Identifying pathways to slow cardiac aging

Cardiovascular disease is the leading cause of death worldwide, and is caused in part by age-related cardiac structural dysfunction. A team of bioengineers published a paper in Nature Aging on Dec. 22 that helps advance our understanding of how hearts age, and sheds light on a possible pathway to slow cardiac aging.

The researchers used fruit flies to show that Lamin C, a protein responsible for maintaining the structural integrity of heart cells' nuclei, declines as flies age. This study uncovered that Lamin decline is responsible for the age-induced structural remodeling in fruit fly hearts, and it could be a potential target to slow down, or even help reverse, cardiac aging in humans.

The team then quantified this change by segmenting and measuring nuclear stiffness with atomic force microscopy. This is when they discovered that cardiomyocyte nuclei stiffen during natural aging; after running a genetic anlysis, the researchers found that the expression of nuclear lamins decreases as flies age.

The team was able to verify that these results also applied to mice and primates. This indicates that a role for Lamins may apply to human heart aging as well, which could have tremendous therapeutic value, as targeting lamin-stimulating pathways could potentially help avoid this cardiac aging-related mechanical change.

Natalie J. Kirkland et al, Age-dependent Lamin changes induce cardiac dysfunction via dysregulation of cardiac transcriptional programs, Nature Aging (2022). DOI: 10.1038/s43587-022-00323-8

Researchers use quantum mechanics to see objects without looking at them

We see the world around us because light is being absorbed by specialized cells in our retina. But can vision happen without any absorption at all—without even a single particle of light? Surprisingly, the answer is yes.

Imagine that you have a camera cartridge that might contain a roll of photographic film. The roll is so sensitive that coming into contact with even a single photon would destroy it. With our everyday classical means there is no way  to know whether there's film in the cartridge, but in the quantum world it can be done. Anton Zeilinger, one of the winners of the 2022 Nobel Prize in Physics, was the first to experimentally implement the idea of an interaction-free experiment using optics.

Now, in a study exploring the connection between the quantum and classical worlds,  researchers have discovered a new and much more effective way to carry out interaction-free experiments. They used transmon devices—superconducting circuits that are relatively large but still show quantum behavior—to detect the presence of microwave pulses generated by classical instruments. Their research was recently published in Nature Communications.

Quantum coherence refers to the possibility that an object can occupy two different states at the same time—something that quantum physics allows for. However, quantum coherence is delicate and easily collapses, so it wasn't immediately obvious that the new protocol would work. To the research  team's pleasant surprise, the first runs of the experiment showed a marked increase in detection efficiency. They went back to the drawing board several times, ran theoretical models confirming their results, and double-checked everything. The effect was definitely there. They also also demonstrated that even very low-power microwave pulses can be detected efficiently using their protocol.

The experiment also showed a new way in which quantum devices can achieve results that are impossible for classical devices—a phenomenon known as quantum advantage. Researchers generally think that achieving quantum advantage will require quantum computers with many qubits, but this experiment demonstrated genuine quantum advantage using a relatively simpler setup.

Shruti Dogra et al, Coherent interaction-free detection of microwave pulses with a superconducting circuit, Nature Communications (2022). DOI: 10.1038/s41467-022-35049-z

Using an ethylene carbonate solvent with a sodium iodide salt to create a new kind of refrigerator

A pair of researchers  used a commonly known, naturally occurring phenomenon to build a new kind of environmentally safe refrigerator.

In their paper published in the journal Science, they describe how expanding on the idea of using salt to melt road ice to design and build a new kind of refrigerator.

For many years, people around the world have used salt to melt road ice to make travel easier. Though technically, the salt does not melt the ice, its dark color attracts heat, allowing the ice below it to melt, which than allows the salt to mix with the water. And it does not refreeze because the salt dramatically lowers the freezing point of the water.

It was on this part of the process that the researchers focused. They noted that a similar process could result in cooling a material simply by mixing it with sodium iodide (NaI) salt due to the phase transition. The second material in this case was an ethylene carbonate (EC) solvent. They further noted that repeatedly cooling a material should also cool the environment in which it is contained. And to make that happen, all they had to do was remove the salt, and then add it again.

The researchers call their process "ionocaloric" refrigeration, and built such a refrigerator to prove that it was viable. They started with a box and then added a mixing device to mix their two ingredients and another device that performed electrodialysis to remove the salt. Then tested the resulting device to determine if it would keep the temperature inside the box at a steady cool temperature, and if so, if it was more or less efficient than other refrigeration devices.

Their testing showed that their refrigerator was able to maintain a cool temperature and that it was approximately as efficient as refrigerators now on the market. The big advantage of the approach is that it does not emit any hydrofluorocarbons or other pollutants. They acknowledge that it does have one drawback—it takes quite a while for the mixed solution to cool.

Drew Lilley et al, Ionocaloric refrigeration cycle, Science (2022). DOI: 10.1126/science.ade1696

Emmanuel Defay, Cool it, with a pinch of salt, Science (2022). DOI: 10.1126/science.adf5114

Brown algae removes carbon dioxide from the air and stores it in slime

Brown algae take up large amounts of carbon dioxide from the air and release parts of the carbon contained therein back into the environment in mucous form. This mucus is hard to break down for other ocean inhabitants, thus the carbon is removed from the atmosphere for a long time, according to a new study.

Researchers reveal that the algal mucus called fucoidan is particularly responsible for this carbon removal and estimate that brown algae could thus remove up to 550 million tons of carbon dioxide from the air every year.

Algae take up carbon dioxide from the atmosphere and use the carbon to grow. They release up to a third of the carbon they absorb back into the seawater, for example in the form of sugary excretions. Depending on the structure of these excretions, they are either quickly used by other organisms or sink toward the seafloor.

Fucoidan made up about half of the excretions of the brown algae species the researchers studied, the so-called bladderwrack.

Fucoidan is a recalcitrant molecule. The fucoidan is so complex that it is very hard for other organisms to use it. No one seems to like it. As a result, the carbon from the fucoidan does not return to the atmosphere quickly. "This makes the brown algae particularly good helpers in removing carbon dioxide from the atmosphere in the long term—for hundreds to thousands of years.

Buck-Wiese, Hagen et al, Fucoid brown algae inject fucoidan carbon into the ocean, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2210561119. doi.org/10.1073/pnas.2210561119

New bacterial therapy approach to treat lung cancer

Lung cancer is one of the deadliest cancers  around the world. Many of the currently available therapies have been ineffective, leaving patients with very few options. A promising new strategy to treat cancer has been bacterial therapy, but while this treatment modality has quickly progressed from labouratory experiments to clinical trials in the last five years, the most effective treatment for certain types of cancers may be in combination with other drugs.

Researchers report that they have developed a preclinical evaluation pipeline for characterization of bacterial therapies in lung cancer models. Their new study, published December 13, 2022, by Scientific Reports, combines bacterial therapies with other modalities of treatment to improve treatment efficacy without any additional toxicity. This new approach was able to rapidly characterize bacterial therapies and successfully integrate them with current targeted therapies for lung cancer.

The team used RNA sequencing to discover how cancer cells were responding to bacteria at the cellular and molecular levels. They built a hypothesis on which molecular pathways of cancer cells were helping the cells to be resistant to the bacteria therapy. To test their hypothesis, the researchers blocked these pathways with current cancer drugs and showed that combining the drugs with bacterial toxins is more effective in eliminating lung cancer cells. They validated the combination of bacteria therapy with an AKT-inhibitor as an example in mouse models of lung cancer.

This new study describes an exciting drug development pipeline that has been previously unexplored in lung cancer—the use of toxins derived from bacteria.

The preclinical data presented in the manuscript provides a strong rationale for continued research in this area, thereby opening up the possibility of new treatment options for patients diagnosed with this lethal disease.

