Microtubules are dynamic filaments that constantly grow and shrink again and, in this way, are responsible for many important processes in cells. The research team observed that intermediate filaments stabilise microtubules: when intermediate filaments are added to microtubules, shrinkage is suppressed and thus the lifespan of the microtubules is extended. To investigate whether this is actually due to direct interactions between the two filaments, a single microtubule was positioned crossed with a single intermediate filament.

Dr Laura Schaedel, who shares first authorship of the publication with Charlotta Lorenz (PhD student at the Institute for X-ray Physics at the University of Göttingen), explains: “The intermediate filament was ‘pulled’ over the microtubule like a bow over a violin string.” Lorenz adds, “This allows the two filaments to bind to each other. However, this bond is broken again shortly afterwards due to the pulling. The process of ‘tearing apart’ provides information about the strength of the bond.” Professor Stefan Klumpp from the Institute for the Dynamics of Complex Systems at Göttingen University, who led the project together with Professor Sarah Köster from the Institute for X-ray Physics, says, “In addition, we used models and simulations to show that the direct interaction leads to stabilisation.” The stabilisation of dynamic microtubules can be an important issue for biological cells, for example to regulate their local stability. “The interactions that we observed are important because they enable better understanding of cellular processes,” says Köster.

These results are in turn relevant for understanding many other processes, such as those involved in diseased cells. The new method to take direct measurements of the actual interaction of two different biopolymers can also be applied to other protein filaments, as well as to non-biological fibres.

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The findings shed light on how the hippocampus contributes to memory and exploration, potentially leading to therapies that restore hippocampal function, which is impacted in memory-related aging and neurodegenerative diseases such as dementia, the study authors said.

In the study, scientists monitored participants’ brain activity and tracked their eye movements while looking at different complex pictures. The scientists discovered that as we visually scan our environment and absorb new information, our hippocampus becomes activated, using short-term memory to better process new visual information to help us rapidly reevaluate situations.

How our memory helps us scan new environments

Imagine walking down the street and noticing an awkwardly parked car on your neighbor’s lawn. Maybe you quickly dismiss it and move on. But when you see an ambulance and fire truck approaching your location, you connect the dots and look back to see the scene of an accident. By using short-term memory to guide where you look, the hippocampus allows you to reexamine the car and form a lasting memory of the accident.

“At any given moment, your brain rapidly initiates eye movements that you are typically unaware of,” said corresponding author James Kragel, a postdoctoral research fellow at Northwestern University Feinberg School of Medicine. “Our findings suggest the hippocampus uses memory to inform where your eyes look, thereby priming the visual system to learn and reevaluate our environment on the fly.

“If you didn’t look back and see the crash, you might not encode that important information, but in using short-term memory retrieval, you can tie those clues together and remember details that cue bigger memories. It all comes down to building connections among these disparate elements that allow you to remember them later in a much easier way.”

The study will be published June 18 in the journal Science Advances.

“These findings emphasize that although hippocampal-dependent memory is typically considered a thing of the past, in fact, it operates in the moment to optimize our behavior and decision-making,” said senior study author Joel Voss, associate professor of medical social sciences, neurology, and psychiatry and behavioral sciences at Feinberg. “This is key to understanding hippocampal function and developing effective treatments for memory disorders.”

“It is as if you are using your memory to plan for what to expect, and then when it mismatches with what is actually unfolding, your hippocampus gets activated to reevaluate and update your current perception of what is going on,” Kragel said.

Tracking eye movements to learn more about memory

The study was conducted on patients with epilepsy who were undergoing neurosurgical monitoring at Northwestern Memorial Hospital to localize the source of their seizures. They had electrodes implanted in their brains to map seizure-related brain activity. During their stay in the epilepsy-monitoring unit, participants performed a memory task in which they studied lists of complex scenes with multiple people and objects (e.g. someone sitting at a park bench with food on the table, things happening in the background) followed by a memory test.

During the test, the participants indicated whether a presented scene was old or new. Throughout the task, the authors simultaneously recorded eye movements and neural activity to link hippocampal activity to memory-guided behaviors.

