Why Your DNA Isn't Your Destiny

The remote, snow-swept expanses of northern Sweden are an unlikely place to begin a story about cutting-edge genetic science. The kingdom's northernmost county, Norrbotten, is nearly free of human life; an average of just six people live in each square mile. And yet this tiny population can reveal a lot about how genes work in our everyday lives.

Norrbotten is so isolated that in the 19th century, if the harvest was bad, people starved. The starving years were all the crueler for their unpredictability. For instance, 1800, 1812, 1821, 1836 and 1856 were years of total crop failure and extreme suffering. But in 1801, 1822, 1828, 1844 and 1863, the land spilled forth such abundance that the same people who had gone hungry in previous winters were able to gorge themselves for months. (See the top 10 scientific discoveries of 2009.)

In the 1980s, Dr. Lars Olov Bygren, a preventive-health specialist who is now at the prestigious Karolinska Institute in Stockholm, began to wonder what long-term effects the feast and famine years might have had on children growing up in Norrbotten in the 19th century — and not just on them but on their kids and grandkids as well. So he drew a random sample of 99 individuals born in the Overkalix parish of Norrbotten in 1905 and used historical records to trace their parents and grandparents back to birth. By analyzing meticulous agricultural records, Bygren and two colleagues determined how much food had been available to the parents and grandparents when they were young.

Around the time he started collecting the data, Bygren had become fascinated with research showing that conditions in the womb could affect your health not only when you were a fetus but well into adulthood. In 1986, for example, the Lancet published the first of two groundbreaking papers showing that if a pregnant woman ate poorly, her child would be at significantly higher than average risk for cardiovascular disease as an adult. Bygren wondered whether that effect could start even before pregnancy: Could parents' experiences early in their lives somehow change the traits they passed to their offspring? (See the top 10 medical breakthroughs of 2009.)

It was a heretical idea. After all, we have had a long-standing deal with biology: whatever choices we make during our lives might ruin our short-term memory or make us fat or hasten death, but they won't change our genes (later debunked) — our actual DNA. Which meant that when we had kids of our own, the genetic slate would be wiped clean.

What's more, any such effects of nurture (environment) on a species' nature (genes) were not supposed to happen so quickly. Charles Darwin, whose On the Origin of Species celebrated its 150th anniversary in November, taught us that evolutionary changes take place over many generations and through millions of years of natural selection. But Bygren and other scientists have now amassed historical evidence suggesting that powerful environmental conditions (near death from starvation, for instance) can somehow leave an imprint on the genetic material in eggs and sperm. These genetic imprints can short-circuit evolution and pass along new traits in a single generation. (See TIME's photo-essay on Charles Darwin.)

For instance, Bygren's research showed that in Overkalix, boys who enjoyed those rare overabundant winters — kids who went from normal eating to gluttony in a single season — produced sons and grandsons who lived shorter lives. Far shorter: in the first paper Bygren wrote about Norrbotten, which was published in 2001 in the Dutch journal Acta Biotheoretica, he showed that the grandsons of Overkalix boys who had overeaten died an average of six years earlier than the grandsons of those who had endured a poor harvest. Once Bygren and his team controlled for certain socioeconomic variations, the difference in longevity jumped to an astonishing 32 years. Later papers using different Norrbotten cohorts also found significant drops in life span and discovered that they applied along the female line as well, meaning that the daughters and granddaughters of girls who had gone from normal to gluttonous diets also lived shorter lives. To put it simply, the data suggested that a single winter of overeating as a youngster could initiate a biological chain of events that would lead one's grandchildren to die decades earlier than their peers did. How could this be possible?

Meet the Epigenome
The answer lies beyond both nature and nurture. Bygren's data — along with those of many other scientists working separately over the past 20 years — have given birth to a new science called epigenetics. At its most basic, epigenetics is the study of changes in gene activity that do not involve alterations to the genetic code but still get passed down to at least one successive generation. These patterns of gene expression are governed by the cellular material — the epigenome — that sits on top of the genome, just outside it (hence the prefix epi-, which means above). It is these epigenetic "marks" that tell your genes to switch on or off, to speak loudly or whisper. It is through epigenetic marks that environmental factors like diet, stress and prenatal nutrition can make an imprint on genes that is passed from one generation to the next.

