Response network analysis of differential gene expression in human epithelial lung cells during avian influenza infections

<p>Abstract</p> <p>Background</p> <p>The recent emergence of the H5N1 influenza virus from avian reservoirs has raised concern about future influenza strains of high virulence emerging that could easily infect humans. We analyzed differential gene expression of lung epithelial cells to compare the response to H5N1 infection with a more benign infection with Respiratory Syncytial Virus (RSV). These gene expression data are then used as seeds to find important nodes by using a novel combination of the Gene Ontology database and the Human Network of gene interactions. Additional analysis of the data is conducted by training support vector machines (SVM) with the data and examining the orientations of the optimal hyperplanes generated.</p> <p>Results</p> <p>Analysis of gene clustering in the Gene Ontology shows no significant clustering of genes unique to H5N1 response at 8 hours post infection. At 24 hours post infection, however, a number of significant gene clusters are found for nodes representing "immune response" and "response to virus" terms. There were no significant clusters of genes in the Gene Ontology for the control (Mock) or RSV experiments that were unique relative to the H5N1 response. The genes found to be most important in distinguishing H5N1 infected cells from the controls using SVM showed a large degree of overlap with the list of significantly regulated genes. However, though none of these genes were members of the GO clusters found to be significant.</p> <p>Conclusions</p> <p>Characteristics of H5N1 infection compared to RSV infection show several immune response factors that are specific for each of these infections. These include faster timescales within the cell as well as a more focused activation of immunity factors. Many of the genes that are found to be significantly expressed in H5N1 response relative to the control experiments are not found to cluster significantly in the Gene Ontology. These genes are, however, often closely linked to the clustered genes through the Human Network. This may suggest the need for more diverse annotations of these genes and verification of their action in immune response.</p

Distributed Management of Massive Data: an Efficient Fine-Grain Data Access Scheme

This paper addresses the problem of efficiently storing and accessing massive data blocks in a large-scale distributed environment, while providing efficient fine-grain access to data subsets. This issue is crucial in the context of applications in the field of databases, data mining and multimedia. We propose a data sharing service based on distributed, RAM-based storage of data, while leveraging a DHT-based, natively parallel metadata management scheme. As opposed to the most commonly used grid storage infrastructures that provide mechanisms for explicit data localization and transfer, we provide a transparent access model, where data are accessed through global identifiers. Our proposal has been validated through a prototype implementation whose preliminary evaluation provides promising results

Observations of radio pulses from CU Virginis

The magnetic chemically peculiar star CU Virginis is a unique astrophysical laboratory for stellar magnetospheres and coherent emission processes. It is the only known main sequence star to emit a radio pulse every rotation period. Here we report on new observations of the CU Virginis pulse profile in the 13 and 20\,cm radio bands. The profile is known to be characterised by two peaks of 100$\%$ circularly polarised emission that are thought to arise in an electron-cyclotron maser mechanism. We find that the trailing peak is stable at both 13 and 20\,cm, whereas the leading peak is intermittent at 13\,cm. Our measured pulse arrival times confirm the discrepancy previously reported between the putative stellar rotation rates measured with optical data and with radio observations. We suggest that this period discrepancy might be caused by an unknown companion or by instabilities in the emission region. Regular long-term pulse timing and simultaneous multi-wavelength observations are essential to clarify the behaviour of this emerging class of transient radio source.Comment: Accepted by MNRAS Letters; 5 pages, 2 figures, 3 table

The Arctic predictability and prediction on seasonal-to-interannual timescales (APPOSITE) data set version 1

