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Cell death is essential to your health − an immunologist explains when cells decide to die with a bang or take their quiet leave

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Cell death is essential to your health − an immunologist explains when cells decide to die with a bang or take their quiet leave

Programmed cell such as apoptosis is a common stage of cellular .
Nanoclustering/Science Photo Library via Getty Images

Zoie Magri, Tufts University

Living cells work better than dying cells, right? However, this is not always the case: your cells often sacrifice themselves to keep you healthy. The unsung hero of life is death.

While death may seem passive, an unfortunate ending that just “happens,” the death of your cells is often extremely purposeful and strategic. The intricate details of how and why cells die can have significant effects on your overall .

There are over 10 different ways cells can “decide” to die, each serving a particular purpose for the organism. My own research explores how immune cells switch between different types of programmed death in scenarios like cancer or injury.

Programmed cell death can be broadly divided into two types that are crucial to health: silent and inflammatory.

Quietly exiting: silent cell death

Cells can often become damaged because of age, stress or injury, and these abnormal cells can make you sick. Your body runs a tight ship, and when cells step out of line, they must be quietly eliminated before they overgrow into tumors or cause unnecessary inflammation where your immune system is activated and causes fever, swelling, redness and pain.

Your body swaps out cells every day to ensure that your tissues are made up of healthy, functioning ones. The parts of your body that are more likely to see damage, like your skin and gut, turn over cells weekly, while other cell types can take months to years to recycle. Regardless of the timeline, the death of old and damaged cells and their replacement with new cells is a normal and important bodily .

Silent cell death, or apoptosis, is described as silent because these cells die without causing an inflammatory reaction. Apoptosis is an active process involving many proteins and switches within the cell. It’s designed to strategically eliminate cells without alarming the rest of the body.

Sometimes cells can detect that their own functions are failing and turn on executioner proteins that chop up their own DNA, and they quietly die by apoptosis. Alternatively, healthy cells can order overactive or damaged neighbor cells to activate their executioner proteins.

Apoptosis is important to maintaining a healthy body. In fact, you can thank apoptosis for your fingers and toes. Fetuses initially have webbed fingers until the cells that form the tissue between them undergo apoptosis and die off.

Microscopy image of mouse foot at embryonic stage
The toes of this embryonic mouse foot are forming through apoptosis.
Michal Maňas/Wikimedia Commons, CC BY-SA

Without apoptosis, cells can grow out of control. A well-studied example of this is cancer. Cancer cells are abnormally good at growing and dividing, and those that can resist apoptosis form very aggressive tumors. Understanding how apoptosis works and why cancer cells can disrupt it can potentially improve cancer treatments.

Other conditions can benefit from apoptosis research as well. Your body makes a lot of immune cells that all respond to different targets, and occasionally one of these cells can accidentally target your own tissues. Apoptosis is a crucial way your body can eliminate these immune cells before they cause unnecessary damage. When apoptosis fails to eliminate these cells, sometimes because of genetic abnormalities, this can to autoimmune diseases like lupus.

Another example of the role apoptosis plays in health is endometriosis, an understudied disease caused by the overgrowth of tissue in the uterus. It can be extremely painful and debilitating for patients. Researchers have recently linked this out-of-control growth in the uterus to dysfunctional apoptosis.

Whether it’s for or maintenance, your cells are quietly exiting to keep your body happy and healthy.

Going out with a bang: inflammatory cell death

Sometimes, it is in your body’s best interest for cells to raise an alarm as they die. This can be beneficial when cells detect the presence of an infection and need to eliminate themselves as a target while also alerting the rest of the body. This inflammatory cell death is typically triggered by bacteria, viruses or stress.

Rather than quietly shutting down, cells undergoing inflammatory cell death will make themselves burst, or lyse, killing themselves and exploding inflammatory messengers as they go. These messengers tell your immune cells that there is a threat and prompts them to treat and fight the pathogen.

An inflammatory death would not be healthy for maintenance. If the normal recycling of your skin or gut cells caused an inflammatory reaction, you would feel sick a lot. This is why inflammatory death is tightly controlled and requires multiple to initiate.

