Connect with us

The Conversation

A common parasite could one day deliver drugs to the brain − how scientists are turning ‘Toxoplasma gondii’ from foe into friend

Published

on

theconversation.com – Bill Sullivan, Professor of Pharmacology and Toxicology, Indiana University – 2024-08-07 07:34:55

Toxoplasma is often transmitted to people from contaminated food or cat feces.

Dr_Microbe/iStock via Getty Images Plus

Bill Sullivan, Indiana University

Parasites take an enormous toll on human and veterinary health. But researchers may have found a way for patients with brain disorders and a common brain parasite to become frenemies.

A new study published in Nature Microbiology has pioneered the use of a single-celled parasite, Toxoplasma gondii, to inject therapeutic proteins into brain cells. The brain is very picky about what it lets in, including many drugs, which limits treatment options for neurological conditions.

As a professor of microbiology, I’ve dedicated my career to finding ways to kill dangerous parasites such as Toxoplasma. I’m fascinated by the prospect that we may be able to use their weaponry to instead treat other maladies.

Microbes as medicine

Ever since scientists realized that microscopic organisms can cause illness – what’s called the 19th-century germ theory of disease – humanity has been on a quest to keep infectious agents out of our bodies. Many people’s understandable aversion to germs may make the idea of adapting these microbial adversaries for therapeutic purposes seem counterintuitive.

But preventing and treating disease by co-opting the very microbes that threaten us has a history that long predates germ theory. As early as the 1500s, people in the Middle East and Asia noted that those lucky enough to survive smallpox never got infected again. These observations led to the practice of purposefully exposing an uninfected person to the material from an infected person’s pus-filled sores – which unbeknownst to them contained weakened smallpox virus – to protect them from severe disease.

Scan of yellowed book pages with illustration of person covered in smallpox pustules on left page and Japanese text on the right

The concept of inoculation developed with smallpox outbreaks several centuries ago.

MS Japanese 63/Wellcome Collection, CC BY

This concept of inoculation has yielded a plethora of vaccines that have saved countless lives.

Viruses, bacteria and parasites have also evolved many tricks to penetrate organs such as the brain and could be retooled to deliver drugs into the body. Such uses could include viruses for gene therapy and intestinal bacteria to treat a gut infection known as C. diff.

Why can’t we just take a pill for brain diseases?

Pills offer a convenient and effective way to get medicine into the body. Chemical drugs such as aspirin or penicillin are small and easily absorbed from the gut into the bloodstream.

Biologic drugs such as insulin or semaglutide, on the other hand, are large and complex molecules that are vulnerable to breaking down in the stomach before they can be absorbed. They are also too big to pass through the intestinal wall into the bloodstream.

All drugs, especially biologics, have great difficulty penetrating the brain due to the blood-brain barrier. The blood-brain barrier is a layer of cells lining the brain’s blood vessels that acts like a gatekeeper to block germs and other unwanted substances from gaining access to neurons.

Toxoplasma offers delivery service to brain cells

Toxoplasma parasites infect all animals, including humans. Infection can occur in multiple ways, including ingesting spores released in the stool of infected cats or consuming contaminated meat or water. Toxoplasmosis in otherwise healthy people produces only mild symptoms but can be serious in immunocompromised people and to gestating fetusus.

Unlike most pathogens, Toxoplasma can cross the blood-brain barrier and invade brain cells. Once inside neurons, the parasite releases a suite of proteins that alter gene expression in its host, which may be a factor in the behavioral changes it causes in infected animals and people.

Scientists retooled Toxoplasma to deliver drugs to neurons.

In a new study, a global team of researchers hijacked the system Toxoplasma uses to secrete proteins into its host cell. The team genetically engineered Toxoplasma to make a hybrid protein, fusing one of its secreted proteins to a protein called MeCP2, which regulates gene activity in the brain – in effect, giving the MeCP2 a piggyback ride into neurons. Researchers found that the parasites secreted the MeCP2 protein hybrid into neurons grown in a petri dish as well as in the brains of infected mice.

