“Bats are an exciting group to study because they have evolved so many different hunting strategies,” said Page. “In this review, we look broadly across bats worldwide to investigate the patterns and processes underlying the sensory and cognitive adaptations bats have evolved to successfully hunt their prey.”

Bats hunting in open spaces, high above the forest or over water, depend primarily on their echolocation systems. When they receive an echo from a prey, they produce more and more frequent signals — producing what is called a feeding buzz — as they go in for the kill. In contrast, bats that hunt in more enclosed, cluttered spaces often cannot use echolocation alone to find their prey. The echoes that bounce off vegetation are difficult to distinguish from the echoes of the prey. These bats are very good at listening for sounds emitted by prey.

Bats from New Zealand, which forage up to 40% of the time hunting on the forest floor, listen for movement and use their sense of smell to detect prey in the leaf litter. Vampire bats are able to recognize the sounds of a specific individual’s breathing pattern, returning to feed on the same blood night after night. Desert-dwelling long-eared bats listen for the sounds made by scorpions as they move through the environment, and use these sounds to pinpoint their prey.

“Searching for prey takes a lot of time and energy, but one of the amazing things that bats do to minimize search effort is to eavesdrop on prey as they communicate — and also to eavesdrop on other bats to find out where they are catching prey,” said Bernal.

As male túngara frogs call, hoping to attract a mate, fringe-lipped bats perceive the mating calls as a dinner bell. Katydids also call to attract mates. Different bat species respond to different katydid calls, divvying up available food. And like the frogs, some moths also form groups of singing males to attract females — and end up attracting bats at the same time.

Bats observe other bats as they hunt, paying special attention to locations where bats are making feeding buzzes, indicating abundant patches of prey. Bats tend to have hearing abilities that match their hunting strategies. Bats relying purely on echolocation to find food tend to emit loud, far-reaching echolocation calls and have smaller ears, while gleaners have large ears, lower-frequency hearing and produce quieter echolocation calls. No matter which hunting strategy they use or where they hunt, bats seem to be adept at learning from one another. Not only do they learn from their own species, they also learn from other bat species.

“We are puzzled as we look at bat family trees to see where different hunting strategies have arisen as bats evolve,” said Page. “If so many bat species have low-frequency hearing and can thus detect prey mating signals, and these mating signals are excellent beacons of high density prey patches, why aren’t more bat species taking advantage of these loud, conspicuous signals?”

“Despite the fact that bats are an excellent group to learn about the sensory adaptations of predators, the vast majority of bats are poorly studied,” said Bernal. “Perhaps more research will help us to understand how predation strategies evolved. These are the questions that will drive new generations of students to keep looking for answers.”

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Scientists at the University of Warwick in collaboration with colleagues in China, France, Switzerland and Heriot-Watt University have developed a technique that uses light to activate a cancer-killing compound of Iridium that attacks, for the first time, a vital energy source in cancer cells even under hypoxia, significantly opening up the range of cancers that can be treated using the technique.

The technique is detailed in a paper published today (23 September 2019) in Nature Chemistry and could lead to another tool for clinicians to use in the fight against cancer, and potentially even vaccinate patients against future cancers.

Photodynamic therapy (PDT) uses light to kill cancer tumours in the body by activating a chemical compound called a photosensitiser, which creates species that can attack cancer cells in the presence of light. Using this method, clinicians can direct the light to specific regions of the cancer tumour and spare normal tissue from damage.

Current methods mainly rely on the presence of oxygen and many tumours are ‘hypoxic’, which means that they are deficient in normal oxygen often due to poor blood supplies. The international team of scientists have now developed a compound of the metal Iridium that will kill cancer cells in culture even when oxygen concentration is low.

The technique can treat any tumours where light can be administered, and would be particularly suited to treat bladder, lung, esophageal, brain and skin cancers. There are around 10,000 bladder cancer cases in the UK per year, of which about 5,000 might potentially benefit from this kind of treatment.

Professor Peter Sadler from the University of Warwick’s Department of Chemistry said: “All the time in cancer treatment, clinicians are trying to fight resistance. Drugs can kill the cancer cells initially, but with repeated treatment the cells become resistant, they learn how to chemically modify the drug or counteract its mechanism of action. Researchers are looking for novel ways in which the cancer cell will die. If they have become resistant to other cancer drugs, they may not be resistant to this treatment because the way it kills the cancer cells is different.

