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Friday, November 4, 2011

Every Kind of Happiness




Sita Devi“Supremely famous is that city of Janakpur, where Sita Devi, the goddess of fortune herself appeared, making it like an ocean full of every type of happiness.” (Janaki Mangala, Svayamvara Ki Taiyari, 5)
taham̐ basa nagara janakapura parama ujāgara|
sīya lacchi jaham̐ pragaṭī saba sukha sāgara ||
“Don’t think that I’m wasting your time”, is the undertone to this verse from Tulsidas’ Janaki Mangala. The poet is setting the scene for his song about the marriage of the most beautiful couple. Should one be unfamiliar with where these events took place, Goswami Tulsidas is ensuring that they know that the place is supremely famous nonetheless. Even if one has never followed any Vedic teaching and doesn’t know who Sita Devi and Lord Rama are, hearing of their marriage ceremony and how it took place on that fateful day many thousands of years ago can still prove to bring every type of happiness to the heart, which can accept an unlimited amount of nectar, provided that it is of the transcendental variety.
Sita and RamaWhy the qualification? Why is the soul limited in accepting happiness of the material variety? If we find something pleasurable, how can we say that there is a limit to enjoying it? For instance, does a dog tire of enjoying sex life, a drunkard his beer and wine, and an obese person their fatty foods? Actually, the overindulgence in these areas is considered detrimental. The alcoholic may love getting drunk all the time, but deep down they know that something is wrong, as do others. The obese person has the most visible negative consequences to their behavior, and the dog is not viewed to be very intelligent for its lack of discrimination in conjugal affairs.
These defects point to the fact that the living beings are limited in their ability to enjoy certain things. There is a constraint put on the individual by their body type. The skeptic at this point may raise the argument that the limit is there for everything, so what is the point to even mentioning it? Ah, but there is no limit when one is swimming in a pool of spiritual nectar. What is the difference? How can we tell if something is spiritual? Isn’t everything we see around us a collection of earth, water, fire, air and ether manifested in different ways and perceived of by the senses attached to the body? If everything is seen through the material medium, how can we claim anything to be spiritual?
The spiritual is detected by certain properties, the foremost of which is eternality. Every living being is limited in the duration of their outward manifestation, even the trees that live for thousands of years. Spirit is the energy behind such manifestations and their movements, and since there is always energy, we can understand that spirit is always in existence. From the Bhagavad-gita, we learn that the spiritual energy is localized within each individual, which means that there are many fragments of spirit. Those embodied fragments existed prior to their current births and they will remain in existence even after impending deaths. We can take the information from the authority of the Gita, and we can also perceive for ourselves the importance of spirit, how it ensures that the living being can eat, sleep, mate and defend only when there is the vital force within the body.
“While contemplating the objects of the senses, a person develops attachment for them, and from such attachment lust develops, and from lust anger arises.” (Lord Krishna, Bhagavad-gita, 2.62)
Krishna speaking to ArjunaThe spiritual is tied to the fountainhead of all energy. Generally, that origin is referred to as God, but since He is also knowledgeable, eternal and blissful but on a larger scale, He can be described as the Supreme Spirit. Unlike the material energy, the spiritual energy provides lasting happiness. We can tell that we’re in connection with the spiritual energy when there is a fervent desire to remain connected with God, and when all good qualities descend from there. Among the many detriments to overindulgence in the material energy is the loss of rationale, the rise of anger and frustration, and the misguided belief that more indulgence will lead to more happiness. The sober person is always more capable at treading the difficult waters of life than is the intoxicated person. Intoxication is marked by the effect it has on the behavior of the person. In this sense intoxication can also come from greed, lust, anger and other emotions that arise from the failure to satisfy the senses, despite repeated attempts at material interaction.
The spiritual interaction, however, has the opposite effect. Therefore we can realize the presence of the spiritual by the effect it has on behavior. Rather than just study examples involving others, one can take the plunge themselves, extending some faith to the words of the Vaishnavas, those who always remain connected with the divine consciousness, which is the all-pervasive aspect of the Supreme Spirit. Tulsidas says that the city of Janakpur is like an ocean full of every type of happiness because he has experienced it himself. Not that he necessarily lived there or went there regularly. Rather, just by situating the mind there, especially at the time of the svayamvara held by the famed King Janaka, one can find peace and felicity for extended periods of time. Moreover, no amount of repeated mental trips to this place will prove detrimental to the mind. On the contrary, with each successive visit, the pool of nectar becomes sweeter and sweeter, leaving the pilgrim wondering why they ever left in the first place.
Where do these delights come from? Why Janakpur and not another place? The goddess of fortune, Lakshmiji herself, appeared in that great land many thousands of years ago. In addition to being the Supreme Spirit, God is also described as the husband of the goddess of fortune by the Vedas. We may think that we are responsible for the results of our actions, but in actuality the material nature is a much stronger force, as is the influence of the countless other living entities populating the earth. Therefore any good fortune we do receive actually comes from Lakshmi. Money is considered a type of incarnation of Lakshmi, good fortune that can come and go on a whim.
