Sex matters when it comes to immune responses against infection and disease, study shows

A University of Alberta-led study shows that when it comes to susceptibility to infections and other health conditions, sex matters.
The research, published in the journal Frontiers in Immunology, was led by U of A immunologist Shokrollah Elahi. Elahi and his team looked at how anemia — a condition in which a person lacks enough mature red blood cells to carry oxygen in the body — can be due to an iron deficiency or loss of blood, and can generate different immunological responses in males versus females.
Knowing females are generally more predisposed than males to anemia due to monthly blood loss or pregnancy and childbirth, Elahi said looking at the impact of anemia on the immune systems in a controlled environment was the key.
“We have shown in this study that females in general have more immature red blood cells in their blood circulation than males. One main reason for the presence of immature red blood cells in the blood circulation is anemia. In particular, the proportion of these cells expands in anemic women and these immature red blood cells in return suppress the immune system, making females more susceptible to infections,” said Elahi, who is also a member of the Women and Children’s Health Research Institute (WCHRI), the Cancer Research Institute of Northern Alberta (CRINA) and the Li Ka Shing Institute of Virology. “Anemia results in the suppression of the immune system.”
Elahi’s group further found that women have more immature red blood cells in their blood circulation after their menstrual cycle than before it. The finding suggests women’s immune systems might be less active after menstruation and their odds of getting an infection increase.
According to Elahi, childbirth and menstrual cycles contribute to women being more anemic than men, but the proof-of-concept study shows that anemia suppresses the female immune system more and makes women more prone to infections. The study also highlights the importance of anemia as a condition that can impair the immune system and cause females to be more susceptible than males to infections.

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Mental illness associated with poor sleep quality according to large study

People who have been diagnosed with a mental illness are more likely to have poor sleep quality compared to the general population, according to the largest study of its kind ever conducted.
The CAMH-led study, “Accelerometer-derived sleep measures and lifetime psychiatric diagnoses,” has just been published in the journal PLOS Medicine.
“The differences in sleep patterns indicated worse sleep quality for participants with a previous diagnosis of mental illness, including waking up more often and for longer periods of time,” said senior author Dr. Shreejoy Tripathy, an Independent Scientist at CAMH’s Krembil Centre for Neuroinformatics. He also emphasized that gauging the quality of sleep was just as important as measuring the total amount with regard to its impact on mental health.
“The relationship between sleep and mental health is bi-directional,” said lead author Dr. Michael Wainberg, a postdoctoral researcher at the Krembil Centre for Neuroinformatics. “Poor sleep contributes to poor mental health and poor mental health contributes to poor sleep. Sleep pattern differences were a feature of all mental illnesses we studied regardless of diagnosis.”
The study was based on data collected from 89,205 participants in the United Kingdom who agreed to wear an accelerometer on their wrist that tracked body movement 24 hours a day for seven days. They also consented to having their data stored in a digital biobank for research purposes. The authors used computational algorithms — including machine learning — to summarize this vast amount of data into ten metrics, including bedtime, wake time, naps and the longest duration of uninterrupted sleep. They then compared these metrics between participants who had received a previous diagnosis of mental illness in their lifetime and those who had not.
“We know that up to 80 per cent of people with mental health disorders can have problems with falling asleep, staying asleep or waking up earlier than they intended,” said CAMH psychiatrist and sleep disorder specialist Dr. Michael Mak. “We know that sleep disturbances cause a great burden to society, including an economic one. And we know that treatments that improve sleep quality, whether it is therapy or some types of medication, can improve mental health outcomes.”
This is the first large-scale transdiagnostic study of objectively measured sleep and mental health, and the study’s unique methodology allowed for sleep monitoring to be conducted in each individual’s natural home sleep environment rather than in a laboratory setting.
“Until now nobody has looked at objectively measured sleep in the context of mental illness at quite this scale before,” said Dr. Tripathy. “Part of why we wanted to do this study is that with the emergence of smartphones and wearables, we have access to data streams that we never had before.”
The Krembil Centre for Neuroinformatics is currently developing a patient data biobank similar to the one in the UK that was used for this study. The core goal of the CAMH BrainHealth Databank is to use patient data, including the use of wearables outside of a hospital setting, to deliver improved, personalized mental health care in the present, while also accelerating future clinical research, discovery and innovation.
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Phage therapy research brings scientists a step closer to harnessing viruses to fight antibiotic resistance

