Stars’ twinkle reveals their character.

In 1806, English poet Jane Taylor famously lamented that a little star’s twinkle left her wondering what it was.

Fast-forward 207 years and a new analysis of starlight collected by NASA’s Kepler space telescope shows patterns in the flicker that are directly tied to the amount of boiling taking place on a star’s surface, a key indicator of its size, mass and evolutionary state.

That information, in turn, reveals volumes about any orbiting planets, including those fortuitously positioned from their parent stars for liquid surface water, apparently a key ingredient for life.

“Everything you know about planets is tied to what you know about the host star,” says Fabienne Bastien, an astronomy graduate student at Vanderbilt University.

“We don’t observe the planets directly. We observe the stars and the influence that the planets have on their stars. So in order to make any conclusions about the size of the planet or the mass of the planet as it’s pulling on the star when it’s moving, you need to know the size and the mass of the star very well.”

“That directly impacts whether or not you can claim that you have an Earth-like planet,” she says.

Bastien, who is working on a doctoral dissertation, was analysing archived Kepler data for a totally different reason when she and colleagues chanced upon strange patterns in the data that they didn’t understand.

“It was a complete surprise,” says Bastien.

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Boiling surfaces

It turns out the pattern provides a quick and relatively reliable way to determine a star’s evolutionary state.

Stars like the Sun, which is about 4.6 billion years old, eventually will evolve into red giants as they run out of fuel for nuclear fusion. The new study shows the surfaces of younger dwarf stars boiling more vigorously than older giants.

“What we are looking at here is the gravitational acceleration in the stellar outer layers, what we often call the atmosphere,” says astronomer Joergen Christensen-Dalsgaard, with Aarhus University in Denmark.

“The typical methods used have uncertainties up to 150 per cent. That very imprecise method is the easiest to do, and especially if you’re dealing with 150,000 stars and you need to characterise them all, that’s what you go to because it takes the least amount of resources. Our technique lets us beat that down to 25 per cent, which is very, very good for this field,” added Bastien.

Kepler, which collected data from about 120,000 target stars between May 2009 and May 2013, was designed to search for Earth-like planets in stars’ habitable zones,

For Bastien’s study, which appears in this week’s edition of Nature, astronomers analysed a few thousand stars in the Kepler data archive.

“If you have a large enough sample, then you start to pick out patterns in the way stars of different evolutionary states behave,” she says.

While the study is based on eight-hour flicker patterns in the visible light coming from target stars, scientists translated the data into corresponding audio wavelengths, a poignant conceptualisation that no doubt would have intrigued, and delighted, poet Taylor.


Nicotine exposure gives baby rats addictive personalities.

Results suggest explanation for why people exposed to nicotine in the womb are more likely to become smokers.

Exposure to nicotine in the womb increases the production of brain cells that stimulate appetite, leading to overconsumption of nicotine, alcohol and fatty foods in later life, according to a new study in rats.


Smoking during pregnancy is known to alter fetal brain development and increase the risk of premature birth, low birth weight and miscarriage. Prenatal exposure to nicotine also increases the likelihood of tobacco use and nicotine addiction in later life, but exactly how is unclear.

To understand the mechanisms behind this effect, Sarah Leibowitz, a behavioural neurobiologist at the Rockefeller University in New York, and her colleagues injected pregnant rats with small doses of nicotine — which the researchers say are comparable to the amount a pregnant woman would get from smoking one cigarette a day — and then examined the brains and behaviour of the offspring.


In a paper published today in Journal of Neuroscience1, they found that nicotine increased the production of specific types of neurons in the amygdala and hypothalamus. These cells produce orexin, enkephalin and melanin-concentrating hormone, neuropeptides that stimulate appetite and increase food intake.

Rats exposed to nicotine in the womb had more of these cells and produced more of the neuropeptides than those that were not, and this had long-term consequences on their behaviour. As adolescents, they not only self-administered more nicotine, but also ate more fat-rich food and drank more alcohol.

“These peptide systems stimulate food intake,” says Leibowitz, “but we found that they similarly increase the consumption of drugs and stimulate the brain’s reward mechanisms that promote addiction and substance abuse.”

Leibowitz notes that children whose mothers smoked during pregnancy are more likely to smoke themselves during adolescence and adulthood. Her team’s findings suggest a possible mechanism for that.

The use of nicotine patches or e-cigarettes during pregnancy could have a similar effect. “Whether given subcutaneously, as in our study, or via smoking or patches, the same amount of nicotine would still get into the brain to affect neuronal development and function,” Leibowitz says.

The results highlight the toxic effects of nicotine exposure on brain development, says George Koob, a neurobiologist at the Scripps Research Institute in La Jolla, California. He also adds that the study casts new light on the role of these neuropeptides in reward and motivation.

In earlier work, Leibowitz and her colleagues showed that rats exposed to fat and alcohol in the womb likewise overconsume these substances as adolescents. “Our studies make it very clear that neuronal development in utero is highly sensitive to these substances,” she says, “with each promoting their overconsumption and addictive-like behaviour in the offspring.” 

She and her collaborators are now comparing the effects of nicotine, fat and alcohol to learn more about how this promotion occurs. They are also exploring ways to reverse the effects of prenatal exposure to these substances, thus preventing their overconsumption in later life, which could lead to addiction and obesity.



Source: Nature


9 Truths About Letting Go of Opinions that Taint Us.

I have learned silence from the talkative, toleration from the intolerant, and kindness from the unkind; yet, strange, I am ungrateful to those teachers. ~Khalil Gibran

1. Smoke and Mirrors

The fear of imperfection and/or of not being accepted is, of course, an illusion. Who gets to be the judge and jury on what is deemed beautiful or hideous — successful or stupid? Let me guess:  The tabloids or magazines, possibly Hollywood or the catwalks of Milan? How about TV/movies and the media? Spare a thought about who you give your power over to.  The various outlets that dictate what beauty and normal are seem to be pushing fake, in my opinion.  There are moments where true beauty can shine through these channels, but those flashes are few and far between.  True beauty and acceptance is in the eye of the beholder.  So anyone claiming to know what beauty or normal definitely is needs very close examining if they are not including every member of the human race in their rundown.