This is the final version of the article. Available from the publisher via the DOI in this record. Discussion paper (published on 15 Oct 2015)Recent decades have seen significant developments in seasonal-to-interannual timescale climate prediction capabilities. However, until recently the potential of such systems to predict Arctic climate had not been assessed. This paper describes a multi- 5 model predictability experiment which was run as part of the Arctic Predictability and Prediction On Seasonal to Inter-annual Timescales (APPOSITE) project. The main goal of APPOSITE was to quantify the timescales on which Arctic climate is predictable. In order to achieve this, a coordinated set of idealised initial-value predictability experiments, with seven general circulation models, was conducted. This was the first model 10 intercomparison project designed to quantify the predictability of Arctic climate on seasonal to inter-annual timescales. Here we present a description of the archived data set (which is available at the British Atmospheric Data Centre) and an update of the project's results. Although designed to address Arctic predictability, this data set could also be used to assess the predictability of other regions and modes of climate vari15 ability on these timescales, such as the El Niño Southern Oscillation.This work was supported by the Natural Environment Research Council (grant NE/I029447/1). Helge Goessling was supported by a fellowship of the German Research Foundation (DFG grant GO 2464/1-1). Data storage and processing capacity was kindly provided by the British Atmospheric Data Centre (BADC). Thanks to Yanjun Jiao (CCCma) for his assistance with the CanCM4 simulations and to Bill Merryfield for his comments on a draft of the pape

Parameter identification problems in the modelling of cell motility

We present a novel parameter identification algorithm for the estimation of parameters in models of cell motility using imaging data of migrating cells. Two alternative formulations of the objective functional that measures the difference between the computed and observed data are proposed and the parameter identification problem is formulated as a minimisation problem of nonlinear least squares type. A Levenberg–Marquardt based optimisation method is applied to the solution of the minimisation problem and the details of the implementation are discussed. A number of numerical experiments are presented which illustrate the robustness of the algorithm to parameter identification in the presence of large deformations and noisy data and parameter identification in three dimensional models of cell motility. An application to experimental data is also presented in which we seek to identify parameters in a model for the monopolar growth of fission yeast cells using experimental imaging data. Our numerical tests allow us to compare the method with the two different formulations of the objective functional and we conclude that the results with both objective functionals seem to agree

De Novo Growth Zone Formation from Fission Yeast Spheroplasts

Eukaryotic cells often form polarized growth zones in response to internal or external cues. To understand the establishment of growth zones with specific dimensions we used fission yeast, which grows as a rod-shaped cell of near-constant width from growth zones located at the cell tips. Removing the cell wall creates a round spheroplast with a disorganized cytoskeleton and depolarized growth proteins. As spheroplasts recover, new growth zones form that resemble normal growing cell tips in shape and width, and polarized growth resumes. Regulators of the GTPase Cdc42, which control width in exponentially growing cells, also control spheroplast growth zone width. During recovery the Cdc42 scaffold Scd2 forms a polarized patch in the rounded spheroplast, demonstrating that a growth zone protein can organize independent of cell shape. Rga4, a Cdc42 GTPase activating protein (GAP) that is excluded from cell tips, is initially distributed throughout the spheroplast membrane, but is excluded from the growth zone after a stable patch of Scd2 forms. These results provide evidence that growth zones with normal width and protein localization can form de novo through sequential organization of cellular domains, and that the size of these growth zones is genetically controlled, independent of preexisting cell shape

Trends in incidence and mortality of tuberculosis in Japan : a population-based study, 1997–2016

Japan is still a medium-burden tuberculosis (TB) country. We aimed to examine trends in newly notified active TB incidence and TB-related mortality in the last two decades in Japan. This is a population-based study using Japanese Vital Statistics and Japan Tuberculosis Surveillance from 1997 to 2016. We determined active TB incidence and mortality rates (per 100 000 population) by sex, age and disease categories. Joinpoint regression was applied to calculate the annual percentage change (APC) in age-adjusted mortality rates and to identify the years showing significant trend changes. Crude and age-adjusted incidence rates reduced from 33.9 to 13.9 and 37.3 to 11.3 per 100 000 population, respectively. Also, crude and age-adjusted mortality rates reduced from 2.2 to 1.5 and 2.8 to 1.0 per 100 000 population, respectively. Average APC in the incidence and mortality rates showed significant decline both in men (−6.2% and −5.4%, respectively) and women (−5.7% and −4.6%, respectively). Age-specific analysis demonstrated decreases in incidence and mortality rates for every age category, except for the incidence trend in the younger population. Although trends in active TB incidence and mortality rates in Japan have favourably decreased, the rate of decline is far from achieving TB elimination by 2035

