How human sperm really swim: New research challenges centuries-old assumption

A breakthrough in fertility science by researchers from Bristol and Mexico has shattered the universally accepted view of how sperm ‘swim’.

More than three hundred years after Antonie van Leeuwenhoek used one of the earliest microscopes to describe human sperm as having a “tail, which, when swimming, lashes with a snakelike movement, like eels in water,” scientists have revealed this is an optical illusion.

Using state-of-the-art 3D microscopy and mathematics, Dr Hermes Gadelha from the University of Bristol, Dr Gabriel Corkidi and Dr Alberto Darszon from the Universidad Nacional Autonoma de Mexico, have pioneered the reconstruction of the true movement of the sperm tail in 3D.

Using a high-speed camera capable of recording over 55,000 frames in one second, and a microscope stage with a piezoelectric device to move the sample up and down at an incredibly high rate, they were able to scan the sperm swimming freely in 3D.

The ground-breaking study, published in the journal Science Advances, reveals the sperm tail is in fact wonky and only wiggles on one side. While this should mean the sperm’s one-sided stroke would have it swimming in circles, sperm have found a clever way to adapt and swim forwards.

“Human sperm figured out if they roll as they swim, much like playful otters corkscrewing through water, their one-sided stoke would average itself out, and they would swim forwards,” said Dr Gadelha, head of the Polymaths Laboratory at Bristol’s Department of Engineering Mathematics and an expert in the mathematics of fertility.

“The sperms’ rapid and highly synchronised spinning causes an illusion when seen from above with 2D microscopes — the tail appears to have a side-to-side symmetric movement, “like eels in water,” as described by Leeuwenhoek in the 17th century.

“However, our discovery shows sperm have developed a swimming technique to compensate for their lop-sidedness and in doing so have ingeniously solved a mathematical puzzle at a microscopic scale: by creating symmetry out of asymmetry,” said Dr Gadelha.

“The otter-like spinning of human sperm is however complex: the sperm head spins at the same time that the sperm tail rotates around the swimming direction. This is known in physics as precession, much like when the orbits of Earth and Mars precess around the sun.”

Computer-assisted semen analysis systems in use today, both in clinics and for research, still use 2D views to look at sperm movement. Therefore, like Leeuwenhoek’s first microscope, they are still prone to this illusion of symmetry while assessing semen quality. This discovery, with its novel use of 3D microscope technology combined with mathematics, may provide fresh hope for unlocking the secrets of human reproduction.

“With over half of infertility caused by male factors, understanding the human sperm tail is fundamental to developing future diagnostic tools to identify unhealthy sperm,” adds Dr Gadelha, whose work has previously revealed the biomechanics of sperm bendiness and the precise rhythmic tendencies that characterise how a sperm moves forward.

Dr Corkidi and Dr Darszon pioneered the 3D microscopy for sperm swimming.

“This was an incredible surprise, and we believe our state-of the-art 3D microscope will unveil many more hidden secrets in nature. One day this technology will become available to clinical centres,” said Dr Corkidi.

“This discovery will revolutionize our understanding of sperm motility and its impact on natural fertilization. So little is known about the intricate environment inside the female reproductive tract and how sperm swimming impinge on fertilization. These new tools open our eyes to the amazing capabilities sperm have,” said Dr Darszon.

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‘Little brain’ or cerebellum not so little after all

When we say someone has a quick mind, it may be in part thanks to our expanded cerebellum that distinguishes human brains from those of macaque monkeys, for example.

Sometimes referred to by its Latin translation as the ‘”little brain”‘, the cerebellum is located close to the brainstem and sits under the cortex in the hindbrain. New research at San Diego State University, however, calls the “little” terminology into question.

The cerebellum plays a versatile role, contributing to our five senses as well as pain, movements, thought, and emotion.

It’s essentially a flat sheet with the thickness of a crepe, crinkled into hundreds of folds to make it fit into a compact volume about one-eighth the volume of the cerebral cortex. For this reason, the surface area of the cerebellum was thought to be considerably smaller than that of the cerebral cortex.

By using an ultra-high-field 9.4 Tesla MRI machine to scan the brain and custom software to process the resulting images, an SDSU neuroimaging expert discovered the tightly packed folds actually contain a surface area equal to 80% of the cerebral cortex’s surface area. In comparison, the macaque’s cerebellum is about 30% the size of its cortex.

“The fact that it has such a large surface area speaks to the evolution of distinctively human behaviors and cognition,” said Martin Sereno, psychology professor, cognitive neuroscientist and director of the SDSU MRI Imaging Center. “It has expanded so much that the folding patterns are very complex.”

Unprecedented insights

Collaborating with imaging and cerebellum experts from the United Kingdom, Netherlands and Canada, Sereno used customized open source FreeSurfer software that he originally developed with colleagues while at the University of California San Diego to computationally reconstruct the folded surface of the cerebellum. The software also unfolds and flattens the cerebellar cortex so as to visualize it to the level of each individual folia — or thin leaf like fold.

A pioneer in brain imaging who has leveraged functional MRI to uncover visual maps in the brain, Sereno found that when the cerebellum is completely unfolded, it forms a strange “crepe” four inches wide by three feet long. The findings were published this week in a study in PNAS (Proceedings of the National Academy of Sciences).

“Until now we only had crude models of what it looked like,” Sereno said. “We now have a complete map or surface representation of the cerebellum, much like cities, counties, and states.”

Puzzle pieces

Previous research discovered that while there were many similarities between the cortex and the cerebellum, there was one key difference. In the cerebral cortex, regions representing different parts of the body are arranged roughly like they are in the actual body: juxtaposed and orderly. But in the cerebellum, they were placed more randomly.

“You get a little chunk of the lip, next to a chunk of the shoulder or face, like jumbled puzzle pieces,” Sereno explained.

Those parts of the cerebellum are therefore set up to pull in and coordinate information from disparate parts of the body.

It is intriguing to think that there might be analogs of ‘”fractured somatotopy”‘ in the cognitive parts of the cerebellum that could help support highly complex, sophisticated cognitive functions, such as language or abstract reasoning, Sereno said.

“When you think of the cognition required to write a scientific paper or explain a concept, you have to pull in information from many different sources. And that’s just how the cerebellum is set up.”

Until now, the cerebellum was thought to be involved mainly in basic functions like movement, but its expansion over time and its new inputs from cortical areas involved in cognition suggest that it can also process advanced concepts like mathematical equations.

“Now that we have the first high resolution base map of the human cerebellum, there are many possibilities for researchers to start filling in what is certain to be a complex quilt of inputs, from many different parts of the cerebral cortex in more detail than ever before,” Sereno said.

For instance, there is some recent evidence that people who suffer cerebellum damage have difficulty processing emotion.

“The ‘little brain’ is quite the jack of all trades,” Sereno said. “Mapping the cerebellum will be an interesting new frontier for the next decade.”

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Young kids could spread COVID-19 as much as older children and adults, study suggests

A study from Ann & Robert H. Lurie Children’s Hospital of Chicago discovered that children younger than 5 years with mild to moderate COVID-19 have much higher levels of genetic material for the virus in the nose compared to older children and adults.

Findings, published in JAMA Pediatrics, point to the possibility that the youngest children transmit the virus as much as other age groups. The ability of younger children to spread COVID-19 may have been under-recognized given the rapid and sustained closure of schools and daycare during the pandemic.

“We found that children under 5 with COVID-19 have a higher viral load than older children and adults, which may suggest greater transmission, as we see with respiratory syncytial virus, also known as RSV,” says lead author Taylor Heald-Sargent, MD, PhD, pediatric infectious diseases specialist at Lurie Children’s and Assistant Professor of Pediatrics at Northwestern University Feinberg School of Medicine. “This has important public health implications, especially during discussions on the safety of reopening schools and daycare.”

Dr. Heald-Sargent and colleagues analyzed 145 cases of mild to moderate COVID-19 illness within the first week of symptom onset. They compared the viral load in three age groups — children younger than 5 years, children 5-17 years and adults 18-65 years.

“Our study was not designed to prove that younger children spread COVID-19 as much as adults, but it is a possibility,” says Dr. Heald-Sargent. “We need to take that into account in efforts to reduce transmission as we continue to learn more about this virus.”

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Materials provided by Ann & Robert H. Lurie Children’s Hospital of Chicago. Note: Content may be edited for style and length.

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Pregnant Black and Hispanic women five times more likely to be exposed to coronavirus

Black and Hispanic pregnant women in Philadelphia are five times as likely as white and Asian women to have been exposed to the novel coronavirus, according to a new study led by Scott Hensley, PhD, an associate professor of Microbiology in the Perelman School of Medicine at the University of Pennsylvania, and Karen Marie Puopolo, MD, PhD, an associate professor of Pediatrics and neonatologist at the Children’s Hospital of Philadelphia. The study was published today in Science Immunology.

“Pregnant women are fairly representative of community exposure, and these data provide more evidence, on top of what we already know with COVID-19, that health and socio-economic equity are inextricably linked,” Hensley said, “Hopefully, this will help lead to policies that address these inequities.”

The research team measured levels of SARS-CoV-2 antibodies to estimate rates of exposure to the novel coronavirus in pregnant women cared for at two Philadelphia hospitals. They found that, overall, 6.2 percent of these women possessed antibodies to the virus, but with significant variation across racial and ethnic groups — 9.7 percent in Black women, 10.4 percent in Hispanic/Latina women, 2.0 percent in White/Non-Hispanic women, and 0.9 percent in Asian women.

