The hotter our body temperature, the more our bodies speed up a key defense system that fights against tumors, wounds or infections — ScienceDaily

The hotter our body temperature, the more our bodies speed up a key defence system that fights against tumours, wounds or infections, new research by a multidisciplinary team of mathematicians and biologists from the Universities of Warwick and Manchester has found.

The researchers have demonstrated that small rises in temperature (such as during a fever) speed up the speed of a cellular ‘clock’ that controls the response to infections — and this new understanding could lead to more effective and fast-working drugs which target a key protein involved in this process.

Biologists found that inflammatory signals activate ‘Nuclear Factor kappa B’ (NF-κB) proteins to start a ‘clock’ ticking, in which NF-κB proteins move backwards and forwards into and out of the cell nucleus, where they switch genes on and off.

This allows cells to respond to a tumour, wound or infection. When NF-κB is uncontrolled, it is associated with inflammatory diseases, such as Crohn’s disease, psoriasis and rheumatoid arthritis.

At a body temperature of 34 degrees, the NF-κB clock slows down. At higher temperatures than the normal 37 degree body temperature (such as in fever, 40 degrees), the NF-κB clock speeds up.

Mathematicians at the University of Warwick’s Systems Biology Centre calculated how temperature increases make the cycle speed up.

They predicted that a protein called A20 — which is essential to avoid inflammatory disease — might be critically involved in this process. The experimentalists then removed A20 from cells and found that the NF-kB clock lost its sensitivity to increases in temperature.

Lead mathematician Professor David Rand, Professor of Mathematics and a member of the University of Warwick’s Zeeman Institute for Systems Biology and Infectious Disease Epidemiology (SBIDER), explained that in normal life the 24 hour body clock controls small (1.5 degree) changes in body temperature.

He commented: “the lower body temperature during sleep might provide a fascinating explanation into how shift work, jet lag or sleep disorders cause increased inflammatory disease”

Mathematician Dan Woodcock from the University of Warwick said: “this is a good example of how mathematical modelling of cells can lead to useful new biological understanding.”

While the activities of many NF-kB controlled genes were not affected by temperature, a key group of genes showed altered profiles at the different temperatures. These temperature sensitive genes included key inflammatory regulators and controllers of cell communication that can alter cell responses.

This study shows that temperature changes inflammation in cells and tissues in a biologically organised way and suggests that new drugs might more precisely change the inflammatory response by targeting the A20 protein.

Professor Mike White, lead biologist from the University of Manchester, said the study provides a possible explanation of how both environmental and body temperature affects our health:

“We have known for some time that influenza and cold epidemics tend to be worse in the winter when temperatures are cooler. Also, mice living at higher temperatures suffer less from inflammation and cancer. These changes may now be explained by altered immune responses at different temperatures.”

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Inpatient opioid use and insufficient weaning pre-discharge may increase outpatient opioid prescriptions — ScienceDaily

According to the University of Pittsburgh School of Medicine scientists who conducted the study, theirs is the first large-scale evaluation of the impact of in-hospital opioid prescribing on post-discharge opioid use.

“Most previous studies of opioid use in health care have focused on the outpatient setting,” said lead study author Jason Kennedy, MS, research project manager in Pitt’s Department of Critical Care Medicine. “But opioids are often introduced during hospitalization. That’s something clinicians can control, so we looked at inpatient prescription of these drugs to identify targets that may reduce opioid use once patients are out of the hospital.”

The researchers analyzed the medical records of 357,413 non-obstetrical adults hospitalized between 2010 and 2014 at 12 University of Pittsburgh Medical Center (UPMC) hospitals in southwestern Pennsylvania. The region is one of the areas of the country where opioid addiction is a major public health problem. The researchers focused on the 192,240 patients who had not received an opioid in the year prior to their hospitalization — otherwise known as “opioid naïve” patients.

Nearly half (48 percent) of these patients received an opioid while hospitalized. After discharge, those patients receiving hospital opioids were more than twice as likely to report outpatient opioid use within 90-days (8.4 percent vs. 4.1 percent).

