Thursday, November 09, 2023

SEXISM IN SCIENCE

Women produce skin temperature data that are just as predictable as men


The finding shows that women should not be excluded from clinical studies because of variations in physiological signals due to menstrual cycles

Peer-Reviewed Publication

UNIVERSITY OF CALIFORNIA - SAN DIEGO

Picture of the OURA ring 

IMAGE: 

THE RESEARCHERS USED THE ŌURA RING, A SMART WEARABLE PRODUCED BY FINLAND-BASED COMPANY OURA RING TO TRACK SKIN TEMPERATURE IN THE STUDY.

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CREDIT: OURA RING



Women produce physiological data that is just as predictable as men, at least when it comes to skin temperature. This might seem like common sense, but variations in body signals due to menstrual cycles, such as temperature, were used as an excuse to keep women out of clinical studies for decades. 

The data for the finding was gathered from a wearable device to continuously monitor the skin temperature of 600 people, half female and half male, over six months.

The team found that there were more differences between any two individuals in the study, whether male or female, than between the sexes. The researchers found that skin temperature mostly varied as a function of time of day and whether the subject was awake or asleep, across male and female participants. 

Many women do not have large menstrual cycles, and neither cycles nor sex accounted for significant differences in variability of any group. It’s the first time that a study has continuously tracked human skin temperature over such a long period of time, to the best of the researchers’ knowledge. The team published their findings in the Nov. 1, 2023 issue of the journal Biology of Sex Differences. 

Despite guidelines from the National Institutes of Health that require studies to include females and minorities in clinical studies, women are still disproportionately excluded from research, particularly in drug trials. This is due in part to concerns that menstrual cycles would introduce too many variables in the data. 

And despite the harm to women that results from using medicines designed for men, including higher overdose and side effect rates, no one had yet looked at continuous physiology signals across large groups of men and women to see if women’s cycles really did make the data harder to analyze–until now. The study didn’t find any statistically significant differences, showing that concern is not warranted. 

The team included researchers from the San Diego Supercomputer Center, the Halicioglu Data Science Institute and the Jacobs School of Engineering at the University of California San Diego as well as the UC San Francisco Osher Center for Integrative Health. 

The UC San Diego team has been working with the UC San Francisco team, led by co-senior author Dr. Ashley E. Mason, since 2020 to gather wearable data from around the world and develop tools for detecting disease outbreaks. “If the point is that we can now use wearables to track health over big groups of people, then it makes no sense to exclude whole groups of people from the research” said Mason, a sleep clinician and principal investigator of the broader TemPredict project from which this study grew. 

The team chose to track skin temperature because it’s essentially a way to monitor the state of a person’s endocrine system, said Ben Smarr, the paper’s corresponding author and a professor in the Shu Chien Gene Lay Department of Bioengineering and the Halicioglu Data Science Institute at the University of California San Diego. Temperature has been tied to hormonal changes, daily rhythms and women’s health states by previous research. 

“In this study, the difference between two men is bigger than the difference between the average man and the average woman,” said Lauryn Keeler Bruce, the paper’s first author and a Ph.D. student in the Biomedical Informatics and Systems Biology program at UC San Diego. “In addition, the variability between men and women is not statistically significant.”

Smarr and colleagues used the ŌURA ring, a smart wearable produced by Finland-based company Oura Ring to track skin temperature in the study. The device can also track heart rate, activity, and provides sleep tracking. The ŌURA Ring has become a go-to research tool because it’s easy to use and delivers high-quality data. It has been used in recent publications about medical device adherence, predicting pregnancy outcomes, and tracking COVID-19. 

Through statistical analysis the team developed, they found, in women who cycled, a pattern of variation in nightly maximum skin temperature over a roughly 28-day period, consistent with menstrual cycles. This was not unexpected, as temperature monitoring has been used as a tool to track fertility across many cultures. If anything, the pattern made variations easier to predict for the subjects that experienced it. The data for these females was more predictable than for all the other subjects in the study. 

“This analysis confirms that ovarian rhythms do affect temperature,” the researchers write. “This analysis does not suggest that these rhythms make any given measurement more prone to error.” 

