Tuesday, September 07, 2021

 

Babies wanted: Males need not apply


Japanese scientists make sperm from mouse pluripotent stem cells that lead to healthy, fertile offspring

Peer-Reviewed Publication

KYOTO UNIVERSITY

Frozen sections of 52-day-old samples cultured by the in vitro sperm induction method were immunostained to confirm the formation of sperm. 

IMAGE: IMMUNOFLUORESCENCE ANALYSIS. FROZEN SECTIONS OF 52-DAY-OLD SAMPLES CULTURED BY THE IN VITRO SPERM INDUCTION METHOD WERE IMMUNOSTAINED TO CONFIRM THE FORMATION OF SPERM. RED INDICATES GSCLC MARKERS, GREEN INDICATES SPERM MARKERS, AND WHITE INDICATES NUCLEI view more 

CREDIT: PROVIDED BY TAKUYA SATO, AN ASSISTANT PROFESSOR AT YOKOHAMA CITY UNIVERSITY

For species that rely on sexual reproduction, including mice and men, offspring can only happen if sperm from the male fertilize eggs from the female. Even artificial fertilization techniques depend on donors for both of these cells. However, a new study led by ASHBi researchers shows that mouse pluripotent stem cells can differentiate into functional sperm. These sperm were successfully used to produce healthy, fertile offspring and provide the most comprehensive model yet for generating male germ cells in a test tube.

Pluripotent stem cells have allowed scientists to study how each and every cell in the body is formed. Brain cells, heart cells, and livers cells are just some examples of the cell types made from these stem cells and now being used in patients as experimental cell therapies. However, some cell types remain difficult to make from pluripotent stem cells, particularly sperm cells.

Among all cell types, germ cells are unique for many reasons. First, unlike all other cells, which carry 46 chromosomes, germs cells only have 23 chromosomes, with the egg having all its chromosomes from the mother, and sperm having all its chromosomes from the father.

Furthermore, they are the only cells that parents actually pass to their offspring, which makes them, according to ASHBi Director Mitinori Saitou, one of the authors of the study, “the driving force that sustains and evolves a species.”

Although more research is needed, scientists have made significant strides in producing sperm cells from pluripotent stem cells, at least for mouse. The process is generally broken into three stages that mimic natural development. First, the stem cells are differentiated into primordial germ cells, then into spermatogonia stem cells, which is when the male sex is determined, and finally sperm.

Spermatogonia stem cells are what allow the male to produce sperm for a lifetime, but this second stage has proven to be the most difficult to recreate in the laboratory.

Difficult, but not impossible. Mouse spermatogonia stem cells can be made, but inefficiently, which is why Dr. Yukiko Ishikura, another contributor to the study, concluded that optimizing the differentiation process was needed.

“The differentiation rate is about one week slower than in the mouse body and the contribution of the spermatogonia stem cells to spermatogenesis is low,” she said.

Beginning with mouse pluripotent stem cells, she and colleagues prepared primordial germ cells and examined over 10000 of them in 8 different conditions using what they call a “new reconstituted testis method”.

To validate the best conditions for manufacturing spermatogonia stem cells, they confirmed that the cells shared several properties with those in mouse testis, including the expression of key genes, epigenetics, and the transient upregulation of retrotransposons, which Saitou was especially unexpected.

“Retrotransposon control was recaptured. Retrotransposon regulation is a mechanism to control the effects of retrotransposons on key genes by randomly repeating their regulation,” he said.

The identical epigenetics was also crucial. While genes are made of DNA, their expressions depend on epigenetic factors like DNA methylation. Germ cells show distinct DNA methylation patterns during their development, patterns that are considered crucial for their ability to produce offspring.

To confirm the spermatogonia stem cells behaved just as those produced in the body, the researchers injected their laboratory made spermatogonia stem cells into mouse testes, where the cells were allowed to develop into spermatids. These spermatids were harvested and injected into eggs to grow embryos. The embryos were then used to impregnate mice, which went on to give birth to healthy offspring that were also fertile.

