Ancient climate change solves mystery of vanished South African lakes

Arid regions of South Africa were once home to lakes, a University of Leicester-led study has confirmed

Peer-Reviewed Publication

UNIVERSITY OF LEICESTER

 

IMAGE: ANDREW CARR COLLECTING SEDIMENT SAMPLES DATING TO THE LAST GLACIAL MAXIMUM FROM THE DRY LAKEBED AT SWARTKOLKVLOER. view more 

CREDIT: BRIAN CHASE

New evidence for the presence of ancient lakes in some of the most arid regions of South Africa suggests that Stone Age humans may have been more widespread across the continent than previously thought.

Research jointly led by the University of Leicester argues that more archaeological work in the interior regions of South Africa – a country renowned for its globally-significant archaeological record – may reveal more about our ancient ancestors and their movements. The researchers’ conclusions have been published in the journal PNAS.

South Africa’s Stone Age archaeological record, particularly for the last 150,000 years has been the subject of a great deal of investigation, not least due to the presence of several remarkable coastal caves and rock shelter records. However, the presence of humans, and the resources available to them in the vast interior regions of the country have thus far remained much more enigmatic.

New research by an international team of researchers from South Africa, the United Kingdom, the United States, and France suggests several large bodies of water were sustained in the now arid South African interior during the last Ice Age, particularly 50,000-40,000 years ago, and again 31,000 years ago. Importantly, the group were able to model how much water was required to fill these palaeo-lakes, allowing the climatic changes necessary to create lakes, and the resulting impacts on the region’s hydrology, flora and fauna, to be reconstructed.

Their findings paint a picture of a diverse and fertile region that would have been capable of supporting hunter-gatherer communities of the time.

Team member Dr Andrew Carr from the University of Leicester School of Geography, Geology and the Environment said: “This is currently the best evidence for when these lakes existed. This region has been something of a gap on the map, climatically and archaeologically. We know humans were present at times during the last ice age, as archaeological materials are scattered across the landscape surface. This new work hints at when and why humans used this landscape.

“These areas look inhospitable today, but were seemingly much less so at times in the past, and this has implications for when and how groups of people used the landscape and potentially how they were connected and exchanged ideas.

“It also tells us something about the sensitivity of ecosystems and environments to global climatic change. You can see how these desert landscapes can respond in quite significant ways to global climate changes, and understand how the human species responded and how adaptable it would have been.”

The scientists studied three lakes from the arid western interior of South Africa to as far east as Kimberley. As well as dating shorelines using radiocarbon and luminescence dating methods, they estimated the lake sizes and capacities. Computer models of regional hydrology showed that the conditions necessary to create the studied lakes would have led to widespread changes in the region’s many (presently ephemeral) rivers and lakes as the water table rose.

Dr Carr added: “The next step is to start to look for sites where we can do more direct dating of the occurrence of stone tools in this region. The work shows that at times the region offered a range of resources, and the archaeological ‘gap on the map’ is much more likely to reflect the lack of sites preserving deep archaeological deposits.

“The region is quite challenging for archaeology as most materials lie in the open on the desert surface with no stratigraphic context - hence it's very difficult to know how long it's been there.”

• This research received funding from the National Geographic Society and the University of the Free State.

Andrew Carr collecting sediment samples from a section of exposed Pleistocene lake sediments at Swartkolkvloer.

Brian Stewart surveying the extensive scatters of stone artefacts observed along the margin of a now-dry lakebed near Swartkolkvloer.

View across a now-dry lakebed near Swartkolkvloer. During the last glacial period this and adjacent basin supported what are believed to have been perennial lakes, some up to 60 feet in depth.

View across a now-dry lakebed near Swartkolkvloer. During the last glacial period this and adjacent basin supported what are believed to have been perennial lakes, some up to 60 feet in depth.

CREDIT

Brian Chase

JOURNAL

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.2221082120 

ARTICLE TITLE

Paleolakes and socioecological implications of last glacial "greening" of the South African interior

ARTICLE PUBLICATION DATE

15-May-2023

Investing in safe surgery could cut costs and save lives in LMICs

Peer-Reviewed Publication

UNIVERSITY OF BIRMINGHAM

Investing in developing systems of safe surgery to reduce Surgical Site Infection (SSI) will help to reduce the financial burden on health services in Low- and Middle-Income Countries (LMIC), a new study reveals.