Lakshmi DeviIs Janakpur considered sacred because the kingdom was wealthy? Did Lakshmi appear in Janaka’s land to make him a rich king, full of every type of opulence? As the wife of Lord Narayana, the Supreme Lord who is the source of all men, Lakshmi always serves her husband and tries to make Him happy. She is never divorced from this role, which means that wherever she goes she has the same objectives in mind. When one is graced with Lakshmi’s presence, they are meant to use her association for Narayana’s benefit and no one else’s. As the Supreme Spirit is individually tied to the individual spirit, this proper use of fortune is beneficial to the individual as well.
In Janakpur, Lakshmi appeared as Sita, who was so named by Janaka, a famous king of the time. He found her one day while ploughing a field, and thus named her Sita because she came out of the ground. Her marriage ceremony marked the occasion where Janaka would reunite Lakshmi with Narayana, who had similarly appeared on earth in Ayodhya as Lord Rama, the famed prince of the Raghu dynasty. Janaka had not a hint of sin in him, so he was worthy of having Lakshmi as a daughter. Through her appearance would come Rama as a son-in-law, thus making Janaka supremely fortunate.
What about the happiness? How is Sita’s association full of every type of delight? Well, to find lasting happiness, wouldn’t it make sense to connect with the fountainhead of the spiritual energy, which is inexhaustible? Sita is herself part of the spiritual energy, and coupled with Rama she can give anything to anyone. But the fruit of one’s existence is to taste the happiness that comes from the beloved couple’s association. This means that just by having Sita live there, Janakpur became purified and the source of every type of happiness.
Sita and RamaThere was variety in activity in Janakpur during Sita’s time. Not everyone was a yogi given to meditation. Janaka, though a pious king, was famous for his mastery over mystic yoga, which results in many beneficial qualities, including renunciation. The ability to be dispassionate towards the temporary changes in life is considered an opulence, a praiseworthy trait. George Washington, the first President of the United States, is honored because he voluntarily stepped down from office after serving two terms. He did so to set an example, to show that a ruler shouldn’t remain in power in perpetuity. Janaka had full possession of renunciation, so much so that he was known as Videha, which means bodiless.
Was renunciation the fortune granted to him by Sita? Actually, when Janaka first found his soon-to-be daughter, he immediately became thrilled to the heart. This did not break his Videha status, for spiritual love has nothing to do with the swinging pendulum of enjoyment and renunciation that is concomitant with a material existence. Rather, in spiritual life there is only bliss. Separation and meeting both produce bliss, as do loss and gain, provided that one is connected with the divine consciousness.
The people in Janakpur had different occupations but they all loved Janaka and his eldest daughter very much. In this sense they were better than yogis, as they weren’t purposefully trying for self-realization, renunciation, or enlightenment. They were happy all the time simply because of their association with the goddess of fortune. Their eyes would serve their true purpose when they would see Rama and His younger brother Lakshmana approaching for the svayamvara.
Rama and LakshmanaThe onlookers had different emotions running through their minds at this time. The svayamvara was set up to decide Sita’s nuptials because Janaka did not know anything about her family history or her qualities based on the time of her birth. He decided that whoever could lift Lord Shiva’s bow, which was very auspicious, would win his daughter’s hand in marriage. Seeing Rama approaching, the residents of the town gathered to observe the bow-lifting contest felt a variety of emotions. Some were happy to see such a beautiful youth accompanied by His younger brother, who appeared as almost a twin, except with a different complexion. Rama is of the shyama color, which is dark, and Lakshmana is gaura, or fair. While some were eager with anticipation from the sight of Rama and Lakshmana, others started to worry. They thought that the king had made a mistake with his promise to give away Sita through the contest, for what if Rama couldn’t lift the bow? Lakshmana was the younger brother, so he wouldn’t have tried to lift the bow in Rama’s presence. In ancient times when the strictest rules and regulations of the Vedas were followed, it was considered a sin for a younger brother to get married before the older brother was married. As Lakshmana’s only dharma in life was to please his older brother, he was never really a candidate for marrying Sita.
When the contest took place, nervousness borne of anticipation penetrated the atmosphere. Just like watching a big moment in a game where everything is on the line, many onlookers were so afraid of what might happen should someone else lift the bow or Rama be incapable of rising to the challenge. Some knew that He was going to do it, while others prayed to God to be allowed to have Sita wed Rama.
Sita and RamaThus we see that there was every type of enjoyment available in Janakpur, except that they were all of the spiritual variety. Moreover, that happiness extends to anyone who listens to the accounts of what happened that day. To provide even more emphasis on just how wonderful spiritual happiness is, even someone who is intimately familiar with the marriage of Sita and Rama can listen to the story over and over again and still find tremendous delight, as if the heart auto-expands to make more room for the renewed inflow of spiritual nectar. From the words of his song, Tulsidas revealed the purpose for his writing. Send the mind back to the time of Sita’s marriage, which was situated in the ancient kingdom of Janakpur. As that was the place where the goddess of fortune appeared, it became an abode of auspiciousness. Just compiling the words gave Tulsidas so much pleasure, and that happiness extends to this day to anyone who is fortunate enough to connect with his writings. Every type of spiritual happiness is available to those who love Sita Devi and understand her position as Rama’s beloved.
In Closing:
Janakpur is the most auspicious place,
For its earth did Sita Devi grace.
She is the goddess of fortune, giver of delight,
Divine is her vision, so sweet is her sight.
Residents felt all types of happiness,
Having her around, joyful was even sadness.
Day of ceremony Shri Rama they got to see,
With brother Lakshmana, devoted to Rama was he.
Seeing two princes arrive that day,
Felt boundless joy coming their way.
In bhakti life anything but dull,
Vision of Lord supremely delightful.
Of all good things in Janakpur Sita was the center,
Allowed for residents path of liberation to enter.