The findings provide the most comprehensive reconstitution of male germ cell development yet starting from pluripotent stem cells.

“This is the first study to reconstitute functional sperm from mouse pluripotent stem cells in a test tube. This open new possibilities for male germ cell differentiation,” said Saitou.

CAPTION

We show that we have succeeded in reproducing the entire differentiation process of male germ cells from mouse pluripotent stem cells in vitro.Top: scheme for male germ-cell development in mice. Bottom: scheme for the in vitro reconstitution of male germ-cell development by pluripotent stem cells. E, embryonic day; P, postnatal day.

CREDIT

Provided by Yukiko Ishikura, a postdoctoral researcher at ASHBi Kyoto University

 

ANTI SMOKING LOBBY

Legalization of cannabis threatens clean indoor air and public health


Most localities that allow onsite cannabis smoking lounges do not protect nonsmokers from the ill effects of secondhand cannabis smoke, researchers report in the American Journal of Preventive Medicine

Peer-Reviewed Publication

ELSEVIER

Ann Arbor, September 7, 2021  After years of progress on protections against secondhand tobacco smoke, multiple states and local governments now allow indoor smoking of cannabis at licensed cannabis businesses. A new study in the American Journal of Preventive Medicine, published by Elsevier, found that over 50 localities in the United States allow indoor smoking at these businesses, exposing customers and employees to secondhand cannabis smoke (SHCS).

“While many states maintain strong tobacco smoking and vaping bans to protect public health, our research reveals that some state and local laws exempt cannabis smoke from clean air laws and open the door to smoke-filled businesses, defeating decades of public health advances,” said first author Thomas L. Rotering, MPH, of the Center for Tobacco Control Research and Education, and the Philip R. Lee Institute for Health Policy Studies, University of California, San Francisco, San Francisco, CA, USA.

The researchers systematically searched legal databases, public reporting, government websites, and local laws that address cannabis smoking lounges. They found wide variation in how state and local governments address SHCS exposure in these businesses. All of the 11 states that have legalized adult-use cannabis as of June 2020 prohibit consumption in public places, but six states (Alaska, California, Colorado, Illinois, Massachusetts, and Michigan) allow onsite consumption in licensed cannabis businesses subject to local government approval. No state prohibits local governments from implementing more rigorous requirements. Massachusetts only allows onsite consumption through vaporization or other nonsmoking forms of consumption involving heat.

Although the only effective means of preventing the health problems associated with SHCS is to require a smoke-free environment, most local laws either do not address SHCS or use ineffective ventilation or engineering requirements. Of the 56 localities that permit onsite cannabis consumption businesses, only 9% require that indoors be smoke-free. Twenty-three percent of local governments provide for smoking in isolated rooms but only require that the smoke not drift to nonsmoking areas or that there be a smoke-free employee viewing area. Other common local legal requirements address onsite odor control, ventilation/filtration, and building location. Such requirements are often vague, and the investigators observe that they resemble the tobacco industry’s “accommodation” framework by allowing smoking inside and positioning ventilation or engineering controls as solving secondhand smoke.

“After decades of progress in clearing the indoor air of tobacco smoke, we are seeing it replaced with cannabis smoke using the same discredited arguments the tobacco industry used in its unsuccessful fight against tobacco smoke restrictions. We need to learn from the past and keep the air clean for all,” commented senior investigator Stanton A. Glantz, PhD, retired from the Center for Tobacco Control Research and Education, and the Philip R. Lee Institute for Health Policy Studies, University of California, San Francisco, San Francisco, CA, USA.

Some cannabis advocates argue that designating indoor spaces for renters, tourists, and people experiencing homelessness to smoke or vape is the only reasonable alternative to illegally consuming in public or exposing nonsmokers to SHCS. The investigators suggest that reasonable alternatives may include permitting outside, out-of-view cannabis use at retailers, or allowing only the use of non-inhalable modes of administration that do not pollute the air. Local officials could consider allowing multiunit housing or other places serving these groups to create outdoor, designated consumption smoking areas out of public view.