 Dhruba Deb et al, Design of combination therapy for engineered bacterial therapeutics in non-small cell lung cancer, Scientific Reports (2022). DOI: 10.1038/s41598-022-26105-1

Spontaneous baby movements are important for development of coordinated sensorimotor system

Some guts are better than others at harvesting energy, study shows

New research from the University of Copenhagen suggests that a portion of the Danish population has a composition of gut microbes that, on average, extracts more energy from food than do the microbes in the guts of their fellow Danes. The research is a step towards understanding why some people gain more weight than others, even when they eat the same.

Unfair as it, some of us seem to put on weight just by looking at a plate of Christmas cookies, while others can munch away with abandon and not gain a gram. Part of the explanation could be related to the composition of our gut microbes. This is according to new research conducted at the University of Copenhagen's Department of Nutrition, Exercise and Sports.

The research is published in the journal Microbiome.

Researchers studied the residual energy in the feces of 85 Danes to estimate how effective their gut microbes are at extracting energy from food. At the same time, they mapped the composition of gut microbes for each participant.

The results show that roughly 40% of the participants belong to a group that, on average, extracts more energy from food compared to the other 60%. The researchers also observed that those who extracted the most energy from food also weighed 10% more on average, amounting to an extra nine kilograms.

The results indicate that being overweight might not just be related to how healthily one eats or the amount of exercise one gets. It may also have something to do with the composition of a person's gut microbes.

Following the study, the researchers suspect that a portion of the population may be disadvantaged by having gut bacteria that are a bit too effective at extracting energy. This effectiveness may result in more calories being available for the human host from the same amount of food.

Jos Boekhorst et al, Stool energy density is positively correlated to intestinal transit time and related to microbial enterotypes, Microbiome (2022). DOI: 10.1186/s40168-022-01418-5

About gut bacteria:

• Everyone has a unique composition of gut bacteria—shaped by genetics, environment, lifestyle and diet.
• The collection of gut bacteria, called the gut microbiota, is like an entire galaxy in our gut, with a staggering 100 billion of them per gram of stool.
• Gut bacteria in the colon serve to break down food parts that our body's digestive enzymes can't, e.g., dietary fiber.
• Humans can be divided into three groups based on the presence and abundance of three main groups of bacteria that most of us have: B-type (Bacteroides), R-type (Ruminococcaceae) and P-type (Prevotella).

Brain area necessary for fluid intelligence identified

A team of researchers have mapped the parts of the brain that support our ability to solve problems without prior experience—otherwise known as fluid intelligence.

Fluid intelligence is arguably the defining feature of human cognition. It predicts educational and professional success, social mobility, health, and longevity. It also correlates with many cognitive abilities such as memory.

Fluid intelligence is thought to be a key feature involved in "active thinking"—a set of complex mental processes such as those involved in abstraction, judgment, attention, strategy generation and inhibition. These skills can all be used in everyday activities.

Despite its central role in human behavior, fluid intelligence remains contentious, with regards to whether it is a single or a cluster of cognitive abilities, and the nature of its relationship with the brain. To establish which parts of the brain are necessary for a certain ability, researchers must study patients in whom that part is either missing or damaged. Such "lesion-deficit mapping" studies are difficult to conduct owing to the challenge of identifying and testing patients with focal brain injury. Consequently, previous studies have mainly used functional imaging (fMRI) techniques—which can be misleading.

The new study investigated 227 patients who had suffered either a brain tumour or stroke to specific parts of the brain, using the Raven Advanced Progressive Matrices (APM): the best-established test of fluid intelligence. The test contains multiple choice visual pattern problems of increasing difficulty. Each problem presents an incomplete pattern of geometric figures and requires selection of the missing piece from a set of multiple possible choices. The researchers then introduced a novel "lesion-deficit mapping" approach to disentangle the intricate anatomical patterns of common forms of brain injury, such as stroke.

Their approach treated the relations between brain regions as a mathematical network whose connections describe the tendency of regions to be affected together, either because of the disease process or in reflection of common cognitive ability. This enabled researchers to disentangle the brain map of cognitive abilities from the patterns of damage—allowing them to map the different parts of the brain and determine which patients did worse in the fluid intelligence task according to their injuries.

The researchers found that fluid intelligence impaired performance was largely confined to patients with right frontal lesions—rather than a wide set of regions distributed across the brain. Alongside brain tumours and stroke, such damage is often found in patients with a range of other neurological conditions, including traumatic brain injury and dementia.

These  findings indicate for the first time that the right frontal regions of the brain are critical to the high-level functions involved in fluid intelligence, such as problem solving and reasoning.

Lisa Cipolotti et al, Graph lesion-deficit mapping of fluid intelligence, Brain (2022). DOI: 10.1093/brain/awac304

Holding information in mind may mean storing it among synapses

Between the time you read the Wi-Fi password off the café's menu board and the time you can get back to your laptop to enter it, you have to hold it in mind. If you've ever wondered how your brain does that, you are asking a question about working memory that has researchers have strived for decades to explain. Now  neuroscientists have published a key new insight to explain how it works.

In a study in PLOS Computational Biology, scientists compared measurements of brain cell activity in an animal performing a working memory task with the output of various computer models representing two theories of the underlying mechanism for holding information in mind. The results strongly favoured the newer notion that a network of neurons stores the information by making short-lived changes in the pattern of their connections, or synapses, and contradicted the traditional alternative that memory is maintained by neurons remaining persistently active (like an idling engine).

While both models allowed for information to be held in mind, only the versions that allowed for synapses to transiently change connections ("short-term synaptic plasticity") produced neural activity patterns that mimicked what was actually observed in real brains at work. The idea that brain cells maintain memories by being always "on" may be simpler, but it doesn't represent what nature is doing and can't produce the sophisticated flexibility of thought that can arise from intermittent neural activity backed up by short-term synaptic plasticity.

You need these kinds of mechanisms to give working memory activity the freedom it needs to be flexible. If working memory was just sustained activity alone, it would be as simple as a light switch. But working memory is as complex and dynamic as our thoughts.

Using artificial neural networks with short-term synaptic plasticity, scientists show that synaptic activity (instead of neural activity) can be a substrate for working memory. The important takeaway from this paper is: these 'plastic' neural network models are more brain-like, in a quantitative sense, and also have additional functional benefits in terms of robustness.

Part 1

In addition to matching nature better, the synaptic plasticity models also conferred other benefits that likely matter to real brains. One was that the plasticity models retained information in their synaptic weightings even after as many as half of the artificial neurons were "ablated." The persistent activity models broke down after losing just 10–20 percent of their synapses. And just spiking occasionally requires less energy than spiking persistently.

Furthermore, quick bursts of spiking rather than persistent spiking leaves room in time for storing more than one item in memory. Research has shown that people can hold up to four different things in working memory. 

Leo Kozachkov et al, Robust and brain-like working memory through short-term synaptic plasticity, PLOS Computational Biology (2022). DOI: 10.1371/journal.pcbi.1010776

Part 2

South Asian black carbon causes glacier loss on Tibetan Plateau

Black carbon aerosol is the product of incomplete combustion of fossil fuels and biomass, and has strong light absorption. Black carbon deposition in snow ice reduces the albedo of the snow ice surface, accelerating the melting of glaciers and snow cover, and thus changing the hydrological process and water resources in the region.

The South Asia region adjacent to the Tibetan Plateau is one of the regions with high black carbon emission in the world. Black carbon aerosol from South Asia can transport across the Himalayan Mountains to the inland region of the Tibetan Plateau.

Recently, a  research team analyzed the influence of black carbon aerosols on regional precipitation and glaciers over the Qinghai-Tibet Plateau.

Their findings were published in Nature Communications on Nov. 30.

The researchers found that since the 21st century, the South Asian black carbon aerosols have indirectly affected the material supply of the Tibetan Plateau glaciers by changing water vapour transport in the South Asian monsoon.

Black carbon aerosols in South Asia heat up the middle and upper atmosphere, thus increasing the north-south temperature gradient.

