Tag Archives: environment

Cell Biology

Virginia Tech and Weizmann Institute of Science tackle cell … – Virginia Tech

In any fight, knowing your enemy is critical to staging a defense. The fight to stop cancer or to accelerate wound healing is no exception. The research teams at Virginia Tech and the Weizmann Institute of Israel, along with partners worldwide, are pursuing a deeper understanding of how cells move and spread throughout a living body.

Professor Amrinder Nain at Virginia Tech builds nanoscale suspended bridges to study cell migration. Professor Nir Gov at the Weizmann Institute develops the theoretical and computational framework for how cells migrate on curved surfaces. Their collaborative study combining state-of-the-art experiments and theory to examine cell coiling on fibers has been published in Nature Communications.

This study follows previous research partnering Gov and Nain for exploration of the inner mechanics of cancer. In that work, Nain and his partners from Virginia Tech, Japan, and Israel studied how a cells biology affects the motion of brain cancer cells. That work produced several novel discoveries, but chemistry and biology alone did not provide a complete picture. Needing a more holistic view of cellular behavior to understand how to halt cancer in its tracks, the team shifted from studying the inside of the cell to its outside, observing how it interacted with its environment.

Nain and Virginia Tech colleague Bahareh Behkam had previously identified a cell behavior called coiling, in which a cell wraps itself around a fiber axis to migrate. They found that coiling was more pronounced in cancerous invasive cells than their non-tumorigenic counterparts. Knowing this, they set out to understand the underlying energetic principles governing that coiling behavior.

Again needing Govs expertise, the team launched a new collaborative study with the team from Israel, aimed at discovering how a cell moves using its protrusions, or arm-like structures that extend outward from the front of a cell's soft body.

Nain and his collaborators knew these arms not only allow the cell to move, but also to grasp its environment and pull itself forward. The trick was to observe them in 3D at sufficient resolution. Virginia Tech team member Christian Hernandez-Padilla devised fiber networks and imaging strategies to capture coiling events. Nain then contacted Hari Shroff and Harshad Vishwasrao at the National Institutes of Health (NIH) to ask about using their lattice-light sheet advanced microscope.

We challenged ourselves to determine if coiling could be clearly observed in 3D for detailed measurements, said Nain. All it took was a cold email to Hari at NIH, to which he was extremely receptive. We were jubilant as Christians imaging data trickled in, showing cells coil on fibers in 3D.

In addition to the NIH, the team also reached out to:

Understanding cell migration requires knowing how cells curve around fibrous ropes the suspended bridges on which they eventually move. Nains expertise includes building nanoscale cellular suspended roadways that are fibrous. Compared to the flat landscape of a Petri dish, these fibers are much closer to the landscape of living tissues. By partnering with other experts, the team set the stage for illustrating how cells move inside a body, which could lead to new strategies to stop cancer cells or accelerate wound healing.

To propel itself, a cells jelly-like body first produces the tentacle-like protrusions. These cellular arms can grab onto things by twisting around fibers in the tissues surrounding them. But this behavior has rarely been studied before.

Recent imaging studies inside the body have shown cancer cells moving along individual fibers and navigating through varying fibrous architectures by reaching out and grabbing the fibers, Nain said. We combined our experiments with Nirs computational models to understand the energetics of coiling. This had never been attempted before, and it challenged our groups.

The group studied coiling on suspended fibers of various diameters, including flat ribbons pioneered in the Behkam lab. Researchers found that as a cell settled onto a fiber, its tentacle wrapped a few times around the fiber, giving the cell a firm grip. Hernandez-Padilla performed imaging at the NIH and developed the framework to quantify 3D coiling events from the voluminous data recorded.

In Israel, postdoctoral fellow Rajkumar Sadhu created a theoretical model that describes how a cell may get its shape and move when outside forces act on its membrane. Govs team found that energy minimization was a major driver. Picture a membrane trying to remain as flat as possible, avoiding sharp corners that would require more energy to navigate.

Complicated shapes such as the coiling result from protein complexes, themselves curved, bending the membrane as it follows their shape. Curved proteins also connect with the cytoskeleton, the structural component giving the cell its shape. The cytoskeleton grows and pushes outward during cellular movement, driving the protrusions.

These forces, arising from energy conservation and cytoskeleton dynamics, are responsible for the coiling. The model correctly predicted that the coiling would cease when the fiber had sharp corners, as in the case of the flat ribbons.

While this balance of energy between movement and cell biology happens in very small ways, it holds enormous implications for the future. Understanding how cells behave in their environment opens the door to understanding cell migration during developmental, disease, and repair biology.

In addition to the scientific advances of this project, Gov commented on the value of this work to the collaborative enterprise.

This collaboration already produced several publications and demonstrates how science is being done today through collaborations between people from different countries, continents, and ethnic and national backgrounds, he said. Beyond the curiosity and love of science, what unites us are the liberal ideals of freedom, human rights, and mutual respect and solidarity between all people.

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Virginia Tech and Weizmann Institute of Science tackle cell ... - Virginia Tech

Neuroscience

Human Brain Organoids Reveal How Microglia Develop and Function – Neuroscience News

Summary: Researchers have developed human brain organoids that contain microglia, the immune cells of the brain. These organoids allow researchers to study how microglia develop and function in a more realistic setting than previous models.

The researchers found that microglia are influenced by the environment in which they develop and that they play a role in both development and disease. Their findings could lead to new treatments for neurological disorders.

Key Facts:

Source: Salk Institute

Situated at the intersection of the human immune system and the brain are microglia, specialized brain immune cells that play a crucial role in development and disease. Although the importance of microglia is undisputed, modeling and studying them has remained a difficult task.

Unlike some human cells that can be studied outside of the body or in nonhuman models, human microglia are difficult to study when removed from the human-brain-like environment.

To overcome this barrier, Salk scientists developed an organoid modela three-dimensional collection of cells that mimics features of human tissues. This model allows researchers to study human microglial development and function for the first time in living human-derived tissue.

Further, the scientists examined patient-derived microglia from children with macrocephalic autism spectrum disorder (a condition where infant head circumference is greater than 97 percent of other infants) to determine whether brain environment influences the development of more reactive microglia.

The findings, published inCellon May 11, 2023, highlight the importance of immune cell and brain interaction, and improve the understanding of neurodegenerative and developmental diseases, such as autism spectrum disorder and Alzheimers disease.

Outside of the brain environment, microglia lose almost all function and meaning, says ProfessorRusty Gage, senior author and holder of the Vi and John Alder Chair for Research on Age-Related Neurodegenerative Disease.

We knew that if we found a way to replicate the human brain environment in an organoid in order to study human microglia, then we would finally have a tool for examining how the heathy and diseased brain influence microglia and, reciprocally, how healthy and diseased microglia influence the brain.

Emerging roughly 10 years ago, organoids have become a prevalent tool to bridge the gap between cell and human studies. Organoids can mimic human development and organ generation better than other laboratory systems, allowing researchers to study how drugs or diseases affect human cells in a more realistic setting.

Brain organoids are typically grown in culture dishes, but the organoids are structurally and functionally limited by the lack of blood vessels, short survival time, and inability to sustain diverse cell types (like microglia).