Despite the riskiness of this grenadelike death, many infections would be impossible to fight without it. Many bacteria and viruses need to around or inside your cells to survive. When specialized sensors on your cells detect these threats, they can simultaneously activate your immune system and remove themselves as a home for pathogens. Researchers call this eliminating the niche of the pathogen.

Cells die in many ways, lysis.

Inflammatory cell death plays a major role in pandemics. Yersinia pestis, the bacteria behind the Black Death, has evolved various ways of stopping human immune cells from mounting a response. However, immune cells developed the ability to sense this trickery and die an inflammatory death. This ensures that additional immune cells will infiltrate and eliminate the bacteria despite the bacteria’s best attempts to prevent a fight.

Although the Black Death is not as common nowadays, close relatives Yersinia pseudotuberculosis and Yersinia enterocolitica are behind outbreaks of food-borne illnesses. These infections are rarely fatal because your immune cells can aggressively eliminate the pathogen’s niche by inducing inflammatory cell death. For this reason, however, Yersinia infection can be more dangerous in immunocompromised people.

The virus behind the COVID-19 pandemic also causes a lot of inflammatory cell death. Studies show that without cell death the virus would freely live inside your cells and multiply. However, this inflammatory cell death can sometimes get out of control and contribute to the lung damage seen in patients, which can greatly affect survival. Researchers are still studying the role of inflammatory cell death in COVID-19 infection, and understanding this delicate balance can help improve treatments.

In good times and bad, your cells are always ready to sacrifice themselves to keep you healthy. You can thank cell death for keeping you alive.The Conversation

Zoie Magri, Ph.D. Candidate in Immunology, Tufts University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Americans own guns to protect themselves from psychological as well as physical threats

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theconversation.com – Nick Buttrick, Assistant Professor of Psychology, University of Wisconsin- – 2024-10-31 07:24:00

Many gun owners cite protection as a reason to carry a firearm.

RJ Sangosti/MediaNews Group/The Denver Post via Getty Images

Nick Buttrick, University of Wisconsin-Madison

Kamala Harris, Donald Trump, Tim Walz and JD Vance all have something in common. All four of them, along with an estimated 42% of American adults, have lived in a home with at least one gun.

Gun ownership in the United States is widespread and cuts across all sorts of cultural divides – including race, class and political ideology. Like all mass experiences in American life, owning a gun can mean very different things to different people.

One thing that American gun owners tend to agree on, no matter their differences, is that guns are for personal protection. In a 2023 Pew survey, 72% of gun owners reported that they owned a firearm at least in part for protection, and 81% of gun owners reported that owning a gun helped them to feel safer. This perspective contrasts to that of gun owners in other developed economies, who generally that guns are more dangerous than safe and that they own a gun for some other reason.

I’m a psychologist who studies contemporary society. In the lab, my colleagues and I have been investigating this feeling of safety that American gun owners report. We’re trying to get a more complete sense of just what people are using their firearms to protect against. Our research suggests it goes much deeper than physical threats.

man wearing a holstered gun sitting down to eat at kitchen table with two others

Social scientists are exploring the motivations and effects of owning a gun.

Cécile Clocheret/AFP via Getty Images

Protection goes beyond the physical

By combining social-scientific research on firearms ownership with a raft of interviews we’ve conducted, we’ve developed a theory that gun owners aren’t just protecting against the specific threat of physical violence. Owners are also using a gun to protect their psychological selves. Owning a gun helps them feel more in control of the world around them and more able to live meaningful, purposeful lives that connect to the people and communities they care for.

This sort of protection may be especially appealing to those who think that the normal institutions of society – such as the police or the government – are either unable or unwilling to keep them safe. They feel they need to take protection into their own hands.

This use of a deadly weapon to comfort and solace may come at a cost, however, as firearms often bring a heightened sense of vigilance with them. Firearm instructors frequently teach owners to be especially aware of their environment and all the potential dangers and threats within. When gun owners look for danger, they often are more likely to find it.

Gun owners may end up perceiving the world as a more dangerous place, institutions as more uncaring or incompetent, and their own private actions as all the more important for securing their lives and their livelihoods.

How gun owners feel during daily life

What does this cycle of protection and threat look like in everyday life? My colleagues and I recently ran a study to investigate. We’re still undergoing peer review, so our work is not final yet.

