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Clinical features of culture-proven Mycoplasma pneumoniae infections at King Abdulaziz University Hospital, Jeddah, Saudi Arabia
OBJECTIVE: This retrospective chart review describes the epidemiology and clinical features of 40 patients with culture-proven Mycoplasma pneumoniae infections at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. METHODS: Patients with positive M. pneumoniae cultures from respiratory specimens from January 1997...
Mycoplasma pneumoniae is a common cause of upper and lower respiratory tract infections. It remains one of the most frequent causes of atypical pneumonia particu-larly among young adults. [1, 2, 3, 4, 5] Although it is highly transmissible, most infections caused by this organism are relatively minor and include pharyn...
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Nitric oxide: a pro-inflammatory mediator in lung disease?
Inflammatory diseases of the respiratory tract are commonly associated with elevated production of nitric oxide (NO•) and increased indices of NO• -dependent oxidative stress. Although NO• is known to have anti-microbial, anti-inflammatory and anti-oxidant properties, various lines of evidence support the contribution ...
Since its discovery as a biological messenger molecule more than 10 years ago, the gaseous molecule nitric oxide (NO • ) is now well recognized for its involvement in diverse biological processes, including vasodilation, bronchodilation, neurotransmission, tumor surveillance, antimicrobial defense and regulation of inf...
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Nitric oxide: a pro-inflammatory mediator in lung disease?
Inflammatory diseases of the respiratory tract are commonly associated with elevated production of nitric oxide (NO•) and increased indices of NO• -dependent oxidative stress. Although NO• is known to have anti-microbial, anti-inflammatory and anti-oxidant properties, various lines of evidence support the contribution ...
the site, time and degree of NO • production in relation to the local redox status, and the acute or chronic nature of the immune response. In addition, our current understanding of the pro-inflammatory or pro-injurious mechanisms of NO • or related RNS is incomplete; this commentary will focus primarily on these latte...
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Surfactant protein-D and pulmonary host defense
Surfactant protein-D (SP-D) participates in the innate response to inhaled microorganisms and organic antigens, and contributes to immune and inflammatory regulation within the lung. SP-D is synthesized and secreted by alveolar and bronchiolar epithelial cells, but is also expressed by epithelial cells lining various e...
Surfactant protein-D (SP-D) is a member of the collagenous subfamily of calcium-dependent lectins (collectins) that includes pulmonary surfactant protein A (SP-A) and the serum mannose-binding lectin [1] [2] [3] . Collectins inter-act with a wide variety of microorganisms, lipids, and organic particulate antigens, and ...
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Gene expression in epithelial cells in response to pneumovirus infection
Respiratory syncytial virus (RSV) and pneumonia virus of mice (PVM) are viruses of the family Paramyxoviridae, subfamily pneumovirus, which cause clinically important respiratory infections in humans and rodents, respectively. The respiratory epithelial target cells respond to viral infection with specific alterations ...
RSV and PVM are viruses of the family Paramyxoviridae, subfamily pneumovirus; they are enveloped, singlestranded, nonsegmented RNA viruses that can cause intense viral bronchiolitis in humans and mice, respectively. In its most severe form, the lower respiratory tract infection caused by pneumoviruses is associated wit...
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Sequence requirements for RNA strand transfer during nidovirus discontinuous subgenomic RNA synthesis
Nidovirus subgenomic mRNAs contain a leader sequence derived from the 5′ end of the genome fused to different sequences (‘bodies’) derived from the 3′ end. Their generation involves a unique mechanism of discontinuous subgenomic RNA synthesis that resembles copy-choice RNA recombination. During this process, the nascen...
The genetic information of RNA viruses is organized very ef®ciently. Practically every nucleotide of their genome is utilized, either as protein-coding sequence or as cis-acting signals for translation, RNA synthesis or RNA encapsidation. As part of their genome expression strategy, several groups of positive-strand RN...
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Sequence requirements for RNA strand transfer during nidovirus discontinuous subgenomic RNA synthesis
Nidovirus subgenomic mRNAs contain a leader sequence derived from the 5′ end of the genome fused to different sequences (‘bodies’) derived from the 3′ end. Their generation involves a unique mechanism of discontinuous subgenomic RNA synthesis that resembles copy-choice RNA recombination. During this process, the nascen...
non-contiguous parts of the nidovirus genome during sg RNA synthesis ( Figure 1B and C). Central to each of these models are short transcription-regulating sequences (TRSs), which are present both at the 3¢ end of the leader and at the 5¢ end of the sg RNA body regions in the genomic RNA. The TRS is copied into the mRN...
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Sequence requirements for RNA strand transfer during nidovirus discontinuous subgenomic RNA synthesis
Nidovirus subgenomic mRNAs contain a leader sequence derived from the 5′ end of the genome fused to different sequences (‘bodies’) derived from the 3′ end. Their generation involves a unique mechanism of discontinuous subgenomic RNA synthesis that resembles copy-choice RNA recombination. During this process, the nascen...
the fulllength minus strand. Sequence requirements for RNA strand transfer during nidovirus discontinuous subgenomic RNA synthesis The EMBO Journal Vol. 20 No. 24 pp. 7220±7228, 2001 Using site-directed mutagenesis of TRSs of the arterivirus equine arteritis virus (EAV), we have shown previously that base pairing betwe...
