Single-cell atlas of the whole human lung

First integrated Human Lung Cell Atlas provides insights into lung diseases

Peer-Reviewed Publication

WELLCOME TRUST SANGER INSTITUTE

The largest and most comprehensive cell map of the human lung is announced in Nature Medicine today (8 June).  Revealing the great diversity of cell types in the lung and key differences between health and disease, the Human Lung Cell Atlas will be a valuable resource for lung researchers.

By combining data from nearly 40 studies, researchers created the first integrated single-cell atlas of the lung, revealing rare cell types and highlighting cellular differences between healthy people. In addition, the study found common cell states between lung fibrosis, cancer and COVID-19, offering new ways of understanding lung disease, which could help identify new therapeutic targets.

The study is part of the global Human Cell Atlas* (HCA) initiative to map every cell type in the human body, to transform our understanding of health, infection and disease.

Lung research has benefited greatly from recent single-cell studies that show which genes are active in each cell. Despite this, the research has been limited so far by the number of samples and individuals included per study. To better understand healthy lungs and determine what goes wrong in disease, a comprehensive atlas has been needed, however this has been difficult to achieve.

Now, a large team of researchers has successfully combined 49 lung datasets, from nearly 40 separate studies, into a single integrated Atlas, using advanced machine learning.  By pooling and integrating datasets from every major single-cell RNA-sequencing lung study published to date, the team created the first integrated Human Lung Cell Atlas. This Atlas spans over 2.4 million cells from 486 individuals and gives new insights into lung biology that were not possible before.

Dr Malte Luecken, a senior author on the paper and Group leader at the Institute of Computational Biology and the Institute of Lung Health and Immunity at Helmholtz Munich, Germany, said: “A comprehensive organ atlas requires many datasets to capture the diversity between both cells and individuals, but combining different datasets is a huge challenge. We developed a benchmarking pipeline to find the optimal method to integrate all datasets into the Atlas, using artificial intelligence, and successfully combined knowledge and data from almost 40 previous lung studies.”

Professor Fabian Theis, a senior author on the paper and Director of the Institute of Computational Biology at Helmholtz Munich, said: “We have created a first reference atlas of the human lung, which includes data from more than a hundred healthy people and reveals how the cells from individuals vary with age, sex, and smoking history. The sheer numbers of cells and individuals involved now gives the power to see rare cell types and identify new cell states that have not previously been described.”

While the core of the Human Lung Cell Atlas is data from healthy lungs, the team also took datasets from more than 10 different lung diseases and projected these onto the healthy data, to understand disease states.

The team discovered that different lung diseases shared common immune cell states, including the finding that a subset of macrophages (a type of immune cell) shared similar gene activity in lung fibrosis, cancer and COVID-19. The shared states indicate that these cells could play a similar role in scar formation in the lung in all three diseases, and provide pointers for potential therapeutic targets. 

Professor Martijn Nawijn, a senior author on the paper and Professor at the University Medical Center Groningen, the Netherlands, said: “This is the first effort to compare healthy and diseased lungs in one study in an integrated way.  Our study not only supports the presence of lung fibrosis in COVID-19, it allows us to identify and define a shared cell state between lung fibrosis, COVID-19 and lung cancer patients.  Finding these shared disease-associated cells is really exciting, and reveals a totally different way of looking at lung diseases, opening possibilities for novel treatment targets and developing treatment response biomarkers. Our findings also suggest that therapies working for one disease may help alleviate others.”

The Lung Atlas Integration project was an international collaborative effort with nearly 100 partners from more than 60 departments, including key researchers from Helmholtz Munich, University Medical Center Groningen and Northwestern University. The team are part of the Human Cell Atlas Lung Biological Network**, which has its roots in the Chan Zuckerberg Initiative Seed Networks for the Human Cell Atlas, and the European Union funded lung network DiscovAIR. At the start of the COVID-19 pandemic in 2020, the single-cell lung communities came together rapidly, forming the HCA Lung Biological Network to help understand COVID-19, which then led to the global effort to integrate all the data.

Lisa Sikkema, the first author on the paper and PhD student at the Institute of Computational Biology at Helmholtz Munich, said: “One of the big problems in creating the integrated lung cell atlas was with cell type annotation. Different research groups used different names for the same cell type, or the same name for different cells, so as a team we worked to standardise them using the data in the atlas. The atlas is a first step towards a consensus annotation of the human lung, which will help bring together the field of lung research.”

The first integrated major organ within the Human Cell Atlas initiative, the Human Lung Cell Atlas is publically available for researchers globally, as a central resource to study the lung in health and disease.

