Saturday, September 09, 2023

 

Sepsis – as common as cancer, as deadly as a heart attack


Peer-Reviewed Publication

LUND UNIVERSITY





In 2016, the research team conducted an initial study in southern Sweden (Skåne) where they revealed that sepsis is much more common than previously believed. The incidence turned out to be 750 adults per 100,000 individuals. In the latest study in the same region, the results showed that more than four percent of all hospitalizations involved the patient suffering from sepsis, and 20 percent of all sepsis patients died within three months. 

“This makes sepsis as common as cancer with similar negative long-term consequences, and as deadly as an acute myocardial infarction. Among sepsis survivors, three-quarters also experience long-term complications such as heart attacks, kidney problems, and cognitive difficulties”, says Adam Linder, sepsis researcher and associate professor at the Department of infection medicine at Lund University, as well as a senior physician at Skåne University Hospital.

The European Sepsis Alliance has assigned the researchers with assessing how common sepsis is in the rest of Europe. Given the differing healthcare systems across countries, it wasn't immediately clear how they should proceed to obtain accurate figures. Consequently, the researchers conducted a pilot study southern Sweden to determine if their methods were applicable to other European hospitals.

“Doctors classify patients using diagnostic codes. Since sepsis is a secondary diagnosis resulting from an infection, the condition is significantly underdiagnosed, as the primary disease often dictates the diagnostic code. This makes it challenging to find a way to accurately determine the number of sepsis cases”, says Lisa Mellhammar, sepsis researcher at Lund University and assistant senior physician at Skåne University Hospital.

In the study, which is now published in JAMA Network Open, it was revealed that 7,500 patients in Skåne were associated with sepsis in 2019. During the pandemic, the incidence increased to six percent. However, even without Covid-19, the researchers believe that sepsis should be viewed as an epidemic.

The aim is to use the publication to influence the EU to establish a common surveillance system for sepsis. The team are in contact with authorities and researchers from around thirty European countries and hope that the research project can secure sufficient funding to start soon. There is no indication that the number of sepsis cases would be lower in other parts of Europe than in Sweden. In Swedish hospitals, only two percent of all sepsis patients are antibiotic-resistant, and the researchers speculate that the proportion of resistant cases is higher in many other European countries.

“Although sepsis care has improved in recent years, we need to enhance our diagnostic methods to identify patients earlier and develop alternative treatment methods beyond antibiotics to avoid resistance. Increasing awareness about sepsis among the public and decision-makers is crucial to ensure that resources are allocated appropriately", concludes Adam Linder.

 

Breathe! The shape-shifting ball that supports mental health


A soft ball designed to support mental health by ‘personifying’ breath has been invented by a computer science student in the UK.

Peer-Reviewed Publication

UNIVERSITY OF BATH

Alexz Farrall and his PAWS ball 

IMAGE: ALEXZ FARRALL DEMONSTRATING THE USE OF PAWS view more 

CREDIT: VITTORIA D'ALESSIO, UNIVERSITY OF BATH



A soft ball that ‘personifies’ breath, expanding and contracting in synchronicity with a person’s inhalations and exhalations, has been invented by a PhD student at the University of Bath in the UK. The ball is designed to support mental health, giving users a tangible representation of their breath to keep them focused and to help them regulate their emotions.

Alexz Farrall, the student in the Department of Computer Science who invented the device, said: "By giving breath physical form, the ball enhances self-awareness and engagement, fostering positive mental health outcomes."

Generally, breathing is an ignored activity, yet when done deeply and with focus, it's known to alleviate anxiety and foster wellbeing. Measured breathing is highly rated by mental health practitioners both for its ability to lower the temperature in emotionally charged situations and to increase a person’s receptivity to more demanding mental-health interventions.

Disciplines that frequently include mindful breathing include Cognitive Behavioural Therapy (CBT), Mindfulness-Based Stress Reduction (MBSR), Dialectical Behaviour Therapy (DBT) and trauma-focused therapies.

Most people, however, struggle to sustain attention on their breathing. Once disengaged from the process, they are likely to return to thinking mode and be less receptive to mental-health interventions that require concentration.

“I hope this device will be part of the solution for many people with problems relating to their mental wellbeing," said Mr Farrall.

Focus lowers anxiety

Recent research led by Mr Farrall shows a significant improvement in people’s ability to focus on their breathing when they use his shape-shifting ball. With their attention heightened, study participants were then able to pay closer attention to a guided audio recording from a meditation app.

