Culture

Flies predict changes in their visual environment in order to execute evasive maneuvers, according to new research from the University of Chicago. This reliance on predictive information to guide behavior suggests that prediction may be a general feature of animal nervous systems in supporting quick behavioral changes. The study was published on May 20 in PLOS Computational Biology.

Animals use their sensory nervous systems to take in information about their environments and then carry out certain behaviors in response to what they detect. However, the nervous system takes time to process this sensory information, meaning that the environment can change by the time the previous information has been fully processed.

"This is really important in predator/prey interactions," said senior author Stephanie Palmer, PhD, Associate Professor of Organismal Biology and Anatomy at UChicago. "For a fly, everything is trying to eat you, and you want to avoid being eaten. However, the fly's environment is rapidly changing, and the neurons they have are laggy. We wanted to study how flies were able to execute quick evasive behaviors to avoid being eaten by predators when ongoing feedback from their sensory systems hasn't been processed."

To answer this question, the investigators took a highly interdisciplinary approach. "This is a project born out of this new era of open science sharing," Palmer said. "We were able to take the precise behavioral recordings made by another group and use them for a theoretical, computational neuroscience question: Does the fly's visual system make predictions using the initial detection of a threat that can span the lag time in processing of additional feedback as the fly starts its evasive behavior?"

Previous work from first author Siwei Wang, PhD, a postdoctoral researcher in Palmer's group, looked at a theoretical model of how encoding motion in the fly visual system might work. "I had an idea of how to extend these ideas to prediction, and this study allowed me to compare my model to real life behavioral data to test my theory," Wang said.

Using detailed diagrams of the connectivity between neurons in the fly visual system, the researchers made a simulation of the visual response as they fed in the previously recorded behavioral data set. "We compared what an optimal prediction would look like and what the fly's prediction looks like, and then we broke open the simulation to try to identify which parts were the most important for making these predictions," Palmer said.

The authors first identified that sensory data about the fly's visual world passes though an information bottleneck, where some of the sensory data is thrown out by the fly's brain because it simply does not have enough computing power to handle the amount of information it is taking in. However, the fly cannot indiscriminately discard visual information, because some of it might be useful for making predictions.

The authors identified structures called axonal gap junctions, which are physical channels connecting the neurons, that mediate an optimal form of this information bottleneck and are critical for both filtering out the unnecessary information and preserving the necessary information to make predictions.

The investigators further found that a subpopulation of these vertical motion sensory neurons that are involved in making predictions is unique in that it is also directly connected to the fly's flight steering neurons. This suggests that there is direct input from the neurons responsible for making predictions about the fly's environment to neurons that control the fly's behavior. This direct connection might explain how predictions that the fly is making are able to quickly influence its behavior.

Identification of these structures and the ability of the fly visual system to make predictions is likely to drive insight into how other animals' nervous systems make similar predictions.

"Cracking open the black box of how the fly does this has revealed what we think are universal design principles that the nervous systems of other animals probably also use," Palmer said. "We're interested in searching for another example of prediction-guiding behavior in another animal and asking if what we found in the fly really does apply broadly across species."

Ultimately, this kind of theoretical neuroscience may shed light on how our human brains function. "One of our greatest challenges as humans is understanding how everything inside our head works. Insights from work on flies can be generalizable and actually give us clues to how our brains operate," Palmer said.

Wang said the results could even have implications for understanding neurodegenerative diseases like Alzheimer's disease, where the brain loses the ability to make predictions. If the insights gained from these fly studies hold true in humans, it could help uncover new specific targets for therapeutic intervention. "We're still a long way from that, but this research in flies is setting the ground work to allow others to do that down the line," Wang said.

The immune system is a complex balancing act; if it overreacts or underreacts to foreign molecules, there can be serious health consequences.

For cancer patients, tumor progression is often accompanied by immunosuppression, meaning their bodies can't fight off pathogens the way they should. By contrast, for people with autoimmune diseases like type 1 diabetes, rheumatoid arthritis, and multiple sclerosis, their immune systems overreact and attack the body itself.

Both of these reactions are influenced by a series of molecular checkpoints found in both immune cells and cancer cells. In immune cells, these checkpoints are supposed to prevent the immune system from mounting a response that is too strong and attacks healthy cells. For people with autoimmune diseases, these checkpoint molecules do not function properly. In cancer cells, they bind to immune cell receptors and inhibit their function to a degree that makes patients vulnerable to severe illness and infection.

Dr. Laijun Lai, a research professor in the Department of Allied Health Sciences in the College of Agriculture, Health and Natural Resources, has used bioinformatics and gene engineering techniques to develop a series of recombinant proteins and antibodies for a novel set of checkpoint molecules to address both of these concerns. Lai recently published a paper on the effectiveness of this invention in EMBO Molecular Medicine and has a patent pending for this invention.

Scientists made a major breakthrough when they identified several checkpoints, specifically PD-L1, PD-1 and CTLA-4, within the last decade. There are several FDA-approved medications that produce recombinant proteins to treat autoimmune disease, and antibodies to block the inhibitor activity of these checkpoints for cancer patients. However, not all patients respond to these treatments since there are many other checkpoints at work.

Using a bioinformatics approach, Lai identified three additional checkpoints: CD300c, ERMAP, and TAPBPL found in both immune cells and cancer cells. The bioinformatics approach identified the checkpoints that were most likely to be relevant based on their genetic and structural similarities to previously identified molecules.

