Culture

Philadelphia, May 11, 2020 - Artificial insemination (AI), breeding value estimation, and genomic selection have allowed substantial increases in milk and component yields for Holstein cows. However, their widespread use has also led to challenges including declining fertility, emergence of recessive genetic conditions, and a loss of genetic diversity--more than 99 percent of Holstein bulls born using AI in the last decade trace their male lineage to just two bulls born in the 1960s. Efforts to reconstitute two lost male lineages are reported in a recent article by scientists from the Pennsylvania State University Department of Animal Science and the National Animal Germplasm Program (NAGP), in the Journal of Dairy Science, published by Elsevier and FASS, Inc.

"Introgression of genetic diversity from such lineages into modern Holsteins is a long-term prospect with no guarantee of success," Dr. Chad Dechow said. "Nevertheless, these lines demonstrate the possibility of using semen from the 1950s to reintroduce lost genetic variation." Because the Y chromosome is passed only through males, these reconstituted lines will allow expanded research into Y-chromosome variation and function.

Two lines were identified for reconstitution from semen samples in the NAGP repository. The Netherland Prince line shares no known common male ancestors with the two most common Holstein lines; the Colantha line does not share a common male ancestor after the 1890s. Six calves were born to the Colantha lineage, and nine calves were born to the Netherland Prince lineage at the Penn State Dairy Production Research and Teaching Facility. One generation of mating the lost lineage bulls to elite modern females was sufficient to update the lost lineages to near breed average for most traits.

The breadth of the US Holstein germplasm collection facilitated the introgression of the lost Y chromosomes. Only time will tell whether the collection will have the same utility for yet-unknown issues that emerge.

SUMMARYThrough a combination of lab and field experiments, researchers have developed a better understanding of the factors accounting for different wood decomposition rates among fungi. The new findings reveal how an understanding of fungal trait variation can improve the predictive ability of early and mid-stage wood decay, a critical driver of the global carbon cycle.

THE SITUATIONFungi play a key role in the global carbon cycle as the main decomposers of litter and wood. While current earth system models represent only little of the functional variation in microbial groups, fungi differ greatly in their decomposing ability. The researchers set out to find which traits best explain fungal decomposition ability to help improve the current models.

THE FINDINGS

The hyphal extension rate–or fungal growth rate–is the strongest single predictor of fungal-mediated wood decomposition.
Decomposing ability varies along a spectrum from slow-growing, stress-tolerant fungi that are poor decomposers, to fast-growing, highly competitive fungi that have fast decomposition rates.
Slow growing, stress-tolerant fungi with poor intrinsic wood decaying abilities are more likely to exist in drier forests with high precipitation seasonality. In contrast, fast-growing, highly competitive fungi tend to be found in more favorable environments and decompose wood more quickly, regardless of the local microclimate.

FROM THE RESEARCHERS“Fungi are largely hidden players. We know they are critical for cycling carbon but it has been difficult to determine the effects of different decomposers in causing fast or slow decomposition. As we identify who fungal decomposers are in rotting logs and what allows a particular species to affect these rates, we can better predict carbon cycling around the globe under current and future climates. Our study takes a first step towards this, pairing complementary field and laboratory experiments to find that how fast different fungi grow and what enzymes they produce matter.”- Amy Zanne, associate professor of biology at the George Washington University

"Fungi differ massively in how quickly they decompose wood, releasing carbon back into the ecosystem. Our study identifies different fungal traits that explain this variation, which has great potential to improve predictions of the carbon cycle in forests.”- Nicky Lustenhouwer, lead author and postdoctoral scholar at the University of California, Santa Cruz

"We show that the same processes that determine where a fungus lives—that is, its ability to displace other fungi vs. survive in stressful environments—closely aligns with its decomposition ability. This connection allows us to translate an ecological mechanism into broad-scale patterns in microbial decomposition rates, helping to address a key uncertainty in earth system models."- Daniel Maynard, postdoctoral researcher at Crowther Lab, ETH Zurich

PUBLICATION INFORMATIONThe paper, “A trait-based understanding of wood decomposition by fungi” will be published in the Proceedings of the National Academy of Sciences during the week of Monday, May 11.

To schedule an interview with Dr. Zanne about the new research, please contact Timothy Pierce at [email protected] or 202-994-5647.

Journal

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.1909166117

BOSTON - Hutchinson-Gilford Progeria Syndrome (HGPS) is a fatal condition that is especially prevalent in the skin, cardiovascular and the musculoskeletal systems. There exists a wide gap between existing knowledge of the disease and a potential treatment or cure.

In a study published today in the journal Proceedings of the National Academies of Science, researchers led by Ara Nazarian, PhD, a principal investigator in the Center for Advanced Orthopaedic Studies at BIDMC, investigated the musculoskeletal phenotype of the homozygous G608G BAC-transgenic progeria mouse model, developed at Dr. Collins' lab at the National Institutes of Health, and determined the phenotypic changes of these mice after a five-arm preclinical trial of different treatment combinations with lonafarnib, pravastatin, and zoledronic acid.

