Culture

Researchers have discovered signatures in brain activity that allow them to tell old and new memories apart. A team at Japan's RIKEN Center for Brain Science (CBS) analyzed recordings from mouse brains using a machine-leaning algorithm, which was able to accurately classify memories as recent or remote. They also found robust communication between a frontal brain region and the hippocampus, an area strongly involved in memory formation. This link may form a concrete mechanism that tracks the age of memories. This research was published in the journal Cell Reports.

Identifying the location and persistence of memories in the brain has implications for cases of brain damage, memory loss, and clinical memory impairment. In this study, the researchers were interested in how different brain areas that contain memory traces interact, especially during memory recall. The anterior cingulate cortex (ACC) in the prefrontal brain is known to be anatomically connected to the hippocampus. The team wanted to study this connection more closely, at the level of signals from individual neurons.

They recorded activity in both brain areas before exposing mice to a memory-forming experience (a foot shock), and then again in the same cage both one day and one month later. If mice froze in the same context, it was a behavioral indication that they remembered the shock. But the neuronal recordings also revealed that the ACC and hippocampus, specifically area CA1, are highly synchronized when mice recall the fear memory.

The interactions of the two brain areas changed over time, with ACC and CA1 activity becoming more correlated when an old or 'remote' memory was recalled compared to the recent, one-day memory. Specific frequencies and modes of neural activity became more pronounced between the two areas when the mice recalled the older memory, with the ACC appearing to drive activity in hippocampus in a top-down manner. "While memory is consolidated over time in frontal areas, we think in this case the ACC is facilitating the retrieval of contextual details back from the hippocampus," said senior author and team leader Thomas McHugh of RIKEN CBS.

The evolving pattern of signals over time allowed the researchers to distinguish old and new memories in mice from the brain recordings alone. "We could decode whether a mouse was recalling a recent or remote memory by looking at the correlations in ACC-CA1 interactions," said McHugh. Moreover, the researchers suggest that a small group of CA1 neurons carries the information about memory age.

"While we have known for 20 years that the ACC is important for recalling older memories, how it contributes has remained a mystery" McHugh explained. "We found that it plays in important role in organizing activity in the hippocampus, the part of the brain in which the memory was originally formed. This suggests the hippocampus always plays a role in providing key details of an old experience, at least in the healthy brain."

The team is now focused on understanding how impairments in long-term memory that often accompany aging and disease impacts activity in these brain circuits.

The protectionist policy of US President Donald Trump is criticized on all sides around the world, but seems to suit the Americans, who see this economic model as protecting their interests. Could they be wrong? A study by researchers of the University of Geneva (UNIGE) quantifies the effects of Donald Trump's protectionist policies on unemployment and welfare in Organisation for Economic Co-operation and Development (OECD) countries. Their results, forthcoming in the Journal of the European Economic Association, show that such policies would have a negative impact on welfare and employment in both Mexico and the United States.

While the U.S. administration has been openly implementing protectionist trade policies ever since Donald Trump became president, economists are striving to analyze the effects of such a stark policy reversal. Yet, almost no trade models that economists use to quantify the effects of such trade policy changes include unemployment as an important margin of adjustment. "The unemployment rate is nevertheless an important indicator of a country's economic health", notes Céline Carrère, a professor at the Geneva School of Economics and Management (GSEM) of the UNIGE. "That is why we have been particularly interested in the evolution of unemployment figures in OECD countries."

Reduced welfare through protectionism

The study shows that repealing the North American Free Trade Agreement (NAFTA) - an announcement made by President Trump shortly after taking office - and the imposition of 20% bilateral tariffs between the US and Mexico in all sectors would reduce average welfare by 0.31% in the US and by 6.6% in Mexico. "Furthermore, this policy would increase unemployment by 2.4% in the United States and 48% in Mexico!", emphasizes Frédéric Robert-Nicoud, professor at the GSEM and co-author of this study.

In their study, UNIGE researchers reveal in a second scenario the impact of Trump's economic policy on the automotive industry. "A US increase of trade barriers on motor vehicles against imports from all countries bar Mexico and Canada would lead to a decrease in long-run welfare and employment in both Mexico and the US as well as in major car-producing countries", warns Anja Grujovic, researcher at the Center for Monetary and Financial Studies (CEMFI) in Madrid, Spain.

The GSEM study thus shows that far from favoring his country's industrial players, Donald Trump's protectionist policy has a negative impact on them in the long term. Moreover, it not only affects Americans, but also neighboring OECD countries, such as Mexico. "In this way, we show that protectionism often hides negative aspects that only emerge over time, sometimes after the end of a president's term of office, who can then be satisfied with the results obtained when he was in power", Frédéric Robert-Nicoud concludes.

