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An itching paradox – a molecule that triggers the urge to scratch also turns down inflammation in the skin

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An itching paradox – a molecule that triggers the urge to scratch also turns down inflammation in the skin

Itching, and the subsequent urge to scratch, can make eczema worse.
Kinga Krzeminska/Moment via Getty Images

Marlys Fassett, University of California, San Francisco

Itching can be uncomfortable, but it’s a normal part of your skin’s immune response to external threats. When you’re itching from an encounter with poison ivy or mosquitoes, consider that your urge to scratch may have evolved to get you to swat away disease-carrying pests.

However, for many people who suffer from chronic skin diseases like eczema, the sensation of itch can fuel a vicious cycle of scratching that interrupts sleep, reduces productivity and prevents them from enjoying daily life. This cycle is caused by sensory neurons and skin immune cells working together to promote itching and skin inflammation.

But, paradoxically, some of the mechanisms behind this feedback loop also stop inflammation from getting worse. In our newly published research, my team of immunologists and neuroscientists and I discovered that a specific type of itch-sensing neuron can push back on the itch-scratch-inflammation cycle in the presence of a small protein. This protein, called interleukin-31, or IL-31, is typically involved in triggering itching.

This negative feedback loop – like the vicious cycle – is only possible because the itch-sensing nerve endings in your skin are closely intertwined with the millions of cells that make up your skin’s immune system.

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Your skin has its own immune system.

An itchy molecule

The protein IL-31 is key to the connection between the nervous and immune . This molecule is produced by some immune cells, and like other members of this molecule family, it specializes in helping immune cells communicate with each other.

IL-31 is rarely present in the skin or blood of people who don’t have a history of eczema, allergies, asthma or related conditions. But those with conditions like eczema that cause chronic itch have significantly increased skin production of IL-31. There is strong evidence that IL-31 is one of a small set of proteins that immune cells produce that can bind directly to sensory neurons and trigger itching. Small amounts of purified IL-31 injected directly into skin or spinal fluid to impressively rapid-onset itching and scratching.

However, when my colleagues and I induced rashes in mice by exposing them to dust mites, we found that itch-sensing neurons turned down the dial on inflammation at the site of itching instead of promoting it. They did so by secreting small molecules called neuropeptides that, in this context, directed immune cells to respond less enthusiastically. In sum, we had discovered an inverse relationship between itching and skin inflammation, tethered by a single molecule.

But if IL-31 triggers itching, which can worsen inflammation by making scratch their skin, how does it reduce inflammation?

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We found the answer to this paradox in a little-known function of sensory neurons called neurogenic inflammation. This nerve reflex triggers sensory neurons to release various signaling molecules directly into tissues, specific neuropeptides that promote signs of inflammation like increased blood flow to the skin. Neurogenic inflammation acts within the same nerves that transmit sensory information like itch, pain, touch and temperature, but differs by the path it takes: away from the brain rather than toward it.

We discovered that IL-31 can induce neurogenic inflammation, mapping a direct pathway going from IL-31 through sensory neurons to repress immune cells in the skin. When we engineered mice to be unresponsive to IL-31, we similarly found that they had more activated skin immune cells that produced more inflammation. This means the net effect of IL-31 is to blunt overall inflammation.

IL-31 as potential treatment

Our study shows that IL-31 causes sensory neurons in the skin to perform two very different functions: They signal inward to the spinal cord and brain to stimulate an itching sensation that typically leads to more inflammation, but they also signal back out to the skin and quell inflammation by inhibiting certain immune cells.

Although paradoxical, this makes evolutionary sense. Scratching an itch can feel very satisfying but doesn’t have much utility in the modern world where we’re more likely to suffer from compulsive scratching than encounter stinging nettles. In contrast, unchecked inflammation underlies many chronic autoimmune diseases. Therefore, turning off an immune response in inflamed tissue can be as important as turning it on.

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Our discoveries raise important questions about the implications of modifying IL-31 to treat different diseases. For one, it isn’t clear how IL-31-sensing neurons interface with other neuronal circuits that also regulate skin inflammation. Furthermore, some patients have higher levels of allergic proteins in their blood or develop asthma flares when taking existing that target IL-31. IL-31 is also found in some lung and gut cells – how and why would an itch-inducing molecule be present in internal organs?