Analysing inpatient resource use in India, Ghana, Nigeria and Mexico, researchers discovered that additional investigations and hospital length of stay for a patient with an SSI compared to patient without an SSI were generally higher in clean-contaminated surgical cases compared to contaminated-dirty surgical cases.

Supported by National Institute for Health and Care Research (NIHR) funding, they found that SSI occurred in 7% of clean-contaminated cases, where wounds have no signs of infection at the time of surgery, whilst 27% of contaminated-dirty cases – where the wound encounters bodily fluids – exhibited SSI.

Overall, SSI was associated with an increase in postoperative healthcare costs by 75.3% (€412) after clean-contaminated surgery and 66.6% (€331) after contaminated-dirty surgery.

Publishing their findings in Journal of Hospital Infection, the international group of researchers, led by the University of Birmingham, reveal that the highest and lowest cost increases were in India for clean-contaminated cases (€517) and contaminated-dirty cases (€223). Overall, inpatient costs accounted for 96.4% of total healthcare costs after clean-contaminated surgery and 92.5% after contaminated-dirty surgery.

Study lead Mr Mark Monahan, from the University of Birmingham’s Institute of Applied Health Research, commented: “Surgical site infection is the world’s most common postoperative complication. This is the first multi-continental surgical cost study of its kind and reveals substantial additional postoperative costs associated with SSI across a range of settings.

“Investing in health technologies to reduce SSI could reduce this major financial burden to patients and low-resource health systems – helping to improve the overall quality of healthcare and ultimately saving lives.”

Researchers found that patients with an SSI had higher costs in both postoperative inpatient costs and post-discharge costs compared to patients without an SSI. They discovered that SSI was a statistically significant variable in determining postoperative healthcare costs.

Postoperative inpatient costs made up most of the total healthcare costs in both clean-contaminated and contaminated-dirty cases. An exploratory investigation in Ghana showed that the costs of unresolved SSI persist beyond 30 days.

The experts note that this is an important finding because 37.5% of prospective patients with an SSI were unresolved at 30 days post-surgery, potentially underestimating the true postoperative costs.

The study was part of the wider FALCON trial led by the NIHR Global Health Research Unit on Global Surgery – an initiative led by the University of Birmingham. Carried out in Benin, Ghana, India, Mexico, Nigeria, Rwanda and South Africa, FALCON evaluated measures to reduce SSI rates in patients undergoing surgery with an abdominal incision.

Patients who develop SSI experience pain, disability, poor healing with risk of wound breakdown, prolonged recovery times and psychological challenges. Those patients in LMICs are disproportionately affected by higher rates of SSI compared to those in high-income countries - increasing the risk of catastrophic expenditure, impoverishment, and wider negative community impact.

ENDS

Notes to Editors

• The University of Birmingham is ranked amongst the world’s top 100 institutions, its work brings people from across the world to Birmingham, including researchers and teachers and more than 8,000 international students from over 150 countries.
• ‘The costs of surgical site infection after abdominal surgery in middle income countries: Key resource use In Wound Infection (KIWI)’ - Mark Monahan, James Glasbey, Tracy Roberts, Sue Jowett, Tom Pinkney, Aneel Bhangu, Dion G. Morton, Antonio Ramos de la Medina, Dhruva N. Ghosh, Adesoji O. Ademuyiwa, Faustin Ntirenganya, Stephen Tabiri, on behalf of the NIHR Global Research Health Unit on Global Surgery is published by Journal of Hospital Infection.
• Participating institutions include University of Birmingham; Global Surgery Research Centre, Hospital Español de Veracruz, México; India Hub NIHR Global Health Research Unit on Global Surgery, Ludhiana, India; Christian Medical College, Ludhiana, India; College of Medicine and Lagos University Teaching Hospital, Lagos, Nigeria; University of Rwanda, Kigali, Rwanda; and University for Development Studies and Tamale Teaching Hospital, Tamale, Ghana.