A $2.2 billion industry to help people lose weight through artificial sweeteners may be contributing to type 2 diabetes, according to researchers from the University of South Australia.

A recently published review led by UniSA Professor Peter Clifton reveals that people who use low-calorie sweeteners (LCS) are more likely to gain weight, the exact opposite of what consumers expect.

This is despite controlled clinical trials showing that artificial sweeteners do lead to weight loss.

There has been a 200 per cent increase in LCS usage among children and a 54 per cent increase among adults in the past 20 years, Prof Clifton says.

Low calorie sweeteners are used in place of sucrose, glucose and fructose. They have an intense sweet flavour without the calories, but recent studies have highlighted potential adverse health effects.

Prof Clifton says a US study of 5158 adults over a seven-year period found that those who consumed large quantities of artificial sweeteners gained more weight than non-users.

"Consumers of artificial sweeteners do not reduce their overall intake of sugar. They use both sugar and low-calorie sweeteners and may psychologically feel they can indulge in their favourite foods.

"Artificial sweeteners also change the gut bacteria which may lead to weight gain and risk of type 2 diabetes," he says.

Artificially sweetened beverages (ASB) are also linked with increased risks of death and cardiovascular disease, and strokes and dementia among older people, but it is not clear why.

Prof Clifton cites 13 studies which investigated the effects of ASB intake on the risk of type 2 diabetes, all of which found either no link or a positive one. One study found that substituting ASB for sugar-sweetened beverages or fruit juices was associated with a 5-7 per cent lower risk of type 2 diabetes.

"A better option than low-calorie sweeteners is to stick to a healthy diet, which includes plenty of whole grains, dairy, seafood, legumes, vegetables and fruits and plain water," Prof Clifton says.

With intensifying human activity, many species are threatened with extinction. However, many other species have expanded their range. Is there a general rule to identify which species are "losers" or "winners"? And what is the effect of range changes on the biodiversity of Chinese flora?

A research team led by Prof. MA Keping from the Institute of Botany of the Chinese Academy of Sciences, in collaboration with scientists from the Center for Biodiversity Dynamics in a Changing World (BIOCHANGE) at Aarhus University (Denmark), revealed that narrow-ranged plants in China are more likely to be "losers", whereas widespread species tend to be "winners" under the condition of intensive human activity. This study was published in the journal PNAS on Dec. 17.

China is one of world's most species-rich countries, but it has suffered from long-term, intense human pressure exacerbated by uneven human population distribution across the country. For example, most people in China live southeast of an imaginary diagonal line, known as the "Hu Huanyong Line" for the demographer who created it, which stretches from Heihe City in Heilongjiang Province to Tengchong City in Yunnan Province.

Due to the lack of extensive, dynamic species distribution data, relatively few studies have comprehensively evaluated the impact of humans on large-scale distribution of species in high-diversity organism groups. Furthermore, such assessments are complicated by the confounding effects of natural drivers such as climate.

In order to overcome this knowledge gap, the researchers quantified the impact of humans on the distribution of 9,701 vascular plant species across China. The study factored out the effect of climate by assessing how human activity affects the degree to which each species fills its potential climatic range (i.e., its potential distribution given its statistically estimated climatic niche).

This study found that narrow-ranged species in the human-dominated southeast (i.e., the area below the Hu Huanyong Line) have lower range filling, whereas widespread species have higher range filling relative to their counterparts in the northwest. Furthermore, variation in range filling is strongly associated with human impact factors, with narrow-ranged species having a negative correlation with those factors while widespread species have a positive correlation.

These results suggest that human activity has reduced the range of narrow-ranged species, but expanded the range of widespread species, relative to their climatic potential.

Narrow-ranged species may be more sensitive to human pressure since they are environmentally relatively specialized or poorly dispersed. Conversely, widespread species, as pioneer species, may be more generalistic and/or better dispersed, making them better equipped to exploit human-disturbed habitats.

"With narrow-ranged species becoming replaced by widespread species due to human activities, the Chinese flora risks biotic homogenization," said Dr. XU Wubing, the first author of the study.

Because narrow-ranged species are more numerous than widespread species, negative human impact on species distribution is likely very prevalent. "This highlights the importance of establishing more protected areas as well as widespread, biodiversity-oriented ecosystem restoration to safeguard China's unique, rich flora," said Professor Jens-Christian Svenning, coauthor of the study and director of BIOCHANGE, Aarhus University.

Crucial early diagnosis of dementia in general practice could improve thanks to a computer model designed in a collaboration between Brighton and Sussex Medical School (BSMS) and astrophysicists at the University of Sussex.

