Culture

Toxin-antitoxin function fuels antibiotic-resistance research

Toxin-antitoxin (TA) systems are now known to negatively control plasmid replication, according to Thomas Wood, Biotechnology Endowed Chair and professor of chemical engineering in the Penn State College of Engineering.

Plasmids, or extra-chromosomal bits of DNA, allow bacteria to evade antibiotics, making the antibiotics ineffective in halting a bacterial infection.

The presence or absence of plasmids impacts a bacterium's resistance to antibiotics and its ability to cause infection -- important points related to fighting bacterial infections, according to Wood.

"Each year, there are at least 700,000 deaths worldwide because of bacterial infections, a growing number that is projected to increase to 10 million by 2050," Wood said. "And of course, the effectiveness of antibiotics is critical to healing from any type of bacterial infection."

Wood and his colleagues detail one function of a certain TA system, known as PrpT/PrpA, in a recent issue of the Proceedings of the National Academy of Sciences. The antitoxin, PrpA, prevents plasmids from replicating too many or too few copies, which then leads the bacterium to resist antibiotics at the cellular level.

"Though they are not alive, plasmids are selfish in their behaviors," Wood said. "The plasmid seeks to stay in bacterial cells, so it very carefully controls the number of copies it creates; not too many copies that it becomes a burden to the bacterial cell, and not too few that some bacteria cells do not have a copy."

Though it has been known for decades that plasmids are to blame for antibiotic resistance, this is the first time a TA system has been linked to plasmid replication.

"The antitoxin acts as an unexpected player in the negative control of plasmid replication," Wood said.

While dozens of TA systems exist in each type of bacteria, as in the case of well-studied E.coli, researchers are only now learning what they do, according to Wood.

To help with classification and organization, Wood and his colleagues recently published a paper in Trends in Microbiology to help order all seven ways antitoxins interact with toxins. During the course of his career, Wood has discovered and named the first type in category V and the first two types in category VII -- including the HEPN/MNT system.

Credit: 
Penn State

UMass Amherst researchers discover materials capable of self-propulsion

image: High-speed images of an autonomously jumping polymer shell.

Image: 
UMass Amherst

Imagine a rubber band that was capable of snapping itself many times over, or a small robot that could jump up a set of stairs propelled by nothing more than its own energy. Researchers at the University of Massachusetts Amherst have discovered how to make materials that snap and reset themselves, only relying upon energy flow from their environment. The discovery may prove useful for various industries that want to source movement sustainably, from toys to robotics, and is expected to further inform our understanding of how the natural world fuels some types of movement.

Al Crosby, a professor of polymer science and engineering in the College of Natural Sciences at UMass Amherst, and Yongjin Kim, a graduate student in Crosby's group, along with visiting student researcher Jay Van den Berg from Delft University of Technology in the Netherlands, uncovered the physics during a mundane experiment that involved watching a gel strip dry. The researchers observed that when the long, elastic gel strip lost internal liquid due to evaporation, the strip moved. Most movements were slow, but every so often, they sped up. These faster movements were snap instabilities that continued to occur as the liquid evaporated further. Additional studies revealed that the shape of the material mattered and that the strips could reset themselves to continue their movements.

"Many plants and animals, especially small ones, use special parts that act like springs and latches to help them move really fast, much faster than animals with muscles alone," says Crosby, when explaining the study. "Plants like the Venus flytraps are good examples of this kind of movement, as are grasshoppers and trap-jaw ants in the animal world. Snap instabilities are one way that nature combines a spring and a latch and are increasingly used to create fast movements in small robots and other devices, as well as toys like rubber poppers. However, most of these snapping devices need a motor or a human hand to keep moving. With this discovery, there could be various applications that won't require batteries or motors to fuel movement."

Kim explains that after learning the essential physics from the drying strips, the team experimented with different shapes to find the ones most likely to react in expected ways and that would move repeatedly without any motors or hands resetting them. The team even showed that the reshaped strips could do work, such as climb a set of stairs on their own.

Crosby continues, "These lessons demonstrate how materials can generate powerful movement by harnessing interactions with their environment, such as through evaporation, and they are important for designing new robots, especially at small sizes where it's difficult to have motors, batteries, or other energy sources."

These latest results from Crosby and his group are part of a larger multidisciplinary university research initiative funded by the Army Research Office, an element of the U.S. Army Combat Capabilities Development Command's Army Research Laboratory and led by Sheila Patek, professor of biology at Duke University, that aims to uncover many similar mechanisms from fast-moving biological organisms and translate them into new engineered devices.

"This work is part of a larger multidisciplinary effort that seeks to understand biological and engineered impulsive systems that will lay the foundations for scalable methods for generating forces for mechanical action and energy storing structures and materials," says Ralph Anthenien, branch chief, Army Research Office, an element of the U.S. Army Combat Capabilities Development Command's Army Research Laboratory. "The work will have myriad possible future applications in actuation and motive systems for the Army and DoD."

Credit: 
University of Massachusetts Amherst

New research looks at teen bariatric surgery outcomes by age

Obesity and its duration are significant risk factors for type 2 diabetes, cardiovascular events, multiple cancers and decreased quality of life. According to the Centers for Disease Control and Prevention, obesity affects 20.6% of adolescents ages 12-19 in the United States, meaning a potential lifetime of dealing with this condition. Complications from obesity can also result in a potentially decreased life expectancy of five to 20 years for these youth. In a new study published in Pediatrics, researchers at Children's Hospital Colorado (Children's Colorado) have found that both younger and older adolescents have similar weight loss, resolution of high blood pressure and high cholesterol, nutritional impacts and improvement in quality of life after bariatric surgery. These results strongly indicate that, when working with adolescents with severe obesity, age alone should not dissuade providers and patients from pursuing surgery when medically indicated.

