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Leemor Joshua-Tor. Photo from CSHL

By Daniel Dunaief

Like many of the other talented and driven professionals at Cold Spring Harbor Laboratory, Leemor Joshua-Tor often works far from the kind of spotlight that follows well-known actors or authors.

That changed in April and early May. First, the American Academy of Arts and Sciences elected her a member on April 11. Other members joining the academy this year include Carol Burnett, New York Times columnist Nicholas Kristof, actor Ian McKellen, who played Gandalf in the Hobbit films and Magneto in the X-Men movies, and Israeli writer David Grossman.

Then, on May 2, the National Science Foundation elected the Cold Spring Harbor Laboratory professor and Howard Hughes medical investigator to join its ranks. “I got a huge amount of congratulatory emails from many friends, some of which I haven’t been in touch with for a while,” Joshua-Tor said. “It’s humbling.”

Joshua-Tor’s research covers a range of areas in structural and molecular biology. She works with RNA interference, where she focuses on how small molecules regulate gene expression or translation. She has also worked with Cold Spring Harbor Laboratory President Bruce Stillman on the early stages of DNA replication.

Early this year, Joshua-Tor and Stillman published a paper in eLife Sciences in which they offered more details about the human origin recognition complex. Stillman suggested that Joshua-Tor was the “main driver” for the research, studying the structure of a protein he had isolated years ago. “I am not a structural biologist, but she is an outstanding one and together, we came up with a very satisfying result.”

The origin recognition complex begins the process of replication, recruiting a helicase, which unwinds DNA. It also brings in regulatory factors that ensure smooth timing and then other factors such as polymerase and a clamp that keeps the process flowing and ensures accurate copying of the genetic code. “We don’t know how ORC’s motor activity is used,” Joshua-Tor explained. “We don’t really know what it is on the DNA that the ORC likes to bind to.”

In the recent work, the scientists explored the ORC’s structure and tinkered with it biochemically to understand it. The ORC binds and hydrolyzes the energy molecule adenosine triphosphate, or ATP, in the same way a motor would, although it probably isn’t continuous. “It might use ATP hydrolysis to perform one sort of movement, perhaps a detachment,” Joshua-Tor suggested.

In the early stages of replication, ATP is necessary for the integrity of the ORC complex, as well as the helicase that gets recruited. “We knew from biochemistry that ORC bounds multiple ATP molecules, but we did not know precisely how,” Stillman explained in an email. “The structure told us. ORC does not open the DNA by itself, but loads a protein complex onto the DNA that, when activated, can open the DNA.” Stillman is working on that process now. The next step for the CSHL collaborators is to get a structure of human ORC bound to DNA.

In their recent work, the researchers characterized how mutations involved in ATP hydrolysis affect a condition called Meier-Gorlin syndrome. Of the mutations they characterized, one affects the ability to hydrolyze ATP. Patients with this syndrome have one copy of the gene with typical function and the other that doesn’t. This likely leaves the patient with half of the molecules to do the required job.

The misregulation of replication is often associated with cancer and is something Joshua-Tor and others consider when they conduct these studies.

ATP, meanwhile, is associated with all kinds of activities, including cell adhesion and taking down misfolded proteins. Many processes in the cell connect to these types of molecular machines.

In her research with RNA interference, she is studying how a microRNA called Let7 is produced. Let7 is involved in development. Before cells differentiate when they are stem cells, they make Let7 continuously and then destroy it. She is studying the pathway for this process. Let7 is absent from stem cells and in some cancers.

Interested in science and theater when she was young, Joshua-Tor grew up in Israel, where she participated in activities at the Weizmann Institute of Science. The institute has biology, biochemistry, chemistry, math, computer science and physics, as well as an archeology unit that didn’t exist when she was there. Later, when she was a graduate student, Joshua-Tor returned to the institute and became an instructor.

An important moment in her scientific development occurred when she was in seventh grade. She was learning about elements and she put each one on a card. She brought these cards to class to study them. Her mother gave her a container that had housed her perfumes, which created a positive association for chemistry every time she studied the elements.

Joshua-Tor was also interested in theater, where she was initially in shows and then became an assistant director. The researcher lives with her daughter Avery, who is 8 and attends the Jack Abrams Magnet School. The tandem have a Schnauzer named Charles Darwin. Her daughter is proud of her mother and tells “anyone that would listen” about the awards her mother recently won, Joshua-Tor said.

Joshua-Tor, whose lab now has 11 people, said she is excited for the opportunity to meet some of her fellow honorees this fall.

Stillman expressed pride in “all our scientists and especially when they make major discoveries and they receive such peer recognition,” he wrote in an email. Joshua-Tor is “one of our best, but we have many scientists who will go on to gain substantial peer recognition. This is her turn, at least for these two awards!”

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Under ideal conditions, Asiatic lilies can grow to about six feet tall.

By Ellen Barcel

This is the second article in a three-part series.

Last week we looked at a number of plants that have the word “lily” in their names but aren’t true lilies. Now, let’s take a look at true lilies.

What botanically is a lily? According to the North American Lily Society (www.lilies.org), “The bulb is the most distinguishing characteristic. It is composed of fleshy scales without a protective outer coating. A true lily is never dormant … it must be considered and treated as a living perennial plant. … Lily flowers, though completely varied in size, shape and color, always have six tepals and six anthers.” The society also comments on the fact that lilies are very fragrant flowers and have leaves on the same stem as the flowers.

