Culture

Here is a link to watch a video interview with Dr. Beatrice Aramini about this topic on the Oncotarget YouTube Channel

Oncotarget published "Cancer stem cells and macrophages: molecular connections and future perspectives against cancer" which reported that Cancer stem cells have been considered the key drivers of cancer initiation and progression due to their unlimited self-renewal capacity and their ability to induce tumor formation.

Macrophages, particularly tumor-associated macrophages, establish a tumor microenvironment to protect and induce CSCs development and dissemination.

Many studies in the past decade have been performed to understand the molecular mediators of CSCs and TAMs, and several studies have elucidated the complex crosstalk that occurs between these two cell types.

The aim of this Oncotarget review is to define the complex crosstalk between these two cell types and to highlight potential future anti-cancer strategies.

The aim of this Oncotarget review is to define the complex crosstalk between these two cell types and to highlight potential future anti-cancer strategies

Dr. Beatrice Aramini from The University of Modena and Reggio Emilia said, "Cancer stem cells (CSCs) constitute a cancer cell subpopulation similar to the other stem cell types in terms of self-renewal and multilineage differentiation potential but drive tumor development besides heterogeneity and dissemination of cancer cells."

The role of ALDH as a possible marker for lung cancer stem cell: as ALDH cells in cancer cell lines, as well as those extracted from lung cancer tissue, for the properties that it showed as forming spheres in culture tumor cells lines as well as in cells extracted from lung cancer tissue.

However, currently there is no specific or standard marker in lung cancer cells that can define this subpopulation of cells, probably due to the complex localization of these markers and their epigenetic regulation.

A theory regarding the role of CSCs in cancer progression is based on the premise that tumor tissue is hierarchically organized into different types of cells wherein CSC subpopulation is at the top of this hierarchy, with the other levels consisting of more differentiated tumor cells or cells with a limited proliferative potential.

Another essential characteristic that places CSCs at the top of the tumor cell hierarchy is their unlimited proliferation potential, which allows them to repopulate the tumor even if bulk tumor cells have been removed.

The Aramini Research Team concluded in their Oncotarget Review, "Generating new information about the interaction between TAMs and CSCs will be one of the most important challenges for the development of more effective targeted cancer therapies."

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DOI - https://doi.org/10.18632/oncotarget.27870

Full text - https://www.oncotarget.com/article/27870/text/

Correspondence to - Beatrice Aramini - beatrice.aramini@unimore.it

Keywords -
cancer stem cells,
macrophages,
future perspectives,
cancer,
target treatments

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Journal

Oncotarget

DOI

10.18632/oncotarget.27870

A technology that is widely used by commercial genetic testing companies is "extremely unreliable" in detecting very rare variants, meaning results suggesting individuals carry rare disease-causing genetic variants are usually wrong, according to new research published in the BMJ.

After hearing of cases where women had surgery scheduled after wrongly being told they had very rare genetic variations in the gene BRCA1 that could significantly increase risk of breast cancer, a team at the University of Exeter conducted a large-scale analysis of the technology using data from nearly 50,000 people. They found that the technology wrongly identified the presence of very rare genetic variants in the majority of cases.

The team analysed SNP chips, which test genetic variation at hundreds-of-thousands of specific locations across the genome. While excellent at detecting common genetic variation that can increase the risk of diseases such as type 2 diabetes, geneticists have long known they are less reliable at detecting rarer variation. However, this problem is less well known outside the genetic research community, and SNP chips are widely used by commercial companies that offer genetic testing direct to consumers.

Caroline Wright, Professor in Genomic Medicine at the University of Exeter Medical School, senior author on the paper, said: "SNP chips are fantastic at detecting common genetic variants, yet we have to recognise that tests that perform well in one scenario are not necessarily applicable to others. We've confirmed that SNP chips are extremely poor at detecting very rare disease-causing genetic variants, often giving false positive results that can have profound clinical impact. These false results had been used to schedule invasive medical procedures that were both unnecessary and unwarranted."

The team compared data from SNP chips with data from the more reliable tool of next generation sequencing in 49,908 participants of UK Biobank, and an additional 21 people who shared results of their consumer genetic tests via the Personal Genome Project.

The study concluded that SNP chips performed extremely well in detecting common genetic variants. However, the rarer the variation was, the less reliable the results became. In very rare variants, present in fewer than 1 in 100,000 individuals, typical of those causing rare genetic disease, 84 per cent were false positives in UK Biobank. In the data from commercial customers, 20 of 21 individuals analysed had at least one false positive rare disease-causing variant that had been incorrectly genotyped.

Dr Leigh Jackson, Lecturer in Genomic Medicine at the University of Exeter and co-author of the paper, said: "The number of false positives on rare genetic variants produced by SNP chips was shockingly high. To be clear: a very rare, disease-causing variant detected using a SNP chip is more likely to be wrong than right. Although some consumer genomics companies perform sequencing to validate important results before releasing them to consumers, most consumers also download their "raw" SNP chip data for secondary analysis, and this raw data still contain these incorrect results. The implications of our findings are very simple: SNP chips perform poorly for detecting very rare genetic variants and the results should never be used to guide a patient's medical care, unless they have been validated."

Recreational drinking, smoking, and drug use is linked to premature heart disease in young people, particularly younger women, finds research published online in the journal Heart.

Those who regularly use 4 or more substances are 9 times as likely to be affected, the findings indicate.

The numbers of new cases of heart disease (atherosclerotic cardiovascular disease) have been increasing in young adults, but the potential role of recreational substance use isn't entirely clear.

To probe this further, the researchers explored whether the recreational use of tobacco, cannabis, alcohol, and illicit drugs, such as amphetamine and cocaine, might be linked to prematurely and extremely prematurely furred up arteries.

They drew on information supplied to the 2014-2015 nationwide Veterans Affairs Healthcare database and the Veterans with premaTure AtheroscLerosis (VITAL) registry.

Extremely premature heart disease was defined as an 'event', such as a heart attack, angina, or stroke before the age of 40, while premature heart disease was defined as an event before the age of 55 in men and before the age of 65 in women.

In all, there were 135,703 people with premature heart disease and 7716 with extremely premature heart disease. They were compared with 1,112, 45 patients who didn't have premature heart disease.

Recreational use of any substance was independently associated with a higher likelihood of premature and extremely premature heart disease.

Patients with premature heart disease were more likely to smoke (63% vs 41%), drink (32% vs 15%), and to use cocaine (13% vs 2.5%), amphetamines (3% vs 0.5%), and cannabis (12.5% vs 3%).

