Culture

Researchers at the National Institutes of Health found evidence that specific immune cells may play a key role in the devastating effects of cerebral malaria, a severe form of malaria that mainly affects young children. The results, published in the Journal of Clinical Investigation, suggest that drugs targeting T cells may be effective in treating the disease. The study was supported by the NIH Intramural Research Program.

"This is the first study showing that T cells target blood vessels in brains of children with cerebral malaria," said Dorian McGavern, Ph.D., chief of the Viral Immunology and Intravital Imaging Section at the NIH's National Institute of Neurological Disorders and Stroke (NINDS) who co-directed the study with Susan Pierce, Ph.D., chief of the Laboratory of Immunogenetics at the National Institute of Allergy and Infectious Diseases (NIAID). "These findings build a bridge between mouse and human cerebral malaria studies by implicating T cells in the development of disease pathology in children. It is well established that T cells cause the brain vasculature injury associated with cerebral malaria in mice, but this was not known in humans."

More than 200 million people worldwide are infected annually with mosquito-borne parasites that cause malaria. In a subset of those patients, mainly young children, the parasites accumulate in brain blood vessels causing cerebral malaria, which leads to increased brain pressure from swelling. Even with available treatment, cerebral malaria still kills up to 25% of those affected resulting in nearly 400,000 deaths annually. Children who survive the infection will often have long-lasting neurological problems such as cognitive impairment.

The researchers, led by Drs. Pierce and McGavern, examined brain tissue from 23 children who died of cerebral malaria and 11 children who died from other causes. The scientists used state-of-the-art microscopy to explore the presence of cytotoxic lymphocytes (CTLs) in the brain tissue samples. CTLs are a type of T cell in our immune system that is responsible for controlling infections throughout the body.

Current treatment strategies for cerebral malaria focus on red blood cells, which are thought to clog blood vessels and create potentially fatal blockages leading to extreme pressure in the brain. However, findings in the mouse model demonstrated that CTLs damage blood vessels, leading to brain swelling and death. The role of CTLs in cerebral malaria in children hasn't been thoroughly investigated prior to this study.

The results of the current study demonstrate an increased accumulation of CTLs along the walls of brain blood vessel in the cerebral malaria tissue samples compared to non-cerebral malaria cases. In addition, the CTLs were shown to contain and release effector molecules, which damage cells, suggesting that CTLs play a critical role in cerebral malaria by damaging the walls of brain blood vessels.

"The disease appears to be an immunological accident in which the CTLs are trying to control a parasitic infection but end up injuring brain blood vessels in the process," said Dr. McGavern.

"In separate studies we discovered that treatment of mice with a drug that targets T cells rescued over 60% of otherwise fatal cases of experimental cerebral malaria," said Dr. Pierce. "Given our findings of T cells in the brain vasculature of children who died of the disease, we are excited by the possibility that this drug may be the first therapy for cerebral malaria."

The impact of HIV coinfection on the risk of developing cerebral malaria is not known. The NIH researchers compared CTL patterns in the cerebral malaria cases that were co-infected with HIV and those that were HIV negative. In the HIV-negative cases, the CTLs were seen lining up against the inside wall of brain blood vessels. In the HIV-positive cases, the CTLs had migrated across the surface to the outside of the vessels. There were also significantly more CTLs present in the HIV-positive cases.

Together these findings suggest that CTLs may play an important role in cerebral malaria and that HIV infection may worsen the disease.

Additional research is needed to uncover the role of T cells in human cerebral malaria. Future studies will also investigate how targeting T cells may help treat the disease. Plans for a clinical trial are underway to test the effects of a specific T cell blocker in cerebral malaria patients in Malawi.

This past September, researchers at KOTO reported four incidents of rare decays from a type of subatomic particle called a kaon. However, the decays should be too rare to detect yet, according to the standard model of particle physics--a theory that describes how matter interacts through fundamental forces like electromagnetism. The decays' presence also violates a well-known theoretical connection between charged and neutral kaon decays, so particle theorists will not accept the findings until this discrepancy is resolved. Recently, scientists Kitahara et al. have found a potential explanation as to why KOTO recognized those rare decays while larger experiments have missed them. They suggest that because KOTO is smaller than other detectors, it may not fully capture the subsequent decay of a new particle from a neutral kaon decay if the new particle flies a long distance before it decays. The presence of such rare decays of the kaon, if confirmed by further experiments, could force physicists to modify the standard model.

