Connect with us

The Conversation

‘Pac-Man with a ponytail’ proteins regulate everything from night vision to heartbeats – studying what GRKs look like could improve an array of drugs

Published

on

theconversation.com – Priyanka Naik, Ph.D. Candidate in Structural Biology, Purdue University – 2025-03-07 07:18:00

Rhodopsin kinase – GRK1 – is a GRK found in the retina of your eyes.
Priyanka Naik, CC BY-ND

Priyanka Naik, Purdue University

Each cell in your body relies on precise communication with other cells to function properly. At the center of this process are the molecular switches that turn communication signals in the body on and off. These molecules are key players in health and disease. One such molecular switch is G protein-coupled receptor kinases, or GRKs for short.

From vision to heart function and cell growth, GRKs play a vital role in maintaining physiological balance. When they go awry, they can contribute to cardiovascular disease, inflammatory illnesses like rheumatoid arthritis and multiple sclerosis, neurodegenerative diseases like Alzheimer’s, and multiple types of cancer.

Their involvement in a broad range of diseases makes GRKs an attractive drug target. Around 30% to 40% of all drugs currently on the market focus on these proteins. However, designing drugs that selectively target specific GRKs is a difficult task. Because they are structurally similar to each other and to other proteins, molecules binding to one GRK might also bind to many other enzymes and cause unwanted side effects.

A better understanding of how GRKs interact with their targets can help researchers develop better drugs. So my work in the Tesmer Lab at Purdue University focuses on uncovering more information on the structure of GRKs.

What do G protein-coupled receptor kinases look like?

What researchers know about the structure of GRKs has advanced significantly over the past two decades, revealing the intricate mechanisms by which they function.

The ability to physically look at proteins is highly useful for drug development. Seeing a protein’s structure is like looking at a jigsaw puzzle – you can find the missing piece by knowing its shape. Similarly, knowing a protein’s shape helps scientists design molecules that fit perfectly into it, making drugs more effective.

GRKs consist of several modules, or domains, that serve a particular purpose. Together, these modules assemble into a structure resembling a Pac-Man with a ponytail.

The kinase domain – the Pac-Man – is the catalytic center where the protein does its main job: adding a phosphate group to its target to control its activity. It has two subdomains – one small and one large lobe – connected by a hinge that can open and close. Like Pac-Man, this domain closes around reactants and reopens to release products.

Array of spiral ribbons arranged into roughly three sections
The three domains of GRKs resemble a Pac-Man with a ponytail. Shown here is GRK2.
Priyanka Naik, CC BY-ND

The RH domain – the ponytail – stabilizes the kinase domain. It guides and docks the GRK to its target protein.

Humans have seven GRKs, each specialized for different tissues and functions, and each unique in structure. Some regulate vision, while others affect your brain, kidney and immune functions, among others. Their structural differences dictate how they interact with their targets, and understanding these distinctions is key to designing drugs that can selectively target each one.

In 2003, researchers in the lab where I work uncovered the first known structure of a GRK – specifically, GRK2, which is involved in heart functions and cell proliferation – by using a technique called macromolecular crystallography. This involved bombarding a GRK2 sample with X-rays and tracing where they bounce off to determine where each atom of the protein is located.

Current state of GRK research

By determining how the three modules of GRK2 are arranged and where its target molecules would bind, my colleagues and I can design drugs that strongly interact with GRK2.

Irregularly shaped lump resembling a drumette
GRK2 with Paxil bound to its active site.
Priyanka Naik, CC BY-ND

For example, in 2012, one of my colleagues discovered that the antidepressant Paxil could inhibit GRK2. To build on this discovery, our team designed drugs with similar shapes to Paxil to identify ones that effectively and selectively inhibit GRK2. The goal was to develop treatments that could target GRK2-related diseases such as heart failure and breast cancer without interfering with other proteins, thereby minimizing side effects.

After determining what Paxil looks like when bound to GRK2, we designed a series of derivative compounds that better fit into GRK2’s active site – the missing jigsaw puzzle pieces. Some of these compounds were able to better block GRK2 compared with Paxil, improving the ability of heart muscle cells to contract. While the research is still in its early stages, our findings suggest that these compounds could potentially be used to treat heart failure.

