Targeting enzyme could alleviate muscle wasting for cancer patients

Targeting a specific enzyme in the muscle could help cancer patients preserve muscle mass and potentially prolong their survival, according to research from UTHealth Houston.

A study led by Yi-Ping Li, PhD, professor in the Department of Integrative Biology and Pharmacology with McGovern Medical School at UTHealth Houston, found that an enzyme known as UBR2 plays a critical role in cancer-induced muscle wasting, also called cancer cachexia.

The results were published today in the scientific journal PNAS.

“The findings will fill a key gap in understanding how cancer causes muscle mass and function loss,” said Li, senior author of the study and a faculty member with The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences.

Cancer cachexia is a complication developed in the late stages of cancer in roughly 60% of all cancer patients. Cachexia patients waste away by losing body weight, primarily due to progressive loss of muscle mass, causing respiratory and heart failure. Approximately 30% of all cancer patients die of cachexia, making the complication a major determinant of cancer survival.

Historically, there has been no treatment of cancer cachexia due to poor understanding of its origins. Therefore, a key focus of Li’s lab over the past two decades has been to decipher the molecular mechanisms through which cancer causes cachexia.

Building upon a series of discoveries in mice, his lab recently identified the role of the enzyme UBR2. This is the key enzyme in muscle that seeks out subtypes of the contractile protein myosin heavy chain, a critical component for sustaining muscle contraction, for destruction in response to cancer.

Cancer causes an increase of UBR2 in muscle, and blocking the increase of or removing UBR2 spares mice from tumor-caused muscle mass and function loss. By examining the muscle of cancer patients, researchers obtained evidence that UBR2 is increased, which is associated with loss of the specific subtype of myosin heavy chain preferentially lost in cachexia.

Li said this discovery is significant for the future of cancer cachexia therapy.

“We have learned in animal studies that muscle wasting in cancer hosts can be ameliorated by blocking UBR2 increase through repurposing some existing drugs,” he said. “Based on the findings, we plan to conduct clinical trials for the therapy of cancer cachexia.”

Song Gao, PhD, former postdoctoral research fellow with McGovern Medical School, was the first author of the study. Co-authors with the Department of Integrative Biology and Pharmacology at McGovern Medical School included Yong Zhou, PhD, assistant professor, as well as former faculty members Guohua Zhang, PhD; Zicheng Zhang, MD, PhD; James Z. Zhu; and Li Li, PhD.

Other co-authors were George G. Rodney Jr., PhD, and Reem S. Abo-Zahrah, PhD, both with Baylor College of Medicine in Houston; Lindsey Anderson, PhD, and Jose M. Garcia, MD, PhD, both with VA Puget Sound Health Care System in Seattle; and Yong Tae Kwon, PhD, with Seoul National University in South Korea.

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Metabolism, not genes, may offer more insight into risk of some diseases

Our ancestry can be detected not only in our genes, but also in our metabolism, a new Yale-led study has found.

In an analysis of the metabolic profiles of healthy American babies, researchers found surprising differences among ethnic groups which may help make screening for inherited metabolic disorders, cystic fibrosis, or hypothyroidism much more accurate than traditional genetic disease screens.

“We don’t want to miss a baby who is potentially sick, and we don’t want to put families through the burdens and concerns that can stem from a false-positive test,” said Curt Scharfe, associate professor of genetics at Yale School of Medicine and senior author of the study published in the journal Molecular Genetics and Metabolism.

For the study, Scharfe and colleagues analyzed data collected from more than 400,000 babies, representing 17 self-reported ethnic groups, who were part of California’s newborn screening program. Specifically, they wanted to know if these ethnic differences could be detected in metabolites, molecules that provide energy by breaking down food or body tissue such as fat, found in the blood of the infants.

The question was not only of academic interest but of concern to pediatricians. For instance, it is known that babies of African heritage are more likely to have elevated blood biomarkers indicating cystic fibrosis than babies born to white parents, even though babies born to white parents are far more likely to eventually develop the disease. Researchers hope that using ancestry to interpret these differences in marker levels might offer more accurate ways to assess risks than traditional genetic tests.

