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Vitamin B12 is an essential nutrient that is not made by plants; consequently, unfortified plant-based foods are not a reliable supply. Recent estimates suggest high rates of vitamin B12 deficiency among the vegetarian and vegan populations, particularly in pregnant women or women of child-bearing age who, for ethical and health reasons, are shifting towards higher consumption of plant-based foods in ever-increasing numbers. Vitamin B12 plays crucial metabolic roles across the life-course and in particular during pregnancy and in early development (first 1000days of life). Evidence now implicates vitamin B12 deficiency with increased risk to a range of neuro, vascular, immune, and inflammatory disorders. However, the current UK recommended nutrient intake for vitamin B12 does not adequately consider the vitamin B12 deficit for those choosing a plant-based diet, including vegetarianism and in particular veganism, representing a hidden hunger. We provide a cautionary note on the importance of preventing vitamin B12 deficits for those individuals choosing a plant-based diet and the health professionals advising them.

Vitamin B12 is an essential nutrient that is not made by plants; consequently, unfortified plant-based foods are not a reliable supply. Recent estimates suggest high rates of vitamin B12 deficiency among the vegetarian and vegan populations, particularly in pregnant women or women of child-bearing age who, for ethical and health reasons, are shifting towards higher consumption of plant-based foods in ever-increasing numbers. Vitamin B12 plays crucial metabolic roles across the life-course and in particular during pregnancy and in early development (first 1000 days of life). Evidence now implicates vitamin B12 deficiency with increased risk to a range of neuro, vascular, immune, and inflammatory disorders. However, the current UK recommended nutrient intake for vitamin B12 does not adequately consider the vitamin B12 deficit for those choosing a plant-based diet, including vegetarianism and in particular veganism, representing a hidden hunger. We provide a cautionary note on the importance of preventing vitamin B12 deficits for those individuals choosing a plant-based diet and the health professionals advising them.

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Background Use of modifed texture diets—thickening of liquids and modifying the texture of foods—in the hope of preventing aspiration, pneumonia and choking, has become central to the current management of dysphagia. The efectiveness of this intervention has been questioned. We examine requirements for a valid informed consent pro‑ cess for this approach and whether the need for informed consent for this treatment is always understood or applied by practitioners. Main text Valid informed consent requires provision of accurate and balanced information, and that agreement is given freely by someone who knows they have a choice. Current evidence, including surveys of practitioners and patients in diferent settings, suggests that practice in this area is often inadequate. This may be due to patients’ communication difculties but also poor communication—and no real attempt to obtain consent—by practitioners before people are ‘put on’ modifed texture diets. Even where discussion occurs, recommendations may be infu‑ enced by professional misconceptions about the efcacy of this treatment, which in turn may poison the well for the informed consent process. Patients cannot make appropriate decisions for themselves if the information provided is fawed and unbalanced. The voluntariness of patients’ decisions is also questionable if they are told ‘you must’, when ‘you might consider’ is more appropriate. Where the decision-making capacity of patients is in question, inappropriate judgements and recommendations may be made by substitute decision makers and courts unless based on accurate information. Conclusion Research is required to examine the informed consent processes in diferent settings, but there is ample reason to suggest that current practice in this area is suboptimal. Staf need to refect on their current practice regarding use of modifed texture diets with an awareness of the current evidence and through the ‘lens’ of informed consent. Education is required for staf to clarify the importance of, and requirements for, valid informed consent and for decision making that refects people’s preferences and values.

Cobalamin (vitamin B12 ) is a cofactor for essential metabolic reactions in multiple eukaryotic taxa, including major primary producers such as algae, and yet only prokaryotes can produce it. Many bacteria can colonize the algal phycosphere, forming stable communities that gain preferential access to photosynthate and in return provide compounds such as B12 . Extended coexistence can then drive gene loss, leading to greater algal-bacterial interdependence. In this study, we investigate how a recently evolved B12 -dependent strain of Chlamydomonas reinhardtii, metE7, forms a mutualism with certain bacteria, including the rhizobium Mesorhizobium loti and even a strain of the gut bacterium E. coli engineered to produce cobalamin. Although metE7 was supported by B12 producers, its growth in co-culture was slower than the B12 -independent wild-type, suggesting that high bacterial B12 provision may be necessary to favour B12 auxotrophs and their evolution. Moreover, we found that an E. coli strain that releases more B12 makes a better mutualistic partner, and although this trait may be more costly in isolation, greater B12 release provided an advantage in co-cultures. We hypothesize that, given the right conditions, bacteria that release more B12 may be selected for, particularly if they form close interactions with B12 -dependent algae.

Cobalamin (vitamin B12) is a cofactor for essential metabolic reactions in multiple eukaryotic taxa, including major primary producers such as algae, and yet only prokaryotes can produce it. Many bacteria can colonize the algal phycosphere, forming stable communities that gain preferential access to photosynthate and in return provide compounds such as B12. Extended coexistence can then drive gene loss, leading to greater algal–bacterial interdependence. In this study, we investigate how a recently evolved B12-dependent strain of Chlamydomonas reinhardtii, metE7, forms a mutualism with certain bacteria, including the rhizobium Mesorhizobium loti and even a strain of the gut bacterium E. coli engineered to produce cobalamin. Although metE7 was supported by B12 producers, its growth in co-culture was slower than the B12-independent wild-type, suggesting that high bacterial B12 provision may be necessary to favour B12 auxotrophs and their evolution. Moreover, we found that an E. coli strain that releases more B12 makes a better mutualistic partner, and although this trait may be more costly in isolation, greater B12 release provided an advantage in co-cultures. We hypothesize that, given the right conditions, bacteria that release more B12 may be selected for, particularly if they form close interactions with B12-dependent algae.

A scoping review to identify and describe what field tests have been developed and used to measure exercise capacity and/or inform exercise prescription in the exercise component of pulmonary rehabilitation of COPD patients.