To createabrainorganoid model thatcontainsmature microgliaand enables us to research them, we used a noveltransplantationtechnique to create a human-brain-like environment says co-first author Abed Mansour, aformerpostdoctoral researcher in Gages lab and now an assistant professor at the Hebrew University of Jerusalem.

So we could finally make a human brain organoid that had all the features necessary to orchestrate human microglia growth, behavior, and function.

Unlike previous models, the researchers created a human brain organoid that had microgliaanda human-brain-like environment, which finally allowed them to look at environmental influences on microglia throughout brain development.

They found that a characteristic protein called SALL1 appeared as early as eleven weeks into development and served to confirm microglial identity and promote mature function. Additionally, they found that brain environment-specific factors, like the proteins TMEM119 and P2RY12, were necessary for microglia to function.

Creating a human brain model that can effectively replicate the human brain environment is very exciting, says Associate ProfessorAxel Nimmerjahn, another author of the study.

With this model, we can finally investigate how human microglia function within the human brain environment.

As the team learned more about microglia, the importance of the relationship between brain environment and microglia became clearespecially in disease scenarios.

The labpreviously examinedneurons derived from people with autism spectrum disorder and found their neurons grew faster and had more complex branches than neurotypical counterparts.

With the new organoid model, the team could ask whether those neuronal differences altered the brain environment and influenced microglia development.

To do so, they compared microglia derived from skin samples from three individuals with macrocephalic autism spectrum disorder versus three neurotypical individuals with macrocephaly.

The researchers found that individuals with autism spectrum disorder exhibited the neuronal differences the team had previously noted, and that the microglia were influenced by those differences in their growth environment.

Because of this neuron-dependent environmental change, the microglia became more reactive to damage or intrudersa finding that may explain the brain inflammation observed in some individuals with autism spectrum disorder.

Since this was a preliminary study with a small sample size, the team plans to examine more microglia from additional people in the future to verify their findings. They also aim to expand their research to study other developmental and neurodegenerative diseases to see how microglia are contributing to disease onset.

Rather than deconstruct the brain, we decided to construct it ourselves, says co-first author Simon Schafer, a former postdoctoral researcher in Gages lab and now an assistant professor at Technical University of Munich.

By building our own brain model we can work from the bottom up and see solutions that may be impossible to see from the top down. We are eager to continue improving on our model and unravelling the relationship between the brain and immune system.

Other authors include Monique Pena, Saeed Ghassemzadeh, Lisa Mitchell, Amanda Mar, Daphne Quang, Sarah Stumpf, and Clara Baek of the Salk Institute; Johannes C. M. Schlachetzki, Addison J. Lana, and Christopher K. Glass of UC San Diego; Irene Santisteban of the Technical University of Munich; and Raghad Zaghal of the Hebrew University of Jerusalem.

Funding: The work was supported by the National Institutes of Health (R01 AG056306, R01 AG057706, R01 AG056511, R01 AG061060, R01 NS108034, U19 NS123719, NCI CCSG: P30 014195, NCI CCSG: P30 014195), the American Heart Association and Paul G. Allen Frontiers Group (grant 19PABHI34610000), the Brain and Behavior Research Foundation (27685 and 30421), the German Research Foundation (500300695), the Milky Way Research Foundation, Annette C. Merle-Smith and the Robert and Mary Jane Engman Foundation, the European Molecular Biology Organization (ALTF 1214-2014), the Human Frontier Science Program (LT001074/2015), the European Research Council, the Chapman Foundation, the JBP Foundation and the Helmsley Charitable Trust.

Author: Salk CommunicationsSource: Salk InstituteContact: Salk Communications Salk InstituteImage: The image is credited to Neuroscience News

Original Research: Open access.An in vivo neuroimmune organoid model to study human microglia phenotypes by Rusty Gage et al. Cell

Abstract

An in vivo neuroimmune organoid model to study human microglia phenotypes

Microglia are specialized brain-resident macrophages that play crucial roles in brain development, homeostasis, and disease. However, until now, the ability to model interactions between the human brain environment and microglia has been severely limited.

To overcome these limitations, we developed aninvivoxenotransplantation approach that allows us to study functionally mature human microglia (hMGs) that operate within a physiologically relevant, vascularized immunocompetent human brain organoid (iHBO) model.

Our data show that organoid-resident hMGs gain human-specific transcriptomic signatures that closely resemble theirinvivocounterparts.Invivotwo-photon imaging reveals that hMGs actively engage in surveilling the human brain environment, react to local injuries, and respond to systemic inflammatory cues.

Finally, we demonstrate that the transplanted iHBOs developed here offer the unprecedented opportunity to study functional human microglia phenotypes in health and disease and provide experimental evidence for a brain-environment-induced immune response in a patient-specific model of autism with macrocephaly.

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Human Brain Organoids Reveal How Microglia Develop and Function - Neuroscience News

Neuroscience

Grey Matters celebrates the 10th anniversary of ‘An Evening with … – Dailyuw

On May 5, Grey Matters hosted their 10th annual An Evening with Neuroscience event, which featured numerous panelists sharing their expertise on neuroscience to the general public.

The event started with a series of interactive neuroscience activities, followed by a brain dissection, and ended with an open forum for questions. The annual event serves as a space where the UW community can not only interact with researchers, psychologists, and clinicians, but also learn about the brain. This years evening began with a dissection of a human brain and spinal cord.

Grey Matters is a student-run organization at UW focused on making science accessible to everyone. The group strives to produce scientific literature digestible to the general public.

Assistant professor Sam Golden and associate professor Ajay Dhaka from the department of biological structure presented the different parts of the brain, their functions, and the ways in which they interact with the body. This was an educational demonstration, meant to be understood by the general public.

Moving toward the forum section of the event, panelists held a Q&A for audience members covering the neuroscience field.

Some of the more prominent topics that came up were issues regarding funding and resource allocation, particularly with international research. Ananya Chowdhury, a research scientist at the Allen Institute for Brain Science, described her experience as an international researcher, and how limiting borders can be for the exploration of the neuroscience field. Dr. Thabele Leslie-Mazwi, chair of the department of neurology, noted that this was a significant problem he noticed as well.

Theres no geography of talent, Leslie-Mazwi said. Theres no geography of motivation, though theres definitely a geography of opportunity.

One guest asked how caution should be applied to newer neuroscience research.

To answer this, Oliver Rollins, assistant professor of American ethnic studies, discussed the intersections between predicting predisposed violence in people based on brain chemistry and the systemic inequalities that affect individuals growing up.

Rollins described how often neuroscientists analyze at-risk behaviors of individuals without looking at factors in the environment around them that have an equal, if not greater, impact on their brains.

If we cant think about embedded inequalities like sexism, or racism, or any of these things which absolutely affect social behaviors, it raises the question of what this model is actually predicting, Rollins said.