Among those who used the ball, there was an average 75% reduction in anxiety and a 56% increase in protection against worry-induced thoughts. In contrast, those relying only on the audio recordings experienced a 31% reduction in anxiety (recording 44% more anxiety than their counterparts).

Additionally, those accessing the ball alongside audio guidance showed significantly higher Heart Rate Variability (indicative of better stress resilience and emotional regulation) than those using only audio, demonstrating the superior calming effect of a combined ball+audio approach.

The study’s results were presented earlier this year at the CHI Conference on Human Factors in Computing Systems – the premier international conference of human-computer interaction.

Stop the drop out

Explaining how the device supports a user, Mr Farrall said: "When an individual holds the ball, their breath becomes a physical thing between their hands. They can feel and see the flow of air as the object expands and contracts.

“This allows them to become more aware of their own internal sensations and more receptive to psychological change. It gives a personalised and engaging experience, and is accessible to everyone.”

Mental health issues costs the NHS around £118 billion annually, yet the demand for services significantly exceeds supply, leaving many unable to access mental health support. While digital technologies like apps have emerged to bridge this gap, many people don’t use them for long enough to enjoy the promised benefits, with one study showing that only 3.9% of users stick with an app programme over a 15-day period.

Mr Farrall’s interactive ball – named the Physical Artefact for Well-being Support (PAWS) – offers a potential solution by giving people an extra incentive to actively participate in managing their mental health. In time, Mr Farrall hopes his ball will be a tool used both by mental-health professionals and private individuals.

"I want this device to be a genuine catalyst for mental health improvement, not just in clinical settings but also for home users," he said.

Professor Jason Alexander, who supervises Mr Farrall’s project from the Department of Computer Science at Bath, said: “The beauty of PAWS is that the concept is so simple – letting someone ‘feel’ their breath – yet it has the potential to revolutionise the delivery and outcomes of mental health support not only in the UK but worldwide.”

Haptic feedback

The ball works through haptic feedback, where sensors attached to the user's body transmit data about their respiration patterns to the ball via a computer.

In the Bath study, the PAWS prototype used an electronic and pneumatic circuit to convert pulmonary activity to pneumatic activation. Future versions, however, will leverage Bluetooth technology and smart geometric structures to eliminate the need for wires, and make the device easier and more comfortable to use.

Plans for a larger study are underway to delve deeper into the potential benefits of PAWS. This next study will incorporate insights from mental health experts and people who have spent some time using the ball.

Video explainer: https://youtu.be/HhH6vv7v-FA

 

A system to keep cloud-based gamers in sync


By synchronizing media streams transmitted from the cloud to two devices, researchers could improve cloud gaming and AR/VR applications


Reports and Proceedings

MASSACHUSETTS INSTITUTE OF TECHNOLOGY




CAMRBIDGE, MA – Cloud gaming, which involves playing a video game remotely from the cloud, witnessed unprecedented growth during the lockdowns and gaming hardware shortages that occurred during the heart of the Covid-19 pandemic. Today, the burgeoning industry encompasses a $6 billion global market and more than 23 million players worldwide.

However, interdevice synchronization remains a persistent problem in cloud gaming and  the broader field of networking. In cloud gaming, video, audio, and haptic feedback are streamed from one central source to multiple devices, such as a player’s screen and controller, which typically operate on separate networks. These networks aren’t synchronized, leading to a lag between these two separate streams. A player might see something happen on the screen and then hear it on their controller a half second later.

Inspired by this problem, scientists from MIT and Microsoft Research took a unique approach to synchronizing streams transmitted to two devices. Their system, called Ekho, adds inaudible white noise sequences to the game audio streamed from the cloud server. Then it listens for those sequences in the audio recorded by the player’s controller.

Ekho uses the mismatch between these noise sequences to continuously measure and compensate for the interstream delay.

In real cloud gaming sessions, the researchers showed that Ekho is highly reliable. The system can keep streams synchronized to within less than 10 milliseconds of each other, most of the time. Other synchronization methods resulted in consistent delays of more than 50 milliseconds.

And while Ekho was designed for cloud gaming, this technique could be used more broadly to synchronize media streams traveling to different devices, such as in training situations that utilize multiple augmented or virtual reality headsets.  

“Sometimes, all it takes for a good solution to come out is to think outside what has been defined for you. The entire community has been fixed on how to solve this problem by synchronizing through the network. Synchronizing two streams by listening to the audio in the room sounded crazy, but it turned out to be a very good solution,” says Pouya Hamadanian, an electrical engineering and computer science (EECS) graduate student and lead author of a paper describing Ekho.

