Formicamycin biosynthesis involves a unique reductive ring contraction

Fasamycin natural products are biosynthetic precursors of the formicamycins. Both groups of compounds are polyketide natural products that exhibit potent antibacterial activity despite displaying different three-dimensional topologies. We show here that transformation of fasamycin into formicamycin metabolites requires two gene products and occurs via a novel two-step ring expansion-ring contraction pathway. Deletion of forX, encoding a flavin dependent monooxygenase, abolished formicamycin production and leads to accumulation of fasamycin E. Deletion of the adjacent gene forY, encoding a flavin dependent oxidoreductase, also abolished formicamycin biosynthesis and led to the accumulation of new lactone metabolites that represent Baeyer–Villiger oxidation products of the fasamycins. These results identify ForX as a Baeyer–Villiger monooxygenase capable of dearomatizing ring C of the fasamycins. Through in vivo cross feeding and biomimetic semi-synthesis experiments we showed that these lactone products represent biosynthetic intermediates that are reduced to formicamycins in a unique reductive ring contraction reaction catalyzed by ForY

From individual responses to population effects : integrating a decade of multidisciplinary research on blue whales and sonar

Funding: Office of Naval Research (GrantNumber(s): N00014-19-1-2464).As ecosystems transform under climate change and expanding human activities, multidisciplinary integration of empirical research, conceptual frameworks and modelling methods is required to predict, monitor and manage the cascading effects on wildlife populations. For example, exposure to anthropogenic noise can lead to changes in the behaviour and physiology of individual marine mammals, but management is complicated by uncertainties on the long-term effects at a population level. We build on a decade of diverse efforts to demonstrate the strengths of integrating research on multiple stressors for assessing population-level effects. Using the case study of blue whales exposed to military sonar in the eastern north Pacific, we model how behavioural responses and environmental effects induced by climate change affect female survival and reproductive success. Environmental changes were predicted to severely affect vital rates, while the current regime of sonar activities was not. Simulated disturbance had a stronger effect on reproductive success than adult survival, as predicted by life-history theory. We show that information on prey resources is critical for robust predictions, as are data on baseline behavioural patterns, energy budgets, body condition and contextual responses to noise. These results will support effective management of the interactions between sonar operations and blue whales in the study area, while providing pragmatic guidance for future data collection to reduce key uncertainties. Our study provides important lessons for the successful integration of multidisciplinary research to inform the assessment of the effects of noise and other anthropogenic stressors on marine predator populations in the context of a changing environment.Publisher PDFPeer reviewe

Higher-order modulations in the skyrmion-lattice phase of Cu2_2OSeO3_3

Using small angle neutron scattering, we have investigated higher-order peaks in the skyrmion-lattice phase of Cu$_2$OSeO$_3$, in which two different skyrmion lattices, SkX1 and SkX2, are known to form. For each skyrmion-lattice phase, we observed two sets of symmetrically inequivalent peaks at the higher-order-reflection positions with the indices $(110)$ and $(200)$. Under the condition where the SkX1 and SkX2 coexist, we confirmed the absence of the scattering at $\mathbf{Q}$ positions combining reflections from the two phases, indicating a significantly weak double-scattering component. Detailed analysis of the peak profile, as well as the temperature and magnetic-field dependence of the peak intensity, also supports the intrinsic higher-order modulation rather than the parasitic double scattering. The two higher-order modulations show contrasting magnetic-field dependence; the former $(110)$ increases as the field is increased, whereas the latter $(200)$ decreases. This indicates that, in Cu$_2$OSeO$_3$, skyrmions are weakly distorted, and the distortion is field-dependent in a way that the dominant higher-order modulation switches from $(110)$ to $(200)$ under field. Monte Carlo simulations under sweeping external magnetic field qualitatively reproduce the observed magnetic-field dependence, and suggests that the higher-order modulations correspond to the superlattices of weak swirlings appearing in the middle of the original triangular-latticed skyrmions.Comment: 13 pages, 14 figure

