This process is very different from that in other places. Beijing, for example, is probably the best-studied megacity in the world in terms of its air pollution. However, in the atmosphere of the Chinese capital, particle formation follow different chemical pathways. In China, the gases from emissions such as traffic and wood burning react in the atmosphere during the day when they are exposed to light resulting in the formation of less volatile fumes capable of forming particles during the haze.

Such a pathway was also expected in New Delhi, however the opposite happens. Haze formation from the condensation of directly emitted fumes occurs at night, without photooxidation, driven by increased emissions together with a sharp decrease in temperatures. This work has shown for the first time that semi-volatile gases can form such particles at night, contributing to the haze.

The measurements were carried out in January and February 2019. For this purpose, the researchers from India, Sweden and Switzerland set up a station in the center of New Delhi with measuring equipment that included instruments to determine the number and size of the particles, as well as their chemical composition.

The mass spectrometers deployed are very sensitive and can detect thousands of different molecules in the air of New Delhi, whereby the particle concentrations sometimes reached hundreds of thousands of particles within the volume of air corresponding to a sugar cube. Some of the instruments came from PSI, others from partners such as the Indian Institute of Technology Kanpur and the University of Stockholm.

A second measuring station was also set up in the city with scaled-down equipment to verify that the formation of particulates is indeed a regional phenomenon. Switzerland's contribution was financed by the Swiss Agency for Development and Cooperation.

It took four years of data analysis and peer review before the results were ready to be published in Nature Geoscience.

Suneeti Mishra et al, Rapid night-time nanoparticle growth in Delhi driven by biomass-burning emissions, Nature Geoscience (2023). DOI: 10.1038/s41561-023-01138-x

Part 2

Why do people pull their faces when applying make-up?

This is called 'Mascara Mouth' or 'Mascara face'. Intense focus, raised eyebrows, and a slightly open mouth, combine to create a familiar 'look' when trying to achieve the perfect lash.

‘Mascara face’, as it’s sometimes called, is thought to be a result of nerves in our brains cross-firing. The two nerves controlling our eyeball and eyelid movements are rooted in a very similar part of the brain to another nerve that controls the opening and closing of our jaw. So, it’s possible that when the two nerves in charge of eye movements are activated, they trigger off the nearby mouth-opening nerve.

This is only a theory, though. A simpler explanation is that we’ve learnt that opening our mouths stretches our skin, which helps with applying make-up, so people keep doing it.

The FDA Just Approved The First Fast-Acting Nasal Spray For Migraines

The US Food and Drug Administration has approved a fast-acting nasal spray from Pfizer designed to treat migraines, the US pharmaceutical giant said Friday.

​Pfizer said it expected the drug, marketed under the name Zavzpret, to be available in pharmacies in July 2023.

​The FDA approval of Zavzpret marks a significant breakthrough for people with migraine who need freedom from pain and prefer alternative options to oral medications.

​A Phase 3 study of the drug found that it delivered pain relief to some migraine sufferers in as little as 15 minutes.

​As a nasal spray with rapid drug absorption, Zavzpret offers an alternative treatment option for people who need pain relief or cannot take oral medications due to nausea or vomiting.

​The treatment for a condition generally tackled with orally taken medicines was double-blind tested on a sample of 1,405 people, with half taking a single spray dose and the remainder receiving a placebo.

​The spray was found to reduce pain significantly when assessed two hours after the onset of a migraine, which as well as causing often severe headaches can include nausea and sensitivity to light or noise.

​Pfizer acquired Zavzpret, also known as Zavegepant, last year for some $10 billion from Biohaven, along with other migraine treatments from the firm.

​source: News agencies

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Air travel: Turbulence increases as climate change becomes worse

Atmospheric turbulence accounts for 71% of in-flight weather-related injuries, and according to scientists turbulence is only worsening with global warming. While winter is typically the most turbulent season, modeling suggests that by the year 2050, summers will be as turbulent as winters were back in the 1950s.

The paper, "Clear‑air turbulence trends over the North Atlantic in high‑resolution climate models," has been published in the international journal Climate Dynamics.

Clear-air turbulence (CAT) is one of the more dangerous weather-related hazards. It usually develops in cloud-free environments of the upper-level atmosphere; offering no visual clues to pilots and undetectable by onboard radar, these events seemingly come out of nowhere. Prolonged exposure to turbulence will shorten the fatigue life, which is the time the aircraft can be in service. Aircraft fittings can be damaged and severe structural damage can result from more intense clear-air turbulence. In extremely rare cases, this could even lead to the break-up of the aircraft. During moderate turbulence, unrestrained items of cargo, passenger luggage or passengers themselves can collide, causing damage or injury.

The intensity of a jet stream depends on latitudinal horizontal temperature gradients. Due to the steepening of the pole-to-equator temperature gradient in the upper troposphere and lower stratosphere, jet streams are expected to intensify in wind shear with anthropogenic climate change.

The study used three global climate  modeling simulators covering the period 1950–2050 in the formation analysis.

Based on the assessment, for every 1 °C of global near-surface warming, moderate CAT events will increase by 14% in summer and autumn and by 9% for winter and spring. Moderate turbulence is described as inflicting vertical accelerations of up to 0.5g.

With increased turbulence in all seasons, more fights will encounter CAT events on current flight paths. One option for airlines will be to attempt to avoid areas where CAT forms. This might cause longer transatlantic flight times and thousands of additional hours of accumulated flight and fuel costs—a good reminder that the seatbelt sign is there for a reason, and keeping yours on even when the light is off might be the safest plan in the future.

Isabel H. Smith et al, Clear-air turbulence trends over the North Atlantic in high-resolution climate models, Climate Dynamics (2023). DOI: 10.1007/s00382-023-06694-x

Where did Earth's water come from? Not melted meteorites, according to scientists

Water makes up 71% of Earth's surface, but no one knows how or when such massive quantities of water arrived on Earth.

A new study published in the journal Nature brings scientists one step closer to answering that question.

Researchers analyzed melted meteorites that had been floating around in space since the solar system's formation 4 1/2 billion years ago. They found that these meteorites had extremely low water content—in fact, they were among the driest extraterrestrial materials ever measured. These results, which let researchers rule them out as the primary source of Earth's water, could have important implications for the search for water—and life—on other planets. It also helps researchers understand the unlikely conditions that aligned to make Earth a habitable planet.

After analyzing the achondrite meteorite samples, researchers discovered that water comprised less than two millionths of their mass. For comparison, the wettest meteorites—a group called carbonaceous chondrites—contain up to about 20% of water by weight, or 100,000 times more than the meteorite samples.

This means that the heating and melting of planetesimals leads to near-total water loss, regardless of where these planetesimals originated in the solar system and how much water they started out with. Researchers discovered that, contrary to popular belief, not all outer solar system objects are rich in water. This led them to conclude that water was likely delivered to Earth via unmelted, or chondritic, meteorites.

Megan Newcombe, Degassing of early-formed planetesimals restricted water delivery to Earth, Nature (2023). DOI: 10.1038/s41586-023-05721-5. www.nature.com/articles/s41586-023-05721-5

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Study: Experimental COVID shot made via egg-based technology elicits higher antibody proportion than mRNA vax

An experimental COVID-19 vaccine produced with technology based on a decades-old method, elicited virus-neutralizing antibodies in higher proportion than the amount induced by mRNA immunizations, a Phase 1 clinical trial has found.

The investigational vaccine was developed in New York City and tested in Thailand where the shots were produced using a form of egg-based technology. The fact that researchers are still racing to develop new COVID-19 vaccines highlights an ongoing need, especially in low- and middle-income countries—and for good reason.

There is a need for SARS-CoV-2 vaccines that can be produced at low cost locally in low- and middle-income countries and this is one such experiment.

The study analyzed antibody responses elicited by the investigational vaccine known as NDV-HXP-S, which is produced in hens' eggs.

The research found that the investigational vaccine prompted a higher proportion of neutralizing antibodies against SARS-CoV-2 in volunteers compared with the proportion of neutralizing antibodies produced by a separate group of people who were vaccinated with Pfizer's mRNA vaccine.

A neutralizing antibody is one that defends healthy cells from a virus by neutralizing the pathogen's efforts to get inside. For instance, a neutralizing antibody can stop a virus from making a conformational change—swapping its structure for a new shape. Viral shape-shifting is a way to infect a cell.

Neutralizing antibodies differ from binding antibodies, which latch onto the pathogen and alert warrior cells of the immune system that a viral invasion is underway. While people who were vaccinated with NDV-HXP-S had a higher proportion of neutralizing antibodies, their binding to neutralizing antibody ratios were lower than those who were vaccinated with Pfizer's mRNA vaccine. When all variables were taken into account, the team concluded that the antibody responses between the two vaccines were comparable.