Epigenetics brings both good news and bad. Bad news first: there's evidence that lifestyle choices like smoking and eating too much can change the epigenetic marks atop your DNA in ways that cause the genes for obesity to express themselves too strongly and the genes for longevity to express themselves too weakly. We all know that you can truncate your own life if you smoke or overeat, but it's becoming clear that those same bad behaviors can also predispose your kids — before they are even conceived — to disease and early death.

The good news: scientists are learning to manipulate epigenetic marks in the lab, which means they are developing drugs that treat illness simply by silencing bad genes and jump-starting good ones. In 2004 the Food and Drug Administration (FDA) approved an epigenetic drug for the first time. Azacitidine is used to treat patients with myelodysplastic syndromes (usually abbreviated, a bit oddly, to MDS), a group of rare and deadly blood malignancies. The drug uses epigenetic marks to dial down genes in blood precursor cells that have become overexpressed. According to Celgene Corp. — the Summit, N.J., company that makes azacitidine — people given a diagnosis of serious MDS live a median of two years on azacitidine; those taking conventional blood medications live just 15 months. (See 25 people who mattered in 2009.)

Since 2004, the FDA has approved three other epigenetic drugs that are thought to work at least in part by stimulating tumor-suppressor genes that disease has silenced. The great hope for ongoing epigenetic research is that with the flick of a biochemical switch, we could tell genes that play a role in many diseases — including cancer, schizophrenia, autism, Alzheimer's, diabetes and many others — to lie dormant. We could, at long last, have a trump card to play against Darwin.

The funny thing is, scientists have known about epigenetic marks since at least the 1970s. But until the late '90s, epigenetic phenomena were regarded as a sideshow to the main event, DNA. To be sure, epigenetic marks were always understood to be important: after all, a cell in your brain and a cell in your kidney contain the exact same DNA, and scientists have long known that nascent cells can differentiate only when crucial epigenetic processes turn on or turn off the right genes in utero.

More recently, however, researchers have begun to realize that epigenetics could also help explain certain scientific mysteries that traditional genetics never could: for instance, why one member of a pair of identical twins can develop bipolar disorder or asthma even though the other is fine. Or why autism strikes boys four times as often as girls. Or why extreme changes in diet over a short period in Norrbotten could lead to extreme changes in longevity. In these cases, the genes may be the same, but their patterns of expression have clearly been tweaked. (See the best pictures of 2009.)

Biologists offer this analogy as an explanation: if the genome is the hardware, then the epigenome is the software. "I can load Windows, if I want, on my Mac," says Joseph Ecker, a Salk Institute biologist and leading epigenetic scientist. "You're going to have the same chip in there, the same genome, but different software. And the outcome is a different cell type."

How to Make a Better Mouse
As momentous as epigenetics sounds, the chemistry of at least one of its mechanisms is fairly simple. Darwin taught us that it takes many generations for a genome to evolve, but researchers have found that it takes only the addition of a methyl group to change an epigenome. A methyl group is a basic unit in organic chemistry: one carbon atom attached to three hydrogen atoms. When a methyl group attaches to a specific spot on a gene — a process called DNA methylation — it can change the gene's expression, turning it off or on, dampening it or making it louder. (See more about DNA.)

The importance of DNA methylation in altering the physical characteristics of an organism was proposed in the 1970s, yet it wasn't until 2003 that anyone experimented with DNA methylation quite as dramatically as Duke University oncologist Randy Jirtle and one of his postdoctoral students, Robert Waterland, did. That year, they conducted an elegant experiment on mice with a uniquely regulated agouti gene — a gene that gives mice yellow coats and a propensity for obesity and diabetes when expressed continuously. Jirtle's team fed one group of pregnant agouti mice a diet rich in B vitamins (folic acid and vitamin B12). Another group of genetically identical pregnant agouti mice got no such prenatal nutrition.

The B vitamins acted as methyl donors: they caused methyl groups to attach more frequently to the agouti gene in utero, thereby altering its expression. And so without altering the genomic structure of mouse DNA — simply by furnishing B vitamins — Jirtle and Waterland got agouti mothers to produce healthy brown pups that were of normal weight and not prone to diabetes.

