‘Gene therapy is a game changer for our son’

A five-month-old becomes the first person in England to get a drug with a list price of £1.79m.

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Newly discovered African ‘climate seesaw’ drove human evolution

While it is widely accepted that climate change drove the evolution of our species in Africa, the exact character of that climate change and its impacts are not well understood. Glacial-interglacial cycles strongly impact patterns of climate change in many parts of the world, and were also assumed to regulate environmental changes in Africa during the critical period of human evolution over the last ~1 million years. The ecosystem changes driven by these glacial cycles are thought to have stimulated the evolution and dispersal of early humans.

A paper published in Proceedings of the National Academy of Sciences (PNAS) this week challenges this view. Dr. Kaboth-Bahr and an international group of multidisciplinary collaborators identified ancient El Niño-like weather patterns as the drivers of major climate changes in Africa. This allowed the group to re-evaluate the existing climatic framework of human evolution.

Walking with the rain

Dr. Kaboth-Bahr and her colleagues integrated 11 climate archives from all across Africa covering the past 620 thousand years to generate a comprehensive spatial picture of when and where wet or dry conditions prevailed over the continent. “We were surprised to find a distinct climatic east-west ‘seesaw’ very akin to the pattern produced by the weather phenomena of El Niño, that today profoundly influences precipitation distribution in Africa,” explains Dr. Kaboth-Bahr, who led the study.

The authors infer that the effects of the tropical Pacific Ocean on the so-called “Walker Circulation” — a belt of convection cells along the equator that impact the rainfall and aridity of the tropics — were the prime driver of this climate seesaw. The data clearly shows that the wet and dry regions shifted between the east and west of the African continent on timescales of approximately 100,000 years, with each of the climatic shifts being accompanied by major turnovers in flora and mammal fauna.

“This alternation between dry and wet periods appeared to have governed the dispersion and evolution of vegetation as well as mammals in eastern and western Africa,” explains Dr. Kaboth-Bahr. “The resultant environmental patchwork was likely to have been a critical component of human evolution and early demography as well.”

The scientists are keen to point that although climate change was certainly not the sole factor driving early human evolution, the new study nevertheless provides a novel perspective on the tight link between environmental fluctuations and the origin of our early ancestors.

“We see many species of pan-African mammals whose distributions match the patterns we identify, and whose evolutionary history seems to articulate with the wet-dry oscillations between eastern and western Africa,” adds Dr. Eleanor Scerri, one of the co-authors and an evolutionary archaeologist at the Max Planck Institute for the Science of Human History in Germany. “These animals preserve the signals of the environments that humans evolved in, and it seems likely that our human ancestors may have been similarly subdivided across Africa as they were subject to the same environmental pressures.”

Ecotones: the transitional regions between different ecological zones

The scientists’ work suggests that a seesaw-like pattern of rainfall alternating between eastern and western Africa probably had the effect of creating critically important ecotonal regions — the buffer zones between different ecological zones, such grassland and forest.

“Ecotones provided diverse, resource-rich and stable environmental settings thought to have been important to early modern humans,” adds Dr. Kaboth-Bahr. “They certainly seem to have been important to other faunal communities.”

To the scientists, this suggests that Africa’s interior regions may have been critically important for fostering long-term population continuity. “We see the archaeological signatures of early members of our species all across Africa,” says Dr. Scerri, “but innovations come and go and are often re-invented, suggesting that our deep population history saw a constant saw-tooth like pattern of local population growth and collapse. Ecotonal regions may have provided areas for longer term population continuity, ensuring that the larger human population kept going, even if local populations often went extinct.”

“Re-evaluating these patterns of stasis, change and extinction through a new climatic framework will yield new insights into the deep human past,” says Dr. Kaboth Bahr. “This does not mean that people were helpless in the face of climatic changes, but shifting habitat availability would certainly have impacted patterns of demography, and ultimately the genetic exchanges that underpin human evolution.”

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Ethnic diversity helps identify more genomic regions linked to diabetes-related traits

By including multi-ethnic participants, a large scale genetic study has identified more regions of the genome linked to type 2 diabetes-related traits than if the research had been conducted in Europeans alone.

