A Complex Mosaic of Interactions

While the spread of food production led to the gradual replacement of local foragers in most parts of the world, foraging lifeways have persisted in several regions of contemporary Africa among populations such as the San in the south, the Hazda in the east and the Mbuti of the central African rainforest. However, the present study shows that, thousands of years ago, the ancestors of these groups once formed an overlapping genetic cline that stretched across much of eastern and southern Africa.

“Restricted gene flow between regional forager groups in contemporary eastern, southern, and central Africa, whether due to climactic and environmental factors or as a result of encapsulation by food producing groups, has likely contributed substantially to the spatial genetic structure we can see across the continent today,” says Ke Wang.

“We are still at a point where we learn a lot from every individual,” Steven Goldstein adds, “the interactions between hunter-gatherers, pastoralists, and farmers were more complex even into recent centuries than we previously understood.”

To better understand these interactions and their impact on subsistence strategies, the researchers focused their investigations on key groups and regions previously identified as significant contributors to changes in food production: eastern and southern forager groups, eastern African Pastoral Neolithic and Iron Age groups, and Iron Age groups related to present-day Bantu speakers.

Mixture and migration during the Pastoral Neolithic

Genomic analysis of the six individuals here reported from Kenya’s Pastoral Neolithic period (between 4,500 and 1,200 years ago) revealed greater ancestral complexity than previously reported individuals from the same region, supporting previous studies that have proposed early herders migrated south along multiple simultaneous but geographically distinct routes.

“In such a scenario,” Dr. Emmanuel Ndiema of the National Museums of Kenya explains, “a single base population in northern Africa may have branched into many as some herding groups moved along the Nile corridor, some through southern Ethiopia, and possibly some through eastern Uganda.”

Along the way, migrating pastoralists would have encountered different populations and formed varying inter-community relationships, ultimately resulting in varying integration of diverse ancestries. This model may explain why archaeologists observe stark differences in material culture, settlement strategies and burial traditions between Pastoral Neolithic populations whose ancestries are in fact closely related.

The Iron Age and the Bantu Expansion

Some of the most exciting findings come from the site of Kakapel Rockshelter in western Kenya, where the National Museums of Kenya and the MPI-SHH have teamed up to investigate early farming in the region.

At Kakapel, two individuals dated to roughly 300 and 900 years ago show significant increases in ancestry related to people speaking Nilotic languages today, such as the Dinka from South Sudan, compared to previously published genomes from the Central Rift Valley. This suggests that genetic turnover must have been region-specific and could have involved multiple divergent migrations. Genomic analysis revealed that the 900-year-old individual had close affinity with Dinka populations, but also showed influence from West-Eurasian or North-African groups, suggesting that the population that this individual represents formed between Pastoral Neolithic-related herders and incoming Nilotic (Nile Valley) agropastoralists — not from a major migration of groups with western African ancestries.

Similar evidence is detected from Botswana, where analysis detected the first archaeogenetic support for the hypotheses that herders from eastern Africa spread to southern Africa before the arrival of Bantu-speaking farmers. Despite raising questions about the uniformity of the Bantu Expansion, the current study documents the arrival of people with Bantu-related ancestry in Botswana during the first millennium CE and their subsequent admixture with eastern African pastoralist and southern African forager populations.

“We identified Bantu-related ancestry in Uganda, western Congo, Tanzania and Kenya, which is consistent with the well-documented genetic homogenization caused by the Bantu expansion,” says Stephan Schiffels of the MPI-SHH, “but we also see highly variable patterns of Bantu admixture with regional forager and pastoralist populations in southern Africa.”

“While supraregional studies can help reveal population interactions on a continental scale,” says Schiffels, “we want to emphasize the importance of regionally focused studies to better understand local patterns of cultural and population changes in the future.”

The island of Sri Lanka in the Indian Ocean, just south of the Indian subcontinent, is home to the earliest fossils of our species, Homo sapiens, in South Asia. It also preserves clear evidence for human occupation and the use of tropical rainforest environments outside of Africa from ~48,000 to 3,000 years ago — refuting the idea that these supposedly resource-poor environments acted as barriers for migrating Pleistocene humans. The question as to exactly how humans obtained rainforest resources — including fast-moving food sources like monkeys and squirrels — remains unresolved.

