Scientists discover genetic 'off switch' in legume plants that limits biological ability to source nutrients

A genetic "off switch" that shuts down the process in which legume plants convert atmospheric nitrogen into nutrients has been identified for the first time by a team of international scientists.

Legumes like beans, peas and lentils are unique among crops for their ability to interact with soil bacteria to convert or "fix" nitrogen into a usable form of nutrients. However, this energy-intensive biological process is reduced when nitrogen is already abundant in the soil either through natural processes or through the application of synthetic fertilizer.

The latest discovery of the genetic regulator that turns off nitrogen fixation when soil nitrate levels are high allowed scientists to remove the gene in model legumes, ensuring they continued to fix nitrogen regardless of the soil environment.

Increasing the biological ability of legumes to fix nitrogen could help increase crop growth and yield while also reducing the need for synthetic fertilizers, which contribute to agriculture's environmental footprint.

Dugald Reid, Zinc mediates control of nitrogen fixation via transcription factor filamentation, Nature (2024). DOI: 10.1038/s41586-024-07607-6. www.nature.com/articles/s41586-024-07607-6

Researchers discover how mitochondrial transfer restores heart muscle

Transferring mitochondria from a patient's healthy skeletal muscle to damaged, ischemic heart tissue has been shown to restore heart muscle, increase energy production, and improve ventricular function.

 Researchers realized the probability of recovery was much higher if they added mitochondria.

To date, 16 children have undergone autologous mitochondria transplantation. Of these, 80% were able to come off ECMO, compared with a historical rate of 40%.

But mitochondrial transfer has faced skepticism—in part because no one really knew why it works.

The researchers earlier thought that  it was mitochondria going into cells and taking over and generating all of the cell's power. But what didn't make sense was that they only needed very small amounts of mitochondria for the heart muscle to recover. The math didn't add up.

A new study published in the journal Nature, found a surprising explanation. The transferred mitochondria trigger the cell to destroy its low-performing mitochondria through autophagy—a kind of cellular housekeeping.

This gives cells a better pool of mitochondria, improving their bioenergetics and fitness. This insight could ultimately improve care for broad range of heart conditions.

The research team is now investigating whether mitochondrial transfer could improve the success of cardiac transplantation when the heart is donated after circulatory death (DCD). DCD hearts could potentially expand the donor pool, but have ischemic damage and thus are difficult to transplant. The researchers think treatment with mitochondria will help with their recovery.

Ruei-Zeng Lin et al, Mitochondrial transfer mediates endothelial cell engraftment through mitophagy, Nature (2024). DOI: 10.1038/s41586-024-07340-0

Scientists determine that connexin molecules allow cells to send messages to each other

Researchers have gained new knowledge of how drugs bind to connexin molecules. These molecules form channels that allow neighboring cells to send direct messages to one another. Dysfunctions of these channels are involved in neurological and cardiac diseases. The new understanding of how drugs bind and act on them should help develop therapies to treat such conditions.

Adjacent cells can communicate directly through relatively large channels called gap junctions, which allow cells to freely exchange small molecules and ions with each other or with the outside environment. In this way, they can coordinate activities in the tissues or organs that they compose and maintain homeostasis.

Such channels are created from proteins known as connexins. Six connexins situated in the cell membrane create a hemichannel; this hemichannel joins with a hemichannel in a neighboring cell to create a two-way channel.

When connexin channels do not work properly, they cause changes in intercellular communication that have been linked to many different diseases. These include cardiac arrhythmias, diseases of the central nervous system such as epilepsy, neurodegenerative diseases and cancer.

As a result, the search is on for drugs that target connexins.

So understanding of the structure of connexins and how drugs bind to connexin channels to block or activate them is vital for treatment of these diseases. Indeed, of the 21 types of connexins known to exist in humans, few of them are currently evaluated as drug targets.

Find more information here:  Xinyue Ding et al, Structural basis of connexin-36 gap junction channel inhibition, Cell Discovery (2024). DOI: 10.1038/s41421-024-00691-y

Lichen partnerships challenged by changes in climate

Lichen, which people may think of as a single organism, is in fact a community of several species that depend on each other for survival. Lichen symbiosis includes at least one fungus and one alga, along with other fungi and bacteria in roles that are still being investigated by biologists.

The continued health of lichens is vital to the future of our Northern forests because they provide a critical winter food source for many animals. They are also valuable "sentinels" of air quality and environmental health. For these reasons, scientists are eager to understand how they may be affected by climate change.

New research published in Science Advances from the University of Minnesota investigated symbiosis in boreal oak lichen, a variety widespread on several tree species across Minnesota and the Northwoods.

Using multiple research methods, the team found:

• The partner organisms that make up lichen symbioses are not always in sync—one organism may have an extreme response to changes in moisture while its partner remains unaffected.
• These differences may drive one partner to "go it alone" under some conditions, disrupting the symbiosis—other research has observed this in corals.
• The team used gas exchange data to show asymmetries in carbon balance are widespread across evolutionarily disparate lichen groups.

Part 1

At summer temperatures, wetting with anything more than water vapor leads to unsustainable carbon losses for boreal oak lichen, which may explain why it prefers humid environments like bogs. Scientists already knew this species is vulnerable to heating and drying, now we can start to understand exactly how and why—all key insights into the threats from future climate change.
n simple cases of symbiosis, such as a clownfish and a sea anemone, the needs of the partner organisms may be well-balanced and complimentary. The research shows that symbiosis in lichens is more complex, and each organism may react differently when faced with changing weather conditions or environmental stress.

"Unexpectedly, the alga just does its own thing: once active, it doesn't seem to respond at all to the major changes that the fungus undergoes when we add liquid water. It shouldn't be a surprise that the different organisms that make up lichen symbioses respond to different cues, but it has often been far too easy to lose sight of that when working with such seemingly closely integrated symbioses."

Future research will focus on unpacking when the components of lichen symbiosis are and aren't coordinated. The team hopes to better understand what each organism does under different circumstances.

 Abigail R. Meyer et al, Symbionts out of sync: Decoupled physiological responses are widespread and ecologically important in lichen associations, Science Advances (2024). DOI: 10.1126/sciadv.ado2783

Part 2

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Why male mammals don't breast feed

New mathematical model sheds light on the absence of breastfeeding in male mammals

Being nursed by a single parent could be an evolutionary strategy to curb the spread of harmful microbes in mammals, according to a novel theory developed by mathematicians.

The rainforests of Malaysia are home to the only known case of a wild male mammal that produces milk. The Dayak fruit bat is a vanishingly rare case of male milk production, despite the fact that the potential for breastfeeding remains in place in most male mammals.

Male Dyak's fruit bats, Dyacopterus spadiceus, are able to feed their young milk from their own mammary glands. This species has one of the only known natural occurrences of paternal lactation.

In the 1970s, evolutionary theorists posited that the near absence of lactation in males, even though offspring could benefit from the extra nutrition provided, could be attributed to the uncertainty of paternity: As male mammals can't be sure they are the biological father, this reduces their evolutionary drive to invest heavily in offspring care, including breastfeeding.

Now, mathematicians from the University of York have suggested a complementary perspective. Their hypothesis, published in Nature Communications, suggests that the reason male mammals don't breastfeed might be driven by the rich community of microbes that lives in breast milk, which plays an important part in establishing the gut microbiome of the infant.

The theory demonstrates how the transmission of the milk microbiome from both parents would allow harmful microbes to spread through mammalian populations. Maternal-only lactation stops this, as restricting transmission of the milk microbiome to females in effect acts as a sieve, retaining just the microbes with beneficial effects.

When both parents are involved in feeding, the chance of a microbe being passed along and getting an initial foothold in a population is essentially doubled. So this new theory suggests selection against the transmission of harmful microbes through mammary milk could be an additional selection pressure against male lactation.

Breast milk is a living substance and it plays a key role in establishing the gut microbiome of mammals, which is a complex ecosystem of bacteria, viruses and fungi, along with their genetic material. This ecosystem plays a crucial role in health, including by helping to protect animals against disease, helping to digest food and in many other ways we are only just discovering.

While microbes are not inherently harmful or beneficial; it's their presence and abundance that dictate the overall health of this internal community. A 'wrong actor' at the early point of an animal's life could change the microbiome at a pivotal moment.

The mathematical model highlights the advantage of being fed by just one parent, but the researchers say it makes evolutionary sense for this to be the mother because there has already been an inevitable transmission of microbes during birth and perhaps also in the womb.