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Crystal structure of murine sCEACAM1a[1,4]: a coronavirus receptor in the CEA family
CEACAM1 is a member of the carcinoembryonic antigen (CEA) family. Isoforms of murine CEACAM1 serve as receptors for mouse hepatitis virus (MHV), a murine coronavirus. Here we report the crystal structure of soluble murine sCEACAM1a[1,4], which is composed of two Ig-like domains and has MHV neutralizing activity. Its N-...
Carcinoembryonic antigen (CEA; CD66e) was initially discovered as a tumor antigen (Gold and Freedman, 1965) . A large group of related glycoproteins within the Ig superfamily (IgSF) is now called the CEA family. These anchored or secreted glycoproteins are expressed by epithelial cells, leukocytes, endothelial cells an...
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Crystal structure of murine sCEACAM1a[1,4]: a coronavirus receptor in the CEA family
CEACAM1 is a member of the carcinoembryonic antigen (CEA) family. Isoforms of murine CEACAM1 serve as receptors for mouse hepatitis virus (MHV), a murine coronavirus. Here we report the crystal structure of soluble murine sCEACAM1a[1,4], which is composed of two Ig-like domains and has MHV neutralizing activity. Its N-...
for the ecto-domain and the modulation of gene expression by CEACAM1 signaling are not well understood. All four isoforms of murine CEACAM1a, as well as murine CEACAM2, can serve as receptors for mouse hepatitis virus (MHV) strain A59 (MHV-A59) when the recombinant murine proteins are expressed at high levels in a hams...
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Synthesis of a novel hepatitis C virus protein by ribosomal frameshift
Hepatitis C virus (HCV) is an important human pathogen that affects ∼100 million people worldwide. Its RNA genome codes for a polyprotein, which is cleaved by viral and cellular proteases to produce at least 10 mature viral protein products. We report here the discovery of a novel HCV protein synthesized by ribosomal f...
Hepatitis C virus (HCV) is a positive-stranded RNA virus with a genome size of~9.6 kb. Infection by this virus frequently leads to chronic infection, which in turn may lead to severe liver diseases including liver cirrhosis and hepatocellular carcinoma. The ®rst HCV genomic sequence, which was named the HCV-1 sequence,...
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Synthesis of a novel hepatitis C virus protein by ribosomal frameshift
Hepatitis C virus (HCV) is an important human pathogen that affects ∼100 million people worldwide. Its RNA genome codes for a polyprotein, which is cleaved by viral and cellular proteases to produce at least 10 mature viral protein products. We report here the discovery of a novel HCV protein synthesized by ribosomal f...
this 17 kDa protein was unclear, and it was thought to be a truncated core protein. In this report, we demonstrate that this 17 kDa protein is synthesized by ribosomal frameshift and is derived mostly from the coding sequence that overlaps the core protein reading frame. This protein is highly conserved among different...
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Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra α-helical domain
The key enzyme in coronavirus polyprotein processing is the viral main proteinase, M(pro), a protein with extremely low sequence similarity to other viral and cellular proteinases. Here, the crystal structure of the 33.1 kDa transmissible gastroenteritis (corona)virus M(pro) is reported. The structure was refined to 1....
Transmissible gastroenteritis virus (TGEV) belongs to the Coronaviridae, a family of positive-strand RNA viruses. Coronaviruses have the largest RNA viral genomes known to date (28 500 nucleotides in the case of TGEV) and share a similar genome organization and common transcriptional and translational strategies with t...
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Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra α-helical domain
The key enzyme in coronavirus polyprotein processing is the viral main proteinase, M(pro), a protein with extremely low sequence similarity to other viral and cellular proteinases. Here, the crystal structure of the 33.1 kDa transmissible gastroenteritis (corona)virus M(pro) is reported. The structure was refined to 1....
coronavirus main proteinases. Because of the large phylogenetic distance between the two groups of enzymes, we will use the term coronavirus M pro throughout this article. Sequence comparisons ( Figure 1 ) and experimental data obtained for other coronavirus homologues allow us to predict that the mature form of the TG...
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Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra α-helical domain
The key enzyme in coronavirus polyprotein processing is the viral main proteinase, M(pro), a protein with extremely low sequence similarity to other viral and cellular proteinases. Here, the crystal structure of the 33.1 kDa transmissible gastroenteritis (corona)virus M(pro) is reported. The structure was refined to 1....
at the P2 position, glutamine at the P1 position, and small Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra a-helical domain The EMBO Journal Vol. 21 No. 13 pp. 3213±3224, 2002 ã European Molecular Biology Organization aliphatic residues at the P1¢ position. (iii) Coron...
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Discontinuous and non-discontinuous subgenomic RNA transcription in a nidovirus
Arteri-, corona-, toro- and roniviruses are evolutionarily related positive-strand RNA viruses, united in the order Nidovirales. The best studied nidoviruses, the corona- and arteriviruses, employ a unique transcription mechanism, which involves discontinuous RNA synthesis, a process resembling similarity-assisted copy...
Positive (+)-strand RNA viruses have developed a wide range of strategies to express their genes. One recurring strategy, employed by many non-related viruses, entails the synthesis of subgenomic (sg) mRNAs (Miller and Koev, 2000) . While the genome invariably serves as the mRNA for the viral replicase, the sgRNAs medi...
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i0zym7iq
Discontinuous and non-discontinuous subgenomic RNA transcription in a nidovirus
Arteri-, corona-, toro- and roniviruses are evolutionarily related positive-strand RNA viruses, united in the order Nidovirales. The best studied nidoviruses, the corona- and arteriviruses, employ a unique transcription mechanism, which involves discontinuous RNA synthesis, a process resembling similarity-assisted copy...
genome are taken up by the replicase polyprotein gene. Downstream, there are multiple smaller genes, which are expressed from a nested set of up to eight sg mRNAs. In the case of the arteri-and coronaviruses, these sg mRNAs are chimeric and both 3¢-and 5¢-coterminal with the genome: they all possess a 5¢ common leader ...