Researchers also pointed out that none of their female subjects constantly had a 28-day cycle. “No one was a textbook example,” Keeler Bruce said.

Researchers hope that other teams will adopt their methodology. Being able to continuously monitor physiological signals, such as temperature, is crucial in capturing a more accurate picture of a person’s health, Smarr said. “In order to know what disturbs a pattern, you need to know what the pattern is in the first place,” he said. 

The team plans to examine data from pregnant people throughout pregnancy next. They also plan to examine the differences in activity patterns between male and female subjects. 

Funders include the  Medical Technology Enterprise Consortium (MTEC), the Start Small foundation, and Oura Health. 

Variability of temperature measurements recorded by a wearable device by biological sex 

https://doi.org/10.1186/s13293-023-00558-z

UC San Diego

Department of Biomedical Informatics: Lauryn Keeler Bruce

Shu Chien-Gene Lay Department of Bioengineering: Patrick Kasl and Benjamin L. Smarr 

Bioinformatics and Systems Biology: Severine Soltani 

Department of Electrical and Computer Engineering: Varun K. Viswanath

Halicioglu Data Science Institute: Iklay Altintas, Amaranath Gupta and Benjamin L. Smarr 

San Diego Supercomputer Center: Saubhasis Dasgupta, Iklay Altintas and Amaranath Gupta 

 

UC San Francisco Osher Center for Integrative Health: Wendy Hartogensis, Frederick M. Hecht, Anoushka Chowdhary, Claudine Anglo, Keena Pandya and Ashley Mason  

City University New York, Baruch College: Stephan Dilchert





 

 

New research: Fivefold increase in the melting of Greenland's glaciers over the last 20 years

In the largest survey of its kind ever conducted researchers from the University of Copenhagen firmly establish that Greenland’s glaciers are melting at an unprecedented pace.

Peer-Reviewed Publication

UNIVERSITY OF COPENHAGEN - FACULTY OF SCIENCE

The Ujaraannaq valley 1936 

IMAGE: 

GLACIER IN THE UJARAANNAQ VALLEY IN WEST GREENLAND TAKEN FROM A SEAPLANE IN 1936

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CREDIT: (CREDIT: THE AGENCY FOR DATA SUPPLY AND INFRASTRUCTURE)

New research: Fivefold increase in the melting of Greenland's glaciers over the last 20 years

In the largest survey of its kind ever conducted, using both satellite imagery and old aerial photos from the Danish National Archives, researchers from the University of Copenhagen firmly establish that Greenland’s glaciers are melting at an unprecedented pace. Melting has increased fivefold in the past 20 years. The study eliminates any lingering doubts about the impact of climate change on Greenland's more than 20,000 glaciers.

Based on the most comprehensive monitoring of Greenland’s glaciers to date, Danish researchers have been able to cast aside any doubt regarding the impact of climate change on the planet.

Their new results document that, compared to the 80s and 90s, when glaciers shrank by an average of about five meters a year, melting has increased fivefold during the past 20 years, so that today, 25 meters per year are lost.

The new study shows the response of Greenland’s glaciers to climate change over a 130-year period. The past two decades stand out in particular, as melting during this period increased even more dramatically.

The study has been published today in the scientific journal Nature Climate Change. [link] https://www.nature.com/articles/s41558-023-01855-6

A number of studies in recent years have shown that Greenland's largest glaciers are under massive pressure due to climatic changes and rising temperatures. However, doubts remained about the extent of the melting glaciers, of which there are approx. 22,000 in Greenland, partly due to inadequate measurement methods. But any doubts that may have existed before have now been dispelled by the Danish researchers.

"In this article, we make it clear that Greenland's glaciers are all melting, and that things have moved exceptionally fast over the past 20 years. There is no doubt about the extent anymore and actually no reason to investigate the claim further," says Assistant Professor Anders Bjørk from the Department of Geosciences and Natural Resource Management. 

200,000 aerial photos from the Danish National Archives

According to the researcher, previous doubts were warranted to a certain extent. Indeed, the possibilities of investigating and documenting the extent to which glaciers melted away over extended periods of time were limited prior to the era of satellite imagery.