Dr Alexander Misharin, a senior author on the paper and Associate Professor at Northwestern University Feinberg School of Medicine, USA, said: “The Human Lung Cell Atlas is a huge resource for the scientific and medical community. Openly available to researchers, new disease data can be mapped onto the HLCA, transforming research into lung biology and disease. As the first whole reference atlas of a major organ, the HLCA also represents a milestone towards achieving a full Human Cell Atlas which will transform our understanding of biology and disease and lay the foundation for a new era of healthcare”.

ENDS

Contact Details:
Dr Samantha Wynne,
Human Cell Atlas Scientific Communications Manager,
HCA UK Office, Wellcome Sanger Institute,
Cambridge, CB10 1SA, UK
Email: press@humancellatlas.org
 

Notes to Editors:

*The Human Cell Atlas (HCA)
The Human Cell Atlas (HCA) is an international collaborative consortium which is creating comprehensive reference maps of all human cells—the fundamental units of life—as a basis for understanding human health and for diagnosing, monitoring, and treating disease. The HCA is likely to impact every aspect of biology and medicine, propelling translational discoveries and applications and ultimately leading to a new era of precision medicine.

The HCA was co-founded in 2016 by Dr Sarah Teichmann at the Wellcome Sanger Institute (UK) and Dr Aviv Regev, then at the Broad Institute of MIT and Harvard (USA). A truly global initiative, there are now more than 2,900 HCA members, from 94 countries around the world. https://www.humancellatlas.org

**The Human Cell Atlas Lung Biological Network is a group of scientists who collaborate to map the cell types and states present in human airways. This group is coordinated by Pascal Barbry, Alexander Misharin, Martijn Nawijn and Jay Rajagopal.

Publication:
An integrated cell atlas of the lung in health and disease. Lisa Sikkema et al. (2023). Nature Medicine. DOI :10.1038/s41591-023-02327-2

Funding:
This work was supported by many funders including: The Chan Zuckerberg Initiative, European Union H2020 (Discovair), Fondation pour la Recherche Médicale, National Infrastructure France Génomique, Wellcome, The Netherlands Lung Foundation, The German Center for Lung Research, the Helmholtz Association and the European Respiratory Society. Please see the paper for full list of funders.

Selected Websites:

Helmholtz Munich
Helmholtz Munich is a leading biomedical research center. Its mission is to develop breakthrough solutions for better health in a rapidly changing world. Interdisciplinary research teams focus on environmentally triggered diseases, especially the therapy and prevention of diabetes, obesity, allergies, and chronic lung diseases. With the power of artificial intelligence and bioengineering, researchers accelerate the translation to patients. Helmholtz Munich has more than 2,500 employees and is headquartered in Munich/Neuherberg. It is a member of the Helmholtz Association, with more than 43,000 employees and 18 research centers the largest scientific organization in Germany. More about Helmholtz Munich (Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH): www.helmholtz-munich.de/en [helmholtz-munich.de] 

University Medical Center Groningen
The University Medical Center Groningen (UMCG) is one of the largest hospitals in the Netherlands and is the largest employer in the Northern Netherlands. More
characterized by a combination of fundamental and patient oriented clinical research. The interaction between these two stimulates the development of new clinical and research opportunities. Problems that occur in the clinical practice act as a catalyst which sets new fundamental research in motion, whereas fundamental research can come up with new clinical possibilities. The UMCG focuses on healthy ageing in all priority areas: research, clinical care and education. Together we push boundaries for a sustainable future of health. https://umcgresearch.org/

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JOURNAL

Nature Medicine

DOI

10.1038/s41591-023-02327-2 

METHOD OF RESEARCH

Meta-analysis

SUBJECT OF RESEARCH

Human tissue samples

ARTICLE TITLE

An integrated cell atlas of the lung in health and disease

ARTICLE PUBLICATION DATE

8-Jun-2023

Mouse models of adolescent binge drinking reveal key long-lasting brain changes

Peer-Reviewed Publication

PENN STATE

 

IMAGE: PENN STATE NEUROSCIENCE DOCTORAL STUDENT AVERY SICHER WORKS IN THE LAB, DOING PATCH-CLAMP ELECTROPHYSIOLOGY. view more 

CREDIT: DAN LESHER / PENN STATE

UNIVERSITY PARK, Pa — Heavy alcohol consumption may cause permanent dysregulation of neurons, or brain cells, in adolescents, according to a new study in mice. The findings suggest that exposure to binge-levels of alcohol during adolescence, when the brain is still developing, lead to long-lasting changes in the brain’s ability to signal and communicate — potentially setting the stage for long-term behavioral changes and hinting towards the mechanisms of alcohol-induced cognitive changes in humans.

“What we’re seeing here,” said Nikki Crowley, assistant professor in biology and biomedical engineering and Huck Early Chair in Neurobiology and Neural Engineering, “is that if adolescent binge drinking knocks neurons off this trajectory, they might not be able to get back, even if the alcohol consumption stops.”