"We observed that Lonafarnib did not improve bone or cartilage indices; however, treatment combinations with pravastatin and zoledronic acid significantly improved bone mechanical properties and cartilage structural parameters," said Nazarian.

The changes demonstrated in the cortical bone structure, rigidity and strength of the HGPS G608G mouse model may increase the risk for bending and deformation of bones, which could result in the skeletal dysplasia characteristic of HGPS. Cartilage abnormalities seen in this model resemble the changes observed in age-matched wild type animals, such as decreased cartilage thickness and volume. Such changes might mimic prevalent degenerative joint diseases, including osteoarthritis (OA), in the elderly.

More animal studies will be necessary before investigating the ability of this disease model to help with OA studies. But Nazarian is optimistic about the possibilities offered by this animal model.

"Osteoarthritis is a chronic debilitating disease that degrades articular cartilage and is one of the most common causes of chronic disability and pain in the elderly," said Cubria, previously a postdoctoral fellow at BIDMC and Harvard Medical School. "Accelerated aging animal models, such as this mouse model could offer a meaningful opportunity to study degenerative joint diseases."

In addition to Nazarian, coauthors include co-lead authors M. Belen Cubria and Sebastian Suarez, Aidin Masoudi, Ramin Oftadeh, Pramod Kamalapathy, Lamya Karim, and Brian D. Snyder, all of BIDMC; and Amanda DuBose, Michael R. Erdos, Wayne A. Cabral, and Francis S. Collins, of the National Institutes of Health.

Researchers at the University of Maryland, Baltimore County (UMBC) have developed a new solution to render an essential detail in many video games: human skin. The research is published in the Proceedings of the Association for Computing Machinery on Computer Graphics and Interactive Techniques. Marc Olano, associate professor of computer science and electrical engineering at UMBC, led this research alongside Tiantian Xie, Ph.D. '22, computer science. Xie, under the guidance of Olano, has worked with researchers at the gaming company Epic Games, developing a keen understanding of gamers' user experience, including the precise level of realism and detail that players are looking for in human characters.

Game developers seek to create visuals that are as realistic as possible without stepping into the "uncanny valley." This term describes when the graphics in a game attempt to portray a human as closely as possible, and gets close to mimicking real life, but not quite close enough, in a way users find disturbing. This creates an unpleasant feeling in users that might distract from their enjoyment of the game.

In many games, human skin is rendered in such a way that it looks like a plastic object. This plastic look can occur because animators aren't accounting for subsurface scattering - a key element of how light interacts with a textured 3D surface. Subsurface scattering is animators' main priority when it comes to transforming skin from looking like plastic to looking truly real.

Olano's method builds upon research developed by large gaming companies to create realistic depictions of human skin that will also load quickly within a gaming interface. "Our method adds an ability to adaptively estimate how many samples you actually need to get the look that you want without having to do a lot of additional computation to get a smooth image," explains Olano.

The method minimizes the amount of computation needed to create photo-realistic images. Previous techniques were either not realistic enough, or ran too slowly for use in games, negatively affecting the gaming experience. The new method is based on techniques developed for offline film production rendering. Xie, the first author of the paper, states, "Offline rendering techniques are not suitable for real-time rendering because adding the technique itself in real-time introduces a large overhead. Our technique eliminates this overhead."

Olano and his team created an algorithm to determine the pixels that would need to be rendered differently than the others due to light gradient change. Their sampling method uses temporal variance to lower the overall number of changes within each frame while still maintaining a realistic depiction of subsurface scattering. Since fewer changes are needed per frame, the method creates an efficient way of rendering realistic skin within the capabilities of today's computing power.

The algorithm used by Olano's team is built upon a foundation of research that is known and accessible to game developers. This offers a promising path for the gaming industry to pursue realism while maintaining an awareness of the computational ability of an average gaming system. Developers may be able to begin using this technique soon to create more realistic human figures in games, growing the gaming market even more.

The 2018 opening of a FreshDirect warehouse in Mott Haven, Bronx, significantly increased truck and vehicle flow within that neighborhood, leading to small upticks in air and noise pollution, according to a new study led by scientists at Columbia University Mailman School of Public Health. Results are published in the International Journal of Environmental Research and Public Health.

Between June 2017 and May 2020, the researchers collected measurements of traffic, air quality, and noise at eight sites near the warehouse, including four residential homes and a public housing complex. They observed an increase in truck and vehicle flow, especially during the overnight hours, with an overall traffic increase between 10 and 40 percent. The increased traffic at one monitoring site was not adequately predicted by the facility’s environmental assessment prior to construction. Based on their analyses of traffic-related pollution in the area, the researchers estimated increases of 0.06 dBA (noise) and 0.003 µg/m3 (black carbon air pollution).