"Bariatric surgery has become recognized as the safest and most effective treatment for severe obesity in adults; however, little was known about the relative merits and risks of these procedures in the youngest of teens compared to older adolescents," said Sarah B. Ogle, DO, a surgery fellow at Children's Colorado. "Thus, discussing the option of surgery in young adolescents with intractable severe obesity makes more sense than continuing ineffective treatments, given the proven benefits of surgery. This study is an exciting step toward demonstrating the safety and efficacy of bariatric surgery in the youngest adolescents."

Specifically, the study compared outcomes data of 228 adolescents enrolled in the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS). Each of these patients underwent bariatric surgery. Sixty-six of them were between the ages of 13 and 15 at the time of surgery while 162 of them were between the ages of 16 and 19.

Baseline data were collected within 30 days of surgery. Participants were then evaluated at six months, 12 months, and then annually, for five years after surgery. Researchers compared weight loss, comorbidity resolution, nutritional abnormalities and quality of life between the younger and older adolescents participating in the study.

No significant differences in the remission of high blood pressure or high cholesterol were observed between the age groups. Weight loss and quality of life were similar in the two groups. Further, younger adolescents were less likely to develop elevated transferrin, which plays a central role in iron metabolism, and low vitamin D.

"Younger teens have less commonly been considered eligible for surgery due to their age, but the findings in this analysis should shift the focus from a concern about age to more important factors that should drive decision-making. These include providing the patient with the best opportunity to reach a normal BMI after surgery, reversal of serious complications of obesity, and treatment that will most likely increase the lifespan," said Thomas H. Inge, MD, PhD, Teen-LABS principal investigator, and director of pediatric surgery and the bariatric center at Children's Colorado. "While these results are promising, longer term study of this early intervention is needed to fully evaluate the impact of surgery to reverse late effects of childhood severe obesity that develop over the decades."

Credit: 
Children's Hospital Colorado

Halved risk for severe retinal disease in extremely premature infants

image: Prof. Ann Hellstrom, Sahlgrenska Academy, University of Gothenburg.

Image: 
Photo by Elin Lindstrom

Risk for a severe form of retinopathy of prematurity, which can cause blindness in extremely premature babies, was halved when the newborns were given a new supplement combining various fatty acids. This was shown in a Swedish study led from the University of Gothenburg.

The study, now published in JAMA Pediatrics, is described as groundbreaking in its field. It documents a clear fall in retinopathy of prematurity (ROP) among extremely premature (EP) infants (born before 28 weeks' gestation), whose retinal blood vessels are not fully developed. The condition can cause visual impairment and, at worst, blindness after retinal detachment.

The study included 206 EP babies in the neonatal wards at the university hospitals in Gothenburg, Lund, and Stockholm over a period exceeding three years, 2016-19.

Roughly half of these newborns were given prophylactic nutritional supplements, orally, with the omega-3 fatty acid DHA (50 milligrams per day and kilogram of body weight), combined with the omega-6 fatty acid arachidonic acid (twice as much). Today, the latter fatty acid is not included in the supplements routinely administered to EP babies immediately after birth.

In the group of EP infants given the fatty acid supplement, 16 of 101 (15.8 percent) had severe ROP. The corresponding proportion in the control group was 35 of 105 (33.3 percent).

In adults, high levels of omega-6 fatty acids are associated with inflammation and cardiovascular disease. In the fetal period, arachidonic acid is an essential building block for cellmembranes and act as signaling molecules between cells. The omega-3 fatty acid DHA is a vital component for blood vessels and nerve tissue.

Ann Hellström, Professor of Pediatric Ophthalmology at Sahlgrenska Academy, University of Gothenburg, and chief physician at Sahlgrenska University Hospital, is in charge of the study.

In previous studies, the research group have shown the connection between ROP and low arachidonic acid levels in EP babies' blood. Administering arachidonic acid as a supplement has been a topic of debate, and further clinical studies on how to devise an optimal mix of fatty acids have been called for.

"In our study, we're taking a step toward answering that question by showing such a distinct reduction in one of the severe neurovascular complications that can arise after extremely preterm birth" Hellström says.

Other results in the study showed no significant differences between the two groups in terms of the incidence of the lung disease bronchopulmonary dysplasia, or in the degree of intraventricular cerebral hemorrhage, which is also common in EP infants. Sepsis occurred in slightly fewer of those who received the fatty acid supplement: 42 of 101 babies, against 53 of 105 in the control group.

Every year, approximately a thousand EP babies in Sweden are screened for ROP. Four of ten born before 30 weeks' gestation suffer from the disease to some degree. In Sweden, blindness can usually be prevented with laser treatment. Worldwide, however, some 20,000 infants go blind or suffer from severe visual impairment annually as a result of ROP.

Credit: 
University of Gothenburg

Astronomers spot bizarre activity from one of the strongest magnets in the Universe

image: Artist's impression of the active magnetar Swift J1818.0-1607.

Image: 
Carl Knox, OzGrav.

Astronomers from the ARC Centre of Excellence for Gravitational Wave Discovery (OzGrav) and CSIRO have just observed bizarre, never-seen-before behaviour from a 'radio-loud' magnetar--a rare type of neutron star and one of the strongest magnets in the Universe.

Their new findings, published today in the Monthly Notices of the Royal Astronomical Society (MNRAS), suggest magnetars have more complex magnetic fields than previously thought - which may challenge theories of how they are born and evolve over time.

