Diagram comparing the nose shape of a Neanderthal with that of a modern human by Dr Macarena Fuentes-Guajardo.
Neanderthal genes comprise some 1 to 4% of the genome of present-day humans whose ancestors migrated out of Africa, and new research has shown that their lingering presence shapes the immune systems and metabolism of people of non-African ancestry. Some of these genetics changes are detrimental, but are slowly being replaced by human versions.
A multi-institution research team including Cornell University has developed a new suite of computational genetic tools to address the genetic effects of interbreeding between humans of non-African ancestry and Neanderthals that took place some 50 000 years ago. (The study applies only to descendants of those who migrated from Africa before Neanderthals died out, and in particular, those of European ancestry.)
In a study published in eLife, the researchers reported that some Neanderthal genes are responsible for certain traits in modern humans, including several with a significant influence on the immune system. Overall, however, the study shows that modern human genes are winning out over successive generations.
“Interestingly, we found that several of the identified genes involved in modern human immune, metabolic and developmental systems might have influenced human evolution after the ancestors’ migration out of Africa,” said study co-lead author April (Xinzhu) Wei, an assistant professor of computational biology in the College of Arts and Sciences. “We have made our custom software available for free download and use by anyone interested in further research.”
Using a vast dataset from the UK Biobank consisting of genetic and trait information of nearly 300 000 British people of non-African ancestry, the researchers analysed more than 235 000 genetic variants likely to have originated from Neanderthals. They found that 4303 of those differences in DNA are playing a substantial role in modern humans and influencing 47 distinct genetic traits, such as how fast someone can burn calories or a person’s natural immune resistance to certain diseases.
Unlike previous studies that could not fully exclude genes from modern human variants, the new study leveraged more precise statistical methods to focus on the variants attributable to Neanderthal genes.
While the study used a dataset of almost exclusively white individuals living in the United Kingdom, the new computational methods developed by the team could offer a path forward in gleaning evolutionary insights from other large databases to delve deeper into archaic humans’ genetic influences on modern humans.
“For scientists studying human evolution interested in understanding how interbreeding with archaic humans tens of thousands of years ago still shapes the biology of many present-day humans, this study can fill in some of those blanks,” said senior investigator Sriram Sankararaman, an associate professor at the University of California, Los Angeles. “More broadly, our findings can also provide new insights for evolutionary biologists looking at how the echoes of these types of events may have both beneficial and detrimental consequences.”
Showing people how their behaviour compares to their peers is a commonly used method to improve behaviour. But after the burnouts of the pandemic, it wasn’t clear whether this was still a good idea for highly stressed healthcare workers.
Recent research published in JAMA Network Open throws new light onto the relationship between peer comparison and job satisfaction among clinicians, challenging prior findings that such feedback increases job dissatisfaction and burnout.
Researchers found that behavioural interventions aimed at improving performance can be designed to protect clinician job satisfaction and improve quality of care. To avoid negative impact, the research team discovered it is important for clinicians to have control over the behaviour being evaluated or encouraged, such as ordering tests or whether to prescribe medication.
“Our research demonstrates that peer comparison aimed at improving performance can be designed in a manner that safeguards clinician job satisfaction,” said lead author Dr Jason Doctor at the University of Southern California. “Prior findings to the contrary don’t appear tied to peer comparison, but rather clinicians being measured for things they don’t have full control over.”
The Importance of Methodology in Peer Comparison
Performance feedback using peer comparison is a widely used approach in healthcare to change behaviour. Study authors emphasize the importance of methodology when conducting peer comparison intervention. They note the present study gave clinicians full agency over the outcome, kept performance private, did not restrict the number of top performers, and was successful in improving clinician behaviour without lowering job satisfaction.
Doctor and his team assessed data from their previously published research that assessed the impact of three interventions – Suggested Alternatives, Accountable Justification, and Peer Comparison – to reduce inappropriate antibiotic prescribing. In this study, they focused on on peer comparison, where clinicians received an email informing them of their ranking, from highest to lowest, for inappropriate prescriptions compared to their peers.
The findings contribute to the ongoing dialogue surrounding healthcare quality improvement and clinician well-being.
“By better understanding behavioural interventions and developing more effective strategies, healthcare organisations can foster a sense of ownership and agency, leading to improved job satisfaction and decreased burnout rates,” said Doctor.