Hamadanian is joined on the paper by Doug Gallatin, a software developer at Microsoft; Mohammad Alizadeh, an associate professor of electrical engineering and computer science and a member of the Computer Science and Artificial Intelligence Laboratory (CSAIL); and senior author Krishna Chintalapudi, a principal researcher at Microsoft Research. The paper will be presented at the ACM SIGCOMM conference.

 

Off the clock

At the heart of interstream delay in cloud gaming is a fundamental problem in networking known as clock synchronization.

“If the controller and the screen could look at their watches and at the same time see the same thing, then we could synchronize everything to the clock. But a lot of theoretical work on clock synchronization shows that there are certain bounds you can never overcome,” Hamadanian says.

Many approaches attempt clock synchronization by ping-pong messaging, where a device sends a ping message to the server, which sends a pong message back. The device counts how long it takes the message to return, and cuts that value in half to calculate the network delay.

But the path over the network is likely asymmetric, so it may take more time for the message to reach the server than it does for the return message. Therefore, this method is unreliable and can introduce hundreds of milliseconds of error. Humans can typically perceive interstream delay once it reaches 10 milliseconds. 

“So if something happens on the screen, we want it to happen within 10 milliseconds on the controller, as well,” Hamadanian explains.

He and his collaborators decided to try listening to game audio to synchronize these separate streams.  

In cloud gaming, the microphone on the player’s controller records audio in the room, including game audio played by the speakers on the screen, which it sends back to the server. But using this for synchronization is unreliable because the room audio contains background noise.

So they designed Ekho to add identical sequences of extremely low-volume white noise, known as pseudo noise, to the game audio before it is streamed to the player’s screen. It uses these pseudo-noise segments for synchronization.

Before building Ekho, the researchers conducted a user study to prove that players could not hear the pseudo noise in the game audio. These noise sequences are also resilient to compression, which is important because audio sent from the controller is highly compressed to speed the data transfer.

 

Pseudo noise, real success

The Ekho-Estimator module adds pseudo-noise sequences to the game audio. When it receives the recorded game audio from the controller, it listens for those markers and tries to line up the streams. This enables it to precisely calculate the inter-stream delay.

The Ekho-Estimator sends that information to the Ekho-Compensator module, which either skips a few milliseconds of sound or adds a few milliseconds of silence to the game audio being sent by the server, which synchronizes the streams.

They tested Ekho on real cloud streaming sessions and found that it was superior to other synchronization methods, even when the microphone quality was poor or background noise was picked up by the recording.

Ekho limited interstream delay to less than 10 milliseconds for nearly 87 percent of the time during streams. No other method the team tested was able to cut that delay to less than 50 milliseconds.

“The traditional way of doing this, which involves trying to measure the synchronization error using the underlying network, the errors are significantly larger. When we started this project, were weren’t sure whether this could even be done. But the accuracy we can get down to with Ekho, at sub-millisecond levels, it is unheard of,” says Chintalapudi.

Impressed by these results, the researchers want to see how well Ekho performs in more complex situations, such as synchronizing five controllers to the same screen device. Also, since Ekho was targeted for cloud gaming, it has range limitations. Future work could seek to enhance Ekho so it can synchronize devices at either end of a very large room, like a concert hall.

“Using inaudible white noise as a sort of ‘timekeeper’ is a great example of how out-of-the-box thinking can produce unexpected results,” says Alizadeh. “The technique could improve user experience, not just in cloud gaming but potentially in any multidevice streaming scenario.”

Do ‘forever chemicals’ increase breast cancer risk?


UMass Amherst researcher will be the first to examine the effects of PFAS chemicals on breast tissue through new grant


Grant and Award Announcement

UNIVERSITY OF MASSACHUSETTS AMHERST

Lead researcher 

IMAGE: KATHERINE REEVES IS ASSOCIATE DEAN OF GRADUATE AND PROFESSIONAL STUDIES AND PROFESSOR OF EPIDEMIOLOGY IN THE UMASS AMHERST SCHOOL OF PUBLIC HEALTH AND HEALTH SCIENCES. view more 

CREDIT: UMASS AMHERST





A University of Massachusetts Amherst cancer epidemiology researcher will explore for the first time how women’s breast tissue is affected by exposure to per- and polyfluoroalkyl (PFAS) substances that have been widely used in consumer products with non-stick, water- and stain-resistant coatings.

 

“Our overall goal is to understand if PFAS contribute to breast cancer development,” says Katherine Reeves, associate dean of graduate and professional studies and professor of epidemiology in the School of Public Health and Health Sciences.