Note how the lily buds are on top of the stems filled with leaves. Photo by Ellen Barcel

There are over 100 species in the genius Lilium. Check the variety you are considering because the cultural requirements are not necessarily the same across the board. In general, lily bulbs are planted in fall since they need a cold winter to thrive. Like daffodils, if they are planted in the deep south, they need to be refrigerated first before planting.

Lilies need a fair amount of sunshine to thrive and do best in a moist but well-drained soil. They do well in an acidic soil, down as low as a pH of 5.5 but do tolerate a higher pH. Remove spent flowers but take no more than one-third of the stem since it’s filled with the leaves, which are helping the plant grow.

Always check the package tag, but in general, lilies need to be planted deeply as they grow very tall. Since once planted, lilies will return year after year, you need to periodically apply fertilizer. I prefer natural fertilizers like compost, compost tea or fish emulsion, but the choice is yours. With Long Island’s generally sandy soil, make sure you add compost when planting them.

• Easter lily (Lilium longiflorum) is a scented native of the Ryukyu Islands. The white Easter lily is sold throughout the United States, usually for the holiday. Easter lilies are hardy in zones 7 to 9. As a result, you may find that your holiday plant will not survive in your garden if there is an unusually cold winter or if you have not heavily mulched the bed where they are growing over winter. Be careful with Easter lilies as they are toxic to cats.

Lilies come in a variety of colors including red, yellow, white, pink and orange. Photo by Ellen Barcel

• Tiger lily (L. lancefolium also known as L. tigrinum) is one of several lilies known collectively as tiger lilies and are natives of Asia, known for their showy orange flowers. Bulblets can form along the stem at the leaf axis and can be used to propagate these plants.

• Asiatic lilies (L. asiatica) tend to bloom earlier than Oriental lilies. They come in many colors and sizes ranging from just about a foot tall to about six feet tall.

• Oriental lilies (L. oriental) bloom in mid to late summer and can grow quite tall, some almost eight feet tall. Flowers tend to be white, pink, red or bicolored.

• Dwarf Oriental lilies are as their name implies quite small, some that can easily be grown in containers. They are hardy in zones 5 through 9, so yes, you can comfortably grow them on Long Island.

Next week we’ll take a look at daylilies.

Ellen Barcel is a freelance writer and master gardener. To reach Cornell Cooperative Extension and its Master Gardener program, call 631-727-7850.

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Rhubarb Pie

By Barbara Beltrami

Rhubarb. You either like it or you don’t. Or you never liked it when you were a kid, but now you do. Or maybe you’ve never even had it. But here it is growing and appearing in gardens or produce departments as another harbinger of spring into summer. It can be eaten raw or cooked, in a dessert, sauce, salsa or chutney; but it does require sugar as on its own it is very sour. And just remember: It’s the stalks you eat, not the leaves. They’re poisonous.

Most people think of rhubarb as strawberry’s other half. That’s probably because strawberries and rhubarb ripen pretty much simultaneously and do complement each other. There are lots of strawberry festivals going on and next week I will write about them. But for now, let’s just talk about rhubarb, for which there are no festivals that I know of. What a shame.

Rhubarb Pie

Rhubarb Pie

YIELD: Makes 8 servings

INGREDIENTS:

Two 9-inch or larger pie crusts, preferably homemade

5 cups washed, trimmed and sliced rhubarb

1¼ cups sugar

5 tablespoons all-purpose flour

Dash of nutmeg

Dash of cinnamon

Pinch of salt

2 tablespoons unsalted butter

DIRECTIONS: Preheat oven to 450 F. Roll out one pie crust to a few inches larger than the bottom of the pie plate and drape the excess over the rim. In a large bowl, make the filling by mixing the rhubarb, sugar, flour, nutmeg, cinnamon and salt. Spread filling evenly over crust, dot with butter. Roll out the top crust the same way and place evenly over filling. Wet your fingers with ice water, then fold and press edges together on top of rim, and with a small pointed knife, make a few slits in the crust. Bake 15 minutes at 450 F, then another 20 to 25 minutes at 350 F. Pie is ready when crust is golden and some juice bubbles through slits. Serve with vanilla ice cream, sweetened whipped cream or crème fraiche.

Rhubarb Crumble

Rhubarb Crumble

YIELD: Makes 4 to 6 servings

INGREDIENTS:

For the topping:

1 cup flour

1/3 cup oats (not quick cooking)

¾ cup sugar

1/8 teaspoon salt

2/3 stick of unsalted butter, melted

1/2 cup chopped almonds

For the rhubarb mixture:

Butter for greasing baking dish

2½–3 pounds rhubarb, washed, trimmed and cut into one-inch pieces (you should end up with about 2 pounds or 8 cups)

1/3 cup sugar

¼ cup flour

1 teaspoon vanilla extract

¼ teaspoon salt

DIRECTIONS: Preheat oven to 375 F. Generously grease an 8-inch by 8-inch ceramic or glass baking dish. For the topping, in a medium bowl combine the flour, oats, sugar, salt, melted butter and almonds. Refrigerate one hour or until ready to use. For the rhubarb mixture, in a large bowl thoroughly combine the rhubarb, sugar, flour, vanilla extract, and salt. Pour into baking dish. Sprinkle topping evenly over mixture and bake about 45 minutes or until top is golden and slightly crispy and filling is bubbly. Serve warm with vanilla or strawberry ice cream or whipped cream.