After accounting for potentially influential factors, such as high blood pressure, diabetes, and high cholesterol, those who smoked tobacco were nearly twice as likely to have premature heart disease while those who drank recreationally were 50% more likely to do so.

Cocaine users were almost 2.5 times as likely to have premature heart disease, while those who used amphetamines were nearly 3 times as likely to do so. Cannabis users were more than 2.5 times as likely to have premature heart disease while those using other drugs were around 2.5 times as likely to do so.

The higher the number of substances used recreationally, the greater was the risk of premature heart disease, ranging from a doubling in risk with the use of 1 substance to a 9-fold heightened risk for those using 4 or more.

Similar trends were observed among those who had extremely premature heart disease, with recreational substance use associated with 1.5 to 3 times higher odds of heart disease.

The associations were even stronger among women with premature and extremely premature heart disease than among similarly affected men.

This is an observational study, and as such can't establish causality. And the researchers acknowledge that they were unable to gather information on other potentially influential factors, such as the dose and duration of recreational substance use.

In a linked editorial, Dr Anthony Wayne Orr of LSU Health Shreveport, Louisiana, points out that use of cocaine and methamphetamine have been associated with faster cell ageing and neurocognitive decline, with higher than average loss of grey matter.

And epidemiological studies suggest that 1 in 5 young adults misuse several substances and that these 'polysubstance users' often start using at younger ages, and so have worse health over the long term, he says.

The growing body of published research on these issues "suggests the need for a nationwide education campaign on the potential long-term damage being done to the cardiovascular system in patients with substance use disorders," he argues.

These people need to be aware of the long term consequences for their health beyond the risk of an overdose, while doctors should screen patients with a history of substance misuse, he says.

"We are only young once, and we should do everything in our power to maintain that state as long as we can," he concludes.

Ageism, sexism, and Western ideals of the nuclear family have excluded grandmothers from national and international policy initiatives to save newborn lives in the Global South, suggests an analysis published in the online journal BMJ Global Health.

This is despite published research indicating that they are a valuable and influential resource for children's health and survival in many cultures, the study author points out.

Around three out of 4 newborn deaths in the Global South occur in the first week of life--40% of them on the first day, and most of them at home.

But Initiatives to promote the survival of newborns across the Global South have primarily focused on strengthening health services and on young mothers within a nuclear family unit, to the exclusion of caregiver roles and practices within the wider family, says the author.

And extra funds invested in programmes to cut the newborn death rate have had relatively little impact.

To explore the role of the wider family in the care of newborns, and specifically that of grandmothers, the author reviewed relevant published studies of 70 different cultures in the three continents of Africa, Asia, and Latin America.

Cultures in the Global South tend to be collectivist rather than individualist, as in the West. They feature hierarchy based on age and experience, with elders as teachers of younger generations, and interdependency and shared decision-making valued over autonomy.

The studies revealed that grandmothers' knowledge is not always up to date and that some of their newborn practices may be harmful.

But where initiatives have recognised the value of grandmothers, such as in Nepal, Uttar Pradesh in India, Malawi, Burkina Faso and Senegal, these have been successful and prove that grandmothers may not be as resistant to change as is often assumed, notes the author.

The studies also revealed numerous examples of the significant role and influence of experienced older women, or grandmothers, on newborn care, both as authoritative advisors and direct caregivers within multi-generational family systems.

These roles extend from pregnancy onwards and include care of sick newborns, acting as breastfeeding coaches, and providing vital emotional and social support networks.

And across all three continents, the studies showed that grandmothers have similar core roles in newborn care, irrespective of variations in cultural practice.

"A growing body of evidence from across non-western, collectivist societies reveals the culturally designated role of these experienced, older women as newborn advisors and caregivers," writes the author.

"Unfortunately, at the global level, newborn research, policies and interventions continue to focus primarily on medical technologies and services, [and] to a lesser extent on mothers."

She adds: "While all research reviewed provides evidence of grandmothers' influence on newborn care, surprisingly, some does not explicitly recommend their inclusion in future programmes.

"Unfortunately, there is continued reluctance to explicitly involve grandmothers in interventions addressing newborn and other [mother and child health] issues.

"This appears to be related to: the often-repeated idea that grandmothers are barriers to change; a narrow perception of grandmothers focusing on their harmful traditional practices; and gender and ageist biases toward older women."

Future research should be grounded within a family systems framework that reflects collectivist cultures, argues the author.

And initiatives to save newborn lives should "aim not only to strengthen health services, but also influential family caregivers, particularly grandmothers and the indigenous social support networks of which they are a part," she concludes.

A new first-of-its-kind study has questioned whether pub operators can effectively and consistently prevent COVID-19 transmission - after researchers observed risks arising in licensed premises last summer.

Led by the University of Stirling, the research was conducted in May to August last year in a wide range of licensed premises which re-opened after a nationwide lockdown, and were operating under detailed guidance from government intended to reduce transmission risks.

While observed venues had made physical and operational modifications on re-opening, researchers found that practices were variable and a number of incidents of greater concern were observed - these included close physical interaction between customers and with staff, which frequently involved alcohol intoxication and were rarely effectively stopped by staff.

The new study - published in the Journal of Studies on Alcohol and Drugs - is the first in the world to examine the operation of COVID-19 measures in licensed premises and its findings will inform governments, public health experts, and policymakers in the UK and other countries as they consider the impact of the pandemic on hospitality and the risks of lifting restrictions.

Professor Niamh Fitzgerald, Director of the University of Stirling's Institute for Social Marketing and Health, led the research, which was funded by the Scottish Government Chief Scientist Office.

Professor Fitzgerald said: "Our study explored and observed business practices and behaviours of customers and staff in licensed premises in summer 2020 with a view to understanding if and how COVID-19 transmission risks could be managed in settings where alcohol is served. We interviewed business owners and representatives prior to re-opening to understand the challenges being faced. When pubs reopened last July, following the initial UK lockdown, our team visited premises to observe how government measures designed to reduce transmission risks in hospitality settings were working in practice, including any incidents likely to increase those risks.

"Businesses expressed an intention to work within the guidance, but there were commercial and practical challenges to making this a reality. Upon re-opening, substantial efforts to change the layout of bars were observed and appeared to be working well in many premises, but problems were common including staff not wearing personal protective equipment, or with the management of toilets, queues and other 'pinch points'. We also observed several incidents of greater concern -including customers shouting, embracing or repeatedly interacting closely with several households and staff - which were rarely addressed by staff.

