Basal autophagy is involved in the degradation of the ERAD component EDEM1

Little is known about the fate of machinery proteins of the protein quality control and endoplasmic reticulum(ER)-associated degradation (ERAD). We investigated the degradation of the ERAD component EDEM1, which directs overexpressed misfolded glycoproteins to degradation. Endogenous EDEM1 was studied since EDEM1 overexpression not only resulted in inappropriate occurrence throughout the ER but also caused cytotoxic effects. Proteasome inhibitors had no effect on the clearance of endogenous EDEM1 in non-starved cells. However, EDEM1 could be detected by immunocytochemistry in autophagosomes and biochemically in LC3 immuno-purified autophagosomes. Furthermore, influencing the lysosome-autophagy pathway by vinblastine or pepstatin A/E64d and inhibiting autophagosome formation by 3-methyladenine or ATGs short interfering RNA knockdown stabilized EDEM1. Autophagic degradation involved removal of cytosolic Triton X-100-insoluble deglycosylated EDEM1, but not of EDEM1-containing ER cisternae. Our studies demonstrate that endogenous EDEM1 in cells not stressed by the expression of a transgenic misfolded protein reaches the cytosol and is degraded by basal autophagy. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. Received 15 January 2009; received after revision 16 February 2009; accepted 17 February 2009 V. Le Fourn, K. Gaplovska-Kysela: These authors equally contributed to this work.     

The Documentary Real: Thinking Documentary Aesthetics

In this article we consider the growing interest in recent years in the use of documentary strategies in the wold of contemporary art, film and performing arts and explore some of the central epistemological assumptions underpinning the persistent idea that the documentary should be equated with ‘non-fiction’. Following Stella Bruzzi we argue that if documentary theory maintains objectivity as the primary measure of value, it will inevitably and continuously arrive at the conclusion that the documentary genre is fundamentally flawed. Instead, we propose to move beyond the ‘realist epistemology’ of documentary theory and focus on the ‘documentary real’, i.e. the specific performativity of the reality constructed in and by the documentary genre. In the last paragraphs, we introduce the various articles that address the “documentary real” in this special issue.     

A common variant associated with prostate cancer in European and African populations

With the increasing incidence of prostate cancer, identifying common genetic variants that confer risk of the disease is important. Here we report such a variant on chromosome 8q24, a region initially identified through a study of Icelandic families. Allele -8 of the microsatellite DG8S737 was associated with prostate cancer in three case-control series of European ancestry from Iceland, Sweden and the US. The estimated odds ratio (OR) of the allele is 1.62 (P = 2.7 x 10(-11)). About 19% of affected men and 13% of the general population carry at least one copy, yielding a population attributable risk (PAR) of approximately 8%. The association was also replicated in an African American case-control group with a similar OR, in which 41% of affected individuals and 30% of the population are carriers. This leads to a greater estimated PAR (16%) that may contribute to higher incidence of prostate cancer in African American men than in men of European ancestry.     

线性矩阵不等式及其在控制系统中的应用

详细综述了LMI在控制系统中的发展现状和应用,主要涉及了不确定系统的鲁棒性能和鲁棒稳定性、不确定系统的鲁棒控制器设计、LMI在时滞系统中的应用及存在的问题、不确定系统的鲁棒滤波应用状况、不确定系统的模型验证应用等,并分析了基于LMI方法的变结构控制、极点配置、模糊控制等其它相关内容.给出了上述控制问题的LMI描述及相关求解方法,最后并指出了LMI进一步的应用研究方向.     