An important missing piece of the story is what GRK2 looks like when bound to its primary target in the cells. These protein complexes are highly shape-shifting, making traditional imaging methods very difficult.

However, recent advances in imaging have made it possible to determine the structure of these molecules. Cryogenic electron microscopy, or cryo-EM, flash-freezes proteins and bombards them with electrons to capture their structure. These studies have thus far revealed what GRK1 and GRK2 look like when bound to two different target proteins, offering critical insights into how they work.

YouTube video
Cryo-EM was the subject of the 2017 Nobel Prize in chemistry.

My work focuses on uncovering how GRK2 function is different from GRK1. These proteins play different physiological roles – GRK1 primarily regulates vision, while GRK2 is involved in heart function and cell proliferation. Identifying structural differences in different GRKs will help researchers design drugs that only target the GRK of interest, thus preventing side effects.

By combining cutting-edge imaging techniques with decades of research, scientists in my lab and others hope to one day unlock the full therapeutic potential of GRKs, offering pinpointed treatments for a wide range of diseases.The Conversation

Priyanka Naik, Ph.D. Candidate in Structural Biology, Purdue University

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

Read More

The post ‘Pac-Man with a ponytail’ proteins regulate everything from night vision to heartbeats – studying what GRKs look like could improve an array of drugs appeared first on theconversation.com

The Conversation

Daylight saving time and early school start times cost billions in lost productivity and health care expenses

Published

on

theconversation.com – Joanna Fong-Isariyawongse, Associate Professor of Neurology, University of Pittsburgh – 2025-03-07 13:55:00

Daylight saving time kicks in on March 9, 2025, but some say it leads to more heart attacks, depression and car accidents.
Lord Henri Voton/E+ via Getty Images

Joanna Fong-Isariyawongse, University of Pittsburgh

Investigations into the 1986 Space Shuttle Challenger disaster revealed that key decision-makers worked on little sleep, raising concerns that fatigue impaired their judgment. Similarly, in 1989, the Exxon Valdez oil spill resulted in a massive environmental catastrophe. The official investigation revealed the third mate, in charge of steering the ship, was running on too little sleep, among other problems.

While these specific disasters were not caused by daylight saving time, they are conclusively linked to fatigue, based on postaccident investigations and reports. They underscore the well-documented dangers of sleep deprivation and fatigue-related errors. Yet a vast body of research shows that every year, the shift to daylight saving time needlessly exacerbates these risks, disrupting millions of Americans’ sleep and increasing the likelihood of accidents, health issues and fatal errors.

Imagine a world where one simple decision – keeping our clocks aligned with the natural cycle of the Sun – could save lives, prevent accidents and improve mental well-being. It’s not just about an hour of lost sleep; it’s about how small disruptions ripple through our health, our workplaces and even our children’s futures.

I’m a neurologist who specializes in sleep health. I’ve seen firsthand the negative impacts of poor sleep; it has enormous personal and economic consequences.

Yet despite overwhelming research supporting better sleep policies – such as delaying school start times to align with adolescent biology and the adoption of permanent standard time – these issues remain largely overlooked in public policy discussions.

Sleep deprivation comes with real costs

Chronic sleep deprivation does more than leave people tired. It costs an estimated US$411 billion annually in lost productivity and health care costs. Poor sleep leads to workplace mistakes, car accidents and long-term health issues that strain businesses, families and the economy as a whole.

Fortunately, there’s a fix. Smarter sleep policies – such as permanent standard time and later school start times – can boost efficiency, improve health and save lives.

In a classroom setting, students take an exam.
Sleep-deprived teens have lower test scores and graduation rates.
skynesher/E+

Up before dawn

Teenagers are the most sleep-deprived age group in the U.S. Multiple studies and surveys show that anywhere from 71% to 84% of high school students report getting insufficient sleep.

This is largely due to early school start times, which force teens to wake up before their biological clocks are ready. If you have a teenager, you probably see it every day: The teen struggling to wake up before sunrise, rushing out the door without breakfast, then waiting in the dark for the school bus.

More than 80% of public middle and high schools in the U.S. start before 8:30 a.m., with 42% starting before 8 a.m. and 10% before 7:30 a.m. As a result, some districts have bus pickups as early as 5 a.m.

