| 1. |
- Abelev, Betty, et al.
(author)
-
Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
-
In: Journal of High Energy Physics. - 1029-8479. ; :11
-
Journal article (peer-reviewed)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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| 2. |
- Abelev, Betty, et al.
(author)
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Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
-
In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
-
Journal article (peer-reviewed)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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| 3. |
- Lozano, Rafael, et al.
(author)
-
Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
-
In: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
-
Journal article (peer-reviewed)abstract
- Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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| 4. |
- Abelev, Betty, et al.
(author)
-
Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
- 2012
-
In: Journal of High Energy Physics. - 1029-8479. ; :7
-
Journal article (peer-reviewed)abstract
- We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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| 5. |
- Murray, Christopher J. L., et al.
(author)
-
Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
-
In: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051
-
Journal article (peer-reviewed)abstract
- Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation.
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| 6. |
- Stanaway, Jeffrey D., et al.
(author)
-
Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017
- 2018
-
In: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994
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Journal article (peer-reviewed)abstract
- Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
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| 7. |
- Feigin, Valery L., et al.
(author)
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Global, regional, and national burden of stroke and its risk factors, 1990-2019 : a systematic analysis for the Global Burden of Disease Study 2019
- 2021
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In: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 20:10, s. 795-820
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Journal article (peer-reviewed)abstract
- Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12.2 million (95% UI 11.0-13.6) incident cases of stroke, 101 million (93.2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6.55 million (6.00-7.02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11.6% [10.8-12.2] of total deaths) and the third-leading cause of death and disability combined (5.7% [5.1-6.2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70.0% (67.0-73.0), prevalent strokes increased by 85.0% (83.0-88.0), deaths from stroke increased by 43.0% (31.0-55.0), and DALYs due to stroke increased by 32.0% (22.0-42.0). During the same period, age-standardised rates of stroke incidence decreased by 17.0% (15.0-18.0), mortality decreased by 36.0% (31.0-42.0), prevalence decreased by 6.0% (5.0-7.0), and DALYs decreased by 36.0% (31.0-42.0). However, among people younger than 70 years, prevalence rates increased by 22.0% (21.0-24.0) and incidence rates increased by 15.0% (12.0-18.0). In 2019, the age-standardised stroke-related mortality rate was 3.6 (3.5-3.8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3.7 (3.5-3.9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62.4% of all incident strokes in 2019 (7.63 million [6.57-8.96]), while intracerebral haemorrhage constituted 27.9% (3.41 million [2.97-3.91]) and subarachnoid haemorrhage constituted 9.7% (1.18 million [1.01-1.39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79.6 million [67.7-90.8] DALYs or 55.5% [48.2-62.0] of total stroke DALYs), high body-mass index (34.9 million [22.3-48.6] DALYs or 24.3% [15.7-33.2]), high fasting plasma glucose (28.9 million [19.8-41.5] DALYs or 20.2% [13.8-29.1]), ambient particulate matter pollution (28.7 million [23.4-33.4] DALYs or 20.1% [16.6-23.0]), and smoking (25.3 million [22.6-28.2] DALYs or 17.6% [16.4-19.0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries.
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| 8. |
- Micah, Angela E., et al.
(author)
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Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050
- 2021
-
In: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10308, s. 1317-1343
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Research review (peer-reviewed)abstract
- Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
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| 9. |
- Gangopadhyay, Anjasha, et al.
(author)
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Optical studies of two stripped-envelope supernovae – SN 2015ap (Type Ib) and SN 2016P (Type Ic)
- 2020
-
In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 497:3, s. 3770-3789
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Journal article (peer-reviewed)abstract
- We present the photometric and spectroscopic studies of a Type Ib SN 2015ap and a Type Ic SN 2016P. SN 2015ap is one of the bright (MV = −18.04 mag) Type Ib while SN 2016P lies at an average value among the Type Ic SNe (MV = −17.53 mag). Bolometric light-curve modelling of SNe 2015ap and 2016P indicates that both the SNe are powered by 56Ni + magnetar model with 56Ni masses of 0.01 and 0.002 M⊙, ejecta masses of 3.75 and 4.66 M⊙, spin period P0 of 25.8 and 36.5 ms, and magnetic field Bp of 28.39 × 1014 and 35.3 × 1014 G, respectively. The early spectra of SN 2015ap show prominent lines of He with a ‘W’ feature due to Fe complexes while other lines of Mg ii, Na i, and Si ii are present in both SNe 2015ap and 2016P. Nebular phase [O i] profile indicates an asymmetric profile in SN 2015ap. The [O i]/[Ca ii] ratio and nebular spectral modelling of SN 2015ap hint towards a progenitor mass between 12 and 20 M⊙.
