Comet Catalina Suggests Comets Delivered Carbon to Rocky Planets (Planetary Science)

In early 2016, an icy visitor from the edge of our solar system hurtled past Earth. It briefly became visible to stargazers as Comet Catalina before it slingshot past the Sun to disappear forevermore out of the solar system.

Among the many observatories that captured a view of this comet, which appeared near the Big Dipper, was the Stratospheric Observatory for Infrared Astronomy, NASA’s telescope on an airplane. Using one of its unique infrared instruments, SOFIA was able to pick out a familiar fingerprint within the dusty glow of the comet’s tail – carbon.

Now this one-time visitor to our inner solar system is helping explain more about our own origins as it becomes apparent that comets like Catalina could have been an essential source of carbon on planets like Earth and Mars during the early formation of the solar system. New results from SOFIA, a joint project of NASA and the German Aerospace Center, were published recently in the Planetary Science Journal.

“Carbon is key to learning about the origins of life,” said the paper’s lead author, Charles “Chick” Woodward, an astrophysicist and professor at the University of Minnesota’s Minnesota Institute of Astrophysics, in Minneapolis. “We’re still not sure if Earth could have trapped enough carbon on its own during its formation, so carbon-rich comets could have been an important source delivering this essential element that led to life as we know it.”

Frozen in Time

Originating from the Oort Cloud at the farthest reaches of our solar system, Comet Catalina and others of its type have such long orbits that they arrive on our celestial doorstep relatively unaltered. This makes them effectively frozen in time, offering researchers rare opportunities to learn about the early solar system from which they come.

SOFIA’s infrared observations were able to capture the composition of the dust and gas as it evaporated off the comet, forming its tail. The observations showed that Comet Catalina is carbon-rich, suggesting that it formed in the outer regions of the primordial solar system, which held a reservoir of carbon that could have been important for seeding life.

While carbon is a key ingredient of life, early Earth and other terrestrial planets of the inner solar system were so hot during their formation that elements like carbon were lost or depleted. While the cooler gas giants like Jupiter and Neptune could support carbon in the outer solar system, Jupiter’s jumbo size may have gravitationally blocked carbon from mixing back into the inner solar system. So how did the inner rocky planets evolve into the carbon-rich worlds that they are today?

Primordial Mixing

Researchers think that a slight change in Jupiter’s orbit allowed small, early precursors of comets to mix carbon from the outer regions into the inner regions, where it was incorporated into planets like Earth and Mars. Comet Catalina’s carbon-rich composition helps explain how planets that formed in the hot, carbon-poor regions of the early solar system evolved into planets with the life-supporting element.

“All terrestrial worlds are subject to impacts by comets and other small bodies, which carry carbon and other elements,” said Woodward. “We are getting closer to understanding exactly how these impacts on early planets may have catalyzed life.”

Observations of additional new comets are needed to learn if there are many other carbon-rich comets in the Oort Cloud, which would further support that comets delivered carbon and other life-supporting elements to the terrestrial planets. 

SOFIA is a joint project of NASA and the German Aerospace Center. NASA’s Ames Research Center in California’s Silicon Valley manages the SOFIA program, science, and mission operations in cooperation with the Universities Space Research Association, headquartered in Columbia, Maryland, and the German SOFIA Institute at the University of Stuttgart. The aircraft is maintained and operated by NASA’s Armstrong Flight Research Center Building 703, in Palmdale, California.

Featured image: Illustration of a comet from the Oort Cloud as it passes through the inner solar system with dust and gas evaporating into its tail. SOFIA’s observations of Comet Catalina reveal that it’s carbon-rich, suggesting that comets delivered carbon to the terrestrial planets like Earth and Mars as they formed in the early solar system. Credits: NASA/SOFIA/Lynette Cook

Reference: Charles E. Woodward, Diane H. Wooden et al., “The Coma Dust of Comet C/2013 US10 (Catalina): A Window into Carbon in the Solar System”, Planetary Science Journal, 2(1), 2021.

Provided by NASA

Huntington’s Disease Driven By Slowed Protein-building Machinery in Cells (Neuroscience)

New study shows that mutant huntingtin protein slows ribosomes

In 1993, scientists discovered that a single mutated gene, HTT, caused Huntington’s disease, raising high hopes for a quick cure. Yet today, there’s still no approved treatment.

One difficulty has been a limited understanding of how the mutant huntingtin protein sets off brain cell death, says neuroscientist Srinivasa Subramaniam, PhD, of Scripps Research, Florida. In a new study published in Nature Communications on Friday, Subramaniam’s group has shown that the mutated huntingtin protein slows brain cells’ protein-building machines, called ribosomes.