Rhubarb Sauce

Rhubarb Sauce

YIELD: Makes 2 to 4 servings

INGREDIENTS:

1 pound rhubarb, washed, trimmed and cut into one-inch pieces

1/3–1/2 cup sugar or to taste

DIRECTIONS: In a medium saucepan over medium-low heat, cook rhubarb and sugar together, stirring occasionally, until they reach a mushy but thick consistency, about 20 to 30 minutes. (Rhubarb will release a lot of water, but you can add about ¼ cup of water to start, if you wish.) That’s it! Serve on vanilla ice cream.

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'Exodus' by Terence Netter

By Irene Ruddock

Terence Netter

Terence Netter, who divides his time between Setauket and Saint-Georges-sur-Cher, France, has had an illustrious career that includes teaching, painting and wide-ranging administrative work in the arts. Locally, he is known for his achievements as the first director of the Staller Center for the Arts at Stony Brook University, and, of course, for the visionary power of his paintings. Honored recently for these contributions by Gallery North, Netter is referred to as a “community treasure.”

As Staller Center director for 19 years, what was your vision for the center?

My goal was to make the center a major showcase for the arts. I am delighted to see how it has grown under the present leadership continuing to ever expand this goal.

What inspired you to evolve into painting landscapes in a minimalist style?

I changed my style of paintings to do works which evoke a sense of peace. When I moved to France, I became a practitioner and devotee of Zen Mediation which is an ancient technique of emptying one’s mind of distractions to enter a zone of peace. It calms your spirit so that you feel at one with the universe. My present painting process is a form of this meditation, and my newer paintings are an indication of this change. I call them “Zenscapes.”

 

‘Sunrise at Low Tide’ by Terence Netter

As a Christian, how do you reconcile Christianity and Zen Meditation?

The tradition of Christianity includes meditation. I was imbued with this through my study with the Jesuits. I find that both are traditions of finding peace in this ever more contentious and noisy world. Prayer and meditation are both ways of searching for the great mysteries of life and both have led me to paint in a peaceful manner.

How are art and religion entwined?

They are very much alike. The great philosopher Hegel said that art is the sensuous expression of the visual, and religion is the imaginative. Art and religion are two different forms of expressing the fact that the human spirit continues to evolve toward the infinite.

You often speak of achieving peace in your paintings. How do you define peace?

St. Thomas Aquinas says that “Peace is the tranquility of order.”

I’ve noticed that you often have the sun or moon in your paintings. What is the significance?

It’s the circle of life. The sun represents male power as exemplified by the god Apollo while the moon is represented by the goddess Venus. If you really want the answer to that, you will have to speak with my psychiatrist!

You also describe yourself as a teacher. What is your goal as a teacher?

I feel more complete as a person in the act of teaching. It is, for me, a way of growing. I teach in order to learn. I want to show students that life is an adventure in an unknown country — it is a “vision quest.” My goal as a teacher is to inspire young minds to open up, remove prejudices, and to set people on the path to finding truth. I encourage the study of the great thinkers who have influenced me such Hegel, Rahner, Kant and Chardin, to inspire the reflection necessary for growth. To grow, you have to be plugged into the spirit of the times — the Zeitgeist!

In your lectures, you talk about the search for the meaning of art through the centuries. What is your definition of the meaning of art?

I believe that art is nature reborn through the free consciousness of the human spirit. Artists create a new world for people to enter. Art is the visual expression of that infinitely evolving human spirit which is why each generation has to create their own vision of art.

Why did you choose the Loire Valley for your second home?

I went there when I was young and decided to take my wife Therese to visit on our 30th anniversary. We bought a little farmhouse and that is where I now do most of my painting. There I was inspired to paint the French Perspectives series and others that express “emotions recollected in tranquility.” My paintings have been described as capturing that special light and perfumed air of the Loire Valley.

You have mentioned that you spend time writing in France. Can you share with our readers what you are writing?

Yes, I am writing my memoirs!

Where can we see your art?

In Setauket, I am exhibiting my selected works at Gallery North (90 North Country Road, Setauket) until June 17 and in New York City I am represented by the Woodward Gallery. I am especially honored to be in many museums and private collections in the States and in Europe.

What do you want the viewer to feel or see when they view your paintings?

I want the viewer’s mind and eye to take a walk beyond the here and now. I hope that they experience that there is more beyond the horizon — the possibility of existence beyond the reach of our senses, even though we can’t see it. Most of all, I wish that they sense the deep peace that I am trying to evoke in my paintings.

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Treatment options vary wildly

By David Dunaief, M.D.

Dr. David Dunaief

With summer almost here and — believe it or not — beach weather around the corner, millions of Americans will expose their toes. Some will be more self-conscious about it than others because of a disease called onychomycosis, better known as nail fungus.

Nail fungus usually affects toenails but can also affect fingernails. It turns the nails yellow, makes them potentially brittle, creates growth underneath the nail (thickening of the nails) and may cause pain.

Many patients are bothered by this disorder. Most patients consider getting treatment for cosmetic reasons, but there are also medical reasons to treat, including the chronic or acute pain caused by nail cutting or pressure from bedsheets and footwear. There is an increased potential risk for infections, such as cellulitis, in those with compromised immune systems (1).

Onychomycosis is not easy to treat and can be quite uncomfortable. Onychomycosis affects approximately 8 percent of the population (2). The risk factors are unclear but may be relate to family history, tinea pedis (athlete’s foot), older age, swimming, diabetes, psoriasis, suppression of the immune system and/or living with someone affected by it (3).