A genetic deficiency in MECP2 causes a rare brain development disorder called Rett syndrome. Gene therapy trials using viruses to deliver the MeCP2 protein to treat Rett syndrome are underway. If Toxoplasma can deliver a form of MeCP2 protein into brain cells, it may provide another option to treat this currently incurable condition. It also may offer another treatment option for other neurological problems that arise from errant proteins, such as Alzheimer’s and Parkinson’s disease.

The long road ahead

The road from laboratory bench to bedside is long and filled with obstacles, so don’t expect to see engineered Toxoplasma in the clinic anytime soon.

The obvious complication in using Toxoplasma for medical purposes is that it can produce a serious, lifelong infection that is currently incurable. Infecting someone with Toxoplasma can damage critical organ systems, including the brain, eyes and heart.

However, up to one-third of people worldwide currently carry Toxoplasma in their brain, apparently without incident. Emerging studies have correlated infection with increased risk of schizophrenia, rage disorder and recklessness, hinting that this quiet infection may be predisposing some people to serious neurological problems.

The widespread prevalence of Toxoplasma infections may also be another complication, as it disqualifies many people from using it for treatment. Since the billions of people who already carry the parasite have developed immunity against future infection, therapeutic forms of Toxoplasma would be rapidly destroyed by their immune systems once injected.

In some cases, the benefits of using Toxoplasma as a drug delivery system may outweigh the risks. Engineering benign forms of this parasite could produce the proteins patients need without harming the organ – the brain – that defines who we are.The Conversation

Bill Sullivan, Professor of Pharmacology and Toxicology, Indiana University

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

Read More

The post A common parasite could one day deliver drugs to the brain − how scientists are turning ‘Toxoplasma gondii’ from foe into friend appeared first on theconversation.com

The Conversation

Rents rise faster after disasters, but a federal program can help restrain excesses

Published

on

theconversation.com – Anthony W. Orlando, Assistant Professor of Finance, Real Estate and Law, California State Polytechnic University, Pomona – 2025-01-14 13:02:00

Two people embrace on Jan. 9, 2025, in Altadena, Calif., amid property destroyed by the Eaton Fire.
Justin Sullivan/Getty Images

Anthony W. Orlando, California State Polytechnic University, Pomona

The wildfires raging across Los Angeles are setting the scene for a real estate nightmare.

Thousands of homes and other structures are destroyed and hundreds of thousands of residents have been evacuated at various times. Many will not return for months, if ever. Homeless in an instant, they are now flooding the housing market, desperately seeking shelter.

The Los Angeles housing market is poorly equipped for this crisis. It is already one of the nation’s most expensive markets to buy or rent a place to live, largely due to a significant and growing shortage of affordable housing. That shortage will become only more dire with the destruction of so many fire-ravaged buildings.

For the past two years, I have been studying the effects of natural disasters like this one on rental housing markets. As a professor of real estate, I have analyzed the question from a distance, sifting through data.

This time, however, as a resident of Pasadena, I have seen the carnage up close. I watched the Eaton Fire spread across the mountains from my back porch. I helped friends evacuate before their neighborhood was consumed in flames. Now, they’re sitting at my dining table as they process what they’ve lost and search for a new place to live.

Unfortunately, from my research, I have no doubts about what comes next.

Why disasters drive up rents

Scarcity is the enemy of affordability. This is one of the central tenets of economics. When too many people chase too few goods, prices rise.

So, you might expect that a natural disaster, which destroys housing and inundates the remaining units with new renters, would drive up rents, at least in the short run.

That is exactly what my research has found – but it’s not just the short run.

Two years ago, I worked with a team of researchers to prepare a report for the Brookings Institution, where we compiled a database of natural disasters across a variety of major markets throughout the country from 2000 to 2020. We measured the change in rents in places such as Atlanta, Detroit, Miami and San Francisco that landlords were asking for apartments in disaster-impacted neighborhoods. We then compared those cities with similar neighborhoods that weren’t impacted by the disasters.

We found that natural disasters increased rents during those two decades by 4% to 6%. That means rents were at least 4% higher than they would have been in the absence of the disaster.

These rent hikes were especially clear and pernicious after wildfires in California.