Food manufacturers are under increasing pressure to limit the amount of free sugars in their products. Many have reformulated products to replace sucrose, glucose and fructose with alternative sweeteners, but some of these have been associated with additional health concerns. Rare sugars are "monosaccharides and their derivatives that hardly exist in nature", and there is increasing evidence that they could have health benefits. This review aimed to scope the existing literature in order to identify the most commonly researched rare sugars, to ascertain their proposed health benefits, mechanisms of action and potential uses, and to highlight knowledge gaps. A process of iterative database searching identified 55 relevant articles. The reported effects of rare sugars were noted, along with details of the research methodologies conducted. Our results indicated that the most common rare sugars investigated are D-psicose and D-tagatose, with the potential health benefits divided into three topics: glycaemic control, body composition and cardiovascular disease. All the rare sugars investigated have the potential to suppress postprandial elevation of blood glucose and improve glycaemic control in both human and animal models. Some animal studies have suggested that certain rare sugars may also improve lipid profiles, alter the gut microbiome and reduce pro-inflammatory cytokine expression. The present review demonstrates that rare sugars could play a role in reducing the development of obesity, type 2 diabetes, and/or cardiovascular disease. However, understanding of the mechanisms by which rare sugars may exert their effects is limited, and their effectiveness when used in reformulated products is unknown.

We expressed a bacterial glucan synthase (Agrobacterium GlgA) in the cytosol of developing endosperm cells in wheat grains, to discover whether it could generate a glucan from cytosolic ADP-glucose. Transgenic lines had high glucan synthase activity during grain filling, but did not accumulate glucan. Instead, grains accumulated very high concentrations of maltose. They had large volumes during development due to high water content, and very shrivelled grains at maturity. Starch synthesis was severely reduced. We propose that cytosolic glucan synthesized by the glucan synthase was immediately hydrolysed to maltose by cytosolic β-amylase(s). Maltose accumulation resulted in a high osmotic potential in developing grain, drawing in excess water that stretched the seed coat and pericarp. Loss of water during grain maturation then led to shrinkage when the grains matured. Maltose accumulation is likely to account for the reduced starch synthesis in transgenic grains, through signalling and toxic effects. Using bioinformatics, we identify an isoform of β-amylase likely to be responsible for maltose accumulation. Removal of this isoform through identification of TILLING mutants or genome editing, combined with co-expression of heterologous glucan synthase and a glucan branching enzyme, may in future enable elevated yields of carbohydrate through simultaneous accumulation of starch and cytosolic glucan., The Plant Journal, 106 (5), ISSN:0960-7412, ISSN:1365-313X

Supplementary Material 4

Supplementary Material 1

Since the description of the Deoxyribonucleic Acid (DNA) molecule (Watson, 1968) and the discovery of its importance as the building block of genetic material, scientific researchers have been developing ways to alter DNA in humans, plants, animals and microorganisms. This alteration is commonly known as genetic engineering. The sciences of biotechnology and molecular biology are based on the techniques of genetic engineering and have been developing since the late 1970s. The techniques, materials and equipment used in the laboratories of both disciplines are very similar. What started as theoretic research in the 1970s has now moved into the mainstream of applied science. Genetic engineering techniques are used to manufacture drugs, foods , beverages, improve plant crops, alter food -animal characteristics, develop vaccines and to improve disease resistance in plants and animals, among the many applications. In the city of Brisbane, Australia in 1993 there were more than fifty public and private research groups using these techniques. In 1983 there were fewer than ten such groups ( author, personal observation). This same sort of growth has been occurring in science -based organisations around the world (Sleigh, 1991). The Genetic Manipulation Advisory Committee (GMAC) (1991) reported that there were 72 organisations in Australia undertaking genetic engineering in 1283 different research projects as of June 30th, 1991. The techniques used in genetic engineering laboratories involve : - carcinogenic, mutagenic and teratogenic chemicals - flammable, toxic and corrosive chemicals - electronic and high voltage equipment - lasers - very high and very low temperatures (200 degree Celsius) - in vitro experimentation - in vivo experimentation (Innes, Gelfand, Snisky and Whitte 1990; Karam, Chao and Warr 1990). The literature shows that all of these techniques present potential hazards to laboratory staff. (see literature review) The challenge for Occupational Health and Safety (OH&S) in institutions where genetic engineering research is conducted is to minimise the risk of the consequences of these hazards to staff. This can be done by developing an OH&S management programme that includes: induction, training, setting safety regulations, preparing safety manuals, monitoring compliance with regulations and ongoing health surveillance. OH&S managers must not only be cognisant of the hazards involved and their consequences, they must also gather data on the following: - What current knowledge staff have of hazards. - What perceptions staff have of the risks posed by each hazard. -What the staff expectations are about the consequence of hazard exposure. - How staff attitudes differ on their personal level of control of risk exposure. The researcher's background has been a combination of scientific research, scientific instrument marketing and recruitment of scientific staff. This has resulted in daily contact with staff in a wide variety of scientific organisations for the last fifteen years. During the course of this contact it has become more evident that, over time, there has been a growing divergence of attitudes to laboratory safety compliance enforcement between government and tertiary organisations and private industry. Private industry has been becoming increasingly strict, particularly in the enforcement of wearing protective clothing and restriction of laboratory access. There appears to have been a much slower change of attitude in government and tertiary facilities.

Supplementary Material 2

Supplementary Material 3

The corrinoid B12 is synthesized only by prokaryotes yet is widely required by eukaryotes as an enzyme cofactor. Microalgae have evolved B12 dependence on multiple occasions, and we previously demonstrated that experimental evolution of the non-B12-requiring alga Chlamydomonas reinhardtii in media supplemented with B12 generated a B12-dependent mutant (hereafter metE7). This clone provides a unique opportunity to study the physiology of a nascent B12 auxotroph. Our analyses demonstrate that B12 deprivation of metE7 disrupts C1 metabolism, causes an accumulation of starch and triacylglycerides, and leads to a decrease in photosynthetic pigments, proteins, and free amino acids. B12 deprivation also caused a substantial increase in reactive oxygen species, which preceded rapid cell death. Survival could be improved without compromising growth by simultaneously depriving the cells of nitrogen, suggesting a type of cross protection. Significantly, we found further improvements in survival under B12 limitation and an increase in B12 use efficiency after metE7 underwent a further period of experimental evolution, this time in coculture with a B12-producing bacterium. Therefore, although an early B12-dependent alga would likely be poorly adapted to coping with B12 deprivation, association with B12-producers can ensure long-term survival whilst also providing a suitable environment for evolving mechanisms to tolerate B12 limitation better.