“The ribosome has to keep moving along to build the proteins, but in Huntington’s disease, the ribosome is slowed,” Subramaniam says. “The difference may be two, three, four-fold slower. That makes all the difference.”

Cells contain millions of ribosomes each, all whirring along and using genetic information to assemble amino acids and make proteins. Impairment of their activity is ultimately devastating for the cell, Subramaniam says.

“It’s not possible for the cell to stay alive without protein production,” he says.

The team’s discoveries were made possible by recent advancements in gene translation tracking technologies, Subramaniam says. The results suggest a new route for development of therapeutics, and have implications for multiple neurodegenerative diseases in which ribosome stalling appears to play a role.

Huntington’s disease affects about 10 people per 100,000 in the United States. It is caused by an excessive number of genetic repeats of three DNA building blocks. Known by the letters CAG, short for cytosine, adenine and guanine, 40 or more of these repeats in the HTT gene causes the brain degenerative disease, which is ultimately fatal. The more repeats present, the earlier the onset of symptoms, which include behavioral disturbances, movement and balance difficulty, weakness and difficulty speaking and eating. The symptoms are caused by degeneration of brain tissue that begins in a region called the striatum, and then spreads. The striatum is the region deep in the center of the brain that controls voluntary movement and responds to social reward.

For their experiments, the scientists used striatal cells engineered to have three different degrees of CAG repeats in the HTT gene. They assessed the impact of the CAG repeats using a technology called Ribo-Seq, short for high-resolution global ribosome footprint profiling, plus mRNA-seq, a method that allows a snapshot of which genes are active, and which are not in a given cell at a given moment.

The scientists found that in the Huntington’s cells, translation of many, not all, proteins were slowed. To verify the finding, they blocked the cells’ ability to make mutant huntingtin protein, and found the speed of ribosome movement and protein synthesis increased. They also assessed how mutant huntingtin protein impacted translation of other genes, and ruled out the possibility that another ribosome-binding protein, Fmrp, might be causing the slowing effect.

Further experiments offered some clues as to how the mutant huntingtin protein interfered with the ribosomes’ work. They found it bound directly to ribosomal proteins and the ribosomal assembly, and not only affected speed of protein synthesis, but also of ribosomal density within the cell.

Many questions remain, Subramaniam says, but the advance offers a new direction for helping people with Huntington’s disease.

“The idea that the ribosome can stall before a CAG repeat is something people have predicted. We can show that it’s there,” Subramaniam says. “There’s a lot of additional work that needs to be done to figure out how the CAG repeat stalls the ribosome, and then perhaps we can make medications to counteract it.”

In addition to Subramaniam, the authors of the paper, “Mutant Huntingtin Stalls Ribosomes and Represses Protein Synthesis in a Cellular Model of Huntington Disease,” include Mehdi Eshraghi, Pabalu Karunadharma, Neelam Shahani, Nicole Galli, Manish Sharma, Uri Nimrod Ramírez-Jarquín, Katie Florescu, and Jennifer Hernandez of Scripps Research; Juliana Blin and Emiliano P Ricci of the RNA Metabolism in Immunity and Infection Lab, Laboratory of Biology and Cellular Modelling of Lyon, France; Audrey Michel of RiboMaps of Cork, Ireland; and Nicolai Urban of the Max Planck Neuroscience Institute in Jupiter, Florida.

Featured image: Disease-causing huntingtin, shown in red, interacts with ribosomes, shown in green, in a striatal neuron. The nucleus is blue. © Image by Nicolai Urban of Max Planck Institute for Neuroscience in Jupiter, Florida.

Reference: Eshraghi, M., Karunadharma, P.P., Blin, J. et al. Mutant Huntingtin stalls ribosomes and represses protein synthesis in a cellular model of Huntington disease. Nat Commun 12, 1461 (2021).

Provided by Scripps Research Institute

How Bone Marrow Regenerates After Chemotherapy? (Medicine)

Researchers from Osaka University identify the molecular mechanism underlying bone marrow regeneration after chemotherapy

Chemotherapy has a damaging effect on hematopoietic stem and progenitor cells (HSPCs) in bone marrow. However, once chemotherapy ends, HSPCs regenerate, a process that has remained unknown–until now. In a new study, researchers from Osaka University have identified the molecular mechanism by which HSPCs recover after injury.

HSPCs reside in the bone marrow and give rise to several types of blood cells, such as red blood cells (which carry oxygen), some white blood cells (which are important for the immune system) and platelets (which are necessary to stop bleeding). Because HSPCs constantly divide to generate new cells, they are particularly sensitive to injury induced by, for example, chemotherapy. Interestingly, HSPCs have the capability to regenerate upon injury.