As the day progresses, the strength of the brain's global signal fluctuation shows an unexpected decrease, according to a study published on February 18 in the open-access journal PLOS Biology by Csaba Orban and a multi-disciplinary team of scientists from the Faculty of Engineering, Yong Loo Lin School of Medicine and N.1 Institute of Health at the National University of Singapore.

Circadian rhythms govern diverse aspects of physiology including sleep/wake cycles, cognition, gene expression, temperature regulation, and endocrine signaling. But despite the clear influence of circadian rhythms on physiology, most studies of brain function do not report or consider the impact of time of day on their findings.

To address this gap in knowledge, the team analysed functional magnetic resonance imaging (fMRI) data of approximately 900 subjects who were scanned between 8 am and 10 pm on two different days as part of the Human Connectome Project (HCP; http://www.humanconnectomeproject.org/). Multiple studies have shown that the brain's global signal fluctuates more strongly when one is drowsy (e.g. after insufficient sleep), and fluctuates less when one is more alert (e.g. after coffee). Based on known circadian variation in sleepiness, the authors hypothesized that global signal fluctuation would be lowest in the morning, increase in the mid-afternoon and dip in the early evening.

Instead, they observed a cumulative decrease in global signal fluctuation as the day progressed. This global decrease was most prominent in visual and somatosensory brain regions, which are known for expressing dynamic fluctuations within individuals over time. Across the whole brain, time of day was also associated with marked decreases in resting-state functional connectivity - the correlated activity between different brain regions when no explicit task is being performed.

"We were surprised by the size of the overall time-of-day effects, since the global fMRI signal is affected by many factors and there is substantial variation across individuals. At the present moment we don't have a good explanation of the directionality of our findings. However, the fact that we also observed slight time-of-day-associated variation in the breathing patterns of participants suggests that we may also need to consider clues outside of the brain to fully understand these effects," said Csaba Orban, first author of the study.

Based on the findings, the authors recommend that researchers explicitly report the time of day of fMRI scans and other experimental protocols and measurements, as this could help account for between-study variation in results and potentially even failure to replicate findings.

"We hope these findings will motivate fellow neuroscientists to give more consideration to potential effects of time of day on measures of brain activity, especially in other large-scale studies where subjects are often scanned throughout the day for logistical reasons," said Thomas Yeo, the study's senior author.

A multidisciplinary study led by UB researchers has developed a new experimental tool that enables the application of focalized damage on an in vitro neuronal network of only a few millimetres and record the evolution of the whole network. The objective is to understand the response mechanisms that take place in the brain neuronal circuits, and which prevent a total propagation of the damage while they recover the functionality of the affected circuits. One of the main conclusions is that the network quickly activates self-regulation mechanisms that reinforce the existing connections and restore the functionality of the circuit.

The study, led by Jordi Soriano, researcher at the Institute of Complex Systems of the UB (UBICS), is framed within a multidisciplinary collaboration between UBICS, the Institute of Neurosciences of the UB (UBNeuro), the Institute of Photonic Sciences (ICFO) and Rovira i Virgili University.

The study, published in the journal eNEURO, "shows the great ability of neuronal networks to self-regulate and self-modulate to respond to sudden changes or severe alterations; it is also a good example of the importance of modelling neuronal networks as a complex system, where the whole is richer than the sum of its parts", notes Soriano.

The brain, and in general biological neuronal networks, has response mechanisms towards neuronal loss caused by damage or by a disease. In stroke, for instance, loss of blood supply causes the death of a focalized group of neurons and the alteration of the function of damaged neuronal circuits which, at the same time, alters the function of the neighbouring circuits, potentially starting an avalanche of deterioration. Understanding how these mechanisms work at a network level is intricate due to the sheer size of the brain and the intrinsic difficulty of monitoring in detail the evolution of a great number of neurons before and after the damage. This difficulty can be addressed through the design of in vitro models such as the one proposed by the researchers.

In the experiments, researchers recorded the activity of the whole neuronal network to set their characteristic functionality. They next used a high-power laser to remove a group of neurons and, then, they recorded the network again, to monitor its development over time.

Researchers saw that the closest group of neurons to the affected area loses activity immediately, but it regains activity gradually thanks to the action of the whole network. "Surprisingly, in only fifteen minutes this group reaches activity levels that are similar to the ones from before the damage took place, despite having lost a significant number of impulses from the affected area", says Soriano. "Since fifteen minutes are not enough -continues the researcher- to set new connections, we conclude that the network acts by reinforcing the existing connections, re-driving the flow of neuronal stimuli to the neighbours of the affected area, preventing their deterioration from happening, and therefore, a progressive collapse of the network".