Policymakers should be made aware that ventilation and other engineering interventions cannot fully protect workers and patrons. “Health authorities and local leaders should educate policymakers on the science of secondhand smoke remediation and advocate for the same standards for secondhand cannabis smoking and vaping that apply to tobacco, particularly because other cannabis administration modes do not pollute the air,” said the authors in their paper. “Where onsite smoking or vaping is permitted, even measures such as truly separate indoor and outdoor smoking areas may reduce but not eliminate SHCS exposure to patrons, staff, and residents.”

 ABOLISH THE WAGE SYSTEM

Eliminating cash could benefit average U.S. families

New study shows tax cuts could offset giving up physical currency

Peer-Reviewed Publication

UNIVERSITY OF GEORGIA

Soon, $50 and $100 bills may be a thing of the past. That’s the future some economists are predicting—and want. 

But will people be better off without paper money? New research from the University of Georgia suggests they could be—as long as certain taxes are lowered too. 

“Our analysis of the costs and benefits of proposals to eliminate currency implies that doing away with big bills like $50s and $100s could benefit the average person, even though they like using cash,” said William D. Lastrapes, co-author on the study and the Bernard B. and Eugenia A. Ramsey Chair of Private Enterprise in the Terry College of Business. “Less cash means less tax evasion, so the government can reduce other taxes.”  

The case for getting rid of cash

Physical currency has an anonymity to it. The government doesn’t know you have it if you don’t report it and loses out on tax revenue from those “hidden” dollars. Cash transactions are also largely untraceable. Because of that, people paying for illegal goods or services and those who are simply trying to avoid paying taxes are more likely to do so in cash—and often in $50 and $100 bills. 

Published in the European Economic Review, the study uses macroeconomic modeling to predict how eliminating physical currency would affect individuals’ overall well-being from producing and consuming goods and services. 

The model builds in subtle tradeoffs that the economy faces when cash is used for transactions. When people use cash to hide their income from the IRS and reduce their taxes, for example, the government loses revenue to pay for valuable services or to pay down government debt. But at the same time, tax avoidance in effect lowers tax rates that consumers and businesses face, increasing productivity of labor and capital. That boosts the nation’s GDP and is good for the economy. 

When the model is matched to actual data on how people use cash and hide income from the IRS, it showed that people would be worse off if the Federal Reserve System, the U.S. central bank that issues cash, simply eliminated cash. The federal government would gain more revenue but overall production would fall because of the higher effective tax rates. And consumers would lose out on the privacy and convenience of cash.

But if the government also reduces statutory income tax rates—making the cash suppression policy revenue neutral—the model predicts that people overall will actually be better off without cash.

The model focused on the average American household. A more general version of the model shows that lower-income households, who are more likely to use cash for day-to-day transactions, will likely be more negatively affected by eliminating cash. But there are ways for the government to compensate for that.

“You’re going to have to provide them with some offset,” Lastrapes said. “What we’re suggesting is to take cash away but reduce taxes. It turns out this more than just compensates for not having cash, but it can actually make people better off.”

“My co-authors and I will be the first to admit that our paper does not provide the final word on cash-suppression policies and that more research is needed to be confident in what should be done. But our view is that models like ours that account for many of the unintended consequences of such policies and that carefully measure overall costs and benefits are essential for determining the right path.”

Transatlantic slave trade introduced novel pathogenic viruses in the Americas


Cutting-edge genetic techniques are shedding new light on how European colonists and their enslavement of African people may have contributed to epidemics among Indigenous communities in North America


Peer-Reviewed Publication

ELIFE

The transatlantic slave trade may have introduced new pathogenic viruses from Africa to North America that affected Indigenous communities, shows an analysis of ancient DNA published in eLife.  

The findings suggest that European colonists brought new viruses, including smallpox, measles and mumps, to North America, which caused outbreaks that led to major population declines in Native American communities. This discovery adds new information about the legacy of the transatlantic slave trade in North America.