Part 1

This theory fits with a pattern of strategies mammals have adopted in an evolutionary bid to limit the spread of potentially harmful elements. Notably, in humans, mitochondrial DNA is exclusively passed down from the mother. This mechanism serves as a natural filter, maintaining genetic integrity by suppressing the proliferation of detrimental mutations. Additionally, the prevalence of monogamous relationships among certain species has been suggested as an adaptive response aimed at minimizing the transmission of sexually transmitted infections (STIs).

Maternal transmission as a microbial symbiont sieve, and the absence of lactation in male mammals, Nature Communications (2024). DOI: 10.1038/s41467-024-49559-5

Part 2

What type of Gold nanoparticles kill cancer

Gold particles of the size of billionths of a meter are lethal to cancer cells. This fact has been known for a long time, as has a simple correlation: The smaller the nanoparticles used to fight the cancer cells, the faster they die. However, a more interesting, more complex picture of these interactions is emerging from the latest research  using a novel microscopic technique.

Smaller kills faster—this is what was previously thought about gold nanoparticles used to fight cancer cells. Scientists thought that small nanoparticles would simply find it easier to penetrate the interior of a cancer cell, where their presence would lead to metabolic disturbances and ultimately cell death.

The reality, however, turns out to be more complex, as demonstrated by research carried out by scientists.

Nanoparticles can be produced using a variety of methods, yielding particles of different sizes and shapes. Shortly after starting their own experiments with gold nanoparticles, researchers  noticed that biology does not follow the popular rule that their toxicity is greater the smaller they are.

Spherical nanoparticles of 10 nanometers in size  turned out to be practically harmless to the glioma cell line studied. However, high mortality was observed in cells exposed to nanoparticles as large as 200 nanometers, but with a star-shaped structure.

Elucidation of the stated contradiction became possible thanks to the use of the first holotomographic microscope.

Part 1

A typical CT scanner scans the human body using X-rays, and reconstructs its spatial internal structure section by section. In biology, a similar function has recently been performed by the holotomographic microscope. Here, cells are also swept by a beam of radiation, though not high-energy radiation, but electromagnetic radiation. Its energy is chosen so that the photons do not disturb cell metabolism.

The result of the scan is a set of holographic cross-sections containing information about the distribution of refractive index changes. Since light refracts differently on the cytoplasm and differently on the cell membrane or nucleus, it is possible to reconstruct a three-dimensional image of both the cell itself and its interior.

Unlike other high-resolution microscopy techniques, holotomography does not require the preparation of samples or the introduction of any foreign substances into the cells. The interactions of gold nanoparticles with cancer cells could therefore be observed directly in the incubator, where the latter were cultured, in an undisturbed environment--what's more, with nanometric resolution--from all sides simultaneously and practically in real time.

The unique features of holotomography allowed the physicists to determine the causes of the unexpected behavior of cancer cells in the presence of gold nanoparticles. A series of experiments was conducted on three cell lines: two glioma and one colon. Among others, it was observed that although the small, spherical nanoparticles easily penetrated the cancer cells, the cells regenerated and even started to divide again, despite the initial stress.

In the case of colon cancer cells, the gold nano particles were quickly pushed out of them. The situation was different for the large star-shaped nanoparticles. Their sharp tips perforated the cell membranes, most likely resulting in increasing oxidative stress inside the cells. When these cells could no longer cope with repairing the increasing damage, the mechanism of apoptosis, or programmed death, was triggered.

Researchers used the data from the  experiments to build a theoretical model of the process of nanoparticle deposition inside the cells under study. The final result is a differential equation into which suitably processed parameters can be substituted—for the time being only describing the shape and size of nanoparticles—to quickly determine how the uptake of the analyzed particles by cancer cells will proceed over a given period of time and how they kill the cancer cells.

Joanna Depciuch et al, Modeling Absorption Dynamics of Differently Shaped Gold Glioblastoma and Colon Cells Based on Refractive Index Distribution in Holotomographic Imaging, Small (2024). DOI: 10.1002/smll.202400778

Part 2

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Kids given 'digital pacifiers' to calm tantrums fail to learn how to regulate emotions, study finds

Tantrums are part of growing up. How these outbursts of anger or frustration are managed, however, can impact children's emotional development.

An international team of researchers has investigated how giving children digital devices acting as "digital pacifiers" to avoid or manage tantrums impacts children's later anger management skills. They found that children who were routinely given digital devices when they threw a tantrum had more difficulties regulating their emotions. The researchers also stressed the importance of letting children experience negative emotions and the crucial role parents play in the process.

Children learn much about self-regulation—that is, affective, mental, and behavioral responses to certain situations—during their first few years of life. Some of these behaviors are about children's ability to choose a deliberate response over an automatic one. This is known as effortful control, which is learned from the environment, first and foremost through children's relationship with their parents.

In recent years, giving children digital devices like smart phones or tablets to control their responses to emotions, especially if they're negative, has become common. Children are fascinated by digital content, so this is an easy way to stop tantrums and it is very effective in the short term.

But researchers found  that when parents used digital emotion regulation more often, children showed poorer anger and frustration management skills. Children who were given devices more often as they experienced negative emotions also showed less effortful control at the follow-up assessment.

Tantrums cannot be cured by digital devices. And the researchers recommend new training and counseling methods  for parents. 

Cure for tantrums? Longitudinal associations between parental digital emotion regulation and children's self-regulatory skills, Frontiers in Child and Adolescent Psychiatry (2024). DOI: 10.3389/frcha.2024.1276154

Most kids get antibiotics for pink eye, study shows. Experts say they're usually not needed

Doctors are prescribing antibiotics to most kids and teens who have pink eye, despite guidelines that discourage their use, researchers reported this week.

More than two-thirds of  children and teens who saw a doctor for pink eye left with a prescription for antibiotic eye drops, their research found. The American Academy of Ophthalmology recommends that doctors do not routinely give out antibiotics for what's also called conjunctivitis, which usually clears up on its own.

Antibiotics don't work at all on viruses—the most common cause of pink eye. And even mild eye infections from bacteria will resolve on their own in most cases, the medical group says.

Pink eye is highly contagious and causes red, swollen and sometimes itchy eyes. Often, a chilled, wet towel and artificial tears are enough to ease symptoms.

But antibiotics shouldn't be overused if they aren't going to help. Moreover, the misuse can lead to resistance. 

There are more supportive measures you can take to make your child or you feel comfortable without resorting to antibiotic eye drops.

Daniel J. Shapiro et al, Antibiotic Treatment and Health Care Use in Children and Adolescents With Conjunctivitis, JAMA Ophthalmology (2024). DOI: 10.1001/jamaophthalmol.2024.2211

The beginnings of fashion: Paleolithic eyed needles and the evolution of dress

A team of researchers led by an archaeologist  are the first to suggest that eyed needles were a new technological innovation used to adorn clothing for social and cultural purposes, marking the major shift from clothes as protection to clothes as an expression of identity.

Eyed needle tools are an important development in prehistory because they document a transition in the function of clothing from utilitarian to social purposes.

From stone tools that prepared animal skins for humans to use as thermal insulation, to the advent of bone awls and eyed needles to create fitted and adorned garments, why did we start to dress to express ourselves and to impress others?

Dr. Gilligan and his co-authors reinterpret the evidence of recent discoveries in the development of clothing in their new Science Advances paper, "Paleolithic eyed needles and the evolution of dress."

Why do we wear clothes? We assume that it's part of being human, but once you look at different cultures, you realize that people existed and functioned perfectly adequately in society without clothes. What intrigued the researchers 's the transition of clothing from being a physical necessity in certain environments, to a social necessity in all environments.

Part 1

The earliest known eyed needles appeared approximately 40,000 years ago in Siberia. One of the most iconic of Paleolithic artifacts from the Stone Age, eyed needles are more difficult to make when compared to bone awls, which sufficed for creating fitted clothing. Bone awls are tools made of animal bones that are sharpened to a point. Eyed needles are modified bone awls, with a perforated hole (eye) to facilitate the sewing of sinew or thread.
As evidence suggests bone awls were already being used to create tailored clothes, the innovation of eyed needles may reflect the production of more complex, layered clothing, as well as the adornment of clothes by attaching beads and other small decorative items onto garments.
We know that clothing up until the last glacial cycle was only used on an ad hoc basis. The classic tools that we associate with that are hide scrapers or stone scrapers, and we find them appearing and going away during the different phases of the last ice ages.
Clothing became an item of decoration because traditional body decoration methods, like body painting with ocher or deliberate scarification, weren't possible during the latter part of the last ice age in colder parts of Eurasia, as people were needing to wear clothes all the time to survive.