The study also found that:

  • Those who took an opioid for more than three-quarters of their hospital stay were 32 percent more likely than those who took an opioid for less than one-fourth of their stay to be prescribed an opioid within 90 days of leaving the hospital.
  • Those who used an opioid within 12 hours of discharge were twice as likely as those who stopped taking an opioid more than 24 hours before discharge to be prescribed an opioid within 90 days of leaving the hospital.
  • 33 percent received an opioid during the 24 hours prior to discharge from the hospital.
  • 20 percent of those receiving opioids in the ICU received intravenous opioids on transfer to the medical ward.

The findings suggest some inpatient interventions that might reduce opioid use in outpatient settings, Mr. Kennedy said.

“Reducing use of opiates near the end of a hospital stay, especially in the 24 hours before discharge, may reduce outpatient prescription of opioids,” he said. “And weaning ICU patients off of intravenous opioids, the most potent way of administering these pain killers, before transitioning them to the medical ward may also help reduce outpatient usage.”

Further study, ideally with randomized, controlled trials, would be necessary to provide definitive guidance to doctors and other health care providers, he added.

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Scientists find link between increases in local temperature and antibiotic resistance — ScienceDaily

Bacteria have long been thought to develop antibiotic resistance largely due to repeated exposure through over-prescribing. But could much bigger environmental pressures be at play?

Seeking to better understand the distribution of antibiotic resistance across the U.S., a multidisciplinary team of epidemiologists from Boston Children’s Hospital and the University of Toronto have found that higher local temperatures and population densities correlate with a higher degree of antibiotic resistance in common bacterial strains. The findings were published today in Nature Climate Change.

“The effects of climate are increasingly being recognized in a variety of infectious diseases, but so far as we know this is the first time it has been implicated in the distribution of antibiotic resistance over geographies,” says the study’s lead author, Derek MacFadden, MD, an infectious disease specialist and research fellow at Boston Children’s Hospital. “We also found a signal that the associations between antibiotic resistance and temperature could be increasing over time.”

“Estimates outside of our study have already told us that there will already be a drastic and deadly rise in antibiotic resistance in coming years,” says the paper’s co-senior author John Brownstein, PhD, who is Chief Innovation Officer and director of the Computational Epidemiology Group at Boston Children’s and professor of pediatrics at Harvard Medical School (HMS). “But with our findings that climate change could be compounding and accelerating an increase in antibiotic resistance, the future prospects could be significantly worse than previously thought.”

During their study, the team assembled a large database of U.S. antibiotic resistance information related to E. coli, K. pneumoniae, and S. aureus, pulling from various streams of hospital, laboratory and disease surveillance data documented between 2013 and 2015. Altogether, their database comprised more than 1.6 million bacterial pathogens from 602 unique records across 223 facilities and 41 states.

Not surprisingly, when looking at antibiotic prescription rates across geographic areas, the team found that increased prescribing was associated with increased antibiotic resistance across all the pathogens that they investigated.

Then, comparing the database to latitude coordinates as well as mean and medium local temperatures, the team found that higher local average minimum temperatures correlated the strongest with antibiotic resistance. Local average minimum temperature increases of 10 degrees Celsius were found to be associated with 4.2, 2.2 and 3.6 percent increases in antibiotic resistant strains of E. coli, K. pneumoniae, and S. aureus, respectively.

More unsettling still, when looking at population density, the team found that an increase of 10,000 people per square mile was associated with three and six percent respective increases in antibiotic resistance in E. coli and K. pneumoniae, which are both Gram-negative species. In contrast, the antibiotic resistance of Gram-positive S. aureus did not appear to be significantly affected by population density.

“Population growth and increases in temperature and antibiotic resistance are three phenomena that we know are currently happening on our planet,” says the study’s co-senior author Mauricio Santillana, PhD, who is a faculty member in the Computational Health Informatics Program at Boston Children’s and an assistant professor at HMS. “But until now, hypotheses about how these phenomena relate to each other have been sparse. We need to continue bringing multidisciplinary teams together to study antibiotic resistance in comparison to the backdrop of population and environmental changes.”

MacFadden says the transmission factor is of particular interest for further scientific research.