The prefrontal cortex is a key brain region for executive functioning, risk assessment and decision-making. According to Crowley, it’s not fully formed in adolescents and is still maturing in humans until around age 25. Disruptions to its development in young people may have serious and long-lasting consequences, added Crowley.

“Heavy binge drinking is problematic for everyone, and should be avoided, but adolescent brains appear to be particularly vulnerable to the consequences, which in humans, will follow them for decades,” Crowley said.

The team, led by Avery Sicher, a doctoral student in Penn State’s neuroscience program, used a model of adolescent ethanol exposure in mice to understand how different populations of neurons in the cortex, the outermost layer of the brain, are changed by voluntary binge alcohol consumption. In this model, mice are known to consume alcohol in patterns that approximate human binge drinking — defined by the National Institute on Alcohol Abuse and Alcoholism as a pattern of alcohol consumption that leads to a blood alcohol concentration of 0.08% or higher, usually in about two hours. Binge drinking is considered to be one of the most dangerous patterns of alcohol misuse, and understanding its impact on the developing brain can help inform treatment.

Sicher and her colleagues gave mice access to alcohol during a 30-day period. Due to their faster development and shorter lifespan, this corresponded to roughly ages 11-18 in human years. They then looked at the electrophysiological properties of different neurons throughout the prefrontal cortex to understand how adolescent binge drinking influenced the wiring and firing of these circuits. Sicher et al. used whole-cell patch clamp electrophysiology, combined with techniques such as optogenetics, which allowed the team to isolate individual neurons and record measurements related to intrinsic excitability, such as the resting membrane potential and the ability for each neuron to fire action potentials. This allowed them to understand how these neurons had changed their ability to signal with other neurons.

They found that somatostatin neurons, a key population of cells that provides inhibition of neurotransmitter release from other cell types throughout the brain and helps to “dampen the noise,” appeared to be permanently dysregulated in the mice that binge drank as compared to mice that were only provided water throughout development. Somatostatin neurons release both inhibitory neurotransmitters, like GABA, as well as inhibitory peptides like somatostatin, and proper functioning of these neurons is necessary for a healthy brain. The neurons were more excitable — meaning they were signaling too much and dampening the activity of other key neurons — as far out as 30 days after the mice stopped drinking alcohol, when the mice have transitioned into adulthood.

“Neurons have a relatively fixed developmental trajectory — they need to get where they are going and sync up with the right partners during specific periods of development in order to function properly,” explained Crowley.

David Starnes, an undergraduate biology student in Schreyer’s Honor College, performed somatostatin cell counts to quantify cell density before and after ethanol consumption. He found that while the electrophysiology data suggested these neurons wire differently, the number of SST neurons does not appear to change as a result of binge drinking.

Other authors on the paper include Keith Griffith, a research technician in the lab and former undergraduate in Engineering Science and Mechanics, Grace Smith, a graduate student in Biomedical Engineering, Dakota Brockway, a graduate student in neuroscience, and Nigel Dao, a former research technician in the lab and current doctoral student at New York University. This research was supported by the National Institutes of Health and the Huck Institutes of the Life Sciences at Penn State.

To learn more about Sicher’s neuroscience research, watch this short video from the Huck Institutes’ Student Spotlight series. The paper is currently available in the online version of the journal Neuropharmacology and will be published in the Aug. 15 issue.

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DOI

10.1016/j.neuropharm.2023.109561 

Black, Hispanic survivors of breast cancer have higher death rates from second cancers

Peer-Reviewed Publication

JOHNS HOPKINS MEDICINE

 

IMAGE: THIS GRAPHIC SHOWS THE PERCENT OF CANCER DEATHS FROM A SECOND CANCER AMONG BREAST CANCER SURVIVORS OVER TIME. EACH COLOR LINE REPRESENTS A DIFFERENT RACE/ETHNICITY, WITH PURPLE REPRESENTING ASIANS, BLACK REPRESENTING HISPANICS, RED REPRESENTING NON-HISPANIC BLACKS AND BLUE REPRESENTING NON-HISPANIC WHITES. view more 

CREDIT: IMAGE COURTESY OF KALA VISVANATHAN

Hispanic and non-Hispanic Black female survivors of breast cancer experience higher death rates after being diagnosed with a second primary cancer than members of other ethnic and racial groups, according to recent research from investigators at the Johns Hopkins Kimmel Cancer Center.

In a study of nearly 40,000 adult survivors of breast cancer, the risk of death from a second cancer was 12% higher among non-Hispanic Black survivors and 8% higher among Hispanic survivors compared with non-Hispanic white survivors. Survivors in racial and ethnic minorities were diagnosed with second cancers up to six years younger than non-Hispanic white survivors, and within a shorter time from their first cancer.

Additionally, non-Hispanic Black survivors had a 44% higher risk of cardiovascular disease-related death after a second cancer diagnosis than non-Hispanic white survivors. These results were published March 9 in the Journal of the National Cancer Institute.