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| 10. |
- Karthic, Anandakrishnan, et al.
(author)
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Computational Analysis Reveals Monomethylated Triazolopyrimidine as a Novel Inhibitor of SARS-CoV-2 RNA-Dependent RNA Polymerase (RdRp)
- 2022
-
In: Molecules. - : MDPI AG. - 1420-3049. ; 27:3
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Journal article (peer-reviewed)abstract
- The human population is still facing appalling conditions due to several outbreaks of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) virus. The absence of specific drugs, appropriate vaccines for mutants, and knowledge of potential therapeutic agents makes this situation more difficult. Several 1, 2, 4-triazolo [1, 5-a] pyrimidine (TP)-derivative compounds were comprehensively studied for antiviral activities against RNA polymerase of HIV, HCV, and influenza viruses, and showed immense pharmacological interest. Therefore, TP-derivative compounds can be repurposed against the RNA-dependent RNA polymerase (RdRp) protein of SARS-CoV-2. In this study, a meta-analysis was performed to ensure the genomic variability and stability of the SARS-CoV-2 RdRp protein. The molecular docking of natural and synthetic TP compounds to RdRp and molecular dynamic (MD) simulations were performed to analyse the dynamic behaviour of TP compounds at the active site of the RdRp protein. TP compounds were also docked against other non-structural proteins (NSP1, NSP2, NSP3, NSP5, NSP8, NSP13, and NSP15) of SARS-CoV-2. Furthermore, the inhibition potential of TP compounds was compared with Remdesivir and Favipi-ravir drugs as a positive control. Additionally, TP compounds were analysed for inhibitory activity against SARS-CoV RdRp protein. This study demonstrates that TP analogues (monomethylated triazolopyrimidine and essramycin) represent potential lead molecules for designing an effective inhibitor to control viral replication. Furthermore, in vitro and in vivo studies will strengthen the use of these inhibitors as suitable drug candidates against SARS-CoV-2.
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| 11. |
- Kumar, Pradeep, et al.
(author)
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Density functional theoretic studies of host-guest interaction in gas hydrates
- 2014
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In: Computational and Theoretical Chemistry. - : Elsevier. - 2210-271X .- 2210-2728. ; 1029, s. 26-32
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Journal article (peer-reviewed)abstract
- Recently we reported the host-guest interaction between a dodecahedral water cage and a variety of guest species that include diatomic (CO, H-2, N-2, O-2), triatomic (CO2, O-3) and polyatomic (CH4, NH3) molecules at the MP2/CBS limit (Kumar and Sathyamurthy, 2011). Since high computational costs involved in the application of MP2 and CCSD (T) methods limit the size of the clathrate that can be studied, the performance of the density functional theoretic method using functionals like B3LYP, M06-HF, M06-L, M06-2X and BLYP-D3 is evaluated for its ability to predict the interaction energy as well as the geometry. The computed results are compared with the estimated CCSD/CBS values, which were obtained with the help of the MP2/CBS values reported earlier. The DFT/BLYP-D3 method seems to be the best; the functionals M06-2X and M06-HF performed reasonably well, while B3LYP failed to predict any attraction between the guest and the host. (C) 2013 Elsevier B.V. All rights reserved.
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| 12. |
- Kumar, R. P. S. Abhijith, et al.
(author)
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Stabilization of the C-20 cage by encapsulation of H+ and He2+ ions
- 2014
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In: Current Science. - 0011-3891. ; 106:9, s. 1255-1259
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Journal article (peer-reviewed)abstract
- It is shown by ab initio calculations using second-order Moller-Plesset perturbation theory and 6-31g*, aug-cc-pVDZ and aug-cc-pVTZ basis sets and coupled cluster singles, doubles and perturbative triples method with the 6-31g* basis set, that it is possible to stabilize the cage structure of the smallest fullerene C-20 by encapsulating small cations like H+ and He2+. While the latter stabilizes the cage structure by charge transfer, the former prefers to form a covalent linkage with the carbon atoms.