About the National Institute for Health and Care Research

The mission of the National Institute for Health and Care Research (NIHR) is to improve the health and wealth of the nation through research. We do this by:

•         Funding high quality, timely research that benefits the NHS, public health and social care;

•         Investing in world-class expertise, facilities and a skilled delivery workforce to translate discoveries into improved treatments and services;

•         Partnering with patients, service users, carers and communities, improving the relevance, quality and impact of our research;

•         Attracting, training and supporting the best researchers to tackle complex health and social care challenges;

•         Collaborating with other public funders, charities and industry to help shape a cohesive and globally competitive research system;

•         Funding applied global health research and training to meet the needs of the poorest people in low- and middle-income countries.

NIHR is funded by the Department of Health and Social Care. Its work in low- and middle-income countries is principally funded through UK Aid from the UK government.

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JOURNAL

Journal of Hospital Infection

METHOD OF RESEARCH

Randomized controlled/clinical trial

SUBJECT OF RESEARCH

People

ARTICLE TITLE

• ‘The costs of surgical site infection after abdominal surgery in middle income countries: Key resource use In Wound Infection (KIWI)’

UC San Diego researchers present new wireless system for greater 5G access

Reports and Proceedings

UNIVERSITY OF CALIFORNIA - SAN DIEGO

A new paper on wireless connectivity from the lab of Dinesh Bharadia, an affiliate of the UC San Diego Qualcomm Institute (QI) and faculty member with the Jacobs School of Engineering’s Department of Electrical and Computer Engineering, introduces a new technique for increasing access to the 5G-and-beyond millimeter wave (mmWave) network. 

“Energy grids and mmWave/sub-THz networks share a remarkable similarity; both face fundamental challenges in efficient distribution,” said Bharadia. “Just as energy grids generate substantial amounts of energy but encounter significant hurdles in efficiently delivering it to homes, the utilization of mmWave/sub-THz networks for seamless data connectivity presents a similar predicament. Despite abundantly available bandwidth in these spectra, the efficient distribution of data with these spectra to user devices remains a formidable challenge.”

The paper, “mmFlexible: Flexible Directional Frequency Multiplexing for Multi-user mmWave Networks,” was presented by Ph.D. student and lead author Ish Kumar Jain at the IEEE International Conference on Computer Communications in New York on Wednesday, May 17. 

Sharing Access

With the introduction of more automation and greater speeds and processing power behind wireless networks, the infrastructure that connects people to these resources has fallen behind.

Jain was drawn to the challenge of creating a device that could bridge this gap and give people greater access to the 5G mmWave network. 

5G mmWave systems use radio frequencies to connect everything from “smart” cars to handheld devices and virtual reality sets to wireless networks. The advancement from 4G to 5G allows for higher speeds and bandwidth overall.

Part of the problem, Jain says, is that the jump from 4G to 5G opened up far more resources and processing power than existing infrastructure could handle. mmWave systems depend on a “pencil beam” distribution model in which a base station sends out a single beam of coverage, like shining a light in the dark. Everyone within that beam has access to all resources that the 5G mmWave network has to offer, regardless of whether their devices can process them.

This can lead to a waste of bandwidth that might otherwise have been leveraged by users in other regions. Even shifting this beam, like a lighthouse rotating slowly at timed intervals, creates lag for those who fall beyond its range.

To address the combined issues of wasted bandwidth and lag, Jain, Rohith Reddy Vennam and Raghav Subbaraman, also Ph.D. students in Bharadia’s Wireless Communication, Sensing and Networking Group (WCSNG), set out to determine whether they could create an antenna array that served users in multiple directions without sacrificing distance and power. 

The team designed a prototype device that works in concert with a novel array of antennas to divide a single frequency band into multiple usable beams. Called a delay phased array, this antenna arrangement leverages 5G mmWave’s sheer amount of bandwidth to connect multiple regions to the network and can be tailored to deliver greater connection to those who need it.

This new, programmable array can also be built using existing technologies and scaled up with a very high number of antennas to support all future devices. 

Through experiments run in QI’s Atkinson Hall on the UC San Diego campus, the team found mmFlexible decreased lag by 60-150%.

“It’s very exciting to see new generations of applications coming up,” said Jain. “But I feel, in the future, the number of [wireless] devices will grow and so will their demand for wireless spectrum. These are the key things that motivate me to further explore these innovative techniques.”

