Researchers found that animal models who carry a change in DNA known as germline alteration rs55705857 developed gliomas much more frequently — and in half the time — compared to animal models without the alteration. In addition to brain tumors, the findings are relevant to other cancers and diseases.

“While we understand much of the biologic function of germline alterations within genes that code for proteins, we know very little about the biologic function of germline alterations outside of genes that code for proteins. In some way, these germline alterations interact with other mutations in cells to accelerate tumor formation,” says co-lead author Robert Jenkins, M.D., Ph.D., a genetics researcher at Mayo Clinic in Rochester. “Based on this new understanding of its mechanism of action, future research may lead to novel and specific therapies that target the rs55705857 alteration.”

The study offers new knowledge that may help clinicians determine, pre-surgery, whether a patient has a glioma.

“We expected that rs55705857 would accelerate low-grade glioma development, but we were surprised by the magnitude of that acceleration,” says co-lead author Daniel Schramek, Ph.D., a researcher at Lunenfeld-Tannenbaum Research Institute.

There are many alterations, likely thousands, outside of genes associated with the development of cancer and other diseases, but the mechanism of action is only understood for very few, Dr. Schramek says.

This study demonstrates that, with the tools of modern molecular/cell biology, it is possible to decipher much of the mechanism of action of such alterations.

Dr. Jenkins is a Ting Tsung and Wei Fong Chao Professor in Individualized Medicine Research and researcher in Mayo Clinic’s Department of Laboratory Medicine and Pathology.

Dr. Schramek is a senior investigator and holds a Kierans & Janigan Research Chair at the LTRI and is an associate professor, Department of Molecular Genetics, Faculty of Medicine, University of Toronto.

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An international team of climate scientists led by the research group of Sonia Seneviratne, Professor for Land-?Climate Dynamics at ETH Zurich, now analysed the possible influence of climate change on this extreme weather event. Their study published by the World Weather Attribution group estimates that human-caused climate change made soil moisture drought conditions in the Northern Hemisphere at least 20 times more likely, threatening crop production and adding further pressure to food prices and food security.

Intense agricultural and ecological droughts

For their study, the researchers analysed soil moisture levels in June, July and August 2022, across the whole Northern Hemisphere, excluding the tropics. They also focused on Western and Central Europe, which experienced particularly severe drought with substantially reduced crop yields. Soil moisture dryness in the top metre of soil, known as the root zone where plants extract water, is often referred to as agricultural and ecological drought.

Human-caused climate change made agricultural and ecological droughts in the North Hemisphere extratropics at least 20 times more likely, the researchers found. They calculated that drought conditions like this summer’s can be expected around once in 20 years in today’s climate. If humans had not warmed the planet, the agricultural drought conditions in the Northern Hemisphere would only have been expected around once in 400 years or less.

In the case of West-Central Europe, human-induced climate change made the agricultural and ecological drought about 3 to 4 times more likely. This does not mean that climate change has had less influence on Europe than elsewhere in the Northern Hemisphere; the different sizes of the regions mean the results cannot be directly compared.

“The 2022 summer has shown how human-induced climate change is increasing the risks of agricultural and ecological droughts in densely populated and cultivated regions of the North Hemisphere,” Seneviratne says.

High temperatures as human-made driver

The main factor driving the heightened agricultural and ecological drought risk were increasing temperatures, with changes to rainfall relatively less important. Climate change increased temperatures across the Northern Hemisphere to such an extent that a summer as hot as this year’s would have been virtually impossible without human-induced climate change, the scientists found.

“The results of our analysis also give us an insight on what is looming ahead,” says Dominik Schumacher, postdoc in Seneviratnes research group and first author of the study. “With further global warming we can expect stronger and more frequent summer droughts in the future.”

“That’s why we need to phase-out the burning of fossil fuels if we want to stabilise climate conditions and avoid a further worsening of such drought events,” concludes Seneviratne.

This article is based on a press release by the World Weather Attribution group, an international collaboration that analyses and communicates the possible influence of climate change on extreme weather events.