As antibiotics increasingly develop resistance to bacteria that cause infection, scientists have moved a step closer to harnessing viruses as an alternative form of therapy.
Phage therapy is the concept of using viruses (known as phage) to kill bacteria, instead of using antibiotics. A growing number of infections, including pneumonia, tuberculosis, gonorrhoea, and salmonellosis, are becoming harder to treat, resulting in higher death rates, longer hospital stays and higher costs.
Bacteriophages (or phage for short) are viruses that kill bacteria. Unlike other viruses, they cannot harm humans and represent a promising alternative to antibiotics. Phage therapy was first used in 1919, when Parisian microbiologist Felix d’Herelle gave a phage cocktail to a 12-year-old boy, apparently curing his severe dysentery. Yet despite early promise, research dried up in the 40s as the world began to adopt the quick medical fix of antibiotics. Now, phage research is resurging as part of the solution to antibiotic resistance.
However, despite some remarkable case studies of phage therapy working in individuals, research has hit a number of obstacles. Among them is the challenge of recreating the way viruses behave in the body in lab environments.
Until now, experiments have largely focussed on exposing bacteria to phage in a flask. Here, the bacteria interact with each other and evolve swiftly — their DNA changes and they too become resistant to phage, meaning any infection would persist. However, these flasks do not replicate how bacteria operate in organs such as the lungs, where they exist in “microenvironments” such as capillaries or air sacs known as alveoli.
Now, researchers at the University of Exeter have developed a new way to mimic these microenvironments, in which a single bacterium would colonise a specific area. Rather than mixing with lots of other bacteria, phage were introduced to each of these compartments in turn.
Using this method, the team found that in these microenvironments Escherichia coli, a bacterium that is often responsible for food poisoning, does not become genetically resistant to phage, and the majority of the bacterial population is killed by phage.
Dr Stefano Pagliara, a biophysicist in the Living Systems Institute, leading this research at the University of Exeter, said: “Antibiotic resistance could prove a greater killer than COVID — 19 if we don’t find new ways to fight infection. Phage therapy shows great promise as being part of the picture, and our research has helped overcome some of the obstacles so far, by mimicking how bacteria behave in small vessels in our bodies. If phage therapy could one day become even a small part of routine care, it could help save thousands of lives.”
The research, published in PLoS Biology, lays the foundation for understanding how the environment affects the interaction between bacteria and phage, which is paramount for developing successful phage therapies to overcome the current antimicrobial resistance crisis.
The team also found that some Escherichia coli cells in these microenvironments could survive treatment with phage without acquiring genetic resistance. They found instead that these bacteria survived because they displayed less phage receptors, so that phage had less access to these cells compared to the rest of the bacterial population and so these cells survived.
Co-author Professor Edze Westra, at the University of Exeter, said: “A key aspect of whether phage can kill bacteria is the number of phage receptors the bacteria have. More receptors means a better chance of phage defeating the bacteria. Our research indicates that if we can find new ways of promoting the production of phage receptors in bacteria, we could improve the prospects of phage therapy as a viable alternative to antibiotics.”
The research was carried out in collaboration with the Defence Science and Technology Laboratory [Dstl], the science inside UK Defence and Security. Assoc Prof Sarah Harding, Dstl Senior Principal Scientist said: “Understanding how different bacterial species interact with bacteriophage in different environments is really important if phage therapy is to be considered a viable treatment option in the future. We will build on these findings to develop new ways of treating infections caused by the pathogens of biodefence interest.”

