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Daniel Dunaief

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Photo courtesy of SBU

By Daniel Dunaief

Predicting extreme heat events is at least as important as tracking the strength and duration of approaching hurricanes.

Ping Liu

Extreme heat waves, which have become increasingly common and prevalent in the western continental United States and in Europe, can have devastating impacts through wildfires, crop failures and human casualties.

Indeed, in 2003, extreme heat in Europe caused over 70,000 deaths, which was the largest number of deaths from heat in recent years.

Recently, a trio of scientists at Stony Brook University’s School of Marine and Atmospheric Sciences (SoMAS) received $500,000 from the National Oceanographic and Atmospheric Administration to study heat events by using and analyzing NOAA’s Seamless System for Prediction and EArth System Research, or SPEAR, to understand heat waves and predict future such events.

The first objective is to evaluate simulations in the SPEAR model, by looking at how effectively this program predicts the frequency and duration of heat events from previous decades, said Ping Liu, who is the Principal Investigator on the project and is an Associate Professor at SoMAS.

Liu was particularly pleased to receive this funding because of the “urgent need” for this research, he explained in an email.

The team will explore the impact of three scenarios for increases in overall average temperature from pre-Industrial Revolution levels, including increases of 1.5 degrees Celsius, 2 degrees Celsius and four degrees Celsius, which are the increases the IPCC Assessment Reports has adopted.

Answering questions related to predicting future heat waves requires high-resolution modeling products, preferably in a large ensemble of simulations from multiple models, for robustness and the estimation of uncertainties, the researchers explained in their proposal.

“Our evaluations and research will provide recommendations for improving the SPEAR to simulate the Earth system, supporting NOAA’s mission of ‘Science, Service and Stewardship,’” they explained.

Kevin Reed, Professor, and Levi Silvers, research scientist, are joining Liu in this effort.

Liu and Reed recently published a paper in the Journal of Climate and have conducted unfunded research on two other projects. Liu brought Silvers into the group after Reed recommended Silvers for his background in climate modeling and dynamics.

Reed, who is Interim Director of Academic, Research and Commercialization Programs for The New York Climate Exchange, suggested that the research the heat wave team does will help understand the limitations of the SPEAR system “so that we can better interpret how the modeling system will project [how] blocking events and heat will be impacted by climate change.”

An expert in hurricanes, Reed added that blocking events, which can cause high pressure systems to stall and lead to prolonged heat waves, can also lead to unique hurricane tracks, such as Hurricane Sandy in 2012.

“A longer term goal of many of my colleagues at Stony Brook University is to better understand these connections,” said Reed, who is Associate Provost for Climate and Sustainability Programming and was also recently appointed to the National Academies’ Board on Atmospheric Sciences and Climate.

Liu will use some of the NOAA funds to recruit and train a graduate student, who will work in his lab and will collaborate with Reed and Silvers.In the bigger picture, the Stony Brook researchers secured the NOAA backing in the same year that the university won the bidding to develop a climate solutions center on Governors Island.

Reed suggested that the “results of the work can be shared with our partners and can help to inform future societally relevant climate research projects.”

Focus on two regions

The systems that have caused an increase in heat waves in the United States and Europe are part of a trend that will continue amid an uneven distribution of extreme weather, Liu added.

Heat waves are becoming more frequent and severe, though the magnitude and impact area vary by year, Liu explained.

The high pressure systems look like ridges on weather maps, which travel from west to east.

Any slowing of the system, which can also occur over Long Island, can cause sustained and uncomfortable conditions.

Over the past several years, Liu developed computer algorithms to detect high pressure systems when they become stationary. He published those algorithms in two journal papers, which he will use in this project.

Personal history

Born and raised in Sichuan, China, Liu moved to Stony Brook from Hawaii, where he was a scientific computer programmer, in November of 2009.

He and his wife Suqiong Li live in East Setauket with their 16-year old daughter Mia, who is a student at Ward Melville High School and  a pianist who has received classical training at the Manhattan School of Music. Mia has been trained by award-winning teacher Miyoko Lotto.

Outside of the lab, Liu, who is five-feet, seven-inches tall, enjoys playing basketball on Thursday nights with a senior basketball team.

Growing up in China, Liu was always interested in weather phenomenon. When he was earning his PhD in China at the Institute for Atmospheric Physics at the Chinese Academy of Sciences in Beijing, he had limited computer resources, working in groups with IBM and, at times, Dell computer. He built several servers out of PC parts.

With air trapped inside the basin surrounded by tall mountains, Sichuan is particularly hot in the summer, which motivated him to pursue the study of heat waves.

Liu appreciated how Stony Brook and Brookhaven National Laboratory had created BlueGene, which he used when he arrived.

As for the future of his work, Liu believes predicting extreme heat waves is increasingly important “to help planners from local to federal levels cope with a climate that is changing rapidly and fostering more frequent and more severe heat events,” he explained.

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Shohei Ohtani. Photo by Mogami Kariya/Wikimedia Commons

By Daniel Dunaief

Daniel Dunaief

You know when you were younger and your parents, grandparents, teachers and adults in general urged you to “make every second count.”

“A second,” you’d scoff incredulously. “How much could I do in a second? It took me longer than a second just to say those words, and those, and those, and they don’t seem to count for much.”

