Patients with rheumatoid arthritis have unique and complex autoantibody patterns, study reveals

Patients with rheumatoid arthritis (RA) all have a unique and diverse set of antibodies that are involved in the development of the disease. Researchers unveiled the complexity of these antibodies using powerful lab tools capable of analyzing our immune system at molecular levels. Their discovery suggests that current assumptions about the origin of RA are too simple. Their findings may point towards improved diagnostics.

Rheumatoid arthritis is a chronic autoimmune disease that primarily affects the joints, causing pain, stiffness, and swelling. It arises when the immune system mistakenly attacks the body's own tissues, leading to inflammation in the joints and potentially other organs.

The exact cause of RA remains unknown, but a crucial role is played by antibodies, special proteins made by the immune system to help fight off infections. They recognize and attack specific targets, like viruses or bacteria. Some antibodies are wrongly produced, causing them to attack our own body. Normally, our body's immune system is equipped with a 'filter' that cleans up these so-called autoantibodies. Researchers think that this mechanism is malfunctioning in RA patients.

The extend to which this filter is malfunctioning, now appears to be much greater than expected. Research  published in Nature Communications reveals that it's not just a handful of different RA-associated autoantibodies that evade the filter. On the contrary, the researchers found an extremely broad variety of these antibodies.

The team used novel mass spectrometry tools that profile specific antibodies typically seen in the blood of RA patients, which are called anti-citrullinated protein antibodies (ACPAs). They discovered that each RA patient possesses a unique and diverse set of ACPAs.

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Their findings challenge previous assumptions about the backgrounds of RA, that overlooked the antibodies' diversity and complexity. This shows that RA is not just a disease occurring due to small errors, but a big structural problem in the immune system. 

The study also revealed that these ACPAs are extensively modified with sugar molecules, known as Fab glycans. Intriguingly, some antibodies had multiple sugar molecules attached. This is much more then researchers normally observe in antibody profiles.

Having extra glycans aboard, may help the ACPA antibodies pass the filter of the immune system. The immune system uses several very strict checks during antibody production, to make sure all antibodies are correct. Wrongly produced antibodies are then detected and removed. Scientists suspect that glycans could help ACPAs trick the control system, allowing ACPAs to pass through the filter and form the onset of RA.
Current efforts to develop treatments for RA are mainly geared towards eliminating autoantibodies directly. This strategy may not be effective, say the researchers. When you realize that there is such an extreme diversity in RA-related autoantibodies, it seems virtually impossible to eliminate them. A better approach may be to intervene earlier in the disease process, by targeting the malfunctioning filtering mechanism that allows autoantibodies to pass through.

Understanding these unique proteins is important, as it could ultimately also help doctors diagnose RA better. Even though RA remains an incurable disease, with an earlier diagnosis you can take better measures to control its progression.

Eva Maria Stork et al, Antigen-specific Fab profiling achieves molecular-resolution analysis of human autoantibody repertoires in rheumatoid arthritis, Nature Communications (2024). DOI: 10.1038/s41467-024-47337-x

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Brain imaging study reveals connections critical to human consciousness

In a paper titled, "Multimodal MRI reveals brainstem connections that sustain wakefulness in human consciousness," published in Science Translational Medicine, a group of researchers at Massachusetts General Hospital and Boston Children's Hospital, created a connectivity map of a brain network that they propose is critical to human consciousness.

The study involved high-resolution scans that enabled the researchers to visualize brain connections at submillimeter spatial resolution. This technical advance allowed them to identify previously unseen pathways connecting the brainstem, thalamus, hypothalamus, basal forebrain, and cerebral cortex.
Together, these pathways form a "default ascending arousal network" that sustains wakefulness in the resting, conscious human brain. The concept of a "default" network is based on the idea that specific networks within the brain are most functionally active when the brain is in a resting state of consciousness. In contrast, other networks are more active when the brain is performing goal-directed tasks.

To investigate the functional properties of this default brain network, the researchers analyzed 7 Tesla resting-state functional MRI data from the Human Connectome Project. These analyses revealed functional connections between the subcortical default ascending arousal network and the cortical default mode network that contributes to self-awareness in the resting, conscious brain.

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The complementary structural and functional connectivity maps provide a neuroanatomic basis for integrating arousal and awareness in human consciousness. The researchers released the MRI data, brain mapping methods, and a new Harvard Ascending Arousal Network Atlas, to support future efforts to map the connectivity of human consciousness.

This connectivity results suggest that stimulation of the ventral tegmental area's dopaminergic pathways has the potential to help patients recover from coma because this hub node is connected to many regions of the brain that are critical to consciousness.
The human brain connections that they identified can be used as a roadmap to better understand a broad range of neurological disorders associated with altered consciousness, from coma, to seizures, to sudden infant death syndrome (SIDS).

The researchers are currently conducting clinical trials to stimulate the default ascending arousal network in patients with coma after traumatic brain injury, with the goal of reactivating the network and restoring consciousness.

 Brian Edlow et al, Multimodal MRI reveals brainstem connections that sustain wakefulness in human consciousness, Science Translational Medicine (2024). DOI: 10.1126/scitranslmed.adj4303. www.science.org/doi/10.1126/scitranslmed.adj4303

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Scientists identify new brain circuit in mice that controls body's inflammatory reactions

The brain can direct the immune system to an unexpected degree, capable of detecting, ramping up and tamping down inflammation, shows a new study in mice by  researchers.

The brain is the center of our thoughts, emotions, memories and feelings. Thanks to great advances in circuit tracking and single-cell technology, we now know the brain does far more than that. It is monitoring the function of every system in the body.

Future research could identify drugs that can target this newfound brain circuit to help treat a vast range of disorders and diseases in which the immune system goes haywire. This new discovery could provide an exciting therapeutic venue to control inflammation and immunity.

Recent work by scientists is revealing the importance of the body-brain axis, a vital pathway that conveys data between the organs and the brain. For example, they discovered that sugar and fat entering the gut use the body-brain axis to drive the craving and strong appetite for sugary and fatty foods.

They  found all these ways in which the body is informing the brain about the body's current state. 

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The scientists looked for connections the brain might have with inflammation and innate immunity, the defense system shared by all animals and the most ancient component of the immune system. Whereas the adaptive immune system remembers previous encounters with intruders to help it resist them if they invade again, the innate immune system attacks anything with common traits of germs. The relative simplicity of innate immunity lets it respond to new insults more quickly than adaptive immunity.

Prior studies in humans revealed that electrically stimulating the vagus nerve—a bundle of thousands of nerve fibers linking the brain and the body's internal organs—could reduce the response linked to a specific inflammatory molecule.
However, much remained unknown about the nature of this body-brain system: for instance, the generality of the brain's modulation of immunity and the inflammatory response, the selective lines of communication between the body and the brain, the logic of the underlying neural circuit, and the identity of the vagal and brain components that monitor and regulate inflammation.
Researchers turned to a bacterial compound that sets off innate immune responses. The scientists found that giving this molecule to mice activated the caudal nucleus of the solitary tract, or cNST, which is tucked inside the brainstem. The cNST plays a major role in the body-brain axis and is the primary target of the vagus nerve.
The scientists showed that chemically suppressing the cNST resulted in an out-of-control inflammatory response to the immune insult: levels of pro-inflammatory molecules released by the immune system were more than three times higher than usual, and levels of anti-inflammatory immune compounds were roughly three times lower than normal.

In contrast, artificially activating the cNST reduced pro-inflammatory molecule levels by nearly 70% and increased anti-inflammatory chemical levels almost tenfold.

Similar to a thermostat, this newfound brain circuit helps increase or decrease inflammatory responses to keep the body responding in a healthy manner.

A body–brain circuit that regulates body inflammatory responses, Nature (2024). DOI: 10.1038/s41586-024-07469-y

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The journey of inhaled plastic particle pollution

With recent studies having established the presence of nano and microplastic particles in the respiratory systems of both human and bird populations, a new study has modeled what happens when people breathe in different kinds of plastic particles and where they end up.

Researchers used computational fluid-particle dynamics (CFPD) to study the transfer and deposition of nano and microplastic particles of different sizes and shapes depending on the rate of breathing.

