Viral immune modulators perturb the human molecular network by common and unique strategies

Viruses must enter host cells to replicate, assemble and propagate. Because of the restricted size of their genomes, viruses have had to evolve efficient ways of exploiting host cell processes to promote their own life cycles and also to escape host immune defence mechanisms. Many viral open reading frames (viORFs) with immune-modulating functions essential for productive viral growth have been identified across a range of viral classes. However, there has been no comprehensive study to identify the host factors with which these viORFs interact for a global perspective of viral perturbation strategies. Here we show that different viral perturbation patterns of the host molecular defence network can be deduced from a mass-spectrometry-based host-factor survey in a defined human cellular system by using 70 innate immune-modulating viORFs from 30 viral species. The 579 host proteins targeted by the viORFs mapped to an unexpectedly large number of signalling pathways and cellular processes, suggesting yet unknown mechanisms of antiviral immunity. We further experimentally verified the targets heterogeneous nuclear ribonucleoprotein?U, phosphatidylinositol-3-OH kinase, the WNK (with-no-lysine) kinase family and USP19 (ubiquitin-specific peptidase 19) as vulnerable nodes in the host cellular defence system. Evaluation of the impact of viral immune modulators on the host molecular network revealed perturbation strategies used by individual viruses and by viral classes. Our data are also valuable for the design of broad and specific antiviral therapies.     

The intense starburst HDF 850.1 in a galaxy overdensity at z ≈ 5.2 in the Hubble Deep Field

The Hubble Deep Field provides one of the deepest multiwavelength views of the distant Universe and has led to the detection of thousands of galaxies seen throughout cosmic time. An early map of the Hubble Deep Field at a wavelength of 850?micrometres, which is sensitive to dust emission powered by star formation, revealed the brightest source in the field, dubbed HDF?850.1 (ref. 2). For more than a decade, and despite significant efforts, no counterpart was found at shorter wavelengths, and it was not possible to determine its redshift, size or mass. Here we report a redshift of z = 5.183 for HDF?850.1, from a millimetre-wave molecular line scan. This places HDF?850.1 in a galaxy overdensity at z?≈?5.2, corresponding to a cosmic age of only 1.1?billion years after the Big Bang. This redshift is significantly higher than earlier estimates and higher than those of most of the hundreds of submillimetre-bright galaxies identified so far. The source has a star-formation rate of 850 solar masses per year and is spatially resolved on scales of 5 kiloparsecs, with an implied dynamical mass of about 1.3?×?10(11) solar masses, a significant fraction of which is present in the form of molecular gas. Despite our accurate determination of redshift and position, a counterpart emitting starlight remains elusive.     

Morphology and larval development of Polydora cf. websteri (Polychaeta: Spionidae) in a tropical region of north-eastern Brazil

Polydora websteri belongs to a group of the Spionidae known as the Polydora complex, members of which are known for building tubes within the shells of mussels and for their ability to infest commercially valuable bivalves, which causes serious losses for malacoculture. P. websteri is a species subjected to increasing research due to the global scale at which these infestations occur. In this paper, we describe the larval development of P.cf. websteri associated with the oyster Crassostrea cf. brasiliana in a tropical region of north-east Brazil. The main structures of all stages of development were analysed and compared to other populations of P. websteri. Ovigerous capsules of P.cf. websteri were cultured in the laboratory and the larval stages were analysed until metamorphosis. Ovigerous capsules were present in all sampling intervals, indicating that this population exhibits continuous reproduction. Up to 21 capsules per tube were found, and the number of eggs per capsule varied from 20 to 40. All observed eggs developed into larvae. Larval development from egg to recruitment stage did not exceed 13 days. Metamorphosis occurred when larvae attained 17 chaetigers, at which stage important diagnostic characteristics were revealed, such as the spines on chaetiger 5. The developmental stages of P.cf. websteri larvae, and the morphological features found at each stage, are in accordance with what has been recorded for temperate populations. In our study, the planktonic stage was found to be of shorter duration than elsewhere, which might be associated with the higher temperatures at which larvae were cultured compared to previous studies.     

