Why go back to the Moon?

by Lucie AUBOURG

The United States is returning to the Moon 60 years after JFK's famous speech.

On September 12, 1962, then US president John F Kennedy informed the public of his plan to put a man on the Moon by the end of the decade.

It was the height of the Cold War and America needed a big victory to demonstrate its space superiority after the Soviet Union had launched the first satellite and put the first man in orbit.

"We choose to go to the Moon," Kennedy told 40,000 people at Rice University, "because that challenge is one that we are willing to accept, one we are unwilling to postpone, and one which we intend to win."

Sixty years on, the United States is about to launch the first mission of its return program to the Moon, Artemis. But why repeat what has already been done?

Criticism has risen in recent years, for example from Apollo 11 astronaut Michael Collins, and the Mars Society founder Robert Zubrin, who have long advocated for America to go directly to Mars.

But NASA argues re-conquering the Moon is a must before a trip to the Red Planet. Here's why.

Long space missions

NASA wants to develop a sustainable human presence on the Moon, with missions lasting several weeks –- compared to just a few days for Apollo.

The goal: to better understand how to prepare for a multi-year round trip to Mars.

In deep space, radiation is much more intense and poses a real threat to health.

Low Earth Orbit, where the International Space Station (ISS) operates, is partly shielded from radiation by the Earth's magnetic field, which isn't the case on the Moon.

"We choose to go to the Moon," Kennedy told 40,000 people at Rice University, "because 

that challenge is one that we are willing to accept, one we are unwilling to postpone, and

 one which we intend to win"

From the first Artemis mission, many experiments are planned to study the impact of this radiation on living organisms, and to assess the effectiveness of an anti-radiation vest.

What's more, while the ISS can often be resupplied, trips to the Moon—a thousand times further—are much more complex.

To avoid having to take everything with them, and to save costs, NASA wants to learn how to use the resources present on the surface.

In particular, water in the form of ice, which has been confirmed to exist on the lunar south pole, could be transformed into rocket fuel by cracking it into its separate hydrogen and oxygen atoms.

Testing new gear

NASA also wants to pilot on the Moon the technologies that will continue to evolve on Mars. First, new spacesuits for spacewalks.

Their design was entrusted to the company Axiom Space for the first mission which will land on the Moon, in 2025 at the earliest.

Other needs: vehicles —both pressurized and unpressurized—so that the astronauts can move around, as well as habitats.

Finally, for sustainable access to an energy source, NASA is working on the development of portable nuclear fission systems.

Solving any problems that arise will be much easier on the Moon, only a few days away, than on Mars, which can only be reached in at least several months.

ASA also wants to test on the Moon the technologies that will continue to evolve on Mars.

Establishing a waypoint

A major pillar of the Artemis program is the construction of a space station in orbit around the Moon, called Gateway, which will serve as a relay before the trip to Mars.

All the necessary equipment can be sent there in "multiple launches," before finally being joined by the crew to set off on the long voyage, Sean Fuller, responsible for the Gateway program, told AFP.

"Kind of like you're stopping at your gas station to make sure you get all the stuff, and then you're off on your way."

Maintaining leadership over China

Apart from Mars, another reason put forward by the Americans for settling on the Moon is to do so before the Chinese, who plan to send taikonauts by the year 2030.

China is the United States' main competition today as the once proud Russian space program has withered.

"We don't want China suddenly getting there and saying, "This is our exclusive territory,'" NASA boss Bill Nelson said in a recent interview.

For the sake of science

While the Apollo missions brought back to Earth nearly 400 kilograms of lunar rock, new samples will make it possible to further deepen our knowledge of this celestial object and its formation.

"The samples that we collected during the Apollo missions changed the way we view our solar system," astronaut Jessica Meir told AFP. "I think we can expect that from the Artemis program as well."

She expects further scientific and technological breakthroughs too, just like during the Apollo era.

To the Moon and beyond: NASA's Artemis program

© 2022 AFP

Growth of psychiatric mental health nurse practitioners helped offset drop in psychiatrists treating Medicare patients

Peer-Reviewed Publication

HARVARD T.H. CHAN SCHOOL OF PUBLIC HEALTH

Boston, MA—The mental health system is increasingly reliant on psychiatric mental health nurse practitioners (PMHNPs) to meet the psychiatric needs of Medicare patients, according to a new study led by researchers at Harvard T.H. Chan School of Public Health. 