Anatomical niches where sensory neurons and immune cells converge are present throughout the human body. If an itchy molecule like IL-31 can use neuronal circuitry to dampen an immune response in the skin, similar molecules like those used in migraine drugs could be repurposed to treat skin conditions, too.The Conversation

Marlys Fassett, Associate Professor of Dermatology, University of California, San Francisco

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

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The Conversation

Pagers and walkie-talkies over cellphones – a security expert explains why Hezbollah went low-tech for communications

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theconversation.com – Richard Forno, Principal Lecturer in Computer Science and Electrical Engineering, University of Maryland, Baltimore County – 2024-09-18 16:32:21

A officer examines a damaged car after thousands of pagers exploded simultaneously across Lebanon on Sept. 17, 2024.
AP Photo/Hussein Malla

Richard Forno, University of Maryland, Baltimore County

Electronic pagers across Lebanon exploded simultaneously on Sept. 17, 2024, killing 12 and wounding more than 2,700. The following day, another wave of explosions in the country came from detonating walkie-talkies. The attacks appeared to target members of the militant group Hezbollah.

The pagers attack involved explosives planted in the communications devices by Israeli operatives, according to U.S. officials cited by The New York Times. Hezbollah had recently ordered a shipment of pagers, according to the report.

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Secretly attacking the supply chain is not a new technique in intelligence and military operations. For example, the U.S. National Security Agency intercepted computer hardware bound for overseas customers, inserted malware or other surveillance tools and then repackaged them for delivery to certain foreign buyers, a 2010 NSA internal document showed. This differs from accessing a specific person’s device, such as when Israel’s Shin Bet secretly inserted explosives into a cellphone to remotely kill a Hamas bombmaker in 1996.

Hezbollah, a longtime adversary of Israel, had increased its use of pagers in the wake of the Hamas attack on Israel on Oct. 7, 2023. By shifting to relatively low-tech communication devices, pagers and walkie-talkies, Hezbollah apparently sought an advantage against Israel’s well-known sophistication in tracking targets through their phones.

pieces of a destroyed electronic device
The second wave of explosions in Lebanon involved walkie-talkies.
AP Photo

Cellphones: The ultimate tracker

As a former cybersecurity professional and current security researcher, I view cellular devices as the ultimate tracking tool for both government and commercial entities – in addition to users, criminals and the mobile phone provider itself. As a result, mobile phone tracking has contributed to the fight against terrorism, located missing people and helped solve crimes.

Conversely, mobile phone tracking makes it easy for anyone to record a person’s most intimate movements. This can be done for legitimate purposes such as tracking ‘s movements, helping you find your car in a parking lot, and commercial advertising, or nefarious ends such as remotely spying on a lover suspected of cheating or tracking political activists and journalists. Even the U.S. military remains concerned with how its soldiers might be tracked by their phones.

Mobile device tracking is conducted in several ways. First, there is the network location data generated by the phone as it moves past local cell towers or Stingray devices, which enforcement agencies use to mimic cell towers. Then there are the features built into the phone’s operating system or enabled by downloaded apps that may lead to highly detailed user tracking, which users unwittingly agree to by ignoring the software’s privacy policy or terms of service.

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This collected data is sometimes sold to governments or other companies for additional data mining and user profiling. And modern smartphones also have built-in Bluetooth, Wi-Fi and GPS capabilities that can help with locating and tracking user movements around the world, both from the ground and via satellites.

Your phone contains many sensors that make it useful – and easy to track.

Mobile devices can be tracked in real time or close to it. Common technical methods include traditional radio direction-finding techniques, using intelligence satellites or drones, deploying “man in the middle” tools like Stingrays to impersonate cellular towers to intercept and isolate device traffic, or installing malware such as Pegasus, made by Israeli cyberarms company NSO to report a device’s location.

Nontechnical and slower techniques of user tracking include potentially identifying general user locations from their internet activity. This can be done from website logs or the metadata contained in content posted to social , or contracting with data brokers to receive any collected location data from the apps that a user might install on their device.