Magnetars are a rare type of rotating neutron star with some of the most powerful magnetic fields in the Universe. Astronomers have detected only thirty of these objects in and around the Milky Way--most of them detected by X-ray telescopes following a high-energy outburst.

However, a handful of these magnetars have also been seen to emit radio pulses similar to pulsars--the less magnetic cousins of magnetars that produce beams of radio waves from their magnetic poles. Tracking how the pulses from these 'radio-loud' magnetars change over time offers a unique window into their evolution and geometry.

In March 2020, a new magnetar named Swift J1818.0-1607 (J1818 for short) was discovered after it emitted a bright X-ray burst. Rapid follow-up observations detected radio pulses originating from the magnetar. Curiously, the appearance of the radio pulses from J1818 were quite different to those seen from other radio-loud magnetars.

Most radio pulses from magnetars maintain a consistent brightness across a wide range of observing frequencies. However, the pulses from J1818 were much brighter at low frequencies than high frequencies - similar to what is seen in pulsars, another more common type of radio-emitting neutron star.

In order to better understand how J1818 would evolve over time, a team led by scientists from the ARC Centre of Excellence for Gravitational Wave Discovery (OzGrav) observed it eight times using the CSIRO Parkes radio telescope (also known as Murriyang) between May and October 2020.

During this time, they found the magnetar underwent a brief identity crisis: in May it was still emitting the unusual pulsar-like pulses that had been detected previously; however, by June it had started flickering between a bright and a weak state. This flickering behaviour reached a peak in July where they saw it flicking back and forth between emitting pulsar-like and magnetar-like radio pulses.

"This bizarre behaviour has never been seen before in any other radio-loud magnetar," explains study lead author and Swinburne University/CSIRO PhD student Marcus Lower. "It appears to have only been a short-lived phenomenon as by our next observation it had settled permanently into this new magnetar-like state."

The scientists also looked for pulse shape and brightness changes at different radio frequencies and compared their observations to a 50-year-old theoretical model. This model predicts the expected geometry of a pulsar, based on the twisting direction of its polarised light.

"From our observations, we found that the magnetic axis of J1818 isn't aligned with its rotation axis," says Lower.

"Instead, the radio-emitting magnetic pole appears to be in its southern hemisphere, located just below the equator. Most other magnetars have magnetic fields that are aligned with their spin axes or are a little ambiguous."

"This is the first time we have definitively seen a magnetar with a misaligned magnetic pole."

Remarkably, this magnetic geometry appears to be stable over most observations. This suggests any changes in the pulse profile are simply due to variations in the height the radio pulses are emitted above the neutron star surface. However, the August 1st 2020 observation stands out as a curious exception.

"Our best geometric model for this date suggests that the radio beam briefly flipped over to a completely different magnetic pole located in the northern hemisphere of the magnetar," says Lower.

A distinct lack of any changes in the magnetar's pulse profile shape indicate the same magnetic field lines that trigger the 'normal' radio pulses must also be responsible for the pulses seen from the other magnetic pole.

The study suggests this is evidence that the radio pulses from J1818 originate from loops of magnetic field lines connecting two closely spaced poles, like those seen connecting the two poles of a horseshoe magnet or sunspots on the Sun. This is unlike most ordinary neutron stars which are expected to have north and south poles on opposite sides of the star that are connected by a donut-shaped magnetic field.

This peculiar magnetic field configuration is also supported by an independent study of the X-rays pulses from J1818 that were detected by the NICER telescope on board the International Space Station. The X-rays appear to come from either a single distorted region of magnetic field lines that emerge from the magnetar surface or two smaller, but closely spaced, regions.

These discoveries have potential implications for computer simulations of how magnetars are born and evolve over long periods of time, as more complex magnetic field geometries will change how quickly their magnetic fields are expected to decay over time. Additionally, theories that suggest fast radio bursts can originate from magnetars will have to account for radio pulses potentially originating from multiple active sites within their magnetic fields.

Catching a flip between magnetic poles in action could also afford the first opportunity to map the magnetic field of a magnetar.

"The Parkes telescope will be watching the magnetar closely over the next year" says scientist and study co-author Simon Johnston, from the CSIRO Astronomy and Space Science.

Credit: 
The Australian Research Council Centre of Excellence for Gravitational Wave Discovery

February special issue of SLAS Discovery focuses on hit discovery methodologies

Oak Brook, IL - The February edition of SLAS Discovery is a Special Issue on Hit Discovery Methodologies edited by Mark Wigglesworth, Ph.D., (Medicines Discovery Catapult, Stockport, EN, UK) and Peter Hodder, Ph.D. (Amgen, Thousand Oaks, CA, USA).

The focus of this Special Issue is to highlight the use of hit discovery methodologies and technologies and their usage in both small molecule and large molecule drug discovery. The February issue exemplifies how technologies, both new and existing, have been applied successfully to find hits.

Additionally, the issue houses a list of the most downloaded articles from SLAS journals, many of which reflect the focus on the implementation, characterization and progression of hit discovery.

The February issue of SLAS Discovery includes nine articles of original research in addition to the cover article.