The international MAGIC collaboration, made up of more than 400 global academics, conducted a genome-wide association meta-analysis led by the University of Exeter. Now published in Nature Genetics, their findings demonstrate that expanding research into different ancestries yields more and better results, as well as ultimately benefitting global patient care.

Up to now, nearly 87 per cent of genomic research of this type has been conducted in Europeans. This means that the way these findings are implemented may not optimally benefit people from non-European ancestries.

The team analysed data across a wide range of cohorts, encompassing more than 280,000 people without diabetes. Researchers looked at glycaemic traits, which are used to diagnose diabetes and monitor sugar and insulin levels in the blood.

The researchers incorporated 30 percent of the overall cohort with individuals of East Asian, Hispanic, African-American, South Asian and sub-Saharan African origin. By doing so, they discovered 24 more loci — or regions of the genome -linked to glycaemic traits than if they had conducted the research in Europeans alone.

Professor Inês Barroso, of the University of Exeter, who led the research, said: “Type 2 diabetes is an increasingly huge global health challenge- with most of the biggest increases occurring outside of Europe. While there are a lot of shared genetic factors between different countries and cultures, our research tells us that they do differ, in ways that we need to understand. It’s critical to ensuring we can deliver a precision diabetes medicine approach that optimises treatment and care for everyone.”

First author Dr Ji Chen, of the University of Exeter, said: “We discovered 24 additional regions of the genome by including cohorts which were more ethnically diverse than we would have done if we’d restricted our work to Europeans. Beyond the moral arguments for ensuring research is reflective of global populations, our work demonstrates that this approach generates better results.”

The team found that though some loci were not detected in all ancestries, they were still useful to capture information about the glycaemic trait in that ancestry. Co-author Cassandra Spracklen, Assistant Professor at the University of Massachusetts-Amherst, said: “Our findings matter because we’re moving towards using genetic scores to weigh up a person’s risk of diabetes. We know that scores developed exclusively in individuals of one ancestry don’t work well in people of a different ancestry. This is important as increasingly healthcare is moving towards a more precise approach. Failing to account for genetic variation according to ancestry will impact our ability to accurately diagnose diabetes.”

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Materials provided by University of Exeter. Note: Content may be edited for style and length.

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Global warming already responsible for one in three heat-related deaths

Between 1991 and 2018, more than a third of all deaths in which heat played a role were attributable to human-induced global warming, according to a new article in Nature Climate Change.

The study, the largest of its kind, was led by the London School of Hygiene & Tropical Medicine (LSHTM) and the University of Bern within the Multi-Country Multi-City (MCC) Collaborative Research Network. Using data from 732 locations in 43 countries around the world it shows for the first time the actual contribution of human-made climate change in increasing mortality risks due to heat.

Overall, the estimates show that 37% of all heat-related deaths in the recent summer periods were attributable to the warming of the planet due to anthropogenic activities. This percentage of heat-related deaths attributed to human-induced climate change was highest in Central and South America (up to 76% in Ecuador or Colombia, for example) and South-East Asia (between 48% to 61%).

Estimates also show the number of deaths from human-induced climate change that occurred in specific cities; 136 additional deaths per year in Santiago de Chile (44.3% of total heat-related deaths in the city), 189 in Athens (26.1%), 172 in Rome (32%), 156 in Tokyo (35.6%), 177 in Madrid (31.9%), 146 in Bangkok (53.4%), 82 in London (33.6%), 141 in New York (44.2%), and 137 in Ho Chi Minh City (48.5%). The authors say their findings are further evidence of the need to adopt strong mitigation policies to reduce future warming, and to implement interventions to protect populations from the adverse consequences of heat exposure.

Dr Ana M. Vicedo-Cabrera, from the University of Bern and first author of the study, said: “We expect the proportion of heat-related deaths to continue to grow if we don’t do something about climate change or adapt. So far, the average global temperature has only increased by about 1°C, which is a fraction of what we could face if emissions continue to grow unchecked.”