Nearly half of cancer survivors live for more than 10 years, and approximately one in five people diagnosed with cancer has a prior cancer history, according to the National Cancer Institute. Therefore, says senior study author Kala Visvanathan, M.D., M.H.S., director of the Cancer Genetics and Prevention Service at the Kimmel Cancer Center and a member of the Women’s Malignancy Program at Johns Hopkins, it’s important to determine risk factors associated with second cancers so they can best be prevented, or diagnosed and managed as early as possible.

There could be many contributing factors to the poor survival observed after a second cancer, including diagnosis of aggressive tumors, cumulative treatment and type of treatment received, lifestyle factors and social determinants of health, says Visvanathan, who is also director of the cancer epidemiology track at the Johns Hopkins Bloomberg School of Public Health.

“We believe this to be one of the first studies to comprehensively examine the racial and ethnic disparities in survival outcomes after a second cancer,” Visvanathan says. “The findings are extremely concerning given the increasing prevalence of second cancer at a young age among women diagnosed with breast cancers. A multipronged approach is needed to identify biological factors, and patient-, provider- and systems-level contributors to survival outcomes among breast cancer survivors.”

Zhengyi Deng, Ph.D., a former doctoral student at the Bloomberg School of Public Health, was the study’s lead author. The research team evaluated information from 39,029 adult female survivors of breast cancer who developed a second primary cancer in 2000–2014, as recorded in the national Surveillance, Epidemiology and End Results (SEER) 18 Program database. The database, maintained by the National Cancer Institute, covers 18 U.S. cancer registries and represents nearly 28% of the population. Participants were followed until Dec. 31, 2016, or at least two years after the second cancer diagnosis.

Participants’ ethnicity was categorized as Hispanic, non-Hispanic Asian, non-Hispanic Black and non-Hispanic white. Non-Hispanic American Indian or Alaska Native, and Pacific Islander, were excluded from study due to a small number of records. Investigators looked at several variables, including five-year survival rate; demographics including age and year of diagnosis, marital and insurance status, and initial treatments; median household income and education level; and cause of death.

Overall, there were 39,029 second cancers and 15,117 deaths after second cancers. The strongest associations with cancer deaths were among non-Hispanic Black survivors with a second breast or uterine cancer and among Hispanic survivors with a second breast cancer. Secondary cancers occurred at an earlier age in Hispanic (mean age: 62.2), non-Hispanic Asian (mean age: 63.4) and non-Hispanic Black (mean age: 63.5) survivors compared with non-Hispanic white survivors (mean age: 68.8).

Breast cancer was the most common second cancer across all racial and ethnic groups, followed by lung, colorectal and uterine cancer. Second cancers in non-Hispanic Black women were less likely to be diagnosed at a local stage compared with other groups. And, Hispanic and non-Hispanic Black survivors were more likely than members of other groups to need chemotherapy for their first and second cancer.

Looking at cancer mortality, non-Hispanic Black survivors had the highest cumulative mortality during the entire follow-up, followed by Hispanic, non-Hispanic white and non-Hispanic Asian survivors. Later stage at presentation and more aggressive tumor characteristics contributed to increased cancer mortality among Hispanic and non-Hispanic Black survivors after second cancers.

A prior study from the team, the results of which were published last summer in NPJ Breast Cancer, found that cancer survivors with a second cancer had a 27% increased risk of cancer death and 18% increased risk of death from any cause compared to survivors with primary cancers. The research team is continuing studies of patients with second cancers.

Study co-authors were Miranda Jones, Mei-Cheng Wang and Antonio Wolff of Johns Hopkins. The work was supported by the Breast Cancer Research Foundation. Visvanathan received research funding from Cepheid and holds a patent. Wolff also holds a patent. The Johns Hopkins University is managing these relationships in accordance with its conflict-of-interest policies.

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JOURNAL

JNCI Journal of the National Cancer Institute

Study shows metformin lowers the risk of getting long COVID

Peer-Reviewed Publication

UNIVERSITY OF MINNESOTA MEDICAL SCHOOL

MINNEAPOLIS/ST. PAUL (06/09/2023) — In a new study published in The Lancet Infectious Diseases, University of Minnesota researchers found that metformin, a drug commonly used to treat diabetes, prevents the development of long COVID. 

The study, called COVID-OUT, investigated if early outpatient COVID-19 treatment with metformin, ivermectin or fluvoxamine could prevent long COVID. Long COVID is a chronic illness that can affect up to 10% of people who have had COVID-19. 

“The results of this study are important because long COVID can have a significant impact on people's lives,” said Carolyn Bramante, MD, principal investigator and an assistant professor at the U of M Medical School. “Metformin is an inexpensive, safe and widely available drug, and its use as a preventive measure could have significant public health implications.”