Teenagers are going through a natural shift in their circadian rhythms by about two hours. This shift, driven by hormones and biology, makes it hard for them to fall asleep before around 11 p.m. The bodies of teens aren’t wired for these schedules, yet schools and society have designed a system that forces them to function at their worst.

Declining scores, drowsy driving and depression

Sleep-deprived teens have lower grades and test scores, more car crashes caused by drowsy driving, more alcohol and drug use and higher rates of depression, anxiety suicide and aggressive behavior, including carrying weapons.

Along with the health benefits, studies have found that moving school start times to 8:30 am or later could add $8.6 billion to the economy within two years, partly by increased graduation rates.

While concerns about increased transportation costs exist, such as the need for additional buses or drivers due to staggered school start times, some districts have found that optimizing bus routes can offset expenses, making the change cost-neutral or even cost-saving. For instance, a study in Boston found that reorganizing bus schedules using advanced algorithms reduced the number of buses needed and improved efficiency, which allowed high school students to start later and better align with their natural sleep cycles. This change not only supported adolescent sleep health but also saved the district $5 million annually.

YouTube video
Studies show that daylight saving time does not reduce energy use.

More heart attacks, car wrecks and suicide

Every March, most Americans shift their clocks forward for daylight saving time. Studies show this change disrupts sleep and leads to measurable adverse outcomes, including a significant increase in heart attacks. These effects linger for days after the shift, as sleep-deprived workers struggle to adjust.

The mental health impact is also severe. Suicide rates increase in the weeks following the switch, particularly for those already vulnerable to depression.

Unlike daylight saving time, standard time follows the body’s natural circadian rhythm, which is primarily regulated by exposure to sunlight. Our internal clocks are most stable when morning light exposure occurs early in the day, signaling the body to wake up and regulate key biological functions such as hormone production, alertness and metabolism. In contrast, daylight saving time artificially extends evening light, delaying the body’s release of melatonin and making it harder to fall asleep at a biologically appropriate time.

Studies have found that adopting permanent standard time could prevent up to 5,000 suicides annually by reducing seasonal depression, decrease errors, injuries and absenteeism in the workplace and make roads safer, potentially preventing 1,300 traffic deaths each year.

Times are changing

The U.S. tried permanent daylight saving time in 1974. It was so unpopular that Congress repealed it within nine months.

Russia tried it too, in 2011, but switched back three years later. The United Kingdom dropped permanent daylight saving time in 1971 after three years, and Portugal in 1996 after four. All of these countries found that the switch caused widespread public dissatisfaction, health concerns, more morning car accidents and disrupted work schedules. No country is currently on year-round daylight saving time.

These examples provide real-world evidence that permanent DST is undesirable due to public dissatisfaction, safety concerns and negative health effects – all three countries attempted it and ultimately reversed course. Since 2022, there has been renewed debate, largely driven by former U.S. Sen. Marco Rubio’s Sunshine Protection Act, which aims to make DST permanent.

However, the name is misleading because it doesn’t “protect” sunshine but rather eliminates critical morning light, which is essential for regulating circadian rhythms. Major health organizations, along with the National Safety Council, strongly oppose permanent DST due to its well-documented risks.

There are signs that suggest the U.S. is finally waking up to these problems. Out of 13,000 school districts, 1,000 have independently adopted later school start times. California and Florida have enacted laws requiring high schools to start no earlier than 8:30 a.m. California’s mandate went into effect in 2022, and Florida’s is set to begin in 2026.

Permanent standard time and later school start times are not radical ideas. They’re practical, evidence-based solutions based on human biology. Implementing these changes nationally would require congressional action. However, current federal law already allows states to adopt permanent standard time, as Arizona and Hawaii have done, setting a precedent for the rest of the country.The Conversation

Joanna Fong-Isariyawongse, Associate Professor of Neurology, University of Pittsburgh

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

Read More

The post Daylight saving time and early school start times cost billions in lost productivity and health care expenses appeared first on theconversation.com

Continue Reading

The Conversation

How Trump’s $2B court battle over foreign aid could reshape executive authority

Published

on

theconversation.com – Charles Wise, Professor Emeritus of Public Affairs, The Ohio State University – 2025-03-07 11:58:00

A sign outside of the U.S. Agency for International Development building in Washington, D.C.
Bryan Dozier/Middle East Images/AFP via Getty Images

Charles Wise, The Ohio State University

Amid the chaos of the Trump administration’s first few weeks in office, a court case regarding the president’s legal right to stop payment of nearly US$2 billion in U.S. Agency for International Development contracts poses an important legal question whose answer may show just how strong the country’s separation of powers actually is.

