Carbapenemases: a problem in waiting?

Carbapenems are stable to most prevalent beta-lactamases, and chromosomal carbapenemases are restricted to Stenotrophomonas maltophilia, to a few Bacteroides fragilis, and to rare pathogens. Nevertheless, an acquired metallo-beta-lactamase called IMP-1 is beginning to emerge in Pseudomonas aeruginosa and Enterobacteriaceae isolates in Japan, and has also been found in isolates from Singapore. Furthermore, IMP-producing Acinetobacter spp. have been identified in Italy and Hong Kong. Recently a second group of acquired metallo-carbapenemases, the VIM types, has been recorded from P. aeruginosa isolates in five Eurasian countries. Weak carbapenemases belonging to molecular class D are emerging in A. baumannii world-wide, with two sub-groups apparent. A few acquired carbapenemases belonging to molecular class A also have been reported. Finally it has also been shown that enzymes with feeble carbapenemase activity (e.g. AmpC types and some SHV enzymes) may confer resistance in exceptionally impermeable strains; counterwise, even potent carbapenemases, such as IMP-1, may only give a small reduction in susceptibility in Enterobacteriaceae that lack permeability lesions. Is the emergence of carbapenemase a problem waiting to happen?     

Measurement of dietary exposure: a challenging problem which may be overcome thanks to metabolomics?

The diet is an important environmental exposure, and its measurement is an essential component of much health-related research. However, conventional tools for measuring dietary exposure have significant limitations being subject to an unknown degree of misreporting and dependent upon food composition tables to allow estimation of intakes of energy, nutrients and non-nutrient food constituents. In addition, such tools may be inappropriate for use with certain groups of people. As an alternative approach, the recent techniques of metabolite profiling or fingerprinting, which allows simultaneous monitoring of multiple and dynamic components of biological fluids, may provide metabolic signals indicative of food intake. Samples can be analysed through numerous analytical platforms, followed by multivariate data analysis. In humans, metabolomics has been applied successfully in pharmacology, toxicology and medical screening, but nutritional metabolomics is still in its infancy. Biomarkers of a small number of specific foods and nutrients have been developed successfully but less targeted and more high-throughput methods, that do not need prior knowledge of which signals might be discriminatory, and which may allow a more global characterisation of dietary intake, remain to be tested. A proof a principle project (the MEDE Study) is currently underway in our laboratories to test the hypothesis that high-throughput, non-targeted metabolite fingerprinting using flow injection electrospray mass spectrometry can be applied to human biofluids (blood and urine) to characterise dietary exposure in humans.     

Fuelling flight in a parasitic wasp: which energetic substrate to use?

1. Flight is an energy‐demanding behaviour in insects. In parasitic wasps, strategies of nutrient acquisition and allocation, resulting life‐history trade‐offs and relationships with foraging strategies and resource availability have received much attention. However, despite the ecological importance of dispersal between host and food patches, and the great impact energy diverted to flight should have on lifetime reproductive success, the eco‐physiology of flight in parasitoids is poorly understood. 2. The objective of this study is to (i) identify the energetic resources used to fuel flight, and (ii) relate nutrient type and rate of utilisation to selective pressures in terms of resource availability posed by the environment. 3. Using a flight mill and biochemical assays, we compared flight performance and nutrient dynamics during flight between two reproductive modes of the parasitoid Venturia canescens Gravenhorst, which is known to thrive preferentially in contrasted environments (i.e. natural vs. anthropogenic habitat), differing notably in host and food distribution. 4. Biochemical analyses of different nutrient types showed that glycogen is the flight fuel used by this species, yet no significant differences in its dynamics in flight were found between the two reproductive modes. 5. Results suggest that both glycogen quantity and flight performance are related to the diverging ecological conditions experienced by thelytokous and arrhenotokous strains.     

What drives bacteria to produce a biofilm?

Nearly 40 years ago, Dr. R.J. Gibbons made the first reports of the clinical relevance of what we now know as bacterial biofilms when he published his observations of the role of polysaccharide glycocalyx formation on teeth by Streptococcus mutans [Sci. Am. 238 (1978) 86]. As the clinical relevance of bacterial biofilm formation became increasingly apparent, interest in the phenomenon exploded. Studies are rapidly shedding light on the biomolecular pathways leading to this sessile mode of growth but many fundamental questions remain. The intent of this review is to consider the reasons why bacteria switch from a free-floating to a biofilm mode of growth. The currently available wealth of data pertaining to the molecular genetics of biofilm formation in commonly studied, clinically relevant, single-species biofilms will be discussed in an effort to decipher the motivation behind the transition from planktonic to sessile growth in the human body. Four potential incentives behind the formation of biofilms by bacteria during infection are considered: (1) protection from harmful conditions in the host (defense), (2) sequestration to a nutrient-rich area (colonization), (3) utilization of cooperative benefits (community), (4) biofilms normally grow as biofilms and planktonic cultures are an in vitro artifact (biofilms as the default mode of growth).     

Is ligation the only solution to the pyrophosphate problem?