Articles of Original Research include:

A Homogeneous Cell-Based Membrane Potential Assay to Identify Compounds that Promote Readthrough of Premature Termination Codons in the Cystic Fibrosis Transmembrane Conductance Regulator Ion Channel

High-Throughput Screening and Triage Assays Identify Small Molecules Targeting cMyc in Cancer Cells

Development of a High-Throughput Affinity Mass Spectrometry (AMS) Platform Using Laser Diode Thermal Desorption Ionization Coupled to Mass Spectrometry (LDTD-MS)

Rapid Compound Integrity Assessment for High-Throughput Screening Hit Triaging

High-Throughput Mechanism of Inhibition

AI Driven Iterative Screening for Hit Finding

Toward the Efficient Discovery of Actionable Chemical Matter From DNA-Encoded Libraries

An Automated High-Throughput Fluorescence in Situ Hybridization (FISH) Assay Platform for Use in the Identification and Optimization of siRNA-Based Therapeutics

Comparison of Approaches for Determining Bioactivity Hits from High-Dimensional Profiling Data

Other articles include:

European Lead Factory: Collaborative Innovation in Hit Discovery

High-Throughput Mass Spectrometry for Hit Identification: Current Landscape & Future Perspectives

Credit: 
SLAS (Society for Laboratory Automation and Screening)

Just add mushrooms: Making meals more nutritious

image: New research finds that adding a mushroom serving to the diet increased the intake of several micronutrients, including shortfall nutrients such as vitamin D, without any increase in calories, sodium or fat.

Image: 
Mushroom Council

February 1, 2021 - Researchers have identified another good reason to eat more mushrooms. New research , published in Food Science & Nutrition (January 2021) found that adding a mushroom serving to the diet increased the intake of several micronutrients, including shortfall nutrients such as vitamin D, without any increase in calories, sodium or fat.

Dr. Victor L. Fulgoni III and Dr. Sanjiv Agarwal modeled the addition of mushrooms to National Health and Nutrition Examination Survey (NHANES) 2011-2016 dietary data looking at a composite of white, crimini and portabella mushrooms at a 1:1:1 ratio; one scenario including UV-light exposed mushrooms; and one scenario including oyster mushrooms for both 9-18 years and 19+ years of age based on an 84g or ½ cup equivalent serving.

Key findings include:

Adding an 84g serving of mushrooms increased several shortfall nutrients including potassium and fiber. This was true for the white, crimini and portabella 1:1:1 mix and the oyster mushrooms.

The addition of a serving (84 g) of mushrooms to the diet resulted in an increase in dietary fiber (5%-6%), copper (24%-32%), phosphorus (6%), potassium (12%-14%), selenium (13%-14%), zinc (5%-6%), riboflavin (13%-15%), niacin (13%-14%), and choline (5%-6%) in both adolescents and adults; but had no impact on calories, carbohydrate, fat or sodium.

When commonly consumed mushrooms are exposed to UV-light to provide 5 mcg vitamin D per serving, vitamin D intake could meet and slightly exceed the recommended daily value (98% - 104%) for both the 9 -18 year and 19+ year groups as well as decrease inadequacy of this shortfall nutrient in the population.

A serving of UV-light exposed commonly consumed mushrooms decreased population inadequacy for vitamin D from 95.3% to 52.8% for age group 9-18 years and from 94.9% to 63.6% for age group 19+ years.

"This research validated what we already knew that adding mushrooms to your plate is an effective way to reach the dietary goals identified by the DGA ," said Mary Jo Feeney, MS, RD, FADA and nutrition research coordinator to the Mushroom Council. "Data from surveys such as NHANES are used to assess nutritional status and its association with health promotion and disease prevention and assist with formulation of national standards and public health policy (CDC, 2020)."

Mushrooms are fungi - a member of the third food kingdom - biologically distinct from plant and animal-derived foods that comprise the USDA food patterns yet have a unique nutrient profile that provides nutrients common to both plant and animal foods. Although classified into food grouping systems by their use as a vegetable, mushrooms' increasing use in main entrees in plant-forward diets is growing, supporting consumers' efforts to follow food-based dietary guidance recommendations to lower intake of calories, saturated fatty acids, and sodium while increasing intake of under-consumed nutrients including fiber, potassium and vitamin D. Often grouped with vegetables, mushrooms provide many of the nutrient attributes of produce, as well as attributes more commonly found in meat, beans or grains.

According to the USDA's FoodData Central , 5 medium raw, white mushrooms (90g) contain 20 calories, 0g fat, 3g protein and are very low in sodium (0mg/

Mushrooms are one of the best dietary sources of sulfur-containing antioxidant amino acid ergothioneine and tripeptide glutathione Ergothioneine and glutathione contents in mushrooms depends upon the mushroom varieties, and oyster mushrooms contain more amounts of these sulfur-containing antioxidants than commonly consumed mushrooms: white button, crimini, or portabella mushrooms. The addition of a serving of commonly consumed mushrooms and oyster mushrooms would be expected to add 2.24 and 24.0 mg ergothioneine, respectively, and 3.53 and 12.3 mg glutathione, respectively, to the NHANES 2011-2016 diets based on published literature values.

At this time, the USDA FoodData Central database does not include analytical data on ergothioneine. However, the Mushroom Council is currently supporting research to analyze mushrooms for bioactives/ergothioneine for possible inclusion in USDA FoodData Central database.

More Research from the Mushroom Council Still to Come

With mushrooms growing in awareness and consideration among consumers nationwide, in 2019, the Mushroom Council made a $1.5 million multi-year investment in research to help broaden understanding of the food's nutritional qualities and overall health benefits.

In addition to the analysis of mushrooms for bioactives/ergothioneine for inclusion in USDA FoodData Central database, additional research projects approved include:

Health promoting effects of including mushrooms as part of a healthy eating pattern.

Mushrooms' relationship with cognitive health in older adults.

Mushrooms' impact on brain health in an animal model.

Nutritional impact of adding a serving of mushrooms to USDA Food Patterns.

Since 2002, the Council has conducted research that supports greater mushroom demand by discovering nutrient and health benefits of mushrooms. Published results from these projects form the basis for communicating these benefits to consumers and health influencers.