On Jan. 20, 2025, President Donald Trump issued an executive order pausing all foreign aid funding, most of which is administered by USAID. A little more than two weeks later, USAID laid off all but a few hundred of its 10,000 workers.

U.S. District Judge Amir Ali issued a temporary order on Feb. 13 for the administration to not end or pause any existing foreign aid contracts – and again ordered on Feb. 25 that the administration needed to pay the $2 billion owed to various aid organizations for completed work.

After the Trump administration filed an emergency appeal of the decision to the Supreme Court, the justices, in a 5-4 ruling on March 5, found that the federal judge’s decision can temporarily take effect while the district court considers the merits of the case.

Now, the Trump administration is facing a deadline imposed by Judge Ali of 11 a.m. on March 10, 2025, to announce a new timeline for delivering the frozen foreign aid payments.

Amy Lieberman, a politics and society editor at The Conversation U.S., spoke with Charles Wise, an expert on public administration and law, to understand what is fueling this court case and why it has become a test of how far Trump can push the boundaries of presidential power.

Two white men and a white woman all wearing black robes face a man with white hair and a dark suit and smile at him.
Supreme Court Justices Brett Kavanaugh, left, Amy Coney Barrett, center, and former Justice Anthony Kennedy speak with President Donald Trump after his speech at the U.S. Capitol in March 4, 2025.
Chip Somodevilla/Getty Images

What is most important to understand about the Supreme Court’s ruling on USAID funding?

The Trump administration issued a blanket executive order freezing all USAID funds on Jan. 20, 2025. There have been many twists and turns in this case since then, but the Washington, D.C., district court determined in February that the organizations that receive USAID funding to deliver food or health care to people in need, as well as other recipients of USAID money in foreign countries, would suffer irreparable harm.

The U.S. District Court in Washington, D.C., also said that the administration did not follow proper procedures in the law. The Administrative Procedure Act has a set of standards that requires the president to do certain things before making any unilateral kind of action to withhold funds.

The Supreme Court’s March 5 order is not the final ruling on the case, but it does allow the U.S. District Court decision to stand – at least for now. This ruling requires the government to release funds to USAID recipients. The Supreme Court’s decision also directs the district court to clarify what the government must do to comply with the district court’s order, including considering the feasibility of the timeline within which the government must release the money.

This is all taking place in a very short time frame, in the context of the D.C. district court issuing a temporary restraining order. It is saying: Let’s freeze the existing situation in place so we can have a full hearing on this issue.

Why is this case important?

Any administration is prohibited from just withholding funds for any program it doesn’t like without following the procedures prescribed by law. This case matters because the D.C. district court’s decision puts boundaries on what the Trump administration can do to withhold funds that Congress has appropriated. It forces the administration to follow the laws that Congress and previous presidents have agreed on and adopted.

It ultimately comes down to a contest between the branches of government, and, specifically, the presidency and Congress. This is where Articles 1 and 2 of the U.S. Constitution – and how they divided powers between the president and Congress – comes in. The Trump administration claimed that the court should have respected the president’s Article 2 powers to administer the federal government’s spending. The D.C. court acknowledged the president’s powers under Article 2 but said it has to be balanced against Congress’ right, under Article 1, to appropriate funds.

A blonde woman wearing a blue shirt and holding an orange flower walks past people and wheels a suitcase outside.
A terminated federal worker leaves the offices of the U.S. Agency for International Development in Washington, D.C., on Feb. 28, 2025, after being fired.
Bryan Dozier/Middle East/AFP via Getty Images

What happens if Trump and his administration do not abide by this order?

Trump’s officials have a decision to make. Are they going to follow the executive order or the court’s order? That’s not a fun place to be. Administrative officials take an oath to uphold the Constitution and the laws of the U.S., which subjects them to court decisions.

The president himself is not responsible for distributing USAID funds. State Department officials are responsible for dispersing the funds, and Secretary of State Marco Rubio was appointed as the acting administrator of USAID on Feb. 3, 2025.