Accordingly, the convective activity in South Asia is enhanced, which causes convergence of water vapor in South Asia. Meanwhile, black carbon also increases the number of cloud condensation nuclei in the atmosphere."

These changes in meteorological conditions caused by black carbon aerosols make more water vapor form precipitation in South Asia, and less water vapor transmit to the Tibetan Plateau. As a result, precipitation in the central and southern Tibetan Plateau decreases during monsoon, especially in the southern part of the Tibetan Plateau.

The decrease of precipitation further leads to the decrease of material supply of glaciers. From 2007 to 2016, the reduced material supply accounted for 11.0% of the average glacier material loss on the Tibetan Plateau and 22.1% in the southern part of the plateau.

"The transboundary transport and deposition of black carbon aerosols in South Asia accelerate glacier ablation on the Tibetan Plateau. Meanwhile, the reduction of plateau summer precipitation will reduce the material supply of plateau glacier, which will increase the amount of glacier material deficit.

Junhua Yang et al, South Asian black carbon is threatening the water sustainability of the Asian Water Tower, Nature Communications (2022). DOI: 10.1038/s41467-022-35128-1

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Gastroesophageal reflux disease raises risk for periodontitis: Study

Patients with gastroesophageal reflux disease (GERD) have an increased risk for periodontitis development, according to a study published online Nov. 19 in Biomedicines.

Researchers conducted a retrospective cohort study to examine the association between GERD and subsequent periodontitis risk using epidemiological data from the Taiwan National Health Insurance Research Database from 2008 to 2018. A total of 20,125 participants with a minimum age of 40 years were included in the GERD group and propensity-matched in a 1:1 ratio with non-GERD participants.

The researchers found that the incidence rate of periodontitis was significantly higher in patients with versus those without GERD (30.0 versus 21.7 per 1,000 person-years; adjusted hazard ratio, 1.36). Patients with GERD had a higher risk for periodontitis in analyses stratified for age (adjusted hazard ratios, 1.31 and 1.42 for age 40 to 54 and 55 to 69 years, respectively), sex (adjusted hazard ratios, 1.40 and 1.33 for men and women, respectively), and presence and absence of comorbidity (adjusted hazard ratios, 1.36 and 1.40, respectively) compared with those without GERD. The risk for periodontitis was increased with an increasing number of emergency room visits among the GERD cohort (one or more versus less than one; adjusted hazard ratio, 5.19).

"Clinicians should pay more attention to the development of periodontitis while caring for patients with GERD," the authors write. "On the other hand, dentists may consider GERD as an etiology of unexplained periodontitis."

Parental astigmatism may increase risk for child astigmatism

Parental astigmatism may confer an independent and dose-dependent association with child astigmatism, according to a study published online Dec. 21 in JAMA Network Open.

Researchers examined the association between parental astigmatism (an optical system with astigmatism is one where rays that propagate in two perpendicular planes have different foci. If an optical system with astigmatism is used to form an image of a cross, the vertical and horizontal lines will be in sharp focus at two different distances) and child astigmatism. The analysis included 5,708 familial trios, each comprising a child aged 6 to 8 years and both parents, participating in the Hong Kong Children Eye Study.

The researchers found that astigmatism of ≥1.0 D in both parents was associated with greater odds of refractive astigmatism (RA; odds ratio, 1.62) and corneal astigmatism (CA; odds ratio, 1.94) in the child. When both parents had astigmatism ≥2.0 D, the risk increased further (odds ratios, 3.10 and 4.31, respectively), with higher parental astigmatism conferring higher risks for both RA and CA in children. There was a significant association between each parental astigmatism and corresponding child astigmatism (odds ratios, 0.76, 0.82, 1.70, and 1.33 for maternal RA, paternal RA, maternal CA, and paternal CA, respectively).

"The findings of this cross-sectional study suggest that parental astigmatism may confer an independent and dose-dependent association with child astigmatism," the authors write. "Children with parents with astigmatism should have early eye examinations for timely detection of astigmatism to facilitate age-appropriate vision correction and visual development."

Researchers discover that soap film on bubbles is cooler than the air around it

A team of researchers has discovered that the film that makes up ordinary soap bubbles is cooler than the surrounding air.

Bubbles exist in a wide variety of environments, from beer glasses to clothes and dish washers to crests on waves. They even exist in tiny environments, like in the space between human teeth. A lot of research has been done with bubbles, much of it focused on controlling them during industrial processes.

 In their work, the researchers created bubbles using ordinary dish soap, water and glycerol. After discovering a temperature difference, the team refocused their efforts to learn more. They tried changing the temperature of the air, the humidity level and also the proportions of the ingredients used to make the bubbles. They found that they were able to make bubbles that were up to 8 degrees Celsius cooler than the air around them. They also found that changing the amount of glycerol impacted the temperature of the resulting bubbles—more of it yielded higher temperatures.

The researchers suggest the cooler films could be the result of evaporation as the bubbles form. They noted also that as the bubbles persisted, their films slowly grew warmer, eventually matching the ambient air temperature. They suggest the large temperature differences they found with some bubbles might have an impact on bubble stability, and conclude that more work is required to find out why the films are cooler and if it might be a useful attribute.

 François Boulogne et al, Measurement of the Temperature Decrease in Evaporating Soap Films, Physical Review Letters (2022). DOI: 10.1103/PhysRevLett.129.268001. On Arxiv: arxiv.org/abs/2212.07104

Ketamine found to increase brain noise

An international team of researchers found that ketamine, being an NMDA receptor inhibitor, increases the brain's background noise, causing higher entropy of incoming sensory signals and disrupting their transmission between the thalamus and the cortex. This finding may contribute to a better understanding of the causes of psychosis in schizophrenia. An article with the study's findings has been published in the European Journal of Neuroscience.

Schizophrenic spectrum disorders affect approximately one in 300 people worldwide. The most common manifestations of these disorders are perceptual disturbances such as hallucinations, delusions and psychoses. A drug called ketamine can induce a mental state similar to psychosis in healthy individuals. Ketamine inhibits NMDA receptors involved in the transmission of excitatory signals in the brain. An imbalance of excitation and inhibition in the central nervous system can affect the accuracy of sensory perception. Similar changes in the functioning of NMDA receptors are currently thought to be one of the causes of perception disorders in schizophrenia. However, it is still unclear how exactly this process occurs in the brain regions involved.

To find out, neuroscientists 

studied how the brains of laboratory rats on ketamine process sensory signals. The researchers examined beta and gamma oscillations occurring in response to sensory stimuli in the rodent brain's thalamo-cortical system , a neural network connecting the cerebral cortex with the thalamus responsible for the transmission of sensory information from the organs of perception to the brain.

Beta oscillations are brainwaves in the range of 15 to 30 Hz, and gamma waves are those in the range of 30 to 80 Hz. These frequencies are believed to be critical for encoding and integrating sensory information.

In the experiment, rats were implanted with microelectrodes to record the electrical activity in the thalamus and the somatosensory cortex , a region of the brain which is responsible for processing sensory information coming from the thalamus. The researchers stimulated the rats' whiskers (vibrissae) and recorded the brain's responses before and after ketamine administration.

A comparison of the two datasets revealed that ketamine increased the power of beta and gamma oscillations in the cortex and the thalamus even in the resting state before a stimulus was presented, while the amplitude of the beta/gamma oscillations in the 200–700 ms post-stimulus period was significantly lower at all recorded cortical and thalamic sites following ketamine administration.

The post-stimulation time lapse of 200–700 ms is long enough to encode, integrate and perceive the incoming sensory signal. The observed decrease in the power of sensory stimulus-induced oscillations can be associated with impaired perception.

Part 1

Analysis also revealed that by inhibiting NMDA receptors, ketamine administration added noise to gamma frequencies in the post-stimulation 200–700 ms period in one thalamic nucleus and in one layer of the somatosensory cortex. It can be assumed that this observed increase in noise, ie a reduction in the signal-to-noise ratio, also indicates the neurons' impaired ability to process incoming sensory signals.