For example, only one of Greenland’s approximately 22,000 glaciers was continuously monitored using so-called mass balance measurements, which began in the mid-1990s. At the same time, there were areas of Greenland covered by glacier that seemed unaffected by rising temperatures just a few years back.

"Previously, we saw areas in northern Greenland, for example, that were lagging behind and melting less compared to the hardest hit glaciers. This generated a bit of doubt about how serious things were in these areas. At the same time, no one before us had ever shed light on such a long period of time, which precipitated doubts as well. But now, the picture is conclusive: The melting of all glaciers is in full swing, there is no longer any doubt," says Anders Bjørk.

To gain a full overview, the researchers closely studied 1,000 of Greenland's glaciers, a representative amount for the entire country. They tracked the melting of glaciers over the past 130 years using satellite images and 200,000 old aerial photos from the Danish National Archives, which had previously been used to make maps.

"Slightly more than 1,000 glaciers is an enormous number to study, but we did so because we simply wanted to be absolutely certain to get a comprehensive picture of developments over the last 130 years," says Anders Bjørk.

Sea level rise and lack of water

While Anders Bjørk says that there is no longer much reason to look into whether glaciers are melting or not, the development still needs to be closely monitored. Over the past twenty years, melting glaciers have contributed to about 21% of observed sea level rise.

"Of course, we’ll be keeping a close eye on developments. We’re in a new era where glaciers are generally in retreat, with major consequences for sea levels that will rise faster and faster," he says.

Paradoxically, the melting of glaciers in Greenland will lead to a lack of water. Glaciers will reach a point at which they become so small that meltwater rivers will be diminished or disappear altogether. Among other things, this means that Greenland’s ecosystems will change and that renewable energy will face unforeseen hurdles:

"Today, there is already a very real problem in Greenland that the sites where hydroelectric power plants were built 15-20 years ago, based upon the melt from smaller glaciers, do not get enough water because the ice is gone and not being formed again," says the researcher.

As a researcher and private person, what do you think about the extent of the melt that your study presents?

"I think it's quite disturbing. Because we’re well aware of where this is headed in the future. Temperatures will continue to rise and glaciers will melt faster than they do now," says Anders Bjørk, adding:

"But our study also shows that glaciers respond to climate change very quickly, which is in itself positive because it tells us that it’s not too late to minimise warming. Everything that we can do to reduce CO2 emissions now will result in slower sea level rise in the future."

About the study

  • In combination with satellite observations, the researchers used an untapped archive of aerial photos to document the development of more than 1,000 land-terminating glaciers in Greenland.
  • The researchers' observations cover all of Greenland's major regions over a 130-year period and, for the first time ever, make it possible to document the extent of glacial retreat during the 21’ century, throughout Greenland, within the 130-year time scale.
  • Over thirteen decades of observation, scientists have observed a significant and widespread retreat among Greenland's glaciers.
  • The pace at which glaciers have retreated over the past two decades has accelerated dramatically.
  • Furthermore, despite the wide range of climate zones and glacier characteristics across Greenland, scientists find that this latest acceleration in retreat is ubiquitous and includes Earth's northernmost glaciers.
  • Together, these findings indicate that the rate of retreat observed in the twenty-first century is exceptional for Greenland when viewed in a century-long context.
  • The study was conducted by a group of researchers from the University of Copenhagen and GEUS together with American colleagues.
  • The study has been published in the scientific journal Nature Climate Change.

  

The open Heinkel seaplane made for the mapping expeditions.

CAPTION

The open Heinkel seaplane over the Stauning Alps in East Greenland, 1933.

CREDIT

P20 – (Credit: The Agency for Data Supply and Infrastructure)

 

Vigorous exercise, rigorous science: What scientists learned from firefighters in training


Analysis of body fluids yields clue about respiratory infections

Peer-Reviewed Publication

DOE/PACIFIC NORTHWEST NATIONAL LABORATORY




The 11 young firefighters went through a rigorous training exercise, carrying up to 40 pounds of gear over hilly terrain during a 45-minute training exercise in the California sun. Gloves, helmets, flashlights, goggles, and more weighted them down as they sprinted through the countryside wearing fire-resistant clothing to show they were ready to serve as wildland firefighters.