“As transmission of antibiotic resistant organisms increases from one host to another, so does the opportunity for ongoing evolutionary selection of resistance due to antibiotic use,” MacFadden says. “We hypothesize that temperature and population density could act to facilitate transmission and thus increases in antibiotic resistance.”

“The bottom line is that our findings highlight a dire need to invest more research efforts into improving our understanding of the interconnectedness of infectious disease, medicine and our changing environment,” Brownstein concludes.

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Chemists could point way to new antibiotics — ScienceDaily

In a discovery that points to potential new antibiotic medicines, scientists from Rice University and the University of Michigan have deciphered the workings of a common but little-understood bacterial switch that cuts off protein production before it begins.

Many gram-positive bacteria use T-box riboswitches to regulate production of proteins that utilize amino acids, the basic building blocks of all proteins. A study in Nature Communications describes how one of these switches, a glycine regulator in Bacillus subtilis, flips and locks into the “on” position via a snap-lock mechanism. Engaging the lock increases production of proteins that utilize glycine, the simplest amino acid. Researchers also detailed the switch’s “off” position: A single glycine at the tip of the locking arm blocks protein production.

“T-box riboswitches are intriguing because they are regulated — turned on or off — by molecules central to protein production,” said study co-author Edward Nikonowicz, professor of biosciences at Rice. “While they were discovered a quarter century ago, it’s not been entirely clear how they operate. By highlighting their structural and kinetic details, we hope to spur interest in these switches as potential targets for new antibiotics.”

New antibiotics could help avert a looming health crisis, Nikonowicz said. The Centers for Disease Control and Prevention expects antibiotic-resistant bacteria to kill at least 23,000 people in the U.S. this year, and if current trends go unchecked, the World Health Organization estimates that by 2050, drug-resistant pathogens will kill 10 million people per year worldwide.

T-box riboswitches like the one highlighted in the new study are vital to many gram-positive bacteria, a broad class that includes pathogens that cause tuberculosis, gangrene, botulism, anthrax, inflammation of the inner heart lining and other diseases.

T-box riboswitches are located on strands of messenger RNA (mRNA), blueprints for proteins that are copied directly from a cell’s DNA. In complex organisms such as animals and plants, the writing, or “transcription,” of mRNA takes place in a vault-like DNA storage facility called the nucleus. Only after mRNA leaves the vault can its message be used, or “translated,” into a new protein. Because bacteria have no nucleus, “transcription” of mRNA and “translation,” decoding of mRNA by ribosomes to make new proteins, happen in close proximity.

“Riboswitches are common in many bacteria, but not in humans, making them such attractive targets for new drugs,” said study co-author Nils Walter, the Francis S. Collins Collegiate Professor of Chemistry, Biophysics and Biological Chemistry at the University of Michigan. “T-box riboswitches regulate transcription, the writing of the messenger RNA itself, but use a locking arm borrowed from the translation machinery, making it a unique jack-of-all-trades.”

The mRNA blueprints are used to build proteins, the workhorses of biology. Cells employ millions of proteins at a given time, but each of these is made from the same 20 building blocks, the amino acids that T-box riboswitches help regulate in gram-positive bacteria. To make a protein, cells string amino acids end to end, like beads on a necklace, based on the order specified in mRNA instructions.

The locking arm trigger in the glycine T-box riboswitch is part of another molecule called transfer RNA (tRNA). There are many types of tRNA in cells, but each acts like a kind of car, shuttling payloads to the ribosome, where proteins are strung together. Each type of tRNA can only carry one type of amino acid.

In the new study, Walter and Nikonowicz designed an experiment in which glycine-specific tRNA molecules, some loaded with glycine and others unloaded, would pass by and randomly attach to a T-box riboswitch.

“Ed’s team was able to attach a fluorescent marker to the tRNA in a such a way that it wouldn’t interfere with their binding,” Walter said. “My lab employed a technique called ‘single molecule fluorescence microscopy’ to probe the dynamic associations of single T-box riboswitches with the tRNA, either when the glycine cargo was attached or not.”

Each time a tRNA with a fluorescent tag attached took up a position on the T-box riboswitch, a bright signal appeared in the microscope. By measuring exactly how long the signal lasted, and thus how long the molecules stayed in position, the team was able to reconstruct the binding speed and ultimately the locking mechanism for the switch.