“We were surprised by the degree to which PMHNPs are the de facto mental health prescribers in parts of the country,” said corresponding author Michael Barnett, associate professor of health policy and management at Harvard Chan School. “In the states where PMHNPs have no restrictions on prescribing medications, these providers account for 50% of all mental health prescriber visits in rural areas, which was much greater than we had anticipated.” 

The study will be published in the September 2022 issue of Health Affairs. 

Mental health access is a public health crisis that the COVID-19 pandemic has exacerbated. While demand for mental health treatment is soaring, the supply of psychiatrists accepting insurance is dropping, particularly in rural areas.  

To assess how the mental health workforce and patient population have changed over time, Barnett and his colleagues analyzed fee-for-service Medicare claims during 2011-2019. The team focused on the number of PMHNPs and psychiatrists billing Medicare, the volume of outpatient and psychiatric services by provider group, and how these numbers varied by rurality and scope-of-practice regulations, which can restrict whether a PMHNP is able to prescribe medications. 

The findings showed that PMHNPs provided nearly 1 in 3 mental health prescriber visits to Medicare patients nationally by 2019. The number of PMHNPs also increased 162% during 2011-2019, while psychiatrists billing Medicare dropped by 6%. During this period, without growth in the PMHNP workforce, there would have been a decline of nearly 30% in mental health specialist visits in Medicare. Instead, the drop was 12%.  

“This work puts the spotlight on PMHNPs as a critical part of the mental health workforce,” said Barnett. “This is so important because we desperately need new solutions to address the current mental health crisis in this country. Policy that targets the PMHNP workforce could be a key part of the national effort to expand mental health access.” 

Co-author Arno Cai is also from Harvard Chan School. 

This research was supported by the National Institute on Aging (K23 AG058806-01) and the National Institute of Mental Health (R01 MH112829-01) in the National Institutes of Health.  

“Trends In Mental Health Care Delivery By Psychiatrists And Nurse Practitioners In Medicare, 2011–19,” Arno Cai, Ateev Mehrotra, Hayley D. Germack, Alisa B. Busch, Haiden A. Huskamp, and Michael L. Barnett, Health Affairs, September 2022, doi: 10.1377/ hlthaff.2022.00289. 

Visit the Harvard Chan School website for the latest news, press releases, and multimedia offerings. 

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Harvard T.H. Chan School of Public Health brings together dedicated experts from many disciplines to educate new generations of global health leaders and produce powerful ideas that improve the lives and health of people everywhere. As a community of leading scientists, educators, and students, we work together to take innovative ideas from the laboratory to people’s lives—not only making scientific breakthroughs, but also working to change individual behaviors, public policies, and health care practices. Each year, more than 400 faculty members at Harvard Chan School teach 1,000-plus full-time students from around the world and train thousands more through online and executive education courses. Founded in 1913 as the Harvard-MIT School of Health Officers, the School is recognized as America’s oldest professional training program in public health. 

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JOURNAL

Health Affairs

DOI

10.1377/hlthaff.2022.00289 

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Trends In Mental Health Care Delivery By Psychiatrists And Nurse Practitioners In Medicare, 2011–19

ARTICLE PUBLICATION DATE

6-Sep-2022

OUR FRIENDLY FUNGUY

Can fungi help Texas’ grasses cope with climate change?

From humid east to arid west, Texas is a living lab for Rice study of range limits

Grant and Award Announcement

RICE UNIVERSITY

 

IMAGE: SKIDMORE COLLEGE STUDENT SAR LINDNER (LEFT) OBSERVES AS RICE UNIVERSITY GRADUATE STUDENT ALI CAMPBELL EXAMINES A GRASS STEM FOR SIGNS OF SYMBIOTIC FUNGI DURING A FIELD SAMPLING EXPEDITION NEAR HUNTSVILLE, TEXAS. view more 

CREDIT: JEFF FITLOW/RICE UNIVERSITY

HOUSTON – (Sept. 6, 2022) – As anyone who’s crossed Texas on Interstate 10 can tell you, the Lone Star State is where east meets west. For Rice University biologist Tom Miller, the sharp divide between East Texas’ humid piney woods and West Texas’ parched desert is also a living laboratory where he and his students can learn about boundaries that aren’t found on maps.

