Saturday July 4, 2020



January 11


Sweet and Sour Science

Japanese researchers unravel the mystery of miracle fruit.

Imagine sucking on a lemon that tastes as sweet as honey, or munching on what you think is a crunchy candy only to discover it’s a pickled onion. Such is the taste-bud trickery experienced at so-called flavor-tripping parties. The secret to the flavorful deceptions is a small red berry from West Africa called miracle fruit, which itself has very little flavor, but can make sour or acidic foods taste extremely sweet when eaten soon after the berry contacts the tongue. So bizarre is the fruit’s effect that just one taste was enough to convince Japanese food scientist Keiko Abe, of the University of Tokyo, to launch into an entirely new area of study.

In the early 1980s, Abe was researching oryzacystatin, the first recognized plant protease inhibitor, which she had identified and cloned from rice. But, one day in 1989, Yoshie Kurihara of Yokohama National University, who worked on miracle fruit and had managed to successfully cultivate the plant, visited Abe’s lab. She brought with her miracle fruit and lemons.

“Eating the fruits, I was surprised and excited,” says Abe. “The sourness [of the lemons] disappeared.”

“It made me change my interest from protease inhibitor biochemistry to taste science,” she adds. “Since then, I have been working on taste chemical biology.” Abe focused specifically on miraculin, the protein in miracle fruit responsible for its flavor-transforming powers.

More than twenty years after her first taste of the berries, Abe has finally exposed miraculin’s trick. “At long last, my group succeeded in unveiling the molecular mechanism that makes miraculin a miracle,” she says.

Previous studies had shown that inhibitors of the human sweet taste receptor could diminish miraculin’s effect, but there was no formal proof that the protein and the receptors interacted. Furthermore, a mere ability to bind the receptor wouldn’t explain why miraculin didn’t taste sweet on its own but rather made acidic compounds taste sweet.

Abe and her team expressed the sweet taste receptor in cultured human cells and then observed miraculin’s function using fluorescence to measure intracellular calcium concentrations, which increase when the receptor is active. At neutral pH in miraculin’s presence, calcium levels inside the cells remained low. At acidic pH, however, the cells fluoresced brightly.

Although miraculin didn’t activate the receptors at neutral pH, it was still bound and could inhibit their activation by other sweeteners. “So the miraculin has been sitting there, it’s ready to go, but it is not actually turning the key to turn on the sweet taste receptor, and therefore you’re not getting a perception of taste,” says Steven Munger, a chemosensory neurobiologist from the University of Maryland School of Medicine. “Adding the acid changes the shape of the miraculin, and that in turn changes the shape of the receptor, which turns it on.”

Using their in vitro model, Abe’s team also determined the precise part of the receptor with which miraculin interacts. They now plan to determine the X-ray crystallographic structure of that interaction. They also hope to use miraculin to answer further questions about sweet taste receptor biology. As taste biologist Paul Breslin of Philadelphia’s Monell Chemical Senses Center and Rutgers University points out: “It is very hard to study sucrose in an in vitro system because it is sweet at such a high concentration relative to things like miraculin . . . and those high concentrations tend to osmotically muck everything up.”

“The sweet taste receptor-binding ability of miraculin is stronger than that of any other sweetener known,” says Abe. Besides being an interesting phenomenon, this strong binding makes miraculin a “calorically negligible” sweetener says Munger. Consequently, Abe says, “We are interested in a large-scale production of miraculin . . . because developing sweeteners for antidiabetes and antiobesity uses is of pressing importance.”

Besides the need to solve the logistics of cost-efficient, large-scale production, some modifications might need to be made to miraculin before it is used as a food additive. “The sweetness is very long-lasting,” explains Munger. In fact, it can last up to a couple of hours.

Munger has first-hand experience with this problem of sustained receptor binding. “The first time I ever tried it was at a smell and taste meeting in Japan . . .but unfortunately, the session was followed by a social hour where there was beer.” There is enough acid in beer to trigger the miraculin, Munger explains. “It tasted very wrong.”

Source: The Scientist 

January 10

A Court Order

A three-judge panel from the US Court of Appeals on Tuesday (June 26) decided against industry groups that had challenged the legality of the Environmental Protection Agency’s (EPA) regulation of greenhouse pollutants.

