মঙ্গলবার, ২৫ ডিসেম্বর, ২০১২

Doctor Who Roleplay [Private]

Here's the general idea: I'd like to try my hand at writing a season of Doctor Who. I'd like it to have a major, underlying story arc, along with individual "episodes" or chapters. We'd only really have to plan for the major plot; the chapters we could plot as we go.

I'd like you to play the Doctor, and which Doctor you play is entirely up to you (though I will say that I have a preference for Eleven, and I will make puppy eyes at you while making such an observation). You may even make an original regeneration.

I will play an OC, and I can promise you that's not as Sue-ish as it sounds. I don't do undeveloped characters; my characters arrive with plenty of depth, and they continue to develop as the roleplay occurs. We'll both be developing and playing NPCs as necessary.

I only have one plot idea. I'm not married to it, but here's a summary:

"The Doctor always had an eye for good companions. The shop girl, the doctor, the mouthy temp, the little girl and her Roman: each has been a light for humanity in their own brilliant and often surprising way.

And then those lights began to flicker.

Well, to be fair, it was the literal, man-made lights that flickered first. It became a trend that the Doctor noticed in his travels; wherever he was, regardless of its location in space and time, the lights were flickering. Even the bulb on his TARDIS was not immune to the trend. Then, he noticed an even more disturbing trend: Time itself was unraveling. Each flickering light signified another row of stitches plucked from its fabric. Tugging the strands was a dark force with her sights on the beginning of Time itself. If the force were allowed to continue, the power to reconstruct the tapestry of the past, present, and future would lie in her hands.

The Doctor could not allow this, and so he traveled. He found a young woman who was broken, raw, unpredictable and completely unlike any companion that he had found before. He laid all of time and space before her, offered to take her anywhere that she pleased, and silently prayed that she would not notice the flickering lights which pursued them.

Time could be rewritten, he once claimed. This adventure would be the ultimate test of that theory, for under no circumstances could his new companion know the truth: the dark force pursuing them is none other than the companion's future self, and only the retribution or damnation that she finds at the Doctor's side can save Time from its beginning."

Again, I'm not married to this, and it is subject to revision/additional ideas. I'd like the plot to involve some or all of the following things:
- Flickering lights indicating...something. In this case, the lights flicker when something from the future (but still intertwined with the present) becomes unwound.
- A unique Companion. As the plot currently stands, they'll represent some of the worst of humanity rather than the best.
- the Doctor saving Time and Space from something other than the end of Time in Space (or the end of Planet Earth). I'd like our conflict to be a foil to this usual trope, somehow; if we could make the Doctor save Time and Space from the beginning of time and space, that would be fabulous.
- This is unrelated to the current plot, but something with convergent realms/universes could also be fun.

Source: http://feedproxy.google.com/~r/RolePlayGateway/~3/R1r-aZcQQy4/viewtopic.php

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Nasty storms blamed 1 death, make travel tough

This NOAA satellite image taken Tuesday, December 25, 2012 at 10:45 AM EST shows a low pressure system over the Southern Plains and Lower Mississippi Valley moving into the Southeast with rain and thunderstorms. Snow and snow showers over the Central Plains and Mid Mississippi Valley. Farther north, snow showers are seen over northern New England. (AP PHOTO/WEATHER UNDERGROUND)

This NOAA satellite image taken Tuesday, December 25, 2012 at 10:45 AM EST shows a low pressure system over the Southern Plains and Lower Mississippi Valley moving into the Southeast with rain and thunderstorms. Snow and snow showers over the Central Plains and Mid Mississippi Valley. Farther north, snow showers are seen over northern New England. (AP PHOTO/WEATHER UNDERGROUND)

(AP) ? Freezing rain and sleet made for a sloppy Christmas trek in parts of the nation's midsection, while residents along the Gulf Coast faced thunderstorms, high winds and tornadoes that were doing damage in some areas.

Winds toppled a tree onto a pickup truck in the Houston area, killing the driver. Icy roads already were blamed for a 21-vehicle pileup in Oklahoma, where authorities warned would-be travelers to stay home.

Trees fell on a few houses in central Louisiana's Rapides Parish but there were no injuries reported so far and crews were cutting trees out of roadways to get to people in their homes, said sheriff's Lt. Tommy Carnline. Possible damage also was reported near McNeil, Miss.

Fog blanketed highways, including arteries in the Atlanta area where motorists slowed as a precaution. In New Mexico, drivers across the eastern plains had to fight through snow, ice and low visibility.