That's why the appearance of eyed needles is particularly important because it signals the use of clothing as decoration.
Eyed needles would have been especially useful for the very fine sewing that was required to decorate clothing."

Clothing therefore evolved to serve not only a practical necessity for protection and comfort against external elements, but also a social, aesthetic function for individual and cultural identity.

The regular wearing of clothing allowed larger and more complex societies to form, as people could relocate to colder climates while also cooperating with their tribe or community based on shared clothing styles and symbols. The skills associated with the production of clothing contributed to a more sustainable lifestyle and enhanced the long-term survival and prosperity of human communities.
Covering the human body regardless of climate is a social practice that has endured.

Ian Gilligan, Palaeolithic eyed needles and the evolution of dress, Science Advances (2024). DOI: 10.1126/sciadv.adp2887. www.science.org/doi/10.1126/sciadv.adp2887

Part 2

Researchers discover 1 in 5 bacteria can break down plastic

Researchers discovered that nearly 20% of the bacterial strains they studied could degrade plastic, though they needed some encouragement to do so.

Some of the world's smallest organisms could play a significant role in solving the problem of plastic pollution. Increasingly, it is being discovered how certain bacteria can break down plastic into small particles, which can then be recycled.

Moreover, this research reveals that many more bacteria than previously thought can degrade certain types of plastics.

The external conditions are crucial because a plastic bottle doesn't just disappear when it lies in the soil for a while. Bacteria are like people in that sense. Just like us, they don't do things automatically; they need encouragement. People only start running when they are chased by a tiger.

Similarly, bacteria surrounded by a lot of sugar, and thus energy, won't do something that requires too much effort. However, if they are "hungry," they will. This was evident during lab experiments where  the researchers added plastic models to plates with bacteria. At one point, they even "fed" the bacteria perforated pieces of plastic.

 The researchers made two discoveries. First, they noticed that a remarkable number of bacteria could degrade plastics under the right conditions: as much as 18% of the strains studied. They also discovered that a gene called "Lipase A" plays a significant role. When it was present in large numbers, the organisms broke down plastic more quickly.

This research expands the pool of bacteria that we can potentially use to degrade plastic.

Jo-Anne Verschoor et al, Polyester degradation by soil bacteria: identification of conserved BHETase enzymes in Streptomyces, Communications Biology (2024). DOI: 10.1038/s42003-024-06414-z

Risk of deadly fungus from climate change
Rising temperatures could cause mutations in fungi that mean they grow more aggressively or develop drug resistance. During a survey of fungal infections in 96 Chinese hospitals, researchers discovered a fungus, Rhodosporidiobolus fluvialis, not seen before in humans. The infection was resistant to the two most common antifungal drugs — fluconazole and caspofungin. In the lab, when the fungus was exposed to higher temperatures, it quickly mutated and developed resistance against a third drug, amphotericin B, making it essentially untreatable. This is a remarkable and truly unexpected finding, which bodes badly for the future.

Pan-drug resistance and hypervirulence in a human fungal pathogen are enabled by mutagenesis induced by mammalian body temperature

https://www.nature.com/articles/s41564-024-01720-y?utm_source=Live+...

How gut bacteria affect cancer drugs
A holistic view of the gut microbiome can help to predict how people with certain cancers will respond to a type of immunotherapy. Researchers developed a scoring system based on the ratio between two different populations of gut microbes: one linked to resistance to immune checkpoint inhibitors and the other associated with positive responses. The score also included quantification of Akkermansia muciniphila, a microbe that has gained attention owing to its potential role in influencing immune responses. The work “is a breakthrough from a diagnostic point of view”.

Gut microbiome discovery provides roadmap for life-saving cancer therapies

https://www.cell.com/cell/fulltext/S0092-8674(24)00538-5?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867424005385%3Fshowall%3Dtrue

https://www.nature.com/articles/d41586-024-02070-9?utm_source=Live+...

Are viruses living organisms?

I saw several answers on Quora where people say viruses are not living.

But the question is really complicated. And Biologists are divided.

When the Nature journal recently conducted a poll, 14% of the readers who responded said they are undecided, 46 percent said viruses are living organisms, while 35% said, they are not living.

Some viewed viruses as in between chemistry and biology, because viruses can be considered dead or alive at different times. For example, a dormant virus in a test tube is not alive until it finds a host. Then it comes alive and replicates with the help of the host.

“Chemistry becomes biology when chemistry is self-replicating and evolving,” according to some biotechnologists . “Viruses fit very well to this definition. They just wait for the perfect conditions (a suitable host cell) to replicate and evolve. So viruses are 100% living organisms,” they say.

Others suggested that the real question is whether the word ‘alive’ has any scientific meaning at all. “The divide between live and dead material is artificially imposed by us as biologists and more generally by us as people,” they say. “We like categorising everything in neat little boxes, but nature is not so easily categorised.”

And the debate goes on!

Would you like to join?

But are questions in science decided using polls?

NO!

Source: Springer Nature

Losing Both Ovaries Could Come at a Serious Cost to The Brain, Researchers Find

The ovaries are involved in far more than just reproduction. The two oval-shaped glands that float on either side of the uterus don't just produce and release eggs, they also pump out hormones that help keep a person's heart, bones, brain, and immune system healthy as they age.
A new brain imaging study has scientists concerned that the surgical removal of both ovaries can have overlooked health consequences in the long run.

The analysis included data from more than 1,000 females over the age of 50 in the US. Participants who had both ovaries removed before the age of 40 showed reduced white matter in several parts of their brain compared to 907 females under the age of 50 who had not undergone the same procedure.

Participants who had both ovaries removed after age 40 also showed reduced white matter integrity, but significantly less so than those who underwent the surgery younger.

The observed changes resembled vascular brain disease more closely than Alzheimer's, the researchers note, but it's also true that these are "early, preclinical features of [Alzheimer's disease] pathology."

Recent research has found that patients who've had both of their ovaries removed before they hit menopause face a higher risk of cognitive impairment and dementia later in life. But this is one of the first studies to try and figure out why.
Part 1

To date, male brains have been the focus of the vast majority of neurological studies. Of all published brain imaging papers out there, less than 0.5 percent consider and explore the way hormones – including those produced by the gonads – can impact brain health and development.
In general, male brains possess greater white volume matter compared to female brains. Some scientists suspect this is due to differences in how sex hormones, produced by the testes and ovaries, impact the developing brain.

While testosterone is often thought of as a male hormone, it is also produced by the ovaries, and it plays a critical role in the female body. The hormone is also linked to white matter integrity in the brain.

If the ovaries are taken out of the body before menopause, the sudden loss of testosterone could have negative effects on the brain's development.

In the current brain imaging analysis, participants who had both their ovaries removed before age 40 commonly took estrogen to replace what their sex gonads once made. But this hormone replacement therapy had no impact on their white matter integrity.

"[I]t may be hypothesized that the explanation for our results is in part due to loss of testosterone," the team of researchers suggests.

"Additional studies to replicate this finding are clearly needed."

Many unanswered questions still exist to this day about what role the ovaries play in the lifelong health of female-bodied individuals and what happens when they are removed.
Part 2

For years now, scientists have debated the costs of removing the ovaries for benign conditions, and if so, at what age it is safest to do so.

In cases of cancer, it's vital that the ovaries are excised to save the patient, but bilateral oophorectomies are also commonly used to treat endometriosis, ovarian cysts, and non-cancerous fibroids.

In the US, just over half of all people undergoing a hysterectomy have both of their ovaries removed as well, and more than a third of that group are under the age of 44.

In light of recent evidence, some experts argue that the risks and benefits of removing both ovaries at a young age are not being weighed appropriately by surgeons or patients. For children and adolescents, removal of both ovaries for benign conditions may be 'unnecessary' and come with lifelong risks.

If both ovaries are removed during a person's reproductive years, the body can enter early menopause, and this increases the risk of severe chronic health conditions that include bone density loss, impaired sexual health, cardiovascular disease, cognitive impairment, sleep apnea, and arthritis.

There are numerous reasons the ovaries should be spared when possible. Protecting the brain from possible harm is just one of them.

https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.13852

Part 3

Pillars of Creation Star in New Visualization from NASA’s Hubble and Webb Telescopes

Without science is old really gold?

People argue that old is gold. "Oh, those old golden days!" They become nostalgic very often. 

But what type of gold is it? Without science?  

