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Chronic infections are difficult to treat with antibiotics but are caused primarily by drug-sensitive pathogens. Dormant persister cells that are tolerant to killing by antibiotics are responsible for this apparent paradox. Persisters are phenotypic variants of normal cells and pathways leading to dormancy are redundant, making it challenging to develop anti-persister compounds. Biofilms shield persisters from the immune system, suggesting that an antibiotic for treating a chronic infection should be able to eradicate the infection on its own. We reasoned that a compound capable of corrupting a target in dormant cells will kill persisters. The acyldepsipeptide antibiotic (ADEP4) has been shown to activate the ClpP protease, resulting in death of growing cells. Here we show that ADEP4-activated ClpP becomes a fairly nonspecific protease and kills persisters by degrading over 400 proteins, forcing cells to self-digest. Null mutants of clpP arise with high probability, but combining ADEP4 with rifampicin produced complete eradication of Staphylococcus aureus biofilms in vitro and in a mouse model of a chronic infection. Our findings indicate a general principle for killing dormant cells—activation and corruption of a target, rather than conventional inhibition. Eradication of a biofilm in an animal model by activating a protease suggests a realistic path towards developing therapies to treat chronic infections. Dormant bacterial persister cells evade antibiotic destruction and their survival gives rise to some chronic infections; this study reveals that persister cells can be eradicated with a compound activating the bacterial protease ClpP, providing an effective biofilm treatment in vitro and in mouse chronic infection models. An anti-persister antibiotic Concerns about the ability of today's antibiotics to cope with future infections are compounded by the dual nature of the bacterial response to the drugs. Some bacteria develop genetic resistance, but others become tolerant, able to survive in the presence of antibiotics by forming dormant cells known as persisters in which the enzymatic targets of the antibiotics are inactive. Kim Lewis and colleagues sought compounds with the potential to kill persisters by corrupting targets within these energy-limited cells. They demonstrate that the acyldepsipeptide antibiotic ADEP4 activates ClpP protease and the cell's proteolytic machinery, killing persister cells by forcing them to degrade a range of cellular proteins. This is a potentially important result, suggesting that combining compounds such as ADEP4 with conventional antibiotics could provide new and robust strategies for the control of chronic infections.

▪ Abstract  Contaminated soils and waters pose a major environmental and human health problem, which may be partially solved by the emerging phytoremediation technology. This cost-effective plant-based approach to remediation takes advantage of the remarkable ability of plants to concentrate elements and compounds from the environment and to metabolize various molecules in their tissues. Toxic heavy metals and organic pollutants are the major targets for phytoremediation. In recent years, knowledge of the physiological and molecular mechanisms of phytoremediation began to emerge together with biological and engineering strategies designed to optimize and improve phytoremediation. In addition, several field trials confirmed the feasibility of using plants for environmental cleanup. This review concentrates on the most developed subsets of phytoremediation technology and on the biological mechanisms that make phytoremediation work.

The primary technical function of an electric utility company is to supply electrical energy to its customers economically and at acceptable levels of reliability. The aspects of economics and reliability are however, competing constraints, since increased reliability of supply generally requires increased capital investment, which leads to higher prices for electricity. Traditional capital budgeting criteria, such as positive net present value, have been found to inhibit sound economic capital investment decision-making within the bulk electricity transmission environment. It is submitted that the results of this investigation will enable the operators of bulk electricity transmission systems to match the level of investment in reliability related infrastructure, with customers’ reliability preferences. To do this it is necessary to incorporate the economic valueof- service reliability to customers into the economic evaluation used by utility planners.

Baselines and benchmarks (B&Bs) are needed to evaluate the ecological status and fisheries potential of coral reefs. B&Bs may depend on habitat features and energetic limitations that constrain biomass within the natural variability of the environment and fish behaviors. To evaluate if broad B&Bs exist, we compiled data on the biomass of fishes in ~1000 reefs with no recent history of fishing in 19 ecoregions. These reefs spanned the full longitude and latitude of Indian and Pacific Ocean reefs and included older high-compliance fisheries closures (>15 yr closure) and remote reef areas (>9 h travel time from fisheries markets). There was no significant change in biomass over the 15 to 48 yr closure period but closures had only ~40% of the biomass (740 kg ha−1, lower confidence interval [LCI] = 660 kg ha−1, upper confidence interval [UCI] = 810 kg ha−1, n = 157) of remote tropical reefs (1870 [1730, 2000] kg ha−1, n = 503). Remote subtropical reefs had lower biomass (950 [860, 1040] kg ha−1, n = 329) than tropical reefs. Closures and remote reef fish biomass responded differently to environmental variables of coral cover, net primary productivity, and light, indicating that remote reefs are more limited by productivity and habitat than closures. Closures in fished seascapes are unlikely to achieve the biomass and community composition of remote reefs, which suggests fisheries benchmarks will differ substantially from wilderness baselines. A fishery benchmark (B₀) of ~1000 kg ha−1 adjusted for geography is suggested for fisheries purposes. For ecological purposes, a wilderness baseline of ~1900 kg ha−1 is appropriate for including large and mobile species not well protected by closures.