At least three tornadoes were reported in Texas, though only one building was damaged, according to the National Weather Service. Tornado watches were in effect across southern Louisiana and Mississippi.

More than 180 flights nationwide were canceled by midday, according to the flight tracker FlightAware.com. More than half were canceled by American Airlines and its regional affiliate, American Eagle.

American is headquartered and has its biggest hub at Dallas/Fort Worth International Airport.

Christmas lights also were knocked out with more than 70,000 people without power in east Texas, Arkansas, Mississippi and Louisiana.

Meanwhile, blizzard conditions were possible for parts of Illinois, Indiana and western Kentucky with predictions of 4 to 7 inches of snow. Much of Oklahoma and Arkansas braced under a winter storm warning of an early mix of rain and sleet forecast to eventually turn to snow. About a dozen counties in Missouri were under a blizzard warning from Tuesday night to noon Wednesday.

Some mountainous areas of Arkansas' Ozark Mountains could get up to 10 inches of snow, which would make travel "very hazardous or impossible" in the northern tier of the state from near whiteout conditions, the National Weather Service said.

The holiday may conjure visions of snow and ice, but twisters this time of year are not unheard of. Ten storm systems in the last 50 years have spawned at least one Christmastime tornado with winds of 113 mph or more in the South, said Chris Vaccaro, a National Weather Service spokesman in Washington, via email.

The most lethal were the storms of Dec. 24-26, 1982, when 29 tornadoes in Oklahoma, Missouri, Arkansas, Tennessee and Mississippi killed three people and injured 32; and those of Dec. 24-25, 1964, when two people were killed and about 30 people injured by 14 tornadoes in seven states.

Quarter-sized hail reported early Tuesday in western Louisiana was expected to be just the start of a severe weather threat on the Gulf Coast, said meteorologist Mike Efferson at the weather service office in Slidell, La.

Storms along the Gulf Coast could bring winds up to 70 mph, heavy rain, more large hail and dangerous lightning in Louisiana and Mississippi, Efferson said. Furthermore, warm, moist air colliding with a cold front could produce dangerous straight-line winds.

The storm was moving quickly as it headed into northeast Louisiana and Mississippi into the late afternoon and early evening, said Bill Adams at the weather service's Shreveport, La., office.

In Mississippi, Gov. Phil Bryant urged residents to have a plan for any severe weather.

"It only takes a few minutes, and it will help everyone have a safe Christmas," Bryant said.

___

AP Business Writer Daniel Wagner in Washington and Associated Press Writer Ramit Plushnick-Masti in Houston contributed to this report.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/f70471f764144b2fab526d39972d37b3/Article_2012-12-25-Christmas%20Weather/id-20d38f1fdb38474b800b452305e7e0b0

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সোমবার, ২৪ ডিসেম্বর, ২০১২

Snappgrip ? One handed picture snapping for your iPhone or Samsung Galaxy S3

Snappgrip is a UK based Kickstarter project that will provide a snap on camera controller for your iPhone 4, 5 or Samsung Galaxy S3. It’s made up of 2 parts. A protective case and the Snappgrip which snaps into the case and houses the controls. Using Bluetooth, this accessory features one-handed controls for?shutter, zoom and [...]

Source: http://the-gadgeteer.com/2012/12/23/snappgrip-one-handed-picture-snapping-for-your-iphone-or-samsung-galaxy-s3/

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Is a career as a Paralegal right for you? - Guide to Distance Learning

When your career hits a glass ceiling, a dead end, or otherwise stalls out, going back to school to learn a new trade of set of skills is a smart plan of action. With distance learning and on-line degree programs, more people have more options about their education, and thus have more options for their future.

he job market for paralegal services is supposed to increase, photo by expertinfantry

In a recent article on Yahoo! Education, one of the careers spotlighted as being desirable as a second career was that of a paralegal. According to the Department of Labor, demand for paralegals is expected to grow substantially in the next few years as employers try to increase efficiency and reduce their overhead and costs of legal services.

What is a paralegal? Well, the definition varies slightly from country to country. Basically, a paralegal is anyone who assists a qualified lawyer in the legal profession. That?s a pretty vague definition, admittedly. In Canada, paralegals are licensed and monitored by the government, and the profession is regulated. In America, the duties of a paralegal can be different from state to state, city to city, or law firm to law firm. But in essence, anyone working under the direct supervision of a lawyer is considered a paralegal.