Each molecule binds to a specific immune cell receptor to send an inhibitory signal and uses different mechanisms to check immune cell responses.

"The expression pattern of our molecules are different from existing checkpoint molecules and, probably, a different subset of patients will respond to them," Lai says.

Lai's group used genetic engineering to develop recombinant proteins from the genetic blueprint of these proteins. Lai has demonstrated that these recombinant proteins can successfully suppress T-Cell function in animal models of autoimmune diseases.

On the other side, Lai's group developed antibodies that can block the inhibitory activity of these checkpoint molecules. He found the antibodies enhance antitumor immunity and inhibit tumor growth in animal models.

These therapies can be combined with exiting antibodies for PD-L1, PD-1 and CTLA-4, or on their own for patients who do not respond to those treatments.

"Our antibodies against these checkpoint molecules have the potential to be used in the treatment of cancer patients who are resistant to the anti-PD-1, PDL1, and CTLA-4 antibodies and can also be used in combination with existing antibodies to enhance the antitumor effects," Lai says.

A University of Otago study has revealed how earthquake upheaval has affected New Zealand's coastal species.

Lead author Dr Felix Vaux, of the Department of Zoology, says earthquakes are typically considered devastating events for people and the environment, but the positive opportunities that they can create for wildlife are often overlooked.

For the Marsden-funded study, published in Journal of Phycology, the researchers sequenced DNA from 288 rimurapa/bull-kelp plants from 28 places across central New Zealand.

"All specimens from the North Island were expected to be the species Durvillaea antarctica, but unexpectedly 10 samples from four sites were Durvillaea poha - about 150 km from the nearest population on the Kaik?ura Peninsula," Dr Vaux says.

The range expansion of the seaweed seems to be associated with the, often forgotten, 1855 Wairarapa earthquake - New Zealand's strongest recorded earthquake since European colonisation, at magnitude 8.2.

"Uplift and landslides around Wellington cleared swathes of coastline of Durvillaea antarctica, and this seems to have allowed a previously South Island restricted species - Durvillaea poha - to colonise and establish itself in the North Island.

"This exciting discovery highlights that frequent tectonic activity may be reshaping New Zealand's biodiversity, including its marine environments, and it reminds us that recent events - such as the 2016 Kaik?ura earthquake, may have long-lasting effects on the environment."

Dr Vaux believes an increase in the species diversity of bull-kelp in the North Island is likely to be positive for the intertidal community as Durvillaea provides a sheltered habitat for numerous animals - including crustaceans, molluscs such as pāua, spiders and fish.

"Our discovery is exciting because it indicates that tectonic disturbance can not only change population structure within a species, but it can also create ecological opportunity and shift the distribution of organisms.

"While many range shifts have been linked to climate change, tectonic disturbance should not be overlooked as a potential facilitator of range expansion. In our fast-changing world, it is becoming increasingly important to understand the forces that shape the distribution of species," he says.

Palo Alto, CA--In a new study, researchers found that recreational boats and high-speed ferries contribute significant underwater noise in San Francisco Bay, a highly urbanized coastline that is increasingly becoming a stop along the migratory routes of gray and humpback whales and home to bottlenose dolphins and harbor porpoises.

The study is the first of its kind to use radar to track boats not broadcasting information through the Automatic Identification System (AIS), a navigation safety system required onboard large commercial ships. The findings add to the growing evidence that smaller vessels, which are not required to broadcast data through the AIS, contribute significant underwater noise along urban coastlines.

Using the ProtectedSeas Marine Monitor (M2), an autonomous vessel-tracking system and high-definition camera, the research team, led by Samantha Cope, a researcher at the California-based Anthropocene Institute, tracked all types of vessel for 11 days in a region of San Francisco Bay where high-speed ferry, recreational, and commercial shipping traffic are common. The findings were recently published in the Journal of the Acoustical Society of America.

At the time of the study Cope was a master's student in the Hines Lab at the San Francisco State University Estuary & Ocean Science (EOS) Center. In collaboration with SF State Professor Emeritus Roger Bland, the team combined hydrophone measurements of underwater sound from the EOS Center research pier with data from the M2 to trace the noise produced by individual vessels.

"With the recent influx of gray and humpback whales coming into the bay to feed within the last five years and more frequent carcasses that have washed ashore, it's important that we quantify the threats to these marine mammals," said Cope. "This is one of only a few studies to quantify vessel noise within the bay."

Boat noise pollution can impact these animals' abilities to find food, mates and navigate their underwater environment, putting them at an increased risk for collisions with vessels.

While larger vessels tended to produce the loudest noise, the researchers found that the biggest noise polluters by area were high-speed ferries, which made up 80 percent of the vessels observed in the study and covered 17 times more area than large commercial ships. Ferries, which make frequent trips across the Bay every day, are tracked by AIS but are also unique to San Francisco Bay and are an important part of the suite of threats to the marine mammals that come into the Bay.

"This is really cutting-edge research, and we're very proud to have done it first here in the Bay," said SF State Professor of Geography & Environment Ellen Hines, a study co-author, adding that the tracking technology has garnered interest from international researchers. "This has so many applications and is something that can be done remotely, easily and sustainably."

According to Cope, the level of noise exposure due to recreational boats, which were primarily tracked by radar and not AIS, covered roughly twice as much area as exposure levels from large commercial ships.

"The M2 was a valuable tool for this type of analysis along an urban coastline where there are large amounts of recreational, non-AIS traffic," said Cope.