Pentatricopeptide repeat (PPR) proteins are important RNA regulators in chloroplasts and mitochondria, aiding in RNA editing, maturation, stabilisation or intron splicing, and in transcription and translation of organellar genes. In this review, we summarise all PPR proteins documented so far in plants and the green alga Chlamydomonas. By further analysis of the known target RNAs from Arabidopsis thaliana PPR proteins, we find that all organellar-encoded complexes are regulated by these proteins, although to differing extents. In particular, the orthologous complexes of NADH dehydrogenase (Complex I) in the mitochondria and NADH dehydrogenase-like (NDH) complex in the chloroplast were the most regulated, with respectively 60 and 28% of all characterised A. thaliana PPR proteins targeting their genes.

Additional file 1.

Perioperative complications and deaths occurred while developing a novel surgical model of pediatric kyphosis in 10 to 12 kg male farm-raised Yorkshire piglets. All piglets appeared clinically normal preoperatively. Intraoperative complications included tachycardia, respiratory acidosis, and death. Postoperatively, clinical signs included posterior paresis, head pressing, prolonged anesthetic recovery, difficulty rising, and sudden death. Necropsies were performed on all piglets. Some morbidity and mortality were accurately attributed to the spinal surgery. However, the index piglet for this report died suddenly approximately 16 to 18 h after surgery. Necropsy of this animal revealed clear, serosanguineous pleural and pericardial effusions along with myocardial hemorrhage and hepatic lesions, consistent with mulberry heart disease and hepatosis dietetica, respectively. Serum vitamin E and selenium levels from this animal were below age-specific lab reference ranges. Clinical signs of vitamin E and selenium deficiency are most common in fast-growing weaner piglets. The added stress of major surgery may exacerbate the condition in young piglets. Resolution of morbidity and mortality in both juvenile and adult pigs occurred upon the use of an alternate vendor able to provide feed analyses meeting industry standards, although serum levels of vitamin E and selenium in similar ages and breed of swine were still occasionally slightly below reference ranges.

Ostreococcus tauri, a picoeukaryotic alga that contributes significantly to primary production in oligotrophic waters, has a highly streamlined genome, lacking the genetic capacity to grow without the vitamins thiamine (B1) and cobalamin (B12). Here we demonstrate that the B12 and B1 auxotrophy of O. tauri can be alleviated by co-culturing with a heterotrophic bacterial partner Dinoroseobacter shibae, a member of the Rhodobacteraceae family of alpha-proteobacteria, genera of which are frequently found associated with marine algae. D. shibae lacks the complete pathway to synthesise three other B-vitamins: niacin (B3), biotin (B7), and p-aminobenzoic acid (a precursor for folate, B9), and the alga is in turn able to satisfy the reciprocal vitamin requirements of its bacterial partner in a stable long-term co-culture. Bioinformatics searches of 197 representative marine bacteria with sequenced genomes identified just nine species that had a similar combination of traits (ability to make vitamin B12, but missing one or more genes for niacin and biotin biosynthesis enzymes), all of which were from the Rhodobacteraceae. Further analysis of 70 species from this family revealed the majority encoded the B12 pathway, but only half were able to make niacin, and fewer than 13% biotin. These characteristics may have either contributed to or resulted from the tendency of members of this lineage to adopt lifestyles in close association with algae. This study provides a nuanced view of bacterial-phytoplankton interactions, emphasising the complexity of the sources, sinks and dynamic cycling between marine microbes of these important organic micronutrients.

The ptm mutant of Arabidopsis does not show a genomes uncoupled mutant phenotype and PTM is therefore unlikely to function in chloroplast-to-nucleus signaling as previously reported.

The important plant hormone salicylic acid (SA; 2-hydroxybenzoic acid) regulates several key plant responses including, most notably, defence against pathogens. A key enzyme for SA biosynthesis is isochorismate synthase (ICS), which converts chorismate into isochorismate, and for which there are two genes in Arabidopsis thaliana. One (AtICS1) has been shown to be required for increased SA biosynthesis in response to pathogens and its expression can be stimulated throughout the leaf by virus infection and exogenous SA. The other (AtICS2) appears to be expressed constitutively, predominantly in the plant vasculature. Here, we characterise the enzymatic activity of both isozymes expressed as hexahistidine fusion proteins in Escherichia coli. We show for the first time that recombinant AtICS2 is enzymatically active. Both isozymes are Mg2+-dependent with similar temperature optima (ca. 33°C) and similar Km values for chorismate of 34.3 ± 3.7 and 28.8 ± 6.9 µM for ICS1 and ICS2, respectively, but reaction rates were greater for ICS1 than for ICS2, with respective values for Vmax of 63.5 ± 2.4 and 28.3 ± 2.0 nM s−1 and for kcat of 38.1 ± 1.5 and 17.0 ± 1.2 min−1. However, neither enzyme displayed isochorismate pyruvate lyase (IPL) activity, which would enable these proteins to act as bifunctional SA synthases, i.e. to convert chorismate into SA. These results show that although Arabidopsis has two functional ICS enzymes, it must possess one or more IPL enzymes to complete biosynthesis of SA starting from chorismate.

