Spatial genomics approach shows cancers grow uniformly, challenging the idea of 'two-speed' entities

Researchers have discovered that cancer grows uniformly throughout its mass, rather than at the outer edges. The work, published in the journal eLife, challenges decades-old assumptions about how the disease grows and spreads.

The researchers challenge the old idea  that a tumour is a 'two-speed' entity with rapidly dividing cells on the surface and slower activity in the core. For the last 50 years, researchers have hypothesized that tumors grow faster at their outer edges. Cancer cells on the surface are thought to have natural advantages compared to cells deep within. For example, peripheral cells have better access to nutrients and oxygen from surrounding healthy tissues. They can also get rid of their waste more easily. As a tumor grows, its center gets further and further away from the blood vessels in the area where it is growing. The cells in a tumor's core get less and less oxygen and nutrients. The cells are also under more mechanical pressure, with compression limiting their ability to divide.

Instead, this work shows they are uniformly growing masses, where every region is equally active and has the potential to harbour aggressive mutations.

These  findings have implications for tumor evolution. The constant churn of cells dying and being replaced by new ones throughout the tumour volume gives cancer many opportunities for evolutionary innovations, such as escaping from immune surveillance.

The researchers made the discovery thanks to spatial genomics, a technique used to study the genetic information of cells in their exact locations within a tissue.

The team obtained data from previous studies where hundreds of small samples were taken from different parts of liver tumors, both in two- and three-dimensional space. This provided a detailed map of the mutations throughout the tumor.
They looked at the mutations in each of the samples, and developed a method to measure the direction and spread of these mutations, allowing them to calculate the angles between the positions of parent cells and their mutated offspring.

In the surface growth model, these angles would point outwards. Instead, the researchers found the angles were spread evenly in all directions, showing uniform growth throughout the tumor.

The study also looked at how mutations were spread within the tumor. If cancer cells grew mostly at the edges, mutations would be more clustered. They found that mutations were spread out, suggesting that cells were dividing all over the tumor.
Part 1

To validate their findings further, the researchers used computer simulations to create different virtual tumors, some with surface growth and others with volume growth. The researchers compared the patterns of mutations from the simulations to the patterns found in the real tumor data.

They found that mutation patterns in the real tumors matched the patterns from the volume growth simulations but not the surface growth simulations.

One of the limitations of the study is that it focused on liver cancer, so the findings might not apply universally to all types of cancer. Another limitation is that the study mainly provides insights into the early stages of tumor growth, which might not fully capture the behavior of larger or metastatic types of cancer.

Arman Angaji et al, High-density sampling reveals volume growth in human tumours, eLife (2024). DOI: 10.7554/eLife.95338.2

Part 2

Why are South Asians more diabetic prone?

A genetic predisposition to having lower insulin production and less healthy fat distribution are major causes of early-onset type 2 diabetes in  South Asian people, according to new research. These genetic factors also lead to quicker development of health complications, earlier need for insulin treatment, and a weaker response to some medications.

The findings, published in Nature Medicine, reinforce the need to understand how genetic variation across different population groups can influence the onset of diseases, treatment responses, and disease progression.

Key discoveries from the study include:

• Genetic signatures in South Asians: The younger age of onset in South Asians is strongly linked to genetic signatures that lead to both lower insulin production and unfavorable patterns of body fat distribution and obesity. The most significant genetic signature influencing whether a South Asian person develops type 2 diabetes, and at a young age, is a reduced ability of pancreatic beta cells to produce insulin. This genetic signature also increases the risk of gestational diabetes and the progression of gestational diabetes to type 2 diabetes after pregnancy.

• • Treatment responses: The genetic signatures identified in the study provide vital clues about how different people may respond to type 2 diabetes treatments. For example, individuals with high genetic risk for low insulin production were less likely to respond to common medications such as sodium-glucose co-transporter 2 inhibitors and were more likely to require insulin therapy.

  • High genetic-risk group identified: The study identified a subset of people with extreme genetic signatures for both low insulin production and unfavorable fat distribution. These individuals were found to develop type 2 diabetes an average of eight years earlier and at lower body mass index. Over time, these individuals were more likely to need insulin treatment and were at higher risk for diabetes complications such as eye and kidney disease.

Part 1

This work also tells us how important it is to move away from a 'one-size-fits-all' approach to managing type 2 diabetes, and we hope that this will allow us to find ways to offer more precise treatments that treat the condition more effectively and reduces the development of diabetes complications.

Genes & Health will contribute to future efforts to ensure that precision medicine approaches are developed and bring real benefits to south Asian communities living with, and at risk of, type 2 diabetes.

Genetic basis of early onset and progression of type 2 diabetes in south Asians, Nature Medicine (2024). DOI: 10.1038/s41591-024-03317-8. www.nature.com/articles/s41591-024-03317-8 

Part 2

Long COVID brain fog linked to lung function

In patients with long COVID, lower pulmonary gas exchange may be associated with impaired cognitive function, according to a study presented at the annual meeting of the Radiological Society of North America (RSNA).

People with long COVID may exhibit a wide variety of symptoms, including difficulty concentrating ("brain fog"), change in sense of smell or taste, fatigue, joint or muscle pain, dyspnea (shortness of breath), digestive symptoms, and more. These symptoms may persist for weeks, months, or even years after COVID-19 infection.

In pulmonary gas exchange, oxygen moves from the lungs to the bloodstream, while carbon dioxide moves from the bloodstream to the lungs.

If these findings can be generalized to the long COVID population, the study suggests that there may be a causative relationship between cognitive dysfunction and lung dysfunction, suggesting a potential treatment strategy using methods that target improved gas exchange, say the researchers.

Source: https://www.rsna.org/annual-meeting

A mathematical definition of cell death?

Cellular death is a fundamental concept in the biological sciences. Given its significance, its definition depends on the context in which it takes place, and lacks a general mathematical definition.

Researchers now propose a new mathematical definition of death based on whether a potentially dead cell can return to a predefined "representative state of living," which are the states of being that we can confidently call "alive." The researchers' work could be useful for biological researchers and future medical research.

The paper is published in Physical Review Research.

While it's not something we like to think about, death comes for us all eventually, whether you're an animal, a plant, or even a cell. And even though we can all differentiate between what is alive and dead, it might be surprising to know that death at a cellular level lacks a widely recognized mathematical definition.

Given that cell death plays such an important role in various biological processes and can have important health implications, it's of critical importance to understand what we really mean by cellular death, especially in research.

The scientific goal is to understand the inherent difference between life and nonlife, mathematically; why the transition from nonlife to life is so difficult, while the other way around is so easy. 

The  aim in this project was to develop a mathematical definition and computational method to quantify the life-death boundary. Researchers were able to do this by exploiting an important feature of biological reaction systems, specifically enzymatic reactions within cells.

Part 1

The researchers proposed a mathematical definition of cell death. It's based on the way cellular states, including metabolism, can be controlled by modulating the activities of enzymes. They define dead states as those states from which cells cannot return to an apparent "living" state, regardless of the modulation of any biochemical processes.
This led them to develop a computational method for quantifying the life-death boundary, which they call "stoichiometric rays." The method was developed by focusing on enzymatic reactions and the second law of thermodynamics, which states that systems naturally move from ordered to disordered states.

Researchers could use these methods to better understand, control, and possibly even reverse, cellular death in controlled lab experiments.
The conclusion : We naively believe that death is irreversible, but it is not so trivial and does not have to be the case. Should death come more under our control, human beings, our understanding of life, and society will change completely. In this sense, to understand death is crucial in terms of science and also in terms of social implications. This is one step towards that goal.

Yusuke Himeoka et al, A theoretical basis for cell deaths. Physical Review Research (2024). On arXiv. DOI: 10.48550/arxiv.2403.02169

Part 2

The sound of traffic increases stress and anxiety, research shows

Manmade sounds such as vehicle traffic can mask the positive impact of nature soundscapes on people's stress and anxiety, according to a study published November 27, 2024, in the open-access journal PLOS ONE 

Existing research shows that natural sounds, like birdsong, can lower blood pressure, heart, and respiratory rates, as well as self-reported stress and anxiety. Conversely, anthropogenic soundscapes, like traffic or aircraft noise, are hypothesized to have negative effects on human health and well-being in a variety of ways.