 

The research will be funded with a two-year, $405,000 grant from the National Institute of Environmental Health Sciences. According to the Center for Disease Control and Prevention, almost everyone in the U.S. has a measurable exposure to PFAS, one of several groups of substances called “forever chemicals” because they don’t break down naturally in the environment.

 

“We’re exposed to them in a variety of ways,” Reeves explains. “Drinking water is certainly a very common one. Even though these chemicals are being phased out, we’re still using the consumer products that have these – think of the couch you bought 15 years ago that you Scotch-Guarded. You’re still being exposed. And the health effects are not entirely known.” 

Previous experimental studies in animals have shown that PFAS have detrimental effects on mammary gland development and function. “There are some human studies showing that women with higher exposure to these PFAS chemicals breastfeed for a shorter period of time,” Reeves says, possibly because their breasts stop producing milk. 

In the new research, Reeves will use preexisting data and biospecimens from the Susan G. Komen for the Cure Tissue Bank, an extraordinary resource that includes some 9,000 samples of breast tissue donated by healthy volunteers, along with their medical and reproductive history. Reeves and team will examine data from 286 postmenopausal breast tissue donors who also provided a blood sample and gave access to their mammograms and measurements of their terminal duct lobular (TDL) units. TDL produces milk after childbirth, and the “involution,” or turning on of that process, happens naturally with aging. 

“Most breast cancers come out of these terminal ductal lobular units, and a greater degree of involution is associated with a lower breast cancer risk,” Reeves explains. 

The researchers will measure the concentrations of the five most common PFAS chemicals in the blood serum samples. “We will ask the question, do we see an association between the concentration of PFAS that women have circulating and the level to which there is involution of the breast,” Reeves says. “We’re expecting to see that PFAS concentrations will be associated with less involution, meaning that there is a higher breast cancer risk.”

The researchers will also use the volunteers’ digital mammogram files to examine breast density. “We’ve known for years that higher mammographic density is related to an increased breast cancer risk,” Reeves says. “And we’re going to ask the question, is PFAS concentration in the blood related to the density that we see in the breast.”

Higher PFAS concentrations associated with greater breast density would indicate a higher breast cancer risk. It’s possible that PFAS exposure itself is associated with denser breasts, Reeves says, though many other factors, including genetics and weight, are involved. 

“We’re taking advantage of these well-established biomarkers of future breast cancer risk to look at associations between PFAS and those biomarkers,” Reeves says.

The findings also will likely foreshadow the long-term effects of new, similar chemicals as the legacy PFAS chemicals are phased out. This information may inform public health guidelines and new policies related to these classes of chemicals.

“It’s too early for us to study the health effects of these newer chemicals, but the mechanisms involved with these legacy chemicals can shed light on the health effects that we might expect to see from the newer chemicals that are being introduced today,” Reeves says.


Food supplementation with coconut oil can cause obesity, study shows


In experiments with mice, researchers at the State University of Campinas observed alterations in feed consumption, weight gain, anxious behavior and an increase in central nervous system, adipose tissue and liver inflammation.

Peer-Reviewed Publication

FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO

An article published in the Journal of Functional Foods describes a study in which mice given an oral supplement of extra-virgin coconut oil developed significant alterations in food intake, weight gain, anxious behavior, and central nervous system, adipose tissue and liver inflammation.

The researchers also found that the capacity of key metabolic hormones leptin and insulin to activate cellular mechanisms responsible for satiety and control of blood sugar levels was impaired, and that the biochemical mechanisms involved in fat synthesis were stimulated.

“The findings suggest that although the process is slow and silent, coconut oil supplementation for long periods can lead to significant metabolic alterations that contribute to the development of obesity and associated comorbidities,” said Marcio Alberto Torsoni, a researcher in the Metabolic Disturbance Laboratory (LabDiMe) at the State University of Campinas’s School of Applied Sciences (FCA-UNICAMP) in São Paulo state, Brazil. He has a PhD in functional and molecular biology and has completed postdoctoral fellowships at UNICAMP’s School of Medical Sciences and the University of Michigan in the US.

LabDiMe is linked to the Obesity and Comorbidities Research Center (OCRC), one of FAPESP’s Research, Innovation and Dissemination Centers (RIDCs), and the Metabolic Programming and Perinatal Management Center (MPPM), a recipient of funding from the US National Institutes of Health (NIH).