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ARTICLE TITLE

mmFlexible: Flexible Directional Frequency Multiplexing for Multi-user mmWave Networks

Tonsillectomy both clinically and cost effective for adults

Peer-Reviewed Publication

NEWCASTLE UNIVERSITY

 

IMAGE: DR JAMES O’HARA, CLINICAL SENIOR LECTURER AT NEWCASTLE UNIVERSITY AND CONSULTANT EAR, NOSE AND THROAT SURGEON AT NEWCASTLE UPON TYNE HOSPITALS NHS FOUNDATION TRUST. view more 

CREDIT: STEVEN BARBER/DR JAMES O’HARA

Scientists say tonsil removal is both clinically and cost effective for adults who get recurrent severe sore throats.

The biggest study of its kind, carried out by Newcastle University, revealed that patients who had a tonsillectomy had 50% less sore throats over two years, compared to patients who did not undergo tonsillectomy. Publishing today (17 May) in The Lancet, the study was funded by the National Institute for Health and Care Research (NIHR).

Experts also found that a tonsillectomy for those aged 16 years and over was cost effective in comparison to treatment with painkillers and ad hoc antibiotics.

Tonsillectomy assurance

A tonsillectomy, cutting out the two lumps of lymphoid tissue found at either side of the back of the throat, is an operation that has been widely used to improve the quality of life for patients.  

However, in recent years, less adult tonsillectomies have been reportedly carried out on NHS patients.

Dr James O’Hara, Clinical Senior Lecturer at Newcastle University and Consultant Ear, Nose and Throat surgeon at Newcastle Upon Tyne Hospitals NHS Foundation Trust, said: “Tonsillectomy has been branded as an ‘intervention of limited clinical value’ due to a lack of studies to support the operation.

“Over the last 20 years, the number of tonsillectomies being performed in the UK has halved whilst hospital admissions for complicated tonsillitis have more than doubled.

“There has been variation across the UK in referrals from primary care for tonsillitis, with some patients having to experience three times the recommended number of episodes before being referred for a tonsillectomy.

“Our research should level the threshold for referral for this problem, and clinicians can now be assured that tonsillectomy is effective for those who suffer with recurrent tonsillitis.”

In the study, commissioned by the NIHR, almost 500 patients were randomised to either early tonsillectomy or given treatment such as painkillers and antibiotics.

Participants were only recruited if they met the current national guidance for offering tonsillectomy - seven episodes of tonsillitis in a year, five per year for two years, or three episodes for three years.

Those in the clinical trial who underwent the operation suffered half the number of days with sore throats over the following two years, including the two weeks of sore throats following the procedure.

Cost effective procedure

The Newcastle-led research also showed that it is more cost effective for the NHS to offer tonsillectomy to eligible patients than to treat them by other conventional methods.

Dr O’Hara said: “Whilst we now know that tonsillectomy is effective, patients still need to weigh up the potential benefits in reducing longer-term sore throats with 14 days of pain following the operation.

“There is also a risk of one in five patients bleeding following the operation, with some having to return to hospital. Further research is needed to improve the tonsillectomy operation to make it less painful and reduce the risk of bleeding.”

Professor Andrew Farmer, Director of NIHR’s Health Technology Assessment Programme, said: “These new results provide important findings suggesting that tonsillectomy benefits this group of patients compared to repeated courses of antibiotics and painkillers.

“Once again, high quality independently funded research is providing evidence which could improve health and social care practice and treatments."

Newcastle University and Newcastle Hospitals are both part of Newcastle Health Innovation Partners (NHIP). NHIP is one of eight prestigious Academic Health Science Centres (AHSCs) across the UK, bringing together partners to deliver excellence in research, health education and patient care.

 

Reference:

Conservative management versus tonsillectomy in adults with recurrent acute tonsillitis in the UK (NATTINA): a multicentre, open-label, randomised controlled trial. Janet Wilson et al. The Lancet. 

 

Patient case study

Secondary school teacher, Elinor Barwick, was the first patient recruited to the Newcastle-led trial as her recurrent acute tonsillitis was impacting her life.

Elinor had suffered terrible sore throats for many years, however, things got significantly worse when she became a teacher as she needed to speak all the time, leaving her in a lot of pain and discomfort.

Elinor’s tonsillitis often meant it was hard to swallow both liquids and food. In addition, her tonsillitis would leave her unable to speak as her throat would become extremely tight and swollen, and she would develop flu-like symptoms – all of which would impact her job and quality of life.