A new discovery of 33 ancient tombs in Egypt's southern city of Aswan  revealed "new information on diseases" prevalent at the time and how much people suffered in ancient times.

The tombs date back to the Ancient Egyptian Late Period and the Greco-Roman Periods, which collectively lasted from the seventh century BC until around the fourth century AD.

The burials were found by a joint Egyptian-Italian archaeological mission.

The studies of the mummies "indicate that 30 to 40 percent of those buried died in their youth, as newborns or as adolescents".

Preliminary studies on the remains showed that "some suffered from infectious diseases, while others had bone disorders".

The remains of several adult women showed signs of pelvic bone trauma.

Other mummies indicated "anemia, malnutrition, chest diseases, tuberculosis and signs of osteoporosis".

And there was no 'right treatment' as there was no 'science', the   pursuit and application of knowledge and understanding of the natural and social world following a systematic methodology based on evidence. 

People tried a few things based on their imagination and primitive understanding of things and people still suffered and died young.  

"Golden days"?

Source: News agencies and Science Art Lab.

Scientists developing a monoclonal antibody to neutralize Nipah virus one of the deadliest zoonotic pathogens

Nipah virus is a highly pathogenic zoonotic paramyxovirus causing regular outbreaks in humans and animals in South and Southeast Asia.

Just like Ebolavirus, SARS, SARS-CoV-2, and Marburg virus, the Nipah pathogen originated in bats. The name Nipah is derived from the name of the Malaysian village where pig farmers were infected in the late 1990s. Measles virus, although not of bat origin, is another member of the paramyxovirus family and stands out as one of the most contagious viruses known to science. While Nipah is less contagious than measles, it is capable of much higher mortality.

No licensed vaccines or therapies exist for patients infected with Nipah virus.

People infected with Nipah virus can be afflicted with dangerous respiratory impairment and brain swelling, symptoms that fuel the extraordinary fatality rates. Mortality ranges from a low of 40% to a high of 90%. The virus has been responsible for several relatively recent outbreaks in Bangladesh and India.

An experimental monoclonal antibody has now been engineered to target the deadly Nipah virus, an emerging zoonotic pathogen with a human mortality rate ranging as high as a staggering 90%.

Urgency underlies the development of therapeutics against a wide range of zoonotic viruses. The emerging pathogens have the potential to spur pandemics—or fall into the hands of malevolent forces that may use them for purposes of bioterrorism.

 Monoclonal antibodies are laboratory-produced molecules engineered to serve as substitute antibodies that can restore, enhance, modify or mimic the immune system's attack on cells that aren't wanted.

 Researchers hypothesized that a mAb (monoclonal antibody) against the prefusion conformation of the F glycoprotein may confer better protection than m102.4. To test this, two potent neutralizing mAbs against the Nipah virus F protein, hu1F5 and hu12B2, were compared in a hamster model. Hu1F5 provided superior protection to hu12B2 and was selected for comparison with m102.

In hamsters, the team found that administering hu1F5 one day after infection in hamsters led to 100% survival. It's important to note that hu1F5 also protected African green monkeys from Nipah virus even when given as late as five days after infection. In that arm of the research, all six infected animals survived. Hu1F5 also outperformed the earlier monoclonal antibody, m102.4, which protected only one out of six treated animals from death.

The team also introduced several mutations into the antibody to extend its half-life and reported that the monoclonal antibody that had superior performance in animal testing is progressing toward a phase 1 human clinical trial.

Larry Zeitlin et al, Therapeutic administration of a cross-reactive mAb targeting the fusion glycoprotein of Nipah virus protects nonhuman primates, Science Translational Medicine (2024). DOI: 10.1126/scitranslmed.adl2055

Nanorobot kills cancer cells in mice with hidden weapon

Researchers have developed nanorobots that kill cancer cells in mice. The robot's weapon is hidden in a nanostructure and is exposed only in the tumor microenvironment, sparing healthy cells. The study is published in the journal Nature Nanotechnology.

The research group has previously developed structures that can organize so-called death receptors on the surface of cells, leading to cell death. The structures exhibit six peptides (amino acid chains) assembled in a hexagonal pattern. "This hexagonal nanopattern of peptides becomes a lethal weapon".

If you were to administer it as a drug, it would indiscriminately start killing cells in the body, which would not be good. To get around this problem, the researchers have hidden the weapon inside a nanostructure built from DNA.

The art of building nanoscale structures using DNA as a building material is called DNA origami and is something the research team has been working on for many years. Now they have used the technique to create a 'kill switch' that is activated under the right conditions.

They have managed to hide the weapon in such a way that it can only be exposed in the environment found in and around a solid tumor. This means that they have created a type of nanorobot that can specifically target and kill cancer cells.

The key is the low pH, or acidic microenvironment that usually surrounds cancer cells, which activates the nanorobot's weapon. In cell analyses in test tubes, the researchers were able to show that the peptide weapon is hidden inside the nanostructure at a normal pH of 7.4, but that it has a drastic cell-killing effect when the pH drops to 6.5.

They then tested injecting the nanorobot into mice with breast cancer tumors. This resulted in a 70 percent reduction in tumor growth compared to mice given an inactive version of the nanorobot.

They now need to investigate whether this works in more advanced cancer models that more closely resemble the real human disease.

The researchers also plan to investigate whether it is possible to make the nanorobot more targeted by placing proteins or peptides on its surface that specifically bind to certain types of cancer.

A DNA Robotic Switch with Regulated Autonomous Display of Cytotoxic Ligand Nanopatterns, Nature Nanotechnology (2024). DOI: 10.1038/s41565-024-01676-4 , www.nature.com/articles/s41565-024-01676-4

AI model finds the cancer clues at lightning speed

have developed an AI model that increases the potential for detecting cancer through sugar analyses. The AI model is faster and better at finding abnormalities than the current semi-manual method.

Glycans, or structures of sugar molecules in our cells, can be measured by mass spectrometry. One important use is that the structures can indicate different forms of cancer in the cells.

However, the data from the mass spectrometer measurement must be carefully analyzed by humans to work out the structure from the glycan fragmentation. This process can take anywhere from hours to days for each sample and can only be carried out with high confidence by a small number of experts in the world, as it is essentially detective work learned over many years.

The process is thus a bottleneck in the use of glycan analyses, for example for cancer detection, when there are many samples to be analyzed.

Researchers  have developed an AI model to automate this detective work. The AI model, named Candycrunch, solves the task in just a few seconds per test. The results are reported in a scientific article in the journal Nature Methods.

The AI model was trained using a database of over 500,000 examples of different fragmentations and associated structures of sugar molecules. The training has enabled Candycrunch to calculate the exact sugar structure in a sample in 90% of cases.

Predicting glycan structure from tandem mass spectrometry via deep learning, Nature Methods (2024). DOI: 10.1038/s41592-024-02314-6

Researchers thwart resistant bacteria's strategy

Antibiotic resistant bacteria are experts in evolving new strategies to avoid being killed by antibiotics. One such bacterium is Pseudomonas aeruginosa, which is naturally found in soil and water, but also hospitals, nursing homes and similar institutions for persons with weakened immune systems are home for strains of this bacterium.

As many P. aeruginosa strains found in hospitals are resistant to most antibiotics in use, science is forced to constantly search for new ways to kill them.

Now, a team of researchers has discovered a weakness in P. aeruginosa with the potential to become the target for a new way to attack it.

The team discovered a mechanism, that reduces the formation of biofilm on the surface of P. aeruginosa. The formation of sticky, slimy biofilm is a powerful tool used by bacteria to protect themselves against antibiotics—a trick also used by P. aeruginosa.

This biofilm can be so thick and gooey that antibiotic cannot penetrate the cell surface and reach its target inside the cell. 

The researchers now worked with three newly discovered genes in a lab-grown strain of P. aeruginosa. When they overexpressed these genes, they saw a strong reduction of biofilm. Of significance is that the system affected by the genes is part of the P. aeruginosa core genome, meaning that it is universally found in all the P. aeruginosa strains sequenced so far.

Being part of P. aeruginosa's core genome, this system has been found in all investigated strains of P. aeruginosa, including a large variety of strains isolated from patients. So, there is reason to think that reduction of biofilm via this system should be effective in all known strains of P. aeruginosa.

Bacteria strains can evolve individually and mutate quickly and constantly when they are under pressure. It is not uncommon for patients infected with a P. aeruginosa strain to initially respond well to antibiotic treatment but then become resistant as the strain evolves resistance during treatment. Strains mutate, but their common core genome does not change.

