Kinesin-1 and dynein at the nuclear envelope mediate the bidirectional migrations of nuclei

The molecular motors kinesin-1 dynein navigate migrating nuclei around cytoplasmic roadblocks

LEM-3 – A LEM Domain Containing Nuclease Involved in the DNA Damage Response in C. elegans

The small nematode Caenorhabditis elegans displays a spectrum of DNA damage responses similar to humans. In order to identify new DNA damage response genes, we isolated in a forward genetic screen 14 new mutations conferring hypersensitivity to ionizing radiation. We present here our characterization of lem-3, one of the genes identified in this screen. LEM-3 contains a LEM domain and a GIY nuclease domain. We confirm that LEM-3 has DNase activity in vitro. lem-3(lf) mutants are hypersensitive to various types of DNA damage, including ionizing radiation, UV-C light and crosslinking agents. Embryos from irradiated lem-3 hermaphrodites displayed severe defects during cell division, including chromosome mis-segregation and anaphase bridges. The mitotic defects observed in irradiated lem-3 mutant embryos are similar to those found in baf-1 (barrier-to-autointegration factor) mutants. The baf-1 gene codes for an essential and highly conserved protein known to interact with the other two C. elegans LEM domain proteins, LEM-2 and EMR-1. We show that baf-1, lem-2, and emr-1 mutants are also hypersensitive to DNA damage and that loss of lem-3 sensitizes baf-1 mutants even in the absence of DNA damage. Our data suggest that BAF-1, together with the LEM domain proteins, plays an important role following DNA damage – possibly by promoting the reorganization of damaged chromatin

Centriole movements in mammalian epithelial cells during cytokinesis

<p>Abstract</p> <p>Background</p> <p>In cytokinesis, when the cleavage furrow has been formed, the two centrioles in each daughter cell separate. It has been suggested that the centrioles facilitate and regulate cytokinesis to some extent. It has been postulated that termination of cytokinesis (abscission) depends on the migration of a centriole to the intercellular bridge and then back to the cell center. To investigate the involvement of centrioles in cytokinesis, we monitored the movements of centrioles in three mammalian epithelial cell lines, HeLa, MCF 10A, and the p53-deficient mouse mammary tumor cell line KP-7.7, by time-lapse imaging. Centrin1-EGFP and α-Tubulin-mCherry were co-expressed in the cells to visualize respectively the centrioles and microtubules.</p> <p>Results</p> <p>Here we report that separated centrioles that migrate from the cell pole are very mobile during cytokinesis and their movements can be characterized as 1) along the nuclear envelope, 2) irregular, and 3) along microtubules forming the spindle axis. Centriole movement towards the intercellular bridge was only seen occasionally and was highly cell-line dependent.</p> <p>Conclusions</p> <p>These findings show that centrioles are highly mobile during cytokinesis and suggest that the repositioning of a centriole to the intercellular bridge is not essential for controlling abscission. We suggest that centriole movements are microtubule dependent and that abscission is more dependent on other mechanisms than positioning of centrioles.</p

Bringing KASH under the SUN: the many faces of nucleo-cytoskeletal connections

The nucleus is the most prominent cellular organelle, and its sharp boundaries suggest the compartmentalization of the nucleoplasm from the cytoplasm. However, the recent identification of evolutionarily conserved linkers of the nucleoskeleton to the cytoskeleton (LINC) complexes, a family of macromolecular assemblies that span the double membrane of the nuclear envelope, reveals tight physical connections between the two compartments. Here, we review the structure and evolutionary conservation of SUN and KASH domain–containing proteins, whose interaction within the perinuclear space forms the “nuts and bolts” of LINC complexes. Moreover, we discuss the function of these complexes in nuclear, centrosomal, and chromosome dynamics, and their connection to human disease

The SUN protein UNC-84 is required only in force-bearing cells to maintain nuclear envelope architecture

The nuclear envelope (NE) consists of two evenly spaced bilayers, the inner and outer nuclear membranes. The Sad1p and UNC-84 (SUN) proteins and Klarsicht, ANC-1, and Syne homology (KASH) proteins that interact to form LINC (linker of nucleoskeleton and cytoskeleton) complexes connecting the nucleoskeleton to the cytoskeleton have been implicated in maintaining NE spacing. Surprisingly, the NE morphology of most Caenorhabditis elegans nuclei was normal in the absence of functional SUN proteins. Distortions of the perinuclear space observed in unc-84 mutant muscle nuclei resembled those previously observed in HeLa cells, suggesting that SUN proteins are required to maintain NE architecture in cells under high mechanical strain. The UNC-84 protein with large deletions in its luminal domain was able to form functional NE bridges but had no observable effect on NE architecture. Therefore, SUN-KASH bridges are only required to maintain NE spacing in cells subjected to increased mechanical forces. Furthermore, SUN proteins do not dictate the width of the NE