In this new study, published in Science Advances, an international team of researchers from the Max Planck Institute for the Science of Human History (MPI-SHH) in Germany, Griffith University in Australia and the Department of Archaeology, Government of Sri Lanka, present evidence for the earliest use of bow-and-arrow technologies by humans anywhere outside of Africa. At ~48,000 years old, these tools are earlier than the first similar technology found in Europe. Clear evidence for use on the preserved bone arrowheads shows that they were likely used for hunting difficult-to-catch rainforest prey. Not only that, but the scientists show that other bone tools may have been used for making nets or clothing in tropical settings, dramatically altering traditional assumptions about how certain human innovations were linked with specific environmental requirements.

Hunting in the open and sheltering from the cold?

European cultural products in the form of cave art, amazingly detailed bone carvings, bone tool technologies, and tailored clothing have been frequently held up as the pinnacle of Late Pleistocene human cultural development. There, symbolic and technological innovations have been seen as key survival mechanisms equipping expanding populations to face cold northern climates. Meanwhile, discoveries of older bow-and-arrow technology and artistic or symbolic behaviors in open grassland or coastal settings in Africa have framed ‘savannah’ and marine environments, respectively, as key drivers behind early hunting and cultural experiments by Pleistocene humans in their evolutionary homeland.

As co-author of the new study, Patrick Roberts of the MPI-SHH argues that “this traditional focus has meant that other parts of Africa, Asia, Australasia, and the Americas have often been side-lined in discussions of the origins of material culture, such as novel projectile hunting methods or cultural innovations associated with our species.” Nevertheless, the last twenty years have highlighted how Pleistocene humans occupied and adapted to a variety of extreme environments as they migrated beyond Africa, including deserts, high-altitude settings and tropical rainforests such as those of Sri Lanka.

A tropical home

The new study saw scientists turn to the beautifully preserved material culture from the cave of Fa-Hien Lena, deep in the heart of Sri Lanka’s Wet Zone forests. As co-author Oshan Wedage, PhD at MPI-SHH, states, “Fa-Hien Lena has emerged as one of South Asia’s most important archaeological sites since the 1980s, preserving remains of our species, their tools, and their prey in a tropical context.” Some of the main finds from the site include remarkable single and doubled pointed bone tools that scientists had suspected were used in the exploitation of tropical resources. Direct proof had been lacking, however, in the absence of detailed high-powered microscopic analysis.

Michelle Langley of Griffith University, the lead author of the new study, is an expert in the study of microscopic traces of tool use and the creation of symbolic material culture in Pleistocene contexts. Applying cutting edge methods to the Fa-Hien Lena material confirmed the researchers’ hypothesis. As Langley states, “the fractures on the points indicate damage through high-powered impact — something usually seen in the use of bow-and-arrow hunting of animals. This evidence is earlier than similar findings in Southeast Asia 32,000 years ago and is currently the earliest clear evidence for bow-and-arrow use beyond the African continent.”

The evidence for early human innovation did not stop there. Applying the same microscopic approach to other bone tools, the team identified implements which seem to have been associated with freshwater fishing in nearby tropical streams, as well as the working of fiber to make nets or clothing. “We also found clear evidence for the production of colored beads from mineral ochre and the refined making of shell beads traded from the coast, at a similar age to other ‘social signaling’ materials found in Eurasia and Southeast Asia, roughly 45,000 years ago,” says Michelle Langley. Together, this reveals a complex, early human social network in the tropics of South Asia.

A flexible toolkit for new hunting grounds

The new study highlights that archaeologists can no longer link specific technological, symbolic, or cultural developments in Pleistocene humans to a single region or environment. “The Sri Lankan evidence shows that the invention of bows-and-arrows, clothing, and symbolic signaling occurred multiple times and in multiple different places, including within the tropical rainforests of Asia,” says co-author Michael Petraglia of the MPI-SHH. In addition to insulation in cold environments, clothes may have also helped against tropical mosquitoes, “and instead of just hunting large grassland mammals,” adds zooarchaeologist Noel Amano, another MPI-SHH co-author, “bows and arrows helped humans procure small, tree-dwelling primates and rodents.”