People of African heritage are also known to have greater genetic diversity than those from ethnic groups because they are descendants of the world’s oldest ancestral population. Modern humans emigrated from Africa to regions across the planet; other ethnic groups are descendants of these original migrants, and have enough variation in their DNA to make them genetically identifiable.

But metabolic lineages can tell a different story, the researchers found. For instance, while there is a clear delineation between genetic variants among African-Americans and Americans of European descent, researchers found that metabolically these two groups are more closely related. Conversely, while people of Japanese and Chinese descent, for instance, are closely related genetically, the researchers found larger differences in their metabolic profiles.

“This attests to the role of environment in forming our metabolism,” Scharfe said. “Where people share the same culture and food, metabolic profiles are more similar. Where people are separated by circumstances, such as language or lifestyles, then differences in metabolism are greater than genetic variations.”

Scharfe cautions that more work needs to be done before findings can be applied clinically. Researchers only analyzed 41 out of many hundreds of metabolites and relied on parents own reports of their ethnic heritage, which might not always correspond to reality.

“This is just a first snap shot, but understanding our metabolic ancestry has a promising future,” Scharfe said.

Gang Peng, an associate research scientist of biostatistics and bioinformatics in Yale’s departments of Biostatistics and Genetics, is the first author of the study.

Story Source:

Materials provided by Yale University. Original written by Bill Hathaway. Note: Content may be edited for style and length.

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Lucy Letby: Mother begged ‘don’t let my baby die’, trial hears

A twin boy collapsed after nurse Lucy Letby injected him with air, her murder trial hears.

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Covid: Life expectancy still down in many countries

Life expectancy improved last year in some European countries but not in others, researchers say.

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Covid: Time running out to protect vulnerable, campaigners warn

Campaigners urge the government to pay for a drug they say will help protect vulnerable people this winter.

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Cost of living crisis: ‘I am shivering while I’m on dialysis’

Two people explain the worries the row over benefit rises is having on their lives.

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How I Think About My Life and Work

I often think about my life as a flow of experiential explorations.

I’ve found it overwhelming to consider the vast array of possibilities that life presents objectively. Traversing just a fraction of this space could occupy endless lifetimes, so that framing doesn’t bring much clarity and leaves me adrift.

Instead I create clarity by thinking of experiences as a summation of different vibes. A vibe is the inner, subjective flavor of an experience, similar to qualia. It’s what I experience internally when living through an outer experience. This includes my emotions and the thoughts I have along the way.

I typically find it much easier to create clarity regarding the inner experience I want. Even when I don’t have clarity about the outer experience, I can collapse the inner experience into something relatively crisp.

My inner desires are often reactive. If I’m over-stressed, I automatically want to feel more relaxed and at ease. If I’m bored, I want to experience more excitement and stimulation. If I feel happy and engaged with life or if I’m in a nice productive flow, I usually want more of the same – until my inner mood tells me I want to shift. When I take stock of any inner experience, I naturally think about what I’d like to experience next, like I’m laying out some kind of story progression.

Most of the time this is an unconscious process. The conscious part is simply paying attention to what’s arising. I notice whatever vibes I’m experiencing in the moment, especially the pervasive ones that have been with me for days. Once I clarify where I am, I tend sense a pulling sensation to move in a new direction.

Sometimes I feel pulled in multiple directions, but if I consciously list out the vibes that are pulling at me, it’s not hard to clarify my preferences. In those cases usually all of those vibes are correct, and I really want to experience a combo of them, such as a peaceful adventure or a cozy connection.

Guided by Inner Experience

So generally I like to think about life based on the inner quality of my experience. I like to make decisions about my human life as if it’s the same as my spiritual (or inner) life. I find that my life works better when I do that. By contrast when I make decisions that only seem reasonable on the physical plane but feel misaligned at the level of energy, emotions, and inner experiences, the results are usually poor. Not only do I not enjoy those experiences, but I usually fail to get the physical reality results I was aiming for.

However, when I flip this around and focus primarily on the inner experience – meaning that this inner world is where I set my true priorities – my outer world seems to flow along pretty well too. Where the outer world isn’t working so well for me, I normally sense that it’s because I haven’t assumed enough responsibility for the vibes I want to explore and express into that part of life. Or I’m still dealing with internally conflicted vibes in those areas, and I need to resolve those objections.