"We concluded that, despite the efforts of bar operators and guidance from government, potentially significant risks of COVID-19 transmission persisted in at least a substantial minority of observed bars, especially when customers were intoxicated. Closures of premises can eliminate these risks, but also cause significant hardship for business owners and staff."

The UK entered national lockdown on March 20 last year. In Scotland, licensed premises were permitted to reopen indoor spaces from July 15, with strict safety rules in place to minimise the risk
of transmission. Premises operating to a one-metre physical distancing limit had to install appropriate signage, all customers had to be seated, staff had to wear face coverings, and improved ventilation and noise reduction measures had to be introduced. Following a large outbreak in early August linked to licensed premises in Aberdeen, it was made a legal requirement for customer details to be collected for contact tracing, and guidance was strengthened around queuing, standing and table service.

Interviews

Prior to the restrictions being lifted, the research team conducted interviews with stakeholders - including representatives from major relevant Scottish and UK trade associations - to gauge the sector's thoughts and feelings around implementing COVID-19 measures in licensed premises.

While businesses expressed a willingness to work within government guidance to protect customers and staff, support consumer confidence and enable a return to trading, the interviews - conducted in May and June - also identified commercial challenges of doing so, including financial implications and a risk of compromising the customer experience.

Interviewees felt that there were factors that would help moderate transmission risks, including existing legal requirements on premises (for example, prohibition on selling to drunk customers); industry expertise in managing customer behaviour, including drunkenness; new norms such as allowing table service only; and public anxiety around COVID-19 generally leading to more responsible behaviours. They acknowledged that staff would need to be trained and skilled in implementing the new measures - but also felt that some customers may not appreciate, or respond to, intervention.

Licensed premises observations

Twenty-nine observations of licensed premises took place in July and August, with the researchers monitoring premises for up to two hours while posing as customers. The study found that:

Venues had introduced new layouts, signage, queuing systems, noise and toilet management, and provided hand sanitising stations - however, stations were infrequently used. Two of the venues routinely administered sanitiser to customers' hands on entry.

Most venues required customers to provide contact details to support contact tracing, however, nine businesses observed did not - including one venue visited after this was made mandatory by the Scottish Government in August.

While staff wore personal protective equipment (PPE) in most venues, in several, staff wore no PPE, wore masks inappropriately, or removed them to talk to other staff or customers.

Most venues distanced their tables by one metre or more, or had installed partitions between booths, however, several had tables closer together than that without partitions.

One-way systems were implemented to help regulate the flow of customers - although this measure was sometimes ignored - and pinch points were problematic in nearly all venues, with entrances, corridors, doorways or bar counter areas leading to bottlenecks and people congregating, often unchallenged. Fewer than half of venues offered table service only - which helps avoid any possibility of queuing for service at the bar - and, in at least one venue observed in July, a continuous queue formed in the one-metre space between tables.

Fewer than half of venues had a basic system (for example, a sign on a door) in place to limit the number of customers entering toilets - while most had no measures to ensure physical distancing inside those areas, with no cubicles or sinks condemned. Overcrowding and poor physical distancing was observed to be a problem within toilet areas in some premises.

Incidents

A wide range of incidents with potential to increase transmission risk were observed in all but three venues, with multiple incidents reported in most. Incidents deemed to be of greater concern - due to the repeated or continuous nature of the potential risk, the large number of customers involved, or the involvement of staff - were observed in eleven venues. These included: various combinations of singing, shouting or playing music; mixing between groups; standing and moving around the bar without distancing; customers taking photographs with other customers and staff; shaking hands or embracing others who did not appear to be in their household. Notably, in all but one of the venues visited in August, customers were witnessed singing loudly or shouting, and with just one example of effective staff intervention to suppress customer noise.

The research team identified factors which interacted to give rise to the more serious incidents, including: physical set up and operation of premises, a social atmosphere, customer behaviour, alcohol consumption and staff practices. All but one of these incidents were observed in the evening; all but two occurred in premises located in a town or village, rather than a city; all but three allowed bar service (rather than table service only); and customers often appeared to be regulars.

In the majority of premises, no staff intervention in incidents or attempts to enforce restrictions were observed. In some cases, staff intervened in a light-hearted way - for example, by gently or playfully reprimanding customers - but such interventions were largely ineffective. Enforcement by external agencies - such as environmental health or police officers - was not observed in any of the venues.

The research report notes that Scottish Government guidance does not go into detail on exactly how bar or security staff might be expected to effectively and safely intervene in customer breaches of distancing, or in the management of situations which would normally require close contact between customers and staff - such as the removal of very drunk or belligerent customers from the premises.

Evidence

Professor Fitzgerald said: "Our study makes a unique contribution by providing the first evidence, including direct observation data, of how premises operated in practice when allowed to reopen during the COVID-19 pandemic. Overall, our findings suggest grounds for uncertainty about the extent to which new rules can be consistently and effectively implemented in a sector where interaction between tables, households and strangers is the norm, and alcohol is routinely consumed.

"Despite the efforts of licensed premises, and detailed guidance from Government, potentially significant risks of COVID-19 transmission persisted in a substantial minority of observed bars - especially when customers were intoxicated. Blanket closures, curfews or alcohol sales bans are more likely to be deemed necessary to control virus spread, if such risks cannot be acceptably, quickly and cost-effectively reduced through support and/or sanctions for premises operators. Such blanket actions may also have benefits in terms of protecting staff from occupational exposure and reducing pressure on emergency services from alcohol-related injuries or disorder. However, attention also needs to be paid to the impact of closures on businesses, economic activity, employee hardship, and ownership patterns in the sector, as well as any risks posed by diversion of some drinking to the home."

Feathers are a sleek, intricate evolutionary innovation that makes flight possible for birds, but in addition to their stiff, aerodynamic feathers used for flight, birds also keep a layer of soft, fluffy down feathers between their bodies and their outermost feathers to regulate body temperature.

Using the Smithsonian's collection of 625,000 bird specimens, Sahas Barve, a Peter Buck Fellow at the Smithsonian's National Museum of Natural History, led a new study to examine feathers across 249 species of Himalayan songbirds, finding that birds living at higher elevations have more of the fluffy down--the type of feathers humans stuff their jackets with--than birds from lower elevations. Published on Feb. 15 in the journal Ecography, the study also finds that smaller-bodied birds, which lose heat faster than larger birds, tend to have longer feathers in proportion to their body size and thus a thicker layer of insulation.

