Monday, October 17, 2022


Association of Health Insurance, Geography, and Race and Ethnicity With Disparities in Receipt of Recommended Postpartum Care in the US

JAMA Health Forum. 2022;3(10):e223292. doi:10.1001/jamahealthforum.2022.3292

 Original Investigation

October 14, 2022

Key Points

Question  Does receipt and content of recommended postpartum care differ across health insurance type, rural or urban residence, and race and ethnicity?

Findings  In this cross-sectional survey of 138 073 patients who attended a postpartum visit, statistically significant self-reported differences in the content of postpartum care were found across health insurance type, rural or urban residency, and race and ethnicity. Intersectional differences (eg, insurance by geography) were consistently larger than differences across individual categories (eg, insurance alone).

Meaning  The findings of this population-based survey study suggest that inequities in the content of postpartum care received are extensive across patients’ insurance type, rural or urban residence, and racial and ethnic identities, and these disparities are compounded for patients with multiple intersecting disadvantaged identities.

Abstract

Importance  Little is known about the quality of postpartum care or disparities in the content of postpartum care associated with health insurance, rural or urban residency, and race and ethnicity.

Objectives  To examine receipt of recommended postpartum care content and to describe variations across health insurance type, rural or urban residence, and race and ethnicity.

Design, Settings, and Participants  This cross-sectional survey of patients with births from 2016 to 2019 used data from the Pregnancy Risk Assessment Monitoring System (43 states and 2 jurisdictions). A population-based sample of patients conducted by state and local health departments in partnership with the Centers for Disease Control and Prevention were surveyed about maternal experiences 2 to 6 months after childbirth (mean weighted response rate, 59.9%). Patients who attended a postpartum visit were assessed for content at that visit. Analyses were performed November 2021 to July 2022.

Exposures  Medicaid or private health insurance, rural or urban residence, and race and ethnicity (non-Hispanic White or racially minoritized groups).

Main Outcomes and Measures  Receipt of 2 postpartum care components recommended by national quality standards (depression screening and contraceptive counseling), and/or other recommended components (smoking screening, abuse screening, birth spacing counseling, eating and exercise discussions) with estimated risk-adjusted predicted probabilities and percentage-point (pp) differences.

Results  Among the 138 073 patient-respondents, most (59.5%) were in the age group from 25 to 34 years old; 59 726 (weighted percentage, 40%) were insured by Medicaid; 27 721 (15%) were rural residents; 9718 (6%) were Asian, 24 735 (15%) were Black, 22 210 (15%) were Hispanic, 66 323 (60%) were White, and fewer than 1% were Indigenous (Native American/Alaska Native) individuals. Receipt of both depression screening and contraceptive counseling both significantly lower for Medicaid-insured patients (1.2 pp lower than private; 95% CI, –2.1 to –0.3), rural residents (1.3 pp lower than urban; 95% CI, –2.2 to –0.4), and people of racially minoritized groups (0.8 pp lower than White individuals; 95% CI, –1.6 to –0.1). The highest receipt of these components was among privately insured White urban residents (80%; 95% CI, 79% to 81%); the lowest was among privately insured racially minoritized rural residents (75%; 95% CI, 72% to 78%). Receipt of all other components was significantly higher for Medicaid-insured patients (6.1 pp; 95% CI, 5.2 to 7.0), rural residents (1.1 pp; 95% CI, 0.1 to 2.0), and people of racially minoritized groups (8.5 pp; 95% CI, 7.7 to 9.4). The highest receipt of these components was among Medicaid-insured racially minoritized urban residents (34%; 95% CI, 33% to 35%), the lowest was among privately insured White urban residents (19%; 95% CI, 18% to 19%).

Conclusions and Relevance  The findings of this cross-sectional survey of postpartum individuals in the US suggest that inequities in postpartum care content were extensive and compounded for patients with multiple disadvantaged identities. Examining only 1 dimension of identity may understate the extent of disparities. Future studies should consider the content of postpartum care visits.