Currently, only two-thirds of people with dementia in the UK receive a formal diagnosis, and many receive it late in the disease process, meaning that a large number are missing out on the care that could help them achieve a good quality of life.

The team, led by Dr Elizabeth Ford, Senior Lecturer in Primary Care Research at BSMS, used data from GP patient records to create a list of 70 indicators related to the onset of dementia and recorded in the five?years before diagnosis. Working with data scientists from astrophysics, they then tried several types of machine-learning models to identify patterns of clinical information in patient records before a dementia diagnosis. The best model was able to identify 70% of dementia cases before the GP, but also threw up a number of false positives.

Dr Ford said: "Patients appear to be exhibiting a wide range of indicators prior to being diagnosed with dementia. It can be really hard for GPs to connect all these indicators and make the link with dementia, but with a computer programme, we can potentially do that. Early diagnosis could make a significant difference to the care dementia patients then receive.

"These findings are exciting but they spark the need for discussion with GPs and patients about what place this kind of technology should have in the GP clinic. As technology develops, we need to have wider conversations on whether we are happy with computers working out our chance of having life-changing conditions like dementia."

Seb Oliver, Professor of Astrophysics in the School for Mathematical and Physical Sciences, said: "It has been fantastic working on this project with Dr Ford and her team. It is always amazing to see how statistical methods such as AI and machine-learning can be used to extract useful information from data, whether that be images from space telescopes or GP patient records. Of course the statistics are only one part of the understanding and it is really exciting to work in new areas to try to understand the different challenges that those present."

Extracting nectar from flowers that may be dancing in the wind requires precise, millisecond timing between the brain and muscles.

By capturing and analyzing nearly all of the brain signals sent to the wing muscles of hawk moths (Manduca sexta), which feed on such nectar, researchers have shown that precise timing within rapid sequences of neural signal spikes is essential to controlling the flight muscles necessary for the moths to eat.

The research shows that millisecond changes in timing of the action potential spikes, rather than the number or amplitude of the spikes, conveys the majority of information the moths use to coordinate the five muscles in each of their wings. The importance of precise spike timing had been known for certain specific muscles in vertebrates, but the new work shows the general nature of the connection.

"We were able to record simultaneously nearly every signal the moth's brain uses to control its wings, which gives us an unprecedented and complete window into how the brain is conducting these agile and graceful maneuvers," said Simon Sponberg, Dunn Family Professor in the School of Physics at the Georgia Institute of Technology. "These muscles are coordinated by subtle shifts in the timing at the millisecond scale rather than by just turning a knob to create more activity. It's a more subtle story than we might have expected, and there are hints that this may apply more generally."

The research was reported December 16 in the journal Proceedings of the National Academy of Sciences. The work was supported by the National Science Foundation, the Esther A. & Joseph Klingenstein Fund, and the Simons Foundation.

Researchers Joy Putney, Rachel Conn and Sponberg set out to study how the brain coordinates agile activities such as running or flying that require compensating for perturbations in the air or variations on the ground. While the size of the signals could account for gross control of the behavior, the fine points of choreographing the tasks had to come from elsewhere, they reasoned.

Recording motor control signals in humans and other vertebrates would be a daunting task because so many neurons are used to control so many muscles in even simple behaviors. Fortunately, the researchers knew about the hawk moth, whose flight muscles are each controlled by a single or very few motor neurons. That allowed the researchers to study neural signals by measuring the activity of the corresponding muscles, using tiny wires inserted through the insect's exoskeleton.

Putney and Conn determined the location of each wing muscle inside the moth exoskeleton, and learned where to create tiny holes for the wires - two for each muscle - that capture the signals. After inserting the wires in the anesthetized moths, the graduate students closed the holes with superglue to hold the wires in place. Connections to a computer system allowed recording and analysis.

"The first time I did the surgery by myself, it took six hours," said Putney. "Now I can do it in under an hour."

While connected to the computer, the moths were able to fly on a tether as they viewed a moving 3D-printed plastic flower. To measure the torque forces the moths created as they attempted to track the flower, the wired-up moths were suspended from an accelerometer. The torque information was then correlated with the spiking signals recorded from each wing muscle.

The importance of the work relates to the completeness of the signal measurement, which brought out the importance of the timing codes to what the moth was doing, Putney said.

"People have recorded lots of muscles together before, but what we have shown is that all of these muscles are using timing codes," she said. "The way they are using these codes is consistent, regardless of the size of the muscle and how it is attached to the body."