The results of the modeling, published in the journal Environmental Advances, have pinpointed hotspots in the human respiratory system where plastic particles can accumulate, from the nasal cavity and larynx and into the lungs. The paper based on these results is titled, "Transport and deposition of microplastics and nanoplastics in the human respiratory tract."

Evidence 's mounting on the significant impact of nano and microplastics on respiratory health and the UTS study would provide essential insights for the development of targeted strategies to mitigate potential risks and ensure effective health interventions.
Experimental evidence has strongly suggested that these plastic particles amplify human susceptibility to a spectrum of lung disorders, including chronic obstructive pulmonary disease, fibrosis, dyspnea (shortness of breath), asthma, and the formation of what are called frosted glass nodules.
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Plastic particle air pollution is now pervasive and inhalation ranks as the second most likely pathway for human exposure.
The primary types are intentionally manufactured, including a wide array of cosmetics and personal care products such as toothpaste.

The secondary ones are fragments derived from the degradation of larger plastic products, such as water bottles, food containers and clothes.
Extensive investigations have identified synthetic textiles as a principal source of indoor airborne plastic particles, while the outdoor environment presents a multitude of sources encompassing contaminated aerosols from the ocean to particles originating from wastewater treatment.
Researchers' modelling found that breathing rate along with particle size and shape determined where in the respiratory system plastic particles would be deposited.

Faster breathing rates led to heightened deposition in the upper respiratory tract, particularly for larger microplastics, whereas slower breathing facilitated deeper penetration and deposition of smaller nanoplastic particles.
Particle shape was another factor, with non-spherical microplastic particles showing a propensity for deeper lung penetration compared to spherical microplastics and nanoplastics, potentially leading to different health outcomes.

These findings highlight the imperative consideration of breathing rates and particle sizes in health risk assessments associated with respiratory exposure to nano and microplastic particles.

Xinlei Huang et al, Transport and deposition of microplastics and nanoplastics in the human respiratory tract, Environmental Advances (2024). DOI: 10.1016/j.envadv.2024.100525

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Tire toxicity faces fresh scrutiny after fish fatalities

For decades, concerns about automobile pollution have focused on what comes out of the tailpipe. Now, researchers and regulators say, we need to pay more attention to toxic emissions from tires as vehicles roll down the road.

At the top of the list of worries is a chemical called 6PPD, which is added to rubber tires to help them last longer. When tires wear on pavement, 6PPD is released. It reacts with ozone to become a different chemical, 6PPD-q, which can be extremely toxic—so much so that it has been linked to repeated fish kills in the US.

The trouble with tires doesn't stop there. Tires are made primarily of natural rubber and synthetic rubber, but they contain hundreds of other ingredients, often including steel and heavy metals such as copper, lead, cadmium, and zinc.

As car tires wear, the rubber disappears in particles, both bits that can be seen with the naked eye and microparticles. Testing by a British company, Emissions Analytics, found that a car's tires emit 1 trillion ultrafine particles per kilometer driven—from 5 to 9 pounds of rubber per internal combustion car per year.

And what's in those particles is a mystery, because tire ingredients are proprietary. You've got a chemical cocktail in these tires that no one really understands and is kept highly confidential by the tire manufacturers.

Regulators have only begun to address the toxic tire problem, though there has been some action on 6PPD.

Native American tribes have petitioned the Environmental Protection Agency to prohibit the chemical. The EPA said it is considering new rules governing the chemical. "We could not sit idle while 6PPD kills the fish that sustain us", they say.

But, tragically,  today there is no alternative to 6PPD.

One outstanding research question is whether 6PPD-q affects people, and what health problems, if any, it could cause. A study published in Environmental Science & Technology Letters found high levels of the chemical in urine samples from a region of South China, with levels highest in pregnant women.

The discovery of 6PPD-q, Molden said, has sparked fresh interest in the health and environmental impacts of tires.

Source: Environmental Science & Technology Letters

**More than half of cats on farm died after drinking milk from cows infected with bird flu**
In yet another sign that bird flu is spreading widely among mammals, a new report finds more than half of cats at the first Texas dairy farm to have cows test positive for bird flu this spring died after drinking raw milk.

Published this week in the Emerging Infectious Diseases journal, the report details the early stages of the investigation into the spread of bird flu among the country's dairy farms.

Cats at the Texas farm had been fed raw milk from cows that turned out to be infected with avian influenza, also known as H5N1. A day after the farm noticed cows were getting sick, the cats started getting sick. In the end, more than half of the cats perished.
"The cats were found dead with no apparent signs of injury and were from a resident population of [approximately] 24 domestic cats that had been fed milk from sick cows," the scientists wrote in their report.

Tests of the samples collected from the brains and lungs of dead cats yielded results suggesting "high amounts of virus," and autopsies revealed "microscopic lesions consistent with severe systemic virus infection," in the eyes and brain, they said.
And some human beings too got infected with this bird flu virus.

In late March 2024, a human case of influenza A(H5N1) virus infection was identified after exposure to dairy cattle presumably infected with bird flu. Some bird flu infections of people have been identified in which the source of infection was unknown.
Source: The U.S. Centers for Disease Control and Prevention

https://www.cdc.gov/flu/avianflu/avian-in-humans.htm

Enzymes Discovered in Gut Bacteria Can Change a Donor's Blood Groups

When a life hangs in the balance, blood transfusions can help sustain a patient – but only if the donor's blood type is a match.
A new discovery by researchers from Denmark and Sweden could help in those emergency situations, while also easing global shortages in blood supplies.
The team identified a mixture of enzymes made by a species of bacteria found in our guts that can, in lab studies, transform red blood cells into the universal type O with "remarkably high efficiencies" – improving on an idea hatched 40 years ago.

Like virtually all cells in the human body, red blood cells are covered in a fuzz of unique sugary structures. These vary from person to person, with some sporting type A structures and others type B. Some have both A and B, and others have neither, which is designated O.

Immune systems that have never seen types A or B will attack and destroy these cells on sight if they receive them in a transfusion, whereas type O blood is far more widely accepted for most recipients.

Because of this versatility, type O blood stocks are often used up, especially in medical emergencies where doctors must act quickly without knowing a patient's blood type.
Converting red blood cells into the universal type O is not a new idea. The technique was pioneered back in 1982, when scientists discovered an enzyme extracted from coffee beans that could strip type B cells of their surface sugars.

But that enzyme reaction was very inefficient, making large-scale use impractical, and despite early promise in clinical trials, safety concerns were raised. For unknown reasons, donor blood was sometimes still incompatible in recipients despite donor cells being stripped of nearly all their antigens.

So scientists went back to the drawing board, discovering other enzymes in collections of gut bacteria as recently as 2019.
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What's tricky is that there are now, as of 2022, more than 40 blood group systems beyond the ABO system and rhesus factor most are familiar with.

Even within the A and B blood groups, there are subtypes, with varying lengths and densities of the signature molecules protruding from the red cells' membranes.
Scientists recently reported the discovery of remarkably efficient enzymes, not only against A and B antigens but also against their extensions.

published paper

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Based on previous work by other teams, the researchers selected a few candidate enzymes made by the gut bacterium Akkermansia muciniphila and treated red blood cells – from multiple donors and various A and B subtypes – with them.

Importantly, for potential clinical use, the enzymes were incubated with high concentrations of red blood cells, at room temperature and for only 30 minutes – improving on the longer processing and less efficient conditions of previous candidates.

"These mild conditions without additives (for example, dextran) together with excellent enzyme efficacies are important feasibility parameters in clinical applications.
Crucially, the chosen enzymes also removed all four known extensions of group A and B antigens from red blood cells, in addition to the shorter, canonical A and B antigens of other blood subtypes.

Removing the long, sugary extensions reduced the incompatibility of treated B-type cells with plasma samples to less than 9 percent, and made reactions less severe where they did happen.

More work is required to understand why a small fraction of apparently sugarless red blood cells still cross-react with group O plasmas, and to improve the conversion of group A blood cells.

However, in finding enzymes that remove a greater variety of A and B antigens, the researchers say their study uncovers "a missing link" in the production of universal blood for transfusion and potentially organs for transplantation.