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In a study of the relative effects of genetics, aging and the environment on how some 20,000 human genes are expressed, the researchers found that aging and environment are far more important than genetic variation in affecting the expression profiles of many of our genes as we get older. The level at which genes are expressed — that is, ratcheted up or down in activity — determines everything from our hormone levels and metabolism to the mobilization of enzymes that repair the body.

“How do your genetics — what you got from your sperm donor and your egg donor and your evolutionary history — influence who you are, your phenotype, such as your height, your weight, whether or not you have heart disease?” said Peter Sudmant, UC Berkeley assistant professor of integrative biology and a member of the campus’s Center for Computational Biology. “There’s been a huge amount of work done in human genetics to understand how genes are turned on and off by human genetic variation. Our project came about by asking, ‘How is that influenced by an individual’s age?’ And the first result we found was that your genetics actually matter less the older you get.”

In other words, while our individual genetic makeup can help predict gene expression when we are younger, it is less useful in predicting which genes are ramped up or down when we’re older — in this study, older than 55 years. Identical twins, for example, have the same set of genes, but as they age, their gene expression profiles diverge, meaning that twins can age much differently from each other.

The findings have implications for efforts to correlate diseases of aging with genetic variation in humans, Sudmant said. Such studies should perhaps focus less on genetic variants that impact gene expression when pursuing drug targets.

“Almost all human common diseases are diseases of aging: Alzheimer’s, cancers, heart disease, diabetes. All of these diseases increase their prevalence with age,” he said. “Massive amounts of public resources have gone into identifying genetic variants that predispose you to these diseases. What our study is showing is that, well, actually, as you get older, genes kind of matter less for your gene expression. And so, perhaps, we need to be mindful of that when we’re trying to identify the causes of these diseases of aging.”

Sudmant and his colleagues reported their results this week in the journal Nature Communications.

Medawar’s hypothesis

The findings are in line with Medawar’s hypothesis: Genes that are turned on when we are young are more constrained by evolution because they are critical to making sure we survive to reproduce, while genes expressed after we reach reproductive age are under less evolutionary pressure. So, one would expect a lot more variation in how genes are expressed later in life.

“We’re all aging in different ways,” Sudmant said. “While young individuals are closer together in terms of gene expression patterns, older individuals are further apart. It’s like a drift through time as gene expression patterns become more and more erratic.”

This study is the first to look at both aging and gene expression across such a wide variety of tissues and individuals, Sudmant said. He and his colleagues built a statistical model to assess the relative roles of genetics and aging in 27 different human tissues from nearly 1,000 individuals and found that the impact of aging varies widely — more than twentyfold — among tissues.

“Across all the tissues in your body, genetics matters about the same amount. It doesn’t seem like it plays more of a role in one tissue or another tissue,” he said. “But aging is vastly different between different tissues. In your blood, colon, arteries, esophagus, fat tissue, age plays a much stronger role than your genetics in driving your gene expression patterns.”

Sudmant and colleagues also found that Medawar’s hypothesis does not hold true for all tissues. Surprisingly, in five types of tissues, evolutionary important genes were expressed at higher levels in older individuals.

“From an evolutionary perspective, it is counterintuitive that these genes should be getting turned on, until you take a close look at these tissues,” Sudmant said. These five tissues happen to be the ones that constantly turn over throughout our lifespan and also produce the most cancers. Every time these tissues replace themselves, they risk creating a genetic mutation that can lead to disease.

“I guess this tells us a little bit about the limits of evolution,” he said. “Your blood, for instance, always has to proliferate for you to live, and so these super-conserved, very important genes have to be turned on late in life. This is problematic because it means that those genes are going to be susceptible to getting somatic mutations and getting turned on forever in a bad, cancerous way. So, it kind of gives us a little bit of a perspective on what the limitations of living are like. It puts bounds on our ability to keep living.”

Sudmant noted that the study indirectly indicates the effect on aging of one’s environment, which is the impact of everything other than age and genetics: the air we breathe, the water we drink, the food we eat, but also our levels of physical exercise. Environment amounts to up to a third of gene expression changes with age.

Sudmant is conducting similar analyses of the expressed genes in several other organisms — bats and mice — to see how they differ and whether the differences are related to these animals’ different lifespans.