Researchers said these data can inform clinical practice and care for pregnant women during the coronavirus pandemic, and be used to better understand the prevalence of the virus in the community, and how socio-economic factors and inequities may affect its spread.

“Identifying the disparity in virus exposure will ideally help lead to the discovery of what is causing these differences, including factors rooted in systemic racism, and inform public health measures aimed at preventing further infections,” Puopolo said.

As of June 2020 — the time period encompassed in this study — there were 23,160 confirmed cases of COVID-19 in the city of Philadelphia, which has a population size of nearly 1.6 million people. This suggests an infection rate of approximately 1.4 percent, which is more than 4 times lower than the estimates based on the research team’s serological data.

Researchers analyzed 1,293 women who gave birth between April and June at Pennsylvania Hospital and the Hospital of the University of Pennsylvania, which combined represent 50 percent of live births during that time in Philadelphia. The research team’s serological test utilized a SARS-CoV-2 spike protein receptor binding domain antigen and a modified ELISA protocol. Researchers used samples stored at the Penn Medicine Biobank collected from 834 people prior to the pandemic and 31 people who recovered from known Covid-19 infections to test the efficacy of their antibody test. The researchers also tested samples from 140 pregnant women collected before the pandemic. Based on these data, the overall false positive rate is ~1.0 percent in the serological assay used for this study.

The researchers caution that the clinical meaning of the detected antibody remains unknown. Additionally, estimates of virus prevalence need to be interpreted carefully until studies directly comparing pregnant women and the general population are completed.

Additional authors from Penn and CHOP include Dustin D. Flannery, Sigrid Gouma, Miren B. Dhudasia, Sagori Mukhopadhyay, Madeline R. Pfeifer, Emily C. Woodford, Jeffrey S. Gerber, Claudia P. Arevalo, Marcus J. Bolton, Madison E. Weirick, Eileen C. Goodwin, Elizabeth M. Anderson, Allison R. Greenplate, Justin Kim, Nicholas Han, Ajinkya Pattekar, Jeanette Dougherty, Oliva Kuthuru, Divij Mathew, Amy E. Baxter, Laura A. Vella, JoEllen Weaver, Anurag Verma, Rita Leite, Jeffrey S. Morris, Daniel J. Rader, Michal A. Elovitz, and E. John Wherry.

This work was supported by institutional funds from the University of Pennsylvania (AI082630) and National Institutes of Health grants (UL1TR001878). The study was also generously supported by Jeffrey Lurie, owner of the Philadelphia Eagles, and Philadelphia 76ers star player Joel Embiid, and co-managing partners Josh Harris and David Blitzer. E.J.W. is supported by the Parker Institute for Cancer Immunotherapy, which supports the cancer immunology program at Penn.

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Researchers discover ‘Marie Kondo’ protein which aids in organizing fruit fly embryos

Researchers at the University of Colorado School of Medicine have discovered a protein in fruit fly embryos, dubbed Marie Kondo, that destroys maternal proteins. Much like namesake, author and clutter consultant Marie Kondo, this gene removes unnecessary molecules, keeping embryos organized.

Fertilized egg cells are loaded with maternal molecules that control the earliest steps of embryonic development. A critical stage of development is when the embryo destroys these inherited molecules and begins to make its own. These molecules include proteins and messenger RNAs (which encode instructions for making proteins). Existing research had identified how messenger RNAs are destroyed, but how maternal proteins are discarded, however, has been unknown.

According to the study, published in the journal eLife, researchers discovered the presence of the Marie Kondo protein by screening ~150 possible enzymes using a trick where destruction of maternal proteins could be seen with fluorescent microscopy. After months of work, they identified the enzyme and gave it the name “Marie Kondo.”

“Ordinarily, when we talk about getting rid of maternal gene products, we tend to focus on mRNA, or the coded information for making a protein,” says Olivia Rissland, assistant professor of biochemistry and molecular genetics at the University of Colorado School of Medicine and study co-author. “However, we don’t often talk about destruction of the proteins themselves. One implication of our study is that, during early stages of development, destruction of maternal proteins might be more tightly controlled than we had thought.”

Rissland says this discovery opens the door to more research into embryonic protein destruction. “The reason why we started looking at these proteins is because they control RNA. Now, we want to see what other proteins are destroyed and how protein destruction affects early development, not just in fruit flies, but in other animals too.”

Further information: https://elifesciences.org/digests/53889/an-enzyme-that-sparks-joy

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Materials provided by University of Colorado Anschutz Medical Campus. Original written by Kelsea Pieters. Note: Content may be edited for style and length.

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