When choosing work and personal projects, I like to think about the vibes I want to explore. I think deeply about what the inner experience will be like from start to finish. I want to create interesting, varied, and meaningful inner explorations. Overall that approach keeps me feeling satisfied and fulfilled with life.

When I complete a major project, I like to do a postmortem on it. I’ve included a couple of those as bonuses with the Amplify course. I think about what went right and what could be improved for next time. I also journal a lot about the project, taking note of what I enjoyed and what I wish I’d done differently. I use those insights to make choices for future projects.

I think many people choose projects based on the external results they seek to gain. Or they get projects assigned to them by others. I like to choose projects mainly based on what the inner adventure will be like. I make those choices differently each time, which naturally infuses my projects with plenty of variety.

Beyond Happiness

Choosing to be happy is too vague for me. Happiness doesn’t have enough resolution. There are many different vibes that I enjoy and appreciate when I experience them, and they’re more specific than happiness.

Here’s how I think about my life purpose these days. I recently updated it to this:

Consistently invest my precious freedom to create, invite, attract, and enjoy the exploration of different vibrational combos, such as: abundance, wealth, intensity, coziness, lightness, relaxation, oneness, presence, optimism, fun, playfulness, vibrancy, sexiness, ease, comfort, power, order, love, warmth, nurturing, inspiration, wonder, beauty, awe, gracefulness, appreciation, caring, compassion, generosity, adventure, trust, honesty, stability, openness, curiosity, courage, wildness, boldness, pleasure, silliness, mischief, indulgence, excitement, naughtiness, freedom, immersion, imagination, connection, self-expression, creativity, cooperation, co-creation, service, simplifying, accessibility, accomplishment, achievement, speed, efficiency, intelligence, patience, reflection, and celebration. Expand my experiential range and abundantly serve the expansion of life’s range.

I think of my life as an exploration of different vibes. When I was younger, I often focused on vibes I could express with single words, such as abundance or courage. At this time in my life, I prefer mash-ups of different combos. I especially like exploring vibes that may seem a bit contradictory.

For instance, I enjoy caring about people while also challenging them. I love being honest and mischievous. Mixing coziness with wildness is a fun combo too.

You could say that I love being a vibrational mixologist. I love exploring the rich complexity of which vibes combine well, like complementary flavors in a drink.

It’s easy to use my inner purpose to as a basis for the purpose of my business and work as well:

Invite our community members (and other growth-oriented people) to explore different vibrational combos to expand their experiential range, such as: abundance, wealth, intensity, coziness, lightness, relaxation, oneness, presence, optimism, fun, playfulness, vibrancy, sexiness, ease, comfort, power, order, love, warmth, nurturing, inspiration, wonder, beauty, awe, gracefulness, appreciation, caring, compassion, generosity, adventure, trust, honesty, stability, openness, curiosity, courage, wildness, boldness, pleasure, silliness, mischief, indulgence, excitement, naughtiness, freedom, immersion, imagination, connection, self-expression, creativity, cooperation, co-creation, service, simplifying, accessibility, accomplishment, achievement, speed, efficiency, intelligence, patience, reflection, and celebration. Help them invest in growth explorations and meaningful upgrades they’ll treasure!

It takes time to get used to different vibes and to integrate them into our lives. Initially we may want to practice certain vibes individually, and then we can build upon that with endless combos.

Serving the Flow of Life

I feel that this kind of exploration is what life wants from me – and from all of us. When I look at life, I see the ongoing exploration of possibilities. I find that when I support this expansion by doing my part to contribute some interesting explorations, life seems to give me plenty of support as well. Perhaps that’s why I haven’t had a job in more than 30 years.

I consider freedom to be a precious gift because with sufficient freedom, I can access more of the possibility space. I can explore some aspect of life deeply for many weeks in a row. I can go on fun travel adventures. I can connect with a variety of different people. And I have lots of space for reflecting on experiences and considering next steps, especially through journaling.

A nice way to create value for people is to invite them into vibrational explorations together. This can be done in so many ways. Writing blog posts can have that effect by invite people to consider fresh possibilities. I also love doing this through speaking, workshops, coaching, courses, and Conscious Growth Club.