“Multiple outbreaks in what is now Mexico killed millions of Indigenous people, Africans and some Europeans in the 16th century. But the exact pathogens responsible for some of these outbreaks is not currently known,” explains first author Axel Guzmán-Solís, a former student at the International Laboratory for Human Genome Research, Universidad Nacional Autónoma de México, Mexico, and who is now a PhD student at the Icahn School of Medicine at Mount Sinai, New York, US. “We wanted to understand what viruses were circulating in Mexico during this period.” 

To do this, Guzmán-Solís and the team extracted ancient viral DNA from the teeth of probable victims of these outbreaks buried at a Colonial-era hospital and chapel. They included victims who were Indigenous as well as those who were of African descent. The team then used this DNA to reconstruct the genomes of viruses present in those samples. This allowed them to identify ancient human hepatitis B virus and human B19 parvovirus from different individuals. By comparing these virus’ genomes to others, they found that the viruses likely originated in Africa.

“Our results suggest that the viruses were introduced to the Americas by colonists engaged in the slave trade,” says co-senior author Daniel Blanco-Melo, a former postdoctoral researcher at the Icahn School of Medicine at Mount Sinai in New York who is now an Assistant Professor at the Fred Hutchinson Cancer Research Center in Seattle, U.S. “The cruel, unsanitary and overcrowded conditions on the ships that transported millions of people across the Atlantic was a favourable setting for  the spread of infectious diseases. Therefore, this gruesome practice likely introduced new pathogens to Indigenous people who had no immunity to them.” He adds that the conditions that colonists forced Africans and Native Americans to live in during this time would have also promoted the spread of the diseases and may have fueled epidemics.

The study is not able to determine whether these individuals were infected in Africa, during the forced transport, or if the viruses occurred after the Africans’ arrival in North America. It is also unable to say whether the viruses caused the victims’ deaths. But it does provide evidence that these viruses, which can cause serious disease, were circulating in the affected populations.

“Our findings also suggest that multiple, newly introduced viruses were circulating at the same time, which may explain why the epidemics proved so deadly for Indigenous communities,” says co-senior author Maria Ávila-Arcos, Principal Investigator at the International Laboratory for Human Genome Research, Universidad Nacional Autónoma de México. “Together, this work demonstrates how the new field of paleovirology can help us learn more about the possible role of these and other pathogens in colonial epidemics and better understand the role of human actions in spreading them.”

###

Media contact 

Emily Packer, Media Relations Manager

eLife

e.packer@elifesciences.org

+44 (0)1223 855373

About eLife

eLife is a non-profit organisation created by funders and led by researchers. Our mission is to accelerate discovery by operating a platform for research communication that encourages and recognises the most responsible behaviours. We aim to publish work of the highest standards and importance in all areas of biology and medicine, including Genetics and Genomics, and Microbiology and Infectious Disease, while exploring creative new ways to improve how research is assessed and published. eLife receives financial support and strategic guidance from the Howard Hughes Medical Institute, the Knut and Alice Wallenberg Foundation, the Max Planck Society and Wellcome. Learn more at https://elifesciences.org/about.

To read the latest Genetics and Genomics research published in eLife, visit https://elifesciences.org/subjects/genetics-genomics.

And for the latest in Microbiology and Infectious Disease, see https://elifesciences.org/subjects/microbiology-infectious-disease.

Massage stones help scientists uncover role of prefrontal cortex in sensory perception


Peer-Reviewed Publication

UNIVERSITY OF TORONTO

Composite image for sensory perception study - U of Toronto 

IMAGE: UNIVERSITY OF TORONTO STUDY MEASURED PERCEPTION BASED ON A VARIETY OF VISUAL AND AURAL INPUTS. view more 

CREDIT: ISTOCK

TORONTO, ON – An image of a beautiful beach conjures up certain sensations – one can imagine the warmth of the sun as it caresses the skin, and the sound of the water as waves break on the shore. But how is it that the human brain produces these impressions even when an individual isn’t actually standing on a beach, basking in the sun’s rays and listening to the sound of the waves?

