Morphological changes to Escherichia coli O157:H7, commensal E. coli and Salmonella spp in response to marginal growth conditions,with special reference to mildly stressing temperatures

Certain rod-shaped bacteria have been reported to form elongated filamentous cells when exposed to marginal growth conditions, including refrigeration temperatures. To expand upon these observations, the filamentation of commensal Escherichia coli, E. coli O157:H7 and Salmonella spp was investigated, following exposure to certain, mildly stressing, levels of temperature, pH or water activity (aw), with levels of cellular protein being monitored during cell elongation, in some experiments. Our studies indicated that cellular filamentation could be demonstrated in all 15 strains of the above organisms tested, following exposure to marginal conditions achieved by incubation at high or low temperatures, high or low pH values and low aw. The level of environmental stress causing filamentation tended to be specific to the particular organisms. For example, Salmonella spp formed filamentous cells at 44 degrees C, whereas E. coli strains, including O157, grew by binary fission at that temperature, but formed filamentous cells at 46 degrees C. In addition, plate count techniques to enumerate bacteria during filamentation, failed to reflect the increase in cell biomass that was occurring, whereas measurements of protein concentration demonstrated the increase quite strikingly. These findings have important implications for our understanding of the ability of food-borne pathogens to cause disease, since the infectious dose of a microorganism implicated in an outbreak of such disease is typically determined by a viable count method, which could underestimate the number of potential infectious units present in a food that had been stored in such a way as to provide marginal growth conditions.     

Field sports and conservation in the United Kingdom

Many natural habitats exist on privately owned land outside protected areas, but few governments can afford to enforce or subsidize conservation of this biodiversity. Even in some developed countries, conservation subsidy schemes have only achieved limited success. Fortunately, some landowners may be willing to accept management costs in return for other benefits, although this remains controversial when it involves the killing of charismatic species. For example, participants in British field sports, such as fox hunting and game-bird shooting, may voluntarily conserve important habitats that are required by quarry species. Here we report results from a multidisciplinary study that addressed this issue by focusing on three sites across central England. We found that landowners participating in field sports maintained the most established woodland and planted more new woodland and hedgerows than those who did not, despite the equal availability of subsidies. Therefore, voluntary habitat management appears to be important for biodiversity conservation in Britain. Current debates on the future of field sports in Britain, and similar activities globally, may benefit from considering their utility as incentives to conserve additional habitat on private land.     

Mutations in the gene encoding peroxisomal alpha-methylacyl-CoA racemase cause adult-onset sensory motor neuropathy

Sensory motor neuropathy is associated with various inherited disorders including Charcot-Marie-Tooth disease, X-linked adrenoleukodystrophy/adrenomyeloneuropathy and Refsum disease. In the latter two, the neuropathy is thought to result from the accumulation of specific fatty acids. We describe here three patients with elevated plasma concentrations of pristanic acid (a branched-chain fatty acid) and C27-bile-acid intermediates. Two of the patients suffered from adult-onset sensory motor neuropathy. One patient also had pigmentary retinopathy, suggesting Refsum disease, whereas the other patient had upper motor neuron signs in the legs, suggesting adrenomyeloneuropathy. The third patient was a child without neuropathy. In all three patients we discovered a deficiency of alpha-methylacyl-CoA racemase (AMACR). This enzyme is responsible for the conversion of pristanoyl-CoA and C27-bile acyl-CoAs to their (S)-stereoisomers, which are the only stereoisomers that can be degraded via peroxisomal beta-oxidation. Sequence analysis of AMACR cDNA from the patients identified two different mutations that are likely to cause disease, based on analysis in Escherichia coli. Our findings have implications for the diagnosis of adult-onset neuropathies of unknown aetiology.     

Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence

Morphine is a powerful pain reliever, but also a potent inducer of tolerance and dependence. The development of opiate tolerance occurs on continued use of the drug such that the amount of drug required to elicit pain relief must be increased to compensate for diminished responsiveness. In many systems, decreased responsiveness to agonists has been correlated with the desensitization of G-protein-coupled receptors. In vitro evidence indicates that this process involves phosphorylation of G-protein-coupled receptors and subsequent binding of regulatory proteins called beta-arrestins. Using a knockout mouse lacking beta-arrestin-2 (beta arr2-/-), we have assessed the contribution of desensitization of the mu-opioid receptor to the development of morphine antinociceptive tolerance and the subsequent onset of physical dependence. Here we show that in mice lacking beta-arrestin-2, desensitization of the mu-opioid receptor does not occur after chronic morphine treatment, and that these animals fail to develop antinociceptive tolerance. However, the deletion of beta-arrestin-2 does not prevent the chronic morphine-induced up-regulation of adenylyl cyclase activity, a cellular marker of dependence, and the mutant mice still become physically dependent on the drug.     

Voice-selective areas in human auditory cortex

The human voice contains in its acoustic structure a wealth of information on the speaker's identity and emotional state which we perceive with remarkable ease and accuracy. Although the perception of speaker-related features of voice plays a major role in human communication, little is known about its neural basis. Here we show, using functional magnetic resonance imaging in human volunteers, that voice-selective regions can be found bilaterally along the upper bank of the superior temporal sulcus (STS). These regions showed greater neuronal activity when subjects listened passively to vocal sounds, whether speech or non-speech, than to non-vocal environmental sounds. Central STS regions also displayed a high degree of selectivity by responding significantly more to vocal sounds than to matched control stimuli, including scrambled voices and amplitude-modulated noise. Moreover, their response to stimuli degraded by frequency filtering paralleled the subjects' behavioural performance in voice-perception tasks that used these stimuli. The voice-selective areas in the STS may represent the counterpart of the face-selective areas in human visual cortex; their existence sheds new light on the functional architecture of the human auditory cortex.     

A nanometre-scale electronic switch consisting of a metal cluster and redox-addressable groups

So-called bottom-up fabrication methods aim to assemble and integrate molecular components exhibiting specific functions into electronic devices that are orders of magnitude smaller than can be fabricated by lithographic techniques. Fundamental to the success of the bottom-up approach is the ability to control electron transport across molecular components. Organic molecules containing redox centres-chemical species whose oxidation number, and hence electronic structure, can be changed reversibly-support resonant tunnelling and display promising functional behaviour when sandwiched as molecular layers between electrical contacts, but their integration into more complex assemblies remains challenging. For this reason, functionalized metal nanoparticles have attracted much interest: they exhibit single-electron characteristics (such as quantized capacitance charging) and can be organized through simple self-assembly methods into well ordered structures, with the nanoparticles at controlled locations. Here we report scanning tunnelling microscopy measurements showing that organic molecules containing redox centres can be used to attach metal nanoparticles to electrode surfaces and so control the electron transport between them. Our system consists of gold nanoclusters a few nanometres across and functionalized with polymethylene chains that carry a central, reversibly reducible bipyridinium moiety. We expect that the ability to electronically contact metal nanoparticles via redox-active molecules, and to alter profoundly their tunnelling properties by charge injection into these molecules, can form the basis for a range of nanoscale electronic switches.