Other recent studies have also shown the power of environment over gene expression. For instance, fruit flies exposed to a drug called geldanamycin show unusual outgrowths on their eyes that can last through at least 13 generations of offspring even though no change in DNA has occurred (and generations 2 through 13 were not directly exposed to the drug). Similarly, according to a paper published last year in the Quarterly Review of Biology by Eva Jablonka (an epigenetic pioneer) and Gal Raz of Tel Aviv University, roundworms fed with a kind of bacteria can feature a small, dumpy appearance and a switched-off green fluorescent protein; the changes last at least 40 generations. (Jablonka and Raz's paper catalogs some 100 forms of epigenetic inheritance.)

Can epigenetic changes be permanent? Possibly, but it's important to remember that epigenetics isn't evolution. It doesn't change DNA. Epigenetic changes represent a biological response to an environmental stressor. That response can be inherited through many generations via epigenetic marks, but if you remove the environmental pressure, the epigenetic marks will eventually fade, and the DNA code will — over time — begin to revert to its original programming. That's the current thinking, anyway: that only natural selection causes permanent genetic change. (See "The Year in Health 2009: From A to Z.")

And yet even if epigenetic inheritance doesn't last forever, it can be hugely powerful. In February 2009, the Journal of Neuroscience published a paper showing that even memory — a wildly complex biological and psychological process — can be improved from one generation to the next via epigenetics. The paper described an experiment with mice led by Larry Feig, a Tufts University biochemist. Feig's team exposed mice with genetic memory problems to an environment rich with toys, exercise and extra attention. These mice showed significant improvement in long-term potentiation (LTP), a form of neural transmission that is key to memory formation. Surprisingly, their offspring also showed LTP improvement, even when the offspring got no extra attention.

All this explains why the scientific community is so nervously excited about epigenetics. In his forthcoming book The Genius in All of Us: Why Everything You've Been Told About Genetics, Talent and IQ Is Wrong, science writer David Shenk says epigenetics is helping usher in a "new paradigm" that "reveals how bankrupt the phrase 'nature versus nurture' really is." He calls epigenetics "perhaps the most important discovery in the science of heredity since the gene." (See the top 10 nonfiction books of 2009.)

Geneticists are quietly acknowledging that we may have too easily dismissed an early naturalist who anticipated modern epigenetics — and whom Darwinists have long disparaged. Jean-Baptiste Lamarck (1744-1829) argued that evolution could occur within a generation or two. He posited that animals acquired certain traits during their lifetimes because of their environment and choices. The most famous Lamarckian example: giraffes acquired their long necks because their recent ancestors had stretched to reach high, nutrient-rich leaves.

In contrast, Darwin argued that evolution works not through the fire of effort but through cold, impartial selection. By Darwinist thinking, giraffes got their long necks over millennia because genes for long necks had, very slowly, gained advantage. Darwin, who was 84 years younger than Lamarck, was the better scientist, and he won the day. Lamarckian evolution came to be seen as a scientific blunder. Yet epigenetics is now forcing scientists to re-evaluate Lamarck's ideas. (See TIME's video on Charles Darwin and Abraham Lincoln.)

Solving the Overkalix Mystery
By early 2000, it seemed clear to Bygren that the feast and famine years in 19th century Norrbotten had caused some form of epigenetic change in the population. But he wasn't sure how this worked. Then he ran across an obscure 1996 paper by Dr. Marcus Pembrey, a prominent geneticist at University College London.

Published in the Italian journal Acta Geneticae Medicae et Gemellologiae, Pembrey's paper, now considered seminal in epigenetic theory, was contentious at the time; major journals had rejected it. Although he is a committed Darwinist, Pembrey used the paper — a review of available epigenetic science — to speculate beyond Darwin: What if the environmental pressures and social changes of the industrial age had become so powerful that evolution had begun to demand that our genes respond faster? What if our DNA now had to react not over many generations and millions of years but, as Pembrey wrote, within "a few, or moderate number, of generations"?

This shortened timetable would mean that genes themselves wouldn't have had enough years to change. But, Pembrey reasoned, maybe the epigenetic marks atop DNA would have had time to change. Pembrey wasn't sure how you would test such a grand theory, and he put the idea aside after the Acta paper appeared. But in May 2000, out of the blue, he received an e-mail from Bygren — whom he did not know — about the Overkalix life-expectancy data. The two struck up a friendship and began discussing how to construct a new experiment that would clarify the Overkalix mystery.