In their experiments, the researchers activated the biofilm reducing system by overexpressing genes. But they also discovered that the system is naturally stimulated by cell wall stress.

So, if we stress the cell wall, it may naturally lead to a reduction in biofilm, making it easier for antibiotic to penetrate the cell wall, Currently, cell wall-targeted drugs are not widely used against P. aeruginosa, but perhaps, they could start to be used as additives to help reduce biofilm production and improve access of the existing antibiotics to the cells.

When combating infectious bacteria, there are only a limited number of targets to attack. Targets found in both bacterial and human cells cannot be attacked, as the antibiotics would also affect human cells.

Bacterial cells and human cells have some targets in common, such as the process that replicates DNA and the processes controlling basic glucose metabolism or respiration in cells.

Part 1

Among the targets unique to bacteria are various protein functions and also the bacterial cell wall is considered a suitable target, as it is very different from the human cell wall.

The uncharacterized PA3040-3042 operon is part of the cell envelope stress response and a tobramycin resistance determinant in a clinical isolate of Pseudomonas aeruginosa", Microbiology Spectrum (2024). DOI: 10.1128/spectrum.03875-23. journals.asm.org/doi/10.1128/spectrum.03875-23

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Scientists turn white fat cells into calorie-burning beige fat

A new study shows that suppressing a protein turns ordinary fat into a calorie burner and may explain why drug trials attempting the feat haven't been successful.

Researchers  have figured out how to turn ordinary white fat cells, which store calories, into beige fat cells that burn calories to maintain body temperature.

The discovery could open the door to developing a new class of weight-loss drugs and may explain why clinical trials of related therapies have not been successful.

Until now, researchers thought creating beige fat might require starting from stem cells. The new study published July 1 in the Journal of Clinical Investigation, showed that ordinary white fat cells can be converted into beige fat simply by limiting production of a protein.

Many mammals have three "shades" of fat cells: white, brown and beige. White fat serves as energy reserves for the body, while brown fat cells burn energy to release heat, which helps maintain body temperature.

Beige fat cells combine these characteristics. They burn energy, and unlike brown fat cells, which grow in clusters, beige fat cells are embedded throughout white  fat deposits.

Humans and many other mammals are born with brown fat deposits that help them maintain body temperature after birth. But, while a human baby's brown fat disappears in the first year of life, beige fat persists.

Humans can naturally turn white fat cells into beige ones in response to diet or a cold environment. Scientists tried to mimic this by coaxing stem cells into becoming mature beige fat cells.

But stem cells are rare, and the researchers wanted to find a switch he could flip to turn white fat cells directly into beige ones. They knew a protein called KLF-15 plays a role in metabolism and the function of fat cells.

Part 1

Researchers decided to investigate how the protein functioned in mice, which retain brown fat throughout their lives. They found that KLF-15 was much less abundant in white fat cells than in brown or beige fat cells.

When they then bred mice with white fat cells that lacked KLF-15, the mice converted them from white to beige. Not only could the fat cells switch from one form into another, but without the protein, the default setting appeared to be beige.

The researchers then looked at how KLF-15 exerts this influence. They cultured human fat cells and found that the protein controls the abundance of a receptor called Adrb1, which helps maintain energy balance.

Scientists knew that stimulating a related receptor, Adrb3, caused mice to lose weight. But human trials of drugs that act on this receptor have had disappointing results.
A different drug targeting the Adrb1 receptor in humans is more likely to work, according to Feldman, and it could have significant advantages over the new, injectable weight-loss drugs that are aimed at suppressing appetite and blood sugar.

This approach might avoid side effects like nausea because its activity would be limited to fat deposits, rather than affecting the brain. And the effects would be long lasting, because fat cells are relatively long-lived.
These discoveries could have a big impact on treating obesity.

Source: Journal of Clinical Investigation (2024)

https://www.jci.org/articles/view/172360

Part 2 

Scientists discover a new set of cells that control the blood-brain barrier

Researchers have discovered a new set of cells that can protect blood vessel structure in the central nervous system (CNS) known as the blood-brain barrier. Their findings have been published in the journal Science Advances.

They identified a new set of astrocytes (type of brain cells) that can control the integrity of the blood-brain barrier.

The blood-brain barrier (BBB) is a selective semi-permeable membrane between the blood and the interstitium of the brain, allowing cerebral blood vessels to regulate molecule and ion movement between the blood and the brain.

With age, or in brain disorders, the function of the blood-brain barrier is reduced.

This newly discovered subset of astrocytes expressed a protein found in bone tissue called dentin matrix protein 1 (DMP-1). These cells generate 'endfeet' and transfer mitochondria (energy generating cells) to endothelial cells which line the blood vessels of the CNS.

Reduction in the function of these astrocytes inhibited mitochondrial transfer and caused leakage of the blood-brain barrier. Mitochondrial transfer from astrocytes to blood vessel cells was identified as crucial to the maintenance of the blood-brain barrier.

Delin Liu et al, Regulation of blood-brain barrier integrity by Dmp1 -expressing astrocytes through mitochondrial transfer, Science Advances (2024). DOI: 10.1126/sciadv.adk2913

Incredible Hydrothermal Environment Discovered Deep Beneath The Ocean

A stunning new wonderland has been discovered, hidden deep beneath the ocean waves of the Arctic Circle. Off the coast of Svalbard, in Norway, more than 3,000 meters (9,842 feet) down, a field of hydrothermal vents unfolds along the Knipovich Ridge, an underwater mountain range previously thought to be fairly unremarkable. Instead, like underfloor heating, volcanic activity below the seafloor causes heat to seep through, creating havens of warmth and chemical reactions where life can gather and thrive. The field, measuring at least a kilometer in length and 200 meters in width, has been named Jøtul, for the giants of Norse mythology that live beneath mountains. In this case, the giant is Earth's internal processes, released through cracks in the seafloor. Water penetrates into the ocean floor where it is heated by magma. The overheated water then rises back to the sea floor through cracks and fissures. On its way up the fluid becomes enriched in minerals and materials dissolved out of the oceanic crustal rocks. These fluids often seep out again at the sea floor through tube-like chimneys called black smokers, where metal-rich minerals are then precipitated. Hydrothermal vent fields are some of the most interesting undersea environments. They're usually very deep beneath the ocean surface, so far down that light from the Sun can't penetrate the vast volume of water above them. At these depths, conditions are permanently dark, freezing cold, and surrounded by crushing pressures. This environment isn't exactly conducive to life, but hydrothermal vents act as strange oases. The minerals seeping out and dissolving in the water provide the basis for a food web reliant, not on photosynthesis as most life closer to the surface is, but chemosynthesis – harnessing chemical reactions for energy, rather than sunlight. These environs make for a much more dynamic and thriving deep seafloor than might be expected, giving us a clue about how life might emerge on worlds very different from our own.

https://www.nature.com/articles/s41598-024-60802-3

How insulin-triggering nutrients vary from person to person, with implications for personalized nutrition

When it comes to managing blood sugar levels, most people think about counting carbs. But new research  shows that, for some, it may be just as important to consider the proteins and fats in their diet.

The study, published in Cell Metabolism, is the first large-scale comparison of how different people produce insulin in response to each of the three macronutrients: carbohydrates (glucose), proteins (amino acids) and fats (fatty acids).

The findings reveal that production of the blood sugar-regulating hormone insulin is much more dynamic and individualized than previously thought, while showing for the first time a subset of the population who are hyper-responsive to fatty foods.

Glucose is the well-known driver of insulin, but it is surprising to see such high variability, with some individuals showing a strong response to proteins, and others to fats, which had never been characterized before.

Insulin plays a major role in human health, in everything from diabetes, where it is too low, to obesity, weight gain and even some forms of cancer, where it is too high. These findings lay the groundwork for personalized nutrition that could transform how we treat and manage a range of conditions.

For the study, the researchers conducted tests on pancreatic islets from 140 deceased male and female donors across a wide age range. The islets were exposed to each of the three macronutrients, while the researchers measured the insulin response alongside 8,000 other proteins.

Although most donors' islet cells had the strongest insulin response to carbohydrates, approximately 9% responded strongly to proteins, while another 8% of the donor cells were more responsive to fats than any other nutrient—even glucose.

This research challenges the long-held belief that fats have negligible effects on insulin release in everyone. With a better understanding of a person's individual drivers of insulin production, we could potentially provide tailored dietary guidance that would help people better manage their blood sugar and insulin levels.

The research team also examined a subset of islet cells from donors who had type 2 diabetes. As expected, these donor cells had a low insulin response to glucose. However, the researchers were surprised to see that their insulin response to proteins remained largely intact.

