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101.
Deepak Bhasin Jonathan P. Etter Somsundaram N. Chettiar May Mok Pui-Kai Li 《Bioorganic & medicinal chemistry letters》2013,23(24):6864-6867
STAT3 is constitutively active in a large variety of cancers. The search for STAT3 inhibitors led to the discoveries of LLLs 3 and 12, which are substituted anthraquinones. LLL12 is an extremely potent compound that exhibits high levels of antiproliferative activity. Herein the synthesis and evaluation of compounds containing either an anthraquinone or 1,4-naphthoquinone moiety are reported. Analogs were evaluated in several cancer cell lines. Interestingly, it was found that the anthraquinones did not follow the same trends as the 1,4-naphthoquinones in regards to potency. LLL12, which contains a sulfonamide at position 1, was found to be the most potent of the anthraquinones. In contrast, the methyl ketone and methyl ester derivatives (LLLs 3.1 and 5.1) were found to be the most potent of the 1,4-naphthoquinones. Selected 1,4-naphthoquinones were also evaluated in the STAT3 fluorescence polarization assay in order to evaluate their abilities to bind to the STAT3 SH2 domain. They were found to have similar affinities, and their activities suggest that STAT3 is one of their molecular targets. 相似文献
102.
103.
BJARNI K. KRISTJÁNSSON HILMAR J. MALMQUIST FINNUR INGIMARSSON THÓRÓLFUR ANTONSSON SIGURÐUR S. SNORRASON SKÚLI SKÚLASON 《Biological journal of the Linnean Society. Linnean Society of London》2011,103(4):761-771
The common occurrence of parallel phenotypic patterns suggests that a strong relationship exists between ecological dynamics and micro‐evolution. Comparative studies from a large number of populations under varying sets of ecological drivers could contribute to a better understanding of this relationship. We used data on morphology of arctic charr (Salvelinus alpinus) and ecological factors from 35 Icelandic lakes to test the hypothesis that morphological patterns among monomorphic charr populations from different lakes are related to interlake variation in ecological characteristics. There is extensive phenotypic diversity among populations of Icelandic charr, and populations are easily distinguished based on overall body morphology. The results obtained in the present study showed that the morphological diversity of charr was related to large‐scale diversity in lake ecology. Variation in charr morphology was related to water origin (e.g. spring fed versus run‐off), bedrock age, and fish community structure. The present study shows how various ecological factors can shape the biological diversity that we observe. © 2011 The Linnean Society of London, Biological Journal of the Linnean Society, 2011, 103 , 761–771. 相似文献
104.
KLARA BJÖRG JAKOBSDÓTTIR þÓRA DÖGG JÖRUNDSDÓTTIR SIGURLAUG SKÍRNISDÓTTIR SIGRÍÐUR HJÖRLEIFSDÓTTIR GUÐMUNDUR Ó. HREGGVIÐSSON ANNA KRISTÍN DANÍELSDÓTTIR CHRISTOPHE PAMPOULIE 《Molecular ecology resources》2006,6(2):337-339
Nine out of 22 microsatellite primers tested were successfully amplified on three samples of cod Gadus morhua L. (two contemporary and one archived otolith samples). All loci were polymorphic (5–23 alleles/locus). The average observed heterozygosity across loci and samples was 0.625, ranging from 0.294 to 0.895 at each locus. All loci were under Hardy–Weinberg equilibrium, except PGmo56 that showed significant excess of heterozygotes in all studied samples. The isolated loci were suitable for degraded DNA and therefore useful for conducting a long‐term temporal study with DNA obtained from archived otoliths of cod. 相似文献
105.
Zhai G Teumer A Stolk L Perry JR Vandenput L Coviello AD Koster A Bell JT Bhasin S Eriksson J Eriksson A Ernst F Ferrucci L Frayling TM Glass D Grundberg E Haring R Hedman AK Hofman A Kiel DP Kroemer HK Liu Y Lunetta KL Maggio M Lorentzon M Mangino M Melzer D Miljkovic I;MuTHER Consortium Nica A Penninx BW Vasan RS Rivadeneira F Small KS Soranzo N Uitterlinden AG Völzke H Wilson SG Xi L Zhuang WV Harris TB Murabito JM Ohlsson C Murray A de Jong FH Spector TD Wallaschofski H 《PLoS genetics》2011,7(4):e1002025
Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands--yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15 × 10(-36)), SULT2A1 (rs2637125; p = 2.61 × 10(-19)), ARPC1A (rs740160; p = 1.56 × 10(-16)), TRIM4 (rs17277546; p = 4.50 × 10(-11)), BMF (rs7181230; p = 5.44 × 10(-11)), HHEX (rs2497306; p = 4.64 × 10(-9)), BCL2L11 (rs6738028; p = 1.72 × 10(-8)), and CYP2C9 (rs2185570; p = 2.29 × 10(-8)). These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS. 相似文献
106.