The study found that listening to a natural soundscape reduced self-reported stress and anxiety levels, and also enhanced mood recovery after a stressor. However, the benefits of improved mood associated with the natural soundscape was limited when traffic sounds were included.

The natural soundscape alone was associated with the lowest levels of stress and anxiety, with the highest levels reported after the soundscape that included 40 miles per hour traffic.

The authors conclude that reducing traffic speed in urban areas might influence human health and well-being not only through its safety impacts, but also through its effect on natural soundscapes.

The study shows that listening to natural soundscapes can reduce stress and anxiety, and that anthropogenic sounds such as traffic noise can mask potential positive impacts. Reducing traffic speeds in cities is therefore an important step towards more people experiencing the positive effects of nature on their health and well-being.

Natural soundscapes enhance mood recovery amid anthropogenic noise pollution, PLOS ONE (2024). DOI: 10.1371/journal.pone.0311487

Brains grew faster as humans evolved

Modern humans, Neanderthals, and other recent relatives on our human family tree evolved bigger brains much more rapidly than earlier species, a new study of human brain evolution has found.

Scientists found that brain size increased gradually within each ancient human species rather than through sudden leaps between species. The research, published November 26 in the Proceedings of the National Academy of Sciences, overturns long-standing ideas about human brain evolution.

The team assembled the largest-ever dataset of ancient human fossils spanning 7 million years and used advanced computational and statistical methods to account for gaps in the fossil record. These innovative approaches provided the most comprehensive view yet of how brain size evolved over time.

This study completely changes our understanding of how human brains evolved. It was previously thought that brain size jumps dramatically between species, like new upgrades between the latest computer models. This study instead shows a steady, incremental 'software update' happening within each species over millions of years.

The research challenges old ideas that some species, like Neanderthals, were unchanging and unable to adapt and instead highlights gradual and continuous change as the driving force behind brain size evolution.

Big evolutionary changes don't always need dramatic events. They can happen through small, gradual improvements over time, much like how we learn and adapt today, say the researchers.

The researchers also uncovered a striking pattern: While larger-bodied species generally had bigger brains, the variation observed within an individual species did not consistently correlate with body size. Brain size evolution across long evolutionary timescales extending millions of years is therefore shaped by different factors to those observed within individual species—highlighting the complexity of evolutionary pressures on brain size.

The conclusion:  Our hallmark large brains arose primarily from gradual changes within individual species.

Thomas A. Püschel et al, Hominin brain size increase has emerged from within-species encephalization, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2409542121

Biologists identify traits correlating with all bird extinctions since 1500

Looking to inform the conservation of critically endangered bird species, biologists have completed an analysis identifying traits that correlate with all 216 bird extinctions since 1500.

Species most likely to go extinct sooner were endemic to islands, lacked the ability to fly, had larger bodies and sharply angled wings, and occupied ecologically specific niches, according to research published this month. The work appears in the journal Avian Research.

While some of these findings mirror previous research on extinct birds, they are the first to correlate bird traits with the timing of extinctions.

The team simultaneously analyzed a broad range of biogeographical, ecological and life history traits previously associated with extinction and extinction risk for bird species that have gone extinct as well as those that lack recent confirmed sightings and have therefore disappeared.

While only around 2% of the world's bird species have gone extinct since 1500, the year Kittelberger's analysis begins, even more had already disappeared by then. Before 1500, however, there is not as reliable a record of the birds that went extinct and data on their traits and characteristics.

This timing coincides with the rise of scientific observation, resulting in systematic documentation of plant and animal life.

Today, 1,314 bird species are at risk of extinction, according to the IUCN Red List of Threatened Species, or about 12% of the total.

Importantly, they examine biological correlates of bird extinctions through the lens of when birds went extinct, providing a novel extinction timing element that helps better inform why birds with certain traits disappeared when they did.

By identifying traits that most predispose birds to extinction, the findings can help guide conservation efforts of hundreds of species that are at peril.

 Kyle D. Kittelberger et al, Correlates of avian extinction timing around the world since 1500 CE, Avian Research (2024). DOI: 10.1016/j.avrs.2024.100213

Researchers characterize 28 bacteria that produce bioactive substances, offering pharmaceutical potential

Researchers  have characterized 28 actinomycetes and investigated their biotechnological potential.

The results of the study show that all actinomycetes have an inhibiting effect against a panel of test bacteria and yeasts. The researchers have now published their findings in the journal Current Research in Microbial Sciences.

Actinomycetes are bacteria that are known to produce bioactive substances. Two thirds of the antibiotics in use today were originally isolated from these bacteria. The actinomycetes now being investigated were deposited in the DSMZ collection decades ago, but have not yet been characterized in detail.

In their study, the researchers investigated the natural compound synthesis potential of 28 actinomycetes and were able to prove that they have an inhibiting effect against selected other microorganisms. These include clinically relevant antibiotic-resistant bacteria that are on the World Health Organization's Bacterial Priority Pathogens List. The DSMZ's actinomycetes collection contains more than 6,000 strains, some of which have not yet been further analyzed.

Imen Nouioui et al, Biotechnological and pharmaceutical potential of twenty-eight novel type strains of Actinomycetes from different environments worldwide, Current Research in Microbial Sciences (2024). DOI: 10.1016/j.crmicr.2024.100290

Drinking plenty of water helps with a variety of conditions from obesity to migraines, researchers find

Public health recommendations generally suggest drinking eight cups of water a day. And many people just assume it's healthy to drink plenty of water. Now researchers at UC San Francisco have taken a systematic look at the available evidence. They concluded that drinking enough water can help with weight loss and prevent kidney stones, as well as migraines, urinary tract infections and low blood pressure.

The study, which analyzed 18 randomized controlled trials, was published on Nov. 25 in JAMA Network Open.

The researchers found the most evidence in favor of drinking water to prevent kidney stones and to help people lose weight.

Drinking eight cups of water a day significantly decreased the likelihood of getting another kidney stone.

Several studies found that drinking about six cups of water a day helped adults lose weight. But a study that included adolescents found that drinking a little more than eight cups of water a day had no effect.

Still, the authors said that encouraging people to drink water before meals would be a simple and cheap intervention that could have huge benefits, given the increased prevalence of obesity.

Other studies indicated that water can help prevent migraines, control diabetes and low blood pressure, and prevent urinary tract infections.

Adults with recurrent headaches felt better after three months of drinking more water.

Drinking about four more cups of water a day helped diabetic patients whose blood glucose levels were elevated.

Drinking an additional six cups a day of water also helped women with recurrent urinary tract infections. It reduced the number of infections and increased the amount of time between them.

And drinking more water helped young adults with low blood pressure.

On the other hand, someone who suffers from frequent urination at times may benefit from drinking less.

There isn't a one-size fits all approach for water consumption.

Hakam N, et al. Outcomes in Randomized Clinical Trials Testing Changes in Daily Water Intake: A Systematic Review. JAMA Network Open. (2024) DOI: 10.1001/jamanetworkopen.2024.47621

**

No 'one size fits all' treatment for type 1 diabetes, study finds

Factors beyond carbohydrates have a substantial influence on blood glucose levels meaning current automated insulin delivery systems miss vital information required for glucose regulation, a new study has found.

A team of researchers  analyzing automated insulin delivery data from people with type 1 diabetes (T1D) has discovered that unexpected patterns in insulin needs are just as common as well-established ones.

The study, published as a preprint on JMIRx Med, aimed to identify patterns in changes in insulin needs and to analyze how frequently these occur in people with T1D who use OpenAPS, a state-of-the-art, automated insulin delivery system (AID).

The results support the hypothesis that factors beyond carbohydrates play a substantial role in euglycemia—the state when blood glucose levels are within the standard range.

However, without measurable information about these factors, AID systems are left to adjust insulin cautiously with the effect of blood glucose levels becoming too low or high.