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| 13. |
- Roy, Rupak, et al.
(author)
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SN 2007uy-metamorphosis of an aspheric Type Ib explosion
- 2013
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 434:3, s. 2032-2050
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Journal article (peer-reviewed)abstract
- The supernovae (SNe) of Type Ibc are rare and the detailed characteristics of these explosions have been studied only for a few events. Unlike Type II SNe, the progenitors of Type Ibc have never been detected in pre-explosion images. So, to understand the nature of their progenitors and the characteristics of the explosions, investigation of proximate events is necessary. Here we present the results of multiwavelength observations of Type Ib SN 2007uy in the nearby (similar to 29.5 Mpc) galaxy NGC 2770. Analysis of the photometric observations revealed this explosion as an energetic event with peak absolute R-band magnitude -18.5 +/- 0.16, which is about 1 mag brighter than the mean value (-17.6 +/- 0.6) derived for well observed Type Ibc events. The SN is highly extinguished, E(B - V) = 0.63 +/- 0.15 mag, mainly due to foreground material present in the host galaxy. From optical light curve modelling we determine that about 0.3 M-circle dot radioactive Ni-56 is produced and roughly 4.4 M-circle dot material is ejected during this explosion with liberated energy similar to 15 x 10(51) erg, indicating the event to be an energetic one. Through optical spectroscopy, we have noticed a clear aspheric evolution of several line-forming regions, but no dependency of asymmetry is seen on the distribution of Ni-56 inside the ejecta. The SN shock interaction with the circumstellar material is clearly noticeable in radio follow-up, presenting a synchrotron self-absorption dominated light curve with a contribution of free-free absorption during the early phases. Assuming a Wolf-Rayet (WR) star, with wind velocity greater than or similar to 10(3) km s(- 1), as a progenitor, we derive a lower limit to the mass-loss rate inferred from the radio data as M 2.4 10(-5) M-circle dot yr(-1), which is consistent with the results obtained for other Type Ibc SNe bright at radio frequencies.
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| 14. |
- Andersson, C. David, 1978-, et al.
(author)
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Physical Mechanisms Governing Substituent Effects on Arene-Arene Interactions in a Protein Milieu
- 2020
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In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 124:30, s. 6529-6539
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Journal article (peer-reviewed)abstract
- Arene-arene interactions play important roles in protein-ligand complex formation. Here, we investigate the characteristics of arene-arene interactions between small organic molecules and aromatic amino acids in protein interiors. The study is based on X-ray crystallographic data and quantum mechanical calculations using the enzyme acetylcholinesterase and selected inhibitory ligands as a model system. It is shown that the arene substituents of the inhibitors dictate the strength of the interaction and the geometry of the resulting complexes. Importantly, the calculated interaction energies correlate well with the measured inhibitor potency. Non-hydrogen substituents strengthened all interaction types in the protein milieu, in keeping with results for benzene dimer model systems. The interaction energies were dispersion-dominated, but substituents that induced local dipole moments increased the electrostatic contribution and thus yielded more strongly bound complexes. These findings provide fundamental insights into the physical mechanisms governing arene-arene interactions in the protein milieu and thus into molecular recognition between proteins and small molecules.
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| 15. |
- Berg, Lotta, et al.
(author)
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The Nature of Activated Non-classical Hydrogen Bonds : A Case Study on Acetylcholinesterase-Ligand Complexes
- 2016
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In: Chemistry - A European Journal. - : Wiley-VCH Verlagsgesellschaft. - 0947-6539 .- 1521-3765. ; 22:8, s. 2672-2681
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Journal article (peer-reviewed)abstract
- Molecular recognition events in biological systems are driven by non-covalent interactions between interacting species. Here, we have studied hydrogen bonds of the CHY type involving electron-deficient CH donors using dispersion-corrected density functional theory (DFT) calculations applied to acetylcholinesterase-ligand complexes. The strengths of CHY interactions activated by a proximal cation were considerably strong; comparable to or greater than those of classical hydrogen bonds. Significant differences in the energetic components compared to classical hydrogen bonds and non-activated CHY interactions were observed. Comparison between DFT and molecular mechanics calculations showed that common force fields could not reproduce the interaction energy values of the studied hydrogen bonds. The presented results highlight the importance of considering CHY interactions when analysing protein-ligand complexes, call for a review of current force fields, and opens up possibilities for the development of improved design tools for drug discovery.
