Light-Driven H2 Evolution and C═C or C═O Bond Hydrogenation by Shewanella oneidensis : A Versatile Strategy for Photocatalysis by Nonphotosynthetic Microorganisms

Photocatalytic chemical synthesis by coupling abiotic photosensitizers to purified enzymes provides an effective way to overcome the low conversion efficiencies of natural photosynthesis while exploiting the high catalytic rates and selectivity of enzymes as renewable, earth-abundant electrocatalysts. However, the selective synthesis of multiple products requires more versatile approaches and should avoid the time-consuming and costly processes of enzyme purification. Here we demonstrate a cell-based strategy supporting light-driven H2 evolution or the hydrogenation of C═C and C═O bonds in a nonphotosynthetic microorganism. Methylviologen shuttles photoenergized electrons from water-soluble photosensitizers to enzymes that catalyze H2 evolution and the reduction of fumarate, pyruvate, and CO2 in Shewanella oneidensis. The predominant reaction is selected by the experimental conditions, and the results allow rational development of cell-based strategies to harness nature’s intrinsic catalytic diversity for selective light-driven synthesis of a wide range of products

The feasibility of using pedometers and brief advice to increase activity in sedentary older women:a pilot study

Background: People over the age of 70 carry the greatest burden of chronic disease, disability and health care use. Participation in physical activity is crucial for health, and walking accounts for much of the physical activity undertaken by sedentary individuals. Pedometers are a useful motivational tool to encourage increased walking and they are cheap and easy to use. The aim of this pilot study was to evaluate the feasibility of the use of pedometers plus a theory-based intervention to assist sedentary older women to accumulate increasing amounts of physical activity, mainly through walking. Methods: Female participants over the age of 70 were recruited from primary care and randomised to receive either pedometer plus a theory-based intervention or a theory-based intervention alone. The theory-based intervention consisted of motivational techniques, goal-setting, barrier identification and self-monitoring with pedometers and daily diaries. The pedometer group were further randomised to one of three target groups: a 10%, 15% or 20% monthly increase in step count to assess the achievability and acceptability of a range of targets. The primary outcome was change in daily activity levels measured by accelerometry. Secondary outcome measures were lower limb function, health related quality of life, anxiety and depression. Results: 54 participants were recruited into the study, with an average age of 76. There were 9 drop outs, 45 completing the study. All participants in the pedometer group found the pedometers easy to use and there was good compliance with diary keeping (96% in the pedometer group and 83% in the theory-based intervention alone group). There was a strong correlation (0.78) between accelerometry and pedometer step counts i.e. indicating that walking was the main physical activity amongst participants. There was a greater increase in activity (accelerometry) amongst those in the 20% target pedometer group compared to the other groups, although not reaching statistical significance (p = 0.192). Conclusion: We have demonstrated that it is feasible to use pedometers and provide theory-based advice to community dwelling sedentary older women to increase physical activity levels and a larger study is planned to investigate this further.Publisher PDFPeer reviewe

Utilization of the PICO framework to improve searching PubMed for clinical questions

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Fast mode decomposition in few-mode fibers

Retrieval of the optical phase information from measurement of intensity is of a high interest because this would facilitate simple and cost-efficient techniques and devices. In scientific and industrial applications that exploit multi-mode fibers, a prior knowledge of spatial mode structure of the fiber, in principle, makes it possible to recover phases using measured intensity distribution. However, current mode decomposition algorithms based on the analysis of the intensity distribution at the output of a few-mode fiber, such as optimization methods or neural networks, still have high computational costs and high latency that is a serious impediment for applications, such as telecommunications. Speed of signal processing is one of the key challenges in this approach. We present a high-performance mode decomposition algorithm with a processing time of tens of microseconds. The proposed mathematical algorithm that does not use any machine learning techniques, is several orders of magnitude faster than the state-of-the-art deep-learning-based methods. We anticipate that our results can stimulate further research on algorithms beyond popular machine learning methods and they can lead to the development of low-cost phase retrieval receivers for various applications of few-mode fibers ranging from imaging to telecommunications

Evolution of Salmonella enterica Virulence via Point Mutations in the Fimbrial Adhesin