Type 1 diabetes is a chronic condition in which the body produces too little insulin, a hormone needed to regulate blood glucose.

The principal treatment for T1D is insulin that is injected or pumped. The amount and timing of insulin must be skillfully matched to carbohydrate intake to avoid increased blood glucose levels.

Beyond carbohydrates, various other factors such as exercise, hormones, and stress impact insulin needs.

However, how often these factors cause significant unexpected effects on blood glucose levels has been little explored, meaning that despite all advances, insulin dosing remains a complex task that can go wrong and result in blood glucose levels outside the range that protects people with T1D from adverse health effects.

The findings highlight the complexity of glucose regulation in T1D and demonstrate the heterogeneity in insulin needs among people with T1D, underlining the need for personalized treatment approaches.

For factors beyond carbohydrates to become more systematically included in clinical practice, scientists need to find a way to measure and quantify their impact and utilize this information in insulin-dosing. This could also aid more accurate blood glucose forecasting, which the study showed is not consistently possible from information about insulin and carbohydrates alone.

Isabella Degen et al, Beyond Expected Patterns in Insulin Needs of People With Type 1 Diabetes: Temporal Analysis of Automated Insulin Delivery Data, JMIRx Med (2024)

Light-up brain tissue could stop seizures
Pulses of green light can shut down the hyperactive neurons that cause seizures. Researchers used a virus to deliver genes for light-sensitive proteins into brain tissue taken from people with epilepsy, then implanted fiber-optic cables into neural regions that were prone to misfiring because of the disease. Using a remote-control system, they flipped on the light when a seizure began, temporarily disabling the neurons that were driving it. If the viral-delivery system can be adapted to living people, “we’ll be able to give people much more subtle, effective control over their seizures”.

Genetic Engineering & Biotechnology News | 
Reference: 

https://www.nature.com/articles/s41593-024-01782-5?utm_source=Live+...

Malaria vaccine delivered by mosquito bites

A trial is looking at delivering malaria immunity through bites from mosquitoes infected with modified versions of Plasmodium falciparum, one of the parasites that cause the disease. The parasites are genetically engineered to stop developing around six days after they enter the body, during a crucial phase of infection where they replicate in liver cells. In the trial, almost 90% of participants exposed to the modified parasites avoide... after being bitten by malaria-transmitting mosquitoes.

Nature | 
Reference:

https://www.nejm.org/doi/10.1056/NEJMoa2313892

COVID caused cancer tumours to shrink in mice – new study

A fascinating new study, published in the Journal of Clinical Investigation, has revealed an unexpected potential benefit of severe COVID infection: it may help shrink cancer.

This surprising finding, based on research conducted in mice, opens up new possibilities for cancer treatment and sheds light on the complex interactions between the immune system and cancer cells – but it certainly doesn’t mean people should actively try to catch COVID.

The study here focused on a type of white blood cell called monocytes. These immune cells play a crucial role in the body’s defence against infections and other threats. However, in cancer patients, monocytes can sometimes be hijacked by tumour cells and transformed into cancer-friendly cells that protect the tumour from the immune system.

What the researchers discovered was that severe COVID infection causes the body to produce a special type of monocyte with unique anti-cancer properties. These “induced” monocytes are specifically trained to target the virus, but they also retain the ability to fight cancer cells.

https://www.jci.org/articles/view/179527

A fossil first: Scientists find 1.5-million-year-old footprints of two different species of human ancestors at same spot

More than a million years ago, on a hot savanna teeming with wildlife near the shore of what would someday become Lake Turkana in Kenya, two completely different species of hominins may have passed each other as they scavenged for food.

Scientists know this because they have examined 1.5-million-year-old fossils they unearthed and have concluded they represent the first example of two sets of hominin footprints made about the same time on an ancient lake shore. The discovery will provide more insight into human evolution and how species cooperated and competed with one another, the scientists said.

"Hominin" is a newer term that describes a subdivision of the larger category known as hominids. Hominins include all organisms, extinct and alive, considered to be within the human lineage that emerged after the split from the ancestors of the great apes. This is believed to have occurred about 6 million to 7 million years ago.

The discovery, published in Science , offers hard proof that different hominin species lived contemporaneously in time and space, overlapping as they evaded predators and weathered the challenges of safely securing food in the ancient African landscape.

Hominins belonging to the species Homo erectus and Paranthropus boisei, the two most common living human species of the Pleistocene Epoch, made the tracks, the researchers said.

Their presence on the same surface, made closely together in time, places the two species at the lake margin, using the same habitat.

If the hominins didn't cross paths, they traversed the shore within hours of each other.

While skeletal fossils have long provided the primary evidence for studying human evolution, new data from fossil footprints are revealing fascinating details about the evolution of human anatomy and locomotion, and giving further clues about ancient human behaviors and environments.

With these kinds of data, we can see how living individuals, millions of years ago, were moving around their environments and potentially interacting with each other, or even with other animals. That's something that we can't really get from bones or stone tools.

The footprints are significant because they fall into the category of "trace fossils"—which can include footprints, nests and burrows. Trace fossils are not part of an organism but offer evidence of behavior. Body fossils, such as bones and teeth, are evidence of past life, but are easily moved by water or a predator.

Trace fossils cannot be moved.

 Kevin G. Hatala, Footprint evidence for locomotor diversity and shared habitats among early Pleistocene hominins, Science (2024). DOI: 10.1126/science.ado5275. www.science.org/doi/10.1126/science.ado5275

Researchers discover that a key mechanism in fat cells protects the body against energetic excess

A research team has identified an essential mechanism in fat cells (adipocytes) that enables them to enlarge safely to store energy. This process avoids tissue damage and protects the body from the toxic effects of accumulating fat molecules (lipids) in inappropriate places.

The results, published in Nature Communications, signify a major advance in the understanding of metabolic diseases. Moreover, this discovery opens the door to the development of new therapeutic strategies to combat diseases related to chronic energetic excess, such as overweight, obesity, lipodystrophy, and metabolic syndrome, and their grave cardiovascular and metabolic complications.

In modern societies, characterized by sedentary lifestyles and high-calorie diets, adipose tissue is a key determinant of metabolic health. Adipocytes can enlarge to store energy in the form of fat, preventing excess lipids from accumulating in organs like the liver or in the blood vessel wall (especially in the heart and the brain), where they could cause irreparable damage.

Nevertheless, this process is not risk-free. When adipocytes are overloaded with fat they can rupture, releasing their toxic contents and generating inflammation and metabolic alterations.

The team found that when an adipocyte accumulates fat and its surface is under increased tensile stress, the caveolae flatten, releasing a 'reservoir' of membrane that allows the cell to enlarge without breaking apart. Conversely, when fat reserves diminish, these structures regroup to reduce the excess membrane and restore cellular stability.

As well as physically protecting adipocytes, caveolae also play an essential role in coordinating cell metabolism. Molecular components of these membrane structures travel to other cell compartments, conveying signals that adjust metabolic activity to match the level of energy reserves. This capacity for internal communication makes caveolae key elements for efficient caveolar function.

However, when these structures are absent or malfunction, adipocytes become more rigid, vulnerable to rupture, and less efficient at storing energy. The result, is an inflammatory reaction that compromises the body's metabolic health. This phenomenon is linked to conditions such as lipodystrophy, in which the body cannot store fat, leading to severe metabolic and cardiovascular alterations.

Plasma membrane remodeling determines adipocyte expansion and mechanical adaptability, Nature Communications (2024). DOI: 10.1038/s41467-024-54224-y

Study finds standing desks may not be the healthy alternative people think

Standing desks became popular thanks to phrases like "sitting is the new smoking," which highlighted the dangers of a sedentary lifestyle.

A new study, however, has found standing desks might do more harm than good, not improving heart health but actually leading to circulation problems.
The study focused on 83,000 people who wore devices to track their sitting, standing and other physical activity over nearly seven years.

Researchers found sitting for more than 10 hours a day was associated with a higher risk of heart disease. Simply standing did not mitigate this risk, however.

Standing for extended periods was instead found to increase the risk of circulatory problems—such as blood pooling in the legs—which could lead to varicose veins. If left untreated, varicose veins can lead to bleeding, ulcers or other complications.