To work as a paralegal, potential employees need to have either an AA (associates of arts, a two year degree) in paralegal studies, or a certificate in paralegal studies. A bachelor?s degree in the field is a plus, but not mandatory to get your foot in the door.

When going to school for paralegal studies, some of the courses required will include (but not be limited to) Probate and Family Law, Real Estate, Litigation, Legal Research, Corporate Law, Legal Writing and Reasoning, Technology, Ethics, Legal Procedures, Torts. A paralegal isn?t a lawyer, but the more they know about the law, the more valuable they are as an asset to a law firm. These courses are usually designed to give the student a broad general understanding of the law, its concepts, and procedures and processes.

However, since different lawyers in different fields of law all hire paralegals, getting specific knowledge in real estate law, estate planning, government law, or criminal trials (just to name a few examples) can be beneficial and help the student find a job in the future. Paralegal is such a general term, that there is a lot of room under the umbrella for different types of paralegal work.

Sound interesting? Ok, now its your turn to do some research and find out more details about the distance learning programs available, to see which one is right for you ? or to see if the profession in general is a good fit.

Kaplan University offers two degrees, an Associate of Applied Science in Paralegal Studies, and a Postbaccalaureate Pathway to Paralegal Studies Certificate.

Everest University Online offers an Associate in Science Paralegal.

Boston University Online offers a Paralegal Certificate.

Virginia College has two degrees available through their online program, an Associate of Science Paralegal Studies, and a Bachelor of Science Paralegal Studies.

Source: http://www.distancelearning.com/is-a-career-as-a-paralegal-right-for-you/

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Make money online today!: How Autoresponders Work - ubafylei's ...

How Autoresponders Work

At some point in our Internet lives, a majority of us have received a message from an autoresponder.? It could have been a short response letting you know that the individual is away, or an email thanking you for something that you have done.? Perhaps it was even an email letting you know about upcoming products, or even an email letting you know that a message you tried to send couldn?t be delivered.

Each one of these messages is all but a different version of a useful program known as an autoresponder.? Autoresponders are very useful tools, as they will automatically send out an answer to any email that they receive.? The answer that they send out however, will all depend on the messages that you have the program set up with.? Autoresponders are very flexible, and most will hold a variety of pre set messages.

The very first autoresponders were used with email providers or email transfer agents.? Whenever an email you sent out couldn?t be delivered to the recipient, it would send you an automatic response letting you know that your mail couldn?t be delivered.? Although these programs were somewhat helpful, they weren?t all that sophisticated.

Over the years, autoresponders have changed quite a bit, proving to be very useful with big companies and even Internet marketing.? These days, autoresponders are used by businesses and companies to give immediate response and feedback to interested clients and subscribers.? This could include a response about programs, information about pricing, specific details regarding a product, and even a time that someone from the company can get in touch with the client.

In the world of Internet marketing, staying in touch with clients is easier than ever with an autoresponder.? They will save you a quite a bit of time, especially when you think about how long it would take you to personally send email responses to each and every email you get.? If you run a business, you probably get hundreds of emails a day.? An autoresponder can simplify your life, by sending out a preset message response to each and every email you receive.

You can set up an autoresponder using either one or two methods ? an outsourced ASP model and server side model.? When using an outsourced ASP model, the company wishing to use the autoresponder will their business model will contract through an outside provider.? This outside provider will then give the company user access to a web based system, or control panel.? From the control panel, the company or individual can set up the autoresponder, preset messages, and decide how the autoresponder will handle the many different types of emails. One of the best services we have found is www.Automatic-Responder.com their service is top notch. To use these types of services, the individual or company will have to pay the autoresponder provider a flat monthly fee.

Server side autoresponders are a bit different.? Basically, they are programs that a company or individual installs themselves and runs it on their own computer or server.? You can save money with these programs, as you don?t have to pay a provider to operate the autoresponder.? Although server side autoresponders weren?t user friendly in the beginning, they have become easier and easier to operate over the years ? and are now the most popular type of autoresponder.

In all actuality, autoresponders are great to have.? They are very reliable, and can easily save you a lot of time. The way the different types work can be a bit perplexing, although most are easy to use and easy to implement into your website.? If you own or operate an online business ? an autoresponder is something you should never find yourself without.