There are many organisms that can affect the nail. The most common class is dermatophytes, but others are yeast (Candida) and nondermatophytes. A test commonly used to differentiate the organisms is a KOH (potassium hydroxide) preparation, which is a simple microscopic exam of skin and nail shavings. This is important since some medications work better on one type than another. Also, yellow nails alone may not be caused by onychomycosis; they can be a sign of the autoimmune disease psoriasis.

There are a plethora of therapies available for treatment. These range from over-the-counter alternative therapies to prescription topical medications to systemic, or oral, prescription therapies to laser therapies and, finally, surgery. I am regularly asked which treatment works best.

With all of these options, how is one to choose? Well, there are several important criteria, including effectiveness, length of treatment and potential adverse effects. The bad news is that none of the treatments are foolproof, and the highest “cure” rate is around two-thirds. Oral medications tend to be the most efficacious, but they also have the most side effects. The treatments can take from around three months to one year. So there is no overnight success. Unfortunately, the recurrence rate of fungal infection is thought to be approximately 20 to 50 percent with patients who have experienced “cure” (4).

Fortunately, most cases of nail fungus are benign, with only a fraction leading to infections. Infection is most common in those with diabetic neuropathy, where the patient loses feeling in their feet. Let’s look at the evidence.

Oral antifungals

There are several options for oral antifungals, including terbinafine (Lamisil), fluconazole (Diflucan) and itraconazole. These medications tend to have the greatest success rate, but the disadvantages are their side effects.

In a small but randomized controlled trial (RCT), terbinafine was shown to work better in a head-to-head trial than fluconazole (5). Of those treated, 67 percent of patients experienced a clearing of the fungus in their toenails with terbinafine, whereas 21 and 32 percent experienced these benefits with fluconazole, depending on the duration. The patients in the terbinafine group were treated with 250 mg of the drug for 12 weeks. Those in the fluconazole group were treated with 150 mg of the drug for either 12 or 24 weeks, with those in the 24-week group experiencing the better results.

Thus, this would imply that terbinafine is the more effective drug. This is a small trial, but the results are intriguing. The disadvantage of terbinafine is the risk of potential hepatic (liver) damage and failure, though it’s an uncommon occurrence. Liver enzymes need to be checked while using terbinafine. Its advantages are the efficacy and the duration.

Another approach to reducing side effects is to give oral antifungals in a pulsed fashion. In a RCT, fluconazole 150 or 300 mg was shown to have significant benefit compared to the control arm when given on a weekly basis (6). However, the efficacy was not as great as with terbinafine or itraconazole (7).

Topical medication

A commonly used topical medication is ciclopirox (Penlac). The advantage of this lacquer is that there are minor potential side effects. However, the disadvantages are that it takes approximately a year of daily use, and its efficacy is not as great as the oral antifungals. In two randomized controlled trials, the use of ciclopirox showed a 7 percent “cure” rate in patients, compared to 0.4 percent in the placebo groups (8). There is also a significant rate of fungus recurrence. In one trial, ciclopirox had to be applied daily for 48 weeks. These results were in patients with mild to moderate levels of fungus in the surface area of the infected nails.

Laser therapy

Of the treatments, laser therapy would seem to be the least innocuous. However, there are very few trials showing significant benefit with this approach. A study with one type of laser treatment (Nd:YAG 1064-nm laser) did not show a significant difference after five sessions (9). This was only one type of laser treatment, but it does not bode well. To make matters worse, many laser treatments are not covered by insurance, and they can be expensive. Another research paper that reviewed the current literature concluded that laser therapies are lacking in randomized clinical trials (10).The advantage of laser treatment is the mild side effects. The disadvantages are the questionable efficacy and the cost. We need more research to determine if they are effective.

Alternative therapy

The success of using this product is largely due to its ingredients, which includes menthol, camphor and eucalyptus oil.

Vicks VapoRub may have a place in the treatment of onychomycosis. In a very small pilot trial with 18 patients, 27.8 percent or 5 of the patients experienced complete “cure” of their nail fungus (11). Additionally, partial improvement occurred in the toenails of 10 patients. But what is more interesting is that all 18 patients rated the results as either “satisfying” or “very satisfying.” The gel was applied daily for 48 weeks. The advantages are low risk of side effects and low cost. The disadvantages are a lack of larger studies for efficacy, the duration of use and a lower efficacy when compared to oral antifungals.

So when it comes to onychomycosis, what should one do? None of the treatments are perfect. Oral medications tend to be the most efficacious but also have the most side effects. If treatment is for medical reasons, then oral may be the way to go. If you have diabetes, then treatment may be of the utmost importance.

If you decide on this approach, discuss it with your doctor; there are appropriate precautionary tests, such as liver enzyme monitoring with terbinafine (Lamisil), that need to be done on a regular basis. However, if treatment is for cosmetic reasons, then topical medications or alternative approaches may be the better initial choice. No matter what you and your physician agree upon as the appropriate treatment, have patience. The process may take a while; nails, especially in toes, grow very slowly.