2. Self-Realization and Repair Kits

When you can out these undesirable contracts you can begin to repair them.  We have to discover why we felt the lack and how we are feeling now about the same issue. Then we must align it to our higher self by breaking down the agreement piece by piece and offer it up to the light to be cleansed.

3. Inherent Beauty and Perfection

We need to look at ourselves and find the beauty inherent in us, not always trying to fish out our perceived faults. When you treat yourself with loving kindness and nurture your self-esteem with positive thoughts, you will begin to shift into alignment with your higher self.

4. Dissecting Agreements

When we were young we had no inhibitions and sang at the top of our voices, danced our hearts out (whether someone was looking or not) and thought we were princesses and superheroes. Then one day someone came along and made you feel less than what you felt about yourself. You may have paused to take it in – then you made a crucial decision. Either you agreed with what they said or you didn’t. That is why some of us can still dance freely and not be bothered whilst others cringe at the thought of dancing in public – this could be due to an earlier experience of being made to feel like you were ‘no good’ by someone who was only giving you one piece of the puzzle.

Care about people’s approval and you will be their prisoner. ~Lao Tzu

5. Piecing Together Your Puzzle 

When I said that the person was only giving one piece of the puzzle I mean that they have a preference based on their version of reality. That is one person’s perspective in a sea of other possible candidates – ones who may have loved your form of expression.  This person could have also been a child, an acquaintance, a stranger or it could have been someone you trusted and loved deeply. The latter is often the case and can make the hurt twice as potent.  However, we must consider that some things are said in the heat of the moment and not really meant by the offender, so we really need to see why we made the agreement.

6. That Tricky Enigma Called Universal Appeal

You need to know that you can never have universal appeal.  You or your talents may not be one person’s cup of tea but what about all the other people in the world who will resonate with your particular brand of uniqueness?  However, ultimately you need to please only you. When you do this then you are immediately accepted and no outside influence can make you feel anything other than what you know yourself to be.

7. Acknowledge the Good

We sometimes tend to disregard the ones who encourage us, leaving only space in our thoughts for the ones who hurt us. Why is this, I wonder?  Everyone has the urge to be liked and accepted for who they are. This is normal. But what we need to redefine is whatis normal? Every soul is special and has equally unique attributes, abilities and ways of expressing themselves creatively. There should be no judgment.

8. Identify the Judge 

When judgment rears its head, we must question the one doing the judging.   Tell that judge that you are in love with your differences.  Viva la difference!  Without freedom of expression this world would be a very dull place.  Without diversity in hair colour, body shapes, talents, voices, tastes, etcetera we would be tantamount to sheep running around in a field day in and day out – baa-baa-boring!

9. Know Thyself! 

Only then will you begin to discover, on the deepest level, that which you truly are and what you have accomplished – not only in this lifetime but in the countless life experiences you have had.  Draw on that wealth of talents you have stored, that which you haven’t even begun to extract from your being.  When you do, there is nothing anyone can say or do to you that would ever hurt you.  You will be resolute as to who you are and nobody can take that away from you — unless you allow them to.

When you are living with the statement ‘be the best you can be’ and you are doing this with all your integrity and might — you have nothing to fear.

Empowerment comes from fearing no-thing and facing every day with courage and love in your heart. Strive to be and do the best you can in every situation, then you will be living in your integrity.  Words or energy that does not fit with your frequency or vibration will not be allowed to penetrate your field of self.  You will have become the master of your life and your reality.


Weighing the Evidence: Studies Collide over How Aging Impacts Obesity Risk.



A meta-analysis found that carrying extra pounds becomes less risky with age, but two new studies dispute the “obesity paradox

Few phenomena have created as divisive a rift recently among health professionals as the so-called “obesity paradox,” the repeated finding that obese people with certain health conditions live longer than slender people with the same ailments. And when a January meta-analysis involving nearly three million research subjects suggested that overweight people in the general population also live longer than their slimmer counterparts, the head of Harvard University’s nutrition department, Walter Willett, called the work “a pile of rubbish.” A few new studies suggest that these paradoxes may largely be artifacts of flawed research designs, but some experts disagree, accusing the new studies of being inaccurate. Among the biggest questions raised by this new research is the impact of age: whether obesity becomes more or less deadly as people get older and why.

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The January meta-analysis, led by U.S. Centers for Disease Control and Prevention senior scientist Katherine Flegal, pooled data from 97 studies of the general global population and reported that, in sum, overweight individuals—those with a body mass index of 25 to 29.9—were 6 percent less likely to die over various short time periods than people of normal weight (with a BMI 18.5 to 24.9) were. For people over the age of 65, however, being overweight conferred a 10 percent survival advantage. Flegals’ findings also suggest that obesity, which has always been considered a major health risk, is not always dangerous and that it becomes less so with age: Adults with grade 1 obesity (BMIs of 30 to 34.9), she found, were no more likely to die than were normal weight adults; for grade 2 obesity (BMI of 35 to 39.9), the increased death risk for adults of all ages was 29 percent, but restricting the analysis to adults over the age of 65, the increased death risk associated with grade 2 obesity was not statistically significant.. The older a person is, the analysis seemed to say, the safer extra pounds become.

Two new studies, however, challenge the notion that extra weight, whether a little or a lot, can be safe. They also suggest that age is closely related to weight-related health risk and that added pounds could be more, not less, dangerous in old age than in youth. In a March 2013 analysis published in the American Journal of Epidemiologyand based on U.S. National Health Interview Survey data, Ryan Masters, a Robert Wood Johnson Foundation Health and Society Scholar at Columbia University, and his colleagues reported that grade 1 obesity (a BMI of 30 to 34.9) increases the death risk 45- to 54-year-old men by 10 percent but that among 75- to 84-year-olds, the increased death risk is 59 percent. (For women the percentages were even larger—15 percent and 72 percent, respectively.) Mortality risks for being overweight, they found, increased with age too. In a follow-up study published online last week in theAmerican Journal of Public Health, Masters and his colleagues concluded that, overall, obesity was responsible for 18 percent of all deaths among 40- to 85-year-olds between 1986 and 2006—a figure that is more than four times higher than some previous estimates.