Excessive consumption of animal fat is associated with a heightened risk of cardiovascular disease, as well as obesity and diabetes. One of the components of this diet is cholesterol, but this type of fat also contains saturated fatty acids, which can activate inflammatory processes via the toll-like receptor 4 (TLR-4) and may lead to disease.

Saturated fatty acids can also be obtained from other sources, such as plants. They account for 90% of the lipids in coconut oil, for example. Although short-chain fatty acids make up a large proportion, and these are beneficial because they reduce inflammation, saturated fatty acids in coconut oil are sufficient to activate inflammatory pathways and cause damage to different kinds of cells.

“Consumption of coconut oil as part of one’s usual diet or as a food supplement has increased considerably in the population,” Torsoni said. The problem is that in most cases it is consumed without the guidance of a nutritionist, who can adjust the daily dose in accordance with the needs of the individual concerned.

Experimental model


To find out whether daily consumption of coconut oil for long periods could cause health problems, the research group used an animal model involving healthy mice given a daily dose of coconut oil for eight weeks. This amount of coconut oil was equivalent in calories to about a soup spoonful (13 g) per day, or 5% of the calories from saturated fat in the diet of an adult person of the right weight for their age and height.

Coconut oil should be used in small amounts as seasoning or part of a sauce, preferably with fresh or minimally processed vegetables, Torsoni said. This is the advice of the Health Ministry’s Dietary Guidelines for the Brazilian Population, which also recommends an “adequate and healthy diet ... harmonious in quantity and quality, meeting the needs of variety, balance, moderation, and pleasure”.

“Coconut oil isn’t recommended as a supplement to treat diseases or recoup good health,” said Torsoni, whose research has been supported by FAPESP (16/23484-1, 18/01863-6, 19/07615-7 and 21/11772-0).


About São Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at www.fapesp.br/en and visit FAPESP news agency at www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.

JOURNAL

Journal of Functional Foods

DOI

10.1016/j.jff.2023.105600

ARTICLE TITLE

Supplementation with CO induces lipogenesis in adipose tissue, leptin and insulin resistance in healthy Swiss mice

 

Argonne shares urban science success story as part of UN Habitat Assembly


Researchers from Argonne’s CROCUS Urban Integrated Field Laboratory discussed making communities more resilient to climate change

Business Announcement

DOE/ARGONNE NATIONAL LABORATORY

16x9_IMG_1808 

IMAGE: ARGONNE RESEARCHERS WERE PART OF A PANEL AT THE UN HABITAT ASSEMBLY IN NAIROBI, KENYA HELD JUN. 5 TO 9 IN NAIROBI, KENYA. THEY DISCUSSED ARGONNE’S CROCUS INITIATIVE AS A MODEL FOR PROGRAMS TO MAKE URBAN COMMUNITIES AROUND THE WORLD MORE RESILIENT TO CLIMATE CHANGE. view more 

CREDIT: (IMAGE BY ARGONNE NATIONAL LABORATORY.)




The panel was held at a United Nations conference in Nairobi, Kenya.

By 2030, more than 60% of the world’s population will live in cities. Climate change is one of the major looming concerns for urban areas worldwide, in part because of the ways in which climate change compounds vulnerabilities related to poverty, a lack of natural resources, pollution and the fast pace of urbanization itself. Therefore, one important goal that has drawn attention is a commitment to make cities and human settlements more inclusive, safe, resilient and sustainable.

This goal, called SDG 11, is one of the Sustainable Development Goals of the United Nations (UN). The UN has adopted a set of 17 Sustainable Development Goals and a transformative plan, known as the 2030 Agenda for Sustainable Development, for realizing these goals by the end of this decade.

The UN is working closely with researchers, experts and leaders from many countries and communities around the globe to identify collaborative approaches to address the complex challenges posed by climate change, improve the resilience and sustainability of cities and human settlements, and to further the attainment of the aspirations captured in SDG 11.

In line with this endeavor, researchers at the U.S. Department of Energy’s (DOE) Argonne National Laboratory were featured experts on a panel discussion hosted by the U.S. Department of Housing and Urban Development and the University of Chicago at the Second UN Habitat Assembly in Nairobi, Kenya.

The focus of the presentation centered on Argonne’s Community Research on Climate and Urban Science (CROCUS) Urban Integrated Field Laboratory.

CROCUS is a partnership between Argonne, several Chicago-area civic organizations and multiple universities, many of which are minority serving institutions. CROCUS is funded by DOE’s Office of Biological and Environmental Research as one of four nationwide Urban Integrated Field Laboratories. At its core, CROCUS seeks to make Chicago a model for scientific research to understand the relationships between climate change and urban systems, an effort naturally complementary to the UN’s sustainable urbanization goals.