Genes that make bacteria resistant to antibiotics are much more widespread in our environment than was previously realised. A new study published in Microbiome shows that bacteria in almost all environments carry resistance genes, with a risk of them spreading and aggravating the problem of bacterial infections that are untreatable with antibiotics.
“We have identified new resistance genes in places where they have remained undetected until now. These genes can constitute an overlooked threat to human health,” says Erik Kristiansson, a professor in the Department of Mathematical Sciences.
According to the World Health Organisation (WHO), antibiotic resistance is one of the greatest threats to global health. When bacteria become resistant to antibiotics, it becomes difficult or impossible to treat illnesses such as pneumonia, wound infections, tuberculosis and urinary tract infections. According to the UN Interagency Coordination Group on Antimicrobial Resistance (IACG) 700,000 people die each year from infections caused by antibiotic-resistant bacteria.
Looking for resistance genes in new environments
The genes that make bacteria resistant have long been studied, but the focus has traditionally been on identifying those resistance genes that are already prevalent in pathogenic bacteria. Instead, in the new study from Sweden, researchers have looked at large quantities of DNA sequences from bacteria to analyse new forms of resistance genes in order to understand how common they are. They have traced the genes in thousands of different bacterial samples from different environments, in and on people, in the soil and from sewage treatment plants. The study analysed 630 billion DNA sequences in total.
“The data requires a great deal of processing before information can be obtained. We have used metagenomics, a methodology, that allows vast quantities of data to be analysed,” says Juan Inda Díaz, a doctoral student in the Department of Mathematical Sciences, and the article’s lead author.
The study showed that the new antibiotic resistance genes are present in bacteria in almost all environments. This also includes human microbiomes and, more alarmingly, pathogenic bacteria, which can lead to more infections that are difficult to treat. The researchers found that resistance genes in bacteria that live on and in humans and in the environment were ten times more abundant than those previously known. And of the resistance genes found in bacteria in the human microbiome, 75% were not previously known at all.
The researchers stress the need for more knowledge about the problem of antibiotic resistance.
“Prior to this study, there was no knowledge whatsoever about the incidence of these new resistance genes. Antibiotic resistance is a complex problem, and our study shows that we need to enhance our understanding of the development of resistance in bacteria and of the resistance genes that could constitute a threat in the future,” says Kristiansson.
Preventing bacterial outbreaks in healthcare
The research team is currently working on integrating the new data into the international EMBARK project (Establishing a Monitoring Baseline for Antibiotic Resistance in Key environments). The project is coordinated by Johan Bengtsson-Palme, an assistant professor in the Department of Life Sciences at Chalmers, and aims to take samples from sources such as wastewater, soil and animals to get an idea of the way in which antibiotic resistance is spreading between humans and the environment.
“It is essential for new forms of resistance genes to be taken into account in risk assessments relating to antibiotic resistance. Using the techniques we have developed enables us to monitor these new resistance genes in the environment, in the hope that we can detect them in pathogenic bacteria before they are able to cause outbreaks in a healthcare setting,” says Bengtsson-Palme.
The method used by the researchers is called metagenomics, and is not new, but so far has not been used to analyse new types of antibiotic resistance genes in such large quantities. Metagenomics is a method of studying the metagenome, which is the complete gene set of all different organisms in a given sample or within a given environment. Using the method, it is also possible to study microorganisms that cannot be grown in a lab.
A deficiency of the amino acid taurine is a driver of ageing in animals, according to a new study published in Science. The same study also found that taurine supplements can slow down the ageing process in worms, mice, and monkeys and can even extend the healthy lifespans of middle-aged mice by up to 12%.
“For the last 25 years, scientists have been trying to find factors that not only let us live longer, but also increase healthspan, the time we remain healthy in our old age,” says study leader Vijay Yadav, PhD, assistant professor of genetics & development at Columbia University. “This study suggests that taurine could be an elixir of life within us that helps us live longer and healthier lives.”
Anti-ageing molecules within us
Many studies into ageing have found that various molecules carried through the bloodstream are associated with ageing. Less certain is whether these molecules actively direct the ageing process or are just passengers going along for the ride. If a molecule is a driver of ageing, then restoring its youthful levels would delay ageing and increase healthspan, the years we spend in good health.