These weren’t just short-term effects. It took 18 months for the full effects to be felt in the market, and they never fully went away. Even four years after the disaster, renters were still paying 2% to 3% more than they would have been without the disaster.

In short, we found that disasters permanently change rental housing markets. They eliminate older, affordable housing, allowing developers to build newer, higher-end and even luxury housing in its place. Those changes drive up insurance costs, and the disasters motivate cities to adopt stricter building codes that in turn add to construction costs for the sake of weathering future disasters better.

How much rents increase, however, depends on how communities and the authorities respond to the disaster.

A burnt-out area following a big fire.
Burned homes are seen from above near the Los Angeles neighborhood of Pacific Palisades on Jan. 9, 2025, after massive fires engulfed whole neighborhoods and displaced thousands of people.
Josh Edelson AFP via Getty Images

Federal aid can slow the growth of rents

We found that rents did not grow as fast when the government stepped in to help.

Specifically, we investigated markets where Congress had used the Community Development Block Grant Disaster Recovery – CDBG-DR – program, providing grants through the Department of Housing and Urban Development. This federal funding typically comes with strings attached and “rental requirements” often mandating that a significant portion of the money be used to build affordable housing.

At least one of these disaster relief grants was issued every year from 2003 to 2020. In some years, Congress allocated as many as 27 different grants across the country to different disaster-impacted areas.

In these markets, we found that rents still rose after disasters – but at a significantly slower pace than in the markets where Congress didn’t send these disaster relief funds.

We dug deeper into several case studies in 2024 to understand why the CDBG-DR program is associated with lower rent hikes over the long run. In this new study, we found that housing markets that benefited from these disaster relief grants were able to build more rental units, easing the housing shortage. They improved affordability by tackling the scarcity problem directly.

Rental units were the key to solving the rent crisis. These cities, where affordability was better post-disaster, didn’t build more single-family homes than the other cities. They built more apartment units.

In these markets, these disaster relief grants saved the average renter between $780 and $1,080 in annual housing costs in 2023.

We believe that this finding shows why it is important not only to rebuild the houses destroyed in disasters like the Los Angeles fires but also to create new rental opportunities in all kinds of housing.

Hope in the aftermath

Here in Los Angeles, the clock is already ticking.

News reports are mounting of landlords raising rents to eye-popping levels.

Fortunately, there are government policies and programs that can help Angelenos find shelter today and that may help the Los Angeles housing market not get even less affordable tomorrow.The Conversation

Anthony W. Orlando, Assistant Professor of Finance, Real Estate and Law, California State Polytechnic University, Pomona

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

Read More

The post Rents rise faster after disasters, but a federal program can help restrain excesses appeared first on theconversation.com

Continue Reading

The Conversation

How the CIA director helps the US navigate a world of spies, threats and geopolitical turbulence

Published

on

theconversation.com – Matthew Clary, Senior Lecturer in Political Science, Auburn University – 2025-01-14 12:44:00

The CIA is the U.S.’s premiere spy agency.
Mark Wilson/Getty Images

Matthew Clary, Auburn University

Today, the United States is navigating an increasingly unsettled world. The positions advising the president on national security are as important as ever. One such position, the director of the Central Intelligence Agency, is key to providing the president and Cabinet with timely intelligence and analysis.

So, what is the job of director of the CIA? What role does the director play in U.S. national security? How has the position changed over time?

The CIA’s role in national security

The CIA director leads the government agency responsible for conducting espionage and covert action. The CIA director is a Cabinet level position but reports to the director of national intelligence.

The CIA was established by the National Security Act of 1947 as America’s premiere civilian-led foreign intelligence agency. The agency carries out espionage and covert action exclusively outside the U.S.

The CIA is organized into five directorates – analysis, operations, science and technology, digital innovation, and support – and 11 regional and topical mission centers. The number of CIA employees is classified.

Espionage activities include the use of spies tasked with collecting useful information from influential people in countries around the world. This information, referred to as human intelligence, often provides depth and context about threats posed to the U.S.