Indeed, researchers have seen hints about the importance of precision timing in higher animals, and Sponberg believes the hawk moth research should encourage more study into the role of timing. The importance and prevalence of timing across the moth's motor program also raises questions about how nervous systems in general create precise and coordinated motor commands.

"We think this raises a question that can't be ignored any longer - whether or not this timing could be the real way that the brain is orchestrating movement," Sponberg said. "When we look at specific signals in vertebrates, even up to humans, there are hints that this timing could be there."

The study could also lead to new research on how the brain produces the agile motor control needed for agile movement.

"Now that we know that the motor control is really precise, we can start trying to understand how the brain integrates precise sensory information to do motor control," Sponberg said. "We want to really understand not only how the brain sets up signals, but also how the biophysics of muscles enables the precise timing that the brain uses."

Good aerobic fitness does not protect children against obesity-induced insulin resistance, which is a key risk factor of type 2 diabetes, a new study from Finland shows. However, more physical activity and less sedentary time were associated with reduced insulin resistance also in obese children. Published in Medicine & Science in Sports & Exercise, the findings are based on the Physical Activity and Nutrition in Children (PANIC) Study carried out in the University of Eastern Finland. The study involved researchers from the University of Eastern Finland, the University Jyväskylä, the Norwegian School of Sports Science, the University of Cambridge and the University of Exeter.

Good aerobic fitness does not protect against insulin resistance

It is a generally accepted idea that good aerobic fitness reduces the risk of type 2 diabetes, and it has also been thought to protect against other obesity-induced adverse changes in the glucose metabolism. However, this idea is based on studies whose methodology does not allow a distinction between the roles of aerobic fitness and body fat percentage as risk factors of insulin resistance and type 2 diabetes.

"Our study clearly shows that aerobic fitness is not associated with insulin resistance when body composition is taken into consideration properly. Moreover, good aerobic fitness doesn't seem to protect against obesity-induced insulin resistance. It seems that the role of poor aerobic fitness as a risk factor of type 2 diabetes has been grossly exaggerated," says Researcher Eero Haapala, PhD, from the Faculty of Sport and Health Sciences at the University of Jyväskylä. Dr Haapala is also an Adjunct Professor of Paediatric Exercise Physiology at the University of Eastern Finland.

Development of insulin resistance can be prevented

The researchers found that more brisk physical activity and less sedentary time were associated with reduced insulin resistance regardless of the level of aerobic fitness and body fat percentage. Getting more physical activity and less sedentary time also protected obese children against the development of insulin resistance.

"A key take-home message from our study is that more physical activity and less sedentary time play key roles in the prevention of type 2 diabetes already in childhood. For obese children, these seem to be especially important," Dr Haapala notes.

The study analysed 452 children between 6 and 8 years of age, exploring associations between their aerobic fitness, body fat percentage, physical activity, sedentary time and insulin resistance. Aerobic fitness was assessed using a maximal exercise test on a cycle ergometer, and body fat percentage by DXA measurement. Physical activity and sedentary time were measured using a combined movement and heart rate sensor, and insulin resistance was assessed by measuring glucose and insulin levels from blood samples.

Researchers from the Moscow Institute of Physics and Technology, along with their colleagues from Germany and the U.S., have achieved a breakthrough on the way to new types of nonvolatile memory devices. The team came up with a unique method for measuring the electric potential distribution across a ferroelectric capacitor -- the device underlying the memory of the future, which would be orders of magnitude faster than the current flash and solid-state drives, withstanding 1 million times as many rewrite cycles. The paper was published in Nanoscale.

Electronics companies worldwide pursue new nonvolatile memory technologies to enable vastly faster access speeds and longer lifetimes compared with the flash and solid-state drives of today. One of the leading contenders is hafnium dioxide-based memory. The material it uses is a dielectric already known to the microelectronics industry. Subjected to certain temperature treatment and alloying, a few nanometer-thick hafnium dioxide layer can form metastable crystals that possess ferroelectric properties -- that is, they "remember" the direction of the electric field applied to them.

The new memory cell is a zirconium-hafnium oxide film merely 10 nanometers thick, interlaid between two electrodes. Its structure resembles a conventional electric capacitor. To make ferroelectric capacitors usable as memory cells, their remnant polarization has to be maximized; and to ensure that, engineers need a detailed understanding of the processes that occur in the nanofilm. This involves explaining how the electric potential is distributed across the film following voltage application and polarization reversal. Since the discovery of a ferroelectric phase in hafnium oxide 10 years ago, the potential distribution at the nanoscale has only been modeled, but not directly measured. The latter has been reported in the recent paper in Nanoscale.

