Lead author Dr Ian Towle, of the Sir John Walsh Research Institute in the Faculty of Dentistry, says the “surprisingly large” monkey lemur, Archaeolemur, had novel anatomical features not seen in living lemurs, such as lacking a ‘tooth comb’ in the front of the mouth for grooming.

“These extinct lemurs are so different to those alive today. They also show fascinating similarities to monkeys and apes, including humans,” he says.

The study, published in the American Journal of Biological Anthropology, aimed to assess the diet of Archaeolemur by analysing chipping in 447 teeth, comparing chipping frequencies to those of other primates.

The results were surprising — with these remarkable extinct lemurs with dentitions resembling baboons in shape; but presenting tooth chipping patterns similar to fossil hominins such as Neanderthals.

“Archaeolemur tooth chipping patterns are unlike any living primate, with their front teeth showing substantial fractures, often with numerous tooth chips on a single tooth, yet very little chipping on their back teeth.

“Similar tooth fracture patterns are observed in fossil hominins, such as Neanderthals. Typically, in Neanderthals these fracture patterns are thought to be related to tool-use behaviours,” Dr Towle says.

The results fit with previous research on Archaeolemur, in particular evidence that their large and robust front teeth may have been used to process a diet containing hard and tough foods.

Dr Towle thinks the study raises the “fascinating possibility” that stone tools do not necessarily explain the high rate of fractures on Neanderthal teeth.

“Archaeolemur shows similar tooth chipping patterns, yet there is no evidence to suggest they were capable of, or used, such tools.

“Studying extinct primates not only provides crucial insight into their diet and behaviour, but also elucidates our own evolutionary history.”

Given the overlap in skull and dental shape, and potential similarities in diet and behaviour, it is perhaps not surprising that Archaeolemur  was thought to be an ape when first discovered in Madagascar over 100 years ago.

“Archaeolemur is a brilliant example of convergent evolution, showing remarkable similarities to monkeys and apes. This species also highlights the extent to which lemurs in Madagascar diversified into a variety of ecological niches.”

Dr Carolina Loch, also from Sir John Walsh Research Institute, and who mentored Dr Towle during his tenure as postdoctoral fellow at the SJWRI, says the research is another great example of the “breadth and depth of multidisciplinary research” at the Faculty of Dentistry.

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Their results were published this week in the Proceedings of Royal Society B.

“We essentially reverse-engineered the inner working of the wing musculoskeletal system — how the muscles and skeleton work in hummingbirds to flap the wings,” said first author and Penn State mechanical engineering graduate student Suyash Agrawal. “The traditional methods have mostly focused on measuring activity of a bird or insect when they are in natural flight or in an artificial environment where flight-like conditions are simulated. But most insects and, among birds specifically, hummingbirds are very small. The data that we can get from those measurements are limited.”

The researchers used muscle anatomy literature, computational fluid dynamics simulation data and wing-skeletal movement information captured using micro-CT and X-ray methods to inform their model. They also used an optimization algorithm based on evolutionary strategies, known as the genetic algorithm, to calibrate the parameters of the model. According to the researchers, their approach is the first to integrate these disparate parts for biological fliers.

“We can simulate the whole reconstructed motion of the hummingbird wing and then simulate all the flows and forces generated by the flapping wing, including all the pressure acting on the wing,” Cheng said. “From that, we are able to back-calculate the required total muscular torque that is needed to flap the wing. And that torque is something we use to calibrate our model.”

With this model, the researchers uncovered previously unknown principles of hummingbird wing actuation.

The first discovery, according to Cheng, was that hummingbirds’ primary muscles, that is, their flight engines, do not simply flap their wings in a simple back and forth motion, but instead pull their wings in three directions: up and down, back and forth, and twisting — or pitching — of the wing. The researchers also found that hummingbirds tighten their shoulder joints in both the up-and-down direction and the pitch direction using multiple smaller muscles.