“That's one of the sharpest aridity gradients on the planet,” Miller said of the climatic shift from east to west Texas. “And it’s an important boundary for species. A lot of species that occur in eastern North America hit their westernmost limits in Texas.”

Miller, an associate professor of biosciences at Rice, and his research group study range limits, invisible biological dividing lines between where a species can survive and where it can’t. In a world of changing climate, those lines are moving, and Miller and his students want to study and understand how they are moving and why.

Miller’s team studies grasses and other species at eight field sites along a 580-mile stretch of I-10 from lush Lafayette, Louisiana, to sandy Sonora, Texas, about 170 miles west of San Antonio. Thanks to a grant from the National Science Foundation, they’ve begun a first-of-its-kind study to find out whether a strange, ancient marriage between native Texas grasses and their hidden fungal partners could position the plants to better withstand droughts that are expected to be more frequent and severe due to climate change.

“Range limits arise from stress,” Miller said. “As plants go from very wet to very dry places, their drought stress increases. We expect drought stress to be an important limit on how far west a lot of species can make it, particularly eastern species. Because the further west you go, the greater the drought stress.

“The unique thing about this study is that we're trying to understand the role that microbes and microbial symbionts play in determining the range limits of plants,” he said.

The grass species in the study are varieties that thrive in cooler months. Each hosts Epichloë endophytes, symbiotic fungi that live inside the plant. In exchange for living a protected life inside their hosts, the fungi supplies the plants with alkaloid chemicals that previous studies have shown both improve drought tolerance and discourage predation by sickening grass-eating animals.

In their experiments, Miller and his students remove the fungal partner from some grasses and leave it in others. At each field site, partnered and unpartnered plants are grown in plots near one another, and the difference between them reveals the effects of the fungus.

“We’ll plant at all of these places from Louisiana to West Texas, and we’ll compare how important that microbial effect is as the grasses go from east to west and their drought stress increases,” he said. “That's going to allow us to build models that will tell us what role the microbes play in generating range limits and possibly extending range limits.

“That is new,” Miller said. “To my knowledge, this will be the first study to do that.”

Global warming is already raising temperatures in Texas and a 2021 report from the Texas State Climatologist’s office predicts that the number of 100-degree days each summer will nearly double by 2036 compared to the average number of such days from 2001-2020.

Ranges of plants and animals will shift in response, and the wet-dry gradient that has defined Central Texas for centuries may shift as droughts become more frequent and more intense. One might easily imagine drought-tolerant and drought-intolerant plants marching right along with such a shift, followed by all the insects and animals that depend on them. But the real world is far more complex, Miller said. Even slight variations in average rainfall, soil moisture and many other factors can push the balance one way or the other.

“For plants, there’s also the question of whether they can shift to a new range,” he said. “Most rely on either the wind or animals to carry their seeds to new places, and climate change could impact both, making range shifts impossible for some plants.”

Better understanding the beneficial relationship between native Texas grasses and their microbial partners will unlock pieces of the range-shifting puzzle that today are hidden from ecologists, conservation biologists and others who track species ranges, Miller said.

“The ways that climate maps onto geography are already changing and will continue to change,” Miller said. “What do these microbial associations mean for how species will shift in response to climate change? Are microbes going to facilitate expansion into new habitats? Could they potentially inhibit expansion into other habitats?

“Microbial associations are a hidden layer in this large-scale biogeographic problem, and we want to unlock that layer and inform this bigger discussion about how plants and animals in Texas are going to respond to climate change,” Miller said.

-30-

CAPTION

From left to right, Rice University graduate student Ali Campbell opens a grass stem and collects a thin layer of tissue, which will be examined later under a microscope for the presence of symbiotic fungi.

CREDIT

Jeff Fitlow/Rice University

CAPTION

Rice University biosciences graduate student Joshua Fowler collects samples of grass species and their symbiotic microbial partners at a field site near Huntsville, Texas.