The researchers plan to continue their work in the region, including a collaboration with the Marine Mammal Center tracking vessel traffic near the Golden Gate Bridge, which will allow them to capture information about all of the boats entering and leaving the Bay.

FINDINGS

A new multi-institution study led by a team of researchers at the David Geffen School of Medicine demonstrated that blocking a protein called ABCB10 in liver cells protects against high blood sugar and fatty liver disease in obese mice. Furthermore, ABCB10 activity prompted insulin resistance in human liver cells.

The findings are the first to show that ABCB10 transports biliverdin out of the mitochondria - the cell's "energy generating powerhouses." Biliverdin is the precursor of bilirubin, a substance with antioxidant properties. Consequently, ABCB10 transport activity causes an increase in bilirubin synthesis inside liver cells undergoing fatty liver disease.

BACKGROUND

Non-alcoholic fatty liver disease is closely linked to obesity and other disorders related to insulin resistance and is becoming increasingly common throughout the world, affecting an estimated 100 million people in the United States.

The liver filters everything that people consume and sorts it for the nutrients that will stay in the body or for the toxins that it will expel. The liver is also one of the organs richest in mitochondria - the small organelles in cells that convert food into usable energy through a process called metabolism. Consequently, the mitochondria produce high levels of free radicals, as well as antioxidants to keep these free radicals at healthy levels. Both free radicals and antioxidants play a key role in regulating metabolism and are elevated in insulin resistance and fatty liver disease.

One of these antioxidants is bilirubin, a yellow-bile substance that is released from the breakdown of biliverdin - its green-bile precursor. Bilirubin is produced at high levels in livers from people with fatty liver disease. Both biliverdin and bilirubin are found naturally in the body and released during the breakdown of heme - the deep red iron-containing molecule in red blood cells, which can be seen in the changing color of bruises - from green (biliverdin) to yellow (bilirubin).

Previous research established that mild increases in blood bilirubin content could be associated with protection from metabolic diseases. However, the effects of bilirubin content inside mitochondria and their relationship to fatty liver disease and insulin resistance, remained unknown. This current study shows that increased bilirubin content inside the mitochondria driven by ABCB10 activity is contributing to fatty liver disease.

METHODS

In the study, the researchers removed the ABCB10 protein selectively from the livers of mice to test whether ABCB10 removal impacted the ability of obese mice to tolerate glucose, if they developed fat in the liver and how well the mitochondria in their livers were working to convert nutrients into usable energy.

In lean mice, the researchers found no difference in metabolism and health when ABCB10 was removed from their livers, while in obese mice they found that removing ABCB10 protected against insulin resistance and fatty liver disease.

Secondly, the researchers measured bilirubin in the mitochondria of liver cells using fluorescent sensors, as well as testing purified ABCB10 to determine what ABCB10 transports. They found that ABCB10 transports biliverdin out of the mitochondria and increases bilirubin production in liver cells, with ABCB10 removal decreasing mitochondrial bilirubin content to levels observed in lean mice.

Thirdly, the researchers found that when they restored bilirubin content in the mitochondria, the benefits on the function of mitochondria resulting from the removal of ABCB10 were reversed.

IMPACT

These findings shed light on the relevance of the association of some genetic ABCB10 variants with insulin resistance in Type 2 diabetes. While still very early to draw any conclusions, these findings could inspire the development of therapies that target ABCB10 or mitochondrial bilirubin in the liver to reverse fatty liver disease in obese individuals.

Using the Five-hundred-meter Aperture Spherical radio Telescope (FAST), a research team led by Prof. HAN Jinlin from National Astronomical Observatories of Chinese Academy of Sciences (NAOC) has discovered 201 pulsars, including many very faint pulsars, 40 millisecond pulsars (MSPs), and 16 pulsars in binaries.

These discoveries were published in Research in Astronomy and Astrophysics.

Pulsars are compact remnants of the death of bright, massive stars. They have the strongest magnetic field, highest density and fastest rotation of any celestial body in the Universe, and show significant relativistic effects in systems of binary compact stars.

Since the first pulsars were discovered in 1968, about 3,000 pulsars have been found in total. Among them, about 400 have a period less than 30 milliseconds and are very stable in rotation.

Prof. HAN and his team designed a snapshot survey strategy so that a small patch of sky can be stared for five minutes by FAST and can be fully covered in 21 minutes. This survey is known as the Galactic Plane Pulsar Snapshot (GPPS). The entire visible sky near the Milky Way will be completely hunted for pulsars in the next five years.

This is the first sensitive search for weak pulsars down to the microJy level and has been selected as one of FAST's five key science projects. Such a survey can detect pulsars with a flux density down to 5 microJy, about a magnitude weaker than previous surveys by other radio telescopes over the world.

Up to now, GPPS has searched about 5% of the planed sky and has discovered 201 pulsars. "At this early stage of the project, this is an impressive total," said Prof. R.N. Manchester of CSIRO Astronomy and Space Science, Australia.

Among the newly discovered pulsars, some have strange pulse dispersion properties. Dispersion is the measure of total electron density along the path from a pulsar to Earth and is a good indicator of pulsar distance. The higher the dispersion measure, the greater the distance. GPPS has uncovered pulsars with very high dispersion measures that challenge the best current models of electron density distribution in the Milky Way.

