Yos9p: a sweet-toothed bouncer of the secretory pathway

In this issue of Molecular Cell, Bhamidipati et al., (2005) and Kim et al., (2005), and Szathmary et al. (2005), and demonstrate that Yos9p selectively binds to aberrant glycoproteins in the endoplasmic reticulum (ER) and targets them for destruction through the ER-associated protein degradation pathway.     

ROS: really involved in oxygen sensing

The role of reactive oxygen species (ROS) in the cellular response to cellular oxygen sensing has been controversial. Three papers in this issue of Cell Metabolism (Brunelle et al., Guzy et al., 2005; Mansfield et al., 2005) used genetic tools to establish that ROS produced by mitochondria are required for the normal induction of HIF (hypoxia-inducible factor), which is a master regulator of oxygen-sensitive gene expression, by low oxygen.     

GCN2 whets the appetite for amino acids

In response to amino acid starvation, the kinase GCN2 in yeast activates amino acid biosynthesis. Two recent studies (Maurin et al., 2005; Hao et al., 2005) reveal that GCN2 in the brain of mice restricts intake of diets lacking essential amino acids.     

The D box asserts itself

New findings (Burton et al., 2005; Kraft et al., 2005) demonstrate the direct recognition of D and KEN boxes, short sequence elements in substrates of the anaphase-promoting complex/cyclosome (APC/C), by APC/C coactivators and indicate a special role for the D box in the assembly of catalytically active APC/C.     

Connecting mitochondria and innate immunity

Viral infection results in the activation of multiple signaling pathways, but how these pathways are coordinated remains a mystery. Two studies, one published in this issue of Cell (Seth et al., 2005) and the other in Molecular Cell (Xu et al., 2005), identify a new intracellular signaling protein that is required for activating type I interferon expression in response to viral infection. In addition,Seth et al. (2005) show that the function of this protein, which they call MAVS, requires that it be localized to the mitochondria. This observation establishes an unexpected link between innate immunity and an organelle with evolutionary origins in aerobic bacteria.     

Regulation of Akt/PKB Ser473 phosphorylation

For years the Akt/PKB research field has been in turmoil, trying to understand how the activating phosphorylation of Akt/PKB at Ser473 is regulated. In the past month, papers in a recent issue of Molecular Cell (Gao et al., 2005) and in Science (Sarbassov et al., 2005) may have identified the phosphatase and kinase acting on this residue.     

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。     

Scube activity is necessary for Hedgehog signal transduction in vivo

The Hedgehog (HH) signaling pathway is a central regulator of embryonic development, controlling the pattern and proliferation of a wide variety of organs. Previous studies have implicated the secreted protein, Scube2, in HH signal transduction in the zebrafish embryo (Hollway et al., 2006; Kawakami et al., 2005; Woods and Talbot, 2005) although the nature of the molecular function of Scube2 in this process has remained undefined. This analysis has been compounded by the fact that removal of Scube2 activity in the zebrafish embryo leads to only subtle defects in HH signal transduction in vivo (Barresi et al., 2000; Hollway et al., 2006; Ochi and Westerfield, 2007; van Eeden et al., 1996; Wolff et al., 2003). Here we present the discovery of two additional scube genes in zebrafish, scube1 and scube3, and demonstrate their roles in facilitating HH signal transduction. Knocking down the function of all three scube genes simultaneously phenocopies a complete loss of HH signal transduction in the embryo, revealing that Scube signaling is essential for HH signal transduction in vivo. We further define the molecular role of scube2 in HH signaling.     

Linking epithelial-mesenchymal transition to the well-known polarity protein Par6

Epithelial-mesenchymal transition (EMT) is involved in the formation of the body plan, tissue remodeling, and cancer progression. Two recent reports in Science (Barrios-Rodiles et al., 2005; Ozdamar et al., 2005) have decisively advanced our understanding of EMT. Par6 was identified as a key player in the control of tight junction (TJ) stability. This new study provides further insight into the protein networks involved in topologically regulated control of epithelial cell polarity and plasticity.     

A nose by any other name (should smell as sweetly)

The standard view that the control of mating behavior by pheromones is mediated by the vomeronasal organ, and not by the main olfactory epithelium, has recently been called into question. In this issue of Cell, two independent studies (Boehm et al., 2005; Yoon et al., 2005) examine the inputs from each of these olfactory pathways to a population of neurons that plays a central role in mating behavior.     

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.     

Can 1000 reviews be wrong? Actin, alpha-Catenin, and adherens junctions

Coupling between cell adhesion and the actin cytoskeleton is thought to require a stable link between the cadherin-catenin complex and actin that is mediated by alpha-catenin. In this issue of Cell, the Weis and Nelson groups call this static model into question, showing that alpha-catenin can directly regulate actin dynamics (Drees et al., 2005 and Yamada et al., 2005).     

青岛沿海的自由生聚缩虫属纤毛虫(原生动物,纤毛门,缘毛目)

涉及近年来采集自青岛沿海的自由生聚缩虫属纤毛虫14种,包括9个国内新纪录:交替聚缩虫Zoothamnium alternans Claparède & Lachmann,1859,弗氏聚缩虫Z. foissneri Ji et al.,2005,黑凯聚缩虫 Z. hiketes Precht,1935,海洋聚缩虫 Z. marinum Mereschkowski, 1879,霉聚缩虫Z. mocedo Entz,1884,倪氏聚缩虫 Z. nii Ji et al.,2005,拟树状聚缩虫 Z. pararbuscula Ji et al., 2005,王氏聚缩虫Z.wangi Ji et al., 2005,许氏聚缩虫 Z. xuianum Sun et al.,2005;以及其他5个已知种:群栖聚缩虫Z. commune Kahl, 1933,双缘聚缩虫Z. duplicatum Kahl,1933,巨大聚缩虫Z.maximum Song,1986,羽状聚缩虫Z.plumula Kahl,1933,中国聚缩虫Z.sinense Song,1991.对以上各种作了简要的综合性描述,并给出了种检索表.     