Global warming is affecting our health in several ways, from direct impacts linked to wildfires and extreme weather, to changes in the spread of vector-borne diseases, among others. Perhaps most strikingly is the increase in mortality and morbidity associated with heat. Scenarios of future climate conditions predict a substantial rise in average temperatures, with extreme events such as heatwaves leading to future increases in the related health burden. However, no research has been conducted into what extent these impacts have already occurred in recent decades until now.

This new study focused on human-made global warming through a ‘detection & attribution’ study that identifies and attributes observed phenomena to changes in climate and weather. Specifically, the team examined past weather conditions simulated under scenarios with and without anthropogenic emissions. This enabled the researchers to separate the warming and related health impact linked with human activities from natural trends. Heat-related mortality was defined as the number of deaths attributed to heat, occurring at exposures higher than the optimum temperature for human health, which varies across locations.

While on average over a third of heat-related deaths are due to human-induced climate change, impact varies substantially across regions. Climate-related heat casualties range from a few dozen to several hundred deaths each year per city, as shown above, depending on the local changes in climate in each area and the vulnerability of its population. Interestingly, populations living in low and middle-income countries, which were responsible for a minor part of anthropogenic emissions in the past, are those most affected.

In the UK, 35% of heat-related deaths could be attributed to human-induced climate change, which corresponds to approximately 82 deaths in London, 16 deaths in Manchester, 20 in West Midlands or 4 in Bristol and Liverpool every summer season.

Professor Antonio Gasparrini from LSHTM, senior author of the study and coordinator of the MCC Network, said: “This is the largest detection & attribution study on current health risks of climate change. The message is clear: climate change will not just have devastating impacts in the future, but every continent is already experiencing the dire consequences of human activities on our planet. We must act now.”

The authors acknowledge limitations of the study including being unable to include locations in all world regions — for example, large parts of Africa and South Asia — due to a lack of empirical data.

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Covid-19: UK in early stages of third wave – scientist

A scientist advising the government says there has been exponential growth in the number of new cases.

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Covid-19: ‘Very few’ Covid hospital patients had two jabs, NHS boss says

NHS boss Chris Hopson adds it’s “incredibly striking” how busy hospitals are with non-Covid patients.

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NHS calls for ban on toy neodymium magnets amid child safety fears

In England, 65 children have needed urgent surgery after swallowing magnets in the last three years.

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Depressive symptoms linked to rapid kidney function decline

In a study of adults with normal kidney function, those who had frequent depressive symptoms were more likely to later experience a rapid decline in kidney function. The study will appear in an upcoming issue of CJASN.

Depression is a common condition in middle-aged and older adults, and it can contribute to a variety of mental and physical problems. Previous research has found a link between depressive symptoms and rapid kidney function decline in patients with chronic kidney disease (CKD). To look for a potential link in adults with normal kidney function as well, a team led by Xianhui Qin, MD (Nanfang Hospital, Southern Medical University, in China) examined information on 4,763 individuals with healthy kidneys when they enrolled in the China Health and Retirement Longitudinal Study (CHARLS).

At the start of the study, 39% of participants had high depressive symptoms, and during a median follow-up of 4 years, 260 (6%) participants experienced rapid kidney function decline. There was a significant association between depressive symptoms at the start of the study and rapid decline in kidney function during follow-up. Participants with frequent depressive symptoms were 1.4-times more likely to experience rapid kidney function decline than participants with infrequent depressive symptoms, after adjustments.

“CKD is a leading risk factor for cardiovascular disease, kidney failure, and mortality worldwide. Therefore, the identification of more modifiable risk factors may possibly reduce the huge burden of CKD and its related complications by leading to early detection and prevention,” said Dr. Qin. “While our study does not show causality, it demonstrated that high depressive symptoms were significantly associated with rapid decline in kidney function among Chinese adults with normal kidney function. If further confirmed, our data provide some evidence for depressive symptom screening and effective psychosocial interventions to improve the prevention of CKD.”

An accompanying Pantiet Voice article provides the perspective of a two-time kidney transplant recipient with an American-Born Chinese background.