Elinor, of Gosforth, Newcastle, was recruited to trial and was one of the participants given the tonsillectomy procedure.

The mother-of-one said: “Recurrent tonsillitis would impact my life as it would leave me in a lot of pain and, at times, made day-to-day life very difficult.

“When I was asked to be part of the trial I didn’t hesitate to say ‘yes’ because it was being led by Newcastle University and would benefit patients like myself.

“Since I have had my tonsils removed, I’ve not had a day off work due to tonsillitis and my quality of life has very much improved as I no longer suffer from severe sore throats.

“It is great that research into the importance of tonsillectomies in adults with recurrent acute tonsillitis has taken place in Newcastle to help patients like myself in the future.”

 

Ends

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JOURNAL

The Lancet

METHOD OF RESEARCH

Randomized controlled/clinical trial

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Conservative management versus tonsillectomy in adults with recurrent acute tonsillitis in the UK (NATTINA): a multicentre, open-label, randomised controlled trial.

ARTICLE PUBLICATION DATE

17-May-2023

Examining mental health, education, employment, and pain in sickle cell disease

JAMA Network Open

Peer-Reviewed Publication

JAMA NETWORK

About The Study: The findings of this cross-sectional analysis of 2,200 individuals with sickle cell disease (SCD) suggest that employment status, sex, age, and depression are associated with pain frequency. Depression screening for these patients is warranted, especially among those experiencing higher pain frequency and severity. Comprehensive treatment and pain reduction must consider the full experiences of patients with SCD, including impacts on mental health. 

Authors: Kelly M. Harris, Ph.D., C.C.C.-S.L.P., of the Washington University in St. Louis School of Medicine, is the corresponding author. 

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ 

(doi:10.1001/jamanetworkopen.2023.14070)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

#  #  #

Embed this link to provide your readers free access to the full-text article  

http://jamanetwork.com/journals/jamanetworkopen/fullarticle/10.1001/jamanetworkopen.2023.14070?utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_term=051823

About JAMA Network Open: JAMA Network Open is an online-only open access general medical journal from the JAMA Network. On weekdays, the journal publishes peer-reviewed clinical research and commentary in more than 40 medical and health subject areas. Every article is free online from the day of publication.

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JOURNAL

JAMA Network Open

How to repair a damaged heart: Key mechanism behind heart regeneration in zebrafish revealed

Peer-Reviewed Publication

HUBRECHT INSTITUTE

 

IMAGE: ZEBRAFISH HEART 60 DAYS AFTER INJURY SHOWING THE STRUCTURE OF THE HEART MUSCLE CELLS HAVE COMPLETELY REGENERATED. view more 

CREDIT: CREDIT: PHONG NGUYEN, COPYRIGHT HUBRECHT INSTITUTE.

Cardiovascular diseases, such as heart attacks, are a leading cause of death worldwide resulting from a limited self-healing power of the heart. Unlike humans, zebrafish have the remarkable capacity to recover from cardiac damage. Researchers from the group of Jeroen Bakkers (Hubrecht Institute) have used the zebrafish to shed light on their regenerative success. They discovered a new mechanism that functions as a switch to push the heart muscle cells to mature in the regeneration process. Importantly, this mechanism was evolutionary conserved as it had a very similar effect on mouse and human heart muscle cells. The results of the study, published in Science on May 18th, show that examining the natural heart regeneration process in zebrafish and applying these discoveries to human heart muscle cells could contribute to the development of new therapies against cardiovascular diseases.

 

It is estimated that 18 million people die from cardiovascular diseases every year. Many of these deaths are related to heart attacks. In such an event, a blood clot prevents the supply of nutrients and oxygen to parts of the heart. As a result, the heart muscle cells in the obstructed part of the heart die, which eventually leads to heart failure. Although therapies exist that manage the symptoms, there is no treatment that is able to replace the lost tissue with functional, mature heart muscle cells and thereby cure the patients.