According to the best information on electron distribution in the Milky Way, these pulsars ought to be located outside the Milky Way. However, it is more likely that these pulsars are located inside the Milky Way. The electron density in the Milky Way, especially in the direction of its spiral arms, is probably underestimated. In other words, the newly discovered pulsars reveal more electrons in the Milky Way's spiral arms than had ever been known. The new measurements effectively improve the knowledge of the Milky Way electron distribution.

About 40 pulsars found in the survey have a period less than 30 milliseconds, making them newly discovered MSPs. "The GPPS survey has already increased the number of known MSPs by nearly 10 percent, a remarkable achievement," said Prof. Manchester. Among them, 14 have a companion around, so do the two long-period pulsars. "No doubt some of these will turn out to be excellent probes of gravitational theories," he added.

In addition, GPPS has discovered many pulsars with special features. For example, some produce emissions that switch on and off or emit just a few pulses over many minutes. In addition, for many previously known pulsars, the FAST survey has obtained data with extremely high signal-to-noise ratio, which has improved the parameters for 64 pulsars.

"FAST has the promise for the study of compact objects in the universe, and helps us learn more about the fundamental physics and astrophysics," said Prof. Jim Cordes from Cornell University, a reviewer of the study.

Turns out the old adage, "monkey see, monkey do," does ring true -- even when it comes to cannabis use. However, when cannabis use involves youth it's see, think, then do, says a team of UBC Okanagan researchers.

The team found that kids who grow up in homes where parents consume cannabis will more than likely use it themselves. Parental influence on the use of cannabis is important to study as it can help with the development of effective prevention programs, explains Maya Pilin, a doctoral psychology student in the Irving K. Barber Faculty of Arts and Social Sciences.

"Adolescence is a critical period in which drug and alcohol experimentation takes place and when cannabis use is often initiated," says Pilin. "Parents are perhaps the most influential socializing agent for children and early adolescents."

Pilin says it has long been assumed that parental use of cannabis contributes to higher levels of adolescent use. However, while there has been research about parental use of alcohol and whether their children drink, there is less known about pathways to cannabis use.

"What we found mirrors closely what has been found in past research with alcohol use -- that parental use influences adolescents' use as well," she says.

For their research, the team used data from a survey of almost 700 students in Grades 7 to 9, which is when previous studies demonstrate that cannabis use increases dramatically. Each year over a three-year period, the students were asked if one or both of their parents used cannabis, if so, how frequently and whether they also use it. As the students aged, their cannabis use began and increased.

This data was collected before cannabis was decriminalized in Canada in 2017.

"We wanted to try and explain, how parental use, while their kids were in Grade 7, would be associated with their kids' use by ninth grade," says Dr. Sarah Dow-Fleisner, a researcher with the School of Social Work. "We hypothesized that early parental use would impact how teens think about cannabis use, in particular whether parental use early in adolescence would be associated with more positive expectations and perceptions of cannabis use by Grade 8, and whether that would lead to an increased chance of using cannabis by Grade 9. What we thought is exactly what we found."

UBCO Psychology Professor Dr. Marvin Krank funded the research and collected the data for the study in collaboration with Okanagan valley school districts.

"This work is an important extension of previous studies about how parents influence their children's cannabis use in subtle ways," he says. "Children of parents who use cannabis have more associations and positive thoughts that quickly come to mind in response to cues associated with cannabis use. Such quick and automatic thinking influences their choices often without their awareness."

Analyzing parental and then subsequent teen use of cannabis can provide important information in terms of intervention. Effective interventions need to consider the way youth think about cannabis use and how that has been shaped by parents, says Pilin.

Understanding the reasons for early cannabis use is essential to developing effective prevention programs in these formative years, explains Dr. Dow-Fleisner, as early use of cannabis is associated with harmful effects on mental and social developmental outcomes. It also increases the chance of experimentation with other drugs and greatly increases the risk of being diagnosed with a substance-use disorder in adulthood.

"What is important is that we do see across the literature that parent use and experiences with cannabis in early adolescence are linked with cannabis use later in adolescence, and part of this relationship has to do with the way teens think about cannabis," she adds. "It helps us think about ways to intervene and prevent cannabis use -- our interventions must address how youth think about substance use based on their familial and personal experiences."

People with bipolar disorder may not take their medication because of side effects, fear of addiction and a preference for alternative treatment - according to research from Norfolk and Suffolk NHS Foundation Trust (NSFT) and the University of East Anglia (UEA).

Nearly half of people with bipolar disorder do not take their medication as prescribed leading to relapse, hospitalisation, and increased risk of suicide.

A new study, published today, reveals six key factors that stop people taking their medication as prescribed.

These include whether they are experiencing side effects, difficulties in remembering to take medication and a lack of support from family, friends and healthcare professionals.

A patient's own beliefs and knowledge about bipolar disorder and its treatment was also found to affect whether or not they take their meds, as well as fear of addiction, and a preference for alternative treatment.

The new study comes from a team of pharmacists, psychiatrists, and experts in behavioural science from NSFT, UEA, Devon Partnership Trust, and the University of Lyon.

Asta Ratna Prajapati, consultant pharmacist at NSFT and a post-graduate researcher at UEA's School of Pharmacy, led the research. The study was funded by a Health Education England (HEE) / National Institute for Health Research Clinical Doctoral Research Fellowship.

He said: "Bipolar disorder is a mental health condition that causes extreme mood swings that include emotional highs, known as mania or hypomania, and depressive lows.

