灵芝三萜类化合物抗癌作用机制的研究进展

<正>INTRODUCTION Ganoderma lucidum(Fr.)P.Karst.,a species of higher fungus called"Lingzhi"in Chinaor"Reishi"and"Mannendake"in Japan,has been used in the traditional Chinese medicine(TCM)for prevention and treatment     

Heterotrimeric G proteins: new tricks for an old dog

Heterotrimeric G proteins are well known for their function in signal transduction downstream of seven transmembrane receptors. More recently, however, genetic analysis in C. elegans and in Drosophila has revealed a second, essential function of these molecules in positioning the mitotic spindle and attaching microtubules to the cell cortex. Five new publications in Cell (Afshar et al., 2004; Du and Macara, 2004 [this issue of Cell]; Hess et al., 2004), Developmental Cell (Martin-McCaffrey et al., 2004), and Current Biology (Couwenbergs et al., 2004) show that this function is conserved in vertebrates and--like the classical pathway--involves cycling of G proteins between GDP and GTP bound conformations.     

CAR: three new models for a problem child

By comparison with its older and better-behaved cousins in the nuclear receptor superfamily, CAR (NR1I3) has always been an oddball. Three new crystal structures recently described in Molecular Cell reveal the molecular basis for some of its bad habits (Xu et al., 2004; Suino et al., 2004; Shan et al., 2004).     

When pouring water on the fire makes it burn brighter

By comparison with its older and better-behaved cousins in the nuclear receptor superfamily, CAR (NR1I3) has always been an oddball. Three new crystal structures recently described in Molecular Cell reveal the molecular basis for some of its bad habits (Xu et al., 2004; Suino et al., 2004; Shan et al., 2004).     

For catch bonds, it all hinges on the interdomain region

Tensile mechanical force was long assumed to increase the detachment rates of biological adhesive bonds (Bell, 1978). However, in the last few years, several receptor-ligand pairs were shown to form "catch bonds," whose lifetimes are enhanced by moderate amounts of force. These include the bacterial adhesive protein FimH binding to its ligand mannose (Thomas et al., 2002; Thomas et al., 2006), blood cell adhesion proteins P- and L-selectin binding to sialyl Lewis X (sLe(X))-containing ligands (Marshall et al., 2003; Evans et al., 2004; Sarangapani et al., 2004), and the myosin-actin motor protein interaction (Guo and Guilford, 2006). The structural mechanism behind this counterintuitive force-enhanced catch bond behavior is of great interest.     

Silence of the rings

Two recent papers (de Napoles et al., 2004 and Wang et al., 2004) have linked monoubiquitylation of histone H2A to the activities of E3 ubiquitin ligases that reside in Polycomb-group repressor complexes.     

Lack of an Additive Effect between the Deletions of Klf5 and Nkx3-1 in Mouse Prostatic Tumorigenesis

Prostate cancer is one of the most common malignancies.The development and progression of prostate cancer are driven by a series of genetic and epigenetic events including gene amplification that activates oncogenes and chromosomal deletion that inactivates tumor suppressor genes.Whereas gene amplification occurs in human prostate cancer,gene deletion is more common,and a large number of chromosomal regions have been identified to have frequent deletion in prostate cancer,suggesting that tumor suppressor inactivation is more common than oncogene activation in prostatic carcinogenesis (Knuutila et al.,1998,1999;Dong,2001).Among the most frequently deleted chromosomal regions in prostate cancer,target genes such as NKX3-1 from 8p21,PTENfrom 10q23 andATBF1 from 16q22 have been identified by different approaches (He et al.,1997;Li et al.,1997;Sun et al.,2005),and deletion of these genes in mouse prostates has been demonstrated to induce and/or promote prostatic carcinogenesis.For example,knockout of Nkx3-1 in mice induces hyperplasia and dysplasia (Bhatia-Gaur et al.,1999;Abdulkadir et al.,2002) and promotes prostatic tumorigenesis (Abate-Shen et al.,2003),while knockout of Pten alone causes prostatic neoplasia (Wang et al.,2003).Therefore,gene deletion plays a causal role in prostatic carcinogenesis (Dong,2001).     

ATP-dependent chromatin remodeling complex SWI/SNF in cardiogenesis and cardiac progenitor cell development

The recent identification of cardiac progenitor cells (CPCs) provides a new paradigm for studying and treating heart disease.To realize the full potential of CPCs for therapeutic purposes,it is essenti...     