What surprised me was that just sharing more of my inner and outer journey also created a lot of value for people. As long as I keep having new growth experiences, I can share what I learn from them. People have expressed lots of appreciation for this type of sharing over the years. And these explorations have helped me clarify more vibrational combos that I love. For instance, I think of this writing session as inspired cozy reflection time.

Fresh Vibrational Combos Create Fresh Solutions

A key benefit of this type of exploration is that I discover solutions where I didn’t expect to find them. I think we have a tendency to mono-focus on some vibes to the point of stuckness.

For instance, I often see people trying to create more success, achievement, or efficiency in their lives, but they get stuck pretty easily with those vibes. I get more success by not focusing on success. Instead I like to move towards vibes like curiosity and playfulness and learning.

When I focused intensely on success and achievement, I went bankrupt. That made me feel humble enough to start looking at different vibrational directions, and I found that other vibes were much better for me. I eventually became a millionaire with that approach, and it happened with a nice easy flow and wasn’t a struggle to get there. Financial abundance showed up without trying to force it so directly. I got there by exploring other vibes like fun, curiosity, adventure, compassion, wonder, service, etc. I rekindled an adventurous spirit, which has served me well.

That makes sense to me because when I think of abundance, I think of spaciousness and freedom, and those vibes seem more proximate to playfulness and curiosity than they do to a hard-ass focus on success. If I’m vibing with abundance, how much do I really care about traditional business success? That kind of success usually seems boring, stressful, or shallow to me. It lacks nuance.

I think the reason that kind of success doesn’t appeal to me is because it’s too rooted in this physical reality and doesn’t translate well to the spiritual side. When I think of spiritual success, I imagine being able to float freely across a wide range of interesting vibes and having the ability to explore them adeptly in many diverse combinations. So it’s a much broader framing of success. It’s also more resilient because I can develop these skills with or without money. Money often seems to enjoy participating in these explorations, but money doesn’t fuel them. The vibes summon the experiences, including the experience of financial flow.

Vibrational Practice

A key skill is to deliberately practice experiencing vibes that seem interesting. I still like to do this by relaxing on a couch and just imagining scenes that encapsulate certain vibes. I try to go beyond overly simplistic vibes like happiness, and I like to imagine more sophisticated combos playing out. It’s the difference between visualizing a very on-the-nose scene from a straightforward action movie versus visualizing a multi-layered dialogue from a movie like Casablanca, where characters communicate a great deal through subtext and body language.

I realize now that my inner visualization skill was pretty weak when I was younger. I imagined my goals coming through very directly, like an action movie explosion or car chase. But I eventually realized that reality appreciates vibrational richness and complexity. People like this too. I think that most of us don’t want overly simplistic and routine lives. We want to explore many different subtleties with lots of variety.

I love to think about life and business in terms of vibrational range. When I see a part of the vibrational space that I haven’t explored yet, I feel drawn to go explore it sooner or later. This gradually expands my vibrational range.

It’s like training to be a chef and learning to work with a greater variety of ingredients, so many more delicious meals can be created, not just for oneself but for the benefit of others as well.

When I think about serving others, I figure that a good way to help people is to encourage and invite them to expand their vibrational range. Help them to explore areas of the possibility space where they haven’t explored very much yet. Show them where the open waters are. Play the role of tour guide for the areas that are familiar to me, and also encourage people to keep exploring beyond that, so they can serve the expansion of life as well.

Confidence Doesn’t Matter

In addition to the success vibe, another vibe that I consider to be overstretched is confidence. Many people seem to think they need more confidence to get what they want. I find this vibe overly blunt and shallow though. What’s actually interesting about it? Not much. I generally see confidence as a pretty lame and uninteresting vibe.

When I’m really engaged with life in ways that resonate with me, I’m not really vibing with confidence. If you told me I seemed confident when speaking, for instance, I might give you a confused look. I really don’t care about feeling confident or being seen as confident. For whatever reason that vibe just looks and feels really dorky to me.