Findings from the research suggest that even in regions with previously limited vaccine-production infrastructure, it's possible to manufacture robust COVID shots at low cost. Western countries averse to technology sharing early in the pandemic, a factor that left scores of people in low- and middle-income countries with few opportunities for vaccination. Now, the tide is turning, albeit three years after the global SARS-CoV-2 pandemic was declared.

"Locally produced vaccines can increase vaccine access and vaccine independence, especially for low- and middle-income countries. The NDV-HXP-S vaccine is designed to help close this gap because it can be economically produced in influenza vaccine manufacturing plants that are located in [these countries]. Moreover, it can be stored and distributed without the need for freezers.

Part1

Although mRNA vaccines have dominated the U.S. response to the pandemic, the technology underlying those shots is expensive. The finicky, temperature-sensitive ingredients required for mRNA vaccines may be difficult to store in far-flung regions of the globe. To address the global need for a low-cost vaccine that can be produced locally, scientists have been developing alternatives, such as NDV-HXP-S.

The vaccine's initials, NDV-HXP-S, stand for Newcastle disease virus, HexaPro, and spike protein. Producing the vaccine involves a vector, which in this case is the Newcastle disease virus, an agent that infects birds. The vaccine is manufactured by way of egg-based technology, which has been used for decades to produce annual flu shots. The Newcastle viral vector is not used in the production of influenza vaccines.

The vector works exquisitely well in the NDV-HXP-S production process, ferrying vaccine components into embryonated chicken eggs. The result, in the case of the vaccine used in Thailand, is an inactivated vaccine, which is a viral particle displaying SARS-C0V-2's spike protein on its surface.

"NDV-HXP-S can be used as a live vaccine or as an inactivated vaccine

The team analyzed antibody responses after Thai volunteers were vaccinated in the phase 1 clinical study. Researchers studied serum samples from 210 Thai volunteers who received either a placebo or the inactivated NDV-HXP-S vaccine.

They compared antibodies from the Thai volunteers to those from 20 people who received the Pfizer mRNA vaccine in New York City. Antibodies elicited by NDV-HXP-S tended to target the receptor binding domain of the virus rather than the spike protein's S2 subunit, the researchers found.

"Neutralizing activity of sera from NDV-HXP-S vaccinees was comparable to that of [Pfizer] vaccinees, whereas spike protein binding activity of the NDV-HXP-S vaccinee samples was lower than that of sera obtained from mRNA vaccines," the researchers say. This led them to calculate ratios between binding and neutralizing antibody titers.

This work show that a vaccine candidate that can be produced locally in [low- and middle-income countries] at low-cost induces neutralizing antibody titers to SARS-CoV-2 comparable to those observed in cohorts having received mRNA-based COVID-19 vaccines.

Juan Manuel Carreño et al, An inactivated NDV-HXP-S COVID-19 vaccine elicits a higher proportion of neutralizing antibodies in humans than mRNA vaccination, Science Translational Medicine (2023). DOI: 10.1126/scitranslmed.abo2847

Part 2

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Deactivating mosquito sperm: A human bite back!

New  research makes it likely that proteins responsible for activating mosquito sperm can be shut down, preventing them from swimming to or fertilizing eggs.

The study could help control populations of Culex, the common house mosquito that transmits brain-swelling encephalitis and West Nile Virus.

During mating, mosquitoes couple tail to tail, and the males transfer sperm into the female reproductive tract. It can be stored there awhile, but it still has to get from point A to point B to complete fertilization. 

Key to completing that journey are the specialized proteins secreted during ejaculation that activate the sperm flagella, or 'tails,' that power their movement.

Without these proteins, the sperm cannot penetrate the eggs. They'll remain immotile, and will eventually just degrade.

The study, detailed in the journal PLOS ONE, details a full portrait of all the proteins in the insect's sperm, allowing researchers to find the specific ones that maintain the quality of the sperm while they're inactive, and that also activate them to swim.

To get this detailed information the researchers  worked with a team of graduate and undergraduate students who isolated as many as 200 male mosquitoes from a larger population. They then extracted enough sperm from the tiny reproductive tracts for mass spectrometry equipment to detect and identify the proteins.

Previously, the team determined that sperm need calcium upon entering a reproductive tract to power forward motion. They can now look in the completed protein profile they've created, find the calcium channel proteins, and design experiments to target these channels.

This kind of protein profiling offers a path toward controlling mosquitoes that is more environmentally friendly than other methods that can have unintended, toxic effects. 

This  work sets the foundation for a form of biological control, which most would agree is preferable.

The operative word is control, rather than eradicate. Even though immobilizing the sperm would be 100% effective for the treated mosquitoes, it is not possible or desirable to kill all mosquitoes. This technology would change the proportion of fertile to infertile males in a given mosquito population, rather than wiping them all out.

The team is hoping that information about sperm motility regulators in Culex will also apply to other species of mosquitoes. And other pests too! What we learn in one system, such as mosquitoes, can translate to others.

Catherine D. Thaler et al, Using the Culex pipiens sperm proteome to identify elements essential for mosquito reproduction, PLOS ONE (2023). DOI: 10.1371/journal.pone.0280013

A new way to remove waste from the brain after hemorrhage

Intracerebral hemorrhage, and bleeding into the brain tissue, is a devastating neurological condition affecting millions of people annually. It has a high mortality rate, while survivors are affected by long-term neurological deficits. No medication has been found to support brain recovery following hemorrhage.

In an international collaboration, researchers investigated whether a protein called cerebral dopamine neurotrophic factor (CDNF) has potential as a treatment for brain hemorrhage.

Researchers suggest that cerebral dopamine neurotrophic factor, a protein being currently tested for Parkinson's disease treatment, also has therapeutic effects and enhances immune cell's response after brain hemorrhage.

The authors found that the administration of cerebral dopamine neurotrophic factor accelerates hemorrhagic lesion resolution, reduces brain swelling, and improves functional outcomes in an animal model of brain hemorrhage.

They found that found that cerebral dopamine neurotrophic factor acts on immune cells in the bleeding brain, by increasing anti-inflammatory mediators and suppressing the production of the pro-inflammatory cytokines that are responsible for cell signaling. This is a significant step towards the treatment of injuries caused by brain hemorrhage, for which we currently have no cure.

The administration of cerebral dopamine neurotrophic factor also resulted in the alleviation of cell stress in the area that surrounds the hematoma.

Finally, the researchers demonstrated that systemic administration of cerebral dopamine neurotrophic factor promotes scavenging by the brain's immune cells after brain hemorrhage and has beneficial effects in an animal model of brain hemorrhage. 

Kuan-Yin Tseng et al, Augmenting hematoma-scavenging capacity of innate immune cells by CDNF reduces brain injury and promotes functional recovery after intracerebral hemorrhage, Cell Death & Disease (2023). DOI: 10.1038/s41419-022-05520-2

Casting light on counterfeit products through nano-optical technology

Each year, an estimated two trillion dollars is lost globally due to counterfeit products ranging from jewelry to medicine. As current security labels and product authentication methods are rapidly becoming obsolete or easy to hack, there is a rising urgency for more secure anti-counterfeiting labels.

A research team fabricated a 3D printed nano optical security label that provides 33100 possible combinations for heightened security in optical anti-counterfeiting. 

The research team achieved such a feat by exploiting higher dimensional structured light, i.e., colored Orbital Angular Momentum (OAM) beams, through the fabrication of 3D printed spiral phase plates. Importantly, these plates were miniaturized down to a diameter smaller than that of a strand of human hair and further integrated with structural color filters—spiky looking structures that allow specific colors of light through.

In their study, they included color, spatial position, and OAM of light (one degree of freedom of light) onto a small colored vortex beam (CVB) generator (25 μm). With only 10-by-10 CVB unit array to demonstrate, the optical security label they designed could open pathways for the next generation of optical anti-counterfeiting.
We see things clearly when we hold them up to the light. What this team has done is to learn how to use the natural light that surrounds us and extract tiny beams from it that carry information encoded in not just color, but also by how much we 'twist' its wavefront. This optical version of the combination lock that utilizes high-dimensional structured light provides us with a powerful platform for advanced anti-counterfeiting and information security.

Casting light on counterfeit products through nano-optical technology (2023, March 14)
retrieved 18 March 2023 from https://phys.org/news/2023-03-counterfeit-products-nano-opticaltech...

The video shows the optical security label or photonic tally, consisting of colored vortex beam array. The photonic tally turns into colorful dots when overlapped with each other. During this process, the color and OAM (orbital angular momentum) information is decoded. Credit: Singapore University of Technology and Design

New tool for organ repair: curvature of the environment

A ball, a saddle, or a flat plate. The curvature of biomaterials inhibits or stimulates bone cells to make new tissue. This is what TU Delft engineers show in research published in Nature Communications. This study of geometries could be an important step in research into repairing damaged tissues. In this video, Amir Zadspoor (professor of Biomaterials and Tissue Biomechanics) and Lidy Fratila-Apachitei (assistant professor of Biomaterials) explain exactly how this new tool for organ repair works.