 

Zebrafish as a role model

Unlike humans, some species like zebrafish can regenerate their hearts. Within 90 days after damage, they fully restore their cardiac function. The surviving heart muscle cells are able to divide and produce more cells. This unique feature provides zebrafish hearts with a source of new tissue to replace the lost heart muscle cells. Previous studies successfully identified factors that could stimulate heart muscle cells to divide. Nevertheless, what happens to the newly formed heart muscle cells afterwards had not been studied before. Phong Nguyen, first author of the study, explains: “It is unclear how these cells stop dividing and mature enough so that can they contribute to normal heart function. We were puzzled by the fact that in zebrafish hearts, the newly formed tissue naturally matured and integrated into the existing heart tissue without any problems.”.

 

LRRC10 drives maturation

To study maturation of the newly formed tissue in detail, the researchers developed a technique for which thick slices of injured zebrafish hearts were cultured outside the body. This allowed them to perform live imaging on the movement of calcium in heart muscle cells. The regulation of calcium moving in and out of heart muscle cells is important for controlling heart contractions and can predict the maturity of the cell. They found that after the heart muscle cells divide, calcium movements changed over time. “The calcium movement in the newly divided cell was initially very similar to embryonic heart muscle cells, but over time the heart muscle cells assumed a mature type of calcium movement. We found that the cardiac dyad, a structure that helped to move calcium within the heart muscle cell, and specifically one of its components, LRRC10, was crucial in deciding whether heart muscle cells divide or progress through maturation. Heart muscle cells that lack LRRC10 continued to divide and remained immature,” says Nguyen. 

 

From fish to human

After Nguyen and his colleagues established the importance of LRRC10 in stopping cell division and initiating maturation of zebrafish heart muscle cells, they moved on to test if their findings could be translated to mammals. To this end, they induced the expression of LRRC10 in mouse and lab-grown human heart muscle cells. Strikingly, LRRC10 changed the calcium handling, reduced cell division and increased the maturation of these cells in a similar manner as observed in zebrafish hearts. Nguyen: “It was exciting to see that the lessons learned from the zebrafish were translatable as this opens new possibilities for the use of LRRC10 in the context of new therapies for patients”.

 

Clinical impact

The results of the study, published in Science, show that LRRC10 has the potential to drive the maturation of heart muscle cells further through the control of their calcium handling. This could help scientists who are trying to solve the lack of regenerative capacity of the mammalian heart by transplanting lab-grown heart muscle cells into the damaged heart. Although this potential therapy is promising, results showed that these lab-grown cells are still immature and cannot communicate properly with the rest of the heart, leading to abnormal contractions called arrhythmias. “Although more research is needed to precisely define how mature these lab-grown heart muscle cells are when treated with LRRC10, it is possible that the increase in maturation will improve their integration after transplantation,” says Jeroen Bakkers, last author of the study. Bakkers continues: “Additionally, current models for cardiac diseases are frequently based on immature lab-grown heart muscle cells. 90% of promising drug candidates found in the lab fail to make it to the clinic and the immaturity of these cells could be one contributing factor for this low success rate. Our results indicate LRRC10 could improve the relevance of these models as well”. LRRC10 could thus have an important contribution to generate lab-grown heart muscle cells that more accurately represent a typical adult human heart, therefore improving the chances of developing successful new treatments against cardiovascular diseases.

 

Publication

Interplay between calcium and sarcomeres directs cardiomyocyte maturation during regeneration. Phong D. Nguyen*, Iris Gooijers†, Giulia Campostrini†, Arie O. Verkerk, Hessel Honkoop, Mara Bouwman, Dennis E. M. de Bakker, Tim Koopmans, Aryan Vink, Gerda E. M. Lamers, Avraham Shakked, Jonas Mars, Aat A. Mulder, Sonja Chocron, Kerstin Bartscherer, Eldad Tzahor, Christine L. Mummery, Teun P. de Boer, Milena Bellin, Jeroen Bakkers*. Science, 2023.

 

The study is the result of a collaboration between the Hubrecht Institute, LUMC, AMC, UMC Utrecht and Weizmann Institute. The study was financed with the help of the Dutch Heart Foundation, Dutch CardioVascular Alliance and Stichting Hartekind.