In 2022, researchers used a similar strategy (with different enzymes) to convert donated lungs from group A blood type to the universal type O under lab conditions. This new work might improve those efforts enough to satisfy the safety standards required for human transplant trials.
Lab-grown red blood cells are also in human trials to test whether they last longer than donated blood. If so, that could reduce the demand on blood supplies and also help patients requiring repeat transfusions avoid complications.

https://www.nature.com/articles/s41564-024-01663-4

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Researchers develop near-chromosome-level genome for the Mojave poppy bee

Scientists have developed a near chromosome-level genome for the Mojave poppy bee, a specialist pollinator of conservation concern, according to a recent paper published in the Journal of Heredity.

Putting together the Mojave poppy bee genome is part of the Beenome100 project, a first-of-its-kind effort to create a library of high-quality, highly detailed genome maps of 100 or more diverse bee species.

The expectation is that these genomes will help researchers answer the big questions about bees, such as what genetic differences make a bee species more vulnerable to climate change or whether a bee species is likely to be more susceptible to a pesticide.

The Mojave poppy bee and Las Vegas bearpoppy are also being considered for listing under the Endangered Species Act. Both species will be evaluated for potential declining populations and vulnerability to extinction due to climate change and to habitat loss from urban development and mining in their native region.

Researchers assembled the genome or genetic map that will help further to understand the Mojave poppy bee's biological traits.

The genome, with additional genetic sampling of individuals, will also potentially give us insights into the genetic basis for host-plant specialization, susceptibility to pesticides, and susceptibility to drought and climate tolerance.

Rena M Schweizer et al, Reference genome for the Mojave poppy bee (Perdita meconis), a specialist pollinator of conservation concern, Journal of Heredity (2023). DOI: 10.1093/jhered/esad076

Male chicks play more than females!

Play is widespread, but far from ubiquitous, across the animal kingdom. Especially common in mammals, play is also known to occur in taxa as diverse as birds, fish, octopuses, and even insects. But what is its function, given that natural selection never selects fun for its own sake? One prominent hypothesis is that play is beneficial to individuals because it allows them to practice skills needed later in life.

Now, a study in Frontiers in Ethology has shown that male baby chickens play far more than females. This result is of interest given that domestic chickens are directly descended from a species—red jungle fowl—with a pronounced difference between the sexes in morphology, coloration, and behaviour.

This difference is mainly because males engage more in social and object play.

The researchers distinguished 12 distinct play behaviors. Examples of locomotor play were frolicking and wing flapping. Object play included chasing an object or pecking at it or exchanging it with another chick. Social play included sparring, jumping, and sparring stand-offs.

Object play was more frequently seen than social play, while locomotor play was least common. Both females and males showed every type of playful behavior. However, the frequency of play differed between them: male chicks played more overall than females. This was due to males engaging more often in object and social play, while there was no difference between the sexes in the frequency of locomotor play.

The researcher concluded that these sex differences in chicks in the frequency of play can be explained by the high degree of sexual dimorphism of adult junglefowl. This means that male chicks would benefit more from practicing various skills related to physical ability and social tactics.

The present study indicates that a possible function is to prepare animals for specific challenges they may encounter later in life. In a species like the chicken, where only males compete for territories, it makes sense that they engage in more social play as young.

Rebecca Oscarsson et al, Male chicks play more than females—sex differences in chicken play ontogeny, Frontiers in Ethology (2024). DOI: 10.3389/fetho.2024.1392378. www.frontiersin.org/articles/1 … ho.2024.1392378/full

Weak magnetic field may have supported diversification of life on Earth

An unusual reduction in the strength of Earth's magnetic field between 591 and 565 million years ago coincided with a significant increase in the oxygen levels in the atmosphere and oceans, according to a paper published in Communications Earth & Environment. The authors propose that the weakening of the magnetic field may have led to the increase in oxygen, which is  thought to have supported the evolution of some of the earliest complex organisms.

Between 600 and 540 million years ago, life on Earth consisted of soft-bodied organisms known as the Ediacaran fauna, the earliest known complex multicellular animals. The fossil record shows that these organisms significantly diversified in complexity and type between 575 and 565 million years ago. Previous research has suggested that this diversification is linked to a significant increase in atmospheric and oceanic oxygen levels that occurred over the same period. However, it is not yet clear why this increase in oxygen occurred.

Researchers analyzed the magnetic properties of 21 plagioclase crystals, a common mineral in Earth's crust, which were extracted from a 591-million-year-old rock formation in Brazil. Plagioclase crystals contain tiny magnetic minerals that preserve the intensity of the Earth's magnetic field at the time they are formed.
Analysis of the crystals showed that at their point of formation, Earth's magnetic field was the weakest ever recorded—some 30 times weaker than both the current magnetic field intensity, and that measured from similar crystals formed approximately 2,000 million years ago.
The authors combined their results with previous measurements to establish that the Earth's magnetic field was at this weak level for at least 26 million years, from 591 to 565 million years ago. This overlaps with the rise in oxygen, which occurred between 575 and 565 million years ago.

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The authors propose that the weakened magnetic field may have allowed more hydrogen to escape to space, resulting in a greater percentage of oxygen in Earth's atmosphere and oceans, which may in turn have supported the diversification in the types and complexity of organisms.

John Tarduno, Near-collapse of the geomagnetic field may have contributed to atmospheric oxygenation and animal radiation in the Ediacaran Period, Communications Earth & Environment (2024). DOI: 10.1038/s43247-024-01360-4. www.nature.com/articles/s43247-024-01360-4

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Testing for residual cancer cells before blood cell transplant therapy is important and practical, new study finds

Patients in remission after battling a high-risk blood cancer are likely to have better outcomes if no trace of the cancer is detectable before the patients receive donor blood cells.

The finding appearing in JAMA Oncology emphasizes the importance and practicality of testing for measurable residual disease (MRD)—a condition that refers to evidence of lingering cancer cells in the body after people receive apparently successful chemotherapy treatment in adults with acute myeloid leukemia.

The good news is this testing is doable.  You don't need to be at a specialized center with customized technology and high levels of expertise—testing can be done using commercially available kits potentially at any major modern hospital lab. It is now a matter of implementation.

In a study of 537 patients with AML treated throughout the United States, scientists used a method called targeted ultra-deep DNA sequencing to see if they could find specific, leftover cancer-related gene mutations in the blood of patients who were in remission, but still awaiting a bone marrow transplant from donors to restore their healthy blood supply.
The scientists were looking at DNA in blood for mutations in the FLT3 gene, which is among the most common seen in patients with AML. They found that if as little as 1 in 10,000 molecules of DNA tested contained a mutation, it corresponded with a higher risk of the cancer returning, and lower chances of survival with current standard treatments.

Measurable Residual FLT3-ITD before Allogeneic Transplant for Acute Myeloid Leukemia, JAMA Oncology (2024). DOI: 10.1001/jamaoncol.2024.0985

The brain structure that produces norepinephrine also helps control visual attention

The locus coeruleus (LC) is a small region of the brainstem that produces norepinephrine, a chemical with powerful effects on arousal and wakefulness which plays an important role in the body's response to stress or panic. Now, research shows it plays a specific role in visual sensory processing as well.

In a study, titled "Locus coeruleus norepinephrine selectively controls visual attention" and published in Neuron, neuroscientists artificially increased neuronal activity in the LC by briefly shining light on genetically modified neurons. They saw that this manipulation selectively enhanced performance in non-human primates performing a visual attention task, underscoring the crucial role that attention plays in sensory perception.

Researchers now have found a brain structure that has strong signals related to whether the subjects are paying attention to a stimulus or not, and they see big differences in how its neurons respond depending on where that attention is directed.

Previous research has shown that LC activation, coupled with its ensuing norepinephrine production, might improve performance on tasks that require attention to discern between visual stimuli.

Distinguishing the effects of attention from other factors, like decision-making or motor movements, is crucial. 

 Those processes take place in other parts of the brain, and can contribute to performance independently. Understanding how a relatively small brain structure like the LC impacts such an important function as attention is also one step toward solving the overall puzzle of the brain.

Locus coeruleus norepinephrine contributes to visual spatial attention by selectively enhancing perceptual sensitivity, Neuron (2024). DOI: 10.1016/j.neuron.2024.04.001. www.cell.com/neuron/fulltext/S0896-6273(24)00239-3

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First report of wound treatment by a wild animal using a pain-relieving plant

Even though there is evidence of certain self-medication behaviours in animals, so far it has never been known that animals treat their wounds with healing plants.