 

When the training was over, they immediately went to the medical tent—not to rest and recover but to give samples of their blood, saliva, and urine for analysis by a team of scientists equipped with needles, test tubes, cold packs, and the gear of their own trade.

 

Then, the scientists from the Department of Energy’s Pacific Northwest National Laboratory (PNNL) analyzed more than 4,700 molecules—proteins, lipids, and metabolites—from each of the firefighters, looking to understand what happens when the body undergoes intense physical exercise. Measuring and interpreting the data from thousands of such measurements is a specialty of PNNL scientists who explore issues related to climate science and human health by analyzing millions of sensitive measurements using mass spectrometry each year.

 

For this study, the intent was to increase safety for first responders and others.

 

“Heat stress can be life threatening,” said Kristin Burnum-Johnson, a corresponding author of the study. “We wanted to take an in-depth look at what’s happening in the body and see if we’re able to detect danger from exhaustion in its earliest stages. Perhaps we can reduce the risk of strenuous exercise for first responders, athletes, and members of the military.”

 

As expected, the team detected hundreds of molecular changes in the firefighters. The differences before and after exercise underscored the body’s efforts at tissue damage and repair, maintenance of fluid balance, efforts to keep up with increased energy and oxygen demand, and the body’s attempts to repair and regenerate its proteins and other important substances.

 

But in the saliva, the team found some unexpected results. There was a change in the microbial mix of the mouth—the oral microbiome—showing that the body was increasingly on the lookout for bacterial invaders. Scientists also saw a decrease in signaling molecules important for inflammation and for fighting off viral infections.

 

A decrease in inflammation makes sense for people exercising vigorously; less inflammation allows people to breathe in air more quickly, meeting the body’s eager demand for more oxygen. Having fewer inflammatory signals in the respiratory system helps the body improve respiration and blood flow.

 

Less inflammation, better breathing

But less inflammation leaves the body more vulnerable to viral respiratory infection—which is exactly what other scientists have noted in elite athletes and others who exercise vigorously. Some studies have shown that a person is up to twice as likely to come down with a viral respiratory infection in the days after an especially energetic workout.

 

“People who are very fit might be more prone to viral respiratory infection immediately after vigorous exercise. Having less inflammatory activity to fight off an infection could be one cause,” said Ernesto Nakayasu, a corresponding author of the paper. He notes that the work provides a molecular basis for what clinicians have noticed in their patients who do strenuous workouts.

 

The team hopes that the findings will help explain why come people are more vulnerable to respiratory infection after a workout.

 

The research was published Oct. 18 in Military Medical Research.

 

In addition to Nakayasu and Burnum-Johnson, PNNL authors included Marina A. Gritsenko, Young-Mo Kim, Jennifer E. Kyle, Kelly G. Stratton, Carrie D. Nicora, Nathalie Munoz, Yuqian Gao, Karl K. Weitz, Vanessa L. Paurus, Kent J. Bloodsworth, Kelsey A. Allen, Lisa M. Bramer, Fernando Montes, Kathleen A. Clark, Grant Tietje, and Justin Teeguarden.

 

The work was funded by PNNL. Some of the mass spectrometry measurements were done at the Environmental Molecular Sciences Laboratory, a Department of Energy Office of Science user facility at PNNL.

 

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Incheon National University researchers push the limits of gas sensing technology


They propose an innovative approach for creating organic–inorganic hybrid gas sensors which achieve impressive durability, selectivity, and sensitivity


Peer-Reviewed Publication

INCHEON NATIONAL UNIVERSITY

Progress in gas sensing technology will help keep industrial workplaces safe 

IMAGE: 

IN AN INDUSTRIAL SETTING, THE CONCENTRATION OF HARMFUL GASES SHOULD BE CONSTANTLY MONITORED TO PREVENT HEALTH ISSUES AMONG WORKERS. THANKS TO RECENT ADVANCES IN ORGANIC SEMICONDUCTOR-BASED GAS SENSORS, GAS SENSING DEVICES COULD BECOME CHEAPER, SMALLER, POWERFUL, AND DURABLE.

