Investigators also detected human-made chemicals called perfluoroalkyl substances (PFAS) in the tissues of adult killer whales. Thresholds for health effects of PFAS in marine mammals are not established, but the chemical has been linked to reproductive and endocrine effects in wildlife. In addition, polychlorinated biphenyls (PCBs), which have long been banned, were detected in the blubber of 7 of the 8 killer whales in the study at levels that exceeded the proposed threshold for toxicological effects in marine mammals.

“Levels of pollutants in top predators give not only an indication of ecosystem health, but of the persistence of chemicals, passive mobility in the environment, and active biotransport with migrating animals,” the authors wrote. “Our results are relevant for the continued environmental monitoring of contaminants in the Arctic.”

Story Source:

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

The work centers around a large gene responsible for an inner-ear protein, otoferlin. Mutations in otoferlin are linked to severe congenital hearing loss, a common type of deafness in which patients can hear almost nothing.

“For a long time otoferlin seemed to be a one-trick pony of a protein,” said Colin Johnson, associate professor of biochemistry and biophysics in the OSU College of Science. “A lot of genes will find various things to do, but the otoferlin gene had appeared only to have one purpose and that was to encode sound in the sensory hair cells in the inner ear. Small mutations in otoferlin render people profoundly deaf.”

In its regular form, the otoferlin gene is too big to package into a delivery vehicle for molecular therapy, so Johnson’s team is looking at using a truncated version instead.

Research led by graduate student Aayushi Manchanda showed the shortened version needs to include a part of the gene known as the transmembrane domain, and one of the reasons for that was unexpected: Without the transmembrane domain, the sensory cells were slow to mature.

“That was surprising since otoferlin was known to help encode hearing information but had not been thought to be involved in sensory cell development,” Johnson said.

Findings were published today in Molecular Biology of the Cell.

Scientists in Johnson’s lab have been working for years with the otoferlin molecule and in 2017 they identified a truncated form of the gene that can function in the encoding of sound.

To test whether the transmembrane domain of otoferlin needed to be part of the shortened version of the gene, Manchanda introduced a mutation that truncated the transmembrane domain in zebrafish.

Zebrafish, a small freshwater species that go from a cell to a swimming fish in about five days, share a remarkable similarity to humans at the molecular, genetic and cellular levels, meaning many zebrafish findings are immediately relevant to humans. Embryonic zebrafish are transparent and can be easily maintained in small amounts of water.

“The transmembrane domain tethers otoferlin to the cell membrane and intracellular vesicles but it was not clear if this was essential and had to be included in a shortened form of otoferlin,” Manchanda said. “We found that the loss of the transmembrane domain results in the sensory hair cells producing less otoferlin as well as deficits in hair cell activity. The mutation also caused a delay in the maturation of the sensory cells, which was a surprise. Overall the results argue that the transmembrane domain must be included in any gene therapy construct.”

At the molecular level, Manchanda found that a lack of transmembrane domain led to otoferlin failing to properly link the synaptic vesicles filled with neurotransmitter to the cell membrane, causing less neurotransmitter to be released.

“Our study suggests otoferlin’s ability to tether the vesicles to the cell membrane is a key mechanistic step for neurotransmitter release during the encoding of sound,” Manchanda said.

The National Institutes of Health supported the study.

Story Source:

Materials provided by Oregon State University. Original written by Steve Lundeberg. Note: Content may be edited for style and length.

That theory, the “Oxygen Control Hypothesis,” suggests that the size of these early multicellular organisms was limited by the depth to which oxygen could diffuse into their bodies. The hypothesis makes a simple prediction that has been highly influential within both evolutionary biology and geosciences: Greater atmospheric oxygen should always increase the size to which multicellular organisms can grow.

It’s a hypothesis that’s proven difficult to test in a lab. Yet a team of Georgia Tech researchers found a way — using directed evolution, synthetic biology, and mathematical modeling — all brought to bear on a simple multicellular lifeform called a ‘snowflake yeast’. The results? Significant new information on the correlations between oxygenation of the early Earth and the rise of large multicellular organisms — and it’s all about exactly how much O2 was available to some of our earliest multicellular ancestors.

“The positive effect of oxygen on the evolution of multicellularity is entirely dose-dependent — our planet’s first oxygenation would have strongly constrained, not promoted, the evolution of multicellular life,” explains G. Ozan Bozdag, research scientist in the School of Biological Sciences and the study’s lead author. “The positive effect of oxygen on multicellular size may only be realized when it reaches high levels.”

“Oxygen suppression of macroscopic multicellularity” is published in the May 14, 2021 edition of the journal Nature Communications. Bozdag’s co-authors on the paper include Georgia Tech researchers Will Ratcliff, associate professor in the School of Biological Sciences; Chris Reinhard, associate professor in the School of Earth and Atmospheric Sciences; Rozenn Pineau, Ph.D. student in the School of Biological Sciences and the Interdisciplinary Graduate Program in Quantitative Biosciences (QBioS); along with Eric Libby, assistant professor at Umea University in Sweden and the Santa Fe Institute in New Mexico.