Pembrey and Bygren knew they needed to replicate the Overkalix findings, but of course you can't conduct an experiment in which some kids starve and others overeat. (You also wouldn't want to wait 60 years for the results.) By coincidence, Pembrey had access to another incredible trove of genetic information. He had long been on the board of the Avon Longitudinal Study of Parents and Children (ALSPAC), a unique research project based at the University of Bristol, in England. Founded by Pembrey's friend Jean Golding, an epidemiologist at the university, ALSPAC has followed thousands of young people and their parents since before the kids were born, in 1991 and 1992. For the study, Golding and her staff recruited 14,024 pregnant mothers — 70% of all the women in the Bristol area who were pregnant during the 20-month recruitment period.

The ALSPAC parents and kids have undergone extensive medical and psychological testing every year since. Recently, I met an ALSPAC baby, Tom Gibbs, who is now a sturdy 17-year-old. I accompanied him as clinicians measured his height (178 cm, or 5 ft. 8 in., not including spiked blond hair), the bone density of his left femur (1.3 g/sq cm, which is above average) and a host of other physical traits.

All this data collection was designed from the outset to show how the individual's genotype combines with environmental pressures to influence health and development. ALSPAC data have offered several important insights: baby lotions containing peanut oil may be partly responsible for the rise in peanut allergies; high maternal anxiety during pregnancy is associated with the child's later development of asthma; little kids who are kept too clean are at higher risk for eczema. (See the most common hospital mishaps.)

But Pembrey, Bygren and Golding — now all working together — used the data to produce a more groundbreaking paper, the most compelling epigenetic study yet written. Published in 2006 in the European Journal of Human Genetics, it noted that of the 14,024 fathers in the study, 166 said they had started smoking before age 11 — just as their bodies were preparing to enter puberty. Boys are genetically isolated before puberty because they cannot form sperm. (Girls, by contrast, have their eggs from birth.) That makes the period around puberty fertile ground for epigenetic changes: If the environment is going to imprint epigenetic marks on genes in the Y chromosome, what better time to do it than when sperm is first starting to form?

When Pembrey, Bygren and Golding looked at the sons of those 166 early smokers, it turned out that the boys had significantly higher body mass indexes than other boys by age 9. That means the sons of men who smoke in prepuberty will be at higher risk for obesity and other health problems well into adulthood. It's very likely these boys will also have shorter life spans, just as the children of the Overkalix overeaters did. "The coherence between the ALSPAC and Overkalix results in terms of the exposure-sensitive periods and sex specificity supports the hypothesis that there is a general mechanism for transmitting information about the ancestral environment down the male line," Pembrey, Bygren, Golding and their colleagues concluded in the European Journal of Human Genetics paper. In other words, you can change your epigenetics even when you make a dumb decision at 10 years old. If you start smoking then, you may have made not only a medical mistake but a catastrophic genetic mistake.

Exploring Epigenetic Potential
How can we harness the power of epigenetics for good? In 2008 the National Institutes of Health (NIH) announced it would pour $190 million into a multilab, nationwide initiative to understand "how and when epigenetic processes control genes." Dr. Elias Zerhouni, who directed the NIH when it awarded the grant, said at the time — in a phrase slightly too dry for its import — that epigenetics had become "a central issue in biology." (See TIME's health and medicine covers.)

This past October, the NIH grant started to pay off. Scientists working jointly at a fledgling, largely Internet-based effort called the San Diego Epigenome Center announced with colleagues from the Salk Institute — the massive La Jolla, Calif., think tank founded by the man who discovered the polio vaccine — that they had produced "the first detailed map of the human epigenome."

The claim was a bit grandiose. In fact, the scientists had mapped only a certain portion of the epigenomes of two cell types (an embryonic stem cell and another basic cell called a fibroblast). There are at least 210 cell types in the human body — and possibly far more, according to Ecker, the Salk biologist, who worked on the epigenome maps. Each of the 210 cell types is likely to have a different epigenome. That's why Ecker calls the $190 million grant from NIH "peanuts" compared with the probable end cost of figuring out what all the epigenetic marks are and how they work in concert.