Mott Haven has multiple major sources of air pollution, including two interstate highways, a large food distribution hub in nearby Hunts Point, and two waste transfer stations. As a result, the neighborhood experiences average air pollution levels higher than the Bronx or New York City as a whole. The area has a very high incidence of child asthma emergency department visits compared to the Bronx and New York City. Other health concerns include elevated obesity, diabetes, and hypertension rates, which can be exacerbated by air pollution, and disturbances and health effects from traffic-related noise. In addition, Mott Haven has nearly double the rate of pedestrian injury hospitalizations than New York City as a whole.

"Even small increases in air pollution are a concern to this community which is already overburdened by high levels of air pollution and related health risks," says senior author Markus Hilpert, PhD, associate professor of environmental health sciences. "In most New York City neighborhoods, air pollution levels have been in decline, and air pollution sources have been reduced or removed, not added. Mott Haven, which had higher than average amounts of pollutants from traffic and other sources even before the opening of this warehouse, is an exception."

"Air pollution is known to have disproportionate impacts on the health of populations with lower socio-economic status and ethnic and racial minorities," adds first author Jenni A. Shearston, MPH, a doctoral student in environmental health science at Columbia Mailman School. "Rather than building facilities that increase traffic, a known risk factor for negative health outcomes including asthma, New York City should invest in environmental structures such as public parks and open spaces to benefit the health of vulnerable groups."

The authors acknowledge several limitations to their study. Air quality and noise were only measured before the warehouse opened, and not after. Estimates for warehouse-related air pollution increases are based on assessments of traffic contributions to air pollution and noise derived from actual air pollution, noise, and traffic measurements, as well as the measured warehouse-related changes in traffic. In addition, construction of the warehouse could have increased traffic before the facility opened, which would minimize any observed changes. The warehouse may also have opened earlier than the estimated date of October 2018. Furthermore, the facility may increase traffic further in the future if their business continues to grow, making estimations of the impact of the facility on traffic even further underestimated.

(BOSTON) -- Stroke is the leading cause of serious long-term disability in the US with approximately 17 million individuals experiencing it each year. About 8 out of 10 stroke survivors suffer from "hemiparesis", a paralysis that typically impacts the limbs and facial muscles on one side of their bodies, and often causes severe difficulties walking, a loss of balance with an increased risk of falling, as well as muscle fatigue that quickly sets in during exertions. Oftentimes, these impairments also make it impossible for them to perform basic everyday activities.

To allow stroke patients to recover, many rehabilitation centers have looked to robotic exoskeletons. But although there are now a range of exciting devices that are enabling people to walk again who initially were utterly unable to do so, there remains significant active research trying to understand how to best apply wearable robotics for rehabilitation after stroke. Despite the promise, recent clinical practice guidelines now even recommend against the use of robotic therapies when the goal is to improve walking speed or distance.

In 2017, a multidisciplinary team of mechanical and electrical engineers, apparel designers, and neurorehabilitation experts at Harvard's Wyss Institute for Biologically Inspired Engineering and John A. Paulson School of Engineering and Applied Sciences (SEAS), and Boston University's (BU) College of Health & Rehabilitation Sciences: Sargent College showed that an ankle-assisting soft robotic exosuit, tethered to an external battery and motor, was able to significantly improve biomechanical gait functions in stroke patients when worn while walking on a treadmill. The cross-institutional and cross-disciplinary team effort was led by Wyss faculty members Conor Walsh, Ph.D. and Lou Awad, P.T., D.P.T., Ph.D, together with Terry Ellis, Ph.D., P.T., N.C.S. from BU.

Now, the same team took a critical step forward in translating their technology towards a rehabilitation strategy. Using an untethered version of the exosuit that carries its own battery and motor, they showed in a cohort of six post-stroke survivors with hemiparesis that their device could significantly increase individuals' walking speed by an average 0.14 meters per second, with one individual walking as much as 0.28 meters per second faster. These same individuals, when asked to walk as far as they can in 6 minutes, were able to go 32 meters farther, on average, with one person traveling over 100 meters farther. These findings are published in IEEE Open Journal of Engineering in Medicine and Biology (OJEMB).

"The vast majority of people who have had a stroke walk slowly and cannot walk very far. Faster and farther walking after physical therapy are among the most important outcomes desired by both, patients and clinicians. If neither speed nor distance are changed by a therapy, it would be difficult to consider that therapy to be effective," said Wyss Institute Associate Faculty member Lou Award, P.T., D.P.T., Ph.D., the study's first author who co-corresponded the findings to IEEE OJEMB together with Walsh. "The levels of improvement in speed and distance that we found in our exploratory study exceeded our expectations for an immediate effect without any training and highlight the promise of the exosuit technology." Awad also is Assistant Professor at BU's College of Health and Rehabilitation: Sargent College and Director of the Neuromotor Recovery Laboratory.