The ruling retains the EPA’s authority to regulate and develop future rules to regulate gasses involved in global warming. rThe decision keeps intact a 2007 Supreme Court ruling that required the EPA to regulate carbon dioxide and other greenhouse gasses.

The plaintiffs argued that the science used by the EPA to set limits was too uncertain and was unable to specify a precise number at which greenhouse gases become a threat, and that the EPA was “delegating” its decision making to outside experts.  But the judges countered that the EPA, just as any decision-making entity, must base its rulings on the scientific evidence available.

January 09

Forging Vaccines

Opinion: The Risk of Forgoing Vaccines

Herd immunity, or the protection of individuals who are not vaccinated due to generally high vaccination rates within a population, does not currently exist in many pockets of the US.

By Juliette K. Tinker | April 3, 2012

In his book The Selfish Gene, Richard Dawkins devises a population of birds to explain reciprocal altruism. In this population, there is a deadly disease that is spread by ticks. The birds can groom themselves to remove ticks, and thus protect themselves from disease, in all but one spot—the top of the head. On that spot, they must rely on other birds to remove their ticks. Thus, for the birds in this population to survive, they must work together. If they don’t, and some birds decide to “cheat” by having their ticks removed by “suckers,” but not reciprocating, the population will suffer.  As fewer and fewer birds help their peers remove ticks, the population will become overrun with disease.

Given the direct benefit to the individual of immunity against disease, vaccination, is not completely altruistic.  However, immunization provides a significant benefit to society. One can liken a human newborn, or a person who cannot get vaccinated, to a vulnerable bird with ticks on the top of its head.  As individuals, we cannot fully protect these people from infectious disease, and instead we rely on herd immunity. If society is made up mostly of “suckers” that have expended the energy and cost to get vaccinated, then the vulnerable will be protected due to the absence or reduction of disease transmission. But if a significant percentage of individuals decides against vaccination, for one reason or another, we may lose herd immunity, and infectious disease will spread.

Unfortunately, we are beginning to see signs of this phenomenon, due in part to parents refusing to vaccinate their children because of the fear that it could cause autism—the now completely debunked message delivered by Andrew Wakefield in 1998.

In 2010, Idaho was ranked last in the country for routine childhood vaccination rates. Low rates have been a trend in this state for the last several years, and are likely due to limited access to vaccines as well as vaccine refusal.  According to theNational Immunization Survey, Idaho has only a 63.7 percent vaccination rate for the early childhood vaccination schedule (aged 19-35 months). These rates of vaccination are nowhere near the 85-95 percent levels required for herd immunity protection against most diseases. Unfortunately this means many children in Idaho are running the risk of diseases like pertussis, measles, and meningitis.  And Idaho is not alone; other states, such as Montana, New Jersey, and Utah, also report low rates for early routine vaccinations. These rates are lower than some developing countries, and while overall childhood vaccination in the United States remains reassuringly high (levels at 90 percent or higher on average), these pockets of vulnerability are very concerning to public health officials.

Indeed, we are already seeing evidence of disease reemergence. In 2000, there was no endemic transmission of measles in United States, and this disease was declared eliminated. However, measles is one of the most transmissible diseases on earth, requiring vaccination rates of higher than 95 percent to achieve herd immunity. And in 2011, the country had more than 200 cases, many of which were imported from Europe, which is currently experiencing large measles outbreaks, with over 26,000 cases in 36 countries, as reported by the World Health Organization. Whooping cough is also on the rise. From January to October 2010, there were 455 infants hospitalized in California and 10 deaths due to Bordetella pertussis, the highest number of cases in over 60 years, according to the Centers for Disease Control and Prevention.

Parental refusal has contributed to this increase in disease transmission.  It is clear that Andrew Wakefield’s work, though it has been thoroughly debunked and removed from the literature, is far from forgotten.

As a scientist I recognize that we are not always the best communicators. When it comes to vaccines, this is particularly relevant. It is not enough to make safe vaccines that protect people from disease; we must convince the public that they are safe and effective. This may be a tall order given the current cultural climate, but one that is imperative for immunization programs to be effective. Showing data and statistics that refute claims by detractors does not do much to stop the spread of fear about vaccine safety.  However, there are real lives that are saved by vaccines, and information about vaccine-preventable diseases may be the best way to inform. Among the many differences between us and the tick-pickers is that we are capable of seeing the future and the need to protect the population. Even if this means we have to go against individualism and act a little bit like a sucker.