Experimental data and source code files for the paper 'Combining SIMS and mechanistic modelling to reveal nutrient kinetics in an algal-bacterial mutualism'. The zipped folder 'ExperimentData.zip' contains data files with the data obtained from Secondary Ion Mass Spectrometry (SIMS), Isotope Ratio Mass Spectrometry (IRMS), growth measurements and the B12 bioassay as described in the paper. The zipped folder 'MatlabCode.zip' contains the Matlab source code and data files that were used to solve the model equations and to run the global parameter optimisations for the axenic cultures and the co-culture. The file 'odefun.m' defines the model ODEs and the file 'model_run.m' specifies the solver used to solve the model ODEs. The file 'Gf_global_optimisation.m' runs the global parameter optimisation with the objective function being minimised defined by the file 'Gf_obj_function.m' and the non-linear constraints defined by the file 'nonlconstraints.m'. The file 'initial_conditions.m' specifies the initial conditions for the culture and the file 'parameters.m' specifies the model parameter values. The folders 'growth' and 'SIMSdata' contain the relevant Matlab data files needed for the parameter optimisations. The output of the global parameter optimisations can also be found in the relevant folders. The zipped folder ‘PythonCode.zip’ contains the source code files used for the global parameter optimisation in Supplementary Figure S5. The file ‘experimental_data_global_import_result.npz’ is a NumPy array containing all the experimental results from which the fit is based. The file ‘data_global_fit.py’ is the main fit script that launched 32 basin-hoppers to optimize the fit to the data. It thus loads the data (which clarifies what the previous file contains), defines the cost functions and runs the fit. The file ‘utils.py’ is a small utilities file, which contains two functions for saving figures and files. It is used by the global fit file, so is submitted here for completion. The file ‘cysolver2.pyx’ is the finite difference solver called by the main fitting script in order to evaluate the co-culture model forward in time given initial conditions and parameters. It is in Cython, the C-based python for fast calculation. The folder ‘basin_hopping_result.zip’ is an archive containing the 32 Numpy files that correspond to the 32 results obtained on 22nd of March 2017 when the solver was run. The result used for Supplementary Figure S5 is #6 (from #0 to #31). Below is a list of the labels used to help identify the cultures relevant to the isotope labelling experiments in the paper. List of cultures: A: preliminary experiment, algal pre-culture (unlabelled) Aii: main experiment, algal pre-culture (unlabelled) Bii: main experiment, bacteria pre-culture (unlabelled) 1: preliminary experiment, algal pre-labelling culture 1ii: main experiment, algal pre-labelling culture 2: preliminary experiment, algal data for the labelled co-culture 2ii: main experiment, the labelled co-culture 3: preliminary experiment, unlabelled axenic culture of algae 4: preliminary experiment, unlabelled co-culture 5: preliminary experiment, axenic bacteria with 0.1% glycerol 5ii: main experiment, axenic bacteria with 0.1% glycerol 6: main experiment, axenic bacteria with no glycerol 7: main experiment, axenic bacteria with 0.01% glycerol 8: main experiment, axenic bacteria with 0.001% glycerol &nbsp

Tables S1-3, Figures S1-15

MIQE checklist for qRT-PCR

Importance: Understanding causes and correlates of health loss among children and adolescents can identify areas of success, stagnation, and emerging threats and thereby facilitate effective improvement strategies. Objective: To estimate mortality and morbidity in children and adolescents from 1990 to 2017 by age and sex in 195 countries and territories. Design, Setting, and Participants: This study examined levels, trends, and spatiotemporal patterns of cause-specific mortality and nonfatal health outcomes using standardized approaches to data processing and statistical analysis. It also describes epidemiologic transitions by evaluating historical associations between disease indicators and the Socio-Demographic Index (SDI), a composite indicator of income, educational attainment, and fertility. Data collected from 1990 to 2017 on children and adolescents from birth through 19 years of age in 195 countries and territories were assessed. Data analysis occurred from January 2018 to August 2018. Exposures: Being under the age of 20 years between 1990 and 2017. Main Outcomes and Measures: Death and disability. All-cause and cause-specific deaths, disability-adjusted life years, years of life lost, and years of life lived with disability. Results: Child and adolescent deaths decreased 51.7% from 13.77 million (95% uncertainty interval [UI], 13.60-13.93 million) in 1990 to 6.64 million (95% UI, 6.44-6.87 million) in 2017, but in 2017, but aggregate disability increased 4.7% to a total of 145 million (95% UI, 107-190 million) years lived with disability globally. Progress was uneven, and inequity increased, with low-SDI and low-middle-SDI locations experiencing 82.2% (95% UI, 81.6%-82.9%) of deaths, up from 70.9% (95% UI, 70.4%-71.4%) in 1990. The leading disaggregated causes of disability-adjusted life years in 2017 in the low-SDI quintile were neonatal disorders, lower respiratory infections, diarrhea, malaria, and congenital birth defects, whereas neonatal disorders, congenital birth defects, headache, dermatitis, and anxiety were highest-ranked in the high-SDI quintile. Conclusions and Relevance: Mortality reductions over this 27-year period mean that children are more likely than ever to reach their 20th birthdays. The concomitant expansion of nonfatal health loss and epidemiological transition in children and adolescents, especially in low-SDI and middle-SDI countries, has the potential to increase already overburdened health systems, will affect the human capital potential of societies, and may influence the trajectory of socioeconomic development. Continued monitoring of child and adolescent health loss is crucial to sustain the progress of the past 27 years..

Importance: Understanding causes and correlates of health loss among children and adolescents can identify areas of success, stagnation, and emerging threats and thereby facilitate effective improvement strategies.Objective: To estimate mortality and morbidity in children and adolescents from 1990 to 2017 by age and sex in 195 countries and territories.Design, Setting, and Participants: This study examined levels, trends, and spatiotemporal patterns of cause-specific mortality and nonfatal health outcomes using standardized approaches to data processing and statistical analysis. It also describes epidemiologic transitions by evaluating historical associations between disease indicators and the Socio-Demographic Index (SDI), a composite indicator of income, educational attainment, and fertility. Data collected from 1990 to 2017 on children and adolescents from birth through 19 years of age in 195 countries and territories were assessed. Data analysis occurred from January 2018 to August 2018.Exposures: Being under the age of 20 years between 1990 and 2017.Main Outcomes and Measures: Death and disability. All-cause and cause-specific deaths, disability-adjusted life years, years of life lost, and years of life lived with disability.Results: Child and adolescent deaths decreased 51.7% from 13.77 million (95% uncertainty interval [UI], 13.60-13.93 million) in 1990 to 6.64 million (95% UI, 6.44-6.87 million) in 2017, but in 2017, but aggregate disability increased 4.7% to a total of 145 million (95% UI, 107-190 million) years lived with disability globally. Progress was uneven, and inequity increased, with low-SDI and low-middle-SDI locations experiencing 82.2% (95% UI, 81.6%-82.9%) of deaths, up from 70.9% (95% UI, 70.4%-71.4%) in 1990. The leading disaggregated causes of disability-adjusted life years in 2017 in the low-SDI quintile were neonatal disorders, lower respiratory infections, diarrhea, malaria, and congenital birth defects, whereas neonatal disorders, congenital birth defects, headache, dermatitis, and anxiety were highest-ranked in the high-SDI quintile.Conclusions and Relevance: Mortality reductions over this 27-year period mean that children are more likely than ever to reach their 20th birthdays. The concomitant expansion of nonfatal health loss and epidemiological transition in children and adolescents, especially in low-SDI and middle-SDI countries, has the potential to increase already overburdened health systems, will affect the human capital potential of societies, and may influence the trajectory of socioeconomic development. Continued monitoring of child and adolescent health loss is crucial to sustain the progress of the past 27 years.

Summary Photosynthetic microbes exhibit light‐dependent electron export across the cell membrane, which can generate electricity in biological photovoltaic (BPV) devices. How electrons are exported remains to be determined; the identification of mechanisms would help selection or generation of photosynthetic microbes capable of enhanced electrical output. We show that plasma membrane NADPH oxidase activity is a significant component of light‐dependent generation of electricity by the unicellular green alga Chlamydomonas reinhardtii. NADPH oxidases export electrons across the plasma membrane to form superoxide anion from oxygen. The C. reinhardtii mutant lacking the NADPH oxidase encoded by RBO1 is impaired in both extracellular superoxide anion production and current generation in a BPV device. Complementation with the wild‐type gene restores both capacities, demonstrating the role of the enzyme in electron export. Monitoring light‐dependent extracellular superoxide production with a colorimetric assay is shown to be an effective way of screening for electrogenic potential of candidate algal strains. The results show that algal NADPH oxidases are important for superoxide anion production and open avenues for optimizing the biological component of these devices.

Increasing feed efficiency is a key target in ruminant science which requires a better understanding of rumen microbiota. This study investigated the effect of a shift from a non-grazing to a grazing diet on the rumen bacterial, methanogenic archaea, fungal, and protozoal communities. A systems biology approach based on a description of the community structure, core microbiota, network analysis, and taxon abundance linked to the rumen fermentation was used to explore the benefits of increasing depth of the community analysis. A total of 24 sheep were fed ryegrass hay supplemented with concentrate (CON) and subsequently ryegrass pasture (PAS) following a straight through experimental design. Results showed that concentrate supplementation in CON-fed animals (mainly starch) promoted a simplified rumen microbiota in terms of network density and bacterial, methanogen and fungal species richness which favored the proliferation of amylolytic microbes and VFA production (+48%), but led to a lower (ca. 4-fold) ammonia concentration making the N availability a limiting factor certain microbes. The adaptation process from the CON to the PAS diet consisted on an increase in the microbial concentration (biomass of bacteria, methanogens, and protozoa), diversity (+221, +3, and +21 OTUs for bacteria, methanogens, and fungi, respectively), microbial network complexity (+18 nodes and +86 edges) and in the abundance of key microbes involved in cellulolysis (Ruminococcus, Butyrivibrio, and Orpinomyces), proteolysis (Prevotella and Entodiniinae), lactate production (Streptococcus and Selenomonas), as well as methylotrophic archaea (Methanomassiliicoccaceae). This microbial adaptation indicated that pasture degradation is a complex process which requires a diverse consortium of microbes working together. The correlations between the abundance of microbial taxa and rumen fermentation parameters were not consistent across diets suggesting a metabolic plasticity which allowed microbes to adapt to different substrates and to shift their fermentation products. The core microbiota was composed of 34, 9, and 13 genera for bacteria, methanogens, and fungi, respectively, which were shared by all sheep, independent of diet. This systems biology approach adds a new dimension to our understanding of the rumen microbial interactions and may provide new clues to describe the mode of action of future nutritional interventions.

Supplemental material, AUT823910_Lay_Abstract for Examining the impact of physical activity on sleep quality and executive functions in children with autism spectrum disorder: A randomized controlled trial by Choi Yeung Andy Tse, Hong Paul Lee, Ka Shing Kevin Chan, Boades Veronica Edgar, Alison Wilkinson-Smith and Wing Him Elvis Lai in Autism

Importance: Understanding causes and correlates of health loss among children and adolescents can identify areas of success, stagnation, and emerging threats and thereby facilitate effective improvement strategies. Objective: To estimate mortality and morbidity in children and adolescents from 1990 to 2017 by age and sex in 195 countries and territories. Design, Setting, and Participants: This study examined levels, trends, and spatiotemporal patterns of cause-specific mortality and nonfatal health outcomes using standardized approaches to data processing and statistical analysis. It also describes epidemiologic transitions by evaluating historical associations between disease indicators and the Socio-Demographic Index (SDI), a composite indicator of income, educational attainment, and fertility. Data collected from 1990 to 2017 on children and adolescents from birth through 19 years of age in 195 countries and territories were assessed. Data analysis occurred from January 2018 to August 2018. Exposures: Being under the age of 20 years between 1990 and 2017. Main Outcomes and Measures: Death and disability. All-cause and cause-specific deaths, disability-adjusted life years, years of life lost, and years of life lived with disability. Results: Child and adolescent deaths decreased 51.7% from 13.77 million (95% uncertainty interval [UI], 13.60-13.93 million) in 1990 to 6.64 million (95% UI, 6.44-6.87 million) in 2017, but in 2017, aggregate disability increased 4.7% to a total of 145 million (95% UI, 107-190 million) years lived with disability globally. Progress was uneven, and inequity increased, with low-SDI and low-middle–SDI locations experiencing 82.2% (95% UI, 81.6%-82.9%) of deaths, up from 70.9% (95% UI, 70.4%-71.4%) in 1990. The leading disaggregated causes of disability-adjusted life years in 2017 in the low-SDI quintile were neonatal disorders, lower respiratory infections, diarrhea, malaria, and congenital birth defects, whereas neonatal disorders, congenital birth defects, headache, dermatitis, and anxiety were highest-ranked in the high-SDI quintile. Conclusions and Relevance: Mortality reductions over this 27-year period mean that children are more likely than ever to reach their 20th birthdays. The concomitant expansion of nonfatal health loss and epidemiological transition in children and adolescents, especially in low-SDI and middle-SDI countries, has the potential to increase already overburdened health systems, will affect the human capital potential of societies, and may influence the trajectory of socioeconomic development. Continued monitoring of child and adolescent health loss is crucial to sustain the progress of the past 27 years.