While that may be true most of the time for most of us, it’s certainly not the case for sport’s best paid athlete, the baseball sensation Shohei Ohtani, who signed a $700 million contract to play for the Los Angeles Dodgers over the next decade.

To borrow from the Tom Cruise movie “Jerry Maguire,” the Dodgers showed him the money!

Wait, don’t go if you’re not a sports fan. This isn’t about baseball. It’s about money!

Just for fun, let’s take a closer look at the approximately $33.5 million Sports Insider Andrew Petcash estimates Ohtani will earn per year after taxes and fees.

Assuming he’s paid for every second of each year, that means, he earns $1.06 each second. That’s what he’ll earn each second he sleeps, eats, sits in traffic, brushes his teeth or waits for an announcer to say his name so he can run on the field.

Assuming he has a healthy 60 beats per minute heart rate, that means each time his heart goes “lub-dub,” he earns about a dollar.

According to a website called covers.com, the average time to sing “The National Anthem” is 115.4 seconds, which means Ohtani makes $122.32 each time he listens to the national anthem of a country where he’s earning much more than a living.

Extending the math a bit, Ohtani clears $3,824.74 per hour.

As for each day, he’ll make $91,780.82. At that rate, it will take the star pitcher and home run hitter (yes, he can do both) 11 days to make a million dollars.

Each month, his after tax take home pay will be $2.79 million. Assuming Ohtani, who is single, follows the General Rule for engagement rings, namely, that he should spend at least two months of salary on the ring, some lucky future partner may be in line for a ring that costs $5.58 million. That assumes the value of the ring comes from what he’s taking home and not his overall salary. If he chose a ring based on his gross pay, he’d spend a whopping $11.7 million, which is the equivalent of 16 average priced homes in Setauket.

So, speaking of cash, what does $33.5 million look like? If you stacked dollar bills, which are 0.0043 inches wide, one on top of the other without any extra space between the bills, the pile of money would reach 12,004 feet. That would stretch 2.3 miles into the sky. 

Now, if he were to try to hold that money — and no one uses cash anymore, so why would he – he would need more than a few teammates. There are $454 dollar bills in a pound, which means that $33.5 million weighs 73,788 pounds. 

Realistically, dollar bills aren’t the most likely currency for someone who earns over $1 for every second. Maybe you’d prefer to stack $1,000 bills? That would still present a pile of money that’s about 12 feet tall. Imagine how much money you’d make if you were standing downwind of that pile during a sudden gust? That sounds like the winner’s circle for a future game show. 

Of course, you say, the first player since Babe Ruth to demonstrate proficiency as a pitcher and a home run hitter is not getting paid for every second, but, rather, for the magic he works on the field.

If we want to break it down just to the time he’s paid during games, the average time for a baseball game in 2023 was two hours and 42 minutes. The season has 162 games. Let’s throw in 19 additional games, assuming his Dodgers win each series in the maximum number of games and become World Series champions. That means, he’s a part of 29,322 minutes of baseball or 1.8 million seconds. Assuming his paycheck covers games and not all the practice time and spring training, he clears $38.88 per second. So, depending on how you look at it, he earns somewhere between $1.06 for every second of each year and $38.88 for each second he plays. 

Yeah, and you thought your lawyer was charging you a pretty penny!

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Zhe Qian

By Daniel Dunaief

Addition and subtraction aren’t just important during elementary school math class or to help prepare tax returns.

As it turns out, they are also important in the molecular biological world of healthy or diseased cells.

Some diseases add or subtract methyl groups, with a chemical formula of CH3, or phosphate groups, which has a phosphorous molecule attached to four oxygen molecules.

Nicholas Tonks. Photo courtesy of CSHL

Adding or taking away these groups can contribute to the progression of a disease that can mean the difference between sitting comfortably and watching a child’s performance of The Wizard of Oz or sitting in a hospital oncology unit, waiting for treatment for cancer.

Given the importance of these units, which can affect the function of cells, researchers have spent considerable time studying enzymes such as kinases, which add phosphates to proteins.

Protein tyrosine phosphatases, which Professor Nicholas Tonks at Cold Spring Harbor Laboratory purified when he was a postdoctoral researcher, removes these phosphate groups.

Recent PhD graduate Zhe Qian, who conducted research for six years in Tonks’s lab while a student at Stony Brook University, published a paper in the journal Genes & Development demonstrating how an antibody that interferes with a specific type of protein tyrosine phosphatase called PTPRD alters the way breast cancer spreads in cell cultures.

“The PTPs are important regulators of the process of signal transduction — the mechanisms by which cells respond to changes in their environment,” explained Tonks. “Disruption of these signal transduction mechanisms frequently underlies human disease.”

To be sure, Tonks cautioned that the study, which provides a proof of concept for the use of antibodies to manipulate signaling output in a cancer cell, is a long way from providing another tool to combat the development or spread of breast cancer.

The research, which formed the basis for Qian’s PhD project, offers an encouraging start on which to add more information.

Blocking the receptor

Qian, who goes by the name “Changer,” suggested that developing a compound or small molecule to inhibit or target the receptor for this enzyme was difficult, which is “why we chose to use an antibody-based method,” he said.

By tying up a receptor on the outside of the cell membrane, the antibody also doesn’t need to enter the cell to reach its target.

The Antibody Shared Resource, led by Research Associate Professor Johannes Yeh, created antibodies to this particular receptor. Yeh created an antibody is shaped like a Y, with two arms with specific attachments for the PTPD receptor.