Source: The Scientist 

October 24

Israeli scientific discoveries

 An Israeli team has made medical history with its ability to transform skin stem cells from heart-disease patients into healthy heart tissue.


Be still your beating hearts: Making medical history, scientists from Israel have been able to transform human stem cells from older diseased patients into brand-new, healthy, beating heart tissue.

This could mean that heart disease might someday be repaired by using cells from a person’s own body, eliminating the need for risky surgical implants and transplants.

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Using stem-cell technology, Technion-Israel Institute of Technology researchers from Haifa showed that their lab-produced cardiac muscle cells are also capable of merging into existing heart muscles.

The news is causing a media sensation around the globe.

“The good thing about it is that the research has increased public awareness to science that Israel isn’t only portrayed with hostility, but that it’s a country bringing good news for the world,” Prof. Lior Gepstein, head researcher in the advance, tells ISRAEL21c.

A decade from clinical trials

It will take five to 10 years before this basic science can get to the point of clinical trials, Gepstein emphasizes. People with advanced heart disease today might never benefit from the research,published in the current issue of the European Heart Journal. The advance is more likely to be applicable to people who are now 30 years old and younger.

Still, the breakthrough is monumental.

“What is new and exciting about our research is that we have shown that it’s possible to take skin cells from an elderly patient with advanced heart failure and end up with his own beating cells in a laboratory dish that are healthy and young — the equivalent to the stage of his heart cells when he was just born,” says Gepstein.

Skin cells from patients aged 51 and 61 were transformed into healthy heart muscle cells by adding to the cell nucleus three genes and valpoic acid, a small molecule. Gepstein’s team avoided a transcription factor typically used in creating stem cells because it’s thought to cause cells to develop out of control and become tumors.

The new heart muscle cells, cardiomyocytes, grew in a lab dish with existing heart tissues, and within 24 to 48 hours both kinds of tissue were beating together as one.

“The tissue was behaving like a tiny microscopic cardiac tissue composed of approximately 1,000 cells in each beating area.”

This culture was then implanted into the hearts of healthy rats, where it connected well to the existing cardiac muscle.

An empire of stem-cell research

Over the last decade, Israel has created what Gepstein calls an “empire” in stem-cell research, with nodes of highly focused research taking place at the country’s best research institutes. He focuses on the heart, but there are labs concentrating on diabetes, Parkinson’s disease or on repairing nerve damage.

Israeli scientists today use pluripotent stem cells, which come from skin or blood samples. Cultivating stem cells this way circumvents ethical considerations of embryonic stem-cell research, and also guarantees that patients wouldn’t need to take anti-rejection drugs for the rest of their lives, since the progenitor cells originate from the patients’ own bodies.

The early pioneering work, such as that of Benjamin Rubinoff at Hadassah University Medical Center in Jerusalem, was done with embryonic stem cells. Of the world’s first 10 scientific papers dealing with human embryonic stem cells, nearly all were authored in Israel.

Gepstein explains that Israel never faced the ethical challenges in embryonic stem-cell research that plague most US states. That’s because in Jewish law, an embryo is not considered human until 40 days after conception. Using younger embryos therefore doesn’t raise ethical problems, and Israel was free to move ahead in the field. Today, Israelis excel at maintaining pluripotent stem-cell cultures, growing them and coaxing them into new cell types, Gepstein says.


October 23

Top Doc for more than 5 years in a Row



This year Castle Connolly and American Registry launched their first milestone anniversary plaques for the physicians most consistently honored as Top Doctors that included, Dr. Leonard Bielory, New York Metro Area Top Doctor for 5 years in a row!

This was originally reached in 2006, but has since been consistently appointed to received this award for the past 10 years.

Only a small percentage of physicians have earned the prestigious recognition of New York Metro Area Top Doctor at all. Many, many fewer have earned it five years in a row.  Each year your award has been a result of Castle Connolly's rigorous peer nominated, expert reviewed selection process.


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Location: Springfield, NJ
Today's Date: July 04, 2020
Station Director: Leonard Bielory, M.D
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