Technical Progress and Improvement in Systems of Wage Payments

In recent years, in connection with the resolutions of the 20th Congress of the Communist Party of the Soviet Union, a great deal of work has been carried out in our country in straightening out the wage system in industry. In this connection, along with widespread production of work quotas based on the capabilities of the machines, and new fundamentals used in the setting of rates, the forms and systems of payment of wages are being improved. These changes are intimately interrelated with the uninterrupted progress of technology, and the qualitative changes occurring in the foundation of industry in material technology.

A new approach to intranet search based on information extraction

This paper is concerned with 'intranet search'. By intranet search, we mean searching for information on an intranet within an organization. We have found that search needs on an intranet can be categorized into types, through an analysis of survey results and an analysis of search log data. The types include searching for definitions, persons, experts, and homepages. Traditional information retrieval only focuses on search of relevant documents, but not on search of special types of information. We propose a new approach to intranet search in which we search for information in each of the special types, in addition to the traditional relevance search. Information extraction technologies can play key roles in such kind of 'search by type' approach, because we must first extract from the documents the necessary information in each type. We have developed an intranet search system called 'Information Desk'. In the system, we try to address the most important types of search first - finding term definitions, homepages of groups or topics, employees' personal information and experts on topics. For each type of search, we use information extraction technologies to extract, fuse, and summarize information in advance. The system is in operation on the intranet of Microsoft and receives accesses from about 500 employees per month. Feedbacks from users and system logs show that users consider the approach useful and the system can really help people to find information. This paper describes the architecture, features, component technologies, and evaluation results of the system. Copyright 2005 ACM

UNC-83 is a nuclear-specific cargo adaptor for kinesin-1-mediated nuclear migration

Intracellular nuclear migration is essential for many cellular events including fertilization, establishment of polarity, division and differentiation. How nuclei migrate is not understood at the molecular level. The C. elegans KASH protein UNC-83 is required for nuclear migration and localizes to the outer nuclear membrane. UNC-83 interacts with the inner nuclear membrane SUN protein UNC-84 and is proposed to connect the cytoskeleton to the nuclear lamina. Here, we show that UNC-83 also interacts with the kinesin-1 light chain KLC-2, as identified in a yeast two-hybrid screen and confirmed by in vitro assays. UNC-83 interacts with and recruits KLC-2 to the nuclear envelope in a heterologous tissue culture system. Additionally, analysis of mutant phenotypes demonstrated that both KLC-2 and the kinesin-1 heavy chain UNC-116 are required for nuclear migration. Finally, the requirement for UNC-83 in nuclear migration could be partially bypassed by expressing a synthetic outer nuclear membrane KLC-2::KASH fusion protein. Our data support a model in which UNC-83 plays a central role in nuclear migration by acting to bridge the nuclear envelope and as a kinesin-1 cargo-specific adaptor so that motor-generated forces specifically move the nucleus as a single unit

Automatic extraction of titles from general documents using machine learning

In this paper, we propose a machine learning approach to title extraction from general documents. By general documents, we mean documents that can belong to any one of a number of specific genres, including presentations, book chapters, technical papers, brochures, reports, and letters. Previously, methods have been proposed mainly for title extraction from research papers. It has not been clear whether it could be possible to conduct automatic title extraction from general documents. As a case study, we consider extraction from Office including Word and PowerPoint. In our approach, we annotate titles in sample documents (for Word and PowerPoint, respectively) and take them as training data, train machine learning models, and perform title extraction using the trained models. Our method is unique in that we mainly utilize formatting information such as font size as features in the models. It turns out that the use of formatting information can lead to quite accurate extraction from general documents. Precision and recall for title extraction from Word are 0.810 and 0.837, respectively, and precision and recall for title extraction from PowerPoint are 0.875 and 0.895, respectively in an experiment on intranet data. Other important new findings in this work include that we can train models in one domain and apply them to other domains, and more surprisingly we can even train models in one language and apply them to other languages. Moreover, we can significantly improve search ranking results in document retrieval by using th