“The bone marrow is a very active organ because it has to constantly produce new blood cells,” says corresponding author of the study Masaru Ishii. “Once it loses its function, such as during chemotherapy, deadly conditions such as anemia, neutropenia and bleeding can occur. In this study, we wanted to understand how hematopoietic stem cells residing in the bone marrow regenerate upon chemotherapy-induced injury to recover their full function.”

ILC2s produce GM-CSF after chemotherapy: A. Single cell RNA-seq analysis of hematopoietic cells isolated from mice that underwent chemotherapy revealed a specific cluster expressing GM-CSF, as highlighted by the circle. Further analysis demonstrated that this cluster represents ILC2s. B. Flow cytometry analysis demonstrated that GM-CSF levels were elevated in ILC2s after chemotherapy. © Osaka University

To achieve their goal, the researchers focused on a specific subset of blood cells that are produced from HSPCs, so-called group 2 innate lymphoid cells (ILC2s). While ILC2s exist in a number of tissues and play an important role in the immune system and tissue repair, those residing in bone marrow are thought to have a distinct role specific to their location. However, the nature of their function was unclear. To unravel the biological role of ILC2s, the researchers treated mice with 5-fluorouracil (5-FU), a chemotherapeutic agent toxic to HSPCs, and transplanted fresh, undamaged HSPCs into these mice, akin to a stem cell transplantation therapy in patients with leukemia. Interestingly, the researchers found that the injured HSPC microenvironment in 5-FU-treated mice promoted the proliferation of the transplanted HSPCs. By analyzing this finding at the molecular level, the researchers found that ILC2s in the bone marrow of treated mice produced granulocyte-macrophage colony-stimulating factor (GM-CSF) to aid in the process of HSPC regeneration.

But how exactly do ILC2s know that they should produce GM-CSF after bone marrow injury? To answer this question, the researchers widened their focus to investigate if there are other cells or molecules that direct ILC2s to the production of GM-CSF. They found that progenitors of antibody-producing B cells in the bone marrow produced interleukin (IL)-33 after injury, which in turn activated ILC2s, demonstrating how multiple molecular players are required to recover the damaged bone marrow. Importantly, the researchers showed that the transfer of isolated ILC2s to 5-FU-treated mice accelerates hematopoietic recovery, while the reduction of ILC2s results in the opposite effect, suggesting that ILC2s may serve as a sensor of bone marrow damage.

Adoptive transfer of ILC2s accelerates hematopoietic recovery: A. ILC2s from wild-type (WT) or GM-CSF-knockout (KO) mice were expanded in vitro prior to injection into WT mice that underwent chemotherapy. B. Mice that were transferred with ILC2s from WT mice showed a significantly increased number of hematopoietic progenitor cells in the bone marrow. © Osaka University

“These are striking results that show the bone marrow regenerates after chemotherapy,” says first author of the study Takao Sudo. “Our results may contribute to the development of a novel therapeutic approach for chemotherapy-induced myelosuppression.”

The article, “Group 2 innate lymphoid cells support hematopoietic recovery under stress conditions,” was published in Journal of Experimental Medicine at DOI:

Featured image: Schematic of a novel mechanism of hematopoietic recovery: After chemotherapy, bone marrow-resident group 2 innate lymphoid cells (ILC2s) receive cytokine signals from dying cells and support hematopoietic recovery through secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) © Osaka University

Provided by Osaka University

Drug Found Effective For Weight Loss In Patients With Obesity And Diabetes (Medicine)

A drug approved for diabetes has now been shown to also help patients with diabetes lose on average 10 percent of their body weight, UT Southwestern reports in a landmark international study.

Semaglutide, an injectable medication taken once a week, offers a nonsurgical way to reduce weight and treat obesity. It could help the more than 70 million adults in the United States who struggle with this chronic condition, says Ildiko Lingvay, M.D., M.P.H., M.S.C.S., professor of internal medicine and population and data sciences at UTSW and lead author of the study, published today in The Lancet.

People with diabetes benefit greatly from weight loss, yet they have a much harder time losing weight compared with those without diabetes, Lingvay says. This study is the first to evaluate the weight loss effect of this medication exclusively in patients with Type 2 diabetes.

This multicenter study was conducted at 149 sites in 12 countries across North America, Europe, South America, the Middle East, South Africa, and Asia from June 2018 to June 2020. It is one of the studies conducted as part of the Semaglutide Treatment Effect for People (STEP) with obesity program. “In the four clinical trials completed so far, people treated with this medication lost on average 10 to 17 percent of their body weight, which is a huge step forward compared with all other medications currently available to treat obesity,” says Lingvay. “With this drug, results are getting close to what we see with bariatric surgery, which is 20 to 30 percent weight loss.”