Americans' circle of confidantes is down to two



 Other Sciences / Social Sciences 
Although the average Facebook user may have some 130 "friends," in reality, Americans have, on average, slightly more than two confidantes, down from three 25 years ago, but the size of this social network has stabilized since 2004, finds a new Cornell study.
Although this shrinking social network "makes us potentially more vulnerable," said Matthew Brashears, assistant professor of sociology, the good news is that "we're not as socially isolated as scholars had feared."
Brashears' study is published online and in press in the journal Social Networks.
The findings confirm Brashears' 2006 findings from a paper with Miller McPherson and Lynn Smith-Lovin of Duke University, which reported that between 1985 and 2004, the average size of the group with whom we discuss important matters had shrunk by about one-third (from about three people to two).
"We also reported that that the level of social isolation -- the percentage of the population that reports not discussing important matters with anyone at all -- in the U.S. had increased dramatically to roughly 25 percent from about 8 percent," said Brashears.
These findings were challenged by prominent sociologists who claimed that the results were the result of survey errors.
In the new study, Brashears used new data from a nationally representative experiment. He found that "modern discussion networks have decreased in size, which is consistent with other researchers' findings, but that social isolation has not become more prevalent," said Brashears.
The level of social isolation, he said, is so variable from survey to survey that it is not possible at this point to make generalizations about its true level, although it is possible to measure the overall size of our discussion networks.
Provided by Cornell University
"Americans' circle of confidantes is down to two." November 2nd, 2011. http://www.physorg.com/news/2011-11-americans-circle-confidantes.html
Posted by
Robert Karl Stonjek

The 7 Wonders of the world.