Elite soccer players are more likely to develop dementia, suggests new study

Elite male soccer players were 1.5 times more likely to develop neurodegenerative disease than population controls, according to an observational study published in The Lancet Public Health journal.

Among male soccer players playing in the Swedish top division, 9% (537 out of 6,007) were diagnosed with neurodegenerative disease, compared to 6% (3,485 out of 56,168) population controls.

The soccer players were both amateur and professional. Sweden was a prominent soccer nation during the 20th century and many of the players from the top division were competing at the highest international level. However, due to ideals of sportsmanship and amateurism, soccer clubs in Sweden were not allowed to pay salaries to their soccer players until the late 1960s.

In recent years, there have been growing concerns about exposure to head trauma in soccer (soccer) and whether it can lead to increased risk of neurodegenerative disease later in life. A previous study from Scotland suggested that soccer players were 3.5 times more likely to develop neurodegenerative disease. Following this evidence, certain footballing associations implemented measures to reduce heading in younger age groups and training settings.

While the risk increase in this study is slightly smaller than in the previous study from Scotland, it confirms that elite [soccer players] have a greater risk of neurogenerative disease later in life. As there are growing calls from within the sport for greater measures to protect brain health, this new study adds to the limited evidence base and can be used to guide decisions on how to manage these risks.

The authors caution that although 9% of soccer players and 6% of controls were diagnosed with neurodegenerative disease during their study, most participants were still alive at the end of data collection, so the lifetime risks of developing neurodegenerative disease for both groups are likely to be higher.

The risk of neurodegenerative disease was 1.5 times higher for outfield players than controls but was not significantly higher for goalkeepers compared to controls. Accordingly, in a direct comparison, outfield players had a risk of neurodegenerative disease 1.4 times higher than that of goalkeepers.

Soccer players had a risk of Alzheimer's disease and other dementias 1.6 times that of controls—with 8% (491 out of 6,007) of soccer players being diagnosed with the condition compared to 5% (2889 out of 56,168) of controls.

Part 1

The authors discuss some limitations of their study. The findings' generalizability to soccer players playing today is uncertain. As neurodegenerative disease usually occurs later in life, most players in the study who were old enough to have developed one of these conditions played elite soccer during the mid-20th century. Since then, soccer has changed in many ways that may impact the risk of neurodegenerative disease. It may be that switching from leather to synthetic balls (that do not soak up water and become heavier), having more rigorous training and better equipment, or switching towards a playstyle associated with less head trauma may have reduced the risk. On the other hand, the risk might be higher among soccer players who nowadays train and play more intensely from a young age. The study also looked at male elite soccer players only, so the study's generalizability to female elite players and to male and female amateur and youth players is uncertain.

Neurodegenerative disease among male elite football (soccer) players in Sweden: a cohort study, The Lancet Public Health (2023). DOI: 10.1016/S2468-2667(23)00027-0 , www.thelancet.com/journals/lan … (23)00027-0/fulltext

Part 2

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An extra X chromosome-linked gene may explain decreased viral infection severity in females

It has long been known that viral infections can be more severe in males than females, but the question as to why has remained a mystery—until possibly now. The key may lie in an epigenetic regulator that boosts the activity of specialized anti-viral immune cells known as natural killer (NK) cells.

In a study published March 16 in the peer-reviewed journal Nature Immunology, a collaborative team of  researchers have found that female mouse and human NK cells have an extra copy of an X chromosome-linked gene called UTX. UTX acts as an epigenetic regulator to boost NK cell anti-viral function, while repressing NK cell numbers.

While it is well-known that males have more NK cells compared to females, researchers did not understand why the increased number of NK cells was not more protective during viral infections. It turns out that females have more UTX in their NK cells than do males, which allows them to fight viral infections more efficiently.

The researchers noted that this held true whether or not the mice had gonads (ovaries in females; testes in males), indicating that the observed trait was not linked to hormones. Furthermore, female mice with lower UTX expression had more NK cells which were not as capable of controlling viral infection.

This implicates UTX as a critical molecular determinant of sex differences in NK cells.

The findings suggest that therapies involving immune responses need to move beyond a "one-size-fits-all" approach and toward a precision medicine model, also known as personalized medicine, that tailors treatments that take into account people's individual differences, such as genetics, environment and other factors that influence health and disease risk, the researchers write.

Mandy I. Cheng et al, The X-linked epigenetic regulator UTX controls NK cell-intrinsic sex differences, Nature Immunology (2023). DOI: 10.1038/s41590-023-01463-8

How tumors transform blood vessels

Increasingly dense cell clusters in growing tumors convert blood vessels into fiber-filled channels. This makes immune cells less effective, as findings by researchers suggest.

It was almost ten years ago that researchers first observed that tumours occurring in different cancers—including colorectal cancer, breast cancer and melanoma—exhibit channels leading from the surface to the inside of the cell cluster. But how these channels form, and what functions they perform, long remained a mystery.

Through a series of elaborate and detailed experiments, scientists  have found possible answers to these questions. There is a great deal of evidence to suggest that these channels, which the researchers have dubbed tumour tracks, were once blood vessels.

These blood vessels start out by supplying the fast-growing cell clusters with glucose and oxygen. But then the vessels undergo a process that strips them of their original function of transporting blood: the vessel walls change and the vessel cavity gradually fills up.

This filler material consists mainly of cells and newly formed protein fibers, which make up what is known as the extracellular matrix. Collagen fibers are found here, as are fibronectin fibers. The latter play a role in growth processes that take place mainly during embryonic development or wound healing. In their article, the researchers show that the fibers within the tumor tracks are capable of trapping immune cells.

While this happens, the immune cells stretch out along the channels and stick to the loose fibronectin fibers. In this elongated form, the immune cells switch from fighting diseases to supporting healing processes. Instead of attacking the tumour cells, they excrete molecules that stimulate growth, thus helping the cancer cells to multiply.

It becomes clear that the tension of extracellular matrix fibers plays a key and previously unknown role in tumor development: in healthy tissue, the fibronectin fibers are stretched extremely taut; only in tumor tissue are they slack. In this looser, more relaxed form, surrounded by transformed blood vessel walls, the fibronectin fibers evidently create a recess in which cancer cells can grow undisturbed.

Charlotte M. Fonta et al, Infiltrating CD8+ T cells and M2 macrophages are retained in tumor matrix tracks enriched in low tension fibronectin fibers, Matrix Biology (2023). DOI: 10.1016/j.matbio.2023.01.002

Devadarssen Murdamoothoo et al, Tenascin‐C immobilizes infiltrating T lymphocytes through CXCL12 promoting breast cancer progression, EMBO Molecular Medicine (2021). DOI: 10.15252/emmm.202013270

Sweetener reduces mouse immune response

In high doses, the calorie-free sugar substitute sucralose suppresses the immune system in mice. The sweetener impairs the rodents’ T cells, immune cells that fight.... Once the mice stopped being fed sucralose, their T-cell responses recovered. The researchers say that it is unlikely that eating sucralose in normal amounts is harmful to humans. There might even be a bright side for autoimmune conditions: mice predisposed to type 1 diabetes were less likely to develop the condition after consuming the sweetener.

https://www.nature.com/articles/s41586-023-05801-6.epdf?sharing_tok...

https://www.nature.com/articles/d41586-023-00784-w?utm_source=Natur...

When someone sneezes on Everest, their germs can last for centuries

Almost five miles above sea level in the Himalayan mountains, the rocky dip between Mount Everest and its sister peak, Lhotse, lies windswept, free of snow. 

According to new research, mountaineers visiting this place are leaving behind a frozen legacy of hardy microbes, which can withstand harsh conditions at high elevations and lie dormant in the soil for decades or even centuries.

The research not only highlights an invisible impact of tourism on the world’s highest mountain, but could also lead to a better understanding of environmental limits to life on Earth, as well as where life may exist on other planets or cold moons.

The research not only highlights an invisible impact of tourism on the world’s highest mountain, but could also lead to a better understanding of environmental limits to life on Earth, as well as where life may exist on other planets or cold moons. The findings were published last month in Arctic, Antarctic, and Alpine Research.

There is a human signature frozen in the microbiome of Everest, even at that elevation.

In decades past, scientists have been unable to conclusively identify human-associated microbes in samples collected above 26,000 feet. This study marks the first time that next-generation gene sequencing technology has been used to analyze soil from such a high elevation on Mount Everest, enabling researchers to gain new insight into almost everything and anything that’s in them.