Whereas the majority of pathogenic Salmonella serovars are capable of infecting many different animal species, typically producing a self-limited gastroenteritis, serovars with narrow host-specificity exhibit increased virulence and their infections frequently result in fatal systemic diseases. In our study, a genetic and functional analysis of the mannose-specific type 1 fimbrial adhesin FimH from a variety of serovars of Salmonella enterica revealed that specific mutant variants of FimH are common in host-adapted (systemically invasive) serovars. We have found that while the low-binding shear-dependent phenotype of the adhesin is preserved in broad host-range (usually systemically non-invasive) Salmonella, the majority of host-adapted serovars express FimH variants with one of two alternative phenotypes: a significantly increased binding to mannose (as in S. Typhi, S. Paratyphi C, S. Dublin and some isolates of S. Choleraesuis), or complete loss of the mannose-binding activity (as in S. Paratyphi B, S. Choleraesuis and S. Gallinarum). The functional diversification of FimH in host-adapted Salmonella results from recently acquired structural mutations. Many of the mutations are of a convergent nature indicative of strong positive selection. The high-binding phenotype of FimH that leads to increased bacterial adhesiveness to and invasiveness of epithelial cells and macrophages usually precedes acquisition of the non-binding phenotype. Collectively these observations suggest that activation or inactivation of mannose-specific adhesive properties in different systemically invasive serovars of Salmonella reflects their dynamic trajectories of adaptation to a life style in specific hosts. In conclusion, our study demonstrates that point mutations are the target of positive selection and, in addition to horizontal gene transfer and genome degradation events, can contribute to the differential pathoadaptive evolution of Salmonella

Exploring Fold Space Preferences of New-born and Ancient Protein Superfamilies

The evolution of proteins is one of the fundamental processes that has delivered the diversity and complexity of life we see around ourselves today. While we tend to define protein evolution in terms of sequence level mutations, insertions and deletions, it is hard to translate these processes to a more complete picture incorporating a polypeptide's structure and function. By considering how protein structures change over time we can gain an entirely new appreciation of their long-term evolutionary dynamics. In this work we seek to identify how populations of proteins at different stages of evolution explore their possible structure space. We use an annotation of superfamily age to this space and explore the relationship between these ages and a diverse set of properties pertaining to a superfamily's sequence, structure and function. We note several marked differences between the populations of newly evolved and ancient structures, such as in their length distributions, secondary structure content and tertiary packing arrangements. In particular, many of these differences suggest a less elaborate structure for newly evolved superfamilies when compared with their ancient counterparts. We show that the structural preferences we report are not a residual effect of a more fundamental relationship with function. Furthermore, we demonstrate the robustness of our results, using significant variation in the algorithm used to estimate the ages. We present these age estimates as a useful tool to analyse protein populations. In particularly, we apply this in a comparison of domains containing greek key or jelly roll motifs

High pre-diagnosis inflammation-related risk score associated with decreased ovarian cancer survival

BACKGROUND: There is suggestive evidence that inflammation is related to ovarian cancer survival. However, more research is needed to identify inflammation-related factors that are associated with ovarian cancer survival and to determine their combined effects. METHODS: This analysis used pooled data on 8,147 women with invasive epithelial ovarian cancer from the Ovarian Cancer Association Consortium. Pre-diagnosis inflammatory-related exposures of interest included alcohol use, aspirin use, other nonsteroidal anti-inflammatory drug use, body mass index, environmental tobacco smoke exposure, history of pelvic inflammatory disease, polycystic ovarian syndrome, and endometriosis, menopausal hormone therapy use, physical inactivity, smoking status, and talc use. Using Cox proportional hazards (PH) models, the relationship between each exposure and survival was assessed in 50% of the data. A weighted inflammation-related risk score (IRRS) was developed and its association with survival was assessed using Cox PH models in the remaining 50% of the data. RESULTS: There was a statistically significant trend of increasing risk of death per quartile of the IRRS (HR=1.09, 95% CI 1.03-1.14). Women in the upper quartile of the IRRS had 31% higher death rate compared to the lowest quartile (95% CI 1.11-1.54). CONCLUSIONS: A higher pre-diagnosis IRRS was associated with increased mortality risk after an ovarian cancer diagnosis. Further investigation is warranted to evaluate whether post-diagnosis exposures are also associated with survival. IMPACT: Given that pre- and post-diagnosis exposures are often correlated and many are modifiable, our study results can ultimately motivate the development of behavioral recommendations to enhance survival among ovarian cancer patients

Analysis of laser radiation using the Nonlinear Fourier transform

Modern high-power lasers exhibit a rich diversity of nonlinear dynamics, often featuring nontrivial co-existence of linear dispersive waves and coherent structures. While the classical Fourier method adequately describes extended dispersive waves, the analysis of time-localised and/or non-stationary signals call for more nuanced approaches. Yet, mathematical methods that can be used for simultaneous characterisation of localized and extended fields are not yet well developed. Here, we demonstrate how the Nonlinear Fourier transform (NFT) based on the Zakharov-Shabat spectral problem can be applied as a signal processing tool for representation and analysis of coherent structures embedded into dispersive radiation. We use full-field, real-time experimental measurements of mode-locked pulses to compute the nonlinear pulse spectra. For the classification of lasing regimes, we present the concept of eigenvalue probability distributions. We present two field normalisation approaches, and show the NFT can yield an effective model of the laser radiation under appropriate signal normalisation conditions