The study, moreover, strengthens the importance of in vitro models as a complementary tool to understand the complexity of the brain and its alterations. In this context, the study is part of the European project MESO-BRAIN, which counts on the participation of the UB researcher Jordi Soriano, to design model neuronal cultures to copy the structure and dynamics of brain regions, allowing researches to study in a controlled way the action of drugs and genetic therapies to treat neurodegenerative diseases.

First-of-its-kind study accounts for when couples are most likely to start trying to conceive, finding couples conceive quicker in late fall and early winter, especially in southern states.

In the US, birthdays peak in early September, but in Northern states--and Scandinavia--the peak comes earlier, in the summer or even spring. Although many factors likely go into the popularity of birthday months (a spike in November is popularly attributed to Valentine's Day), seasons themselves may play a role in how easy it is to conceive, according to a new Boston University School of Public Health (BUSPH) study.

The first-of-its-kind study, published in the journal Human Reproduction, finds that, although couples in North America and Denmark are most likely to start trying in September, it's in late November and early December that they have the best chances of conceiving, especially at lower latitudes.

"There are a lot of studies out there that look at seasonal patterns in births, but these studies don't take into account when couples start trying, how long they take to conceive, or how long their pregnancies last," says study lead author Dr. Amelia Wesselink, postdoctoral associate in epidemiology at BUSPH. "After accounting for seasonal patterns in when couples start trying to conceive, we found a decline in fecundability in the late spring and a peak in the late fall," she says. ("Fecundability" refers to the odds of conceiving within one menstrual cycle.) "Interestingly, the association was stronger among couples living at lower latitudes."

The North Americans were more likely than Danes to begin trying to conceive in the fall (possibly in the hopes of giving birth when work is less busy in the summer, Wesselink says, which may be more important in the U.S. than Scandinavia).

But, after taking those patterns into account, season affected fecundability for North Americans by 16 percent, while Danes got only an 8% seasonal boost in the fall and dip in the spring. In southern U.S. states, the seasonal variation was even stronger, at 45%, with a peak in quick conceptions in late November. Meanwhile, the relationship between season and fecundability turned out to be about the same in Denmark and in northern states and Canada.

The study used data on 14,331 pregnancy-planning women who had been trying to conceive for no more than six months, including 5,827 U.S. and Canadian participants in the BUSPH-based Pregnancy Study Online (PRESTO) and 8,504 Danish participants in the Snart Gravid and Snart Foraeldre studies based at Aarhus University in Denmark. These studies follow women with detailed surveys every two months until they either conceive or have tried to conceive for 12 menstrual cycles, gathering data on everything from intercourse frequency and menstruation, to smoking and diet, to education and income.

The findings did not significantly change after controlling for seasonally-varying factors, including intercourse frequency, sugar-sweetened beverage intake, smoking, and medication use.

"Although this study cannot identify the reasons for seasonal variation in fertility, we are interested in exploring several hypotheses on seasonally-varying factors and how they affect fertility, including meteorological variables such as temperature and humidity, vitamin D exposure, and environmental exposures such as air pollution," Wesselink says.

PULLMAN, Wash. -- A Washington State University research team has developed a way to address a major safety issue with lithium metal batteries - an innovation that could make high-energy batteries more viable for next-generation energy storage.

The researchers used a formulation for their batteries that led to the formation of a unique, protective layer around their lithium anode, protecting the batteries from degradation and allowing them to work longer under typical conditions. Led by Min-Kyu Song, assistant professor in the WSU School of Mechanical and Materials Engineering, the researchers report on the work in the journal, Nano Energy. 

Lithium metal is considered the "dream material" for batteries, Song said. That's because among known solid materials, it has the highest energy density, meaning that batteries could run twice as long and hold more energy than the ubiquitous lithium-ion batteries that power most modern-day electronics. While lithium-ion batteries work by passing lithium ions between a graphite anode and a lithium cobalt oxide cathode, the anode in a lithium-metal battery is made of the high-energy lithium metal.

"If we can directly use lithium metal, we can improve the energy density of batteries dramatically," Song said.

While the advantages of lithium metal have been known for decades, researchers have never been able to make them work safely. As electrons travel between the anode and cathode through the external circuit to power a device, Christmas-tree like dendrites begin to form on the lithium metal. The dendrites grow until they cause electric shorts, fires, or explosions. Even if they don't catch on fire, the lithium metal batteries also very rapidly lose their ability to charge.