Finding such a clear pattern across so many species underscores how important feathers are to a bird's ability to adapt to its environment and suggests that adding down may be a strategy common to all songbirds, or passerines as they are known to researchers. Furthermore, finding that birds from colder environments tend to have more down may one day help researchers predict which birds are most vulnerable to climate change simply by studying their feathers.

"The Himalayas are seeing some of the fastest rates of warming on Earth," Barve said. "At the same time, climate change is driving an increase in the frequency and intensity of extremely cold events like snowstorms. Being able to accurately predict the temperatures a bird can withstand could give us a new tool to predict how certain species might respond to climate change."

The research was inspired by a tiny bird called a goldcrest during a frigid morning of field work in the Sho-kharkh forest of the Himalayas. Barve found himself wondering how this bird, which weighs about the same as a teaspoon of sugar, was able to flit about the treetops in icy air that was already numbing his fingers. Shoving his hands back into the pockets of his thick down jacket, the question that formed in Barve's mind was "Do Himalayan birds wear down jackets?"

To answer that question, Barve and his co-authors used a microscope to take photos of the chest feathers of 1,715 specimens from the Smithsonian's collections representing 249 species from the cold, high-altitude Himalayan Mountains. Then, Barve and his co-authors used those super-detailed photos to determine exactly how long each feather's downy section was relative to its total length. The team was able to do that by looking at the fluffy downy section of each feather close to its base when compared to the streamlined ends of most birds' feathers.

After meticulously logging the relative lengths of all those downy sections, Barve analyzed the results and found that the smallest birds and the birds from the highest elevations, where temperatures are at their coldest, tended to have the highest proportion of down on their body feathers. The analysis showed that high-elevation birds had up to 25% more down in their feathers, and the smallest bird had feathers that were three times as long as the largest birds, proportionately to their body size.

Past research suggested that birds from colder habitats sported added downy insulation, but Barve said this is the first study to analyze this pattern for such a large number of species in cold environments and across 15,000 feet of elevation.

"Seeing this correlation across so many species makes our findings more general and lets us say these results suggest all passerine birds may show this pattern," Barve said. "And we never would have been able to look at so many different species and get at this more general pattern of evolution without the Smithsonian's collections."

Carla Dove, who runs the museum's Feather Identification Lab and contributed to the study, said she was excited to work together with Barve to use the Smithsonian's collections in a new way. "Sahas looked at more than 1,700 specimens. Having them all in one place in downtown Washington, D.C., as opposed to having to go to the Himalayas and study these birds in the wild, obviously makes a big difference. It allowed him to gather the data he needed quickly before the COVID lockdowns swept the globe, and then work on the analysis remotely."

Barve said he is following up this study with experiments looking into just how much insulation birds get from their feathers and then will tie that to the feather's structure and proportion of down. One day, Barve aims to develop a model that will allow scientists to look at the structure of a feather and predict how much insulation it gives the bird--a capability that could help researchers identify species vulnerable to climate change.

Dove said the potential to use these results to eventually understand how some birds might cope with climate change highlights the importance of museum collections. "We have more than 620,000 bird specimens collected over the past 200 years waiting for studies like this. We don't know what our specimens will be used for down the line; that's why we have to maintain them and keep enhancing them. These specimens from the past can be used to predict the future."

PITTSBURGH, Feb. 15, 2021 - By capitalizing on a convergence of chemical, biological and artificial intelligence advances, University of Pittsburgh School of Medicine scientists have developed an unusually fast and efficient method for discovering tiny antibody fragments with big potential for development into therapeutics against deadly diseases.

The technique, published today in the journal Cell Systems, is the same process the Pitt team used to extract tiny SARS-CoV-2 antibody fragments from llamas, which could become an inhalable COVID-19 treatment for humans. This approach has the potential to quickly identify multiple potent nanobodies that target different parts of a pathogen--thwarting variants.

"Most of the vaccines and treatments against SARS-CoV-2 target the spike protein, but if that part of the virus mutates, which we know it is, those vaccines and treatments may be less effective," said senior author Yi Shi, Ph.D., assistant professor of cell biology at Pitt. "Our approach is an efficient way to develop therapeutic cocktails consisting of multiple nanobodies that can launch a multipronged attack to neutralize the pathogen."

Shi and his team specialize in finding nanobodies--which are small, highly specific fragments of antibodies produced by llamas and other camelids. Nanobodies are particularly attractive for development into therapeutics because they are easy to produce and bioengineer. In addition, they feature high stability and solubility, and can be aerosolized and inhaled, rather than administered through intravenous infusion, like traditional antibodies.

By immunizing a llama with a piece of a pathogen, the animal's immune system produces a plethora of mature nanobodies in about two months. Then it's a matter of teasing out which nanobodies are best at neutralizing the pathogen--and most promising for development into therapies for humans.

That's where Shi's "high-throughput proteomics strategy" comes into play.

"Using this new technique, in a matter of days we're typically able to identify tens of thousands of distinct, highly potent nanobodies from the immunized llama serum and survey them for certain characteristics, such as where they bind to the pathogen," Shi said. "Prior to this approach, it has been extremely challenging to identify high-affinity nanobodies."

After drawing a llama blood sample rich in mature nanobodies, the researchers isolate those nanobodies that bind specifically to the target of interest on the pathogen. The nanobodies are then broken down to release small "fingerprint" peptides that are unique to each nanobody. These fingerprint peptides are placed into a mass spectrometer, which is a machine that measures their mass. By knowing their mass, the scientists can figure out their amino acid sequence--the protein building blocks that determine the nanobody's structure. Then, from the amino acids, the researchers can work backward to DNA--the directions for building more nanobodies.

Simultaneously, the amino acid sequence is uploaded to a computer outfitted with artificial intelligence software. By rapidly sifting through mountains of data, the program "learns" which nanobodies bind the tightest to the pathogen and where on the pathogen they bind. In the case of most of the currently available COVID-19 therapeutics, this is the spike protein, but recently it has become clear that some sites on the spike are prone to mutations that change its shape and allow for antibody "escape." Shi's approach can select for binding sites on the spike that are evolutionarily stable, and therefore less likely to allow new variants to slip past.

