8,010 research outputs found
Direct Interaction of Pericentrin with Cytoplasmic Dynein Light Intermediate Chain Contributes to Mitotic Spindle Organization
Pericentrin is a conserved protein of the centrosome involved in microtubule organization. To better understand pericentrin function, we overexpressed the protein in somatic cells and assayed for changes in the composition and function of mitotic spindles and spindle poles. Spindles in pericentrin-overexpressing cells were disorganized and mispositioned, and chromosomes were misaligned and missegregated during cell division, giving rise to aneuploid cells. We unexpectedly found that levels of the molecular motor cytoplasmic dynein were dramatically reduced at spindle poles. Cytoplasmic dynein was diminished at kinetochores also, and the dynein-mediated organization of the Golgi complex was disrupted. Dynein coimmunoprecipitated with overexpressed pericentrin, suggesting that the motor was sequestered in the cytoplasm and was prevented from associating with its cellular targets. Immunoprecipitation of endogenous pericentrin also pulled down cytoplasmic dynein in untransfected cells. To define the basis for this interaction, pericentrin was coexpressed with cytoplasmic dynein heavy (DHCs), intermediate (DICs), and light intermediate (LICs) chains, and the dynamitin and p150Glued subunits of dynactin. Only the LICs coimmunoprecipitated with pericentrin. These results provide the first physiological role for LIC, and they suggest that a pericentrin–dynein interaction in vivo contributes to the assembly, organization, and function of centrosomes and mitotic spindles
Evolution of Conversations in the Age of Email Overload
Email is a ubiquitous communications tool in the workplace and plays an
important role in social interactions. Previous studies of email were largely
based on surveys and limited to relatively small populations of email users
within organizations. In this paper, we report results of a large-scale study
of more than 2 million users exchanging 16 billion emails over several months.
We quantitatively characterize the replying behavior in conversations within
pairs of users. In particular, we study the time it takes the user to reply to
a received message and the length of the reply sent. We consider a variety of
factors that affect the reply time and length, such as the stage of the
conversation, user demographics, and use of portable devices. In addition, we
study how increasing load affects emailing behavior. We find that as users
receive more email messages in a day, they reply to a smaller fraction of them,
using shorter replies. However, their responsiveness remains intact, and they
may even reply to emails faster. Finally, we predict the time to reply, length
of reply, and whether the reply ends a conversation. We demonstrate
considerable improvement over the baseline in all three prediction tasks,
showing the significant role that the factors that we uncover play, in
determining replying behavior. We rank these factors based on their predictive
power. Our findings have important implications for understanding human
behavior and designing better email management applications for tasks like
ranking unread emails.Comment: 11 page, 24th International World Wide Web Conferenc
Centrosome defects and genetic instability in malignant tumors
Genetic instability is a common feature of many human cancers. This condition is frequently characterized by an abnormal number of chromosomes, although little is known about the mechanism that generates this altered genetic state. One possibility is that chromosomes are missegregated during mitosis due to the assembly of dysfunctional mitotic spindles. Because centrosomes are involved in spindle assembly, they could contribute to chromosome missegregation through the organization of aberrant spindles. As an initial test of this idea, we examined malignant tumors for centrosome abnormalities using antibodies to the centrosome protein pericentrin. We found that centrosomes in nearly all tumors and tumor-derived cell lines were atypical in shape, size, and composition and were often present in multiple copies. In addition, virtually all pericentrin-staining structures in tumor cells nucleated microtubules, and they participated in formation of disorganized mitotic spindles, upon which chromosomes were missegregated. All tumor cell lines had both centrosome defects and abnormal chromosome numbers, whereas neither was observed in nontumor cells. These results indicate that centrosome defects are a common feature of malignant tumors and suggest that they may contribute to genetic instability in cancer
Detection of viral antigen, IgM and IgG antibodies in cerebrospinal fluid of Chikungunya patients with neurological complications
BACKGROUND: During Chikungunya virus (CHIKV) epidemic in Nagpur, India, we identified some suspected Chikungunya patients with neurological complications. Early and cost-effective diagnosis of these patients remains problematic despite many new advanced diagnostic methods. A reliable diagnostic test, which could be performed in any standard pathology laboratory, would help to obtain definitive early diagnosis of CHIKV patients with neurological complications. In our laboratory, in-house ELISA protocol for viral antigen, immunoglobulin M (IgM) and IgG detection has been developed and assessed for the diagnosis of CHIKV patients with neurological complications. METHOD: Cerebrospinal fluid samples of forty-six patients who developed neurological symptoms within two months of CHIKV infections along with control subjects were included in the study and were analyzed for the presence of antigens and of IgM and IgG using an ELISA protocol. RESULTS: The ELISA method for antigen detection yielded 80% sensitivity and 87% specificity for the diagnosis of CHIKV patients with neurological complications. The sensitivity for detection of IgM 48% or IgG 63% was significantly lower than the antigen assay (80%). CONCLUSION: The detection of viral antigen in CSF of CHIKV patients with neurological complications by ELISA method gave a more reliable diagnosis than antibodies detection that can be used to develop an immunodiagnostic assay with increased sensitivity and specificity