Adherens junction protein nectin-4 is the epithelial receptor for measles virus

Measles virus is an aerosol-transmitted virus that affects more than 10 million children each year and accounts for approximately 120,000 deaths. Although it was long believed to replicate in the respiratory epithelium before disseminating, it was recently shown to infect initially macrophages and dendritic cells of the airways using signalling lymphocytic activation molecule family member 1 (SLAMF1; also called CD150) as a receptor. These cells then cross the respiratory epithelium and transport the infection to lymphatic organs where measles virus replicates vigorously. How and where the virus crosses back into the airways has remained unknown. On the basis of functional analyses of surface proteins preferentially expressed on virus-permissive human epithelial cell lines, here we identify nectin-4 (ref. 8; also called poliovirus-receptor-like-4 (PVRL4)) as a candidate host exit receptor. This adherens junction protein of the immunoglobulin superfamily interacts with the viral attachment protein with high affinity through its membrane-distal domain. Nectin-4 sustains measles virus entry and non-cytopathic lateral spread in well-differentiated primary human airway epithelial sheets infected basolaterally. It is downregulated in infected epithelial cells, including those of macaque tracheae. Although other viruses use receptors to enter hosts or transit through their epithelial barriers, we suggest that measles virus targets nectin-4 to emerge in the airways. Nectin-4 is a cellular marker of several types of cancer, which has implications for ongoing measles-virus-based clinical trials of oncolysis.     

Regional econometric income forecast accuracy

Econometric prediction accuracy for personal income forecasts is examined for a region of the United States. Previously published regional structural equation model (RSEM) forecasts exist ex ante for the state of New Mexico and its three largest metropolitan statistical areas: Albuquerque, Las Cruces and Santa Fe. Quarterly data between 1983 and 2000 are utilized at the state level. For Albuquerque, annual data from 1983 through 1999 are used. For Las Cruces and Santa Fe, annual data from 1990 through 1999 are employed. Univariate time series, vector autoregressions and random walks are used as the comparison criteria against structural equation simulations. Results indicate that ex ante RSEM forecasts achieved higher accuracy than those simulations associated with univariate ARIMA and random walk benchmarks for the state of New Mexico. The track records of the structural econometric models for Albuquerque, Las Cruces and Santa Fe are less impressive. In some cases, VAR benchmarks prove more reliable than RSEM income forecasts. In other cases, the RSEM forecasts are less accurate than random walk alternatives. Copyright © 2005 John Wiley & Sons, Ltd.     

Range Extension and Channel Capacity Increase in Impulse-Radio Ultra-Wideband Communications

We theoretically analyze the channel capacity of a 5th-order Gaussian pulse-based ultra-wideband (UWB) system and experimentally demonstrate 2 Gbit/s UWB-over-fiber transmission systems incorporating wireless transmission. Both electrical and photonic UWB pulse generation methods are employed and its performance is compared. By utilizing optimum UWB pulse design and employing a digital signal processing (DSP) receiver, a bit-error-rate above the forward error correction (FEC) limit for 8 meters of wireless ...     

Prediction of final data with use of preliminary and/or revised data

In the case of US national accounts the data are revised for the first few years and every decade, which implies that we do not really have the final data. In this paper we aim to predict the final data, using the preliminary data and/or the revised data. The following predictors are introduced and derived from a context of the non-linear filtering or smoothing problem, which are: (1) prediction of the final data of time t given the preliminary data up to time t- 1, (2) prediction of the final data of time t given the preliminary data up to time t, (3) prediction of the final data of time t given the preliminary data up to time T, (4) prediction of the final data of time t given the revised data up to time t -1 and the preliminary data up to time t- 1, and (5) prediction of the final data of time t given the revised data up to time t-1 and the preliminary data up to time t. It is shown that (5) is the best predictor but not too different from (3). The prediction problem is illustrated using US per capita consumption data.     

Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis

Widespread demyelination and axonal loss are the pathological hallmarks of multiple sclerosis. The multifocal nature of this chronic inflammatory disease of the central nervous system complicates cellular therapy and puts emphasis on both the donor cell origin and the route of cell transplantation. We established syngenic adult neural stem cell cultures and injected them into an animal model of multiple sclerosis--experimental autoimmune encephalomyelitis (EAE) in the mouse--either intravenously or intracerebroventricularly. In both cases, significant numbers of donor cells entered into demyelinating areas of the central nervous system and differentiated into mature brain cells. Within these areas, oligodendrocyte progenitors markedly increased, with many of them being of donor origin and actively remyelinating axons. Furthermore, a significant reduction of astrogliosis and a marked decrease in the extent of demyelination and axonal loss were observed in transplanted animals. The functional impairment caused by EAE was almost abolished in transplanted mice, both clinically and neurophysiologically. Thus, adult neural precursor cells promote multifocal remyelination and functional recovery after intravenous or intrathecal injection in a chronic model of multiple sclerosis.