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JAMA Health Forum – Health Policy, Health Care Reform, Health Affairs | JAMA Health Forum | JAMA Network

Association of Neighborhood Conditions and Resources for Children With Life Expectancy at Birth in the US

Key Points

Question  Are neighborhood conditions and resources for children associated with life expectancy at birth in the US?

Findings  In this cross-sectional study of residents from 65 662 US Census tracts, neighborhood conditions and resources for children explained substantial variability in life expectancy at birth. Neighborhood conditions and resources for children had a stepwise association with life expectancy at birth, with the lowest life expectancy in the communities with the lowest neighborhood conditions and resources for children.

Meaning  The study’s findings suggest that neighborhood conditions and resources for children are potentially important targets for health policy aimed at improving life expectancy for socially vulnerable populations in the US.

Abstract

Importance  To address inequities in life expectancy, we must understand the associations of modifiable socioeconomic and structural factors with life expectancy. However, the association of limited neighborhood resources and deleterious physical conditions with life expectancy is not well understood.

Objective  To evaluate the association of community social and economic conditions and resources for children with life expectancy at birth.

Design, Setting, and Participants  This cross-sectional study examined neighborhood child opportunity and life expectancy using data from residents of 65 662 US Census tracts in 2015. The analysis was conducted from July 6 to October 1, 2021.

Exposures  Neighborhood conditions and resources for children in 2015.

Main Outcomes and Measures  The primary outcome was life expectancy at birth at the Census tract level based on data from the US Small-Area Life Expectancy Estimates Project (January 1, 2010, to December 31, 2015). Neighborhood conditions and resources for children were quantified by Census tract Child Opportunity Index (COI) 2.0 scores for 2015. This index captures community conditions associated with children’s health and long-term outcomes categorized into 5 levels, from very low to very high opportunity. It includes 29 indicators in 3 domains: education, health and environment, and social and economic factors. Mixed-effects and simple linear regression models were used to estimate the associations between standardized COI scores (composite and domain-specific) and life expectancy.

Results  The study included residents from 65 662 of 73 057 US Census tracts (89.9%). Life expectancy at birth across Census tracts ranged from 56.3 years to 93.6 years (mean [SD], 78.2 [4.0] years). Life expectancy in Census tracts with very low COI scores was lower than life expectancy in Census tracts with very high COI scores (−7.06 years [95% CI, −7.13 to −6.99 years]). Stepwise associations were observed between COI scores and life expectancy. For each domain, life expectancy was shortest in Census tracts with very low compared with very high COI scores (education: β = −2.02 years [95% CI, −2.12 to −1.92 years]); health and environment: β = −2.30 years [95% CI, −2.41 to −2.20 years]; social and economic: β = −4.16 years [95% CI, −4.26 to −4.06 years]). The models accounted for 41% to 54% of variability in life expectancy at birth (R2 = 0.41-0.54).

Conclusions and Relevance  In this study, neighborhood conditions and resources for children were significantly associated with life expectancy at birth, accounting for substantial variability in life expectancy at the Census tract level. These findings suggest that community resources and conditions are important targets for antipoverty interventions and policies to improve life expectancy and address health inequities.

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Association of Neighborhood Conditions and Resources for Children With Life Expectancy at Birth in the US | Health Disparities | JAMA Network Open | JAMA Network

Air pollution tips the scale for obesity in women

Peer-Reviewed Publication

UNIVERSITY OF MICHIGAN

Obesity has been a major global health issue in recent decades as more people eat unhealthy diets and fail to exercise regularly.

A new University of Michigan study suggests there is another factor that tips the scale in women's weight, body mass index, waist circumference and body fat—air pollution. 

Women in their late 40s and early 50s exposed long-term to air pollution—specifically, higher levels of fine particles, nitrogen dioxide and ozone—saw increases in their body size and composition measures, said Xin Wang, epidemiology research investigator at the U-M School of Public Health and the study's first author. 