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i0zym7iq
Discontinuous and non-discontinuous subgenomic RNA transcription in a nidovirus
Arteri-, corona-, toro- and roniviruses are evolutionarily related positive-strand RNA viruses, united in the order Nidovirales. The best studied nidoviruses, the corona- and arteriviruses, employ a unique transcription mechanism, which involves discontinuous RNA synthesis, a process resembling similarity-assisted copy...
1991) and serve as templates for transcription (Sawicki and Sawicki, 1990) , has led to an alternative model, in which discontinuous transcription takes place during minus-strand synthesis (Sawicki and Sawicki, 1990 . This latter view is gaining increasing experimental support (Schaad and Baric, 1994; Chang et al., 199...
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i0zym7iq
Discontinuous and non-discontinuous subgenomic RNA transcription in a nidovirus
Arteri-, corona-, toro- and roniviruses are evolutionarily related positive-strand RNA viruses, united in the order Nidovirales. The best studied nidoviruses, the corona- and arteriviruses, employ a unique transcription mechanism, which involves discontinuous RNA synthesis, a process resembling similarity-assisted copy...
replicase gene and there is no obvious TRS; a related motif, UGUUUAGU, was postulated to direct the synthesis of mRNA 2 (Snijder et al., 1990b,c) . Snijder et al. (1990c) characterized the 5¢ end of BEV mRNA 5 by primer extension and hybridization analysis. A comparison with the putative 5¢ end of the BEV genome, as de...
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Debate: Transfusing to normal haemoglobin levels will not improve outcome
Recent evidence suggests that critically ill patients are able to tolerate lower levels of haemoglobin than was previously believed. It is our goal to show that transfusing to a level of 100 g/l does not improve mortality and other clinically important outcomes in a critical care setting. Although many questions remain...
Anaemia is a common condition in critically ill patients, and RBC transfusions are often used in the treatment and management of this patient population. In fact, one study [1] reported that 25% of all critically ill patients received RBC transfusions. Many laboratory studies [2] [3] [4] [5] [6] [7] [8] have examined t...
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Debate: Transfusing to normal haemoglobin levels will not improve outcome
Recent evidence suggests that critically ill patients are able to tolerate lower levels of haemoglobin than was previously believed. It is our goal to show that transfusing to a level of 100 g/l does not improve mortality and other clinically important outcomes in a critical care setting. Although many questions remain...
outcomes in a critical care setting. We first explore the reasons why a reduction in the total number of allogeneic blood transfusions would be beneficial. Second, we examine the current evidence for using a lower transfusion strategy, specifically that employed in the Transfusion Requirements In Critical Care (TRICC) ...
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The 21st International Symposium on Intensive Care and Emergency Medicine, Brussels, Belgium, 20-23 March 2001
The 21st International Symposium on Intensive Care and Emergency Medicine was dominated by the results of recent clinical trials in sepsis and acute respiratory distress syndrome (ARDS). The promise of extracorporeal liver replacement therapy and noninvasive ventilation were other areas of interest. Ethical issues also...
This year's symposium was dominated by the results of recent clinical trials. After 10 years of 'magic bullet' trials in sepsis, a number of successful therapeutic options are now emerging. In addition, recent advances in our understanding of the soup of mediators observed in sepsis offer yet more tantalizing targets f...
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0m32ecnu
Prokaryotic-style frameshifting in a plant translation system: conservation of an unusual single-tRNA slippage event
Ribosomal frameshifting signals are found in mobile genetic elements, viruses and cellular genes of prokaryotes and eukaryotes. Typically they comprise a slippery sequence, X XXY YYZ, where the frameshift occurs, and a stimulatory mRNA element. Here we studied the influence of host translational environment and the ide...
The elongation phase of protein synthesis is a precise process and mechanisms exist to promote translational ®delity (reviewed in Czworkowski and Moore, 1996) . However, a growing number of examples have been described of highly ef®cient`programmed' frameshift sites (see Farabaugh, 1996 Farabaugh, , 2000 . Such framesh...
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0m32ecnu
Prokaryotic-style frameshifting in a plant translation system: conservation of an unusual single-tRNA slippage event
Ribosomal frameshifting signals are found in mobile genetic elements, viruses and cellular genes of prokaryotes and eukaryotes. Typically they comprise a slippery sequence, X XXY YYZ, where the frameshift occurs, and a stimulatory mRNA element. Here we studied the influence of host translational environment and the ide...
al., 1994; Rettberg et al., 1999) . The slippery sequence consists of two homopolymeric triplets, conforming in the vast majority of cases to the motif X-XXY-YYZ. Frameshifting at this sequence is thought to occur by simultaneous (also referred to as`dual' or`tandem') slippage of the peptidyl and aminoacyl tRNAs, which...
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0m32ecnu
Prokaryotic-style frameshifting in a plant translation system: conservation of an unusual single-tRNA slippage event
Ribosomal frameshifting signals are found in mobile genetic elements, viruses and cellular genes of prokaryotes and eukaryotes. Typically they comprise a slippery sequence, X XXY YYZ, where the frameshift occurs, and a stimulatory mRNA element. Here we studied the influence of host translational environment and the ide...
al., 1992) . In mechanistic terms, the position of the tRNAs during the slippage event is a key issue. Evidence supports the view that in the vast majority of cases, the slippery sequence-decoding tRNAs are present in the P-and A-sites of the ribosome (see Atkins et al., 2001 for a review). However, there are a few exc...