Taurine first came into Yadav’s view during his previous research into osteoporosis that uncovered taurine’s role in building bone. Around the same time, other researchers were finding that taurine levels correlated with immune function, obesity, and nervous system functions.
“We realised that if taurine is regulating all these processes that decline with age, maybe taurine levels in the bloodstream affect overall health and lifespan,” Yadav says.
Taurine declines with age, supplementation increases lifespan in mice
First, Yadav’s team looked at levels of taurine in the bloodstream of mice, monkeys, and people and found that the taurine abundance decreases substantially with age. In people, taurine levels in 60-year-old individuals were only about one-third of those found in 5-year-olds.
“That’s when we started to ask if taurine deficiency is a driver of the ageing process, and we set up a large experiment with mice,” Yadav says.
The researchers started with close to 250 14-month-old female and male mice (about 45 years old in people terms). Every day, the researcher fed half of them a bolus of taurine or a control solution. At the end of the experiment, Yadav and his team found that taurine increased average lifespan by 12% in female mice and 10% in males. For the mice, that meant three to four extra months, equivalent to about seven or eight human years.
Taurine supplements in middle age improves health in old age
To learn how taurine impacted health, Yadav brought in other ageing researchers who investigated the effect of taurine supplementation on the health and lifespan in several species.
These experts measured various health parameters in mice and found that at age 2 (60 in human years), animals supplemented with taurine for one year were healthier in almost every way than their untreated counterparts.
The researchers found that taurine suppressed age-associated weight gain in female mice (even in “menopausal” mice), increased energy expenditure, increased bone mass, improved muscle endurance and strength, reduced depression-like and anxious behaviours, reduced insulin resistance, and promoted a younger-looking immune system, among other benefits.
“Not only did we find that the animals lived longer, we also found that they’re living healthier lives,” Yadav says.
At a cellular level, taurine improved many functions that usually decline with age: The supplement decreased the number of “zombie cells” (old cells that should die but instead linger and release harmful substances), increased survival after telomerase deficiency, increased the number of stem cells present in some tissues (which can help tissues heal after injury), improved the performance of mitochondria, reduced DNA damage, and improved the cells’ ability to sense nutrients.
Similar health effects of taurine supplements were seen in middle-aged rhesus monkeys, which were given daily taurine supplements for six months. Taurine prevented weight gain, reduced fasting blood glucose and markers of liver damage, increased bone density in the spine and legs, and improved the health of their immune systems.
Randomised clinical trial needed
The researchers do not know yet if taurine supplements will improve health or increase longevity in humans, but two experiments they conducted suggest taurine has potential.
In the first, Yadav and his team looked at the relationship between taurine levels and approximately 50 health parameters in 12 000 European adults aged 60 and over. Overall, people with higher taurine levels were healthier, with fewer cases of type 2 diabetes, lower obesity levels, reduced hypertension, and lower levels of inflammation. “These are associations, which do not establish causation,” Yadav says, “but the results are consistent with the possibility that taurine deficiency contributes to human ageing.”
The second study tested if taurine levels would respond to an intervention known to improve health: exercise. The researchers measured taurine levels before and after a variety of male athletes and sedentary individuals finished a strenuous cycling workout and found a significant increase in taurine among all groups of athletes (sprinters, endurance runners, and natural bodybuilders) and sedentary individuals.
“No matter the individual, all had increased taurine levels after exercise, which suggests that some of the health benefits of exercise may come from an increase in taurine,” Yadav says.
Only a randomized clinical trial in people will determine if taurine truly has health benefits, Yadav adds. Taurine trials are currently underway for obesity, but none are designed to measure a wide range of health parameters.
Other potential anti-ageing drugs – including metformin, rapamycin, and NAD analogues – are being considered for testing in clinical trials.
“I think taurine should also be considered,” Yadav says. “And it has some advantages: Taurine is naturally produced in our bodies, it can be obtained naturally in the diet, it has no known toxic effects (although it’s rarely used in concentrations used ), and it can be boosted by exercise.
“Taurine abundance goes down with age, so restoring taurine to a youthful level in old age may be a promising anti-ageing strategy.”