Medications from this drug class have been used for more than a decade to treat people with diabetes. Semaglutide is currently approved by the Food and Drug Administration to lower blood sugar in people with diabetes at a dose of 0.5 mg or 1 mg once weekly. The FDA is evaluating use of a higher weekly 2.4 mg dose for chronic weight management.

The STEP 2 study, a randomized, double-blind, double-dummy, placebo-controlled phase 3 clinical trial reported in The Lancet, involved more than 1,200 adults with Type 2 diabetes who were overweight or obese at the time. Over 68 weeks, they injected semaglutide or a placebo once a week. A body mass index (BMI) over 30, or a BMI over 27 along with other comorbidities, was required to participate.

“In this study, more than a quarter of participants lost over 15 percent of their body weight, which is by far the best result we had with any weight loss medicine in patients with diabetes,” she says.

Ildiko Lingvay, M.D., M.P.H., M.S.C.S. © UT Southwestern Medical Center

Other STEP trials investigating a weekly dose of semaglutide 2.4 mg in obese adults without diabetes reported even greater weight loss of 15 to 16 percent body weight.

The drug works by suppressing appetite centers in the brain to reduce caloric intake, Lingvay adds.

“The medication continually tells the body that you just ate, you’re full,” she says.

Participants took the subcutaneous injection with a pre-filled pen and tiny needle once a week. They also met with a registered dietitian to help them follow a reduced calorie meal plan.

Average weight loss among participants treated with semaglutide 2.4 mg was 21.4 pounds, compared with 7.7 pounds in the placebo group. About 69 percent of participants treated with semaglutide 2.4 mg lost 5 percent or more of their body weight, which can improve comorbidities such as high blood pressure. Half of those taking semaglutide 2.4 mg achieved weight loss of 10 percent or more, and 25 percent attained weight loss of 15 percent or greater.

For someone with diabetes, losing weight can be especially challenging.

“People with diabetes lose much less weight than their peers without diabetes,” Lingvay says. “For people with diabetes, a 10 percent weight loss is a phenomenal accomplishment.”

The drug is recommended for lifelong use and is not intended to be stopped once weight loss is achieved, she adds.

“Obesity is a chronic medical condition,” Lingvay says. “It is not something you treat like the flu.”

Side effects, including nausea, vomiting, and diarrhea, were mostly mild, and very few patients stopped taking the medication because of them.

The study was funded by Novo Nordisk, which designed and oversaw the trial. Lingvay has received research funding, advisory/consulting fees and/or other support from Novo Nordisk, and her other disclosures can be found in the manuscript.

Featured image: One participant in the STEP 2 clinical trial, Vickie Sanchez, lost 60 pounds over 18 months while taking the weekly injectable medication semaglutide. The above pictures were taken before (left) and at the end of her trial period. © UT Southwestern Medical Center

Reference: Melanie Davies, Louise Færch et al., “Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial”, the Lancet, 2021. DOI:

Provided by UT Southwestern Medical Center

Putting A Protein Into Overdrive to Heal Spinal Cord Injuries (Medicine)

Scar-forming cells that overproduce the protein SOX2 made new neurons, improving recovery in mice

Using genetic engineering, researchers at UT Southwestern and Indiana University have reprogrammed scar-forming cells in mouse spinal cords to create new nerve cells, spurring recovery after spinal cord injury. The findings, published online today in Cell Stem Cell, could offer hope for the hundreds of thousands of people worldwide who suffer a spinal cord injury each year.

Cells in some body tissues proliferate after injury, replacing dead or damaged cells as part of healing. However, explains study leader Chun-Li Zhang, Ph.D., professor of molecular biology and a W.W. Caruth, Jr. Scholar in Biomedical Research at UTSW, the spinal cord typically does not generate new neurons after injury – a key roadblock to recovery. Because the spinal cord acts as a signal relay between the brain and the rest of the body, he adds, its inability to self-repair permanently halts communication between these two areas, leading to paralysis, loss of sensation, and sometimes life-threatening consequences such as an inability to control breathing or heart rate.

Zhang notes that the brain has some limited capacity to produce new nerve cells, relying on progenitor cells to turn on distinct regenerative pathways. Using this knowledge as inspiration, he and his colleagues looked for cells that might have similar potential for regeneration in the spinal cord.

\Working with a mouse model of spinal cord injury, the researchers looked in the animals’ injured spinal cords for a marker normally found in immature neurons. Not only was this marker also present in the spinal cord after injury, Zhang says, but he and his team tracked down the cells that produce it: non-neuronal cells called NG2 glia.

NG2 glia serve as progenitors for cells called oligodendrocytes, which produce the insulating fat layer that surrounds neurons. They are also well-known to form glial scars following injury. Zhang’s team showed that when the spinal cord was injured, these glia transiently adopted molecular and morphological markers of immature neurons.