The team employed a technique known as high-energy X-ray photoemission spectroscopy. The specialized methodology developed at MIPT relies on the so-called standing-wave mode of the powerful monochromatic X-ray beam, which requires a synchrotron light source to produce. The machine used in the study is located in Hamburg, Germany. It was used to perform measurements on the hafnium oxide-based memory cell prototypes manufactured at MIPT.

"If used for the industrial production of nonvolatile memory cells, the ferroelectric capacitors developed in our lab could endure 10 billion rewrite cycles, which is 100,000 times more than state-of-the-art flash drives can survive," said study co-author Andrei Zenkevich, who heads the Laboratory of Functional Materials and Devices for Nanoelectronics at MIPT.

A further advantage of ferroelectric memory devices is that external radiation has absolutely no effect on them, unlike their semiconductor-based analogues. This means that the flash-like memory of the future could even weather cosmic ray exposure and operate in outer space.

A recent study by scientists from the National University of Singapore (NUS) revealed that the current biodiversity crisis may be much broader than widely assumed, and may affect even species thought to be common and tolerant of fragmentation and habitat loss.

Specifically, the research team found that the effective population size and genetic diversity of a common fruit bat species - the Sunda fruit bat (Cynopterus brachyotis) - that was believed to remain widely unaffected by urbanisation, has shrunk significantly over the last 90 years. By comparing historic DNA from museum samples collected in 1931 and modern samples collected in 2011 and 2012, the NUS team found a nearly 30-fold reduction in effective population size and corresponding levels of decline in genetic diversity estimates.

"This bat species carries a genomic signature of a steep breakdown in population-genetic diversity. The extreme bottleneck event that led to a reduction in genetic diversity happened some time in the early Anthropocene (around the 1940s) when humans' impact on this planet became dominant," explained first author Dr Balaji Chattopadhyay, who recently finished a postdoctoral fellowship at the NUS Department of Biological Sciences at the Faculty of Science.

Understanding the decline in population-genetic diversity of the Sunda fruit bat

An effective pollinator and seed disperser, Cynopterus brachyotis represents an important keystone bat species in Singapore's ecosystem. This bat species is also widely distributed in human-dominated landscapes across tropical Southeast Asia.

In order to understand the effects of human-mediated changes such as urbanisation on the evolutionary trajectory of Singapore's population of Cynopterus brachyotis, the NUS team reconstructed and compared diverse models of historic demography. The researchers sequenced and examined over 634 million DNA reads of Cynopterus brachyotis genome and generated multiple datasets for the study.

Their findings suggest that Singapore's Cynopterus brachyotis population underwent a continuous decline that started approximately 195 generations ago (i.e. 1,600 years ago), and experienced a recent genetic bottleneck - or a sharp reduction in population size - nine generations ago, roughly in 1940. Genetic bottlenecks increase the vulnerability of a species to unpredictable events and can accelerate extinction of small populations. While bottlenecks following human interference have been documented in many endangered species, this study suggests that even common human commensals may not be immune to the effects of bottlenecks.

"Cynopterus brachyotis is a generalist fruit bat that tolerates urbanised settings. As such, it is an unlikely victim of habitat degradation and fragmentation. The unexpected loss in genetic diversity in this common species, largely due to urbanisation and human-mediated changes, indicates that the modern environmental crisis can generate adverse silent effects that only become apparent much later, when the impact of low genetic diversity may take hold in a population," explained Assistant Professor Frank Rheindt from the NUS Department of Biological Sciences, leader of the laboratory group that conducted the study.

"This phenomenon has been characterised as extinction debt, when actual extinction occurs with a time lag, long after the critical damage was done. Hence, an increased understanding of baseline levels and rates of loss of genetic diversity across organismic groups like Cynopterus brachyotis bats and habitats may, in the future, become imperative for informed conservation action," he added.

This research was conducted in collaboration with the National Parks Board (NParks) Singapore which supported the sampling of contemporaneous populations of the bats. The findings were published in the journal Current Biology on 16 December 2019.

"Our research also underscores the importance of strong museum collections facilitating the DNA-sampling of time series. More global support is needed for modern cryo-collections, which are generally under-funded," said Asst Prof Rheindt.

Asst Prof Rheindt is looking to extend the research by investigating multiple other animal species in Singapore and Southeast Asia to better characterise extinction risk.

Coffee can help reduce the risk of developing type 2 diabetes - but only filtered coffee, rather than boiled coffee. New research from Chalmers University of Technology and Umeå University, both in Sweden, show that the choice of preparation method influences the health effects of coffee.

Many previous studies have shown a connection between high coffee intake and a reduced risk of developing type 2 diabetes. Now, a study from Chalmers University of Technology and Umeå University, offers new insight into this connection, using a novel method to help differentiate between the effects of filtered coffee and boiled coffee.