These findings suggest that psychosis may be triggered by an increase in background noise impairing the function of thalamo-cortical neurons. This, in turn, could be caused by a malfunction of NMDA receptors affecting the balance of inhibition and excitation in the brain. The noise makes sensory signals less defined or pronounced. In addition, this may cause spontaneous outbursts of activity associated with a distorted perception of reality.

"The discovered alterations in thalamic and cortical electrical activity associated with ketamine-induced sensory information processing disorders could serve as biomarkers for testing antipsychotic drugs or predicting the course of disease in patients with psychotic spectrum disorders.

 Yi Qin et al, The psychotomimetic ketamine disrupts the transfer of late sensory information in the corticothalamic network, European Journal of Neuroscience (2022). DOI: 10.1111/ejn.15845

Thomas J. Reilly, Ketamine: Linking NMDA receptor hypofunction, gamma oscillations and psychosis (commentary on Qin et al., 2022), European Journal of Neuroscience (2022). DOI: 10.1111/ejn.15872

Part 2 

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How chronic blood cancer transitions to aggressive disease

A type of chronic leukemia can simmer for many years. Some patients may need treatment to manage this type of blood cancer—called myeloproliferative neoplasms (MPN)—while others may go through long periods of watchful waiting. But for a small percentage of patients, the slower paced disease can transform into an aggressive cancer, called secondary acute myeloid leukemia, that has few effective treatment options. Little has been known about how this transformation takes place.

But now, researchers  have identified an important transition point in the shift from chronic to aggressive leukemia. They have shown that blocking a key molecule in the transition pathway prevents this dangerous disease progression in mice with models of the disease and in mice with tumors sampled from human patients.

Tim Kong et al, DUSP6 mediates resistance to JAK2 inhibition and drives leukemic progression, Nature Cancer (2022). DOI: 10.1038/s43018-022-00486-8

Quasicrystal formed during accidental electrical discharge

Quasicrystals, as their name suggests, are crystal-like substances. They possess characteristics not found in ordinary crystals, such as a non-repeating arrangement of atoms. To date, quasicrystals have been found embedded in meteorites and in the debris from nuclear blasts. In this new effort, the researchers found one embedded in a sand dune in Sand Hills, Nebraska.

A team of researchers  has found an incidence of a quasicrystal formed during an accidental electrical discharge.

Study of the quasicrystal showed it had 12-fold, or dodecagonal, symmetry—something rarely seen in quasicrystals. Curious as to how it might have formed and how it ended up in the sand dune, the researchers did some investigating. They discovered that a power line had fallen on the dune, likely the result of a lightning strike. They suggest the electrical surge from either the power line or the lightning could have produced the quasicrystal.

The researchers note that the quasicrystal was found inside of a tubular piece of fulgurite, which they suggest was also formed during the electrical surge due to fusing of melted sand and metal from the power line. 

In looking at the quasicrystal using an electron microscope, the researchers were able to make out its composition. In so doing, they found bits of silicon dioxide glass, which told them that temperatures inside the sand dune during the electrical discharge had to have reached at least 1,710 degrees Celsius. They also found that the quasicrystal had been retrieved from an area of transition between melted aluminum alloy and silicate glass. Their work confirmed that the object they were studying was, indeed, a quasicrystal, and that it had a previously unseen composition.

The researchers conclude that finding a quasicrystal in such a place suggests that others are likely out there, as well, having formed due to lightning strikes or downed power lines. They also suggest their work could lead to techniques to create quasicrystals in the lab.

Luca Bindi et al, Electrical discharge triggers quasicrystal formation in an eolian dune, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2215484119

Human brain organoids implanted into mouse cortex respond to visual stimuli for first time

 A team of engineers and neuroscientists has demonstrated for the first time that human brain organoids implanted in mice have established functional connectivity to the animals' cortex and responded to external sensory stimuli. The implanted organoids reacted to visual stimuli in the same way as surrounding tissues, an observation that researchers were able to make in real time over several months thanks to an innovative experimental setup that combines transparent graphene microelectrode arrays and two-photon imaging.

Madison N. Wilson, Martin Thunemann, Xin Liu, Yichen Lu, Francesca Puppo, Jason W. Adams, Jeong-Hoon Kim, Mehrdad Ramezani, Donald P. Pizzo, Srdjan Djurovic, Ole A. Andreassen, Abed AlFatah Mansour, Fred H. Gage, Alysson R. Muotri, Anna Devor, Duygu Kuzum. Multimodal monitoring of human cortical organoids implanted in mice reveal functional connection with visual cortex. Nature Communications, 2022; 13 (1) DOI: 10.1038/s41467-022-35536-3

Researchers identify 100,000 new types of viruses

A groundbreaking  study has discovered about 100,000 new types of previously unknown viruses , a ninefold increase in the amount of RNA viruses known to science until now. The viruses were discovered in global environmental data from soil samples, oceans, lakes, and a variety of other ecosystems. The researchers believe that the discovery may help in the development of anti-microbial drugs and in protecting against agriculturally harmful fungi and parasites. 

Self-assembling proteins can store cellular 'memories'

As cells perform their everyday functions, they turn on a variety of genes and cellular pathways. Researchers have now coaxed cells to inscribe the history of these events in a long protein chain that can be imaged using a light microscope.

Cells programmed to produce these chains continuously add building blocks that encode particular cellular events. Later, the ordered protein chains can be labeled with fluorescent molecules and read under a microscope, allowing researchers to reconstruct the timing of the events.

This technique could help shed light on the steps that underlie processes such as memory formation, response to drug treatment, and gene expression.

If the technique could be extended to work over longer time periods, it could also be used to study processes such as aging and disease progression, the researchers say.

Recording of cellular physiological histories along optically readable self-assembling protein chains, Nature Biotechnology (2022). DOI: 10.1038/s41587-022-01586-7

Dry eye disease affects how the eye's cornea heals itself after injury

People with a condition known as dry eye disease are more likely than those with healthy eyes to suffer injuries to their corneas. Studying mice, researchers at Washington University School of Medicine in St. Louis have found that proteins made by stem cells that regenerate the cornea may be new targets for treating and preventing such injuries.

Dry eye disease occurs when the eye can't provide adequate lubrication with natural tears. People with the common disorder use various types of drops to replace missing natural tears and keep the eyes lubricated, but when eyes are dry, the cornea is more susceptible to injury.

We have drugs to treat this condition, but they only work well in about 10% to 15% of patients. In this new study involving genes that are key to eye health, researchers identified potential targets for treatment that appear different in dry eyes than in healthy eyes. 

The researchers analyzed genes expressed by the cornea in several mouse models—not only of dry eye disease, but also of diabetes and other conditions. They found that in mice with dry eye disease, the cornea activated expression of the gene SPARC. They also found that higher levels of SPARC protein were associated with better healing.

Lin, Joseph B. et al, Dry eye disease in mice activates adaptive corneal epithelial regeneration distinct from constitutive renewal in homeostasis, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2204134120. doi.org/10.1073/pnas.2204134120

COVID-19 vaccines, prior infection reduce transmission of omicron, finds study 

Vaccination and boosting, especially when recent, helped to limit the spread of COVID-19 in California prisons during the first omicron wave, according to an analysis by researchers.

 The study demonstrates the benefits of vaccination and boosting, even in settings where many people are still getting infected, in reducing transmission. And it shows the cumulative effects from boosting and the additional protection that vaccination gives to those who were previously infected. The likelihood of transmission fell by 11% for each additional dose.

A lot of the benefits of vaccines to reduce infectiousness were from people who had received boosters and people who had been recently vaccinated.

Vaccinated residents with breakthrough infections were significantly less likely to transmit them: 28% versus 36% for those who were unvaccinated. But the likelihood of transmission grew by 6% for every five weeks that passed since someone's last vaccine shot.