The researchers weren’t surprised to find microorganisms left by humans. Microbes are everywhere, even in the air, and can easily blow around and land some distance away from nearby camps or trails.

If somebody even blew their nose or coughed, that's the kind of thing that might show up. Certain microbes which have evolved to thrive in warm and wet environments like our noses and mouths were resilient enough to survive in a dormant state in such harsh conditions.

Most of the microbial DNA sequences they found were similar to hardy, or “extremophilic” organisms previously detected in other high-elevation sites in the Andes and Antarctica. The most abundant organism they found using both old and new methods was a fungus in the genus Naganishia that can withstand extreme levels of cold and UV radiation.

But researchers also found microbial DNA for some organisms heavily associated with humans, including Staphylococcus, one of the most common skin and nose bacteria, and Streptococcus, a dominant genus in the human mouth.

At high elevation, microbes are often killed by ultraviolet light, cold temperatures and low water availability. Only the hardiest critters survive. Most—like the microbes carried up great heights by humans—go dormant or die, but there is a chance that organisms like Naganishia may grow briefly when water and the perfect ray of sunlight provides enough heat to help it momentarily prosper. But even for the toughest of microbes, Mount Everest is a Hotel California: “You can check out any time you like/ But you can never leave.”

The researchers don’t expect this microscopic impact on Everest to significantly affect the broader environment. But this work does carry implications for the potential for life far beyond Earth, if one day humans step foot on Mars or beyond.

https://www.colorado.edu/today/2023/03/14/when-someone-sneezes-ever...

How DNA-PK Facilitates Repair from Double-Stranded DNA Breaks

Study shows new way to spur brain immune cells to clear toxic waste linked to Alzheimer's disease

A newly discovered "energy switch" in the immune cells of the brain may lead to the development of drugs for Alzheimer's disease, the most common form of dementia.

Scientists discovered that after blocking and turning off this "switch," brain immune cells called microglia were able to remove toxic proteins that can build up and lead to Alzheimer's disease.

Microglia tend to be damaged in people with the disease, which makes them less capable of clearing cellular toxic waste. To restore the clean-up function, the scientists "switched off" their inefficient metabolism by preventing a key enzyme from attaching to energy-generating parts of the immune cells.

The findings from lab experiments set the stage for developing drugs that can specifically target metabolism in brain immune cells in order to treat Alzheimer's disease, which contributes to 60% to 70% of all dementia cases globally. Such drugs are of high interest in health care. 

Researchers had previously shown that drugs that activated the toxic protein led to less toxic waste build-up in the brain, which improved the condition of mice with Alzheimer's disease. But how this worked was not clear.

The researchers now cracked the puzzle with their latest experiments on cells from mice with Alzheimer's. Their work revealed that the translocator protein is critical for the microglia immune cells of the brain to generate their own energy.

Microglia perform the important function of "gobbling up" and removing beta amyloid, a toxic protein whose build-up in the brain causes damage and death to nerve cells, resulting in Alzheimer's disease. To do their job properly and remove the toxic waste, the immune cells need a lot of energy.

The researchers showed that without the translocator protein, microglia from mice with Alzheimer's had an energy problem and could not remove the beta amyloid, which resulted in the disease worsening in the mice.

 Microglia lacking the translocator protein resembled damaged microglia observed in aging and Alzheimer's disease. These damaged microglia inefficiently produced energy and could not clean up toxic waste in mice with Alzheimer's disease.

The experiments also demonstrated that when the translocator protein is absent, an enzyme called hexokinase-2, which metabolizes sugar, kicks into action in microglia to compensate. The enzyme promotes an inefficient way for cells to produce energy. What was surprising was that hexokinase-2 became activated when it stuck to the energy-generating parts of cells called mitochondria.

The researchers found that hexokinase-2 was also activated in microglia when exposed to more toxic forms of beta amyloid, just as happens in Alzheimer's disease. The scientists believe this finding helps to partly explain how microglia fail in patients with Alzheimer's disease and when people age.
Part1

To manipulate the enzyme's role in microglia energy production, the  researchers developed a light-activated tool. Their tool involves shining blue light onto a genetically modified version of the hexokinase-2 enzyme to "switch off" one of its functions.

When this happens, it blocks the enzyme's ability to stick to the energy-generating parts of the microglia and forces the cells to stop relying on an inefficient method of energy production. Experimental results showed that this improves their ability to clear beta amyloid by nearly 20 percent.

However, if hexokinase-2's sticking ability is not blocked and its function is disrupted by simply inactivating the enzyme, it does not help the microglia to clear away waste. This insight provides a critical clue for future drug targets.

Lauren H. Fairley et al, Mitochondrial control of microglial phagocytosis by the translocator protein and hexokinase 2 in Alzheimer's disease, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2209177120

Part 2

Researchers create virus-resistant, safely restrained E. coli for medical, industrial applications

In a step forward for genetic engineering and synthetic biology, researchers have modified a strain of Escherichia coli bacteria to be immune to natural viral infections while also minimizing the potential for the bacteria or their modified genes to escape into the wild. The work promises to reduce the threats of viral contamination when harnessing bacteria to produce medicines such as insulin as well as other useful substances, such as biofuels.

Currently, viruses that infect vats of bacteria can halt production, compromise drug safety, and cost millions of dollars.

 So far, based on extensive laboratory experiments and computational analysis, Researchers haven't found a virus that can break the bacterium. 

The work also provides the first built-in safety measure that prevents modified genetic material  from being incorporated into natural cells.

Akos Nyerges et al, A swapped genetic code prevents viral infections and gene transfer, Nature (2023). DOI: 10.1038/s41586-023-05824-z. www.nature.com/articles/s41586-023-05824-z

Why Are Electric Vehicle Fires So Hard To Put Out?

Antibody fragment-nanoparticle therapeutic eradicates cancer
A novel cancer therapeutic, combining antibody fragments with molecularly engineered nanoparticles, permanently eradicated gastric cancer in treated mice, a multi-institutional team of researchers found.

The results of the “hit and run” drug delivery system, published in the March issue of Advanced Therapeutics, were the culmination of more than five years of collaboration between various research groups.
Targeted cancer treatments such as antibody and nanoparticle therapies have seen narrow clinical use because of each therapy’s limitations, but the new therapeutic – an evolution of what the researchers call Cornell prime dots, or C’ dots – combines the best attributes of both into an ultrasmall, powerfully effective system.

As silica nanoparticles just 6 nanometers in size, C’ dots are small enough to penetrate tumors and safely pass through organs once injected into the body. Scientists first developed them more than 15 years ago and published a 2018 study that found an antibody fragment-nanoparticle hybrid to be especially effective in finding tumors.

This collaborative work with AstraZeneca set off the search for a new, molecularly engineered therapeutic version of this immuno-conjugate.

AstraZeneca “site engineered” fragments of antibodies so they would effectively attach to the C’ dots and target HER2 proteins associated with gastric cancer. The researchers optimized fragment conjugation to the C’ dot surface, along with specialized inhibitor drugs developed by AstraZeneca. This enabled the nanoparticles to carry about five times more drugs than most antibodies.

The final product was a version of C’ dots, armed with cancer-targeting antibody fragments and a large drug payload, all packed into a sub-7-nanometer, drug-immune conjugate therapy – a first of its kind in that size class, according to the researchers.

https://onlinelibrary.wiley.com/doi/10.1002/adtp.202200209

How can you generate electricity from living plants?

In simple terms, electrons are a waste product of bacteria living around plant roots – plants excrete organic matter into the soil, which is broken down by bacteria. In the breakdown process electrons are released. It is possible to harvest them using inert electrodes and turn them into electricity, without affecting the plant’s growth in any way.

Dry Cleaning Chemical Could Be Major Cause of Parkinson's, Scientists Warn

The chemical trichloroethylene (TCE), once used widely in everything from producing decaf coffee to typewriter correction fluids, has been highlighted in a new study as potentially being a significant cause of many cases of Parkinson's disease.

Having already been associated with increased risks of cancer and miscarriages, TCE isn't used as widely as it once was, but the researchers behind the new report suggest that its role in Parkinson's disease has been largely overlooked.

They pull together evidence of the extent to which TCE has been used in industrial processes, review previous studies linking the chemical with Parkinson's, and investigate several cases where TCE and the disease could well be linked.

TCE is a simple, six-atom molecule that can decaffeinate coffee, degrease metal parts, and dry clean clothes. It was being used to do everything from clean engines to anesthetize patients. The colorless chemical was first linked to Parkinsonism in 1969.

While TCE use is now much more restricted in the EU and certain US states, globally it continues to be in demand, particularly from China. Even in areas where the chemical is banned, the researchers argue, we're still being exposed to it due to the ongoing contamination of water and soil.