Reach contributing writer Sophia Moran at news@dailyuw.com. Twitter: @sophiasmoran

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Grey Matters celebrates the 10th anniversary of 'An Evening with ... - Dailyuw

Cardiology

Radiation Scatter 101: Risks, Dangers and Latest Solutions – Diagnostic and Interventional Cardiology

Invented in 1896 by Enrico Salvioni, the fluoroscope remains a flagship technology of modern medicine. The live video X-ray image it provides can guide a catheter safely through a living patients circulatory system, delivering a therapeutic action precisely where needed. As an interventional cardiologist, Id be blind without my fluoroscope, and the life-saving procedures it permits would be impossible.

Unfortunately, the machines great power comes from the X-ray beam it uses to penetrate and image the human bodys interior. The very high frequency, short wavelength electromagnetic radiation generated in its X-ray tube is a well-known danger to living beings, and must be very carefully controlled. Most of us who work with radiation in medical applications believe we are controlling it, but that may stem more from complacency than from facts.

Within the last decade, studies have revealed that interventional cardiology and cardiac electrophysiology staff experience increased rates of cancer, skin lesions, cataracts and orthopedic illnesses as compared with their unexposed colleagues, even though they had adhered to international and federal radiation dose limits. These maladies increased with the amount of time spent conducting interventions.

While the diagnostic and treatment benefits of radiologic medicine are far too valuable to give up, we deny its downside at our peril: an increased risk of debilitating and potentially lethal health effects for the doctors, nurses, technicians and other staff who work in the catheterization lab daily and absorb small amounts of scatter radiation repeatedly over the course of their careers.

This risk is compounded by the trend toward higher-power machines to produce sharper images. Its the Catch-22 of a life in the catheterization lab: the better fluoroscopes get at helping our patients, the more they seem to hurt our healthcare team.

While most healthcare providers know about the dangers of direct radiation and take steps to avoid exposure, the threat of scatter radiation is less commonly understood. But over time, it can be just as dangerous. To help them grasp the concept, I tell my students to think of a high-tech heist movie, where the treasure to be stolen is protected behind a wall of crisscrossing laser beams: when you break one beam the alarm sounds. Its much the same with scatter radiation in the cath lab, except that the beams are invisible and harmful, and no alarm sounds when we move through them.

Thats why its a good idea, from time to time, to refresh our understanding of the risks and dangers of scatter radiation during fluoroscopic interventions, along with the best practices and new technologies that are making it easier to stay safer in the cath lab. With these in place, we no longer have to choose between improving our patients health and protecting our own.

Over more than a century using radiation in medical applications, weve learned a lot about what it can do, for better and worse. Unseen but for the damage it leaves behind, ionizing radiation is dangerous both acutely in higher doses and cumulatively in lower doses over time, as happens with scatter radiation in the catheterization lab.

The damage it can wreak on the human body takes one or more of the following forms:

Direct effects. These injuries result from acute overexposure to a directed radiation beam or proximity to a radioactive substance such as uranium, and can include all levels of burns to the skin and underlying tissue, radiation sickness, and death. Modern medical equipment is designed to prevent such massive overdoses.

Stochastic effects. Like an insidious poison, low doses of radiation repeated over time can increase ones risk of acquiring naturally occurring cancers. This is because radiation damages the genetic code deep within cell nuclei, increasing the chance that mistakes in the repair process could lead to a cancer-causing mutation to be incorrectly inserted into ones DNA. Stochastic effects for cath lab staff also include cataracts and cognitive problems.

Genetic effects. Damage to a chromosome that is repaired with an incorrect sequence can cause serious genetic mayhem, and it can be passed on to subsequent generations.

Embryo and fetus effects. A developing child is particularly vulnerable to radiations dose-dependent effects, which can include death or congenital abnormalities that appear at birth or later in life.

For fluoroscope users like me, no list of radiations dangers would be complete without mentioning the pain, fatigue and occasionally debilitating effects caused by wearing heavy garments, an antiquated but still technically effective way to protect staff. In fact, Ive known cath lab colleagues who were forced to retire from the field due to long-term damage caused by these cumbersome devices. With 12 years of training required for each interventional cardiologist, losing them to back pain seems a terrible waste of resources. Thankfully, lighter, lead-free alternatives are proliferating along with non-apparel methods to protect the whole room, and these will form the core of an effective 21st century fix for the problem.

The solution to radiation exposure is radiation protection, and when it comes to policies that can best protect cath lab staff from scatter radiation, the guiding principle must be ALARA, the acronym for as low as reasonably achievable. It means in all instances ones mindset should be to use the minimum amount of radiation to get the job done and produce the least exposure. This is especially important when it comes to personal protective equipment, as forgetting to don it before entering the danger zone can lead to real trouble. A protective gear checklist to review when suiting up can help, as well as maintaining an environment where staff are encouraged to continually check each others safety status.

Time, distance, shielding and dose monitoring are the time-tested pillars of radiation protection in medical settings. Combined with an ALARA mindset, they imply the following directives:

Time. Minimize your time operating the fluoroscope or being in the room while its on.

Distance. Maximize your distance from the radiation source. Two steps away from the table cuts your exposure by half.

Shielding. Put as much shielding as possible between you and the radiation source.

Monitoring. Wear a personal dosimeter to monitor and gauge your exposure.

Ultimately, all cath lab staff should be fully educated on scatter radiations dangers and the policies, practices, and technologies in use to defeat it.

Fluoroscopic image quality can suffer from insufficient power, usually because the image is too noisy or cluttered for a low dose scan. High dose settings (sometimes called detail mode) can improve image quality by boosting contrast, but this sends more radiation to the patient and more scatter into the room. In practice most of the time, the low power setting produces an excellent though slightly less sharp image, with no practical reduction in diagnostic value.

The following habits can also minimize overexposure due to machine settings:

Higher magnification and frame rates increase radiation overall, so use lower settings for these features unless a higher one is necessary.

Use the fluoro save feature to save the last image and reduce the need for more imaging.

Place lead drapes under the patient table, avoiding obstructions to C-arm travel.

Put the X-ray source under the patient table as far away as possible to reduce scatter radiation by directing it through the table and patient before it reaches staff, and place the X-ray detector as close to the patent as possible to produce the sharpest image.

Use tubing extensions to maintain a two-step distance from the table during imaging.

Avoid using the fluoroscope if a non-radiological imaging device can do the job; ultrasound, magnetic resonance imaging (MRI), optical coherence tomography (OCT), intravascular ultrasound (IVUS) or transesophageal echo (TEE) might be a safer alternative.

Other factors that can affect radiation scatter include larger patients. Modern fluoroscopes with automatic brightness control (ABC) will increase their power to penetrate patients with thicker or denser than average bodies. In these cases, the fluoroscopist should check if the ABC can be turned off and still produce an acceptable image.

A technological fix is always tempting, but we must remember that scatter radiation is a problem that sprang from a previous technological fix the use of X-rays to image the inner body. Every device designed to solve this problem will likely have positive and negative aspects that warrant careful consideration, and you may have to change the way you practice to reap all the benefits they promise.

Anyone who has worn leaden shielding garments for this type of work will be quick to suggest lightening the load, and modern medical science is answering the call with lead-free alternatives that dramatically reduce weight without sacrificing shielding power. Removing toxic lead from shielding also prevents it from finding its way into our environment, which is another win for healthcare.