Finally, the directions for building the most potent and diverse nanobodies can then be fed into vats of bacterial cells, which act as mini factories, churning out orders of magnitude more nanobodies compared to the human cells required to produce traditional antibodies. Bacterial cells double in 10 minutes, effectively doubling the nanobodies with them, whereas human cells take 24 hours to do the same.

"This drastically reduces the cost of producing these therapeutics," said Shi.

Shi and his team believe their technology could be beneficial for more than just developing therapeutics against COVID-19--or even the next pandemic.

"The possible uses of highly potent and specific nanobodies that can be identified quickly and inexpensively are tremendous," said Shi. "We're exploring their use in treating cancer and neurodegenerative diseases. Our technique could even be used in personalized medicine, developing specific treatments for mutated superbugs for which every other antibiotic has failed."

Experts have devised a novel approach to selecting photos for police lineups that helps witnesses identify culprits more reliably.

In a paper published by the Proceedings of the National Academy of Sciences, researchers - from the University of California San Diego and Duke University in the United States and the University of Birmingham in the U.K. - show for the first time that selecting fillers who match a basic description of the suspect but whose faces are less similar, rather than more, leads to better outcomes than traditional approaches in the field.

The counterintuitive technique improves eyewitness performance by about 10 percent.

"In practice, police tend to err on the side of picking facially similar fillers for their lineups," said John Wixted, the paper's senior author and a professor in the UC San Diego Department of Psychology. "What our study shows is that it is, contrary to intuition, actually better to pick fillers who are facially dissimilar. Doing it this way continues to protect the innocent to the same degree while helping witnesses to correctly identify the guilty more frequently."

In a study of 19,732 participants, the researchers played a mock-crime video depicting a white male stealing an office laptop and then provided photographs of one suspect (either the perpetrator or an innocent suspect) plus five police lineup fillers. The fillers always matched the most basic description of the perpetrator but they varied in how much they facially resembled him. Facial similarity among photos was scored by an additional set of participants on a scale of 1 to 7, with 7 being most similar.

The researchers found that picking fillers who were facially dissimilar enhanced the ability of eyewitnesses to accurately pick out the perpetrator when he was in the lineup, without increasing the likelihood of wrongly identifying an innocent suspect when the real perpetrator was not in the lineup.

In a typical police lineup, one photo of the suspect is displayed, plus photos of five or more "fillers" who are known to be innocent. To create a fair lineup in which the suspect does not stand out, fillers are selected if they are similar in basic appearance to the suspect (height, weight, race, hair color and length, etc.), or if they have facial features included in a witness's description of the culprit. Often, a combined approach is used, in which fillers with similar facial features are selected from a pool of description-matched photos.

For decades, experts have disagreed on and puzzled over the question of what is most effective, while also being fair to the suspect. There are concerns that using fillers that are too facially similar to the suspect will confuse eyewitnesses and protect guilty suspects by making the identification task too difficult. Conversely, if the fillers are too facially dissimilar to the suspect, there are concerns that this would put an innocent suspect at risk of being falsely identified.

The new approach relied on insights from signal detection theory - which considers the memory strengths that are generated by each face in the lineup in the mind of the eyewitness - to deduce that selecting fillers who are not facially similar to the suspect from a pool of acceptable description-matched photos actually increases the ability of eyewitnesses to discriminate between innocent and guilty suspects.

Importantly, this approach did not have any effect on the number of "false alarms," in which an innocent suspect is incorrectly identified.

Scientists say they have discovered a potential new target for immunotherapy of malignant brain tumors, which so far have resisted the ground-breaking cancer treatment based on harnessing the body's immune system. The discovery, reported in the journal CELL, emerged from laboratory experiments and has no immediate implications for treating patients.

Scientists from Dana-Farber Cancer Institute, Massachusetts General Hospital, and the Broad Institute of MIT and Harvard said the target they identified is a molecule that suppresses the cancer-fighting activity of immune T cells, the white blood cells that seek out and destroy virus-infected cells and tumor cells.

The scientists said the molecule, called CD161, is an inhibitory receptor that they found on T cells isolated from fresh samples of brain tumors called diffuse gliomas. Gliomas include glioblastoma, the most aggressive and incurable type of brain tumor. The CD161 receptor is activated by a molecule called CLEC2D on tumor cells and immune-suppressing cells in the brain, according to the researchers. Activation of CD161 weakens the T cell response against tumor cells.

To determine if blocking the CD161 pathway could restore the T cells' ability to attack the glioma cells, the researchers disabled it in two ways: they knocked out the gene called KLRB1 that codes for CD161, and they used antibodies to block the CD161-CLEC2D pathway. In an animal model of gliomas, this strategy strongly enhanced the killing of tumor cells by T cells, and improved survival of the animals. The researchers were also encouraged because blocking the inhibitory pathway appeared to reduce T-cell exhaustion - a loss of cell-killing function in T cells that has been a been a major hurdle in immunotherapy.

In addition, "we showed that this pathway is also relevant in a number of other major human cancer types," including melanoma, lung, colon, and liver cancer, said Kai Wucherpfennig, MD, PhD, director of the Center for Cancer Immunotherapy Research at Dana-Farber. He is corresponding author of the report along with Mario Suva, MD, PhD, of Massachusetts General Hospital; Aviv Regev, PhD, of the Broad Institute, and David Reardon, MD, clinical director of the Center for Neuro-Oncology at Dana-Farber.

Many cancer patients are now being treated with immunotherapy drugs that disable "immune checkpoints" - molecular brakes exploited by cancer cells to suppress the body's defensive response by T cells against tumors. Disabling these checkpoints unleashes the immune system to attack cancer cells. One of the most frequently targeted checkpoints is PD-1. However, recent trials of drugs that target PD-1 in glioblastomas have failed to benefit patients. In the current study, the researchers found that fewer T cells from gliomas contained PD-1 than CD161. As a result, they said, "CD161 may represent an attractive target, as it is a cell surface molecule expressed by both CD8 and CD4 T cell subsets [the two types of T cells involved in response against tumor cells] and a larger fraction of T cells express CD161 than the PD-1 protein."

Prior to the current study, the researchers said little was known about the expression of genes and the molecular circuits of immune T cells that infiltrate glioma tumors, but fail to halt their growth. To open a window on these T cell circuits, the investigators took advantage of new technologies for reading out the genetic information in single cells - a method called single-cell RNA-seq. They applied RNA-seq to glioma-infiltrating T cells from fresh tumor samples from 31 patients and created an "atlas" of pathways that regulate T cell function. In analyzing the RNA-seq data, the researchers identified the CD161 protein, encoded by the KLRB1 gene, as a potential inhibitory receptor. They then used CRISPR/Cas9 gene-editing technology to inactivate the KLRB1 gene in T cells and showed that CD161 inhibits the tumor cell-killing function of T cells.