In a concerning trend, a study of 17 000 people has revealed that public confidence in vaccines has plunged across sub-Saharan Africa since the COVID pandemic. The study, published in Human Vaccines & Immunotherapeutics, covered eight countries including South Africa – which saw one of the biggest falls in trust.
The findings come as the World Health Organization and UNICEF have reported the largest sustained fall in uptake of routine childhood immunisations in three decades. Six million fewer children in Africa received routine shots for diseases including tetanus, polio, diphtheria and measles over the past two years, and rising outbreaks threaten to reverse decades of progress against preventable diseases.
Previously, this was attributed to pdisruption of vaccination programs by the pandemic – however these new findings, which followed a study carried out by a team from London School of Hygiene & Tropical Medicine (LSHTM) and the Africa Centres for Disease Control and Prevention, suggest there could be other possible reasons too.
“Our study paints a worrying picture of declining vaccine confidence trends across many sub-national regions in sub-Saharan Africa, notably in the Democratic Republic of Congo, where confidence losses are particularly large,” states lead author Dr Alex de Figueirido, a Research Fellow at LSHTM.
The team’s results could be an early warning sign of wider scale loss in vaccine confidence, say the authors. Critically, regional losses in confidence – as seen in this study – could lead to clusters of non-vaccinated people which could have a negative impact on ‘herd immunity’ – the point at which a population is protected from a disease, either by enough people being vaccinated or by people having developed antibodies through having the disease.
The research involved face-to-face interviews with over 17 000 adults across eight sub-Saharan African countries: the Democratic Republic of Congo (DRC), Ivory Coast, Kenya, Niger, Nigeria, Senegal, South Africa and Uganda. The experts used sampling methods to get an accurate cross section of the population and to gain a picture of vaccine confidence at both national and regional levels.
Interviewees’ age, sex, religion, employment status and highest education level were recorded to help the researchers to analyse whether social background affected confidence in vaccines. The interviews were carried out in 2020 and again in 2022, after the pandemic.
Respondents were asked to say how strongly they agreed with statements such as ‘Vaccines are important for all ages’, ‘Vaccines are important for children’ and ‘Vaccines are safe’. They were also asked specifically about COVID vaccines, rating their agreement that COVID vaccines would be important, safe and effective – both before they had been developed (in 2020) and then after they had been developed and rolled out, in 2022.
Findings showed a fall in people’s view that vaccines are important for children across all eight countries between 2020 and 2022, particularly in DRC (20% decline), followed by Uganda (14%) and Nigeria (10.5%). In Nigeria and DRC, public confidence in vaccine safety and effectiveness also declined, and fewer people agreed that ‘vaccines are important for all ages’ in Ivory Coast, Kenya, Nigeria, South African and Uganda.
When it came to COVID vaccines, people thought they were less important in 2022 than they had in 2020 in seven out of the eight countries, with the biggest loss of trust in DRC, South Africa and Uganda. People in DRC, Kenya, Niger, Senegal and Nigeria thought that the COVID vaccine was less effective in 2022 than they had expected it to be in 2020. However, trust in the safety of the COVID vaccine stayed consistent over the two years.
In 2022, the over-60s were more likely than younger adults to agree that vaccines are generally safe, effective and important for children, but no other links were found between vaccine confidence and sex, education, employment status or religious affiliation.
“Early warning signals of confidence losses – such as those detected in this study – can provide time to respond, in the case of other epidemics, pandemics or other emerging crises,” adds co-author, Professor of Anthropology, Risk and Decision Science Heidi Larson, who is the Founding Director of the Vaccine Confidence Project at LSHTM.
“Confidence monitoring at sub-national resolutions can also provide clearer signals to the regions and groups facing confidence losses and can better prepare policymakers and stakeholders for potential losses in vaccine uptake.”
A thorough investigation is now needed to find out whether loss of confidence in COVID vaccines will trigger mistrust of other immunisation programmes, say the study authors.
“Considering global decreases in routine immunisation rates over the past two years, vaccine confidence losses could prove to be highly disruptive at this time when there are concerted efforts to address losses in routine immunization rates post pandemic. We need to understand the impact of the COVID pandemic on confidence in routine immunisation programmes, not just in Africa, but across the world,” says Dr Defigueirido.
“Understanding the role of the COVID pandemic and associated policies on wider vaccine confidence can inform post-COVID vaccination strategies and help rebuild immunisation system resilience.”