Once the antibody attaches, it grabs two of these receptors at the same time, causing a dimerization of the protein. Binding to these proteins causes them to lose their functionality and, ultimately, destroys them.

Cell cultures of breast cancer treated with this antibody became less invasive.

Limited presence

One of the potential complications of finding a new target for any treatment is the side effects from such an approach.

If, for example, these receptors also had normal metabolic functions in a healthy cell, inhibiting or killing those receptors could create problematic side effect.

In this case, however,  the targeted receptor is expressed in the spine and the brain. Antibodies normally don’t cross the blood-brain barrier.

Qian and Tonks don’t know if the antibody would affect the normal function of the brain. Further research would help address this and other questions.

Additionally, as with any possible treatment, future research would also need to address whether cancer cells developed resistance to such an approach.

In the time frame Qian explored, the cells in culture didn’t become resistant.

If the potential therapeutic use of this antibody becomes viable, future researchers and clinicians might combine several treatments to develop ways to contain breast cancer.

Eureka moment

In his research, Qian studied the effect of these antibodies on fixed cell, which are dead but still have the biochemical features of a living cell He also studied living cells.

When the antibody attaches to the receptor, it becomes visible through a staining process. Most antibody candidates stain living cells. Only the successful one showed loss-of-signal in living staining.

The antibody Qian used not only limited the ability of the receptor to send a signal, but also killed the receptor. The important moment in his research occurred when he discovered the antibody suppressed cancer cell invasion in cell culture.

Outside of the lab, Qian enjoys swimming, which he does between four and five times per week. Indeed, he combined his athletic and professional pursuits when he recently raised funds for Swim Across America.

“I not only want to do research, but I also want to call more attention to cancer research in the public,” said Qian.

The Swim Across America slogan suggests that each stroke is for someone who “couldn’t be with us” because of cancer. In the lab, Qian thinks each time he pipettes liquids during one of his many experiments it is for someone who couldn’t make it as well.

Qian, who currently lives in Hicksville, grew up in Suchow City, which is a village west of Shanghai and where Cold Spring Harbor Asia is located. 

Qian has been living on Long Island since he arrived in the United States. Qian graduated from Stony Brook University in October and is currently looking for a job in industry.

Looking back, Qian is pleased with the work he’s done and the contribution he’s made to breast cancer research. He believes the antibody approach offers a viable alternative or complement to searching for small molecules that could target or inhibit proteins or enzymes important in the development of cancer.

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Pixabay photo

By Daniel Dunaief

Daniel Dunaief

We have friends who live close to us who are pregnant. Okay, that sounds weird, right? She’s pregnant, and he looks sheepish, like he’s not sure what’s coming.

That’s not entirely fair. He was socially awkward before he brought his small package of genetic material to the pregnancy party. Why would anyone imagine he would be any different in the months before he makes a head first dive down the rabbit hole into the wonders and challenges of parenthood?

Now, if their families are anything like others I’ve known, they are bound to have a wide range of pre and post delivery discussions.

“Are you going to name the baby after my side of the family?”

“Make sure you put sugar, spice and everything nice in the crib or the baby will become colicky like your Aunt Michelle. She was one of the most miserable babies we’ve ever seen and that’s because her mother forgot about the sugar and spice under the crib.”

One of the most fascinating and sometimes confounding parts of the baby discussion, which can extend well into the years that follow, is the family credit for various traits.

To wit, “He’s incredibly serious and focused just like his Uncle Oswald. That Oswald was a man with a purpose from the time he was born, just like your little baby Joey.”

Or maybe, “Morgan has the same broad smile, laugh or sense of humor as her Aunt Carol.”

Each family can dig in, sharing ways that the developing child has characteristics they are convinced come from one side of the family, often from the speaker who has a proprietary interest in propagating the enduring myth of a family heritage.

Such talk suggests somehow that heredity is much more important than environment. The credit can go beyond physical characteristics such as long eyelashes, rounded shoulders, or sparkling eyes: they can include artistic talent, an ability to relate to other people, or a proficiency for languages.

That somehow seems un-American. After all, we the people generally believe that hard work can help people become proficient in any area, developing the kind of talent that differentiates them in their field and allowing them to control their destiny.

Such strong genetic links, while providing an appealing way to connect to ancestors and to those who aren’t around to smile and play with their descendants, is akin, if you’ll pardon the pun, to linking someone’s last name to their profession.

“Oh, the Jones family? Sure, they all became teachers. The Berringtons went into the clothing business, while the Shimmers all became dentists. They all have such gifted dental hands.”

Such blanket statements about where someone’s exceptionalism originated also throws the other sides of the family into the shadows, as if their only role were to ensure the ongoing survival of the dominant and more important family tree.

Family trees, however, like the trees that people decorate around this time of year, have bilateral symmetry, with people decorating each side in popcorn, cranberries and/or holiday lights.

Rarely does anyone do a deep dive into the other side of a family, learning whether the Jones family had faster legs, a quicker wit, better grades or a stronger work ethic.

Then again, the point of these claims isn’t to be scientific, thorough or even fair. It’s a way to connect the children of today with those who came before. Even if people don’t believe in reincarnation, focus on genes, or contemplate the enduring qualities of any family culture, they might feel tremendous joy and comfort hoping that this person’s unwritten life includes future chapters that reflect a familial past that need not be exclusive to one branch, one side or one person.