"Our comprehensive atlas of T cell expression programs across the major classes of diffuse gliomas thus identifies the CD161-CLEC2D pathway as a potential target for immunotherapy of diffuse gliomas and other human cancers," the authors of the report said.

This strategy was tested in two different animal models created by implanting "gliomaspheres" - 3-dimensional clusters of tumor cells from human patients - into rodents, which developed aggressive tumors that invaded the brain. The scientists subsequently injected T cells with the KLRB1 gene edited out into the cerebrospinal fluid of some of the animals, and T cells that hadn't had the KLRB1 gene deleted. Transfer of the gene-edited T cells slowed the growth of the tumors and "conferred a significant survival benefit," in both of the animal models of gliomas, the scientists said.

Employing cardiovascular disease prevention strategies in mid-life may delay or stop the brain alterations that can lead to dementia later in life, according to a study in the Journal of the American College of Cardiology.

Atherosclerosis, or buildup of fats, cholesterol and other substances in and on artery walls, is the underlying cause of most cardiovascular diseases, which is the leading cause of death around the world. Dementia is also among the top causes of death and disability around the world, with 50 million people currently living with dementia. The presence of atherosclerosis has been linked to cognitive impairment in advanced stages of the disease, but little is known about how they influence each other, especially since both can be asymptomatic for long periods of time earlier in life.

Using 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans of 547 participants from the Progression of Early Subclinical Atherosclerosis study, researchers sought to determine the association between brain metabolism, subclinical atherosclerosis and cardiovascular risk factors in asymptomatic, middle-aged adults. They found that cardiovascular risk is associated with brain hypometabolism, including the cerebral areas known to be affected in dementia. Hypertension was the modifiable cardiovascular disease risk factor with the strongest association.

According to researchers, these results underscore the need to control cardiovascular disease risk factors early in life to potentially reduce the brain's later vulnerability to cognitive dysfunction.

Engineers at the University of California San Diego have developed a soft, stretchy skin patch that can be worn on the neck to continuously track blood pressure and heart rate while measuring the wearer's levels of glucose as well as lactate, alcohol or caffeine. It is the first wearable device that monitors cardiovascular signals and multiple biochemical levels in the human body at the same time.

"This type of wearable would be very helpful for people with underlying medical conditions to monitor their own health on a regular basis," said Lu Yin, a nanoengineering Ph.D. student at UC San Diego and co-first author of the study published Feb. 15 in Nature Biomedical Engineering. "It would also serve as a great tool for remote patient monitoring, especially during the COVID-19 pandemic when people are minimizing in-person visits to the clinic."

Such a device could benefit individuals managing high blood pressure and diabetes--individuals who are also at high risk of becoming seriously ill with COVID-19. It could also be used to detect the onset of sepsis, which is characterized by a sudden drop in blood pressure accompanied by a rapid rise in lactate level.

One soft skin patch that can do it all would also offer a convenient alternative for patients in intensive care units, including infants in the NICU, who need continuous monitoring of blood pressure and other vital signs. These procedures currently involve inserting catheters deep inside patients' arteries and tethering patients to multiple hospital monitors.

"The novelty here is that we take completely different sensors and merge them together on a single small platform as small as a stamp," said Joseph Wang, a professor of nanoengineering at UC San Diego and co-corresponding author of the study. "We can collect so much information with this one wearable and do so in a non-invasive way, without causing discomfort or interruptions to daily activity."

The new patch is a product of two pioneering efforts in the UC San Diego Center for Wearable Sensors, for which Wang serves as director. Wang's lab has been developing wearables capable of monitoring multiple signals simultaneously--chemical, physical and electrophysiological--in the body. And in the lab of UC San Diego nanoengineering professor Sheng Xu, researchers have been developing soft, stretchy electronic skin patches that can monitor blood pressure deep inside the body. By joining forces, the researchers created the first flexible, stretchable wearable device that combines chemical sensing (glucose, lactate, alcohol and caffeine) with blood pressure monitoring.

"Each sensor provides a separate picture of a physical or chemical change. Integrating them all in one wearable patch allows us to stitch those different pictures together to get a more comprehensive overview of what's going on in our bodies," said Xu, who is also a co-corresponding author of the study.

Patch of all trades

The patch is a thin sheet of stretchy polymers that can conform to the skin. It is equipped with a blood pressure sensor and two chemical sensors--one that measures levels of lactate (a biomarker of physical exertion), caffeine and alcohol in sweat, and another that measures glucose levels in interstitial fluid.

The patch is capable of measuring three parameters at once, one from each sensor: blood pressure, glucose, and either lactate, alcohol or caffeine. "Theoretically, we can detect all of them at the same time, but that would require a different sensor design," said Yin, who is also a Ph.D. student in Wang's lab.

The blood pressure sensor sits near the center of the patch. It consists of a set of small ultrasound transducers that are welded to the patch by a conductive ink. A voltage applied to the transducers causes them to send ultrasound waves into the body. When the ultrasound waves bounce off an artery, the sensor detects the echoes and translates the signals into a blood pressure reading.

The chemical sensors are two electrodes that are screen printed on the patch from conductive ink. The electrode that senses lactate, caffeine and alcohol is printed on the right side of the patch; it works by releasing a drug called pilocarpine into the skin to induce sweat and detecting the chemical substances in the sweat. The other electrode, which senses glucose, is printed on the left side; it works by passing a mild electrical current through the skin to release interstitial fluid and measuring the glucose in that fluid.

The researchers were interested in measuring these particular biomarkers because they impact blood pressure. "We chose parameters that would give us a more accurate, more reliable blood pressure measurement," said co-first author Juliane Sempionatto, a nanoengineering Ph.D. student in Wang's lab.

"Let's say you are monitoring your blood pressure, and you see spikes during the day and think that something is wrong. But a biomarker reading could tell you if those spikes were due to an intake of alcohol or caffeine. This combination of sensors can give you that type of information," she said.

In tests, subjects wore the patch on the neck while performing various combinations of the following tasks: exercising on a stationary bicycle; eating a high-sugar meal; drinking an alcoholic beverage; and drinking a caffeinated beverage. Measurements from the patch closely matched those collected by commercial monitoring devices such as a blood pressure cuff, blood lactate meter, glucometer and breathalyzer. Measurements of the wearers' caffeine levels were verified with measurements of sweat samples in the lab spiked with caffeine.