The WSU research team developed a battery in which they packed selenium disulfide, a non-toxic chemical used in dandruff shampoo, into a porous carbon structure for their cathode. They added two additives to the liquid electrolytes that are typically explored in next-generation lithium batteries.

The two additives worked synergistically and formed a protective layer on the lithium metal surface that was dense, conductive, and robust enough to suppress the growth of dendrites while allowing good cycling stability, Song said. When tested at typical current densities people would use for electronics, the protected lithium metal anode was able to re-charge 500 times and retained high efficiency.

"Such a unique protective layer led to little morphological changes of the lithium anode over cycling and effectively mitigated the growth of lithium dendrites and unwanted side reactions," he said.

The researchers believe their technology can be scalable and cost-effective.

"If commercialized, this novel formulation has real potential," Song said. "Compared to solid-state batteries which are still years away, you don't have to change the manufacturing procedures, and this would be applicable to real industry much sooner, opening up a promising route toward the development of high-energy lithium metal batteries with a long cycle life."

The researchers are continuing to work on the battery, developing a separator that will further protect the battery materials from deterioration and enhance safety without compromising performance.

The Cuatro Cienegas Basin, located in Chihuahuan Desert in Mexico, was once a shallow sea that became isolated from the Gulf of Mexico around 43 million years ago.

This basin has an unusual characteristic of being particularly nutrient-poor and harboring a 'lost world' of many below-ground and above-ground aquatic microbes of ancient marine ancestry.

Because of these characteristics, it is an invaluable place for researchers to study and understand how life may have existed on other planets in our solar system.

In a recent study published in the journal eLIFE a team of researchers, including lead author Jordan Okie of Arizona State University's School of Earth and Space Exploration and senior author Jim Elser of the School of Life Sciences, conducted experiments in the Cuatro Cienegas Basin.

Their goal was to shed light on how fundamental features of an organism's genome - its size, the way it encodes information, and the density of information--affect its ability to thrive in an extreme environment.

"This area is so poor in nutrients that many of its ecosystems are dominated by microbes and may have similarities to ecosystems from early Earth, as well as to past wetter environments on Mars that may have supported life," says lead author Okie.

For their experiment, researchers conducted field monitoring, sampling, and routine water chemistry for 32 days in a shallow, nutrient-poor pond called Lagunita in the Cuatro Cienegas Basin.

First, they installed mescocosms (miniature ecosystems) that served as a control group and remained separate from the rest of the pond. They then added a fertilizer solution that was rich in nitrogen and phosphorus to increase microbial growth in the pond.

At the end of the experiment, they examined how the community in the pond changed in response to the additional nutrients, focusing on their ability to process biochemical information within their cells.

J. Craig Venter Institute associate professor Christopher Dupont, who is a senior author on the study, stated, "We hypothesized that microorganisms found in oligotrophic (low nutrient) environments would, out of necessity, rely on low-resource strategies for replication of DNA, transcription of RNA, and translation of protein. Conversely, a copiotrophic (high nutrient) environment favors resource-intensive strategies."

Ultimately, they found that indeed a nutrient-enriched community became dominated by species that could process biochemical information at a faster rate whereas the original low-nutrient community harbored species with reduced costs of biochemical information processing.

"This study is unique and powerful because it takes ideas from the ecological study of large organisms and applies them to microbial communities in a whole-ecosystem experiment," says Elser. "By doing so, we were able, perhaps for the first time, to identify and confirm that there are fundamental genome-wide traits associated with systematic microbial responses to ecosystem nutrient status, without regard to the species identity of those microbes."

What this may suggest for life on other planets is that organisms, no matter where they are, have to have information-processing machinery fine-tuned to the key resources around them. In turn, the supply of these resources will depend on the planetary environment.

"This is very exciting, as it suggests there are rules of life that should be generally applicable to life on Earth and beyond," says Okie.

Nuclei can be round, like a soccer ball, or oblong, like a football. Others are slightly oblong but misshapen, like a potato. One of the only two ways to observe the third shape, rarely encountered, is when the nucleus wobbles like a lopsided top.

Researchers had previously seen these rare triaxial nuclei wobble on their shorter, transverse axes. But University of Notre Dame researchers and collaborators recently discovered that the nuclei also wobble on their intermediate axes. Their research, "Longitudinal Wobbling Motion in 187Au," was published recently in the premier physics journal, Physical Review Letters.

The work took four to five days to complete once the team assembled at Argonne National Laboratory, in Illinois. Notre Dame physics graduate student, Nirupama Sensharma, who was the first author on the paper, spent about a year analyzing the data. Her work was highlighted recently in Nature.