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An eco-friendly toxic cocktail could be a new weapon against malaria

Mosquitoes can and do feed on HMBPP-supplemented beetroot juice. This is the findings of a study at Stockholm University. HMBPP is a metabolite which is produced by Malaria parasite, Plasmodium. The researchers have shown that it is possible to mimic a blood meal so closely that mosquitoes naturally prefer this artificial solution by using HMBPP supplementation as well as an addition of a protein/lipid mixture to any plant juice, particularly beetroot juice.
Mosquitoes can be tricked into feeding on the beetroot-based mix with an addition of toxins. The researchers tested four different types of toxins, containing capsaicin, savory oil, boric acid and fipronil sulfone (insecticide) and compared them to a control meal. The tendency to land and ingest the insecticide cocktail was on a level that matched the non-toxic meal, which in turn caused all the tested mosquitoes to die within 100-350 minutes post feeding.
“This mixture, that we call pink juice, is a harmless, inert, eco-friendly solution, but it is naturally toxic for female mosquitos when ingested by them, says Noushin Emami, associate professor, Department of Molecular Biosciences, Stockholm University.
“Altogether, we here provide a proof-of-concept for a specialised and eco-friendly feeding trap that can be deployed where needed. We hope to see it tested in a field setting and in combination with other vector control approaches.,” says Noushin Emami.
Noushin Emami’s group researches mosquito blood meal uptake and specific attractants and stimulants. The phagostimulant HMBPP is taking aim at eliminating mosquito borne diseases by modifying mosquito behaviours and thus allowing to specifically control their populations. Being able to target only blood seeking species of mosquitoes and at the same time not affecting other organisms is paramount in today’s age of declining global biodiversity, pesticide health hazards and emerging pesticide resistance.
“There are a number of new, exciting, high tech approaches targeting mosquitoes which are entering a large-scale testing but I believe that there is a lot of potential in developing very simple, but highly effective solutions based on simple molecules and using materials which are not only affordable but also accessible to almost anyone. We used beetroot in this study to demonstrate exactly this point.,” says Noushin Emami.
Background
Over the past 1.5 years, the viral COVID-19 pandemic has been dominating the headlines worldwide. In 2015-2016, the Zika virus epidemic had scientists, global health experts and the public worrying over its spread. While the SARS-CoV-2 virus is airborne, the Zika virus spreads through mosquito vectors — and it is not the only pathogen that takes advantage of these flying, buzzing, biting insects for its’ spread to new species and geographical locations. Other mosquito-borne pathogens are the Chikungunya virus, dengue virus, the malaria (Plasmodium) parasite and others. The latter two pathogens alone claim over 300 million cases and 440,000 deaths annually.
In the study, mosquitoes spanning the An. coluzzii, An. arabiensis, An. gambiae s.s., An. gambiae s.l., Ae. aegypti and the European Culex pipiens/torrentium species, were found dead.
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Materials provided by Stockholm University. Note: Content may be edited for style and length.

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How recovery from COVID-19's impact on energy demand could help meet climate targets

The pandemic-related drop in greenhouse gas emissions in 2020 was likely the largest on record in a single year, but how our recovery might affect future emissions is less clear. New modeling examines alternative scenarios and how they could impact climate mitigation targets.
A group of IIASA researchers in the Energy, Climate, and Environment Program performed a bottom-up assessment of changes in energy-related demand and estimated how new patterns of travel, work, consumption, and production might reduce or increase climate mitigation challenges.
“Many people have been wondering what the large changes in societies that came with the COVID-19 pandemic and its lockdowns mean for climate change,” says Jarmo Kikstra, lead author of the study. “If societies are just moving back to old practices, the answer is that there is virtually no effect. However, if some of the changes in energy-use practices persist, climate mitigation challenges will be affected.”
The research, published in Nature Energy, shows that a low energy demand recovery could reduce a hypothetical tax on all carbon emissions by 19% for a scenario that is on track for reaching the Paris Agreement’s goal of limiting global warming to 1.5°C. This scenario would also lower energy supply investments until 2030 by US$1.8 trillion and soften the pressure to quickly implement renewable energy technologies.
“Our key finding is that missing the opportunity to retain low-energy practices in lifestyle and business would lead to a more difficult energy transition. Our economic recovery and climate mitigation policies should embed strategies to retain the low energy demand practices observed during the pandemic, such as low-carbon mobility in cities and increased tele-conferencing,” says coauthor Adriano Vinca.
According to the authors, this is especially true when it comes to transportation. In particular, the different recovery narratives of transportation energy demand strongly influence CO2 emission trends.