Companies such as RadPad and Vitalcare Products produce a range of lead-free pads, table skirts, drapes, and other innovative shield types that are sterilizable and disposable. They are a simple and less expensive way to put shielding where needed, they keep the ALARA principle alive, and they serve as a helpful adjunct to more complicated, high-tech systems.

The Zero-gravity drape wrap from TIDI Products is one such step up in technical complexity. It offers security, light weight and ease of movement through a suspended lead-acrylic head shield that protects the operator from overexposure while working with the fluoroscope. Its chief advantage is in reducing strain on the back, neck, shoulder, hips, knees and ankles.

Of course, the holy grail of cath lab radiation protection will be a system that protects everyone in the room, and early attempts at such systems have begun to appear.

For example, Egg Medicals EggNest cath lab table reduces overall scatter by up to 91%, and Ramparts IC M1 123 independently adjustable acrylic shielding panels give it multiple vascular access points and may block enough X-ray scatter that lead aprons are not required.

Radiaction Medicals approach to full room protection relies on intuitive controls and an ingenious design to reduce scatter radiation by up to 90%, with up to a 97% reduction to the operators head, face and neck. The device doesnt impede access to the patient, and data indicate it may eliminate the need for up to 75% of protective lead apparel. It attaches unobtrusively to the fluoroscopes C-arm and deploys robotically on command, extending shielding panels that conform to the patients body and to the rotational angle of the C-arm. Afterward, the Radiaction device retracts quickly, minimizing its small footprint even further.

The EggNest radiation protection system reduces radiation exposure without compromising workflow. Image courtesy of Egg Medical.

Safer fluoroscopic interventions are both possible and necessary, but addressing the dangers of scatter radiation in interventional suites requires a commitment from all involved, from staff who must religiously follow safety protocols to administrators who must provide appropriate, effective tools to ensure our workplace safety. Fortunately for all of us, awareness is spreading, technology is progressing, and a bright future of long, healthy careers in radiologic medicine is well within our grasp.

Mohammad Sahebjalal, MD, is an Interventional Consultant Cardiologist at Musgrove Park Hospital. He was appointed in 2017 making him, at the time, one of the youngest interventional consultants in the UK.

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Link:

Radiation Scatter 101: Risks, Dangers and Latest Solutions - Diagnostic and Interventional Cardiology

Organic Chemistry

Could Chemicals Have Caused Michael J. Fox’s Parkinson’s? It’s … – American Council on Science and Health

From a chemist's perspective, perhaps the most intriguingpart ofFox's recentinterview with Jane Pauleyof CBS Newswas his admission that he may have inadvertently donesomethingthatcontributed to his development of Parkinson's. Pauley,alluding toaprior commentthat Fox made in 2022 during an award ceremony, asked"Is it possible youdidsome damage?"

His answer:

"Yeah, very possible. ... I mean, there's so many ways that you can, that I could've hurt myself. I could've hit my head. I could've drank too much at a certain developmental period. Most likely I think is, that I was exposed to some kind of chemical. What we say is that genetics loads the gun and environment pulls the trigger."

Why is this quote so intriguing? Because it's happened before, albeit under different circumstances.And the culprit was indeed "some kind of chemical," but it wasn't alcohol or anything in the environment. In 1982a group of heroin addicts who injected a bad batch of an analog of Demeroldeveloped severe Parkinson's symptoms in days, not years. The drug, which is called MPPPwas contaminated with a highly neurotoxic impurity and the results wereboth astonishing and horrifying. The incident can be traced back to 1976 when a graduate student made a bad mistake in the lab. Thereis even a bookabout the incident, although the author gets the chemistry wrong.

Nope, it was not heroin

Demerolis now rarely used and MPPP the Demerol analog that did the damage was certainly notthe cause of Fox's disease; this drug is long gone. But it left a legacy that contributed to the understanding of Parkinson's.

###

(Below is an updated version of a similar article I wrote on this topic in 2017.)

Frozen Addicts, Garage Drugs, And Funky Brain Chemistry

In the 1970s chemists in the illicit drug business began exploring a new class of psychoactive drugs, which were structurally related to the synthetic opiate Demerol. The following story is trulyone-in-a-million. It encompassesthe first"designer drug," (1)the organic chemistry used to make it, and what can (and did) happen when a reaction procedure is not conducted properly. On a "positive" note, theincident did result ina deeper understanding of the molecular mechanism of Parkinson's Disease. It also makes for a fascinating story.

The story began in 1947 when Demerol was discovered at Hoffman-La-Roche. At that time, drug companies were searching for pain-killing drugs that did not have the baggage of standard opioid drugs, such as hydrocodoneand oxycodone (2). In fact, desmethylprodine(MPPP), which is considered to be the first designer drug,was also discovered at Roche around that time, but, unlike Demerol, it was never approved.

Figure 2. The chemical structures of Demerol (L) andDesmethylprodine (R)

Similar chemicals can act very differently

Even people with little or no chemistry knowledgecansee that the two molecules in Figure 1 arenearly identical in structure. The only difference is thefunctional group (red circle) that isfound on the piperidine ring (green circle). In Demerol, the carbonyl group (carbon double bond to oxygen) is attached to the piperidinering. But inMPPP, an isomer (2) of Demerol, the carbonyl group and oxygen atom are switched, so that oxygen is attached to thepiperidine ring. While this may seem like a trivial difference, chemically it is anything butsomething that Barry Kidston, a chemistry grad student,would find out the hard way in 1976.

Barry Kidston Photo: Facebook

Things start to go South

Kidstonwas interested in discoveringlegal narcotics for his own use. Since MPPP, which hasmorphine-like properties, was neitherapproved, nor designated as aScheduleI drug (3),it was perfectly legal to make or usesomething that Kidston did for months. Then he got a little sloppy with his chemistry, and the results were disastrous. The mishap was simply a matter of his failure to control the temperature of the MPPP-formingreaction. For organic chemists, the results of this mistakeare not only logical but predictable. What happened after that was anything but.

The chemical reactionbelow showsthe final step in Kidston'sMPPP synthesis (its precursor, HPMP, is easy to synthesize). It's a common, usuallytrivial procedure called acylation (Figure 3).

Figure 3. Synthesis of MPPP. When HPMP is reacted with propionic anhydride MPPP, the desired drug, is formed. But ifthe reaction temperature rises about 30oC some ofthe MPPP is converted to MPTP, a toxic impurity,

Any organic chemist will tell you that thebond denoted by the yellow arrow is just dying to break, and it doesn't take much to give it its wish. A little extra heat and that bond breaks, and then through a process called elimination,the propionylgroup (blue oval) departs and is replaced by a carbon-carbon double bond. Then, instead of pure MPPP, you have the drug plus unwanted MPTP as an impurity.

If you're asking yourself "What's the harm in having a bit of an impurity in there?" the answer is "usually not much." But in this particular case, the impurity did something unprecedentedin the brain, which is what makes this storyso unique.