Sensharma worked with Umesh Garg, professor in the Department of Physics, to develop an experiment using an isotope of gold to find out if the nucleus wobbled as predicted in a theoretical model developed by Stefan Frauendorf, also a professor in the Department of Physics. Frauendorf had hypothesized that triaxial nuclei would have two different types of wobbling motion.

The fundamental research, which Garg said does not have an immediate application for technology, was chosen as an editor's selection in the journal. It was also highlighted as a synopsis in Physics, the online magazine of the American Physical Society. Papers selected for coverage must include an experimental breakthrough, or provide a theory with a new perspective, among other criteria.

"Where its importance lies is in confirming the predictive power of the underlying theoretical framework, generating more confidence in other predictions about nuclear physics," Garg said. "This, among other things, can help us understand how various processes happen in stellar environments, and how heavy elements, like gold, are formed in the universe."

In 2016 Frauendorf suggested an experiment on a gold nucleus after predicting the wobbling should exist.

"Professor Garg's group created an outstanding experiment to measure the distribution of radiation," Frauendorf said, noting that the experiment validated his prediction.

The work, funded by the U.S. Department of Energy, was completed at the Argonne National Laboratory inside an instrument called Gammasphere. Gammasphere is the world's most powerful gamma ray spectrometer, and collects gamma ray data following the fusion of heavy ions. Inside Gammasphere, a beam of ions and the target nucleus combine to create a much heavier, highly excited nucleus that gives off gamma rays. By observing the pattern and properties of the gamma rays, researchers can discover the structure of the nucleus - and a wobbling nucleus has a very specific structure.

Initially, Garg and his collaborators planned to look for wobbling in 189Au, but ended up accidentally populating another isotope of gold, 187Au, more strongly. The mistake was a serendipitous one.

"That one was right, it turns out," Garg said. "But that's how science goes; if we had done the experiment exactly as planned, I probably would have come back and said, this doesn't very much seem like what we're looking for."

Using "BPA-free" plastic products could be as harmful to human health -- including a developing brain -- as those products that contain the controversial chemical, suggest scientists in a new study led by the University of Missouri and published in the Proceedings of the National Academy of Sciences.

For decades, scientists have studied BPA extensively in animal models with results indicating the chemical plays a role in early pregnancy loss, placental diseases and various negative health outcomes after birth. As these adverse health effects have become more widely known, companies have turned to using alternative chemicals to develop plastic products -- namely water bottles and food containers -- and often labeling them "BPA-free." However, MU scientist Cheryl Rosenfeld warns these chemical alternatives, such as bisphenol S (BPS), still aren't safe for people to use.

In the study, Rosenfeld and her colleagues focused on examining the effects of BPS on a mouse's placenta. She said the placenta serves as a historical record of what an unborn child faces while in the womb; the placenta also can transfer whatever the mother might be exposed to in her blood, such as harmful chemicals, into the developing child.

"Synthetic chemicals like BPS can penetrate through the maternal placenta, so whatever is circulating in the mother's blood can easily be transferred to the developing child," said Rosenfeld, a professor of biomedical sciences in the College of Veterinary Medicine, investigator in the Bond Life Sciences Center, and research faculty member for the Thompson Center for Autism and Neurobehavioral Disorders at MU. "This mouse model is the best model we have now to simulate the possible effects of BPS during human pregnancy, because the placenta has a similar structure in both mice and humans."

Rosenfeld adds that the placenta serves as a primary source of serotonin for fetal brain development in both mice and humans. Serotonin, while commonly associated with the feeling of happiness, is a natural chemical that can impact a person's functions, including their emotions and physical activities such as sleeping, eating and digesting food.

"The placenta responds to both natural chemicals as well as synthetic chemicals that the body misinterprets as natural chemicals, but the body doesn't have the ability to mitigate the detrimental effects of such industrial-made chemicals," Rosenfeld said. "More importantly, these chemicals have the ability to lower the placenta's serotonin production. Lower levels of serotonin can compromise fetal brain development because during this critical time in development the brain relies on the placenta to produce serotonin. Thus, developmental exposure to BPA or even its substitute, BPS, can lead to longstanding health consequences."

Rosenfeld's research is an example of an early step in translational medicine, or research that aims to improve human health by determining the relevance of animal science discoveries to people. This research can provide the foundation for precision medicine, or personalized human health care. Precision medicine will be a key component of the NextGen Precision Health Initiative -- the University of Missouri System's top priority -- by helping to accelerate medical breakthroughs for both patients in Missouri and beyond.