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Molecular scales on biological membranes

A large proportion of biologically relevant processes take place at membranes. Studying the dynamics of these processes in real time and without disturbing the biological system is still a major methodological challenge. A team led by Petra Schwille, director at the Max Planck Institute of Biochemistry, and Nikolas Hundt from the Ludwig-Maximilians-Universität München has now developed a new method for this purpose: Mass-Sensitive Particle Tracking (MSPT). Using MSPT, the movements and reactions of individual unlabeled proteins on biological membranes can be determined solely by their mass.
Cellular processes on membranes are often fast and short-lived. Molecules assemble briefly, separate again, interact with different partners and move along or through the membrane. It is therefore important to not only study static snapshots of these processes, but also to understand their dynamics. But how can this be achieved methodically? Petra Schwille from the Max Planck Institute of Biochemistry and Nikolas Hundt from the Ludwig Maximilians University together with their team have developed the method Mass-Sensitive Particle Tracking — MSPT, which allows to analyze proteins during dynamic processes on membranes.
The starting point for the biophysicists were recent advancements in mass photometry, which could already be used to determine the molecular mass of unlabeled molecules in solution. What is new about MSPT is that the dynamics of membrane-associated proteins can now be tracked in their biologically plausible environment. In this process, individual proteins are identified by their molecular mass without the need for labeling. Frederik Steiert, one of the first authors of the publication, says: “We can now track directly on biological membranes what mass individual proteins have, how they move and how they interact. This allows us to study the dynamics of biological systems in greater detail.” Analyzing dynamic processes is particularly important in biology as many processes at the membrane are transient.
Mass determination by light scattering
What principles is the new method based on? When light hits a particle, the light is scattered. The intensity of the scattered light depends on the mass of the particle. Videos in which individual proteins on membranes are made directly visible are recorded with a microscope. With the aid of analysis software, these proteins can be tracked and their scattering signal, and thus their mass, can be determined. This is currently possible for proteins with a molecular weight of at least 50 kDa, i.e. for a large part of all known proteins. Another advantage of the new MSPT method is that proteins do not have to be labeled. Labeling can be achieved, for example, by attaching fluorescent tags to molecules. However, labeling poses the risk that proteins could be impaired in their function or that the fluorescent labels could bleach during the experiment. By using MSPT, in contrast, methodological problems that can arise from labeling are prevented.
MinDE protein system
To demonstrate the potential of the method for biological questions, the biophysicists used an established system from the Schwille laboratory: the MinDE protein system from the bacterium Escherichia coli (E. coli). MinD and MinE proteins are involved in E. coli cell division. Tamara Heermann, another first author, says: “The method permits us to characterize properties of dynamical systems that were previously not measurable. This allowed us not only to verify established findings about the Min system, but also to gain new insights.” By using MSPT, the team was able to show that the complexes of MinD proteins are larger than initially thought. In addition, the experiments provide first insights that MinE can act as a connecting piece for MinD proteins and that it can thus initiate the membrane release of larger complexes.
As reported in the new paper, MSPT provides valuable insights for elucidating dynamic processes at biological membranes. However, the researchers are continuously working on improving the method even further. In the future, the method should also be applicable for integral membrane proteins and it should allow the detection of even smaller proteins.
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Nanosilver no ‘silver bullet’ in long-term treatment of infections