Data came from 1,654 white, Black, Chinese,and Japanese women from the Study of Women's Health Across the Nation. These women, whose baseline median age was nearly 50 years, were tracked from 2000 to 2008. 

Annual air pollution exposures were assigned by linking residential addresses with hybrid estimates of air pollutant concentrations. The researchers examined the associations between the pollution and the participants' body size and composition measures. One question they sought to answer was whether these associations differed by physical activity.

Exposure to air pollution was linked with higher body fat, higher proportion fat and lower lean mass among midlife women. For instance, body fat increased by 4.5%, or about 2.6 pounds.

Researchers explored the interaction between air pollution and physical activity on body composition. High levels of physical activity—which had been based on the frequency, duration and perceived physical exertion of more than 60 exercises—was an effective way to mitigate and offset exposure to air pollution, the research showed.  

Since the study focused on midlife women, the findings can't be generalized to men or women in other age ranges, Wang said. 

The findings appear in Diabetes Care

The study's co-authors are Carrie Karvonen-Gutierrez (U-M), Ellen Gold (UC Davis), Carol Derby (Albert Einstein College of Medicine), Gail Greendale (UCLA), Xiangmei Wu (California Environmental Protection Agency), Joel Schwartz (Harvard) and Sung Kyun Park (U-M).

Study: Longitudinal Associations of Air Pollution With Body Size and Composition in Midlife Women: The Study of Women’s Health Across the Nation

MORE THAN SMOKING

Cancer deaths in Italy: environmental pollution plays an important role

Peer-Reviewed Publication

UNIVERSITÀ DI BOLOGNA

 NEWS RELEASE 

Today, cancer represents the second leading cause of death in the world after cardiovascular diseases. In the last decades of cancer research, lifestyle - especially physical inactivity, poor diet, obesity, alcoholism, and smoking - and random or genetic factors have been identified as major causes in the development of tumors. Nevertheless, there is a growing understanding of how environmental pollution is among the main factors inducing cancer proliferation.

To further investigate this issue, a group of scholars from the University of Bologna, the University of Bari, and the CNR (National Research Council) used advanced artificial intelligence methods to analyze the relationship between cancer mortality, socio-economic factors, and environmental pollution sources in Italy on a regional and provincial level. The results and the analysis of the investigation have been published in the journal Science of the Total Environment, while the entire ten-year dataset with cancer mortality rates for all Italian municipalities has been published in the journal Nature Scientific Data, an open-access and user-friendly journal.

"Contrary to what has been believed so far, our analysis showed that the distribution of cancer mortality among Italian citizens is neither random nor spatially well-defined," explains Roberto Cazzolla Gatti, professor at the Department of Biological, Geological, and Environmental Sciences at the University of Bologna as well as first author of the study. "Instead, cancer mortality exceeds the national average especially where environmental pollution is higher, even if in these areas living habits are generally healthier."

Researchers took into consideration 35 environmental sources of pollution such as industries, pesticides, incinerators, and motor vehicle traffic. Among these, they found that air quality is the most important factor in terms of its association with the average cancer mortality rate. This is followed by the presence of sites to be reclaimed, urban areas, motor vehicle density and pesticides. Moreover, other specific sources of environmental pollution are relevant for specific types of tumour. For instance, cultivated areas are associated with tumours of the gastrointestinal system, roads and steelworks proximity with bladder tumours, industrial activities in urban areas with prostate tumour and lymphomas.

The Italian province with the highest cancer mortality rate in the decade 2009-2018 was Lodi. It was followed by those of Naples, Bergamo, Pavia, Sondrio, and Cremona. The highest-ranked province in central Italy is Viterbo (11th position), followed by Rome (18th). In southern Italy, in addition to the province of Naples in second place, only that of Caserta (8th) is in the top 10 for cancer mortality. Anyone can check the ten-year mortality rate in its municipality by visiting the open-access dataset published by the authors of the study.