Nikonowicz said he and Walter began the glycine T-box riboswitch project about 2 1/2 years ago.

“Glycine was the simplest case, in part because there’s an additional domain in the T-box sensing other amino acids,” he said. “There are questions about what this domain does and how it operates. Given what we’ve already learned about the glycine T-box riboswitch, I’d like to extend this work to see what we can learn from other types of T-boxes.”

Walter added the findings could also pay off in the emerging field of RNA nanotechnology, in which scientists are attempting to use RNA templates for precision engineering of complex structures.

“In the active, locked position, the T-box-tRNA complex has a very stable three-dimensional shape,” he said. “It’s possible these could be exploited for ultra-stable ring-like complexes in novel biomimetic architectures.”

Replacement neurons, blood vessels fill in stroke cavity; gel provides scaffolding — ScienceDaily

In a first-of-its-kind finding, a new stroke-healing gel helped regrow neurons and blood vessels in mice with stroke-damaged brains, UCLA researchers report in the May 21 issue of Nature Materials.

“We tested this in laboratory mice to determine if it would repair the brain in a model of stroke, and lead to recovery,” said Dr. S. Thomas Carmichael, Professor and Chair of neurology at UCLA. “This study indicated that new brain tissue can be regenerated in what was previously just an inactive brain scar after stroke.”

The results suggest that such an approach may someday be a new therapy for stroke in people, said Dr. Tatiana Segura, a former Professor of Chemical and Biomolecular Engineering at UCLA who is now a professor at Duke University. Carmichael and Segura collaborated on the study.

The brain has a limited capacity for recovery after stroke and other diseases. Unlike some other organs in the body, such as the liver or skin, the brain does not regenerate new connections, blood vessels or new tissue structures. Tissue that dies in the brain from stroke is absorbed, leaving a cavity, devoid of blood vessels, neurons or axons, the thin nerve fibers that project from neurons.

To see if healthy tissue surrounding the cavity could be coaxed into healing the stroke injury, Segura engineered a gel to inject into the stroke cavity that thickens to mimic the properties of brain tissue, creating a scaffolding for new growth.

The gel is infused with molecules that stimulate blood vessel growth and suppress inflammation, since inflammation results in scars and impedes regrowth of functional tissue.

After 16 weeks, stroke cavities in mice contained regenerated brain tissue, including new neural networks — a result that had not been seen before. The mice with new neurons showed improved motor behavior, though the exact mechanism wasn’t clear.

“The new axons could actually be working,” said Segura. “Or the new tissue could be improving the performance of the surrounding, unharmed brain tissue.”

The gel was eventually absorbed by the body, leaving behind only new tissue.

This research was designed to explore recovery in acute stroke, or the period immediately following stroke — in mice, that is five days; in humans, that is two months. Next, Carmichael and Segura are determining if brain tissue can be regenerated in mice long after the stroke injury. More than 6 million Americans are living with the long-term outcomes of stroke, known as chronic stroke.

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Are humans causing cancer in wild animals? Humans may influence cancer in many other species on the planet — ScienceDaily

As humans, we know that some of our activities can cause cancer to develop in our bodies. Smoking, poor diets, pollution, chemicals used as additives in food and personal hygiene products, and even too much sun are some of the things that contribute to an increased risk of cancer.

But, are human activities also causing cancer in wild animals? Are we oncogenic — a species that causes cancer in other species?

Researchers from Arizona State University’s School of Life Sciences think so and are urgently calling for research into this topic. In a paper published online today in “Nature Ecology & Evolution,” Mathieu Giraudeau and Tuul Sepp, both postdoctoral researchers in the lab of ASU life sciences professor Kevin McGraw, say that humans are changing the environment in a way that causes cancer in wild animal populations.

“We know that some viruses can cause cancer in humans by changing the environment that they live in — in their case, human cells — to make it more suitable for themselves,” said Sepp. “Basically, we are doing the same thing. We are changing the environment to be more suitable for ourselves, while these changes are having a negative impact on many species on many different levels, including the probability of developing cancer.”