We recruited a group of over 150 firearms owners who told us that they regularly carry their guns, along with over 100 demographically matched Americans who have never owned a gun. Over two weeks, our research team texted the participants at two random times each day, asking them to fill out a survey telling us what they were doing and how they were feeling.

To get a sense of how guns change the psychological landscape of their owners, we divided our gun-carrying group into two. When we texted one half of the group, before we asked any other questions, we simply asked whether they had their gun accessible and why they’d made that decision. For the other half of our gun-owning participants, and for our non-gun-owning control group, firearms and firearm carrying never came up.

When subtly reminded of guns in general – regardless of whether their gun was accessible – our participants reported feeling more safe and in control and that their lives were more meaningful. Thanks to our random-assignment procedure, we can be pretty confident that it was thinking about guns, as opposed to any differences in the underlying groups themselves, that caused this particular increase in psychological well-being.

About half of the times that we texted, the gun owners told us that they had a gun accessible at that moment. When a gun was handy, our participants told us that they were feeling more vigilant and anxious, and that their immediate situation was more chaotic. This result didn’t seem to be driven by owners choosing to have guns available when they were putting themselves into objectively more dangerous situations: We found the same pattern when we looked just at moments when our participants were sitting at home, watching television.

Raising fear and promising rescue

Contemporary American gun ownership may have conflicting messages embedded within it. First, a gun is a thing you can use to bolster your fundamental psychological needs to feel safe, to feel in control and to feel like you matter and belong. Second, a gun focuses your attention on the dangers of the world.

By both fueling a sense of danger and holding out the promise of rescuing you from the fear, messaging around guns may end up locking some owners into a sort of doom loop.

woman posing in front of fireplace holding her pistol

A sense of responsibility goes along with gun ownership for the vast majority of Americans who own a firearm.

Matt McClain/The Washington Post via Getty Images

My collaborators and I are currently exploring whether stressing other parts of gun ownership may owners to move beyond this negative spiral. For instance, while owners often about “danger,” they also talk frequently about “responsibility.”

Being a responsible gun owner is central to many owners’ identities. In one study, 97% of owners reported that they were “more responsible than the average gun owner,” and 23% rated themselves as being in the top 1% of responsibility overall. This, of course, is statistically impossible.

To more fully understand the many ways responsible firearm ownership can look, we are in the process of interviewing gun owners from all around the state of Wisconsin, a notably diverse state when it comes to gun ownership. We’re tapping into as many of the ways of owning a gun as we can, talking with protective owners, hunters, sport shooters, collectors, folks in urban , folks in rural areas, , women, young people, old people, liberals, conservatives, and, of course, trying to capture the complex ways that race shapes ownership.

Who do gun owners feel they are responsible for? What kinds of actions do they think responsible owners take?

We hope to learn more about the many different ways that people conceptualize what a gun can do for them. American gun cultures are complex and distinct things. By exploring the worldviews that firearm ownership, we can better understand what it means to live in the U.S. .The Conversation

Nick Buttrick, Assistant Professor of Psychology, University of Wisconsin-Madison

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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In Hawaii, parasites and viruses team up in the battle against fruit flies – an entomologist explains the implication for global pest control

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theconversation.com – Kelsey Coffman, Assistant Professor of Entomology & Plant Pathology, of Tennessee – 2024-10-31 07:25:00

Diachasmimorpha longicaudata, a parasitoid wasp that helps control pests.

Sheina Sim, CC BY

Kelsey Coffman, University of Tennessee

Take a stroll along one of the beaches on Hawaii Island in late summer, and you’ll likely stumble upon almond-shaped fruits lying in the sand. Known as false kamani nuts, or tropical almonds, they fall from tall, shady Terminalia catappa trees that line the many picturesque ocean views on the island.

But what may not be clear to the casual beachgoer is that there’s a fight for survival occurring within the flesh of these unassuming fruits. Tropical almonds are one of many active battlegrounds in a war between a global agricultural pest, a parasitic wasp and a beneficial virus.

As an entomologist who studies insect viruses, I want to untangle the complex interactions that insects have evolved with microbes. The findings might researchers tackle global food security issues.