"Of course, these results do not question the fact that a healthier lifestyle helps to reduce the risk of cancer, just as they don’t question the efforts to get to the genetic basis that may favour the onset of cancer," adds Cazzolla Gatti. "Our results, however, give us good reason to believe that living in a highly polluted area can cancel out the benefits that come with a healthy lifestyle and induce the development of cancers with a higher frequency."

Every year in Italy, there are 400,000 new cases of malignant tumours, with an annual average of about three deaths per thousand people according to the Italian cancer registries. On both national and regional level, the analysis carried out by the scholars showed the relevance of the environment on the onset of tumours even if compared to other socio-economic factors and lifestyle. Moreover, it was possible to determine on a provincial level what potential sources of pollution could cause an excess of cancer mortality compared to the national average, thus also providing a focus on environmental factors that are mostly associated with specific types of cancer.

"From a global health perspective, following the approach known as One Health, it is now evident that the quality of life of our species is closely dependent on that of the environment in which we live and of the entire planet," explains Cazzolla Gatti. "It is, therefore, necessary to give the highest priority not only to research for cancer cures but also to the reduction and prevention of environmental contamination. These are essential actions in the difficult fight against cancer onset. We need to know how to cure our planet to be able to avoid getting sick.”

According to the study, Italian regions with a relatively high cancer mortality rate have a relatively high degree of pollution, despite registering a relatively low frequency of the usual cancer risk factors such as being overweight, smoking, having a low income, high meat consumption, and low fruit and vegetable consumption. Furthermore, on a provincial level, for both malignant and benign tumors in general and for 16 out of 23 specific types of cancer, significant spatial associations were found with certain sources of pollution and explained more than half of the association between environment and cancer. This confirmed that, in most cases, being exposed to a contaminated environment has a significant impact on cancer mortality in Italy.

"Data show good, albeit preliminary, evidence that a better lifestyle and greater attention to socio-economic and health issues can only partially reduce the risk of dying from cancer if the quality of the environment is overlooked," explains Cazzolla Gatti. “This could explain why we have observed that people living in northern Italian regions - particularly in those located in the Po Valley, between the Lombardy and Veneto regions, which are highly industrialized areas - and exposed to very high levels of environmental pollution show a significant excess of cancer mortality compared to those who live in the central-southern regions (except for some other highly polluted areas, such as the so-called Terra dei Fuochi (Land of Fires) in the Campania region), even though they enjoy better health, have higher incomes, consume more food of plant origin than animal one, and have easier access to health care.”

The entire ten-year database (2009-2018) on cancer mortality rates developed by researchers from ISTAT (Italian National Institute of Statistics) registers has been published with open access. In the database, 23 cancer macro-categories in Italy on a municipal, provincial, and regional level are considered. "We want to make a complete, up-to-date and ready-to-use data source on cancer mortality in Italy easily accessible to be consulted by interested bodies and local and national authorities, and to provide researchers useful data to carry out further studies," Cazzolla Gatti concludes.

The study was published in open access in the journal Science of the Total Environment under the title “The spatial association between environmental pollution and long-term cancer mortality in Italy”, while the entire dataset can be found in Nature Scientific Data. The authors of the study are Roberto Cazzolla Gatti (University of Bologna), Arianna Di Paola (CNR - National Research Council, Institute for BioEconomy), Alfonso Monaco (University of Bari 'Aldo Moro'), Alena Velichevskaya (Tomsk State University, Russia), Nicola Amoroso (INFN - National Institute for Nuclear Physics, Bari Section), Roberto Bellotti (University of Bari 'Aldo Moro').