If Rubio and other officials refuse to comply with the court’s order, the D.C. judge, Amir Ali, can hold those officials in contempt of court. Ali has a variety of tools he can use – one is to levy fines against them individually. He could say they have to pay a thousand dollars per day for each day they don’t execute the court’s order.

What will happen next in this case?

The Supreme Court said in a brief opinion on March 5 that the Feb. 26, 2025, deadline for the government to pay USAID and its contractors had already passed and instructed Ali to “clarify what obligations the Government must fulfill to ensure compliance” with paying USAID.

The government has argued to the court that the timeline the judge initially set was too fast – they couldn’t do it that fast.

Now, a few things are going to happen. Ali has ordered the government to develop and release a new schedule to release funds and to have that ready by March 10.

The second part is that the district court judge will probably schedule a hearing on the merits of the case, in which Ali will be assessing the administration’s argument about whether the administration has violated the Administrative Procedure Act. Ultimately, the Trump administration could appeal Ali’s decision, and the case could wind up back at the Supreme Court.The Conversation

Charles Wise, Professor Emeritus of Public Affairs, The Ohio State University

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

Read More

The post How Trump’s $2B court battle over foreign aid could reshape executive authority appeared first on theconversation.com

Continue Reading

The Conversation

Pause in aid has introduced uncertainty into Ukraine’s military planning − forever changing its war calculus

Published

on

theconversation.com – Benjamin Jensen, Professor of Strategic Studies at the Marine Corps University School of Advanced Warfighting; Scholar-in-Residence, American University School of International Service – 2025-03-07 07:27:00

Is the Sun setting on Ukraine’s offensive capabilities?
Diego Herrera Carcedo/Anadolu via Getty Images

Benjamin Jensen, American University School of International Service

War is a numbers game. Each side involved must marshal the supplies, troops and firepower needed to sustain the fight, thwart advancing armies and, hopefully, prevail.

But it’s also a game of uncertainty.

For the past three years, Ukraine’s military planners have had to approach every battle with a series of cold calculations: How much ammunition is left? How many air defense interceptors can be fired today, without running short tomorrow? Do we have the men and equipment needed to advance or hold position?

But now, with U.S. military assistance on hold and European support constrained by economic realities, that uncertainty is growing.

As an expert on warfare, I know this isn’t just a logistical problem; it’s a strategic one. When commanders can’t predict their future resource base, they are forced to take fewer risks, prioritize defense over offense and hedge against worst-case scenarios.

In war, uncertainty doesn’t just limit options. It shapes the entire battlefield and fate of nations.

Trump orders a pause

On March 3, 2025, President Donald Trump announced a suspension to all U.S. military aid to Ukraine. It followed a fractious Oval Office meeting between the U.S. president and Volodymyr Zelenskyy, after which Trump declared the Ukrainian leader “not ready for peace.”

Two days later, Central Intelligence Agency Director John Ratcliffe announced Washington was also pausing all intelligence sharing and ordered key allies such as the United Kingdom to limit the information they give Kyiv.

National security adviser Michael Waltz has linked the pause to ongoing U.S.-Ukrainian negotiations, stating that weapons supplies and intelligence sharing will resume once Ukraine agrees to a date for peace talks with Russia.

A man in a blue suit and red ties shouts at another seated man.
U.S. President Donald Trump and Ukrainian President Volodymyr Zelenskyy argue in the Oval Office on Feb. 28, 2025.
Andrew Harnik/Getty Images

A critical supplier of weapons

Any pause, no matter how long, will hurt Ukraine.

The U.S. has been the largest provider of military assistance to Kyiv since Russia’s 2022 invasion, followed by the European Union.

While the level of support is debated – it is often skewed by how one calculates equipment donations using presidential drawdown authority, through which the president can dip into the Department of Defense’s inventory – the U.S. has undoubtedly delivered critical weapons systems and a wide range of ammunition.

Though this assistance has decreased U.S. military stockpiles, it has helped Washington invest in its domestic defense industry and expand weapons production.

In addition, while Europe is starting to increase its own defense expenditures, EU members are stuck with flat economic growth and limits on how much they can borrow to invest in their own militaries, much less Ukraine.

This makes the U.S. a critical partner for Ukraine for at least another two years while Europe expands its military capacity.