CREDIT

Jeff Fitlow/Rice University

Grant information:

“The geographic footprint of host-symbiont mutualism” | National Science Foundation | Division of Environmental Biology

https://www.nsf.gov/awardsearch/showAward?AWD_ID=2208857

VIDEO is available at:

https://youtu.be/dYuayCB6scE
DESCRIPTION: Rice University biologist Tom Miller’s research group studies range limits, invisible biological dividing lines between where species can survive and where they can’t. In a world of changing climate, those lines are moving, and Miller and his students are using Texas as a “living laboratory” to better understand those changes. Thanks to a grant from the National Science Foundation, they’re conducting a first-of-its-kind study at eight sites along a 580-mile stretch of I-10 from Lafayette, Louisiana, to Sonora, Texas. The goal is to find out whether a strange, ancient marriage between native Texas grasses and their hidden fungal partners could position the plants to better withstand droughts that are expected to be more frequent and severe due to climate change.

High-resolution IMAGES are available for download at:

https://news-network.rice.edu/news/files/2022/09/0906_GRASSES-268-lg.jpg
CAPTION: From left, students Joshua Fowler, Ali Campbell and Sar Lindner carry gear they will use at a field site near Huntsville, Texas, to collect samples of native grass species as well as symbiotic fungi that live inside the grass. (Photo by Jeff Fitlow/Rice University)

https://news-network.rice.edu/news/files/2022/09/0906_GRASSES-388-lg.jpg
CAPTION: Skidmore College student Sar Lindner (left) observes as Rice University graduate student Ali Campbell examines a grass stem for signs of symbiotic fungi during a field sampling expedition near Huntsville, Texas. (Photo by Jeff Fitlow/Rice University)

https://news-network.rice.edu/news/files/2022/09/0906_GRASSES-4p-lg.jpg
CAPTION: From left to right, Rice University graduate student Ali Campbell opens a grass stem and collects a thin layer of tissue, which will be examined later under a microscope for the presence of symbiotic fungi. (Photo by Jeff Fitlow/Rice University)

https://news-network.rice.edu/news/files/2022/09/0906_GRASSES-503-lg.jpg
CAPTION: Rice University biosciences graduate student Joshua Fowler collects samples of grass species and their symbiotic microbial partners at a field site near Huntsville, Texas. (Photo by Jeff Fitlow/Rice University)

This release can be found online at news.rice.edu.

Follow Rice News and Media Relations via Twitter @RiceUNews.

Located on a 300-acre forested campus in Houston, Rice University is consistently ranked among the nation’s top 20 universities by U.S. News & World Report. Rice has highly respected schools of Architecture, Business, Continuing Studies, Engineering, Humanities, Music, Natural Sciences and Social Sciences and is home to the Baker Institute for Public Policy. With 4,240 undergraduates and 3,972 graduate students, Rice’s undergraduate student-to-faculty ratio is just under 6-to-1. Its residential college system builds close-knit communities and lifelong friendships, just one reason why Rice is ranked No. 1 for lots of race/class interaction and No. 1 for quality of life by the Princeton Review. Rice is also rated as a best value among private universities by Kiplinger’s Personal Finance.

How changes in length of day change the brain and subsequent behavior

UC San Diego researchers illuminate the role of key neurons, which alter function in response to seasonal changes in light exposure

Peer-Reviewed Publication

UNIVERSITY OF CALIFORNIA - SAN DIEGO

 

IMAGE: IN THIS SCHEMATIC, SUNLIGHT CUES NEURONAL SIGNALS IN THE SUPRACHIASMATIC NUCLEUS, THE BRAIN’S MASTER CLOCK, WHICH IN TURN COORDINATES BIOLOGICAL CLOCKS REGULATING FUNCTIONS THROUGHOUT THE BODY, AND CONSEQUENTIAL BEHAVIORS. view more 

CREDIT: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

Seasonal changes in light — longer days in summer, shorter in winter — have long been associated with human behaviors, affecting everything from sleep and eating patterns to brain and hormonal activity. Seasonal affective disorder (SAD) is a prime example: A type of depression related to diminished exposure to natural sunlight, typically occurring during winter months and more often at higher latitudes when daylight hours are shortest.

Bright light therapy has proven an effective remedy for treating SAD, plus maladies such as non-seasonal major depression, postpartum depression and bipolar disorder, but how seasonal changes in day length and light exposure affect and alter the brain at the cellular and circuit levels has kept scientists largely in the dark.

In a new study, publishing September 2, 2022 in Science Advances, researchers at University of California San Diego School of Medicine used a mouse model to illuminate a process in which affected neurons switch expression of neurotransmitters in response to day length stimuli, triggering related behavioral changes. 

The work was led by senior study author Davide Dulcis, PhD, associate professor in the Department of Psychiatry at UC San Diego School of Medicine and a member of the Center for Circadian Biology at UC San Diego. 