“We are creating a blueprint and tools to be used nationally and globally when it comes to addressing climate change, particularly as it relates to community partnerships,” said Argonne Environmental Science Division Director Cristina Negri. ​“We’re interested in knowing what the climate impacts will be on a city like Chicago, and how studying them — with guidance from the community — will serve as a model for other cities.”

Negri highlighted the scientific mission of CROCUS, which is driven by the needs of under-resourced and historically disinvested communities. ​“Our approach to science is centered on empowering these communities to guide our research focus and accompany us on our scientific journey. We aim for our science to be truly pertinent and relevant to their needs.”

In response to climate change, Negri mentioned the growing consideration of what she called ​“nature-based solutions” in urban communities. These solutions involve the integration of green spaces within cities to mitigate some of the extreme heat or flooding caused by climate change.

“What sets our approach apart is our focus on bringing climate science to the street level,” Negri said. ​“Instead of solely considering regional climate models, we are exploring variations between neighborhoods, which could help us understand at a very granular level how local climate dynamics and potential interventions, such as nature-based solutions, may work in different communities.”

The CROCUS initiative at Argonne exemplifies the laboratory’s commitment to collaborative research and community engagement in addressing the complex challenges posed by climate change. By fostering partnerships and working directly with underrepresented communities, CROCUS aims to provide real insights and tools that can be ultimately leveraged both locally and globally to promote the sustainability of cities in the U.S. and worldwide.

Argonne National Laboratory seeks solutions to pressing national problems in science and technology. The nation’s first national laboratory, Argonne conducts leading-edge basic and applied scientific research in virtually every scientific discipline. Argonne researchers work closely with researchers from hundreds of companies, universities, and federal, state and municipal agencies to help them solve their specific problems, advance America’s scientific leadership and prepare the nation for a better future. With employees from more than 60 nations, Argonne is managed by UChicago Argonne, LLC for the U.S. Department of Energy’s Office of Science.

The U.S. Department of Energy’s Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, visit https://​ener​gy​.gov/​s​c​ience.

UTHSC researchers awarded $3.69 million to study genetics mediating response to THC, the major psychoactive component in cannabis

Grant and Award Announcement

UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER

Dr. Megan Mulligan and Dr. Bob Moore 

IMAGE: MEGAN MULLIGAN, PHD, AND BOB MOORE, PHD view more 

CREDIT: COURTESY UTHSC




Researchers at the University of Tennessee Health Science Center have received a five-year grant totaling $3.69 million from the National Institute on Drug Abuse to study how genetic differences influence behavioral and physiological responses to tetrahydrocannabinol (THC), the major psychoactive component in cannabis.

Increased legalization for medical and/or recreational use and more favorable public perspectives has led to an increased use of cannabis. At the same time, the amount of THC in cannabis and derived products has dramatically increased. Recognizing a current lack of research on how high levels of THC impact health and behavior, principal investigators Bob Moore, PhD, professor in the Department of Pharmaceutical Sciences, and Megan Mulligan, PhD, associate professor in the Department of Genetics, Genomics & Informatics (GGI), are conducting research to identify genetic differences in bran effector signaling pathways that mediate individual differences in response to THC.

Their research aims to identify genetic variation in cannabinoid receptor signaling pathways mediating the response to delta-9-tetrahydrocannabinol (THC). The team will use a pharmacogenomic screen in a recombinant inbred mouse population with different genetic backgrounds to help identify the specific genes and molecular signaling pathways responsible for variation in physiological response following exposure to a high dose of THC, similar to what may be present in current high-potency cannabis and derived products.

“This is the first screen for initial response to THC in a genetic population of any animals,” said Dr. Mulligan. “We are positive that we will be able to identify gene variants in cannabinoid receptor signaling and metabolic pathways that underlie differences in THC response in rodents, and we expect these responses and pathways to be similar in humans.”

The team, which includes co-investigators Byron Jones, PhD, professor in the Department of Genetics, Genomics and Informatics, and Xusheng Wang, PhD, associate professor in the Department of Genetics, Genomics and Informatics, hopes to make a significant impact in better understanding the genetic regulation of cannabinoid receptor signaling in the brain. The study’s findings will be important for future investigations into the impact of THC over the lifespan and in other biological systems beyond the brain.