These conditions affect the design of Ukraine’s military campaigns. Planners in Kyiv have to balance predictions about the enemy’s strengths and possible courses of action with assessments of their own resources.

This war ledger helps evaluate where to attack and where to defend.

Uncertainty skews such calculation. The less certain a military command is about its resource base, the more precarious bold military maneuvers become.

It is through this fog of uncertainty that any pause in assistance shapes the course of the war in Ukraine and the bargaining leverage of all parties at the negotiating table.

A new uncertain world

The White House has indicated that the pause in military aid and intelligence sharing will be lifted once a date for peace talks is set.

But even if U.S. weapons and intel begin to flow again, Ukrainian generals will have to fight the duration of the war under the knowledge that its greatest backer is willing to turn off the taps when it suits them.

And the consequences of this new uncertain world will be felt on the battlefield.

Ukraine now faces a brutal trade-off: stretch limited resources to maintain an active defense across the front, or consolidate forces, cede ground and absorb the political costs of trading space for time.

Material supply has shaped operational tempo over the course of the war. When Moscow expects Kyiv to be low on ammunition, it presses the attack. In fact, key Russian gains in eastern Ukraine in 2024 coincided with periods of critical supply shortages.

Russia used its advantage in artillery shells, which at times saw Moscow firing 20 artillery shells to every Ukrainian artillery shell fired, and air superiority to make advances north and west of the strategic city of Avdiivka.

Looking to the front lines in 2025, Russia could use any pause in supplies to support its ongoing offensive operations that stretch from Kherson in southern Ukraine to Kharkiv in the north and efforts to dislodge Ukrainian units in the Russian Kursk region.

This means Ukraine will have to decide where to hold the line and where to conduct a series of delaying actions designed to wear down Russian forces.

Trading space for time is an old military tactic, but it produces tremendous political costs when the terrain is your sovereign territory.

As such, the military logic of delaying actions creates political risks in Ukraine – sapping civilian morale and undermining support for the government’s war management.

A horrible choice

This dilemma will drive where and how Ukraine weights its efforts on the battlefield.

First, long-range strike operations against Russia will become increasingly less attractive. Every drone that hits an oil refinery in Russia is one less warhead stopping a Russian breakthrough in the Donbas or counterattack in Kursk. Ukraine will have to reduce the complexity of its defensive campaign and fall back along lines deeper within its own territory.

Second, Russia doesn’t fight just on the battlefield – it uses a coercive air campaign to gain leverage at the negotiating table. With U.S. military aid on hold, Moscow has a prime opportunity to escalate its strikes on Ukrainian cities and infrastructure, forcing Kyiv into painful choices about whether to defend its front lines or its political center of gravity.

From Vietnam to Ukraine, airpower has historically been a key bargaining tool in negotiations.

President Richard Nixon bombed North Vietnam to force concessions. Russia may now do the same to Ukraine.

Seen in this light, Russia could intensify its missile and drone campaign against Ukrainian cities and infrastructure – both to weaken defenses and to apply psychological and economic pressure. And because Kyiv relies on Western assistance, including intelligence and systems such as U.S.-built Patriot surface-to-air missiles to defend its skies, this coercive campaign could become effective.

As a result, Ukraine could be faced with a horrible choice. It may have to concentrate dwindling air defenses around either key military assets required to defend the front or its political center of gravity in Kyiv. Interception rates of Russian drones and missiles could drop, leading to either opportunities for a Russian breakout along the front or increased civilian deaths that put domestic pressure on Ukrainian negotiators.

Uncertainty reigns supreme

The real problem for Ukraine going forward is that even if the U.S. resumes support and intelligence sharing, the damage is done.

Uncertainty, once introduced, is hard to remove. It increases the likelihood that Ukraine’s leaders will stockpile munitions to reduce the risk of future pauses, rather than use them to take the fight to Russia.

And with battlefield decision-making now limited, Ukraine’s military strategists will increasingly look toward the least worst option to hold the line until a lasting peace is negotiated.The Conversation

Benjamin Jensen, Professor of Strategic Studies at the Marine Corps University School of Advanced Warfighting; Scholar-in-Residence, American University School of International Service

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

Read More

The post Pause in aid has introduced uncertainty into Ukraine’s military planning − forever changing its war calculus appeared first on theconversation.com

Continue Reading

Trending