 

Fighting cancer on earth and in space using high-energy protons

High-energy proton experiments optimize production of medical imaging isotopes while providing insight into how to protect astronauts from space radiation

DOE/US DEPARTMENT OF ENERGY


The Science

Scientists on Earth use high-energy protons to create isotopes to detect and treat cancer. In space, however, these same high-energy protons can pose a risk to spacecraft and the health of the astronauts traveling in them. These risks mean spacecraft must have protective shielding. Unfortunately, scientists have a great deal of uncertainty concerning the risks posed by these high-energy protons. To learn more about the risks and about using these protons to produce isotopes, scientists measured the cross sections (probabilities) for high-energy proton reactions used to produce important new radiopharmaceuticals. 

The Impact

Measuring these cross sections allows scientists to optimize the quantity and purity of medical isotopes needed in the fight against cancer. These include producing the pharmaceuticals arsenic-72-HBED and gallium-68-DOTATOC using high-energy protons from particle accelerators. Doctors use these pharmaceuticals to show where tumors have spread in the body. However, high-energy protons are also a dangerous type of space radiation. Better understanding their behavior and reactions allows scientists to improve the design of shielding that protects astronauts and electronics in spacecraft. This will allow us to explore other planets in our solar system, while also helping understand how nuclei absorb and release energy. 

Summary

Researchers from Brookhaven National Laboratory, Los Alamos National Laboratory, and Lawrence Berkeley National Laboratory performed a series of experiments using proton beams from the Brookhaven Linac Isotope Producer, the Los Alamos Isotope Production Facility, and the Berkeley Laboratory 88-Inch Cyclotron. These experiments measured production rates for 78 sotopes from the proton bombardment of niobium and arsenic targets with energies up to 200 MeV, including two radionuclides used for Positron Emission Tomography (PET) and one used to monitor the dose from proton beams in accelerators. 

The team compared this large body of production data to predictions made using state-of-the-art nuclear reaction modeling codes to explore how quickly the energy from an incoming proton spreads throughout the entire nucleus when the two collide. The results showed a significantly slower rate of energy dissipation in the nucleus compared to what scientists previously believed. This decrease, in turn, leads to an increase in the emission of additional “secondary” high-energy protons and neutrons, and also shows strikingly different rates when producing isotopes with different proton-to-neutron ratios. Taken together, these results provide guidance for the optimized production of the two PET radionuclides and will help in the design of shielding for spacecraft and their occupants from “secondary” particles caused by protons in cosmic radiation. 

 

Funding

This research was supported by the Department of Energy Isotope Program, managed by the Office of Science for Isotope R&D and Production, and was carried out by Lawrence Berkeley National Laboratory, Los Alamos National Laboratory, and Brookhaven National Laboratory.

Bringing custom microbes to the business of recycling plastic

Peer-Reviewed Publication

DOE/OAK RIDGE NATIONAL LABORATORY

Adam Guss 

IMAGE: ORNL’S ADAM GUSS AND COLLEAGUES USED SYNTHETIC BIOLOGY TO DEVELOP A CUSTOM MICROBE CAPABLE OF CONVERTING DECONSTRUCTED MIXED PLASTIC WASTE INTO VALUABLE NEW MATERIALS. view more 

CREDIT: CARLOS JONES, ORNL/U.S. DEPT. OF ENERGY

Scientists working on a solution for plastic waste have developed a two-step chemical and biological process to break down and upcycle mixed plastics into valuable bioproducts.

The project, which involves multiple institutions, draws on synthetic biology expertise at the Department of Energy’s Oak Ridge National Laboratory to engineer a microbe that converts deconstructed plastic waste into building blocks for next-generation materials.

The new process, described in the journal Science, would replace a system that now requires painstaking, costly sorting of materials, which has resulted in only about 5% of plastics being recycled in the United States.

The project is led by the National Renewable Energy Laboratory and also brings together scientists from  the Massachusetts Institute of Technology, the University of Wisconsin-Madison and ORNL under the Bio-Optimized Technologies to keep Thermoplastics out of Landfills and the Environment, or BOTTLE, Consortium.

Different plastics contain different polymers, each with unique chemical building blocks. The BOTTLE researchers developed a process to convert mixed plastics to a single chemical product, working toward a solution that would allow recyclers to skip sorting.