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| 16. |
- Dastidar, Raya, et al.
(author)
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SN 2015ba : a Type IIP supernova with a long plateau
- 2018
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 479:2, s. 2421-2442
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Journal article (peer-reviewed)abstract
- We present optical photometry and spectroscopy from about a week after explosion to similar to 272 d of an atypical Type IIP supernova, SN 2015ba, which exploded in the edge-on galaxy IC 1029. SN 2015ba is a luminous event with an absolute V-band magnitude of -17.1 +/- 0.2 mag at 50 d since explosion and has a long plateau lasting for similar to 123 d. The distance to the SN is estimated to be 34.8 +/- 0.7 Mpc using the expanding photosphere and standard candle methods. High-velocity H Balmer components constant with time are observed in the late-plateau phase spectra of SN 2015ba, which suggests a possible role of circumstellar interaction at these phases. Both hydrodynamical and analytical modelling suggest a massive progenitor of SN 2015ba with a pre-explosion mass of 24-26 M-circle dot. However, the nebular spectra of SN 2015ba exhibit insignificant levels of oxygen, which is otherwise expected from a massive progenitor. This might be suggestive of the non-monotonical link between O-core masses and the zero-age main sequence mass of pre-supernova stars and/or uncertainties in the mixing scenario in the ejecta of supernovae.
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| 17. |
- Dastidar, R., et al.
(author)
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The optical properties of three Type II supernovae : 2014cx, 2014cy, and 2015cz
- 2021
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 504:1, s. 1009-1028
-
Journal article (peer-reviewed)abstract
- We present the photometric and spectroscopic analysis of three Type II supernovae (SNe): 2014cx, 2014cy, and 2015cz. SN 2014cx is a conventional Type IIP with shallow slope (0.2 mag/50 d) and an atypical short plateau (∼86 d). SNe 2014cy and 2015cz show relatively large decline rates (0.88 and 1.64 mag/50 d, respectively) at early times before settling to the plateau phase, unlike the canonical Type IIP/L SN light curves. All of them are normal luminosity SN II with an absolute magnitude at mid-plateau of M50V,14cx=−16.6±0.4mag, M50V,14cy=−16.5±0.2mag, and M50V,15cz=−17.4±0.3mag. A relatively broad range of 56Ni masses is ejected in these explosions (0.027–0.070 M⊙). The spectra shows the classical evolution of SNe II, dominated by a blue continuum with broad H lines at early phases and narrower metal lines with P Cygni profiles during the plateau. High-velocity H i features are identified in the plateau spectra of SN 2014cx at 11 600 kms −1, possibly a sign of ejecta-circumstellar interaction. The spectra of SN 2014cy exhibit strong absorption profile of H i similar to normal luminosity events whereas strong metal lines akin to sub-luminous SNe. The analytical modelling of the bolometric light curve of the three events yields similar progenitor radii within errors (478, 507, and 660 R ⊙ for SNe 2014cx, 2014cy, and 2015cz, respectively), a range of ejecta masses (15.0, 22.2, and 20.6 M ⊙ for SNe 2014cx, 2014cy, and 2015cz), and a modest range of explosion energies (3.3–7.2 foe where 1 foe=10 51erg).
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| 18. |
- Feigin, Valery L., et al.
(author)
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Global, regional, and national burden of neurological disorders, 1990–2016 : a systematic analysis for the Global Burden of Disease Study 2016
- 2019
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In: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 18:5, s. 459-480
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Journal article (peer-reviewed)abstract
- Background: Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders.Methods: We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach.Findings: Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247–308]) and second leading cause of deaths (9·0 million [8·8–9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34–44] and DALYs by 15% [9–21]) whereas their age-standardised rates decreased (deaths by 28% [26–30] and DALYs by 27% [24–31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6–46·1]), migraine (16·3% [11·7–20·8]), Alzheimer's and other dementias (10·4% [9·0–12·1]), and meningitis (7·9% [6·6–10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05–1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5–90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22·3% [11·8–35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8–17·5] of DALYs are risk attributable).Interpretation: Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies.Funding: Bill & Melinda Gates Foundation.