References: (1) J Am Acad Dermatol. 1999 Aug.;41:189–196; Dermatology. 2004;209:301–307. (2) J Am Acad Dermatol. 2000;43:244–248. (3) J Eur Acad Dermatol Venereol. 2004;18:48–51. (4) Dermatology. 1998;197:162–166; uptodate.com. (5) Pharmacoeconomics. 2002;20:319–324. (6) J Am Acad Dermatol. 1998;38:S77. (7) Br J Dermatol. 2000;142:97–102; Pharmacoeconomics. 1998;13:243–256. (8) J Am Acad Dermatol. 2000;43(4 Suppl.):S70-S80. (9) J Am Acad Dermatol. 2013 Oct.;69:578–582. (10) Dermatol Online J. 2013 Sept. 14;19:19611. (11) J Am Board Fam Med. 2011;24:69–74.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com or consult your personal physician.

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By Bob Lipinski

Bob Lipinski

Countless articles and books include information, charts, diagrams and so forth on how we are supposed to pair cheese with wine and which combinations are made in heaven. (I’ve had a few that were probably made in hell!) Some of the more enlightened folk even recommend and discuss pairing cheese with beer, especially with the tremendous growth of craft beers and brewpubs.

But what about pairing cheese with spirits — you know … whiskey, vodka, brandy, rum, liqueurs and even grappa? It’s really not difficult once you understand the basics of spirits and how their flavors can interact with many cheeses that same way wine does.

As with cheese and wine, your cheese and spirits should complement each other. The secret is to avoid having either overpowered by the other, and spirits with an alcoholic beverage hovering around 40 percent the task becomes greater.

Be certain to slightly chill the spirits to around 65 to 68 degrees. Higher temperatures will certainly bring the alcohol to the forefront of your nose and mouth. Choose your favorite glass, and, if you like drinking your spirits over ice, refrigerate them instead.

The spirits and cheese recommendations below are from a recent tasting I conducted:

Moletto Gin, Veneto, Italy (86 proof) Perhaps the most incredible gin I’ve ever encountered! Yes, the familiar juniper berry notes along with rosemary, mint, basil and hint of citrus are there, but the kicker is an initial burst of fresh tomatoes! This gin was macerated for 45 days with San Marzano tomatoes from Italy. Recommended cheeses: Bel Paese, Boulette d’Avesnes, Leyden or mozzarella.

Moletto Grappa di Arneis, Italy (80 proof) Bouquet and flavor of spicy cherries, dried flowers, herbs, spices and dried fruits. Subtle hints of black pepper, raisins and apricot are present in the aftertaste. Recommended cheeses: Creamy Gorgonzola, herbed cheese, Gouda or Montasio.

Le Reviseur “V.S.” Single Estate, Cognac France (80 proof) A full, warming bouquet and flavor of dried fruits (raisins, dates, cherries), along with spices and dark berries. Hints of chocolate and plums are present in an ultra-smooth taste. Recommended cheeses: brie, Camembert, Livarot or Roquefort.

Laird’s “Straight Apple Brandy” New Jersey (100 proof) A brandy made from about 20 pounds of apples and aged around three years in charred oak barrels. An intense aroma of cider, baked apples, cloves and vanilla. Warming in the mouth with hints of honey, caramel and spices and a smooth finish. The aftertaste remains for some time. Recommended cheeses: Bondon, cheddar, Petit-Suisse or Pont l’Évêque.

Charles Goodnight “Bourbon,” 6 years old, Kentucky (100 proof) A heady bouquet of oak, caramel, smoky tobacco and vanilla. Warming flavors of spices, coconut and toasted almonds. Surprisingly smooth with an aftertaste of honey. Recommended cheeses: Asiago, Kefalotyri, Monterey Jack or Parmigiano-Reggiano.

Bob Lipinski, a local author, has written 10 books, including “101: Everything You Need to Know About Whiskey” and “Italian Wine & Cheese Made Simple” (available on Amazon.com). He conducts training seminars on wine, spirits and food and is available for speaking engagements. He can be reached at www.boblipinski.com or [email protected].

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Gabor Balazsi in his lab. Photo by Aleksandrs Nasonovs

By Daniel Dunaief

It started with a bang. When he was young and living with his parents, Gabor Balazsi’s curiosity sometimes got the better of him, at the expense of his parents’ house.

The future Henry Laufer associate professor of physical and quantitative biology at Stony Brook University was holding bare wires in his native home in Transylvania when he plugged in an appliance. The current surged through his body, preventing him from releasing the wires. Fortunately, his mother came in and “unplugged me.”

These days, Balazsi, is much more focused on the kinds of behavior that turns the instructions for a cell into something more dangerous, like cancer or a drug-resistant strain of a disease.

Balazsi recently received a $1.8 million, five-year grant from the National Institutes of Health to study how gene networks change, often to the detriment of human health, as is the case when they are active in cancer or when they are resisting treatment. The grant is called Maximizing Investigators’ Research Award.

“Cancer cells often don’t look the same in a matter of months and drug-resistant microbes may look the same in a matter of days,” Balazsi said. He would like to know “what causes them to change and how can we prevent them from changing to their advantage and our disadvantage?”

In a way, Balazsi is trying to figure out a code that is akin to the popular 1970s game Simon in which a player has to repeat a growing number of flashing lights and sounds. With each turn, the game increases the number of flashing lights and sounds, going from a single red, to red, green, yellow and green until the player can no longer recall the entire code.

He is looking for a similar key to a sequence of events that transforms a cell, except that in the cancer, there are millions of interacting lights, many of which are invisible. The cancer biologist tries to reconstruct the sequence in which some of these lights turned on by observing visible lights that are currently on.

He is exploring the “pattern that leads to the outcome” through changes of networks in yeast cells, he said. He is also hoping to explore pathogenic fungi. The pattern, he said, will change depending on the circumstances, which include the environment and initial mutations.

