Respiratory Syncytial Virus Matrix Protein Induces Lung Epithelial Cell Cycle Arrest through a p53 Dependent Pathway

Respiratory syncytial virus (RSV) is the major cause of viral respiratory infections in children. Our previous study showed that the RSV infection induced lung epithelial cell cycle arrest, which enhanced virus replication. To address the mechanism of RSV-induced cell cycle arrest, we examined the contribution of RSV-matrix (RSV-M) protein. In this report, we show that in both the A549 cell line and primary human bronchial epithelial (PHBE) cells, transfection with RSV-M protein caused the cells to proliferate at a slower rate than in control cells. The cell cycle analysis showed that RSV-M protein induced G1 phase arrest in A549 cells, and G1 and G2/M phase arrest in PHBE cells. Interestingly, RSV-M expression induced p53 and p21 accumulation and decreased phosphorylation of retinoblastoma protein (Rb). Further, induction of cell cycle arrest by RSV-M was not observed in a p53-deficient epithelial cell line (H1299). However, cell cycle arrest was restored after transfection of p53 cDNA into H1299 cells. Taken together, these results indicate that RSV-M protein regulates lung epithelial cell cycle through a p53-dependent pathway, which enhances RSV replication

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Merton City Knowledge

This paper serves as a proposal to the London Borough of Merton as to why it should adopt a city planning and management concept called City Knowledge. The concept of City Knowledge is defined, explained and illustrated with examples from cities in Europe and the United States. It details how the idea is a change in the way a municipality should employ this scheme. Real life examples are used to show how City Knowledge could benefit the borough, with special attention to a case study involving safety in the Housing and Social Services Department. The situations are tailored in such a way that the reader can easily relate to them

Construction of a medicinal leech transcriptome database and its application to the identification of leech homologs of neural and innate immune genes

<p>Abstract</p> <p>Background</p> <p>The medicinal leech, <it>Hirudo medicinalis</it>, is an important model system for the study of nervous system structure, function, development, regeneration and repair. It is also a unique species in being presently approved for use in medical procedures, such as clearing of pooled blood following certain surgical procedures. It is a current, and potentially also future, source of medically useful molecular factors, such as anticoagulants and antibacterial peptides, which may have evolved as a result of its parasitizing large mammals, including humans. Despite the broad focus of research on this system, little has been done at the genomic or transcriptomic levels and there is a paucity of openly available sequence data. To begin to address this problem, we constructed whole embryo and adult central nervous system (CNS) EST libraries and created a clustered sequence database of the <it>Hirudo </it>transcriptome that is available to the scientific community.</p> <p>Results</p> <p>A total of ~133,000 EST clones from two directionally-cloned cDNA libraries, one constructed from mRNA derived from whole embryos at several developmental stages and the other from adult CNS cords, were sequenced in one or both directions by three different groups: Genoscope (French National Sequencing Center), the University of Iowa Sequencing Facility and the DOE Joint Genome Institute. These were assembled using the phrap software package into 31,232 unique contigs and singletons, with an average length of 827 nt. The assembled transcripts were then translated in all six frames and compared to proteins in NCBI's non-redundant (NR) and to the Gene Ontology (GO) protein sequence databases, resulting in 15,565 matches to 11,236 proteins in NR and 13,935 matches to 8,073 proteins in GO. Searching the database for transcripts of genes homologous to those thought to be involved in the innate immune responses of vertebrates and other invertebrates yielded a set of nearly one hundred evolutionarily conserved sequences, representing all known pathways involved in these important functions.</p> <p>Conclusions</p> <p>The sequences obtained for <it>Hirudo </it>transcripts represent the first major database of genes expressed in this important model system. Comparison of translated open reading frames (ORFs) with the other openly available leech datasets, the genome and transcriptome of <it>Helobdella robusta</it>, shows an average identity at the amino acid level of 58% in matched sequences. Interestingly, comparison with other available Lophotrochozoans shows similar high levels of amino acid identity, where sequences match, for example, 64% with <it>Capitella capitata </it>(a polychaete) and 56% with <it>Aplysia californica </it>(a mollusk), as well as 58% with <it>Schistosoma mansoni </it>(a platyhelminth). Phylogenetic comparisons of putative <it>Hirudo </it>innate immune response genes present within the <it>Hirudo </it>transcriptome database herein described show a strong resemblance to the corresponding mammalian genes, indicating that this important physiological response may have older origins than what has been previously proposed.</p

Réparation de poésie : 15e livre des artistes d'art postal : ...Où les grands esprits se rassemblent = Réparation de poésie : 15e livre des artistes d'art postal : ...Dove I spiriti grandi sincontranno = Réparation de poésie : 15e livre des artistes d'art postal : Where Great Spirits Gather

The 15th edition of this Quebec collective’s annual publication comprises Mail Art projects by 46 artists from six countries. The works, some of which include short poetic texts, employ drawing, collage, silkscreening, photocopying, painting, digital imagery, objects, postcards or recycled materials. Themes addressed include: the passage of time, sexuality, solidarity, reprography, agriculture and aesthetic taste. Texts primarily in French or English