Mechanisms involved in the neurotoxic and cognitive effects of developmental methamphetamine exposure

Methamphetamine exposure in utero leads to a variety of higher‐order cognitive deficits, such as decreased attention and working, and spatial memory impairments in exposed children (Piper et al., 2011; Roussotte et al., 2011; Kiblawi et al., 2011). As with other teratogens, the timing of methamphetamine exposure greatly determines its effects on both neuroanatomical and behavioral outcomes. Methamphetamine exposure in rodents during the third trimester human equivalent period of brain development results in distinct and long‐lasting route‐based and spatial navigation deficits (Williams et al., 2003; Vorhees et al., 2005, 2008, 2009;). Here, we examine the impact of neonatal methamphetamine‐induced neurotoxicity on behavioral outcomes, neurotransmission, receptor changes, plasticity proteins, and DNA damage. Birth Defects Research (Part C) 108:131–141, 2016. © 2016 Wiley Periodicals, Inc.     

Where do we stand now? Mouse early embryo patterning meeting in Freiburg, Germany (2005)

Mechanism underlying mammalian preimplantation development has long been a subject of controversy and the central question has been if any "determinants" play a key role in a manner comparable to the non-mammalian "model" system. During the last decade, this issue has been revived (Pearson, 2002; Rossant and Tam, 2004) by claims that the axes of the mouse blastocyst are anticipated at the egg ("prepatterning model"; Gardner, 1997; Gardner, 2001; Piotrowska et al., 2001; Piotrowska and Zernicka-Goetz, 2001; Zernicka-Goetz, 2005), suggesting that a mechanism comparable to that operating in non-mammals may be at work. However, recent studies by other laboratories do not support these claims ("regulative model"; Alarcon and Marikawa, 2003; Chroscicka et al., 2004; Hiiragi and Solter, 2004; Alarcon and Marikawa, 2005; Louvet-Vallee et al., 2005; Motosugi et al., 2005) and the issue is currently under hot debate (Vogel, 2005). Deepening our knowledge of this issue will not only provide an essential basis for understanding mammalian development, but also directly apply to ongoing clinical practices such as intracytoplasmic sperm injection (ICSI) and preimplantation genetic diagnosis (PGD). These practices were originally supported by a classical premise that mammalian preimplantation embryos are highly regulative (Tarkowski, 1959; Tarkowski, 1961; Tarkowski and Wroblewska, 1967; Rossant, 1976), in keeping with the "regulative model". However, if the "prepatterning model" is correct, the latter will require critical reassessment.     

Finding the fittest fold: using the evolutionary record to design new proteins

For many years, the holy grail of protein engineering has been the design of artificial amino acid sequences that fold into stable proteins with desired functions. In the current issue of Nature, two papers from the Ranganathan group (Russ et al., 2005; Socolich et al., 2005) report remarkable success in the design of artificial WW domains. Their method, termed statistical coupling analysis (Lockless and Ranganathan, 1999), does not use structural or physicochemical information but instead extracts information about essential patterns of amino acids from the evolutionary record.     

Unification of the genera Nonlabens, Persicivirga, Sandarakinotalea and Stenothermobacter into a single emended genus, Nonlabens, and description of Nonlabens agnitus sp. nov

Phylogenetic analyses based on 16S rRNA gene sequences showed that a bacterial isolate, designated JC2678(T), represents a distinct phyletic line within the suprageneric monophyletic clade containing the genera Nonlabens, Persicivirga, Stenothermobacter and Sandarakinotalea. The polyphasic data presented in this study demonstrated that the members belonging to the Nonlabens-like clade overall constitute a single genus. Therefore, it is proposed to transfer the members of genera Persicivirga O'Sullivan et al. 2006, Stenothermobacter Lau et al. 2006 and Sandarakinotalea Khan et al. 2006 to the genus Nonlabens Lau et al. 2005. Thus, P. dokdonensis (Yoon et al. 2006) Nedashkovskaya et al. 2009, P. ulvanivorans Barbeyron et al. 2010, P. xylanidelens O'Sullivan et al. 2006, Sandarakinotalea sediminis Khan et al. 2006 and Stenothermobacter spongiae Lau et al. 2006 should be transferred to Nonlabens dokdonensis comb. nov., Nonlabens ulvanivorans comb. nov., Nonlabens xylanidelens comb. nov., Nonlabens sediminis comb. nov. and Nonlabens spongiae comb. nov., respectively. In addition, strain JC2678(T) (=KACC 14155(T)=JCM 17109(T)) is proposed to constitute a novel species belonging to the genus Nonlabens with the name of Nonlabens agnitus sp. nov.     

All roads lead to FoxO

Stress-activated kinases control metabolism by antagonizing the early steps of insulin signal transduction. Two papers now demonstrate that Jnk, the prototypical stress-activated kinase, controls life span in Drosophila and C. elegans by promoting phosphorylation of the forkhead protein FoxO (Oh et al., 2005; Wang et al., 2005). The findings provide yet another mechanism by which metabolic and stress responses are integrated via phosphorylation of FoxO proteins.     

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).