A global pest challenge

At the center of this conflict are invasive fruit flies in the Tephritidae, many of which have spread across the globe and wreak havoc on hundreds of commercial fruits and vegetables.

In Hawaii, several species of tephritid fruit fly invaded, starting in the late 1800s. They have caused major economic losses to fruit production across the islands. Scientists and fruit growers have undertaken enormous efforts to control these flies since their initial introductions, but they remain a serious economic problem.

One reliable method of control has been to release tiny insects called parasitoid wasps into the wild that can hunt down immature fruit flies and target them for annihilation. The term parasitoid an organism that spends its as a parasite and eventually kills its host.

Parasitoid wasps use an elongated stinger, known as an ovipositor, to drill into fruits where flies are developing and pierce the fly’s body to lay an egg within. Wasp eggs hatch inside the fly host and gradually devour the entire fly from the inside out.

Human use of parasitoid wasps or other natural enemies to control pest populations is known as biological control, or biocontrol. It was so successful in Hawaii that several species of parasitoid wasp have established wild populations on the islands. They have helped continuously suppress multiple fruit fly pests to this day.

The release of nonnative insects for biocontrol could have unforeseen negative consequences for local ecosystems. Therefore, federal agencies like the U.S. Department of Agriculture have strict regulations for new and existing biocontrol programs.

The enemy of my enemy is my friend

So, how do wasps achieve the impressive feat of reducing fruit fly pest populations? Once laid inside a fly host, the wasp must face the fly’s immune system, which will try to suffocate the egg before it hatches.

This inhospitable has forced wasps to evolve an arsenal of microscopic substances, also known as molecular factors, to combat fly defenses. These include a cocktail of different molecules introduced by the wasp mother at the time of egg-laying.

The goal of these factors is to manipulate the fruit fly’s physiological processes, like its development from egg to adult and its immune response to invading parasites. By interacting with molecular components, like proteins, that make up insect physiological pathways, parasitoid wasp factors can delay insect host development and suppress host immunity to allow the wasp offspring to feed on fly tissue unharmed.

This is the origin story of an unlikely partnership that many species of parasitoid wasp have formed with beneficial viruses. Virus particles multiply to massive quantities within the reproductive organs of female wasps during their development. Wasp mothers then use their ovipositor like a hypodermic needle to inject virus particles into host insects during egg-laying.

The virus particles turn into biological weapons that infect cells of the wasp’s host. This infection disrupts processes like the fly’s immune response. Developing wasps benefit from the virus’s activity and return the favor by passing on the virus to future wasp generations.

Not all heroes wear capes

Diachasmimorpha longicaudata is a small, bright orange wasp with a distinctively long ovipositor. The literal translation of longicaudata is “long-tailed” in Latin. But don’t let its charismatic appearance fool you.

D. longicaudata is ferocious in its ability to feast on several species of fruit fly pests, such as the Mediterranean fruit fly, Ceratitis capitata, and the oriental fruit fly, Bactrocera dorsalis. Because of D. longicaudata’s ability to attack a wide variety of fruit fly pests, pest management specialists around the world have released the wasps into agricultural ecosystems, where they dependably establish new populations and sustained pest control.

Like many parasitoids, D. longicaudata has formed an alliance with a virus known as Diachasmimorpha longicaudata entomopoxvirus, or DlEPV.

DlEPV replicates within the venom gland of female wasps, which stores billions of virus particles. Virus particles are so densely packed in there that they often cause the venom gland to appear iridescent blue.

DlEPV particles are highly lethal when injected into flies in the lab. The virus freezes the fly’s development and replicates with abandon until the fly’s ultimate demise.

In contrast, the alliance between wasp and virus is so strong that curing D. longicaudata wasps of their DlEPV infection causes the wasp offspring to die inside the fly .

A new potential path forward

My colleagues and I published a study showing that DlEPV may play a critical role in helping D. longicaudata make a meal out of so many different fruit fly pests. We found a link between D. longicaudata survival and DlEPV lethality within different fruit fly host species.

When we infected C. capitata and B. dorsalis flies with DlEPV, the virus successfully replicated and killed large swaths of fly hosts. However, DlEPV couldn’t replicate within the melon fly, Zeugodacus cucurbitae, a fly species that D. longicaudata wasps cannot use as hosts.