“It’s like when we do fitness training and a trainer says to tighten your core to be more agile,” Cheng said. “We found that hummingbirds are using similar kind of a mechanism. They tighten their wings in the pitch and up-down directions but keep the wing loose along the back-and-forth direction, so their wings appear to be flapping back and forth only while their power muscles, or their flight engines, are actually pulling the wings in all three directions. In this way, the wings have very good agility in the up and down motion as well as the twist motion.”

While Cheng emphasized that the results from the optimized model are predictions that will need validation, he said that it has implications for technological development of aerial vehicles.

“Even though the technology is not there yet to fully mimic hummingbird flight, our work provides essential principles for informed mimicry of hummingbirds hopefully for the next generation of agile aerial systems,” he said.

The other authors were Zafar Anwar, a doctoral student in the Penn State Department of Mechanical Engineering; Bret W. Tobalske of the Division of Biological Sciences at the University of Montana; Haoxiang Luo of the Department of Mechanical Engineering at Vanderbilt University; and Tyson L. Hedrick of the Department of Biology at the University of North Carolina.

The Office of Naval Research funded this work.

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While the Diprotodon — the extinct megafauna species that is distantly related to wombats but was the size of a small car — is commonly (but incorrectly) thought of as Australia’s ‘giant wombat’, researchers from Griffith University have shed light on a large species that does belong in the modern-day wombat family.

The complete skull of this true fossil giant wombat, found in a Rockhampton cave in Queensland and estimated to be around 80,000 years old, has been described for the first time by a team led by Associate Professor Julien Louys from Griffith’s Australian Research Centre for Human Evolution.

Associate Professor Louys said the discovery provided unprecedented insights into the biology and appearance of these previously little known ‘gentle giants’.

“The extinct megafauna of Australia never ceases to amaze and intrigue not just Australians, but people all over the world,” he said.

“Although one of the most charismatic of the giant mammals to go extinct, Diprotodon is commonly referred to as a ‘giant wombat’. But this is incorrect as Diprotodon belongs to an entirely different family — equivalent to saying a hippo is just a giant pig.

“There were however, true giant wombats. These have traditionally been poorly known, but the discovery of the most complete skull of one of these giants, Ramsayia, has provided us with an opportunity to reconstruct what this creature looked like, where and when it lived, and how the evolution of giant wombats took place in Australia.”

The cranium and mandible of the Ramsayia magna fossil was discovered from the rear of the front chamber of Lower Johansons Cave in Rockhampton in the early 2000s, but it was only through subsequent excavations and analysis by Associate Professor Louys’s team that is was confirmed as belonging to a previously described but very poorly known species.

Extinct giant wombats of the family Vombatidae (broadly defined as twice the size of modern wombats) are rarer than the fossil diprotodontids that are often popularly — and incorrectly — referred to as giant wombats.

Associate Professor Louys said this giant wombat — Ramsayia — had extensive cranial sinuses, which had not been previously reported for a wombat.

“This indicates that the wombat had a large, rounded skull for the attachment of specific and strong chewing muscles,” he said.

“The giant wombat also possessed a ‘premaxillary spine’, an indication that it had a large, fleshy nose.

“In this paper, we show that all true giant wombats evolved large body sizes first, then individually became quite specialised to eat different types of grasses.

“We also dated this species as being about 80,000 years old. This is the first date for this species and is much earlier than human arrival in Australia, although we still don’t know exactly when or why this species became extinct.”

The research ‘Cranial remains of Ramsayia magna from the Late Pleistocene of Australia and the evolution of gigantism in wombats (Marsupialia, Vombatidae)’ has been published in Papers In Palaeontology.

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The researchers said the results indicate that rocatinlimab has the potential to change the genetic makeup of a person’s atopic dermatitis for the long term, and possibly help sustain lasting results without continued use. Rocatinlimab inhibits OX40 — an immune molecule involved in activating inflammatory cells that play a key role in the development of atopic dermatitis and other inflammatory diseases.