Scientists who have collaborated with Balazsi suggested his understanding of several scientific disciplines enables him to conduct innovative research.

“He bridges two fields, biology and biophysics, allowing him not only to describe biological processes but also to model them and make predictions that can then be tested,” Marsha Rosner, the Charles B. Huggins professor at the University of Chicago, wrote in an email.

While Balazsi doesn’t treat patients, he is focused on understanding and controlling the processes that lead a cell or group of cells to change from a uniform function and task to a heterogeneous one, where the cells may follow a different path using a previously inactive network of genes.

By understanding what causes these changes, he hopes to find ways to slow their progress or prevent the kind of deviations that lead to combinations that are destructive to humans, such as when the cellular machinery copies itself uncontrollably.

Balazsi and Rosner collaborated on one paper and are continuing to work together. “Our work demonstrates one mechanism by which cells move from a homogeneous population to a more complex population that contains cells that promote cancer,” Rosner explained. “This mechanism is not based on mutations in genes, but rather on changes in the way that genes interact with each other in cells.”

On a fundamental level, Balazsi explained that researchers have developed considerable understanding, but still not enough, of what happens in normal conditions. He is seeking to discover the logic cells use to survive under stressful conditions.

Balazsi would like to determine if there is “anything we can do to decrease the tendency of cells to deviate from normality,” he said.

Balazsi welcomes this new funding, which will give him the freedom to pursue research questions at a basic level. Instead of supporting a single project, this financial support contributes to multiple projects.

The next step in funding his lab will be to approach the National Cancer Institute. Without much experience in applying for cancer grants, Balazsi plans to attend a think tank workshop in June in Seattle. Attendance at this meeting, which is hosted by Sage Bionetworks and the NCI, required an application and selection of participants.

To some degree, Balazsi may be able to relate to the heterogeneity that he hopes to study in cells. A physicist by training, Balazsi explained that he “wandered into biology.” He would like to steer away from major trends that mobilize many researchers. If many people are working on something, he does not want to be enriching big crowds but would prefer to try new things and test new ideas.

A resident of East Setauket, Balazsi lives with his wife Erika and their daughter Julianna, who is 6. Julianna is already doing some experiments at home and is exploring the yard.

When Balazsi was young, his parents tried to encourage him to become a doctor, which didn’t work because he didn’t like blood or hospitals as a child. In addition to his unexpected electric shock, Balazsi also explored how ethanol burns while flowing, which caused some additional damage to his house. “My parents,” he recalled, “weren’t happy.”

As for his work, Balazsi would like his work with these first steps, in understanding cellular processes, will have a translational element for people some time down the road.

“Whatever we do, hopefully, they can be implemented in actual cancer cells that are coming from patients one day,” he said, or they could have some relevance for people who are attempting to fight off “pathogenic microbes.”

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A common concern is that after paying premiums on a long-term care policy for years, it will never be accessed for care. Stock photo

By Nancy Burner, ESQ.

Nancy Burner, Esq.

With the ever-changing health care landscape both federally and on a state level, and the aging of the baby boomers, it may be time to take a second look at long-term care insurance. Historically, New York State residents have had the opportunity to receive long-term care benefits through the Medicaid program.

New York has been one of the most generous states in providing care for disabled and aged residents. But you do not have to be a health care expert to see that state and federal budgets are threatening to curtail Medicaid benefits, and many current programs cannot be relied upon to provide the same amount of care that they have in the past.

To battle these changes, a proper estate plan should provide an arsenal to protect against catastrophic health care costs. It is often advisable to consider all available resources when putting together a long-term care estate plan.

We do not have a crystal ball that will show the future of Medicaid or what the needs of each individual will be. But we do know that the baby boomers represent a critical mass of individuals moving toward unprecedented longevity.

In addition, we know that a large percentage of these individuals living longer will likely need care. Further, while many baby boomers and their relatives traditionally cared for aging parents, the economics facing future generations shows that third-party caregivers will be the norm, not the exception.

For clients facing these looming questions of who will provide care, where will the care be provided and how will it be paid for, long-term care insurance is one possible solution. Prudent estate planning may require putting together a team of professionals to help make decisions to protect your assets and autonomy, regardless of what the future holds. This team may include an elder law attorney, financial advisor and an insurance professional. Working together, they can provide you with options for protecting assets to avail yourself of public benefits, preserving and growing assets and purchasing insurance products that make sense in your plan.

Long-term care insurance can often pay for home care assistance or the cost of a nursing facility. If you start accessing your long-term care benefit while living at home and then transition into a nursing facility, the proper planning could make a huge difference in the amount paid toward the cost of care.

Also, many individuals do estate/elder law planning by creating irrevocable trusts, which commences the five-year look-back period for Medicaid nursing home care. They purchase long-term care insurance to cover the initial five-syear period.

Some clients find themselves in a position where they have high income and therefore fear that they will never qualify for Medicaid. Some have income that exceeds the lower Medicaid rate charged by the facility. This leaves them in the dubious position of not qualifying for Medicaid and therefore forced to pay the higher private pay rate.

Needless to say, current daily rates for nursing home care can be financially ruinous. Fortunately, there is a federal law that states that if an individual is eligible for Medicaid but for the fact that their monthly income exceeds the Medicaid rate at the nursing facility, the facility must allow that individual to pay privately at the Medicaid rate. This offers a large savings in the cost of nursing care; and, in the final analysis, the individual is never a Medicaid recipient.