UC Berkeley graduate students Ryo Yamamoto and Ryan Chung are co-first authors of the paper. Other co-authors are Juan Manuel Vazquez, Huanjie Sheng, Philippa Steinberg and Nilah Ioannidis. The work was supported by the National Institute of General Medical Sciences (R35GM142916) of the National Institutes of Health.

Whereas the shortest way between two points is a straight connection, it might not be the most efficient path to follow. Complex currents often affect the motion of microswimmers and make it difficult for them to reach their destination. At the same time, making use of these currents to navigate as fast as possible is a certain evolutionary advantage. Whereas such strategies allow biological microswimmers to better access food or escape a predator, microrobots could this way be directed to perform specific tasks.

The optimal path in a given current can readily be determined mathematically, yet fluctuations perturb the motion of microswimmers and deviate them from the optimal route. Thus, they have to readjust their motion in order to account for environmental changes. This typically requires the help of an external interpreter and takes away their autonomy.

“Thanks to evolution, some microorganisms have developed autonomous strategies that enable directed motion towards larger concentration of nutrients or light,” first author of the study Lorenzo Piro explains. Inspired by this idea, the researchers from the Department of Living Matter Physics at the MPI-DS designed strategies that allow microswimmers to navigate optimally in a nearly autonomous way.

Light as a guide for autonomous navigation

When an external interpreter defines the navigation pattern, microswimmers on average follow a well-defined path. Thus, it is a good approach to guide the microswimmer along that path within the current. This can be achieved autonomously via external stimuli, despite the presence of fluctuations. This principle could be applied to swimmers that respond to variation of light, such as certain algae, in which case the optimal path can simply be illuminated. Remarkably, the resulting performances are comparable to externally supervised navigation. “These new strategies can moreover conveniently be applied to more complex scenario such as navigation on curved surfaces or in presence of random currents,” concludes Ramin Golestanian, director at MPI-DS.

Possible applications of the study thus range from targeted drug delivery at the microscale to the optimal design of autonomous micromachines.

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Up to 70 percent of mothers develop postnatal depressive mood, also known as baby blues, after their baby is born. Analyses show that this can also affect the development of the children themselves and their speech. Until now, however, it was unclear exactly how this impairment manifests itself in early language development in infants.

In a study, scientists at the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig have now investigated how well babies can distinguish speech sounds from one another depending on their mother’s mood. This ability is considered an important prerequisite for the further steps towards a well-developed language. If sounds can be distinguished from one another, individual words can also be distinguished from one another. It became clear that if mothers indicate a more negative mood two months after birth, their children show on average a less mature processing of speech sounds at the age of six months. The infants found it particularly difficult to distinguish between syllable-pitches. Specifically, they showed that the development of their so-called Mismatch Response was delayed than in those whose mothers were in a more positive mood. This Mismatch Response in turn serves as a measure of how well someone can separate sounds from one another. If this development towards a pronounced mismatch reaction is delayed, this is considered an indication of an increased risk of suffering from a speech disorder later in life.

“We suspect that the affected mothers use less infant-directed-speech,” explains Gesa Schaadt, postdoc at MPI CBS, professor of development in childhood and adolescence at FU Berlin and first author of the study, which has now appeared in the journal JAMA Network Open. “They probably use less pitch variation when directing speech to their infants.” This also leads to a more limited perception of different pitches in the children, she said. This perception, in turn, is considered a prerequisite for further language development.

The results show how important it is that parents use infant-directed speech for the further language development of their children. Infant-directed speech that varies greatly in pitch, emphasizes certain parts of words more clearly — and thus focuses the little ones’ attention on what is being said — is considered appropriate for children. Mothers, in turn, who suffer from depressive mood, often use more monotonous, less infant-directed speech. “To ensure the proper development of young children, appropriate support is also needed for mothers who suffer from mild upsets that often do not yet require treatment,” Schaadt says. That doesn’t necessarily have to be organized intervention measures. “Sometimes it just takes the fathers to be more involved.”