The Edgeworth-Kuiper debris disk

(Abridged) The Edgeworth-Kuiper belt with its presumed dusty debris is a natural reference for extrsolar debris disks. We employ a new algorithm to eliminate the inclination and the distance selection effects in the known TNO populations to derive expected parameters of the "true" EKB. Its estimated mass is M_EKB=0.12 M_earth, which is by a factor of \sim 15 larger than the mass of the EKB objects detected so far. About a half of the total EKB mass is in classical and resonant objects and another half is in scattered ones. Treating the debiased populations of EKB objects as dust parent bodies, we then "generate" their dust disk with our collisional code. Apart from accurate handling of collisions and direct radiation pressure, we include the Poynting-Robertson (P-R) drag, which cannot be ignored for the EKB dust disk. Outside the classical EKB, the radial profile of the optical depth approximately follows tau \sim r^-2 which is roughly intermediate between the slope predicted analytically for collision-dominated (r^-1.5) and transport-dominated (r^-2.5) disks. The cross section-dominating grain size still lies just above the blowout size (\sim 1...2 \microm), as it would without the P-R transport. However, if the EKB were by one order of magnitude less massive, the optical depth profile would fall off as tau \sim r^-3, and the cross section-dominating grain size would shift from \sim 1...2\microm to ~100 \microm. These properties are seen if dust is assumed to be generated only by known TNOs. If the solar system were observed from outside, the thermal emission flux from the EKB dust would be about two orders of magnitude lower than for solar-type stars with the brightest known infrared excesses observed from the same distance. Herschel and other new-generation facilities should reveal extrasolar debris disks nearly as tenuous as the EKB disk. The Herschel/PACS instrument should be able to detect disks at a \sim 1...2M_EKB level.Comment: 18 pages, 14 figures, accepted for publication in A&

An evaluation of the effectiveness of a computer-assisted reading intervention

Background. A cost-effective method to address reading delays is to use computer-assisted learning, but these are not always effective. Methods. We evaluated a commercially available computer system which uses visual mnemonics, in a randomised controlled trial with 78 English speaking children (mean age 7;7 years) who their schools identified as needing reading support. School based individual tutorials usually took place 2-3 times/week. Only the experimental group received the intervention in the first 10 months, thereafter both the experimental and control groups received the intervention for 6 months. Results. After 10 months the experimental group had significantly higher standardised scores than the waiting list control group of decoding, phonological awareness, naming speed, phonological short-term memory and executive loaded working memory. Conclusions. The computer-assisted intervention was effective and this suggests that this medium can be used for reading interventions with English speaking children

Healthcare-associated Viral Gastroenteritis among Children in a Large Pediatric Hospital, United Kingdom

Enteric viruses introduced from the community are major causes of these illnesses

Stakes sensitivity and credit rating: a new challenge for regulators

The ethical practices of credit rating agencies (CRAs), particularly following the 2008 financial crisis, have been subject to extensive analysis by economists, ethicists, and policymakers. We raise a novel issue facing CRAs that has to do with a problem concerning the transmission of epistemic status of ratings from CRAs to the beneficiaries of the ratings (investors, etc.), and use it to provide a new challenge for regulators. Building on recent work in philosophy, we argue that since CRAs have different stakes than the beneficiaries of the ratings in the ratings being accurate, what counts as knowledge (and as having ‘epistemic status’) concerning credit risk for a CRA may not count as knowledge (as having epistemic status) for the beneficiary. Further, as it stands, many institutional investors (pension funds, insurance companies, etc.) are bound by law to make some of their investment decisions dependent on the ratings of officially recognized CRAs. We argue that the observation that the epistemic status of ratings does not transmit from CRAs to beneficiaries makes salient a new challenge for those who think current regulation regarding the CRAs is prudentially justified, namely, to show that the harm caused by acting on a rating that does not have epistemic status for beneficiaries is compensated by the benefit from them acting on a CRA rating that does have epistemic status for the CRA. Unlike most other commentators, therefore, we offer a defeasible reason to drop references to CRAs in prudential regulation of the financial industry

The relation between executive functioning, reaction time, naming speed and single word reading in children with typical development and language impairments

Background. Few investigations have examined the relationship between a comprehensive range of executive functioning (EF) abilities and reading. Aims. Our investigation identified components of EF that independently predicted single word reading, and determined whether their predictive role remained when additional variables were included in the regression analyses. This provided information about the EF processes that are related to reading, and the unity and diversity of EF. Sample. This consisted of 160 children: 88 were typically developing with no language difficulties; 72 had language impairments. Method. The assessments involved decoding, ten measures of EF, reaction time, naming speed, non-verbal and verbal age-equivalent scores. Results and conclusions. In the first regression analysis, which only concerned the EF variables, the following verbal forms of EF had significant relationships with decoding: working memory; fluency; planning; and inhibition. Further regression analyses included additional predictor variables: reaction time; naming speed, and age-equivalent scores. These analyses indicated that most of the EF variables continued to predict decoding even when entered with competitor variables. Furthermore, after the entry of executive functioning variables there were no group differences in decoding (typical versus language difficulties). We discuss the contribution of EF and other variables to reading abilities

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente