The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: A systematic analysis from the Global Burden of Disease Study 2016

Background: A key component of achieving universal health coverage is ensuring that all populations have access to quality health care. Examining where gains have occurred or progress has faltered across and within countries is crucial to guiding decisions and strategies for future improvement. We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) to assess personal health-care access and quality with the Healthcare Access and Quality (HAQ) Index for 195 countries and territories, as well as subnational locations in seven countries, from 1990 to 2016. Methods Drawing from established methods and updated estimates from GBD 2016, we used 32 causes from which death should not occur in the presence of effective care to approximate personal health-care access and quality by location and over time. To better isolate potential effects of personal health-care access and quality from underlying risk factor patterns, we risk-standardised cause-specific deaths due to non-cancers by location-year, replacing the local joint exposure of environmental and behavioural risks with the global level of exposure. Supported by the expansion of cancer registry data in GBD 2016, we used mortality-to-incidence ratios for cancers instead of risk-standardised death rates to provide a stronger signal of the effects of personal health care and access on cancer survival. We transformed each cause to a scale of 0-100, with 0 as the first percentile (worst) observed between 1990 and 2016, and 100 as the 99th percentile (best); we set these thresholds at the country level, and then applied them to subnational locations. We applied a principal components analysis to construct the HAQ Index using all scaled cause values, providing an overall score of 0-100 of personal health-care access and quality by location over time. We then compared HAQ Index levels and trends by quintiles on the Socio-demographic Index (SDI), a summary measure of overall development. As derived from the broader GBD study and other data sources, we examined relationships between national HAQ Index scores and potential correlates of performance, such as total health spending per capita. Findings In 2016, HAQ Index performance spanned from a high of 97\ub71 (95% UI 95\ub78-98\ub71) in Iceland, followed by 96\ub76 (94\ub79-97\ub79) in Norway and 96\ub71 (94\ub75-97\ub73) in the Netherlands, to values as low as 18\ub76 (13\ub71-24\ub74) in the Central African Republic, 19\ub70 (14\ub73-23\ub77) in Somalia, and 23\ub74 (20\ub72-26\ub78) in Guinea-Bissau. The pace of progress achieved between 1990 and 2016 varied, with markedly faster improvements occurring between 2000 and 2016 for many countries in sub-Saharan Africa and southeast Asia, whereas several countries in Latin America and elsewhere saw progress stagnate after experiencing considerable advances in the HAQ Index between 1990 and 2000. Striking subnational disparities emerged in personal health-care access and quality, with China and India having particularly large gaps between locations with the highest and lowest scores in 2016. In China, performance ranged from 91\ub75 (89\ub71-93\ub76) in Beijing to 48\ub70 (43\ub74-53\ub72) in Tibet (a 43\ub75-point difference), while India saw a 30\ub78-point disparity, from 64\ub78 (59\ub76-68\ub78) in Goa to 34\ub70 (30\ub73-38\ub71) in Assam. Japan recorded the smallest range in subnational HAQ performance in 2016 (a 4\ub78-point difference), whereas differences between subnational locations with the highest and lowest HAQ Index values were more than two times as high for the USA and three times as high for England. State-level gaps in the HAQ Index in Mexico somewhat narrowed from 1990 to 2016 (from a 20\ub79-point to 17\ub70-point difference), whereas in Brazil, disparities slightly increased across states during this time (a 17\ub72-point to 20\ub74-point difference). Performance on the HAQ Index showed strong linkages to overall development, with high and high-middle SDI countries generally having higher scores and faster gains for non-communicable diseases. Nonetheless, countries across the development spectrum saw substantial gains in some key health service areas from 2000 to 2016, most notably vaccine-preventable diseases. Overall, national performance on the HAQ Index was positively associated with higher levels of total health spending per capita, as well as health systems inputs, but these relationships were quite heterogeneous, particularly among low-to-middle SDI countries. Interpretation GBD 2016 provides a more detailed understanding of past success and current challenges in improving personal health-care access and quality worldwide. Despite substantial gains since 2000, many low-SDI and middle- SDI countries face considerable challenges unless heightened policy action and investments focus on advancing access to and quality of health care across key health services, especially non-communicable diseases. Stagnating or minimal improvements experienced by several low-middle to high-middle SDI countries could reflect the complexities of re-orienting both primary and secondary health-care services beyond the more limited foci of the Millennium Development Goals. Alongside initiatives to strengthen public health programmes, the pursuit of universal health coverage hinges upon improving both access and quality worldwide, and thus requires adopting a more comprehensive view-and subsequent provision-of quality health care for all populations

Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: A systematic analysis from the Global Burden of Disease Study 2016

Copyright © 2018 The Author(s). Published by Elsevier Ltd. Background A key component of achieving universal health coverage is ensuring that all populations have access to quality health care. Examining where gains have occurred or progress has faltered across and within countries is crucial to guiding decisions and strategies for future improvement. We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) to assess personal health-care access and quality with the Healthcare Access and Quality (HAQ) Index for 195 countries and territories, as well as subnational locations in seven countries, from 1990 to 2016. Methods Drawing from established methods and updated estimates from GBD 2016, we used 32 causes from which death should not occur in the presence of effective care to approximate personal health-care access and quality by location and over time. To better isolate potential effects of personal health-care access and quality from underlying risk factor patterns, we risk-standardised cause-specific deaths due to non-cancers by location-year, replacing the local joint exposure of environmental and behavioural risks with the global level of exposure. Supported by the expansion of cancer registry data in GBD 2016, we used mortality-to-incidence ratios for cancers instead of risk-standardised death rates to provide a stronger signal of the effects of personal health care and access on cancer survival. We transformed each cause to a scale of 0-100, with 0 as the first percentile (worst) observed between 1990 and 2016, and 100 as the 99th percentile (best); we set these thresholds at the country level, and then applied them to subnational locations. We applied a principal components analysis to construct the HAQ Index using all scaled cause values, providing an overall score of 0-100 of personal health-care access and quality by location over time. We then compared HAQ Index levels and trends by quintiles on the Socio-demographic Index (SDI), a summary measure of overall development. As derived from the broader GBD study and other data sources, we examined relationships between national HAQ Index scores and potential correlates of performance, such as total health spending per capita. Findings In 2016, HAQ Index performance spanned from a high of 97·1 (95% UI 95·8-98·1) in Iceland, followed by 96·6 (94·9-97·9) in Norway and 96·1 (94·5-97·3) in the Netherlands, to values as low as 18·6 (13·1-24·4) in the Central African Republic, 19·0 (14·3-23·7) in Somalia, and 23·4 (20·2-26·8) in Guinea-Bissau. The pace of progress achieved between 1990 and 2016 varied, with markedly faster improvements occurring between 2000 and 2016 for many countries in sub-Saharan Africa and southeast Asia, whereas several countries in Latin America and elsewhere saw progress stagnate after experiencing considerable advances in the HAQ Index between 1990 and 2000. Striking subnational disparities emerged in personal health-care access and quality, with China and India having particularly large gaps between locations with the highest and lowest scores in 2016. In China, performance ranged from 91·5 (89·1-93·6) in Beijing to 48·0 (43·4-53·2) in Tibet (a 43·5-point difference), while India saw a 30·8-point disparity, from 64·8 (59·6-68·8) in Goa to 34·0 (30·3-38·1) in Assam. Japan recorded the smallest range in subnational HAQ performance in 2016 (a 4·8-point difference), whereas differences between subnational locations with the highest and lowest HAQ Index values were more than two times as high for the USA and three times as high for England. State-level gaps in the HAQ Index in Mexico somewhat narrowed from 1990 to 2016 (from a 20·9-point to 17·0-point difference), whereas in Brazil, disparities slightly increased across states during this time (a 17·2-point to 20·4-point difference). Performance on the HAQ Index showed strong linkages to overall development, with high and high-middle SDI countries generally having higher scores and faster gains for non-communicable diseases. Nonetheless, countries across the development spectrum saw substantial gains in some key health service areas from 2000 to 2016, most notably vaccine-preventable diseases. Overall, national performance on the HAQ Index was positively associated with higher levels of total health spending per capita, as well as health systems inputs, but these relationships were quite heterogeneous, particularly among low-to-middle SDI countries. Interpretation GBD 2016 provides a more detailed understanding of past success and current challenges in improving personal health-care access and quality worldwide. Despite substantial gains since 2000, many low-SDI and middle- SDI countries face considerable challenges unless heightened policy action and investments focus on advancing access to and quality of health care across key health services, especially non-communicable diseases. Stagnating or minimal improvements experienced by several low-middle to high-middle SDI countries could reflect the complexities of re-orienting both primary and secondary health-care services beyond the more limited foci of the Millennium Development Goals. Alongside initiatives to strengthen public health programmes, the pursuit of universal health coverage hinges upon improving both access and quality worldwide, and thus requires adopting a more comprehensive view - and subsequent provision - of quality health care for all populations

Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: a systematic analysis from the Global Burden of Disease Study 2016.

BACKGROUND: A key component of achieving universal health coverage is ensuring that all populations have access to quality health care. Examining where gains have occurred or progress has faltered across and within countries is crucial to guiding decisions and strategies for future improvement. We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) to assess personal health-care access and quality with the Healthcare Access and Quality (HAQ) Index for 195 countries and territories, as well as subnational locations in seven countries, from 1990 to 2016. METHODS: Drawing from established methods and updated estimates from GBD 2016, we used 32 causes from which death should not occur in the presence of effective care to approximate personal health-care access and quality by location and over time. To better isolate potential effects of personal health-care access and quality from underlying risk factor patterns, we risk-standardised cause-specific deaths due to non-cancers by location-year, replacing the local joint exposure of environmental and behavioural risks with the global level of exposure. Supported by the expansion of cancer registry data in GBD 2016, we used mortality-to-incidence ratios for cancers instead of risk-standardised death rates to provide a stronger signal of the effects of personal health care and access on cancer survival. We transformed each cause to a scale of 0-100, with 0 as the first percentile (worst) observed between 1990 and 2016, and 100 as the 99th percentile (best); we set these thresholds at the country level, and then applied them to subnational locations. We applied a principal components analysis to construct the HAQ Index using all scaled cause values, providing an overall score of 0-100 of personal health-care access and quality by location over time. We then compared HAQ Index levels and trends by quintiles on the Socio-demographic Index (SDI), a summary measure of overall development. As derived from the broader GBD study and other data sources, we examined relationships between national HAQ Index scores and potential correlates of performance, such as total health spending per capita

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Construction et analyse de mutants de la machinerie de photoproduction d'hydrogène chez la cyanobactérie modèle Synechocystis

Photosynthetic organisms are attractive organisms for hydrogen production using water and solar energy, while preserving fresh water and arable soils without adding fertilizers. The model cyanobacterium Synechocystis PCC 6803 produces small and transitory amounts of H₂ thanks to its bidirectional [NiFe] hydrogenase Hox. The Hox complex with its 5 protein subunits (HoxEFUYH) catalyzes the reversible reaction 2H⁺ + 2e⁻ ↔ H₂. The [NiFe] catalytic site of the Hox enzyme is assembled using a six-subunits HypABCDEF complex and matured by the HoxW protease that cleaves HoxH and activates its [NiFe]-containing center. Engineering cyanobacteria for hydrogen production relies on a better understanding of the role of hydrogenase in the cyanobacterium metabolism. During my PhD, I have constructed and analyzed 7 sophisticated mutants of Synechocystis, allowing the simultaneous over-expression (constitutive or regulated by the growth temperature) of the hoxEFUYH and hypABCDEF genes. We demonstrated that the simultaneous over-production of the HoxEFUYH and HypABCDEF proteins, combined to an increase in nickel availability led to an approximately 20-fold increase of the active hydrogenase level. Moreover, using a deleted hox-operon mutant we showed that hydrogenase is dispensable in standard phototrophic growth conditions. Comparing the phenotypes of different mutants constructed in this study enables us to demonstrate for the first time that the hydrogenase operates in cell protection against oxidative stress (H₂O₂) and sugar stress (glucose or glycerol). Besides, I have also participated to the characterization of a new regulator (AbrB2) of the expression of the hydrogenase. This transcription factor represses the hoxEFUYH operon and is involved in the tolerance to stress induced by diamide or nickel. For the first time in cyanobacteria, a redox control of the activity of this regulator by a post-translational gluthathionylation was identified. Collectively, our findings showed that several genetic and physiological strategies should be combined in a single strain to strongly increase hydrogen production in Synechocystis. Meanwhile the presently constructed mutants proved to be very powerful tools to achieve this goal.Les microorganismes photosynthétiques suscitent un intérêt biotechnologique grandissant pour la production de dihydrogène (H₂) à partir d'eau et d'énergie solaire en préservant l'eau douce et les terres cultivables sans ajout d'engrais. La cyanobactérie modèle Synechocystis PCC 6803 est capable de produire du H₂ de manière faible et transitoire grâce à une hydrogénase [NiFe] bidirectionnelle Hox. Cette enzyme possède 5 sous-unités protéiques (HoxEFUYH) qui catalysent la réaction réversible : 2H⁺ + 2e⁻ ↔ H₂. Le site actif [NiFe] de cette enzyme est assemblé par un complexe de six protéines HypABCDEF. L’hydrogénase est ensuite maturée par une protéase HoxW qui clive la sous-unité HoxH et active le site catalytique [NiFe]. L’ingénierie de cyanobactéries pour la photoproduction biologique d’H₂ passe par une meilleure compréhension du rôle de l'hydrogénase dans le métabolisme cyanobactérien. Au cours de ma thèse, j’ai construit et analysé 7 mutants sophistiqués de Synechocystis permettant la surexpression simultanée (constitutive ou régulée par la température de croissance) des gènes hoxEFUYHW et hypABCDEF. On a ainsi montré que la surproduction simultanée des protéines HoxEFUYHW et HypABCDEF combinée à une augmentation de la disponibilité de nickel dans le milieu conduit à une augmentation de l’activité hydrogénase d’un facteur 20. D’autre part, un mutant dépourvu de l'opéron hoxEFUYH a permis également de montrer que l'hydrogénase n'est pas indispensable à la croissance dans les conditions photoautotrophiques standard. La comparaison des phénotypes des divers mutants construits durant ce travail a permis également de montrer pour la première fois que l’hydrogénase joue un rôle dans la défense cellulaire contre le stress oxydant induit par le H₂O₂, par la présence de glucose ou de glycérol dans le milieu de culture. Par ailleurs, j'ai participé à la caractérisation d'un nouveau régulateur de l'expression de l’hydrogénase. Ce facteur de transcription (AbrB2) qui réprime l’opéron hoxEFUYH est impliqué dans la tolérance au stress induit par le diamide ou le nickel. Un contrôle redox de l'activité de ce régulateur par une modification post-traductionnelle de glutathionylation a été mise en évidence pour la première fois chez les cyanobactéries. L'ensemble de ces résultats démontre que l’on doit combiner plusieurs stratégies génétiques et physiologiques pour augmenter fortement la production d’hydrogène chez Synechocystis, et que nos mutants sont des outils très importants vers cet objectif

Construction and analysis of mutants of the hydrogen photoproduction machine in the model cyanobacterium Synechocystis

Les microorganismes photosynthétiques suscitent un intérêt biotechnologique grandissant pour la production de dihydrogène (H₂) à partir d'eau et d'énergie solaire en préservant l'eau douce et les terres cultivables sans ajout d'engrais. La cyanobactérie modèle Synechocystis PCC 6803 est capable de produire du H₂ de manière faible et transitoire grâce à une hydrogénase [NiFe] bidirectionnelle Hox. Cette enzyme possède 5 sous-unités protéiques (HoxEFUYH) qui catalysent la réaction réversible : 2H⁺ + 2e⁻ ↔ H₂. Le site actif [NiFe] de cette enzyme est assemblé par un complexe de six protéines HypABCDEF. L’hydrogénase est ensuite maturée par une protéase HoxW qui clive la sous-unité HoxH et active le site catalytique [NiFe]. L’ingénierie de cyanobactéries pour la photoproduction biologique d’H₂ passe par une meilleure compréhension du rôle de l'hydrogénase dans le métabolisme cyanobactérien. Au cours de ma thèse, j’ai construit et analysé 7 mutants sophistiqués de Synechocystis permettant la surexpression simultanée (constitutive ou régulée par la température de croissance) des gènes hoxEFUYHW et hypABCDEF. On a ainsi montré que la surproduction simultanée des protéines HoxEFUYHW et HypABCDEF combinée à une augmentation de la disponibilité de nickel dans le milieu conduit à une augmentation de l’activité hydrogénase d’un facteur 20. D’autre part, un mutant dépourvu de l'opéron hoxEFUYH a permis également de montrer que l'hydrogénase n'est pas indispensable à la croissance dans les conditions photoautotrophiques standard. La comparaison des phénotypes des divers mutants construits durant ce travail a permis également de montrer pour la première fois que l’hydrogénase joue un rôle dans la défense cellulaire contre le stress oxydant induit par le H₂O₂, par la présence de glucose ou de glycérol dans le milieu de culture. Par ailleurs, j'ai participé à la caractérisation d'un nouveau régulateur de l'expression de l’hydrogénase. Ce facteur de transcription (AbrB2) qui réprime l’opéron hoxEFUYH est impliqué dans la tolérance au stress induit par le diamide ou le nickel. Un contrôle redox de l'activité de ce régulateur par une modification post-traductionnelle de glutathionylation a été mise en évidence pour la première fois chez les cyanobactéries. L'ensemble de ces résultats démontre que l’on doit combiner plusieurs stratégies génétiques et physiologiques pour augmenter fortement la production d’hydrogène chez Synechocystis, et que nos mutants sont des outils très importants vers cet objectif.Photosynthetic organisms are attractive organisms for hydrogen production using water and solar energy, while preserving fresh water and arable soils without adding fertilizers. The model cyanobacterium Synechocystis PCC 6803 produces small and transitory amounts of H₂ thanks to its bidirectional [NiFe] hydrogenase Hox. The Hox complex with its 5 protein subunits (HoxEFUYH) catalyzes the reversible reaction 2H⁺ + 2e⁻ ↔ H₂. The [NiFe] catalytic site of the Hox enzyme is assembled using a six-subunits HypABCDEF complex and matured by the HoxW protease that cleaves HoxH and activates its [NiFe]-containing center. Engineering cyanobacteria for hydrogen production relies on a better understanding of the role of hydrogenase in the cyanobacterium metabolism. During my PhD, I have constructed and analyzed 7 sophisticated mutants of Synechocystis, allowing the simultaneous over-expression (constitutive or regulated by the growth temperature) of the hoxEFUYH and hypABCDEF genes. We demonstrated that the simultaneous over-production of the HoxEFUYH and HypABCDEF proteins, combined to an increase in nickel availability led to an approximately 20-fold increase of the active hydrogenase level. Moreover, using a deleted hox-operon mutant we showed that hydrogenase is dispensable in standard phototrophic growth conditions. Comparing the phenotypes of different mutants constructed in this study enables us to demonstrate for the first time that the hydrogenase operates in cell protection against oxidative stress (H₂O₂) and sugar stress (glucose or glycerol). Besides, I have also participated to the characterization of a new regulator (AbrB2) of the expression of the hydrogenase. This transcription factor represses the hoxEFUYH operon and is involved in the tolerance to stress induced by diamide or nickel. For the first time in cyanobacteria, a redox control of the activity of this regulator by a post-translational gluthathionylation was identified. Collectively, our findings showed that several genetic and physiological strategies should be combined in a single strain to strongly increase hydrogen production in Synechocystis. Meanwhile the presently constructed mutants proved to be very powerful tools to achieve this goal

Overproduction of the cyanobacterial hydrogenase and selection of a mutant thriving on urea, as a possible step towards the future production of hydrogen coupled with water treatment.

Using a combination of various types of genetic manipulations (promoter replacement and gene cloning in replicating plasmid expression vector), we have overproduced the complex hydrogenase enzyme in the model cyanobacterium Synechocystis PCC6803. This new strain overproduces all twelve following proteins: HoxEFUYH (hydrogen production), HoxW (maturation of the HoxH subunit of hydrogenase) and HypABCDEF (assembly of the [NiFe] redox center of HoxHY hydrogenase). This strain when grown in the presence of a suitable quantities of nickel and iron used here exhibits a strong (25-fold) increase in hydrogenase activity, as compared to the WT strain growing in the standard medium. Hence, this strain can be very useful for future analyses of the cyanobacterial [NiFe] hydrogenase to determine its structure and, in turn, improve its tolerance to oxygen with the future goal of increasing hydrogen production. We also report the counterintuitive notion that lowering the activity of the Synechocystis urease can increase the photoproduction of biomass from urea-polluted waters, without decreasing hydrogenase activity. Such cyanobacterial factories with high hydrogenase activity and a healthy growth on urea constitute an important step towards the future development of an economical industrial processes coupling H2 production from solar energy and CO2, with wastewater treatment (urea depollution)

The AbrB2 autorepressor, expressed from an atypical promoter, represses the hydrogenase operon to regulate hydrogen production in Synechocystis strain PCC6803.

International audienceWe have thoroughly investigated the abrB2 gene (sll0822) encoding an AbrB-like regulator in the wild-type strain of the model cyanobacterium Synechocystis strain PCC6803. We report that abrB2 is expressed from an active but atypical promoter that possesses an extended -10 element (TGTAATAT) that compensates for the absence of a -35 box. Strengthening the biological significance of these data, we found that the occurrence of an extended -10 promoter box and the absence of a -35 element are two well-conserved features in abrB2 genes from other cyanobacteria. We also show that AbrB2 is an autorepressor that is dispensable to cell growth under standard laboratory conditions. Furthermore, we demonstrate that AbrB2 also represses the hox operon, which encodes the Ni-Fe hydrogenase of biotechnological interest, and that the hox operon is weakly expressed even though it possesses the two sequences resembling canonical -10 and -35 promoter boxes. In both the AbrB2-repressed promoters of the abrB2 gene and the hox operon, we found a repeated DNA motif [TT-(N(5))-AAC], which could be involved in AbrB2 repression. Supporting this hypothesis, we found that a TT-to-GG mutation of one of these elements increased the activity of the abrB2 promoter. We think that our abrB2-deleted mutant with increased expression of the hox operon and hydrogenase activity, together with the reporter plasmids we constructed to analyze the abrB2 gene and the hox operon, will serve as useful tools to decipher the function and the regulation of hydrogen production in Synechocystis