The first step in the process relies on oxygen and catalysts to break down large polymer molecules into their smaller chemical building blocks. The process was applied to a mixture of three common plastics: polystyrene, or PS, used in disposable coffee cups; polyethylene terephthalate, or PET, used in single-use beverage bottles, polyester clothing and carpets; and high-density polyethylene, or HDPE, used in many common consumer plastics and often associated with milk jugs.

“This is a potential entry point into processing plastics that cannot be recycled at all today,” said Gregg Beckham, a senior research fellow at NREL and head of BOTTLE.

The oxidation process breaks down these plastics into a complex mixture of chemical compounds — including benzoic acid, terephthalic acid and dicarboxylic acids — that would require advanced and costly separations to yield pure products. That is where biology comes into play.

BOTTLE colleagues engineered a soil microbe, Pseudomonas putida, to biologically convert or “funnel” the mixture of small-molecule intermediates to single products: either polyhydroxyalkanoates, or PHAs, which are an emerging form of biodegradable bioplastics; or beta-ketoadipate, which can be used to make new performance-advantaged nylon materials.

The experiment built on a process developed by ORNL’s Adam Guss and colleagues at NREL to engineer the bacterium with desired traits from other organisms. The process, outlined in the journal Metabolic Engineering, converted deconstructed PET into building blocks for a superior nylon product that is more water- and heat-resistant — ideal for applications such as automotive parts.

“We took a combinatorial approach to pathway assembly, basically finding the best combination of genes from different organisms that allowed us to get robust utilization of PET in Pseudomonas putida,” Guss said. “ORNL specializes in modifying nonmodel microbes to add traits useful for biotechnology, tapping our deep expertise in synthetic biology as well as transcriptomics and proteomics to discover new metabolic pathways.”

“Biological funneling simply means we’ve engineered the metabolic network of a microbe to direct the carbon from a large number of substrates to a single product,” said NREL’s Allison Werner, a co-author on the Science paper. “To do this, we take DNA from nature — usually other microbes — and paste it into Pseudomonas putida’s genome. The DNA is transcribed into RNA, which in turn is translated into proteins that perform diverse biochemical transformations, forming a new metabolic network and ultimately enabling us to capture more carbon and to tune where it goes.”

Guss and colleagues have spent years perfecting P. putida to convert the plant biopolymer lignin, derived from bioenergy crops, into advanced bioproducts as part of DOE’s Center for Bioenergy Innovation and Agile BioFoundry. In 2020, Guss led a team that announced it had engineered the microbe to simultaneously digest five of the most abundant compounds of lignocellulosic biomass.

In the next steps for BOTTLE, “we’re continuing to expand the range of molecules that P. putida can eat as we work to break down more types of plastics and also more real-world plastics that have additional additives,” Guss said.

“Plastics are major environmental pollutants and are largely made using fossil carbon,” he said. “This research sits at that intersection of breaking down today’s plastic waste and converting it into building blocks for the next generation of plastics that are both recyclable-by-design and biodegradable.”

Funding was provided by DOE’s Advanced Manufacturing Office and Bioenergy Technologies Office. The work was performed as part of the BOTTLE Consortium.

UT-Battelle manages ORNL for the Department of Energy’s Office of Science, the single largest supporter of basic research in the physical sciences in the United States. The Office of Science is working to address some of the most pressing challenges of our time. For more information, please visit energy.gov/science.

Editor’s note: This article was adapted from an NREL announcement.

Digital transformation in construction industry requires more support, study shows

Researchers identify the main obstacles preventing efficient digital transformation in the engineering and construction industry

Peer-Reviewed Publication

XI'AN JIAOTONG-LIVERPOOL UNIVERSITY

Digital transformation in the engineering and construction industry. 