How can two groups looking at similar populations come to such different conclusions? In part, the discrepancy stems from how the researchers consider age. Although the CDC researchers separated out the impacts of obesity and overweight at younger and older ages, they didn’t account for potential age-related influences that, according to Masters, strongly affect the relationship between weight and mortality. One such factor is selection bias. When scientists invite individuals to participate in survey-based studies, those who sign up are usually the healthy ones. This effect is likely to be magnified in elderly populations and particularly in obese elderly populations, Masters says. The small percentage of obese elderly people who participate in studies are likely to be in much better condition than the ones who don’t, which can make it seem as if obesity is less dangerous in old age than it really is. When Masters and his colleagues controlled for this effect using statistical methods and then calculated the mortality risks associated with obesity in the U.S. National Health Interview Survey data, they found that obesity was far deadlier in old age than the CDC meta-analysis had suggested it to be.

Masters and his colleagues accounted for two other potentially important age-related effects as well. One is that people born in 1950 tend to live to older ages than people born in 1930. And the latter group tends to live to older ages than people born in 1910, because those born later spend more of their lives reaping the benefits of public health interventions such as sanitation, refrigeration and modern medicine. The second is that  people born later also spend more of their lives exposed to relatively new environmental influences that are thought to drive the obesity epidemic—ubiquitous processed foods and sugar-sweetened beverages, hormone-disrupting chemicals, and sedentary behaviors. “People who are born later get a greater duration of exposure to all those obesity-inducing environmental changes,” Masters says, and “this cohort-based exposure is the key component to trying to understand not only your likelihood of being obese in America, but the chance for obesity to negatively impact your health and thus impact your mortality risk.” Although grade 1 obesity accounted for 3.4 percent of deaths at age 66 among white men born from 1915 to 1919, it accounted for 5.8 percent of deaths at age 66 for white men born 20 years later, Masters found. Ultimately, according to the new studies, the research suggesting obesity to be “safe” in old age didn’t account for the fact that the seniors being followed had not been obese for very long; future seniors who gain significant weight at a younger age and keep it on will have a much greater mortality risk.

Willett—the Harvard nutrition professor who strongly opposes the notion of anobesity paradox—largely agrees with the new findings and the idea that birth period shapes obesity-related mortality risk. “This is likely to become even more important as the current cohort of adolescents and young adults gets older, as it is true that the adverse effects of overweight are cumulative over a lifetime,” he says. Willett thinks, however, that there are many other spurious causes for the obesity paradox, too, including the fact that as people get sicker, they often lose weight, a trend that associates slimness with poor health even though in these cases slimness hasn’tcaused poor health. (Masters attempted to control for this so-called “reverse causation” by excluding people from his analysis who had a BMI under 18.5.) Other researchers try to account for this effect by excluding sick people from their analyses: In a study published online in August, for instance, Harvard nutrition researcher Chandra Jackson and her colleagues analyzed data from the general U.S. population and found that mortality risk appeared to decrease with increasing BMI among people with diagnosed diabetes; when they excluded those with diabetes, excess weight increased death risk. “It is imperative to address the methodological concerns that could lead to misleading conclusions,” says Jackson, who agrees that the obesity paradox is likely specious and that birth period could have important confounding effects, too.

Others are not convinced by the new findings. Flegal, the lead author of the CDC meta-analysis, says she does not think that her findings were biased by cohort effects, in part because many of the studies included in her analysis did not pool mortality estimates from wildly different age groups. She also says there’s little evidence that her findings were affected by selection bias. Neil Mehta, a professor of global health at Emory University who also studies the impact of obesity on mortality, says that the statistical method used by Masters and his colleagues “is questionable,” in part because it does not properly separate certain interrelated variables. The new findings ultimately inflate the risks of obesity in old age because older people, he says, suffer from many health problems and tend to die of a variety of causes. Yet Mehta agrees that “obesity duration matters a lot to mortality—the longer you are obese the higher the risk of dying,” a notion that his research supports, too.

Eric Reither, a sociologist at Utah State University and a co-author of the new studies with Masters, notes that their research is not necessarily at odds with Flegal’s work. “They also find that obesity contributes to premature mortality,” he says. “I would say that we build upon their research.” And although the new studies do little to settle the overall obesity paradox controversy, they do suggest that the impact of weight may be importantly dependent on age. “When people talk about the effect of [being] overweight or obesity on mortality risk, they often think it exists in a vacuum—that to be overweight at age 20 is to be overweight at age 60 is to be overweight at age 75,” Masters says. Instead of simply focusing on how age might influence the impact of obesity, he explains, scientists should consider that obesity might fundamentally shape the way people age—even if, right now, there’s no consensus on how it does so or even the nature of its influence.

Solving the Mystery of the Shrinking Moon.

Have you ever noticed how the moon appears much bigger at the horizon, just as it is rising over the nearby buildings or treetops, than it does later in the evening when it is directly overhead? Of course, the moon’s size does not change, but our perception of its size changes based on its position in the sky. In this activity you’ll investigate Emmert’s law, which helps explain the full-moon illusion, and estimate the size of the perceived increase in size of the moon when it is near the horizon. Then you could check out the real moon and see how this activity holds up to the full-moon illusion.


A full moon rising over the horizon often seems to be unusually large, but looks smaller as it moves up in the sky. The actual size of the moon stays the same. So what is the basis for this illusion? One well-supported theory is that the brain “thinks” the sky overhead is closer than the sky at the horizon and it adjusts the size of the moon’s image accordingly. When the moon is near the horizon, your brain miscalculates the moon’s true distance and size, making it seem larger in relation to its surroundings.

One way to explore this illusion is with afterimages. These occur when certain light-sensing cones in your eyes become fatigued after staring at a bright—or brightly colored—object. You can manipulate afterimages to mimic your perception of the moon at different places in the sky. Although the actual size of a specific afterimage on your retina doesn’t change, its perceived size can, depending on your perception of how far away the surface on which you view it seems to be. This phenomenon is known as Emmert’s law.