Now biologists have observed this in a male Sumatran orangutan who sustained a facial wound. He ate and repeatedly applied sap from a climbing plant with anti-inflammatory and pain-relieving properties commonly used in traditional medicine. He also covered the entire wound with the green plant mesh. Thus, medical wound treatment may have arisen in a common ancestor shared by humans and orangutans.

While sick and avoidance behavior can be regularly observed in non-human animals, self-medication in the form of ingestion of specific plant parts is widespread in animals but exhibited at low frequencies. The closest relatives to humans, the great apes, are known to ingest specific plants to treat parasite infection and to rub plant material on their skin to treat sore muscles.

Recently a chimpanzee group in Gabon was observed applying insects to wounds. However, the efficiency of this behavior is still unknown. Wound treatment with a biologically active substance has so far not been documented.

In a study published in Scientific Reports, cognitive and evolutionary biologists from  report evidence of active wound treatment with a healing plant in a wild male Sumatran orangutan.

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The study  took place at the Suaq Balimbing research site in Indonesia, which is a protected rainforest area home to approximately 150 critically endangered Sumatran orangutans.

During daily observations of the orangutans, the biologists noticed that a male named Rakus had sustained a facial wound, most likely during a fight with a neighbouring male.

Three days after the injury, Rakus selectively ripped off leaves of a liana with the common name Akar Kuning (Fibraurea tinctoria), chewed on them, and then repeatedly applied the resulting juice precisely onto the facial wound for several minutes. As a last step, he fully covered the wound with the chewed leaves.

This and related liana species that can be found in tropical forests of Southeast Asia are known for their analgesic and antipyretic effects and are used in traditional medicine to treat various diseases, such as malaria. Analyses of plant chemical compounds show the presence of furanoditerpenoids and protoberberine alkaloids, which are known to have antibacterial, anti-inflammatory, anti-fungal, antioxidant, and other biological activities of relevance to wound healing.

Observations over the following days did not show any signs of the wound becoming infected and after five days the wound was already closed.

Interestingly, Rakus also rested more than usual when being wounded. Sleep positively affects wound healing as growth hormone release, protein synthesis and cell division are increased during sleep. 

Like all self-medication behavior in non-human animals, the case reported in this study raises questions about how intentional these behaviors are and how they emerge.

The behavior of Rakus appeared to be intentional as he selectively treated his facial wound on his right flange, and no other body parts, with the plant juice. The behavior was also repeated several times, not only with the plant juice but also later with more solid plant material until the wound was fully covered. The entire process took a considerable amount of time.

It is possible, that wound treatment with Fibraurea tinctoria by the orangutans at Suaq emerges through individual innovation.

Orangutans at the site rarely eat the plant. However, individuals may accidentally touch their wounds while feeding on this plant and thus unintentionally apply the plant's juice to their wounds. As Fibraurea tinctoria has potent analgesic effects, individuals may feel an immediate pain release, causing them to repeat the behaviour several times.

Since the behaviour has not been observed before, it may be that wound treatment with Fibraurea tinctoria has so far been absent in the behavioural repertoire of the Suaq orangutan population. Like all adult males in the area, Rakus was not born in Suaq, and his origin is unknown.

This possibly innovative behavior presents the first report of active wound management with a biological active substance in a great ape species and provides new insights into the existence of self-medication in our closest relatives and in the evolutionary origins of wound medication more broadly.

Isabelle Laumer, Active self-treatment of a facial wound with a biologically active plant by a male Sumatran orangutan, Scientific Reports (2024). DOI: 10.1038/s41598-024-58988-7. www.nature.com/articles/s41598-024-58988-7

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Nano-drugs hitching a ride on bacteria could help treat pancreatic cancer

Many pancreatic tumors are like malignant fortresses, surrounded by a dense matrix of collagen and other tissue that shields them from immune cells and immunotherapies that have been effective in treating other cancers. Employing bacteria to infiltrate that cancerous fortification and deliver these drugs could aid treatment for pancreatic cancer, according to newly published findings from a team of researchers.

The paper is published in the journal Med.

Tumor collagen is a tough barrier

Pancreatic cancer is well known for its deadliness and has among the lowest five-year survival rates among common cancers. While there are several drivers behind the disease's dismal prognosis, one that's the focus of this study is the matrix surrounding many pancreatic tumors, which acts as an effective barrier against treatment.

The barrier is a collection of collagen, connective tissue, proteins that facilitate fibrosis and other cells. Recent studies have highlighted the role of this barrier in counteracting treatment attempts with immunotherapies—treatments that work by spurring on or tamping down the patient's immune system—such as immune checkpoint inhibitors. Analyzing patient tumour samples, the research team found genetic evidence that a specific type of collagen, called oncogenic collagen, is indeed a barrier to immunotherapy-based treatments.

That really dense extracellular matrix, made up of immunosuppressive cells, collagens and other cells is a critical problem if we want to use immunotherapies against these pancreatic cancers.

So researcher s  applied a bacterium that could both penetrate through the tough collagen barrier and deliver immunotherapeutic "nano-drugs."

The team chose a strain of the bacterium Escherichia coli with a track record of safe use in humans and known affinity for low-oxygen environments such as tumors to serve as a drug delivery vehicle. They engineered "protein cages" containing a pair of drugs—one breaks down collagen and the other is an anticancer immune checkpoint inhibitor—and attached them to the E. coli.

E. coli has great motility, meaning it can move by itself, and it actively targets hypoxic environments like tumors. And the researchers found that it was able to penetrate deep into the tumor site to deliver drugs.

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The team tested its E. coli-based delivery system in mouse models of pancreatic ductal adenocarcinoma, or PDAC, the most common and lethal form of pancreatic cancer, which was the focus of the study.

Mice treated with the therapeutic-laden bacteria experienced delayed tumour growth and significantly longer survival compared with mice that received other treatments. Postmortem analyses also showed that tumors treated with the nano-drug-carrying E. coli had the greatest infiltration of cancer-fighting immune cells among all treatments.

Zhaoting Li et al, Nanodrug-bacteria conjugates-mediated oncogenic collagen depletion enhances immune checkpoint blockade therapy against pancreatic cancer, Med (2024). DOI: 10.1016/j.medj.2024.02.012

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Centipedes used in traditional Chinese medicine offer leads for kidney treatment

A venomous, 8-inch centipede may be the stuff of nightmares, but it could save the life of those affected by kidney disease. Researchers report in the Journal of Natural Products that the many-legged critter—used in traditional Chinese medicine—contains alkaloids that in cell cultures reduced inflammation and renal fibrosis, which both contribute to kidney disease.

Some 1,500 species of animals are used in traditional Chinese medicine, but little is known about many of the secondary metabolites their bodies produce for specialized functions such as immobilizing prey. The few compounds that have been studied, such as toad venom for cancer treatment, have proved to be fruitful leads for drug development.

The researchers 

decided to examine the secondary metabolites produced by the Chinese red-headed centipede (Scolopendra subspinipes mutilans). The venomous centipede has been used for thousands of years in treatments for conditions including epilepsy, tuberculosis, burns and cardiovascular disease.

The researchers mixed a sample of dried centipede powder with ethanol to extract numerous compounds from the animals and then separated and identified the constituents with techniques such as chromatography and spectrometry. The team found 12 new quinoline and isoquinoline alkaloids, including some with unusual molecular structures, along with a half dozen other alkaloids that had previously been detected in this species or in plants.

In cell cultures, some of the alkaloids showed anti-inflammatory behavior, while a portion also reduced renal fibrosis. This buildup of connective tissue is associated with chronic kidney disease and is stimulated by inflammation. Finally, the researchers identified a protein that plays a role in renal fibrosis and that was targeted by the most effective dual-function alkaloid. This information could provide a lead for developing treatments for kidney disease, according to the researchers.