Instead of confidence, I’d rather explore more interesting combos like curiosity, playfulness, and honesty. Confidence is a confusing vibe because when a person looks confident, that may not actually be what they’re experiencing on the inside. In situations where I might appear confident, like while coaching someone, I’m actually experiencing something quite different internally, such as curiosity or compassion. Or I’m tuning in to a flow of inspired ideas. Or I’m focused on co-creating solutions together. There’s no need for confidence there – that isn’t part of my framing.

Telling yourself to be confident is like eating bread for every meal. You can surely concoct more interesting vibrational meals. Even if you sense that some form of confidence is present, it’s probably the least interesting part of the experience.

Vibes can be funny that way. Some vibes that seem popular in the outer world just don’t align with my actual inner experiences. Paying too much attention to popular vibes tripped me up a lot. It took years to unload enough of that social conditioning, so I could figure out what actually worked for me and which vibrational combos I enjoy and appreciate.

Once I know which vibes I want to move towards, it becomes much easier to choose external experiences then. In those cases it’s mainly a matter of identifying accessible actions to shift my outer reality into alignment with those vibes. To do this I get into resonance with the vibes I want, and then I let them guide my actions. I pay attention to what I feel naturally inspired to do when I’m connecting with those vibes. This leads me to take a lot of action, and my reality gradually shifts.

Personalizing Vibes

I like the exploration process of personalizing vibes and figuring out how they best resonate with me. Consider a vibe like wealth. Do you want to feel wealthy? What does that vibe mean to you? I had mixed associations to that vibe for a while. I associated it with greed, unfairness, and injustice. So of course I couldn’t get into resonance with it. But I also liked some things about it, like how it could connect with freedom, abundance, and more possibilities. So I pulled this vibe away from the negative associations, and I framed my version of wealth as being about gaining more access to possibilities. So it’s not material wealth per se. It’s experiential wealth. My version of wealth isn’t about acquiring. It’s about living and experiencing.

I also like to pull my version of wealth further into the service side. I think about wealth as enriching people’s lives, sharing a wealth of ideas, and inviting people into worthwhile experiences together. This helps my mind explore this type of vibe within an appealing range, so it doesn’t conflict with other vibes I like.

Otherwise if I don’t personalize a vibe to strip out the unwanted bits, those mixed associations can block me from exploring it altogether. Then I have to take a deeper look at my objections to a vibe and resolve those objections. I see this as part of the personalization process, so I take my objections seriously and treat them as problems that need to be solved. I don’t try to ram a vibe into my life when I don’t feel aligned with it. I prefer to sculpt a misshapen vibe into one that looks beautiful to me, so it naturally harmonizes with other vibes that I like.

Productivity is another interesting vibe. My objections are that it can be boring, stressful, or overly routine. I might even associate it with being caged and losing freedom. So I have to pull this vibe to better align with fun, freedom, and exploration. That’s why I like to work in waves that align with motivation and inspiration as opposed to following a rigid routine. This approach works well for me. When I want to be lazy, I give myself full permission to be intensely lazy. When I crave adventure, I go out and explore. And when I’m inspired by fascinating creative ideas, I love to intensely focus on the creative process and see it all the way across the finish line.

Exploring Harmonious Co-Creation

One experience I really want to have next is to do this kind of exploration socially with other people who resonate with it. That’s why I’m hosting a fresh deep dive into the Submersion course soon. We’ll be starting on November 1st and running through December 30th, with weekly Zoom calls along the way. On those calls we can practice together, pooling our collective intentions to summon interesting vibrational combos to invite into our lives. If you’re signed up for my email newsletter or if you already bought the Submersion course, I’ll email you an invite for this between now and November 1st. It’s free for everyone who bought the course already, and for everyone else, all you need to do is get the course between now and November 1st, and you can participate in the social exploration for no extra cost. This is one of our most popular courses, so I imagine that a lot of people will want to explore it as a social experience.

I’m especially curious to see what effect it has if we focus our intentional energy for our good and for the highest good of all. Imagine lots of people holding the intention to help uplift each other. Imagine people sending you love and healing energy from all around the world. And let’s also send vibes of peace, healing, forgiveness, freedom, and positive transformation to the people on earth who most appear to need it right now. Let’s send more energy into the vision of a world we want to create and experience together. I’m really craving this kind of collective exploration right now.