 A sheet of blue construction paper (A blue pen or pencil can be used instead, but the colored paper is best.)
 Glue or tape
 A sheet of yellow construction paper (A white sheet of paper can be used instead, but is less preferable.)
 A timer or a clock that shows seconds
 A helper
 An area with a clear view of the horizon and the zenith (the region of the sky directly overhead) (This part of the activity should be done mid-morning or mid-afternoon—to avoid looking at the sun—and on a day that is fairly cloudless with a lot of blue sky.)

 Cut a square out of the blue construction paper sheet, about one to two inches on each side.
 Lay the yellow sheet of construction paper down in the landscape position (long-ways horizontal). Fold the paper in half (taking the right side of the paper and folding it over the left side). Then unfold the paper.
 Using glue or tape, attach the blue square to the yellow sheet of construction paper, in the middle of either the left or right half of the yellow sheet. Be careful not to cover the top of the square or yellow sheet with the tape or glue.
 If you do not have construction paper, you may draw a solid blue square on either the right or left side of a plain white sheet of paper, as described.

 You can complete the first part of this activity inside: Hold the yellow paper with the blue square in front of you. Stare at the blue square for 30 seconds. (Use a timer with a buzzer or have a helper watch a clock for you.) Without changing the distance between your head and the yellow paper, switch from looking at the blue square to looking at the empty half of the yellow paper. Do you see the afterimage of the square? If you cannot clearly see an afterimage, try repeating this step until you can.
 Once the afterimage fades, keep your head the same distance from the paper as it was before and again stare at the blue square for 30 seconds. Then look for the afterimage on the empty half of the yellow paper. But this time try moving your head away from or closer to the yellow paper. How does the size of the afterimage change as you change the distance between your head and the yellow sheet? If you could not clearly see a change, try repeating this step until you can.
 Overall, how did the size of the afterimage change as you changed the distance between your head and the yellow paper?
 Next, go outside to an area with a clear view of the horizon and zenith. Do not do this at noon, when the sun is directly overhead or at twilight when the sun is low on the horizon, because this interferes with your observation of the afterimage at the zenith (the sky directly overhead) or the horizon. Mid-morning or mid-afternoon is probably the best time to do this, and the day should be fairly cloudless with a lot of blue sky to look at. Remember: when choosing the section of the sky to use, be sure that it does not coincide with where the sun is—you should never  look directly into the sun.
 Stare at the blue square on the yellow sheet for 30 seconds and then look at the horizon. Is there an apparent change in the size of the afterimage? In other words, does the afterimage look smaller, larger or the same size as the blue square? You can repeat this step a few times if you are unsure of your observations.
 Next stare at the blue square for 30 seconds and then look at the zenith. Is there an apparent change in the size of the afterimage? Does the afterimage look smaller, larger or the same size as the blue square? Again, you can repeat this step if you are unsure of your observations.
 Overall, did the afterimage appear smaller, larger or the same size at the horizon compared with its appearance at the zenith?
 Extra: Try the first part of this activity again (before you go outside), but this time try to quantify how the size of the afterimage changes depending on the distance between your head and the yellow sheet. (Be sure to always stare at the blue square from the same distance.) You could put the yellow sheet on a wall next to a ruler to estimate the size of the afterimage. Alternatively you could draw several different size squares (some bigger and some smaller than the blue square) nested together on the yellow sheet and try to see in which square the afterimage fits best. How does the distance between your head and the afterimage quantitatively correlate to the afterimage size?
 Extra: Try to estimate the change in the size of the afterimage at the zenith compared with the horizon. To do this you could cut out several squares (a white sheet of paper would work), some smaller and some larger than the blue square, and hold them out at arm’s length when looking at the afterimages. Try to find the squares that are most similar in size to the afterimages. Based on your findings, what is roughly the magnitude of the change of the full moon’s apparent size between the horizon and the zenith?
 Extra: Try to estimate the change in the size of the afterimage at 45 degrees above the horizon; that is, halfway between the horizon and the zenith. (Be sure to avoid the part of the sky with the sun.) What is the relative size of the afterimage at 45 degrees above the horizon, and how does it compare with the afterimage’s sizes at the zenith and the horizon?

Observations and results
When you stared at the blue square, and then looked at the yellow sheet and moved your head away from or closer to the sheet, did the size of the afterimage increase with distance? Did the afterimage look bigger on the horizon compared with its size at the zenith?

Whereas the actual size of the afterimage on your retina doesn’t change, the perceivedsize of the afterimage actually grows as you increase the distance between you and the surface on which you view the afterimage. (Or, in other words, the perceived afterimage size decreases as you get closer to the surface you’re viewing it on.) This phenomenon is known as Emmert’s law. One theory for why we perceive the full moon to be larger at the horizon compared with the zenith is that we perceive the sky overhead, at the zenith, as being closer than the sky at the horizon. In this activity this should have been apparent using afterimages; the afterimage at the horizon should have appeared larger than the afterimage at the zenith (although maybe only by a little, such as approximately 1.3 to 1.5 times larger at the horizon, depending on the exact conditions).


Lab-Made Egg and Sperm Precursors Raise Prospect for Infertility Treatment.

A technical tour de force, which involved creating primordial germ cells from mouse skin cells, is prompting scientists to consider attempting this experiment with human cells

Since last October, molecular biologist Katsuhiko Hayashi has received around a dozen e-mails from couples, most of them middle-aged, who are desperate for one thing: a baby. One menopausal woman from England offered to come to his laboratory at Kyoto University in Japan in the hope that he could help her to conceive a child. “That is my only wish,” she wrote.


The requests started trickling in after Hayashi published the results of an experiment that he had assumed would be of interest mostly to developmental biologists. Starting with the skin cells of mice in vitro, he created primordial germ cells (PGCs), which can develop into both sperm and eggs. To prove that these laboratory-grown versions were truly similar to naturally occurring PGCs, he used them to create eggs, then used those eggs to create live mice. He calls the live births a mere ‘side effect’ of the research, but that bench experiment became much more, because it raised the prospect of creating fertilizable eggs from the skin cells of infertile women. And it also suggested that men’s skin cells could be used to create eggs, and that sperm could be generated from women’s cells. (Indeed, after the research was published, the editor of a gay and lesbian magazine e-mailed Hayashi for more information.)