A peer-delivered program for managing diabetes and chronic pain was shown to be beneficial for rural adults in communities that might otherwise lack access to physician-led services. Trained community members in rural Alabama delivered a diabetes self-management program that incorporated cognitive behavioral approaches to overcoming pain as a barrier to physical activity. Peer trainers were African American women who had personal experiences with diabetes and were lifelong community members. Similarly, participants were mostly low-income African American women recruited through community connections and assigned to the intervention by town block randomization. Adults who completed the 10-week program showed significant improvements in functional status, pain, and quality of life, when compared to a peer-led general health advice control group. At the end of the program, adults in the cognitive behavioral therapy-based program were more likely to report having no pain or finding alternative exercises when pain prevented them from walking. These results demonstrate that peers trained to deliver CBT-based interventions can improve health outcomes in areas where access is limited.

A study across five academic medical centers examined the reaction of patients to the use of an electronic consultation (eConsult) service for primary care provider-to-specialist consultation. This focus group study of adult primary care patients was conducted to better understand patients' opinions, as most previous eConsult studies focused on clinical and financial impacts and clinician responsibility. Fifty-two participants across five focus groups were introduced to the eConsult model and were asked to discuss potential benefits and drawbacks, as well as acceptability of a hypothetical copay and preferences for involvement in future eConsult decision making and communication. Participants in all five focus groups reacted favorably to the eConsult concept; quicker access to specialty care and convenience were cited as key benefits, with approval rates particularly high among those having a trusted primary care provider. Some patients wanted to be involved in eConsult decision making and communication. They also expressed a decreased enthusiasm about eConsults if a copay were to be introduced. A small number of participants were also concerned about potential misuse of the system and about the exclusion of the patient's illness narrative in the eConsult exchange.

Researchers in Japan have identified a new quality control system that allows cells to remove damaged and potentially toxic proteins from their surroundings. The study, which will be published February 18 in the Journal of Cell Biology, finds that the Clusterin protein and heparan sulfate proteoglycans combine to bring misfolded proteins into cells for degradation. The findings may lead to new therapeutic targets for neurodegenerative disorders, including Alzheimer’s disease.

A number of diseases are believed to be caused by the gradual buildup of misfolded proteins that can aggregate together and damage neurons and other cells in the body. To help prevent this damage, cells have developed numerous quality control systems that recognize misfolded proteins within the cell and either fold them back into their correct shape or else degrade them before they start to aggregate.

“However, approximately 11% of human proteins exist outside of the cell, where they are subjected to even more stresses that may cause them to misfold,” says Eisuke Itakura, an assistant professor in the Department of Biology at Chiba University in Japan. “In addition, Alzheimer’s disease, the most prevalent cause of dementia affecting 47.5 million people worldwide, is characterized by aggregates of amyloid β protein in the extracellular space. Despite this, how aberrant extracellular proteins are degraded remains poorly understood.”

A protein called Clusterin can bind to misfolded extracellular proteins and prevent them from aggregating. In the new study, Itakura and colleagues discovered that Clusterin can escort misfolded proteins into the cell and deliver them to the cell’s garbage-disposal units—the lysosomes—where they can be degraded. The researchers also discovered that, after binding to misfolded proteins, Clusterin enters cells by binding to proteins known as heparan sulfate proteoglycans, which are present on the surface of almost all human cells.

Itakura and colleagues found that, together, Clusterin and heparan sulfate proteoglycans allow many different cell types to internalize and degrade a wide variety of misfolded extracellular proteins. “We therefore think that this pathway is a general extracellular protein quality control system responsible for the clearance of misfolded proteins from diverse tissues and body fluids,” Itakura says.

Intriguingly, the researchers also found that Clusterin and heparan sulfate proteoglycans can import amyloid β into cells for degradation. Mutations in the gene encoding Clusterin have been linked to an increased risk of developing Alzheimer’s disease, and experiments in rats have shown that injecting Clusterin into the brain can prevent amyloid β–induced neurodegeneration. “Our results therefore suggest new avenues for the possible treatment or prevention of disorders such as Alzheimer’s disease that are associated with aberrant extracellular proteins,” Itakura says.

The accumulation of aberrant proteins in the body will cause various neurodegenerative diseases. Amyloid β, one of these aberrant proteins, is a known risk factor for Alzheimer's disease. Eisuke Itakura, an assistant professor at Chiba University, says, "Human cells have functions for maintaining homeostasis. Scientists are now actively studying the typical intracellular protein degradation systems by autophagy and proteasome, but our knowledge of how cells act on aberrant external substances is still limited."