Tucked within the hypothalamus of the human brain is a small structure called the suprachiasmatic nucleus (SCN), each consisting of approximately 20,000 neurons. (The average human brain contains roughly 86 billion neurons and another 85 billion non-neuronal cells.) 

The SCN is the body’s timekeeper, regulating most circadian rhythms — physical, mental and behavioral changes that follow a 24-hour cycle and affect everything from metabolism and body temperature to when hormones are released. The SCN operates based on input from specialized photosensitive cells in retina, which communicate changes in light and day length to our body.

In the new study, Dulcis and colleagues describe how SCN neurons coordinate with each other to adapt to different lengths of daylight, changing at cellular and network levels. Specifically, they found that in mice, whose brains function similarly to humans, the neurons changed in mix and in expression of key neurotransmitters that, in turn, altered brain activity and subsequent daily behaviors. 

Seasonal changes in light exposure have also been shown to alter the number of neurotransmitter-expressing neurons in the paraventricular nucleus (PVN), a region of the brain that plays essential roles in controlling stress, metabolism, growth, reproduction, immune and other autonomic functions. 

“The most impressive new finding in this study is that we discovered how to artificially manipulate the activity of specific SCN neurons and successfully induce dopamine expression within the hypothalamic PVN network,” said Dulcis. 

“We revealed novel molecular adaptations of the SCN-PVN network in response to day length in adjusting hypothalamic function and daily behavior,” added first author Alexandra Porcu, PhD, a member of Dulcis’ lab. “The multi-synaptic neurotransmitter switching we showed in this study might provide the anatomical/functional link mediating the seasonal changes in mood and the effects of light therapy.”  

The authors suggest their findings provide a novel mechanism explaining how the brain adapts to seasonal changes in light exposure. And because the adaptation occurs within neurons exclusively located in the SCN, the latter represents a promising target for new treatments for disorders associated with seasonal changes in light exposure.  

Co-authors include: Anna Nilsson, Sathwik Booreddy, Samuel A. Barnes and David K. Welsh, all at UC San Diego. 

# # #

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JOURNAL

Science Advances

DOI

10.1126/sciadv.abn9867 

Emergency departments not set up to meet basic care needs of frail older people

Absence of dignity and respect, clear timely communication, involvement in decision-making. Changes in clinical practice and service design needed to meet growing demand

Peer-Reviewed Publication

BMJ

Emergency departments in England don’t seem to be set up to meet the basic care needs of frail older patients, suggest the findings of a small qualitative study published online in the Emergency Medicine Journal.

Treatment with dignity and respect, clear and timely explanations of what’s happening and what’s wrong, and the opportunity to have a say in their care—all key tenets of patient-centred care—often seem to be missing, the feedback suggests.

Changes in clinical practice and service design are required to meet the needs of a significant and growing number of older people living with frailty, concludes a linked editorial.

Frailty refers to reduced capacity to recover from health issues, combined with a need for help with basic activities of daily living. It’s a consequence of cumulative physiological decline associated with ageing.

Relatively little is known, however, about the impact of frailty on older people’s experiences of, and preferences for, emergency care.

In a bid to find out, the researchers carried out in-depth interviews with 24 older people (75+) living with frailty and 16 of their carers with current or recent experience of emergency care in three separate hospital emergency departments in England between January and June 2019. 

The interview sample aimed to reflect frailty, age, sex, ethnicity, mental capacity, place of residence, mode of arrival (ambulance or independent), whether seen in ‘major’ or ‘minor’ emergency departments, and on different days of the week and different times of the day.

Over two-thirds (68%) were women; 43% were aged 75–84; and over half (57%) were aged over 85. Most were white British: 12 had frailty scores of 5 (mild); the rest had scores of 6-7 (moderate to severe).

A fall was the primary reason for emergency department attendance for 1 in 3; other common conditions included breathing difficulties, heart problems, stomach/back pain or confusion.

Feedback showed that the interviewees were very reluctant to be taken to an emergency department, often because of previous negative experiences, and fear they wouldn’t come out again, and they felt helpless/resigned when attendance couldn’t be avoided. 

Staff attitudes were, on the whole, seen as very caring and reassuring. But interviewees were less enthusiastic about their experiences of very basic care.