IMAGE: IN A RECENT STUDY, RESEARCHERS HAVE IDENTIFIED THE MAIN OBSTACLES PREVENTING EFFICIENT DIGITAL TRANSFORMATION IN THE ENGINEERING AND CONSTRUCTION INDUSTRY. view more 

CREDIT: XJTLU

In recent years, the engineering and construction industries have been exploring the use of digital technologies to boost productivity and improve safety, quality, and sustainability. However, digital transformation in this industry has been slow compared to other sectors due to certain obstacles.

In a paper recently published in the journal Engineering, Construction, and Architectural Management, researchers from Xi’an Jiaotong-Liverpool University and the University of Lincoln identify, classify, and rank the main obstacles preventing digital transformation in this sector.

The researchers identified barriers through a systematic literature review and expert validation, then surveyed 192 construction professionals in China on the impact of the obstacles. They found that the three main problems are a lack of laws and regulations, a lack of support and leadership, and a lack of resources and professionals.

Changing legislation

The lack of laws and regulations is the most significant among the barriers identified, according to Dr Fangyu Guo, assistant professor at XJTLU’s Department of Civil Engineering and corresponding author of the paper.

“The lack of laws and regulations has a negative effect on digital transformation because construction companies need governmental regulations as guidelines to determine their strategies and adapt their organisational structure.

“Well-established standards and regulations are critical for directing an effective digital transformation and motivating stakeholders to invest more in various digital technologies and tools,” Guo says.

Leadership and resources

A lack of support and leadership also negatively influences digital transformation. Most employees may be unfamiliar with the new technologies, and insufficient support from senior management will reduce their willingness to adapt to the change.

“It is important for senior management in construction firms to give ongoing support and motivation to employees during the implementation of digital transformation,” says Dr Guo.

The lack of resources and professionals is another obstacle. There is currently a large digital skills gap in the industry, so developing the next generation of digital skills and relevant talents is crucial to digital transformation.

The researchers suggest firms must develop strategic plans and training programmes to obtain potential talents who can use digital technologies and possess long-term business intelligence.

The study offers insights for governments and construction companies to improve their understanding of these barriers and their impacts. The findings will help to establish policies that can use digital transformation to enhance construction project management.

The research team consists of Kaiyang Wang, Dr Fangyu Guo, and Dr Cheng Zhang from XJTLU, and Professor Dirk Schaefer from the University of Lincoln.

 

Back to the future of photosynthesis

Resurrecting billon-year-old enzymes reveals how photosynthesis adapted to the rise of oxygen

Peer-Reviewed Publication

MAX-PLANCK-GESELLSCHAFT

Rubisco complexes 

IMAGE: CRYO-ELECTRON MICROSCOPE IMAGE OF TWO RUBISCO COMPLEXES INTERACTING WITH EACH OTHER. IF A SUBUNIT ESSENTIAL FOR SOLUBILITY IS MISSING, INDIVIDUAL ENZYME COMPLEXES CAN INTERACT WITH EACH OTHER IN THIS WAY AND FORM THREAD-LIKE STRUCTURES, SO-CALLED FIBRILS. UNDER NORMAL CONDITIONS, HOWEVER, RUBISCO DOES NOT FORM SUCH FIBRILS. view more 

CREDIT: MPI F. TERRESTRIAL MICROBIOLOGY/ L. SCHULZ

The central biocatalyst in photosynthesis, Rubisco, is the most abundant enzyme on earth. By reconstructing billion-year-old enzymes, a team of Max Planck researchers has deciphered one of the key adaptations of early photosynthesis. Their results not only provide insights into the evolution of modern photosynthesis but also offer new impulses for improving it.

Present day life fully depends on photosynthetic organisms like plants and algae that capture and convert CO2. At the heart of these processes lies an enzyme called Rubisco that captures more than 400 billion tons CO2 annually. Organisms alive today make staggering amounts of it: the mass of Rubisco on our planet outweighs that of all humans. In order to assume such a dominant role in the global carbon cycle, Rubisco had to adapt constantly to changing environmental conditions.