New research from the University of Technology Sydney (UTS) has found that pathogens that form biofilms can evolve to survive nanosilver treatment. The study is the first to demonstrate that long-term nanosilver treatment can increase the risk of recurrent infections.
The research is published in the Journal of Nanobiotechnology.
Nanosilver is a potent antimicrobial that is currently used in medical devices such as internal catheters, as well as wound dressings, in particular for burn wounds, to fight or prevent infections. It is also one of the most commercialised antimicrobial nanoparticles, and has been incorporated into consumer products from personal care products, such as soaps and toothpaste, to washing machines and fridges, even children’s products, such as in kids socks to prevent odour.
Researchers at UTS’s iThree Institute studied nanosilver adaptation phenomena in the bacterium Pseudomonas aeruginosa, in its biofilm form of growth, and observed a novel adaptation mechanism not seen in previous planktonic growth studies. Following prolonged treatment, nanosilver killed 99.99% of the bacterial population with only 0.01% cells surviving for longer. This minute fraction of ‘persisters’ resumed normal growth upon discontinuation of the nanoparticle treatment.
“Understanding how pathogens develop adaptation mechanisms to nanoparticles is key in our effort to overcome the phenomena, including in biofilms as the major form of growth of pathogenic bacteria. This is to protect the efficacy of important alternative antimicrobials, like nanosilver, in this era of increasing antibiotic resistance,” said lead author Dr Cindy Gunawan.
The study first author, Dr Riti Mann, said the research findings will also help develop strategies on the better management of nanoparticle use as antimicrobials, in particular those that involving long-term exposures.
“Based on this study, we recommend monitoring patients not only during, but also after prolonged use of nanoparticle treatment for safeguarding against recurrent infections.
“The scientific evidence that bacteria can adapt to nanoparticles means we need effective regulation of the use of nanoparticles, with clear risks versus benefits assessment and clear antimicrobial targets. With limited development of new effective antibiotics over the past decades, we need to preserve the efficacy of the alternative antimicrobials to fight untreatable infections, saving lives and billions of dollars in healthcare,” said Dr Gunawan.
The bacterium used in the study, Pseudomonas aeruginosa, often attach themselves on catheter surfaces, as well as to wounds and lung linings, growing biofilms, which can be difficult to control.
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Nearly 6 million children are driven into severe hunger by the hot, dry shifts of a strong el Niño