Bin-Yuan Hu et al, Structurally Diverse Alkaloids with Anti-Renal-Fibrosis Activity from the Centipede Scolopendra subspinipes mutilans, Journal of Natural Products (2024). DOI: 10.1021/acs.jnatprod.4c00044

Genetics, not lack of oxygen, causes cerebral palsy in quarter of cases: Study

The world's largest study of cerebral palsy (CP) genetics has discovered genetic defects are most likely responsible for more than a quarter of cases in Chinese children, rather than a lack of oxygen at birth as previously thought.

The study, published in Nature Medicine, used modern genomic sequencing and found mutations were significantly higher in CP cases with birth asphyxia, indicating a lack of oxygen could be secondary to the underlying genetic defect. The results are consistent with smaller studies globally.

More than 1,500 Chinese children with CP were involved in this research project. 

24.5% of Chinese children in the study had rare genetic variations linked to cerebral palsy. This revelation mirrors  earlier findings in  Australian cerebral palsy cohort, where up to one-third of cases have genetic causes.

This research shows at least some babies who experience birth asphyxia and are diagnosed with CP may have improper brain development as a result of the underlying genetic variants rather than a lack of oxygen.

Crucially, clinically actionable treatments were found in 8.5% of cases with a genetic cause. It is exciting to see how genetic pathways to cerebral palsy inform tailored treatments for these individuals.

Cerebral palsy affects movement and posture and is the most common motor disability in children. The disorder is diagnosed in up to 2 per 1,000 children globally and is sometimes in association with epilepsy, autism and intellectual difficulties. Symptoms often emerge during infancy and early childhood and can range from mild to severe.

The research team identified 81 genes with causation mutations in the children with CP. These genes are known to play important roles in neural and embryonic development and may affect the molecular pathways responsible for respiration.

These results highlight the need for early genetic testing in children with cerebral palsy, especially those with risk factors like birth asphyxia, to ensure they receive the right medical care and treatment.

Yangong Wang et al, Exome sequencing reveals genetic heterogeneity and clinically actionable findings in children with cerebral palsy, Nature Medicine (2024). DOI: 10.1038/s41591-024-02912-z

Mantle movements shape Earth's surface

The movement of tectonic plates shapes the rocky features of Earth's surface. Plates' convergence can form mountain ranges or ocean trenches, and their divergence can form oceanic ridges. But it's not just the plates themselves that influence Earth's topography. The mantle layer underneath exerts its own subtle influence, which can be seen even in places located far from tectonic plate edges, and is referred to as residual topography.

To better understand how the mantle affects topography,  researchers building on previous work focused on the oceans, created two new databases. The paper is published in the Journal of Geophysical Research: Solid Earth.

One compiles 26,725 measurements of crust thickness around the globe, the largest such database to date, along with estimates of seismic velocity. The other contains laboratory analysis of seismic velocity as a function of temperature, density, and pressure. Together these measurements helped disentangle crustal influences on topography from mantle influences to identify residual topography.

The researchers found that differences in the temperature and chemical structure of the mantle can cause swells and basins in the landscape distinct from those that form at the edges of tectonic plates. These features can rise or fall by up to 2 kilometers and stretch for hundreds to thousands of kilometers—all within the interior of plates.

Some of the highest swells (about 2 kilometers), which are thought to correspond to locations where the mantle is particularly hot, can be found in the Afar–Yemen–Red Sea region, western North America, and Iceland. Some of the deepest basins (deeper than about 1.5 kilometers), where the mantle is thought to be cooler, are in areas near the Black, Caspian, and Aral seas, as well as in the East European Plain. This pattern of swells and basins may control—to some extent—the locations where significant erosion and sedimentary deposition occur.

These topographical features can develop slowly over millions of years, but they nonetheless control important geological processes. According to the researchers, these findings could help explain the existence of magmatism found far from plate boundaries. They also could help scientists understand the elusive effects of flow in Earth's mantle on the surface through geologic time.

Simon N. Stephenson et al, Continental Residual Topography Extracted From Global Analysis of Crustal Structure, Journal of Geophysical Research: Solid Earth (2024). DOI: 10.1029/2023JB026735

Ice shelves fracture under weight of meltwater lakes, study shows

When air temperatures in Antarctica rise and glacier ice melts, water can pool on the surface of floating ice shelves, weighing them down and causing the ice to bend. Now, for the first time in the field, researchers have shown that ice shelves don't just buckle under the weight of meltwater lakes—they fracture.

As the climate warms and melt rates in Antarctica increase, this fracturing could cause vulnerable ice shelves to collapse, allowing inland glacier ice to spill into the ocean and contribute to sea level rise.

Ice shelves are important for the Antarctic Ice Sheet's overall health as they act to buttress or hold back the glacier ice on land. Scientists have predicted and modeled that surface meltwater loading could cause ice shelves to fracture, but no one had observed the process in the field, until now.

The new study, published in the Journal of Glaciology, may help explain how the Larsen B Ice Shelf abruptly collapsed in 2002. In the months before its catastrophic breakup, thousands of meltwater lakes littered the ice shelf's surface, which then drained over just a few weeks.

 Alison F. Banwell et al, Observed meltwater-induced flexure and fracture at a doline on George VI Ice Shelf, Antarctica, Journal of Glaciology (2024). DOI: 10.1017/jog.2024.31

Fetal Organoids Generated From Human Amniotic Fluid

A minimally invasive strategy for creating fetal organoids could facilitate precision medicine in the womb.

Moments after birth, a baby takes a first breath as the placenta, which has served as the fetus’ lungs during gestation, transfers responsibility to the baby's own organs. However, for patients born with congenital diaphragmatic hernia (CDH), a rare condition where the diaphragm fails to close, causing impaired lung development, entry into the world is more precarious. More severe cases of the disease lead to multiorgan damage, and approximately thirty percent of infants diagnosed with CDH never leave the hospital.

Diagnostic imaging and genetic screens help clinicians catch congenital fetal diseases in utero, but models for studying organ development and disease progression are limited. Over the last decade, organoids have become an increasingly popular platform for modeling organ function and disease. However, the generation of fetal organoids is complicated by ethical and legal restrictions on the harvesting of the human tissues needed to generate the mini-organs.

Now, reporting in Nature Medicine, researchers generated fetal organoids using cells derived from human amniotic and tracheal fluids. These mini-organs offer a minimally invasive approach for disease modeling during an active pregnancy and may eventually inform the development of personalized prenatal interventions.

Part 1

Scientists use patient cells to generate organoids that possess certain features and functions of the modeled organ while retaining the individual's genetic fingerprint. However, many of these platforms require lengthy dedifferentiation protocols to revert somatic cells into a state of pluripotency and then reprogram them to develop as another cell type. In contrast to organoids generated from pluripotent stem cells, primary organoids use tissue-specific stem cells or progenitor cells and therefore require minimal manipulation.3 While the organoid field is relatively advanced in terms of using adult tissues, researchers can only generate primary fetal organoids using tissue from terminated pregnancies. “This made it basically impossible to [generate organoids] compatible with the continuation of pregnancy, and therefore in a personalized medicine fashion”.
During gestation, the fetus floats in a protective pool of amniotic fluid.6 The yellowish liquid contains a concoction of nutrients and antibodies produced by the parent as well as less glamorous contributions from the fetus, including urine. It also includes fetal cells sloughed off during development, which doctors can extract and analyze for signs of disease.

“Those cells historically have been thought to be dead cells or cells that were shed from the lining of the amniotic fluid cavity.
Part 2

Most amniotic fluid cells are epithelial, but scientists knew very little about these cell populations. Everything changed when researchers started to look at the single cell level at what happened in the amniotic fluid.
used single-cell RNA sequencing to characterize the amniotic fluid of 12 patients and discovered subpopulations of epithelial cells that expressed markers typical of progenitors for the lung, kidney, and small intestine. The researchers cultured the tissue-specific progenitor cells, fed them a chemical cocktail to support growth, and watched as they proliferated, differentiated, and self-organized into 3D epithelial organoids. The mini-organs shared some transcriptomic and protein features found in their tissues of origin. For example, lung epithelial cells that developed and differentiated in culture had elevated expression of airway markers compared to their nondifferentiated counterparts. Similarly, kidney epithelial organoids expressed markers associated with renal tubules, which are integral components of the kidneys’ filtration system.