"Around half of people with bipolar disorder don't take their medication which can lead to a relapse of symptoms. And this can have a knock-on impact with problems at work, strained relationships with family and friends, hospitalisation, and an increased risk of suicide.

"We wanted to better understand what stops people from taking their medication."

The research team looked at the evidence for what hinders people taking their medication for bipolar disorder. The research team carried out a systematic review and included 57 studies, mostly surveys and interviews, involving 32894 patients and healthcare professionals. The majority (79 per cent) of the studies were conducted in the USA and Europe.

"We found six key factors that affect whether people take their medication. The main reason being what the medication is like, whether there are side effects, and whether it works," said Prajapati.

"Secondly, we found that a patient's beliefs and knowledge about bipolar disorder and its treatment could stop them taking medication.

"We also found that how patients felt taking their medication had an impact - for example a fear of addiction or worry about negative side effects.

"Other factors included a lack of support, difficulty remembering taking medication and not wanting to take it for reasons including preferring alternative treatment.

"We recommend that the prescribers talk to patients about their thoughts and experiences of the medications they take, paying particular attention to these issues which may stop patients taking their meds."

The research team are now developing a tool to identify people who struggle to take their medication and their individual reasons. They hope it will help prescribers and patients work together and offer bespoke support to make medication taking easier.

'Mapping modifiable determinants of medication adherence in bipolar disorder (BD) to the theoretical domains framework (TDF): a systematic review is published in the Psychological Medicine Journal on May 19, 2021.

Researchers at the University of Eastern Finland have found a potential neuroprotective effect of a protein modification that could be a therapeutic target in early Alzheimer's disease. The new study investigated the role of MECP2, a regulator of gene expression, in Alzheimer's disease related processes in brain cells. The study found that phosphorylation of MECP2 protein at a specific amino acid decreases in the brain as Alzheimer's disease is progressing. Abolishing this phosphorylation of MECP2 in cultured mouse neurons upon inflammatory stimulation enhanced their viability and increased the expression of important genes in the maintenance and protection of neurons. The results obtained in the study call attention to modifications of MECP2 as potential targets for developing specific therapies against AD and other neurodegenerative diseases. The study was recently published in the Cells journal.

Alzheimer's disease is the most common form of dementia with more than 40 million people living with the disease worldwide. No therapies currently exist for the effective prevention or treatment of the disease. Long before severe symptoms of Alzheimer's disease, such as memory loss and confusion occur, connections between neurons are lost and neurons are dying in the brain. Neurons are not the only cell type that contributes to Alzheimer's disease progression. Microglia, the immune cells of the brain, have been shown to contribute to neuronal damage and loss. While mildly activated microglia can protect neurons by removing harmful substances and cell debris, their chronic activation can lead to secretion of neurotoxic factors and engulfment of healthy neurons.

"The function of MECP2 phosphorylation has been almost exclusively studied in neurons. As it has become evident that microglia are involved in the pathogenesis of many neurodegenerative diseases, we chose to focus on microglial cells and co-cultures of neurons with microglia. To additionally model the activation of microglia, we induced inflammation through treatment with different compounds", says Early Stage Researcher Rebekka Wittrahm.

In post-mortem brain samples from different stages of Alzheimer's disease, this study found that phosphorylation of the MECP2 protein decreased at the amino acid serine 423 in the early stages of Alzheimer's disease. Accordingly, the question arose whether MECP2 unphosphorylated at serine 423 would change cellular processes when expressed in cultured microglia or neuron-microglia co-cultures. To study this question, both wild type MECP2 and a variant where serine 423 was mutated to prevent phosphorylation were expressed in the different cell culture models. In microglia cells, the researchers found that overexpression of wildtype MECP2 led to a decrease in phagocytic uptake of particles. Upon activation of the microglia, expression of wildtype MECP2 enhanced their inflammatory response to stimulation. For most of the analyzed parameters, blocked phosphorylation of MECP2 serine 423 did not lead to major changes as compared to the wild type protein.

In contrast to the results from microglial monocultures, the expression of the proteins in neurons co-cultured with microglia cells revealed several differences between wild type and the mutated MECP2. RNA sequencing analysis revealed that blocking of the serine 423 phosphorylation upon microglial activation increased the expression of several neuronal genes that are known to contribute to maintenance and protection of the cells.

"More extensive experiments are needed but it is conceivable that the dephosphorylation of MECP2 at serine 423 might be a mechanism of the cells to mediate neuroprotection in the early stages of Alzheimer's disease," Rebekka Wittrahm considers.

In summary, the results of this study suggest that MECP2 serine 423 is an essential phosphorylation site that might play a role in regulating neuronal gene expression upon neuroinflammation. The study calls attention to the idea that modification sites of MECP2 are potential targets for developing specific therapies against Alzheimer's disease and other neurodegenerative diseases in the future.

The latest findings show that with clever science, a single fingerprint left at a crime scene could be used to determine whether someone has touched or ingested class A drugs.

In a paper published in Royal Society of Chemistry's Analyst journal, a team of researchers at the University of Surrey, in collaboration with the National Centre of Excellence in Mass Spectrometry Imaging at the National Physical Laboratory (NPL) and Ionoptika Ltd reveal how they have been able to identify the differences between the fingerprints of people who touched cocaine compared with those who have ingested the drug - even if the hands are not washed. The smart science behind the advance is the mass spectrometry imaging tools applied to the detection of cocaine and its metabolites in fingerprints.