These included not having access to, and being helped to, eat or drink, which included several patients with diabetes; little assistance with toileting; and long uncomfortable waits on hard trolleys. 

A quarter of the interviewees said they had waited 12 or more hours in the emergency department before being admitted to a ward.

Interviewees felt that communication and involvement in decision-making could be improved, including involving next of kin, who were viewed as critical to supporting vulnerable older people during sometimes very protracted waits. 

And interviewees weren’t always clear whom they had seen or whom they needed to speak to if they had queries. Staff didn't always take time to speak slowly and clearly to ensure that information was received and understood either.

A calm, quiet environment also emerged as an important preference among the interviewees, with noisy busy departments proving particularly challenging for them.

This is a small study, involving patients/carers at just three sites, so may not be typical of  emergency departments throughout England, note the authors.

But they point out: “Our research suggests that frailty can result in a particular vulnerability in [emergency departments] if physical (environment, personal comfort, waiting) and emotional (sense of dignity, communication, involvement, family support) needs are not met.”

Emergency department care needs to be more ‘frailty friendly’, they say.

“While the [emergency department] environment and waiting times may be harder to change, healthcare professionals can help older people living with frailty by being mindful of their comfort, physical needs, the flow of information and the importance of patient/carer involvement. Indeed, in an environment where waiting times may be extending, the importance of a person centred environment becomes even greater.

“More broadly and given the challenges of more fundamental changes to the fabric of the [emergency department] and the pressures on this part of the healthcare system, policy makers and practitioners need to consider service development changes when responding to the needs of older people living with frailty requiring urgent and emergency care,” they conclude.

In a linked editorial, Mary Dawood, of Imperial College NHS Trust, London, and Rosa McNamara, of St Vincent’s University Hospital, Dublin, Ireland, point out that the number of over 60s is set to reach 1.4 billion by 2030 and 2.1 billion by 2050, while the number of over 80s is expected to quadruple to 395 million during the same period.

“Frailty in particular is an emerging and immediate global public health concern which has significant implications for clinical practice in emergency medicine,” they write.

The research findings poignantly show that “older people have the same desires and needs as younger people using the emergency department: to be treated with dignity, to be respected, to be listened to and to have regular communication with staff. 

“To our shame, these interviews have drawn into sharp focus just how disenfranchised and marginalised frail older people feel when using our services. Unlike younger fitter patients, they are less able or inclined to complain or voice dissatisfaction when their needs are not being met. 

“We urgently need to reflect on and rectify this, redesigning our services for all our patients, keeping in mind the needs of older people, although similar, are much more urgent and the ramifications of not getting it right, far greater.”

They conclude: Older people are not asking for special treatment or something that is unrealistic or undeliverable, they simply want to matter and that is what all our patients expect and hope for in our [emergency departments].”

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JOURNAL

Emergency Medicine Journal

DOI

10.1136/emermed-2022-212420 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Emergency care for older people living with frailty: patient and carer perspectives

ARTICLE PUBLICATION DATE

6-Sep-2022

Pioneering mathematical formula paves way for exciting advances in health, energy, and food industry

Diffusive movement through permeable material can be modelled exactly for first time

Peer-Reviewed Publication

UNIVERSITY OF BRISTOL

 

IMAGE: A GROUNDBREAKING NEW EQUATION HAS BEEN DEVELOPED TO MODEL DIFFUSIVE MOVEMENT THROUGH PERMEABLE MATERIAL EXACTLY FOR THE VERY FIRST TIME. view more 

CREDIT: UNIVERSITY OF BRISTOL

A groundbreaking mathematical equation has been discovered, which could transform medical procedures, natural gas extraction, and plastic packaging production in the future.

The new equation, developed by scientists at the University of Bristol, indicates that diffusive movement through permeable material can be modelled exactly for the very first time. It comes a century after world-leading physicists Albert Einstein and Marian von Smoluchowski derived the first diffusion equation and marks important progress in representing motion for a wide range of entities from microscopic particles and natural organisms to man-made devices.

Until now, scientists looking at particle motion through porous materials such as biological tissues, polymers, various rocks and sponges, have had to rely on approximations or incomplete perspectives.

The findings, published today in the journal Physical Review Research, provide a novel technique presenting exciting opportunities in a diverse range of settings including health, energy, and the food industry.