Natural immunity from a prior infection also had a protective effect, and the risk of transmitting the virus was 23% for someone with a reinfection compared to 33% for someone who had never been infected.

Those with hybrid immunity, from both infection and vaccination, were 40% less likely to transmit the virus. Half of that protection came from the immunity that one acquires from fighting an infection and the other half came from being vaccinated.

 Infectiousness of SARS-CoV-2 breakthrough infections and reinfections during the Omicron wave, Nature Medicine (2022). DOI: 10.1038/s41591-022-02138-x , www.nature.com/articles/s41591-022-02138-x

Good hydration linked to healthy aging

Adults who stay well-hydrated appear to be healthier, develop fewer chronic conditions, such as heart and lung disease, and live longer than those who may not get sufficient fluids, according to a National Institutes of Health study published in eBioMedicine.     Using health data gathered from 11,255 adults over a 30-year period, researchers analyzed links between serum sodium levels—which go up when fluid intake goes down—and various indicators of health. They found that adults with serum sodium levels at the higher end of a normal range were more likely to develop chronic conditions and show signs of advanced biological aging than those with serum sodium levels in the medium ranges. Adults with higher levels were also more likely to die at a younger age. 

The results suggest that proper hydration may slow down aging and prolong a disease-free life.

The study expands on research the scientists published in March 2022, which found links between higher ranges of normal serum sodium levels and increased risk for heart failure. Both findings came from the Atherosclerosis Risk in Communities (ARIC) study, which includes sub-studies involving thousands of  adults.

The researchers found that adults with higher levels of normal serum sodium—with normal ranges falling between 135-146 milliequivalents per liter (mEq/L)—were more likely to show signs of faster biological aging. This was based on indictors like metabolic and cardiovascular health, lung function, and inflammation. 

The conclusion therefore was people whose serum sodium is 142 mEq/L or higher would benefit from evaluation of their fluid intake. Doctors may also need to defer to a patient's current treatment plan, such as limiting fluid intake for heart failure. The authors also cited research that finds about half of people worldwide don't meet recommendations for daily total water intake, which often starts at 6 cups (1.5 liters).  

Decreased body water content is the most common factor that increases serum sodium, which is why the results suggest that staying well hydrated may slow down the aging process and prevent or delay chronic disease.

Natalia I. Dmitrieva et al, Middle-age high normal serum sodium as a risk factor for accelerated biological aging, chronic diseases, and premature mortality, eBioMedicine (2023). DOI: 10.1016/j.ebiom.2022.104404

Duping antibodies with a decoy, researchers aim to prevent rejection of transplanted cells

Researchers  have developed a novel, potentially life-saving approach that may prevent antibodies from triggering immune rejection of engineered therapeutic and transplant cells.

Rejection mediated by antibodies—as opposed to the chemical assault initiated by immune cells—has proven particularly tricky to resolve, a factor holding held back the development of some of these treatments. The new strategy, described in the Monday, Jan. 2, 2023 issue of Nature Biotechnology, involved using a "decoy" receptor to capture the antibodies and take them out of circulation before they could kill the therapeutic cells, that they treat as invading foreigners. The tactic may also be useful for organ transplants.

The most celebrated cellular therapies  are chimeric antigen receptor (CAR) T-cell therapies. These CAR-T therapies are often used to successfully treat specific forms of lymphomas, a type of often-deadly cancer. But deploying them against solid tumors has proved much more difficult. Until recently, most CAR-T therapies have been made using the patient's own cells, but the long-term commercial viability of cellular therapies of all types will rely on "allogeneic" cells—mass-produced therapeutic cells grown from a source outside the patient. As with transplanted organs, the recipient's immune system is likely to treat any outsider cells, or tissues developed from them, as foreign and to reject them. This issue is likely to be a severe obstacle in any type of allogeneic cell transplantation.

Part1

Normally when an antibody binds to a cell, it acts as a sort of tag, calling out for an immune cell to bind to the antibody and set off an efficient process of destroying the tagged cell. To stop this chain reaction, researchers devised a method to catch the antibodies before they bind to cells, preventing activation of the immune response.

The researchers genetically engineered three types of cells—insulin-producing pancreatic islet cells, thyroid cells, and CAR-T cells—so that each type made and displayed large numbers of a protein called CD64 on their surfaces.

On these engineered cells, CD64, which tightly binds the antibodies responsible for this type of immune rejection, acted as a kind of decoy, capturing the antibodies and binding them to the engineered cell, so they wouldn't activate immune cells.

Indeed this was the case when this approach was tested. This is clear proof-of-concept for this approach.

Tobias Deuse, Protection of cell therapeutics from antibody-mediated killing by CD64 overexpression, Nature Biotechnology (2023). DOI: 10.1038/s41587-022-01540-7. www.nature.com/articles/s41587-022-01540-7

Part2

Black Hole Tidal Disruption Event (Animation)

New type of entanglement lets scientists 'see' inside nuclei

Nuclear physicists have found a new way to use the Relativistic Heavy Ion Collider (RHIC) to see the shape and details inside atomic nuclei. The method relies on particles of light that surround gold ions as they speed around the collider and a new type of quantum entanglement that's never been seen before.

Through a series of quantum fluctuations, the particles of light (a.k.a. photons) interact with gluons—gluelike particles that hold quarks together within the protons and neutrons of nuclei. Those interactions produce an intermediate particle that quickly decays into two differently charged "pions" (π). By measuring the velocity and angles at which these π⁺ and π^- particles strike RHIC's STAR detector, the scientists can backtrack to get crucial information about the photon—and use that to map out the arrangement of gluons within the nucleus with higher precision than ever before.
This technique is similar to the way doctors use positron emission tomography (PET scans) to see what's happening inside the brain and other body parts. But in this case, physicists are talking about mapping out features on the scale of femtometers—quadrillionths of a meter—the size of an individual proton.
Even more amazing, the STAR physicists say, is the observation of an entirely new kind of quantum interference that makes their measurements possible.
Physicists measure two outgoing particles and clearly their charges are different—they are different particles—but they see interference patterns that indicate these particles are entangled, or in sync with one another, even though they are distinguishable particles! This is the first-ever experimental observation of entanglement between dissimilar particles.
That discovery may have applications well beyond the lofty goal of mapping out the building blocks of matter.
James Brandenburg, Tomography of ultra-relativistic nuclei with polarized photon-gluon collisions, Science Advances (2023). DOI: 10.1126/sciadv.abq3903. www.science.org/doi/10.1126/sciadv.abq3903

Scientists found the structure and function of newly discovered CRISPR immune system

 Biochemists in their new research papers  described the structure and function of a newly discovered CRISPR immune system that—unlike better-known CRISPR systems that deactivate foreign genes to protect cells—shuts down infected cells to thwart infection.

CRISPR, a manageable acronym for the mouthful "Clustered Regularly Interspaced Short Palindromic Repeats," has captured the imaginations of scientists and lay people alike, with its gene-editing potential. Study of CRISPR DNA sequences and CRISPR-associated (Cas) proteins, which are actually bacterial immune systems, is still a young field, although it's receiving widespread attention for its gene-editing applications.

Identified as a distinct immune system within the last five years, the Class 2, type V Cas12a2 is somewhat similar to the better-known CRISPR-Cas9, which binds to target DNA and cuts it—like molecular scissors—effectively shutting off a targeted gene. But CRISPR-Cas12a2 binds a different target than Cas9, and that binding has a very different effect.

The Cas12a2 protein undergoes major conformational changes upon binding to RNA that opens an indiscriminate active site for DNA destruction. "Cas12a2 destroys the DNA and RNA in target cells, causing them to go senescent."

Using cryo-electron microscopy or "cryo-EM," the researchers demonstrated this unique aspect of CRISPR-Cas12a2, including its RNA-triggered degradation of single-stranded RNA, single-stranded DNA and double-stranded DNA, resulting in a naturally occurring defensive strategy called abortive infection.