“There is an increasing interest in reducing the side effects of cancer treatment as much as possible and anything that can be selective in what it targets will help with that. The compound that we have developed would not be very toxic at all, we would give it to the cancer cells, allow a little time for it to be taken up, then we would irradiate it with light and activate it in those cells. We would expect killing of those cancer cells to occur very quickly compared with current methods.”

Once light-activated, the Iridium compound attacks the energy producing machinery in the cancer cells — a vital co-enzyme called nicotinamide adenine dinucleotide (NADH) — and catalytically destroys that co-enzyme or changes it into its oxidised form. This upsets the energy-producing machinery in a cancer cell and effectively cuts off the tumour’s power source.

Our bodies need coenzyme nicotinamide adenine dinucleotide (NADH) to generate energy. Cancer cells have a very high requirement for NADH, because they need a lot of energy to divide and multiple rapidly.

The researchers even found that the compound still works in the presence of oxygen, by converting it into a ‘toxic’ type of oxygen that will kill the cancer cells.

The team of scientists also noted that as the cancer cells die, they change their chemistry in such a way that they will generate an immune reaction in the body, what is known as an immunotherapeutic response. This suggests that those treated by this technique might be immunised against attack by that cancer, and will be investigated further in future research.

Professor Vas Stavros (University of Warwick) commented: “The power of light to change the reactivity of chemical molecules dramatically within a thousandth of a millionth of a second can now be harnessed to treat resistant cancers.”

Professor Martin Paterson (Heriot-Watt University) commented: “This breakthrough illustrates the power of modern computation to understand the effects of light on chemical molecules to provide drugs of the future with truly unique mechanisms of action.”

Professor Hui Chao (Sun Yat-Sen University) commented: “Now we have a potential new drug which can not only selectively kill cancer cells with normal oxygen supplies, but also hypoxic cancer cells which often resist treatment by photodynamic therapy.”

Professor Peter Sadler added: “The ability of metal compounds to induce an immunogenic response in the body that may effectively vaccinate a person against future attack by cancer is an exciting development. It is very speculative, but we are looking further into the hallmarks of that.

“Importantly we were fortunate to have had 3 highly talented young Royal Society Newton International Fellows in our team working on this challenging interdisciplinary project, who will undeniably contribute towards the future of this crucially important research.”

Iridium was first discovered in 1803, and its name comes from the Latin for ‘rainbow’. From the same family as platinum, it is hard, brittle, and is the world’s most corrosion-resistant metal. Yellow in colour, its melting point is more than 2400° Celsius. It is used in satellites and spacecraft due to its resistance to extreme environments, and is commonly believed to have been enriched in the earth’s crust by a meteorite that wiped out the dinosaurs 66 million years ago.

With this new approach, the researchers hope to dramatically expand the CRISPR-based tools available to biomedical engineers, opening up a new and diverse frontier of genome engineering technologies.

In a study appearing on Sept. 23 in Nature Biotechnology, Charles Gersbach, the Rooney Family Associate Professor of Biomedical Engineering at Duke, and Adrian Oliver, a post-doctoral fellow in the Gersbach lab who led the project, describe how they successfully harnessed Class 1 CRISPR systems to turn target genes on and off and edit the epigenome in human cells for the first time.

CRISPR-Cas is a defense system in which bacteria use RNA molecules and CRISPR-associated (Cas) proteins to target and destroy the DNA of invading viruses. The discovery of this phenomenon and the repurposing of the molecular machinery set off a genome-editing revolution as researchers learned how to wield the tool to specifically target and edit DNA in human cells.

CRISPR-Cas9, the most commonly used genome editing tool today, is categorized as a Class 2 CRISPR system. Class 2 systems are less common in the bacterial world, but they are theoretically simpler to work with, as they rely on only one Cas protein to target and cleave DNA.

Class 1 systems are not so simple, relying on multiple proteins working together in a complex called Cascade (CRISPR-associated complex for antiviral defense) to target DNA. After binding, Cascade recruits a Cas3 protein that cuts the DNA.