The exosuit deployed in this study weighs less than five kilograms and targets the limbs of stroke survivors during distinct phases of the gait cycle. Fully mobile, it is powered by a battery and initiated by an actuator unit both worn at the hips. It delivers mechanical power to the ankles via a cable-based mechanism, whereby the cables and other parts of the exosuit are anchored to the body by lightweight functional textiles. Adding further to its low weight and potential to reduce gait asymmetries is the fact that patients wear it only on the impaired paretic side, unlike rigid exoskeleton systems - many of which need to be worn on both sides.

Walsh's team designed the exosuit to assist with plantar flexion, the ankle movement that pushes the foot down into the ground during the stance phase of the gait cycle, and with dorsiflexion, in which the foot is lifted up and the toes pulled toward the shin during the swing phase. Both these movements are variably impaired in post-stroke hemiparetic walking, and survivors often exhibit a "drop foot", an inability to raise the foot from the ankles. Walsh, whose group has pioneered and broadly validated soft exosuit technology over the last years, is also the Paul A. Maeder Professor of Engineering and Applied Sciences at SEAS, and the Founder of the Harvard Biodesign Lab.

To demonstrate broad applicability for their approach in stroke survivors with hemiparesis, the team focused on six hemiparetic individuals with varying severities and types of impairments that were all entered a chronic phase. After an initial clinical assessment of patients, and adjustments of the exosuit to individuals, the researchers performed a series of tests on a 30-meter walkway. Wearing the exosuit unpowered did not cause any disadvantages with regards to participants' walking speeds, distances, or energy costs compared to when they were not wearing the exosuit. When the exosuit was then powered on, "we saw important and immediate improvements in walking speed and distance which are meaningful outcomes that make a real difference in everyday lives of individuals who have sustained a stroke. It's these kind of clinically meaningful outcomes that stimulate excitement among physical therapists and others in the rehabilitation community", said co-author Ellis, Ph.D., P.T., N.C.S., Director of the Center for Neurorehabilitation at Sargent College and Associate Professor and Chair of Physical Therapy at BU.

"Our engineering and clinical teams at Harvard and Boston University are highly motivated by these results to refine the technology and study its immediate impact in stroke survivors with a wide range of walking abilities. We are also eager to explore therapeutic applications in both clinical settings and day-to-day walking in the home and community," said Awad.

"This study by the team beautifully shows how exosuit technology developed at the Wyss Institute and its partners could make a real difference in the lives of many stroke survivors, and it is a compelling demonstration of how the Institute's translation model rapidly creates and drives new solutions to some of our major health problems that can change the lives of patients for the better," said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children's Hospital, as well as Professor of Bioengineering at SEAS.

Anxiety-prone people can blame serotonin cleanup proteins gone awry in their amygdala, according to research in marmosets recently published in JNeurosci. Targeting the amygdala with anti-anxiety medication could provide quicker relief.

The same event or set of life circumstances could send one person into the depths of anxiety or despair while leaving another unaffected. This distinction, called trait anxiety, arises from the proteins involved in serotonin signaling, a neurotransmitter implicated in anxiety and depression.

Quah et al. measured the level of gene expression for genes encoding serotonin transporters -- the protein tasked with cleaning up serotonin after its release -- and those encoding receptors in marmosets. The researchers focused on brain areas involved in emotional processing, such as the amygdala and prefrontal cortex. Marmosets with greater trait anxiety had high levels of gene expression for serotonin transporters in their amygdalae. The research team administered selective serotonin reuptake inhibitors (SSRIs), a common anxiety medication, directly into the amygdalae of anxious marmosets. This provided immediate symptom relief -- an effect that normally takes several weeks to appear if the drug is taken orally.

What The Viewpoint Says: Ways in which mental health care might change as a result of the COVID-19 pandemic are described.

Authors: John Torous, M.D., of Beth Israel Deaconess Medical Center and Harvard Medical School is Boston, 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/jamapsychiatry.2020.1640)

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

What The Viewpoint Says: Questions about how the COVID-19 pandemic will alter telepsychiatry practice are examined in this article.

Authors: Jay H. Shore, M.D., M.P.H., of the Colorado School of Public Health and Anschutz Medical Campus of the University of Colorado in Aurora, 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/jamapsychiatry.2020.1643)

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

What The Study Did: Nearly 14,000 current and former National Football League (NFL) players were included in an observational study that examined whether a greater amount of repeated head impacts throughout a professional football career were associated with increased risk of death.

Authors: Brittany L. Kmush, Ph.D., of Syracuse University in Syracuse, New York, 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.2020.4442)

Editor's Note: The article includes funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

What The Study Did: Nearly 60 articles were reviewed to assess the rate of preexposure prophylaxis (PrEP) use for HIV prevention among at-risk teens in the United States and to provide recommendations for how to improve access to and use of PrEP.

Authors: Allison L. Agwu, M.D., Sc.M., of the Johns Hopkins University School of Medicine in Baltimore, 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/jamapediatrics.2020.0824)

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

After analysing organic residues from ancient pots, a team of scientists led by the University of Bristol has uncovered new evidence of dairying by hunter-gatherers in the landlocked South African country of Lesotho in the mid-late first millennium AD.