While archaeologists have long focused on the uniqueness of European markers of behavioural modernity, the new study is part of a growing awareness that many regions of the world saw extraordinary and complex new technologies emerge at the end of the Palaeolithic. “Humans at this time show extraordinary resourcefulness and the ability to exploit a range of new environments,” notes Nicole Boivin, Director at the MPI-SHH and study coauthor. “These skills enabled them to colonize nearly all of the planet’s continents by about 10,000 years ago, setting us clearly on the path to being the global species we are today.”

Still, many people do react with the typical allergic symptoms: sneezing, a runny nose, and itchy, swollen nasal passages. Others have a much more severe reaction: a life-threatening asthma attack.

To treat the root cause of allergies and asthma, researchers need to know exactly what sets these patients apart from healthy individuals.

In a new Science Immunology study, published on June 12, 2020, scientists at La Jolla Institute for Immunology (LJI) offer a clue to why non-allergic people don’t have a strong reaction to house dust mites. They’ve uncovered a previously unknown subset of T cells that may control allergic immune reactions and asthma from ever developing in response to house dust mites — and other possible allergens.

“We discovered new immune cell subsets and new therapeutic opportunities,” says Grégory Seumois, Ph.D., instructor and director of LJI’s Sequencing Core and co-leader of the new study. “This new population of cells could be one, out of many unknown mechanisms, that explains why healthy people don’t develop inflammation when they breathe in allergens.”

“The study highlights the power of unbiased single-cell genomics approaches to uncover novel biology,” says LJI Professor Pandurangan Vijayanand, M.D. Ph.D., senior author of the new study.

The study builds on the Vijayanand lab’s expertise in linking gene expression to disease development. The team also took advantage of the Immune Epitope Database, an LJI-led resource that houses information on how the immune system interacts with allergens like house dust mites.

Why house dust mites? These microscopic critters are hard to avoid, which means nearly everyone has been exposed. Even in people without a house dust mite (HDM) allergy, the immune system is likely to react in some way as it learns to recognize HDM molecules. This makes HDM a useful model for studying what causes allergies and asthma attacks.

The LJI team used a technique part of the “genomic revolution” arsenal of tools, called single-cell RNA-seq (or single cell transcriptomics) to see exactly which genes and molecules specific T cells produce in response to HDM allergens. They tested cells from four groups of people: people with asthma and HDM allergy, people with asthma but no HDM allergy, people with only HDM allergy, and healthy subjects.

Their analysis suggests that a subset of helper T cells, called interleukin (IL)-9 Th2 expressing HDM-reactive cells, is more prevalent in the blood of people with HDM-allergic asthma compared with those who are only allergic to HDM. Further analysis suggested that those IL9-TH2 cells are enriched in a group of molecules/genes that increased the cytotoxic potential of those cells. In other words, those specific T cells could kill other cells and drive inflammation.

In contrast, another subset of T cells stood out in the non-allergic subjects. These T cells express an “interferon response signature” and were enriched for a gene that encodes a protein called TRAIL. The work done by Seumois and his colleagues suggest that TRAIL could be important because it could dampen the activation of helper T cells.

This finding may mean that people with this specific cell population could have less T-cell driven inflammation in response to HDM allergens. At last, this could provide a clue to why some people develop allergies and asthma while others do not.

“Now if functional studies confirm this dampening effect, we’re curious if there is a way to boost the activation of these T cells or induce their proliferation in asthmatic or allergic populations,” says Seumois. “Can we act on those cells very early on, before asthma has developed?”

For example, genomics studies like this one may someday help identify children at risk of developing asthma and allergies. Early detection could open the door to preemptively acting on immune cells before development of allergy and asthma.

While Seumois emphasizes that there is much more work to be done, he says the transcriptomic method used for this study could accelerate future asthma and allergy research. “This is the first large-scale, single-cell, RNA-seq transcriptomic analysis for LJI,” says Seumois. “Now that we have developed the bench know-how and analysis pipeline, it could be applied to many diseases.”