On the inside I want immerse myself in the feeling of all of us stepping into our collective power and intentionality together. I want to mash-up the vibes of oneness, power, love, connection, abundance, and creativity. I want us to harmonize beautifully together. This is a really nice fit for going through the Submersion course together because the course is about upgrading your relationship with reality. I’d love to go through this upgrade process with a very aligned group who resonates with doing this together.

I want to have the experience of co-creating a renewed sense of hope and positive energy flow. I want to invite people to release misaligned vibes and to shift back into alignment with lightness, creativity, and optimism. Remember that we’re all powerful creators here.

So that’s how I’ve been thinking about my life and work lately. I see life as a flow of vibrational explorations. Reality offers a vast field of possibilities to navigate. When I create vibrational clarity – by understanding what kind of inner experience I want next – that level of clarity trickles down to all the low-level decisions and gets me into a lovely and sustainable flow of action.

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BioNTech: Could Covid vaccine technology crack cancer?

BioNTech’s mRNA cancer trials started long before the pandemic, and have shown some early encouraging signals.

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How fluctuating oxygen levels may have accelerated animal evolution

Oxygen levels in the Earth’s atmosphere are likely to have “fluctuated wildly” one billion years ago, creating conditions that could have accelerated the development of early animals, say researchers.

Scientists believe atmospheric oxygen developed in three stages, starting with what is known as the Great Oxidation Event around two billion years ago, when oxygen first appeared in the atmosphere. The third stage, around 400 million years ago, saw atmospheric oxygen rise to levels that exist today. 

What is uncertain is what happened during the second stage, in a time known as the Neoproterozoic Era, which started about one billion years ago and lasted for around 500 million years, during which time early forms of animal life emerged.  

The question scientists have tried to answer is - was there anything extraordinary about the changes to oxygen levels in the Neoproterozoic Era that may have played a pivotal role in the early evolution of animals - did oxygen levels suddenly rise or was there a gradual increase? 

Fossilised traces of early animals - known as Ediacaran biota, multi-celled organisms that required oxygen - have been found in sedimentary rocks that are 541 to 635 million years old. 

To try to answer the question, a research team at the University of Leeds supported by the Universities of Lyon, Exeter and UCL, used measurements of the different forms of carbon, or carbon isotopes, found in limestone rocks taken from shallow seas. Based on the isotope ratios of the different types of carbon found, the researchers were able to calculate photosynthesis levels that existed millions of years ago and infer atmospheric oxygen levels. 

As a result of the calculations, they have been able to produce a record of oxygen levels in the atmosphere over the last 1.5 billion years, which tells us how much oxygen would have been diffusing into the ocean to support early marine life.

Dr Alex Krause, a biogeochemical modeller who completed his PhD in the School of Earth and Environment at Leeds and was the lead scientist on the project, said the findings give a new perspective on the way oxygen levels were changing on Earth. 

He added: “The early Earth, for the first two billion years of its existence, was anoxic, devoid of atmospheric oxygen. Then oxygen levels started to rise, which is known as the Great Oxidation Event.  

“Up until now, scientists had thought that after the Great Oxidation Event, oxygen levels were either low and then shot up just before we see the first animals evolve, or that oxygen levels were high for many millions of years before the animals came along.

“But our study shows oxygen levels were far more dynamic. There was an oscillation between high and low levels of oxygen for a long time before early forms of animal life emerged. We are seeing periods where the ocean environment, where early animals lived, would have had abundant oxygen — and then periods where it does not.”

Dr Benjamin Mills, who leads the Earth Evolution Modelling Group at Leeds and supervised the project, said: “This periodic change in environmental conditions would have produced evolutionary pressures where some life forms may have become extinct and new ones could emerge.” 

Dr Mills said the oxygenated periods expanded what are known as “habitable spaces” — parts of the ocean where oxygen levels would have been high enough to support early animal life forms. 

He said: “It has been proposed in ecological theory that when you have a habitable space that is expanding and contracting, this can support rapid changes to the diversity of biological life. 

“When oxygen levels decline, there is severe environmental pressure on some organisms which could drive extinctions. And when the oxygen-rich waters expand, the new space allows the survivors to rise to ecological dominance. 