Credit: 
FLM Harvest

Why do psychiatric drugs help some, but not others? Study offers clues

When it comes to developing drugs for mental illnesses, three confounding challenges exist:

Men and women experience them differently, with things like depression and anxiety far more common in females.

A drug that works for one person may not work for another, and side effects abound.

New CU Boulder research, published in the journal eLIfe, sheds light on one reason those individual differences may exist. Turns out a key protein in the brain called AKT may function differently in males than females.

The study also offers a closer look at where, precisely, in the brain things may go wrong with it, marking an important step toward more targeted and less harmful therapies.

"The ultimate goal is to find the kink in the armor of mental illness - the proteins in the brain that we can specifically target without impacting other organs and causing side effects," says Charles Hoeffer, an assistant professor of integrative physiology at the Institute for Behavioral Genetics. "Personalization is also key. We need to stop hitting every mental illness with the same hammer."

Discovered in the 1970s and best known for its potential role in causing cancer when mutated, AKT has more recently been identified as a key player in promoting "synaptic plasticity." That's the brain's ability to strengthen connections between neurons in response to experience.

"Let's say you see a shark and you're scared and your brain wants to form a memory. You have to make new proteins to encode that memory," explains Hoeffer.

AKT is one of the first proteins to come online, cranking the gears up on a host of downstream proteins in that memory factory. Without it, researchers have suspected, we can't learn new memories or extinguish old ones to make room for new, less harmful ones.

Previous studies have linked mutations in the AKT gene to a host of problems, from schizophrenia and post-traumatic stress disorder to autism and Alzheimer's.

But, as Hoeffer's previous research has discovered, not all AKTs are created equal:

Different flavors, or isoforms, function differently in the brain. For instance, AKT2 found exclusively in the star-shaped brain cells called astroglia, is often implicated in brain cancer.

AKT3 appears to be important for brain growth and development. And AKT1, in combination with AKT2 in the prefrontal cortex of the brain, appears to be critical for learning and memory.

"These subtle differences could be really important if you wanted to personalize treatments for people," explains Marissa Ehringer, an associate professor of integrative physiology who partnered with Hoeffer on some of the research.

Three years in the making, the study adds an important new wrinkle to the story. Following National Institutes of Health guidelines that in the past six years began to require researchers to include both male and female animals in studies, it looked closely at how different gendered mice responded to the loss of various AKT isoforms.

"We found the difference between males and females to be so great it became the focus of our work," Hoeffer said. "It was like night and day."

For instance, male mice whose AKT1 was functioning normally, were much better than those missing the protein when it came to "extinction learning" - replacing an old memory, or association, that's not useful any more. (Imagine letting go of the memory of your favorite route home from work because you've moved or disassociating a loud sound with danger).

For female mice, it didn't make much of a difference.

Far more research is needed and underway, but Hoeffer suspects many other key proteins in the brain share similar nuances - with different flavors serving different purposes or acting differently in men and women.

With one in five U.S. adults living with mental illness and women as much as four times as likely to experience mental illness during their lifetimes, he hopes that by disentangling all those nuances, he can move the dial toward better, safer treatments.

"To help more people suffering from mental illness we need much more knowledge about the difference between male and female brains and how they could be treated differently," Hoeffer said. "This study is an important step in that direction."

Credit: 
University of Colorado at Boulder

Unmatched dust storms raged over Western Europe during Ice age maximum

image: The story in brief.

Image: 
TiPES/HP

Every late winter and early spring, huge dust storms swirled across the bare and frozen landscapes of Europe during the coldest periods of the latest ice age. These paleo-tempests, which are seldom matched in our modern climate frequently covered Western Europe in some of the thickest layers of ice-age dust found anywhere previously on Earth. This is demonstrated by a series of new estimates of the sedimentation and accumulation rates of European loess layers obtained by Senior Research Scientist Denis-Didier Rousseau from Ecole Normale Supérieure in Paris, France, and colleagues. The work, which is published in Quaternary Science Reviews is part of the TiPES project on tipping points in the Earth system, coordinated by The University of Copenhagen.

In the study Denis-Didier Rousseau and colleagues reinterpreted layers in loess from Nussloch, Germany. Loess is a fine-silt-sized earth type found all over the world. It mainly consists of aeolian sediments, which is material transported by the wind from dry areas without vegetation such as deserts of any type, moraines, or dried-out river beds.

Within the aeolian sediments, darker layers of paleosol alternate within the loess layers. Every layer in the loess represents a shift in climatic conditions. At Nussloch the paleosols stem from periods of milder climate, called interstadials during the ice age. The aeolian layers were deposited during the cold periods and consist mainly of dust and silt from the dry riverbeds of the Rhine river.

Traditionally in the academic field of paleo-climate, it has been assumed that interstadial paleosols developed on top of the underlying layer, by accumulation when the shift to a relatively mild climate allowed a richer biology to flourish in the region.

Into the dust

But careful sampling and accurate dating of the loess sedimentation from Nussloch with luminescence and C14 by Denis-Didier Rousseau and colleagues have now shown that this is not the case. Instead, in Europe, paleosols developed down into the underlying layer, not on top of the dust.

"In Europe, the paleosols are being embedded in the aeolian deposits. And when you are considering this, you have to take into account the thickness of the paleosol when you evaluate the dust deposition. Then we found aeolian accumulation and sedimentation rates which are much more precise than they were previously," says Denis-Didier Rousseau.

From this, it has been possible to construct new age models and recalculate sedimentation rates and mass balance for European loess layers in a range of samples from Brittany, Northern France Eastward to Ukraine on an almost longitudinal transect.