Source: http://easyonlineturnkey.blogspot.com/2012/12/how-autoresponders-work.html

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Source: http://ubafylei.posterous.com/make-money-online-today-how-autoresponders-wo

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রবিবার, ২৩ ডিসেম্বর, ২০১২

Peru's capital highly vulnerable to major quake

Map shows all significant earthquakes in the Peruvian region since

Map shows all significant earthquakes in the Peruvian region since

In this Nov. 26, 2012 photo, Jaime Arevalo moves a stone as he works to build a new shack home on the top of a mountain in the Nueva Rinconada neighborhood on the outskirts of Lima, Peru. Seismologists, engineers and civil defense officials agree that Lima is due for an earthquake but is acutely vulnerable and sorely unprepared. At the biggest risk, apart from tsunami-vulnerable Callao, are places like Nueva Rinconada. A treeless moonscape in the southern district of San Juan de Miraflores, it is a haven for economic refugees from Peru's countryside who continue to arrive daily and cobble together precarious homes on lots they score into steep hillsides with pickaxes. (AP Photo/Rodrigo Abd)

In this Oct. 17, 2012 photo, Doris Morante, behind right, stands with her daughter Galia, 6, amid new shacks built on a hill in San Juan de Lurigancho on the outskirts of Lima, Peru. Seismologists, engineers and civil defense officials agree that Lima is due for an earthquake but is acutely vulnerable and sorely unprepared. More than two in five of capital residents inhabit rickety structures built on unstable, sandy soil and wetlands, which amplify a quake's destructive power, or in the hillside settlements ringing the capital that sprang up spontaneously over a generation as people fled conflict and poverty in the interior, experts say. (AP Photo/Rodrigo Abd)

In this Nov. 5, 2012 photo, homes cover the Rimac neighborhood of Lima, Peru. Seismologists, engineers and civil defense officials agree that Lima is due for an earthquake but is acutely vulnerable and sorely unprepared. More than two in five of capital residents inhabit rickety structures built on unstable, sandy soil and wetlands, which amplify a quake's destructive power, or in the hillside settlements ringing the capital that sprang up spontaneously over a generation as people fled conflict and poverty in the interior, experts say. (AP Photo/Rodrigo Abd)

In this Oct. 19, 2012 photo, Maria Estancia Ventanilla holds up one of the walls of her new home being built on the outskirts of Lima, Peru. Seismologists, engineers and civil defense officials agree that Lima is due for an earthquake but is acutely vulnerable and sorely unprepared. More than two in five of capital residents inhabit rickety structures built on unstable, sandy soil and wetlands, which amplify a quake's destructive power, or in the hillside settlements ringing the capital that sprang up spontaneously over a generation as people fled conflict and poverty in the interior, experts say. (AP Photo/Rodrigo Abd)

LIMA, Peru (AP) ? The earthquake all but flattened colonial Lima, the shaking so violent that people tossed to the ground couldn't get back up. Minutes later, a 50-foot (15-meter) wall of Pacific Ocean crashed into the adjacent port of Callao, killing all but 200 of its 5,000 inhabitants. Bodies washed ashore for weeks.

Plenty of earthquakes have shaken Peru's capital in the 266 years since that fateful night of Oct. 28, 1746, though none with anything near the violence.

The relatively long "seismic silence" means that Lima, set astride one of the most volatile ruptures in the Earth's crust, is increasingly at risk of being hammered by a one-two, quake-tsunami punch as calamitous as what devastated Japan last year and traumatized Santiago, Chile, and its nearby coast a year earlier, seismologists say.

Yet this city of 9 million people is sorely unprepared. From densely clustered, unstable housing to a dearth of first-responders, its acute vulnerability is unmatched regionally. Peru's National Civil Defense Institute forecasts up to 50,000 dead, 686,000 injured and 200,000 homes destroyed if Lima is hit by a magnitude-8.0 quake.

"In South America, it is the most at risk," said architect Jose Sato, director of the Center for Disaster Study and Prevention, or PREDES, a non-governmental group financed by the charity Oxfam that is working on reducing Lima's quake vulnerability.

Lima is home to a third of Peru's population, 70 percent of its industry, 85 percent of its financial sector, its entire central government and the bulk of international commerce.

"A quake similar to what happened in Santiago would break the country economically," said Gabriel Prado, Lima's top official for quake preparedness. That quake had a magnitude of 8.8.

Quakes are frequent in Peru, with about 170 felt by people annually, said Hernando Tavera, director of seismology at the country's Geophysical Institute. A big one is due, and the chances of it striking increase daily, he said. The same collision of tectonic plates responsible for the most powerful quake ever recorded, a magnitude-9.5 quake that hit Chile in 1960, occurs just off Lima's coast, where about 3 inches of oceanic crust slides annually beneath the continent.