“If the scientific community sees us having success in identifying how genetics regulates responses to THC, then this approach could be used as a screen to understand whole system effects of new drug candidates,” Dr. Moore said. “I hope it will bring a new approach to potentially identify unwanted side-effects of new therapies and guide medicinal chemists in the drug development effort.”


 

Archaeology: Mummification balm ingredients reflect Ancient Egyptian noblewoman’s high status


Peer-Reviewed Publication

SCIENTIFIC REPORTS





The ingredients of balms used in the mummification of ancient Egyptian noblewoman named Senetnay — whose remains were excavated by Howard Carter in 1900 CE — are described in a study published in Scientific Reports. The origins and complexity of the balms provide clues as to the high status of the individual.

Previous research has identified that Senetnay lived in Egypt around 1,450 BCE, was wet nurse to the Pharaoh Amenhotep II during his infancy, and bore the title “Ornament of the King”. After her death, her mummified organs were stored in four jars in a royal tomb in the Valley of the Kings.

Barbara Huber, Nicole Boivin and colleagues analysed the substances found within six balm samples from two jars that were used to store Senetnay’s lungs and liver. They report that both balms contained beeswax, plant oils, animal fats, the naturally occurring petroleum product bitumen, and resins from the family of coniferous trees that includes pines and larches. The authors also identified the presence of the compounds coumarin and benzoic acid within samples from both jars. Coumarin has a vanilla-like scent and is found in a wide range of plants including cinnamons and pea plants, while benzoic acid occurs in fragrant resins and gums obtained from several types of trees and shrubs.

While the composition of the balms from both jars appeared to be very similar, the authors identified two substances that were only present in the jar used to store Senetnay’s lungs. These were a compound known as larixol — which is found in larch resin — and another fragrant resin that they suggest is either dammar, which is obtained from dipterocarp trees that grow in India and southeast Asia, or a resin obtained from Pistacia trees — a group that is part of the cashew family. The presence of these ingredients in only one of the two jars could indicate that different balms were used to preserve different organs.

Based on a review of previous analyses of mummification balms, the authors report that the composition of those applied to Senetnay’s organs was relatively complex compared to others from the same period. Additionally, they suggest that most of the potential ingredients would likely have been imported from locations outside Egypt. The authors propose that the complexity of the balms and use of imported ingredients used in the mummification of Senetnay reflect her high social status and indicate that she was a highly valued member of the Pharaoh’s entourage.

###

Article details

Biomolecular characterization of 3500-year-old ancient Egyptian mummification balms from the Valley of the Kings

DOI: 10.1038/s41598-023-39393-y

Please link to the article in online versions of your report (the URL will go live after the embargo ends): https://www.nature.com/articles/s41598-023-39393-y.

 

Biodiversity: Gardens could be an Eden for vulnerable plants


Peer-Reviewed Publication

SCIENTIFIC REPORTS





Conservation gardening — the practice of planting declining native species in urban and rural green spaces — could help to address the increasing issue of plant biodiversity losses in Germany, reports a paper published in Scientific Reports. The authors find that on average across Germany, 41 percent of plants (988 species) on the Red List of Threatened Species would suit conservation gardening, and that this approach could be expanded to boost biodiversity in other countries.  

Although there is increasing public awareness of the importance of plant biodiversity in green spaces, there is a continuing strong preference for tidy gardens with ornamental plants. While local plants may also be grown, gardens tend to show low levels of diversity and plant choices are heavily influenced by availability and personal experience.

Ingmar Staude and colleagues obtained the most recent Red List data for endangered and vulnerable plants across all 16 German states. The authors included extinct in the wild species as conservation gardens can provide new habitats for these plants. They then collated data from the NaturaDB database to categorise which of these threatened species were suitable for gardening. Finally, they used data from plant and seed producer websites to assess the commercial availability of listed species. Based on this data, the authors created a web app to provide lists of plants for gardeners and local authorities so that they could easily select suitable plants for conservation gardening. 

The number of Red List species ranged from 515 to 1,123 in different German states, with a median of 41 percent (988 species) of these being suitable for conservation gardening. In Hamburg, 53 percent (352 of 670) of threatened species could be grown, while in Bavaria only 29 percent (321 of 1,123 species) were suitable. Of the total suitable species, 650 (66 percent) were commercially available for purchase. Additionally, the authors calculate that 45 percent of conservation gardening-suitable threatened plants prefer dry soils, compared to 27 percent of conventional garden plants.

These findings indicate that many threatened species are both suitable for gardening and are commercially available. The authors also suggest that, overall, these plants may also be more tolerant of drier conditions. Together, this presents a new approach to reducing biodiversity loss.