Despite the innovative nature of the research, the public attention surprised Hayashi and his senior professor, Mitinori Saitou. They have spent more than a decade piecing together the subtle details of mammalian gamete production and then recreating that process in vitro — all for the sake of science, not medicine. Their method now allows researchers to create unlimited PGCs, which were previously difficult to obtain, and this regular supply of treasured cells has helped to drive the study of mammalian reproduction. But as they push forward with the scientifically challenging transition from mice to monkeys and humans, they are setting the course for the future of infertility treatments — and perhaps even bolder experiments in reproduction. Scientists and the public are just starting to grapple with the associated ethical issues.

“It goes without saying that [they] really transformed the field in the mouse,” says Amander Clark, a fertility expert at the University of California, Los Angeles. “Now, to avoid derailing the technology before it’s had a chance to demonstrate its usefulness, we have to have conversations about the ethics of making gametes this way.”

Back to the beginning
In the mouse, germ cells emerge just after the first week of embryonic development, as a group of around 40 PGCs. This little cluster goes on to form the tens of thousands of eggs that female mice have at birth, and the millions of sperm cells that males produce every day, and it will pass on the mouse’s entire genetic heritage. Saitou wanted to understand what signals direct these cells throughout their development.

Over the past decade, he has laboriously identified several genes — including Stella,Blimp1 and Prdm14 — that, when expressed in certain combinations and at certain times, play a crucial part in PGC development. Using these genes as markers, he was able to select PGCs from among other cells and study what happens to them. In 2009, from experiments at the RIKEN Center for Developmental Biology in Kobe, Japan, he found that when culture conditions are right, adding a single ingredient — bone morphogenetic protein 4 (Bmp4) — with precise timing is enough to convert embryonic cells to PGCs. To test this principle, he added high concentrations of Bmp4 to embryonic cells. Almost all of them turned into PGCs. He and other scientists had expected the process to be more complicated.

Saitou’s approach — meticulously following the natural process — was in stark contrast to work that others were doing, says Jacob Hanna, a stem-cell expert at the Weizmann Institute of Science in Rehovot, Israel. Many scientists try to create specific cell types in vitro by bombarding stem cells with signalling molecules and then picking through the resulting mixture of mature cells for the ones they want. But it is never clear by what process these cells are formed or how similar they are to the natural versions. Saitou’s efforts to find out precisely what is needed to make germ cells, to get rid of superfluous signals and to note the exact timing of various molecules at work, impressed his colleagues. “There’s a really beautiful hidden message in this work — that differentiation of cells [in vitro] is really not easy,” says Hanna. Harry Moore, a stem-cell biologist at the University of Sheffield, UK, regards the careful recapitulation of germ-cell development as “a triumph”.

Until 2009, Saitou’s starting point had been cells taken from a live mouse epiblast — a cup-like collection of cells lining one end of the embryo that forms at the end of the first week of development, just before the PGCs emerge. But to truly master the process, Saitou wanted to start with readily available, cultured cells.

That was a project for Hayashi, who in 2009 had returned to Japan from the University of Cambridge, UK, where, like Saitou before him, he had completed a four-year stint in the laboratory of a pioneer in the field, Azim Surani. Surani speaks highly of the two scientists, saying that they “complement each other in temperament and in their style and approach to solving problems”. Saitou is “systematic” and “single-minded about setting and accomplishing his objectives”, whereas Hayashi “works more intuitively, and takes a broader view of the subject and has outwardly a more relaxed approach”, he says. “Together they form a very strong team indeed.”

Hayashi joined Saitou at Kyoto University, which he quickly found was different from Cambridge. There was much less time spent on theoretical discussions than Hayashi was used to; instead, one jumped into experiments. “In Japan we just do it. Sometimes that can be very inefficient, but sometimes it makes a huge success,” he says.

Hayashi tried to use epiblast cells — Saitou’s starting point — but instead of using extracted cells as Saitou did, he tried to culture them as a stable cell line that could produce PGCs. That did not work. Hayashi then drew on other research showing that one key regulatory molecule (activin A) and a growth factor (basic fibroblast growth factor) could convert cultured early embryonic stem cells into cells akin to epiblasts. That sparked the idea of using these two factors to induce embryonic stem cells to differentiate into epiblasts, and then to apply Saitou’s previous formula to push these cells to become PGCs. The approach was successful.

To prove that these artificial PGCs were faithful copies, however, they had to be shown to develop into viable sperm and eggs. The process by which this happens is complicated and ill understood, so the team left the job to nature — Hayashi inserted the PGCs into the testes of mice that were incapable of producing their own sperm, and waited to see whether the cells would develop. Saitou thought that it would work, but fretted. “It seemed like a 50/50 chance,” he says. “We were excited and worried at the same time.” But, on the third or fourth mouse, they found testes with thick, dark seminiferous tubules, stuffed with sperm. “It happened so properly. I knew they would generate pups,” says Hayashi. The team injected these sperm into eggs and inserted the embryos into female mice. The result was fertile males and females.

They repeated the experiment with induced pluripotent stem (iPS) cells — mature cells that have been reprogramed to an embryo-like state. Again, the sperm were used to produce pups, proving that they were functional — a rare accomplishment in the field of stem-cell differentiation, where scientists often argue over whether the cells that they create are truly what they seem to be. “This is one of the few examples in the entire field of pluripotent-stem-cell research where a fully functional cell type has been unequivocally generated starting from a pluripotent stem cell in a dish,” says Clark.

They expected eggs to be more complex, but last year, Hayashi made PGCs in vitrowith cells from a mouse with normal coloring and then transferred them into the ovaries of an albino mouse. The resulting eggs were fertilized in vitro and implanted into a surrogate. “I knew it had worked,” he says, when he saw the pups’ dark eyes pressing through their translucent eyelids.