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Materials provided by American Society of Nephrology. Note: Content may be edited for style and length.

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Candy-like models used to make STEM accessible to visually impaired students

About 36 million people have blindness including 1 million children. Additionally, 216 million people experience moderate to severe visual impairment. However, STEM (science, technology, engineering and math) education maintains a reliance on three-dimensional imagery for education. Most of this imagery is inaccessible to students with blindness. A breakthrough study by Bryan Shaw, Ph.D., professor of chemistry and biochemistry at Baylor University, aims to make science more accessible to people who are blind or visually impaired through small, candy-like models.

The Baylor-led study, published May 28 in the journal Science Advances, uses millimeter-scale gelatin models — similar to gummy bears — to improve visualization of protein molecules using oral stereognosis, or visualization of 3D shapes via the tongue and lips. The goal of the study was to create smaller, more practical tactile models of 3D imagery depicting protein molecules. The protein molecules were selected because their structures are some of the most numerous, complex and high-resolution 3D images presented throughout STEM education.

“Your tongue is your finest tactile sensor — about twice as sensitive as the finger tips — but it is also a hydrostat, similar to an octopus arm. It can wiggle into grooves that your fingers won’t touch, but nobody really uses the tongue or lips in tactile learning. We thought to make very small, high-resolution 3D models, and visualize them by mouth,” Shaw said.

The study included 396 participants in total — 31 fourth- and fifth-graders as well as 365 college students. Mouth, hands and eyesight were tested at identifying specific structures. All students were blindfolded during the oral and manual tactile model testing.

Each participant was given three minutes to assess or visualize the structure of a study protein with their fingertips, followed by one minute with a test protein. After the four minutes, they were asked whether the test protein was the same or a different model than the initial study protein. The entire process was repeated using the mouth to discern shape instead of the fingers.

Students recognized struc¬tures by mouth at 85.59% accuracy, similar to recognition by eyesight using computer animation. Testing involved identical edible gelatin models and nonedible 3D-printed models. Gelatin models were correctly identified at rates comparable to the nonedible models.

“You can visualize the shapes of these tiny objects as accurately by mouth as by eyesight. That was actually surprising,” Shaw said.

The models, which can be used for students with or without visual impairment, offer a low-cost, portable and convenient way to make 3D imagery more accessible. The methods of the study are not limited to molecular models of protein structures — oral visualization could be done with any 3D model, Shaw said.

Additionally, while gelatin models were the only edible models tested, Shaw’s team created high-resolution models from other edible materials, including taffy and chocolate. Certain surface features of the models, like a proteins pattern of positive and negative surface charge, could be represented using different flavor patterns on the model.

“This methodology could be applied to images and models of anything, like cells, organelles, 3D surfaces in math or 3D pieces of art — any 3D rendering. It’s not limited to STEM, but useful for humanities too,” said Katelyn Baumer, doctoral candidate and lead author of the study.

Shaw’s lab sees oral visualization through tiny models as a beneficial addition to the multisensory learning tools available for students, particularly those with extraordinary visual needs. Models like the ones in this study can make STEM more accessible to students with blindness or visual impairment.

“Students with blindness are systematically excluded from chemistry, and much of STEM. Just look around our labs and you can see why — there is Braille on the elevator button up to the lab and Braille on the door of the lab. That’s where accessibility ends. Baylor is the perfect place to start making STEM more accessible. Baylor could become an oasis for people with disabilities to learn STEM,” Shaw said.

Shaw isn’t new to high-profile research related to visual impairment. He has received recognition for his work on the White Eye Detector app. Shaw and Greg Hamerly, Ph.D., associate professor of computer science at Baylor, built the mobile app which serves as a tool for parents to screen for pediatric eye disease. Shaw’s inspiration for the app came after his son, Noah, was diagnosed with retinoblastoma at four months of age.

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Climate change-resistant corals could provide lifeline to battered reefs

In 2015, nearly half of Hawai’i’s coral reefs were affected by the most severe bleaching event to date. Coral bleaching occurs when warmer-than-normal ocean temperatures prompt corals to expel the algae that normally live inside them and on which the corals rely for food.