Dustiest region on Earth

The results show, that during the last glacial maximum, Western Europe was dustier than China which has otherwise been presumed to be the dustiest region on Earth in the coldest periods of the ice ages.

The new estimations of ice age dust accumulation in Europe fit a range of climate model simulations. The result thus has the potential to aid the understanding of the abrupt warming and cooling periods during the ice ages called Dansgaard/Oeschger events which bear the marks of climate tipping points.

Credit: 
University of Copenhagen - Faculty of Science

Research catches up to world's fastest-growing plant

image: From left: Todd Michael and Joseph Ecker

Image: 
Salk Institute

LA JOLLA--(February 1, 2021) Wolffia, also known as duckweed, is the fastest-growing plant known, but the genetics underlying this strange little plant's success have long been a mystery to scientists. Now, thanks to advances in genome sequencing, researchers are learning what makes this plant unique--and, in the process, discovering some fundamental principles of plant biology and growth.

A multi-investigator effort led by scientists from the Salk Institute is reporting new findings about the plant's genome that explain how it's able to grow so fast. The research, published in the February 2021 issue of Genome Research, will help scientists to understand how plants make trade-offs between growth and other functions, such as putting down roots and defending themselves from pests. This research has implications for designing entirely new plants that are optimized for specific functions, such as increased carbon storage to help address climate change.

"A lot of advancement in science has been made thanks to organisms that are really simple, like yeast, bacteria and worms," says Todd Michael, first author of the paper and a research professor in Salk's Plant Molecular and Cellular Biology Laboratory. "The idea here is that we can use an absolutely minimal plant like Wolffia to understand the fundamental workings of what makes a plant a plant."

Wolffia, which is found growing in fresh water on every continent except Antarctica, looks like tiny floating green seeds, with each plant only the size of a pinhead. It has no roots and only a single fused stem-leaf structure called a frond. It reproduces similar to yeast, when a daughter plant buds off from the mother. With a doubling time of as little as a day, some experts believe Wolffia could become an important source of protein for feeding Earth's growing population. (It's already eaten in parts of Southeast Asia, where it's known as khai-nam, which translates as "water eggs.")

To understand what adaptations in Wolffia's genome account for its rapid growth, the researchers grew the plants under light/dark cycles, then analyzed them to determine which genes were active at different times of the day. (Most plants' growth is regulated by the light and dark cycle, with the majority of growth taking place in the morning.)

"Surprisingly, Wolffia only has half the number of genes that are regulated by light/dark cycles compared to other plants," Michael says. "We think this is why it grows so fast. It doesn't have the regulations that limit when it can grow."

The researchers also found that genes associated with other important elements of behavior in plants, such as defense mechanisms and root growth, are not present. "This plant has shed most of the genes that it doesn't need," Michael adds. "It seems to have evolved to focus only on uncontrolled, fast growth."

"Data about the Wolffia genome can provide important insight into the interplay between how plants develop their body plan and how they grow," says HHMI Investigator and Professor Joseph Ecker, who is also director of Salk's Genomic Analysis Laboratory and a coauthor of the paper. "This plant holds promise for becoming a new lab model for studying the central characteristics of plant behavior, including how genes contribute to different biological activities."

One focus of Michael's lab is learning how to develop new plants from the ground up, so that they can be optimized for certain behaviors. The current study expands knowledge of basic plant biology as well as offers the potential for improving crops and agriculture. By making plants better able to store carbon from the atmosphere in their roots, an approach pioneered by Salk's Harnessing Plants Initiative, scientists can optimize plants to help address the threat of climate change.

Michael plans to continue studying Wolffia to learn more about the genomic architecture of plant development by using this simplified plant to understand the networks that control fate.

Credit: 
Salk Institute

Early functional SARS-COV-2 specific T cell response may prevent severe infection

Humoral and cellular adaptive immunity are two immune mechanisms that act against pathogens. Humoral immunity is mediated by antibodies, while cellular immunity does not involve antibodies and is, instead, facilitated by T cells. Studying how these immune mechanisms mediate SARS-CoV-2 infections could be beneficial in controlling the progression of the disease. However, their roles in viral control or disease pathogenesis is not fully understood and only a few studies have thoroughly monitored COVID-19 patients longitudinally, especially during the acute phase of infection.

To fill this knowledge gap, the team of researchers at Duke-NUS investigated the changes in virological and immunological parameters in 12 patients with symptomatic acute SARS-CoV-2 infection from onset of the disease to recovery or death.

"We found that patients who control SARS-Cov-2 infection with only mild symptoms are characterised by an early induction of IFN-γ secreting SARS-CoV-2 specific T cells. The amount of humoral response, however, does not predict the level of COVID-19 disease severity," said Dr Anthony Tanoto Tan, Senior Research Fellow at the Duke-NUS' Emerging Infectious Diseases (EID) programme and the co-author of this study.

"Our data supports the idea that SARS-CoV-2 specific T cells play an important role in the rapid control of viral infection and eventual clearance of the disease," added Dr Martin Linster, Senior Research Fellow with Duke-NUS' EID programme and the co-author of this study.

This work is a continuation of the team's previous publication in Nature, where they analysed SARS-CoV-2 specific T cell response in COVID-19 patients at convalescence. In this study, they have expanded the analysis to the full timeline of SARS-CoV-2 infection from onset to outcome.

"It is time that T cell monitoring should be considered in providing a comprehensive understanding of the immune response against SARS-CoV-2. This would also mean that a vaccine will likely be more effective if a holistic induction of both antibodies and T cells occurs," said Professor Antonio Bertoletti, from Duke-NUS' EID programme, who is the corresponding author of this study.