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CREDIT: IMAGE CREDIT: BRIAN BOUCHERON FROM FLICKR HTTPS://WWW.FLICKR.COM/PHOTOS/88138723@N00/1207094703





The world has become increasingly industrialized over the past few centuries, bringing all sorts of technology and conveniences to the masses. However, workers in industrial environments are often at the risk of exposure to many dangerous gases, such as nitrogen dioxide (NO2). Inhaling this gas can lead to serious respiratory diseases like asthma and bronchitis, and severely compromise the health of industrial workers. Constant monitoring of NOlevels is thus needed to ensure a safe workplace.

To help with this, many types of selective gas sensors have been developed using different organic and inorganic materials. Some of them, such as gas chromatography sensors or electrochemical gas sensors, are highly sophisticated, yet expensive and bulky. On the other hand, resistive and capacitive sensors based on semiconductors seem to be a promising alternative, with organic semiconductor (OSC) gas sensors representing a low-cost and flexible option. Nonetheless, these gas sensors still face some performance issues, including low sensitivity and poor stability for sensor applications.

Against this backdrop, a team of researchers from Korea, led by Professor Yeong Don Park from the Department of Energy and Chemical Engineering at Incheon National University, set out to find innovative strategies to take OSC NO2 sensor technology to the next level. Their study was made available online on August 15, 2023, and published in Volume 473 of the Chemical Engineering Journal on October 1, 2023. It was carried out in collaboration with researchers from Jeonbuk National University, including Professor Min Kim.

To this end, the team proposed a hybrid organic–inorganic gas sensor design based on the combination of a conductive organic polymer and perovskite nanocrystals. They incorporated a CsPbBr3 perovskite into a conductive polymer matrix to enhance its gas sensing performance while maintaining sensing speed. They further modified the surface of the perovskite nanocrystals with zwitterionic polymer ligands. Once hydrated, these ligands greatly improved the affinity of the sensor for NO2 gas molecules, thus resulting in improved absorption. 

Further experiments revealed that the proposed design outperformed conventional sensors in terms of chemical sensitivity to NO2. Moreover, their system was highly resistant to oxidation, thanks to the protective action of the perovskite nanocrystals. Thus, it could withstand storage in ambient conditions for several weeks, showcasing impressive durability and higher potential for long-term installation. “Our findings suggest a new approach for the development and design of gas sensors based on various material composites to achieve both superior sensitivity and selectivity,” highlights Prof. Park, while discussing the results.

Given that OSCs can be designed to be flexible, lightweight, and relatively inexpensive when mass produced, they could pave the way to the widespread adoption of gas sensors in various contexts. “Beyond specific settings like industrial sites, OSC gas sensors could enable individuals to readily access information about air pollution levels through commonplace devices like smartwatches,” explains Prof. Park. He further adds, “Moreover, these sensors have the potential to advance diagnostic technology by facilitating the early detection of medical conditions. Therefore, it has potential not only for industrial safety but also in the realms of food safety, chemical substance monitoring, and medical diagnosis.

Here’s hoping that gas sensing technologies continue to evolve so that harmful compounds never go unnoticed!

 

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Reference

DOI: https://doi.org/10.1016/j.cej.2023.145482  

Authors: Duho Jang1, Haedam Jin2, Min Kim3,*, and Yeong Don Park1,*

Affiliations:        

1Department of Energy and Chemical Engineering, Incheon National University

2Graduate School of Integrated Energy-AI, Jeonbuk National University

3School of Chemical Engineering, Clean Energy Research Center, Jeonbuk National University

 

*Corresponding authors’ emails: minkim@jbnu.ac.kr (M. Kim); ydpark@inu.ac.kr (Y. Don Park)

 

About Incheon National University

Incheon National University (INU) is a comprehensive, student-focused university. It was founded in 1979 and given university status in 1988. One of the largest universities in South Korea, it houses nearly 14,000 students and 500 faculty members. In 2010, INU merged with Incheon City College to expand capacity and open more curricula. With its commitment to academic excellence and an unrelenting devotion to innovative research, INU offers its students real-world internship experiences. INU not only focuses on studying and learning but also strives to provide a supportive environment for students to follow their passion, grow, and, as their slogan says, be INspired.