In the paper, Giraudeau and Sepp and a team of international researchers, point out many pathways and previous scientific studies that show where human activities are already taking a toll on animals. These include chemical and physical pollution in our oceans and waterways, accidental release of radiation into the atmosphere from nuclear plants, and the accumulation of microplastics in both land- and water-based environments. In addition, exposure to pesticides and herbicides on farmlands, artificial light pollution, loss of genetic diversity and animals eating human food are known to cause health problems.

“Cancer in wild populations is a completely ignored topic and we wanted to stimulate research on this question,” shared Giraudeau. “We recently published several theoretical papers on this topic, but this time, we wanted to highlight the fact that our species can strongly influence the prevalence of cancer in many other species of our planet.

“Cancer has been found in all species where scientists have looked for it and human activities are known to strongly influence cancer rate in humans. So, this human impact on wild environments might strongly influence the prevalence of cancer in wild populations with additional consequences on ecosystem functioning,” he said.

Even something such as artificial light and light pollution, as well as food meant for humans, are negatively affecting wild animals.

Sepp said: “It is already known in human studies that obesity and nutrient deficiency can cause cancer, but these issues have been mostly overlooked in wild animals. At the same time, more and more wild species are in contact with anthropogenic food sources. In humans, it’s also known that light at night can cause hormonal changes and lead to cancer. Wild animals living close to cities and roads face the same problem — there is no darkness anymore. For example, in birds, their hormones — the same that are linked to cancer in humans — are affected by light at night. So, the next step would be to study if it also affects their probability of developing tumors.”

While these scientists are urgently calling for studies on cancer and its causes in wild animal populations, they realize that this is no easy subject to study.

“The next step is definitely to go into the field and measure cancer rate in wild populations,” said Giraudeau. “We are now trying to develop some biomarkers to be able to study this. I think it would be interesting to measure cancer prevalence in wild animals in human-impacted environments and also in more preserved areas for the same species.”

If humans are the cause of cancer in wild animals, then many species may be more threatened than people realize. Yet Tuul said, there is reason to hold out hope.

“To me, the saddest thing is that we already know what to do. We should not destroy the habitats of wild animals, pollute the environment, and feed wild animals human food,” shared Sepp. “The fact that everybody already knows what to do, but we are not doing it, makes it seem even more hopeless.

“But I see hope in education. Our kids are learning a lot more about conservation issues than our parents did. So, there is hope that the decision-makers of the future will be more mindful of the anthropogenic effects on the environment.”

Novel drug protects memory function in mice exposed to simulated cosmic radiation — ScienceDaily

Planning a trip to Mars? You’ll want to remember your anti-radiation pills.

NASA and private space companies like SpaceX plan to send humans to the red planet within the next 15 years — but among the major challenges facing future crewed space missions is how to protect astronauts from the dangerous cosmic radiation of deep space.

Now the lab of UCSF neuroscientist Susanna Rosi, PhD, has identified the first potential treatment for the brain damage caused by exposure to cosmic rays — a drug that prevents memory impairment in mice exposed to simulated space radiation. The study was published May 18, 2018 in Scientific Reports.

Humans venturing beyond the Earth’s protective magnetic fields will be exposed to levels of cosmic radiation estimated to be 1000 times higher than what we experience on Earth or even in the International Space Station’s low-earth orbit. Protecting astronauts from this harmful radiation will be key to making deep space exploration — and perhaps one day colonization — possible.

Rosi, who is Director of Neurocognitive Research in the UCSF Brain and Spinal Injury Center and a professor in the departments of Physical Therapy and Rehabilitation Science and of Neurological Surgery, has conducted NASA-funded research for the past four years to understand how deep space radiation may affect astronauts’ brains.

Rosi’s team has previously found that exposing mice to simulated space radiation causes problems with memory, social interactions, and anxiety, and has linked these symptoms of radiation exposure to activation of cells called microglia — part of the brain’s immune system. Activated microglia drive brain inflammation similar to what is seen in neurodegenerative disorders such as Alzheimer’s disease, and also seek out and consume synapses, the information-bearing connections between brain cells.