The study on organic residue analysis from South African hunter-gatherer pots is being published today in Nature Human Behaviour.
Extensive archaeological evidence shows that Early Iron Age agricultural communities settled in the coastal regions of KwaZulu-Natal in South Africa from around AD 400.

Although these farmers appear to have been in contact with local lowland hunter-gatherer groups, it was long assumed that they had little or no direct contact with hunter-gatherers already occupying the mountainous regions of Lesotho, as they did not settle the region until the 19th century due to the unsuitability of the mountains for crop cultivation.

Over the past several decades however, remains of domestic animal bones have been uncovered in several sites in the Maloti-Drakensberg Mountains in Lesotho in hunter-gatherer contexts dating to the 1st and 2nd millennia AD.

At one site in particular - Likoaeng - domestic animal bones were found in association with an Early Iron Age potsherd and some fragments of iron. This discovery led to the suggestion that the hunter-gatherers occupying the site were following a 'hunters-with-sheep' mode of subsistence that incorporated the keeping of small numbers of livestock into what was otherwise a foraging economy and that they must have obtained these animals and objects through on-going contact with agricultural groups based on the coast.

In the past five years however, several studies have sequenced DNA from supposed domestic animal bones from these highland sites, and instead found them to belong to wild species. This led to the suggestion that the presence of domestic animals in the highlands, and therefore the level of contact, had been overestimated, yet the zooarchaeologists involved stand by their original morphological assessment of the bones.

Lead researcher, Helen Fewlass, now based at the Max Planck Institute for Evolutionary Anthropology (Leipzig) but who carried out the work as part of her master's project in the University of Bristol's Department of Anthropology and Archaeology, said: "We used organic residue analysis to investigate fats that become absorbed into the porous clay matrix of a pot during its use.

"We extracted and analysed lipid residues from pots from two hunter-gatherer sites with domestic livestock remains in the highlands of Lesotho, Likoaeng and Sehonghong, dating to the mid-late first millennium AD and compared them to lipids extracted from pots from a recent nearby agricultural settlement, Mokatlapoli.

"This allowed us to explore the subsistence practices of the hunter-gatherers occupying these sites to see if there was any evidence for their contact with farming groups."

The team found that dairy residues were present in approximately a third of the hunter-gatherer pots. They directly radiocarbon dated a dairy residue from Likoaeng to AD 579-654 and another from Sehonghong to AD 885-990. The results confirm the presence of domestic animals at these sites in the 1st millennium AD.

The team also observed patterning in the stable carbon isotopic values of fatty acids in the residues, which imply that different methods of animal husbandry were practised by the 1st millennium hunter-gatherer groups compared to the recent agricultural group occupying the same region.

The stable carbon isotopic values of dairy residues from the agricultural site clearly reflect the introduction of crops such as maize and sorghum into the region in the late nineteenth century and the foddering of domestic animals upon them.

As the hunter-gatherer groups must have learnt animal husbandry techniques, the results support the notion that hunter-gatherer groups in the highlands of Lesotho had on-going contact with farming communities in the lowlands, rather than just obtaining the animals through raids or long-distance exchange networks. Based on the direct date of the dairy residue from Likoaeng, contact must have been established within a few centuries of the arrival of agricultural groups in the coastal regions of South Africa.

The results also have implications for the on-going debate about the molecular vs morphological assessment of the faunal remains. The results of the organic residue analysis support the osteoarchaeological evidence for the presence of domestic animals at Likoaeng and Sehonghong. However, as large amounts of milk can be generated from one domestic animal, the prevalence of dairy residues does not tell us how many domestic animals were present.

Direct radiocarbon dating of domestic faunal remains in these contexts has been hampered by poor collagen preservation. The new method (published earlier this month in Nature) for direct dating of fats extracted from potsherds represents a new avenue for placing the arrival and presence of domestic animals in the area in a secure chronological context.

Helen Fewlass added: "The presence of dairy fats in pots from Likoaeng and Sehonghong in highland Lesotho shows that hunter-gatherers in the mountains had adopted at least sporadic use of livestock from agricultural groups in South Africa not long after their arrival in the 1st millennium AD."

Co-author, Dr Emmanuelle Casanova, from the University of Bristol's Organic Geochemistry Unit - part of the School of Chemistry, added: "In addition to the identification of dairying practices we were able apply a brand-new dating method for pottery vessels to verify the antiquity of the dairy residues which perfectly fits with the age of the hunter-gatherer groups."

This study represents the first analysis and direct radiocarbon dating of organic residues from pottery from south-eastern Africa. The high level of preservation found implies that the method has great potential for further applications in the region. This mountainous area of Lesotho has other hunter-gatherer sites containing pottery in contexts dating to the 1st and 2nd millennium AD so there is potential to expand this type of analysis to other sites in the region to understand whether this practise was relatively isolated or ubiquitous.

Investigators at the Stanford University School of Medicine and several other institutions have shown that a new type of vaccination can substantially enhance and sustain protection from HIV.