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0m32ecnu
Prokaryotic-style frameshifting in a plant translation system: conservation of an unusual single-tRNA slippage event
Ribosomal frameshifting signals are found in mobile genetic elements, viruses and cellular genes of prokaryotes and eukaryotes. Typically they comprise a slippery sequence, X XXY YYZ, where the frameshift occurs, and a stimulatory mRNA element. Here we studied the influence of host translational environment and the ide...
An investigation into the functionality of the frameshift signal of the coronavirus infectious bronchitis virus (IBV; U-UUA-AAC) in E.coli revealed that a variant with slippery sequence U-CUA-AAG was highly active (40%) (Brierley et al., 1997) , despite possessing a slippery sequence which should allow only a single-tR...
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0m32ecnu
Prokaryotic-style frameshifting in a plant translation system: conservation of an unusual single-tRNA slippage event
Ribosomal frameshifting signals are found in mobile genetic elements, viruses and cellular genes of prokaryotes and eukaryotes. Typically they comprise a slippery sequence, X XXY YYZ, where the frameshift occurs, and a stimulatory mRNA element. Here we studied the influence of host translational environment and the ide...
it is the tRNAs themselves that are the main determinants in the selection of a single-or dual-tRNA slippage mechanism. Models for the disposition of tRNAs on the ribosome during the unusual single-tRNA slip are discussed. Inokuchi and Yamao (1995) . b Within the context of a programmed ±1 ribosomal frameshift. nd, not...
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Heme oxygenase-1 and carbon monoxide in pulmonary medicine
Heme oxygenase-1 (HO-1), an inducible stress protein, confers cytoprotection against oxidative stress in vitro and in vivo. In addition to its physiological role in heme degradation, HO-1 may influence a number of cellular processes, including growth, inflammation, and apoptosis. By virtue of anti-inflammatory effects,...
The heme oxygenase-1/carbon monoxide (HO-1/CO) system has recently seen an explosion of research interest due to its newly discovered physiological effects. This metabolic pathway, first characterized by Tenhunen et al. [1, 2] , has only recently revealed its surprising cytoprotective properties [3, 4] . Research in HO...
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8qnrcgnk
Heme oxygenase-1 and carbon monoxide in pulmonary medicine
Heme oxygenase-1 (HO-1), an inducible stress protein, confers cytoprotection against oxidative stress in vitro and in vivo. In addition to its physiological role in heme degradation, HO-1 may influence a number of cellular processes, including growth, inflammation, and apoptosis. By virtue of anti-inflammatory effects,...
has little enzymatic activity [27] . This review will focus on the inducible, HO-1, form. In addition to the physiological substrate heme, HO-1 responds to induction by a wide variety of stimuli associated with oxidative stress. Such inducing agents include hypoxia, hyperoxia, cytokines, nitric oxide (NO), heavy metals...
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8qnrcgnk
Heme oxygenase-1 and carbon monoxide in pulmonary medicine
Heme oxygenase-1 (HO-1), an inducible stress protein, confers cytoprotection against oxidative stress in vitro and in vivo. In addition to its physiological role in heme degradation, HO-1 may influence a number of cellular processes, including growth, inflammation, and apoptosis. By virtue of anti-inflammatory effects,...
(E1, E2) in the murine HO-1 gene located at -4 kb (E1) and -10 kbp (E2) of the transcriptional start site [37, 38] . These enhancers mediate the induction of HO-1 by many agents, including heavy metals, phorbol esters, endotoxin, oxidants, and heme. E1 and E2 contain repeated stress-responsive elements, which consist o...
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SseG, a virulence protein that targets Salmonella to the Golgi network
Intracellular replication of the bacterial pathogen Salmonella enterica occurs in membrane-bound compartments called Salmonella-containing vacuoles (SCVs). Maturation of the SCV has been shown to occur by selective interactions with the endocytic pathway. We show here that after invasion of epithelial cells and migrati...
Salmonella enterica serovar Typhimurium (S.typhimurium) is a bacterial pathogen that invades and replicates within a membrane-bound compartment (Salmonellacontaining vacuole; SCV) inside a variety of host cell types. The biogenesis and maturation of the SCV has been studied in detail in both macrophages and epithelial ...
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SseG, a virulence protein that targets Salmonella to the Golgi network
Intracellular replication of the bacterial pathogen Salmonella enterica occurs in membrane-bound compartments called Salmonella-containing vacuoles (SCVs). Maturation of the SCV has been shown to occur by selective interactions with the endocytic pathway. We show here that after invasion of epithelial cells and migrati...
Hensel et al., 1998) . This TTSS translocates effector proteins into the vacuolar membrane and cytosol of the host cell. Several effectors have been identi®ed in recent years, encoded both within and outside the pathogenicity island. SpiC is a SPI-2-encoded protein that prevents interactions between SCVs and endocytic ...
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Viral Discovery and Sequence Recovery Using DNA Microarrays
Because of the constant threat posed by emerging infectious diseases and the limitations of existing approaches used to identify new pathogens, there is a great demand for new technological methods for viral discovery. We describe herein a DNA microarray-based platform for novel virus identification and characterizatio...