 

Evolutionary imbalance explains global plant invasions


Plant species from certain geographic regions are more successful in spreading outside their native ranges than others – but why?

Peer-Reviewed Publication

UNIVERSITY OF KONSTANZ





Human activities – for example, global trade and travel – are driving the spread of plants beyond their natural ranges and around the globe. However, not all species benefit equally from these movements; only some are able to successfully establish populations (i.e. naturalize) in new locations. Data on the global distribution of alien plants reveals that plants originating from certain geographic regions are more successful at naturalizing than others.

The evolutionary imbalance hypothesis (EIH) offers possible explanations for this phenomenon, but has not yet been verified on a global scale. An international research team led by biologist Mark van Kleunen from the University of Konstanz has now succeeded in confirming key predictions of this hypothesis using extensive global data. In their study in Nature Ecology & Evolution, the researchers also discover intriguing similarities in the origins of plants that successfully establish populations outside their natural ranges and those that humans have selected for cultivation and economic use – suggesting that biogeographic factors influence biological and cultural systems in similar ways.

Dating back to Darwin
At its essence, the ideas of the EIH date back to Charles Darwin. "Darwin proposed that geographic barriers divide the Earth's ecosystems into various evolutionary arenas," says Trevor Fristoe, first author of the study and ecologist at the Department of Biology at the University of Konstanz. Within each of these arenas, the organisms inhabiting them would be exposed to unique geographic and ecological conditions that influence the intensity of natural selection. "The result is differences in the absolute fitness for species originating from different regions – evolutionary imbalances –, and these differences have consequences for which species are more likely to successfully establish in new areas when barriers are removed," Fristoe continues.

Based on these ideas, the EIH makes predictions about the characteristics of global regions that drive the evolution of particularly successful aliens. For example, larger regions should support larger populations and higher genetic diversity to allow for more efficient natural selection. Species-rich regions should serve as intense proving grounds where species must evolve to persist in the presence of a wide variety of competitors and enemies.

The current study tested these predictions on a global scale. For this, the researchers used an unprecedented data set that included the native and alien distributions of over 99 percent of all known seed plants – over 330,000 species. Consistent with the EIH, they demonstrated that plants originating from vast, species-rich regions are among the most successful alien plants. "Thus, our study confirms two key predictions of the EIH on a global scale," emphasizes Mark van Kleunen, head of the international research team.

Economic plants show a similar pattern
What is more, the data revealed a previously unrecognized link between evolutionary imbalance and the economic use of plants by humans: the native range characteristics that select for successful invaders are also associated with the species that we grow for economic use. “All else equal, humans should chose to cultivate plants with a higher capacity for survival, growth, and proliferation. This has resulted in feedbacks where species with high potential as invaders are also more likely to be intentionally moved around the globe. Our study demonstrates these intriguing links and suggests how evolutionary imbalances in biological and cultural systems may even interact," says van Kleunen.

 

Key facts:

  • EMBARGOED UNTIL THURSDAY, 31 AUGUST 2023, 17:00 CEST (16:00 LONDON TIME, 11:00 U.S. EASTERN TIME)
  • Original publication: T. S. Fristoe et al. (2023) Evolutionary imbalance, climate and human history jointly shape the global biogeography of alien plants. Nature Ecology & Evolution; doi: 10.1038/s41559-023-02172-z
  • International research team led by biologists from Konstanz confirms key predictions of the "evolutionary imbalance hypothesis" on the naturalization success of plants from specific native regions.
  • The study takes into account distribution data from over 330,000 plants – almost all (99.5%) known seed plants.
  • Funding: German Research Foundation (DFG)

 

 

Note to editors:
You can download images here:

Link: https://www.uni-konstanz.de/fileadmin/pi/fileserver/2023/evolutionaeres_ungleichgewicht_vetch.jpg

Caption: Alien individuals of the tufted vetch (Vicia cracca) in interior Alaska. This species has a native distribution spanning much of Eurasia and has successfully established alien populations on every continent but Antarctica.

Image: © Trevor Fristoe

 

Link: https://www.uni-konstanz.de/fileadmin/pi/fileserver/2023/evolutionaeres_ungleichgewicht_goldenrod.jpg

Caption: Among the most invasive plants in Europe (shown invading a meadow in Germany), the Canadian goldenrod (Solidago Canadensis) has a native range that stretches from Alaska, across Canada, and all the way into tropical Mexico.

Image: © Jonas Bleilevens & Trevor Fristoe