Chun-Li Zhang, Ph.D. © UT Southwestern Medical Center

To determine what causes NG2 glia to change, the researchers focused on SOX2, a stem cell protein induced by injury. They genetically manipulated these cells to inactivate the gene that makes this protein. When spinal cords of mice that had been manipulated were cut, the researchers saw far fewer immature neurons in the days following injury, suggesting that SOX2 plays a key role in helping NG2 glia make these cells. However, even with normal levels of SOX2, these immature neurons never matured into replacements for those affected by the injury.

Taking an opposite tack, Zhang and his colleagues used a different genetic manipulation technique to make NG2 glia overproduce SOX2. Excitingly, in the weeks after spinal cord injury, mice with this manipulation produced tens of thousands of new mature neurons. Further investigation showed that these neurons integrated into the injured area, making the new connections with existing neurons that are necessary to relay signals between the brain and body.

Even more promising, says Zhang, is that this genetic engineering led to functional improvements after spinal cord injury. Animals engineered to overproduce SOX2 in their NG2 glia performed markedly better on motor skills weeks after spinal cord injury compared with those that made normal SOX2 amounts. The reasons for this improved performance seemed to be multifold. Not only did these animals have new neurons that appeared to take over for those damaged during injury, Zhang explains, but they also had far less scar tissue at the injury site that could hinder recovery.

Zhang notes that, eventually, researchers may be able to discover safe and effective ways to overproduce SOX2 in human spinal cord injury patients, helping repair their injuries with new neurons while reducing scar tissue formation.

“The field of spinal cord injury has extensively researched trying to heal the damage with stem cells that produce new neurons, but what we’re proposing here is that we may not need to transplant cells from the outside,” Zhang says. “By encouraging NG2 glia to make more SOX2, the body can make its own new neurons, rebuilding from within.”

Other researchers who contributed to this study include Wenjiao Tai, Lei-Lei Wang, Haoqi Ni, Chunhai Chen, Jianjing Yang, Tong Zang, and Yuhua Zou at UTSW and Wei Wu and Xiao-Ming Xu at Indiana University.

This research was supported by grants from The Welch Foundation (I-1724), the Decherd Foundation, the Texas Alzheimer’s Research and Care Consortium (TARCC2020), the Kent Waldrep Foundation Center for Basic Research on Nerve Growth and Regeneration, and National Institutes of Health grants (NS099073, NS092616, NS111776, NS117065, NS088095, NS100531, and NS103481).

Featured image: New spinal neurons converted from glia © UT Southwestern Medical Center

This science news is confirmed by us from UT Southwestern Medical Center

Provided by Southwestern Medical Center

Light In Concert With Force Reveals How Materials Become Harder When Illuminated (Material Science)

When indented by a probe in darkness, wafers of some semiconductors are putty-like. When illuminated by light whose wavelength matches the band gap, they become hard, as electrons and holes freed by the light suppress the propagation of dislocations

Semiconductor materials play an indispensable role in our modern information-oriented society. For reliable performance of semiconductor devices, these materials need to have superior mechanical properties: they must be strong as well as resistant to fracture, despite being rich in nanoscale structures.

Recently, it has become increasingly clear that the optical environment affects the structural strength of semiconductor materials. The effect can be much more significant than expected, especially in light-sensitive semiconductors, and particularly since due to technological constraints or fabrication cost many semiconductors can only be mass-produced in very small and thin sizes. Moreover, laboratory testing of their strength has generally been performed on large samples. In the light of the recent explosion in emerging nanoscale applications, all of this suggests that there is an urgent need for the strength of semiconductor materials to be reappraised under controlled illumination conditions and thin sample sizes.

To this end, Professor Atsutomo Nakamura’s group at Nagoya University, Japan, and Dr. Xufei Fang’s group at the Technical University of Darmstadt have developed a technique for quantitatively studying the effect of light on nanoscale mechanical properties of thin wafers of semiconductors or any other crystalline material. They call it a “photoindentation” method. Essentially, a tiny, pointy probe indents the material while it is illuminated by light under controlled conditions, and the depth and rate at which the probe indents the surface can be measured. The probe creates dislocations – slippages of crystal planes – near the surface, and using a transmission electron microscope the researchers observe the effect of light at a range of wavelengths on dislocation nucleation (the birth of new dislocations) and dislocation mobility (the dislocations’ gliding or sliding away from the point where they were created). The nucleation and mobility are measured separately for the first time and is one of the novelties of the photoindentation technique.