Over the past two decades, technological advances in molecular biology have fuelled progress in the discovery of new pathogens associated with human diseases. The identification of novel viruses such as hepatitis C virus (Choo et al. 1989 ), sin nombre virus (Nichol et al. 1993) , and Kaposi's sarcoma herpesvirus (Chan...
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yy96yeu9
Viral Discovery and Sequence Recovery Using DNA Microarrays
Because of the constant threat posed by emerging infectious diseases and the limitations of existing approaches used to identify new pathogens, there is a great demand for new technological methods for viral discovery. We describe herein a DNA microarray-based platform for novel virus identification and characterizatio...
the global effort to identify a novel virus associated with severe acute respiratory syndrome (SARS) in March 2003, as reported by Ksiazek et al. (2003) . We describe here the experimental details of the microarray methodology for novel virus identification, using the SARS outbreak as an example.
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Conservation of polyamine regulation by translational frameshifting from yeast to mammals
Regulation of ornithine decarboxylase in vertebrates involves a negative feedback mechanism requiring the protein antizyme. Here we show that a similar mechanism exists in the fission yeast Schizosaccharomyces pombe. The expression of mammalian antizyme genes requires a specific +1 translational frameshift. The efficie...
The ef®ciency of +1 ribosomal frameshifting at a speci®c codon is used as a sensor to regulate polyamine levels in mammalian cells. The frameshifting occurs in decoding the gene antizyme 1, which has two partially overlapping open reading frames (ORFs). Protein sequencing showed that the reading-frame shift occurs at t...
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5tkvsudh
Conservation of polyamine regulation by translational frameshifting from yeast to mammals
Regulation of ornithine decarboxylase in vertebrates involves a negative feedback mechanism requiring the protein antizyme. Here we show that a similar mechanism exists in the fission yeast Schizosaccharomyces pombe. The expression of mammalian antizyme genes requires a specific +1 translational frameshift. The efficie...
(Ivanov et al., 1998a; Zhu et al., 1999; Y.Murakami, S.Matsufuji, I.P.Ivanov, R.F.Gesteland and J.F.Atkins, in preparation) . Just like antizyme 1, antizyme 2 mRNA is ubiquitously expressed in the body but is 16 times less abundant than mRNA of antizyme 1 (Ivanov et al., 1998a) . In addition to antizyme 1 and 2, mammal...
5tkvsudh_chunk_2
5tkvsudh
Conservation of polyamine regulation by translational frameshifting from yeast to mammals
Regulation of ornithine decarboxylase in vertebrates involves a negative feedback mechanism requiring the protein antizyme. Here we show that a similar mechanism exists in the fission yeast Schizosaccharomyces pombe. The expression of mammalian antizyme genes requires a specific +1 translational frameshift. The efficie...
al., 1997; Lee et al., 1999) . Spermine negatively regulates the growth of prostatic carcinoma cells at their primary site (Smith et al., 1995) , but at later stages of tumor progression it fails to induce antizyme, which correlates with cells becoming refractory to spermine (Koike et al., 1999) . Lack of antizyme func...
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5tkvsudh
Conservation of polyamine regulation by translational frameshifting from yeast to mammals
Regulation of ornithine decarboxylase in vertebrates involves a negative feedback mechanism requiring the protein antizyme. Here we show that a similar mechanism exists in the fission yeast Schizosaccharomyces pombe. The expression of mammalian antizyme genes requires a specific +1 translational frameshift. The efficie...
an ef®ciency of 20% or more, it is important that the 3¢ base of the quadruplet is the ®rst base of a stop codon. Other important features are a pseudoknot just 3¢ of the shift site and a speci®c sequence 5¢ of the shift site (Matsufuji et al., 1995; Ivanov et al., 1998a) . A pseudoknot 3¢ of the shift site is a common...
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tvxpckxo
A Method to Identify p62's UBA Domain Interacting Proteins
The UBA domain is a conserved sequence motif among polyubiquitin binding proteins. For the first time, we demonstrate a systematic, high throughput approach to identification of UBA domain-interacting proteins from a proteome-wide perspective. Using the rabbit reticulocyte lysate in vitro expression cloning system, we ...
p62 is a novel cellular protein which was initially identified in humans as a phosphotyrosine independent ligand of the src homology 2 (SH2) domain of p56 lck (1, 2) . p56 lck is a member of the c-src family of cytoplasmic tyrosine kinases that is found predominantly in cells of lymphoid origin (3, 4) . In addition to ...
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tvxpckxo
A Method to Identify p62's UBA Domain Interacting Proteins
The UBA domain is a conserved sequence motif among polyubiquitin binding proteins. For the first time, we demonstrate a systematic, high throughput approach to identification of UBA domain-interacting proteins from a proteome-wide perspective. Using the rabbit reticulocyte lysate in vitro expression cloning system, we ...
is one way in which those proteins are targeted to the proteasome for subsequent rapid degradation. This mechanism is particularly important for short-lived regulatory proteins such as cyclins, cyclin-dependent protein kinase-inhibitors, p53, the nuclear factor kappa B precursor, and IκB (13) . The ubiquitinproteasome ...
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tvxpckxo
A Method to Identify p62's UBA Domain Interacting Proteins
The UBA domain is a conserved sequence motif among polyubiquitin binding proteins. For the first time, we demonstrate a systematic, high throughput approach to identification of UBA domain-interacting proteins from a proteome-wide perspective. Using the rabbit reticulocyte lysate in vitro expression cloning system, we ...
and differentiation. We have developed a method that will enable identification of protein(s) that interact with p62's UBA domain.
