Chemists reveal how tau proteins form tangles

MIT chemists have used nuclear magnetic resonance (NMR) spectroscopy to reveal how two different forms of the Tau protein mix to form the tangles seen in the brains of Alzheimer’s patients. 
Credit: Aurelio Dregni/Nadia El-Mammeri/Hong Lab at MIT

One of the hallmarks of Alzheimer’s disease is the presence of neurofibrillary tangles in the brain. These tangles, made of tau proteins, impair neurons’ ability to function normally and can cause the cells to die.

A new study from MIT chemists has revealed how two types of tau proteins, known as 3R and 4R tau, mix together to form these tangles. The researchers found that the tangles can recruit any tau protein in the brain, in a nearly random way. This feature may contribute to the prevalence of Alzheimer’s disease, the researchers say.

“Whether the end of an existing filament is a 3R or 4R tau protein, the filament can recruit whichever tau version is in the environment to add onto the growing filament. It is very advantageous for the Alzheimer’s disease tau structure to have that property of randomly incorporating either version of the protein,” says Mei Hong, an MIT professor of chemistry.

Hong is the senior author of the study, which appears today in Nature Communications. MIT graduate student Aurelio Dregni and postdoc Pu Duan are the lead authors of the paper.

Same symptom – different cause?

Head of the LipiTUM research group Dr. Josch Konstantin Pauling (left) and PhD student Nikolai Köhler (right) interpret the disease-related changes in lipid metabolism using a newly developed network.
Credit: LipiTUM

Machine learning is playing an ever-increasing role in biomedical research. Scientists at the Technical University of Munich (TUM) have now developed a new method of using molecular data to extract subtypes of illnesses. In the future, this method can help to support the study of larger patient groups.

Nowadays doctors define and diagnose most diseases on the basis of symptoms. However, that does not necessarily mean that the illnesses of patients with similar symptoms will have identical causes or demonstrate the same molecular changes. In biomedicine, one often speaks of the molecular mechanisms of a disease. This refers to changes in the regulation of genes, proteins or metabolic pathways at the onset of illness. The goal of stratified medicine is to classify patients into various subtypes at the molecular level in order to provide more targeted treatments.

To extract disease subtypes from large pools of patient data, new machine learning algorithms can help. They are designed to independently recognize patterns and correlations in extensive clinical measurements. The LipiTUM junior research group, headed by Dr. Josch Konstantin Pauling of the Chair for Experimental Bioinformatics has developed an algorithm for this purpose.

Autistic individuals have poorer health and healthcare

Autistic man at home looking out of a window 
Credit: NicolasMcComber

These findings, published in Molecular Autism, have important implications for the healthcare and support of autistic individuals.

Many studies indicate that autistic people are dying far younger than others, but there is a paucity of research on the health and healthcare of autistic people across the adult lifespan. While some studies have previously suggested that autistic people may have significant barriers to accessing healthcare, only a few small studies have compared the healthcare experiences of autistic people to others.

In the largest study to date on this topic, the team at the Autism Research Centre (ARC) in Cambridge used an anonymous, self-report survey to compare the experiences of 1,285 autistic individuals to 1,364 non-autistic individuals, aged 16-96 years, from 79 different countries. 54% of participants were from the UK. The survey assessed rates of mental and physical health conditions, and the quality of healthcare experiences.

The team found that autistic people self-reported lower quality healthcare than others across 50 out of 51 items on the survey. Autistic people were far less likely to say that they could describe how their symptoms feel in their body, describe how bad their pain feels, explain what their symptoms are, and understand what their healthcare professional means when they discuss their health. Autistic people were also less likely to know what is expected of them when they go to see their healthcare professional, and to feel they are provided with appropriate support after receiving a diagnosis of any kind.

Researchers from Goethe University Frankfurt develop new biobattery for hydrogen storage

Model of a potential bacterial hydrogen storage system: during the day, electricity is generated with the help of a photovoltaic unit, which then powers the hydrolysis of water. The bacteria bind the hydrogen produced in this way to CO2, resulting in the formation of formic acid. This reaction is fully reversible, and the direction of the reaction is steered solely by the concentration of the starting materials and end products. During the night, the hydrogen concentration in the bioreactor decreases and the bacteria begin to release the hydrogen from the formic acid again. This hydrogen can then be used as an energy source.
Credit: Goethe University

A team of microbiologists from Goethe University Frankfurt has succeeded in using bacteria for the controlled storage and release of hydrogen. This is an important step in the search for carbon-neutral energy sources in the interest of climate protection. The corresponding paper has now been published in the renowned scientific journal Joule.

The fight against climate change is making the search for carbon-neutral energy sources increasingly urgent. Green hydrogen, which is produced from water with the help of renewable energies such as wind or solar power, is one of the solutions on which hopes are pinned. However, transporting and storing the highly explosive gas is difficult, and researchers worldwide are looking for chemical and biological solutions. A team of microbiologists from Goethe University Frankfurt has found an enzyme in bacteria that live in the absence of air and bind hydrogen directly to CO2, in this way producing formic acid. The process is completely reversible – a basic requirement for hydrogen storage. These acetogenic bacteria, which are found, for example, in the deep sea, feed on carbon dioxide, which they metabolize to formic acid with the aid of hydrogen. Normally, however, this formic acid is just an intermediate product of their metabolism and further digested into acetic acid and ethanol. But the team led by Professor Volker Müller, head of the Department of Molecular Microbiology and Bioenergetics, has adapted the bacteria in such a way that it is possible not only to stop this process at the formic acid stage but also to reverse it. The basic principle has already been patented since 2013.

New sensors allow the exact measurement of the messenger substance dopamine

Sebastian Kruss (right) and Björn Hill belong to the team that was able to measure the messenger substance dopamine directly.
Credit: RUB, Kramer

Carbon nanotubes shine brighter in the presence of the messenger. In this way, signals between nerve cells can be measured easily and precisely.

Dopamine is an important signaling molecule for nerve cells. So far, its concentration could not be determined spatially and temporally. Thanks to a new process, this is now possible: A research team from Bochum, Göttingen and Duisburg used modified carbon nanotubes that glow brighter in the presence of the messenger substance dopamine. With these sensors, the release of dopamine from nerve cells with a resolution that has not yet been achieved has been made visible. The researchers around Prof. Dr. Sebastian Kruss from the Physical Chemistry of the Ruhr University Bochum (RUB) and Dr. James Daniel and Prof. Dr. Nils Brose from the Max Planck Institute for Multidisciplinary Natural Sciences in Göttingen reports on this in the journal PNAS.

Fluorescence changes in the presence of dopamine

The messenger substance dopamine controls, among other things, the reward center of the brain. If this signal transmission no longer works, diseases such as Parkinson's can occur. In addition, the chemical signals are changed by drugs such as cocaine and play a role in addiction. "However, there was previously no method with which the dopamine signals could be made visible at the same time with high spatial and temporal resolution," explains Sebastian Kruss, head of the functional interfaces and biosystems group at the RUB and member of the Ruhr Explores Solvation Cluster of Excellence, in short RESOLV, and the Research Training Group International Graduate School of Neuroscience (IGSN).

Non-invasive liquid biopsy tracks cancer treatment success in real time

 A non-invasive, blood-based biopsy for kidney cancer can tell doctors how a patient’s disease is responding to treatment.

Known as liquid biopsies, these blood tests could help physicians better treat their patients by allowing them to see which treatments are working in real time without the need for repeated, invasive biopsies of solid tumors.

A clinical study published May 26 in the Journal of Clinical Oncology and led by University of Wisconsin–Madison scientists followed more than 100 patients undergoing treatment for renal cell carcinoma. Researchers isolated and measured circulating tumor cells, which tumors release into the blood. These cells can act as a signal of disease burden in a patient.

Changes in both the number of circulating tumor cells and their molecular profiles were able to predict how long a patient would survive while undergoing either new immune system-based treatments or receiving more traditional kidney cancer drugs.

“Cancer is not a static disease. As the disease progresses, molecular characteristics change over time, and these changes are important to understand how the disease responds to treatment as well as how resistance develops,” says Matthew Bootsma, a researcher in the UW School of Medicine and Public Health and one of the lead authors of the report. “That makes it really important for a clinician to have real-time access to these metrics.”

Finding coherence in quantum chaos

A theoretical breakthrough in understanding quantum chaos could open new paths into researching quantum information and quantum computing, many-body physics, black holes, and the still-elusive quantum to classical transition.

“By applying balanced energy gain and loss to an open quantum system, we found a way to overcome a previously held limitation that assumed interactions with the surrounding environment would decrease quantum chaos,” said Avadh Saxena, a theoretical physicist at Los Alamos National Laboratory and member of the team that published the paper on quantum chaos in Physical Review Letters. “This discovery points to new directions in studying quantum simulations and quantum information theory.”

Quantum chaos differs from classical-physics chaos theory. The latter seeks to understand deterministic, or non-random, patterns and systems that are highly sensitive to initial conditions. The so-called butterfly effect is the most familiar example, whereby the flap of a butterfly’s wings in Texas could, through a bewilderingly complicated but not random chain of cause and effect, lead to a tornado in Kansas.

On the other hand, quantum chaos describes chaotic classical dynamical systems in terms of quantum theory. Quantum chaos is responsible for the scrambling of information occurring in complex systems such as blackholes. It reveals itself in the energy spectra of the system, in the form of correlations between its characteristic modes and frequencies.

It has been believed that as a quantum system loses coherence, or its “quantumness,” by coupling to the environment outside the system—the so-called quantum to classical transition—the signatures of quantum chaos are suppressed. That means they can’t be exploited as quantum information or as a state that can be manipulated.

Models predict that planned phosphorus reductions will make Lake Erie more toxic

Photo by Aerial Associates Photography, Inc. (Zachary Haslick) via NOAA cc 2.0

Reducing levels of the nutrient phosphorus to control harmful algal blooms in places like Lake Erie is actually advantageous to toxic cyanobacteria strains, which can lead to an increase in toxins in the water, according to a new modeling study.

Researchers from Technische Universität Berlin (TU Berlin) detail their findings in a paper published online May 26 in the interdisciplinary journal Science. Two University of Michigan scientists are among the co-authors.

“The big advance here was to integrate our understanding of the microbiology of the blooms into predictive models,” said U-M environmental microbiologist and study co-author Gregory Dick. “The results suggest that biologically informed models are able to reproduce emergent properties of blooms that are not predicted by traditional models.”

Cyanobacteria, also known as blue-green algae, can produce toxins and deplete lakes of oxygen when they die. Phosphorus is an important nutrient for these algae, and efforts are underway worldwide to reduce phosphorus levels and inhibit the growth of cyanobacteria.

Discovery offers starting point for better gene-editing tools

CRISPR has ushered in the era of genomic medicine. A line of powerful tools has been developed from the popular CRISPR-Cas9 to cure genetic diseases. However, there is a last-mile problem – these tools need to be effectively delivered into every cell of the patient, and most Cas9s are too big to be fitted into popular genome therapy vectors, such as the adenovirus-associated virus (AAV).

In new research, Cornell scientists provide an explanation for how this problem is solved by nature: they define with atomic precision how a transposon-derived system edits DNA in RNA-guided fashion. Transposons are mobile genetic elements inside bacteria. A lineage of transposon encodes IscB, which is less than half the size of Cas9 but equally capable of DNA editing. Replacing Cas9 with IscB would definitively solve the size problem.

The researchers’ paper, “Structural Basis for RNA-Guided DNA Cleavage by IscB-ωRNA and Mechanistic Comparison with Cas9,” published May 26 in Science.

The researchers used cryo-electron microscopy (Cryo-EM) to visualize the IscB-ωRNA molecule from a transposon system in high resolution. They were able to capture snapshots of the system in different conformational states. They were even able to engineer slimmer IscB variants, by removing nonessential parts from IscB.

“Next-generation fancy applications require the gene editor to be fused with other enzymes and activities and most Cas9s are already too big for viral delivery. We are facing a traffic jam at the delivery end,” said corresponding author Ailong Ke, professor of molecular biology and genetics in the College of Arts and Sciences. “If Cas9s can be packaged into viral vectors that have been used for decades in the gene therapy field, like AAV, then we can be confident they can be delivered and we can focus research exclusively on the efficacy of the editing tool itself.”

A unique catalyst paves the way for plastic upcycling

Visual of two variations of the catalyst, with a segment of the shell removed to show the interior. The white sphere represents the silica shell, the holes are the pores. The bright green spheres represent the catalytic sites, the ones on the left are much smaller than the ones on the right. The longer red strings represent the polymer chains, and the shorter strings are products after catalysis. All shorter strings are similar in size, representing the consistent selectivity across catalyst variations. Additionally, there are smaller chains produced by the smaller catalyst sites because the reaction occurs more quickly.
Credit: Ames Laboratory

A recently developed catalyst for breaking down plastics continues to advance plastic upcycling processes. In 2020, a team of researchers led by Ames Laboratory scientists developed the first processive inorganic catalyst to deconstruct polyolefin plastics into molecules that can be used to create more valuable products. Now, the team has developed and validated a strategy to speed up the transformation without sacrificing desirable products.

The catalyst was originally designed by Wenyu Huang, a scientist at Ames Lab. It consists of platinum particles supported on a solid silica core and surrounded by a silica shell with uniform pores that provide access to catalytic sites. The overall amount of platinum needed is quite small, which is important because of platinum's high cost and limited supply. During deconstruction experiments, the long polymer chains thread into the pores and contact the catalytic sites, and then the chains are broken into smaller sized pieces that are no longer plastic material (see image for more details).