 

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Jeroen Bakkers is group leader at the Hubrecht Institute and professor of Molecular Cardiogenetics at the UMC Utrecht

 

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About the Hubrecht Institute 

The Hubrecht Institute is a research institute focused on developmental and stem cell biology. Because of the dynamic character of the research, the institute as a variable number of research group, around 20, that do fundamental, multidisciplinary research on healthy and diseased cells, tissues and organisms. The Hubrecht Institute is a research institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), situated on Utrecht Science Park. Since 2008, the institute is affiliated with the UMC Utrecht, advancing the translation of research to the clinic. The Hubrecht Institute has a partnership with the European Molecular Biology Laboratory (EMBL). For more information, visit www.hubrecht.eu. 

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JOURNAL

Science

DOI

10.1126/science.abo6718 

African Killifish could hold secrets to reversing muscle ageing

New research in the African killifish reveals that towards the end of life, our muscles actually reverse to an “early-life” state, clues to preventing muscle wasting

Peer-Reviewed Publication

MONASH UNIVERSITY

 

IMAGE: A JUST-HATCHED KILLIFISH LARVAE STAINED WITH ANTIBODIES AGAINST MYOSIN (RED), ACTININ (GREEN) AND COLLAGEN (BLUE). view more 

CREDIT: DR AVNIKA RUPARELIA

As we age, our muscles start to waste. Called sarcopenia, it happens to us all, yet no one has ever understood why and how it happens. Now new research from the Australian Regenerative Medicine Institute (ARMI) at Monash University has used a surprising animal model – the African killifish – to reveal that towards the end of life, our muscles actually reverse to an “early-life” state, slowing mortality. This finding may provide a clue to slowing, halting or even reversing age-related loss of muscle mass and strength.

The research, published in the Aging Cell and led by Professor Peter Currie and Dr Avnika Ruparelia, who is from ARMI and the University of Melbourne, is important because of the expected dramatic increase in the prevalence and severity of sarcopenia throughout the global population.

According to Professor Currie, “…there is a pressing need to understand the mechanisms that drive sarcopenia, so that we can identify and implement suitable medical interventions to promote healthy muscle ageing,” he said.

The African turquoise killifish, Nothobranchius furzeri has recently emerged as a new model for the study of ageing. Killifish have the shortest known life span of any vertebrate species that can be bred in captivity. Life for a killifish begins with the African rains, creating seasonal rain pools in which fish hatch, grow rapidly and mature in as few as two weeks, and then reproduce daily until the pool dries out.

Importantly, their short life span is accompanied with symptoms of ageing we see in humans – including the appearance of cancerous lesions in the liver and gonads, reduced regenerative capacity of the limbs, in this case the fin, and genetic characteristics that are the hallmark of human ageing such as a reduction in mitochondrial DNA copy number and function and shortening of telomeres.

According to Dr Ruparelia, this study is the first to use the killifish to study sarcopenia.

“In this study, we performed a thorough cellular and molecular characterization of skeletal muscle from early life, aged and extremely old late-life stages, revealing many similarities to sarcopenia in humans and other mammals,” she said.

Surprisingly the researchers also found these same metabolic hallmarks of ageing are reversed during the late-life stage, “suggesting that in extremely old animals, there may be
mechanisms in place that prevent further deterioration of skeletal muscle health, which may ultimately contribute to an extension of their life span,” Dr Ruparelia said.

“Importantly, the late-life stage during which we observed improved muscle health perfectly coincides with a stage when mortality rates decline. We therefore postulate that the improvement in muscle health may be a critical factor contributing to the extension of life span in extremely old individuals.”

To better understand the mechanisms behind this, the research team surveyed the metabolism of fish at different stages of the ageing process. This experiment surprisingly revealed that certain features of the metabolism of the very oldest fish actually were rejuvenated to resemble those of young fish. It highlighted the critical role of lipid metabolism in this process of rejuvenation.  By using drugs that regulate the formation of certain lipids a similar rejuvenation of ageing muscle could be achieved.  

“During extreme old age, there is a striking depletion of lipids, which are the main energy reserves in our cells,” explains senior author Prof Currie.

“We believe that this mimics a state of calorie restriction, a process known to extend life span in other organsims, which results in activation of downstream mechanisms ultimately enabling the animal to maintain nutrient balance and live longer. A similar process is seen in the muscle of highly trained athletes.”