Indeed, because of these vulnerabilities, the leader of Hezbollah earlier this year advised his members to avoid using cellular phones in their activities, noting that Israel’s “surveillance devices are in your pockets. If you are looking for the Israeli agent, look at the phone in your hands and those of your wives and children.”

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Researchers have shown how these features, often intended for the user’s convenience, can be used by governments, companies and criminals to track people in their daily lives and even predict movements. Many people still aren’t aware of how much their mobile devices disclose about them.

Pagers, however, unlike mobile phones, can be harder to track depending on whether they two-way communication.

Why go low-tech

A pager that only receives messages does not a signal that can facilitate tracking its owner. Therefore, Hezbollah’s use of pagers likely made it more challenging to track their operatives – thus motivating Israeli intelligence services’ purported attack on the supply chain of Hezbollah’s pagers.

Using low-tech tactics and personal couriers while avoiding the use of mobile phones and digital tools also made it difficult for the technologically superior Western intelligence agencies to locate Osama bin Laden for years after the 9/11 attacks.

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In general, I believe the adversary in an asymmetric conflict using low-tech techniques, tactics and technology will almost always be able to operate successfully against a more powerful and well-funded opponent.

A well-documented demonstration of this asymmetry in action was the U.S. military’s Millennium Challenge war game in 2002. Among other things, the insurgent Red forces, led by Marine General Paul van Riper, used low-tech tactics including motorcycle couriers instead of cellphones to evade the Blue forces’ high-tech surveillance. In the initial run of the exercise, the Red team won the contest in 24 hours, forcing exercise planners to controversially reset and update the scenario to ensure a Blue team victory.

Lessons for everyone

The preference for terrorist organizations like Hezbollah and al-Qaida to avoid using smartphones is a reminder for everyone that you can be, and likely are being tracked in various ways and for various purposes.

Israel’s purported response to Hezbollah’s actions also a lesson for everyone. From a cybersecurity perspective, it shows that any device in your can be tampered with by an adversary at points along the supply chain – long before you even receive it.The Conversation

Richard Forno, Principal Lecturer in Computer Science and Electrical Engineering, University of Maryland, Baltimore County

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Tiny robots and AI algorithms could help to craft material solutions for cleaner environments

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theconversation.com – Mahshid Ahmadi, Assistant Professor of Materials Science and Engineering, of Tennessee – 2024-09-17 07:31:57

pollution is a global problem, but scientists are investigating new materials that could help clean it up.
AP Photo/Sergei Grits

Mahshid Ahmadi, University of Tennessee

Many human activities release pollutants into the air, and soil. These harmful chemicals threaten the of both people and the ecosystem. According to the World Health Organization, air pollution causes an estimated 4.2 million deaths annually.

Scientists are looking into , and one potential avenue is a class of materials called photocatalysts. When triggered by light, these materials undergo chemical reactions that initial studies have shown can break down common toxic pollutants.

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I am a materials science and engineering researcher at the University of Tennessee. With the help of robots and artificial intelligence, my colleagues and I are making and testing new photocatalysts with the goal of mitigating air pollution.

Breaking down pollutants

The photocatalysts work by generating charged carriers in the presence of light. These charged carriers are tiny particles that can move around and cause chemical reactions. When they into contact with water and oxygen in the environment, they produce substances called reactive oxygen species. These highly active reactive oxygen species can bond to parts of the pollutants and then either decompose the pollutants or turn them into harmless – or even useful – products.

A cube-shaped metal machine with a chamber filled with bright light, and a plate of tubes shown going under the light.
To facilitate the photocatalytic reaction, researchers in the Ahmadi lab put plates of perovskite nanocrystals and pollutants under bright light to see whether the reaction breaks down the pollutants.
Astita Dubey

But some materials used in the photocatalytic process have limitations. For example, they can’t start the reaction unless the light has enough energy – infrared rays with lower energy light, or visible light, won’t trigger the reaction.

Another problem is that the charged particles involved in the reaction can recombine too quickly, which means they join back together before finishing the job. In these cases, the pollutants either do not decompose completely or the process takes a long time to accomplish.

Additionally, the surface of these photocatalysts can sometimes change during or after the photocatalytic reaction, which affects how they work and how efficient they are.