Lead author Toby Kay, who is completing a PhD in Engineering Mathematics, said: “This marks a fundamental step forward since Einstein and Smoluchowski’s studies on diffusion. It revolutionises the modelling of diffusing entities through complex media of all scales, from cellular components and geological compounds to environmental habitats.

“Previously, mathematical attempts to represent movement through environments scattered with objects that hinder motion, known as permeable barriers, have been limited. By solving this problem, we are paving the way for exciting advances in many different sectors because permeable barriers are routinely encountered by animals, cellular organisms and humans.”

Creativity in mathematics takes different forms and one of these is the connection between different levels of description of a phenomenon. In this instance, by representing random motion in a microscopic fashion and then subsequently zooming out to describe the process macroscopically, it was possible to find the new equation.

Further research is needed to apply this mathematical tool to experimental applications, which could improve products and services. For example, being able to model accurately the diffusion of water molecules through biological tissue will advance the interpretation of diffusion-weighted MRI (Magnetic Resonance Imaging) readings. It could also offer more accurate representation of air spreading through food packaging materials, helping to determine shelf life and contamination risk. In addition, quantifying the behaviour of foraging animals interacting with macroscopic barriers, such as fences and roads, could provide better predictions on the consequence of climate change for conservation purposes.

The use of geolocators, mobile phones, and other sensors has seen the tracking revolution generate movement data of ever-increasing quantity and quality over the past 20 years. This has highlighted the need for more sophisticated modelling tools to represent the movement of wide-ranging entities in their environment, from natural organisms to man-made devices.

Senior author Dr Luca Giuggioli, Associate Professor in Complexity Sciences at the University of Bristol, said: “This new fundamental equation is another example of the importance of constructing tools and techniques to represent diffusion when space is heterogeneous, that is when the underlying environment changes from location to location.

“It builds on another long-awaited resolution in 2020 of a mathematical conundrum to describe random movement in confined space. This latest discovery is a further significant step forward in improving our understanding of motion in all its shapes and forms – collectively termed the mathematics of movement – which has many exciting potential applications.”

Paper

‘Diffusion through permeable interfaces: Fundamental equations and their application to first-passage and local time statistics’ by Toby Kay and Luca Giuggioli in Physical Review Research

 

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JOURNAL

Physical Review Research

ARTICLE TITLE

‘Diffusion through permeable interfaces: Fundamental equations and their application to first-passage and local time statistics’

ARTICLE PUBLICATION DATE

6-Sep-2022

Stanford researchers construct most complex, complete synthetic microbiome

Peer-Reviewed Publication

STANFORD UNIVERSITY

Key studies in the last decade have shown that the gut microbiome, the collection of hundreds of bacterial species that live in the human digestive system, influences neural development, response to cancer immunotherapies, and other aspects of health. But these communities are complex and without systematic ways to study the constituents, the exact cells and molecules linked with certain diseases remain a mystery.

Stanford University researchers have built the most complex and well-defined synthetic microbiome, creating a community of over 100 bacterial species that was successfully transplanted into mice. The ability to add, remove, and edit individual species will allow scientists to better understand the links between the microbiome and health, and eventually develop first-in-class microbiome therapies.

Many key microbiome studies have been done using fecal transplants, which introduce the entire, natural microbiome from one organism to another. While scientists routinely silence a gene or remove a protein from a specific cell or even an entire mouse, there is no such set of tools to remove or modify one species among the hundreds in a given fecal sample.

“So much of what we know about biology, we wouldn’t know if it weren’t for the ability to manipulate complex biological systems piecewise,” said Michael Fischbach, Institute Scholar at Sarafan ChEM-H and corresponding author on the study, published in Cell on Sept. 6.

Fischbach, who is an associate professor of bioengineering and of microbiology and immunology, and others saw one solution: Build a microbiome from scratch by growing individually and then mixing its constituent bacteria.

Building the ark

Each cell in the microbiome occupies a specific functional niche, performing reactions that break down and build up molecules. To build a microbiome, the team had to ensure that the final mixture was not only stable, maintaining a balance without any single species overpowering the rest, but also functional, performing all the actions of a complete, natural microbiome. Selecting species to include in their synthetic community was also difficult given the natural variation across individuals; two people selected at random share less than half of their microbial genes.

The researchers, including a team from the Chan Zuckerberg Biohub, decided to build their colony from the most prevalent bacteria and turned to the Human Microbiome Project (HMP), a National Institutes of Health initiative to sequence the full microbial genomes of over 300 adults.