Directing yeast to evolve in record time

“We show that the effect of oxygen is more complex than previously imagined. The early rise in global oxygen should in fact strongly constrain the evolution of macroscopic multicellularity, rather than selecting for larger and more complex organisms,” notes Ratcliff.

“People have long believed that the oxygenation of Earth’s surface was helpful — some going so far as to say it is a precondition — for the evolution of large, complex multicellular organisms,” he adds. “But nobody has ever tested this directly, because we haven’t had a model system that is both able to undergo lots of generations of evolution quickly, and able to grow over the full range of oxygen conditions,” from anaerobic conditions up to modern levels.

The researchers were able to do that, however, with snowflake yeast, simple multicellular organisms capable of rapid evolutionary change. By varying their growth environment, they evolved snowflake yeast for over 800 generations in the lab with selection for larger size.

The results surprised Bozdag. “I was astonished to see that multicellular yeast doubled their size very rapidly when they could not use oxygen, while populations that evolved in the moderately oxygenated environment showed no size increase at all,” he says. “This effect is robust — even over much longer timescales.”

Size — and oxygen levels — matter for multicellular growth

In the team’s research, “large size easily evolved either when our yeast had no oxygen or plenty of it, but not when oxygen was present at low levels,” Ratcliff says. “We did a lot more work to show that this is actually a totally predictable and understandable outcome of the fact that oxygen, when limiting, acts as a resource — if cells can access it, they get a big metabolic benefit. When oxygen is scarce, it can’t diffuse very far into organisms, so there is an evolutionary incentive for multicellular organisms to be small — allowing most of their cells access to oxygen — a constraint that is not there when oxygen simply isn’t present, or when there’s enough of it around to diffuse more deeply into tissues.”

Ratcliff says not only does his group’s work challenge the Oxygen Control Hypothesis, it also helps science understand why so little apparent evolutionary innovation was happening in the world of multicellular organisms in the billion years after the Great Oxygenation Event. Ratcliff explains that geologists call this period the “Boring Billion” in Earth’s history — also known as the Dullest Time in Earth’s History, and Earth’s Middle Ages — a period when oxygen was present in the atmosphere, but at low levels, and multicellular organisms stayed relatively small and simple.

Bozdag adds another insight into the unique nature of the study. “Previous work examined the interplay between oxygen and multicellular size mainly through the physical principles of gas diffusion,” he says. “While that reasoning is essential, we also need an inclusive consideration of principles of Darwinian evolution when studying the origin of complex multicellular life on our planet.” Finally being able to advance organisms through many generations of evolution helped the researchers accomplish just that, Bozdag adds.

These research results were published online as one of the Journal of Applied Physiology‘s Articles in Press on March 25, 2021.

Main points

• The research results revealed that applying an ice pack to a severe muscle injury resulting from eccentric contraction may prolong the time it takes to heal.
• The cause of this phenomenon is that icing delays the arrival of pro-inflammatory macrophages, which are responsible for the phagocytosis (*5), or removal, of damaged tissue. Furthermore, this makes difficult for the macrophages to sufficiently infiltrate the damaged muscle cells.

Research Background

Skeletal muscle injuries encompass a range of damage to muscles; from a microcellular level to a severe level. These injuries include not only those that happen during sports or schools’ physical education lessons but also external injuries that occur as a result of accidents and disasters.

‘RICE treatment’ is a common approach for skeletal muscle injuries, regardless of the extent of the injury. This acronym stands for Rest, Ice, Compression and Elevation and is often used in physical education, sports and even medicine. Ice is commonly applied regardless of the type of muscle injury, yet little is known about the long-term effects of icing.

Ice is used to suppress inflammation, however, inflammation in response to tissue injury is one of the body’s healing mechanisms. This has come to be understood as a vital response for tissue regeneration. In other words, suppressing inflammation with ice may also inhibit the body’s attempt to repair itself.

Experiments investigating the effect of icing muscles after injury have produced conflicting results. Some have reported that it delays muscle regeneration while others have stated that it doesn’t inhibit this process. However, none of the research up until now has investigated the effects of icing using an injury model that mimics common sports injuries caused by muscle contraction.

Using a mouse model of eccentric contraction injury, the current research team decided to observe the effects of post-injury icing. In this mouse model, injuries were induced to resemble severe torn muscles.

Research Methodology and Results

Eccentric contraction was induced by electrically stimulating the leg muscles of the mice and then exerting a stronger force during this stimulation to make the leg muscles move in the opposite direction. After this, the muscles were harvested. Icing was performed by placing polyurethane bags of ice on top of the skin over three 30 minute sessions per day, with each session being 2 hours apart. This was continued until two days after the injury. The icing was based on the usual clinically recommended method.

The researchers investigated the regenerated skeletal muscle two weeks after injury, comparing the icing group with the non-icing group. A significantly higher percentage of smaller regenerated muscle fibers were found in cross-sections from the icing group, with a greater number of medium to large fibers in the non-icing group. In other words, this revealed that skeletal muscle regeneration may be delayed as a result of icing.

Next, the researchers periodically took samples of muscle from the icing and non-icing groups of animals in order to investigate what was happening in the regeneration process up until this point.

In the regeneration process, inflammatory cells gather at the site of the injury, remove the debris from the damaged muscle and then begin to build new muscle. However, the results revealed that it is harder for inflammatory cells to enter the injured muscle cells if ice is applied.

Macrophages are typical of the inflammatory cells that enter the injured muscle. These consist of pro-inflammatory macrophages, which phagocyte damaged tissue thus causing inflammation, and anti-inflammatory macrophages (*6), which suppress the inflammatory reaction and promote repair. It is thought that pro-inflammatory macrophages change their characteristics, becoming anti-inflammatory. The results of this research team’s experiments showed that icing delays the arrival of pro-inflammatory macrophages at the site of the injury.

These results indicate the possibility that macrophages are unable to sufficiently phagocyte the damaged muscle when ice is applied after severe muscle injuries caused by eccentric contraction, consequently delaying the formation of new muscle cells.

Comment from Associate Professor Arakawa

In sports, the mantra of immediately applying ice to an injury is commonplace, regardless of the injury’s severity. However, the mechanism that we illuminated through this research suggests that not icing a severe muscle injury may lead to faster recovery. The idea of immediately cooling any type of injury is also entrenched in schools’ physical education classes. I hope that in the future, the alternative option of speeding up recovery by not cooling severe muscle injuries will become known.

However, even though icing may disrupt the recovery process for severe muscle injuries, there is no denying the possibility that there are degrees of mild muscle injuries that can be iced. The next issue is to work out where to draw the line. We are now in the middle of investigating what effect icing has on slight muscle injuries.

Next, we will continue to investigate how icing should be carried out according to the extent of the muscle injury. We aim to contribute guidelines that will enable people in sports and clinical rehabilitation to make accurate judgements about whether or not to ice an injury.

Glossary

1. Eccentric contraction: Normally, muscles get shorter when they contract. Eccentric contraction is when the opposite happens and the muscles lengthen as they contract. This can occur due to strenuous activity, which overburdens the muscles and can easily cause injury.

2. Macrophage: A type of white blood cell found in the blood. There are two known types of macrophage: pro-inflammatory and anti-inflammatory.

3. Pro-inflammatory macrophage: These are macrophages that immediately gather at the site of a tissue injury after it occurs. They phagocytose the damaged tissue and trigger inflammation.

4. Inflammation: A pathological reaction that occurs when living tissue is damaged. Symptoms include rubefaction (reddening of the skin), feverishness, swelling and pain.

5. Phagocytosis: When macrophages surround and remove damaged tissue.

6. Anti-inflammatory macrophage: It is said that inflammatory macrophages change into this type. They suppress inflammation and recruit substances for tissue repair.

This research received funding from the Japan Society for the Promotion of Science (JSPS KAKENHI grant number JP17K01501).

Scientists have worked on controlling the alignment of magnetic atoms within antiferromagnetic materials to create magnetic switches. Conventionally, this has been done using a ‘field-cooling’ procedure, which heats and then cools a magnetic system containing an antiferromagnet, while applying an external magnetic field. However, this process is inefficient for use in many micro- or nano- structured spintronics devices because the spatial resolution of the process itself is not high enough to be applied in a micro- or nano-scale devices.

“We discovered that we can control the antiferromagnetic state by simultaneously applying mechanical vibration and a magnetic field,” says Jung-Il Hong of DGIST’s Spin Nanotech Laboratory. “The process can replace the conventional heating and cooling approach, which is both inconvenient and harmful to the magnetic material. We hope our new procedure will facilitate the integration of antiferromagnetic materials into spintronics-based micro- and nano-devices.”

Hong and his colleagues combined two layers: a cobalt-iron-boron ferromagnetic film on top of an iridium manganese antiferromagnetic film. The layers were grown on piezoelectric ceramic substrates. Combined application of mechanical vibration and a magnetic field allowed the scientists to control the alignments of magnetic spins repeatedly along any direction desired.

The team aims to continue the search and development of new magnetic phases beyond conventionally classified magnetic materials. “Historically, new material discovery has led to the development of new technologies,” says Hong. “We want our research work to be a seed for new technologies.”

Story Source:

Materials provided by DGIST (Daegu Gyeongbuk Institute of Science and Technology). Note: Content may be edited for style and length.