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To overcome these limitations, scientists on my team are to develop new photocatalytic materials that work efficiently to break down pollutants. We also focus on making sure these materials are nontoxic so that our pollution-cleaning materials aren’t causing further pollution.

A plate of tiny tubes, with some colored dark blue, others light blue, and others transparent.
This plate from the Ahmadi lab is used while testing how perovskite nanocrystals and light break down pollutants, like the blue dye shown. The light blue color indicates partial degradation, while transparent water signifies complete degradation.
Astita Dubey

Teeny tiny crystals

Scientists on my team use automated experimentation and artificial intelligence to figure out which photocatalytic materials could be the best candidates to quickly break down pollutants. We’re making and testing materials called hybrid perovskites, which are tiny crystals – they’re about a 10th the thickness of a strand of hair.

These nanocrystals are made of a blend of organic (carbon-based) and inorganic (non-carbon-based) components.

They have a few unique qualities, like their excellent light-absorbing properties, which come from how they’re structured at the atomic level. They’re tiny, but mighty. Optically, they’re amazing too – they interact with light in fascinating ways to generate a large number of tiny charge carriers and trigger photocatalytic reactions.

These materials efficiently transport electrical charges, which allows them to transport light energy and the chemical reactions. They’re also used to make solar panels more efficient and in LED lights, which create the vibrant displays you see on TV screens.

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There are thousands of potential types of hybrid nanocrystals. So, my team wanted to figure out how to make and test as many as we can quickly, to see which are the best candidates for cleaning up toxic pollutants.

Bringing in robots

Instead of making and testing samples by hand – which takes weeks or months – we’re using smart robots, which can produce and test at least 100 different materials within an hour. These small liquid-handling robots can precisely move, mix and transfer tiny amounts of liquid from one place to another. They’re controlled by a computer that guides their acceleration and accuracy.

A researcher in a white lab coat smiling at the camera next to a fume hood, with plates of small tubes inside it.
The Opentrons pipetting robot helps Astita Dubey, a visiting scientist working with the Ahmadi lab, synthesize materials and treat them with organic pollutants to test whether they can break down the pollutants.
Jordan Marshall

We also use machine learning to guide this process. Machine learning algorithms can analyze test data quickly and then learn from that data for the next set of experiments executed by the robots. These machine learning algorithms can quickly identify patterns and insights in collected data that would normally take much longer for a human eye to catch.

Our approach aims to simplify and better understand complex photocatalytic , helping to create new strategies and materials. By using automated experimentation guided by machine learning, we can now make these systems easier to analyze and interpret, overcoming challenges that were difficult with traditional methods.The Conversation

Mahshid Ahmadi, Assistant Professor of Materials Science and Engineering, University of Tennessee

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

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A public health historian sizes up their records

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theconversation.com – Zachary W. Schulz, Lecturer of History, Auburn – 2024-09-17 07:33:53

The presidential debate on Sept. 10, 2024, did not add much context to what the two candidates would do on beyond their own records.
Visual China Group/Getty Images

Zachary W. Schulz, Auburn University

Health care is a defining issue in the 2024 election – Democratic presidential nominee Kamala Harris and Republican contender Donald Trump have starkly different records on the issue. Rather than focusing on what they promise to do, let’s examine what their past actions reveal about their approaches to Medicare, the Affordable Care Act, public health infrastructure, drug policy and child abuse and domestic violence prevention.

As a specialist in public health history and policy, I have carefully examined both candidates’ records on American health care. With years of experience in the health care field and being a cystic fibrosis patient myself, I have developed a deep understanding of our health care system and the political dynamics that shape it.

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For me, as for many other Americans, health care is more than just a political issue; it is a deeply personal one.

Medicare

During Harris’ time in the Senate, she co-sponsored the Medicare for All Act, which aimed to expand Medicare to all Americans, effectively eliminating private insurance.

At the presidential debate on Sept. 10, 2024, Harris clarified her former support of “Medicare for All” by emphasizing her prior legislative efforts to preserve and expand protections for patients’ rights and access to affordable health care.

Harris’s legislative efforts, primarily around the 2017-2020 period, reflect a commitment to broadening access to Medicare and reducing costs for seniors. During that time, Harris advocated for the Medicare program to negotiate drug prices directly with pharmaceutical companies.

