efficacious selective estrogen receptor degraders (SERDs), such as 16aa and surprisingly, also its enantiomeric pair 16ab. Co-crystal structures of the enantiomeric pair 16aa and 16ab in complex with ERα revealed default (mimics the A-D rings of endogenous ligand estradiol) and core-flipped binding modes, rationalizing the equivalent potency observed for these enantiomers in the ERα degradation and MCF-7 anti-proliferation assays. 相似文献
4.
Partially Redundant Enhancers Cooperatively Maintain Mammalian Pomc Expression Above a Critical Functional Threshold 总被引:1,自引:0,他引:1
5.
Little is known about the effect of exercise training on the expression of adiponectin receptor genes in peripheral blood mononuclear cells (PBMCs). In this study, we investigated the effects of aerobic training on the expression of AdipoR1 and AidpoR2 mRNAs in PBMCs, whole body insulin sensitivity, and circulating adiponectins in men. Thirty young men were randomly assigned to either a control (n=15) or an exercise (n=15) group. Subjects assigned to the exercise group underwent a 12-week jogging and/or running programme on a motor-driven treadmill at an intensity of 60%-75% of the age-based maximum heart rate with duration of 40 minutes per session and a frequency of 5 days per week. Two-way mixed ANOVA with repeated measures was used to test any significant time-by-group interaction effects for the measured variables at p=0.05. We found significant time-by-group interaction effects for waist circumference (p=0.001), VO2max (p<0.001), fasting insulin (p=0.016), homeostasis model assessment for insulin resistance (HOMA-IR) (p=0.010), area under the curve (AUC) for insulin response during the 75-g oral glucose tolerance test (p=0.002), high-molecular weight (HMW) adiponectin (p=0.016), and the PBMC mRNA levels of AdipoR1 (p<0.001) and AdipoR2 (p=0.001). The exercise group had significantly increased mRNA levels of AdipoR1 and AdipoR2 in PBMCs, along with increased whole body insulin sensitivity and HMW adiponectin, decreased waist circumference, and increased VO2max compared with the control group. In summary, the current findings suggest that exercise training modulates the expression of AdipoR1 and AdipoR2 mRNAs in PBMCs, implying that manipulation of the expression of these genes could be a potential surrogate for lifestyle intervention-mediated improvements of whole body insulin sensitivity and glucose homeostasis. 相似文献
6.
Parvinder Pal Singh Naveed Ahmed Qazi Syed Shafi D. Mahendhar Reddy Abid H. Banday P. Bhaskar Reddy K.A. Suri B.D. Gupta N.K. Satti Basant P. Wakhloo H.M. Sampath Kumar G.N. Qazi 《Journal of Molecular Catalysis .B, Enzymatic》2009,56(1):46-54
Lipase catalyzed regio-selective acylation of five iridoid glycosides viz., picroside I&II, catalpol, agnuside and negundoside in the presence of various acyl donors such as vinyl acetate and p-nitrophenyl alkanoates was studied. The regio-selectivity of enzymatic acylation and yields were found to vary amongst different substrates. Monoacylated products were isolated with all the substrates under scrutiny indicating high regio-selective nature of such transformations. A series of acyl esters of picroside-I, picroside-II, catalpol, agnuside and negundoside have been synthesized by this enzymatic trans-esterification methodology. 相似文献
7.
Sampath Amutha Krishnan Kathiravan Sima Singer Liana Jashi Ilan Shomer Benjamin Steinitz Victor Gaba 《In vitro cellular & developmental biology. Plant》2009,45(6):758-768
Regeneration of new shoots in plant tissue culture is often associated with appearance of abnormally shaped leaves. We used
the adventitious shoot regeneration response induced by decapitation (removal of all preformed shoot apical meristems, leaving
a single cotyledon) of greenhouse-grown cotyledon-stage seedlings to test the hypothesis that such abnormal leaf formation
is a normal regeneration progression following wounding and is not conditioned by tissue culture. To understand why shoot
regeneration starts with defective organogenesis, the regeneration response was characterized by morphology and scanning electron
and light microscopy in decapitated cotyledon-stage Cucurbita pepo seedlings. Several leaf primordia were observed to regenerate prior to differentiation of a de novo shoot apical meristem from dividing cells on the wound surface. Early regenerating primordia have a greatly distorted structure
with dramatically altered dorsoventrality. Aberrant leaf morphogenesis in C. pepo gradually disappears as leaves eventually originate from a de novo adventitious shoot apical meristem, recovering normal phyllotaxis. Similarly, following comparable decapitation of seedlings
from a number of families (Chenopodiaceae, Compositae, Convolvulaceae, Cucurbitaceae, Cruciferae, Fabaceae, Malvaceae, Papaveraceae,
and Solanaceae) of several dicotyledonous clades (Ranunculales, Caryophyllales, Asterids, and Rosids), stems are regenerated
bearing abnormal leaves; the normal leaf shape is gradually recovered. Some of the transient leaf developmental defects observed
are similar to responses to mutations in leaf shape or shoot apical meristem function. Many species temporarily express this
leaf development pathway, which is manifest in exceptional circumstances such as during recovery from excision of all preformed
shoot meristems of a seedling. 相似文献
8.
The objectives of the study were to propose a two-stage microfluidization combined with an ultrafiltration (UF) treatment for chitosan mass production and the manipulation of molecular weight and its distribution. The proposed methods are based on the degradation rate and rate constant of various process variables studied. Results obtained were that the rate constants were faster during the earlier reaction period, were higher for those operating at a higher pressure, were better for using concurrent UF treatment to remove small degraded fragments, and the degradation rate constants were faster for 30 °C solutions than that for 50 or 0 °C. A two-stage microfluidization process is proposed. The first stage constitutes of the highest possible concentration solution with concurrent UF treatment at 50 °C, and recycled 5 times. The second stage consists of the highest possible concentration of solutions with concurrent UF treatment at 30 °C, and recycled 5 times. 相似文献
9.
Resolving the polymorphism-in-probe problem is critical for correct interpretation of expression QTL studies 总被引:1,自引:0,他引:1
Adaikalavan Ramasamy Daniah Trabzuni J. Raphael Gibbs Allissa Dillman Dena G. Hernandez Sampath Arepalli Robert Walker Colin Smith Gigaloluwa Peter Ilori Andrey A. Shabalin Yun Li Andrew B. Singleton Mark R. Cookson for NABEC John Hardy for UKBEC Mina Ryten Michael E. Weale 《Nucleic acids research》2013,41(7):e88
10.
Nalini Santanam MingQing Song Rong Rong Ana A. Murphy Sampath Parthasarathy 《Free radical research》2013,47(12):1315-1321
Endometriosis affects younger women of childbearing age. Atherosclerosis is considered as a disease of the old and increases with the ageing process. Both diseases are characterized by the increased presence of activated macrophages and associated increases in growth promoting activity and the production of inflammatory cytokines. In this review, we propose that oxidative stress and the presence of forms of oxidized low-density lipoprotein (LDL) might contribute to both Atherosclerosis and Endometriosis. 相似文献