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| 19. |
- Jha, Abhishek Kumar Rajesh, et al.
(author)
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Comparison of Methods for Calculating Indirect Upstream Carbon Emissions from Information and Communication Technology Manufacturing
- 2023
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In: WSEAS Transactions on Environment and Development. - 1790-5079 .- 2224-3496. ; 19, s. 1045-1057
-
Journal article (peer-reviewed)abstract
- The use of Information Communication technology (ICT) is rapidly increasing in an age ofdigitalization. Measurement of carbon dioxide equivalent (CO2e) emissions from ICT is crucial for reducingthem. Most ICT organizations focus on Scope 1 and 2 emissions as they have greater control over them, commonly ignoring Scope 3 emissions. Scope 3 Category 1 (S3C1) emissions occur throughout the rawmaterial acquisition and manufacturing stages of an ICT product's life cycle accounting for a large portion ofthe sector's overall CO2e emissions and energy consumption. By not reporting Scope 3 emissions, companieslose the ability to reduce their overall CO2e corporate emissions. Although Category 1 and 11 under Scope 3account for 85% of ICT's worldwide CO2e emissions, the methodologies for calculating S3C1 emissions in ICTare understudied. This study focuses on these emissions in the framework of Sustainable Development Goals 9,12, and 13. Product life cycle assessment (PLCA) and Spend-based methods have been used to analyze S3C1emissions in the ICT sector with two case examples of laptop computers and smartphones. The ExcelManagement Life Cycle Assessment (EMLCA) tool has been used for the S3C1 emissions estimation. PLCAand Spend-based methods are compared on their ability to calculate CO2e emissions. It is concluded that theSpend-based is faster than PLCA for predicting ICT emissions with modest uncertainty for smartphone andlaptop components. Furthermore, this work explores the advantages and downsides of both methods.
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| 20. |
- Karthikeyan, S., et al.
(author)
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Influence of the Substituents on the CH...pi Interaction : Benzene-Methane Complex
- 2013
-
In: Journal of Physical Chemistry A. - : American Chemical Society (ACS). - 1089-5639 .- 1520-5215. ; 117:30, s. 6687-6694
-
Journal article (peer-reviewed)abstract
- Recently we showed that the binding energy of the benzene...acetylene complex could be tuned up to 5 kcal/mol by substituting the hydrogen atoms of the benzene molecule with multiple electron-donating/electron-withdrawing groups (J. Chem. Theory Comput. 2012, 8, 1935). In continuation, we have here examined the influence of various substituents on the CH...pi interaction present in the benzene...methane complex using the CCSD(T) method at the complete basis set limit. The influence of multiple fluoro substituents on the interaction strength of the benzene...methane complex was found to be insignificant, while the interaction strength linearly increases with successive addition of methyl groups. The influence of other substituents such as CN, NO2, COOH, Cl, and OH was found to be negligible. The NH2 group enhances the binding strength similarly to the methyl group. Energy decomposition analysis predicts the dispersion energy component to be on an average three times larger than the electrostatic energy component. Multidimensional correlation analysis shows that the exchange-repulsion and dispersion terms are correlated very well with the interaction distance (r) and with a combination of the interaction distance (r) and molar refractivity (MR), while the electrostatic component correlates well when the Hammett constant is used in combination with the interaction distance (r). Various recently developed DFT methods were used to assess their ability to predict the binding energy of various substituted benzene...methane complexes, and the M06-2X, B97-D, and B3LYP-D3 methods were found to be the best performers, giving a mean absolute deviation of similar to 0.15 kcal/mol.
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| 21. |
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| 22. |
- Larsson, Malin, et al.