The research team led by Itakura gained new knowledge of the functions that human cells have for maintaining homeostasis through experiments in petri dishes. The team discovered a system in which cells could capture, degrade and remove aberrant extracellular proteins. This study will be published February 18th in the Journal of Cell Biology.

In these experiments, the team focused on Clusterin, an extracellular molecular chaperone. By developing an original proprietary cell internalization assay in which cells fluoresce when extracellular Clusterin is taken up, they established a new method for visually observing the state of proteolysis in the body (Fig 1).

Itakura's team found that extracellular Clusterin selectively binds to aberrant proteins and forms a complex. They then observed how cells take up this complex using the fluorescence assay and genome-wide CRISPR screening. The team identified that cells lacking a gene related to the heparan sulfate receptor on the cell surface did not take up the aberrant protein-Clusterin complex. They also demonstrated that cells could take up Clusterin complex with amyloid β via the heparan sulfate receptor and that the complex was degraded in organelle lysosomes.

"Clusterin is a type of molecular chaperone that binds to immature proteins to protect them. If we can artificially develop Clusterin that easily binds to amyloid β and inject it into the body, it could be a treatment for Alzheimer's disease," says Itakura.

The heparan sulfate receptor was previously known to be a viral and growth factor receptor. This is the first time that scientists have demonstrated it to be an abnormal protein receptor. The research group has named this homeostasis system "the chaperone- and receptor-mediated extracellular protein degradation (CRED) pathway" and now they are planning to apply it in disease treatment through further research.

Early exposure of babies to household cleaning products is associated with the development of childhood asthma and wheeze by age 3 years, according to new research in CMAJ (Canadian Medical Association Journal).

"Most of the evidence linking asthma to the use of cleaning products comes from adults," says Professor Tim Takaro, the study's lead researcher and a clinician-scientist in Simon Fraser University's Faculty of Health Sciences (SFU). "Our study looked at infants, who typically spend 80%-90% of their time indoors and are especially vulnerable to chemical exposures through the lungs and skin due to their higher respiration rates and regular contact with household surfaces."

Researchers looked at data from questionnaires completed by parents of 2022 children in the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study who were exposed to cleaning products from birth to age 3-4 months. Participants in the CHILD Cohort Study were recruited from mostly urban centres in 4 provinces: Vancouver, BC; Edmonton, Alberta; Winnipeg, Morden and Winkler, Manitoba; and Toronto, Ontario. The children were then assessed at age 3 years to determine whether they had asthma, recurrent wheeze or atopy (allergic sensitization).

Highlights:

While there appears to be an association between early exposure to cleaning products and risk of asthma and wheeze, there appears to be no association with atopy.

The most common cleaning products used were hand dishwashing soap, dishwasher detergent, multisurface cleaners, glass cleaners and laundry soap.

Scented and sprayed cleaning products were associated with the highest risk of respiratory issues.

The majority of children were white (65%), had not been exposed to tobacco smoke up to age 3-4 months (76%) and did not have a parental history of asthma (65%).

The researchers hypothesize that chemicals in cleaning products may damage the respiratory lining by triggering inflammatory pathways of the immune system, leading to asthma and wheeze. The modulation of the infant's microbiome may also play a role.

Data were collected between 2008 and 2015.

"These findings add to our understanding of how early life exposures are associated with the development of allergic airway disease, and identify household cleaning behaviours as a potential area for intervention," says Jaclyn Parks, lead author and a graduate student in SFU's Faculty of Health Sciences.

Reading labels on cleaning products and choosing those that are not sprayed or contain volatile organic compounds will help minimize a child's exposure and balance the risk associated with using cleaning products in an effort to achieve a mould-free, low-allergen home.

"[S]tudies that identify avoidable factors to inform asthma prevention efforts are of paramount importance," writes Dr. Elissa Abrams, Department of Pediatrics, Section of Allergy and Clinical Immunology, University of Manitoba, Winnipeg, Manitoba and the University of British Columbia, Vancouver, BC, in a linked commentary. "The linked study points to small preventive changes that could be considered, especially among families of children at risk of asthma."

While the American Lung Association recommends against using cleaning products that contain volatile organic compounds, fragrance and other irritants, manufacturers in Canada and the United States are not required to list all ingredients in cleaning products. Some "green" products may contain harmful substances, as these products are not regulated.

