Postoperative cisplatin-based chemotherapy significantly improves survival in patients with NSCLC.

HD-GYP is a protein domain of unknown biochemical function implicated in bacterial signaling and regulation. In the plant pathogen Xanthomonas campestris pv. campestris , the synthesis of virulence factors and dispersal of biofilms are positively controlled by a two-component signal transduction system comprising the HD-GYP domain regulatory protein RpfG and cognate sensor RpfC and by cell–cell signaling mediated by the diffusible signal molecule DSF (diffusible signal factor). The RpfG/RpfC two-component system has been implicated in DSF perception and signal transduction. Here we show that the role of RpfG is to degrade the unusual nucleotide cyclic di-GMP, an activity associated with the HD-GYP domain. Mutation of the conserved H and D residues of the isolated HD-GYP domain resulted in loss of both the enzymatic activity against cyclic di-GMP and the regulatory activity in virulence factor synthesis. Two other protein domains, GGDEF and EAL, are already implicated in the synthesis and degradation respectively of cyclic di-GMP. As with GGDEF and EAL domains, the HD-GYP domain is widely distributed in free-living bacteria and occurs in plant and animal pathogens, as well as beneficial symbionts and organisms associated with a range of environmental niches. Identification of the role of the HD-GYP domain thus increases our understanding of a signaling network whose importance to the lifestyle of diverse bacteria is now emerging.

ABsTRAcr Maximal respiratory pressures at the mouth (PEm. and PI,M.) have been measured in 370 normal caucasian children and adults. Age, height, and weight were recorded for all subjects and incorporated in a stepwise multiple regression analysis to determine prediction equations for the maximal respiratory pressures in the children and adults for both sexes. In men Pi,. and PEmax were significantly correlated only with age (p < 0-001 and < 0-035 respectively), whereas in women they were correlated with height (p < 0-035 and < 0-03). In both boys and girls PN., was related to weight (p < 0-0001 and <0-01 respectively) and PEma. to age (p < 0-001 for both). The values for PImax and PEmax in adults were lower than in previously reported series, but in children the values obtained were similar to those reported for several smaller series.In recent years interest has been rekindled in methods for measurement of respiratory muscle function in patients with neuromuscular disease. One of the simplest non-invasive measurements is that of maximal pressures, generated at the mouth, after full inspiration and full expiration-that is, maximal expiratory pressure (PE,,,C) and maximal inspiratory pressure (PI n).

Prokaryotic nitrate reduction can serve a number of physiological roles and can be catalysed by a number of biochemically distinct nitrate reductases. Three distinct nitrate reductase classes can be indentified in prokaryotes, NAS, NAR and NAP. NAS is located in the cytoplasmic compartment and participates in nitrogen assimilation. NAR is usually a three-subunit complex anchored to the cytoplasmic face of the membrane with its active site located in the cytoplasmic compartment and is involved in anaerobic nitrate respiration. NAP is a two-subunit complex, located in the periplasmic compartment, that is coupled to quinol oxidation via a membrane anchored tetraheme cytochrome. It shows considerable functional flexibility by participating in anaerobic respiration or redox energy dissipation depending on the organism in which it is found. The members of all three classes of enzymes bind the bis-molybdopterin guanine dinucleotide cofactor at the active site, but they differ markedly in the number and nature of cofactors used to transfer electrons to this site. Analysis of prokaryotic genome sequences available at the time of writing reveals that the different nitrate reductases are phylogenetically widespread.

Bacteria which can grow in different environments have developed regulatory systems which allow them to exploit specific habitats to their best advantage. In the facultative anaerobe Escherichia coli two transcriptional regulators controlling independent networks of oxygen‐regulated gene expression have been identified. One is a two‐component sensor‐regulator system (ArcB‐A), which represses a wide variety of aerobic enzymes under anaerobic conditions. The other is FNR, the transcriptional regulator which is essential for expressing anaerobic respiratory processes. The purpose of this review is to summarize what is known about FNR. The fnr gene was initially defined by the isolation of some pleiotropic mutants which characteristically lacked the ability to use fumarate and nitrate as reducible substrates for supporting anaerobic growth and several other anaerobic respiratory functions. Its role as a transcripitonal regulator emerged from genetic and molecular studies in which its homology with CRP (the cyclic AMP receptor protein which mediates catabolite repression) was established and has since been particularly important in identifying the structural basis of its regulatory specificities. FNR is a member of a growing family of CRP‐related regulatory proteins which have a DNA‐binding domain based on the helix‐turn‐helix structural motif, and a characteristic β‐roll that is involved in nucleotide‐binding in CRP. The FNR protein has been isolated in a monomeric form (Mr 30 000) which exhibits a high but as yet non‐specific affinity for DNA. Nevertheless, the DNA‐recognition site and important residues conferring the functional specificity of FNR have been defined by site‐directed mutagenesis. A consensus for the sequences that are recognized by FNR in the promoter regions of FNR‐regulated genes, has likewise been identified. The basic features of genes and operons regulated by FNR are reviewed, and examples in which FNR functions negatively as an anaerobic repressor as well as positively as an anaerobic activator, are included. Less is known about the way in which FNR senses anoxia and is thereby transformed into its ‘active’s form, but it seems likely that It is clear that oxygen functions as a regulatory signal controlling several important aspects of mitcrobial physiology, and further studies should reveal the molecular basis of the mechanism by which changes in oxygen tension are sensed. The recent identification of FNR homologues in diverse microorganisms points to the widespread importance of this family of regulatory proteins. Moreover, the function of these proteins is not limited to the regulation of anaerobic respiration but includes roles in the regulation of nitrogen fixation and haemolysin biosynthesis. The ability to over‐ride these regulatory mechanisms may have useful biotechnological applications, and it could also be important in controlling pathogenesis. It is anticipated that further studies will provide insights into the way in which these regulatory proteins with common evolut...