This is a step up from research previously conducted by the University. In 2020 Surrey researchers were able to determine the difference between touch and ingestion if someone had washed their hands prior to giving a sample. Given that a suspect at a crime scene is unlikely to wash their hands before leaving fingerprints, these new findings are a significant advantage to crime forensics.

The Surrey team have continued to use their world-leading experimental fingerprint drug testing approach based on high resolution mass spectrometry. Cocaine and its primary metabolite - benzoylecgonine*, can be imaged in fingerprints produced after either ingestion or contact with cocaine using these techniques. By analysing the images of cocaine and its metabolite in a fingerprint, and exploring the relationship between these molecules and the fingerprint ridges, it is possible to tell the difference between a person who has ingested a drug, and someone who has only touched it.

Dr Melanie Bailey, Reader in Forensic and Analytical Science and EPSRC Fellow at the University of Surrey, said: "Over the decades, fingerprinting technology has provided forensics with a great deal of information about gender and medication. Now, these new findings will inform forensics further when it comes to determining the use of class A drugs.

"In forensic science being able to understand more about the circumstances under which a fingerprint was deposited at a crime scene is important. This gives us the opportunity to reconstruct more detailed information from crime scenes in the future. The new research demonstrates that this is possible for the first time using high resolution mass spectrometry techniques."

Dr Allen Bellew, Applications & Marketing Manager at Ionoptika, commented: "To image these metabolites excreted through the skin requires very powerful analytical tools such as the unique Water Cluster Source that Ionoptika has been developing for over a decade. It's clear that this new technique will be important for forensic science in the future, and as a small business in the UK it's very exciting to see the role that our J105 SIMS instrument has played in its development."

Dr Chelsea Nikula, Higher Research Scientist, NPL said: "This novel application of three different techniques illustrates the capabilities of mass spectrometry imaging to enable next generation forensics analyses. It is great to see that the work we do here at NPL and the facilities we have available to us at the National Centre of Excellence in Mass Spectrometry Imaging helped support this research."

*Benzoylecgonine is a molecule produced in the body when cocaine is ingested, and it is essential in distinguishing those who have consumed the class A drug from those who have handled it.

A pioneering new study led by UCL scientists has revealed, for the first time, a layer of genetic material involved in controlling the production of tau; a protein which plays a critical role in serious degenerative conditions, such as Parkinson's and Alzheimer's disease.

The international research, conducted in mice and cells, also revealed this material is part of a larger family of non-coding genes* which control and regulate other similar brain proteins, such as beta-amyloid associated with Alzheimer's and alpha-synuclein implicated in Parkinson's disease and Lewy body dementia.

Researchers say the breakthrough findings, published in Nature, shed an important new light on how proteins linked to neurological conditions are produced and controlled, and could pave the way for new treatments for a wide range of dementia related diseases.

Lead author, Dr Roberto Simone (UCL Queen Square Institute of Neurology), said: "Tau plays a vital role inside our brain cells: It helps to stabilise and maintain the cytoskeletal structures that allow different materials to be transported to where they need to be. We know that too much tau is detrimental - the excess unused tau converts into toxic species that may be responsible for damaging cells and driving the spread and progression of degenerative disease. However, despite the fact that tau has been studied for more than three decades, until now we did not know how tau protein production is controlled."

For the laboratory-based study, researchers identified a section of genetic material known as 'antisense long non-coding RNA' (lncRNA). They discovered this material does not make tau directly but helps to regulate, fine-tune and repress the production of the protein inside brain cells. This precision provided by antisense lncRNA in tau regulation could be crucial for smooth functioning of the brain's nerve cells.

Research group leader, Professor Rohan de Silva (UCL Queen Square Institute of Neurology) said: "Excitingly, we found that the lncRNA that controls tau is not unique. Other key proteins we know to be involved in neurological conditions, including alpha-synuclein in Parkinson's disease and beta-amyloid in Alzheimer's disease, are controlled by very similar lncRNAs. This means we may have found the key to regulating the production of a whole range of proteins involved in brain function and the development of these devastating conditions.

"It's early days but we hope that these exciting new insights will lead to the development of drugs that can keep tau and other proteins under control, and that these therapies could be life-changing for degenerative brain conditions that as yet, have no treatments to halt, let alone slow their progression."

Other neurological conditions associated with the tau protein include corticobasal degeneration and progressive supranuclear palsy.

Targeting tau to create new treatments

Professor de Silva said: "Genetic studies have previously shown that people who have a particular form of the tau gene - called H1 - are more likely to get Parkinson's disease, corticobasal degeneration and progressive supranuclear palsy. We know that people with the H1 form of the gene produce more tau. We also know the lncRNA we've identified helps to limit tau production, and that studies using post-mortem brain tissue show this lncRNA may be reduced in people with Parkinson's disease.

"So, if we can find a way to boost the levels of this lncRNA, we might be able to reduce the production of tau protein which could help to slow or stop the damage to cells inside the brain."

He added: "That's exactly what we are working on now. Specifically, we are developing a gene therapy to deliver this lncRNA to brain cells and we're currently testing whether this approach can reduce tau levels in mice and other animal models. If it's successful, we hope to take this approach forward to be developed as a new therapy that can one day be tested in people."

Professor David Dexter, Associate Director of Research at Parkinson's UK, said: "This important research provides fantastic new insights into how tau production is controlled inside brain cells, and presents an exciting new opportunity for developing therapies that target this. It's especially exciting to see that similar mechanisms may be involved in controlling the production of many other key proteins implicated in other neurological conditions, as it suggests strategies targeting these mechanisms could be effective across many conditions."