The researchers investigated these relationships with the help of 46 mothers who reported different moods after giving birth. Their moods were measured using a standardized questionnaire typically used to diagnose postnatal upset. They also used electroencephalography (EEG), which helps to measure how well babies can distinguish speech sounds from one another. The so-called Mismatch Response is used for this purpose, in which a specific EEG signal shows how well the brain processes and distinguishes between different speech sounds. The researchers recorded this reaction in the babies at the ages of two and six months while they were presented with various syllables such as “ba,” “ga” and “bu.

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The researchers have been able to show that quantum waves behave significantly differently from their classical counterparts and can be used to increase the precision of distance measurements. Their findings also add to the discussion on physical origin of the anomalous focusing behaviour. The results are now published in the journal of Nature Photonics.

“Interestingly, we started with an idea based on our earlier results and set out to structure quantum light for enhanced measurement precision. However, we then realised that the underlying physics of this application also contributes to the long debate about the origins of the Gouy phase anomaly of focused light fields.,” explains Robert Fickler, group leader of the Experimental Quantum Optics group at Tampere University.

Quantum waves behave differently but point to the same origin

Over the last decades, methods for structuring light fields down on the single photon level have vastly matured and led to a myriad of novel findings. In addition, a better of optics’ foundations has been achieved. However, the physical origin of why light behaves in such an unexpected way when going through a focus, the so-called Gouy phase anomaly, is still often debated. This is despite its widespread use and importance in optical systems. The novelty of the current study is now to put the effect into the quantum domain.

“When developing the theory to describe our experimental results, we realised (after a long debate) that the Gouy phase for quantum light is not only different than the standard one, but its origin can be linked to another quantum effect. This is just like what was speculated in an earlier work,” adds Doctoral researcher Markus Hiekkamäki, leading author of the study.

In the quantum domain, the anomalous behaviour is sped up when compared to classical light. As the Gouy phase behaviour can be used to determine the distance a beam of light has propagated, the speed up of the quantum Gouy phase could allow for an improvement in the precision of measuring distances.

With this new understanding at hand, the researchers are planning to develop novel techniques to enhance their measurement abilities such that it will be possible to measure more complex beams of structured photons. The team expects that this will help them push forward the application of the observed effect, and potentially bring to light more differences between quantum and classical light fields.

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Fossil findings of insect feeding damage on plants are evidence that insects have been using plants as a food source for more than 400 million years. Researchers led by Roy Kirsch and Yannick Pauchet from the Department of Insect Symbiosis are investigating how herbivorous insects are able to break down the hard-to-digest components of their plant food in the first place. In earlier work, they had already shown that pectin-degrading enzymes are widespread in herbivorous beetle species. They were also able to demonstrate that these beetle enzymes were invariably of microbial origin. The question of the current study was therefore how important these enzymes are for the nutrition and fitness of the insect, in this case the mustard leaf beetle Phaedon cochleariae.

“Our goal was to better understand how herbivorous insects deal with the plant cell wall, which makes the bulk of their diet. Pectin is the matrix embedding cellulose and hemicellulose fibers within the plant cell wall, and it is the main constituent of the cell-connecting middle lamellae. Consequently, pectin must be digested first so that cellulase and hemicellulase enzymes can access their substrates and the plant cells are finally freed from their protective cell wall. In this context, the action of pectinases, i.e. pectin-degrading enzymes, are key to efficient digestion of a leaf beetle’s diet,” says first author Roy Kirsch.

To study the role of the pectinases, the researchers generated beetle lines in which these enzymes were not present. This initially turned out to be more difficult than expected.” “Not even a drastic reduction of pectinase activity through knockdown RNAi experiments in leaf beetle larvae was sufficient to effectively inhibit pectin digestion. We were only able to completely knock-out pectinase-encoding genes in the leaf beetles by applying CRISPR/Cas9 genome editing,” says study leader Yannick Pauchet, underlining the importance of the “genetic scissors,” a technology for which Emmanuelle Charpentier and Jennifer Doudna were awarded the 2020 Nobel Prize in Chemistry.

“Pectinase-null mutant” larvae generated in this way turned out to have low survival capacity. A further question now was whether the degradation products of pectin digestion would improve the survival rate of these beetles when applied orally to the beetle larvae. However, as feeding experiments showed, this was not the case. “On the one hand, this result was a bit of a surprise for us. But on the other hand, it was an important indicator that leaf beetles do not digest pectin to use its breakdown products for their own metabolism, but rather disrupt pectin, and likely other plant cell wall polysaccharides, to access the protein-rich cytoplasm of plant cells,” Roy Kirsch summarizes the results.