MPTP (unfortunately) goes to the brain, which becomes its own worst enemy

Any experienced medicinal chemist will look at the structure of MPTP and know that it is very likely to have the properties that will allow it to cross the blood-brain barrier, which it does. This is whenthings wentvery wrong. MPTP itself isn't particularly toxic, but it getsmetabolizedin the brain to MPP+, a chemical that you do not want in your brain. Unfortunately for Kidston, he was the lab rat who would inadvertently provide the science world witha fascinating, but deadly lesson in neurochemistry. Shown below is the metabolism that is responsible for a previously-unheard of event:

Oxidation of MPTP to MPP+ by monoamineoxidase in the brain

A ubiquitous family of enzymes called monoamine oxidases (MAO) is responsible for the formation and metabolism of multiple neurochemicals. As such, it plays a critical role in the regulation of the central nervous system. In this case, MPTP was a substrate forMAO, whichoxidized it to MPP+. Assuming that enzymes can make "mistakes," this is one a doozybecause MPP+ is seriously bad news. It is now known that ithas a particular fondness for the cells in the region of the brain called thesubstantia nigra. And once it gets there, all hell breaks loose (4).MPP+ specifically kills thedopaminergic neurons in thesubstantia nigra, where dopamine is normally made.The absence of dopamine is the hallmark of Parkinson's.

The bad batch of MPPP thatKidstoninjected into himself resulted in the development of strange symptoms within a few days. He experienced bradykinesia a severe slowing of movement. It became so bad that Kidstonwas admitted to a hospital where he was diagnosed with Parkinson's Disease, which is very rare in young people. Nonetheless, Kidston did getParkinson's froma single injection of an impure drug.

Doctors tried a variety of neuroleptic drugs with no success and then used L-dopa, which was first tried on Parkinson's patients (with mixed success) in the 1960s. It worked on Kidston, at least for a while. L-dopaloses effectiveness with time. This happened to Kidston, who became severely depressed and died of a cocaine overdose 18 months later.

The link between MPTPandKidston'sParkinson's Disease was determined by analysis of the residue of the drug that remained on the glassware he used. The impurities were isolated, identified, and tested.Kidstonhadunknowingly writtena chapteron the neurochemistry of Parkinson's Disease at his own expense.

Frozen addicts

The MPP+ story did not end with Kidston. In California in 1982, a cluster of six drug users who had taken "China White" (5)all came down with Parkinson-like symptoms (6). When the drug was analyzed, there it was MPTP, which was a result of a drug dealer trying to do organic synthesis in his garage. The reason forthe term "frozen addicts" could not be more clear:

A Frozen Addict from 1982. Source: Neurology Update.

Organic synthesis is both science and art something that anyone who takes street drugs should consider. It requires both skill and experience to get it right. A drug dealer working in a garage is probably not going to get it right.

Bottom Line

Whatever causedFox's Parkinson's may or may not have been related to an injury, drinking, or exposure to a chemical or drug (note: he did not say that he took any drugs). We will never know.The storiesofBarry Kidston and Fox only 15 years apart (7) intersect only in that two young men were struck by a terrible disease very early in life.Kidston's disease was clearlyself-inflicted and its role in causingParkinson's has been rigorously proven in animal models.On the other hand, what Fox expressed about the possibility ofhis Parkinson's being linked to chemical exposure isn't impossible; it's just unlikely(8).

It is more than 47 years since Kidston's blunder and 30 since Fox's diagnosis. With the exception of Kidson's sloppy chemistry,there is still no clear answer for what causes this awful condition.

Notes:

(1) Although there is no strict definition of a designer drug, it usually refers to a new drug that isderived by synthetic modification ofa psychoactive legal, approved drug.

(2) Neither has anyone else. There are still no good alternatives to opioids for moderate-to-severe pain.

(3) Isomers are chemicals that have the same molecular formula, but different structures and (usually) different properties.

(4) Schedule I drugs are not approved for use in people and have a high addiction potential.

(5) China White is one of the street names for fentanyl, the drug that is now killing opioid addicts in droves.

(6) Almost anyone looking at the chemical structures of MPP+ and the herbicide paraquat (below) would conclude that they would act in a similar manner. That is how similar their structures are.But they do not. Paraquat's primary toxicity is in the lungs. This is almost certainly due to the fact that the herbicide does not have properties that would allow it to cross the blood-brain barrier. Neither does MPP+, but keep in mind that MPP+ enters the brain as its precursor MPTP, which has just the right properties to do so.

The chemical structures of MPP+ and the herbicide Paraquatan eerie resemblance. Source: Science and Education Publishing

(7) Kidston poisoned himself in 1976. Fox was diagnosed in 1991.

(8) No matter what, if any, toxic chemicalFox wasexposed to, the chances of it being a toxic batch of a Demerol analog are essentially nil. Kidston'simpure drug was a one-in-a-million, freaky incident.

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Could Chemicals Have Caused Michael J. Fox's Parkinson's? It's ... - American Council on Science and Health

Physiology

New tusk-analysis techniques reveal surging testosterone in male … – EurekAlert

Graphics //Video

Traces of sex hormones extracted from a woolly mammoth's tusk provide the first direct evidence that adult males experienced musth, a testosterone-driven episode of heightened aggression against rival males, according to a new University of Michigan-led study.

In male elephants, elevated testosterone during musth was previously recognized from blood and urine tests. Musth battles in extinct relatives of modern elephants have been inferred from skeletal injuries, broken tusk tips and other indirect lines of evidence.

But the new study, scheduled for online publication May 3 in the journal Nature, is the first to show that testosterone levels are recorded in the growth layers of mammoth and elephant tusks.

The U-M researchers and their international colleagues report annually recurring testosterone surgesup to 10 times higher than baseline levelswithin a permafrost-preserved woolly mammoth tusk from Siberia. The adult male mammoth lived more than 33,000 years ago.

The testosterone surges seen in the mammoth tusk are consistent with musth-related testosterone peaks the researchers observed in an African bull elephant tusk, according to the study authors. The word "musth" comes from the Hindi and Urdu word for intoxicated.

"Temporal patterns of testosterone preserved in fossil tusks show that, like modern elephants, mature bull mammoths experienced musth," said study lead authorMichael Cherney, a research affiliate at the U-M Museum of Paleontology and a research fellow at the U-M Medical School.

The study demonstrates that both modern and ancient tusks hold traces of testosterone and other steroid hormones. These chemical compounds are incorporated into dentin, the mineralized tissue that makes up the interior portion of all teeth (tusks are elongated upper incisor teeth).

"This study establishes dentin as a useful repository for some hormones and sets the stage for further advances in the developing field of paleoendocrinology," Cherney said. "In addition to broad applications in zoology and paleontology, tooth-hormone records could support medical, forensic and archaeological studies."

Hormones are signaling molecules that help regulate physiology and behavior. Testosterone is the main sex hormone in male vertebrates and is part of the steroid group of hormones. It circulates in the bloodstream and accumulates in various tissues.

Scientists have previously analyzed steroid hormones present in human and animal hair, nails, bones and teeth, in both modern and ancient contexts. But the significance and value of such hormone records have been the subject of ongoing scrutiny and debate.

The authors of the new Nature study say their findings should help change that by demonstrating that steroid records in teeth can provide meaningful biological information that sometimes persists for thousands of years.