“We are starting to have evidence that exposure to deep space radiation might affect brain function over the long term, but as far as I know, no one had explored any possible countermeasures that might protect astronauts’ brains against this level of radiation exposure,” said Rosi, who is a member of the Weill Institute for Neuroscience, the Kavli Institute of Fundamental Neuroscience, and the UCSF Helen Diller Family Comprehensive Cancer Center.

In the new study, the researchers collaborated with co-authors at Loma Linda University in Southern California to expose mice for a day to a dose of radiation comparable to what they might experience in deep space. The experiments were conducted at the NASA Space Radiation Laboratory at Brookhaven National Laboratory in New York, the only facility in the country where such experiments are possible. A week later, after being shipped back to UCSF, some of the mice were treated for 15 days with PLX5622, a drug produced by Berkeley-based pharmaceutical company Plexxikon, Inc, and which the Rosi lab had previously shown to prevent cognitive deficits in a mouse model of cancer radiation therapy when administered prior to irradiation of the brain.

In the present study, the irradiated animals initially displayed no cognitive deficits, but after three months they began showing signs of memory impairment. Normally, when researchers place mice in a room with a familiar and an unfamiliar object, the animals spend more time exploring the new object. But mice that had been exposed to space radiation three months earlier explored the two objects equally — presumably because they didn’t remember having seen one of the objects just the day before.

Remarkably, animals that had been treated with PLX5622 soon after being exposed to radiation performed just like healthy mice on the memory task. The researchers examined the animals’ brains and showed that while the brains of untreated mice were full of activated microglia and had lost significant numbers of synapses, the brains of treated mice looked just like normal. The authors hypothesize that by forcing the brain to replace irritable, radiation-exposed microglia with new, healthy microglia, the drug had allowed the animals avoid the cognitive consequences of radiation.

“This is really neat evidence, first that rebooting the brain’s microglia can protect cognitive function following radiation exposure, and second that we don’t necessarily need to treat immediately following the radiation exposure for the drug to be effective,” Rosi said.

Similar compounds to PLX5622 produced by Plexxikon (inhibitors of a cellular receptor molecule called CSF1R) are already in clinical trials for multiple forms of human cancer, which suggests that the new findings could soon be translated to human use, the researchers say. Beyond spaceflight, these compounds could potentially be used to prevent cognitive impairments following cancer radiation therapy, or in age-related cognitive impairment — which has also been linked to microglia-driven brain inflammation.

“NASA is very interested in finding ways of ensuring both astronaut safety and mission success during deep space travel,” said study co-lead author Karen Krukowski, PhD, a postdoctoral researcher in Rosi’s lab. “But astronauts are a small population — it’s exciting that these findings could potentially help prevent many other forms of cognitive impairment.”

Nanoparticles could offer a new way to help eradicate the disease worldwide — ScienceDaily

A new nanoparticle vaccine developed by MIT researchers could assist efforts to eradicate polio worldwide. The vaccine, which delivers multiple doses in just one injection, could make it easier to immunize children in remote regions of Pakistan and other countries where the disease is still found.

While the number of reported cases of polio dropped by 99 percent worldwide between 1988 and 2013, according to the Centers for Disease Control, the disease has not been completely eradicated, in part because of the difficulty in reaching children in remote areas to give them the two to four polio vaccine injections required to build up immunity.

“Having a one-shot vaccine that can elicit full protection could be very valuable in being able to achieve eradication,” says Ana Jaklenec, a research scientist at MIT’s Koch Institute for Integrative Cancer Research and one of the senior authors of the paper.

Robert Langer, the David H. Koch Institute Professor at MIT, is also a senior author of the study, which appears in the Proceedings of the National Academy of Sciences the week of May 21. Stephany Tzeng, a former MIT postdoc who is now a research associate at Johns Hopkins University School of Medicine, is the paper’s lead author.

“We are very excited about the approaches and results in this paper, which I hope will someday lead to better vaccines for patients around the world,” Langer says.

Global eradication

There are no drugs against poliovirus, and in about 1 percent of cases, it enters the nervous system, where it can cause paralysis. The first polio vaccine, also called the Salk vaccine, was developed in the 1950s. This vaccine consists of an inactivated version of the virus, which is usually given as a series of two to four injections, beginning at 2 months of age. In 1961, an oral vaccine was developed, which offers some protection with only one dose but is more effective with two to three doses.