The time between exposure and disease onset may be decades," write the researchers. Individuals, if they were aware of their exposure to the chemical, may have long since forgotten about it.

Those who worked with the solvent or who lived near a contaminated site may have changed jobs or moved, making retrospective evaluation of potential clusters challenging.

The team behind the new study now wants to see a complete ban on TCE and the closely related perchloroethylene (PCE), as well as the decontamination of sites where TCE exposure is known to have happened in the past.

https://content.iospress.com/articles/journal-of-parkinsons-disease...

Gut Bacterium Linked to Depression in Premenopause

The opportunistic pathogen Klebsiella aerogenes degrades estradiol and induces depressive-like behavior in mice, a study finds.

Klebsiella aerogenes, a bacterium associated with poor clinical outcomes in hospitals, is more prevalent in the gut of premenopausal women with depression than in premenopausal women without it, reports a study published today (March 17) in Cell Metabolism. The authors identified a key enzyme in the bacterium’s genome that degrades the ovarian hormone estradiol. Mice fed this bacterium or a different one engineered to carry the enzyme had lower estradiol levels and evidence of depressive-like behaviors compared to control mice.

Declining estradiol levels have been linked to female depression in humans.

While studies like this one certainly provide indications that [alterations of] gut bacteria can have quite striking phenotypic effects, for humans, there is at this time more smoke than fire. Yet, these data will encourage further studies of the [role of the] microbiome in affective disorders.

https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00053-0

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Scientists use tardigrade proteins for human health breakthrough

Researchers' study of how microscopic creatures called tardigrades survive extreme conditions has led to a major breakthrough that could eventually make life-saving treatments available to people where refrigeration isn't possible. They have shown that natural and engineered versions of tardigrade proteins can be used to stabilize an important pharmaceutical used to treat people with hemophilia and other conditions without the need for refrigeration—even amid high temperatures and other difficult conditions.

The pharmaceutical known as human blood clotting Factor VIII is an essential therapeutic used to treat genetic disease and instances of extreme bleeding. Despite being critical and effective in treating patients in these circumstances, Factor VIII has a serious shortcoming, in that it is inherently unstable. Without stabilization within a precise temperature range, Factor VIII will break down.

In underdeveloped regions, during natural disasters, during space flight or on the battlefield, access to refrigerators and freezers, as well as ample electricity to run this infrastructure, can be in short supply. This often means that people who need access to Factor VIII do not get it. 

This new work provides a proof of principle that we can stabilize Factor VIII, and likely many other pharmaceuticals, in a stable, dry state at room or even elevated temperatures using proteins from tardigrades—and, thus, provide critical lifesaving medicine to everyone everywhere. 

Measuring less than half a millimeter long,  tardigrades- also known as water bears—can survive being completely dried out; being frozen to just above absolute zero (about minus 458 degrees Fahrenheit, when all molecular motion stops); heated to more than 300 degrees Fahrenheit; irradiated several thousand times beyond what a human could withstand; and even survive the vacuum of outer space. They are able to do so, in part, by manufacturing a sugar called trehalose and a protein called CAHS D.

According to the research paper published, researchers fine-tuned the biophysical properties of both trehalose and CAHS D to stabilize Factor VIII, noting that CAHS D is most suitable for the treatment. The stabilization allows Factor VIII to be available in austere conditions without refrigeration, including repeated dehydration/rehydration, extreme heat and long-term dry storage.

The researchers think the same thing can be done with other biologics—pharmaceuticals containing or derived from living organisms—such as vaccines, antibodies, stem cells, blood and blood products.

Maxwell H. Packebush et al, Natural and engineered mediators of desiccation tolerance stabilize Human Blood Clotting Factor VIII in a dry state, Scientific Reports (2023). DOI: 10.1038/s41598-023-31586-9. www.nature.com/articles/s41598-023-31586-9

Researchers discover molecular basis for alkaline taste

Whether or not animals can taste basic or alkaline food and how they do it has remained a mystery until now. A research group recently addressed this question, as they similarly did for sour taste in 2021 on the lower end of the pH scale. Their work, published recently in Nature Metabolism, identified a previously unknown chloride ion channel, which they named alkaliphile (Alka), as a taste receptor for alkaline pH.

The level of pH, which is a scale of how acidic or basic a substance is, must be just right to instigate many biological processes, such as breaking down food and creating enzymatic reactions. While researchers are familiar with sour taste, which is associated with acids and allows people to sense the acidic end of the pH scale, little is known about how animals perceive bases on the opposite end of the pH spectrum. Detecting both acids and bases, which are commonly present in food sources, is important because they can significantly impact the nutritional properties of what animals consume.

Researchers now found that Alka is expressed in the fly's gustatory receptor neurons (GRNs), the counterpart of taste receptor cells of mammals. When facing neutral food versus alkaline food, wild-type flies normally choose neutral foods because of the toxicity of high pH. In contrast, flies lacking Alka lose the ability to discriminate against alkaline food when presented with it. If the pH of a food is too high, it can be harmful and cause health concerns in humans such as muscle spasms, nausea, and numbness. Likewise, after fruit flies eat food with high pH, their lifespan can be shortened.

This work demonstrates that Alka is critical for flies to stay away from harmful alkaline environments. Detecting the alkaline pH of food is an advantageous adaptation that helps animals avoid consuming toxic substances. 

To understand how Alka senses high pH, the researchers performed electrophysiological analyses and found that Alka forms a chloride ion (Cl-) channel that is directly activated by hydroxide ions (OH-). Like olfactory sensory neurons in mammals, the concentration of Cl- inside the fly's GRN is typically higher than outside this nerve cell. The researchers propose that when exposed to high-pH stimuli, the Alka channel opens, leading to negatively charged Cl- flowing from inside to outside the fly's GRN. This efflux of Cl- activates the GRN, ultimately signaling to the fly brain that the food is alkaline and should be avoided.

In addition, the scientists studied how flies detect the taste of alkaline substances using light-based optogenetic tools. They found that when they turned off alkaline GRNs, the flies were no longer bothered by the taste of alkaline food. Conversely, they activated these alkaline GRNs by shining red light on them. Interestingly, when these flies were given sweet food and exposed to red light at the same time, the flies did not want to eat the sweet food anymore. Alkaline taste can make a big impact on what flies choose to eat.

Overall, they have established that Alka is a new taste receptor dedicated to sensing the alkaline pH of food.

Yali Zhang, Alkaline taste sensation through the alkaliphile chloride channel in Drosophila, Nature Metabolism (2023). DOI: 10.1038/s42255-023-00765-3. www.nature.com/articles/s42255-023-00765-3

Bacteria-killing viruses deploy genetic code-switching to deceive hosts

Scientists have confirmed that bacteria-killing viruses called bacteriophages deploy a sneaky tactic when targeting their hosts: They use a standard genetic code when invading bacteria, then switch to an alternate code at later stages of infection.

Their study provides crucial information on the life cycle of phages. It could be a key step toward the development of new technologies such as therapeutics targeting human pathogens or of methods to control phage-bacterial interactions in applications ranging from plant production to carbon sequestration.

Scientists have predicted since the mid-1990s that some organisms may use an alternate genetic code, but the process had never been observed experimentally in phages.

Researchers now obtained the first experimental validation of this theory using uncultivated phages in human fecal samples and the lab's high-performance mass spectrometry to reveal the intricacies of how phage proteins are expressed in the host organism. The work is detailed in Nature Communications.

The scientists confirmed that the phages convert a genome-coding signal that usually halts protein production to instead express a different amino acid entirely, one that supports replication of the phage. That code switch allows the phage to take over the bacteria's biological processes.

These phages use a standard genetic code early on as they infect bacteria, one that's compatible with the bacterial host. Once the phages are integrated into the host, they hijack the machinery and begin pumping out phage proteins. By the late stage of infection, the host bacterium is unable to stop producing phages and dies.

Recognizing this change to an alternate genetic code helps ensure that scientists' assumptions about phage protein structure and function are correct.

Samantha L. Peters et al, Experimental validation that human microbiome phages use alternative genetic coding, Nature Communications (2022). DOI: 10.1038/s41467-022-32979-6

How our native language shapes our brain wiring

Scientists have found evidence that the language we speak shapes the connectivity in our brains that may underlie the way we think. With the help of magnetic resonance tomography, they looked deep into the brains of native German and Arabic speakers and discovered differences in the wiring of the language regions in the brain.

Researchers  compared the brain scans of 94 native speakers of two very different languages and showed that the language we grow up with modulates the wiring in the brain. Two groups of native speakers of German and Arabic respectively were scanned in a magnetic resonance imaging (MRI) machine.