The researchers have discovered that while light has a marginal effect on the generation of dislocations under mechanical loading, it has a much stronger effect on the motion of dislocations. When a dislocation occurs, it is energetically favorable for it to expand and join up (nucleate) with others, and the imperfection gets bigger. Illumination by light does not affect this: the electrons and holes excited in the semiconductor by the light (the “photo-excited carriers”) do not affect the strain energy of the dislocation, and it is this energy that determines the “line tension” of the dislocation that controls the nucleation process.

On the other hand, dislocations can also move in a so-called “glide motion”, during which photo-excited carriers are dragged by dislocations via electrostatic interaction. The effect of photo-excited carriers on this dislocation motion is much more pronounced: if enough carriers are produced, the material becomes much stronger.

This effect is strikingly demonstrated when the same experiment is carried out in complete darkness and then under illumination with light at a wavelength that matches the semiconductor band gap (which produces an increased number of photo-excited carriers). When indented, any solid material initially undergoes “plastic deformation” – changing shape without springing back, somewhat like putty – until the load becomes too great, upon which it cracks. The Nagoya University research group demonstrated that the inorganic semiconductor zinc sulfide (ZnS) in total darkness behaves somewhat like putty, deforming by a huge 45% under shear strain without cracking or falling apart. However, when illuminated at the correct wavelength, it becomes quite hard. At other wavelengths it becomes not quite as hard.

The new findings demonstrate that purely plastic deformation without crack formation in semiconductor materials occurs at the nanoscale. With regards to mechanical behaviour, these semiconductors therefore resemble metallic materials. This newly established, robust experimental protocol makes it possible to evaluate the effect of light on the strength of even non-semiconducting materials that are very thin. Professor Nakamura notes: “One particularly important aspect is that non-semiconductors can exhibit semiconducting properties near the surface, due to oxidation, for instance, and since the starting point of deformation or fracture is often the surface, it is of great significance to establish a method for accurately measuring the strength of materials under controlled illumination conditions at the very surface, on a nanoscale.”

The hardening effect that electron-hole pairs freed by light illumination have on material strength – by suppressing the propagation of dislocations, particularly near the surface – is part of a paradigm shift in the science of material strength. Conventionally, when considering the strength of a material, the atomic arrangement was the smallest unit. In other words, there was a premise that the strength of the material could be understood from the atomic arrangement and elasticity theory. However, recent studies have reported that the strength characteristics of materials change significantly due to external influences such as light and an electric field. Therefore, Professor Nakamura notes, “it is becoming more and more accepted that other viewpoints must be added to the theory of material strength which include the motion of electrons and holes that are smaller than atoms.”

“This study reaffirms the quantum-level effect on the strength of such materials. In this respect, it can be said that this research has achieved one milestone in the paradigm shift in the field of material strength that is currently occurring.”

Dr. Xufei Fang adds: “Now that the creation of devices on the true nanoscale is becoming a reality, the impact of light on the structural strength of various inorganic semiconductors is an issue to be considered.”

Funding information: This study was mainly supported by JST PRESTO (Grant Number JPMJPR199A). A part of this study was financially supported by JSPS KAKENHI (Grant Numbers JP17H06094, JP18H03840, JP19H05786, JP19K22050) and Athene Young Investigator Programme from TU Darmstadt, Germany.

Featured image: Schematic illustration of how light affects the nucleation (birth) of dislocations (slippages of crystal planes) and dislocation motion, when the sample is also placed under mechanical loading. The Nagoya University/Technical University of Darmstadt research collaboration has found clear evidence that propagation of dislocations in semiconductors is suppressed by light. The likely cause is interaction between dislocations and electrons and holes excited by the light. © Atsutomo Nakamura

Reference: Atsutomo Nakamura, Xufei Fang, Ayaka Matsubara, Eita Tochigi, Yu Oshima, Tatsushi Saito, Tatsuya Yokoi, Yuichi Ikuhara, and Katsuyuki Matsunaga, “Photoindentation: A New Route to Understanding Dislocation Behavior in Light”, Nano Lett. 2021.

Provided by Nagoya University

BCAS3-C16orf70 Complex Is A New Actor On The Mammalian Autophagic Machinery (Medicine)

Autophagy is an intracellular degradation process of cytosolic materials and damaged organelles. Researchers at Ubiquitin Project of TMIMS have been studying the molecular mechanism of mitophagy, the selective autophagy process to eliminate damaged mitochondria. PINK1 (a serine/threonine kinase) and Parkin (a ubiquitin ligating enzyme: E3) work together to ubiquitylate the outer membrane proteins of damaged mitochondria, then ubiquitin chains are recognized as signals for autophagy degradation. Dysfunction of mitophagy causes a decrease in mitochondrial quality with overproduction of ROS, and is linked to neurodegenerative diseases like Parkinson’s disease.