Abortive infection is a natural phage resistance strategy used by bacteria and archaea to limit the spread of viruses and other pathogen. For example, abortive infection prevents viral components that have infected a cell from replicating.

The team captured the structure of Cas12a2 in the act of cutting double-stranded DNA.

Incredibly, Cas12a2 nucleases bend the usually straight piece of double-helical DNA 90 degrees, to force the backbone of the helix into the enzymatic active site, where it is cut. It's a change in structure that's extraordinary to observe.

Dymtrenko, Oleg, et al. "Cas12a2 Elicits Abortive Infection via RNA-triggered Destruction of dsDNA," Nature, 04 January 2023. DOI: 10.1038/s41586-022-05559-3 , www.nature.com/articles/s41586-022-05559-3

Bravo, Jack and Hallmark, Thomson, et al. "RNA Targeting Unleashes Indiscriminate Nuclease Activity of CRISPR-Cas12a2," Nature, 04 January 2023. DOI: 10.1038/s41586-022-05560-w , www.nature.com/articles/s41586-022-05560-w

Exercise curbs insulin production in fruit flies

Insulin is an essential hormone for humans and many other living creatures. Its best-known task is to regulate sugar metabolism. How it does this job is well understood. Much less is known about how the activity of insulin-producing cells and consequently the secretion of insulin is controlled.

Researchers  have now presented new information on this question in the scientific journal Current Biology. They used the fruit fly Drosophila melanogaster as their study object. Interestingly, this fly also secretes insulin after a meal. However, in the fly, the hormone does not come from the pancreas as in humans, but is instead released by nerve cells in the brain.

They  figured out that physical activity of the fly has a strong effect on its insulin-producing cells. For the first time, the researchers measured the activity of these cells electrophysiologically in walking and flying Drosophila.

The result: when Drosophila starts to walk or fly, its insulin-producing cells are immediately inhibited. When the fly stops moving, the activity of the cells rapidly increases again and shoots up above normal levels.

The scientists hypothesize that the low activity of insulin-producing cells during walking and flight contributes to the provision of sugars to meet the increased energy demand. They suspect that the increased activity after exercise helps to replenish the fly's energy stores, for example, in the muscles.

The team was also able to demonstrate that the fast, behaviour-dependent inhibition of insulin-producing cells is actively controlled by neural pathways. It is largely independent of changes in the sugar concentration in the fly's blood.

It makes a lot of sense for the organism to anticipate an increased energy demand in this way to prevent extreme fluctuations in blood sugar levels.

Part 1

Insulin has changed little throughout evolution

Do the results allow conclusions to be drawn about humans? Probably.

Although the release of insulin in fruit flies is mediated by different cells than in humans, the insulin molecule and its function have hardly changed in the course of evolution.

In the past 20 years, using Drosophila as a model organism, many fundamental questions have already been answered that could also contribute to a better understanding of metabolic defects in humans and associated diseases, such as diabetes or obesity.

Less insulin means longevity

One exciting point is that reduced insulin activity contributes to healthy aging and longevity. This has already been shown in flies, mice, humans and other species. The same applies to an active lifestyle. Our work shows a possible link explaining how physical activity could positively affect insulin regulation via neuronal signaling pathways.

Sander Liessem et al, Behavioral state-dependent modulation of insulin-producing cells in Drosophila, Current Biology (2022). DOI: 10.1016/j.cub.2022.12.005

Part 2

An Organism That Can Dine Exclusively on Viruses Has Been Found in a World First

A type of freshwater plankton has become the first organism seen thriving on a diet of viruses, according to a new study by researchers.

Viruses are often consumed incidentally by a range wide of organisms, and may even season the diets of certain marine protists. But to qualify as a true step in the food chain – described as virovory – viruses ought to contribute a significant amount of energy or nutrients to their consumer.

The microbe Halteria is a common genus of protist known to flit about as its hair-like cilia propel it through the water. Not only did laboratory samples of the ciliate consume chloroviruses added to its environment, the giant virus fueled Halteria's growth and increased its population size.

The knock-on effects of widespread consumption of chloroviruses in the wild could have a profound impact on the carbon cycle. Known to infect microscopic green algae, chloroviruses cause their hosts to burst apart, releasing carbon and other nutrients into the environment – a process that serious amounts of virus-eating could be limiting.

There's some good stuff inside viruses if you're an organism looking to feed, including amino acids, nucleic acids, lipids, nitrogen, and phosphorus. Surely something would want to make a meal out of that.

While the Paramecium snacked on the viruses, its sizes and numbers barely budged. Halteria, on the other hand, dined on them, using the chlorovirus as a source of nutrients. The ciliate's population grew about 15 times larger in two days, while the virus population dropped a hundredfold.

Fluorescent green dye was used to tag chlorovirus DNA before it was introduced to the two types of plankton. This confirmed that the viruses were being eaten: the vacuoles – microbial equivalent of stomachs – were glowing green from the feeding.

Further analysis revealed that the growth of Halteria in comparison to the decline of the chlorovirus matched the ratios seen in other microscopic predator vs prey relationships in aquatic environments, giving the team more evidence of what was happening.

https://www.pnas.org/doi/10.1073/pnas.2215000120

**

The brain's ability to perceive space expands like the universe

Young children sometimes believe that the moon is following them, or that they can reach out and touch it. It appears to be much closer than is proportional to its true distance. As we move about our daily lives, we tend to think that we navigate space in a linear way. But  scientists have discovered that time spent exploring an environment causes neural representations to grow in surprising ways.

The findings, published in Nature Neuroscience on December 29, 2022, show that neurons in the hippocampus essential for spatial navigation, memory, and planning represent space in a manner that conforms to a nonlinear hyperbolic geometry—a three-dimensional expanse that grows outward exponentially. (In other words, it's shaped like the interior of an expanding hourglass.) The researchers also found that the size of that space grows with time spent in a place. And the size is increasing in a logarithmic fashion that matches the maximal possible increase in information being processed by the brain.

This discovery provides valuable methods for analyzing data on neurocognitive disorders involving learning and memory, such as Alzheimer's disease.

This new study demonstrates that the brain does not always act in a linear manner. Instead, neural networks function along an expanding curve, which can be analyzed and understood using hyperbolic geometry and information theory.It is exciting to see that neural responses in this area of the brain formed a map that expanded with experience based on the amount of time devoted in a given place. The effect even held for miniscule deviations in time when animal ran more slowly or faster through the environment.

In the current study, the scientists found that hyperbolic geometry guides neural responses as well. Hyperbolic maps of sensory molecules and events are perceived with hyperbolic neural maps. The space representations dynamically expanded in correlation with the amount of time the rat spent exploring each environment. And, when a rat moved more slowly through an environment, it gained more information about the space, which caused the neural representations to grow even more.

The findings provide a novel perspective on how neural representations can be altered with experience. The geometric principles identified in our study can also guide future endeavors in understanding neural activity in various brain systems.

You would think that hyperbolic geometry only applies on a cosmic scale, but that is not true. Our brains work much slower than the speed of light, which could be a reason that hyperbolic effects are observed on graspable spaces instead of astronomical ones.

Huanqiu Zhang et al, Hippocampal spatial representations exhibit a hyperbolic geometry that expands with experience, Nature Neuroscience (2022). DOI: 10.1038/s41593-022-01212-4

New approach successfully traces genomic variants back to genetic disorders

Researchers have published an assessment of 13 studies that took a genotype-first approach to patient care. This approach contrasts with the typical phenotype-first approach to clinical research, which starts with clinical findings. A genotype-first approach to patient care involves selecting patients with specific genomic variants and then studying their traits and symptoms; this finding uncovered new relationships between genes and clinical conditions, broadened the traits and symptoms associated with known disorders, and offered insights into newly described disorders. The study was published in the American Journal of Human Genetics.

Genotype-first research can work, especially for identifying people with rare disorders who otherwise might not have been brought to clinical attention.

