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| 1 | The molecular cell death machinery in the simple cnidarian Hydra includes an expanded caspase family and pro-and anti-apoptotic Bcl-2 proteins显示文摘新鲜的水息肉水螅属于门 Cnidaria,它在 bilaterians 的外观前从后生动物的系分叉。以便在 metazoans 理解 apoptosis 的进化,我们开始阐明了在这个模型有机体的分子的细胞死亡机械。基于 EST 和整个水螅染色体集会,我们识别了 15 caspases。我们证明一个人在 apoptosis 期间被激活,四与 N 终端 DED,卡片或 DD 领域有开始者 caspases 的特征,二在 vitro 经历 autoprocessing。另外,我们描述七 Bcl-2-like 和二象 Bak 一样蛋白质。为大多数 Bcl-2 家庭蛋白质,我们观察了 mitochondrial 本地化。当在哺乳动物的房间表示了时,象 HyBak 一样 1 和 2 强烈导致的 apoptosis。禁止的 apoptosis 与显示出特别强壮的保护的效果的 HyBcl-2-like 4 在哺乳动物的房间由 camptothecin 劝诱了的六个 Bcl-2 家庭成员。这蛋白质也与象 HyBak 一样交往了 1 在酵母二混血儿的试金。在它的 BH3 领域的保存白氨酸的变化两个都与象 HyBak 一样废除了相互作用 1 并且 anti-apoptotic 效果。而且,我们 BH-3-only 描述新奇水螅蛋白质。这些之一与 Bcl-2-like 4 交往了并且在哺乳动物的房间导致了 apoptosis。我们的数据显示为房间死亡规定的一个复杂网络的进化在多细胞的组织的最早、最简单的水平产生了,它在此展出了一复杂性实质地高级比在 protostome 模型有机体 Caenorhabditis 和果蝇。 | Margherita Lasi Barbara Pauly Nikola Schmidt Mihai Cikala Beate Stiening Tina Kaisbauer Gerhardt Zenner Tanja Popp Anita Wagner Regina T Knapp Andreas H Huber Michaela Grunert Johannes Soding Charles N David Angelika Bottger | 2010 | Cell Research2010，20，7： | 1 |
| 2 | Efficacy and safety of obinutuzumab for the first-line treatment of follicular lymphoma:a subgroup analysis of Chinese patients enrolled in the phase III GALLIUM study显示文摘Backgrounds:GALLIUM is a global phase Ⅲ study that demonstrated significant improvements in progression-free survival(PFS)for obinutuzumab plus chemotherapy(G-chemo)vs.rituximab plus chemotherapy(R-chemo)in previously untreated patients with follicular lymphoma(FL).This study aimed to report the results of a subgroup of patients in China.Methods:Patients were randomized to G-chemo or R-chemo.Responders received maintenance therapy for 2 years or until disease progression.The primary endpoint was investigator(INV)-assessed PFS.Secondary endpoints included the overall response rate(ORR)and complete response rate(CRR)at the end of induction chemotherapy,overall survival(OS),and safety.Results:Overall,58 patients with FL were randomized to the G-chemo(n=25)and R-chemo arms(n=33).The INV-assessed PFS rate at 3 years was 81.8%in the G-chemo arm,vs.70.2%in the R-chemo arm(hazard ratio 0.35;95%confidence interval:0.09-1.34;P=0.1120).The INV-assessed CRRs(without positron emission tomography[PET])in these arms were 24.0%and 21.2%,respectively,whereas the ORRs were 80.0%and 90.9%,respectively.INV-assessed CRR-PET was 52.6%in the G-chemo,vs.60.9%in the R-chemo.Median OS was not reached in either arm.Grade 3 to 5 adverse events were more frequent in the R-chemo arm(97.0%vs.88.0%).Conclusions:The results of this subgroup analysis were consistent with those of the global population,and they suggest that G-chemo has a positive benefit-risk profile in patients from China with FL.Trial registration:ClinicalTrials.gov,No.NCT01332968. | Xiaonan Hong Yuqin Song Yuankai Shi Qingyuan Zhang Wei Guo Gang Wu Junmin Li Jifeng Feng Anastasiia Kinkolykh Andrea Knapp Tongyu Lin | 2022 | Chinese Medical Journal2022，，4： | 1 |
| 3 | The interleukin-10 family of cytokines显示文摘 | Helmut Fickenscher Simon H?r Heide Küpers Andrea Knappe Sabine Wittmann Heinrich Sticht | 2002 | Trends in Immunology2002，，2： | 1 |
| 4 | False positive head-up tilt:显示文摘 | Fabio M Leonelli Ke Wang Joyce M Evans Abhijit R Patwardhan Michael G Ziegler Andrea Natale Charles S Kim Kathleen Rajikovich Charles F Knapp | 2000 | Journal of the American College of Cardiology2000，，： | 1 |
| 5 | Chemistry-led investigations into the mode of action of NAMPT activators,resulting in the discovery of non-pyridyl class NAMPT activators显示文摘The cofactor nicotinamide adenine dinucleotide(NAD+)plays a key role in a wide range of physiological processes and maintaining or enhancing NAD+levels is an established approach to enhancing healthy aging.Recently,several classes of nicotinamide phosphoribosyl transferase(NAMPT)activators have been shown to increase NAD+levels in vitro and in vivo and to demonstrate beneficial effects in animal models.The best validated of these compounds are structurally related to known urea-type NAMPT inhibitors,however the basis for the switch from inhibitory activity to activation is not well understood.Here we report an evaluation of the structure activity relationships of NAMPT activators by designing,synthesising and testing compounds from other NAMPT ligand chemotypes and mimetics of putative phosphoribosylated adducts of known activators.The results of these studies led us to hypothesise that these activators act via a through-water interaction in the NAMPT active site,resulting in the design of the first known urea-class NAMPT activator that does not utilise a pyridine-like warhead,which shows similar or greater activity as a NAMPT activator in biochemical and cellular assays relative to known analogues. | Siyuan Tang Miguel Garzon Sanz Oliver Smith Andreas Krämer Daniel Egbase Paul W.Caton Stefan Knapp Sam Butterworth | 2023 | Acta Pharmaceutica Sinica B2023，13，2： | 0 |
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