"This really bolsters the case that protein-rich diets could have therapeutic benefits for patients with type 2 diabetes and highlights the need for further research into protein-stimulated insulin secretion.

In the future, the researchers say it could be possible use genetic testing to determine which macronutrients are likely to trigger a person's insulin response.

 Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease, Cell Metabolism (2024). DOI: 10.1016/j.cmet.2024.06.001. www.cell.com/cell-metabolism/f … 1550-4131(24)00226-2

Doctors could soon use facial temperature for early diagnosis of metabolic diseases

A colder nose and warmer cheeks may be a telltale sign of rising blood pressure. Researchers discovered that temperatures in different face regions are associated with various chronic illnesses, such as diabetes and high blood pressure. These temperature differences are not easily perceptible by one's own touch but can instead be identified using specific AI-derived spatial temperature patterns that require a thermal camera and a data-trained model.

The results appeared July 2 in the journal Cell Metabolism. With further research, doctors could one day use this simple and non-invasive approach for early detection of diseases.

The researchers had previously used 3Dfacial structure to predict people's biological age, which indicates how well the body is aging. Biological age is closely related to the risk of diseases, including cancer and diabetes. They were curious if other features of the face, such as temperature, could also predict aging rate and health status.

They 

 analyzed facial temperatures of more than 2,800 Chinese participants between the ages of 21 and 88. Then, the researchers used the information to train AI models that could predict a person's thermal age. They identified several key facial regions where the temperatures were significantly related to age and health, including the nose, eyes and cheeks.

The research team found the temperature of the nose decreases with age at a rate faster than other parts of the face, meaning people with warmer noses have a younger thermal age. At the same time, temperatures around the eyes tend to increase with age.

The team also found that people with metabolic disorders such as diabetes and fatty liver disease had faster thermal aging. They tended to have higher eye area temperatures than their healthy counterparts of the same age. People with elevated blood pressure also had higher cheek temperatures.
By analyzing participants' blood samples, the team revealed that the increase in temperatures around the eyes and cheeks was mainly because of an increase in cellular activities related to inflammation, such as repairing damaged DNAs and fighting infections. The increase in these activities led to a rise in temperatures in certain facial regions.

The thermal clock is so strongly associated with metabolic diseases that previous facial imaging models were not able to predict these conditions.
Part 1

Due to this connection, the team set out to test if exercise could influence thermal age. They asked 23 participants to jump rope for at least 800 times daily for two weeks. To the team's surprise, these participants reduced their thermal age by five years after just two weeks of exercise.

Next, the team wants to explore if they can use thermal facial imaging to predict other diseases, such as sleeping disorders or cardiovascular problems.
Applying thermal facial imaging in clinical settings holds significant potential for early disease diagnosis and intervention.

Yu et al. Thermal Face Image Analyses Reveal Quantitative Hallmarks of Aging and Metabolic Diseases, Cell Metabolism (2024). DOI: 10.1016/j.cmet.2024.05.012. www.cell.com/cell-metabolism/f … 1550-4131(24)00188-8

Treatment with a mixture of antimicrobial peptides found to impede antibiotic resistance

A common infection-causing bacteria was much less likely to evolve antibiotic resistance when treated with a mixture of antimicrobial peptides rather than a single peptide, making these mixtures a viable strategy for developing new antibiotic treatments. Researchers report these findings in a study published July 2 in PLOS Biology.

Antibiotic-resistant bacteria have become a major threat to public health. The World Health Organization estimates that 1.27 million people died directly from drug-resistant strains in 2019 and these strains contributed to 4.95 million deaths.
While bacteria naturally evolve resistance to antibiotics, misuse and overuse of these drugs has accelerated the problem, rendering many antibiotics ineffective. One emerging strategy to combat antibiotic resistance is the use of antimicrobial peptides, which are chains of amino acids that function as broad-spectrum antimicrobial compounds and are key components of the innate immune system in animals, fungi and plants.

In the new study, researchers investigated whether antimicrobial peptide mixtures synthesized in the lab could reduce the risk of the pathogen Pseudomonas aeruginosa from evolving antimicrobial resistance, compared to exposure to a single antimicrobial peptide.

They found that using antimicrobial peptide mixtures carried a much lower risk of the bacteria developing resistance. The mixtures also helped prevent the bacteria from developing cross-resistance to other antimicrobial drugs, while maintaining—or even improving—drug sensitivity.

Overall, the findings suggest that the use of antimicrobial peptide mixtures is a strategy worth pursuing in the search for new, longer-lasting treatments for bacteria.

The researchers suspect that using a cocktail of multiple antimicrobial peptides creates a larger set of challenges for bacteria to overcome, which can potentially delay the evolution of resistance, compared to traditional antibiotics. Furthermore, these cocktails can be synthesized affordably, and previous studies have shown them to be non-toxic in mice.

Bernardo Antunes et al, The evolution of antimicrobial peptide resistance in Pseudomonas aeruginosa is severely constrained by random peptide mixtures, PLoS Biology (2024). DOI: 10.1371/journal.pbio.3002692

Doctor ants: Ants too perform amputations to save injured nestmates!

Saving lives through surgery is no longer exclusive to humans. In a study published July 2 in the journal Current Biology, scientists detail how Florida carpenter ants, a common, brown species native to its namesake, selectively treat the wounded limbs of fellow nestmates—either by wound cleaning or amputation.

When experimentally testing the effectiveness of these "treatments," not only did they aid in recovery, but the research team found the ants' choice of care catered to the type of injury presented to them.

The researchers found that this mechanical care involves one of two routes. The ants would either perform wound cleaning with just their mouthparts or perform a cleaning followed by the full amputation of the leg. To select which route they take, the ants appear to assess the type of injury to make informed adjustments on how best to treat.

In this study, two types of leg injuries were analyzed, lacerations on the femur and those on the ankle-like tibia. All femur injuries were accompanied by initial cleaning of the cut by a nestmate, followed by a nestmate chewing off the leg entirely. In contrast, tibia injuries only received the mouth cleaning. In both cases, intervention resulted in ants with experimentally infected wounds having a much greater survival rate.

Femur injuries, where they always amputated the leg, had a success rate around 90% or 95%. And for the tibia, where they did not amputate, it still achieved about the survival rate of 75%.

Part1

In tibia injuries, the flow of the hemolymph was less impeded, meaning bacteria could enter the body faster. While in femur injuries the speed of the blood circulation in the leg was slowed down.

You may expect, then, if tibia damage results in faster infections, amputating the full leg would be most appropriate, but the opposite is observed. It turns out the speed at which the ants can amputate a leg makes a difference.

An ant-assisted amputation takes at least 40 minutes to complete. Experimental testing demonstrated that with tibia injuries, if the leg was not immediately removed post-infection, the ant would not survive.

"Thus, because they are unable to cut the leg sufficiently quickly to prevent the spread of harmful bacteria, ants try to limit the probability of lethal infection by spending more time cleaning the tibia wound.

The fact that the ants are able to diagnose a wound, see if it's infected or sterile, and treat it accordingly over long periods of time by other individuals—the only medical system that can rival that would be the human one.

And they can do it without studying medicine and learning surgery! It's really all innate behaviour!

Ant behaviors change based on the age of an individual, but there is very little evidence of any learning.

"When you look at the videos where you have the ant presenting the injured leg and letting the other one bite off completely voluntarily, and then present the newly made wound so another one can finish cleaning process—this level of innate cooperation  is quite striking", say the researchers.

Erik Frank et al, Wound-dependent leg amputations to combat infections in an ant society, Current Biology (2024). DOI: 10.1016/j.cub.2024.06.021. www.cell.com/current-biology/f … 0960-9822(24)00805-4

Part 2

Longest Cyclone on Record Crossed The Entire Southern Indian Ocean in 2023

Cyclone Freddy, which crossed the entire southern Indian Ocean before wreaking devastation on southeastern Africa last year, was the longest-lasting tropical cyclone ever recorded at 36 days, the UN confirmed Tuesday.

A panel of experts has been poring over the data surrounding the storm since its remarkable journey in February and March last year.

The United Nations' weather and climate agency concluded it had indeed broken the previous record.

The extreme weather evaluation committee "recognised Tropical Cyclone Freddy's duration of 36.0 days at tropical storm status or higher as the new world record for the longest tropical cyclone duration", the World Meteorological Organization (WMO) said in a statement.