Pyrophosphate linkages are easily formed during the nonenzymatic oligomerization of activated nucleotides. They often form caps which terminate an oligonucleotide with a 5-5 pyrophosphate. Owing to their structural resemblance to the intermediates in enzymatic ligation reactions, it has been suggested that pyrophosphate caps might have been capable of acting as activating groups in chain elongation processes. We argue that an alternative possibility would have been the specific hydrolysis of pyrophosphates.     

Continued declines of Redshank Tringa totanus breeding on saltmarsh in Great Britain: is there a solution to this conservation problem?

Capsule: Over 50% of saltmarsh breeding Common Redshank have been lost since 1985, with current conservation management having only limited success at halting these declines.

Aims: To update population size and trend estimates for saltmarsh-breeding Redshank in Britain, and to determine whether conservation management implemented since 1996 has been successful in influencing grazing intensity and Redshank population trends.

Methods: A repeat national survey of British saltmarsh was conducted in 2011 at sites previously visited in 1985 and 1996. Redshank breeding density and grazing pressure were recorded at all sites; the presence of conservation management was additionally recorded for English sites. Results from all three national surveys were used to update population size and trend estimates, and to investigate changes in grazing pressure and breeding density on sites with and without conservation management.

Results: Of the 21 431 pairs breeding on saltmarsh in 1985, 11 946 pairs remained in 2011, with the highest proportion of this population found in East Anglia. From 1985, British breeding densities declined at a rate of 1 pair km^?2 year^?1, representing a loss of 52.8% of breeding pairs over 26 years, although regional trends varied across different time periods. Grazing pressures did not change markedly with conservation management. Redshank declines were less severe on conservation-managed sites in East Anglia and the South of England where grazing pressures remained low, though were more severe on conservation-managed sites in the North West where heavy grazing persisted.

Conclusion: Saltmarsh-breeding Redshank declines continue and are likely to be driven by a lack of suitable nesting habitat. Conservation management schemes and site protection implemented since 1996 appear not to be delivering the grazing pressures and associated habitat conditions required by this species, particularly in the North West of England, though habitat changes may not be linked to unsuitable grazing management in all regions. An in-depth understanding of grazing practices, how conservation management guidelines could be improved, and the likely success of more long-term management solutions is needed urgently.     

Calcium: just a chemical switch?

The calcium-signature hypothesis has evolved as a concept to explain specificity in signaling pathways that utilise calcium as a second messenger. In plant biology, this hypothesis was purely conceptual and based only upon correlative observations until recently. In the past few years, however, empirical data have emerged from experiments that were specifically designed to tackle the question of how specificity is encoded by calcium. In light of the attractive calcium-signature hypothesis, other potential explanations for signalling specificity have been overshadowed and ignored: it has been assumed that the calcium-signature dogma will explain all plant calcium signaling. However, there is a good deal of evidence supporting a counter-hypothesis in which calcium does not itself encode specificity but is merely an essential 'switch' in signaling. At the very least, both hypotheses are likely to be true in different situations, and it may well be that the calcium-signature hypothesis describes the exception rather than the rule.     

Capture of bacteria from fermentation broth by body feed filtration: a solved problem?

The direct capture of bacteria produced in high cell density fermentation by filtration is not possible once the milliliter-scale has been surpassed. Filtration in the presence of a filter aid (body feed filtration) constitutes a putative and scalable alternative, but only if conditions proposed by industry for large-scale filtration processes, namely, flow rates (for aqueous solutions) in the range of 500-1,500 L/(m(2) x h) and a filter aid concentration of 相似文献   

HLA-B27 misfolding: a solution to the spondyloarthropathy conundrum?

Compelling evidence indicates that HLA-B27 is directly involved in the etiopathogenesis of the spondyloarthropathies (SpAs). Several hypotheses based on its native antigenic structure, the peptides it presents and mimicry with bacterial epitopes, have been proposed. However, these potential mechanisms remain largely unsupported by human studies and transgenic animal models. Recent work demonstrating that HLA-B27 misfolds offers a novel alternative hypothesis. Here, we review this new information on the folding and assembly of HLA-B27, and discuss consequences of misfolding that could be relevant to the pathogenesis of SpAs.     

Why get big in the cold? Towards a solution to a life-history puzzle

The temperature–size rule (TSR), which states that body size increases at lower developmental temperatures, appears to be a near-universal law for ectotherms. Although recent studies seem to suggest that the TSR might be adaptive, the underlying developmental mechanisms are thus far largely unknown. Here, we investigate temperature effects on life-history traits, behaviour and physiology in the copper butterfly Lycaena tityrus in order to disentangle the mechanistic basis for the above rule. In L. tityrus the larger body size produced at a lower temperature was proximately due to a greater increase in mass, which was caused by both behavioural and physiological mechanisms: a much-increased food intake and a higher efficiency in converting ingested food into body matter. These mechanisms, combined with temperature-induced changes at the cellular level, may provide general explanations for the TSR. Body fat and protein content increased in butterflies reared at the higher temperature, indicating favourable growth conditions. As predicted from protandry theory, males showed reduced development times, caused by higher growth rates compared to females. The latter was itself related to a higher daily food consumption, while the total food consumption (due to the females’ longer developmental period) and assimilation was higher in females and may underly the sexual body size dimorphism.