Chaston JM Suen G Tucker SL Andersen AW Bhasin A Bode E Bode HB Brachmann AO Cowles CE Cowles KN Darby C de Léon L Drace K Du Z Givaudan A Herbert Tran EE Jewell KA Knack JJ Krasomil-Osterfeld KC Kukor R Lanois A Latreille P Leimgruber NK Lipke CM Liu R Lu X Martens EC Marri PR Médigue C Menard ML Miller NM Morales-Soto N Norton S Ogier JC Orchard SS Park D Park Y Qurollo BA Sugar DR Richards GR Rouy Z Slominski B Slominski K Snyder H Tjaden BC van der Hoeven R Welch RD Wheeler C Xiang B 《PloS one》2011,6(11):e27909
Members of the genus Xenorhabdus are entomopathogenic bacteria that associate with nematodes. The nematode-bacteria pair infects and kills insects, with both partners contributing to insect pathogenesis and the bacteria providing nutrition to the nematode from available insect-derived nutrients. The nematode provides the bacteria with protection from predators, access to nutrients, and a mechanism of dispersal. Members of the bacterial genus Photorhabdus also associate with nematodes to kill insects, and both genera of bacteria provide similar services to their different nematode hosts through unique physiological and metabolic mechanisms. We posited that these differences would be reflected in their respective genomes. To test this, we sequenced to completion the genomes of Xenorhabdus nematophila ATCC 19061 and Xenorhabdus bovienii SS-2004. As expected, both Xenorhabdus genomes encode many anti-insecticidal compounds, commensurate with their entomopathogenic lifestyle. Despite the similarities in lifestyle between Xenorhabdus and Photorhabdus bacteria, a comparative analysis of the Xenorhabdus, Photorhabdus luminescens, and P. asymbiotica genomes suggests genomic divergence. These findings indicate that evolutionary changes shaped by symbiotic interactions can follow different routes to achieve similar end points. 相似文献
107.
Banerjee C Ulloor J Dillon EL Dahodwala Q Franklin B Storer T Sebastiani P Sheffield-Moore M Urban RJ Bhasin S Montano M 《Immunity & ageing : I & A》2011,8(1):5-7
Objective
With the progressive aging of the human population, there is an inexorable decline in muscle mass, strength and function. Anabolic supplementation with testosterone has been shown to effectively restore muscle mass in both young and elderly men. In this study, we were interested in identifying serum factors that change with age in two distinct age groups of healthy men, and whether these factors were affected by testosterone supplementation.Methods
We measured the protein levels of a number of serum biomarkers using a combination of banked serum samples from older men (60 to 75 years) and younger men (ages 18 to 35), as well as new serum specimens obtained through collaboration. We compared baseline levels of all biomarkers between young and older men. In addition, we evaluated potential changes in these biomarker levels in association with testosterone dose (low dose defined as 125 mg per week or below compared to high dose defined as 300 mg per week or above) in our banked specimens.Results
We identified nine serum biomarkers that differed between the young and older subjects. These age-associated biomarkers included: insulin-like growth factor (IGF1), N-terminal propeptide of type III collagen (PIIINP), monokine induced by gamma interferon (MIG), epithelial-derived neutrophil-activating peptide 78 (ENA78), interleukin 7 (IL-7), p40 subunit of interleukin 12 (IL-12p40), macrophage inflammatory protein 1β (MIP-1β), platelet derived growth factor β (PDGFβ) and interferon-inducible protein 10 (IP-10). We further observed testosterone dose-associated changes in some but not all age related markers: IGF1, PIIINP, leptin, MIG and ENA78. Gains in lean mass were confirmed by dual energy X-ray absorptiometry (DEXA).Conclusions
Results from this study suggest that there are potential phenotypic biomarkers in serum that can be associated with healthy aging and that some but not all of these biomarkers reflect gains in muscle mass upon testosterone administration. 相似文献108.
109.
Dinesh Bansal Pragya Bhasin O.P. Yadav Anita Punia 《Journal of Genetic Engineering and Biotechnology》2012,10(1):39-45
Lepidium sativum L. is a fast growing edible herb which belongs to family Brassicaceae. The seeds of L. sativum are aperient, diuretic, tonic, demulcent, carminative, galatogogue and emmenagogue. They have been used in the treatment of bacterial and fungal infections, as an aperient and also possess antibacterial and antifungal properties. The seeds of this plant possess rapid bone fracture healing ability. Despite of its diverse medicinal properties no molecular data for diversity analysis is available till date. During this study random amplified polymorphic DNA (RAPD) markers were used to detect genetic variations of L. sativum. Initially 50 decamer primers were screened, out of which only 32 primers showed reproducible fragments with easily recordable bands. A total of 414 reproducible and clear bands were distinguished across the selected primers and statistical analysis showed 361 polymorphic bands and 53 monomorphic bands. Cluster analysis of the genotypes based on UPGMA divided the 18 genotypes into two main clusters, with first cluster having only HCS-20 genotype of L. sativum and other having rest of all 17 genotypes. The dendrogram based on similarity matrix revealed 23–66% genetic relatedness among 18 genotypes. The results of the present study can be used for molecular breeding and improvement of L. sativum for various desired traits through hybridization in future. 相似文献
110.
目的减少Finn CA于1984年首次报道的小鼠月经模型的观察时间点,以期为月经生理学研究提供一种较廉价且易操作的月经模型。方法应用成年雌性去势C57BL/6小鼠,给予续贯性激素处理,最末次激素处理后4~6h,实验组小鼠宫腔内注射花生油以诱导子宫内膜蜕膜化反应,对照组小鼠给予同样激素处理但无宫腔油剂注射。分别于油剂处理后31~35h(T3组)、56~70h(T4组)处死小鼠,称量子宫湿重,制作H&E组织切片,运用图像分析软件CAST2,计算全子宫横截面积(TUA)与子宫内膜横截面积(EA)。结果H&E染色子宫组织切片示在单纯雌激素作用下宫内膜呈单层立方上皮,核浆比较高,内膜基质疏松;雌孕激素联合处理后,分泌细胞易见,腺腔内可见分泌物。激素撤退后实验组T3观察到子宫内膜剥离,T4组示子宫内膜修复。对照组子宫内膜始终完整。子宫湿重在激素撤退后,实验组下降较慢。激素撤退后实验组T3的TUA继续上升而EA则维持原水平,T4组TUA与EA均明显下降。结论此模型在子宫内膜剥落期和早期修复期组织学特征与人类子宫内膜有一定的相似性。 相似文献