Story weaving may help give a developing life context and meaning. Ideally, those attributes and connections may remind the family and this new person about the kind of strong and accomplished roots that can help him or her develop into the kind of person he or she chooses to be, which would be a win for everyone.

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Pixabay photo

By Daniel Dunaief

Daniel Dunaief

Rufus is not sure what to do. He’s never there first. He circles the yard carefully, looking back at the fence. Bob sits in his usual seat at the picnic table, talking on his phone.

He doesn’t want to run before the others arrive. He sits under a tree, closes his eyes and allows the smells to fill his ample nostrils.

“Hi,” chirps Peanut, jumping up to reach his face. “Hi, hi, hi, hi!”

“Back up,” Rufus barks, “you’re too close.”

“Sorry, sorry, sorry, sorry,” she says. Peanut repeats herself in that high tone that annoys Rufus. “Even though I can’t see red or green, I know that holiday sweater is hideous,” Rufus said.

Fifi lowers her head.

“On the plus side,” he adds, “your fur looks great.”

Fifi prances in approval. She likes it when others notice that she’s been to the groomer.

Rufus glances at Andrea, Fifi’s human. He likes the way she scratches his ears and looks directly in his eyes.

Finally, the rest of the crew races over, tongues hanging out, fur flying off Oscar as he skids to a stop.

After the customary butt smelling, Oscar, the golden retriever, speaks.

“You had Uncle Doug’s sweet potato?” he asks Cole, an apricot poodle. “Does that taste as good as it smells?”

Cole barks his agreement, although he eats it so quickly he barely tastes anything. “And you had asparagus,” Cole says to Rufus.

Rufus sticks out his tongue. He doesn’t get his usual treat from Bob during Thanksgiving unless he has a few pieces of asparagus, which he hates.

“Stories?” King demands.

A French Mastiff, King regularly reminds the group he has the shortest life expectancy so he can’t waste time on food chatter.

“Bob’s got a new girlfriend,” Rufus starts. “She reminded him to walk me earlier than usual. She makes him shut the bedroom door, but she makes up for it by giving me more leftovers.”

“Nice,” barks Roxie. “Glad someone had a good holiday.”

“What? What? What?” barked Peanut.

A basset hound, Roxie hates her name and her short legs. Her ears also annoy her because they fall in her water when she drinks

“My family had a huge gathering,” Roxie barks. “These new kids thought they could teach me to fetch. I don’t fetch. Do they think I’m a golden retriever?”

“Hey!” Oscar barks.

“No offense,” Roxie adds. “What about you?”

“Aunt Linda spent the entire dinner saying she shouldn’t eat garlic. She didn’t listen to herself and was in the bathroom for an hour, groaning and cursing. How about you, Cole?”

Cole is among the tallest dogs at the run, particularly after he went to the stylist. Cole wanders over to the water bowl, with the rest of the group following closely.

“Cole?” Fifi asks. It is one of the rare times she doesn’t repeat herself.

“We watched movies in the dark,” Cole shrugs.

“There’s more,” says Rufus. “What’s going on?”

“Audrey looked out the window and wiped her eyes all weekend,” Roxie says. “She kept whispering how much she missed her brother.”

“What happened?” Oscar asks.

“I don’t think she’s going to see him again,” Cole says. “When I leaned into her legs, she ran her wet hand over my face. Other than a few walks, she spent most of her time on the couch. She barely ate, so I didn’t eat much, either.”

“Sad, sad, said,” barks Fifi.

Rufus agrees.

“You did what you should have done,” King says, the folds under his lips turning down. “You’re going to help her and we’re going to need to help you.”

“Help? How?” Oscar asks. Whenever Oscar became anxious, he circled the water dishes at the run. He knocks one over.

“My bad,” he says.

“Cole drinks first,” King says. “And we let Cole go to Andrea before the rest of us. We all know she’s the favorite human.”

Fifi nods, indicating she would share.

“How about you, King?” Rufus asks.

“It was great,” King says. “My family welcomed a new baby. At first, they kept me away, but they slowly let me see him. We’re going to be friends.”

“How do you know?” asks Cole.

“He touched his hand to my nose. It was soft and wonderful. He made me feel so young,” King adds.

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From left, Daisy Zavala, Stacey Scott and Krishna Veeramah Photo by John Griffin/Stony Brook University

By Daniel Dunaief

They can’t tell you whether the leading current presidential Republican and Democratic candidates demonstrate signs of cognitive decline or, for that matter whether any real or perceived cognitive decline is greater for one than the other.

Researchers at Stony Brook University, however, have conducted recent studies that may act as a platform to generate a measure of cognitive age that differs from chronological age.

Associate Professors Krishna Veeramah and Stacey Scott and graduate student Daisy Zavala recently published research in the Journal of Gerontology: Biological Sciences in which they studied a combination of cognitive testing done over different time periods and blood tests.

Indeed, the combination of looking at signs of epigenetic changes, or alterations in the environment that affect the way genes work, and studying the effectiveness and variability of tests of memory has the potential to offer some clues about how chronological age may differ from cognitive age. At this point, the scientists have been exploring that relationship, while future work may address not just what is happening, but also why.