This was a large, placebo-controlled randomized clinical trial which enrolled volunteers across the United States. The study found: 

• Those who received metformin were more than 40% less likely to develop long COVID than those who received an identical looking placebo. 
• For participants who started metformin less than four days after their COVID symptoms started, metformin decreased the risk of long COVID by 63%. 
• The effect was consistent across different demographic populations of volunteers who participated and across multiple viral variants, including the Omicron variant. 
• Ivermectin and fluvoxamine did not prevent long COVID.

The study included more than 1,200 participants who were randomly chosen to receive either metformin or placebo, and an additional subset received ivermectin, fluvoxamine or their placebos. Participants were between 30 and 85 years old who qualified as overweight or obese. Over 1,100 of the participants reported on their symptoms for up to 10 months after their initial COVID-19 diagnosis. 

“This long-term outcome from a randomized trial is high-quality evidence that metformin prevents harm from the SARS-CoV-2 virus,” said Dr. Bramante, who is also an internist and pediatrician with M Health Fairview. “While half of our trial had been vaccinated, none had been previously infected with the COVID-19 virus. Further research could show whether it is also effective in those with previous infection or in adults with lower body mass index.” 

Metformin’s ability to stop the virus was predicted by a simulator developed by U of M Medical School and College of Science and Engineering Biomedical Engineering faculty. The model has been highly accurate to date, successfully predicting, among others, the failure of hydroxychloroquine and the success of remdesivir before the results of clinical trials testing these therapies were announced.

Funding was provided by the Parsemus Foundation, Rainwater Charitable Foundation, Fast Grants and the United Health Foundation.This research was also supported by the National Institutes of Health’s National Center for Advancing Translational Sciences under award number [UL1TR002494, KL2TR002492, and UM1TR004406]. 

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The University of Minnesota Medical School, School of Public Health, College of Science and Engineering and M Health Fairview served as the lead site. The trial was also conducted at Northwestern University; University of Colorado, Denver; Olive View – UCLA Education & Research Institute in Los Angeles; Optum Health, and with scientific collaboration from partners at the University of North Carolina at Chapel Hill, Vanderbilt University, and Emory University School of Medicine. 

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health’s National Center for Advancing Translational Sciences.

About the University of Minnesota Medical School
The University of Minnesota Medical School is at the forefront of learning and discovery, transforming medical care and educating the next generation of physicians. Our graduates and faculty produce high-impact biomedical research and advance the practice of medicine. We acknowledge that the U of M Medical School, both the Twin Cities campus and Duluth campus, is located on traditional, ancestral and contemporary lands of the Dakota and the Ojibwe, and scores of other Indigenous people, and we affirm our commitment to tribal communities and their sovereignty as we seek to improve and strengthen our relations with tribal nations. For more information about the U of M Medical School, please visit med.umn.edu.

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JOURNAL

The Lancet Infectious Diseases

DOI

10.1016/S1473-3099(23)00299-2 

METHOD OF RESEARCH

Randomized controlled/clinical trial

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial

ARTICLE PUBLICATION DATE

8-Jun-2023

COI STATEMENT

CTB was supported by grants (KL2TR002492 and UL1TR002494) from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) and by a grant (K23 DK124654–01-A1) from the National Institute of Diabetes and Digestive and Kidney Diseases of the NIH. JBB was supported by grants (UL1TR002489 and UM1TR004406) from NCATS and reports contracted fees and travel support for contracted activities for consulting work paid to the University of North Carolina by Novo Nordisk; grant support by Dexcom, NovaTarg, Novo Nordisk, Sanofi, Tolerion, and vTv Therapeutics; personal compensation for consultation from Alkahest, Altimmune, Anji, AstraZeneca, Bayer, Biomea Fusion, Boehringer Ingelheim, CeQur, Cirius Therapeutics, Corcept Therapeutics, Eli Lilly, Fortress Biotech, GentiBio, Glycadia, Glyscend, Janssen, MannKind, Mellitus Health, Moderna, PendulumTherapeutics,Praetego,Sanofi,StabilityHealth,Terns,Valo, and Zealand Pharma; and stock or stock options in Glyscend, Mellitus Health, Pendulum Therapeutics, PhaseBio, Praetego, and Stability Health. JMN was supported by a grant (K23HL133604) from the National Heart, Lung, and Blood Institute of the NIH. DJO was supported by the Institute for Engineering in Medicine, University of Minnesota Office of Academic and Clinical Affairs COVID-19 Rapid Response Grant, the Earl E Bakken Professorship for Engineering in Medicine, and by grants (U54 CA210190 and P01 CA254849) from the National Cancer Institute of the NIH. TAM was supported in part by the Medtronic Faculty Fellowship. DML receives funding from NIH RECOVER (OT2HL161847). LKS was supported by NIH grants (18X107CF6 and 18X107CF5) through a contract with Leidos Biomedical and by grants from the National Heart, Lung, and Blood Institute of the NIH (T32HL129956), and the NIH (R01LM012982 and R21LM012744). MAP receives grants from the Bill & Melinda Gates Foundation (INV-017069), Minnesota Partnership for Biotechnology and Medical Genomics (00086722), and the National Heart, Lung, and Blood Institute of the NIH (OT2HL156812); and consulting fees from Opticyte and Cytovale. All other authors declare no competing interests.