Remember the Human Genome Project? Completed in March 2000, the project found that the human genome contains something like 25,000 genes; it took $3 billion to map them all. The human epigenome contains an as yet unknowable number of patterns of epigenetic marks, a number so big that Ecker won't even speculate on it. The number is certainly in the millions. A full epigenome map will require major advances in computing power. When completed, the Human Epigenome Project (already under way in Europe) will make the Human Genome Project look like homework that 15th century kids did with an abacus.

But the potential is staggering. For decades, we have stumbled around massive Darwinian roadblocks. DNA, we thought, was an ironclad code that we and our children and their children had to live by. Now we can imagine a world in which we can tinker with DNA, bend it to our will. It will take geneticists and ethicists many years to work out all the implications, but be assured: the age of epigenetics has arrived.

http://www.time.com/time/health/article/0,8599,1951968-1,00.html

Article #2

Jan 4, 2011 ST

This year, change your mind

By Oliver Sacks

 

NEW Year's resolutions often have to do with eating more healthily, going to the gym more, giving up sweets, losing weight - all admirable goals aimed at improving one's physical health. Most people, though, do not realise that they can strengthen their brains in a similar way.

While some areas of the brain are hard-wired from birth or early childhood, others - especially in the cerebral cortex, which is central to higher cognitive powers like language and thought, as well as sensory and motor functions - can be, to a remarkable extent, rewired as we grow older. In fact, the brain has an astonishing ability to rebound from damage - even from something as devastating as the loss of sight or hearing. As a doctor who treats patients with neurological conditions, I see this happen all the time.

For example, one patient of mine who had been deafened by scarlet fever at the age of nine, was so adept at lip-reading that it was easy to forget she was deaf. Once, without thinking, I turned away from her as I was speaking. 'I can no longer hear you,' she said sharply.

'You mean you can no longer see me,' I said.

'You may call it seeing,' she answered, 'but I experience it as hearing.'

Lip-reading, seeing mouth movements, was immediately transformed by this patient into 'hearing' the sounds of speech in her mind. Her brain was converting one mode of sensation into another.

In a similar way, blind people often find ways of 'seeing'. Some areas of the brain, if not stimulated, will atrophy and die. ('Use it or lose it,' neurologists often say.)

But the visual areas of the brain, even in someone born blind, do not entirely disappear; instead, they are redeployed in other senses. We have all heard of blind people with unusually acute hearing, but other senses may be heightened too.

For example, Geerat Vermeij, a biologist at the University of California-Davis who has been blind since the age of three, has identified many new species of molluscs based on tiny variations in the contours of their shells. He uses a sort of spatial or tactile giftedness that is beyond what any sighted individual is likely to have.

The writer Ved Mehta, also blind since early childhood, navigates in large part by using 'facial vision' - the ability to sense objects by the way they reflect sounds, or subtly shift the air currents that reach his face.

Ben Underwood, a remarkable boy who lost his sight at three and died at 16 in 2009, developed an effective, dolphin-like strategy of emitting regular clicks with his mouth and reading the resulting echoes from nearby objects. He was so skilled at this that he could ride a bike and play sports and even video games.

People like Ben Underwood and Ved Mehta, who had some early visual experience but then lost their sight, seem to instantly convert the information they receive from touch or sound into a visual image - 'seeing' the dots, for instance, as they read Braille with a finger.

Researchers using functional brain imagery have confirmed that in such situations, the blind person activates not only the parts of the cortex devoted to touch, but parts of the visual cortex as well.

One does not have to be blind or deaf to tap the brain's mysterious and extra-ordinary power to learn, adapt and grow. I have seen hundreds of patients with various deficits - strokes, Parkinson's and even dementia - learn to do things in new ways, whether consciously or unconsciously, to work around those deficits.

That the brain is capable of such radical adaptation raises deep questions. To what extent are we shaped by, and to what degree do we shape, our own brains? And can the brain's ability to change be harnessed to give us greater cognitive powers? The experiences of many people suggest it can.

One patient I knew became totally paralysed overnight from a spinal cord infection. At first she fell into deep despair, because she couldn't enjoy even little pleasures, like the daily crossword she had loved.