EAIMS: Emergency Analysis Identification and Management System
Social media has great potential as a means to enable civil
protection and law enforcement agencies to more effectively
tackle disasters and emergencies. However, there is currently
a lack of tools that enable civil protection agencies
to easily make use of social media. The Emergency Analysis
Identification and Management System (EAIMS) is a prototype
service that provides real-time detection of emergency
events, related information finding and credibility analysis
tools for use over social media during emergencies. This
system exploits machine learning over data gathered from
past emergencies and disasters to build effective models for
identifying new events as they occur, tracking developments
within those events and analyzing those developments for
the purposes of enhancing the decision making processes of
emergency response agencies
Self-organizing maps: a tool to ascertain taxonomic relatedness based on features derived from 16S rDNA sequence
Exploitation of microbial wealth, of which almost 95% or more is still unexplored, is a growing need. The taxonomic placements of a new isolate based on phenotypic characteristics are now being supported by information preserved in the 16S rRNA gene. However, the analysis of 16S rDNA sequences retrieved from metagenome, by the available bioinformatics tools, is subject to limitations. In this study, the occurrences of nucleotide features in 16S rDNA sequences have been used to ascertain the taxonomic placement of organisms. The tetra- and penta-nucleotide features were extracted from the training data set of the 16S rDNA sequence, and was subjected to an artificial neural network (ANN) based tool known as self-organizing map (SOM), which helped in visualization of unsupervised classification. For selection of significant features, principal component analysis (PCA) or curvilinear component analysis (CCA) was applied. The SOM along with these techniques could discriminate the sample sequences with more than 90% accuracy, highlighting the relevance of features. To ascertain the confidence level in the developed classification approach, the test data set was specifically evaluated for Thiobacillus, with Acidiphilium, Paracocus and Starkeya, which are taxonomically reassigned. The evaluation proved the excellent generalization capability of the developed tool. The topology of genera in SOM supported the conventional chemo-biochemical classification reported in the Bergey manual
Renaissance of the ~1 TeV Fixed-Target Program
This document describes the physics potential of a new fixed-target program
based on a ~1 TeV proton source. Two proton sources are potentially available
in the future: the existing Tevatron at Fermilab, which can provide 800 GeV
protons for fixed-target physics, and a possible upgrade to the SPS at CERN,
called SPS+, which would produce 1 TeV protons on target. In this paper we use
an example Tevatron fixed-target program to illustrate the high discovery
potential possible in the charm and neutrino sectors. We highlight examples
which are either unique to the program or difficult to accomplish at other
venues.Comment: 31 pages, 11 figure
Signal Transduction Pathways in the Pentameric Ligand-Gated Ion Channels
The mechanisms of allosteric action within pentameric ligand-gated ion channels (pLGICs) remain to be determined. Using crystallography, site-directed mutagenesis, and two-electrode voltage clamp measurements, we identified two functionally relevant sites in the extracellular (EC) domain of the bacterial pLGIC from Gloeobacter violaceus (GLIC). One site is at the C-loop region, where the NQN mutation (D91N, E177Q, and D178N) eliminated inter-subunit salt bridges in the open-channel GLIC structure and thereby shifted the channel activation to a higher agonist concentration. The other site is below the C-loop, where binding of the anesthetic ketamine inhibited GLIC currents in a concentration dependent manner. To understand how a perturbation signal in the EC domain, either resulting from the NQN mutation or ketamine binding, is transduced to the channel gate, we have used the Perturbation-based Markovian Transmission (PMT) model to determine dynamic responses of the GLIC channel and signaling pathways upon initial perturbations in the EC domain of GLIC. Despite the existence of many possible routes for the initial perturbation signal to reach the channel gate, the PMT model in combination with Yen's algorithm revealed that perturbation signals with the highest probability flow travel either via the β1-β2 loop or through pre-TM1. The β1-β2 loop occurs in either intra- or inter-subunit pathways, while pre-TM1 occurs exclusively in inter-subunit pathways. Residues involved in both types of pathways are well supported by previous experimental data on nAChR. The direct coupling between pre-TM1 and TM2 of the adjacent subunit adds new insight into the allosteric signaling mechanism in pLGICs. © 2013 Mowrey et al
Measures on short-lived climate pollutants, the potential reduction in emissions, and benefits for near-term climate and air quality
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