"We have identified specific molecules - 'biomarkers' - in the blood of those taking part in the study, which indicate the intake of different sorts of coffee. These biomarkers are then used for analysis when calculating type 2 diabetes risk. Our results now clearly show that filtered coffee has a positive effect in terms of reducing the risk of developing type 2 diabetes. But boiled coffee does not have this effect," says Rikard Landberg, Professor in Food Science at Chalmers, and Affiliated Professor at the Department of Public Health and Clinical Medicine at Umeå University.

With the use of these biomarkers, the researchers were able to show that people who drank two to three cups of filtered coffee a day had a 60% lower risk of developing type 2 diabetes than people who drank less than one cup of filtered coffee a day. Consumption of boiled coffee had no effect on the diabetes risk in the study.

Filtered coffee is the most common method of preparation in many places, including the US and Scandinavia. Boiled coffee in this case refers to an alternative method of coffee preparation sometimes used in Sweden and some other countries, in which coarse ground coffee is simply added directly to boiling water and left to brew for a few minutes. All the data used in the research came from a group of Swedish subjects and was collected in the early 1990s.

According to Rikard Landberg, many people wrongly believe that coffee has only negative effects on health. This could be because previous studies have shown that boiled coffee increases the risk of heart and vascular diseases, due to the presence of diterpenes, a type of molecule found in boiled coffee.

"But it has been shown that when you filter coffee, the diterpenes are captured in the filter. As a result, you get the health benefits of the many other molecules present, such as different phenolic substances. In moderate amounts, caffeine also has positive health effects," he says.

The question is whether diterpenes also negatively influence sugar metabolism and are therefore the cause of why boiled coffee does not help lower the risk of diabetes, in the way that filter coffee does. The researchers still cannot say the exact nature of the link.

Many other types of coffee preparation were not specifically investigated in the study, such as instant, espresso, cafetière, and percolator coffee. These types of coffee were not common among the Swedish study population when the data was collected.

But given that espresso coffee, from classic espresso machines or the now popular coffee-pods, is also brewed without filters, Rikard Landberg believes the health effects could therefore be similar to boiled coffee, in terms of the risk of type 2 diabetes. Coffee made in a cafetière, or French press, is prepared in a similar way to boiled coffee, so it may also not have the positive effect of reducing type 2 diabetes risk. It is unclear whether instant coffee, the most popular type in the UK, would be more similar to filtered or boiled coffee in this respect.

But the researchers are careful to note that no conclusions can be drawn yet regarding these other preparation methods. Rickard Landberg also stresses that the health impacts of coffee do not depend solely on if it is filtered or not. They also vary with how the coffee beans, and the drink in general, are managed.

To differentiate the diabetes risk for boiled and filtered coffee, a new technique called metabolomics was used, in combination with classic dietary questionnaires. Metabolomics makes it possible to identify the blood concentration of specific molecules from a given food or drink and use that as an objective measurement of intake - instead of simply relying on self-reported intakes from the questionnaires, which are prone to large errors.

"Metabolomics is a fantastic tool, not just for capturing the intake of specific foods and drinks, but also for studying the effects that that intake has on people's metabolism. We can derive important information on the mechanisms behind how certain foods influence disease risk," says Lin Shi, Postdoctoral researcher and the lead author of the study.

Pathogens can use a range of toxins to damage their host organism. Bacteria, such as those responsible for causing the deadly Plague, use a special injection mechanism to deliver their poisonous contents into the host cell. Stefan Raunser, Director at the Max Planck Institute for Molecular Physiology in Dortmund, together with his team, has already produced a detailed analysis of this toxin's sophisticated mechanism. They have now succeeded in replacing the toxin in this nano-syringe with a different substance. This accomplishment creates a basis for their ultimate goal to use bacterial syringes as drug transporters in medicine.

As soon as bacteria have entered a host organism, they deploy their lethal weapon. Just like a syringe needle, they insert a channel through the outer protective layer of the host cell. The toxic protein contained in the capsule is then injected and attacks the cell's structural framework. Within just a few minutes, the cell dies.

Raunser's team discovered this lethal mechanism by using cryo-electron microscopy, a technique employed by only a few research groups in the world. What this technique reveals is the three-dimensional structure of proteins in near-atomic resolution."

Targeted injection into body cells

Stefan Raunser's researchers have now found a way to replace the toxin in the bacteria's nano-syringe with different proteins, and then inject them into cells. For the exchange to work, however, the proteins must fulfil certain criteria: they must be a particular size, be positively charged, and must not interact with the toxin capsule. "With this technique, we have taken the first step towards our ultimate goal of using these nano-syringes in medicine to introduce drugs into body cells in a targeted manner," says Raunser, describing the successful research results.