(author)
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On the use of electronic descriptors for QSAR modelling of PCDDs, PCDFs and dioxin-like PCBs£ :
- 2013
-
In: SAR and QSAR in environmental research (Print). - : Taylor & Francis Group. - 1062-936X .- 1029-046X. ; 24:6, s. 461-479
-
Journal article (peer-reviewed)abstract
- The electronic properties of 29 polychlorinated dibenzo-p-dioxins and dibenzofurans and dioxin-like polychlorinated biphenyls that have been included in the toxic equivalency factor system have been investigated and used to derive quantum mechanical (QM) chemical descriptors for QSAR modelling. Their utility in this context was investigated alongside descriptors based on ultraviolet absorption data and traditional 2D descriptors including log Kow, polarizability, molecular surface properties, van der Waals volume and selected connectivity indices. The QM descriptors were calculated using the semi-empirical AM1 method and the density functional theory method B3-LYP/6-31G(∗∗). Atom-specific and molecular quantum chemical descriptors were calculated to compare the electronic properties of dioxin-like compounds regardless of their chemical class, with particular emphasis on the lateral positions. Multivariate analysis revealed differences between the chemical classes in terms of their electronic properties and also highlighted differences between congeners. The results obtained demonstrated the importance of considering molecular orbital energies, but also indicated that the ratios of the coefficients of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) at the lateral carbons were important. In addition, the digitalized UV spectra contained chemical information that provided crucial insights into dioxin-like activity.
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| 23. |
- Majumder, Moumita, et al.
(author)
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CH center dot center dot center dot pi and pi center dot center dot center dot pi interaction in benzene-acetylene clusters
- 2013
-
In: Chemical Physics Letters. - : Elsevier. - 0009-2614 .- 1873-4448. ; 557, s. 59-65
-
Journal article (peer-reviewed)abstract
- Ab initio calculations at the MP2/aug-cc-pVXZ (where, X = D, T and Q) and CCSD(T)/aug-cc-pVDZ levels of theory and certain density functional theoretic calculations were carried out for different configurations of benzene-acetylene clusters. The interaction energy was estimated at the CCSD(T)/CBS limit. For the 1:1 complex, the T-shaped geometry (C-6v symmetry) was found to be the most stable (-2.72 kcal/mol) and the pi center dot center dot center dot pi stacked structure was the least stable (-0.58 kcal/mol). For the 1:2 complex, the ring-shaped (-5.87 kcal/mol) and the double T-shaped (-5.23 kcal/mol) geometries were found to be the most stable and the second most stable, respectively.
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| 24. |
- Mishra, Brijesh Kumar, et al.
(author)
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Tuning the C-H center dot center dot center dot pi Interaction by Different Substitutions in Benzene-Acetylene Complexes
- 2012
-
In: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 8:6, s. 1935-1942
-
Journal article (peer-reviewed)abstract
- The influence of substitutions in aromatic moieties on the binding strength of their complexes is a subject of broad importance. Using a set of various substituted benzenes, Sherrill and co-workers (J. Am. Chem. Soc. 2011, 133, 13244; J. Phys. Chem. A 2003, 107, 8377) recently showed that the strength of a stacking interaction (pi...pi interaction) is enhanced by adding substituents regardless of their nature. Although the binding strength of an activated C-H...pi interaction is comparable to that of a stacking interaction, a similar systematic study is hitherto unknown in the literature. We have computed the stabilization energies of the C-H...pi complex of acetylene and multiple fluoro-/methyl-substituted benzenes at the coupled-cluster single and double (triple) excitation [CCSD(T)]/complete basis set (CBS) limit. The trend for interaction energies was found to be hexafluorobenzene-acetylene < sym-tetrafluorobenzene-acetylene < sym-trifluorobenzene-acetylene < sym-difluorobenzene-acetylene < benzene-acetylene < sym-dimethylbenzene-acetylene < sym-trimethylbenzene-acetylene < sym-tetramethylbenzene-acetylene < hexamethylbenzene-acetylene. Therefore, contrary to the case of stacking interaction (Hohenstein et al. J. Am. Chem. Soc. 2011, 133, 13244), we show here that electron-withdrawing groups weaken the dimer while electron-donating groups trengthen the interaction energy of the dimer. Various recently developed density functional theoretic (DFT) methods were assessed for their performance and the M05-2X, M06-2X, and omega B97X-D methods were found to be the best performers. These best DFT performers were employed in determining the influence of other representative substituents (-NO2, -CN, -COOH, -Br, -Cl, -OH, and -NH2) as an extension to the above work. The results for the complex of acetylene and various para-disubstituted benzenes revealed a trend in binding energies that is in accordance with the ring-activating/deactivating capacity of each of these groups. The stabilization energy was partitioned via the DFT symmetry-adapted perturbation theory (SAPT) method, and both dispersion and electrostatic interactions were seen to be major driving forces for the complex stabilization. Interestingly, the sum of the energy contributors such as dispersion, exchange, induction, etc., is close to zero and the total energy follows the trend of the electrostatic energy. We observe an excellent linear correlation between the optimized intermolecular separation of the different complexes and the exchange/dispersion interaction.