A paper describing the vaccine, which was given to monkeys, will be published online May 11 in Nature Medicine. The findings carry broad implications for immunologists pursuing vaccines for the coronavirus and better vaccines for other diseases, said Bali Pulendran, PhD, professor of pathology and of microbiology and immunology at Stanford.

The key to the new vaccine's markedly improved protection from viral infection is its ability -- unlike almost all vaccines now in use -- to awaken a part of the immune system that most current vaccines leave sleeping.

"Most vaccines aim at stimulating serum immunity by raising antibodies to the invading pathogen," said Pulendran, referring to antibodies circulating in blood. "This vaccine also boosted cellular immunity, the mustering of an army of immune cells that chase down cells infected by the pathogen. We created a synergy between these two kinds of immune activity."

Pulendran, the Violetta L. Horton Professor II, shares senior authorship of the study with Rama Amara, PhD, professor of microbiology and immunology at Yerkes Primate Research Center at Emory University; Eric Hunter, PhD, and Cynthia Derdeyn, PhD, professors of pathology and lab medicine at Emory; and David Masopust, PhD, professor of microbiology and immunology at the University of Minnesota. The lead authors are Prabhu Arunachalam, PhD, a postdoctoral scholar at Stanford; postdoctoral scholars Tysheena Charles, PhD, and Satish Bollimpelli, PhD, of Emory; and postdoctoral scholar Vineet Joag, PhD, of the University of Minnesota.

38 million people with AIDS

Some 38 million people worldwide are living with AIDS, the once inevitably fatal disease caused by HIV. While HIV can be held in check by a mix of antiviral agents, it continues to infect 1.7 million people annually and is the cause of some 770,000 deaths each year.

"Despite over three decades of intense research, no preventive HIV vaccine is yet in sight," Pulendran said. Early hopes for such a vaccine, based on a trial in Thailand whose results were published in 2012, were dashed just months ago when a larger trial of the same vaccine in South Africa was stopped after a preliminary assessment indicated that it barely worked.

Vaccines are designed to arouse the adaptive immune system, which responds by generating cells and molecular weaponry that target a particular pathogen, as opposed to firing willy-nilly at anything that moves.

The adaptive immune response consists of two arms: serum immunity, in which B cells secrete antibodies that can glom onto and neutralize a microbial pathogen; and cellular immunity, in which killer T cells roam through the body inspecting tissues for signs of viruses and, upon finding them, destroying the cells that harbor them.

But most vaccines push the adaptive immune system to fight off infections with one of those arms tied behind its back.

"All licensed vaccines to date work by inducing antibodies that neutralize a virus. But inducing and maintaining a high enough level of neutralizing antibodies against HIV is a demanding task," Pulendran said. "We've shown that by stimulating the cellular arm of the immune system, you can get stronger protection against HIV even with much lower levels of neutralizing antibodies."

In the new study, he and his colleagues employed a two-armed approach geared toward stimulating both serum and cellular immunity. They inoculated three groups of 15 rhesus macaques over a 40-week period. The first group received several sequential inoculations of Env, a protein on the virus's outer surface that's known to stimulate antibody production, plus an adjuvant, a chemical combination often used in vaccines to beef up overall immune response. The second group was similarly inoculated but received additional injections of three different kinds of viruses, each modified to be infectious but not dangerous. Each modified virus contained an added gene for a viral protein, Gag, that's known to stimulate cellular immunity.

A third group, the control group, received injections containing only the adjuvant.

At the end of the 40-week regimen, all animals were allowed to rest for an additional 40 weeks, then given booster shots of just the Env inoculation. After another rest of four weeks, they were subjected to 10 weekly exposures to SHIV, the simian version of HIV.

Monkeys who received only the adjuvant became infected. Animals in both the Env and Env-plus-Gag groups experienced significant initial protection from viral infection. Notably, though, several Env-plus-Gag animals -- but none of the Env animals -- remained uninfected even though they lacked robust levels of neutralizing antibodies. Vaccinologists generally have considered the serum immune response -- the raising of neutralizing antibodies -- to be the defining source of a vaccine's effectiveness.

Even more noteworthy was a pronounced increase in the duration of protection among animals getting the Env-plus-Gag combination. Following a 20-week break, six monkeys from the Env group and six from the Env-plus-Gag group received additional exposures to SHIV. This time, four of the Env-plus-Gag animals, but only one of the Env-only animals, remained uninfected.

Pulendran said he suspects this improvement resulted from the vaccine-stimulated production of immune cells called tissue-resident memory T cells. These cells migrate to the site where the virus enters the body, he said, and park themselves there for a sustained period, serving as sentinels. If they see the virus again, these cells jump into action, secreting factors that signal other immune-cell types in the vicinity to turn the tissue into hostile territory for the virus.

"These results suggest that future vaccination efforts should focus on strategies that elicit both cellular and neutralizing-antibody response, which might provide superior protection against not only HIV but other pathogens such as tuberculosis, malaria, the hepatitis C virus, influenza and the pandemic coronavirus strain as well," Pulendran said.