The income of the individual can include Social Security payments, pensions, distributions from retirement assets, payouts on a long-term care policy, etc. With proper long-term care planning, the assets could be protected in an irrevocable Medicaid asset protection trust while the income is being used to pay for the facility.

While many will need long-term care in their lifetime, not everyone will require prolonged care. A common concern is that after paying premiums on a long-term care policy for years, it will never be accessed for care. It’s the age-old problem of paying for insurance that they hope they will never use. This creates a mental bias against insurance to pay for that kind of care.

Individuals prefer to believe that they will never need long-term care. For those with this concern, there are new policies commonly referred to as “hybrid policies.” These are life insurance policies with a long-term care rider attached. In this way, you can access the policy to cover the cost of care while living, but heirs can receive a death benefit if it is not used up. Some polices also allow the insured to cancel the policy and receive their investment back at any time.

The bottom line is that the landscape is ever changing, the assumptions we relied upon have changed, and if you plan on living long, you need to live and plan smarter. Maybe it’s time to reconsider long-term care insurance. If you can qualify medically and you can afford it, it may be just another necessary tool in your arsenal of weapons for “aging in place” and with autonomy. It may not be for everyone but it could be right for you. Take a second look.

Nancy Burner, Esq. practices elder law and estate planning from her East Setauket office.

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Water lilies are not true lilies.

By Ellen Barcel

This is the first article in a three-part series.

There are many plants in the garden with the word “lily” in their name. But, all are not true lilies (genus Lilium). There’s calla lily, plantain lily and toad lily to name just a few as well as mountain lilies (Ixiolirion tatarcum).

But, why should the gardener be interested in what is a lily and what is not? Why do we care what botanists think? Well, for one thing, many plants that are not true lilies have different garden requirements.

Hostas, though sometimes referred to as plantain lilies, are not true lilies. Photo by Ellen Barcel

Take, for example, the plantain lily — the hosta — which prefers shade or only filtered sun. Lily of the valley too prefers shade. That’s very different from the calla lily, which requires a fair amount of sun. In addition, calla lilies are generally hardy from zone 8 to 10 or 11. Long Island is zone 7; so calla lily bulbs need to be lifted and stored over winter in our area or treated as annuals. You don’t need to lift hostas or lilies of the valley each fall since they are herbaceous perennials and hardy on Long Island.

Then there’s the question of toxicity. Easter lilies are poisonous to cats, and lily of the valley and calla lilies are considered to be highly poisonous (to people as well as pets). On the other hand, the flowers of some daylilies (Hemerocallis) are edible and used in Asian cooking.

So, yes, save those tags, label your plants and follow the directions that came with your purchase for successful “lilies” in your garden.

Some lilies are not lilies at all

I. tatarcum is usually known as the blue mountain lily, Siberian lily or lavender mountain lily. This is a small plant (12 to 15 inches high), a native of Asia, that is hardy in zones 3 to 9. Once planted (usually in fall) it will come back year after year. Its flowers come in shades of blue and violet. Because of its size and hardiness, it makes an ideal plant in the rock garden.

The fragrant, long-lasting flowers make good cut flowers as well, blooming late spring to early summer. So, consider adding some to your cutting garden. One more plus – it’s deer resistant. You need to do very little to this plant to have it come back year after year. To help it multiply, scatter the ripe seeds in other areas of the garden.

Water lilies are not true lilies either but are in the family Nymphaeaceae. Water lilies have leaves (pads) and flowers that float on or show above the water but are rooted in the soil beneath. They are divided into three types: hardy, night blooming (tropical) and day blooming (tropical). To grow water lilies you need a freshwater pond or water feature. If you select hardy ones, then you don’t need to lift the rhizomes over winter.

The toad lily works well in a shade or rock gardens.

The toad lily (genus Tricyrtis) includes a number of species including T. formosana, T. hira (hairy toad lily) and T. macrantha (yellow flowers). Toad lilies are shade-loving perennials, hardy generally from zones 4 to 8 and bloom with delicate purple, plum or lavender flowers that appear in late summer and fall. The plant is somewhat deer resistant and is propagated by division but can also be grown from seed. This is a small plant and works well in a shade garden or rock garden.

In addition to plantain lily, hostas (old name funkia) are sometimes referred to as August lily or Corfu lily. They were once classified in the family Liliaceae (due to the flowers resemblance to true lilies) but are now classified in the family Agavaceae, genus Hosta. Like the true lily, they are herbaceous perennials. They grow from underground corms or rhizomes, doing well in shade. While they are grown primarily for their leaves, they do have flowers, which are usually white or pale purple, sometimes fragrant.

Next week we’ll take a look at true lilies.

Ellen Barcel is a freelance writer and master gardener. To reach Cornell Cooperative Extension and its Master Gardener program, call 631-727-7850. 

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Men as well as women are at risk

By David Dunaief, M.D.

Dr. David Dunaif

Osteoporosis is a very tricky disease. What do osteoporosis, high blood pressure and high cholesterol have in common? They are all asymptomatic until the later stages. You can’t directly measure the progression or risk of osteoporosis fractures; you can only make an educated guess. The medical community does this mainly by using the Fracture Risk Assessment Tool (FRAX) score (1). FRAX estimates the 10-year risk of fracture in an untreated patient. You can find this tool at www.shef.ac.uk/FRAX.