Among the data from 142 subjects who took a host of learning tests from 2012 to 2016 during different time periods in the day, increasing epigenetic age was linked with poorer average processing speed and working memory, as well as with greater variability in test performance.

While the statistical analysis accounted for the fact that increasing chronological age had an effect, biological age had an even bigger impact, Veeramah, who is in the Department of Ecology and Evolution and a population geneticist at Stony Brook University, explained.

The study, which Veeramah described as an “early/pilot study,” and will require further follow up, offers another perspective on the different impacts the aging process can have on cognitive function.

The results matched the scientists’ prediction, which was that people who had greater epigenetic age acceleration processed information more slowly and had poorer memory performance on average across the study.

These individuals were not only performing more poorly on average, but were also more variable in their performance.

“This should give us pause about making judgments about people related to their age and what that means about their abilities,” said Scott, who is in the Psychology department.

This study suggests that “how old you are doesn’t tell you so much about how well you’re doing in your cognitive function,” said Scott. Theoretically, the extent to which a person’s body is older than a chronological age could be an indication of what might accelerate or decelerate cognitive function, although longitudinal studies will test this.

The researchers believe this study will contribute to a body of work that is trying to see if researchers can reliably identify biological age acceleration and, if so, how to slow it down.

Testing design

The researchers gathered data from participants who took tests on smartphones provided to them. These phones didn’t receive calls or messages and didn’t have access to the web.

Participants took tests during different times in the day. About 60 percent of study participants were African American and 20 percent were Hispanic/Latino. They also varied in household income, with most participants earning between $20,000 to $60,000.

In one test, people saw symbols at the top of the screen that they had to match with symbols at the bottom as quickly as possible. In another test, people viewed three red dots on a grid for a few seconds. They were distracted by searching for “E’s” and “F’s” on a screen and then had to place the dots back in their original place on the grid.

Participants completed dozens of tests over two weeks, offering a profile of their performance during different times of the day, situations and activities.

By testing people under various conditions, the researchers could get a more comprehensive, complete and realistic understanding of their cognitive state, which also reflects the way people experience a range of competing stimuli.

The scientists were profiling people “in terms of good and bad days” to get an understanding of their “typical performance,” explained Scott.

The SBU scientists suggested that inconsistency was increasingly proposed as a potential early indicator of dementia.

The “unique aspect” of what these scientists did is comparing epigenetic data to ambulatory cognitive measurements, rather than cognitive tests in a lab setting, Veeramah said.

To test the epigenome, Veeramah explored the degree of methylation of DNA from a single blood sample from each participant using a microarray to look at about a million positions in the human genome.

Adding a CH3 group, or methylating, genes tends to make the DNA coil more tightly, making it less likely to interact with other molecules that might turn it on.

Some parts of DNA show changes in methylation that correlate with age, while others are dependent on other things like the environment or specific cell type.

The underlying assumption is that cells pick up more damage and this includes the DNA sequence with time.

Zavala’s dissertation extends this work to look at more long term implications on cognitive health.

Zavala’s research “looks forward,” Scott explained in an email. “Does someone’s epigenetic age acceleration now at the beginning of the study predict their cognitive performance up to three years later?”

Dinner and a hypothesis

Veeramah and Scott, who got married in 2020, decided to combine their expertise for a research project.

“We were talking about our work over dinner and we thought about what I do and the kind of data we have from this existing sample of people” who participated in this cognitive study, said Scott.

The couple wrote a small grant to the research foundation at Stony Brook, which provided seed funding for this study.

Veeramah, whose research covers a broad scope of topics, suggested that the concept of studying these clocks is a fairly new area.

Researchers have been testing whether obesity, Alzheimer’s, and other factors could correlate with the internal environments that cause the kind of wear and tear often associated with aging.

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A Thanksgiving postcard. Photo courtesy Kenneth C. Brady Digital Archive

By Daniel Dunaief

Daniel Dunaief

Sending a text message to friends and family half way around the world and then getting an instant response is pretty incredible, shortening the distance between any two people.

And yet, as Thanksgiving approaches, I appreciate some of the earlier, albeit slower at times, elements of my younger years.

Take, for example, the postcard. Sure, people still send them, but postcards and letters are not as necessary or, in many cases, even considered. Even if people don’t send us texts, we can follow them on any of the social media sites where they’re showing us how they’re having the time of their lives and eating incredible food.

Over three decades ago, when my father died, I remember the exquisite and bittersweet pain from seeing the handwritten notes he’d left for himself. He didn’t have a smart phone where he could make electronic lists. Reading his pointed and slanted script was so deeply personal that I felt as if the letters and words connected us.

Once, years before he died, my father flew for a business trip. Eager to write to me and without any paper, he took out the barf bag from the seat in front of him, wrote about his travels and shared some dad humor, put it in an envelope and mailed it. I remember smiling broadly at the words he shared and the unconventional papyrus he’d chosen to carry those words.

The modern world of digital pictures and digital cameras gives me the opportunity to relive numerous experiences. I can easily sort those images by year and location, without needing to buy an album, find the right sequence of photos and slip them behind the translucent cover.

Still, remember when we used to bring rolls of film to the drug store for them to develop? We’d come back two or three days later, open up the often small green envelope and pour through the photos, wondering what we caught, what we missed and how the image compared with our memory.

The hit-or-miss nature of those photos made the imperfections somewhere between disappointing and perfect. They were real moments, when hair got in our eyes, when we shared our disappointment about a birthday present, or when we spilled a container of apple juice as we were blowing out candles.