So, a standing desk may not be the solution to reverse a sedentary lifestyle. There are other things you can do, however. Taking short walks throughout the day is a smart way to interrupt periods of inactivity. Stretching and other light exercises are key, as well.
**

Fine particulate air pollution may play a role in adverse birth outcomes

For pregnant women, exposure to fine particulate air pollution (PM2.5) was associated with altered immune responses that can lead to adverse birth outcomes, according to a new study. The study is the first to examine the relationship between PM2.5 and maternal and fetal health on a single-cell level and highlights the health risk of PM2.5 exposure for pregnant women.

The study is published in Science Advances. This study represents a substantial step forward in understanding the biological pathways through which PM2.5 exposure affects pregnancy, maternal health, and fetal development. Its advanced methodology represents a significant innovation for how we study immune responses to environmental exposures.

Previous research has found associations between exposure to PM2.5 and maternal and child health complications including preeclampsia, low birth weight, and developmental delays in early childhood. To understand these associations on a cellular level, the researchers used air quality data collected by the Environmental Protection Agency to calculate study participants' average PM2.5 exposure. Participants were both non-pregnant women and 20-week pregnant women.

The researchers then used an innovative technology to understand how pollution modified the DNA of participants' individual cells. Within each cell they were able to map changes to histones, the proteins that help control the release of cytokines—proteins that help control inflammation in the body and that can affect pregnancy.

The study found that PM2.5 exposure can influence the histone profiles of pregnant women, disrupting the normal balance of cytokine genes and leading to increased inflammation in both women and fetuses. In pregnant women, this increase in inflammation can correspond with adverse pregnancy outcomes.

These findings highlight the importance of minimizing air pollution exposure in pregnant women to protect maternal and fetal health.

Youn Soo Jung et al, Impact of air pollution exposure on cytokines and histone modification profiles at single-cell levels during pregnancy, Science Advances (2024). DOI: 10.1126/sciadv.adp5227. www.science.org/doi/10.1126/sciadv.adp5227

Modified ribosomes could be a possible mechanism of antibiotic resistance

Bacteria modify their ribosomes when exposed to widely used antibiotics, according to research published in Nature Communications. The subtle changes might be enough to alter the binding site of drug targets and constitute a possible new mechanism of antibiotic resistance.

Escherichia coli is a common bacterium which is often harmless but can cause serious infections. Researchers exposed E. coli to streptomycin and kasugamycin, two drugs which treat bacterial infections. Streptomycin has been a staple in treating tuberculosis and other infections since the 1940s, while kasugamycin is less known but crucial in agricultural settings to prevent bacterial diseases in crops.

Both antibiotics tamper with bacteria's ability to make new proteins by specifically targeting their ribosomes. These molecular structures create proteins and are themselves made of proteins and ribosomal RNA. Ribosomal RNA is often modified with chemical tags that can alter the shape and function of the ribosome. Cells use these tags to fine tune protein production.

The study found that, in response to the antibiotics, E. coli begins to assemble new ribosomes that are slightly different from the ones produced under normal conditions. Depending on which antibiotic is used, the new ribosomes lacked certain tags. The tags were specifically lost in the regions where antibiotics latch on to and halt protein production. The study found this made the bacteria more resistant to the drugs.

The researchers think the bacteria's ribosomes might be altering its structure just enough to prevent an antibiotic from binding effectively.

Bacteria are known to develop antibiotic resistance in different ways, including mutations in their DNA. Another common mechanism is their ability to actively pump and transport antibiotics out of the cell, reducing the concentration of the drug inside the cell to levels that are no longer harmful. The study is evidence of an entirely new survival strategy. E. coli is altering its molecular structures with remarkable precision and in real time. It's a stealthy and subtle way of dodging drugs.

The researchers made the findings using advanced nanopore sequencing technology, which read RNA molecules directly.

 Native RNA nanopore sequencing reveals antibiotic-induced loss of rRNA modifications in the A- and P-sites, Nature Communications (2024). DOI: 10.1038/s41467-024-54368-x

New hydrovoltaic cell continuously generates electricity with little water and no sunlight

A team of engineers  has modified the approach used to generate electricity with a hydrovoltaic cell, building one that uses little water and no sunlight. Their study is published in the journal Nature Communications.

Hydrovoltaic cells generate electricity by capturing the energy from interactions between water and other surfaces. Such interactions typically rely on sunlight as the instigating power source. As the researchers with this new effort note, the traditional approach results in a hydrovoltaic cell that needs a continuous source of water and that typically only operates in dry environments. In this new study, the research team  overcame both problems to create a new kind of hydrovoltaic cell.

To allow their cell to operate in virtually any climate, the research team built their cell inside a hermetically sealed container—they call the result a hermetic hydrovoltaic cell (HHC). Inside, they placed a double-layer wicking agent made of tissue paper and carbon black. A small amount of water added to the HHC is continuously circulated due to changes in ambient temperature and capillary flow in the tissue paper.

The HHC generates power using the energy of ambient heat as the instigating power source. Testing showed the cell is capable of producing electricity for up to 160 hours without the addition of any more water. The researchers suggest such a cell would be an ideal candidate for people living in water-poor areas.

Further testing showed that exposure to strong sunlight increased electrical output. The researchers found this was due to energy from the sunlight increasing the rate of absorption by the black carbon, which in turn led to an increased moisture gradient.

 Renxuan Yuan et al, Hermetic hydrovoltaic cell sustained by internal water circulation, Nature Communications (2024). DOI: 10.1038/s41467-024-54216-y

Satellite evidence points to climate-induced poisoning of over 300 African elephants

A new study  has provided further evidence that the deaths of 350 African elephants in Botswana during 2020 were the result of drinking from water holes where toxic algae populations had exploded due to climate change.

The lead author of the report says their analysis shows animals were very likely poisoned by watering holes where toxic blooms of blue-green algae, or cyanobacteria, had developed after a very wet year followed a very dry one.

Botswana is home to a third of all African elephants, and this unprecedented die-off within their largest remaining population underlines the escalating concerns surrounding the impact of drought and climate change on the Okavango Delta, one of the most important ecosystems in the world.

Elephant carcasses were first spotted in the north-eastern sector of the country's Okavango Delta between May and June 2020, but poaching was soon ruled out as the cause.

The event sparked global concern, with a total of 350 elephants now known to have died.

Toxins produced by the algae growing in watering holes was one suspected cause, though evidence has remained inconclusive, in part because it occurred during the COVID-19 pandemic when movements were restricted, and this prevented the collection of samples at the time.

The deaths of 25 elephants in neighboring Zimbabwe from septicemia in the same year cast some doubt on algal toxins being the reason for the Botswana deaths.

However, writing in the journal Science of The Total Environment, the team say their analysis all but confirms toxic algae as the cause.

Combining satellite data and spatial analysis, the team examined the relationship between about 3,000 waterholes and the locations of deceased elephants.

Their analysis revealed waterholes near the carcasses showed elevated algal levels and repeated bloom events in 2020 compared to previous years—particularly during the period associated with the mass mortality event.

The team also showed that decayed elephant carcasses were more spread out across the landscape than fresh carcasses, indicating that the die-off in 2020 was different from typical elephant mortality patterns.

After drinking, elephants were estimated to have walked an average of 16.5 km from the toxic waterholes and died within about 88 hours of exposure.

Southern Africa is projected to become drier and hotter under climate changes, and as a result waterholes across this region will likely be drier for more months of the year. Our findings point to the potential negative effects on water quantity and quality, and the catastrophic repercussions on animals, this could have.

https://www.sciencedirect.com/science/article/pii/S0048969724076824...

Davide Lomeo et al, Remote sensing and spatial analysis reveal unprecedented cyanobacteria bloom dynamics associated with elephant mass mortality, Science of The Total Environment (2024). DOI: 10.1016/j.scitotenv.2024.177525

Homo juluensis: Possible new ancient human species uncovered by researchers

Researcher say they may have found a new human species called Homo juluensis, which includes mysterious groups like the Denisovans—ancient human relatives whose histories are still being uncovered.