“We were looking for the Noah’s Ark of bacterial species in the human gut, trying to find the ones that were almost always there in any individual,” said Fischbach.

They selected over 100 bacterial strains that were present in at least 20% of the HMP individuals. Adding a few species needed for some subsequent studies brought them to 104 species, which they grew in individual stocks and then mixed into one combined culture to make what they call human community one, or hCom1.

Though satisfied that the strains could coexist in the lab, the true test was whether their new colony would take root in the gut. They introduced hCom1 to mice that are carefully designed to have no bacteria present. hCom1 was remarkably stable, with 98% of the constituent species colonizing the gut of these germ-free mice, and the relative abundance levels of each species remaining constant over two months.

Foreign invasion

To make their colony more complete, the researchers wanted to make sure that all vital microbiome functions would be performed by one or more species. They relied on a theory called colonization resistance, which explains that any bacterium, when introduced into an existing colony, will only survive if it can fill a niche not already occupied.

By introducing a complete microbiome, in the form of a human fecal sample, to their colony and tracking any new species that took up residence, they could build a more complete community.

Some were skeptical that this would work. “The bacterial species in hCom1 had lived together for only a few weeks,” said Fischbach. “Here we were, introducing a community that had coexisted for a decade. Some people thought they would decimate our colony.”

Remarkably, hCom1 held its own, and only about 10% of cells in the final community came from the fecal transplant.

They found over 20 new bacterial species that inserted themselves in at least two of their three fecal transplant studies. Adding those to their initial community and removing those that failed to take root in mouse guts gave them a new community of 119 strains, dubbed hCom2. This second iteration, still made from individually growing and then mixing the constituents, made mice even more resistant to fecal challenges than the first.

Final challenge

To demonstrate the utility of their synthetic microbiome, the team took hCom2-colonized mice and challenged them with a sample of E. coli. These mice, like those that were colonized with a natural microbiome, resisted infection.

Prior studies have shown that a healthy natural microbiome leads to protection, but Fischbach and colleagues could take this a step further by iteratively eliminating or modifying certain strains to determine which ones specifically conferred protection. They found several key bacteria and plan to conduct further studies to narrow down to the most critical species.

Fischbach believes that hCom2, or future versions of it, will enable similar reductionist studies that reveal the bacterial agents involved in other areas, like immunotherapy responses.

“We built this consortium for the broader research community. We want to get this into as many hands as possible to have an impact on the field,” said Fischbach.

He also envisions that this method of building a microbiome from the ground up will make engineered microbiome-based therapies possible in the future. As the director of the Stanford Microbiome Therapies Initiative (MITI), an initiative launched in 2019 by Sarafan ChEM-H and the Department of Bioengineering, he aims to construct engineered communities that could one day be transplanted into people to treat or prevent a variety of diseases.

Fischbach is a member of Stanford Bio-X and the Wu Tsai Human Performance Alliance, and is a Chan Zuckerberg Biohub Investigator. Other Stanford authors include Alice Cheng, Po-Yi Ho, Andrés Aranda-Díaz, Feiqiao Yu, Xiandong Meng, Min Wang, Mikhail Iakiviak, Kazuki Nagashima, Aishan Zhao, Pallavi Murugkar, Advait Patil, Katayoon Atabakhsh, Allison Weakley, Ariel Brumbaugh, Steven Higginbottom, Alejandra Dimas, Anthony Shiver, Justin Sonnenburg, and KC Huang.

The work was supported by a Dean’s Postdoctoral Fellowship, the National Institutes of Health, the Human Frontier Science Research Program, the Astellas Foundation for Research on Metabolic Disorders, the Stanford Microbiome Therapies Initiative, the National Science Foundation, the Bill and Melinda Gates Foundation, the Helmsley Foundation, the Howard Hughes Medical Institute, the Leducq Foundation, the Stanford-Coulter Translational Research Grants Program, MAC3 Impact Philanthropies, and the Allen Discovery Center at Stanford on Systems Modeling of Infection.

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JOURNAL

Cell

DOI

10.1016/j.cell.2022.08.003 

ARTICLE TITLE

Design, construction, and in vivo augmentation of a complex gut microbiome

ARTICLE PUBLICATION DATE

6-Sep-2022