The first articulated Neanderthal skeleton to come out of the ground for over 20 years has been unearthed at one of the most important sites of mid-20th century archaeology: Shanidar Cave, in the foothills of Iraqi Kurdistan.

Researchers say the new find offers an unparalleled opportunity to investigate the "mortuary practices" of this lost species using the latest technologies.

Shanidar Cave was excavated in the 1950s, when archaeologist Ralph Solecki uncovered partial remains of ten Neanderthal men, women and children.

Some were clustered together, with clumps of ancient pollen surrounding one of the skeletons. Solecki claimed this showed Neanderthals buried their dead and conducted funerary rites with flowers.

The 'flower burial' captured the public imagination, and prompted a reappraisal of a species that - prior to Shanidar Cave - was thought to have been dumb and animalistic.

It also sparked a decades-long controversy over whether evidence from this extraordinary site did actually point to death rituals, or burial of any kind, and if Neanderthals were really capable of such cultural sophistication.

More than 50 years later, a team of researchers have reopened the old Solecki trench to collect new sediment samples, and discovered the crushed skull and torso bones of another Shanidar Neanderthal.

The discovery has been named Shanidar Z by researchers from Cambridge, Birkbeck and Liverpool John Moores universities.

The work was conducted in conjunction with the Kurdistan General Directorate of Antiquities and the Directorate of Antiquities for Soran Province. The find is announced today in a paper published in the journal Antiquity.

"So much research on how Neanderthals treated their dead has to involve returning to finds from sixty or even a hundred years ago, when archaeological techniques were more limited, and that only ever gets you so far," said Dr Emma Pomeroy, from Cambridge's Department of Archaeology, lead author of the new paper.

"To have primary evidence of such quality from this famous Neanderthal site will allow us to use modern technologies to explore everything from ancient DNA to long-held questions about Neanderthal ways of death, and whether they were similar to our own."

Ralph Solecki died last year aged 101, having never managed to conduct further excavations at his most famous site, despite several attempts.

In 2011, the Kurdish Regional Government approached Professor Graeme Barker from Cambridge's McDonald Institute of Archaeology about revisiting Shanidar Cave. With Solecki's enthusiastic support, initial digging began in 2014, but stopped after two days when ISIS got too close. It resumed the following year.

"We thought with luck we'd be able to find the locations where they had found Neanderthals in the 1950s, to see if we could date the surrounding sediments," said Barker. "We didn't expect to find any Neanderthal bones."

In 2016, in one of the deepest parts of the trench, a rib emerged from the wall, followed by a lumbar vertebra, then the bones of a clenched right hand. However, metres of sediment needed carefully digging out before the team could excavate the skeleton.

During 2018-19 they went on to uncover a complete skull, flattened by thousands of years of sediment, and upper body bones almost to the waist - with the left hand curled under the head like a small cushion.

Early analysis suggests it is over 70,000 years old. While the sex is yet to be determined, the latest Neanderthal discovery has the teeth of a "middle- to older-aged adult".

Shanidar Z has now been brought on loan to the archaeological labs at Cambridge, where it is being conserved and scanned to help build a digital reconstruction, as more layers of silt are removed.

The team is also working on sediment samples from around the new find, looking for signs of climate change in fragments of shell and bone from ancient mice and snails, as well as traces of pollen and charcoal that could offer insight into activities such as cooking and the famous 'flower burial'.

Four of the Neanderthals, including the 'flower burial' and the latest find, formed what researchers describe as a "unique assemblage". It raises the question of whether Neanderthals were returning to the same spot within the cave to inter their dead.

A prominent rock next to the head of Shanidar Z may have been used as a marker for Neanderthals repeatedly depositing their dead, says Pomeroy, although whether time between deaths was weeks, decades or even centuries will be difficult to determine.

"The new excavation suggests that some of these bodies were laid in a channel in the cave floor created by water, which had then been intentionally dug to make it deeper," said Barker. "There is strong early evidence that Shanidar Z was deliberately buried."

CT-scans in Cambridge have revealed the petrous bone - one of the densest in the body; a wedge at the base of the skull - to be intact, offering hope of retrieving ancient Neanderthal DNA from the hot, dry region where "interbreeding" most likely took place as humans spilled out of Africa.

Added Pomeroy: "In recent years we have seen increasing evidence that Neanderthals were more sophisticated than previously thought, from cave markings to use of decorative shells and raptor talons.

"If Neanderthals were using Shanidar cave as a site of memory for the repeated ritual interment of their dead, it would suggest cultural complexity of a high order."