Whatever you want to do, do it now. There are only so many tomorrows.

Shirdi Sai Baba -mantra OM SAI RAM

s

Thursday, November 3, 2011

Unbelievable Perfection...!!! WoW.


Food Costs Threaten World's Poorest

Health risk from eating well-done meat may be underestimated







Mice are often used to test whether substances in food are harmful to humans. This requires that mice and humans metabolise substances in the same way. Humans have certain enzymes in more parts of the body than mice. The health risk associated with harmful substances in food may therefore be underestimated.
Researchers at the Norwegian Institute of Public Health have adopted a mouse type where human enzymes have been inserted to examine whether people may be more sensitive to certain carcinogenic substances from heat-treated foods. They have obtained a better model to assess negative health effects in humans from substances in food using these mice.
The results show that the incidence of intestinal tumours increased from 31 per cent to 80 per cent in “human-like” mice who consumed substances from meat crust (i.e. the surface formed during heat-treatment).

Food mutagens

Heat-processing of food can lead to the formation of carcinogenic substances. The formation of carcinogenic substances – so-called food mutagens – usually occurs at high temperatures when frying or grilling.
There are enzymes called sulfotransferases (SULT) in several places in the human body. These are only found in the livers of normal laboratory mice. SULT-enzymes can make some substances in food less harmful, but they can also transform harmless substances into carcinogenic substances.

Better research

Humans have SULT-enzymes in many organs while normal mice only have them in the liver. Using results from laboratory mice to predict health risk to humans consuming food mutagens can therefore be underestimated. Researchers at the NIPH used laboratory mice with the same amount of SULT-enzymes in the intestines as humans in their experiments.
The mice received the food mutagen often found in highest quantities in the crust of meat and fish. The researchers wanted to study tumour development in the intestines of the “human-like” mice, and compare this with tumour development in normal mice given the same food mutagen.
The results showed that the incidence of intestinal tumours increased from 31 per cent to 80 per cent in “human-like” mice after consuming substances from the meat crust.
This shows that normal laboratory mice are not a good model for assessing the health risk to humans following ingestion of food mutagens from well-done meat and fish.
The study is funded by the Norwegian Research Council.
________________

Reference

Svendsen C, Meinl W, Glatt H, Alexander J, Knutsen HK, Hjertholm H, Rasmussen T, Husøy T. Intestinal carcinogenesis of two food processing contaminants, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 5-hydroxymethylfurfural, in transgenic FVB min mice expressing human sulfotransferases. Mol Carcinog. 2011 Oct 17. doi: 10.1002/mc.20869.

SEVEN SIMPLE STEPS TO MAKE MONEY





It’s easy to come to the realization that you’d like to build wealth. It’s not as easy to actually begin this process. These 7 steps will help you get started on your way to making millions. Get the info here!
The Digerati Life suggests…
#1 Start saving and investing early.
The younger you are, the greater your chance of making a million if you start saving and investing early! The power of compounding is on your side. To start, you can open an online brokerage account — some good ones are Zecco and TradeKing.
#2 Know that any type of work or business can make you rich if it has a market.
Any line of work can potentially make you a millionaire if you’re successful at it, and especially if you’re really good at it. Your skills, if they answer a strong demand, could be your ticket to big things. Many of the wealthy are people who excel at what they do — whether it be in sports, entertainment, sales, real estate, business, art, engineering, writing.
#3 Help yourself succeed with the following traits: positive mindset, can-do attitude, willingness to learn, knowledgeability, persistence, determination, passion and being action-oriented.
#4 Be willing to make sacrifices and to reset priorities.
Stop spending, watch your budget and set aside some money. Try to find some inspiration to help you through the financial challenges. Look into other people’s success stories and take encouragement from their own experiences.
#5 Don’t buy into the belief that you can get rich overnight. The only way you can do so is by being lucky. You can have a windfall fall on your lap tomorrow, but that would be lady fortune smiling upon you — a chance event. Lotteries and casinos are obvious crap shoots. If someone offers you the formula to get rich tomorrow with very little work all for a “small” fee, run away. It’s a scam.
#6 Learn all you can about finance.
Don’t invest blindly. Read up on it, learn how other successful people have made it and do the research via books, the web, workshops, classes or seminars.
#7 Learn all you can about business, if you want to become an entrepreneur.
Don’t get into business blindly. Learn how to run, operate and manage a business before you take on that risk. There are many people with specific talents who entered into business and failed. That’s because it’s not enough to be able to cultivate an idea or a skill, you’ll also need to know something about business before starting one. Either you have the head for business, or get a partner who does.