This research has involved collaborations within UCL and with research groups at the Francis Crick Institute, UK Dementia Research Institute, St George's University of London, Karolinska Institute, Sweden and the University of Trento, Italy.

Funding for this study came from Reta Lila Weston Trust, Wellcome Trust, Medical Research Council (MRC), Parkinson's UK, CBD Solutions, PSP Association and CurePSP.

* Non-coding DNA: Our genome contains coding genes, the parts of our DNA that contain instructions for making proteins, the building blocks of our bodies. However, these coding genes make up only a small part of our genome - a mere 3% of the 3 billion letters (the nucleotides) of our genetic material. Until recently, the remainder of the genome (non-coding) was regarded as junk DNA, without known function. However, it is now clear that the DNA that lies in-between the coding genes is emerging as crucially important not only in human evolution but also in regulating function of cells and influencing the way coding genes produce proteins.

Research has found that strict lockdowns to reduce the spread of COVID-19 might be responsible for delaying normal cardiorespiratory development in children.

The study, the first to examine the topic, is published in the European Journal of Pediatrics. It was carried out by Dr Lee Smith of Anglia Ruskin University (ARU) and a team of academics from Spain, led by Dr Ruben Lopez-Bueno of the University of Zaragoza.

The research involved a group of 89 children from a school in north-eastern Spain. The country introduced a strict six-week lockdown in spring 2020, during which under-15s were unable to leave their homes except for medical reasons.

The children, aged 12-14, took part in fitness tests to measure their maximal oxygen uptake (VO2 max) in November 2019, before the start of the COVID-19 pandemic, and repeated the fitness tests in November 2020.

VO2 max is a well-known cardiorespiratory fitness indicator and levels increase during adolescence, in line with physical growth and development.

The study found that in November 2020, boys and girls in each age group showed lower levels of cardiorespiratory fitness than would be expected with normal VO2 max rate development. Healthy Fitness Zone (HFZ) levels - a standard measure of health based on age and sex - also fell by 3.4% over the 12-month period.

Senior author Dr Lee Smith, Reader in Physical Activity and Public Health at Anglia Ruskin University (ARU), said: "We know that sedentary behaviour has a negative effect on cardiorespiratory fitness and health, but we're unable to say to what extent the delay in development of VO2 max levels we found was caused by COVID-19 restrictions.

"In normal conditions, VO2 max levels tend to increase in adolescents up to a certain age. In our study, each age and sex subgroup showed lower levels in relation to normal VO2 max rate development and specific subgroups, such as boys aged 12 and girls aged 14, displayed reductions in their actual VO2 max levels, which could underscore a higher vulnerability in these groups.

"Our results are perhaps not as pronounced as might have been predicted. This could be because Spain relaxed their lockdown entering the summer. The children were able to take part in physical activity again, helping them to regain cardiorespiratory fitness, and we did not test the group again until November.

"Regardless, if further lockdowns are necessary in future, maintaining access to open spaces such as parks and sports facilities should certainly be considered, particularly for vulnerable groups such as adolescents."

Base editing is a novel gene editing approach that can precisely change individual building blocks in a DNA sequence. By installing such a point mutation in a specific gene, an international research team led by the University of Zurich has succeeded in sustainably lowering high LDL cholesterol levels in the blood of mice and macaques. This opens up the possibility of curing patients with inherited metabolic liver diseases.

Lipoproteins are complex particles that deliver fat molecules to all tissues of the body through the blood system, supplying energy to the cells. One such lipoprotein, the low-density lipoprotein (LDL), can transport thousands of fat molecules, such as cholesterol, per particle. High levels of LDL in the blood are clinically associated with an increased risk of cardiovascular diseases. Since LDL can also carry cholesterol into smaller vessels and thus supply more distant tissues, it can increasingly block the artery lumen, which leads to atherosclerosis.

Introducing a single gene mutation blocks an enzyme

An international research team led by the University of Zurich (UZH) has now demonstrated that a novel precise gene editing approach can reduce high LDL cholesterol levels - substantially and sustainably. The scientists introduced a single point mutation in the gene encoding for an enzyme called PCSK9. This protein is involved in the uptake of LDL cholesterol from the blood into the cells. "The genetic change we induced in mice and macaques successfully blocked PCSK9, which led to a significant reduction of the LDL cholesterol concentrations in the blood. This provides a potential therapy for patients suffering from familial hypercholesterolemia, an inherited form of high cholesterol levels," says study leader Gerald Schwank, professor at the Institute for Pharmacology and Toxicology of UZH.

Adaption of RNA technology used in COVID-19 vaccines

The gene editing technology applied by the researchers uses what are known as base editors. These proteins can change individual bases of the DNA molecule - a single "letter" of a genetic "text" - into another. Adenine base editors, for example, convert an adenine (A) into a guanine (G). And base editors do this much more precisely than previous CRISPR-Cas nucleases, which function as molecular scissors. To control the delivery of the base editor tool into the liver of animals, the researchers adapted the RNA technology used in COVID-19 vaccines. However, instead of encapsulating an RNA encoding the spike protein of SARS-CoV2 into lipid nanoparticles, they encapsulated an RNA encoding for the adenine base editor.