Although the amniotic fluid contained cells from other tissues, the researchers could not grow them into organoids, suggesting that they lack progenitor capabilities. Other research groups have successfully grown fetal organoids from somatic cells floating around the amniotic fluid, and the mini-organs generated using this approach are more complex.
reprogramming methods take up to 20 weeks to generate organoids. If the goal is to use organoids to inform prenatal interventions, timing is critical.
Part 3

Researchers re using these to study various diseases and find solutions to them.

More here: https://www.the-scientist.com/fetal-organoids-generated-from-human-...

New mRNA cancer vaccine triggers fierce immune response to fight malignant brain tumour

Glioblastoma is among the most devastating diagnoses, with median survival around 15 months. The current standard of care involves surgery, radiation and some combination of chemotherapy.

In a first-ever human clinical trial of four adult patients, an mRNA cancer vaccine developed by scientists quickly reprogrammed the immune system to attack glioblastoma, the most aggressive and lethal brain tumour.

The results mirror those in 10 pet dog patients suffering from naturally occurring brain tumors whose owners approved of their participation, as they had no other treatment options, as well as results from preclinical mouse models. The breakthrough now will be tested in a Phase I pediatric clinical trial for brain cancer.

Reported May 1 in the journal Cell, the discovery represents a potential new way to recruit the immune system to fight notoriously treatment-resistant cancers using an iteration of mRNA technology and lipid nanoparticles, similar to COVID-19 vaccines, but with two key differences: use of a patient's own tumor cells to create a personalized vaccine, and a newly engineered complex delivery mechanism within the vaccine.

In less than 48 hours, the researchers could see these tumours shifting from what they refer to as 'cold'—immune cold, very few immune cells, very silenced immune response—to 'hot,' very active immune response.

The 10 pet dogs on which trials were done lived a median of 139 days, compared with a median survival of 30 to 60 days typical for dogs with the condition.

 RNA aggregates harness the danger response for potent cancer immunotherapy, Cell (2024). DOI: 10.1016/j.cell.2024.04.003. www.cell.com/cell/fulltext/S0092-8674(24)00398-2

A 'cosmic glitch' in gravity: New model may explain strange behaviour on a cosmic scale

A group of researchers  have discovered a potential "cosmic glitch" in the universe's gravity, explaining its strange behavior on a cosmic scale.

The paper is published in the Journal of Cosmology and Astroparticle Physics.
For the last 100 years, physicists have relied upon Albert Einstein's theory of "general relativity" to explain how gravity works throughout the universe. General relativity, proven accurate by countless tests and observations, suggests that gravity impacts not simply three physical dimensions but also a fourth dimension: time.

This model of gravity has been essential for everything from theorizing the Big Bang to photographing black holes.
But when we try to understand gravity on a cosmic scale, at the scale of galaxy clusters and beyond, we encounter apparent inconsistencies with the predictions of general relativity. It's almost as if gravity itself stops perfectly matching Einstein's theory. We are calling this inconsistency a 'cosmic glitch': gravity becomes around one percent weaker when dealing with distances in the billions of light years.
For more than twenty years, physicists and astronomers have been trying to create a mathematical model that explains the apparent inconsistencies of the theory of general relativity. Many of those efforts have taken place at Waterloo, which has a long history of cutting-edge gravitational research resulting from ongoing interdisciplinary collaboration between applied mathematicians and astrophysicists.

"Almost a century ago, astronomers discovered that our universe is expanding.
The farther away galaxies are, the faster they are moving, to the point that they seem to be moving at nearly the speed of light, the maximum allowed by Einstein's theory. Our finding suggests that, on those very scales, Einstein's theory may also be insufficient.
The research team's new model of a "cosmic glitch" modifies and extends Einstein's mathematical formulas in a way that resolves the inconsistency of some of the cosmological measurements without affecting existing successful uses of general relativity.

"Think of it as being like a footnote to Einstein's theory," the researchers say. "Once you reach a cosmic scale, terms and conditions apply."

"This new model might just be the first clue in a cosmic puzzle we are starting to solve across space and time".

Robin Y. Wen et al, A cosmic glitch in gravity, Journal of Cosmology and Astroparticle Physics (2024). DOI: 10.1088/1475-7516/2024/03/045

A common type of fiber may trigger bowel inflammation

Inulin, a type of fiber found in certain plant-based foods and fiber supplements, causes inflammation in the gut and exacerbates inflammatory bowel disease in a preclinical model, according to a new study by  investigators. The surprising findings could pave the way for therapeutic diets that may help ease symptoms and promote gut health. 

The study, published March 20 in the Journal of Experimental Medicine, shows that inulin, which is found in foods such as garlic, leeks and sunchoke, as well as commonly used fiber supplements and foods with added fiber, stimulates microbes in the gut to release bile acids that increase the production of molecules that promote intestinal inflammation.

One such protein, IL-33, causes immune cells called group 2 innate lymphoid cells (ILC2s) to become activated, triggering an excessive immune response similar to an allergic reaction. That excessive immune response then exacerbates intestinal damage and symptoms in an animal model of inflammatory bowel disease.
Dietary fiber, including inulin, is considered an essential part of a healthy diet for most people. Gut microbes turn inulin and other types of dietary fiber into short-chain fatty acids that turn on immune cells called regulatory T cells, which help reduce inflammation and have other beneficial effects throughout the body. This led to a remarkable rise in use of dietary fiber as an additive in both foods and supplements, and purified inulin or inulin-rich chicory root is often the main source of the fiber.
Inulin is now everywhere, from clinical trials to prebiotic sodas.
Feeding inulin to mice in the context of a model of inflammatory bowel disease increased the production of certain bile acids by specific groups of gut bacteria. The increased bile acids boosted the production of an inflammatory protein called IL-5 by ILC2s. The ILC2s also failed to produce a tissue-protecting protein called amphiregulin.

In response to these changes, the immune system promotes the production of immune cells called eosinophils, which further ramp up inflammation and tissue damage. Previously, a 2022 study by the same team of investigators showed that this flood of eosinophils may help protect against parasite infections. However, in the inflammatory bowel disease model, this chain reaction exacerbated intestinal inflammation, weight loss and other symptoms like diarrhea. 
Part 1

In translational patient-based studies, the team also analyzed human tissue, blood and stool samples from Weill Cornell Medicine's Jill Roberts Institute for Research in Inflammatory Bowel Disease Live Cell Bank. This analysis revealed that patients with inflammatory bowel disease, like the mice fed inulin, had higher levels of bile acids in their blood and stool and excessive levels of eosinophils in their intestine compared with people without the condition.

The results suggest that the inflammation cascade similar to that in the mice fed inulin is already primed in humans with inflammatory bowel disease, and dietary uptake of inulin may further exacerbate the disease.
These unexpected discoveries may help explain why high-fiber diets often exacerbate inflammatory bowel disease in patients. It may also help scientists develop therapeutic diets to reduce symptoms and gut damage in patients with inflammatory bowel disease or related conditions.

New therapies are urgently needed for these increasingly common gut conditions. Existing biologic therapies can increase the risk of developing infections or autoimmune diseases, which cause the immune system to attack the body. 
The present study shows that not all fibers are the same in how they influence the microbiota and the body's immune system.
These findings could have broader implications for the delivery of precision nutrition to individual patients to promote their overall health based on their unique symptoms, microbiota composition and dietary needs.

Mohammad Arifuzzaman et al, Dietary fiber is a critical determinant of pathologic ILC2 responses and intestinal inflammation, Journal of Experimental Medicine (2024). DOI: 10.1084/jem.20232148

Part 2

 Parrots prefer live calls over pre-recorded videos

A new study managed to accurately date findings from 1st Temple period found in the City of David

A team of archaeologists, antiquities specialists, Bible scholars and mass spectrometry specialists, affiliated with several institutions in Israel working with one colleague from the U.K. and another from the U.S., has dated material uncovered in the First Temple in the city of David, in Jerusalem, to an unpreceded level of accuracy.

In their paper published in the Proceedings of the National Academy of Sciences, the group describes how they used radio-carbon dating, tree ring analysis and other techniques to accurately date artifacts collected from a dig site in one of the oldest parts of Jerusalem.

The ancient history of Israel, and most particularly the city of Jerusalem, has taken on increased significance over the past several decades as religious and political entities have used it to make claims about current rights to certain parts of the city. One such site is believed to be what has been described in ancient texts as the City of David.