Typically, to treat genetic conditions, researchers first identify patients who are experiencing symptoms, then they look for variants in the patients' genomes that might explain those findings. However, this can lead to bias because the researchers are studying clinical findings based on their understanding of the disorder. The phenotype-first approach limits researchers from understanding the full spectrum of symptoms of the disorders and the associated genomic variants.

Genomics has the potential to change reactive medicine into preventative medicine. Studying how taking a genotype-first approach to research can help us learn how to model predictive and precision medicine in the future.

Part 1

The study documents three types of discoveries from a genotype-first approach.

First, the researchers found that this approach helped discover new relationships between genomic variants and specific clinical traits. For example, one NIH study found that having more than two copies of the TPSAB1 gene was associated with symptoms related to the gastrointestinal tract, connective tissues, and the nervous system.

Second, this approach helped researchers find novel symptoms related to a disorder that clinicians previously missed because the patient did not have the typical symptoms. NHGRI researchers identified a person with a genomic variant associated with a known metabolic disorder. Further testing found that the individual had high levels of certain chemicals in their body associated with the disorder, despite having only minor symptoms.

Study reveals average age at conception for men versus women over past 250,000 years

The length of a specific generation can tell us a lot about the biology and social organization of humans. Now, researchers  can determine the average age that women and men had children throughout human evolutionary history with a new method they developed using DNA mutations.

The researchers said this work can help us understand the environmental challenges experienced by our ancestors and may also help us in predicting the effects of future environmental change on human societies.

Through this research on  modern humans, researchers noticed that they could predict the age at which people had children from the types of DNA mutations they left to their children.They  then applied this model to our human ancestors to determine what age our ancestors procreated.

According to the study, published recently in Science Advances, the average age that humans had children throughout the past 250,000 years is 26.9. Furthermore, fathers were consistently older, at 30.7 years on average, than mothers, at 23.2 years on average, but the age gap has shrunk in the past 5,000 years, with the study's most recent estimates of maternal age averaging 26.4 years. The shrinking gap seems to largely be due to mothers having children at older ages. Other than the recent uptick in maternal age at childbirth, the researchers found that parental age has not increased steadily from the past and may have dipped around 10,000 years ago because of population growth coinciding with the rise of civilization. These mutations from the past accumulate with every generation and exist in humans today. Researchers  can now identify these mutations, see how they differ between male and female parents, and how they change as a function of parental age. Children's DNA inherited from their parents contains roughly 25 to 75 new mutations, which allows scientists to compare the parents and offspring, and then to classify the kind of mutation that occurred. When looking at mutations in thousands of children, the researchers noticed a pattern: The kinds of mutations that children get depend on the ages of the mother and the father. Previous genetic approaches to determining historical generation times relied on the compounding effects of either recombination or mutation of modern human DNA sequence divergence from ancient samples. But the results were averaged across both males and females and across the past 40,000 to 45,000 years.

Part1

The researchers built a model that uses de novo mutations—a genetic alteration that is present for the first time in one family member as a result of a variant or mutation in a germ cell of one of the parents or that arises in the fertilized egg during early embryogenesis—to separately estimate the male and female generation times at many different points throughout the past 250,000 years.

The story of human history is pieced together from a diverse set of sources: written records, archaeological findings, fossils, etc. Our genomes, the DNA found in every one of our cells, offer a kind of manuscript of human evolutionary history. The findings from our genetic analysis confirm some things we knew from other sources (such as the recent rise in parental age), but also offer a richer understanding of the demography of ancient humans. These findings contribute to a better understanding of our shared history.

Richard Wang, Human generation times across the past 250,000 years, Science Advances (2023). DOI: 10.1126/sciadv.abm7047. www.science.org/doi/10.1126/sciadv.abm7047

Part 2

Scars mended using transplanted hair follicles in new study

In a new  study involving three volunteers, skin scars began to behave more like uninjured skin after they were treated with hair follicle transplants. The scarred skin harbored new cells and blood vessels, remodeled collagen to restore healthy patterns, and even expressed genes found in healthy unscarred skin.

The findings could lead to better treatments for scarring both on the skin and inside the body, leading to hope for patients with extensive scarring, which can impair organ function and cause disability.

After scarring, the skin never truly regains its pre-wound functions, and until now all efforts to remodel scars have yielded poor results. The new  findings lay the foundation for exciting new therapies that can rejuvenate even mature scars and restore the function of healthy skin.

Scar tissue in the skin lacks hair, sweat glands, blood vessels and nerves, which are vital for regulating body temperature and detecting pain and other sensations. Scarring can also impair movement as well as potentially cause discomfort and emotional distress.

Compared to scar tissue, healthy skin undergoes constant remodeling by the hair follicle. Hairy skin heals faster and scars less than non-hairy skin—and hair transplants had previously been shown to aid wound healing. Inspired by this, the researchers hypothesized that transplanting growing hair follicles into scar tissue might cause scars to remodel themselves. To test their hypothesis,  researchers  transplanted hair follicles into the mature scars on the scalps of three participants in 2017. The researchers selected the most common type of scar, called normotrophic scars, which usually form after surgery. They took and microscope-imaged 3 mm-thick biopsies of the scars just before transplantation, and then again at two, four, and six months afterwards. The researchers found that the follicles inspired profound architectural and genetic shifts in the scars towards a profile of healthy, uninjured skin.

Part1

After transplantation, the follicles continued to produce hair and induced restoration across skin layers. Scarring causes the outermost layer of skin—the epidermis—to thin out, leaving it vulnerable to tears. At six months post-transplant, the epidermis had doubled in thickness alongside increased cell growth, bringing it to around the same thickness as uninjured skin. The next skin layer down, the dermis, is populated with connective tissue, blood vessels, sweat glands, nerves, and hair follicles. Scar maturation leaves the dermis with fewer cells and blood vessels, but after transplantation the number of cells had doubled at six months, and the number of vessels had reached nearly healthy-skin levels by four months. This demonstrated that the follicles inspired the growth of new cells and blood vessels in the scars, which are unable to do this unaided. Scarring also increases the density of collagen fibers—a major structural protein in skin—which causes them to align such that scar tissue is stiffer than healthy tissue. The hair transplants reduced the density of the fibers, which allowed them to form a healthier "basket weave" pattern, reducing stiffness—a key factor in tears and discomfort. The authors also found that after transplantation, the scars expressed 719 genes differently than before. Genes that promoted cell and blood vessel growth were expressed more, while genes that promoted scar-forming processes were expressed less.

Anagen hair follicles transplanted into mature human scars remodel fibrotic tissue, npj Regenerative Medicine (2023). DOI: 10.1038/s41536-022-00270-3 , www.nature.com/articles/s41536-022-00270-3

Part 2

How liver cancer hijacks circadian clock machinery inside cells

The most common type of liver cancer, hepatocellular carcinoma (HCC), is already the third leading cause of cancer-related deaths globally—and cases are on the rise worldwide. While chemotherapy, surgery and liver transplants can help some patients, targeted treatments for HCC could save millions more lives.

Recent studies have offered clues about one potential target: the circadian clock proteins inside cells, which help coordinate changes in the body's functioning over the course of a day. But most of this research only hints at an indirect link between circadian clock function and HCC, for instance the observation that cells collected from patients with liver cancer have disrupted circadian rhythms. Now, a study by researchers not only directly links circadian clock proteins to liver cancer, but also shows precisely how cancer cells hijack circadian clock machinery to divide and spread. The research, just published in the journal Proceedings of the National Academy of Sciences, also found that inhibiting key clock proteins can prevent cancer cells from multiplying.

By targeting the circadian clock, we are not only targeting tumour cells but also the area around the tumor, which can help increase the efficacy of other targeted treatments.