Research in recent years, including from Yannick Pauchet’s project group, has shown that the acquisition of microbial enzymes via horizontal gene transfer contributed to the abundance of leaf beetle species, but also of representatives of other insect families, such as weevils, bark beetles and stick insects. The appropriation of enzymes from other microbial organisms is like an evolutionary shortcut; in any case, it created the conditions for insects to open up pectin-rich plants as a food source in the first place. “There is perhaps some irony in the fact that pectinases probably first evolved in plants to dynamically adapt the pectin structure to the changing needs of the plant. These enzymes were then acquired by plant pathogenic microbes, which in turn donated them to herbivorous insects. Plant adaptation strategies apparently always involve risks and side effects,” says Roy Kirsch.

However, there are also leaf beetle species that harbor symbiotic bacteria that produce pectinases for their hosts. So-called “knockin” experiments, in which a pectinase gene is introduced into the beetle genome using CRISPR-Cas9, are now planned to show how this new beetle trait affects not only interactions between plants and insects, but also interactions between insects and their bacterial partners. Future studies will also focus on other enzymes that do not degrade pectin but other plant cell wall components. The work of Roy Kirsch, Yannick Pauchet and their team shows that for an insect to survive on a host plant, it is not only the adaptation to plant defenses, such as toxins and feeding inhibitors and other secondary metabolites, which is crucial. The scientists rather focus on the primary metabolism, which has been neglected in research on plant-insect interactions so far. “The ability of an insect to digest these primary metabolites is equally important for the evolutionary success of herbivorous insects,” says Yannick Pauchet.

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Perhaps that will change soon. Because the position and shape of the cavities are like a kind of fingerprint: they can be used to identify fossil plant remains. “Until now, it was not known how these cavities were formed,” explains Mahdieh Malekhosseini from the Institute of Geosciences at the University of Bonn. “For example, it was believed that they came from algae or pollen from other plants that somehow got onto the leaf during fossilization. But after analyzing hundreds of these structures, we can rule that out. Instead, we were able to show that calcium oxalate crystals are responsible for the depressions.”

Microlenses for better photosynthesis?

Calcium oxalate is formed by very many living plants; it is considered one of the most common biominerals. What functions it fulfills has not yet been conclusively clarified. However, it is suspected that the crystals serve as calcium stores. In addition, because they are formed in the leaf but often penetrate the leaf surface as they grow, they probably repel pests. “Many insects have an aversion to calcium oxalate — they don’t like to walk on it,” explains Prof. Dr. Jes Rust, who supervised the study. “Some plants also seem to use the crystals as microlenses to use sunlight more efficiently for photosynthesis.”

The crystals are very sensitive to acid. They therefore dissolve during fossilization and can no longer be detected in the millions of years old finds. Often, however, imprints remain in the places where they have sat (in biology one speaks of “druses”). Sometimes organic material or other minerals also accumulate in these depressions, which then sit like tiny beads in the fossil leaf.

“We studied the microstructure of the pits and their distribution on fossil leaves whose species affiliation we knew,” Malekhosseini explains. “In addition, we looked at calcium oxalate crystals in the leaves of present-day plants. We found clear parallels in closely related species. For example, the crystal imprints in a fossil ginkgo leaf strongly resemble the calcium oxalate deposits of a present-day ginkgo in distribution and structure.”

Important insights into evolution

It was already known from the fossils of bare-seeded plants such as firs or pines that they sometimes show imprints of calcium oxalate crystals. However, this was not known of angiosperms — which are most flowers and deciduous trees. “This is a completely new field of research,” explains Jes Rust. “Among other things, we now want to investigate how the ability to form calcium oxalate crystals has developed over the course of evolution.” In doing so, the researchers want to focus on periods when environmental conditions changed rapidly — such as temperature or the intensity of UV radiation. “If the distribution of the drusen also changes after such incisions, then we can draw conclusions about the biological function of the crystals,” says Rust.

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