Mesenchymal–epithelial interactions during digestive tract development and epithelial stem cell regeneration

The gastrointestinal tract develops from a simple and uniform tube into a complex organ with specific differentiation patterns along the anterior–posterior and dorso-ventral axes of asymmetry. It is derived from all three germ layers and their cross-talk is important for the regulated development of fetal and adult gastrointestinal structures and organs. Signals from the adjacent mesoderm are essential for the morphogenesis of the overlying epithelium. These mesenchymal–epithelial interactions govern the development and regionalization of the different gastrointestinal epithelia and involve most of the key morphogens and signaling pathways, such as the Hedgehog, BMPs, Notch, WNT, HOX, SOX and FOXF cascades. Moreover, the mechanisms underlying mesenchyme differentiation into smooth muscle cells influence the regionalization of the gastrointestinal epithelium through interactions with the enteric nervous system. In the neonatal and adult gastrointestinal tract, mesenchymal–epithelial interactions are essential for the maintenance of the epithelial regionalization and digestive epithelial homeostasis. Disruption of these interactions is also associated with bowel dysfunction potentially leading to epithelial tumor development. In this review, we will discuss various aspects of the mesenchymal–epithelial interactions observed during digestive epithelium development and differentiation and also during epithelial stem cell regeneration.     

月地高速再入返回飞行器信息系统设计与实现

探月三期月地高速再入返回飞行器由服务舱和返回器2个舱段组成,信息系统复杂,首先对信息系统的任务进行了分析,在此基础上提出了2层拓扑总线的互联方案、器内多子网自识别路由设计方案、链路层分层方案,脉冲调制编码(PCM)数据体制与高级在轨系统(AOS)数据体制统一设计方案,实现了多信源、多舱段信息管理与融合,提高了上行带宽利用率、器内数据路由和下行遥测灵活性和易扩展性,满足了飞行任务复杂工作模式下的需求,在轨飞行结果表明信息系统满足需求.     

Updating the mechanisms of common fragile site instability: how to reconcile the different views?

Common fragile sites (CFSs) are large chromosomal regions long identified by conventional cytogenetics as sequences prone to breakage in cells subjected to replication stress. The interest in CFSs came from their key role in the formation of DNA damage, resulting in chromosomal rearrangements. The instability of CFSs was notably correlated with the appearance of genome instability in precancerous lesions and during tumor progression. Identification of the molecular mechanisms responsible for their instability therefore represents a major challenge. A number of data show that breaks result from mitotic entry before replication completion but the mechanisms responsible for such delayed replication of CFSs and relaxed checkpoint surveillance are still debated. In addition, clues to the molecular events leading to breakage just start to emerge. We present here the results of recent reports addressing these questions.     

PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans

Ichthyoses comprise a heterogeneous group of genodermatoses characterized by abnormal desquamation over the whole body, for which the genetic causes of several human forms remain unknown. We used a spontaneous dog model in the golden retriever breed, which is affected by a lamellar ichthyosis resembling human autosomal recessive congenital ichthyoses (ARCI), to carry out a genome-wide association study. We identified a homozygous insertion-deletion (indel) mutation in PNPLA1 that leads to a premature stop codon in all affected golden retriever dogs. We subsequently found one missense and one nonsense mutation in the catalytic domain of human PNPLA1 in six individuals with ARCI from two families. Further experiments highlighted the importance of PNPLA1 in the formation of the epidermal lipid barrier. This study identifies a new gene involved in human ichthyoses and provides insights into the localization and function of this yet uncharacterized member of the PNPLA protein family.     

Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis

Hajdu-Cheney syndrome is a rare autosomal dominant skeletal disorder with facial anomalies, osteoporosis and acro-osteolysis. We sequenced the exomes of six unrelated individuals with this syndrome and identified heterozygous nonsense and frameshift mutations in NOTCH2 in five of them. All mutations cluster to the last coding exon of the gene, suggesting that the mutant mRNA products escape nonsense-mediated decay and that the resulting truncated NOTCH2 proteins act in a gain-of-function manner.     

具有固定顺序的重新排序问题

在生产实际中经常会出现顾客订单不同时到达的情况,为了保证先来顾客的需求和工件本身的要求,往往是先安排好的工件保持相对顺序不变,使其与后来顾客的工件重新排序.本文着重研究了这种使先来顾客的工件保持相对固定顺序,在有限错位限制的条件下使总目标函数值最优的重新排序问题。