The high-resolution images not only show the anatomy of the brain, but also allow to derive the connectivity between the brain areas using a technique called diffusion-weighted imaging. The data showed that the axonal white matter connections of the language network adapt to the processing demands and difficulties of the mother tongue.
Arabic native speakers showed a stronger connectivity between the left and right hemispheres than German native speakers. This strengthening was also found between semantic language regions and may be related to the relatively complex semantic and phonological processing in Arabic.

Native German speakers showed stronger connectivity in the left hemisphere language network. They argue that their findings may be related to the complex syntactic processing of German, which is due to the free word order and greater dependency distance of sentence elements.

Brain connectivity is modulated by learning and the environment during childhood, which influences processing and cognitive reasoning in the adult brain. This study provides new insights how the brain adapts to cognitive demands, that is, the structural language connectome is shaped by the mother tongue.

Mechanical engineers explore kitchen uses for 3D printing

Cooking devices that incorporate three-dimensional (3D) printers, lasers, or other software-driven processes may soon replace conventional cooking appliances such as ovens, stovetops, and microwaves. But will people want to use a 3D printer—even one as beautifully designed as a high-end coffee maker—on their kitchen counters to calibrate the exact micro- and macro-nutrients they need to stay healthy? Will 3D food printing improve the ways we nourish ourselves? What sorts of hurdles will need to be overcome to commercialize such a technology?

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COVID origin linked to raccoon dogs

There’s more evidence supporting the hypothesis that SARS-CoV-2 first spilled over from animals to humans at a market in Wuhan, China. An analysis looked at publicly posted genetic data from COVID-positive swabs taken from drains, stalls and the ground at the market in early 2020. Six samples contained DNA from racoon dogs (Nyctereutes procyonoides), which can catch SARS-CoV-2 and spread it to others of their species, even if they don’t have symptoms. “The most logical hypothesis is that raccoon dogs were infected by SARS-CoV-2 and shed the virus,” says virologist Leo Poon. It’s not the final word on the pandemic’s origin, because the study doesn’t confirm whether the animals were actually infected or whether viral RNA in the swabs came from other sources.

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How to defuse the climate time bomb

Global temperatures will reach 1.5 °C above pre-industrial levels in the early 2030s, according to estimates in a new report by the Intergovernmental Panel on Climate Change (IPCC) that United Nations secretary-general António Guterres called a “how-to guide to defuse the climate time bomb”. To stop warming from crossing a dangerous threshold, industrialized nations will need to cut greenhouse-gas emissions in half by 2030 and achieve net zero b.... Cost-effective ways of doing this, such as solar and wind energy, already exist. The report also suggests that large-scale carbon dioxide removal will be needed, which has raised doubt among some scientists because the technology still barely exists.

 Most life on Earth is based on polymers of 20 amino acids that have evolved into hundreds of thousands of different, highly specialized proteins. They catalyze reactions, form backbone and muscle and even generate movement.

But is all that variety necessary? Could biology work just as well with fewer building blocks and simpler polymers?

Some polymer scientists, think so. Thye have developed a way to mimic specific functions of natural proteins using only two, four or six different building blocks—ones currently used in plastics—and found that these alternative polymers work as well as the real protein and are a lot easier to synthesize than trying to replicate nature's design.

As a proof of concept, they used their design method, which is based on machine learning or artificial intelligence, to synthesize polymers that mimic blood plasma. The artificial biological fluid kept natural protein biomarkers intact without refrigeration and even made the natural proteins more resistant to high temperatures—an improvement over real blood plasma.

The protein substitutes, or random heteropolymers (RHP), could be a game-changer for biomedical applications, since a lot of effort today is put into tweaking natural proteins to do things they were not originally designed to do, or trying to recreate the 3D structure of natural proteins. Drug delivery of small molecules that mimic natural human proteins is one hot research field.

Instead, AI could pick the right number, type and arrangement of plastic building blocks—similar to those used in dental fillings, for example—to mimic the desired function of a protein, and simple polymer chemistry could be used to make it.

In the case of blood plasma, for example, the artificial polymers were designed to dissolve and stabilize natural protein biomarkers in the blood. Xu and her team also created a mix of synthetic polymers to replace the guts of a cell, the so-called cytosol. In a test tube filled with artificial biological fluid, the cell's nanomachines, the ribosomes, continued to pump out natural proteins as if they didn't care whether the fluid was natural or artificial.

Basically, all the data shows that we can use this design framework, this philosophy, to generate polymers to a point that the biological system would not be able to recognize if it is a polymer or if it is a protein.

This in a way  fooling the biology. The whole idea is that if you really design it and inject your plastics as a part of an ecosystem, they should behave like a protein. If the other proteins are like, 'Okay, you are part of us,' then that's OK.

The design framework also opens the door to designing hybrid biological systems, where plastic polymers interact smoothly with natural proteins to improve a system, such as photosynthesis. And the polymers could be made to naturally degrade, making the system recyclable and sustainable.

Zhiyuan Ruan, Shuni Li, Alexandra Grigoropoulos, Hossein Amiri, Shayna L. Hilburg, Haotian Chen, Ivan Jayapurna, Tao Jiang, Zhaoyi Gu, Alfredo Alexander-Katz, Carlos Bustamante, Haiyan Huang, Ting Xu. Population-based heteropolymer design to mimic protein mixtures. Nature, 2023; 615 (7951): 251 DOI: 10.1038/s41586-022-05675-0

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Nanoplastics Interfere With Developing Chicken Embryos in Terrifying Ways

A new study of chicken embryos suggests that sufficient concentrations of teensy nanoplastics speckles could interfere with the earliest stages of development, glugging up stem cells from which tissues and organs usually emerge.

These tissue defects, the study authors say, are "far more serious and extensive than has been previously reported" and include heart defects, which have not been described before in animal studies of microplastics.

Under the focused gaze of fluorescent microscopes, biologists  watched injected samples of nanometer-scale glowing plastic particles cross the embryonic gut wall and circulate into multiple organs of the chick embryos.

They used a high concentration of polystyrene particles, that would normally not be present in an organism. But it shows what nanoplastics can do in extreme cases on very young [chicken] embryos.

Nanoplastics are a fraction smaller than microplastics; both are typically produced when synthetic clothes shed plastic microfibers or larger plastics break down into ever smaller pieces under the glare of UV rays or mechanical weathering.

Past animal studies have tried to investigate the potential health risks of polystyrene microplastics, finding biochemical signs of potentially toxic effects as they accumulate in the livers, kidneys, and guts of laboratory mice. While results like those only hint at what might be happening in humans, we have good reason to be concerned. Our dependency on cheaply made plastic goods and synthetic materials is polluting our oceans and air with microscopic shards of plastic polymers making their way into our bodies and out the other side. Studies have found microplastics lodged deep in human lungs, circulating in our blood, and entering the placenta – the vital organ that shields unborn babies from pathogens and other potentially hazardous materials lurking in the mother's blood. But the possible effects of microplastics on the early development of cells and tissues that go on to form organs and bodies are largely unknown. Most studies of that kind have been in aquatic organisms, such as zebrafish.

In these latest lab experiments, the polystyrene nanoplastics (25 nanometers in size) seemed to get stuck on stem cells called neural crest cells, stopping them from migrating into place where they would normally form important tissues and organs.

In all vertebrates, neural crest cells give rise to parts of the heart, arteries, facial structures, and nervous system.

Part 1

A quarter of the chick embryos had one or two abnormally small eyes, while others showed facial deformities, thinning heart muscles, and slow heart rates.

Neural tube defects were also noted, which occur when the neural folds that form the early brain and spinal cord fail to meet and close properly. This all links back to those neural crest cells, the researchers suspect.

https://www.sciencedirect.com/science/article/pii/S0160412023001381...

Part 2

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Photosynthesis 'hack' could lead to new ways of generating renewable energy

Researchers have 'hacked' the earliest stages of photosynthesis, the natural machine that powers the vast majority of life on Earth, and discovered new ways to extract energy from the process, a finding that could lead to new ways of generating clean fuel and renewable energy.

An international team of physicists, chemists and biologists was able to study photosynthesis—the process by which plants, algae and some bacteria convert sunlight into energy—in live cells at an ultrafast timescale: a millionth of a millionth of a second.

Despite the fact that it is one of the most well-known and well-studied processes on Earth, the researchers found that photosynthesis still has secrets to tell. Using ultrafast spectroscopic techniques to study the movement of energy, the researchers found the chemicals that can extract electrons from the molecular structures responsible for photosynthesis do so at the initial stages, rather than much later, as was previously thought.

This 'rewiring' of photosynthesis could improve ways in which it deals with excess energy, and create new and more efficient ways of using its power. The results are reported in the journal Nature.

While photosynthesis is a natural process, scientists have also been studying how it could be used as to help address the climate crisis, by mimicking photosynthetic processes to generate clean fuels from sunlight and water, for example.