What about all those photos from people in the early part of the 20th century? Didn’t they look utterly miserable? Was it the shorter life span, the challenging early days of the camera, bad dentistry and orthodonture or, perhaps, a culture that hadn’t yet suggested saying “cheese” or smiling for the camera?

My theory on those miserable faces, though, is that the pictures took so long to prepare amid challenging weather conditions — it was too hot to wear that overcoat — that people wanted the process to end so they could stop trying to hold a squirming child or ignore the need to scratch an itch.

Maybe I grew up in the sweet spot, where pictures weren’t instant but were easy enough to take that they didn’t require endless retakes. Yes, I have friends and relatives who insisted on taking 37 shots of the same moment, just in case someone was closing their eyes, which triggered the kind of fake smile in me that I recognize in my children when they’re eager to be somewhere else, doing something else, and, most likely, looking down at their phones to see pictures of other people.

This Thanksgiving, I appreciate not only the gifts of the present, with the endless storage space on my phone and the ability to capture life in real time, but also the perspective from a past, where the anticipation of seeing a snapped photograph or receiving a postcard turned the pictures into keepsakes and memory gifts.

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From left, Joshua Rest and Jackie Collier. The blurred image in the background shows the genome structure of Aurantiochytrium limacinum, including the arrays of rDNAs at the chromosome ends, and the two mirusvirus elements that were discovered. Photo by Donna DiGiovanni

By Daniel Dunaief

They were trying for two years to solve a puzzle that didn’t make sense. Then, a combination of another discovery, some extensive analysis, and a deep dive into the past helped them put the pieces together.

Jackie Collier, Associate Professor at the School of Marine and Atmospheric Sciences at Stony Brook University and Joshua Rest, also an Associate Professor in the Department of Ecology and Evolution at Stony Brook, had been looking closely at the genetic sequence of a marine protist called Aurantiochytrium limacinum. A circular section and pieces at the end of the chromosome seemed inconsistent with the rest of the genes and with the specific type of single-celled organism.

But then, they saw a preprint of a paper in 2022 that the prestigious journal Nature published earlier this year that described a new type of virus, called a mirusvirus, which appeared to have genetic similarities and a signature that matched what they saw in their protist.

Mirus means “strange” or unknown in Latin, which was a way to describe the unusual evolutionary traits of these viruses.

Collier and Rest, working with a group of collaborators, found that a high copy circular structure and genetic elements that integrated at the end of one chromosome resembled this mirusvirus.

“From the perspective of the virus folks, ‘mirus’ was apt because the mirusviruses contain features of the two very distinct ‘realms’ of viral diversity,” Collier explained. “Our results confirm that strangeness, and add more strangeness in terms of two different ways to maintain themselves (circular episomes or integrated into a chromosome) in the same host genome.”

Researchers had discovered the mirusvirus by sequencing DNA they took from the ocean. “What our findings do is connect to a host and hopefully eventually prove that there is a protist that contains a mirusvirus genome,” said Collier.

The Aurantiiochytrium protist, which is part of the Thraustochytrids order, intrigues researchers in part because it produces essential omega-3 fatty acids and carotenoids, which enhances its biotechnology potential. This protist also intrigues Collier because it is involved in decomposing dead mangrove leaves in mangrove forests.

Dormant virus

The Stony Brook scientists have been working on analyzing the genome for a paper they recently published in the journal Current Biology since 2019.

“We had been struggling to figure out what that was,” said Collier. “We had a lot of hints that it had some relationship to some kind of viruses, but it wasn’t similar enough to any known virus. We were struggling to figure out what to call this thing,” which they had tentatively designated CE1, for circular element one.

Identifying viral elements provided the “hook” for the paper.

Rest suggested that the different confounding elements in the protist genome came from two different viruses.

At this point, Collier and Rest think the virus may be something like the herpesvirus, which hides out in human nerve cells. That virus enters a latent phase, remaining quiescent until a host becomes stressed.

John Archibald, Lucie Gallot-Lavallee and others from Dalhousie University in Canada, who are collaborators on this study, are creating the kind of conditions, such as lower food or colder temperatures, that might reactivate the viral DNA, causing it to release viral particles.

The research team has detected similar mirusvirus proteins in other Aurantiochytrium isolates and in four other Thraustochytrid genomes. 

Focusing on this protist

Collier started working on thraustochytrids in 2002, after the first outbreak of QPX disease in Raritan Bay hard clams.

Bassem Allam, who is now the Marinetics Endowed professor in Marine Sciences at SBU asked Collier if she would help understand what was going on with the clams which had QPX disease. That was caused by another Thraustochytrid.

The organism that caused QPX is a relative of the protist that interested Collier.  She chose Aurantiochytrium in part because it was the easiest to grow.

When the Gordon and Betty Moore Foundation started a program to develop molecular genetic methods for diverse marine protists about seven years ago, Collier approached Rest for a potential collaboration.

A key piece, half a century old

In her informatics work, Collier followed a path that Google or artificial intelligence might otherwise have missed.

Like traveling back hand over hand in time through older research, Collier pulled up the references from one study after another. Finally, she found an intriguing study from 1972 that had overlaps with their work.

