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41.
Kim TS Hague AB Lee TI Lian B Tegley CM Wang X Burgess TL Qian YX Ross S Tagari P Lin CH Mayeda C Dao J Jordan S Mohr C Cheetham J Viswanadhan V Tasker AS 《Bioorganic & medicinal chemistry letters》2004,14(1):87-90
A series of (4-piperidinylphenyl)aminoethyl amides based on dipeptide anilines were synthesized and tested against cathepsin K, cathepsin L and cathepsin B. These new non-covalent inhibitors exhibited single-digit nM inhibition of the cysteine proteases. Compounds 3 and 7 demonstrated potency in both mouse and human osteoclast resorption assays. 相似文献
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Fournier Thomas Fèvre Jordan Carcaillet Frédérique Carcaillet Christopher 《Plant Ecology》2020,221(7):559-576
Plant Ecology - Changes in community diversity and dynamics after fires in Mediterranean ecosystems are rarely investigated more than a few years after the fire even though pronounced changes can... 相似文献
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This paper examines the history of sex ratio theory and the effects of multiple variables on individual and population sex ratios. It also provides examples where plants have been used to test major predictions of sex ratio theory. Then, using over 200 studies from the literature, dioecious plant species are categorized based on their life form, pollination agent, fruit dispersal agent, and sex ratio. A loglinear analysis is used to look at possible correlations between the sex ratio of a population and other life history characteristics. These data are used to examine the predictions made by De Jong et al. (Journal of Evolutionary Biology 15:7, 2002), that relative pollen and seed dispersal distances can be used to predict sex ratio bias. Despite the limited sample size, strong relationships are still observed. 93% of insect pollinated dioecious vines that have biotically dispersed fruit have male-biased sex ratios. Conversely, 61% of shrubs that are wind pollinated and have abiotic fruit dispersal have female-biased sex ratios. 相似文献
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Jennifer H. E. Baker Alastair H. Kyle Kirsten L. Bartels Stephen P. Methot Erin J. Flanagan Andrew Balbirnie Jordan D. Cran Andrew I. Minchinton 《PloS one》2013,8(10)
Many cancer research efforts focus on exploiting genetic-level features that may be targeted for therapy. Tissue-level features of the tumour microenvironment also represent useful therapeutic targets. Here we investigate the presence of low oxygen tension and sensitivity to NOS inhibition of tumour vasculature as potential tumour-specific features that may be targeted by hypoxic cytotoxins, a class of therapeutics currently under investigation. We have previously demonstrated that tirapazamine (TPZ) mediates central vascular dysfunction in tumours. TPZ is a hypoxic cytotoxin that is also a competitive inhibitor of NOS. Here we further investigated the vascular-targeting activity of TPZ by combining it with NOS inhibitor L-NNA, or with low oxygen content gas breathing. Tumours were analyzed via multiplex immunohistochemical staining that revealed irreversible loss of perfusion and enhanced tumour cell death when TPZ was combined with either low oxygen or a NOS inhibitor. Tumour growth rate was reduced by TPZ + NOS inhibition, and tumours previously resistant to TPZ-mediated vascular dysfunction were sensitized by low oxygen breathing. Additional mapping analysis suggests that tumours with reduced vascular-associated stroma may have greater sensitivity to these effects. These results indicate that poorly oxygenated tumour vessels, also being abnormally organized and with inadequate smooth muscle, may be successfully targeted for significant anti-cancer effects by inhibition of NOS and hypoxia-activated prodrug toxicity. This strategy illustrates a novel use of hypoxia-activated cytotoxic prodrugs as vascular targeting agents, and also represents a novel mechanism for targeting tumour vessels. 相似文献
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Michael B. Krawinkel Gudrun B. Keding Ursula Chavez‐Zander Irmgard Jordan Tzige‐Yohannes Habte 《当今生物学》2008,38(5):312-318
Nutrition of the world's population in the 21st century often appears as an unsolved problem. The challenges are bigger than an increase in agricultural production. From a brief review on the history of food production diverse aspects of the development become evident: innovations with their beneficial and non‐beneficial aspects, e.g. the, green revolution' increasing the rice yields on one hand and the number of landless people on the other. Great differences can be found in agricultural productivity: the yields of the presently area under the plough can be increased. Climate change impacts on the framework of agricultural production with losses and gains of arable land. The challenges of global nutrition cannot be met by innovations in plant breeding and cultivation alone. Socioeconomic factors, education, and health become increasingly important. 相似文献
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SiuShing Wong Zachary M Wilmott Saroj Saurya Ines AlvarezRodrigo Felix Y Zhou KwaiYin Chau Alain Goriely Jordan W Raff 《The EMBO journal》2022,41(11)
Mitotic centrosomes are formed when centrioles start to recruit large amounts of pericentriolar material (PCM) around themselves in preparation for mitosis. This centrosome “maturation” requires the centrioles and also Polo/PLK1 protein kinase. The PCM comprises several hundred proteins and, in Drosophila, Polo cooperates with the conserved centrosome proteins Spd‐2/CEP192 and Cnn/CDK5RAP2 to assemble a PCM scaffold around the mother centriole that then recruits other PCM client proteins. We show here that in Drosophila syncytial blastoderm embryos, centrosomal Polo levels rise and fall during the assembly process—peaking, and then starting to decline, even as levels of the PCM scaffold continue to rise and plateau. Experiments and mathematical modelling indicate that a centriolar pulse of Polo activity, potentially generated by the interaction between Polo and its centriole receptor Ana1 (CEP295 in humans), could explain these unexpected scaffold assembly dynamics. We propose that centrioles generate a local pulse of Polo activity prior to mitotic entry to initiate centrosome maturation, explaining why centrioles and Polo/PLK1 are normally essential for this process. 相似文献