The work by the team involved analysis of artifacts (such as seeds and a bat skull) found among strata dated to between 770 and 420 BC—which has been named the Hallstatt Plateau. The team performed 103 carbon-14 measurements, providing high-resolution results.

The researchers also dated material in the same strata using tree-ring measurements, which allowed for annual resolution. After dating the artifacts, the researchers looked for and found associations between the nature of the artifacts and reported historical events mentioned in several ancient texts, including the Bible.

The team found that they were able to date many of the artifacts to historical events, which allowed them to verify that the city was first settled sometime between the 12th and 10th century BC, and that it expanded westward thereafter. They also found evidence of an earthquake and the rebuilding that occurred thereafter during the 8th century BC—and the Babylonian destruction of the city of Jerusalem in 586 BC.

Johanna Regev et al, Radiocarbon chronology of Iron Age Jerusalem reveals calibration offsets and architectural developments, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2321024121

Israel Antiquities Authority announcement: www.facebook.com/AntiquitiesEN … Ymyxcnz6GBXxmejmabdl

Nanotech opens door to future of insulin medication

An international research team has developed a system using nanotechnology that could allow people with diabetes to take oral insulin in the future. The researchers say the new insulin could be eaten by taking a tablet or even embedded within a piece of chocolate.

The new nano carrier, tested in mice, rats and baboon animal models, could help people with diabetes avoid side-effects linked to insulin injections such as hypoglycemia (a low blood sugar event, when too much insulin has been injected).

These animal studies have shown that the greatest strength of the nano-scale material is that it can react to the body's blood sugar levels. The coating dissolves and releases the insulin when there is a high concentration of blood sugar and importantly does not release the insulin in low blood sugar environments.

The new oral insulin uses a type of nano-scale material that is 1/10,000th the width of a human hair. The material acts similarly to acid resistant coating on tablets, which protects it from being destroyed by stomach acid. But this new coating instead surrounds individual insulin molecules and becomes a "nano carrier"—acting like a courier to ferry insulin molecules in the body to the places it needs to act.

Nicholas J. Hunt et al, Oral nanotherapeutic formulation of insulin with reduced episodes of hypoglycaemia, Nature Nanotechnology (2024). DOI: 10.1038/s41565-023-01565-2

Humans annoy invertebrates

Researchers have known for a while that noise from human activities is disruptive to aquatic life like dolphins and whales, but a new study by University of Denver researchers finds that human-generated noise can mask the harmony of cricket song, with profound effects across 15 species traits.

Among their findings, they report that at a certain noise level, human-generated sounds can reduce the rate of survival to adulthood and affect the number of hatched offspring. The researchers exposed crickets to four levels of sound often encountered in natural settings: silence, 50 decibels, 60 decibels and 70 decibels. At 70 decibels, a level associated with vacuum cleaners and busy streets, survival to adulthood was reduced.

Previous studies have found that human-generated sounds cause changes to birdsong as birds attempt to make themselves heard over traffic, but this is among the first studies to examine human influence on invertebrates as species numbers are collapsing.

Gabrielle T. Welsh et al, Consistent traffic noise impacts few fitness-related traits in a field cricket, BMC Ecology and Evolution (2023). DOI: 10.1186/s12862-023-02190-2

Part1`

Laboratory studies and field research have identified four main ways in which animals are adversely affected by noise pollution: (i) hearing loss, with noise levels of 85 Decibel or higher; (ii) masking, such as the inability to hear important environmental and animal signals; (iii) increased heart rate and breathing; and (iv) behavioral effects. There is considerable intra-species variability, and this varies according to the characteristics of the noise. This may lead to territory abandonment and loss of reproduction.

Marine animals such as whales, which depend on sound for communication, can be affected by noise in various ways. Marine mammals live in a habitat that transmits little light but through which sound propagates well and quickly, even over great distances. For this reason, marine mammals rely on sound to communicate, explore the environment, find their prey and avoid obstacles. Research had shown that higher ambient noise levels also caused the animals to vocalize louder (“Lombard Effect”) and that the duration of the humpback whales’ song was longer when there was low-frequency sonar in the vicinity .

Exposure to noise can produce a wide range of effects on marine mammals. The low-level sound may be audible to animals without producing any visible effects; higher-intensity sound can disturb the animals, causing them either to move away or may produce other behavioral changes. Noise can increase the risk of death by modifying the delicate balance between predators and prey, interfering with the use of sounds in communication, especially in relation to reproduction and navigation.

Part 2

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9819367/#:~:text=Labor...

Wild animals suffer chronic stress, fertility problems and change their migration routes in response to noise. Confined animals are often exposed to high levels of human-generated noise which they cannot escape. Research shows noise causes confined animals pain, fear and cognitive problems.

https://www.aru.ac.uk/news/noise-pollution-is-hurting-animals#:~:te....

Part 3

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Researchers develop a nanoparticle that can penetrate the blood-brain barrier

Researchers  have developed a nanoparticle that can penetrate the blood-brain barrier. Their goal is to kill primary breast cancer tumors and brain metastases in one treatment, and their research shows the method can shrink breast and brain tumors in laboratory studies.

Brain metastases, as these secondary tumors are called, most commonly arise from solid tumors like breast, lung and colon cancer and are often associated with a poor prognosis. When cancer breaches the brain, it can be difficult for treatment to follow, in part because of the blood-brain barrier, a near-impenetrable membrane that separates the brain from the rest of the body.

In teh present study, by loading the particle with two prodrugs that target mitochondria, the energy production center of the cell, the researchers showed that their method could shrink breast and brain tumors in preclinical studies.

Part 1

The new method uses a nanoparticle made of a biodegradable polymer, previously developed by the team, coupled with two drugs also developed by them that take aim at cancer's energy sources. Because cancer cells often have a different form of metabolism than healthy cells, stifling their metabolism can be an effective way to kill tumors without harming other tissues.

One of these drugs is a modified version of a classic chemotherapy drug, cisplatin, which kills cancer cells by damaging DNA in rapidly growing cells, effectively halting their growth. But tumor cells can repair their DNA, sometimes leading to cisplatin resistance.

The research team modified the drug to shift its target from nuclear DNA, the DNA that makes up our chromosomes and genome, to mitochondrial DNA. Mitochondria are our cells' energy sources and contain their own, much smaller genomes—and, importantly for cancer therapeutic purposes, they don't have the same DNA-repair machinery that our larger genomes do.

Because cancer cells can switch between different energy sources to sustain their growth and proliferation, the researchers combined their modified cisplatin, which they call Platin-M and attacks the energy-generating process known as oxidative phosphorylation, with another drug they developed, Mito-DCA, that specifically targets a mitochondrial protein known as a kinase and inhibits glycolysis, a different kind of energy generation.

 Dhar, Shanta, Simultaneous targeting of peripheral and brain tumors with a therapeutic nanoparticle to disrupt metabolic adaptability at both sites, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2318119121. doi.org/10.1073/pnas.2318119121

Part 2

'Quartet Nanocage' vaccine found effective against coronaviruses that haven't even emerged yet

Researchers have developed a new vaccine technology that has been shown in mice to provide protection against a broad range of coronaviruses with potential for future disease outbreaks—including ones we don't even know about. The results are published in the journal Nature Nanotechnology.

This is a new approach to vaccine development called "proactive vaccinology," where scientists build a vaccine before the disease-causing pathogen even emerges.

The new vaccine works by training the body's immune system to recognize specific regions of eight different coronaviruses, including SARS-CoV-1, SARS-CoV-2, and several that are currently circulating in bats and have potential to jump to humans and cause a pandemic.

Key to its effectiveness is that the specific virus regions the vaccine targets also appear in many related coronaviruses. By training the immune system to attack these regions, it gives protection against other coronaviruses not represented in the vaccine—including ones that haven't even been identified yet.

For example, the new vaccine does not include the SARS-CoV-1 coronavirus, which caused the 2003 SARS outbreak, yet it still induces an immune response to that virus.

We don't have to wait for new coronaviruses to emerge. We know enough about coronaviruses, and different immune responses to them, that we can get going with building protective vaccines against unknown coronaviruses now.