A new technique could provide vital information about a community's immunity to infectious diseases including malaria and COVID-19.

The diagnostic test analyses a blood sample to reveal immune markers that indicate whether - and when - a person was exposed to an infection. It was developed to track malaria infections in communities, to assist in the elimination of deadly 'relapsing' malaria, but is now being adapted to track immunity to COVID-19 in more detail than existing tests.

This new diagnostic approach in malaria, published today in Nature Medicine, has the potential to enhance infectious diseases surveillance. This could be of particular benefit in lower income countries where it can enable health authorities to track the spread of a disease such as malaria in a community and target resources where they are most needed. The research was led by researchers from the Walter and Eliza Hall Institute, Australia; Pasteur Institute, France; and Ehime University, Japan.

At a glance

- An international team has developed a new approach to detecting a person's immunity to an infectious disease - providing valuable details about whether and when a person was exposed to the infection.

- The test was developed for detecting recent exposure to malaria, but the research team are now working to adapt it to detect previous exposure to the coronavirus that causes COVID-19.

- By providing a detailed picture of when an infection spread in a community, the test offers new opportunities for improving infection control and elimination strategies - particularly in lower income countries.

Detecting past infections

Exposure to viruses, parasites or bacteria triggers immune responses that lead to antibodies circulating in the blood. These antibodies can remain for years, but over time the amount of different types of antibodies changes.

The new diagnostic technique allows researchers to look in detail at the amounts of different antibodies in the blood, to pinpoint whether - and importantly when - a person has been exposed to a particular infection, said Professor Ivo Mueller, who led the research and has joint appointments at the Walter and Eliza Hall Institute and the Pasteur Institute.

"Many tests for immunity give a simple 'yes or no' answer to whether someone has antibodies to the infectious agent," he said. "In contrast, our test - which was initially developed to look at malaria infections - can pinpoint how long ago a person was exposed to an infection.

"This information is extremely valuable for tracking the spread of an infection in a population. Particularly in lower income countries it may not be possible to monitor the actual spread of the infection, but it is very helpful to look retrospectively at whether the infection has been spreading - and to monitor the effectiveness of infection control programs, and respond to disease resurgence," he said.

The team established this research to understand the spread of relapsing 'vivax' malaria. The parasite causing this form of malaria - the most widespread malaria parasite in the world - can be carried in a dormant state by people and later reawaken to continue to disease spread, causing significant challenges for malaria control.

Professor Mueller said that his team in Melbourne and France were now applying the systems they have established for malaria to detect immunity to the coronavirus that causes COVID-19.

"We have already started to study the blood of people who have had COVID-19 infections to document the types of antibodies they carry. In the next six months we hope to have discovered how these antibodies change over time, meaning we can use this information to explore immunity in wider groups in the community.

"This is not a tool for diagnosing individual people, but rather for monitoring COVID-19 disease spread in populations. In countries in the Asia-Pacific, Africa or Latin America, it is possible that COVID-19 will be spreading undetected in some regions for the coming year - especially as governments try to loosen shutdown restrictions. This test could be invaluable for informing these decisions."

Eliminating malaria

Walter and Eliza Hall Institute researcher and joint lead author Dr Rhea Longley said the malaria blood test had been validated using samples contributed by people living in malaria-endemic regions of Brazil, Thailand and the Solomon Islands.

"Our investigations confirmed that the test could detect people who had been infected with P. vivax in the preceding nine months - and who would thus be at risk of recurring malaria infections," Dr Longley said.

"This information will enable better surveillance and deployment of resources to areas where malaria remains, and targeted treatment of infected individuals. This could be a huge improvement in how vivax malaria is controlled and eventually eliminated."

Further development of the malaria blood test received a recent boost with funding from an Australian Government NHMRC Development Grant, which commenced in 2020.

"We will be working with the Australian biotech company Axxin to develop a diagnostic test for malaria that can be deployed in the field, based on the immune markers our laboratory testing identified," Professor Mueller said. "We plan to continue clinical trials investigating how our test can guide malaria elimination efforts, and having a rapid field test will be an important aspect of this."

Two studies report new Homo sapiens fossils from the site of Bacho Kiro Cave in Bulgaria. "The Bacho Kiro Cave site provides evidence for the first dispersal of H. sapiens across the mid-latitudes of Eurasia. Pioneer groups brought new behaviours into Europe and interacted with local Neanderthals. This early wave largely predates that which led to their final extinction in western Europe 8,000 years later", says Jean-Jacques Hublin, director at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.

An international research team, led by Jean-Jacques Hublin, Tsenka Tsanova and Shannon McPherron of the Max Planck Institute for Evolutionary Anthropology, and Nikolay Sirakov and Svoboda Sirakova of the National Institute of Archaeology with Museum at the Bulgarian Academy of Sciences in Sofia, Bulgaria, renewed excavations at Bacho Kiro Cave in 2015. The most spectacular finds come from a rich, dark layer near the base of the deposits. Here the team uncovered thousands of animal bones, stone and bone tools, beads and pendants and the remains of five human fossils.

