The nuclear envelope: emerging roles in development and disease

The chromosomes of eukaryotic cells are separated from the cytoplasm by the nuclear envelope. The nuclear envelope includes two riveted membranes, plus embedded pore complexes that mediate nuclear import and export. In this sense, the nuclear envelope is truly a border zone. However, the envelope also links directly to chromosomes, and anchors two major infrastructures--the nuclear lamina and Tpr filaments--to the nuclear perimeter. Proteins of the nuclear envelope mediate a variety of fundamental activities, including DNA replication, gene expression and silencing, chromatin organization, cell division, apoptosis, sperm nuclear remodeling, the behavior of pronuclei, cell fate determination, nuclear migration and cell polarity. Furthermore, mutations in nuclear lamins and lamin-binding proteins cause tissue-specific inherited diseases. This special issue of Cell and Molecular Life Sciences is devoted to recent major advances in the characterization of nuclear envelope proteins and their roles. We offer here an overview of the topics covered in this issue of CMLS, and also discuss the emerging recognition that the nuclear envelope is an organelle critical for a wide range of genetic and developmental activity in multicellular organisms.     

Genetic mapping with SNP markers in Drosophila.

Map-based positional cloning of Drosophila melanogaster genes is hampered by both the time-consuming, error-prone nature of traditional methods for genetic mapping and the difficulties in aligning the genetic and cytological maps with the genome sequence. The identification of sequence polymorphisms in the Drosophila genome will make it possible to map mutations directly to the genome sequence with high accuracy and resolution. Here we report the identification of 7,223 single-nucleotide polymorphisms (SNPs) and 1,392 insertions/deletions (InDels) in common laboratory strains of Drosophila. These sequence polymorphisms define a map of 787 autosomal marker loci with a resolution of 114 kb. We have established PCR product-length polymorphism (PLP) or restriction fragment-length polymorphism (RFLP) assays for 215 of these markers. We demonstrate the use of this map by delimiting two mutations to intervals of 169 kb and 307 kb, respectively. Using a local high-density SNP map, we also mapped a third mutation to a resolution of approximately 2 kb, sufficient to localize the mutation within a single gene. These methods should accelerate the rate of positional cloning in Drosophila.     

Mechanism of ubiquitin activation revealed by the structure of a bacterial MoeB-MoaD complex.

The activation of ubiquitin and related protein modifiers is catalysed by members of the E1 enzyme family that use ATP for the covalent self-attachment of the modifiers to a conserved cysteine. The Escherichia coli proteins MoeB and MoaD are involved in molybdenum cofactor (Moco) biosynthesis, an evolutionarily conserved pathway. The MoeB- and E1-catalysed reactions are mechanistically similar, and despite a lack of sequence similarity, MoaD and ubiquitin display the same fold including a conserved carboxy-terminal Gly-Gly motif. Similar to the E1 enzymes, MoeB activates the C terminus of MoaD to form an acyl-adenylate. Subsequently, a sulphurtransferase converts the MoaD acyl-adenylate to a thiocarboxylate that acts as the sulphur donor during Moco biosynthesis. These findings suggest that ubiquitin and E1 are derived from two ancestral genes closely related to moaD and moeB. Here we present the crystal structures of the MoeB-MoaD complex in its apo, ATP-bound, and MoaD-adenylate forms, and highlight the functional similarities between the MoeB- and E1-substrate complexes. These structures provide a molecular framework for understanding the activation of ubiquitin, Rub, SUMO and the sulphur incorporation step during Moco and thiamine biosynthesis.     

Impact of bolus volume on small intestinal intra-luminal impedance in healthy subjects

AIM: To assess the impact of bolus volume on the characteristics of small intestinal (SI) impedance signals.METHODS: Concurrent SI manometry-impedance measurements were performed on 12 healthy volunteers to assess the pattern of proximal jejunal fluid bolus movement over a 14 cm-segment.Each subject was given 34 boluses of normal saline (volume from 1 to 30 mL) via the feeding tube placed immediately above the proximal margin of the studied segment.A bolus-induced impedance event occurred if there was > 12%...     

Role of serum components in the binding and phagocytosis of oxidatively damaged erythrocytes by autologous mouse macrophages

To investigate the role of autologous serum components in the recognition of damaged cells by macrophages, we examined the binding and phagocytosis of damage oxidatively damaged red blood cells with Cu2+ and ascorbate (oxRBCs) by autologous resident mouse peritoneal macrophages. The binding of oxRBCs by macrophages was independent of the presence of serum. However, phagocytosis by macrophages increased with serum concentration, and macrophages showed little ingestion of oxRBCs in a serum-free medium. Macrophages neither bound nor appreciably ingested native RBCs (before oxidation) in either the absence or presence of autologous serum. Mouse macrophages ingested significantly more native as well as oxRBCs in the presence of heat-inactivated fetal calf serum than in the presence of heat-inactivated mouse serum. Pretreated oxRBCs with normal serum were rarely ingested by macrophages in a serum-free medium. Phagocytosis of oxRBCs was significantly inhibited by depletion of IgG or calcium from serum, by heat inactivation of complement, or by antiserum against mouse C3. These results demonstrate that serum components such as IgG, C3, and calcium are involved in phagocytosis of oxRBCs by autologous macrophages.     

An Adaptive Design for Six Sigma（ ADFSS ） ： a Simulated Annealing and Regression Analysis Embedded Approach

Design for six sigma (DFSS) is a powerful approach of designing products,processes,and services with the objective of meeting the needs of customers in a cost-effective manner.DFSS activities are class...     

Hubbard模型的铁磁相变

用Zou-Anderson有效哈密顿量计算了spinon-holon系统的动态横向磁化率。由讨论holon涨落效应,导出一铁磁相互作用,这一相互作用对解释Hubbard模型的铁磁相变有重要的意义。     

香港室内氡水平及其与建筑物表面氡析出率的关系

本文报导用活性炭盒吸附方法对香港室内氡浓度的测量结果及其浓度分布规律。对室内氡浓度与建筑物表面氡析出率的关系进行了分析研究。证实室内空气中的氡主要来源于建材中的镭,而氡浓度水平只决定于室内建筑物表面氡的析出率及通风状况。