The First Knockout Mouse Model of Retinoblastoma

The retinoblastoma susceptibility gene (RB1) was the first tumor suppressor gene identified in humans (Friend, et al., 1986) and the first tumor suppressor gene knocked out by targeted deletion in mice (Jacks, et al., Clarke, et al., Lee, et al., 1992). Children with a germline mutation in one of their RB1 alleles are likely to experience bilateral multifocal retinoblastoma; however, mice with a similar disruption of Rb1 do not develop retinoblastoma. The absence of a knock-out mouse model of retinoblastoma has slowed the progress toward developing new therapies and identifying secondary genetic lesions that occur after disruption of the Rb signaling pathway. Several advances have been made, over the past several years, in our understanding of the regulation of proliferation during retinal development (Zhang, et al., 2004; Dyer J, 2004; Dyer, Cepko, 2001) and we have built upon these earlier studies to generate the first nonchimeric knock-out mouse model of retinoblastoma. These mice are being used as a preclinical model to test new therapies for retinoblastoma and to elucidate the downstream genetic events that occur after inactivation of Rb1 or its related family members.     

十种海洋寡毛类纤毛虫:形态学及分类学修订

利用活体观察和蛋白银染色技术对近年来采自青岛、大亚湾、湛江沿岸水体的10个海洋寡毛类纤毛虫种:侧扁急游虫Strombidium apolatum Wilbert & Song,2005、具头急游虫Strombidium capitatum (Leegaard,1995) Kahl,1932、广东急游虫Strombidium guangdongense Liu,et al.,2016、拟卡氏急游虫Strombidiumparacalkinsi (Lei,et al.,1999) Agatha,2004、拟楔尾急游虫Strombidium parastylifer Song,et al.,2009、铃木急游虫Strombidium suzukii Song,et al.,2009、束腰旋游虫Spirostrombidium cinctum (Kahl,1932) Petz,et al.,1995、杨科夫平游虫Parallelostrombidium jankowski (Song,et al.,2009) Song,et al.,2018、卡尔平游虫Parallelostrombidium kahli (Song,et al.,2009) Song,et al.,2018、最小拟盗虫Strombidinopsis minima (Gruber,1884) Song & Bradbury,1998的形态学开展了比较研究,补充和厘定了有关形态特征、纤毛图式以及性状变异等分类学新信息。     

The ways of PARP

Two papers in this issue of Cell describe two roles of poly(ADP-ribose) polymerase (PARP) in modulating chromatin structure: as a structural component replacing linker histone (Kim et al., 2004) and as a constituent of a corepressor complex poised to dismiss repression upon receipt of an activating signal (Ju et al., 2004).     

Liver function parameters in HIV/HCV co-infected patients treated with amprenavir and ritonavir and correlation with plasma levels

Acute liver toxicity is a frequent adverse event that occurs during antiretroviral therapy and was observed in 6-30% of the patients on treatment, especially in presence of HCV coinfection (Cooper et al., 2002, Maida et al., 2006, Sulkowski et al., 2000). A correlation between HCV-associated liver-fibrosis severity and the risk of HAART associated hepatoxicity has been demonstrated (Aranzabal et al., 2005, Sulkowski et al., 2004). This high liver toxicity rate might be due to increased drug exposure in patients with liver disease (Veronese et al., 2000). It has been reported that patients with chronic hepatitis C show significantly reduced CPY3A4 and CYP2D6 activity in comparison with healthy volunteers (Becquemont et al., 2002). The aim of this study was to evaluate the liver function tests in HCV-co-infected patients treated with fos-amprenavir and ritonavir.     

A novel role for Greatwall kinase in recovery from DNA damage

Activation of the DNA damage response (DDR) is critical for genomic integrity and tumor suppression. The occurrence of DNA damage quickly evokes the DDR through ATM/ATR-dependent signal transduction, which promotes DNA repair and activates the checkpoint to halt cell cycle progression (Halazonetis et al., 2008; Motoyama and Naka, 2004; Zhou and Elledge, 2000). The "turn off" process of the DDR upon satisfaction of DNA repair, also known as "checkpoint recovery", involves deactivation of DDR elements, but the mechanism is poorly understood. Greatwall kinase (Gwl) has been identified as a key element in the G2/M transition (Archambault et al., 2007; Jackson, 2006; Zhao et al., 2008; Yu et al., 2004; Yu et al., 2006; Zhao et al., 2006) and helps maintain M phase through inhibition of PP2A/B55δ (Burgess et al., 2010; Castilho et al., 2009; Goldberg, 2010; Lorca et al., 2010; Vigneron et al., 2009), the principal phosphatase for Cdk-phosphorylated substrates. Here we show that Gwl also promotes recovery from DNA damage and is itself directly inhibited by the DNA damage response (DDR). In Xenopus egg extracts, immunodepletion of Gwl increased the DDR to damaged DNA, whereas addition of wild type, but not kinase dead Gwl, inhibited the DDR. The removal of damaged DNA from egg extracts leads to recovery from checkpoint arrest and entry into mitosis, a process impaired by Gwl depletion and enhanced by Gwl over-expression. Moreover, activation of Cdk1 after the removal of damaged DNA is regulated by Gwl. Collectively, these results defines Gwl as a new regulator of the DDR, which plays an important role in recovery from DNA     