Accurate, efficient and safe

The RNA-lipid nanoparticles formulations were introduced into the animals intravenously, leading to liver-specific uptake and transient production of the base editor tool by the cell machinery. "Up to two-thirds of PCSK9 genes were edited in the mice and up to one-third in the non-human primates, leading to a significant reduction in LDL cholesterol levels," says Schwank. In addition, the scientists carefully assessed whether unspecific editing at undesired locations occurred, but found no indications of such off-target events.

RNA-based therapies for metabolic liver diseases

"Our study shows the feasibility of installing single nucleotide base changes in the liver of non-human primates with high efficiency and accuracy. Approximately 30 percent of all disease-causing hereditary mutations are single base mutations that can, in principle, be corrected with base editors," says Schwank. The new approach could therefore be used to treat a large number of patients suffering from inherited metabolic liver diseases, such as hypercholesterolemia, phenylketonuria or urea cycle disorders. Compared to conventional drugs, genome editing has the advantage that induced changes are sustainable. Thus, if a mutation is repaired in a sufficient number of cells, the patient will be permanently cured.

World-leading eye experts have made a breakthrough that could potentially change the way cataracts are treated - with potential for drug therapy to replace surgery.

Cataract is a clouding of the eye lens that develops over time and affects the quality of vision. It is caused by an accumulation of protein in the lens that reduce the transmission of light to the retina. Previous research led by ARU found that cataracts account for almost half of global cases of blindness.

A significantly developed cataract can only currently be treated by a surgical procedure to remove the cloudy lens and insert an artificial replacement.

A team of international scientists, led by Professor Barbara Pierscionek of Anglia Ruskin University (ARU), has published peer-reviewed research that shows the sophisticated optics of the lens develops much earlier in gestation than has previously been thought possible. They also found how a particular protein (aquaporin) responsible for water passage in the lens disrupts the optical development, leading to cataract formation.

The scientists have spent more than a decade conducting the most precise measurements on optics of the lens at SPring-8, the world's largest and most powerful synchrotron, in Japan.

The synchrotron is a particle accelerator that produces powerful X-rays by accelerating electrons to the speed of light. The X-rays allow measurements to be taken with the highest accuracy yet on optical properties of the eye.

The project team is the first in the world to have measured how the optics in the eye lens develop. Their research was presented earlier this month at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting.

Professor Pierscionek, Deputy Dean (Research and Innovation) for the Faculty of Health, Education, Medicine and Social Care and member of the Medical Technology Research Centre at ARU, said: "Cataracts are one of the main causes of vision loss and blindness worldwide, yet for many people surgery is inaccessible for various reasons.

"Our findings indicate the role of the aquaporin proteins and the crucial importance of this for the lens to work correctly and the eye to see clearly.

"Further research in this area is planned, but this discovery, together with our research on nanotechnologies that indicate drug therapy for cataract is possible, could potentially revolutionise the way cataract is treated, opening up the field for drug-based therapy rather than surgery. This would have exciting implications for public health."

Wednesday 19 May 2021 - New research published today sheds important light on how the production of a key protein in the brain is controlled, which could pave the way for new treatments for a wide range of neurological conditions.

In a study part-funded by Parkinson's UK, researchers investigated a section of genetic material known as antisense long non-coding RNA (lncRNA), which helps fine-tune the production of the protein tau inside brain cells. This precision in tau regulation is crucial for smooth functioning of the nerve cells.

Understanding the mechanism which helps regulate tau production could be the key to developing better treatments for conditions including Parkinson's, Alzheimer's, corticobasal degeneration and progressive supranuclear palsy.

The team's findings, published in Nature, show that tau, along with other key proteins involved in brain function, are controlled by very similar lncRNAs. This insight could help scientists develop the ability to control the production of these proteins and in turn, the development of certain neurological conditions.

The international team comprised of researchers from University College London (UCL), the Francis Crick Institute, University of Trento, Italy and the Karolinska Institute in Stockholm, Sweden.

Lead investigators Professor Rohan de Silva and Dr Roberto Simone from University College London (UCL), said:

"Tau plays a really vital role inside our brain cells. It helps to stabilise and maintain the cytoskeletal structures that allow different materials to be transported to where they are needed. We know that too much tau is detrimental - the excess, unused tau converts into toxic species that may be responsible for damaging cells and driving the spread and progression of disease. However, despite the fact that tau has been studied for more than three decades, until now we did not know how neuronal cells exactly control tau protein production.

"Excitingly, we found that the lncRNA that controls tau is not unique. Other key proteins we know to be involved in neurological conditions, including alpha-synuclein in Parkinson's and beta-amyloid in Alzheimer's, could be controlled by very similar lncRNAs. This means we may have found the key to regulating the production of a whole range of proteins involved in brain function and the development of these devastating conditions.

"It's early days but we hope that these exciting new insights will lead to the development of drugs that can keep tau and other proteins under control, and that these therapies could be life-changing for degenerative brain conditions that as yet, we cannot slow or stop."

Professor David Dexter, Associate Director of Research at Parkinson's UK, said:

"Tau is emerging as one of the key determinants of different rates of progression in Parkinson's so understanding how this protein is regulated may be vital to finding better treatments and a cure for Parkinson's.

"This important research provides fantastic new insights into how tau production is controlled inside brain cells, and presents an exciting new opportunity for developing therapies that target this. It's especially exciting to see that similar mechanisms may be involved in controlling the production of many other key proteins implicated in other neurological conditions, as it suggests strategies targeting these mechanisms could be effective across many conditions."