After a few weeks, though, she asked for the newspaper, so at least she could look at the puzzle, get its configuration, run her eyes along the clues. When she did this, something extraordinary happened. As she looked at the clues, the answers seemed to write themselves in their spaces. Her visual memory strengthened over the next few weeks, until she found she was able to hold the entire crossword and its clues in her mind after a single, intense inspection - and then solve it mentally. She had had no idea, she later told me, that such powers were available to her.

This growth can even happen within a matter of days. Researchers at Harvard found, for example, that blindfolding sighted adults for as few as five days could produce a shift in the way their brains functioned: Their subjects became markedly better at complex tactile tasks like learning Braille.

Neuroplasticity - the brain's capacity to create new pathways - is a crucial part of recovery for anyone who loses a sense or a cognitive or motor ability. But it can also be part of everyday life for all of us.

While it is often true that learning is easier in childhood, neuroscientists now know the brain does not stop growing, even in our later years. Every time we practise an old skill or learn a new one, existing neural connections are strengthened and, over time, neurons create more connections to other neurons. Even new nerve cells can be generated.

I have had many reports from ordinary people who take up a new sport or a musical instrument in their 50s or 60s, and not only become quite proficient, but derive great joy from doing so.

Ms Eliza Bussey, a journalist in her mid-50s who now studies harp at the Peabody conservatory in Baltimore, could not read a note of music a few years ago. In a letter to me, she wrote about what it was like learning to play Handel's Passacaille: 'I have felt, for example, my brain and fingers trying to connect, to form new synapses. I know that my brain has dramatically changed.' Ms Bussey is no doubt right: Her brain has changed.

Music is an especially powerful shaping force, for listening to and especially playing it engages many different areas of the brain, all of which must work in tandem: from reading musical notation and coordinating fine muscle movements in the hands, to evaluating and expressing rhythm and pitch, to associating music with memories and emotion.

Whether it is by learning a new language, travelling to a new place, developing a passion for beekeeping or simply thinking about an old problem in a new way, all of us can find ways to stimulate our brains to grow, in the coming year and those to follow.

Just as physical activity is essential to maintaining a healthy body, challenging one's brain, keeping it active, engaged, flexible and playful, is not only fun. It is essential to cognitive fitness.

The writer is a neurologist and author of The Mind's Eye.

NEW YORK TIMES

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Neuroplasticity - the brain's capacity to create new pathways - is a crucial part of recovery for anyone who loses a sense or a cognitive or motor ability. But it can also be part of everyday life for all of us.

1. Be sure that his attention is what you want. Don't try to get a guy to look your way, you want attention and you want to feel good about yourself.But don't be loud he is going to think your weird and not approachable! Being yourself is good but don't do something crazy to get his attention! You don't want to lead someone on like a puppy taken out for a walk. You could end up in a very awkward or uncomfortable situation. yeah man!
   