Bleaching events are dismaying, but corals can sometimes recover, while others resist bleaching altogether. In a new study in the journal Proceedings of the National Academy of Sciences, researchers led by Katie Barott of the University of Pennsylvania found that these battle-tested, resilient corals could thrive, even when transplanted to a different environment and subjected to additional heat stress. The findings offer hope that hardy corals could serve as a founding population to restore reefs in the future.

“The big thing that we were really interested in here was trying to experimentally test whether you an take a coral that seems to be resistant to climate chage and use that as the seed stock to propagate and put out on a different reef that might be degraded,” Barott says. “The cool thing was we didn’t see any differences in their bleaching response after this transplant.”

Mass coral bleaching events are getting increasingly frequent, raising worries that corals will become victims of climate change in the near future. Yet Barott and colleagues have been studying the corals that resist bleaching, with an eye toward buying corals more time to hang on in the face of warming and acidifying ocean waters.

One strategy they and others have envisioned, and which has been trialed in areas such as the Great Barrier Reef, is coral transplantation. Researchers could replenish reefs damaged by climate change — or other anthropogenic insults, such as sedimentation or a ship grounding — with corals that had proved sturdy and able to survive in the face of tough conditions.

For this to work, however, would require the coral “survivors” to continue to display their resilient characteristics after being moved to a new environment.

“If you take a coral that is resistant to bleaching in its native habitat, it could be that the stress of moving to a new place might make them lose that ability,” Barott says.

Just as a fern that grew well in the shade might wilt if moved to a sunny plot, the conditions of a new environment, including water flow rate, food access, light, and nutrient availability, could could affect the resilience of transplanted corals.

Barott and colleagues went after this question with an experiment in two reefs in Hawaiʻi’s Kāneʻohe Bay on the island of Oʻahu: one closer to shore with more stagnant waters and another farther from shore with higher flow. In each area, the researchers identified coral colonies that had resisted bleaching during the 2015 bleaching event and collected samples from them the following year. Corals are clonal organisms, and so a chunk taken from a colony can regrow and will have the same genetics as the “mother” coral. For each colony, they kept some samples on their native reef and transplanted others to the second reef.

After the corals had spent six months at their new location, the biologists also put coral samples from each site in tanks in the lab and simulated another bleaching event by raising the water temperature over a period of several days.

Carefully tracking the corals’ health and the conditions of the surrounding environment, the team measured photosynthesis rates, metabolism, and calcification rates, as well as the health of the symbiotic algae. They found that bleaching-resistant corals stayed that way, even in a new environment.

“What was really novel is that we had this highly replicated experiment,” Barott says, “and we saw no change in the coral’s bleaching response.”

The researchers also looked at how well the corals reproduced the summer that followed their collection. A coral’s native site conditions had an impact on their future reproductive fitness, they discovered.

“The corals from the ‘happy’ site — the outer lagoon that had higher growth rates prior to the bleaching event — generally seemed a little happier and their fitness was higher,” Barott says. “That tells us that, if you’re going to have a coral nursery, you should pick a site with good conditions because there seems to be some carryover benefit of spending time at a nicer site even after the corals are outplanted to a less ‘happy’ site.”

The “happy” site, the lagoon farther from shore, had higher flow rates than the other reef, which is closer to shore, less salty, and more stagnant. “Higher flow rates are really important for helping corals get rid of waste and get food,” Barott says.

Barott, who started the work as a postdoc at the Hawaiʻi Institute of Marine Biology, is continuing to pursue research on coral resiliency in her lab at Penn, including an investigation of the effects of heat stress and bleaching on reproductive success and the function of coral sperm.

While the results of the transplantation study are promising, she says that it would only be a temporary solution to the threat of climate change.

“I think techniques like this can buy us a little bit of time, but there isn’t a substitute for capping carbon emissions,” she says. “We need global action on climate change because even bleaching-resistant corals aren’t going to survive forever if ocean warming keeps increasing as fast as it is today.”

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