"This important study furthers our understanding of the immune response against SARS-CoV-2. It has far-reaching implications including on COVID-19 vaccine design and the subsequent monitoring of vaccine response," said Professor Patrick Casey, Senior Vice-Dean for Research at Duke-NUS.

The team is now studying more symptomatic COVID-19 patients with varying disease severity to further validate their findings.

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Duke-NUS Medical School

Supersaturation: The barrier between protein folding and misfolding

image: Snake puzzle models of protein folding and amyloid fibril formation. Protein folding under Anfinsen's dogma leads to a unique functional native structure. Protein misfolding out of Anfinsen's dogma leads to amyloid structures. The two reactions are separated by the high free energy barrier of supersaturation. Once this barrier is broken by agitation or seeding, the equilibrium of folding and misfolding will be achieved.

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Osaka University

Correct, or native, protein folding is essential for correct protein function. Protein misfolding can lead to the formation of amyloid fibrils, and amyloidosis, which is implicated in various human neurodegenerative diseases, including Parkinson's, Alzheimer's, and Huntington's diseases. In this study Yuji Goto and colleagues describe, for the first time, a dynamic link between protein folding and misfolding, and the threshold that must be overcome for the formation of amyloid fibrils.

Technological advances are at the forefront of many scientific discoveries. The atomic structures of some amyloid fibrils were recently revealed as a result of advances in solid-state nuclear magnetic resonance and cryogenic electron microscopy. While an important step forward for the field, this development does not fully explain the determining factors of protein misfolding. How are folding and misfolding related? Can folding/unfolding and amyloid polymerization/depolymerization be explained by a single mechanism, and if so what might this look like? These are the questions that researchers at Osaka University sought to answer.

Summarizing their motivation for this work, senior author Masahiro Noji explains: "The thermodynamic hypothesis of protein folding, known as the 'Anfinsen's dogma' describes that the native structure of a protein represents a free energy minimum determined by the amino acid sequence. However, this is not consistent with the misfolding of globular proteins to form amyloid fibrils." Therefore, Yuji Goto and colleagues set out to explore the link between protein folding and misfolding.

Although proteins perform their functions by folding to their native structures, as represented by Anfinsen's dogma, proteins often misfold to form amyloid fibrils, leading to amyloidosis. In their paper, the research team from Osaka University describe a general concept for the link between protein folding and misfolding.

"The supersaturation barrier of a denatured protein separates protein folding and amyloid formation, and misfolding occurs when this barrier breaks down" corresponding author Yuji Goto says. "Our results show a clear link between correct protein folding, as defined by Anfinsen's dogma, and protein misfolding."

Supersaturation can be observed throughout nature in the formation of crystals, including those involved in ice formation. Here, the team at Osaka University show that supersaturation is fundamental to correct protein folding. The supersaturation barrier represents a novel concept that will advance the field of protein folding and contribute to the development of therapeutic strategies to prevent and treat amyloidosis, including those involved in neurodegenerative diseases.

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Osaka University

Batteries that can be assembled in ambient air

image: Battery production in ambient air using a multi-functional separator

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POSTECH

The honor of the 2020 Nobel Prize in Chemistry went to those who developed lithium-ion rechargeable batteries. These batteries have become an essential energy source for electronic devices ranging from small IT devices to electric vehicles. Tesla, a leading U.S. automaker, recently emphasized the need to establish an innovative production system and reduce battery cost. The price of batteries accounts for a large portion of electric vehicles and cost reduction is vital to popularizing them.

A joint research team, led by Professor Soojin Park and Ph.D. candidate Hye Bin Son of POSTECH's Department of Chemistry with Professor Seungmin Yoo of Ulsan College, has successfully developed a multi-functional separator which allows the batteries to function even when the pouch cell is assembled in ambient air. These findings were introduced in the latest online edition of Energy Storage Materials.

Since the electrolyte inside the battery reacts with moisture to cause deterioration, lithium-ion batteries are typically assembled in a dry room which maintains less than 1% humidity levels. However, maintaining a dry room is rather costly.

To solve this issue, studies have been conducted to suppress impurities - such as moisture or hydrofluoric acid - by injecting additives into the electrolytes. But these can cause unwanted side reactions during the battery operation. In fact, when batteries are activated at a high temperature (50? or higher), even a small bit of moisture causes faster performance deterioration. Therefore, there is a need for a material capable of trapping moisture and impurities in the battery without adverse electrochemical reactions to the additives.

To this, the joint research team introduced functional materials that can trap impurities on the surface of the separator to increase thermal stability and improve battery performance. This multi-functional separator demonstrated excellent heat resistance (shrinkage within 10% after 30 minutes of storage at 140?. Conventional separator had 50% shrinkage) and further showed improved electrochemical performance at the high temperature of 55? (79% of the initial capacity maintained after 100 charging cycles).

Additionally, the researchers confirmed the effectiveness of the functional material in the electrolyte in the impurity-filled environment. The silane compound on the surface of the synthesized functional ceramic traps moisture and maintains the ceramic structure well, but the general ceramic material was corroded by the acidified electrolyte. Moreover, through this research, the team confirmed that this multi-functional separator produced in the ambient air this time exhibits superior lifespan than the conventional separators, confirming that it provides stable performance beyond the role of a simple separator.

"This newly developed multi-functional separator shows great stability and excellent electrochemical performance at high energy density," remarked Professor Soojin Park who has long been studying battery separators through various approaches. "With this first successful case of fabricating batteries in ambient air, it is expected to play a big role in reducing battery cost."