Plants accumulate reserves in the daytime to support growth at night. Circadian regulation of diel reserve turnover was investigated by profiling starch, sugars, glucose 6-phosphate, organic acids and amino acids during a light-dark cycle and after transfer to continuous light in Arabidopsis wild-types and in mutants lacking dawn (lhy cca1), morning (prr7 prr9), dusk (toc1, gi) or evening (elf3) clock components. The metabolite time-series were integrated with published time-series for circadian clock transcripts to identify circadian outputs that regulate central metabolism. i) Starch accumulation was slower in elf3 and prr7 prr9. It is proposed that ELF3 positively regulates starch accumulation. ii) Reducing sugars were high early in the T-cycle in elf3, revealing that ELF3 negatively regulates sucrose recycling. iii) The pattern of starch mobilization was modified in all five mutants. A model is proposed in which dawn and dusk/evening components interact to pace degradation to anticipated dawn. iv) An endogenous oscillation of glucose 6-phosphate revealed that the clock buffers metabolism against the large influx of carbon from photosynthesis. v) Low levels of organic and amino acids in lhy cca1 and high levels in prr7 prr9 provide evidence that the dawn components positively regulate the accumulation of amino acid reserves.

IMPORTANCE Understanding causes and correlates of health loss among children and adolescents can identify areas of success, stagnation, and emerging threats and thereby facilitate effective improvement strategies. OBJECTIVE To estimate mortality and morbidity in children and adolescents from 1990 to 2017 by age and sex in 195 countries and territories. DESIGN, SETTING, AND PARTICIPANTS This study examined levels, trends, and spatiotemporal patterns of cause-specific mortality and nonfatal health outcomes using standardized approaches to data processing and statistical analysis. It also describes epidemiologic transitions by evaluating historical associations between disease indicators and the Socio-Demographic Index (SDI), a composite indicator of income, educational attainment, and fertility. Data collected from 1990 to 2017 on children and adolescents from birth through 19 years of age in 195 countries and territories were assessed. Data analysis occurred from January 2018 to August 2018. EXPOSURES Being under the age of 20 years between 1990 and 2017. MAIN OUTCOMES AND MEASURES Death and disability. All-cause and cause-specific deaths, disability-adjusted life years, years of life lost, and years of life lived with disability. RESULTS Child and adolescent deaths decreased 51.7% from 13.77 million (95% uncertainty interval [UI], 13.60-13.93 million) in 1990 to 6.64 million (95% UI, 6.44-6.87 million) in 2017, but in 2017, aggregate disability increased 4.7% to a total of 145 million (95% UI, 107-190 million) years lived with disability globally. Progress was uneven, and inequity increased, with low-SDI and low-middle-SDI locations experiencing 82.2%(95% UI, 81.6%-82.9%) of deaths, up from 70.9%(95% UI, 70.4%-71.4%) in 1990. The leading disaggregated causes of disability-adjusted life years in 2017 in the low-SDI quintile were neonatal disorders, lower respiratory infections, diarrhea, malaria, and congenital birth defects, whereas neonatal disorders, congenital birth defects, headache, dermatitis, and anxiety were highest-ranked in the high-SDI quintile. CONCLUSIONS AND RELEVANCE Mortality reductions over this 27-year period mean that children are more likely than ever to reach their 20th birthdays. The concomitant expansion of nonfatal health loss and epidemiological transition in children and adolescents, especially in low-SDI and middle-SDI countries, has the potential to increase already overburdened health systems, will affect the human capital potential of societies, and may influence the trajectory of socioeconomic development. Continued monitoring of child and adolescent health loss is crucial to sustain the progress of the past 27 years.

Supplemental material, AUT823910_Supplemental_material for Examining the impact of physical activity on sleep quality and executive functions in children with autism spectrum disorder: A randomized controlled trial by Choi Yeung Andy Tse, Hong Paul Lee, Ka Shing Kevin Chan, Boades Veronica Edgar, Alison Wilkinson-Smith and Wing Him Elvis Lai in Autism

Increasing feed efficiency is a key target in ruminant science which requires a better understanding of rumen microbiota. This study investigated the effect of a shift from a non-grazing to a grazing diet on the rumen bacterial, methanogenic archaea, fungal, and protozoal communities. A systems biology approach based on a description of the community structure, core microbiota, network analysis, and taxon abundance linked to the rumen fermentation was used to explore the benefits of increasing depth of the community analysis. A total of 24 sheep were fed ryegrass hay supplemented with concentrate (CON) and subsequently ryegrass pasture (PAS) following a straight through experimental design. Results showed that concentrate supplementation in CON-fed animals (mainly starch) promoted a simplified rumen microbiota in terms of network density and bacterial, methanogen and fungal species richness which favored the proliferation of amylolytic microbes and VFA production (+48%), but led to a lower (ca. 4-fold) ammonia concentration making the N availability a limiting factor certain microbes. The adaptation process from the CON to the PAS diet consisted on an increase in the microbial concentration (biomass of bacteria, methanogens, and protozoa), diversity (+221, +3, and +21 OTUs for bacteria, methanogens, and fungi, respectively), microbial network complexity (+18 nodes and +86 edges) and in the abundance of key microbes involved in cellulolysis (Ruminococcus, Butyrivibrio, and Orpinomyces), proteolysis (Prevotella and Entodiniinae), lactate production (Streptococcus and Selenomonas), as well as methylotrophic archaea (Methanomassiliicoccaceae). This microbial adaptation indicated that pasture degradation is a complex process which requires a diverse consortium of microbes working together. The correlations between the abundance of microbial taxa and rumen fermentation parameters were not consistent across diets suggesting a metabolic plasticity which allowed microbes to adapt to different substrates and to shift their fermentation products. The core microbiota was composed of 34, 9, and 13 genera for bacteria, methanogens, and fungi, respectively, which were shared by all sheep, independent of diet. This systems biology approach adds a new dimension to our understanding of the rumen microbial interactions and may provide new clues to describe the mode of action of future nutritional interventions., This work has been supported by the European Regional Development Fund Program through the Welsh Government (WISE Network) and by the BBRSC (BBS/E/W/10964A01). The authors thank Eleanor Jones, Pauline Rees Stevens, Andrew P. Detheridge, and Wanchang Lin for their contribution to the sample analysis.