• Freddy crossed the Indian Ocean basin in February-March 2023.
• Madagascar and southeastern Africa bore brunt of human and economic losses.
• Freddy was 36 days at tropical storm status or higher, beating record of John (1994)
• Freddy was 2nd longest in terms of distance travelled
• Monitoring of extremes increases understanding of weather and climate impacts.

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Bright Light at Night May Raise Type 2 Diabetes Risk, Study Suggests

The glow of a lightbulb or smartphone at night can mess with the body's circadian rhythm. Now, a new study suggests that exposure to artificial light after midnight may raise the risk of developing type 2 diabetes. The research was conducted among nearly 85,000 people, between the ages of 40 and 69, who wore devices on their wrists, day and night for one week, to track their exposure to different levels of light.

As part of the UK Biobank experiment, the health of the cohort was tracked for as long as nine years. Those volunteers who later went on to develop type 2 diabetes were more likely to have been exposed to light between 12:30 am and 6:00 am, during the week-long study period.

The results do not prove cause and effect, but they do reveal a dose-dependent relationship between brighter light in the middle of the night and the risk of a metabolic disorder, which bolsters the association.

Those participants in the top 10 percent for light exposure at night had as much as a 67 percent higher risk of developing type 2 diabetes than those in the bottom 50th percentile.

Research suggests that exposure to artificial light at night, whether it be yellow light from your reading lamp or blue light from your smartphone or TV, can make it harder to fall asleep. But even when researchers accounted for sleep patterns and duration in the current study, the results held, which suggests another mechanism is at play.
Other possible contributing factors, like a person's sex, their genetic risk for diabetes, their diet, physical activity, daylight exposure, smoking, or alcohol use, also had no impact on the results.

Advising people to avoid night light is a simple and cost-effective recommendation that may ease the global health burden of type 2 diabetes," conclude the authors of the study.
Part 1

In the past, some other observational studies have also linked artificial light at night to insulin resistance, but these experiments did not measure indoor, artificial light sources nearly as closely or for as long.

Emerging evidence in animals and humans suggests exposure to artificial light can disrupt circadian rhythms, leading to reduced glucose tolerance, altered insulin secretion, and weight gain – all of which are tied to an increased risk of metabolic disorders like type 2 diabetes.

One major limitation of the study is that researchers were not able to take into account meal times, which can have an impact on both circadian rhythms and glucose tolerance. Furthermore, some socioeconomic factors, like a person's housing situation, were accounted for at a regional, not an individual level, and only older adults were considered.

There's also the fact that individual bodies respond very differently to light, with some studies suggesting the intensity of light needed to suppress the production of melatonin, which helps regulate our circadian rhythm, can range from 6 to 350 lux.
Nevertheless, previous experiments suggest that when melatonin is disrupted and the circadian rhythm is thrown out of whack, it can lead to the pancreas secreting less insulin. This could be a contributing factor to the development of diabetes.

Far more rigorous studies are needed before scientists can truly understand how light at night impacts the circadian rhythm and what that may do, in turn, to the health of the body's metabolism.

Some studies suggest that even a weekend of camping without artificial light can help reset a person's circadian rhythm. Perhaps that's just what the doctor should order.

https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(24)00110-8/fulltext

Part 2

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Strategies that could stop cats from scratching your furniture, according to science

Many cat owners are familiar with torn cushions, carpets, and couches. The feline instinct to scratch is innate, but is often perceived as a behavioral problem by cat owners, and sometimes leads to interventions that are not cat-friendly.

Now, an international team of researchers has investigated which factors influence undesired scratching behavior in domestic cats. The team has published its findings in Frontiers in Veterinary Science.

Scientists found that  certain factors—such as the presence of children at home, personality traits of cats, and their activity levels—significantly impact the extent of scratching behaviour.

The researchers' results showed that there are several factors that influence cats' scratching behaviour. They saw a clear link between certain environmental and behavioural factors and increased scratching behaviour in cats.

Specifically, the presence of children in the home as well as high levels of play and nocturnal activity significantly contribute to increased scratching. Cats described as aggressive or disruptive also exhibited higher levels of scratching.

Stress, the researchers said, was found to be a leading reason for unwanted scratching. For example, the presence of children, particularly while they are small, might amplify stress and be one of several causes that can make felines stress-scratch. The link between increased scratching and children in the home, however, is not fully understood and further study is needed. Another factor that could also be connected to stress is playfulness. When cats play for a long time, their stress levels can rise because of the uninterrupted stimulation.

Part 1

While some factors that favor scratching—such as the cat's personality or the presence of children—cannot be changed, others can, the researchers said. Placing scratch posts in areas the cat frequently passes or near to their preferred resting spot, or the use of pheromones, for example, can lessen cats' scratching on furniture.

Providing safe hiding places, elevated observation spots, and ample play opportunities can also help alleviate stress and engage the cat in more constructive activities.

The key is to establish multiple short play sessions that mimic successful hunting scenarios. These play sessions are more likely to sustain cats' interest and reduce stress, which ultimately can reduce excessive scratching on furniture. They can also foster the bond between cats and their caretakers, the researchers say.

Understanding the underlying emotional motivations of scratching behavior, such as frustration, which seem to be linked to personality traits and environmental factors, allows caregivers to address these issues directly.

Evaluating Undesired Scratching in Domestic Cats: A Multifactorial Approach to Understand Risk Factors, Frontiers in Veterinary Science (2024). DOI: 10.3389/fvets.2024.1403068

Part 2

Scientists discover PVP-037, a potent vaccine adjuvant

Many vaccines are only partially effective, have waning efficacy, or do not work well in the very young or the very old. For several years researchers have tried improving vaccines by adding compounds known as adjuvants to boost vaccine recipients' immune responses.

Now they've identified a new and promising adjuvant of their own, dubbed PVP-037. The finding is published in Science Advances.

In principle, this compound can be added to any vaccine to enhance its action.

 Adjuvants are like rocket fuel for the immune system. PVP-037 is one of the most active adjuvants scientists 've discovered, and they think it induces a greater, more durable, and broader immune response to vaccines.

The researchers began by screening more than 200,000 small molecules from a Harvard Medical School library in human immune cells—specifically, in primary peripheral blood mononuclear cells, obtained from donors and cultured in their own plasma using a method developed within the Precision Vaccines Program. This yielded about 25 confirmed hits, with PVP-037 being the most active.

PVP-037 belongs to a family of molecules called imidazopyrimidines, which the study found to be active immunomodulators. PVP-037 and its analogs target the innate immune system, stimulating the pattern-recognition receptors TLR7 and TLR8 on antigen-presenting cells such as monocytes and dendritic cells.

An optimized version of PVP-037 demonstrated broad innate immune activation in the donor immune cells, inducing NF-κB and production of TNF and other cytokines, signaling molecules that rally a wider immune response. Notably, PVP-037 did not provoke such a response in cultured cell lines. In live mice, it enhanced antibody responses against influenza and SARS-CoV-2 vaccine proteins.

In addition to inducing robust immune activity, the compound is stable, easy to work with, and lends itself to chemical optimization for medical use. It can be formulated in most standardly-used drug delivery systems, such as oil-in-water emulsions.

 Dheeraj Soni et al, From Hit to Vial: Precision discovery and development of an imidazopyrimidine TLR7/8 agonist adjuvant formulation, Science Advances (2024). DOI: 10.1126/sciadv.adg3747. www.science.org/doi/10.1126/sciadv.adg3747

Fighting COVID-19 with a cancer drug: A new approach to preventing irreversible organ damage in infectious diseases

Twelve years ago, cancer researchers identified a molecule that helps cancer cells survive by shuttling damaging inflammatory cells into tumor tissue. In new research, they show that the same molecule does the same thing in lung tissue infected with COVID-19—and that the molecule can be suppressed with a repurposed cancer drug.

The work, published in Science Translational Medicine, represents a new approach to preventing irreversible organ damage in infectious diseases like COVID-19 and methicillin-resistant Staphylococcus aureus (MRSA).

The two key players in this scenario are inflammatory cells called myeloid cells, and an enzyme called PI3K gamma (phosphatidylinositol 3,4,5-kinase gamma). Myeloid cells belong to our innate immune system—the immunity we're born with before we're exposed to pathogens in the environment—and work very quickly to kill deadly agents like SARS-CoV-2, the virus that causes COVID-19.

This work shows that drugs that can prevent the recruitment of damaging myeloid cells into tissues that are infected with severe agents like COVID-19 or MRSA have a significant benefit in preserving tissue function if given early enough in an infection.