“If you were to look at the individual CRISPR systems of all the bacteria in the world, nearly 90 percent are Class 1 systems,” said Gersbach. “CRISPR-Cas biology is an incredible source for biotechnology tools, but until recently everyone has only been looking at a small slice of the pie.”

To demonstrate the capabilities of the Class 1 system, Oliver attached gene activators to specific sites along a type I E. coli Cascade complex and targeted the system to bind gene promoters, which regulate gene expression levels. Because she did not include the Cas3 protein in the experiment, there was no cutting of the DNA and no change to underlying DNA sequence. The experiment showed that the Cascade activator not only binds to the correct site and can turn up the levels of the target gene, but does so with accuracy and specificity comparable to CRISPR/Cas9.

Oliver repeated the process using type I Cascade complexes from an additional bacterial strain that was particularly robust in working at a variety of target sites. She also showed that the activator domain could be swapped for a repressor to turn target genes off. Again, the researchers noted accuracy and specificity comparable to CRISPR/Cas9 methods.

“We have found Cascade’s structure to be remarkably modular, allowing for a variety of sites to attach activators or repressors, which are great tools for altering gene expression in human cells,” Oliver said. “The flexible nature of Cascade makes it a promising genome engineering technology.”

Gersbach and Oliver were encouraged to investigate the more complicated Class 1 CRISPR systems by their collaborators at nearby North Carolina State University, Professors Rodolphe Barrangou and Chase Beisel, who is now at the Helmholtz Centre for Infection Research in Germany. Barrangou is a microbiologist who has studied the natural biology of diverse CRISPR defense mechanisms for nearly two decades, and Beisel is a chemical engineer who has worked with Barrangou on engineering microorganisms with Class 1 CRISPR systems. They were both curious whether Gersbach’s lab could use these systems in human cells similar to their work with Cas9.

“This work and the resulting technologies are a fantastic example of how collaboration across disciplines and across universities in the North Carolina Research Triangle can be highly innovative and productive” says Barrangou, the Todd R. Klaenhammer Distinguished Professor in Probiotics Research at North Carolina State University.

Now, the team is optimistic that their study, and the related work of others in the field, will incentivize new research into Class 1 CRISPR systems.

“The purpose of this project was to explore the diversity of CRISPR systems,” said Gersbach. “There have been thousands of papers about CRISPR-Cas9 in the last decade, and yet we’re constantly learning new things about it. With this study we’re applying that mindset to the other 90% of what’s out there.”

So far, the team has shown that these Class 1 systems are comparable to to CRISPR-Cas9 in terms of accuracy and application. As they consider future directions, they are curious to explore how these systems differ from their Class 2 counterparts, and how these differences could prove useful for biotechnology applications.

The team is also interested in studying how Class 1 systems could address general challenges for CRISPR-Cas research, especially issues that complicate potential therapeutic applications, like immune responses to Cas proteins and concurrently using multiple types of CRISPR for different genome engineering functions.

“We know CRISPR could have a big impact on human health,” said Gersbach. “But we’re still at the very beginning of understanding how CRISPR is going to be used, what it can do, and what systems are available to us. We expect that this new tool will enable new areas of genome engineering.”

Researchers from the King’s Centre for Military Health Research at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) collected data from 405 women in military families with at least one child, representing around a third of the military population.

The researchers used a screening tool for depression, rather than a diagnosis from a psychiatrist, and women reporting frequent symptoms were considered to have probable depression. Drinking behaviours were also recorded through a self-reported screening tool.

• 7% of military partners met criteria for probable depression, compared to 3% of women from the general population
• 9.7% of military partners reported episodes of weekly, daily or almost daily binge-drinking, compared to 8.9% from the general population

After controlling for other factors linked to poor alcohol behaviours, the researchers found military partners were twice as likely to binge-drink as women in the general population.

Overall, military partners reported consuming alcohol less frequently than women in the general population but reported binge-drinking more often. Binge-drinking was significantly higher when families were separated for more than 2 months due to deployment.

Military families experience various unique challenges, such as frequently moving location and the stress and separation caused by deployment. The researchers say binge-drinking may reflect poor coping strategies used by military partners during the long absences of serving personnel from the family home.