The rumen is a complex ecosystem composed of anaerobic bacteria, protozoa, fungi, methanogenic archaea and phages. These microbes interact closely to breakdown plant material that cannot be digested by humans, whilst providing metabolic energy to the host and, in the case of archaea, producing methane. Consequently, ruminants produce meat and milk, which are rich in high-quality protein, vitamins and minerals, and therefore contribute to food security. As the world population is predicted to reach approximately 9.7 billion by 2050, an increase in ruminant production to satisfy global protein demand is necessary, despite limited land availability, and whilst ensuring environmental impact is minimized. Although challenging, these goals can be met, but depend on our understanding of the rumen microbiome. Attempts to manipulate the rumen microbiome to benefit global agricultural challenges have been ongoing for decades with limited success, mostly due to the lack of a detailed understanding of this microbiome and our limited ability to culture most of these microbes outside the rumen. The potential to manipulate the rumen microbiome and meet global livestock challenges through animal breeding and introduction of dietary interventions during early life have recently emerged as promising new technologies. Our inability to phenotype ruminants in a high-throughput manner has also hampered progress, although the recent increase in >omic> data may allow further development of mathematical models and rumen microbial gene biomarkers as proxies. Advances in computational tools, high-throughput sequencing technologies and cultivation-independent >omics> approaches continue to revolutionize our understanding of the rumen microbiome. This will ultimately provide the knowledge framework needed to solve current and future ruminant livestock challenges., SH, DM, MP, RM-T, SW, IT, HS, JE, SK, GA, and CC acknowledge the support of ERA-net gas co-fund for funding (Project name: RumenPredict). SH, HM and CC acknowledge support from BBSRC (BBL/L026716/1 and BBL/L026716/2) and a British Council Newton Institutional Links funding (Grant 172629373). IM acknowledges funding from the European Research Council under the European Union's Horizon 2020 research and innovation program (Grant 640384). JE acknowledges funding from an EU H2020 Marie Curie Fellowship (706899). CC, AK-S, and EH were supported by the Biotechnology and Biological Sciences Research Council (Grants BBS/OS/GC/000011B and BBS/E/W/0012843D). CN and OM acknowledge the support of the British Council Newton Institutional Links funding (Grant 216425215). SRUC receives financial support from the Scottish Government's Rural and Environment Science and Analytical Services Division (RESAS). RD and RR acknowledge financial support from the Biotechnology and Biological Sciences Research Council (BBSRC BB/N01720X/1). DY-R and AB acknowledge funding from MINECO, Spain (Grant AGL2017-86938-R). GS acknowledges funding from the U.S. Department of Agriculture National Institute of Food and Agriculture foundational (Grant 2015-67015-23246). EP acknowledges funding from CNPq (Grant 401590/2014-3). All authors are also members of the Global Research Alliance Rumen Microbial Genomics network.

Understanding rumen plant-microbe interactions is central for development of novel methodologies allowing improvements in ruminant nutrient use efficiency. This study investigated rumen bacterial colonization of fresh plant material and changes in plant chemistry over a period of 24 h period using three different fresh forages: Lolium perenne (perennial ryegrass; PRG), Lotus corniculatus (bird's foot trefoil; BFT) and Trifolium pratense (red clover; RC). We show using 16S rRNA gene ion torrent sequencing that plant epiphytic populations present pre-incubation (0 h) were substantially different to those attached post incubations in the presence of rumen fluid on all forages. Thereafter primary and secondary colonization events were evident as defined by changes in relative abundances of attached bacteria and changes in plant chemistry, as assessed using Fourier transform infrared (FTIR) spectroscopy. For PRG colonization, primary colonization occurred for up to 4 h and secondary colonization from 4 h onward. The changes from primary to secondary colonization occurred significantly later with BFT and RC, with primary colonization being up to 6 h and secondary colonization post 6 h of incubation. Across all 3 forages the main colonizing bacteria present at all time points post-incubation were Prevotella, Pseudobutyrivibrio, Ruminococcus, Olsenella, Butyrivibrio, and Anaeroplasma (14.2, 5.4, 1.9, 2.7, 1.8, and 2.0% on average respectively), with Pseudobutyrivibrio and Anaeroplasma having a higher relative abundance during secondary colonization. Using CowPI, we predict differences between bacterial metabolic function during primary and secondary colonization. Specifically, our results infer an increase in carbohydrate metabolism in the bacteria attached during secondary colonization, irrespective of forage type. The CowPI data coupled with the FTIR plant chemistry data suggest that attached bacterial function is similar irrespective of forage type, with the main changes occurring between primary and secondary colonization. These data suggest that the sward composition of pasture may have major implications for the temporal availability of nutrients for animal.