The oral vaccine, which consists of a virus that has reduced virulence but is still viable, has been phased out in most countries because in very rare cases, it can mutate to a virulent form and cause infection. It is still used in some developing countries, however, because it is easier to administer the drops than to reach children for multiple injections of the Salk vaccine.

For polio eradication efforts to succeed, the oral vaccine must be completely phased out, to eliminate the chance of the virus reactivating in an immunized person. Several years ago, Langer’s lab received funding from the Bill and Melinda Gates Foundation to try to develop an injectable vaccine that could be given just once but carry multiple doses.

“The goal is to ensure that everyone globally is immunized,” Jaklenec says. “Children in some of these hard-to-reach developing world locations tend to not get the full series of shots necessary for protection.”

To create a single-injection vaccine, the MIT team encapsulated the inactivated polio vaccine in a biodegradable polymer known as PLGA. This polymer can be designed to degrade after a certain period of time, allowing the researchers to control when the vaccine is released.

“There’s always a little bit of vaccine that’s left on the surface or very close to the surface of the particle, and as soon as we put it in the body, whatever is at the surface can just diffuse away. That’s the initial burst,” Tzeng says. “Then the particles sit at the injection site and over time, as the polymer degrades, they release the vaccine in bursts at defined time points, based on the degradation rate of the polymer.”

The researchers had to overcome one major obstacle that has stymied previous efforts to use PLGA for polio vaccine delivery: The polymer breaks down into byproducts called glycolic acid and lactic acid, and these acids can harm the virus so that it no longer provokes the right kind of antibody response.

To prevent this from happening, the MIT team added positively charged polymers to their particles. These polymers act as “proton sponges,” sopping up extra protons and making the environment less acidic, allowing the virus to remain stable in the body.

Successful immunization

In the PNAS study, the researchers designed particles that would deliver an initial burst at the time of injection, followed by a second release about 25 days later. They injected the particles into rats, then sent blood samples from the immunized rats to the Centers for Disease Control for testing. Those studies revealed that the blood samples from rats immunized with the single-injection particle vaccine had an antibody response against poliovirus just as strong as, or stronger than, antibodies from rats that received two injections of Salk polio vaccine.

To deliver more than two doses, the researchers say they could design particles that release vaccine at injection and one month later, and mix them with particles that release at injection and two months later, resulting in three overall doses, each a month apart. The polymers that the researchers used in the vaccines are already FDA-approved for use in humans, so they hope to soon be able to test the vaccines in clinical trials.

The researchers are also working on applying this approach to create stable, single-injection vaccines for other viruses such as Ebola and HIV.

The research was funded by the Bill and Melinda Gates Foundation.

Having an egg a day could reduce risk of stroke by 26 percent — ScienceDaily

People who consume an egg a day could significantly reduce their risk of cardiovascular diseases compared with eating no eggs, suggests a study carried out in China, published in the journal Heart.

Cardiovascular disease (CVD) is the leading cause of death and disability worldwide, including China, mostly due to ischaemic heart disease and stroke (including both haemorrhagic and ischaemic stroke).

Unlike ischaemic heart disease, which is the leading cause of premature death in most Western countries, stroke is the most responsible cause in China, followed by heart disease.

Although ischaemic stroke accounted for the majority of strokes, the proportion of haemorrhagic stroke in China is still higher than that in high income countries.

Eggs are a prominent source of dietary cholesterol, but they also contain high-quality protein, many vitamins and bioactive components such as phospholipids and carotenoids.

Previous studies looking at associations between eating eggs and impact on health have been inconsistent, and most of them found insignificant associations between egg consumption and coronary heart disease or stroke.

Therefore, a team of researchers from China and the UK led by Professor Liming Li and Dr Canqing Yu from the School of Public Health, Peking University Health Science Center, set out to examine the associations between egg consumption and cardiovascular disease, ischaemic heart disease, major coronary events, haemorrhagic stroke and ischaemic stroke.