Over the last year and a half, the 1-in-100-year Covid-19 pandemic drove millions of children into hunger. But every four to seven years, an El Niño causes weather patterns to shift across the tropics, leading to warmer temperatures and precipitation changes and widespread impacts on agriculture, infectious diseases, conflicts and more. During a single bad El Niño, nearly 6 million children are driven into undernutrition as a result, according to a study in Nature Communications. That’s at least 70 percent and perhaps up to three times the number of children who have gone hungry because of the pandemic.
“It would have been very difficult to prepare the world for a pandemic that few saw coming, but we can’t say the same about El Niño events that have a potentially much greater impact on the long-term growth and health of children,” says Amir Jina, an author of the paper and assistant professor at the Harris School of Public Policy. “Scientists can forecast an approaching El Niño up to 6 months in advance, allowing the international community to intervene to prevent the worst impacts. Our study helps to quantify those impacts on child nutrition to guide global public investments in food insecure areas.”
Jina and his coauthors, Jesse Anttila-Hughes and Gordon McCord, provide the first estimate of El Niño’s impacts on child nutrition throughout the global tropics. They do so by assembling data on more than a million children spanning four decades and all developing country regions, a dataset that represents about half of the more than 600 million-strong under-five population globally. Their analysis finds that warmer, drier El Niño conditions increase undernutrition in children across most of the tropics, where 20 percent of children are already deemed severely underweight by the World Health Organization (WHO). That percentage ticks up by 2.9 percent during El Niño years, affecting millions of children.
In the case of the severe 2015 El Niño, the number of children at or below the WHO threshold for severely underweight jumped by nearly 6 percent — or an additional nearly 6 million children driven into hunger. While the children’s weight appears to recuperate with time, the shock on their nutrition at such a young age stunts their growth in later years.
As part of the Sustainable Development Goals, the international community is working to eliminate all forms of undernutrition by 2030, meaning each year about 6 million children would need to rise out of severe hunger. With less than 10 years remaining to meet that goal, the 2015 El Niño erased one year of progress. To offset the impacts of the 2015 El Niño would require providing 134 million children with micronutrient supplements or 72 million food insecure children with food, the study finds.
“Since scientists can point to which places are going to have drought and which places are going to flood months ahead of time, the international community could act proactively to prevent millions of children from falling into undernutrition,” says Gordon McCord from the UC San Diego School of Global Policy and Strategy. “It’s a real tragedy that even in the 21st century so much of the human population is pushed to desperation by predictable climate processes.”
While it is unclear whether climate change will increase the frequency and intensity of El Niño, climate change will cause hot areas to become hotter and dry areas to become drier. When El Niño is layered on top of these overall shifts, there is no doubt that the impacts during El Niño years will be worse than they are now. For example, as areas expect to lose crops with climate change, those same areas will likely lose even more crops during El Niño years.
“These are routine events in the climate that lead to real tragedy around the world,” says Jesse Anttila-Hughes from the University of San Francisco. “Studying El Niño can teach us about the impacts that come from a hotter, drier climate — important lessons as these changes become more global in scale with climate change. But the fact that we live through an El Niño every few years, we know they’re coming, and we still don’t act is a bad sign since many of these climate shifts — from isolated heat waves to hurricanes — will be a lot less predictable as the climate changes.”
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Materials provided by University of Chicago. Note: Content may be edited for style and length.

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When breezy, wear masks outdoors to prevent coronavirus exposure

As the highly infectious delta variant of the coronavirus continues to spread across the United States, guidelines from the Centers for Disease Control and Prevention recommend even the vaccinated wear masks indoors to prevent exposure and transmission.
However, it is less clear what people should do when outside.
In Physics of Fluids, by AIP Publishing, researchers from the Indian Institute of Technology Bombay found when a person coughs outdoors, wind flowing in the same direction can propagate the virus faster over longer distances than in calm conditions.
“The study is significant in that it points to the increased infection risk that coughing in the same direction as the wind could bring about,” co-author Amit Agrawal said. “Based on the results, we recommend wearing masks outdoors, particularly in breezy conditions.”
Other guidelines, such as coughing in an elbow or turning the face away while coughing, should be followed to reduce transmission when socializing outdoors.
Most studies model cough flow using puffs of air or a simple pulsating profile. But a real cough is more complicated, exhibiting turbulent flow with prominent vortical structures swirling like mini whirlpools.
To investigate these vortices, the researchers used a large eddy simulation, a numerical model in computational fluid dynamics that simulatesturbulence. They modeled cough jets in breezy conditions and in calm conditions representing a typical indoor environment.
These simulations show even a light breeze of about 5 mph extends effective social distancing by around 20%, from 3-6 feet to 3.6-7.2 feet, depending on cough strength. At 9-11 mph, spreading of the virus increases in distance and duration.
The researchers found the vortices enable bigger droplets to persist in the air longer than has been typically assumed, increasing the time it takes to adequately dilute the viral load in fresh air. As the cough jet evolves and spreads, it interacts with the wind flowing in the same direction, and the bigger infected droplets become trapped in the jet’s vortices instead of falling relatively quickly to the ground under gravity.
“The increase in residential time of some of the larger droplets will increase the viral load transmitting through the cough jet and, therefore, the chances of infection,” Agrawal said. “Overall, the study highlights increased chances of infection in the presence of even a light breeze.”
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Materials provided by American Institute of Physics. Note: Content may be edited for style and length.

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