Researchers were originally trying to understand why a ring-shaped molecule called a quinone is able to 'steal' electrons from photosynthesis. Quinones are common in nature, and they can accept and give away electrons easily. The researchers used a technique called ultrafast transient absorption spectroscopy to study how the quinones behave in photosynthetic cyanobacteria.

No one had properly studied how this molecule interplays with photosynthetic machineries at such an early point of photosynthesis: so now some scientists thought they were just using a new technique to confirm what they already knew. Instead, they found a whole new pathway, and opened the black box of photosynthesis a bit further.

Using ultrafast spectroscopy to watch the electrons, the researchers found that the protein scaffold where the initial chemical reactions of photosynthesis take place is 'leaky', allowing electrons to escape. This leakiness could help plants protect themselves from damage from bright or rapidly changing light.

Part 1

The physics of photosynthesis is seriously impressive. Observing charge transport through cells opens up remarkable opportunities for new discoveries on how nature operates.

Since the electrons from photosynthesis are dispersed through the whole system, that means we can access them. The fact that we didn't know this pathway existed is exciting, because we could be able to harness it to extract more energy for renewables.

The researchers say that being able to extract charges at an earlier point in the process of photosynthesis, could make the process more efficient when manipulating photosynthetic pathways to generate clean fuels from the Sun. In addition, the ability to regulate photosynthesis could mean that crops could be made more able to tolerate intense sunlight.

Jenny Zhang, Photosynthesis re-wired on the pico-second timescale, Nature (2023). DOI: 10.1038/s41586-023-05763-9. www.nature.com/articles/s41586-023-05763-9

Part 2

Vision: The first molecular processes in the eye when light hits the retina

Researchers have deciphered the molecular processes that first occur in the eye when light hits the retina. The processes—which take only a fraction of a trillionth of a second—are essential for human sight.

It only involves a microscopic change of a protein in our retina, and this change occurs within an incredibly small time frame: it is the very first step in our light perception and ability to see. It is also the only light-dependent step. Researchers have established exactly what happens after the first trillionth of a second in the process of visual perception, with the help of the SwissFEL X-ray free-electron laser of the PSI.

At the heart of the action is our light receptor, the protein rhodopsin. In the human eye it is produced by sensory cells, the rod cells, which specialize in the perception of light. Fixed in the middle of the rhodopsin is a small kinked molecule: retinal, a derivative of vitamin A. When light hits the protein, retinal absorbs part of the energy. With lightning speed, it then changes its three-dimensional form so the switch in the eye is changed from "off" to "on." This triggers a cascade of reactions whose overall effect is the perception of a flash of light.

But what happens in detail when retinal transforms from what is known as the 11-cis form into the all-trans form? This is what the scientists observed now:

The protein absorbs part of the light energy to briefly inflate a tiny amount—"like our chest expanding when we breathe in, only to contract again shortly afterwards."

During this "breathing in" stage, the protein temporarily loses most of its contact with the retinal that sits in its middle. "Although the retinal is still connected to the protein at its ends through chemical bonds, it now has room to rotate." At that moment, the molecule resembles a dog on a loose leash that is free to give a jerk.

Shortly afterwards the protein contracts again and has the retinal firmly back in its grasp, except now in a different more elongated form. "In this way the retinal manages to turn itself, unimpaired by the protein in which it is held."

The transformation of the retinal from 11-cis kinked form into the all-trans elongated form only takes a picosecond, or one trillionth (10-12) of a second, making it one of the fastest processes in all of nature.

The only way of recording and analyzing such rapid biological processes is with an X-ray free-electron laser like the SwissFEL. The SwissFEL allows us to study in detail the fundamental processes of the human body, such as vision.

Valerie Panneels, Ultrafast structural changes direct the first molecular events of vision, Nature (2023). DOI: 10.1038/s41586-023-05863-6. www.nature.com/articles/s41586-023-05863-6

'Vampiric' water use leading to 'imminent' global crisis, UN warns

Humanity's "lifeblood"—water—is increasingly at risk around the world due to "vampiric overconsumption and overdevelopment," the UN warned in a report, published hours ahead of a major summit on the issue was set to begin 0n 22nd March, '23.

The world is "blindly traveling a dangerous path" as "unsustainable water use, pollution and unchecked global warming are draining humanity's lifeblood": United Nations.

If nothing is done, it will be a business-as-usual scenario—it will keep on being between 40 percent and 50 percent of the population of the world that does not have access to sanitation and roughly 20-25 percent of the world will not have access to safe water supply. With the global population increasing every day, in absolute numbers, there'll be more and more people that don't have access to these services.

At the UN conference, governments and actors in the public and private sectors are invited to present proposals for a so-called water action agenda to reverse that trend and help meet the development goal, set in 2015, of ensuring "access to water and sanitation for all by 2030."

Source: AFP

Bats’ weird immunity could stop pandemics

The COVID-19 pandemic has propelled a niche research field to prominence: bat immunology. Bats are a possible source of catastrophic viral outbreaks in people because the animals can tolerate an exceptionally diverse array of viruses, including coronaviruses, rabies and Ebola. The biological mechanisms behind bats’ weird immune systems are slowly emerging: “There’s kind of a peace treaty,” between bats and the pathogens they host, explains virologist Joshua Hayward. Bats’ genomes seem to suck up viral information like a sponge. It is possible that this protects bats from the negative outcomes of viral infections, just as a vaccine would.

'Ghost Particles': Scientists Finally Detect Neutrinos in Particle Collider

The ghost, at long last, is actually in the machine: For the first time, scientists have created neutrinos in a particle collider.

Those abundant yet enigmatic subatomic particles are so removed from the rest of matter that they slide through it like specters, earning them the nickname "ghost particles".

The researchers say this work represents the first direct observation of collider neutrinos and will help us to understand how these particles form, what their properties are, and their role in the evolution of the Universe.

The results, achieved using the FASERnu detector at the Large Hadron Collider, were presented at the 57th Rencontres de Moriond Electroweak Interactions and Unified Theories conference in Italy.

Neutrinos are among the most abundant subatomic particles in the Universe, second only to photons. But they have no electric charge, their mass is almost zero, and they barely interact with other particles they encounter. Hundreds of billions of neutrinos are streaming through your body right now.

Neutrinos are produced in energetic circumstances, such as the nuclear fusion that takes place inside stars, or supernova explosions. And while we may not notice them on a day-to-day basis, physicists think that their mass – however slight – probably affects the Universe's gravity (although neutrinos have pretty much been ruled out as dark matter).

Although their interaction with matter is small, it's not completely nonexistent; now and again, a cosmic neutrino collides with another particle, producing a very faint burst of light.

Underground detectors, isolated from other sources of radiation, can detect these bursts. IceCube in Antarctica, Super-Kamiokande in Japan, and MiniBooNE at Fermilab in Illinois are three such detectors.

Neutrinos produced in particle colliders, however, have long been sought by physicists because the high energies involved are not as well studied as low-energy neutrinos.

Part 1

They can tell us about deep space in ways we can't learn otherwise.

These very high-energy neutrinos in the LHC are important for understanding really exciting observations in particle astrophysics.

FASERnu is an emulsion detector consisting of millimeter-thick tungsten plates alternated with layers of emulsion film. Tungsten was chosen because of its high density, which increases the likelihood of neutrino interaction; the detector consists of 730 emulsion films and a total tungsten mass of around 1 ton.

During particle experiments at the LHC, neutrinos can collide with nuclei in the tungsten plates, producing particles that leave tracks in the emulsion layers, a bit like the way ionizing radiation makes tracks in a cloud chamber.

These plates need to be developed, like photographic film, before the physicists can analyze the particle trails to find out what produced them.

Six neutrino candidates were identified and published back in 2021. Now, the researchers have confirmed their discovery, using data from the third run of the upgraded LHC that began last year, with a significance level of 16 sigma.

That means that the likelihood that the signals were produced by random chance is so low as to be almost nothing; a significance level of 5 sigma is sufficient to qualify as a discovery in particle physics.

The team's results have been presented at the 57th Rencontres de Moriond Electroweak Interaction....

Part 2

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Deceptive daisy's ability to create fake flies explained

A male fly approaches a flower, lands on top of what he thinks is a female fly, and jiggles around. He's trying to mate, but it isn't quite working. He has another go. Eventually he gives up and buzzes off, unsuccessful. The plant, meanwhile, has got what it wanted: pollen.

A South African daisy, Gorteria diffusa, is the only daisy known to make such a complicated structure resembling a female fly on its petals. The mechanism behind this convincing three-dimensional deception, complete with hairy bumps and white highlights, has intrigued people for decades.

Now researchers have identified three sets of genes involved in building the fake fly on the daisy's petals. The big surprise is that all three sets already have other functions in the plant: one moves iron around, one makes root hairs grow, and one controls when flowers are made.