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Pohang University of Science & Technology (POSTECH)

Easily assembled gold nanoparticle scaffolding serves as molecular probe

image: One-step preparation of photoaffinity probes using clickable gold-nanoparticle precursors enables expedient target identification studies

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FIGURE MODIFIED FROM Organic and Biomolecular Chemistry, January 2021, DOI: 10.1039/D0OB01688H

The development of pharmaceutical treatments is difficult -- clinicians and researchers know a certain drug can regulate particular functions, but they might not know how it actually works. Researchers at Tokyo University of Agriculture and Technology (TUAT) have developed a new, streamlined method to better understand the molecular mechanisms underpinning these interactions.

They published their approach on Dec. 17, 2020 in Organic & Biomolecular Chemistry, a journal of the U.K. Royal Society of Chemistry.

"We set out to develop a new gold nanoparticle-based method for target identification of bioactive small molecules that streamlines the current laborious steps so that we can rapidly find out how these molecules work," said Kaori Sakurai, associate professor in the Department of Biotechnology and Life Science at TUAT.

Bioactive small molecules are chemical compounds, such as pharmaceuticals, that can be readily delivered to and interact with a body's cells. By binding to specific proteins, these molecules can rewire a biological process to stop or enhance whatever the initial function was. For example, the bioactive small molecules in an anticancer agent will bind with a protein in cancer cells to inhibit their uncontrolled growth. They can even to trick the cancer cells into programmed cell death.

The challenge is that it's not always clear which proteins are being targeted or whether there are other proteins targeted that may potentially cause unwanted side effects. Using a technology called photoaffinity labeling, researchers can shine light on target proteins and instantaneously tag them, capturing and identifying them. However, photoaffinity labeling requires extensive time and resources to develop the specific tag, ensure it is attached to the right target in the cell and then purify the tagged target protein.

"Photoaffinity labeling is a powerful approach for the discovery of small molecule-target proteins," Sakurai said. "However, its routine use has been hampered by several issues, including inefficient protein labeling and subsequent purification and technical difficulties of making bioactive small molecules into suitable probes."

Sakurai's team previously provided a solution to the first issue by employing a gold nanoparticle as modular scaffolding on which a specific probe can be designed. In the recent paper, they focused on developing a one-step preparation process.

Since gold nanoparticles have surfaces that can hold modular pieces, the researchers can efficiently build customized assemblies by simply mixing building blocks, according to paper co-author Kanna Mori, a graduate student in the Department of Biotechnology and Life Science at TUAT.

"Photoaffinity probes can be easily obtained from the probe precursors, preassembled with three types of building blocks -- each containing a clickable group, a photoreactive group and a water-soluble spacer group--and then rapidly incorporate a small-molecule of interest through 'click chemistry,'" Mori said.

The fabricated small molecule, even after being conjugated to the nanoparticle, behaves as a parent molecule that would naturally bind to a protein, and the photoreactive group reacts to ultraviolet light irradiation that activates the probe. Once activated, the probe can capture and isolate a target protein.

"We demonstrated that clickable photoaffinity probe precursors will provide a rapid access to photoaffinity probes of different types of bioactive small molecules to identify their target proteins," Sakurai said.

Next, the researchers plan to explore the utility of gold-nanoparticle probes in target identification studies in live cells, expanding their work to factor in physiological conditions. They also plan to introduce complex natural products and some pharmaceuticals into the gold-nanoparticles to begin identifying their unknown target proteins.

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Tokyo University of Agriculture and Technology

Socioeconomic, demographic and urban factors influence the spread of COVID-19

Per capita income, population volume and density, the structure of cities, transport infrastructure or whether districts have their own schools are all factors that can affect the spread of COVID-19. This has been confirmed by a study carried out in 73 districts in Barcelona by researchers from the departments of Geography and Economics of the Universitat Rovira i Virgili, the results of which have been published in the Journal of Public Health. The research reveals that the analysis of the characteristics of every district can facilitate decisions on the specific measures to be applied to individual districts in an attempt to effectively reduce the rate of infection.

To carry out the study, the researchers analysed the data provided by the Public Health Agency of Barcelona on the 41,606 people who were infected with the coronavirus during the first two waves of the pandemic in the 73 districts of the capital. Work was done in two different time periods to differentiate the two waves: the first was from 26 February to 15 July and the second was from 16 July to 16 October. This information showed how the individuals in the city were distributed and whether the positive cases followed some sort of territorial pattern in the sense that levels would be low or high in neighbouring districts.

The study found that the characteristics of every district had a direct impact on the spread of the virus. "The results of the model are clear: particular characteristics show that the virus has particular effects in both waves: for example, the higher the population density is, the more cases there are, and the higher the average income is, the fewer cases there are," explains Josep Maria Arauzo, professor of the URV's Department of Economics and one of the authors of the study.

But the study also shows that in the two waves the collective behaviour of the population was different, which may explain why the virus spread differently in different areas. In this regard, the population structure plays a key role since in the first wave the percentage of positive cases was highest among senior citizens. However, as soon as greater social interaction was allowed and the shortcomings of managing nursing homes had been detected, the highest numbers of infections were found in those districts with a younger population while the number of infections in districts with older populations decreased. "We also observed that the presence of educational institutions increased the number of infections, not because of organisational in these institutions but because of the interactions that took place outside them," points out Aaron Gutiérrez, a researcher from the URV's Department of Geography.

"The study shows the importance of taking local differences into account when adopting measures to efficiently combat the pandemic since if the same measures are applied equally in all places these differences will mean that their effects are quite different," concludes the researcher Antoni Domènech.

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Universitat Rovira i Virgili