    
2. 2
   Something you should consider is letting him know you are single. Wearing a "single bracelet" will do the trick and they are stylish. There are very nice ones at www.single-heart.blogspot.com (HAHA SERIOUSLY?)
3. 3
   Be yourself. Everyone probably says this, but it's true. No guy wants a girl that pretends like she is something she is not. Show him that you are a good friend. Listen to the music he listens to. Just don't come on too clingy. No boy wants a girl who just follows him around all day. In addition, if you want to find out more about him, don't stalk the poor guy. Just find out about him from his friends you trust. For example, ask them about his likes and dislikes, what music he is into, what concerts he goes to, if he likes anyone, etc. Be confident in yourself, and it will show that you are an amazing person. Don't be someone you're not. You want him to like you for you. *nods
4. 4
   Try to become his friend. Get to know him better. Yes, you might like him, but first, become his friend. Start liking things that he likes, but don't get too much involved. He might become too crowded. First, try by asking him questions. Don't take it wrong if he says something bad about what you like. That's just his opinion, so don't want to do that because he will like you better just try something different, but don't stop doing what you like to do, because he might like someone who does what they like; if he doesn't like you for who you are, then let him be. Try a new hairstyle, new clothes, etc. It's a good idea to change things up once in a while. Because variety might be the spice of life, and it might help you catch his eye. Try being that girl who is different from all the other okay looking girls. Give him the eyes, because "beauty is common, but a good outlook and great energy are very rare." Guys love when girls look them in the eyes. *nods!
5. 5
   Smile and make eye contact. Whether closed-mouth or open-mouth, do it. Unless it really makes you feel artificial, learn how to shoot people a reassuring smile, letting them know that you're a happy and confident person who wants to enjoy life. The idea is to communicate that you're inviting their company.
6. 6
   Be cute. He will come over and talk to you. Don't be a total wallflower, but if you're just reading a magazine, try and look cute and wait until he can't resist and he might ask what book you're reading. and take the conversation on from there.
7. 7
   Flirt. Do it as much as you want, but remember that too much flirting especially with other guys will likely get him to take notice, but perhaps not in a good way. Don't do too much, but not too little either. Sometimes you might look too girlie, popular, wanna-be etc. If he reacts and you don't think its real, he's just doing it because you're there and you're a girl and he thinks he can do better, but let him know he can't. If he is faking it, call his bluff and say something that makes him know you don't think he is 'all that'. For example, if he comes close, pull a face and offer him gum. This will unbalance his ego.
8. 8
   Start up conversations that have to do with if it's where you are or if he's talking to you. Make sure you don't go on about nothing. Definitely make sense when you talk to him. Don't twirl your hair, flick your eyelashes or giggle nonstop. He can get kind of scared and make fun of you, no matter how old you are, guys will always be the same. Be yourself. Just be who you are, that's the #1 quality guys look for in a girl. (HUH, but sometimes, i can't help giggling)
9. 9
   Hang out with him often but not too often ; you don't always want to be hanging around because you might look like an annoying bug that's always around and never goes away. Try to start a conversation about an interesting topic, for example, if you're at a football game, ask confidently but cutely, "Did I miss any action?". This will tell him that you want to know about the game, but also you want to get his opinion, so he will automatically talk to you about the game (or other topics) the whole game. Start slowly like a movie or party try not to make it so noticeable cause he might not be interested.
10. 10
    
    *Be assertive
    . You are the girl. You have the power. A lot of guys are shy and awkward around girls they like, so don't hold back. Do what you want to do. Boys like a powerful girl. Be decisive. Tell him what you want him to do, etc.--just don't get too bossy. EH ok...
11. 11
    Make him feel special. There's got to be a reason that you want him to notice you, and that's because you noticed him first. Let him know--subtly--that you're interested in who he is, and that you sincerely want to get to know him better.You know, guys hate girl who wear too much make up.They think it looks hot for a while but then it tends to be like this: They break up with you(think your just a doll) nd fall in love with a natural girl. this is bootlicking with intentions!
12. 12
    Don't be a slob. It's a real turn-off for a guy when he notices a girl hasn't brushed her hair,hasn't cleaned her ears(They always look in there) or wears the same outfit every other day. Even if you don't fall within the typical expectations, just looking presentable is always desirable--irrespective of who is the guy or girl.
13. 13
    Just Talk To Him. When it comes down to it, talking to a guy, and flirting with him will get his attention, and if it doesn't then nothing will.
14. 14
    Walk in front of him. It may be very simple, but it works. When coming out of the class, or playing in gym class, just walk in front of him, and he should be able to notice you. If he walks in front of you a lot, he probably likes you. Is this about getting he/she to look at you, and pretending to be nonchalant about it all?
15. 15
    If he's looking your way, give him something to look at (HAHA, im totally thinking about something wrong here.). If he's looking at you you can:
    • Look away shyly, making you seem mysterious because he can't figure out why you did that.
16. 16
    Don't look into his eyes, then walk away .
    • Ignore him. (Quite a traditional pov hur!) Let him watch you by himself. If he is looking only at you, try to share your thoughts. eg. You are in a boring class, using your facial expression and pulled a face at the teacher then looking back at him and smile. Sharing these intimate moments makes you closer to him. 
17. 17
    If you catch him sneaking glances at you, then he is probably interested and trying to keep you in his sight. (Ohhh, commonsensical though)
18. 18
    But most importantly, do not be indecent. Be yourself, not a plastic barbie doll. You can be beautiful without wearing skimpy tiny shorts at gym or tanks with cleavage. Guys think it's attractive, but it's not good for a relationship. 
19. 19
    Find out what he likes and try to get into them too. He'll appreciate the fact you guys have things in common. (Purposely!?)
20. 20
    If you love a boy dress how he likes, but try to still be your self. (No)
21. 21
    Guys love girls that don't act mean or make fun of others. (Imma not mean, *silent wahaha)
22. 22
    On other terms, if you discover that he's been secretly talking to another girl behind your back: do something. On a personal level, you shouldn't let him get away with treating you like that. He's most likely lost interest in you for some reason, and has decided to follow his [probably] irrational impulses, and "fallen in love" with another girl. Again, don't let him think he can get away with feeding you lies and pretending your potential relationship is okay. Giving him a piece of your mind establishes that you're an independent and knowledgeable woman, and you know what's best for you.
23. 23
    If you have never talked to this guy before, however, just smile at him when you pass by. Subtle hints like that will keep you in his mind. he will be saying "Who was she? Great smile, hair face, etc." "I need to find out who she is". He will then be dropping smiles back to you, and one thing will lead to another. I am proof that this will work. just try it out yourself. if you dont get the same results as me, just try saying a simple hi. It will show him you aren't afraid or a coward. This could make the start of great friends, which could make the start of a great boyfriend/girlfriend relationship. (Ah, this will not work 99% of the time)