Germ-cell bounty
Other researchers have been able to replicate the process to generate laboratory-grown PGCs (although none contacted by Nature had used them to produce liveanimals). Artificial PGCs are of particular use to scientists who study epigenetics: the biochemical modifications to DNA that determine which genes are expressed. These modifications — most often the addition of methyl groups to individual DNA bases — in some instances carry a sort of historical record of what an organism has experienced (for example, exposure to foreign chemicals in the womb). In a similar way to how they work in other cells, epigenetic markers push PGCs to their fate during embryonic development, but PGCs are unique because when they develop into sperm and eggs, the epigenetic markers are erased. This allows the cells to create a new zygote that is capable of forming all cell types.

Faults in subtle epigenetic changes are expected to contribute to infertility and the emergence of disorders such as testicular cancer. Already, Surani’s and Hanna’s groups have used the artificial PGCs to investigate the role of individual enzymes in epigenetic regulation, which may one day show how the epigenetic networks are involved in disease.

Indeed, the in vitro-generated PGCs offer millions of cells for scientists to study, instead of the 40 or so that can be obtained by dissecting early embryos, says Hanna. “This is a big deal because here we have these rare cells — PGCs — that are undergoing dramatic genome-wide epigenetic changes that we barely understand,” he says. “The in vitro model has provided unprecedented accessibility to scientists,” agrees Clark.

Clinical relevance
But Hayashi and Saitou have little to offer to the infertile couples begging for their help. Before this protocol can be used in the clinic, there are large wrinkles to be ironed out.

Saitou and Hayashi have found that although the offspring generated by their technique usually seem to be healthy and fertile, the PGCs that these offspring generate in turn are not completely ‘normal’. The second-generation PGCs often produce eggs that are fragile, misshapen and sometimes dislodged from the complex of cells that supports them. When fertilized, the eggs often divide into cells with three sets of chromosomes rather than the normal two, and the rate at which the artificial PGCs successfully produce offspring is only one-third of the rate for normal in vitrofertilization (IVF). Yi Zhang, who studies epigenetics at Harvard Medical School in Boston, Massachusetts, and who has been using Saitou’s method, has also found thatin vitro PGCs do not erase their previous epigenetic programming as well as naturally occurring PGCs. “We have to be aware that these are PGC-like cells and not PGCs,” he says.

In addition, two major technical challenges remain. The first is working out how to make the PGCs convert to mature sperm and eggs without transplanting them back into testes or ovaries; Hayashi is trying to decipher the signals that ovaries and testes give to the PGCs that tell them to become eggs or sperm, which he could then add to artificial PGCs in culture to lead them through these stages.

But the most formidable challenge will be repeating the mouse PGC work in humans. The group has already started tweaking human iPS cells using the same genes that Saitou pinpointed as being important in mouse germ-cell development, but both Saitou and Hayashi know that human signalling networks are different from those in mice. Moreover, whereas Saitou had ‘countless’ numbers of live mouse embryos to dissect, the team has no access to human embryos. Instead, the researchers receive 20 monkey embryos per week from a nearby primate facility, under a grant of ¥1.2 billion (US$12 million) over five years. If all goes well, Hayashi says, they could repeat the mouse work in monkeys within 5–10 years; with small tweaks, this method could then be used to produce human PGCs shortly after.

But making PGCs for infertility treatment will still be a huge jump, and many scientists — Saitou included — are urging caution. Both iPS and embryonic stem cellsfrequently pick up chromosomal abnormalities, genetic mutations and epigenetic irregularities during culture. “There could be potentially far-reaching, multi-generational consequences if something went wrong in a subtle way,” says Moore.

Proof that the technique is safe in monkeys would help to allay concerns. But how many healthy monkeys would need to be born before the method could be regarded as safe? And how many generations should be observed?

Eventually, human embryos will need to be made and tested, a process that will be slowed by restrictions on creating embryos for research. New, non-invasive imaging techniques will enable doctors to sort good from bad embryos with a high degree of accuracy. Embryos that seem to be similar to normal IVF embryos could get the go-ahead for implantation into humans. This might happen with private funding or in countries with less-restrictive attitudes towards embryo research.

When the technology is ready, even more provocative reproductive feats might be possible. For instance, cells from a man’s skin could theoretically be used to create eggs that are fertilized with a partner’s sperm, then nurtured in the womb of a surrogate. Some doubt, however, that such a feat would ever be possible — the Hinxton Group, an international consortium of scientists that discusses stem-cell ethics and challenges, concluded that it would be difficult to get eggs from male XY cells and sperm from female XX cells. “The instructions that the female niche is supplying to the male cell do not coordinate with each other,” says Clark, a member of the consortium.

Saitou used iPS cells from male mice to create sperm and from female mice to create eggs, but he says that the reverse should be possible. If so, eggs and sperm from the same mouse could be generated and used for fertilization, producing something never seen before: a mouse created by self-fertilization. Neither Hayashi nor Saitou is ready to try this. “We would only do this [in mice] if there were a good scientific reason,” says Saitou. Right now he does not see one.

The two scientists already feel some pressure from patients and Japanese funding agencies to move forward. The technique could be a last hope for women who have had no luck with IVF, or for people who had cancer in childhood and have lost the ability to produce sperm or eggs. Hayashi warns those who write to him that a viable infertility treatment could be 10 or even 50 years in the future. “My impression is that it is very far away. I don’t want to give people unfeasible hope,” he says.

Patients see the end result — success in mice — and often ignore the years of painstaking work that led to such a technical tour de force. They do not realize that switching from mice to humans means starting again almost from scratch, says Hayashi. The human early embryo is so different from the mouse that it is almost “like starting over on a process that took more than ten years”.

Source: Nature. 




DARPA to Genetically Engineer Humans by Adding a 47th Chromosome

We’re no molecular biologists over here, but have you ever seen the sci-fi flick Gattaca?