In Autophagy machinery, cellular components targeted for degradation are engulfed by phosphatidylinositol-3-phosphate (PI3P)-rich membranes. Membranes are elongated and enclosed to form autophagosomes, which then fuse with lysosomes to degrade the cargo inside. Many proteins function in autophagy machinery and they were initially identified by genetic screens in the budding yeast Saccharomyces cerevisiae, and Caenorhabditis elegans. Essential autophagy proteins are evolutionarily conserved from yeast to humans. However, in mammals, there should be unidentified autophagic proteins, and accessory components, whose single gene deletions only manifest as mild defects in autophagy activity, might be missed by these types of genetic screens.

In this study, by immunoprecipitating WIPI1, the well-known autophagy protein, upon Parkin-mediated mitophagy-inducing conditions, researchers identified human BCAS3 (Breast Carcinoma Amplified Sequence 3) and C16orf70 (chromosome 16 open reading frame 70) as novel autophagic proteins.

While BCAS3 and C16orf70 are dispersed throughout the cytosol under normal condition, they accumulated around the damaged mitochondria after mitophagy induction. They also formed puncta in the cytosol in response to amino-acid starvation, which suggests that BCAS3 and C16orf70 are recruited to the autophagosome in both non-selective and selective autophagy. Researchers then found that BCAS3 and C16orf70 interact each other, and this interaction is required for their accumulation on the autophagosome formation site.

Autophagy efficiencies in response to mitochondrial damage and amino-acid starvation were not affected by BCAS3 and/or C16orf70 gene deletions at least in cultured cells. On the other hand, overexpression of the BCAS3-C16orf70 complex impairs the assembly of several autophagy core proteins. These findings demonstrate important accessory functions of BCAS3 and C16orf70 in autophagy machinery.

Furthermore, in silico structural modeling of BCAS3 followed by mutational analyses in immunocytochemistry and in vitro phosphoinositide-binding assays indicate that BCAS3 directly binds phosphatidylinositol-3-phosphate on the autophagosome membranes.

This work was conducted by researchers in TMIMS, The University of Tokushima, and National Institute of Advanced Industrial Science and Technology (AIST), Japan.

This work was supported by JSPS KAKENHI Grant JP17J03737, JP18H05500, JP18K06237, JP18KK0229, JP19H04966, JP20K06628, JP18H02443, JP19H05712, JP19H00997, 16K21680, 18K11543, the Chieko Iwanaga Fund for Parkinson’s Disease Research, the Takeda Science Foundation and Joint Usage and Joint Research Programs, the Institute of Advanced Medical Sciences, Tokushima University and Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from AMED under grant numbers JP19am0101114.

Featured image: The confocal microscopy image of cell induced mitophagy. Autophagic membranes engulf the damaged mitochondria. TOMM20 (blue) is mitochondrial outer membrane protein and WIPI2 (red) is well-known autophagy protein. BCAS3-C16orf70 (green) accumulate around the damaged mitochondria and clearly merge with WIPI2 in response to mitophagy (Kojima et al., Autophagy 2021). © TMIMS

Reference: Waka Kojima, Koji Yamano, Hidetaka Kosako, Kenichiro Imai, Reika Kikuchi, Keiji Tanaka & Noriyuki Matsuda (2021) Mammalian BCAS3 and C16orf70 associate with the phagophore assembly site in response to selective and non-selective autophagy, Autophagy, DOI: 10.1080/15548627.2021.1874133

Provided by Tokyo Metropolitan Institute of Medical Science

Instrument at BESSY II Shows How Light Activates MoS2 Layers to Become Catalysts (Material Science)

MoS2 thin films of superposed alternating layers of molybdenum and sulfur atoms form a two-dimensional semiconducting surface. However, even a surprisingly low-intensity blue light pulse is enough to alter the properties of the surface and make it metallic. This has now been demonstrated by a team at BESSY II.

The exciting thing is that the MoS2 layers in this metallic phase are also particularly active catalytically. They can then be employed, for example, as catalysts for splitting of water into hydrogen and oxygen. As inexpensive catalysts, they could facilitate the production of hydrogen – an energy carrier whose combustion produces no CO2, only water.

Physicist Dr. Nomi Sorgenfrei and her team have constructed a new instrument at BESSY II to precisely measure the changes in samples using temporally-resolved electron spectroscopy for chemical analysis (trESCA) when irradiating the samples with low-intensity, ultra-short light pulses. These light pulses are generated at BESSY II using femtosecond time-slicing (femtoslicing) and are therefore both low intensity and extremely short duration. The new instrument, named SurfaceDynamics@FemtoSpeX, can also rapidly obtain meaningful measurements of electron energies, surface chemistry, and transient alterations using these low-intensity light pulses.