In the new study, researchers surveyed 1,029 adults from 35 countries who were recruited through social media. Between 23 and 29 March 2020, participants completed the Brief HEXACO Inventory — which ranks six broad personality domains — and shared information on their demographics, perceived threat level of COVID-19, quarantine behaviors, and toilet paper consumption in recent weeks.

The most robust predictor of toilet paper stockpiling was the perceived threat posed by the pandemic; people who felt more threatened tended to stockpile more toilet paper. Around 20 percent of this effect was also based on the personality factor of emotionality — people who generally tend to worry a lot and feel anxious are most likely to feel threatened and stockpile toilet paper. The personality domain of conscientiousness — which includes traits of organization, diligence, perfectionism and prudence — was also a predictor of stockpiling.

Other observations were that older people stockpiled more toilet paper than younger people and that Americans stockpiled more than Europeans. The researchers pointed out that the variables studied explained only twelve percent of the variability in toilet paper stockpiling, which suggests that some psychological explanations and situational factors likely remain unaccounted for. “Subjective threat of COVID-19 seems to be an important trigger for toilet paper stockpiling. However, we are still far away from understanding this phenomenon comprehensively,” concludes Theo Toppe, co-author of the study.

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The study is one of the first to evaluate the cost-effectiveness of using elastomeric masks in a health care setting during the COVID-19 pandemic, said Sricharan Chalikonda, MD, MHA, FACS, lead study author and chief medical operations officer for Pittsburgh-based Allegheny Health Network (AHN), where the study took place.

Disposable N95 masks are the standard face covering when health care providers require high-level respiratory protection, but during the pandemic, providers experienced widespread supply chain shortages and price increases, Dr. Chalikonda said. He said hospitals need a long-term solution.

“We don’t know if there will be a shortage of N95s again. We don’t know how long the pandemic will last and how often there will be virus surges,” he said. “We believe now is the time to invest in an elastomeric mask program.”

Dr. Chalikonda said an immediate supply of elastomeric masks in a health care system’s stockpile of personal protective equipment is “game changing” given the advantages.

Benefits of elastomeric masks

Elastomeric masks are made of a tight-fitting, flexible, rubber-like material that can adjust to nearly all individuals’ faces and can withstand multiple cleanings, Dr. Chalikonda said. These devices, which resemble gas masks, use a replaceable filter. According to the Centers for Disease Control and Prevention (CDC), elastomeric masks offer health care workers equal or better protection from airborne infectious substances compared with N95 masks.

Like many hospitals during the COVID-19 crisis, AHN was disinfecting and reusing N95 masks for a limited number of uses. However, Dr. Chalikonda said, “Many caregivers felt the N95 masks didn’t fit quite as well after disinfection.”

At the end of March, AHN began a one-month trial of a half-facepiece elastomeric mask covering the nose and mouth. The mask holds a P100-rated cartridge filter, meaning it filters out almost 100 percent of airborne particles.

Until AHN could procure more elastomeric masks, the system began its program for P100 elastomeric mask “super-users”: those providers who have the most frequent contact with COVID-19 patients. At each of AHN’s nine hospitals in Pennsylvania and Western New York, the first providers to receive the new masks were respiratory therapists, anesthesia providers, and emergency department and intensive care unit (ICU) doctors and nurses. Initially, providers shared the reusable masks with workers on other shifts, and the masks underwent decontamination between shifts using vaporized hydrogen peroxide similar to the technique used to sterilize disposable N95 masks.

As more masks became available, workers kept their own mask and disinfected it themselves according to the manufacturer’s guidelines. Gradually AHN provided more staff with the new masks.

Among nearly 2,000 health care providers receiving fit testing for an elastomeric mask (as required for any mask to make sure no unfiltered air penetrates it), 94 percent could wear one, the investigators reported. The small number of workers without a proper fit received an alternate type of respirator mask.

After a month of use, no one wearing an elastomeric mask chose to return to an N95 mask, according to the authors. Regarding the elastomeric masks, Dr. Chalikonda said, “Our clinicians were very comfortable with the fit, knowing it was an equivalent if not superior amount of protection, and that these masks were intended to be reused.”

Furthermore, patients were receptive to their care providers wearing this type of respirator, he noted.