In that 1997 film, society is structured around eugenics as people are bioengineered to be ‘perfect specimens’, and one’s entire life and position in the world is based on their genetics. Those conceived naturally without genetic screening are proclaimed “invalid” and only allowed menial jobs, despite the innate talents and skills they may possess. Alternately, the 2011 movie In Time portrays a dystopic future where humans are genetically programmed to stop aging at 25 and could live forever — so long as they earn enough “time credits” to afford to stay alive; the poor perish swiftly under an artificially skyrocketing cost of living that times out their clocks, while the rich who steer the technocracy are gaming the system and living indefinitely.

Such nightmare scenarios place obvious restrictions on the natural right to life, liberty and the pursuit of happiness.

Back in reality, alarmingly similar ends are being pursued.


DARPA, the Department of Defense’s research arm, has just put out a new solicitation for a project called, “Advanced Tools for Mammalian Genome Engineering” on the government’s Federal Small Business Innovation Research (SBIR) site.

This project isn’t just for engineering any mammal’s genome, however; it’s specifically for the bioengineering of humans.

The proposal explains the project’s details:

The ability to deliver exogenous DNA to mammalian cell lines is a fundamental tool in the development of advanced therapeutics, vaccines, and cellular diagnostics, as well as for basic biological and biomedical research… The successful development of technologies for rapid introduction of large DNA vectors into human cell lines will enable the ability to engineer much more complex functionalities into human cell lines than are currently possible.

The project’s stated objective is to “improve the utility of Human Artificial Chromosomes (HACs).” (Gallows humor jokes about how DARPA wants to literally HAC(k) you can be made at any time.) A Wikipedia entry explains in relatively plain language what a HAC is and what it does:

A human artificial chromosome (HAC) is a microchromosome that can act as a new chromosome in a population of human cells. That is, instead of 46 chromosomes, the cell could have 47 with the 47th being very small, roughly 6-10 megabases in size, and able to carry new genes introduced by human researchers.


So DARPA and its team of associated scientists want to introduce an entirely new 47th chromosome into human genetics as a vector platform for inserting bio-alterations and wholesale genetic “improvements” into our DNA.

The agency hopes that development of a new chromosome will allow a solution to the limitations of current “state-of-the-art” gene transfer technologies (including plasmids, adenovirus-, lentivirus-, and retrovirus-vectors, cDNA, and minigene constructs). The proposal explains that existing approaches must be improved due to known drawbacks in the scientists’ failure to control their results, causing a few minor major problems:

These include random DNA insertion into the host genome, variation in stable integration sites between cell lines, variation in the copy number and expression level of DNA that is delivered, limitations on the number and size of DNA constructs that can be delivered, and immunological responses to foreign DNA.

Yet these techniques are already in use? How reassuring.

Ever hear the term ‘playing God’? Scientists who work in these fields not only refer to themselves as “genome engineers,” but “biological designers” in their journal articles. This January 2013 piece in the journal Molecular Systems Biology introduces the topic with a chilling description:

The phrase ‘genome-scale engineering’ invokes a future in which organisms are custom designed to serve humanity. Yet humans have sculpted the genomes of domesticated plants and animals for generations. Darwin’s contemporary William Youatt described selective breeding as ‘that which enables the agriculturalist, not only to modify the character of his flock, but to change it altogether. It is the magician’s wand, by means of which he may summon into life whatever form and mold he pleases’ (Youatt, 1837).

It’s impossible to even compile an accurate listing of all the potential slippery slopes at play here, yet it is clear that this entails a momentous grasp at controlling life, which not only empowers an already dictatorial technocratic elite, but emboldens a delusional and destructive cadre intent on overwriting the existing species now on Earth.

Watch the 30-second promo video below where an investment firm (with their creepy all seeing eye logo) nonchalantly projects that within 50 years, science will displace natural life by a factor of 50-to-1 with artificial lab-created species – including plants, animals, humans, bacteria and viruses.
Fidelity Investments Forecasts the Creation of 50x More Synthetic Biological Species than Known Natural Species.


Source: Nature. 

Does Israel’s New Polio Outbreak Threaten Global Eradication Efforts?

An expert sheds light on what polio virus found in the nation’s sewers means for the world

Public health advocates have long set their sights on wiping out polio worldwide, but recent resurgences of the pernicious disease raise questions about its future eradication.

Several months ago a wild strain of the virus surfaced in a sewer system in Rahat in southern Israel, and now it has reportedly been detected throughout the country. Israel’s government this week launched a nationwide vaccination campaign, attempting to inoculate all children under nine years of age with oral polio vaccine (OPV), a form of the vaccine containing a live, weakened form of the virus. Most of these children were already vaccinated as babies with inactivated polio vaccine (IPV), otherwise known as the dead-virus vaccine. But people who were injected with IPV can still be healthy carriers of the disease and shed the virus in feces.


Scientific American spoke with Bruce Aylward, assistant director general for Polio, Emergencies and Country Collaboration at the World Health Organization, to find out more about the situation in Israel and how recent events there are affecting global efforts to wipe out the disease.

What is happening in Israel right now?
What we know is that there is widespread detection of a wild polio virus at a number of sites that we have sampled, going back three-plus months. This virus is very similar to a strain that was detected in December of last year in Egypt, in the sewage there. This original virus came from Pakistan. Whether it went into Egypt and then Israel or Israel and then Egypt or [whether it spread via] two separate importations—it is unclear.

The virus has only been found in sewage at this point. There have not been any clinical cases of this so far; no children have been paralyzed. In the past [Israel] has detected [polio] virus from surrounding countries and it has disappeared very quickly, but this time it is persisting for longer. The virus can’t live in the sewage itself and multiply. What we are seeing is persistence of [people excreting] the virus.

How high is Israel’s vaccination coverage?
This is a country with quite high immunization coverage—about 94 percentage of coverage. It’s with the inactivated virus, the dead-vaccine virus that Dr. [Jonas] Salk made in the 1950s (versus the live vaccine coverage that [Albert] Sabin developed, which we mainly use in the vaccination program). Since the kids don’t have intestinal immunity, or not very much, the disease is managing to spread.