Scientists had isolated a Thraustochytrid from an estuary in Virginia using the same kinds of methods Collier and Rest used to grow Aurantiochytrium. Using electron microscopy, these earlier researchers characterized its ultrastructure. Along the way, these 1970’s scientists noticed that starved cells released viral particles, which Collier and Rest believe might be the first record of a mirusvirus.

The researchers wrote a short paper that the prestigious journal Science published.

A cat connection

While Collier, who lives in Lake Grove, and Rest, who is a resident of Port Jefferson, are collaborators at Stony Brook, they have also have a feline connection.

In the beginning of the pandemic, a feral cat delivered kittens in Rest’s garage. Rest’s family initially tried to raise them, but allergies made such a pet arrangement untenable. 

A cat lover, Collier was searching for kittens. She adopted two of the kittens, bottle feeding them starting at three days old. When Collier and Rest speak by zoom, Rest’s children Julia, nine, and Jonah, five, visit with the cats virtually.

As for their work, Collier and Rest are intrigued by the possibility of gathering additional pieces to answer questions about this virus.

“For me, the most intriguing question is how common our observations will turn out to be — do many Thraustochytrids have latent mirusviruses?” she explained.

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METRO photo

By Daniel Dunaief

Daniel Dunaief

We’ve come a long way from the “my dog ate my homework” days.

I mean, come on, let’s give our society the credit it’s due. We have taken the blame game, the finger pointing and the it-couldn’t-be-me-because-butter-wouldn’t-melt-in-my-mouth game to an entirely new stratosphere.

Gone are the days of simple, linear and mostly nonsensical excuses.

Let’s start in Washington, DC, which is the biggest clown show this side of the Atlantic and where the notion of a democracy gets battle tested nearly every day

Who is responsible for the national debt? That, of course, depends on whom you ask. The democrats point to former President Trump, while the republicans accuse President Biden and the Democrats.

Maybe those wily politicians are onto something. You see, if no one takes responsibility for anything and we can point fingers at the other side reflexively and without any effort to compromise and work together, we can live without consequence, create our own economics and come up with judgmental and schoolyard bully nicknames for the other side.

Brilliant! Blame someone else convincingly enough and not only do you not have to look in the mirror or come up with solutions, but you can also turn your entire reason for being into defeating the other side or, at the very least, enjoying their losses.

Look, I’m a Yankees fan. I know all about Schadenfreude. The next best thing to a Yankees victory, and it’s a close second, is a Red Sox loss.

But I digress. People have turned blaming others into a fine art. In sports, athletes and coaches deploy the modern blame game to excuse their losses or to step back from accepting responsibility or, perish the thought, to give the other team credit.

Like a zebra in the Serengeti to a hungry lion, referees in their striped uniforms in football games become convenient targets. They took away a victory by calling a game against us. Athletes and coaches can dig their verbal claws and teeth into those officials, who stole what would certainly have been a more favorable outcome.

How about school? It couldn’t possibly be the fault of our angelic children, who were busy watching these athletes on TV or on their phones the night before, for doing poorly on a test. It has to be the teacher’s fault. If teachers could only inspire their classes, our children would learn and excel. 

You know who I like to blame? I like to focus on tall people. Don’t get me wrong. Some of my best friends are tall. It’s just that, well, have you noticed that tall people get a lot of attention? Some of them are CEOs of big companies and make enormous salaries. They are also picked first in gym, which gives them the confidence to become successful.

While we’re affixing blame, let’s also shake our heads at gym class. Sure, it’s healthy to run around and have a few moments when we’re not listening to teachers who may or may not inspire us, but gym class can bruise egos and create a Darwinian world where height, which is kind of the fault of our parents and their parents and on and on, is an advantage.

Hey, I’m not whining. Okay, well, maybe I am, but it’s not me and it’s certainly not my fault. I blame society, commentators on TV, coaches, politicians, teachers, my parents, your parents, the parents of the kid who served as a bad role model for my kids, and maybe Adam, Eve and the snake for putting us in this position.

Oh, and you can be sure butter wouldn’t melt in my mouth. I have a dairy allergy, which, ironically, is the fault of my dairy farmer grandfather.

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Christopher Vakoc with graduate student Junwei Shi. Photo by Gina Motisi/ CSHL.

By Daniel Dunaief

It is the type of miraculous conversion that doesn’t involve religion, and yet it may one day lead to the answer to passionate prayers from a group of people on a mission to help sick children.

Researchers in the lab of Professor Christopher Vakoc at Cold Spring Harbor Laboratory have been working tirelessly to understand the fundamental biology of Rhabdomyosarcoma, or RMS, which is a type of connective tissue cancer that afflicts between 400 and 500 people each year in the United States, with more than half receiving the diagnosis before they turn 10 years old.

As a part of her PhD research, Martyna Sroka searched for a way to convert the processes involved in this cancer into something benign.

Using a gene editing tool enhanced by another former member of Vakoc’s lab, Sroka disrupted a signal she had spent years trying to find in a protein called NF-Y, causing cancerous cells in a dish to differentiate into normal muscle cells, a conversion that offers future promise for treatment.

Sroka, who is now working as a scientist in a biotechnology company focused on the development of oncology drugs, described how RMS cells look small and round in a microscope. After disrupting this protein, the “differentiated cells become elongated and spindle-like, forming those long tubular structures,” she explained.

She often grew cells on plastic dishes and the differentiated RMS cells spanned the entire diameter of a 15 centimeter plate, providing a striking visual change that highlighted that conversion.