The researchers showed that two key clock proteins, known as CLOCK and BMAL1, are critical for the replication of liver cancer cells in cell culture. When CLOCK and BMAL1 are suppressed, cancer cells' replication process was interrupted—ultimately causing cell death, or apoptosis. Triggering apoptosis, during which a cell stops dividing, then self-destructs, is the goal of many modern cancer treatments.

Among other findings, they showed that eliminating the clock proteins reduced levels of the enzyme Wee1 and increased levels of the enzyme inhibitor P21. That's exactly what you want, because when it comes to cancer cell proliferation, P21 is a brake and Wee1 is a gas pedal.

Finally, the researchers tested their findings in vivo. Mice injected with unmodified human liver cancer cells grew large tumors, but those injected with cells modified to suppress CLOCK and BMAL1 showed little to no tumour growth.

 Meng Qu et al, Circadian regulator BMAL1::CLOCK promotes cell proliferation in hepatocellular carcinoma by controlling apoptosis and cell cycle, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2214829120

Cells that cooperate live longer

New research: When cells exchange metabolic products with other cells, they live longer.  The fact that these exchanges directly impact cell lifespans could play a significant role in future research into human aging processes and age-related diseases. The study appears in the latest issue of Cell.

Metabolism is inextricably linked to aging. While it helps maintain vital processes, makes us grow, and triggers cellular repairs, it also produces substances that damage our cells and cause us to age. The metabolic processes that occur within cells are highly complex. The exchange of substances between cells in a community is one important factor, because it has a substantial impact on the metabolism occurring inside a cell.

Cells are in constant contact with neighboring cells—within tissues, for instance. They release some substances and consume others from their surrounding environment. In a recent study researchers investigated whether the exchange of metabolic products (known as metabolites) affects the lifespan of cells.

The researchers used yeast cells and performed experiments to establish their lifespan. Yeast cells are a key model in basic research, a dominant microorganism in biotechnology, and important in medicine because they can cause fungal infections. They  found that the cells lived around 25% longer when they exchanged more metabolites with each other. So obviously wanted to identify the substances and exchange processes that are behind this life-prolonging effect.

Part1

To do so, the researchers employed a special analytical system supported by mass spectrometry that allowed them to precisely track the exchange of metabolites between cells. They found that young cells, which were still able to divide well and often, released amino acids that were consumed by older cells.

Amino acids are the building blocks that make up proteins. The research team discovered that the exchange of the amino acid methionine extended the lives of the cells involved. Methionine occurs in all organisms and plays a key role in protein synthesis, as well as many other cellular processes. Interestingly, it was the young cells' metabolism that prolonged the lives of the old cells.

The cells which within the community consumed methionine, released glycerol. In turn, the presence of glycerol affected methionine producing cells, causing them to live longer. Glycerol is needed for building cell membranes and plays a part in protecting cells. It's a win-win situation. As cells engage in this collaborative exchange, they prolong the lifespan of their community as a whole.

This study of yeast cell communities is the first to show that metabolite exchange directly impacts the lifespan and aging process of the cells. The researchers suspect this also applies to other types of cells, such as those in the human body, and are aiming to investigate this in further studies.

Clara Correia-Melo et al, Cell-cell metabolite exchange creates a pro-survival metabolic environment that extends lifespan, Cell (2023). DOI: 10.1016/j.cell.2022.12.007

Part 2

Rate of scientific breakthroughs slowing over time: Study

The rate of ground-breaking scientific discoveries and technological innovation is slowing down despite an ever-growing amount of knowledge, according to an analysis released recently of millions of research papers and patents.

While previous research has shown downturns in individual disciplines, the study is the first that 'emphatically, convincingly documents this decline of disruptiveness across all major fields of science and technology'.

The researchers gave a "disruptiveness score" to 45 million scientific papers dating from 1945 to 2010, and to 3.9 million US-based patents from 1976 to 2010.

From the start of those time ranges, research papers and patents have been increasingly likely to consolidate or build upon previous knowledge, according to results published in the journal Nature.

The ranking was based on how the papers were cited in other studies five years after publication, assuming that the more disruptive the research was, the less its predecessors would be cited.

The biggest decrease in disruptive research came in physical sciences such as physics and chemistry.

"The nature of research is shifting" as incremental innovations become more common.

One theory for the decline is that all the "low-hanging fruit" of science has already been plucked.

If that were the case, disruptiveness in various scientific fields would have fallen at different speeds. If that were the case, disruptiveness in various scientific fields would have fallen at different speeds.

But instead the declines are pretty consistent in their speeds and timing across all major fields indicating that the low-hanging fruit theory is not likely to be the culprit.

Instead, the researchers pointed to what has been dubbed "the burden of research," which suggests there is now so much that scientists must learn to master a particular field they have little time left to push boundaries.

This causes scientists and inventors to focus on a narrow slice of the existing knowledge, leading them to just come up with something more consolidating rather than disruptive. 

Another reason could be that "there's increasing pressure in academia to publish, publish, publish, because that's the metric that academics are assessed on.

The researchers called on universities and funding agencies to focus more on quality, rather than quantity, and consider full subsidies for year-long sabbaticals to allow academics to read and think more deeply.

 This work showed that "ultra-specialization" and the pressure to publish had increased over the years.

Researchers blamed a global trend of academics being "forced to slice up their papers" to increase their number of publications, saying it had led to "a dulling of research."

Michael Park et al, Papers and patents are becoming less disruptive over time, Nature (2023). DOI: 10.1038/s41586-022-05543-x

Human-approved medication brings back 'lost' memories in mice

Students sometimes pull an all-nighter to prepare for an exam. However, research has shown that sleep deprivation is bad for your memory. Now,  neuroscientists have discovered that what you learn while being sleep deprived is not necessarily lost, it is just difficult to recall.

These neuro-scientists have found a way to make this "hidden knowledge" accessible again days after studying while sleep-deprived using optogenetic approaches, and the human-approved asthma drug roflumilast. These findings were published in the journal Current Biology.

 Using genetic techniques, the scientists caused a light-sensitive protein (channelrhodopsin) to be produced selectively in neurons that are activated during a learning experience. This made it possible to recall a specific experience by shining light on these cells.

In the experiment,  the genetically engineered mice were given a spatial learning task in which they had to learn the location of individual objects, a process that heavily relies on neurons in the hippocampus. The mice then had to perform this same task days later, but this time with one object moved to a novel location. The mice that were deprived of sleep for a few hours before the first session failed to detect this spatial change, which suggests that they cannot recall the original object locations.

However, when the researchers reintroduced them to the task after reactivating the hippocampal neurons that initially stored this information with light, they did successfully remember the original locations. This shows that the information was stored in the hippocampus during sleep deprivation, but couldn't be retrieved without the stimulation.

The molecular pathway set off during the reactivation is also targeted by the drug roflumilast, which is used by patients with asthma or COPD. When scientists gave mice that were trained while being sleep deprived roflumilast just before the second test, they remembered, exactly as happened with the direct stimulation of the neurons. As roflumilast is already clinically approved for use in humans, and is known to enter the brain, these findings open up avenues to test whether it can be applied to restore access to 'lost' memories in humans.

The discovery that more information is present in the brain than we previously anticipated, and that these "hidden" memories can be made accessible again—at least in mice—opens up all kinds of exciting possibilities.

 Youri G. Bolsius et al, Recovering object-location memories after sleep deprivation-induced amnesia, Current Biology (2022). DOI: 10.1016/j.cub.2022.12.006

Method reviews could stop useless science

“I’ve lost count of the number of times that a board member has remarked that the way a study has been designed means it won’t yield any informative data,” says experimental psychologist and ethical-review-board chair Daniël Lakens. To counter this trend, his university has introduced a methodological review board that highlights flaws before data col... — such as sample sizes that are too small to test a hypothesis.

An interesting thought indeed "Researchers blamed a global trend of academics being "forced to slice up their papers" to increase their number of publications, saying it had led to "a dulling of research."
So, Dr Krishna - where does this lead scientists to? Does it indicate a progressive movement towards applied Physics?