The study found that the three sets of genes have been brought together in the daisy petals in a new way to build fake lady flies. The "iron moving" genes add iron to the petal's normally reddish-purple pigments, changing the color to a more fly-like blue-green. The root hair genes make hairs expand on the petal to give texture. And the third set of genes make the fake flies appear in apparently random positions on the petals.

"This daisy didn't evolve a new 'make a fly' gene. Instead it did something even cleverer—it brought together existing genes, which already do other things in different parts of the plant, to make a complicated spot on the petals that deceives male flies.

The researchers say the daisy's petals give it an evolutionary advantage, by attracting more male flies to pollinate it. The plants grow in a harsh desert environment in South Africa, with only a short rainy season in which to produce flowers, get pollinated, and set seed before they die. This creates intense competition to attract pollinators—and the petals with fake lady flies make the South African daisy stand out from the crowd.

 Beverley J. Glover, Multiple gene co-options underlie the rapid evolution of sexually deceptive flowers in Gorteria diffusa, Current Biology (2023). DOI: 10.1016/j.cub.2023.03.003. www.cell.com/current-biology/f … 0960-9822(23)00270-1

SARS-CoV-2 can alter genome structure of our cells

People infected with SARS-CoV-2, the virus that causes COVID-19, may experience genome structure changes that not only may explain our immunological symptoms after infection, but also potentially link to long COVID, according to a new study by researchers.

This particular finding is quite unique and has not been seen in other coronaviruses before. It is a  unique mechanism of SARS-CoV-2 that is associated with its severe impacts on human health.

The genetic materials in our cells are stored in a structure called chromatin. Some viruses of other categories have been reported to hijack or change our chromatin so that they can successfully reproduce in our cells. Whether and how SARS-CoV-2 may affect our chromatin was not known. In this study, researchers used leading-edge methods and comprehensively characterized the chromatin architecture in human cells after a COVID-19 infection.

Researchers found that many well-formed chromatin architectures of a normal cell become de-organized after infection. For example, there is one type of chromatin architecture termed A/B compartments that can be analogous to the yin and yang portions of our chromatin. After SARS-CoV-2 infection, they found that the yin and yang portions of the chromatin lose their normal shapes and start to mix together. Such mixing may be a reason for some key genes to change in infected cells, including a crucial inflammation gene, interleukin-6,  that can cause cytokine storm in severe COVID-19 patients.

In addition, this work found that chemical modifications on chromatin were also altered by SARS-CoV-2. The changes of chemical modifications of chromatin were known to exert long-term effects on gene expression and phenotypes. Therefore, this finding may provide an unrealized new perspective to understand the viral impacts on host chromatin that can associate with long COVID.

Finding the mechanisms will offer therapeutic strategies to safeguard our chromatin and to better fight this virus.

 Ruoyu Wang et al, SARS-CoV-2 restructures host chromatin architecture, Nature Microbiology (2023). DOI: 10.1038/s41564-023-01344-8

New study finds co-infection with 'superbug' bacteria increases SARS-CoV-2 replication

Global data shows nearly 10 percent of severe COVID-19 cases involve a secondary bacterial co-infection—with Staphylococcus aureus, also known as staph A, being the most common organism responsible for co-existing infections with SARS-CoV-2. Researchers  have found that the addition of a "superbug"—methicillin-resistant Staphylococcus aureus (MRSA)—into the mix could make the COVID-19 outcome even more deadly.

The mystery of how and why the combination of these two pathogens contributes to the severity of the disease remains unsolved. However,  researchers have made significant progress toward solving this "whodunit."

New research  has revealed that IsdA, a protein found in all strains of staph A, enhanced SARS-CoV-2 replication by 10- to 15-fold. The findings of this study are significant and could help inform the development of new therapeutic approaches for COVID-19 patients with bacterial co-infections.

Interestingly, the study, which was recently published in iScience, also showed that SARS-CoV-2 did not affect the bacteria's growth. This was contrary to what the researchers had initially expected.

https://www.cell.com/iscience/fulltext/S2589-0042(23)00052-4?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2589004223000524%3Fshowall%3Dtrue

Revealing Atomic Structures with a "Neutron" Camera

Researchers have developed a new kind of "camera" that sees the local disorder in materials. Its key feature is a variable shutter speed: because the disordered atomic clusters are moving, when the team used a slow shutter, the dynamic disorder blurred out, but when they used a fast shutter, they could see it. The new method doesn't work like a conventional camera--it uses neutrons to measure atomic positions with a shutter speed of around one picosecond, a trillion times faster than normal camera shutters.

Novel drug makes mice skinny even on sugary, fatty diet

Researchers have developed a small-molecule drug that prevents weight gain and adverse liver changes in mice fed a high-sugar, high-fat Western diet throughout life.

When  this drug is given to the mice for a short time, they start losing weight. They all become slim.

The research team discovered the drug by first exploring how magnesium impacts metabolism, which is the production and consumption of energy in cells. This energy, called ATP, fuels the body's processes.

Magnesium plays many key roles in good health, including regulating blood sugar and blood pressure and building bones. But the researchers found that too much magnesium slows energy production in mitochondria, which are cells' power plants. It puts the brake on, it just slows down.

Deleting MRS2, a gene that promotes magnesium transport into the mitochondria, resulted in more efficient metabolism of sugar and fat in the power plants. The result: skinny, healthy mice.

Liver and adipose (fat) tissues in the rodents showed no evidence of fatty liver disease, a complication related to poor diet, obesity and type 2 diabetes.

The drug, which the researchers call CPACC, accomplishes the same thing. It restricts the amount of magnesium transfer into the power plants. In experiments, the result was again: skinny, healthy mice. 

Lowering the mitochondrial magnesium mitigated the adverse effects of prolonged dietary stress.

A drug that can reduce the risk of cardiometabolic diseases such as heart attack and stroke, and also reduce the incidence of liver cancer, which can follow fatty liver disease, will make a huge impact. 

Travis R. Madaris, Manigandan Venkatesan, Soumya Maity, Miriam C. Stein, Neelanjan Vishnu, Mridula K. Venkateswaran, James G. Davis, Karthik Ramachandran, Sukanthathulse Uthayabalan, Cristel Allen, Ayodeji Osidele, Kristen Stanley, Nicholas P. Bigham, Terry M. Bakewell, Melanie Narkunan, Amy Le, Varsha Karanam, Kang Li, Aum Mhapankar, Luke Norton, Jean Ross, M. Imran Aslam, W. Brian Reeves, Brij B. Singh, Jeffrey Caplan, Justin J. Wilson, Peter B. Stathopulos, Joseph A. Baur, Muniswamy Madesh. Limiting Mrs2-dependent mitochondrial Mg2+ uptake induces metabolic programming in prolonged dietary stress. Cell Reports, 2023; 42 (3): 112155 DOI: 10.1016/j.celrep.2023.112155

'Forever Chemicals' May Reduce Fertility in Women by Up to 40%, Study Finds

Robust chemicals once used in everything from cosmetics to waterproofing to food containers to firefighting foam could have a significant impact on the fertility of women worldwide.

A new study led by researchers from the Icahn School of Medicine at Mount Sinai in the US uncovered evidence in a sample of women in Singapore linking plasma concentrations of perfluoroalkyl substances (PFAS) with an increase in the difficulty of becoming pregnant.

Though the nature of this connection isn't clear, the results add to growing concerns that concentrations of so-called 'forever chemicals' across Earth's surface are silently putting our health at risk and could do for some time to come.

Per- and poly-fluoroalkyl substances such as PFAS are synthetic compounds that have found a wide range of applications in different consumer products since the mid-20th century. Useful as a barrier against water or oily substances, they're commonly encountered as non-stick and stain-resistant coatings.

One of their perks is the strength of the carbon-fluoride bond, which resists degradation. Unfortunately, this also happens to be one of their liabilities, allowing them to persist for years in the environment in ever-increasing concentrations.

Given that these materials are so widespread and encompass a vast catalog of thousands of variants, the chances of potential toxins hiding out in their midst have become too great to ignore.

"PFAS can disrupt our reproductive hormones and have been linked with delayed puberty onset and increased risks for endometriosis and polycystic ovary syndrome in few previous studies," says the new study's senior author.

What this study adds is that PFAS may also decrease fertility in women who are generally healthy and are naturally trying to conceive.

Just why this is the case is still a matter of speculation, though it's a good bet PFAS might interrupt the typical functioning of reproductive hormones in some way.

This study strongly implies that women who are planning pregnancy should be aware of the harmful effects of PFAS and take precautions to avoid exposure to this class of chemicals, especially when they are trying to conceive.

https://www.sciencedirect.com/science/article/abs/pii/S004896972300...

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