Homo juluensis lived approximately 300,000 years ago in eastern Asia, hunted wild horses in small groups, and made stone tools and possibly processed animal hides for survival before disappearing around 50,000 years ago.

It was proposed that the new species include the enigmatic Denisovans, a population known primarily through DNA evidence from a few physical remains found in Siberia, and a few fossils found in Tibet and Laos. More research is clearly needed to test this relationship, which is primarily based on similarities between jaw and teeth fossils from these different sites.

This study clarifies a hominin fossil record that has tended to include anything that cannot easily be assigned to Homo erectus, Homo neanderthalensis or Homo sapiens.

 Christopher J. Bae et al, Making sense of eastern Asian Late Quaternary hominin variability, Nature Communications (2024). DOI: 10.1038/s41467-024-53918-7

Scientists develop self-sustained protein transport and tissue assembly in artificial cells

In a new Nature Communications study, scientists have developed a novel method for artificial cells to interact with their external environment without the need for complex modification processes.

This method could open new frontiers in tissue engineering, drug delivery, and cell processes.

Biological cells are protected by a membrane, made of phospholipids, which modulates interactions with the outside environment. Recreating this in artificial cells is challenging, requiring manual external modification of the membrane.

This is particularly true for protein translocation or movement across the membrane. The present study addresses this problem by developing a method in which artificial cells modify their own membrane.

For the study, the researchers aimed to functionalize the cell membrane to enable protein transport across the membrane and assemble them into tissue-like structures afterward.

Biological channels typically use ion channels and transporters to exchange substances across the membrane. In artificial cells, this interaction has to be replicated manually. The researcher can change the membrane composition to achieve this, which is very different from how natural cells interact with their environment.

To overcome this problem, the researchers developed a method with which you can encode modification of the outer membrane, and thereby interact with the external environment, into the artificial cell genome.

To do so, the researchers chose a pore-forming protein called α-hemolysin. This is a protein produced by Staphylococcus aureus, the bacteria responsible for causing staph infections. It is technically termed a toxin since it forms holes in cell membranes.

But it has the unique ability to be expressed as a soluble monomer, which upon contact with a lipid bilayer (cell membrane) spontaneously assembles into a transmembrane protein.

The researchers not only used the α-Hemolysin as a pore-forming protein but also modified the artificial cells to produce the protein themselves. By having a self-sustaining system, the researchers do not need to add the protein each time.

Part 1

The modified α-hemolysin successfully traveled to the cell membrane and embedded itself. Following this, the peptide inserts could successfully translocate across the membrane, demonstrating protein transport.

Peptides containing up to 50 amino acids could be inserted into α-hemolysin without disrupting pore formation, membrane insertion, and protein functionality.

The researchers further found that the translocated peptides remained accessible on the external side of the membrane. This suggests they could be used for assembling tissue-like structures, as their accessibility allows for further interactions and organization in the external environment.
By generating one population of artificial cells that translocate negatively charged peptides across their membrane and another population of artificial cells that translocate positively charged peptides, we can create a tissue-like structure because artificial cells with a negatively charged outer membrane will bind to artificial cells with a positively charged membrane.
The researchers also added a system to detect if the cells can communicate with each other, where cells produce a visible (fluorescent) signal when they receive a signal from other cells. This could help with the creation of more complex and functional artificial tissues for future applications.

With the possibility of developing artificial tissues and potential drug delivery systems, the novel method demonstrates a pivotal step in cell research.

 Alexander Harjung et al, Encoding extracellular modification of artificial cell membranes using engineered self-translocating proteins, Nature Communications (2024). DOI: 10.1038/s41467-024-53783-4, www.nature.com/articles/s41467-024-53783-4

Part 2

New spin quantum battery can be charged without an external field

Over the past few years, some researchers have been working on alternative energy storage systems that leverage the principles of quantum mechanics. These systems, known as quantum batteries, could be more efficient and compact than conventional battery technologies, while also achieving faster charging times.

In a recent paper published in Physical Review Letters, a research group  introduced a new spin quantum battery, a battery that leverages the spin degrees of freedom of particles to store and release energy. This battery is charged in a unique and advantageous way, without the need for an external field.

This  quantum battery can be seen as the intercalation of two collections of ½-spins, the simplest possible quantum systems. By properly changing the interaction between the elements of the two chains, for example by shifting one with respect to the other, it becomes possible to trap energy into the quantum battery in a stable way.

This allows their battery to be charged via a new mechanism that does not rely on the presence of an external field.

 Riccardo Grazi et al, Controlling Energy Storage Crossing Quantum Phase Transitions in an Integrable Spin Quantum Battery, Physical Review Letters (2024). DOI: 10.1103/PhysRevLett.133.197001. On arXiv: DOI: 10.48550/arxiv.2402.09169

Proof-of-concept study demonstrates self-assembling electronics

Researchers have demonstrated a new technique for self-assembling electronic devices. The proof-of-concept work was used to create diodes and transistors, and paves the way for self-assembling more complex electronic devices without relying on existing computer chip manufacturing techniques.

The paper, "Guided Ad infinitum Assembly of Mixed-Metal Oxide Arrays from Liquid Metal," is published open access in the journal Materials Horizons.

Julia J Chang et al, Guided Ad infinitum Assembly of Mixed-Metal Oxide Arrays from Liquid Metal, Materials Horizons (2024). DOI: 10.1039/D4MH01177E

Cooperative motion by atoms protects glass from fracturing

What if glass doesn't break?

We've all experienced the moment of panic when a glass slips from our hands, shattering into pieces upon hitting the ground. What if this common mishap could become a thing of the past?

Now, a new discovery by researchers  has offered insights into how glass resists breakage, potentially paving the way for highly durable, break-resistant materials. The breakthrough has wide ranging implications for glass-related industries.

Details of their findings are published in the journal Acta Materialia.

Glass, while strong, is prone to breaking when stress exceeds its tolerance, but interestingly, the movement of atoms and molecules within glass can relax internal stress, making the material more resistant to fractures.

Although we know that some atoms 'jump' into nearby empty spaces, how this process alleviates stress has long been a mystery till now.

Scientists uncovered a previously unknown mechanism of stress relaxation in ionic glass, a model system of glass now.

Their research utilized state-of-the-art synchrotron radiation experiments and computer simulations to observe atomic motions in glass on a nanosecond-to-microsecond timescale.

The team discovered that when some atoms within the glass "jump" into nearby empty spaces, surrounding groups of atoms slowly move together to fill the void. This interplay of atomic jumps and collective motion reduces internal stress, protecting the glass from breaking under external force.

The research team plans to explore whether similar atomic mechanisms operate in other types of glass. Their ultimate goal is to establish universal guidelines for designing glass with superior impact resistance, which could revolutionize applications requiring durable materials.

 Makina Saito et al, Discovery of collective nonjumping motions leading to Johari–Goldstein process of stress relaxation in model ionic glass, Acta Materialia (2024). DOI: 10.1016/j.actamat.2024.120536

Scientists discover a natural flu defense mechanism that activates in the nasal cavity during pregnancy

Scientists have discovered that pregnancy may trigger a natural immunity to boost protection against severe flu infection. Their work is published in the journal Science Advances.

Contrary to the common belief that pregnancy increases vulnerability to infections, researchers found that it strengthened an immune defense in mice, blocking the Influenza A virus from spreading to the lungs, where it can cause severe infection.

A mother needs to stay healthy to protect her developing baby, so the immune system adapts to provide stronger defenses. This fascinating response in the nasal cavity  is the body's way of adding an extra layer of protection, which turns on during pregnancy.

The researchers used a mouse model to observe how a certain type of immune cell activates in the nasal cavity of mice during pregnancy, producing a powerful molecule that boosts the body's antiviral defenses, especially in the nose and upper airways.