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Vaccinia virus infection disrupts microtubule organization and centrosome function
We examined the role of the microtubule cytoskeleton during vaccinia virus infection. We found that newly assembled virus particles accumulate in the vicinity of the microtubule-organizing centre in a microtubule- and dynein–dynactin complex-dependent fashion. Microtubules are required for efficient intracellular matur...
Intracellular bacterial and viral pathogens have evolved numerous mechanisms to appropriate and exploit different systems of the host during their life cycles in order to facilitate their spread during entry and exit from the host (Cudmore et al., 1997; Finlay and Cossart, 1997; Dramsi and Cossart, 1998) . In the case ...
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mcuixluu
Vaccinia virus infection disrupts microtubule organization and centrosome function
We examined the role of the microtubule cytoskeleton during vaccinia virus infection. We found that newly assembled virus particles accumulate in the vicinity of the microtubule-organizing centre in a microtubule- and dynein–dynactin complex-dependent fashion. Microtubules are required for efficient intracellular matur...
et al., 1992; Isaacs et al., 1992) and F13L (Hirt et al., 1986) , have been identi®ed. Studies using recombinant viruses have shown that A33R, A34R, B5R and F13L play an important role in IEV assembly (Blasco and Moss, 1991; Engelstad and Smith, 1993; Wolffe et al., 1993 Wolffe et al., , 1997 Roper et al., 1998; Sander...
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mcuixluu
Vaccinia virus infection disrupts microtubule organization and centrosome function
We examined the role of the microtubule cytoskeleton during vaccinia virus infection. We found that newly assembled virus particles accumulate in the vicinity of the microtubule-organizing centre in a microtubule- and dynein–dynactin complex-dependent fashion. Microtubules are required for efficient intracellular matur...
of vaccinia actin-based motility, cell to cell spread still occurs although it is less ef®cient (Wolffe et al., 1997 Sanderson et al., 1998a) , suggesting that additional transport mechanisms must exist. Given these observations, we wondered whether the microtubule cytoskeleton has a function during the life Vaccinia v...
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Towards evidence-based, GIS-driven national spatial health information infrastructure and surveillance services in the United Kingdom
The term "Geographic Information Systems" (GIS) has been added to MeSH in 2003, a step reflecting the importance and growing use of GIS in health and healthcare research and practices. GIS have much more to offer than the obvious digital cartography (map) functions. From a community health perspective, GIS could potent...
"A new wave of technological innovation is allowing us to capture, store, process and display an unprecedented amount of information about our planet and a wide variety of environmental and cultural phenomena. Much of this information will be 'geo-referenced' -that is, it will refer to some specific place on the Earth'...
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Towards evidence-based, GIS-driven national spatial health information infrastructure and surveillance services in the United Kingdom
The term "Geographic Information Systems" (GIS) has been added to MeSH in 2003, a step reflecting the importance and growing use of GIS in health and healthcare research and practices. GIS have much more to offer than the obvious digital cartography (map) functions. From a community health perspective, GIS could potent...
expending large funds and efforts. Ideally, the tools to achieve this goal should be accessible and usable by mainstream practitioners, transparently embedded into routine workflows, and seamlessly incorporated into existing busy work environments [4] .
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Recently published papers: all the usual suspects and carbon dioxide
Looking back over 2003, two themes have dominated the critical care literature. The year started with severe acute respiratory syndrome and ended with reports of an influenza epidemic. In between, the threat of a biological weapon attack escalated then, thankfully, rescinded. The second theme has been the publication o...
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Herpes simplex virus type 1 and normal protein permeability in the lungs of critically ill patients: a case for low pathogenicity?
INTRODUCTION: The pathogenicity of late respiratory infections with herpes simplex virus type 1 (HSV-1) in the critically ill is unclear. METHODS: In four critically ill patients with persistent pulmonary infiltrates of unknown origin and isolation of HSV-1 from tracheal aspirate or bronchoalveolar lavage fluid, at 7 (...
In some critically ill patients herpes simplex virus (HSV)-1 is isolated from the upper or lower respiratory tract [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] . Immunodepressed patients may be susceptible to transmission and acquisition of viral diseases; alternatively, viral reactivation may occu...
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Herpes simplex virus type 1 and normal protein permeability in the lungs of critically ill patients: a case for low pathogenicity?
INTRODUCTION: The pathogenicity of late respiratory infections with herpes simplex virus type 1 (HSV-1) in the critically ill is unclear. METHODS: In four critically ill patients with persistent pulmonary infiltrates of unknown origin and isolation of HSV-1 from tracheal aspirate or bronchoalveolar lavage fluid, at 7 (...
the pulmonary leak index (PLI) could help in determining the extent of tissue injury, as was previously described [18] [19] [20] . This radionuclide technique involves gallium-67-labelled transferrin ( 67 Gatransferrin) and technetium-99m-labelled red blood cells ( 99m Tc-RBCs). In bacterial pneumonia, for instance, th...
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Proteomics computational analyses suggest that the carboxyl terminal glycoproteins of Bunyaviruses are class II viral fusion protein (beta-penetrenes)
The Bunyaviridae family of enveloped RNA viruses includes five genuses, orthobunyaviruses, hantaviruses, phleboviruses, nairoviruses and tospoviruses. It has not been determined which Bunyavirus protein mediates virion:cell membrane fusion. Class II viral fusion proteins (beta-penetrenes), encoded by members of the Alp...
Two classes of viral envelope proteins that mediate virion:cell fusion have been described. Class I and II fusion proteins (aka α-and β-penetrenes) are distinguished, in part, by the location of the "fusion peptide," a cluster of hydrophobic and aromatic amino acids that appears critical for fusing viral and cell membr...