Engineering challenges

One of the biggest challenges in making the patch was eliminating interference between the sensors' signals. To do this, the researchers had to figure out the optimal spacing between the blood pressure sensor and the chemical sensors. They found that one centimeter of spacing did the trick while keeping the device as small as possible.

The researchers also had to figure out how to physically shield the chemical sensors from the blood pressure sensor. The latter normally comes equipped with a liquid ultrasound gel in order to produce clear readings. But the chemical sensors are also equipped with their own hydrogels, and the problem is that if any liquid gel from the blood pressure sensor flows out and makes contact with the other gels, it will cause interference between the sensors. So instead, the researchers used a solid ultrasound gel, which they found works as well as the liquid version but without the leakage.

"Finding the right materials, optimizing the overall layout, integrating the different electronics together in a seamless fashion--these challenges took a lot of time to overcome," said co-first author Muyang Lin, a nanoengineering Ph.D. student in Xu's lab. "We are fortunate to have this great collaboration between our lab and Professor Wang's lab. It has been so fun working together with them on this project."

Next steps

The team is already at work on a new version of the patch, one with even more sensors. "There are opportunities to monitor other biomarkers associated with various diseases. We are looking to add more clinical value to this device," Sempionatto said.

Ongoing work also includes shrinking the electronics for the blood pressure sensor. Right now, the sensor needs to be connected to a power source and a benchtop machine to display its readings. The ultimate goal is to put these all on the patch and make everything wireless.

"We want to make a complete system that is fully wearable," Lin said.

In a new study out of University of California San Diego School of Medicine, researchers found a drug used for heart failure improves symptoms associated with postural orthostatic tachycardia syndrome, otherwise known as POTS. This complex, debilitating disorder affects the body's autonomic nervous system, causing a high heart rate, usually when standing.

Writing in the February 15, 2021 online issue of the Journal of the American College of Cardiology, study authors investigated the drug ivabradine and its effects on heart rate, quality of life and plasma norepinephrine levels in persons living with POTS. Norepinephrine is a stress hormone and neurotransmitter. In blood plasma, it is used as a measure of sympathetic nervous system activity. Trial participants experienced a reduction in heart rate, improvement in their symptoms and overall quality of life one month after taking the drug.

"Ivabradine is a novel agent that's FDA-approved for heart failure, but based on its mechanism we thought it could be helpful for patients with POTS as it reduces heart rate without impacting blood pressure," said Pam Taub, MD, cardiologist at the Cardiovascular Institute at UC San Diego Health and associate professor of medicine at UC San Diego School of Medicine. "When we can lower the heart rate, we're providing these patients with the ability to stand up, something they couldn't do without difficulty before due to their POTS diagnosis."

The study involved 22 individuals whose average age was 32 years. Each participant had been screened and recruited from cardiology clinics at UC San Diego Health from 2018 to 2020.

The study utilized a randomized, double-blinded, placebo-controlled crossover design in which patients started on either ivabradine or a placebo for one month. At the end of the month, all participants underwent a washout period where neither drug nor placebo was taken for one week. After the washout period, the participants who had previously received ivabradine switched to placebo and vice versa for one month.

Over the course of the two months, patients also met with researchers for seven different clinic visits in which plasma norepinephrine levels were measured and head-up tilt testing conducted to observe the patient's heart rate when sitting, lying down or standing up.

"Before the study, these patients would be living with elevated heart rates ranging between 100 to 115 beats per minute when standing," said Taub. "After taking ivabradine twice a day for one month, the standing heart rate decreased significantly to around 77 beats per minute compared to the placebo group. Participants also reported improvement in quality of life measures when on the drug."

The researchers also noted ivabradine was well-tolerated with no significant side effects while other drugs used to lower heart rate, such as beta blockers, can cause fatigue and decreased blood pressure.

Taub said the study was the first randomized clinical trial using ivabradine to treat POTS.

POTS is typically caused by a viral infection, trauma, surgery or enforced bedrest, and most commonly affects young women who are either athletes or highly active. Currently, there is no FDA-approved treatment for POTS and the condition can severely impact quality of life. Other symptoms of POTS include "brain fog," lightheadedness, palpitations, tremors, weakness, blurry vision and fatigue.

Recently, POTS has been identified as a potential "long-hauler" symptom of COVID-19.

"In our contemporary practice, we are seeing patients who have previously been infected with COVID-19 present with symptoms consistent with POTS," said Jonathan Hsu, MD, cardiologist at UC San Diego Health. "Given the similarities, this study leads to the question whether therapy with ivabradine may help patients who experience similar symptoms after a COVID-19 infection, and provide an important area for future study as well."

The authors said they hope ivabradine will be considered as a possible treatment option for those with a confirmed diagnosed of POTS. Currently, the drug is not FDA-approved for the disease and when used clinically it would be "off-label" use.

"Similar to patients with COVID-19, patients with POTS need to be followed carefully," said Taub. "Treatment for POTS needs to be personalized for each individual and with this drug, paired with lifestyle therapy, including exercises specific for POTS, we hope we will see more individuals overcome this unfortunate condition."

[Images and video available: see notes to editors]

Wasps provide crucial support to their extended families by babysitting at neighbouring nests, according to new research by a team of biologists from the universities of Bristol, Exeter and UCL published today [15 February] in Nature Ecology and Evolution.

The findings suggest that animals should often seek to help more distant relatives if their closest kin are less in need.

Dr Patrick Kennedy, lead author and Marie Curie research fellow in the School of Biological Sciences at the University of Bristol, said: "These wasps can act like rich family members lending a hand to their second cousins. If there's not much more you can do to help your immediate family, you can turn your attention to the extended family."

By closely observing twenty thousand baby wasps and their carers on colonies around the Panama Canal, the research team could determine the usefulness of workers on colonies of different sizes. They showed that workers become less useful as the number of colony members rises, due to a surplus of help.

Andy Radford, Professor of Behavioural Ecology, also from Bristol and co-author, explained: "By helping more distant relatives who are more in need--those living next door with fewer carers--workers can pass on more copies of their genes overall. We believe that similar principles of diminishing returns might explain seemingly paradoxical acts of altruism in many other social animals."