A COMPANY WHICH HAS OUTLASTED ECONOMIC DOWNTURNS FOR 216 YEARS





It’s very exciting to see companies excel right off the bat and skyrocket to success, but its even more thrilling to see a company which has consistently done well for a very long time. This company has been in existence for 216 years and they are still going strong! Find out which company has lasted two centuries already!
INC highlights…
Can there be a 216-year-old start-up?
Bill Newlands, president of Beam North America, believes it is possible. As one on the most recognizable liquor brands in the United States—Jim Beam—gears up for another phase, the company is trying to stay quick and nimble while promoting its well-known brands.
The company, which includes brands such as Maker’s Mark, Cruzan Rum, and Suaza Tequila, split off from Fortune Brands this month to be publicly traded company under the name Beam Inc.  Fortune Brands, which sold its golf brand Titleist in July, will continue to house home goods and security companies, such as Master Lock and Moen faucets.
While Fortune Brands has been hit like other suppliers of home goods by the lack of new home construction since the onset of the recession, sales for spirits rose 2.3 percent to $19.2 billion last year, according to the Distilled Spirits Council of the United States. During 2010, Beam’s global revenues increased 7.9 percent to $2.7 billion.
Part of the strategy is keeping people like Frederick Booker Noe III, Jim Beam’s great grandson, and Rob Samuels, the grandson of the founder of Maker’s Mark, at the forefront as a brand ambassadors for the company, while quickly rolling out a series of new products to bring in a new audience.
Newland says a big portion of that audience is a population plenty of big spirits companies ignore: women.
In the past six years, Beam has added 11 of its 14 priority brands, including the much ballyhooed addition of reality TV star Bethenny Frankel’s Skinnygirl Cocktails. The margarita variety quickly became the No. 1 selling ready-to-drink cocktail, and the company recently added white sangria with plans for a white cosmopolitan drink.
Determining that women are more likely to favor drinks with a lower alcohol content and flavored spirits, Beam also launched a less potent variety of Courvoisier cognac blended with red wine, Pucker-flavored vodkas, a variety of Effen vodka inspired by the cucumber water you’d find at spas, as well as Red Stag, a cherry-flavored bourbon made by Jim Beam.
And while about 80 percent of bourbon drinkers are men, Noe says that about half of Red Stag customers are women—and that it’s helping introduce them to the bourbon category. In the last five years, Noe says he’s noticed that women are coming in groups to tastings, where before, they would only visit if with their husband or boyfriend.
Get the entire story at INC!

USE WHAT YOU HAVE WHEN INNOVATING



Innovation: Size Matters

Instead of trying to inflate a small idea, take a big one and tell consumers how it can change their lives

Ooh, that is a big idea, a really, really big idea. The other guys have ideas, but theirs are so small. You’d better watch out, or you may hurt someone with that big thing. And I can see you’re very excited about it, too!
We know what you’re thinking. We’re just a couple of guys overly amused by sophomoric humour, making a lame attempt to get your attention and some cheap laughs, right? Well, kinda.
We admit to not taking ourselves too seriously, but before we rush to judgment, let us make a simple point that leaders too often miss when it comes to innovation: It is easy to make a big idea small and nearly impossible to make a small idea big.
We’ll explain.
By making a big idea small, we mean coming up with a complicated game-changing concept and explaining it in a way that people get instantly. For example, in 2009, Hyundai introduced an “Assurance” program that allowed you to return your new car if you got laid off. As a result, while most of its competitors posted losses, Hyundai’s 2009 February sales increased.
What made this a big idea was the marriage of a powerful insight—a creative insurance mechanism that would have been almost impossible to explain on its own—and spot-on marketing that talked directly to the consumer’s worry about being laid off. It was a big idea that garnered immediate attention from potential customers and the media and produced impressive results.