Worker dies at Fort McMurray ammonium sulphate production plant

Story by Emily Mertz 

Suncor's base plant with upgraders in the oilsands in Fort McMurray Alta, on Monday June 13, 2017. New federal research suggests greenhouse gas emissions from the oilsands may be significantly underestimated, adding to a growing pile of studies that say our understanding of what is going into the atmosphere is incomplete.© Jason Franson, The Canadian Press

A contractor working on the roof of the Chemtrade site in Fort McMurray, Alta., died Thursday.

The company's website says the northern Alberta location is an ammonium sulphate production plant.

The vice-president of the water chemical production company said it was an isolated incident and there was no public danger.

Tim Montgomery said a roofing contractor was doing work on a maintenance building for Chemtrade, which has an operation within the Suncor/Syncrude site. The contractor had done contract work for Chemtrade in the past. Montgomery estimates the man fell more than 25 feet.

"Our deepest sympathy is extended to the family, friends, and colleagues of the individual who sustained fatal injuries while performing services on the roof of our site," Montgomery said in a statement.

"We are working closely with the authorities to support all investigations into this incident.

"Our plant has been safely shut down and our immediate focus is supporting our on-site personnel and all those affected by this tragedy."

The name or age of the worker has not been released.

Counselling services are being provided to staff, Montgomery said.

Occupational Health and Safety is investigating and Chemtrade is fully complying.

Unlocking early Earth chemistry: Salt-induced changes in polyester microdroplet structure

Peer-Reviewed Publication

TOKYO INSTITUTE OF TECHNOLOGY

 

IMAGE: - view more 

CREDIT: TOKYO TECH

Billions of years ago, Earth was an extremely hostile planet with active volcanoes, a harsh atmosphere, and certainly no life! This prebiotic Earth, however, was filled with a wide array of abiotic organic molecules derived from its early environment, which underwent chemical reactions that eventually led to the origin of life. A class of such abiotic molecules abundant during the prebiotic era was the 𝛼-hydroxy acid (𝛼HA)–monomers with structures somewhat similar to those of the 𝛼-amino acids essential to modern life. However, their present abundance in biology is low.

Polyester microdroplets generated from dehydration and rehydration of 𝛼HA monomers were proposed as protocell models and could have been a type of primitive compartment that interacted with and took up various primitive analytes, such as salts within primitive aqueous environments. However, salt–polyester interactions and salt-uptake within polyester microdroplets remains poorly studied due to a lack of appropriate analytical techniques.

To bridge this gap in understanding, a team of researchers led by Special Postdoctoral Researcher Chen Chen from RIKEN (formerly of Tokyo Institute of Technology) and Specially Appointed Associate Professor Tony Z. Jia from the Earth-Life Science Institute at Tokyo Institute of Technology have recently come up with a new strategy for investigating the effect of salt uptake on polyester microdroplets. Their breakthrough, published in Small Methods on May 18, 2023, proposed a novel way of using existing spectroscopic and biophysical methods to characterize salt uptake by polyester microdroplets and understand their salt-mediated behavior.

“Primitive molecules such as 𝛼HAs and polyesters, though not as commonly used by current living systems as amino acids, may have laid the ground for the evolution of primitive chemical systems that led to the origin of life on Earth. Examining the interaction of polyesters with different prebiotic analytes such as salts and determining whether polyester droplets can uptake salts can provide insights into the relevant functions exhibited by primitive compartments,” explains Prof. Jia.

𝛼HAs such as ᴅʟ-3-phenyllactic acid (PA) can undergo dehydration under early Earth mimicking conditions to form gel-like polyesters; further rehydration results in assembly of membraneless microdroplets. These membraneless droplets have previously been found to segregate primitive analytes such as nucleic acids, small organic molecules, and proteins.

Studies have hypothesized that life originated and evolved in ancient aqueous environments. If polyester microdroplets existed in primitive aqueous environments, then they might have also uptaken salts, a major analyte found in primitive aqueous environments, which could have subsequently changed the microdroplets’ structure as well. Thus, the team subjected various 𝛼HAs, such as PA (a neutral monomer), malic acid (a monomer with an acidic side chain), and 4-amino-2-hydroxybutyric acid (a monomer with a basic side chain) to dehydration synthesis, followed by rehydration in aqueous medium to generate neutral, acidic residue-containing, and basic residue-containing polyester microdroplets. In fact, this study was the first to show the plausibility of acidic residue-containing polyester microdroplets! They then incubated the polyester microdroplets in aqueous solutions consisting of different concentrations of different chloride salts (NaCl, KCl, MgCl2, and CaCl2) that may have been abundant in early oceans.