They used data from the China Kadoorie Biobank (CKB) study, an ongoing prospective study of around half a million (512,891) adults aged 30 to 79 from 10 different geographical areas in China.

The participants were recruited between 2004-2008 and were asked about the frequency of their egg consumption. They were followed up to determine their morbidity and mortality.

For the new study, the researchers focused on 416,213 participants who were free of prior cancer, cardiovascular disease (CVD) and diabetes.

From that group at a median follow-up of 8.9 years, a total of 83,977 cases of CVD and 9,985 CVD deaths were documented, as well as 5,103 major coronary events.

At the start of the study period, 13.1% of participants reported daily consumption (usual amount 0.76 egg/day) and 9.1% reported never or very rare consumption (usual amount 0.29 egg/day) of eggs.

Analysis of the results showed that compared with people not consuming eggs, daily egg consumption was associated with a lower risk of CVD overall.

In particular, daily egg consumers (up to one egg/day) had a 26% lower risk of haemorrhagic stroke — the type of stroke with a higher prevalence rate in China than in high-income countries — a 28% lower risk of haemorrhagic stroke death and an 18% lower risk of CVD death.

In addition, there was a 12% reduction in risk of ischaemic heart disease observed for people consuming eggs daily (estimated amount 5.32 eggs/week), when compared with the ‘never/rarely’ consumption category (2.03 eggs/week).

This was an observational study, so no firm conclusions can be drawn about cause and effect, but the authors said their study had a large sample size and took into account established and potential risk factors for CVD.

The authors concluded: “The present study finds that there is an association between moderate level of egg consumption (up to 1 egg/day) and a lower cardiac event rate.

“Our findings contribute scientific evidence to the dietary guidelines with regard to egg consumption for the healthy Chinese adult.”

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Mice brain structure linked with sex-based differences in anxiety behavior — ScienceDaily

Using male individuals has long been a tradition in scientific mice studies. But new research enforces the importance of using a balanced population of male and female mice.

In a paper published May 22 in the journal Cell Reports, scientists studying the locus coeruleus brain structure in mice unexpectedly found substantial differences in the molecular structures of this part of the brain between male and female mice. They found that female mice had a three-fold higher abundance of the prostaglandin receptor EP3 (PTGER3), as well as elevated levels of Slc6a15 and Lin28b, both genes in regions associated with major depressive disorder (MDD).

“This is particularly interesting because many of the same diseases that are targeted by drugs that work on this structure, such as ADHD or depression, also really have differences in prevalence between men and women in the general population,” says senior author Joseph Dougherty of the Department of Genetics at Washington University School of Medicine in St. Louis.

Women are usually two to four times more likely to suffer from depression or anxiety, and ADHD is more commonly found in males. “We thought it really striking that there was this structure in the brain that is the target of these drugs that also has this very profound molecular-level difference between males and females,” he says.

The researchers initially set out to study gene expression in the mouse locus coeruleus, a small nucleus of neurons in the brain that is the primary source for the neurotransmitter norepinephrine. Norepinephrine is a major target of many drugs to treat disorders like ADHD and depression.

“We are the first to take a genome-wide view of all of the genes utilized in this small structure,” adds Dougherty. In this study, he and his team studied mouse noradrenergic neurons found in the locus coeruleus in vivo and identified over 3,000 transcripts it expressed.

Because Dougherty follows current practices mandated by the National Institutes of Health since 2016, his experiments included a balanced population of both male and female mice in the experiment. When they studied the gene expression of the mice, they unexpectedly found these differences in the transcriptome between the male and female mice in this part of the brain structure.

This finding prodded the researchers to test whether this molecular difference had any functional consequences. They next delivered sulprostone, a drug targeting PTGER3, to see if they could influence its activity. When both male and female mice received sulprostone directly to the locus coeruleus via cannula after a simulated stress event, only the females responded. “We could turn off a stress-induced anxiety like behavior, specifically in the female mice, but not in the males,” says Dougherty, who believes that this sex-based difference may help inform how to conduct experimentation around mood disorders and development of therapeutics.

Going forward, Dougherty plans on researching whether these molecular and functional differences in the locus coeruleus of mice are duplicated in the human brain.

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