Don’t Hype a Small Idea

Staying with the automotive theme, we see many insurers spending millions on advertising programs that give you discounts when you choose their company for multiple policies. In other words, if you bring them more business, they will charge you less. In our opinion, with the advent of companies likePriceline.com ( PCLN), consumers now expect a discount when things are bundled, and pointing out that you can give such a discount makes a recipe for cannibalization, not sales growth. Giving a discount for buying multiple products and then hyping the idea is an attempt to make a small idea big. It rarely resonates.
So when it comes to industry-changing ideas, the size of the ideas and the resolve behind them really do matter.
We believe leaders should talk about big ideas. Big ideas get your company attention. They demand a higher price. They increase loyalty. They demonstrate that you know how to listen, invent, and take risks. Great leaders know how to recognize, promote, and successfully launch big ideas.
Small ideas do just the opposite. With all your big talk, you may get someone to look at them, but in the end they will cost you your reputation, your team’s loyalty, and your customer. Far too often, leaders make the mistake of talking about big ideas that are really embarrassingly small.
As we have said in the past, we believe that companies should manage their innovation portfolios just like they manage their financial portfolios.

Low Risk, Low ROI

By definition, this means innovation leaders are intentionally taking some small risks with small ideas. We call these ideas evolutionary innovation. Good leaders do not brag about these ideas, because in addition to being lower risk, these ideas provide a lower return on investment and your competitors are already trying them. If these are the only ideas you’re working on and your head of innovation is bragging about how they are going to change the world, then yes, we suspect you have some overcompensating going on.
Because of the hype, your customers will be interested at first but will quickly turn their heads toward the big, sexy ideas of your competition. You can’t tell them you have big things in store and then not deliver.

BE THE BEST YOU CAN BE: SUCCESSFUL EMPLOYEES



Seven Steps to Coaching Your Employees to Success

Many employers sit their workers down once a year for a review. At that time, the employee finds out what they’ve been doing right or if there are areas in need of improvement. But what happens the other 364 days of the year?
Coaching is a different approach to developing employees’ potential. With coaching, you provide your staff the opportunity to grow and achieve optimal performance through consistent feedback, counseling and mentoring. Rather than relying solely on a review schedule, you can support employees along the path to meeting their goals. Done in the right way, coaching is perceived as a roadmap for success and a benefit. Done incorrectly and employees may feel berated, unappreciated, even punished.
These seven steps, when followed, can help create a positive environment for providing feedback.
Step 1: Build a Relationship of Mutual Trust
The foundation of any coaching relationship is rooted in the manager’s day-to-day relationship with the employee. Without some degree of trust, conducting an effective coaching meeting is impossible.
Step 2: Open the Meeting
In opening a coaching meeting, it’s important for the manager to clarify, in a nonevaluative, nonaccusatory way, the specific reason the meeting was arranged. The key to this step is to restate — in a friendly, nonjudgmental manner — the meeting purpose that was first set when the appointment was scheduled.
Step 3: Get Agreement
Probably the most critical step in the coaching meeting process is getting the employee to agree verbally that a performance issue exists. Overlooking or avoiding the performance issue because you assume the employee understands its significance is a typical mistake of managers. To persuade an employee a performance issue exists, a manager must be able to define the nature of the issue and get the employee to recognize the consequences of not changing his or her behavior. To do this, you must specify the behavior and clarify the consequences.
The skill of specifying the behavior consists of three parts.
  1. Cite specific examples of the performance issue.
  2. Clarify your performance expectations in the situation.
  3. Asks the employee for agreement on the issue.
The skill of clarifying consequences consists of two parts. You should:
  1. Probe to get the employee to articulate his or her understanding of the consequences associated with the performance issue.
  2. Ask the employee for agreement on the issue.