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| 25. |
- Moparthi, Vamsi, et al.
(author)
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Functional role of the MrpA- and MrpD-homologous protein subunits in enzyme complexes evolutionary related to respiratory chain complex I.
- 2014
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In: Biochimica et Biophysica Acta - Bioenergetics. - : Elsevier BV. - 0005-2728. ; 1837:1, s. 178-185
-
Journal article (peer-reviewed)abstract
- NADH:quinone oxidoreductase or complex I is a large membrane bound enzyme complex that has evolved from the combination of smaller functional building blocks. Intermediate size enzyme complexes exist in nature that comprise some, but not all of the protein subunits in full size 14-subunit complex I. The membrane spanning complex I subunits NuoL, NuoM and NuoN are homologous to each other and to two proteins from one particular class of Na(+)/H(+) antiporters, denoted MrpA and MrpD. In complex I, these ion transporter protein subunits are prime candidates for harboring important parts of the proton pumping machinery. Using a model system, consisting of Bacillus subtilis MrpA and MrpD deletion strains and a low copy expression plasmid, it was recently demonstrated that NuoN can rescue the strain deleted for MrpD but not that deleted for MrpA, whereas the opposite tendency was seen for NuoL. This demonstrated that the MrpA-type and MrpD-type proteins have unique functional specializations. In this work, the corresponding antiporter-like protein subunits from the smaller enzymes evolutionarily related to complex I were tested in the same model system. The subunits from 11-subunit complex I from Bacillus cereus behaved essentially as those from full size complex I, corroborating that this enzyme should be regarded as a bona fide complex I. The hydrogenase-3 and hydrogenase-4 antiporter-like proteins on the other hand, could substitute equally well for MrpA or MrpD at pH7.4, suggesting that these enzymes have intermediate forms of the antiporter-like proteins, which seemingly lack the functional specificity.
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| 26. |
- Moparthi, Vamsi, et al.
(author)
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Homologous protein subunits from Escherichia coli NADH:quinone oxidoreductase can functionally replace MrpA and MrpD in Bacillus subtilis
- 2011
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In: Biochimica et Biophysica Acta - Bioenergetics. - : Elsevier BV. - 0005-2728. ; 1807:4, s. 427-436
-
Journal article (peer-reviewed)abstract
- The complex I subunits NuoL, NuoM and NuoN are homologous to two proteins, MrpA and MrpD, from one particular class of Na+/H+ antiporters. In many bacteria MrpA and MrpD are encoded by an operon comprising 6-7 conserved genes. In complex I these protein subunits are prime candidates for harboring important parts of the proton pumping machinery. Deletion of either mrpA or mrpD from the Bacillus subtilis chromosome resulted in a Na+ and pH sensitive growth phenotype. The deletion strains could be complemented in trans by their respective Mrp protein, but expression of MrpA in the B. subtilis Delta mrpD strain and vice versa did not improve growth at pH 7.4. This corroborates that the two proteins have unique specific functions. Under the same conditions NuoL could rescue B. subtilis Delta mrpA, but improved the growth of B. subtilis Delta mrpD only slightly. NuoN could restore the wild type properties of B. subtilis Delta mrpD, but had no effect on the Delta mrpA strain. Expression of NuoM did not result in any growth improvement under these conditions. This reveals that the complex I subunits NuoL, NuoM and NuoN also demonstrate functional specializations. The simplest explanation that accounts for all previous and current observations is that the five homologous proteins are single ion transporters. Presumably, MrpA transports Na+ whereas MrpD transports H+ in opposite directions, resulting in antiporter activity. This hypothesis has implications for the complex I functional mechanism, suggesting that one Na+ channel, NuoL, and two H+ channels, NuoM and NuoN, are present. (C) 2011 Elsevier B.V. All rights reserved.
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| 27. |
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