In addition to collecting intelligence, the CIA analyzes and interprets it. The agency employees thousands of expert analysts who assess the information’s implications for U.S. national security. It is this in-depth analysis that is often presented to the president and Cabinet to inform their decision-making.

Covert action is an activity intended to influence political, economic or military conditions abroad without the role of the U.S. being apparent. Such actions include programs such as disinformation campaigns, counterterrorism operations and military raids such as the one used to kill 9/11 attack organizer Osama bin Laden.

a group of people stand in front of a wall with a three-story concrete building in the background
The CIA tracked 9/11 attack mastermind Osama bin Laden to this house in Pakistan, where U.S. special operations forces killed him.
AP Photo/B.K. Bangash

During the Cold War, from 1947 to 1991, the agency conducted numerous controversial covert actions. These included conducting coups in Iran and Guatemala and attempted or successful political assassinations in Congo, the Dominican Republic, Chile and Cuba. It also carried out highly effective programs such as the U-2 spy plane and Operation Argo, which rescued six Americans stranded in Iran after the 1979 revolution.

Effective espionage and covert action are likely to prove crucial for blunting threats that nations such as China, Russia, Iran and North Korea pose to the U.S. They will be key to monitoring the activities of these nations and enabling the director to deliver timely and valuable analysis to the president.

CIA director’s changed role

During the Cold War, the director of central intelligence had autonomy to conduct these covert actions with limited oversight. The position was extremely powerful at the time because the director was in charge of overseeing all U.S. intelligence activities, not just those of the CIA. This left the director of the CIA as the primary voice on intelligence matters to the president.

Since significant reform of the U.S. intelligence community in 2005 in response to the failure to prevent the 9/11 attacks, the role of the CIA director has changed. The most significant of these changes is that the CIA director no longer manages all U.S. intelligence. The reforms gave that responsibility to the more independent director of national intelligence.

The reform also saw the CIA director’s influence diminished because the position is no longer the primary intelligence adviser to the president. This has created tension between the two positions at times, with the CIA maintaining a high degree of independence from even the director of national intelligence.

In 2017, for example, President Donald Trump restored the CIA director as a formal member of the president’s Cabinet. Later, the CIA director was made a regular attendee of the National Security Council, the president’s principal forum for national security deliberations.

While there is more oversight of the CIA today from Congress and the director of national intelligence, the agency remains relatively independent in conducting espionage and covert action. These include covert actions during the Syrian civil war and during Russia’s invasion of Ukraine.

black and white photo of armed men around a boat on a beach
These Cuban soldiers helped defeat the CIA-organized Bay of Pigs invasion in Cuba in 1961.
Keystone/Getty Images

Another change has been the increased size of the intelligence community. The CIA today is only part of a much larger group of intelligence agencies. These include the Federal Bureau of Investigation, the Defense Intelligence Agency, the National Security Agency and more specialized agencies like the National Geospatial-Intelligence Agency.

In spite of this more capable and larger intelligence community, the CIA remains the premiere U.S. intelligence agency. This ensures that the CIA director will remain a key player in any presidential administration. The director possesses an immense responsibility to protect the U.S. from foreign threats.

Although the CIA director’s role has changed over time, what remains clear is its central importance to the success of U.S. national security efforts. This has become only more apparent given the increasing turbulence in world affairs.

This story is part of a series of profiles of Cabinet and high-level administration positions.The Conversation

Matthew Clary, Senior Lecturer in Political Science, Auburn University

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

Read More

The post How the CIA director helps the US navigate a world of spies, threats and geopolitical turbulence appeared first on theconversation.com

Continue Reading

The Conversation

Terrorist groups respond to verbal attacks and slights by governments with more violence against civilians

Published

on

theconversation.com – Brandon J. Kinne, Professor of Political Science, University of California, Davis – 2025-01-14 07:48:00

Yazidi women in Iraq mourn the victims of Islamic State group attacks.
Ismael Adnan/SOPA Images/LightRocket via Getty Images

Brandon J. Kinne, University of California, Davis; Iliyan Iliev, The University of Southern Mississippi, and Nahrain Bet Younadam, University of Arizona

After an Islamic State group-inspired attack in New Orleans killed 14 people on New Year’s Day 2025, President Joe Biden warned that terrorists would find “no safe harbor” in the U.S.