Post salt uptake, the polyester microdroplets were subjected to a novel analytical technique utilizing inductively coupled plasma mass spectrometry (ICP–MS) to analyze the salt cation concentration within the microdroplets. The analyses were performed in collaboration with researchers from the Pheasant Memorial Lab at the Institute of Planetary Materials at Okayama University, where the ICP–MS was located, as part of a joint use collaborative grant. Furthermore, in collaboration with other members, each with unique specialties, the team then coupled ICP–MS with other spectroscopic and biophysical analytical methods, such as zeta potential analysis, optical density, dynamic light scattering, and micro-Raman imaging to study in detail how salt uptake affects the surface potential, droplet turbidity, size, and internal water distribution, respectively, of the microdroplets.

The results indicated that microdroplets possessed the ability to selectively partition salt cations, leading to differential coalescence of microdroplets, likely due to reduced electrostatic repulsions between the microdroplets as a result of surface charge neutralization by the uptaken salts, which preferentially localized to the droplet surface. The present study highlights that even slight changes in salt-uptake could significantly affect protocell structure, which could potentially account for diversity in chemistries of primitive systems that emerged in different aqueous systems—ranging from freshwater to oceanic to hypersaline under-ocean brines. “The adoption of a novel and highly sensitive strategy for analyzing salt uptake by polyester microdroplets widened the range of known primitive chemicals that could have had an effect on primitive protocell structure and function. This opens new avenues for future investigations regarding the relevance of polyester microdroplets during the origins of life both on and off Earth,” concludes Dr. Chen.

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JOURNAL

Small Methods

DOI

10.1002/smtd.202300119 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Spectroscopic and Biophysical Methods to Determine Differential Salt-Uptake by Primitive Membraneless Polyester Microdroplets

Aston University wins £1.8m to boost West Midlands low carbon markets

Grant and Award Announcement

ASTON UNIVERSITY

 

IMAGE: TIM MILLER view more 

CREDIT: ASTON UNIVERSITY

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• Aston University and local industry to develop technology to convert organic material into commercially valuable products
• Sawdust, diseased trees and dried chicken litter among what can be transformed into sustainable bioproducts
• West Midlands companies are invited to join a cluster to develop new low carbon products for growing markets.

Aston University is to receive £1.8 million to transform the West Midlands into a powerhouse of low-carbon product development and commercialisation.

The University will be building on its existing research facilities to lead the region’s Biochar CleanTech Accelerator as part of the West Midlands Innovation Accelerator.

The project was set up with the aim to secure export contracts for low carbon products worth over £200 million, to be made by a regional industrial cluster.

It is hoped that the development of a low-carbon business cluster in the West Midlands will open up new domestic and export markets to help rebuild the region’s engineering and manufacturing status.

Biochar, a sustainable form of charcoal, can be used as a soil and plant growth enhancer. It stores carbon in the ground, so there are fewer greenhouse gases in the atmosphere. Other products such as oils can be used as low carbon fuels for boilers and engines and the liquid by-product can be used for low carbon weedkiller, fungicide and plant growth.

Aston University’s innovative technology is installed at its urban biochar demonstrator in south Birmingham.

The project is based on the strengths of the University’s Energy and Bioproducts Research Institute (EBRI) and its Centre for the Circular Economy and Advanced Sustainability (CEAS).

Tim Miller, director of engagement at EBRI, said: “This new development has the potential to rebuild product development, engineering and manufacturing in our region.

“The project aims to commercialise knowledge, facilities and the results of long-term university research for the benefit of the environment and our regional economy.

“Using the University’s existing expertise and facilities we have the potential to launch new technology-based opportunities as they emerge and mature,

The Biochar CleanTech Accelerator is part of the West Midlands Innovation Accelerator which was first announced in the government’s 2022 Levelling up White Paper and started this spring. It is funded through a share of a £100m from Innovate UK, to be divided by three regional innovation accelerators over the next two years.

Launched by the West Midlands Combined Authority (WMCA) in March 2023, it will target investment on projects enabling new solutions around Medical and Clean Technologies, to further reinforce the region’s position at the frontier of the UK innovation revolution.

The University will also play a key role in two other projects in the West Midlands Innovation Accelerator.