When studying a scene for the first time, participants often returned their gaze to a location they had just viewed hundreds of milliseconds prior. These “revisitation” eye movements enhanced spatiotemporal memory for scenes (remembering where an object was located or the sequence in which something happened). Brain recordings revealed the brain networks involved in generating these “revisitations,” as hippocampal activity shifted just before their execution. Increases in brain activity followed revisitations, which Kragel believes may form a lasting memory of the scene and its elements.

“This shows that the hippocampal contribution to memory unfolds over just hundreds of milliseconds during ongoing behavior, which is surprising given that the timecourse of its involvement, typically seen in long-term memory retrieval, is usually thought to be days to years,” Voss said.

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Materials provided by Northwestern University. Original written by Kristin Samuelson. Note: Content may be edited for style and length.

Michael Dillon, an associate professor in the University of Wyoming Department of Zoology and Physiology, was part of a research group that examined animals’ ability to respond to climate change likely depends on how well they modify their habitats, such as nests and burrows.

So, how are these animals doing? Are they succeeding, struggling, or are their efforts a mixed bag in adapting their habitats to climate change?

“One of the key reasons that we wrote this paper is that we don’t know the answer to this very important question!,” Dillon says. “We hope the paper will encourage scientists to begin answering this question.”

Dillon is a co-author of a paper, titled “Extended Phenotypes: Buffers or Amplifiers of Climate Change?,” that was published June 16 in Trends in Ecology & Evolution. The journal publishes commissioned, peer-reviewed articles in all areas of ecology and evolutionary science.

The lead author of the paper is Arthur Woods, a professor of biological sciences at the University of Montana. Other contributors to the paper were from the University of Tours in Tours, France; and Stellenbosch University in Stellenbosch, South Africa.

The study investigated extended phenotypes, which are modifications that organisms — birds, insects and mammals — make to their habitats.

“An extended phenotype can range from simply a hole in the ground occupied by an animal to leaves rolled into cavities by insects, to nests of all shapes and sizes built by birds and mammals, to termite mounds and bee colonies,” Dillon says.

Extended phenotypes are important because they filter climate into local sets of conditions immediately around the organism. This is what biologists call the microclimate.

Because extended phenotypes are constructed structures, they often are modified in response to local climate variation and, potentially, in response to climate change. This process is called plasticity of the extended phenotype.

“One example might be a bird nest that is well insulated to protect eggs or young birds from cold. As climates warm, if the bird does not adjust insulation in the nest, it may, in fact, cause the young to overheat,” Dillon explains.

In another prime example, termites build mounds that capture wind and solar energy to drive airflow through the colony, which stabilizes temperature, relative humidity and oxygen levels experienced by the colony.

However, the idea of microclimates is broader than constructed habitats. Microclimates typically differ substantially from nearby climates, which means that the climate in an area may provide little information about what animals experience in their microhabitats.

As an analogy, although a weather station might tell the public that the temperature in Laramie is 90 degrees Fahrenheit, simply by moving from the south to the north side of a building, one can experience microclimates that are strikingly different and often not captured by the weather data, Dillon says.

The same is true of animals of many different sizes. For example, a moose can move from an open sagebrush landscape to a shaded river corridor to cool off; a snake can move from its underground hole to a sunny rock to warm up; and a tiny insect shuttling between the top and bottom of a leaf can experience temperature differences of more than 20 degrees Fahrenheit.

“So, animals use microclimates, both by simply moving but also by building structures, such as nests, burrows, mounds and mines,” Dillon says.

Across the globe, rising levels of carbon dioxide in the Earth’s atmosphere are causing temperatures to rise and precipitation patterns to shift. For biologists, a key problem is to understand current effects of climate change on species, and to predict future effects, including how species’ ranges may shift and what the relative risks of extinction are for different animal species’ groups.

The research team favors a renewed effort to understand how extended phenotypes mediate how organisms experience climate change.

“We need a much better understanding of the basic biophysical principles by which extended phenotypes alter local conditions,” says Sylvain Pincebourde, an ecologist in the Insect Biology Research Institute at the University of Tours and one of the paper’s co-authors.

Another key challenge is to understand how much plasticity there is in extended phenotypes, and how much and how rapidly they can evolve.

“At this point, we pretty much have no idea,” Dillon says. “Can structures that buffer temperature variability keep up with the pace of climate change?”

We have two eyes, but perceive the tree in front of us only once. Our brain therefore has the complicated task of combining the information of both eyes in a meaningful way. To do so, visual stimuli first travel from the retina via so-called ganglion cells to the visual thalamus. There, the information does end up in clearly defined areas — depending on the type and eye-of-origin of retinal ganglion cells transporting the visual stimuli. Signals from the right and left eye are thus clearly separated in the visual thalamus and independently transmitted to the visual cortex. Only in this brain region, the incoming information is combined — at least according to a long-standing theory.

However, recent anatomical studies describe that a surprising number of neurons in the mouse visual thalamus has contact to both eyes. Does the separation of ‘left eye’ and ‘right eye’ information channels not hold true in mice? Scientists from Tobias Bonhoeffer’s department wanted to shed more light on this newly raised question. They further developed an optogenetic method, so that they could activate ganglion cells of both eyes successively with light of different colors and measure the corresponding electrical responses in a thalamic cell.

This analysis shows that indeed a multitude of neurons in the visual thalamus receive input from both retinas. But interestingly, there are only very few cells in which the signal strengths of both eyes are similar. In most cells, one eye dominates with a much higher input strength. The weak signals from the non-dominant eye did not trigger an action potential in the experiment and thus seem to not play a major role in the processing of visual information. “With these results, we can explain the contradictory findings of previous research,” says Tobias Rose, who led the study. “The neurons in the visual thalamus do form connections with both eyes, but are functionally monocular or, so to speak, one-eyed. That means that only the signal strength of one eye is high enough for the cells to respond.”

Selection of input

The spatial arrangement of retinal and thalamic cells and the resulting connection possibilities alone cannot explain the functional monocularity. Instead, the scientists showed that even with equal access to both eyes, thalamic cells establish functional connections with only one eye. Accordingly, there is a clear selection of the input source. In addition, the contact sites with the dominant eye seem to strengthen, while those of the non-dominant eye remain in an immature state.

Future studies aim to reveal how the dominant eye is determined and whether this mechanism also applies to different retinal ganglion cell types. Another interesting research topic are the immature contact sites. At first glance without obvious function, the question arises whether they could be activated when needed — and thus play a role, for example in amblyopia, a form of visual impairment.

With their study, the researchers prove that the mouse visual thalamus indeed transfers visual information in separate channels — presumably similar to humans. In addition, it becomes clear that anatomical data sets may be interpreted with caution: Just because neurons are in contact with each other does not mean that they communicate extensively.

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A decades-long search for a dementia-causing toxin

Interest in the correlations between environmental toxins and neurodegeneration focused the world’s magnifying glass on the island of Guam in the 1950s due to an unexpected increase in cases of neurodegenerative cases among the indigenous CHamoru population. The specific condition that temporarily affected Guam is known as amyotrophic lateral sclerosis-parkinsonism dementia (ALS-PDC) and known locally by the CHamoru term lytico-bodig.

A focus on this isolated cluster of cases led to decades of pursuit of causal toxins found in seeds of Guam’s native cycad tree. These seeds were components of the local cuisine at the time, and increased reliance on this form of food starch during World War II was a plausible hypothesis to explain the increase in neurodegeneration cases shortly after the war.

Several factors likely coalesce

An ebb and flow of sequential disappointments has evolved since the 1950s because the identification of a single causal cycad toxin remains elusive.

But these disappointments have been countered by successes. It is now understood that several factors likely coalesce into a synchronized perfect storm to generate an unusual increase in localized neurodegenerative cases, such as what temporarily happened on Guam. These co-factors may include exposure to high doses of the environmental toxin by the most susceptible gender with the most susceptible genes at the most susceptible age, followed by a latency period before the neuronal damage begins to express itself.

The UOG-UBC collaboration has lasted more than two decades, and various members of the team have authored more than 100 journal articles on various aspects of cycad biology during that time. The toxicology of Guam cycad seeds was the subject of 14 of these publications.

“When I began collaborating with UOG, we had the benefit of building on the foundation of decades of research from Guam,” said co-author Christopher Shaw, UBC neuroscientist. “We used the fact that no plant scientist had been directly involved in any of the previously published research to secure funds to revisit various issues concerning cycad seed toxins.”

Difference between acute and slow-acting toxins

One of the many confusing aspects of this research is that acute toxins, which cause immediate poison reactions following cycad seed ingestion, are distinct from slow-acting toxins, which lead to neurodegeneration.

“The distinctions between these two forms of toxins are often confused, and scientists are constantly reminding the public that many years need to elapse after the exposure to a slow plant toxin before negative health outcomes develop,” said Benjamin Deloso, a cycad biologist with UOG.

Claims of cyanide poisoning inaccurate

Another benefit from the marathon pursuit of the causal cycad toxin is that an enormous body of literature has developed that uncovered which biomolecules are not at play. “This is how science works,” Shaw said. “The aggressive empirical look at each candidate toxin was justified and refined the development of superseding hypotheses that were vigorously tested.”

For example, cassava roots contain sugar-based molecules that liberate cyanide after ingestion by mammals, and cycad seeds contain similar molecules, but cycad seeds contain no free cyanide and the identified sugar-based cycad molecules in cycads are incapable of liberating toxic levels of cyanide following ingestion by mammals. The meticulous research revealed the claims of cyanide as a potential cycad toxin and that cycad seed consumption could cause cyanide poisoning were inaccurate.

“Throwing around fear-mongering buzzwords, like cyanide, is a classic example of a repetition of false information in order to drive a personal agenda,” Deloso said. “There are even petitions being circulated that falsely claim that cycad plants contain cyanide in attempts to force retail nurseries to stop selling cycad plants to pet owners.”

The research team contends that scientists are not immune from the mistake of repeating these sorts of false claims about cycads. This tends to happen when scientists get their information from the gray literature or online encyclopedia style websites that are not vetted by cycad experts.

The authors hope that one outcome of their new publication is a decline in the spread of false information about cycad poisoning, as these untruthful statements damage the international community’s attempts to improve cycad conservation.

In a study published this month in Scientific Reports, researchers from The University of Tokyo Institute of Industrial Science have shown that a recently developed flood forecasting system provides much earlier advance warnings of extreme flooding events than current systems. Floods are one of the most common natural disasters and are increasing in frequency. In 2019, Typhoon Hagibis swept across parts of Japan causing severe flooding that resulted in 86 deaths and approximately 400 billion dollars’ worth of damage. Most urban areas in Japan lie within a floodplain and typhoons can result in rapid and dangerous flooding. Early warning systems can help people to prepare for imminent flooding, but people need sufficient time to do so.

“Current warning systems can provide accurate flooding predictions, but with only a few hours’ notice” says lead author of the study Wenchao Ma. “Because people need more time to respond effectively to flood warnings, we investigated whether a newly developed flood forecasting system could accurately predict flooding locations with a longer lead time.”

Flooding predictions in Japan are currently based on gauged upstream water levels. The new system is based on models of the land surface and river routes that used together can simulate the movement of water in floodplains. These models are combined with meteorological data like rainfall, temperature, and wind speed, and statistical analysis; the result is flood predictions for all rivers in Japan.

One of the main challenges with forecasting floods is a lack of data to validate the techniques used. During a disaster, collecting information about floods is challenging and can be dangerous. To overcome this issue, the team looked at the location and timing of dike breaks during Typhoon Hagibis. Dike breaks are a good indicator of which areas flooded during the typhoon and allowed the researchers to test the ability of the forecasting system to predict flood locations.

“The system was very effective,” explains Kei Yoshimura, senior author. “In fact, we found that the model accurately predicted flooding at 91% of broken dike locations.” Importantly, the system also predicted floods with a 32-hour lead time — a notable improvement on the current system. This extra time could be helpful for disaster preparation and making decisions about evacuation.

As the frequency of flooding is likely to increase in the future, forecasting systems that produce accurate and timely flood warnings are urgently needed in Japan, and the rest of the world.

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Materials provided by Institute of Industrial Science, The University of Tokyo. Note: Content may be edited for style and length.

These results were published in the academic journal NeuroImage on May 23, 2021.

Main Points

• The researchers showed that people who are physically active during childhood (up to 12 years of age) have higher cognitive functions in later life.
• However, they could not find a correlation between cognitive function and post-childhood physical activity.
• The positive association between childhood exercise and cognitive function was evident in the modular (*1) segregation of brain networks, strengthened inter-hemispheric connectivity, greater cortical thickness, lower levels of dendritic arborization and decreased density.
• During childhood, the formation of the brain’s network is susceptible to environmental and experience-related factors. It is thought that exercise during this period optimizes brain network development and is linked to the maintenance and promotion of cognitive function in later life.

Research Background

Research over the previous decade has shown that exercise during childhood affects the development of cognitive functions. Recent findings have indicated that these benefits of childhood exercise extend to the maintenance and promotion of cognitive functions in middle age and later life. However, the changes in brain functionality and structure related to this positive association have yet to be illuminated. This research study investigated the relationship between physical activity in childhood and cognitive function in later life, using MRI (magnetic resonance imaging) to illuminate the structural and functional changes in the brain that are behind this relationship.

Experiment Method

The research group conducted a study on 214 participants ranging in age from 26 to 69 in order to investigate the relationship between childhood exercise and cognitive function, and the underlying functional and structural neural networks and cortical structure. Childhood exercise was assessed via questionnaire. One aspect of cognitive function, response inhibition (the ability to suppress inappropriate behaviors), was measured using a Go/No-go task. The image data from the MRI was analyzed and the following were calculated: structural and functional connectivity (*2), cortical thickness, myelination, the degree of neurite orientation dispersion and density index. The brain was divided into 360 areas in accordance with the Human Connectome Project (*3), and functional and structural parameters were obtained for each area. In the statistical analysis, information obtained through the questionnaire was used as confounders. This included each participant’s educational background, parents’ educational background, number of siblings and exercise during adulthood.

Experiment Results

Firstly, the researchers analyzed the relationship between whether participants exercised during childhood and Go/No-go task performance (false alarm rate). They found that participants who exercised during childhood (up until age 12) had a lower false alarm rate than those who didn’t (Figure 1). Furthermore, this correlation was found regardless of the age of the participant. However, no such relationship was found between task performance and post-childhood exercise.

Next, the research group investigated structural and functional connectivity in the brain relating to Go/No-go task performance in participants who exercised during childhood. From these results, they confirmed that in terms of structural connectivity in the brain, there were positive associations (Figure 2A: connections indicated in red) and negative associations (Figure 2A: connections indicated in blue) between exercise during childhood and the false alarm rate in the Go/No-go task. Large-scale network connectivity was found in over half (73%) of structurally connected areas that were positively associated with the Go/No-go task false alarm rate (Figure 2B, left portion). On the other hand, inter-hemispheric connectivity was found in the majority (88%) of structurally connected areas that were negatively associated with the task’s false alarm rate (Figure 2B, right portion). In terms of connections between functional areas, connections showing positive associations (Figure 3A: connections indicated in red) with the Go/No-go task false alarm rate were identified in participants who exercised during childhood but no negatively associated connections were found. Furthermore, large-scale network connectivity was found in the majority (91%) of connected areas that were positively associated with the task’s false alarm rate (Figure 3B, left portion).

In those participants who did not exercise during childhood, there was no structural or functional connectivity identified in relation to the false alarm rate in the Go/No-go task. Lastly, the researchers investigated cortical structure parameters in relation to the Go/No-go false alarm rate for participants who exercised as children. They found that task performance was negatively associated with cortical density, and positively associated with the degree of neurite orientation dispersion and density.

The above results demonstrate that modular segregation and strengthened inter-hemispheric connections in the brain networks of people who exercised during childhood reduced the number of mistakes that they made in the Go/No-go task.

Glossary

1. Module: A single unit that combines with others to form the entire structure of a system. The human brain has a clear modular structure: it is divided into a number of large-scale networks made up of multiple areas.

2. Structural and Functional Connectivity: This refers to the structural and functional relationships between different areas of the brain. Structural connections between areas of the brain can be identified by anatomical nerve fiber connections, and functional connections are indicated by similarities in patterns of neural activity.

3. Human Connectome Project: This large scale research project began in North America in 2012 and aims to deepen understanding of brain connectivity.

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Materials provided by Kobe University. Note: Content may be edited for style and length.