Cost savings

To determine if the elastomeric masks were cost-effective, the researchers performed a cost-benefit analysis over one month of mask disinfection and reuse comparing the new masks, with the filter replaced monthly, versus N95 masks at one hospital’s 18-bed intensive care unit (ICU). Although the elastomeric mask costs about $20 and the filter costs $10 compared with only $3 at that time for an N95 mask, the research team found the elastomeric masks were “conservatively” 10 times less expensive.

The cost savings, Dr. Chalikonda said, increases the longer they use the elastomeric masks, which often can last for years, and these masks can remain in storage for long periods, thus improving the planning and management of the medical supply stockpile for future outbreaks.

He explained the monthly cost is lower because they can disinfect elastomeric masks much more often, multiple caregivers can share the same mask, and, unlike N95s masks, they do not need to waste the mask after a failed fit test.

Another advantage of an elastomeric respirator program, according to Dr. Chalikonda, is it does not require any additional hospital resources to implement if the hospital already has an N95 mask reuse and resterilization program. The AHN elastomeric mask program presented fewer operational challenges than disinfecting N95 masks, he stated.

Other study authors are Hope Waltenbaugh, MSN, RN, CNOR, NE-BC; Sara Angelilli, MSN, RN, CNOR; Tiffany Dumont, DO; Curt Kvasager, MBA; Timothy Sauber, MD; Nino Servello, CRNA; Anil Singh, MD; and Rafael Diaz-Garcia, MD, FACS.

A letter published today in the New England Journal of Medicine and signed by an international group of 17 leading diabetes experts involved in the CoviDiab Registry project, a collaborative international research initiative, announces the establishment of a Global Registry of new cases of diabetes in patients with COVID-19.

The Registry aims to understand the extent and the characteristics of the manifestations of diabetes in patients with COVID-19, and the best strategies for the treatment and monitoring of affected patients, during and after the pandemic.

Clinical observations so far show a bi-directional relationship between COVID-19 and diabetes. On the one hand, diabetes is associated with increased risk of COVID-19 severity and mortality. Between 20 and 30% of patients who died with COVID-19 have been reported to have diabetes. On the other hand, new-onset diabetes and atypical metabolic complications of pre-existing diabetes, including life-threatening ones, have been observed in people with COVID-19.

It is still unclear how SARS-Cov-2, the virus that causes COVID-19, impacts diabetes. Previous research has shown that ACE-2, the protein that binds to SARS-Cov-2 allowing the virus to enter human cells, is not only located in the lungs but also in organs and tissues involved in glucose metabolism such as the pancreas, the small intestine, the fat tissue, the liver and the kidney. Researchers hypothesise that by entering these tissues, the virus may cause multiple and complex dysfunctions of glucose metabolism. It has also been known for many years that virus infections can precipitate type 1 diabetes.

Francesco Rubino, Professor of Metabolic Surgery at King’s College London and co-lead investigator of the CoviDiab Registry project, said: “Diabetes is one of the most prevalent chronic diseases and we are now realizing the consequences of the inevitable clash between two pandemics. Given the short period of human contact with this new coronavirus, the exact mechanism by which the virus influences glucose metabolism is still unclear and we don’t know whether the acute manifestation of diabetes in these patients represent classic type 1, type 2 or possibly a new form of diabetes.”

Paul Zimmet, Professor of Diabetes at Monash University in Melbourne, Honorary President of the International Diabetes Federation and co-lead investigator in the CoviDiab Registry project said: “We don’t yet know the magnitude of the new onset diabetes in COVID-19 and if it will persist or resolve after the infection; and if so, whether or not or COVID-19 increases risk of future diabetes. By establishing this Global Registry, we are calling on the international medical community to rapidly share relevant clinical observations that can help answer these questions.”

Stephanie Amiel, Professor of Diabetes Research at King’s College London and a co-investigator of the CoviDiab Registry project said: “The registry focuses on routinely collected clinical data that will help us examine insulin secretory capacity, insulin resistance and autoimmune antibody status to understand how COVID-19 related diabetes develops, its natural history and best management. Studying COVID-19-related diabetes may uncover novel mechanisms of disease.”

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