To transfer its toxic charge into the host cell, the injection mechanism must first dock with the cell. But the bacteria must trick the host cell- by pretending that the toxin is a substance that can be safely absorbed - similar to the famous trojan horse trick. To do this, they have areas that are recognized by sensors on the cell surface.

"We are currently looking for the toxin's 'docking stations'. Once we have found them and understood how the toxin binds to the cell surface, we aim to specifically modify the injection mechanism so that it can recognize cancer cells. We could then inject a killer protein exclusively into tumour cells. This would open up completely new possibilities in cancer medicine with minimal side effects," predicts Raunser.

Mothers' and babies' brains can work together as a 'mega-network' by synchronising brain waves when they interact. The level of connectivity of the brain waves varies according to the mum's emotional state: when mothers express more positive emotions their brain becomes much more strongly connected with their baby's brain. This may help the baby to learn and its brain to develop.

The research, published in the journal NeuroImage, used a method called dual electroencephalograhy (EEG) to look at brain signals in both mums and babies while they were interacting with each other. They found that mums and babies tend to synchronise their brain waves - an effect known as interpersonal neural connectivity - particularly in the frequency of 6-9 hertz, the infant alpha range.

By looking at the qualities and structure of the interpersonal neural connectivity using a mathematical method of network analysis, the researchers could see how information flowed within each separate brain, and also how the two brains operated together as a network.

Mothers and babies tend to spend a lot of time together in a positive emotional state, in which their brains are very connected. The study found that positive interaction, with lots of eye contact, enhances the ability of mother and infant brains to operate as a single system. This promotes efficient sharing and flow of information between mother and infant.

"From our previous work, we know that when the neural connection between mothers and babies is strong, babies are more receptive and ready to learn from their mothers," said Dr Vicky Leong in the University of Cambridge's Department of Psychology, who led the study. "At this stage of life, the baby brain has the ability to change significantly, and these changes are driven by the baby's experiences. By using a positive emotional tone during social interactions, parents can connect better with their infants, and stimulate development of their baby's mental capacity."

The results also suggest that babies of depressed mothers may show less evidence of learning because of a weakened neural connection between mother and infant. Mothers who experience a persistently low or negative mental state due to clinical depression tend to have less interaction with their baby. Their speech is often flatter in tone, they make much less eye contact, and they are less likely to respond when their baby tries to get their attention.

"Our emotions literally change the way that our brains share information with others - positive emotions help us to communicate in a much more efficient way," said Dr Leong. "Depression can have a powerfully negative effect on a parent's ability to establish connections with their baby. All the social cues that normally foster connection are less readily available to the child, so the child doesn't receive the optimal emotional input it needs to thrive."

Emotional communication between parents and their children is crucial during early life, yet little is known about its neural underpinnings. This is the first brain imaging study of two related individuals to investigate if and how babies' interpersonal neural connectivity with their mothers is affected by the emotional quality of their social interaction.

As a social species, humans share emotional states with others. This work shows how emotions change the connection between two individuals at a neural level. The researchers say that their findings apply to many other types of affiliative bond, including between couples, close friends, and siblings, where each person is highly attuned to the other. The strength of the effect is likely to depend on how well the two people know each other and the level of trust between them.

Viruses have been part of animals and humans for eons. When viruses invade a cell, they can infiltrate the nucleus with their genome and become part of the genome of the infected organism. Viruses transfer their genes between various organisms, as well as between tissues containing well differentiated cells inside a living creature. But how they uncoat their well-packed genes and release them to cause infection is largely unknown.

Mib1 protein systematically controls virus infection

The research group of Urs Greber, professor at the Institute of Molecular Life Sciences of the University of Zurich (UZH), has now for the first time identified a protein in human cells that is key for successful viral DNA uncoating: the ubiquitin-ligase Mind bomb 1 (Mib1). "The protein enables adenoviruses to uncoat their DNA and discharge it into the nucleus - which is necessary for successful infection," says Greber. If the protein is not produced or fails to work properly, the viruses can penetrate into the cell and reach the nuclear membrane, but they remain stuck on the porous structures of the nuclear envelope. "This finding opens up a new possibility for developing anti-viral therapies that block Mib1 in well differentiated cells," says Greber. At present, there are no effective drugs to combat these widespread viruses.