Using a combination of computational and synthetic approaches, a team from the Max Planck Institute for Terrestrial Microbiology in Marburg, Germany, in collaboration with the University of Singapore has now successfully resurrected and studied billion-year-old enzymes in the lab. In this process, which they describe as “molecular paleontology”, the researchers found that instead of direct mutations in the active center, an entirely new component prepared photosynthesis to adapt to rising oxygen levels.

Rubisco's early confusion

Rubisco is ancient: it emerged approximately four billion years ago in primordial metabolism prior to the presence of oxygen on earth. However, with the invention of oxygen-producing photosynthesis and rise of oxygen in the atmosphere, the enzyme started catalyzing an undesired reaction, in which it mistakes O2 for CO2 and produces metabolites that are toxic to the cell. This confused substrate scope still scars Rubiscos to date and limits photosynthetic efficiency. Even though Rubiscos that evolved in oxygen-containing environments became more specific for CO2 over time, none of them could get completely rid of the oxygen capturing reaction.

The molecular determinants of increased CO2 specificity in Rubisco remain largely unknown. However, they are of great interest to researchers aiming to improve photosynthesis. Interestingly, those Rubiscos that show increased CO2 specificity recruited a novel protein component of unknown function. This component was suspected to be involved in increasing CO2 specificity, however, the true reason for its emergence remained difficult to determine because it already evolved billions of years ago.

Studying evolution by resurrecting ancient proteins in the lab

To understand this key event in the evolution of more specific Rubiscos, collaborators at the Max Planck Institute for Terrestrial Microbiology in Marburg and Nanyang Technological University in Singapore used a statistical algorithm to recreate forms of Rubiscos that existed billions of years ago, before oxygen levels began to rise. The team led by Max Planck researchers Tobias Erb and Georg Hochberg resurrected these ancient proteins in the lab to study their properties. In particular, the scientists wondered whether Rubisco’s new component had anything to do with the evolution of higher specificity.

The answer was surprising, as doctoral researcher Luca Schulz explains: “We expected the new component to somehow directly exclude oxygen from Rubisco catalytic center. That is not what happened. Instead, this new subunit seems to act as a modulator for evolution: recruitment of the subunit changed the effect that subsequent mutations had on Rubisco’s catalytic subunit. Previously inconsequential mutations suddenly had a huge effect on specificity when this new component was present. It seems that having this new subunit completely changed Rubisco’s evolutionary potential.”

An enzyme's addiction to its new subunit

This function as an “evolutionary modulator” also explains another mysterious aspect of the new protein component: Rubiscos that incorporated it are completely dependent on it, even though other forms of Rubisco can function perfectly well without. The same modulating effect explains why: When bound to this small protein component, Rubisco become tolerant to mutations that would otherwise be catastrophically detrimental. With the accumulation of such mutations, Rubisco effectively became addicted to its new subunit.

Altogether, the findings finally explain the reason why Rubisco kept this new protein component around ever since it encountered it. Max Planck Research Group Leader Georg Hochberg explains: “The fact that this connection was not understood until now highlights the importance of evolutionary analysis for understanding the biochemistry that drives life around us. The history of biomolecules like Rubisco can teach us so much about why they are the way they are today. And there are still so many biochemical phenomena whose evolutionary history we really have no idea about. So it’s a very exciting time to be an evolutionary biochemist: almost the entire molecular history of the cell is still waiting to be discovered.”

Scientific journeys back in time can provide invaluable insights for the future

The study also has important implications for how photosynthesis might be improved, says Max Planck Director Tobias Erb: “Our research taught us that traditional attempts to improve Rubisco might have been looking in the wrong place: for years, research focused solely on changing amino acids in Rubisco itself to improve it. Our work now suggests that adding entirely new protein components to the enzyme could be more productive and may open otherwise impossible evolutionary paths. This is uncharted land for enzyme engineering.”