Understanding rumen plant–microbe interactions is central for development of novel methodologies allowing improvements in ruminant nutrient use efficiency. This study investigated rumen bacterial colonization of fresh plant material and changes in plant chemistry over a period of 24 h period using three different fresh forages: Lolium perenne (perennial ryegrass; PRG), Lotus corniculatus (bird’s foot trefoil; BFT) and Trifolium pratense (red clover; RC). We show using 16S rRNA gene ion torrent sequencing that plant epiphytic populations present pre-incubation (0 h) were substantially different to those attached post incubations in the presence of rumen fluid on all forages. Thereafter primary and secondary colonization events were evident as defined by changes in relative abundances of attached bacteria and changes in plant chemistry, as assessedusing Fourier transform infrared (FTIR) spectroscopy. For PRG colonization, primary colonization occurred for up to 4 h and secondary colonization from 4 h onward. The changes from primary to secondary colonization occurred significantly later with BFT and RC, with primary colonization being up to 6 h and secondary colonization post 6 h of incubation. Across all 3 forages the main colonizing bacteria present at all time points post-incubation were Prevotella, Pseudobutyrivibrio, Ruminococcus, Olsenella, Butyrivibrio, and Anaeroplasma (14.2, 5.4, 1.9, 2.7, 1.8, and 2.0% on average respectively), with Pseudobutyrivibrio and Anaeroplasma having a higher relative abundance during secondary colonization. Using CowPI, we predict differencesbetween bacterial metabolic function during primary and secondary colonization.Specifically, our results infer an increase in carbohydrate metabolism in the bacteria attached during secondary colonization, irrespective of forage type. The CowPI data coupled with the FTIR plant chemistry data suggest that attached bacterial function is similar irrespective of forage type, with the main changes occurring between primary and secondary colonization. These data suggest that the sward composition of pasture may have major implications for the temporal availability of nutrients for animal.

From the mid-sixteenth to the mid-nineteenth century Russia was transformed from a moderate-sized, land-locked principality into the largest empire on earth. How did systems of information and communication shape and reflect this extraordinary change? Information and Empire brings together a range of essays to address this complex question. It examines communication networks such as the postal service and the circulation of news, as well as the growth of a bureaucratic apparatus that informed the government about its people. It also considers the inscription of space from the point of view of mapping and the changing public ‘graphosphere’ of signs and monuments. More than a series of institutional histories, this book is concerned with the way Russia discovered itself, envisioned itself and represented itself to its people. Innovative and scholarly, this collection breaks new ground in its approach to communication and information as a fi eld of study in Russia. More broadly, it is an accessible contribution to pre-modern information studies, taking as its basis a country whose history often serves to challenge habitual Western models of development. It is important reading not only for specialists in Russian Studies, but also for students and anyone interested in the history of information and communications.

At the end of 1702, while he was engaged in war with Sweden, Peter the Great decreed that a newspaper be established to spread information about “military and every sort of affairs” to “the people of Muscovy and of neighbouring states”. The newspaper (the word used was kuranty, a seventeenth-century holdover soon to be replaced by the word gazeta) was to be compiled from reports from the state’s various chanceries, all sent to the Monastery Chancery, and printed there in the state printing ho...

Metataxonomic 16S rDNA based studies are a commonplace and useful tool in the research of the microbiome, but they do not provide the full investigative power of metagenomics and metatranscriptomics for revealing the functional potential of microbial communities. However, the use of metagenomic and metatranscriptomic technologies is hindered by high costs and skills barrier necessary to generate and interpret the data. To address this, a tool for Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was developed for inferring the functional potential of an observed microbiome profile, based on 16S data. This allows functional inferences to be made from metataxonomic 16S rDNA studies with little extra work or cost, but its accuracy relies on the availability of completely sequenced genomes of representative organisms from the community being investigated. The rumen microbiome is an example of a community traditionally underrepresented in genome and sequence databases, but recent efforts by projects such as the Global Rumen Census and Hungate 1000 have resulted in a wide sampling of 16S rDNA profiles and almost 500 fully sequenced microbial genomes from this environment. Using this information, we have developed “CowPI,” a focused version of the PICRUSt tool provided for use by the wider scientific community in the study of the rumen microbiome. We evaluated the accuracy of CowPI and PICRUSt using two 16S datasets from the rumen microbiome: one generated from rDNA and the other from rRNA where corresponding metagenomic and metatranscriptomic data was also available. We show that the functional profiles predicted by CowPI better match estimates for both the meta-genomic and transcriptomic datasets than PICRUSt, and capture the higher degree of genetic variation and larger pangenomes of rumen organisms. Nonetheless, whilst being closer in terms of predictive power for the rumen microbiome, there were differences when compared to both the metagenomic and metatranscriptome data and so we recommend, where possible, functional inferences from 16S data should not replace metagenomic and metatranscriptomic approaches. The tool can be accessed at http://www.cowpi.org and is provided to the wider scientific community for use in the study of the rumen microbiome., The work was made possible by a Biotechnology and Biological Sciences Research Council (BBSRC Global Challenges Research Fund for Biological and Data and Resources; BBS/OS/GC/000011B) and was also supported by a BBSRC Institute Strategic Programme Grant, Rumen Systems Biology (BB/E/W/10964A01). The metatranscriptomic sequencing was carried out by The Genome Analysis Centre (TGAC) under the Capacity and Capability Challenge (CCC) program., {"references":["Wilkinson, T.J., Huws, S.A., Edwards, J.E., Kingston-Smith, A., Siu Ting, K., Hughes, M., Rubino, F., Friedersdorff, M. and Creevey, C., 2018. CowPI: A rumen microbiome focussed version of the PICRUSt functional inference software. Frontiers in Microbiology, 9, p.1095."]}

Vitamin B12 is made by only certain prokaryotes yet is required by a number of eukaryotes such as mammals, fish, birds, worms and Protista, including algae. There is still much to learn about how this nutrient is trafficked across the domains of life. Herein, we describe ways to make a number of different corrin analogues with fluorescent groups attached to the main tetrapyrrole-derived ring. A further range of analogues were also constructed by attaching similar fluorescent groups to the ribose ring of cobalamin, thereby generating a range of complete and incomplete corrinoids to follow uptake in bacteria, worms and plants. By using these fluorescent derivatives we were able to demonstrate that Mycobacterium tuberculosis is able to acquire both cobyric acid and cobalamin analogues, that Caenorhabditis elegans takes up only the complete corrinoid, and that seedlings of higher plants such as Lepidium sativum are also able to transport B12.