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Proteomics computational analyses suggest that the carboxyl terminal glycoproteins of Bunyaviruses are class II viral fusion protein (beta-penetrenes)
The Bunyaviridae family of enveloped RNA viruses includes five genuses, orthobunyaviruses, hantaviruses, phleboviruses, nairoviruses and tospoviruses. It has not been determined which Bunyavirus protein mediates virion:cell membrane fusion. Class II viral fusion proteins (beta-penetrenes), encoded by members of the Alp...
common fusion mechanism [9] [10] [11] . Based on sequence similarities, it is likely that E1 of other Alphaviruses and E of other members of the flavivirus genus within the family Flaviviridae are also class II fusion proteins. Members of the two other genuses in the Flaviviridae, hepaciviruises and pestiviruses, appea...
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Proteomics computational analyses suggest that the carboxyl terminal glycoproteins of Bunyaviruses are class II viral fusion protein (beta-penetrenes)
The Bunyaviridae family of enveloped RNA viruses includes five genuses, orthobunyaviruses, hantaviruses, phleboviruses, nairoviruses and tospoviruses. It has not been determined which Bunyavirus protein mediates virion:cell membrane fusion. Class II viral fusion proteins (beta-penetrenes), encoded by members of the Alp...
(hypothetical protein Y75D11A.5, NP508324). We also compared Bunyavirus M sequences to structural proteins of Flaviviruses, including members of the flavivirus genus tick-borne encephalitis virus, strain Neudoerfl (TBEV, P14336); Japanese encephalitis virus, strain JaOARS982 (JEV, P32886), yellow fever virus, strain 17...
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The Structure of a Rigorously Conserved RNA Element within the SARS Virus Genome
We have solved the three-dimensional crystal structure of the stem-loop II motif (s2m) RNA element of the SARS virus genome to 2.7-Å resolution. SARS and related coronaviruses and astroviruses all possess a motif at the 3′ end of their RNA genomes, called the s2m, whose pathogenic importance is inferred from its rigoro...
The virus that causes SARS, like other pathogenic coronaviruses and astroviruses, possesses a linear plus-sense strand RNA genome that has a 59 methylated cap and 39 poly-A tail. The viral replicase is translated directly from the genomic sense-strand RNA, and it then creates a full-length complementary (minus-sense st...
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The Structure of a Rigorously Conserved RNA Element within the SARS Virus Genome
We have solved the three-dimensional crystal structure of the stem-loop II motif (s2m) RNA element of the SARS virus genome to 2.7-Å resolution. SARS and related coronaviruses and astroviruses all possess a motif at the 3′ end of their RNA genomes, called the s2m, whose pathogenic importance is inferred from its rigoro...
structure reveals a dramatic 908 bend and several additional novel tertiary interactions. Although the sequence and three-dimensional structure of the s2m RNA are both unique, comparison of the global fold of the SARS s2m RNA to known RNA tertiary structures reveals that the backbone fold of the s2m RNA mimics that of ...
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Poxvirus Bioinformatics Resource Center: a comprehensive Poxviridae informational and analytical resource
The Poxvirus Bioinformatics Resource Center (PBRC) has been established to provide informational and analytical resources to the scientific community to aid research directed at providing a better understanding of the Poxviridae family of viruses. The PBRC was specifically established as the result of the concern that ...
An effective response to the use of biological organisms as agents of terrorism or warfare, or to the emergence of new infectious diseases requires a multi-disciplinary effort involving various agencies at the local, state and federal levels including public health officials, hospital personnel, epidemiologists and the...
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Poxvirus Bioinformatics Resource Center: a comprehensive Poxviridae informational and analytical resource
The Poxvirus Bioinformatics Resource Center (PBRC) has been established to provide informational and analytical resources to the scientific community to aid research directed at providing a better understanding of the Poxviridae family of viruses. The PBRC was specifically established as the result of the concern that ...
a better understanding of priority pathogens is the need to collect, manage, describe, analyze and publicize the vast amounts of information generated by modern, high-throughput biological research. Therefore, the goal of the Poxvirus Bioinformatics Resource Center (PBRC) is to organize all available information on vir...
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The involvement of survival signaling pathways in rubella-virus induced apoptosis
Rubella virus (RV) causes severe congenital defects when acquired during the first trimester of pregnancy. RV cytopathic effect has been shown to be due to caspase-dependent apoptosis in a number of susceptible cell lines, and it has been suggested that this apoptotic induction could be a causal factor in the developme...
Rubella virus (RV) is the sole member of the Rubivirus genus of the Togaviridae. It has a positive-sense single stranded RNA genome that is 9762 nucleotides (nt) in length and contains two non-overlapping open-reading frames (ORFs). The 5' proximal ORF encodes the p200 polyprotein precursor for the nonstructural protei...
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The involvement of survival signaling pathways in rubella-virus induced apoptosis
Rubella virus (RV) causes severe congenital defects when acquired during the first trimester of pregnancy. RV cytopathic effect has been shown to be due to caspase-dependent apoptosis in a number of susceptible cell lines, and it has been suggested that this apoptotic induction could be a causal factor in the developme...
integrate external stimuli and transmit signals to the nucleus resulting in the activation of transcription factors, which regulate expression of genes required for proliferation, differentiation, survival and apoptosis. Two wellstudied mitogenic pathways are the phosphoinositide 3kinase (PI3K)-Akt pathway and the Ras-...