Objectives: Unilateral multicystic kidney dysplasia (MCKD) is the second most common urinary tract abnormality diagnosed antenatally. Whilst an isolated unilateral MCKD has a good prognosis, a poor outcome must be expected when MCKD is associated with other complex abnormalities. Material: Out of 11,176 cases, 693 fetuses were suspected of having urinary tract abnormalities. Urological findings were confirmed in 548 of them. Unilateral cystic kidney was diagnosed prenatally in 85 cases. Results: The study results in a total of 107 cases with proven MCKD. Eighty-five pregnancies with a prenatal diagnosis of MCKD were analysed. The antenatal diagnosis of MCKD was confirmed in 56 cases. Fifty-one children were found to have unilateral MCKD where this had not been explicitly suspected from antenatal scanning. Conclusion: Unilateral MCKD is a malformation with an excellent prognosis for child survival and global renal function if encountered in isolation. However, our analysis of live infants and autopsy cases demonstrates a high proportion of severe associated malformations of the urinary tract and other organ systems.

BACKGROUND AND AIMS: Most priming studies have been conducted on commercial seed lots of unspecified uniformity and maturity, and subsequent seed longevity has been reported to both increase and decrease. Here a seed lot of Digitalis purpurea L. with relatively uniform maturity and known history was used to analyse the effects of priming on seed longevity in air-dry storage. METHODS: Seeds collected close to natural dispersal and dried at 15 % relative humidity (RH), 15 °C, were placed into experimental storage (60 % RH, 45 °C) for 14 or 28 d, primed for 48 h at 0, -1, -2, -5, -10 or -15 MPa, re-equilibrated (47 % RH, 20 °C) and then returned to storage. Further seed samples were primed for 2 or 48 h at -1 MPa and either dried at 15 % RH, 15 °C or immediately re-equilibrated for experimental storage. Finally, some seeds were given up to three cycles of experimental storage and priming (48 h at -1 MPa). KEY RESULTS: Priming at -1 MPa had a variable effect on subsequent survival during experimental storage. The shortest lived seeds in the control population showed slightly increased life spans; the longer lived seeds showed reduced life spans. In contrast, seeds first stored for 14 or 28 d before priming had substantially increased life spans. The increase tended to be greatest in the shortest lived fraction of the seed population. Both the period of rehydration and the subsequent drying conditions had significant effects on longevity. Interrupting air-dry storage with additional cycles of priming also increased longevity. CONCLUSIONS: The extent of prior deterioration and the post-priming desiccation environment affect the benefits of priming to the subsequent survival of mature seeds. Rehydration-dehydration treatments may have potential as an adjunct or alternative to the regeneration of seed accessions maintained in gene banks for plant biodiversity conservation or plant breeding.

BACKGROUND AND AIMS: Using two parental clones of outcrossing Trifolium ambiguum as a potential model system, we examined how during seed development the maternal parent, number of seeds per pod, seed position within the pod, and pod position within the inflorescence influenced individual seed fresh weight, dry weight, water content, germinability, desiccation tolerance, hardseededness, and subsequent longevity of individual seeds. METHODS: Near simultaneous, manual reciprocal crosses were carried out between clonal lines for two experiments. Infructescences were harvested at intervals during seed development. Each individual seed was weighed and then used to determine dry weight or one of the physiological behaviour traits. KEY RESULTS: Whilst population mass maturity was reached at 33-36 days after pollination (DAP), seed-to-seed variation in maximum seed dry weight, when it was achieved, and when maturation drying commenced, was considerable. Individual seeds acquired germinability between 14 and 44 DAP, desiccation tolerance between 30 and 40 DAP, and the capability to become hardseeded between 30 and 47 DAP. The time for viability to fall to 50 % (p₅₀) at 60 % relative humidity and 45 °C increased between 36 and 56 DAP, when the seed coats of most individuals had become dark orange, but declined thereafter. Individual seed f. wt at harvest did not correlate with air-dry storage survival period. Analysing survival data for cohorts of seeds reduced the standard deviation of the normal distribution of seed deaths in time, but no sub-population showed complete uniformity of survival period. CONCLUSIONS: Variation in individual seed behaviours within a developing population is inherent and inevitable. In this outbreeder, there is significant variation in seed longevity which appears dependent on embryo genotype with little effect of maternal genotype or architectural factors.