"Tusks hold particular promise for reconstructing aspects of mammoth life history because they preserve a record of growth in layers of dentin that form throughout an individual's life," said study co-authorDaniel Fisher, a curator at the U-M Museum of Paleontology and professor in the Department of Earth and Environmental Sciences.

"Because musth is associated with dramatically elevated testosterone in modern elephants, it provides a starting point for assessing the feasibility of using hormones preserved in tusk growth records to investigate temporal changes in endocrine physiology," said Fisher, who is also a professor in the U-M Department of Ecology and Evolutionary Biology.

For the study, researchers sampled tusks from one adult African bull elephant and two adult woolly mammothsa male and a femalefrom Siberia. The samples were obtained in accordance with relevant laws and with appropriate permits.

The researchers used CT scans to identify annual growth increments within the tusks. A tiny drill bit, operated under a microscope and moved across a block of dentin using computer-actuated stepper motors, was used to grind contiguous half-millimeter-wide samples representing approximately monthly intervals of dentin growth.

The powder produced during this milling process was collected and chemically analyzed.

The study required new methods, developed in the laboratory of U-M endocrinologist and study co-authorRich Auchus, to extract steroids from tusk dentin for measurement with a mass spectrometer, an instrument that identifies chemical substances by sorting ions according to their mass and charge.

"We had developed steroid mass spectrometry methods for human blood and saliva samples, and we have used them extensively for clinical research studies. But never in a million years did I imagine that we would be using these techniques to explore 'paleoendocrinology,'" said Auchus, professor of internal medicine and pharmacology at the U-M Medical School.

"We did have to modify the method some, because those tusk powders were the dirtiest samples we ever analyzed. When Mike (Cherney) showed me the data from the elephant tusks, I was flabbergasted. Then we saw the same patterns in the mammothwow!"

The African bull elephant is believed to have been 30 to 40 years old when it was killed by a hunter in Botswana in 1963. According to estimates based on growth layers in its tusk, the male woolly mammoth lived to be about 55 years old. Its right tusk was discovered by a diamond-mining company in Siberia in 2007. Radiocarbon dating revealed that the animal lived 33,291 to 38,866 years ago.

The tusk from the female woolly mammoth was discovered on Wrangel Island, which was connected to northeast Siberia in glacial periods of lower sea level but is now separated from it by the Arctic Ocean. Carbon-dating showed an age of 5,597 to 5,885 years before present. (Wrangel Island is the last known place where woolly mammoths survived, until around 4,000 years ago.)

In contrast to the male tusks, testosterone levels from the female woolly mammoth tusk showed little variation over timeas expectedand the average testosterone level was lower than the lowest values in the male mammoth's tusk records.

"With reliable results for some steroids from samples as small as 5 mg of dentin, these methods could be used to investigate records of organisms with smaller teeth, including humans and other hominids," the authors wrote. "Endocrine records in modern and ancient dentin provide a new approach to investigating reproductive ecology, life history, population dynamics, disease, and behavior in modern and prehistoric contexts."

In addition to Cherney, Fisher and Auchus, the authors of the Nature study are Adam Rountrey and Scott Beld of the U-M Museum of Paleontology; Perrin Selcer of the U-M Department of History and the Program in the Environment; Ethan Shirley of the U-M Museum of Paleontology and the Department of Earth and Environmental Sciences; Bernard Buigues of Mammuthus, France; Dick Mol of the Natural History Museum in Rotterdam, Netherlands; Gennady Boeskorov of the Siberian Branch of the Russian Academy of Sciences; Sergey Vartanyan of the Far-East Branch of the Russian Academy of Sciences; and Alexei Tikhonov of the Russian Academy of Sciences and North-Eastern Federal University in Yakutsk, Russia.

Tusk specimens were CT scanned using laboratories at the U-M School of Dentistry, Ford Motor Co., U-M Department of Earth and Environmental Sciences, and U-M Orthopaedic Research Laboratories. The study received support from U-M's seed funding program for innovative interdepartmental collaborations, Mcubed 3.0.

"This is one of the reasons we come to work every morning at the University of Michigan: to make discoveries that empower us to see the world in new ways," co-authorSelcersaid. "The project shows you the importance of both collaboration across schoolsthanks to Mcubed 3.0and of the university's instrumentation infrastructure."

Study (available once embargo lifts):Testosterone histories from tusks reveal woolly mammoth musth episodes(DOI 10.1038/s41586-023-06020-9)

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New tusk-analysis techniques reveal surging testosterone in male ... - EurekAlert

Biology

Biologists compare and select most effective and nontoxic biocides for mobile toilets and dump wells – Phys.org

This article has been reviewed according to ScienceX's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility:

by Russian Foundation for Basic Research

In agriculture, country houses and many other places without central sewerage, people use mobile toilets or dump wells. To prevent the foul smell in the bench-holes and during transportation of the contents to wastewater treatment facilities, biocides are added, which are chemical compounds that stop the activity of microorganisms.

However, biocides can harm the environment and hinder the work of wastewater treatment facilities. Toxic biocides can also make waste unsuitable for further use as biofertilizers and biofuel production. Russian scientists have proposed the solution to this problem in the journal Biology.

In Russia, about 22.6% of citizens live without central sewerage (according to Rosstat of 2019). In rural areas, this figure rises to 66.5%. Vacuum trucks pump out waste from dump wells and mobile toilets and take it to wastewater treatment facilities. Biocides, such as quaternary ammonium compounds and biguanide derivatives, help prevent the activity of odor-causing microorganisms during storage and transport of waste.

Biocidal agents based on these compoundsfor example, Latrinaare very effective, but make the waste toxic because they decompose very slowly. Thus, they can harm the environment and kill microorganisms in wastewater treatment facilities. Scientists of the Russian Academy of Sciences compared various popular biocides and selected among the most effective ones, which are those that decompose into non-toxic components soon after they have fulfilled their function.

"In dump wells and mobile toilets, urea decomposes slowly, emitting ammonium, which makes the environment alkalineits pH can grow up to 910. Biocides that decompose in an alkaline environment help to accomplish two goals at once: at first, they lower the activity of harmful bacteria, then break up and thus don't harm the environment. We checked the results after 10 daysthe period that is needed, for example, for full admission of toilets on main-line trains," says Yuriy Litti, Ph.D, of the Russian Academy of Sciences.

Scientists selected six biocides that have no smell, are non-toxic in the used concentration and decompose when pH exceeds 7. Together with his colleagues, Yuriy Litti tested the effect of these biocides on the microorganisms, and also checked how well these agents decompose in the presence of alkaline during 10 days.

From six often-used biocides, four turned out to be more environmentally sound: Bronopol (30 mgl), Sharomix (500 mg/l), sodium percarbonate (6 g/l), and the biocidal agent on the base of 2,2 -dibro-3-nitrilopropionamide (500mg/l). Whereas popular biocidal agents like, for example, Latrina, remain for a long time in the environment and do not decompose. Silver citrate and sodium salt of dehydroacetic acid were excluded from the experiment, although they also decompose rapidly in the alkaline environment. They were required in too high a dosage, so the scientists decided that, given the high cost, these options are very expensive for consumers.