While this research represents an important step and has created considerable excitement in the scientific community and among families whose philanthropic and fundraising efforts made such a discovery possible, this finding is a long way from creating a new treatment.

Other research has indicated that disrupting NF-Y could harm normal cells. A potential therapeutic alteration in NF-Y could be transient and would likely include follow ups such as a surgical, radiation or biological approach to remove the converted RMS cells, Vakoc explained.

Nonetheless, the research, which was published in August in the prestigious Proceedings of the National Academy of Sciences, offers a potential roadmap for future discoveries.

“It was a long journey and being able to put the pieces of the puzzle together into a satisfying mechanism, which might have broader implications not only for our basic understanding of the biology of the disease but also for potential novel therapeutic approaches, was extremely exciting and rewarding,” said Sroka.

“It’s great to see so much excitement in the pediatric cancer field, and I am hoping that with time it will translate to much-needed novel therapeutic options for pediatric patients.”

The search

Cancer signals typically involve rewiring a cell’s genetic material, turning it into a factory that creates numerous, unchecked copies of itself.

Sroka and Vakoc were searching for the kind of signal that might force those cells down what they hope is a one-way differentiation path, turning those otherwise dangerous cells into more normal muscle cells that contract.

To find this NF-Y gene and the protein it creates, Sroka, who started working in Vakoc’s lab in the summer of 2017, screened over a 1,000 genes, which Vakoc described as a “heroic effort.”

Encouraged by this discovery and as eager to find new clinical solutions as the families who helped support his research, Vakoc recognizes he needs to strike a balance between trumpeting this development and managing expectations.

Interactions with the public, including families who have or are confronting this health threat, “comes with a lot of responsibility to make sure we’re being as clear as possible about what we’ve done and what have yet to do,” said Vakoc. “It’s going to be a long and uncertain road” to come up with new approaches to this cancer.

Funding families

Some of the families who provided the necessary funding for this work shared their appreciation for the commitment that Vakoc, Sroka and others have made.

“We are very excited about the newest paper [Vakoc and Sroka] published,” said Phil Renna, the Senior Director of Communications at CSHL and Director of the Christina Renna Foundation, which he and his wife Rene formed when their daughter Christina, who passed away at the age of 16, battled the disease. The Christina Renna Foundation has contributed $478,300 to Vakoc’s lab since 2007.

“In just a few short years, he has made a major leap forward. This lights the path of hope for us and our cause,” said Renna.

Renna explained that the lab has had numerous inquiries about this research. He and others recognize that the search for a cure or treatment involves “tough, grinding work” and that considerable basic research is necessary before the research can lead to clinical trials or new therapeutics.

Paul Paternoster, whose wife Michelle succumbed to the disease and who has raised funds, called Vakoc and Sroka “brilliant and incredibly hard working,” and suggested the exciting results “came as no surprise.”

He is “extremely pleased” with the discovery from the “standpoint of what it can lead to, and how quickly it was discovered.”

Paternoster, President of Selectrode Industries Inc., which manufactures welding products and has two factories in Pittsburgh, suggested that this strategy can have implications for other soft tissue sarcomas as well.

The next steps

To build on the discoveries Sroka made in his lab, Vakoc plans to continue to use a technique Junwei Shi, another former member of his lab, developed after he left CSHL and joined the University of Pennsylvania, where he is now a tenured professor.

Shi, whom Vakoc called a “legend” at CSHL for honing the gene editing technique called CRISPR for just this kind of study, is also a co author in this paper.

In future research, Vakoc’s lab plans to take the screens Sroka used to find NF-Y to search to the entire human genome.

“That’s how the family tree of science operates,” said Vakoc. Shi “made a big discovery of CRISPR and has since continued to create new technology and that he is now sharing back” with his lab and applying it to RMS. Additionally, Vakoc plans to expand the testing of this cellular conversion from plastic dishes to animal models

Shi, who worked in Vakoc’s lab from 2009 to 2016 while he earned his PhD at Stony Brook University, expressed satisfaction that his work is paying dividends for Vakoc and others.

“It just feels great that [Vakoc] is still using a tool that I developed,” said Shi in an interview. Many scientists in the field are using it, he added.

For Shi, who was born and raised in southern China, working at Cold Spring Harbor Laboratory fulfilled a lifelong dream.

He recalled how he retrieved data one Saturday morning that indicated an interesting pattern that might reveal the power of a new methodology to improve CRISPR screening.

When Vakoc came to the lab that morning, Shi shared the data, which was a “whole turning point,” Shi said. 

Shi said he appreciates how CSHL has been “a home for me,” where he learned modern molecular biology and genetics.

When he encounters a problem in his lab, he often thinks about how Vakoc would approach it. Similarly, Vakoc suggested he also reflects on how his mentor Gerd Blobel, who is a co-author on the recent paper and is at the Children’s Hospital of Philadelphia, would respond to challenges.

As for the family members of those eager to support Vakoc, these kinds of scientific advances offer hope.

When he started this journey, Renna suggested he would feel satisfied if researchers developed a cure in his lifetime. This paper is the “next step in a marathon, but it makes us very excited,” he said.

To share the encouraging results from Vakoc’s lab with his daughter, Renna tacked up the PNAS paper to the wall in Christina’s bedroom.

 

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