Analysis of the empirical data showed that the light pulse leads to a transient accumulation of charge at the surface of the sample, triggering the phase transition at the surface from a semiconducting to a metallic state.

“This phenomenon should also occur in other representatives of this class of materials, the p-doped semiconducting dichalcogenides, so it opens up possibilities of influencing functionality and catalytic activity in a deliberate way”, Sorgenfrei explains.

Featured image: A new instrument at BESSY II can be used to study molybdenum-sulfide thin films that are of interest as catalysts for solar hydrogen production. A light pulse triggers a phase transition from the semiconducting to the metallic phase and thus enhances the catalytic activity. © Martin Künsting /HZB

Reference: Sorgenfrei, N. L. A. N., Giangrisostomi, E., Jay, R. M., Kühn, D., Neppl, S., Ovsyannikov, R., Sezen, H., Svensson, S., Föhlisch, A., Photodriven Transient Picosecond Top‐Layer Semiconductor to Metal Phase‐Transition in p‐Doped Molybdenum Disulfide. Adv. Mater. 2021, 2006957.

Provided by Helmholtz Berlin

New Test Enables Rapid Detection of Mild Cognitive Impairment As Well As Dementia (Neuroscience)

Researchers from Kanazawa University develop a new efficient way to screen for mild cognitive impairment and dementia

As the global population ages, the rate of dementia is increasing worldwide. Given that early detection is critical for treatment, effective ways to screen for dementia are a high research priority. Now, researchers from Japan have developed a new screening tool that can be administered in a matter of minutes.

People who are performing on the computerized assessment battery for cognition (C-ABC) in a public hall. © Kanazawa University

In a study published in PLOS ONE, researchers from Kanazawa University have revealed a new computerized cognitive test, termed the computerized assessment battery for cognition (C-ABC), which they found to be effective in screening for both dementia and mild cognitive impairment (MCI) in just 5 minutes.

Computerized cognitive tests are frequently chosen over paper-and-pencil versions because they are more precise and do not require training to administer. However, computerized cognitive tests for dementia and MCI generally take 10-30 minutes to complete. Further, the wide range of existing tests can make it difficult for healthcare practitioners to choose one that is suitable for detecting dementia or MCI. The researchers at Kanazawa University aimed to address this by creating a test that could be used to accurately and efficiently screen for both conditions.

“Although patients with dementia usually have disorientation and severe memory disturbance, those with MCI and those with normal cognition rarely have both,” says co-lead author of the study Moeko Noguchi-Shinohara. “We wanted to develop a test that could distinguish these cognitive states in an efficient manner.”

The receiver-operating characteristic (ROC) curves to distinguish mild cognitive impairment (MCI) from normal cognition (NC) in the 50s group (A), 60s group (B) and 70-85 group (C). Straight line, the computerized assessment battery for cognition (C-ABC) combined score (this entire procedure took around 5 min); dotted line, the Item 3 + 6 combined score (this entire procedure took around 2 min). © Kanazawa University

To do this, the researchers collected C-ABC scores from participants in different age groups (50s, 60s, and those aged 70-85 years) with dementia, MCI, and normal cognition. They then conducted a range of statistical tests to determine whether the test could distinguish normal cognition, dementia, and MCI.

“The results were surprising,” explains Masahito Yamada, senior author. “We found that the C-ABC could distinguish individuals with MCI from those with normal cognition using scores from items that only took 5 minutes to complete.”

In fact, in the 75-80 age group, answers from just two questions could distinguish participants with MCI from those with normal cognition, and these two items took just 2 minutes to complete.

“When we compared our C-ABS scores with those from the frequently used Mini-Mental State Examination (MMSE), we found a high correlation. However, the C-ABC is substantially faster to complete than the MMSE, and may be more sensitive to MCI or mild dementia,” says Yamada.

The data indicate that when used with a high cut-off score for sensitivity, the C-ABC is appropriate for initial screening for dementia and MCI. This new tool could make cognitive screening more accessible and efficient, thus enabling earlier detection of MCI or dementia. This, in turn, could improve the treatment options and overall outcome for individuals with MCI or dementia.

Featured image: The computerized assessment battery for cognition (C-ABC). The figures-recognition memory test is shown: “please touch the figures with same color and shape as those presented before.” © Kanazawa University

Reference: Noguchi-Shinohara M, Domoto C, Yoshida T, Niwa K, Yuki-Nozaki S, Samuraki-Yokohama M, et al. (2020) A new computerized assessment battery for cognition (C-ABC) to detect mild cognitive impairment and dementia around 5 min. PLoS ONE 15(12): e0243469.

Provided by Kanazawa University