Governments often condemn terrorist groups in this way, as well as making threats and engaging in what we call “verbal attacks.”

But such an approach may be counterproductive; extremist groups tend to respond to such comments by ratcheting up violence against civilians. That’s what we found when we analyzed six years of data on incidents of terrorist violence and their proximity to government denunciations.

Our study focused primarily on the Islamic State group.

The extremist organization came to the world’s attention in early 2014, when it began seizing territory in Iraq and Syria. At the height of its power in 2015, the Islamic State group controlled over 100,000 square kilometers (39,000 square miles).

Although it has declined substantially since then, the group remains the world’s deadliest terror organization – responsible for nearly 2,000 deaths in 2023.

The rapid metastasis of the Islamic State group – it has affiliates across the Middle East, North Africa and South Asia – combined with the extreme brutality of its tactics, triggered waves of condemnations by foreign governments. Former U.S. president Barack Obama initially referred to the Islamic State group as the “JV team” in 2014, implying that the group was not as formidable an opponent as more established groups like al-Qaida. A year later, he vowed to “destroy” the group.

Our motivating research question is whether these and similar statements affect terrorists’ behavior.

Traditionally, researchers have dismissed statements like this as “cheap talk.” And government officials similarly do not take seriously the possibility that such statements might have unintended consequences or inflict actual costs.

But when extremist groups commit terror attacks, they always have an audience in mind. And the Islamic State group closely monitors how governments respond to its actions.

Terrorist groups use attacks on civilians to illustrate the extreme measures they are willing to take to achieve their goals. Our research suggests that when governments denounce terrorists, reject their demands or make retaliatory threats, targeted groups infer that they are not being taken seriously. As a result, they commit further atrocities against civilians, with the intent of signaling their intentions and capabilities even more forcefully.

To confirm this, we used a large-scale machine-coded dataset known as the Integrated Crisis Early Warning System to extract daily data on all events involving the Islamic State group for the period 2014 to 2020. We then employed a coding system known as CAMEO to identify events where governments threatened, denounced or otherwise verbally attacked the group.

We found that when governments initiated any form of verbal attack against the organization, the Islamic State group responded by targeting civilians, typically within two days of a verbal attack.


Iliyan Iliev, Nahrain Bet Younadam, Brandon J Kinne, CC BY-SA

Our model showed that every three verbal attacks by governments led to an additional, otherwise unexpected attack by the Islamic State group on civilians. These attacks averaged over six deaths per attack, so the humanitarian consequences of this effect are substantial.

Why it matters

Government leaders face enormous pressures to address national security threats, and terrorism is a powerful source of anxiety for citizens.

Yet, counterterrorism is expensive, risky and logistically difficult.

As such, publicly threatening or denouncing an organization offers a tempting alternative strategy. But there has been little research into how government leaders’ words might backfire, encouraging extremists to attack civilians.

At the same time, although the Islamic State group has diminished greatly in capacity, transnational terrorism continues to flourish. And the resurgence of the Islamic State group remains a threat to security in the Middle East and beyond.

What still isn’t known

We extended the analysis to the terrorist groups Boko Haram in Nigeria and Al-Qaida in Iraq, and we found similar results. But further research is needed to determine whether this pattern holds for terrorist groups in general.

Our theory argues that extremists respond so strongly to verbal attacks because they view those remarks as questioning the group’s credibility – a phenomenon we refer to as a “credibility deficit.”

But terrorists have many motivations, including the desire to control territory and repress dissent. We don’t yet know the magnitude of these influences relative to credibility.

The Research Brief is a short take on interesting academic work.The Conversation

Brandon J. Kinne, Professor of Political Science, University of California, Davis; Iliyan Iliev, Associate Professor of Political Science, The University of Southern Mississippi, and Nahrain Bet Younadam, Postdoctoral Research Associate in the School of Government and Public Policy, University of Arizona

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

Read More

The post Terrorist groups respond to verbal attacks and slights by governments with more violence against civilians appeared first on theconversation.com

Continue Reading

Trending