A collection of evidence for the impact of the economic recession on road fatalities in Great Britain.

There was a considerable reduction in the number of fatalities on British roads between 2007 and 2010. This substantial change led to debate as to the cause of the reduction. Multiple sources of information and evidence have been collated including STATS19 road accident data, population data, socio-demographic data, economic patterns, weather trends and traffic and vehicle data. Summary analyses of these data sources show a reduction in overall traffic, a large reduction in HGV traffic, a reduction in young male drivers, a reduction in speeding, and a reduction in drink driving during the recession period. All of these reductions can be associated with a reduction in fatal accidents and have led to the conclusion that the economic recession changed behaviours in such a way that fewer people were killed on the roads in Britain during this period.

Protein-energy malnutrition during early gestation in sheep blunts fetal renal vascular and nephron development and compromises adult renal function.

A nutritionally poor maternal diet can reduce nephron endowment and pre-empt premature expression of markers for chronic renal disease in the offspring. A mechanistic pathway from variation in maternal diet through altered fetal renal development to compromised adult kidney structure and function with adult-onset obesity has not been described. We show that maternal protein-energy malnutrition in sheep blunts nephrogenic potential in the 0.44 gestation (65 days gestation, term ∼147 days) fetus by increasing apoptosis and decreasing angiogenesis in the nephrogenic zone, effects that were more marked in male fetuses. As adults, the low-protein-exposed sheep had reduced glomerular number and microvascular rarefaction in their kidneys compensated for, respectively, by glomerular hypertrophy and increased angiogenic support. In this study, the long-term mild anatomical deficits in the kidney would have remained asymptomatic in the lean state, but when superimposed on the broad metabolic challenge that obesity represents then microalbuminuria and blunted bilateral renal function revealed a long-term physiological compromise, that is only predicted to worsen with age. In conclusion, maternal protein-energy malnutrition specifically impacts fetal kidney vascular development and prevents full functionality of the adult kidney being achieved; these residual deficits are predicted to significantly increase the expected incidence of chronic kidney disease in prenatally undernourished individuals especially when coupled with a Western obesogenic environment.

In vivo localizations of membrane stress controllers PspA and PspG in Escherichia coli.

The phage shock protein (Psp) response in Gram-negative bacteria counteracts membrane stress. Transcription of the PspF regulon (pspABCDE and pspG) in Escherichia coli is induced upon stresses that dissipate the proton motive force (pmf). Using GFP fusions we have visualized the subcellular localizations of PspA (a negative regulator and effector of Psp) and PspG (an effector of Psp). It has previously been proposed that PspA evenly coates the inner membrane of the cell. We now demonstrate that instead of uniformly covering the entire cell, PspA (and PspG) is highly organized into what appear to be distinct functional classes (complexes at the cell pole and the lateral cell wall). Real-time observations revealed lateral PspA and PspG complexes are highly mobile, but absent in cells lacking MreB. Without the MreB cytoskeleton, induction of the Psp response is still observed, yet these cells fail to maintain pmf under stress conditions. The two spatial subspecies therefore appear to be dynamically and functionally distinct with the polar clusters being associated with sensory function and the mobile complexes with maintenance of pmf.

Induction and function of the phage shock protein extracytoplasmic stress response in Escherichia coli.

The phage shock protein (Psp) F regulon response in Escherichia coli is thought to be induced by impaired inner membrane integrity and an associated decrease in proton motive force (pmf). Mechanisms by which the Psp system detects the stress signal and responds have so far remained undetermined. Here we demonstrate that PspA and PspG directly confront a variety of inducing stimuli by switching the cell to anaerobic respiration and fermentation and by down-regulating motility, thereby subtly adjusting and maintaining energy usage and pmf. Additionally, PspG controls iron usage. We show that the Psp-inducing protein IV secretin stress, in the absence of Psp proteins, decreases the pmf in an ArcB-dependent manner and that ArcB is required for amplifying and transducing the stress signal to the PspF regulon. The requirement of the ArcB signal transduction protein for induction of psp provides clear evidence for a direct link between the physiological redox state of the cell, the electron transport chain, and induction of the Psp response. Under normal growth conditions PspA and PspD control the level of activity of ArcB/ArcA system that senses the redox/metabolic state of the cell, whereas under stress conditions PspA, PspD, and PspG deliver their effector functions at least in part by activating ArcB/ArcA through positive feedback.

Identification of a new member of the phage shock protein response in Escherichia coli, the phage shock protein G (PspG).

The phage shock protein operon (pspABCDE) of Escherichia coli is strongly up-regulated in response to overexpression of the filamentous phage secretin protein IV (pIV) and by many other stress conditions including defects in protein export. PspA has an established role in maintenance of the proton-motive force of the cell under stress conditions. Here we present evidence for a new member of the phage shock response in E. coli. Using transcriptional profiling, we show that the synthesis of pIV in E. coli leads to a highly restricted response limited to the up-regulation of the psp operon genes and yjbO. The psp operon and yjbO are also up-regulated in response to pIV in Salmonella enterica serovar Typhimurium. yjbO is a highly conserved gene found exclusively in bacteria that contain a psp operon but is physically unlinked to the psp operon. yjbO encodes a putative inner membrane protein that is co-controlled with the psp operon genes and is predicted to be an effector of the psp response in E. coli. We present evidence that yjbO expression is driven by sigma(54)-RNA polymerase, activated by PspF and integration host factor, and negatively regulated by PspA. PspF specifically regulates only members of the PspF regulon: pspABCDE and yjbO. We found that increased expression of YjbO results in decreased motility of bacteria. Because yjbO is co-conserved and co-regulated with the psp operon and is a member of the phage shock protein F regulon, we propose that yjbO be renamed pspG.