SAI SUDHA - A Lotus of Lyrics Placed at the Divine Feet of SAI

Wednesday, November 2, 2011

Team discovers how a cancer-causing bacterium spurs cell death





Researchers report they have figured out how the cancer-causing bacterium Helicobacter pylori attacks a cell’s energy infrastructure, sparking a series of events in the cell that ultimately lead it to self-destruct.
Caption: Microbiology professor Steven Blanke, doctoral student Prashant Jain and a colleague at Purdue University found a mechanism linking Helicobacter pylori infection, impairment of the mitochondria and cell death. Credit: L. Brian Stauffer
H. pylori are the only bacteria known to survive in the human stomach. Infection with H. pylori is associated with an increased risk of gastric cancer, the second-leading cause of cancer-related deaths worldwide.
“More than half the world’s population is currently infected with H. pylori,” said University of Illinois microbiology professor Steven Blanke, who led the study. “And we’ve known for a long time that the host doesn’t respond appropriately to clear the infection from the stomach, allowing the bacterium to persist as a risk factor for cancer.”
The new study, in Proceedings of the National Academy of Sciences, is the first to show how a bacterial toxin can disrupt a cell’s mitochondria – its energy-generation and distribution system – to disable the cell and spur apoptosis (programmed cell death).
“One of the hallmarks of long-term infection with H. pylori is an increase in apoptotic cells,” Blanke said. “This may contribute to the development of cancer in several ways.” Apoptosis can damage the epithelial cells that line the stomach, he said, “and chronic damage to any tissue is a risk factor for cancer.” An increase in apoptotic cells may also spur the hyper-proliferation of stem cells in an attempt to repair the damaged tissue, increasing the chance of mutations that can lead to cancer.
Previous studies had shown that VacA, a protein toxin produced by H. pylori, induces host cell death, Blanke said, “but the mechanism had been unknown.”
The VacA protein was known to target the mitochondrion, an organelle that produces chemical energy where it is needed in the cell. In healthy cells, mitochondria fuse to form elaborate energy-generating networks in response to cellular needs. Mitochondria are important to a lot of other cellular processes; most important to Blanke and his colleagues, they regulate cell death.
While studying how a cell responds to infection, the researchers noticed that H. pylori induced mitochondrial fission. Instead of fusing and forming filamentous networks to respond to the cell’s energy needs, the mitochondria were breaking into smaller, unconnected organelles.
“Fusion and fission are two dynamic and opposing processes that must be balanced to regulate mitochondrial structure and function,” Blanke said. But infection with H. pylori – or with purified VacA toxin alone – was pushing the mitochondria toward fission.
The researchers found that VacA recruited a host protein, Drp1, to the mitochondria. This protein plays a central role in mitochondrial fission. Further experiments showed that Drp1-mediated fission of the mitochondrial networks was linked to activation of a cell-death-inducing factor, called Bax.
“The link between VacA action at the mitochondria and Bax-dependent cell death had previously been unknown,” Blanke said.
This study provides a first direct link between a bacterial toxin-mediated disruption of mitochondrial dynamics and host cell death, Blanke said. It also opens a new avenue of investigation of other diseases linked to impaired mitochondrial function, he said.
“Hundreds of human diseases and disorders are associated with mitochondrial dysfunction, ranging from cancers to degenerative diseases such as Alzheimer’s disease and Parkinson’s,” Blanke said. “As yet, no one has methodically investigated a potential link between bacterial infections and mitochondrial diseases, despite the fact that several dozen pathogenic bacteria and viruses are known to directly target mitochondria.”
Blanke and his colleagues are beginning to investigate that link.
“To us, finding that a pathogen can disrupt mitochondria in a manner that has striking similarities to what has been observed in known mitochondrial diseases is potentially very exciting,” said Blanke, who also is an affiliate of the Institute for Genomic Biology at Illinois.
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The research team included Illinois doctoral student Prashant Jain and Professor Zhao-Qing Luo, of Purdue University.