Protein analysis

Except for one human tooth, the human fossils were too fragmented to be recognized by their appearance. Instead, they were identified by analysing their protein sequences. "Most Pleistocene bones are so fragmented that by eye, one cannot tell which species of animal they represent. However, the proteins differ slightly in their amino acid sequence from species to species. By using protein mass spectrometry, we can therefore quickly identify those bone specimens that represent otherwise unrecognizable human bones", says Frido Welker, Postdoctoral Research Fellow at the University of Copenhagen and research associate at the Max Planck Institute for Evolutionary Anthropology.

To know the age of these fossils and the deposits at Bacho Kiro Cave, the team worked closely with Lukas Wacker at ETH Zurich, Switzerland, using an accelerator mass spectrometer to produce ages with higher precision than normal and to directly date the human bones.

"The majority of animal bones we dated from this distinctive, dark layer have signs of human impacts on the bone surfaces, such as butchery marks, which, along with the direct dates of human bones, provides us with a really clear chronological picture of when Homo sapiens first occupied this cave, in the interval from 45,820 to 43,650 years ago, and potentially as early as 46,940 years ago", says Helen Fewlass of the Max Planck Institute for Evolutionary Anthropology. "The radiocarbon dates at Bacho Kiro Cave are not only the largest dataset of a single Palaeolithic site ever made by a research team, but also are the most precise in terms of error ranges", say researchers Sahra Talamo from the University of Bologna and Bernd Kromer from the Max Planck Institute in Leipzig.

DNA sequencing

Though some researchers have suggested that Homo sapiens may have already occasionally entered Europe by this time, finds of this age are typically attributed to Neanderthals. To know which group of humans were present at Bacho Kiro Cave, Mateja Hajdinjak and Matthias Meyer of the genetics team led by Svante Pääbo at the Department of Evolutionary Genetics at the Max Planck Institute for Evolutionary Anthropology sequenced the DNA from the fragmented fossils bones.

"Given the exceptionally good DNA preservation in the molar and the hominin fragments identified by protein mass spectrometry, we were able to reconstruct full mitochondrial genomes from six out of seven specimens and attribute the recovered mitochondrial DNA sequences from all seven specimens to modern humans. Interestingly, when relating these mtDNAs to those of other ancient and modern humans, the mtDNA sequences from Layer I fall close to the base of three main macrohaplogroups of present-day people living outside of Sub-Saharan Africa. Furthermore, their genetic dates align almost perfectly with those obtained by radiocarbon", says Mateja Hajdinjak, Postdoctoral Fellow at the Francis Crick Institute in London and research associate at the Max Planck Institute for Evolutionary Anthropology.

The results demonstrate that Homo sapiens entered Europe and began impacting Neanderthals by around 45,000 years ago and likely even earlier. They brought into Bacho Kiro Cave high quality flint from sources up to 180 km from the site which they worked into tools like pointed blades perhaps to hunt and very likely to butcher the remains of the animals found at the site.

"The animal remains from the site illustrate a mix of cold and warm adapted species, with bison and red deer most frequent", says palaeontologist Rosen Spasov from the New Bulgarian University. These were butchered extensively but were also used as a raw material source. "The most remarkable aspect of the faunal assemblage is the extensive collection of bone tools and personal ornaments", says zooarchaeologist Geoff Smith from the Max Planck Institute for Evolutionary Anthropology. Cave bear teeth were made into pendants, some of which are strikingly similar to ornaments later made by Neanderthals in western Europe.

Homo sapiens replaced Neanderthals

Taken together, the Bacho Kiro Cave sediments document the period of time in Europe when Middle Paleolithic Neanderthals were replaced by Upper Paleolithic Homo sapiens (the so-called transition period), and the first Homo sapiens assemblages are what archaeologists call the Initial Upper Paleolithic. "Up to now, the Aurignacian was thought of as the start of the Upper Paleolithic in Europe, but the Initial Upper Paleolithic of Bacho Kiro Cave adds to other sites in western Eurasia where there is an even older presence of Homo sapiens", notes Nikolay Sirakov of the National Institute of Archaeology with Museum at the Bulgarian Academy of Sciences.

"The Initial Upper Paleolithic in Bacho Kiro Cave is the earliest known Upper Palaeolithic in Europe. It represents a new way of making stone tools and new sets of behaviour including manufacturing personal ornaments that are a departure from what we know of Neanderthals up to this time", says Tsenka Tsanova of the Department of Human Evolution at the Max Planck Institute for Evolutionary Anthropology. "The Initial Upper Paleolithic probably has its origin in southwest Asia and soon after can be found from Bacho Kiro Cave in Bulgaria to sites in Mongolia as Homo sapiens rapidly dispersed across Eurasia and encountered, influenced, and eventually replaced existing archaic populations of Neanderthals and Denisovans."