We sequenced the 29,751-base genome of the severe acute respiratory syndrome (SARS)–associated coronavirus known as the Tor2 isolate. The genome sequence reveals that this coronavirus is only moderately related to other known coronaviruses, including two human coronaviruses, HCoV-OC43 and HCoV-229E. Phylogenetic analysis of the predicted viral proteins indicates that the virus does not closely resemble any of the three previously known groups of coronaviruses. The genome sequence will aid in the diagnosis of SARS virus infection in humans and potential animal hosts (using polymerase chain reaction and immunological tests), in the development of antivirals (including neutralizing antibodies), and in the identification of putative epitopes for vaccine development.

Programmed cell death (PCD), important in normal animal physiology and disease, can be divided into at least two morphological subtypes, including type I, or apoptosis, and type II, or autophagic cell death. While many molecules involved in apoptosis have been discovered and studied intensively during the past decade, autophagic cell death is not well characterized molecularly. Here we report the first comprehensive identification of molecules associated with autophagic cell death during normal metazoan development in vivo. During Drosophila metamorphosis, the larval salivary glands undergo autophagic cell death regulated by a hormonally induced transcriptional cascade. To identify and analyze the genes expressed, we examined wild-type patterns of gene expression in three predeath stages of Drosophila salivary glands using serial analysis of gene expression (SAGE) [7]. 1244 transcripts, including genes involved in autophagy, defense response, cytoskeleton remodeling, noncaspase proteolysis, and apoptosis, were expressed differentially prior to salivary gland death. Mutant expression analysis indicated that several of these genes were regulated by E93, a gene required for salivary gland cell death. Our analyses strongly support both the emerging notion that there is overlap with respect to the molecules involved in autophagic cell death and apoptosis, and that there are important differences.

Genome sequences of chicken (low pathogenic avian influenza [LPAI] and highly pathogenic avian influenza [HPAI]) and human isolates from a 2004 outbreak of H7N3 avian influenza in Canada showed a novel insertion in the HA0 cleavage site of the human and HPAI isolate. This insertion likely occurred by recombination between the hemagglutination and matrix genes in the LPAI virus.

Coxsackievirus B3 (CVB3) is a primary cause of viral myocarditis, yet no effective therapeutic against CVB3 is available. Nucleic acid-based interventional strategies against various viruses, including CVB3, have shown promise experimentally, but limited stability and inefficient delivery in vivo remain as obstacles to their potential as therapeutics. We employed phosphorodiamidate morpholino oligomers (PMO) conjugated to a cell-penetrating arginine-rich peptide, P007 (to form PPMO), to address these issues. Eight CVB3-specific PPMO were evaluated with HeLa cells and HL-1 cardiomyocytes in culture and in a murine infection model. One of the PPMO (PPMO-6), designed to target a sequence in the 3 portion of the CVB3 internal ribosomal entry site, was found to be especially potent against CVB3. Treatment of cells with PPMO-6 prior to CVB3 infection produced an approximately 3-log 10 decrease in viral titer and largely protected cells from a virusinduced cytopathic effect. A similar antiviral effect was observed when PPMO-6 treatment began shortly after the virus infection period. A/J mice receiving intravenous administration of PPMO-6 once prior to and once after CVB3 infection showed an ϳ2-log 10 -decreased viral titer in the myocardium at 7 days postinfection and a significantly decreased level of cardiac tissue damage, compared to the controls. Thus, PPMO-6 provided potent inhibition of CVB3 amplification both in cell cultures and in vivo and appears worthy of further evaluation as a candidate for clinical development.

Study characteristicsThis review included information from 13 randomized studies and combined results from 2122 patients to answer our question regarding survival. Key resultsThis review of 13 trials, including patients with esophageal cancer of any cell type, found some evidence that cisplatin-based chemotherapy may help them to live longer. However, chemotherapy may introduce side e ects. Quality of the evidenceThis review used information from randomized studies that is considered to represent the highest quality of evidence.

Preemptive administration of local anesthetic at the incision site reduces postoperative pain compared with placebo but achieves an analgesic effect similar to that of postincisional anesthetic infiltration. Preemptive local anesthetic administered intraperitoneally decreases postoperative pain compared with both placebo and postoperative infiltration. Surgeons should use local analgesia in laparoscopic surgery to decrease postoperative pain, but the timing of administration is significant only for intraperitoneal infiltration.

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The Mammalian Gene Collection (MGC) consortium (http://mgc.nci.nih.gov) seeks to establish publicly available collections of full-ORF cDNAs for several organisms of significance to biomedical research, including human. To date over 15,200 human cDNA clones containing full-length open reading frames (ORFs) have been identified via systematic expressed sequence tag (EST) analysis of a diverse set of cDNA libraries; however, further systematic EST analysis is no longer an efficient method for identifying new cDNAs. As part of our involvement in the MGC program, we have developed a scalable method for targeted recovery of cDNA clones to facilitate recovery of genes absent from the MGC collection. First, cDNA is synthesized from various RNAs, followed by polymerase chain reaction (PCR) amplification of transcripts in 96-well plates using gene-specific primer pairs flanking the ORFs. Amplicons are cloned into a sequencing vector, and full-length sequences are obtained. Sequences are processed and assembled using Phred and Phrap, and analyzed using Consed and a number of bioinformatics methods we have developed. Sequences are compared with the Reference Sequence (RefSeq) database, and validation of sequence discrepancies is attempted using other sequence databases including dbEST and dbSNP. Clones with identical sequence to RefSeq or containing only validated changes will become part of the MGC human gene collection. Clones containing novel splice variants or polymorphisms have also been identified. Our approach to clone recovery, applied at large scale, has the potential to recover many and possibly most of the genes absent from the MGC collection.[Supplemental material is available online at www.genome.org and www.bcgsc.ca/bioinfo/MGC.]A full-open reading frame (ORF) cDNA clone provides the best experimental evidence of transcription, transcript processing, and gene structure. Other approaches for identification of transcribed genomic regions, such as automated gene predictions and expressed sequence tag (EST) data provide useful information; however, computational gene predictions are not fully accurate, and EST data are error-prone and usually only sample a portion of transcripts. The availability of full-ORF cDNA sequence data for all genes within a species would be a key resource for identifying coding regions within the genome, determining the structure of genes including identification of splice variants, and understanding the proteome. Furthermore, access to the cDNA clones would facilitate functional studies of genes and corresponding proteins.The Mammalian Gene Collection (MGC; http:// mgc.nci.nih.gov) project aims to generate a public resource of full-ORF cDNA clones for various species, including human, mouse, and rat (Strausberg et al. 1999(Strausberg et al. , 2002. For human and mouse, significant progress towards these goals has already been achieved via generating and characterizing cDNA libraries originating from a broad variety of tissues and cell lines. In the current paradigm, libraries enriched fo...