The reason the oral vaccination is used in the vaccine campaign is it provides intestinal immunity that is so crucial in stopping the person-to-person transmission spread in settings where you might have a high transmission rate of the virus—like in tropical areas or areas with suboptimal sanitation. For a long time in developed countries Sabin’s vaccine was the vaccine of choice, but the drawback was one in a million times a child can get the disease and get paralyzed. It’s very rare, but it’s a risk.

As global progress was made on eradiation, many countries switched to the inactivated vaccine. One country that solely uses inactivated vaccine is Israel.

So the kids who were vaccinated as babies are protected but they can still be carriers?
With IPV you are protected, but you will still shed the virus. Your goal [with vaccination] is the person doesn’t get polio when you vaccinate and also they don’t spread it. With IPV you protect the individual but don’t do as much to protect the gut and protect the community. With OPV you get both protection of the individual and the community.

What’s the main challenge to getting more people to take oral vaccine in a situation like this?
In countries where people are no longer using the oral vaccination, people are saying, “Why aren’t we using this vaccine now? Because it can cause paralysis, outbreaks, etcetera.”

The inactivated polio vaccine has no serious adverse events associated with it. The oral polio vaccine has extremely rare but real risks. The most common and predictable adverse event is Vaccine-Associated Paralytic Polio, or VAPP. The risk isless than one in a million and it’s mainly associated with the first dose of the vaccine. The [live virus] vaccine itself is not causing paralysis [with VAPP] since [the vaccine contains] a weakened form of the virus. It’s the vaccine virus replicating in the kid and reverting to virulence.

What have other countries done in a situation like Israel’s? 
Other countries, like the Netherlands—IPV-using countries—when they suffered an outbreak due to importation of the virus, they used OPV to stop transmission of the disease. OPV remains the method of choice to rapidly stop an outbreak.

It’s Russian roulette to let a virus circulate in your country knowing you have susceptible kids. Even with 94 percent coverage [via the injected vaccine with the dead virus] you still have 6 percent of the population that can get the virus, and there are still risks among the 94 percent, too. There will be paralytic cases unless you stop transmission of this thing.

How does the disease spread via feces?
Think about the last time you were in a washroom and how many people did not wash their hands. As much as we would like to pretend sanitation is fabulous all over the world, we know that everyone’s personal hygiene is not perfect. Polio is one of those viruses where you only need an incredibly small infectious dose to get infected. If the virus is circulating in an area, there’s a high probability that you could get exposed. It spreads from fecal-oral transmission.

How concerned are you about transmission beyond Israel?
Any persistent transmission anywhere in the world right now is alarming and should be treated like a health emergency to the country, but also to the surrounding areas. The virus is a silent hitchhiker that moves in the guts of people that have been vaccinated. IPV-vaccinated people could be carrying the virus without even knowing it. It’s when you see this persistence—as we’re seeing now—and expansion that is concerning. In Israel, if they don’t stop it and it does spread, there are other countries around it having problems with their immunization campaigns we don’t want to see get reinfected.

Polio recently reemerged in Somalia. How does this strain differ from the Somalia strain?
That’s an African strain. Both are serotype 1 viruses. There are three types of polio. This is the first year in history we have only seen one type of polio. The last type 3 we saw was in November of last year in Nigeria. We’re not seeing type 2. This is the first year we have seen six-plus months without a type 3 virus. The virus found in Israel originated in Pakistan, in south-central Asia. The Somalia virus came from the western African route that is mainly circulating in Nigeria.

What’s the status of the global effort to eradicate polio overall?
We are closer than we’ve ever been. We’re only dealing with one type of virus now and seeing less substrains of that virus. Within Pakistan and Nigeria and Afghanistan—the three parts of the world that never stopped seeing polio—[the viruses] are in the smallest parts of the country we’ve ever seen and the smallest number of cases we’ve seen. Although Israel has been reinfected, it has stopped [the disease] so many times before and will stop it again. Although Somalia has been reinfected—and there is already a big outbreak—it has been reinfected multiple times, too. The key [to beating back polio] is what is happening in Nigeria and Pakistan. Afghanistan is just seeing polio from right across the border in Pakistan.

Manage Vertigo, Improve Your Balance.

Vertigo got you down? How to prevent falls
Falls are the leading cause of injury-related emergency department visits—and the main cause of accidental deaths—among Americans 65 and older.
“Many falls are due to dizziness, or vertigo, which is a common medical problem,” says Judith White, MD, PhD, medical director of the new Balance, Dizziness and Fall Prevention Center at Cleveland Clinic’s Beachwood Family Health and Surgery Center. “Dizziness is a serious condition because it increases a person’s risk of falling by 13 times.”
With winter approaching, people should be especially cautious. “Ice and snow are huge amplifiers for falls,” Dr. White says. “But so are wet floors, uneven pavement and even rugs. If you have any concerns about your balance, get checked by a doctor before you fall.”

What causes vertigo?
In most cases, vertigo is caused by an imbalance in the inner ear and nervous system. These imbalances are called vestibular disorders and may be accompanied by hearing loss.
“A recent study showed that 35 percent of American adults aged 40 and older have evidence of vestibular disorder,” Dr. White says. “If anyone experiences dizziness or balance difficulties, they should ask their physician to refer them to a vestibular specialist. There are many things that can be done to resolve or help the problem.”
To prevent falls, Dr. White recommends the following:
1. Get strong
A strong body, particularly your core, will improve your balance and help you avoid falls. Consult a doctor first, but you could try tai chi, yoga or even standard strength training.
2. Use handrails
Always use handrails when walking up and down stairs. Falls can happen at any age. Making it a rule to use the handrails could save you from a serious injury.
3. Remove hazardous items from the floor
Remove hazardous items from the floor that may trip people, such as stools and scatter rugs.
4. Wear flatter, flexible shoes with good tread
For women, it’s tempting to wear high heels, but flats are a safer option if you are worried about losing your balance. For men and women, be sure to wear shoes that have a good tread so you don’t slip on slippery floors.
5. Safety-proof your home
Place hand grips in the bath and shower and always use handrails when walking up and down stairs.
Tags: dizziness, falling, senior safety, vertigo