There are a number of risks including genetics — family history, advanced age and demographics, with Asians being at highest risk — lifestyle, medications such as steroids and chronic diseases. A specific chronic disease that has come into focus relatively recently is heart disease. We will discuss this in more detail. Also, it does not seem that diabetes, neither type 1 nor type 2, contributes to osteoporosis (2).

When we think of osteoporosis, we tend to associate it predominately with postmenopausal women; however, it does affect a significant number of men.

Back pain, caused by changes in the vertebrae, may be the first sign that you have osteoporosis.

Treatments range from lifestyle modifications including diet, exercise and smoking cessation to supplements and medications. The medications that are considered first-line therapy are bisphosphonates, such as Reclast or Zometa (zoledronic acid), Fosamax (alendronate), Actonel (risedronate), Boniva (ibandronate) and Didronel (etidronate).

While all of these drugs have reduced fractures, zoledronic acid has shown disappointing results in reducing fracture risk in the elderly population.

The relatively new medication on the block is Prolia (denosumab), an injectable human monoclonal antibody that works through a different mechanism of action, though the result is the same; it blocks the osteoclastic (breakdown) activity of the bone (3). It has been shown to increase bone mineral density, or thickening of the bone, and reduce fracture risk. Prolia was approved at the end of 2012, so it has not been on the market nearly as long as the bisphosphonates. However, like bisphosphonates, it does have side effects.

As far as supplements go, exciting news is that melatonin may help to increase bone mineral density. Let’s look at the research.

The forgotten sex: men

Rarely are men the forgotten sex when it comes to medical research, but osteoporosis is an exception. Approximately one-third of fractures occur in men, resulting in a 37 percent mortality rate. One in five men over the age of 50 will experience a fracture with osteoporosis as a contributing factor. The predictions are that these rates will climb precipitously and that men need to be treated appropriately (4). Currently, less than 50 percent of men with osteoporosis are receiving treatment (5).

Is bariatric surgery useful?

Though bariatric surgery has been shown to have a number of benefits for many chronic diseases, osteoporosis is not one of them. In the Swedish Obesity Study, results show that women who underwent bariatric surgery were at 50 percent increased risk of fractures as well as long-term osteoporosis (6). The results in men were not statistically significant. The duration of the study was 25 years. The authors hypothesize that malnutrition may play a role in causing this effect. Supplementation may be important to overcome this, as well as frequent follow-ups with blood tests to track micronutrient levels.

Heart disease, really?

When we think of heart disease, we associate it with lots of complications, but osteoporosis is not typically one of them. Well, think again. In the Hertfordshire Cohort Study, results show that there was a significantly increased risk of wrist fracture of the radius in those with heart disease (7). These results were shown overall. However, when the sexes were analyzed separately, this effect held true for men but was not true for women, although the results in women did trend toward significance. This may be an example where men are at greater risk than women. Therefore, it may be important to think about osteoporosis when someone is diagnosed with heart disease, especially since it is not intuitive. Lifestyle factors could be a contributor to this association, as well as estrogen deficiency.

A bisphosphonate that disappointed

Bisphosphonates are the mainstay of treatment for osteoporosis, increasing bone density and decreasing fracture risk. However, zoledronic acid had surprisingly disappointing results in a randomized controlled trial (RCT) (8). Results showed that while zoledronic acid increased bone density over two years, it did not decrease the risk of fracture in elderly women in nursing homes. This does not necessarily have broad implications for other bisphosphonates. There were also weaknesses in this trial, the most serious being that fracture risk was not a primary end point. Additionally, the study may have been too small. However, this still is a very intriguing study.

Melatonin for osteoporosis

What could melatonin possibly have to do with osteoporosis? There are surprisingly positive results with melatonin. In a very small RCT, melatonin in combination with 800 mg/day of vitamin D3 and 800 mg/day of calcium increased bone density significantly in the spine and femoral neck over a one-year period, compared to the control, or placebo, arm containing vitamin D3 and calcium of similar dosage (9).

Interestingly, with melatonin the amount of calcium excreted through the urine in a 24-hour measurement decreased by 12.2 percent. There was a dose-related curve, where melatonin 3 mg/day in combination with vitamin D3 and calcium showed greater results than 1 mg/day of melatonin, which showed significant results over the control arm.

This was a preliminary study involving 81 postmenopausal women divided into three groups. Fracture risk reduction was not an end point. Larger studies with fracture risk as a primary end point are needed. Having said this, these results are exciting. A caveat: If you’re going to use calcium 800 mg/day, it’s best if you split the dose into 400 mg twice a day; the body does not typically absorb more than 500 mg of calcium at one time.

Though medications such as bisphosphonates and a monoclonal antibody may have an important place in the treatment of osteoporosis, not all medications may be equal. It is important to treat with lifestyle modifications including potentially supplements — melatonin, calcium and vitamin D3 — as well as diet, exercise and overall behavior modifications. Heart disease’s unexpected association with osteoporosis is a good reason to treat the whole patient, not just the disease. And don’t forget that men may have this disease too!

References: (1) uptodate.com. (2) Exp Clin Endocrinol Diabetes. 2001;109 Suppl 2:S493-514. (3) epocrates.com. (4) iofbonehealth.org. (5) J Bone Miner Res. 2014;29:1929-1937. (6) ECO 2015. Abstract T8:OS3.3. (7) Osteoporos Int. 2015;26(7):1893-1901. (8) JAMA Intern Med. Online April 13, 2015. (9) J Pineal Res. Online June 3, 2015.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com or consult your personal physician.

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