ROS-Mediated ABA Signaling

In plants, reactive oxygen species (ROS) are short-lived molecules produced through various cellular mechanisms in response to biotic and abiotic stimuli. ROS function as second messengers for hormone signaling, development, oxygen deprivation, programmed cell death, and plant–pathogen interactions. Recent research on ROS-mediated responses has produced stimulating findings such as the specific sources of ROS production, molecular elements that work in ROS-mediated signaling and homeostasis, and a ROS-regulated gene network (Neill et al., Curr Opin Plant Biol 5:388–395, 2002a; Apel and Hirt, Annu Rev Plant Biol 55:373–399, 2004; Mittler et al., Trends Plant Sci 9:490–498, 2004; Mori and Schroeder, Plant Physiol 135:702–708, 2004; Kwak et al., Plant Physiol 141:323–329, 2006; Torres et al., Plant Physiol 141:373–378, 2006; Miller et al., Physiol Plant 133:481–489, 2008). In this review, we highlight new discoveries in ROS-mediated abscisic acid (ABA) signaling. Drs. Daeshik Cho and June M. Kwak are the corresponding authors for this paper.     

Studies on oligosaccharyl transferase in yeast

In yeast, OT consists of nine different subunits, all of which contain one or more predicted transmembrane segments. In yeast, five of these proteins are encoded by essential genes, Swp1p, Wbp1p, Ost2p, Ost1p and Stt3p. Four others are not essential Ost3p, Ost4p, Ost5p, Ost6p. All yeast OT subunits have been cloned and sequenced (Kelleher et al., 1992; 2003; Kelleher & Gilmore, 1997; Kumar et al., 1994; 1995; Breuer & Bause, 1995) and the structure of one of them, Ost4p, has been solved by NMR (Zubkov et al., 2004). Very recently, the preliminary crystal structure of the lumenal domain of an archaeal Stt3p homolog has been reported (Mayumi et al., 2007). Homologs of all OT subunits have been identified in higher eukaryotic organisms (Kelleher et al., 1992; 2003; Kumar et al., 1994; Kelleher & Gilmore, 1997).     

华南特马豆克期笔石地层分带及全球对比

特马豆克阶是奥陶系底部第一个阶,笔石是特马豆克阶高分辨率地层划分与对比的重要化石类群。江南斜坡带是我国早奥陶世特马豆克期漂浮笔石分异度和丰度最高的相区之一,位于该区的湖南益阳南坝剖面,发育有完整的上特马豆克阶笔石地层,特马豆克阶-弗洛阶界线附近地层连续,上特马豆克阶笔石地层研究已取得较大进展,但下特马豆克阶地层缺乏系统研究。近年来,通过对该剖面笔石标本的不间断采集,新识别出下特马豆克阶笔石带Rhabdinopora flabelliformis parabola带。到目前为止,湖南益阳南坝剖面特马豆克阶可以识别出5个笔石带,自下而上依次为:Rhabdinopora flabelliformis parabola带、Adelograptus tenellus带、Aorograptus victoriae带、Araneograptus murrayi带以及Hunnegraptus copiosus带。基于目前已识别出的笔石带,参考国内外同期笔石地层资料,本文详细讨论华南特马豆克期笔石带序列,并与国内外同期地层进行精确对比。     

The E295K DNA polymerase beta gastric cancer-associated variant interferes with base excision repair and induces cellular transformation

Approximately 30% of human tumors examined for mutations in polymerase beta (pol beta) appear to express pol beta variant proteins (D. Starcevic, S. Dalal, and J. B. Sweasy, Cell Cycle 3:998-1001, 2004). Many of these variants result from a single amino acid substitution. We have previously shown that the K289M and I260M colon and prostate cancer variants, respectively, induce cellular transformation most likely due to sequence-specific mutator activity (S. Dalal et al., Biochemistry 44:15664-15673, 2005; T. Lang et al., Proc. Natl. Acad. Sci. USA 101:6074-6079, 2004; J. B. Sweasy et al., Proc. Natl. Acad. Sci. USA 102:14350-14355, 2005). In the work described here, we show that the E295K gastric carcinoma pol beta variant acts in a dominant-negative manner by interfering with base excision repair. This leads to an increase in sister chromatid exchanges. Expression of the E295K variant also induces cellular transformation. Our data suggest that unfilled gaps are channeled into a homology-directed repair pathway that could lead to genomic instability. The results indicate that base excision repair is critical for maintaining genome stability and could therefore be a tumor suppressor mechanism.