"In an alkaline environment, when pH reached 9, the minimal concentration of Bronopol , Sharomix ,and 2,2 -dibro-3-nitrilopropionamide necessary for stopping the growth of harmful microorganisms, increased by 1.5 to four times. It's useful for our purposes, because by decomposition of urea during its transportation, pH only grows. In the future we plan to study in more detail how selected biocides work not only in the laboratory, but in real conditions. If successful, vacuum cleaners will know which products work best and cause less damage to the environment," said Yuriy Litti.

More information: Nataliya Loiko et al, Biocides with Controlled Degradation for Environmentally Friendly and Cost-Effective Fecal Sludge Management, Biology (2022). DOI: 10.3390/biology12010045

Provided by Russian Foundation for Basic Research

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Biologists compare and select most effective and nontoxic biocides for mobile toilets and dump wells - Phys.org

Biology

Retired Gov. Mifflin biology teacher reflects on 53 years of Earth Days – Reading Eagle

Donald Burger was active in the first Earth Days over 50 years ago as a science teacher in the Gov. Mifflin School District. He now enjoys Earth Day by watching the birds in his Cumru Township backyard feeding station. (BILL UHRICH - READING EAGLE)

Donald Burger relaxes in the sunroom of his Cumru Township home with his wife of 63 years Jean Ann, keeping a list of birds that visit his extensive feeding station outside for the Great Backyard Bird Count sponsored by Cornell University.

A bluebird flies up to a suet log and pecks away at the fat. Burger relates how one day recently he was looking up through the skylight and saw a bald eagle pass over their home.

Those two sights are rather commonplace now, but back during the first Earth Day in 1970, those two birds would not have been so easily found in Berks County, if at all.

Those were heady days for the environmental movement back in the spring of 1970, essentially because there was so much work that needed to be done.

And Burger, a biology teacher who started at Gov. Mifflin High School in 1956, was more than willing to pitch in.

U.S. Sen. Gaylord Nelson, a Wisconsin Democrat, founded the first Earth Day to raise awareness of impending legislation that would become the Clean Air Act.

Over 20 million Americans took part in activities in schools and colleges to highlight the environment.

Back then, there was bipartisan consensus on the importance of environmental protection, and under the administration of Republican President Richard M. Nixon, environmental legislation cascaded through Congress and to his desk for passage:

The Clean Air Act was passed a few months after the first Earth Day.

The Environmental Protection Agency was established in December 1970.

The EPA banned DDT in June 1972, which led to the comeback of the bald eagle, the osprey and the peregrine falcon, all birds that were almost wiped out due to eggshell thinning caused by the pesticide.

The Migratory Bird Treaty Act of 1918 was amended in 1972 to include all hawks and owls, blue jays and crows, providing federal protection to all native bird species in the U.S.

And the Endangered Species Act was passed in December 1973.

Those were teachable moments.

And Burger and his students embraced them all with a particular emphasis on recycling.

There is no away, Burger said, recalling the impetus that became the Gov. Mifflin Ecology Bus, a mobile recycling center that he and over 200 students ran for 11 years.

You throw away things, but they dont go anyplace, he said. Theyre still here.

Ill bet we collected enough material that would have completely filled the gymnasium.

Burger had been particularly concerned about the ubiquitous use of plastics since they persist in the environment. Microplastics have been recently found in the human body with yet unknown health effects.

The plastics dont break down, he said. There hasnt been any evolution of a bacteria that would digest plastic. So it stays in the landfill.

A more recent concern is climate change brought about by global warming.

When you think of deforestation in the Amazon, with the rise of carbon dioxide and of course the warming of the oceans, the North Atlantic, off in Maine, the waters of the Gulf of Maine have warmed, he said. Theres less phytoplankton, and it affects the food web along with excessive fertilization with the runoff into the streams that causes algae blooms.

Burger can see through something as simple as an individual bird how global warming is having an effect on the environment.

We have a little bird, a Carolina wren, I first saw them when we lived in Shillington around 1968, he said.

The bird was at its northern limits in Berks and often died off in severe winters but now is a year-round resident.

In my humble opinion, thats an example of the effect of global warming, he said. A southern bird has come north, and we have it here every day.

Burger can trace his interest in conservation to the inspiration of his own teachers in the Reading School District, with one in particular.

I ended up teaching at Gov. Mifflin for 37 years, he said. I wanted to become Sam Gundy.

Gundy was perhaps the most complete Berks County naturalist of the 20th century. He was mentored by Reading Public Museum founder Levi Mengel, taught biology in the Reading School District before becoming director of the museum, and finally closed out his career as a biology professor at Kutztown University. Gundy died in 2010 at age 92.

Gundy introduced Burger to Hawk Mountain and its curator Maurice Broun, and Burger followed up with taking his students to Hawk Mountain over the years.

Gundy also introduced Burger to the local Baird Ornithological Club, and in 1952 Burger became the youngest president of the organization at age 20.

Now, he said with a smile, Im the oldest former president.

Burger will celebrate his 91st birthday a little over a week after an Earth Day that will include watching the birds at his feeders.

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Retired Gov. Mifflin biology teacher reflects on 53 years of Earth Days - Reading Eagle

Biology

Searching for solutions to the impacts of climate change on human … – UChicago Medicine

The links between climate change and human health are becoming increasingly obvious: Pollution. Extreme weather events. Food scarcity. Pathogen spread.

Meet the University of Chicago Medicine researchers who are tackling this monumental issue, one challenge at a time.

In 2021, He and collaborators published a groundbreaking study showing that by inserting the FTO gene, which affects RNA modification, into rice, the plants grew three times more rice in the lab and 50% more rice in the field. The rice plants also grew longer roots, were better able to withstand stress from drought, and photosynthesized more efficiently. Additional experiments in potato plants yielded similar results.

Now He is the director of the Pritzker Plant Biology Center, a new space to expand his RNA modification work and the research of other scientists searching for innovative ways to promote plant growth and resilience and increase crop yield.

Were considering many layers of pathways for modulating plant growth, he said. RNA modification is one aspect, but were also looking at temperature sensing, because agriculture may have to move north as the climate warms, but northern regions will still be hit by extreme cold fronts, so well need to develop plants that can resist the cold and grow fast. We also need crop plants that can better withstand warm weather. We could even modulate photosynthesis to increase biomass and yield.

In the last several decades weve seen a huge amount of resources being put into human biology and health, and rightfully so, He said. But until now we have not paid enough attention to plant biology, and with climate change, this type of research is just as important.

She studies health disparities caused by social inequity, and wonders how they can be exacerbated by the pressures of climate change. We know that people with lower income, who are experiencing racism or violence, have much higher allostatic load than those who are not facing the same stressors, she said. That chronic activation of stress responses can increase stress hormones like cortisol, and over time that can directly impact health. Chronic stress contributes to a host of health problems, including cardiovascular disease, which is the largest contributor to the racial mortality gap.

Climate change is yet another source of inequity; those with the fewest resources and who are the most vulnerable are disproportionately affected by it, in everything from the rising cost of food to a lack of secure shelter from extreme weather events to increased risk of exposure to pollution and infectious disease.