The coordination of cell growth during fission yeast mating requires Ras1-GTP hydrolysis

The spatial and temporal control of polarity is fundamental to the survival of all organisms. Cells define their polarity using highly conserved mechanisms that frequently rely upon the action of small GTPases, such as Ras and Cdc42. Schizosaccharomyces pombe is an ideal system with which to study the control of cell polarity since it grows from defined tips using Cdc42-mediated actin remodeling. Here we have investigated the importance of Ras1-GTPase activity for the coordination of polarized cell growth during fission yeast mating. Following pheromone stimulation, Ras1 regulates both a MAPK cascade and the activity of Cdc42 to enable uni-directional cell growth towards a potential mating partner. Like all GTPases, when bound to GTP, Ras1 adopts an active conformation returning to an inactive state upon GTP-hydrolysis, a process accelerated through interaction with negative regulators such as GAPs. Here we show that, at low levels of pheromone stimulation, loss of negative regulation of Ras1 increases signal transduction via the MAPK cascade. However, at the higher concentrations observed during mating, hyperactive Ras1 mutations promote cell death. We demonstrate that these cells die due to their failure to coordinate active Cdc42 into a single growth zone resulting in disorganized actin deposition and unsustainable elongation from multiple tips. These results provide a striking demonstration that the deactivation stage of Ras signaling is fundamentally important in modulating cell polarity

Fundamental parameters and infrared excesses of Hipparcos stars

We derive the fundamental parameters (temperature and luminosity) of 107 619 Hipparcos stars and place these stars on a true Hertzsprung-Russell diagram. This is achieved by comparing BT-Settl model atmospheres to spectral energy distributions (SEDs) created from Hipparcos, Tycho, SDSS, DENIS, 2MASS, MSX, AKARI, IRAS and WISE data. We also identify and quantify from these SEDs any infrared excesses attributable to circumstellar matter. We compare our results to known types of objects, focussing on the giant branch stars. Giant star dust production (as traced by infrared excess) is found to start in earnest around 680 Lsun.Comment: 16 pages, 8 figures, accepted MNRA

The Mira variable S Ori: Relationships between the photosphere, molecular layer, dust shell, and SiO maser shell at 4 epochs

We present the first multi-epoch study that includes concurrent mid-infrared and radio interferometry of an oxygen-rich Mira star. We obtained mid-infrared interferometry of S Ori with VLTI/MIDI at four epochs between December 2004 and December 2005. We concurrently observed v=1, J=1-0 (43.1 GHz), and v=2, J=1-0 (42.8 GHz) SiO maser emission toward S Ori with the VLBA at three epochs. The MIDI data are analyzed using self-excited dynamic model atmospheres including molecular layers, complemented by a radiative transfer model of the circumstellar dust shell. The VLBA data are reduced to the spatial structure and kinematics of the maser spots. The modeling of our MIDI data results in phase-dependent continuum photospheric angular diameters between about 7.9 mas (Phase 0.55) and 9.7 mas (Phase 1.16). The dust shell can best be modeled with Al2O3 grains using phase-dependent inner boundary radii between 1.8 and 2.4 photospheric radii. The dust shell appears to be more compact with greater optical depth near visual minimum, and more extended with lower optical depth after visual maximum. The ratios of the SiO maser ring radii to the photospheric radii are between about 1.9 and 2.4. The maser spots mark the region of the molecular atmospheric layers just beyond the steepest decrease in the mid-infrared model intensity profile. Their velocity structure indicates a radial gas expansion. Al2O3 dust grains and SiO maser spots form at relatively small radii of 1.8-2.4 photospheric radii. Our results suggest increased mass loss and dust formation close to the surface near the minimum visual phase, when Al2O3 dust grains are co-located with the molecular gas and the SiO maser shells, and a more expanded dust shell after visual maximum. Silicon does not appear to be bound in dust, as our data show no sign of silicate grains.Comment: Accepted for publication in A&A. See ESO press release 25/07 at http://www.eso.org/public/outreach/press-rel/pr-2007/pr-25-07.htm