These findings shine new light on the effect viruses have on host-parasite rivalries. The presence of these viruses could influence how useful parasitoid wasps are in getting rid of fruit fly pests. In the case of D. longicaudata, its associated virus may be responsible for the decades of reliable aid this wasp has provided to fruit fly biocontrol programs around the world.

This work has also revealed a new potential tool in the war against fruit fly pests. DlEPV is now known as a lethal enemy for several of the world’s most destructive pest species. If researchers can determine precisely how DlEPV exploits fly hosts at a molecular level, they could one day incorporate the same strategies that this virus uses into new fruit fly pest control methods.The Conversation

Kelsey CoffmanUniversity of Tennessee

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Fighting antibiotic resistance at the source – using machine learning to identify bacterial resistance genes and the drugs to block them

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theconversation.com – Abdullahi Tunde Aborode, Mississippi – 2024-10-30 07:41:00

Current methods of identifying resistance mutations in microbes can miss other ways resistance can develop.
koto_feja/iStock via Getty Images Plus

Abdullahi Tunde Aborode, Mississippi State University

Antibiotic resistance is a growing public health problem around the world. When bacteria like E. coli no longer respond to antibiotics, infections become harder to treat.

To develop new antibiotics, researchers typically identify the genes that make bacteria resistant. Through laboratory experiments, they observe how bacteria respond to different antibiotics and look for mutations in the genetic makeup of resistant strains that allow them to survive.

While effective, this method can be time-consuming and may not always capture the full picture of how bacteria become resistant. For example, changes in how genes work that don’t involve mutations can still influence resistance. Bacteria can also exchange resistance genes between each other, which may not be detected if only focusing on mutations within a single strain.

My colleagues and I developed a new approach to identify E. coli resistance genes by computer modeling, allowing us to design new compounds that can block these genes and make existing treatments more effective.

Identifying resistance

To predict which genes contribute to resistance, we analyzed the genomes of various E. coli strains to identify genetic patterns and markers associated with resistance. We then used machine learning algorithms trained on existing data to highlight novel genes or mutations shared across resistant strains that might contribute to resistance.

Microscopy image of rod-shaped E. coli, colored orange
E. coli is one of many bacterial species developing resistance to common antibiotics.
National Institute of Allergy and Infectious Diseases/National Institutes of Health via Flickr, CC BY-NC

After identifying resistance genes, we designed inhibitors that specifically target and block the proteins these genes produce. By analyzing the structure of the proteins these genes code for, we were able to optimize our inhibitors to strongly bind to these specific proteins.

To reduce the likelihood that bacteria would evolve resistance to these inhibitors, we targeted regions of their genome that code for proteins critical to their survival. By interfering with how bacteria carry out important functions, it makes it more difficult for them to develop mechanisms to compensate. We also prioritized compounds that work differently from existing antibiotics to minimize cross-resistance.

Finally, we tested how effectively our inhibitors could overcome antibiotic resistance in E. coli. We used computer simulations to assess how strongly a number of inhibitors bind to target proteins over time. One inhibitor called hesperidin was able to strongly bind to the three genes in E. coli involved in resistance that we identified, suggesting it may be able to combat antibiotic-resistant strains.

A global threat

The World Organization ranks antimicrobial resistance as one of the top 10 threats to global health. In 2019, bacterial antibiotic resistance killed an estimated 4.95 million people worldwide.

By targeting the specific genes responsible for resistance to existing , our approach could to treatments for challenging bacterial infections that are not only more effective but also less likely to contribute to further resistance. It can also help researchers keep up with bacterial threats as they evolve.

Some microbes can transfer resistance to other microbes.

Our predictive approach could be adapted to other bacterial strains, allowing for more personalized treatment strategies. In the future, could potentially tailor antibiotic treatments based on the specific genetic makeup of the bacteria causing the infection, potentially leading to better outcomes.

As antibiotic resistance continues to rise globally, our findings may a crucial tool in the fight against this threat. Further is needed before our methods can be used in the clinic. But by staying ahead of bacterial evolution, targeted inhibitors could help preserve the efficacy of existing antibiotics and reduce the spread of resistant strains.The Conversation

Abdullahi Tunde Aborode, , Mississippi State University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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