An area of particular focus for Tung is the intersection between violence and health inequity. Violence is an outcome of inequity, she said. More than medical and mental healthcare, patients who are affected by violent injury will often say they need access to economic and legal resources. For example, eviction can be equally or more toxic to a person than not being able to fully rehab an injured leg. The chronicity of stress related to housing instability has major downstream effects on peoples lives and wellbeing. Add to that the effects of climate change on housing, which have already exacerbated the affordable housing crisis and increased housing damage due to flooding and other natural disasters.

These climate challenges will not only exacerbate existing health inequities, but will increase the strain on an already struggling healthcare system, making it ever more difficult for those most burdened by the effects of climate change to access the resources they need to survive it. The question isnt so much whether these issues will get worse in the future, but rather, how to address it.

Theres a big movement in the health sciences to place a greater emphasis on the social determinants of health, but this is an existential issue, said Tung. Most of the solutions currently available to us rely on addressing the specific needs of an individual person or patient, but they dont provide opportunities for systemic change. If wealth inequality continues to worsen, it will become even more difficult to sustain the services that we are able to offer. Its a never-ending cycle.

It constantly made me think about how different environments can lead to differences in our health, even when were working with a very similar genome, she said. It made me wonder how the biology works when were exposed to certain chemicals or radiation or even biological factors, like a virus. These things can put an imprint on our bodies, but we dont always know what the long-term effects will be.

Her current research focus is on understanding how exposure to UVB radiation and arsenic affect the role of RNA methylation in cancer development. She studies epitranscriptomics the modifications made to RNA that affect how and which proteins are produced within our cells.

She sees a connection between her work and climate change because it all comes back to one thing: human decisions. Climate change and pollution are deeply connected, He said. The chemicals we make and release into the atmosphere are a huge contributor to climate change. Humans are very innovative. However, we humans also create these unexpected and unintended consequences, but because it takes years for the toxic response to appear, we dont realize it right away.

Perhaps the most obvious connection between her work and climate change is one that has been mostly successfully addressed by policy change. Those who grew up in the 1990s likely remember learning about the hole in the ozone layer, caused by human use of chemicals such as chlorofluorocarbons. Ozone layer depletion allows more UVB rays to reach the planets surface, affecting everything from agriculture to marine ecosystems to cancer rates in humans. Thanks to international agreements reducing the use of chlorofluorocarbons in the 1980s, the ozone hole is slowly shrinking; but in the meantime, its effects still remain.

One of the challenges He faces is determining which RNA changes are significant. Weve seen RNA modifications in response to UV stress a few times, but we dont really know what the implication of that is, she said. There are classical responses, such as DNA damage, but epitranscriptomics is still in its infantry. We are probably one of the few groups looking at the unique connection between epitranscriptomics and the environment, which is helping us understand how dysfunction in the machinery caused by environmental exposures contributes to diseases.

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Searching for solutions to the impacts of climate change on human ... - UChicago Medicine

Anatomy

Anatomy of monster storm: how Cyclone Ilsa is shaping up to devastate the WA coast – The Conversation

Residents along Western Australias northwest coast are bracing for Tropical Cyclone Ilsa, which is expected to be one of the most destructive storms to strike the region in more than a decade.

The Bureau of Meteorology says Cyclone Ilsa will intensify into a category-five storm when it hits the WA coast between Port Hedland and Bidyadanga Thursday night or Friday morning.

Tropical cyclones are huge low-pressure systems that form in tropical waters. They can bring extreme winds, heavy rain and damaging waves, destroying infrastructure and the environment and causing injury and death.

Lets take a look at how Cyclone Ilsa developed, and what we can expect from cyclones in this region in future.

Tropical Cyclone Ilsa is the first system of category-four or higher to cross Australian shores since Cyclone Trevor crossed the coast of the Gulf of Carpentaria in 2019.

Ilsa formed off the Northern Territory coast before tracking southwest towards Western Australias Kimberley region. It developed quickly on Tuesday into a category-two system, which involves wind gusts between 125 km/h and 164 km/h.

The cyclone on Thursday intensified to a category-five storm, which involves winds gusts above 279 km/h. This was due to two main factors: high sea-surface temperatures and favourable conditions in the upper atmosphere.

Tropical cyclones require sea-surface temperatures above 27. This provides warm, moist air that generates a massive amount of energy and fuels the cyclone.

Upper atmospheric conditions influence wind speed. Air is drawn in toward the centre of a tropical cyclone. In the Southern Hemisphere, the air spirals upwards in a clockwise direction then moves outwards to the upper troposphere, away from the storm. This air is known as outflow.

Cyclone Ilsas path led it into a region where the upper level wind was relatively light, which enhanced outflow.

As air moved outwards, more wind or inflow was drawn toward the centre of the system from the sea surface, bringing warmth and moisture. This enabled Cyclone Ilsa to rapidly intensify.

Northwest WA is Australias most cyclone-prone region. Records since 1970 show about 75% of severe cylones to make landfall in Australia occur in this region.

But why? It comes down to two things: the high sea surface temperatures in this part of the Indian Ocean, and the orientation of the coast.

Tropical cyclones tend to move polewards and, in the Southern Hemisphere, often curve southeast. The coast of northwest WA is oriented northeast/southwest, and so perfectly aligned to intercept these cyclones.

Several intense tropical cyclones have developed in the warm waters off northwest WA in recent years. However, the number to reach land in this region has been lower than average. Thats because mid- to higher-level atmospheric winds that steer tropical cyclones have directed many of them away from the WA coast.

Climate change is expected to change tropical cyclone patterns. The overall number is expected to decrease, but their intensity will likely increase, bringing stronger wind and heavier rain.

More intense tropical cyclones are expected because higher sea-surface temperatures will make the atmosphere more warm and moist. Cyclones thrive in such conditions.

But the general frequency of tropical cyclones is expected to reduce under climate change in most ocean basins, including the Indian Ocean.

Tropical cyclones usually form when theres a large difference between temperatures at Earths surface and the upper atmosphere. As the climate warms, this temperature difference is likely to narrow.

Research last year showed the annual number of tropical cyclones forming globally decreased by about 13% during the 20th century compared to the 19th.

The activity of tropical cyclones in any one ocean basin over a year is measured by whats known as the Accumulated Cyclone Energy or ACE Index.

The index is calculated by measuring the cyclones wind speed every six hours squaring it, then adding these values together.

A study has shown the index values for cyclone activity in the Southern Indian Ocean have decreased significantly since 1990.

I specialise in reconstructing long-term natural records of extreme events. Research by myself and colleagues has shown tropical cyclone activity along the WA coast is at its lowest level since approximately 500 CE about 1,500 years ago.

Tropical cyclones maintain energy over warm water, and lose energy once they move over land or cooler oceans.

Cyclone Ilsa is expected to weaken overnight on Friday as it moves east into the Northern Territory.

Climate change will lead to fewer tropical cyclones overall. But those that do occur will be more intense and damaging. So unfortunately, WA can expect regular cyclone impacts even as the climate warms.

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Anatomy of monster storm: how Cyclone Ilsa is shaping up to devastate the WA coast - The Conversation