Dr Ruparelia went on to say, “The idea that muscle ageing may be reversible, and potentially treatable by drugs that can manipulate a cell’s metabolism, is an exciting prospect especially given the social, economic and healthcare costs associated with the ever-growing aged population around the world. We are excited by the potential of the killifish model, and very grateful to the Winston Churchill Trust for funding, and to Hon Dr Kay Patterson for her assistance with establishing the import regulations to establish first and only killifish facility in Australia. We now have a unique opportunity to study biological processes regulating ageing and age-related diseases, and to investigate strategies to promote heathy ageing.”

The publication was the cumulation of a collaboration between researchers from:

• Australian Regenerative Medicine Institute (Australia)
• Monash Biomedicine Discovery Institute (Australia)
• The University of Melbourne (Australia)
• Centre for Muscle Research (Australia)
• Peter MacCallum Cancer Centre (Australia)
• Leibniz Institute on Aging – Fritz Lipmann Institute (Germany)

 

More information

The Currie group is curious about the biological mechanisms of the zebrafish, a freshwater fish that is native to South-East Asia. Zebrafish are used in scientific research to understand human genetics and the biological processes of human diseases. For more information on Professor Peter Currie and his group at ARMI, please visit the Currie Group page. You can contact Dr Avnika Ruparelia or Professor Peter Currie via avnika.ruparelia@unimelb.edu.au and peter.currie@monash.edu respectively.

JOURNAL

Aging Cell

DOI

10.1111/acel.13862 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

The African killifish: A short-lived vertebrate model to study the biology of sarcopenia and longevity

ARTICLE PUBLICATION DATE

16-May-2023

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Interplay between calcium and sarcomeres directs cardiomyocyte maturation during regeneration

ARTICLE PUBLICATION DATE

19-May-2023

Biodiversity discovery: Unknown species ("dark taxa") drive insect diversity

20 insect families globally account for 50% of flying insect biodiversity, whether in local meadows or tropical forests

Peer-Reviewed Publication

MUSEUM FÜR NATURKUNDE, LEIBNIZ INSTITUT FÜR EVOLUTIONS-UND BIODIVERSITÄTSFORSCHUNG

Biodiversity loss ranks among the top three risks to humanity, as stated in the 2023 World Economic Forum Global Risks Report. Understanding biodiversity's basic building blocks is essential to monitor changes, identify influencing factors, and implement appropriate policies. However, much of terrestrial animal diversity, including insects, remains unknown or "dark taxa."

For example, the global biodiversity information portal GBIF has nine times more information on birds than insects and arthropods, despite birds only accounting for 0.2% of biodiversity. Prof. Rudolf Meier, head of the Center for Integrative Biodiversity Discovery at the Museum für Naturkunde Berlin, highlights the importance of this study in addressing this deficit for effective nature conservation. He emphasizes the need to learn more about insects, as their combined biomass and biodiversity far surpass that of all vertebrates, and they are crucial for survival.

To determine the global taxonomic composition of flying insects, researchers used Malaise traps. These standardized traps are widely employed in global biomonitoring programs. However, analyzing samples is challenging when examining individual insects. Thanks to recent advances in sequencing technologies, biodiversity can now be estimated with "DNA barcodes".

Researchers used DNA barcodes to assign 225,261 specimens to 25,000 species to 458 families. Dr. Amrita Srivathsan, the study's lead author, noted the surprising finding that 10-20 families dominate flying insect communities worldwide. This is remarkable as samples were collected from various climates and habitats like tropical rainforests, montane forests, cedar savannas, scrub forests, thorn fields, mangroves, and swamps, with only Australia and Antarctica not being sampled.

Describing insects is a major challenge in understanding life on Earth, with over 80% still undescribed. The authors emphasize that a large fraction of terrestrial animal biodiversity remains unknown to science and will continue to be, unless "dark taxa" become a priority target in biodiversity research.

Publication: Srivathsan, A.; Ang,Y.; Heraty, J.M.; Hwang, W.S.; Jusoh, W. F.A.; Kutty, S.N.; Puniamoorthy, J.; Yeo,D.; Roslin, T.; Meier,R. (2023): Convergence of dominance and neglect in flying insect diversity. Nature Ecology & Evolution
DOI: 10.1038/s41559-023-02066-0

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JOURNAL

Nature Ecology & Evolution

DOI

10.1038/s41559-023-02066-0 

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Nature Ecology & Evolution

ARTICLE PUBLICATION DATE

18-May-2023