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Later, as vice president, Harris cast a tie-breaking vote on the 2022 Inflation Reduction Act, allowing the to negotiate drug prices for Medicare with pharmaceutical companies.

In contrast, during Trump’s presidency, he made several attempts, some of which were successful, to cut funding for Medicare. The 2020 budget proposed by his administration included cuts to Medicare totaling more than US$800 billion over 10 years, primarily by reducing payments to providers and slowing the growth of the program.

The proposed cuts did not take effect because they required Congressional approval, which was not granted. The plan significant opposition due to concerns about potential negative impacts on beneficiaries.

Affordable Care Act

Harris has been a staunch defender of the Affordable Care Act, also known as the ACA or “Obamacare.” As a senator, Harris consistently voted against any efforts to repeal the ACA. She advocated for expanding its provisions, including supporting legislation that aimed to strengthen protections for people with preexisting conditions and increase funding for Medicaid expansion.

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Harris’ record shows a clear commitment to ensuring broader health coverage under the ACA. And, in the recent debate, Harris noted this record and reasserted her commitment to the act.

During his presidency, Trump led multiple efforts to repeal the ACA, including the 2017 American Health Care Act, which would have significantly reduced the scope of expansion and individual mandates.

Although these efforts ultimately failed in the Senate, Trump succeeded in weakening the ACA by eliminating the individual mandate penalty through the 2017 Tax Cuts and Jobs Act. In the debate against Harris, Trump reiterated his position that the Affordable Care Act “was lousy health care,” though he did not ultimately offer a replacement plan, stating only that he has “concepts of a plan.”

Donald Trump claims that as president, he had an obligation to save Obamacare, otherwise known as the Affordable Care Act, but says it is too expensive. He says he has ‘concepts of a plan’ for something to replace the ACA.

Public health infrastructure

Harris’ tenure in the Senate, from January 2017 to January 2021, shows a consistent pattern of supporting public health infrastructure. She co-sponsored several bills aimed at increasing funding for community health centers and expanding access to preventive care.

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Harris also advocated for more federal to address public health emergencies, such as the opioid epidemic and the COVID-19 pandemic.

During Trump’s presidency, however, he made significant cuts to public health programs. The Trump administration proposed budget cuts to the Centers for Disease Control and Prevention and other public health agencies, arguing that they were necessary for fiscal responsibility. These proposals drew criticism for potentially undermining the nation’s ability to respond to public health emergencies, a concern that was underscored by the CDC’s struggles during the early days of the COVID-19 pandemic. Trump frequently has responded to these criticisms by asserting he “cut bureaucratic red tape” rather than essential services.

Drug pricing policy

Harris has also supported legislation to lower drug prices and increase transparency in the pharmaceutical industry. She co-sponsored the Drug Price Relief Act, which aimed to allow the federal government to negotiate drug prices for Medicare directly. She also supported efforts to import cheaper prescription from Canada. Her record reflects a focus on reducing costs for consumers and increasing access to affordable medications.

Trump’s record on drug policy is mixed. While Trump took credit for some decreases in prescription drug prices during his presidency, his administration’s most significant regulatory changes favored pharmaceutical companies. The administration’s attempts to implement a rule allowing the importation of cheaper drugs from Canada faced significant hurdles and did not to immediate changes.

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Trump also ended a rule that would have required pharmaceutical companies to disclose drug prices in television ads, citing concerns over its legality.

Child abuse and domestic violence

Harris has a strong record of advocating for the prevention of child abuse and domestic violence. During her time as California’s attorney general and as a senator, Harris pushed for legislation that increased funding for domestic violence prevention programs and expanded legal protections for survivors. She has consistently supported measures to enhance child welfare services and improve coordination among agencies to protect children.

Trump’s record on these issues is less defined, but his administration did sign into law the Family First Prevention Services Act, which aimed to keep more children safely at home and out of foster care by providing new resources to families. However, critics argue that the Trump administration’s broader cuts to social services and health programs could indirectly undermine efforts to combat child abuse and domestic violence. In addition, some experts suggest that Trump’s family separation policies on the southern border contributed to an increase in child trauma during his administration.The Conversation

Zachary W. Schulz, Lecturer of History, Auburn University

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

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