This natural immunity in pregnancy could change the way we think about flu protection for expectant mothers

Julia Chronopoulos et al, Pregnancy enhances antiviral immunity independent of type I IFN but dependent on IL-17–producing γδ + T cells in the nasal mucosa, Science Advances (2024). DOI: 10.1126/sciadv.ado7087

Countertop workers exposed to serious lung disease

Durable and attractive, engineered stone countertops are a popular feature in modern  kitchens, but the workers who build them are risking their health. A growing number of these countertop workers are developing silicosis, a serious and long-term lung disease, according to a study presented at the annual meeting of the Radiological Society of North America (RSNA).

This is a new and emerging epidemic, and we must increase awareness of this disease process so we can avoid delays in diagnosis and treatment for our patients, say the study authors.

Silicosis is caused by the inhalation of crystalline silica dust produced in construction, coal mining and other industries. The prognosis is poor, with gradually worsening lung function leading to respiratory failure. The disease also makes patients more vulnerable to infection in the lungs, chronic obstructive pulmonary disease, autoimmune disease and lung cancer.

In recent years, a resurgence of silicosis has been reported in engineered countertop workers. Engineered stone countertops are made from quartz aggregate held together with a resin binder. They contain substantially more crystalline silica than natural stone versions. Workers who cut, shape, grind and polish these countertops may be exposed to significant amounts of silica dust.

In a preliminary analysis of 21 workers, 100% were male and Hispanic with a median age of 43 years and a median exposure of 18 years. All patients were symptomatic. Patients commonly had atypical and advanced features of silicosis. Shortness of breath and cough were the most common symptoms.

Primary clinicians recognized silicosis at the initial encounter in only four of 21 cases (19%), while radiologists recognized it in seven of 21 cases (33%). Alternative diagnoses, such as infection, were initially suggested in most cases. Nearly half of the patients (48%) had atypical imaging features.

The results highlight a need for more awareness and better recognition of imaging features associated with silicosis.

Source: https://www.rsna.org/annual-meeting

Galleri blood test can  help diagnose multiple forms of cancer

Did you know that the technology to detect more than 50 cancers with one test existed?

Single-cancer screenings are the norm. The focus is usually on three specific cancers in women (breast, colon and cervical) and two in men (prostate and colon). Lung is a focus for heavy smokers.

Screening for these cancers helps save lives. But it creates what Ofman calls a classic spotlight problem, shining the light over there while other, more aggressive cancers go unscreened.

The Galleri test doesn't target a specific area. It looks for the fingerprint, the biological signal in DNA that has been shed from cancer. It's a very specific marker and detects where that cancer is in the body.

It creates a more effective and efficient screening programme.

And unlike other cancer tests (10%) the false positive rate of the Galleri test is just 0.5%.

Source: Medical news

Climate warming is reducing rice quality

Rice is a food staple for billions of people worldwide, with demand doubling over the past 50 years, and is predominantly grown in Asia before being exported globally. This crop is sensitive to weather conditions and, as such, understanding how yields are affected by climate change is of paramount importance to ensure sustainable food supplies into the future.

Beyond yield, the quality of rice may also be affected, determined by a combination of appearance, palatability, nutritional profile and milling properties.

Research published in Geophysical Research Letters, has highlighted a decline in rice quality in  Asia, coincident with changing temperatures.

Researchers used data collected over 35 years to explore patterns in rice quality from Japan and China. This is based upon head rice rate (HRR), which is a measure of the fraction of milled rice kernels that retain 75% of their length after milling, during which the husk and bran are removed.
The research team explored a number of climate variables via modeling to ascertain which had the greatest effect on HRR; these variables were nighttime temperature, daytime temperature, diurnal temperature, daily averaged temperature, hot days (above 30/35 °C), precipitation, precipitation frequency, soil moisture, solar radiation, cloud cover, relative humidity, daytime vapor pressure deficit, transpiration and carbon dioxide concentration.

Ultimately, the scientists determined that overnight temperatures are the main driver of reduced rice quality. In particular, as nighttime temperatures become warmer, a critical threshold for decline begins at 12 °C and 18 °C for Japan and China respectively. When flowering and grain growth occur in such conditions, rates of photosynthesis and starch accumulation in the grain decrease, leading to lower rice quality as more grains are susceptible to breakage.

Part 1

Following this, daily solar radiation was the second most important factor contributing to rice quality changes (higher solar radiation leading to lower HRR), then daily precipitation (less precipitation corresponding to lower HRR) and lastly daytime vapor pressure deficit (beyond a threshold of 0.5–1 kPa, HRR declines).
The average rice quality across all sites and years for China had a HRR of ~62%, but reduced by 1.45% every decade. In Japan, the average HRR was slightly higher at ~66%, with a prominent rate of decline of 7.6% every decade.

In both countries, there is a strong gradient of diminished rice quality from northern to southern provinces and prefectures, likely linked to southern regions being closer to the equator and therefore experiencing higher nighttime temperatures.
This research is important as projections under both moderate and high emissions scenarios suggest rice quality will continue to decline in the decades to come as climate change progresses.
Given all of this, the likelihood of rice cultivars adapting in tandem with the rate of climate change may pose a hazard to sustainable food supplies, human nutrition and economic stability in years to come.

Xianfeng Liu et al, Warming Leads to Lower Rice Quality in East Asia, Geophysical Research Letters (2024). DOI: 10.1029/2024GL110557

Part 2

Countdown to an ice-free Arctic: Research warns of accelerated timelines

The first summer on record that melts practically all of the Arctic's sea ice, an ominous milestone for the planet, could occur as early as 2027.

For the first time, an international research team used computer models to predict when the first ice-free day could occur in the northernmost ocean. An ice-free Arctic could significantly impact the ecosystem and Earth's climate by changing weather patterns. 

The first ice-free day in the Arctic won't change things dramatically, the team says. It will show that we've fundamentally altered one of the defining characteristics of the natural environment in the Arctic Ocean, which is that it is covered by sea ice and snow year-round, through greenhouse gas emissions.

The findings were published Dec. 3 in the journal Nature Communications. Jahn will also present the results on Dec. 9 at the American Geophysical Union annual meeting in Washington D.C.

The researchers' projected/estimated the first ice-free Arctic day using output from over 300 computer simulations. They found that most models predicted that the first ice-free day could happen within nine to 20 years after 2023, regardless of how humans alter their greenhouse gas emissions. The earliest ice-free day in the Arctic Ocean could occur within three years.
It's an extreme scenario but a possibility based on the models. In total, nine simulations suggested that an ice-free day could occur in three to six years.

The researchers found that a series of extreme weather events could melt two million square kilometers or more of sea ice in a short period of time: A unusually warm fall first weakens the sea ice, followed by a warm Arctic winter and spring that prevents sea ice from forming. When the Arctic experiences such extreme warming for three or more years in a row, the first ice-free day could happen in late summer.

Those kinds of warm years have already happened.

But there's also good news: A drastic cut in emissions could delay the timeline for an ice-free Arctic and reduce the time the ocean stays ice-free, according to the study.

Céline Heuzé et al, The first ice-free day in the Arctic Ocean could occur before 2030, Nature Communications (2024). DOI: 10.1038/s41467-024-54508-3 , dx.doi.org/10.1038/s41467-024-54508-3

Seeing through the mystery of an X-ray emissions mechanism

Scientists who study X-rays, lightning and similar phenomena have observed something curious: In lab experiments replicating these occurrences, electrons accelerated between two electrodes can be of a higher energy than the voltage applied.

This defies an assumption in physics that the energy of the electrons should correspond with the voltage applied.

Recently, a team of  researchers used mathematical modeling to explain the underlying mechanism at play. They published their results in Physical Review Letters.

Through mathematical modeling, they  demonstrated that an energy feedback process is responsible for this occurrence.

According to them when the electrons interact with the material of the electrode, they emit X-rays, which are made of photons—massless, charge-less particles that comprise light. Some of these photons propagate backward, enabling more electrons to release from the other electrode.

A small group of these electrons have energy corresponding to the original energy. Then they accelerate again, and the process continues through several cycles. The researchers modeled this very high energy process.

Their model also helped explain why electrodes of different shapes and materials produced this effect to varying degrees. We get maximum effect when we have flat electrodes, and a minimized effect when the electrodes are needle-like. 