Companies interested in joining the cluster can get further information at https://www.aston.ac.uk/biochar-cleantech-accelerator or emailing biochar@aston.ac.uk

University of Minnesota theoretical physicists help expand the search for new particle

Discovering ‘axions’ could help answer one of the most puzzling questions in physics

Peer-Reviewed Publication

UNIVERSITY OF MINNESOTA

 

IMAGE: THE UNIVERSITY OF MINNESOTA RESEARCHERS’ NEW METHOD OF SEARCHING FOR THE HYPOTHETICAL AXION INVOLVES MEASURING THE “DECAY” OF THE PARTICLE INTO TWO MUONS—KNOWN PARTICLES THAT ARE ESSENTIALLY THE HEAVIER VERSION OF THE ELECTRON—AS ILLUSTRATED IN THE ABOVE IMAGE. view more 

CREDIT: RAYMOND CO, UNIVERSITY OF MINNESOTA

One of the most high-profile mysteries in physics today is what scientists refer to as the “Strong CP Problem.” Stemming from the puzzling phenomenon that neutrons do not interact with electric fields despite being made up of quarks—smaller, fundamental particles that carry electric charges—the Strong CP Problem puts into question the Standard Model of physics, or the set of theories scientists have been using to explain the laws of nature for years.

A team led by University of Minnesota Twin Cities theoretical physicists has discovered a new way to search for axions, hypothetical particles that could help solve this mystery. Working in collaboration with experimental researchers at the Fermilab National Accelerator Laboratory, the physicists’ new strategy opens up previously unexplored opportunities to detect axions in particle collider experiments.

The researchers’ paper is published and featured as the Editor’s suggestion in Physical Review Letters, a peer-reviewed scientific journal published by the American Physical Society.

“As particle physicists, we’re trying to develop our best understanding of nature,” said Zhen Liu, co-author of the paper and an assistant professor in the University of Minnesota School of Physics and Astronomy. “Scientists have been tremendously successful in the past century in finding elementary particles through established theoretical frameworks. So, it’s extremely puzzling why neutrons do not couple to electric fields because in our known theory, we would expect them to. If we do discover the axion, it will be a great advance in our fundamental understanding of the structure of nature.”

One of the primary means for studying subatomic particles, and potentially discovering new ones, is collider experiments. Essentially, scientists force beams of particles to collide—and when they hit each other, the energy they produce creates other particles that pass through a detector, allowing researchers to analyze their properties. 

Liu and his team’s proposed method involves measuring the “decay” product—or what happens when an unstable heavy particle transforms into multiple lighter particles—of the hypothetical axion into two muons—known particles that are essentially the heavier version of the electron. By working backward from the muon tracks in the detector to reconstruct such decays, the researchers believe they have a chance to locate the axion and prove its existence.

“With this research, we’re expanding ways we can search for the axion particle,” said Raymond Co, co-author of the paper and a postdoctoral researcher in the University of Minnesota School of Physics and Astronomy and William Fine Theoretical Physics Institute. “People have never used axion decay into muons as a way to search for the axion particle in neutrino or collider experiments before. This research opens up new possibilities to pave the way for future endeavors in our field.”

Liu and Co, along with University of Minnesota physics and astronomy postdoctoral researcher Kun-Feng Lyu and University of California, Berkeley postdoctoral researcher Soubhik Kumar, are behind the theoretical part of the research. They’re a part of the ArgoNeuT collaboration, which brings together theorists and experimentalists from across the country to study particles through experiments at Fermilab. 

In this paper, the University of Minnesota-led theoretical team worked with the experimental researchers to perform a search for axions using their new method and existing data from the ArgoNeuT experiment. The researchers plan to use the experimental results to further refine their theoretical calculations of the axion production rate in the future.

The research was funded by the U.S. Department of Energy’s Office of Science; the National Science Foundation; the United Kingdom Research and Innovation’s Science and Technology Facilities Council; and the UK’s Royal Society. 

In addition to Liu, Co, Lyu, and Kumar, the team for this paper included researchers Roberto Acciarri, Bruce Baller, Vincent Basque, Flavio Cavanna, Roni Harnik, Ornella Palamara, Wanwei Wu, and Tingjun Yang (Fermi National Accelerator Laboratory); Corey Adams (Argonne National Laboratory); Rory Fitzpatrick and Joshua Spitz (University of Michigan); Bonnie Fleming and Giacomo Scanavini (Yale University); Patrick Green (University of Manchester, University of Oxford); Kevin Kelly (European Organization for Nuclear Research or CERN); Karol Lang (University of Texas at Austin); Ivan Lepetic (Rutgers University); Xiao Luo (University of California, Santa Barbara); Mitchell Soderberg (Syracuse University); and Andrzej Szelc (University of Edinburgh).

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JOURNAL

Physical Review Letters

DOI

10.1103/PhysRevLett.130.221802 

ARTICLE TITLE

First Constraints on Heavy QCD Axions with a Liquid Argon Time Projection Chamber Using the ArgoNeuT Experiment