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The involvement of survival signaling pathways in rubella-virus induced apoptosis
Rubella virus (RV) causes severe congenital defects when acquired during the first trimester of pregnancy. RV cytopathic effect has been shown to be due to caspase-dependent apoptosis in a number of susceptible cell lines, and it has been suggested that this apoptotic induction could be a causal factor in the developme...
was measured in RVinfected cells by caspase activity and cell viability assays, DNA fragmentation analysis, and trypan blue exclusion staining. Involvement of PI3K-Akt and Raf-Raf-MEK-ERK signaling in RV-induced apoptosis was also examined by expression of constitutively active Akt and MEK in RVinfected cells.
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Bioinformatic mapping of AlkB homology domains in viruses
BACKGROUND: AlkB-like proteins are members of the 2-oxoglutarate- and Fe(II)-dependent oxygenase superfamily. In Escherichia coli the protein protects RNA and DNA against damage from methylating agents. 1-methyladenine and 3-methylcytosine are repaired by oxidative demethylation and direct reversal of the methylated ba...
The observed distribution of AlkB domains could most easily be explained by assuming that an ancestral AlkB domain was integrated into the genome of the last common ancestor of the Flexiviridae 2 subfamily. Subsequent Figure 6 Dot plots for Potato virus M (NCBI gi9626090) and Aconitum latent virus (NCBI gi14251191). To...
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Dynamic changes of serum SARS-Coronavirus IgG, pulmonary function and radiography in patients recovering from SARS after hospital discharge
OBJECTIVE: The intent of this study was to examine the recovery of individuals who had been hospitalized for severe acute respiratory syndrome (SARS) in the year following their discharge from the hospital. Parameters studied included serum levels of SARS coronavirus (SARS-CoV) IgG antibody, tests of lung function, and...
Severe acute respiratory syndrome (SARS) is a new infectious disease in humans. The first victim of SARS to be diagnosed was a businessman from the city of Foshan in Guangdong Province, China. SARS patients may present with a spectrum of symptoms and signs, ranging from relatively asymptomatic to fulminant pneumonitis ...
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Protein secretion in Lactococcus lactis : an efficient way to increase the overall heterologous protein production
Lactococcus lactis, the model lactic acid bacterium (LAB), is a food grade and well-characterized Gram positive bacterium. It is a good candidate for heterologous protein delivery in foodstuff or in the digestive tract. L. lactis can also be used as a protein producer in fermentor. Many heterologous proteins have alrea...
Lactic Acid Bacteria (LAB) are anaerobic Gram positive bacteria with a GRAS (Generally Regarded As Safe) status. They are also food grade bacteria, and therefore, they can be used for the delivery of proteins of interest in foodstuff or in the digestive tract. A last advantage compared to other well-known protein produ...
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Protein secretion in Lactococcus lactis : an efficient way to increase the overall heterologous protein production
Lactococcus lactis, the model lactic acid bacterium (LAB), is a food grade and well-characterized Gram positive bacterium. It is a good candidate for heterologous protein delivery in foodstuff or in the digestive tract. L. lactis can also be used as a protein producer in fermentor. Many heterologous proteins have alrea...
heterologous protein production by recombinant lactococci, only one cellularlocation (i.e. cytoplasm, external media or surface anchored) is described. Only a few works report the production of a given protein in different locations using the same backbone vector, the same induction level and or promoter strength, allo...
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Protein secretion in Lactococcus lactis : an efficient way to increase the overall heterologous protein production
Lactococcus lactis, the model lactic acid bacterium (LAB), is a food grade and well-characterized Gram positive bacterium. It is a good candidate for heterologous protein delivery in foodstuff or in the digestive tract. L. lactis can also be used as a protein producer in fermentor. Many heterologous proteins have alrea...
and is also discussed here.
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Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality
Therapeutic application of the recently discovered small interfering RNA (siRNA) gene silencing phenomenon will be dependent on improvements in molecule bio-stability, specificity and delivery. To address these issues, we have systematically modified siRNA with the synthetic RNA-like high affinity nucleotide analogue, ...
Double-stranded small interfering RNA (siRNA) molecules have drawn much attention since it was unambiguously shown that they mediate potent gene knock-down in a variety of mammalian cells (1) . This work followed the discovery of the phenomenon of RNA interference (RNAi) in Caenorhabditis elegans (2) and the demonstrat...
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Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality
Therapeutic application of the recently discovered small interfering RNA (siRNA) gene silencing phenomenon will be dependent on improvements in molecule bio-stability, specificity and delivery. To address these issues, we have systematically modified siRNA with the synthetic RNA-like high affinity nucleotide analogue, ...
2 0 -O-allyl (10) or chemical blocking of the 5 0 -hydroxyl group (11) resulted in a dramatic loss in activity consistent with the proposed in vivo requirement for 5 0 end phosphorylation. Also, more substantial modifications, such as total modification by 2 0 -O-Me (8) or PS modifications of every second or all intern...
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Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality
Therapeutic application of the recently discovered small interfering RNA (siRNA) gene silencing phenomenon will be dependent on improvements in molecule bio-stability, specificity and delivery. To address these issues, we have systematically modified siRNA with the synthetic RNA-like high affinity nucleotide analogue, ...
prime candidate for introducing critical new features into siRNAs without perturbing the overall A-form helical structure they require for activity (22) . Recently, Braasch et al. (8) provided the first evidence that LNA can be used to increase the thermal stability of siRNA molecules without affecting their function. ...
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