This makes sense, because the large surface areas of the flat electrodes are good for the interaction between the electrons and photons and the way they bounce back and forth. When the surface area is reduced, the effect is minimized.

The researchers also examined via simulation and modeling how the phenomenon emerges with different materials.

Tungsten is the standard material used for X-ray production, and we know it's a good material for this. It is a robust material for electron production used in current in X-ray machines.

The researchers said that their findings may be useful for the development of new ways of producing X-rays in the future. Specifically, they said that the work may stimulate new research on the production of energetic electrons from solid materials, potentially making X-rays machines faster and more light weight and compact.

Victor P. Pasko et al, Photoelectric Feedback Mechanism for Acceleration of Runaway Electrons in Gas Discharges at High Overvoltages, Physical Review Letters (2024). DOI: 10.1103/PhysRevLett.133.235301

Toxin in blood of kidney disease patients could contribute to stroke risk, study suggests

Scientists have revealed that a toxin found in the blood of patients with chronic kidney disease (CKD) damages the body's protective blood–brain barrier, likely contributing to the risk of stroke.

Researchers investigated the effect on the central nervous system of "p-cresol sulfate," a molecule produced by the gut microbiome. 

While this molecule is efficiently cleared by the kidneys in healthy people, it accumulates in the blood of patients with CKD.
Investigating the effect of p-cresol sulfate on human tissue and in mice—and replicating their results using blood samples from dialysis patients—the team found that the toxin triggers a process which activates two enzymes that damage the wall of brain blood vessels.

The researchers observed how this impairs the critically protective blood–brain barrier, which acts as a shield to prevent harmful substances and toxins in the body from reaching the brain.

Damage to the blood–brain barrier is known to contribute to the risk of stroke, which can be up to 30 times greater in CKD patients than in the general population.

As part of the study, however, the researchers also found that a class of 'inhibitor' type drugs—which can block chemical reactions in the body—showed promising results in being able to prevent this damage from occurring.

In further tests, the team found that a class of enzyme inhibitor drugs was able to block the damaging effects of blood from CKD patients on cells in vitro.

As well as enhanced stroke risk, patients with CKD, including those not yet requiring dialysis, exhibit significant cognitive decline, a change that seems to be at least partly driven by damage to the brain's blood vessels.

 Sita N. Shah et al, Cerebrovascular damage caused by the gut microbe/host co-metabolite p -cresol sulfate is prevented by blockade of the EGF receptor, Gut Microbes (2024). DOI: 10.1080/19490976.2024.2431651

Research reveals how fructose in diet enhances tumor growth

Fructose consumption has increased considerably over the past five decades, largely due to the widespread use of high-fructose corn syrup as a sweetener in beverages and ultra-processed foods.

New research  shows that dietary fructose promotes tumor growth in animal models of melanoma, breast cancer and cervical cancer. However, fructose does not directly fuel tumors, according to the study published Dec. 4 in the journal Nature.

Scientists discovered that the liver converts fructose into usable nutrients for cancer cells, a compelling finding that could open up new avenues for care and treatment of many different types of cancer.

Using metabolomics—a method of profiling small molecules as they move through cells and across different tissues in the body—the researchers concluded that one way in which high levels of fructose consumption promote tumor growth is by increasing the availability of circulating lipids in the blood. These lipids are building blocks for the cell membrane, and cancer cells need them to grow.

Researchers looked at numerous different cancers in various tissues throughout the body, and they all followed the same mechanism.

Scientists have long recognized that cancer cells have a strong affinity for glucose, a simple sugar that is the body's preferred carbohydrate-based energy source.

In terms of its chemical structure, fructose is similar to glucose. They are both common types of sugar, with the same chemical formula, but they differ in how the body metabolizes them. Glucose is processed throughout the whole body, while fructose is almost entirely metabolized by the small intestine and liver.

Both sugars are found naturally in fruits, vegetables, dairy products and grains. They are also added as sweeteners in many processed foods. 

 The researchers found that added fructose promoted tumor growth without changing body weight, fasting glucose or fasting insulin levels. It had a rather dramatic impact. In some cases, the growth rate of the tumors accelerated by two-fold or even higher.

The researchers attempted to repeat a version of this test by feeding fructose to cancer cells isolated in a dish, the cells did not respond. In most cases they grew almost as slowly as if we gave them no sugar at all.

Part 1

Interestingly, the cancer cells themselves were unable to use fructose readily as a nutrient because they do not express the right biochemical machinery. Liver cells do. This allows them to convert fructose into LPCs, which they can secrete to feed tumors.

Gary Patti, Dietary fructose enhances tumour growth indirectly via interorgan lipid transfer, Nature (2024). DOI: 10.1038/s41586-024-08258-3. www.nature.com/articles/s41586-024-08258-3

Part 2

Serious side effect of using CRISPR-Cas gene scissors uncovered: AZD7648 molecule can destroy parts of genome

Genome editing with various CRISPR-Cas molecule complexes has progressed rapidly in recent years. Hundreds of labs around the world are now working to put these tools to clinical use and are continuously advancing them.

CRISPR-Cas tools allow researchers to modify individual building blocks of genetic material in a precise and targeted manner. Gene therapies based on such gene editing are already being used to treat inherited diseases, fight cancer and create drought- and heat-tolerant crops.

The CRISPR-Cas9 molecular complex, also known as genetic scissors, is the most widely used tool by scientists around the world. It cuts the double-stranded DNA at the exact site where the genetic material needs to be modified. This contrasts with newer gene-editing methods, which do not cut the double strand.

The cut activates two natural repair mechanisms that the cell uses to repair such damage: a fast but imprecise one that reconnects only the ends of the cut DNA, and a slow and precise one that is not activated in every case. The latter requires a copyable template for repair to accurately rejoin the DNA at the cut site.

The slow variant is called homology-directed repair. Researchers want to use this method of repair because it allows the precise integration of individual DNA segments into a desired gene region. The approach is very flexible and can be used to repair different disease genes.

In principle, it could be used to cure any disease.

Part 1

To get the cell to use homology-directed repair, the researchers recently began using a molecule called AZD7648, which blocks fast repair and forces the cell to use homology-directed repair. This approach is expected to accelerate the development of more efficient gene therapies. Initial studies with these new therapies have been good. Too good to be true, as it turned out.

A research group led by Corn has discovered that the use of AZD7648 has serious side effects. The study has been published in the journal Nature Biotechnology.

Although AZD7648 promotes precise repair and thus precise gene editing using the CRISPR-Cas9 system as hoped, in a significant proportion of cells this has led to massive genetic changes in a part of the genome that was expected to be modified without scarring.

The ETH researchers found that these changes resulted in the simple deletion of thousands and thousands of DNA building blocks, known as bases. Even whole chromosome arms broke off. This makes the genome unstable, with unpredictable consequences for the cells edited by the technique.

When the researchers analyzed the genome at the sites where it had been edited, it looked correct and precise. But when they analyzed the genome more broadly, they saw massive genetic changes. These are not seen when you only analyze the short, edited section and its immediate neighborhood.

The extent of the negative effects surprised the researchers. In fact, they suspect that they do not yet have a complete picture of the full extent of the damage because they did not look at the entire genome when analyzing the modified cells, only partial regions.

New tests, approaches and regulations are therefore needed to clarify the extent and potential of the damage.

The development of any new technology is a rocky road. One stumble does not mean we give up on the technology, say the researchers.

Gene therapies based on the CRISPR-Cas system have already been successfully used in clinical practice. In recent years, for example, a hundred patients suffering from the hereditary disease sickle cell anemia have been treated with CRISPR-Cas-based therapeutics—without AZD7648.

"All patients are considered cured and have no side effects".

Grégoire Cullot et al, Genome editing with the HDR-enhancing DNA-PKcs inhibitor AZD7648 causes large-scale genomic alterations, Nature Biotechnology (2024). DOI: 10.1038/s41587-024-02488-6

Part 2

Engineered immune cells to tame inflammation

When the immune system overreacts and starts attacking the body, the only option may be to shut the entire system down and risk developing infections or cancer. But now, scientists  may have found a more precise way to dial the immune system down.