A 7.5-magnitude quake in 1974 a day's drive from Lima in the Cordillera Blanca range killed about 70,000 people as landslides buried villages. Seventy-eight people died in the capital. In 2007, a 7.9-magnitude quake struck even closer, killing 596 people in the south-central coastal city of Pisco.

A shallow, direct hit is the big danger.

More than two in five Lima residents live either in rickety structures built on unstable, sandy soil and wetlands, which amplify a quake's destructive power, or in hillside settlements that sprang up over a generation as people fled conflict and poverty in Peru's interior. Thousands are built of colonial-era adobe.

Most quake-prone countries have rigorous building codes to resist seismic events. In Chile, if engineers and builders don't adhere to them they can face prison. Not so in Peru.

"People are building with adobe just as they did in the 17th century," said Carlos Zavala, director of Lima's Japanese-Peruvian Center for Seismic Investigation and Disaster Mitigation.

Environmental and human-made perils compound the danger.

Situated in a coastal desert, Lima gets its water from a single river, the Rimac, which a landslide could easily block. That risk is compounded by a containment pond full of toxic heavy metals from an old mine that could rupture and contaminate the Rimac, said Agustin Gonzalez, a PREDES official advising Lima's government.

Most of Lima's food supply arrives via a two-lane highway that parallels the river, another potential chokepoint.

Lima's airport and seaport, the key entry points for international aid, are also vulnerable. Both are in Callao, which seismologists expect to be scoured by a 20-foot (6-meter) tsunami if a big quake is centered offshore, the most likely scenario.

Mayor Susana Villaran's administration is Lima's first to organize a quake-response and disaster-mitigation plan. A February 2011 law obliged Peru's municipalities to do so. Yet Lima's remains incipient.

"How are the injured going to be attended to? What is the ability of hospitals to respond? Of basic services? Water, energy, food reserves? I don't think this is being addressed with enough responsibility," said Tavera of the Geophysical Institute.

By necessity, most injured will be treated where they fall, but Peru's police have no comprehensive first-aid training. Only Lima's 4,000 firefighters, all volunteers, have such training, as does a 1,000-officer police emergency squadron.

But because the firefighters are volunteers, a quake's timing could influence rescue efforts.

"If you go to a fire station at 10 in the morning there's hardly anyone there," said Gonzalez, who advocates a full-time professional force.

In the next two months, Lima will spend nearly $2 million on the three fire companies that cover downtown Lima, its first direct investment in firefighters in 25 years, Prado said. The national government is spending $18 million citywide for 50 new fire trucks and ambulances.

But where would the ambulances go?

A 1997 study by the Pan American Health Organization found that three of Lima's principal public hospitals would likely collapse in a major quake, but nothing has been done to reinforce them.

And there are no free beds. One public hospital, Maria Auxiliadora, serves more than 1.2 million people in Lima's south but has just 400 beds, and they are always full.

Contingency plans call for setting up mobile hospitals in tents in city parks. But Gonzalez said only about 10,000 injured could be treated.

Water is also a worry. The fire threat to Lima is severe ? from refineries to densely-backed neighborhoods honeycombed with colonial-era wood and adobe. Lima's firefighters often can't get enough water pressure to douse a blaze.

"We should have places where we can store water not just to put out fires but also to distribute water to the population," said Sato, former head of the disaster mitigation department at Peru's National Engineering University.

The city's lone water-and-sewer utility can barely provide water to one-tenth of Lima in the best of times.

Another big concern: Lima has no emergency operations center and the radio networks of the police, firefighters and the Health Ministry, which runs city hospitals, use different frequencies, hindering effective communication.

Nearly half of the city's schools require a detailed evaluation to determine how to reinforce them against collapse, Sato said.

A recent media blitz, along with three nationwide quake-tsunami drills this year, helped raise consciousness. The city has spent more than $77 million for retention walls and concrete stairs to aid evacuation in hillside neighborhoods, Prado said, but much more is needed.

At the biggest risk, apart from tsunami-vulnerable Callao, are places like Nueva Rinconada.

A treeless moonscape in the southern hills, it is a haven for economic refugees who arrive daily from Peru's countryside and cobble together precarious homes on lots they scored into steep hillsides with pickaxes.

Engineers who have surveyed Nueva Rinconada call its upper reaches a death trap. Most residents understand this but say they have nowhere else to go.