Dr Kennedy added: "The fact that these paper wasps in Central and South America help at other colonies is really bizarre when you consider that most wasps, ants and bees are extremely hostile to outsiders. To solve this puzzling behaviour, we combined mathematical modelling with our detailed field observations."

Dr Kennedy continued: "We ended up being stung a lot. But it was worth it, because our results show that worker wasps can become redundant at home. A wasp on a colony with few larvae but lots of other workers becomes almost useless: the best thing to do is to babysit the larvae of other relatives."

Since Darwin, biologists have been trying to understand how 'altruism' evolves in animals. At first glance, acts of selflessness to help other individuals do not seem to allow individuals to pass on their genes.

Professor Radford said: "In 1964, the legendary biologist W. D. Hamilton figured out the cardinal rule of animal altruism. Lavish help on your family because they share many of your genes. Copies of your genes will triumph in the population."

But the tropical paper wasps studied by the team baffled Hamilton back in 1964. In Brazil, he was surprised to notice that Polistes wasps were leaving their close family on their home nests and flying off to help the neighbours, who are less closely related.

Previous work by co-author Seirian '@WaspWoman' Sumner, Professor of Behavioural Ecology at University College London, showed that over half the workers in a Panamanian population were helping on multiple nests. Wasps usually viciously attack outsiders, so this babysitting suggested something unusual was going on.

Professor Sumner explained: "Wasps offer amazing windows into the evolution of selflessness. There is so much going on in a wasp nest: power struggles, self-sacrifice, groups battling against the odds to survive... If we want to understand how societies evolve, we should look more deeply at wasps."

Ciliopathies are genetic disorders caused by defects in the structure and function of cilia, microtubule-based organelles present on the surface of almost every cell in the human body which play crucial roles in cell signalling. Ciliopathies present a wide range of often severe clinical symptoms, frequently affecting the head and face and leading to conditions such as cleft palate and micrognathia (an underdeveloped lower jaw that can impair feeding and breathing). While we understand many of the genetic causes of human ciliopathies, they are only half the story: the question remains as to why, at a cellular level, defective cilia cause developmental craniofacial abnormalities. Researchers have now discovered that ciliopathic micrognathia in an animal model results from abnormal skeletal differentiation and remodelling. The work from Christian Bonatto Paese, Evan Brooks and others from Samantha Brugmann's lab at the Cincinnati Children's Hospital Medical Center in the USA is published in the journal Development.

The researchers used the avian ta2 mutant as a model for Oral-Facial-Digital syndrome subtype 14 (OFD14), a rare human ciliopathy characterised by micrognathia. They observed defective formation of the jaw bone (mandible) at early stages of development in ta2 mutants. These defects correlated with unchecked progression through the cell cycle and over-proliferation in skeletal progenitor cells. Importantly, these progenitor cells failed to differentiate into mature osteoblasts (the cells that secrete bone), and this failure of differentiation subsequently led to a reduction in bone deposition and hence micrognathia. The researchers also identified excessive bone resorption, a process which normally contributes to final size and shape of the mandible, as an additional causative factor in the ta2 micrognathia. This work informs our understanding of the etiology of human ciliopathic micrognathia.

"We have identified distinct cellular processes that are impaired during the onset of ciliopathic micrognathia," says Samantha Brugmann. "We know from previous work that these processes are responsive to treatment with pharmacological agents, and we are currently testing a number of these agents to determine if 'rescuing' ciliopathic micrognathia is possible. The therapeutic implications are exceptionally real."

"We are also currently trying to uncover how various organ systems respond to loss of cilia and which molecular and signalling pathways are affected, to continue to advance our understanding of how to tackle treatment for patients," says Christian Bonatto Paese.

The paper exemplifies how developmental biology can shine a light on devastating genetic disorders. Brugmann concludes: "The most important impact of this study, to me, is how useful basic science and the avian embryo can be towards uncovering mechanisms for human disease."

Far underneath the ice shelves of the Antarctic, there's more life than expected, finds a recent study in the journal Frontiers in Marine Science.

During an exploratory survey, researchers drilled through 900 meters of ice in the Filchner-Ronne Ice Shelf, situated on the south eastern Weddell Sea. At a distance of 260km away from the open ocean, under complete darkness and with temperatures of -2.2°C, very few animals have ever been observed in these conditions.

But this study is the first to discover the existence of stationary animals - similar to sponges and potentially several previously unknown species - attached to a boulder on the sea floor.

"This discovery is one of those fortunate accidents that pushes ideas in a different direction and shows us that Antarctic marine life is incredibly special and amazingly adapted to a frozen world," says biogeographer and lead author, Dr Huw Griffiths of British Antarctic Survey.

More questions than answers

"Our discovery raises so many more questions than it answers, such as how did they get there? What are they eating? How long have they been there? How common are these boulders covered in life? Are these the same species as we see outside the ice shelf or are they new species? And what would happen to these communities if the ice shelf collapsed?"

Floating ice shelves represent the greatest unexplored habitat in the Southern Ocean. They cover more that 1.5m sq km of the Antarctic continental shelf, but only a total area similar in size to a tennis court has been studied through eight prior boreholes.

Current theories on what life could survive under ice shelves suggest that all life becomes less abundant as you move further away from open water and sunlight. Past studies have found some small mobile scavengers and predators, such as fish, worms, jellyfish or krill, in these habitats. But filter feeding organisms - which depend on a supply of food from above - were expected to be amongst the first to disappear further under the ice.

So, it came as a surprise when the team of geologists, drilling through the ice to collect sediment samples, hit a rock instead of mud at the bottom of the ocean below. They were even more surprised by the video footage, which showed a large boulder covered in strange creatures.

New Antarctic expedition needed

This is the first ever record of a hard substrate (ie a boulder) community deep beneath an ice shelf and it appears to go against all previous theories of what types of life could survive there.

Given the water currents in the region, the researchers calculate that this community may be as much as 1,500km upstream from the closest source of photosynthesis. Other organisms are also known to collect nutrients from glacial melts or chemicals from methane seeps, but the researchers won't know more about these organisms until they have the tools to collect samples of these organisms--a significant challenge in itself.

"To answer our questions we will have to find a way of getting up close with these animals and their environment - and that's under 900 meters of ice, 260km away from the ships where our labs are," continues Griffiths. "This means that as polar scientists, we are going to have to find new and innovative ways to study them and answer all the new questions we have."

Griffiths and the team also note that with the climate crisis and the collapse of these ice shelves, time is running out to study and protect these ecosystems.