Website: http://www.inu.ac.kr/mbshome/mbs/inuengl/index.html

 

About the authors

Professor Yeong Don Park’s research focuses on the fabrication and characterization of conductive polymer-based devices, whereas Professor Min Kim conducts research mainly on the gas adsorption properties of perovskites. By merging these two distinct research fields, one involving organic materials and the other inorganic ones, the authors were able to achieve excellent results by benefiting from the synergistic effects between them.

 EAT YOUR BROCCOLI

Early life exposure to broccoli sprouts protects against colitis in inflammatory bowel disease


Peer-Reviewed Publication

AMERICAN SOCIETY FOR MICROBIOLOGY




Washington, D.C.—High fiber diets, like those that include broccoli sprouts or other cruciferous vegetables, may reduce disease symptoms and improve quality of life in patients with inflammatory bowel disease (IBD), according to a study conducted in mice. The study was published in mSystems, a journal of the American Society for Microbiology.

In the study, the investigators used a popular interleukin-10-knockout (IL-10-KO) mouse model of Crohn’s to investigate the interactions between mice and their immune systems, as well as the broccoli sprout diet, microbes within the Crohn’s-afflicted gut, and how those microbes would use an inactive compound in the broccoli sprouts to make an anti-inflammatory compound in the gut. They also wanted to determine if, and by how much, a diet containing broccoli sprouts alleviates Crohn’s symptoms, given the anti-inflammatory metabolites innately present in the sprouts.

The researchers used 4 groups of IL-10-KO mice in the study. In the first round, they had younger mice enrolled at 4 weeks of age who ate their standard mouse chow the whole time, as well as mice who ate the mouse chow with raw broccoli sprouts mixed in. In the second round, they had the same 2 diet groups, but mice were enrolled at 7 weeks of age. The researchers were particularly interested in understanding the development of IBDs in early life, which is why they studied the Crohn’s mouse models at the juvenile stage (4-6 weeks old) and at the adolescence stage (7-9 weeks old) with hopes to better understand how host-diet-microbial community interactions and disease severity differ by age. 

The mice were fed for 7 days to acclimate to their respective diets before the researchers triggered symptoms, and the mice stayed on their diets for the following 2 weeks while the disease progressed. To trigger symptoms, new healthy mice that host more microbes were added to the cage. Since the IL-10-KO mice in the study can’t produce IL-10, their immune systems have trouble tolerating gut microbiota, and the new microbes in the cage triggered colitis and Crohn’s symptoms. For the next 15-16 days after infection, the researchers regularly weighed the mice and collected fecal samples to assess for signs of colitis development.

At the end of the study, the researchers examined the gut tissues of the euthanized mice and microbial communities present throughout their intestines, as well as the presence of certain markers of inflammation and broccoli metabolites in the blood. The researchers wanted to know what types of microbes were living in particular parts of the gut. In other words, they wanted to understand how the broccoli sprout diet affected microbial biogeography in the Crohn’s models, since they cannot study this in humans. 

DNA was extracted from the intestinal tissue samples collected from the mice and sent for sequencing to identify the bacteria present. Once the sequencing data was returned, the researchers used bioinformatics software and human ingenuity to study the gut microbial ecology of our mouse models.

“We found many exciting results from this study. First, we show that the mice that ate the broccoli sprout diet had a greater concentration of an anti-inflammatory metabolite called sulforaphane in their blood. Even though our mice were immunocompromised and had colitis, this increase in sulforaphane protected them from severe disease symptoms like weight loss, fecal blood and diarrhea,” said Lola Holcomb, lead author and a Ph.D. Candidate in the Graduate School of Biomedical Sciences and Engineering at the University of Maine. Lola is a member of a lab led by Suzanne Ishaq, Ph.D., a corresponding study author and assistant professor of animal and veterinary sciences at the University of Maine, School of Food and Agriculture, Orono, Maine.