“These expanded habitable spaces would have lasted for millions of years, giving plenty of time for ecosystems to develop.”

The findings - “Extreme variability in atmospheric oxygen levels in the late Precambrian”  - are published in the journal Science Advances.

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3D printing plant cells shows promise for studying cell function

A new study from North Carolina State University shows a reproducible way of studying cellular communication among varied types of plant cells by “bioprinting” these cells via a 3D printer. Learning more about how plant cells communicate with each other — and with their environment — is key to understanding more about plant cell functions and could ultimately lead to creating better crop varieties and optimal growing environments.

The researchers bioprinted cells from the model plant Arabidopsis thaliana and from soybeans to study not just whether plant cells would live after being bioprinted — and for how long — but also to examine how they acquire and change their identity and function.

“A plant root has a lot of different cell types with specialized functions,” said Lisa Van den Broeck, an NC State postdoctoral researcher who is the first author of a paper describing the work. “There are also different sets of genes being expressed; some are cell-specific. We wanted to know what happens after you bioprint live cells and place them into an environment that you design: Are they alive and doing what they should be doing?”

The process of 3D bioprinting plant cells is mechanically similar to printing ink or plastics, with a few necessary tweaks.

“Instead of 3D printing ink or plastic, we use ‘bioink,’ or living plant cells,” Van den Broeck said. “The mechanics are the same in both processes with a few notable differences for plant cells: an ultraviolet filter used to keep the environment sterile and multiple print heads — rather than just one — to print different bioinks simultaneously.”

Live plant cells without cell walls, or protoplasts, were bioprinted along with nutrients, growth hormones and a thickening agent called agarose — a seaweed-based compound. Agarose helps provide cells strength and scaffolding, similar to mortar that supports bricks in the wall of a building.

“We found that it is critical to use proper scaffolding,” said Ross Sozzani, professor of plant and microbial biology at NC State and a co-corresponding author of the paper. “When you print the bioink, you need it to be liquid, but when it comes out, it needs to be solid. Mimicking the natural environment helps keep cellular signals and cues occurring as they would in soil.”

The research showed that more than half of the 3D bioprinted cells were viable and divided over time to form microcalli, or small colonies of cells.

“We expected good viability on the day the cells were bioprinted, but we had never maintained cells past a few hours after bioprinting, so we had no idea what would happen days later,” Van den Broeck said. “Similar viability ranges are shown after manually pipetting cells, so the 3D printing process doesn’t seem to do anything harmful to cells.”

“This is a manually difficult process, and 3D bioprinting controls the pressure of the droplets and the speed at which the droplets are printed,” Sozzani said. “Bioprinting provides better opportunity for high throughput processing and control over the architecture of the cells after bioprinting, such as layers or honeycomb shapes.”

The researchers also bioprinted individual cells to test whether they could regenerate, or divide and multiply. The findings showed that Arabidopsis root and shoot cells needed different combinations of nutrients and scaffolding for optimal viability.

Meanwhile, more than 40% of individual soybean embryonic cells remained viable two weeks after bioprinting and also divided over time to form microcalli.

“This shows that 3D bioprinting can be useful to study cellular regeneration in crop plants,” Sozzani said.

Finally, the researchers studied the cellular identity of the bioprinted cells. Arabidopsis root cells and embryonic soybean cells are known for high proliferation rates and a lack of fixed identities. In other words, like animal or human stem cells, these cells can become different cell types.

“We found that bioprinted cells can take on the identity of stem cells; they divide and grow and express specific genes,” Van den Broeck said. “When you bioprint, you print a whole population of cell types. We were able to examine the genes expressed by individual cells after 3D bioprinting to understand any changes in cell identity.”

The researchers plan to continue their work studying cellular communication after 3D bioprinting, including at the single-cell level.

“All told, this study shows the powerful potential of using 3D bioprinting to identify the optimal compounds needed to support plant cell viability and communication in a controlled environment,” Sozzani said.

The research appears in Science Advances and was supported by National Science Foundation EAGER grant MCB #203928 and by BASF Plant Sciences. Tim Horn, assistant professor of mechanical and aerospace engineering at NC State, is a co-corresponding author of the paper.

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