The technology uses engineered T cells that act as immune "referees" to soothe overreacting immune responses. They also can mop up inflammatory molecules.

The new approach could be used to stop the body from rejecting transplanted organs and tissues, such as pancreatic islet cells, which are sometimes used to treat type 1 diabetes. That way, recipients would not need to take harsh immunosuppressant drugs.

This technology can put the immune system back into balance.

The research The team adapted the suppressor cells' anti-inflammatory abilities to work in CD4 immune cells. These are the same cells that are used to make cancer-killing CAR T cells. They also gave these cells a molecular sensor to guide them to their target tissue in the body.

Proof of principle in type 1 diabetes :

The scientists tailored a batch of immune referees to search for human pancreatic islet cells and then produce TGF-Beta and CD25, molecules that can muzzle killer T cells.

They introduced the engineered referee cells into mice that had received a transplant of human islet cells, modeling the treatment for type 1 diabetes.

The referee cells found the vulnerable islet cells and stopped the killer T cells from attacking, and the islet cells survived.

 Nishith R. Reddy et al, Engineering synthetic suppressor T cells that execute locally targeted immunoprotective programs, Science (2024). DOI: 10.1126/science.adl4793. www.science.org/doi/10.1126/science.adl4793

How hummingbirds fly and feed

Scientists explore role of intestinal bacteria in cancer prevention

The link between intestinal bacteria and cancer

Certain intestinal bacteria are found more frequently in some countries such as Norway than in a number of other countries and there is also a higher incidence of bladder cancer, bowel cancer and prostate cancer. These findings may lead to new opportunities for preventing these types of cancer, according to a new study.

Previous studies have shown that a toxin produced by certain bacteria in order to dominate inside the intestine, causes damage to healthy cells and increases the risk of developing bowel cancer.

In a new study, scientists examined the incidence of bladder, colon, rectal and prostate cancer and compared this to the prevalence of two toxin-producing E. coli bacteria in the countries concerned. E. coli is the most common cause of urinary tract infections and bacterial infections in the bloodstream worldwide. Norway has a higher incidence of bladder cancer and colorectal cancer compared with many other countries.

In the course of the study, scientists also found that the prevalence of these two E. coli bacteria was higher in Norway. When they compared equivalent data from several different countries, they discovered a clear pattern: the fewer of these E. coli bacteria that circulate in the population, the lower the incidence of these types of cancer, and vice versa, and the study recently published in The Lancet Microbe confirms this.

In recent years, intense research has been carried out internationally on the link between the toxin produced by these bacteria, called colibactin, and several types of cancer. The research was initiated after groundbreaking studies revealed that colibactin damages DNA in intestinal cells and scientists produced models of intestinal organs and saw that the toxin-producing E. coli resulted in cancer in the models.

Part 1

Scientists have data representing genetic material from 50,000 E. coli samples gathered from four continents. When they studied these, they saw that the ability to produce the toxin is very limited and is primarily found in two particular genotypes of E. coli bacteria. Both of these circulate frequently in Norway and they are also the main genotypes causing infections in the bloodstream in the country.
In contrast, these genotypes of bacteria are rarely found in countries of South Asia.
The scientists involved in this study have therefore put forward a number of hypotheses on which ecological conditions drive these unwanted bacterial families away from certain population groups.
If scientists can succeed in developing vaccines against the harmful type of E. coli that produces colibactin, or a form of probiotics, this would result in notable public health benefits. These measures could eliminate the unwanted colibactin-producing bacteria from the intestines.

Tommi Mäklin et al, Geographical variation in the incidence of colorectal cancer and urinary tract cancer is associated with population exposure to colibactin-producing Escherichia coli, The Lancet Microbe (2024). DOI: 10.1016/j.lanmic.2024.101015. www.sciencedirect.com/science/ … ii/S2666524724002830

Part 2

Genetic risk for schizophrenia linked to a malformed skull

The chromosomal disorder 22q11.2 deletion syndrome (22q) has emerged as one of the strongest risks for schizophrenia. Scientists at St. Jude Children's Research Hospital identified malformed regions of the cerebellum in laboratory models and patients with 22q and found that these malformations were caused by improper skull formation. Further, the researchers linked the skull malformation to the loss of one gene: Tbx1.

The research shows that neurological disorders can stem from sources beyond the nervous system, such as improper skull development. The findings were published today in Nature Communications.

Gene removal blocks skull pocket from forming.

Previous work from scientists found that the deletion of only one 22q gene, Dgcr8, disrupts the flow of auditory information from a lower brain region called the thalamus to the auditory cortex, where sounds are interpreted. This region of the brain is also associated with auditory hallucinations, which are a hallmark symptom of schizophrenia. The researchers called this breakdown in information flow "thalamocortical disruption."

Although thalamocortical disruption occurs late in development, which is consistent with the onset of schizophrenia symptoms, it stays and doesn't go away. However, hallucinations are transient in nature—they come and go.

It seemed that this was just one of the hits that triggered symptoms.

The researchers noticed a part of the brain, the cerebellum, malformed in 22q animal models, specifically, the cerebellum's small lobules called the flocculus and paraflocculus. Most neurodevelopmental disorders arise from defects in genes that play a role in the brain, but the 22q gene the researchers linked to this malformation, Tbx1, was unexpected.

What is interesting about Tbx1 is that it is not very well expressed in the brain, especially the adolescent or adult brain. Rather, it's expressed in the surrounding tissues, namely bone, cartilage and vasculature tissues. It is very unlikely that Tbx1 directly affects the brain at all.

Instead, removing Tbx1 has an indirect but significant effect on brain development. Bone formation relies on immature osteoblast cells correctly growing into mature osteocytes. Tbx1 removal disrupted this cycle, resulting in an underdeveloped pocket in the skull which normally houses the flocculus and paraflocculus.

For a neurological syndrome, the findings are strikingly unusual—with no pocket in the skull for these structures to develop, they appear substantially smaller than normal. The reduction of the flocculus and paraflocculus was validated through magnetic resonance imaging studies of dozens of patients with 22q and a comparative control group.

Part 1

Researchers studied the flocculus and paraflocculus' role in the brain to better understand how their malformation could influence behavior. They found that the neural circuits within the flocculus and paraflocculus are dysfunctional.
The regions also control a reflex that ensures stable vision during head movements and is crucial for face recognition. The researchers found that this reflex is impaired in 22q. This may be a valuable lead for schizophrenia research because patients with schizophrenia have a deficit in face recognition.
The paraflocculus is also connected to the auditory cortex.

Tae-Yeon Eom et al, Tbx1 haploinsufficiency leads to local skull deformity, paraflocculus and flocculus dysplasia, and motor-learning deficit in 22q11.2 deletion syndrome, Nature Communications (2024). DOI: 10.1038/s41467-024-54837-3

Part 2

Researchers reprogram immune cells to decrease rejection of medical implants

Researchers have discovered that using a drug that is a metabolic inhibitor  makes the body more receptive to medical devices such as pacemakers, replacement joints and dental implants.

When doctors surgically place an implant into a human, there will always be an immune response and there's a chance the implant will be rejected.

Scientists used a drug that signals the body to boost or inhibit a particular reaction, called a metabolic modulator. This drug was incorporated into an amorphous polylactide—a biomaterial used to make medical implants—and then the material was implanted in mice.

Using intravital microscopy—a technique that allows us to look inside a living subject under a microscope—the researchers imaged different kinds of immune cells around the implant site for up to 10 weeks.

Their paper is published in the journal Nature Biomedical Engineering.

These findings have significant implications for improving patient recovery times, reducing postsurgical complications like chronic inflammation and implant rejection and potentially saving costs. And they may eventually affect the way medical device manufacturers and pharmaceutical scientists approach medical implants.

Chima V. Maduka et al, Immunometabolic cues recompose and reprogram the microenvironment around implanted biomaterials, Nature Biomedical Engineering (2024). DOI: 10.1038/s41551-024-01260-0

Does CPR help both the conditions of cardiac arrest and heart attacks?