Interestingly, the researchers found that the younger group of mice, the juveniles, responded better to the broccoli sprout diet than their adolescent counterparts did. The younger mice had milder disease symptoms and richer gut microbial communities. Furthermore, the younger mice showed stronger bacterial community similarity to each other (aka, stronger beta-diversity), and stronger adherence to location-specific community composition throughout different parts of the gut. 

“Simply put, we found that of the 4 groups we studied, the younger mice fed a broccoli sprout diet had the mildest disease symptoms and the most robust gut microbiota,” Holcomb said.

The researchers say that broccoli sprouts, which are easily grown and found in grocery stores, could be used as a treatment strategy for patients with IBD.
 

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The American Society for Microbiology is one of the largest professional societies dedicated to the life sciences and is composed of 36,000 scientists and health practitioners. ASM's mission is to promote and advance the microbial sciences.

ASM advances the microbial sciences through conferences, publications, certifications, educational opportunities and advocacy efforts. It enhances laboratory capacity around the globe through training and resources. It provides a network for scientists in academia, industry and clinical settings. Additionally, ASM promotes a deeper understanding of the microbial sciences to diverse audiences.

 

18 organizations, 246 scientists and scholars send letter to new director of NIH, urging shift away from animal use in medical research


Business Announcement

PHYSICIANS COMMITTEE FOR RESPONSIBLE MEDICINE




WASHINGTON, D.C.—A group of scientists, physicians, ethicists, and advocates sent a letter this Wednesday to the newly confirmed director of the National Institutes of Health, Dr. Monica Bertagnolli, urging her to reduce the agency’s use of animals in medical research. Led by the Physicians Committee for Responsible Medicine and co-signed by 246 individuals and 18 organizations, including biotechnology companies, think tanks, and animal protection groups, the letter requests that Dr. Bertagnolli prioritizes funding for developing, validating, and using nonanimal human disease models. It also requests divestment from animal use in research areas where poorly predicted human outcomes have been demonstrated, such as vaccine development and liver toxicity.

The NIH is the largest funder of biomedical research in the world, overseeing a budget of nearly $50 billion   this fiscal year. Despite evidence that animal experiments are unreliable predictors of human physiology and disease states, they remain the presumed “gold standard” in basic and preclinical research by the NIH and others within the research community. This reliance on animals contributes to failures and wasteful spending in the drug development pipeline and puts clinical trial participants at risk by failing to capture unsafe or ineffective products. It also requires that untold numbers of dogs, cats, monkeys, mice, rats, and other animals be bred and used in painful and deadly procedures—estimated to be greater than 100 million per year in the U.S.

The multistakeholder letter urges Dr. Bertagnolli to provide a clear vision that prioritizes the development and use of nonanimal, human-specific research approaches. These models can account for complex and diverse human risk factors in ways that cannot be done with animals, which could contribute to the advancement of personalized medicine and the reduction of health disparities. Rapidly advancing 3D in vitro technologies, like organoids and tissue chips, can reliably mimic human biology and clinical responses in many applications, often within shorter time frames and with lower resource and ethical burdens. The existing barriers to the broader development and use of these nonanimal technologies can be overcome with high-level strategies at the NIH.

Before serving as NIH director, Dr. Bertagnolli served as director of the NIH’s National Cancer Institute since October 2022. A physician-scientist by training, as well as a cancer survivor, Bertagnolli is an advocate for patient-centered research and a champion for addressing health disparities and improving clinical trial diversity.

“The NIH has a huge opportunity here that it can’t let go to waste. We are hopeful that under Dr. Bertagnolli’s leadership, the agency will steer away from the animal use that’s holding us back and toward a human-focused research portfolio,” says Catharine E. Krebs, PhD, medical research specialist with the Physicians Committee. “Scientists, doctors, industry innovators, and the public are here to support her in this goal, to benefit both patients and animals alike.”

For an interview with Dr. Krebs or a copy of the letter, please contact Reina Pohl at 202-527-7326 or rpohl@pcrm.org.

Founded in 1985, the Physicians Committee for Responsible Medicine is a nonprofit organization that promotes preventive medicine, conducts clinical research, and encourages higher standards for ethics and effectiveness in research.