“Atopic dermatitis, the most common type of eczema, is a debilitating chronic inflammatory skin disease that affects 1 in 10 Americans and millions of people worldwide,” said Emma Guttman, MD, PhD,Waldman Professor and System Chair, The Kimberly and Eric J. Waldman Department of Dermatology; Director, Center of Excellence in Eczema; and Director, Laboratory of Inflammatory Skin Diseases, at the Icahn School of Medicine at Mount Sinai. “It often develops at a very young age, causing the skin to become inflamed, red, extremely itchy, painful, and very dry — all symptoms that greatly affect a patient’s quality of life. We are very optimistic about the results of this trial and the potential for disease modification and long-lasting effects to improve patients’ quality of life.”

In this phase 2b multicenter, double-blind, placebo-controlled study, 274 patients were recruited and (rocatinlimab: n=217; placebo: n=57) randomly assigned 1:1:1:1:1 to rocatinlimab every four weeks (150 mg or 600 mg) or every two weeks (300 mg or 600 mg) or subcutaneous placebo up to week 18, with an 18-week active-treatment extension and 20-week follow-up. This trial was conducted at 65 sites within the United States, Canada, Japan, and Germany.

Percent change from baseline in the Eczema Area and Severity Index (EASI) score was assessed as the primary endpoint at week 16, and significance versus placebo was achieved with all active rocatinlimab doses (-48% to -61%) doses compared to placebo (-15%). All active dose cohorts also continued improving after week 16, and most patients maintained the response for at least 20 weeks off treatment.

The results support rocatinlimab as a safe and effective treatment for moderate to severe atopic dermatitis, with potentially long-lasting efficacy and disease modification. Adverse events reported were generally similar between rocatinlimab groups. Common adverse events during the double-blind period included fever, chills, headache, aphthous ulcers (canker sores), and nausea.

“At week 36, all participants had been on the treatment for at least 18 weeks,” added Dr. Guttman, senior author of the study. “By this time, we saw that while the drug achieved the primary endpoints in all doses versus the placebo, it’s also a drug that improves over time, which is really unusual and unique among currently available treatment options.”

Researchers plan to continue this investigation in a phase 3 program in 2023. Future studies will also include a larger study population, longer follow-up, and exploration of combination therapy (such as rocatinlimab plus topical corticosteroids).

The trial is registered on ClinicalTrials.gov (NCT03703102).

CanRisk-Prostate, developed by researchers at the University of Cambridge and The Institute of Cancer Research, London, will be incorporated into the group’s CanRisk web tool, which has now recorded almost 1.2 million risk predictions. The free tool is already used by healthcare professionals worldwide to help predict the risk of developing breast and ovarian cancers.

Prostate cancer is the most common type of cancer in men. According to Cancer Research UK, over 52,000 men are diagnosed with the disease each year and there are more than 12,000 deaths. Over three-quarters (78%) of men diagnosed with prostate cancer survive for over ten years, but this proportion has barely changed over the past decade in the UK.

Testing for prostate cancer involves a blood test that looks for a protein known as a prostate-specific antigen (PSA) that is made only by the prostate gland; however, it is not always accurate. According to the NHS website, around three in four men with a raised PSA level will not have cancer. Further tests, such as tissue biopsies or MRI scans, are therefore required to confirm a diagnosis.

Professor Antonis Antoniou from the Department of Public Health and Primary Care at the University of Cambridge said: “Prostate cancer is the most common cancer in men in the UK, but population-wide screening based on PSA isn’t an option: these tests are often falsely positive, which means that many men would then be biopsied unnecessarily. Also, many prostate tumours identified by PSA tests are slow-growing and would not have been life-threatening. The treatment of these tumours may do more harm than good.