Lead researcher Dr Rachael Gribble from the IoPPN says: ‘While the majority of families cope well with the added pressures of military life, the additional challenges faced by military families may explain the additional mental health needs and higher rates of binge-drinking we found among military partners. More research is needed to help find out more about what contributes to depression and problematic drinking in this population.’

The researchers say that binge-drinking represents an important public health issue for the military community. They urge development of campaigns to reduce alcohol use in military families, suggesting that programmes which successfully tackle dangerous drinking among Service personnel could be extended to their partners.

Senior researcher Professor Nicola Fear from the IoPPN says: ‘Our results indicate that healthcare professionals should be attuned to the impact military life can have on the mental health and wellbeing of family members. There are lots of support options available for military families out there, but these are not always easily accessible.’

This research was published in the European Journal of Psychotraumatology and is funded by the Economic and Social Research Council and the Army Families Federation. It is the first UK-based study to look at the mental health and well-being of women in relationships with members of the UK Armed Forces.

A spokesperson for the Army Families Federation, the independent voice of Army families, said: ‘Isolation, separation and mobility can all impact on Service families’ mental health and emotional wellbeing. Research in these areas helps organisations working with Service families to better understand how they can be supported. We welcome the conclusion of this research by King’s College London that available support could be better signposted for military partners.’

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Professor Peter Coveney, Director of the UCL Centre for Computational Science and study co-author, said: “Our work shows that the behaviour of the chaotic dynamical systems is richer than any digital computer can capture. Chaos is more commonplace than many people may realise and even for very simple chaotic systems, numbers used by digital computers can lead to errors that are not obvious but can have a big impact. Ultimately, computers can’t simulate everything.”

The team investigated the impact of using floating-point arithmetic — a method standardised by the IEEE and used since the 1950s to approximate real numbers on digital computers.

Digital computers use only rational numbers, ones that can be expressed as fractions. Moreover the denominator of these fractions must be a power of two, such as 2, 4, 8, 16, etc. There are infinitely more real numbers that cannot be expressed this way.

In the present work, the scientists used all four billion of these single-precision floating-point numbers that range from plus to minus infinity. The fact that the numbers are not distributed uniformly may also contribute to some of the inaccuracies.

First author, Professor Bruce Boghosian (Tufts University), said: “The four billion single-precision floating-point numbers that digital computers use are spread unevenly, so there are as many such numbers between 0.125 and 0.25, as there are between 0.25 and 0.5, as there are between 0.5 and 1.0. It is amazing that they are able to simulate real-world chaotic events as well as they do. But even so, we are now aware that this simplification does not accurately represent the complexity of chaotic dynamical systems, and this is a problem for such simulations on all current and future digital computers.”

The study builds on the work of Edward Lorenz of MIT whose weather simulations using a simple computer model in the 1960s showed that tiny rounding errors in the numbers fed into his computer led to quite different forecasts, which is now known as the ‘butterfly effect’.

The team compared the known mathematical reality of a simple one-parameter chaotic system called the ‘generalised Bernoulli map’ to what digital computers would predict if every one of the available single-precision floating-point numbers were used.

They found that, for some values of the parameter, the computer predictions are totally wrong, whilst for other choices the calculations may appear correct, but deviate by up to 15%.

The authors say these pathological results would persist even if double-precision floating-point numbers were used, of which there are vastly more to draw on.

“We use the generalised Bernoulli map as a mathematical representation for many other systems that change chaotically over time, such as those seen across physics, biology and chemistry,” explained Professor Coveney. “These are being used to predict important scenarios in climate change, in chemical reactions and in nuclear reactors, for example, so it’s imperative that computer-based simulations are now carefully scrutinised.”

The team say that their discovery has implications for the field of artificial intelligence, when machine learning is applied to data derived from computer simulations of chaotic dynamical systems, and for those trying to model all kinds of natural processes.

More research is needed to examine the extent to which the use of floating-point arithmetic is causing problems in everyday computational science and modelling and, if errors are found, how to correct them.

Professor Bruce Boghosian and Dr Hongyan Wang are at Tufts University, Medford, Massachusetts, United States (Dr Wang now works at Facebook in Seattle). Professor Peter Coveney of UCL is speaking at an event tomorrow in the Science Museum on the future of quantum computing.

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