The new "Quartet Nanocage" vaccine is based on a structure called a nanoparticle—a ball of proteins held together by incredibly strong interactions. Chains of different viral antigens are attached to this nanoparticle using a novel "protein superglue." Multiple antigens are included in these chains, which trains the immune system to target specific regions shared across a broad range of coronaviruses.

This study demonstrated that the new vaccine raises a broad immune response, even in mice that were pre-immunized with SARS-CoV-2.

The new vaccine is much simpler in design than other broadly protective vaccines currently in development, which the researchers say should accelerate its route into clinical trials.

The underlying technology they have developed also has potential for use in vaccine development to protect against many other health challenges.

Proactive vaccination using multiviral Quartet Nanocages to elicit broad anti-coronavirus responses. Nature Nanotechnology (2024). DOI: 10.1038/s41565-024-01655-9

Q: Why do women wear jasmine flowers in their hair?

Krishna: 

Jasmines usually come in summer. In summer you sweat a lot, especially near the sea, where the RH doesn’t allow your sweat to evaporate.

With sweat comes bacteria and body odour. So to camouflage that smell, women usually use sweet-smelling jasmine flowers.

That ‘s the reason given to me.

And I am not surprised. Even in Andhra and Telangana, people use this trick.

Progression of Liver Disease Overview - Animated

Your car may be slowly killing you

You're breathing potential carcinogens inside your car, says study

The air inside all personal vehicles is polluted with harmful flame retardants—including those known or suspected to cause cancer—according to a new study published in Environmental Science & Technology. Car manufacturers add these chemicals to seat foam and other materials to meet an outdated federal flammability standard with no proven fire-safety benefit.

Recent research found that interior materials release harmful chemicals into the cabin air of  cars. 

Considering the average driver spends about an hour in the car every day, this is a significant public health issue. It's particularly concerning for drivers with longer commutes as well as child passengers, who breathe more air pound for pound than adults.

The researchers detected flame retardants inside the cabins of 101 cars (model year 2015 or newer). In total, 99% of cars contained tris (1-chloro-isopropyl) phosphate (TCIPP), a flame retardant under investigation as a potential carcinogen. Most cars had additional organophosphate ester flame retardants present, including tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) and tris (2-chloroethyl) phosphate (TCEP), two California Proposition 65 carcinogens. These and other flame retardants are also linked to neurological and reproductive harms.

About half of the cars were tested in both summer and winter. Warmer weather was linked to higher flame retardant concentrations because off-gassing from interior components like seat foam is increased by higher temperatures. Vehicle interiors can reach up to 150 degrees Fahrenheit.

The researchers also analyzed samples of seat foam from 51 of the cars in the study. Vehicles that contained the suspected carcinogen TCIPP in their foam tended to have higher concentrations of TCIPP in their air, confirming foam as a source of this flame retardant in cabin air.

Incidentally, firefighters are concerned that flame retardants contribute to their very high cancer rates.

You may be able to reduce your exposure to flame retardants in your car by opening your windows and parking in the shade.

But what's really needed is reducing the amount of flame retardants being added to cars in the first place. Commuting to work shouldn't come with a cancer risk. 

 Flame Retardant Exposure in Vehicles is Influenced by Use in Seat Foam and Temperature, Environmental Science & Technology (2024). DOI: 10.1021/acs.est.3c10440

Freshly manufactured automobiles were making people feel ill!
Chemical-rich, and completely unavoidable, these distinct car aromas are but one of many allergens humans are exposed to while riding in automobiles.

From the steering wheel and dashboard, to armrests, headrests seats, and safety restraints, if it was man-made, chances are it was out-gassing noxious chemicals. All told, researchers found more than 275 different chemicals floating within these new car cabins, some of which bordered on being labeled as lethal.
Zero-in on Autocar’s findings surrounding the subject of new car interiors, and how they have the potential to make humans sick, and some disturbing trends begin to surface. The research reports point out eight common substances that are particularly prone to “diffusing” or “off-gassing,” with evidence showing that these toxic fumes continue to expel from surfaces, sometimes even months after assembly.
CAR PLASTICS, VOCS, ALLERGIES, AND YOUR HEALTH
The culprits are hazardous chemicals, like VOCs. Volatile organic compounds (VOCs) are probably the most recognizable evildoer in the world of hazardous inhalants. Some of the more commonplace poisonous compounds beneath this category include: acetaldehyde, acrolein, benzene, ethylbenzene, formaldehyde, styrene, toluene, and xylene.
While many of these dangerous substances have been identified as having an “adverse effect on occupants,” researchers report that, “VOCs can cause symptoms in humans like nausea, headaches, itchy eyes-basically, an allergic reaction.”

https://avalonking.com/blogs/news/toxic-cabin-interiors-why-that-ne....

New telomere findings may offer new insights for cancer treatments

A new study by  researchers shows that an enzyme called PARP1 is involved in repair of telomeres, the lengths of DNA that protect the tips of chromosomes, and that impairing this process can lead to telomere shortening and genomic instability that can cause cancer.

PARP1's job is genome surveillance: When it senses breaks or lesions in DNA, it adds a molecule called ADP-ribose to specific proteins, which act as a beacon to recruit other proteins that repair the break. The new findings, published in Nature Structural & Molecular Biology, are the first evidence that PARP1 also acts on telomeric DNA, opening up new avenues for understanding and improving PARP1-inhibiting cancer therapies.

In normal cells, genomic lesions occur naturally during DNA replication when a cell divides, and PARP1 plays an important role in fixing these errors. But while healthy cells have other DNA repair pathways to fall back on, BRCA-deficient cancers—which include many breast and ovarian tumors—rely heavily on PARP1 because they lack BRCA proteins, which control the most effective form of DNA repair called homologous replication.

When cancer cells can't make BRCA proteins, they become dependent on repair pathways that PARP1 is involved in. So, when you inhibit PARP1—which is the mechanism of several approved cancer drugs—cancer cells have no repair pathway available, and they die.

Deregulated DNA ADP-ribosylation impairs telomere replication, Nature Structural & Molecular Biology (2024). DOI: 10.1038/s41594-024-01279-6

Why parrots sometimes adopt—or kill—each other's babies

Infanticide and adoption in the animal kingdom have long puzzled scientists. While both males and females of many species are known to kill the babies of their rivals to secure sexual or social advantage, other animals have been observed caring for the young of dead or missing comrades.

A team of  biologists has discovered that both these extreme behaviours are surprisingly common among green-rumped parrotlets, a small South American parrot. In a new study in the journal Proceedings of the National Academy of Sciences, the researchers present nearly 30 years of observations revealing what drives the parrotlets to either care for—or kill—one another's babies.

In parrotlets, infanticide and adoption revolve around real estate and love, according to this research. Most of the infanticide attacks happened when a breeding pair was attacked by another pair that was trying to take over a coveted nest site. It also occurred when males wanted to breed with a widow who already had offspring—but we were surprised to find that these new males were just as likely to adopt the offspring as attack them."

Among parrotlets, competition over nesting sites appears to be the primary motivation for attacks. Parrotlets killed or wounded nestlings and eggs at 256 of the nests that the biologists monitored. In most cases, the attacks were carried out by a single parrotlet or a breeding pair that later claimed the nesting site for themselves.

These attacks occurred more often when the parrotlet population was high and competition for good nesting sites was fierce.

It's not that everybody's born a killer, but the urge to breed is very strong. When the resources provided by the environment aren't enough for all individuals to breed, they seek out alternative strategies. Unfortunately, that involves killing innocent little offspring.

Infanticide also occurred in nests where one parent had died and the surviving parent had found a new mate. However, these new mates were just as likely to adopt the unrelated offspring as kill them—and choosing to become a stepparent ultimately did not hurt the parrotlet's reproductive success.

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Adoption may be a lot easier to accept than infanticide, but it's actually more difficult to understand because it challenges Darwin's ideas about natural selection. It 's very interesting to see that the reproductive fitness outcomes 're about even between adoption and infanticide and suggests that they have an alternative strategy—adoption may be a non-violent means of getting genes into the next generation.

Steven R. Beissinger et al, Eviction-driven infanticide and sexually selected adoption and infanticide in a neotropical parrot, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2317305121

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