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First live birth of a chimeric monkey using embryonic stem cell lines



Peer-Reviewed Publication

CELL PRESS

Images showing the green fluorescence signals in different body parts of the live-birth chimeric monkey at the age of 3 days 

IMAGE: 

IMAGES SHOWING THE GREEN FLUORESCENCE SIGNALS IN DIFFERENT BODY PARTS OF THE LIVE-BIRTH CHIMERIC MONKEY AT THE AGE OF 3 DAYS

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CREDIT: CELL/CAO ET AL.




A team of researchers in China has reported for the first time the live birth of a monkey that contains a high proportion of cells derived from a monkey stem cell line. This “chimeric” monkey is composed of cells that originate from two genetically distinct embryos of the same species of monkey. This has previously been demonstrated in rats and mice but, until now, has not been possible in other species, including non-human primates. The details of the research are reported November 9 in the journal Cell.

“This is a long-sought goal in the field,” says senior author Zhen Liu of the Chinese Academy of Sciences (CAS). “This research not only has implications for understanding naive pluripotency in other primates, including humans, but it also has relevant practical implications for genetic engineering and species conservation. Specifically, this work could help us to generate more precise monkey models for studying neurological diseases as well as for other biomedicine studies.”

The monkeys used in the study were cynomolgus monkeys, also known as crab-eating or long-tailed macaques, a primate common in biomedical research. The investigators first established nine stem cell lines using cells removed from 7-day-old blastocyst embryos. They then placed the cell lines in culture to give them enhanced ability to differentiate into different cell types. They performed a number of different tests on the cells to confirm that they were pluripotent—having the ability to differentiate into all of the cell types needed to create a live animal. The stem cells were also labeled with green fluorescent protein so the researchers would be able to determine which tissues had grown out of the stem cells in any animals that developed and survived.

Ultimately, they selected a particular subset of stem cells to inject into early monkey morula embryos (embryos that are 4–5 days old). The embryos were implanted into female macaques, resulting in 12 pregnancies and six live births.

Analysis confirmed that one monkey that was born alive and one fetus that was miscarried were substantially chimeric, containing cells that grew out of the stem cells throughout their bodies. Both were male. The investigators used the green fluorescent protein label to determine which tissues contained cells derived from the injected stem cells. They also used gene sequencing and other tests to confirm the presence of stem-cell-derived tissue across different organs. The tissue types they tested that contained the stem-cell-derived cells included the brain, heart, kidney, liver, and gastrointestinal tract. In the live monkey, the contribution of the stem cells in the different tissue types ranged from 21% to 92%, with an average of 67% across the 26 different types of tissue that were tested. The numbers were lower in the monkey fetus.

In both animals, they also confirmed the presence of stem-cell-derived cells in the testes and in cells that eventually develop into sperm cells.

“In this study, we have provided strong evidence that naive monkey pluripotent stem cells possess the capability of differentiating in vivo into all the various tissues composing a monkey body,” says co-corresponding author Miguel Esteban of BGI Research and CAS. “This study deepens our understanding of the developmental potential of pluripotent stem cells in primate species.”

“This work helps us to better understand naive pluripotency in primate cells,” adds co-corresponding author Qiang Sun of CAS. “In the future, we will try to increase the efficiency of this method for generating chimeric monkeys by optimizing the culture conditions for the stem cells, the cultures for the blastocysts where the stem cells are inserted, or both.”

The investigators also plan to further explore the mechanisms that underlie the survival of the embryos in the host animals, which they say will help improve the efficiency of chimera generation.

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This work was funded by the National Key Research and Development Program of China, the National Natural Science Foundation of China, the Shanghai Municipal Science and Technology Major Project, the Strategic Priority Research Program of the Chinese Academy of Sciences, the Basic Frontier Scientific Research Program of Chinese Academy of Sciences, the National Science and Technology Innovation 2030 Major Program, and Shenzhen Basic Research Project for Excellent Young Scholars.

Cell, Cao et al. “Live Birth of Chimeric Monkey with High Contribution from Embryonic Stem Cells” https://cell.com/cell/fulltext/S0092-8674(23)01087-5

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