Looking for door handle at nucleus entrance

Researchers found the protein by switching off most of the genes in human cells of the lung epithelium using RNA interference one by one, and then testing whether adenoviruses could infect the cells. "When we inhibited the gene for Mib1 or knocked it out using CRISPR-Cas technology, the virus infection rate declined drastically. Practically all adenoviruses remained stuck at the pore structures outside of the nucleus," says Greber. As soon as these cells, after genetic interventions, produced small amounts of Mib1 again, the Mib1 reached the viruses at the nuclear pores, and the viruses uncoated their genes and infected the cells.

Adenoviruses: Life-threatening for people with weakened immune systems

Adenoviruses are widespread in humans and many animals. In humans, they can cause infections in the respiratory system and the gastrointestinal tract, as well as the kidney, liver, eyes and blood cells. For healthy people, the viruses are not life-threatening - the viruses simply settle in immune cells, where they remain for months without damaging the cells or tissue. In a person with a weakened immune system, however - for example stem-cell or organ transplant recipients - adenoviruses can easily spread to other cells and become life-threatening.

Many cells in our body constantly change their shape and move within our tissues. For example, wound healing and the immune system depend on migrating cells. On the other hand, uncontrolled cell migration is a hallmark of metastasis during the development of malignant cancers, so cell migration must be very tightly regulated.

The driving force for cell migration is produced by a protein called actin. Actin monomers act as building blocks by polymerising into rod-like filaments that push the leading edge of the cell forward. The polymerisation of the actin filaments must be balanced by depolymerisation of the filaments at the other end.

Now, scientists at the University of Helsinki, Finland, and Institut Jacques Monod, France, have identified a molecular machinery which drives rapid depolymerisation of actin filaments and recycles the resulting actin monomers for a new round of polymerisation. Two proteins, cyclase-associated protein and cofilin, work together in this.

"By using X-ray crystallography and computer simulations, we could actually see the atomic details of how these two proteins embrace actin filaments and disassemble them into their building blocks. One of the most exciting parts of the project was to see under the microscope how actin filaments suddenly began disappearing when we introduced these two proteins into their vicinity," says PhD student Tommi Kotila, the lead author of the study.

In malignant tumours, cells go haywire in their movements, because their migration machinery is not properly controlled. Because, in cancer cells, the regulation of cyclase-associated protein is often defective, the atomistic structure of this machinery may open new avenues for developing therapeutics to inhibit cell migration in cancer.

"This is a great contribution to our understanding of the basic principles of cell migration. It also helps us understand the molecular basis of the uncontrolled migration of cancer cells," says academy professor Pekka Lappalainen.

A large part of the work inside cells is done by proteins acting as enzymes, transporters, channels, motors, supporting pillars and signaling devices. Proteins are three-dimensionally folded chains of diverse amino acids in a genetically encoded sequence. Whereas scientists have already succeeded in obtaining sequence information from single DNA strands, a further major challenge in bioanalytics is the direct determination of the amino acid sequence from individual proteins. A team of researchers from the University of Cergy-Pontoise, France, the University of Freiburg and the University of Illinois in the US has now been able to differentiate, for the first time, between individual amino acids in short peptides, i.e. protein fragments, using a tiny pore the size of a nanometer. The scientists have thus laid the foundation for direct sequencing of individual proteins. They recently presented their results in the current issue of the journal Nature Biotechnology.

Because previous techniques, such as mass spectrometry, are not sensitive enough, for instance to accurately determine the protein composition of a single cell, the pore forming protein aerolysin was incorporated into an artificial cell membrane and electrodes were used to pass an ion current through the pore, explains Prof. Dr. Jan C. Behrends from the Institute of Physiology at the Medical Faculty of the University of Freiburg. Several years ago, researchers at the Universities of Freiburg and Cergy had already shown that blockades of this current caused by a molecule entering the pore enabled the very sensitive measurement of its size. On this basis, the team was able to show that the sensitivity of the so-called aerolysin pore is so high that short proteins, i.e. peptides, that only differ in a single amino acid can be distinguished from each other.

Using a particularly high-resolution electrophysiological measurement method developed at the University of Freiburg, the team was even able to differentiate between the amino acids leucine and isoleucine with more than 90 percent reliability. These two amino acids have the same composition, and therefore mass, and differ only in the spatial arrangement of the molecular groups. The differentiation of such so-called structural isomers by means of the aerolysin pore proves that the current signal is not exclusively dependent on the molecular mass, as was previously assumed, thereby showing that the new technology is superior, in principle, to mass spectrometry. The researchers in the US showed in simulations that this high resolution is based on a kind of molecular trap within the pore. This trap immobilizes the peptides for about one hundredth of a second, which is what makes accurate measurement possible. This enabled the recently published study to reliably differentiate eleven of the 20 amino acids involved in the construction of proteins, using the nanopore current signal without additional chemical alterations.