I just compiled some of the proses/poems that I could lay my hands on! I know that at least one is missing, and that is pretty sad. I posted it on an old blog and now I can't remember the url :( that's payback for my fickleness!

Well, I promise no exciting reading, but these are stuff that I really felt/ feel for at the point of writing (: I like the 1st & last one best! Yeah, if u notice, I don't exactly write about happy stuff, what a shame!

Oh on a sidenote, I think they sound really cheesy :% 
It seemed like I tried hard to give myself some positive encouragement! which is nonetheless good. mehhh

Poem#1

Close to the ground   and down to earth

Entwined by roots  and confined by fences

Bed of roses  this is what they say

Live in comfort  and live in vain

You, do you want to live this way? 

Extend your exterior   dear lil' one

See how far you can stretch  and try your best

Pardon me for taunting,   but how far do you dare?

Your exterior is thinning,   and it would not hold on

By the second,  does your hair stand?

By the second,  adrenaline gushes through your veins

You wonder with faint regret,  is this a wrong take?

So race your heart,  and your palms sweat

And then,  POP your exterior goes!

Uprooted you are,  and gone are your confinements

Break hold of your exterior  and into the sky you go

Breakaway,   
   Up to the skies is how far you shall go

Hands together, fingers intertwined
A flow of trust you think will everlast
He is your conviction and so are you his
This precious connection is what you perceived

Hands together through all paths
Sweaty palms slide past and fingers barely touched

Across the hills the grip stealthily loosen

Lil' did we know a hill is what we can't surpass

Now lost is the connection you held dear
Temporary is the feeling you staunchly stood by
Withered is the conviction you thought will never die
Now, gone is the ever that didn't last. 

<I Need Inspiration, Not Just Another Life’s Negotiation>

I & Me

me:
and that is it.
stuck in the cyclical throes of mundane humanity

lament upon my motley provisions
tangy sour over unfortunate preconditions
contending with these inadequacies
giving up inspired idiosyncrasies
falling prey to gratifications
looted by false consciousness
then there goes the enacted tragedy
in a self orchestrated symphony

i:
so is that it?
antipathy doesn't warrant sympathetic generosity

without the pursuit, devoid of passion, deprived an individual
...insufferable
...intolerable
...self deprecatory
hence incur the wrath of this philosophy

raise your mantle
even though how subtle
dare as u may strive
strive as u may dare
to dare revolt against commodifying
all life's satisfying
pursue this route affectionately
excluding the constraining technicality
on the contrary of numb complacency
... dawning opportunities
... multiplicity of possibilities
... gamut of emotions on a life roller coaster
i had offered u intriguing perplexity

only then
in the twilight
of your limelight
faced with your life
u shall take pride

and in this i shall continue to conquer
until me shall concur

and this shall be my lil legacy
to boost the supremacy
of me such an infinitely insignificant being
where all matters is my journey
in which i had identified personally