Most other COVID-19 drugs target the virus, either preventing infection in the first place or preventing the virus from making more of itself after infection. The current approach targets the host, keeping the immune system from overreacting or fibers building up in the lungs.

Myeloid cells protect us, but they can also do a lot of damage. 

If you have a little infection, myeloid cells come in, kill bacteria, release alerts that recruit even more potent killer immune cells, and produce substances that can heal the damage. But if you get an infection that's too strong, you get overproduction of these alert signals, and the substances they release to kill these infective agents can also kill yourself. That's what happens in COVID-19.

Part 1

PI3K gamma promotes the movement of myeloid cells into cancerous tissues, as found in the team's work with cancer twelve years ago. In the current work, they show that PI3K gamma also helps move myeloid cells into tissues infected with SARS-CoV-2.

That led them to reason that a cancer drug that inhibits PI3K gamma, called eganelisib, might be effective in suppressing inflammation in COVID-19 by suppressing PI3K gamma's ability to move myeloid cells into infected tissue.

Using a combination of bulk RNA sequencing and bioinformatics, the scientists analyzed tissues from humans and mice to see how SARS-CoV-2 changed the cellular and molecular makeup of infected tissues. They then treated the tissue with eganelisib to see if suppressing PI3K gamma made a difference.
The researchers sequenced COVID-19 patient lung tissue and showed that when patients have COVID-19, a lot of their lung cells are killed and there's a huge increase in myeloid cells. They also found the same thing in infected mice.

When they treated with the drug, they showed that eganelisib prevents entry of myeloid cells into tissue so they can't do all that damage. Further studies will determine if it can actually reverse damage. The team also had the same results in mice infected with MRSA.

Ryan Shepard et al, PI3Kγ inhibition circumvents inflammation and vascular leak in SARS-CoV-2 and other infections, Science Translational Medicine (2024). DOI: 10.1126/scitranslmed.adi6887. www.science.org/doi/10.1126/scitranslmed.adi6887

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Human crying stresses out dogs more than pigs

Some animals can have babies without a sexual partner

Science explains how

A boa constrictor in the U.K. gave birth to 14 babies—without a mate.

 The result of a secret rendezvous? Probably not. Females of species have the ability to reproduce asexually, without sperm from a male. The process is called parthenogenesis, from the Greek words for "virgin" and "birth."

Some plants and insects can do it, as well as some amphibians, reptiles, birds and fish. A stingray named Charlotte that was thought to have become pregnant by this method died this week at an aquarium in North Carolina, though she never delivered and it is unclear if she was ever pregnant.

Some wasps, crustaceans and lizards reproduce only through parthenogenesis. But in other species it's rare and usually only observed in captivity. Scientists have a good idea how it happens, though they aren't clear why it happens.

A female's egg fuses with another cell, often a cell leftover from a process that allows the female to create the egg. That cell, known as a polar body, gives the egg the genetic information it would normally get from sperm. The cell starts dividing and that leads to the creation of an embryo.

The snake, a 6-foot, 13-year-old Brazilian Rainbow Boa named Ronaldo, gave birth last week after having no contact with any other snakes for at least nine years, according to the City of Portsmouth College, which kept the snake.

AP

Re-engineering cancerous tumors to self-destruct and kill drug-resistant cells

Treating cancer can sometimes feel like a game of Whac-A-Mole. The disease can become resistant to treatment, and clinicians never know when, where and what resistance might emerge, leaving them one step behind. But a team of researchers has found a way to reprogram disease evolution and design tumors that are easier to treat.

They created a modular genetic circuit that turns cancer cells into a "Trojan horse," causing them to self-destruct and kill nearby drug-resistant cancer cells. Tested in human cell lines and in mice as proof of concept, the circuit outsmarted a wide range of resistance.

The findings were published today, July 4, in the journal Nature Biotechnology. The researchers also filed a provisional application to patent the technology described in the paper.

Selection gene drives are a powerful new paradigm for evolution-guided anticancer therapy.The idea that we can use a tumor's inevitability of evolution against it is an excellent strategy.

Newer personalized cancer medicines often fail, not because the therapeutics aren't good, but because of cancer's inherent diversity and heterogeneity. Even if a frontline therapy is effective, resistance eventually develops and the medication stops working, allowing the cancer to return.

Clinicians then find themselves back at square one, repeating the process with a new drug until resistance emerges again. The cycle escalates with each new treatment until no further options are available.

You are dealing with an unpredictable opponent. You don't know what is going to be the best drug to treat the tumor. You're always on your back foot, unprepared.

The researchers wondered if, instead, they could get one step ahead. Could they potentially eliminate resistance mechanisms before the cancer cells have a chance to evolve and pop up unexpectedly? Could they force a specific "mole" to pop out on the board, one that they prefer and are prepared to fight?
What started as a thought experiment is proving to work. The team created a modular circuit, or dual-switch selection gene drive, to introduce into non-small lung cancer cells with an EGFR gene mutation. This mutation is a biomarker that existing drugs on the market can target.
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The circuit has two genes, or switches. Switch one acts like a selection gene, allowing the researchers to turn drug resistance on and off, like a light switch. With switch one turned on, the genetically modified cells become temporarily resistant to a specific drug, in this case, to a non-small lung cancer drug.

When the tumor is treated with the drug, the native drug-sensitive cancer cells are killed off, leaving behind the cells modified to resist and a small population of native cancer cells that are drug-resistant. The modified cells eventually grow and crowd out the native resistant cells, preventing them from amplifying and evolving new resistance.
The resulting tumor predominantly contains genetically modified cells. When switch one is turned off, the cells become drug-sensitive again. Switch two is the therapeutic payload. It contains a suicide gene that enables the modified cells to manufacture a diffusible toxin that's capable of killing both modified and neighboring unmodified cells.

It not only kills the engineered cells, but it also kills the surrounding cells, namely the native resistant population.
That's critical. That's the population you want to get rid of so that the tumor doesn't grow back.
The team first simulated the tumor cell populations and used mathematical models to test the concept. Next, they cloned each switch, packaging them separately into viral vectors and testing their functionality individually in human cancer cell lines. They then coupled the two switches together into a single circuit and tested it again. When the circuit proved to work in vitro, the team repeated the experiments in mice.

However, the team didn't just want to know that the circuit worked; they wanted to know it could work in every way. They stress tested the system using complex genetic libraries of resistance variants to see if the gene drive could function robustly enough to counter all the genetic ways that resistance could occur in the cancer cell populations.
And it worked: Just a handful of engineered cells can take over the cancer cell population and eradicate high levels of genetic heterogeneity. It's one of the biggest strengths of the paper, conceptually and experimentally.
The beauty is that they're able to target the cancer cells without knowing what they are, without waiting for them to grow out or resistance to develop because at that point it's too late.
The researchers are currently working on how to translate this genetic circuit so that it can be delivered safely and selectively into growing tumors and eventually metastatic disease.

 Programming tumor evolution with selection gene drives to proactively combat drug resistance, Nature Biotechnology (2024). DOI: 10.1038/s41587-024-02271-7. www.nature.com/articles/s41587-024-02271-7

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Reversing chemotherapy resistance in pancreatic cancer

Pancreatic cancer is a particularly aggressive and difficult-to-treat cancer, in part because it is often resistant to chemotherapy. Now, researchers  have revealed that this resistance is related to both the physical stiffness of the tissue around the cancerous cells and the chemical makeup of that tissue. Their work, published on July 4 in Nature Materials, shows that this resistance can be reversed and reveals potential targets for new pancreatic cancer treatments.

They found that stiffer tissue can cause pancreatic cancer cells to become resistant to chemotherapy, while softer tissue made the cancer cells more responsive to chemotherapy.

The researchers focused their efforts on pancreatic ductal adenocarcinoma, a cancer that starts in the cells lining the ducts of the pancreas and accounts for 90% of pancreatic cancer cases. In these cancers, the network of materials between the cells, known as the extracellular matrix, becomes notably stiffer. Scientists have theorized that this stiff material acts as a physical block, stopping chemotherapy drugs from reaching cancerous cells, but treatments based on this idea have not been effective in humans.

The researchers worked to develop a new system to study these changes to the extracellular matrix and better understand their impact on pancreatic cancer cells. They designed three-dimensional materials that mimicked the biochemical and mechanical properties of both pancreatic tumors and healthy pancreas tissues, and used them to culture cells from pancreatic cancer patients.

They  created a designer matrix that would allow us to test the idea that these cancerous cells might be responding to the chemical signals and mechanical properties in the matrix around them.

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