Scientists at the University of Toronto (U of T) exploring this mystery found that the brain’s prefrontal cortex – a region known primarily for its role in regulating behaviour, impulse inhibition, and cognitive flexibility – produces such general sensations based on information provided by various senses. The findings provide new insights into the poorly understood role of the prefrontal cortex in human perception.

Using a combination of photographs, sounds and even heated massage stones, the researchers investigated patterns of neural activity in the prefrontal cortex as well as the other regions of the brain known to be responsible for processing stimulation from all the senses and found significant similarities.

“Whether an individual was directly exposed to warmth, for example, or simply looking at a picture of a sunny scene, we saw the same pattern of neural activity in the prefrontal cortex,” said Dirk Bernhardt-Walther, professor in the Department of Psychology in the Faculty of Arts & Science at the U of T, and coauthor of a study published in the Journal of Neuroscience describing the findings. “The results suggest that the prefrontal cortex generalizes perceptual experiences that originate from different senses.”

To understand how the human brain processes the torrent of information from the environment, researchers often study the senses in isolation, with much of prior work focused on the visual system. Bernhardt-Walther says that while such work is illuminating and important, it is equally important to find out how the brain integrates information from the different senses, and how it uses the information in a task-directed manner. “Understanding the basics of these capabilities provides the foundation for research of disorders of perception,” he said.

Using functional magnetic resonance imaging (fMRI) technology to capture brain activity the researchers conducted two experiments with the same participants, based on knowing how regions of the brain respond differently depending on the intensity of stimulation.

In the first, the participants viewed a series of images of various scenes – including beaches, city streets, forests, and train stations – and were asked to judge if the scenes were warm or cold and noisy or quiet. Throughout, neural activity across several regions of the brain was tracked.

In the second experiment, participants were first handed a series of massage stones that were either heated to 45℃ or cooled to 9℃, and later exposed to sounds both quiet and noisy – such as birds, people, and waves at a beach.

“When we compared the patterns of activity in the prefrontal cortex, we could determine temperature both from the stone experiment and from the experiment with pictures as the neural activity patterns for temperature were so consistent between the two experiments,” said lead author of the study Yaelan Jung, who recently completed her PhD at U of T working with Bernhardt-Walther and is now a postdoctoral researcher at Emory University.

“We could successfully determine whether a participant was holding a warm or a cold stone from patterns of brain activity in the somatosensory cortex, which is the part of the brain that receives and processes sensory information from the entire body, while brain activity in the visual cortex told us if they were looking at an image of a warm or cold scene,” said Jung.

The patterns were so compatible that a decoder trained on prefrontal brain activity from the stone experiment was able to predict the temperature of a scene depicted in an image as it was viewed.

“It tells us about the relationship between someone feeling warmth by looking at a picture versus actually touching a warm object,” Jung said.

Similarly, the researchers could decode noisy versus quiet sounds from the brain’s auditory cortex and pictures of noisy versus quiet scenes from the visual cortex.

“Overall, the neural activity patterns in the prefrontal cortex produced by participants viewing the images were the same as those triggered by actual experience of temperature and noise level,” said Jung.

The researchers suggest the findings may open a new avenue to study how the brain manages to process and represent complex real-world attributes that span multiple senses, even without directly experiencing them.

“In understanding how the human brain integrates information from different senses into higher-level concepts, we may be able to pinpoint the causes of specific inabilities to recognize particular kinds of objects or concepts,” said Bernhardt-Walther.

“Our results might help people with limitations in one sensory modality to compensate with another and reach the same or very similar conceptual representations in their prefrontal cortex, which is essential for making decisions about their environment.”

Support for the research was provided by the Social Sciences and Humanities Research Council of Canada and the Natural Sciences and Engineering Research Council of Canada.

Scene categories for sensory perception study - U of Toronto (IMAGE)

UNIVERSITY OF TORONTO