“What we need is a way of identifying those men who are at greatest risk, allowing us to target screening and diagnostic tests where they are most needed, while also reducing the harms for those men who have low risk of the disease. This is what CanRisk-Prostate aims to do. For the first time, it combines information on the genetic makeup and prostate cancer family history, the main risk factors for the disease, to provide personalised cancer risks.”

Prostate cancer is one of the most genetically determined of common cancers. Inherited faulty versions of the BRCA2, HOXB13 and possibly BRCA1 genes are associated with moderate-to-high risk of prostate cancer, though such faults are rare in the population. In addition, there are several hundred more common genetic variants that each confer a lower risk, but in aggregate they act like ‘volume control’ that moderate or increase the prostate cancer risk.

Writing in the Journal of Clinical Oncology, the researchers — supported by Cancer Research UK — describe the development of the first comprehensive prostate cancer model using genetic and cancer family history data from almost 17,000 families affected by prostate cancer. It uses data on rare genetic faults in moderate-to-high-risk genes and a risk score based on 268 common low-risk variants, together with detailed cancer family history, to predict the future risks.

One in six men (16%) will develop prostate cancer by the time they are 85 years old. Using the model, the team found that the predicted risk was higher for men who had a father diagnosed with prostate cancer — 27% if the father was diagnosed at an older age (80 years) but as high as 42% if the father was diagnosed at a young age (50 years).

The risks were considerably higher for men with genetic faults. For example, 54% of men who carry an alteration in the BRCA2 gene would develop prostate cancer — however, among men with BRCA2 gene faults, the risks were substantially lower if they also had a small number of the low-risk variants, but much higher if they also had a large number of the low-risk variants.

In practice, say the researchers, clinicians will be able to use any combination of cancer family history, rare and common genetic variants to provide a personalised risk.

To validate their model, the team ran the risk model on an independent cohort of over 170,000 men recruited to UK Biobank, a biomedical database and research resource containing anonymised genetic, lifestyle and health information from half a million UK participants. All of these men were free from prostate cancer when they were recruited to the study, but more than 7,600 developed prostate cancer within the subsequent ten years.

When validating their model, the researchers found that 86% of the UK Biobank participants who developed cancer were in the half of men with the highest predicted risks, which suggests that it may be possible to target screening and diagnostic tests to the subgroup of the population at highest risk, among whom the majority of the cancers will occur.

Dr Tommy Nyberg from the MRC Biostatistics Unit at Cambridge said: “We’ve created the most comprehensive tool to date for predicting a man’s risk of developing prostate cancer. We hope this will help clinicians and genetic counsellors assess their clients’ risk and provide the appropriate follow-up.

“Over the next 12 months, we aim to build this tool into the widely used CanRisk tool, which will facilitate the risk-based clinical management of men seen in family cancer clinics and enable risk-adapted early detection approaches to the population at large.”

Professor Ros Eeles from The Institute of Cancer Research, London and co-author on the study said: “This is an important step forward as it will enable clinicians to have conversations with men about their individual risk of prostate cancer based on the most accurate computer model to date. This will help them in making decisions about screening.”

So far, the data used to develop CanRisk-Prostate has been from men of European ancestry. The team hope to be able to include data from men of other ethnicities as further research is undertaken.

The University of Cambridge recently launched the Early Cancer Institute with the aim of detecting cancer early enough to cure it. It is the first physical institute in the UK dedicated to early cancer. A new Cambridge Cancer Research Hospital is also planned for the near future, bringing together clinical and research expertise in a new, world-class hospital, designed in partnership with patients.

There is also an Early Detection and Diagnosis centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust where a prostate risk clinic has been established to translate these findings into targeted screening programmes.

The research was supported by the Cancer Research UK-funded CanRisk programme. Additional support for CanRisk-Prostate was provided by Prostate Cancer UK, The Institute of Cancer Research, Everyman Campaign, National Cancer Research Network UK, National Cancer Research Institute, NIHR Cambridge Biomedical Research Centre and the NIHR Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust.