Supplementation with amino acid serine eases neuropathy in diabetic mice

From left: Michal Handzlik and Christian Metallo
Photo Credit: Salk Institute

Approximately half of people with type 1 or type 2 diabetes experience peripheral neuropathy—weakness, numbness, and pain, primarily in the hands and feet. The condition occurs when high levels of sugar circulating in the blood damage peripheral nerves. Now, working with mice, Salk Institute researchers, in collaboration with the University of California San Diego, have identified another factor contributing to diabetes-associated peripheral neuropathy: altered amino acid metabolism.

The study, published in Nature, adds to growing evidence that some often-underappreciated, “non-essential” amino acids play important roles in the nervous system. The findings may provide a new way to identify people at high risk for peripheral neuropathy, as well as a potential treatment option. The team included UC San Diego bioengineering professor Prashant Mali, microbiome expert professor Rob Knight and pathologist Nigel A. Calcutt.

“We were surprised that dialing up and down a non-essential amino acid had such a profound effect on metabolism and diabetic complications,” says senior author Christian Metallo, a professor in Salk’s Molecular and Cell Biology Laboratory. “It just goes to show that what we think of as dogma can change under different circumstances, such as in disease conditions.”

Evolutionary Tuning of a Cellular “Powerhouse”

Profiles of the subunits of individual complexes (top) and overall representation of all around 5200 protein signals in MitCOM.
Image Source | Credit: AG Fackler/Pfanner/Becker

Mitochondria are membrane-enclosed structures found in all cells of higher organisms, where they produce most of the necessary energy (“powerhouses of the cell”). In addition, these organelles serve important functions in the synthesis and degradation of certain biomolecules as well as in numerous intercellular signaling processes. In close collaboration, a team of researchers led by Prof. Dr. Nikolaus Pfanner and Prof. Dr. Bernd Fakler from the University of Freiburg Institutes of Biochemistry and Physiology, respectively, and by Prof. Dr. Thomas Becker from the Institute of Biochemistry at the University of Bonn has now applied a newly developed analytical method to comprehensively map the structural organization of proteins in mitochondria. The results provide initial insight into the structure and organization of the mitochondrial proteins in protein machineries of varying complexity, thus laying the foundation for future studies of new protein functions and structures. This study was published in the journal Nature.

Comprehensive picture of the composition of protein complexes indispensable

Mechanical forces in the nervous system play a corrective role

The researchers visualized the forces acting on dendrites during pruning by measuring their lengths (blue/red) and the angles at dendritic branchpoints: A) before, B) after dendrite severing,
Image Credit: WWU - Rumpf Lab

Researchers at Münster University show in the fruit fly how mechanical tearing cuts neural connections

Nerve cells communicate with one another via long processes known as axons and dendrites, or, more generally, neurites. During development, these processes first grow and form connections with other cells, for example synapses with other nerve cells. Any neurites which are not properly linked, or are no longer needed, are removed by a corrective mechanism known as “pruning”. Such pruning processes can appear drastic, and neurites sometimes seem to be severed directly from the nerve cell. Researchers headed by Dr. Sebastian Rumpf from the Institute of Neuro- and Behavioral Biology at Münster University has now found the mechanism of neurite severing. In a study published in the Journal of Cell Biology, the team show that in sensory nerve cells of the fruit fly Drosophila melanogaster, pruning occurs through mechanical tearing.

Mercury Helps to Detail Earth’s Most Massive Extinction Event

The Karoo Basin in South Africa yields clues about the largest mass extinction in earth's history
Photo Credit: Juanita Swart

The Latest Permian Mass Extinction (LPME) was the largest extinction in Earth’s history to date, killing between 80-90% of life on the planet, though finding definitive evidence for what caused the dramatic changes in climate has eluded experts.

An international team of scientists, including UConn Department of Earth Sciences researchers Professor and Department Head Tracy Frank and Professor Christopher Fielding, are working to understand the cause and how the events of the LPME unfolded by focusing on mercury from Siberian volcanoes that ended up in sediments in Australia and South Africa. The research has been published in Nature Communications.

Though the LPME happened over 250 million years ago, there are similarities to the major climate changes happening today, explains Frank:

“It’s relevant to understanding what might happen on earth in the future. The main cause of climate change is related to a massive injection of carbon dioxide into the atmosphere around the time of the extinction, which led to rapid warming.”

Power of cancer drugs may see boost by targeting newly identified pathway

Proteins labeled with colored tags fill the main compartment — but not the nuclei (blue) — of human cervical cancer cells. Green cells contain the protein TRPV2, red cells contain STING, and yellow and orange cells contain a mixture of both. The proteins are part of a newly discovered DNA-protection pathway that potentially could be targeted to improve cancer therapies, according to researchers at Washington University School of Medicine in St. Louis.
Image Credit: Lingzhen Kong

Cells zealously protect the integrity of their genomes, because damage can lead to cancer or cell death. The genome — a cell’s complete set of DNA — is most vulnerable while it is being duplicated before a cell divides. Cancer cells constantly are dividing, so their genomes are constantly in jeopardy.

Researchers at Washington University School of Medicine in St. Louis has identified a previously unknown signaling pathway cells use to protect their DNA while it is being copied. The findings, published in the journal Molecular Cell, suggest that targeting this pathway potentially could boost the potency of cancer therapeutics.

“A cell that can’t protect its genome is going to die,” said senior author Zhongsheng You, a professor of cell biology and physiology. “This entire pathway we found exists to protect the genome so the cell can survive in the face of replication stress. By combining inhibitors of this pathway with chemotherapy drugs that target the DNA replication process, we potentially could make such drugs more effective.”

Pioneering approach advances study of CTCF protein in transcription biology

Scientists at St. Jude collaborated to better understand CTCF. L to R: Beisi Xu, PhD, Chunliang Li, PhD; Judith Hyle; Mohamed Nadhir Djekidel, PhD.
Photo Credit: St. Jude Children's Research Hospital

Scientists at St. Jude Children’s Research Hospital used the auxin-inducible degron 2 system on CTCF, bringing the novel approach to bear on a fundamental protein.

CTCF is a critical protein known to play various roles in key biological processes such as transcription. Scientists at St. Jude Children’s Research Hospital used a next-generation protein degradation technology to study CTCF. Their work revealed the superiority of the approach in addition to providing functional insights into how CTCF regulates transcription. The study, published today in Genome Biology, paves the way for more clear, nuanced studies of CTCF.

Transcription is an essential biological process where DNA is copied into RNA. The process is the first required step in a cell to take the instructions housed in DNA and ultimately translate that code into the amino acid or polypeptide building blocks that become active proteins. Dysregulated transcription plays a role in many types of pediatric cancer. Finding ways to modify or target aspects of the transcriptional machinery is a novel frontier in the search for vulnerabilities that can be exploited therapeutically.

While the biology of CTCF has been extensively studied, how the different domains (parts) of CTCF function in relation to transcription regulation remains unclear.

Fossils of Arctic primate relatives tell climate-adaptation story

Artist's reconstruction of Ignacius dawsonae surviving six months of winter darkness in the extinct warm temperate ecosystem of Ellesmere Island, Arctic Canada.
Illustration Credit: Kristen Miller, Biodiversity Institute, University of Kansas.

Two sister species of near-primate, called “primatomorphans,” dating back about 52 million years have been identified by researchers at the University of Kansas as the oldest to have dwelled north of the Arctic Circle. The findings was published in the peer-reviewed journal PLOS ONE.

According to lead author Kristen Miller, doctoral student with KU’s Biodiversity Institute and Natural History Museum, both species — Ignacius mckennai and I. dawsonae — descended from a common northbound ancestor who possessed a spirit “to boldly go where no primate has gone before.”

The specimens were discovered on Ellesmere Island, Nunavut, Canada, in layers of sediment linked with the early Eocene, an epoch of warmer temperatures that could foretell how ecosystems will fare in coming years due to human-driven climate change.

“No primate relative has ever been found at such extreme latitudes,” Miller said. “They’re more usually found around the equator in tropical regions. I was able to do a phylogenetic analysis, which helped me understand how the fossils from Ellesmere Island are related to species found in midlatitudes of North America — places like New Mexico, Colorado, Wyoming and Montana. Even down in Texas we have some fossils that belong to this family as well.”

Mimicking an Enigmatic Property of Circadian Rhythms through an Artificial Chemical Clock

An innovative temperature-compensation mechanism for oscillating chemical reactions based on temperature-responsive gels has been recently reported by researchers at Tokyo Tech. Their experimental findings, alongside a detailed mathematical analysis, hint at the possibility that circadian rhythms found in nature may all rely on a similar mechanism, allowing their period to remain independent of temperature.

Circadian rhythms are natural, internal oscillations that synchronize an organism's behaviors and physiological processes with their environment. These rhythms normally have a period of 24 hours and are regulated by internal chemical clocks that respond to cues from outside the body, such as light.

Although well studied in animals, plants, and bacteria, circadian rhythms all share an enigmatic property—the oscillation period is not significantly affected by temperature, even though the rate of most biochemical reactions changes exponentially with temperature. This clearly indicates that some sort of temperature-compensation mechanism is at play. Interestingly, some scientists have managed to replicate such temperature-invariant qualities in certain oscillating chemical reactions. However, these reactions are often troublesome and require extremely precise adjustments on the reacting chemicals.

Motile Sperm and Frequent Abortions in Spreading Earth moss

The protein PINC has an influence on the motility of sperm cells (left) and the anchoring of spore capsules (right, dark structures) in the moss Physcomitrella. The fluorescence microscope images in the middle show the male sex organ on the left and a young spore capsule on the right. PINC is marked in magenta.
Image Credit: Volker Lüth / University of Freiburg

Freiburg researchers discover that sperm motility and anchoring of the spore capsule in the spreading earth moss Physcomitrella are influenced by the auxin transporter PINC.

As a component of moors, mosses are important for climate conservation. They are also gaining increasing significance in biotechnology and the manufacture of biopharmaceuticals. For the most varied of rationales, mosses are interesting research objects. One reason for this is because they are particularly similar to the first land plants. As a result, they provide insight into the original function of signaling molecules which regulate growth and development in all land plants today. Researchers at the University of Freiburg and the Excellence Cluster CIBSS – Centre for Integrative Biological Signaling Studies – have discovered that transporters of the hormone auxin influence the fertility of spreading earth moss. Their observations have been published in the scientific journal New Phytologist.

MLU physicists solve mystery of two-dimensional quasicrystal formation from metal oxides

A substructure consisting of rings of different sizes embeds itself seamlessly into a hexagonal structure
 Photo Credit: Dr. Stefan Förster

The structure of two-dimensional titanium oxide breaks up at high temperatures by adding barium; instead of regular hexagons, rings of four, seven and ten atoms are created that order periodically. A team at Martin Luther University Halle-Wittenberg (MLU) made this discovery in collaboration with researchers from the Max Planck Institute (MPI) for Microstructure Physics, the Université Grenoble Alpes and the National Institute of Standards and Technology (Gaithersburg, USA), thereby solving the riddle of two-dimensional quasicrystal formation from metal oxides. Their findings have been published in the renowned journal "Nature Communications".

Hexagons are frequently found in nature. The best-known example is honeycomb, but graphene or various metal oxides, such as titanium oxide, also form this structure. "Hexagons are an ideal pattern for periodic arrangements," explains Dr Stefan Förster, researcher in the Surface and Interface Physics group at MLU’s Institute of Physics. "They fit together so perfectly that there are no gaps." In 2013, this group made an astonishing discovery upon depositing an ultrathin layer containing titanium oxide and barium on a platinum substrate and heating it to around 1,000 degrees centigrade in an ultra-high vacuum. The atoms arranged themselves into triangles, squares and rhombuses that group in even larger symmetrical shapes with twelve edges. A structure with 12-fold rotational symmetry was created, instead of the expected 6-fold periodicity. According to Förster, "Quasicrystals were created that have an aperiodic structure. This structure is made of basic atomic clusters that are highly ordered, even if the systematics behind this ordering is difficult for the observer to discern." The physicists from Halle were the first worldwide to demonstrate the formation of two-dimensional quasicrystals in metal oxides.