Water arrives in tanker trucks at $1 per 200 liters (52 gallons) but is unsafe to drink unless boiled. There is no sanitation; people dig their own latrines. There are no streetlamps, and visibility is erased at night as Lima's bone-chilling fog settles into the hills.

Homes of wood, adobe and straw matting rest on piled-rock foundations that engineers say will crumble and rain down on people below in a major quake.

A recently built concrete retaining wall at the valley's head lies a block beneath the thin-walled wood home of Hilarion Lopez, a 55-year-old janitor and community leader. It might keep his house from sliding downhill, but boulders resting on uphill slopes could shake loose and crush him and his neighbors.

"We've made holes and poured concrete around some of the more unstable boulders," he says, squinting uphill in a strong late morning sun.

He's not so worried if a quake strikes during daylight.

"But if I get caught at night? How do I see a rock?"

___

Associated Press writer Franklin Briceno contributed to this report.

___

Frank Bajak on Twitter: http://twitter.com/fbajak

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/cae69a7523db45408eeb2b3a98c0c9c5/Article_2012-12-23-LT-Peru-Quake-Unreadiness/id-029230fd04954d07bc4783f023301e00

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Chinese medicine yields secrets: Atomic mechanism of two-headed molecule derived from Chang Shan, a traditional chinese herb

Dec. 23, 2012 ? The mysterious inner workings of Chang Shan -- a Chinese herbal medicine used for thousands of years to treat fevers associated with malaria -- have been uncovered thanks to a high-resolution structure solved at The Scripps Research Institute (TSRI).

Described in the journal Nature this week, the structure shows in atomic detail how a two-headed compound derived from the active ingredient in Chang Shan works. Scientists have known that this compound, called halofuginone (a derivative of the febrifugine), can suppress parts of the immune system -- but nobody knew exactly how.

The new structure shows that, like a wrench in the works, halofuginone jams the gears of a molecular machine that carries out "aminoacylation," a crucial biological process that allows organisms to synthesize the proteins they need to live. Chang Shan, also known as Dichroa febrifuga Lour, probably helps with malarial fevers because traces of a halofuginone-like chemical in the herb interfere with this same process in malaria parasites, killing them in an infected person's bloodstream.

"Our new results solved a mystery that has puzzled people about the mechanism of action of a medicine that has been used to treat fever from a malaria infection going back probably 2,000 years or more," said Paul Schimmel, PhD, the Ernest and Jean Hahn Professor and Chair of Molecular Biology and Chemistry and member of The Skaggs Institute for Chemical Biology at TSRI. Schimmel led the research with TSRI postdoctoral fellow Huihao Zhou, PhD.

Halofuginone has been in clinical trials for cancer, but the high-resolution picture of the molecule suggests it has a modularity that would make it useful as a template to create new drugs for numerous other diseases.

The Process of Aminoacylation and its Importance to Life

Aminoacylation is a crucial step in the synthesis of proteins, the end products of gene expression. When genes are expressed, their DNA sequence is first read and transcribed into RNA, a similar molecule. The RNA is then translated into proteins, which are chemically very different from DNA and RNA but are composed of chains of amino acid molecules strung together in the order called for in the DNA.

Necessary for this translation process are a set of molecules known as transfer RNAs (tRNAs), which shuttle amino acids to the growing protein chain where they are added like pearls on a string. But before the tRNAs can move the pearls in place, they must first grab hold of them.

Aminoacylation is the biological process whereby the amino acid's pearls are attached to these tRNA shuttles. A class of enzymes known as aminoacyl-tRNA synthetases is responsible for attaching the amino acids to the tRNAs, and Schimmel and his colleagues have been examining the molecular details of this process for years. Their work has given scientists insight into everything from early evolution to possible targets for future drug development.

Over time what has emerged as the picture of this process basically involves three molecular players: a tRNA, an amino acid and the aminoacyl-tRNA synthetase enzyme that brings them together. A fourth molecule called ATP is a microscopic form of fuel that gets consumed in the process.

The new work shows that halofuginone gets its potency by interfering with the tRNA synthetase enzyme that attaches the amino acid proline to the appropriate tRNA. It does this by blocking the active site of the enzyme where both the tRNA and the amino acid come together, with each half of the halofuginone blocking one side or the other.

Interestingly, said Schimmel, ATP is also needed for the halofuginone to bind. Nothing like that has ever been seen in biochemistry before.

"This is a remarkable example where a substrate of an enzyme (ATP) captures an inhibitor of the same enzyme, so that you have an enzyme-substrate-inhibitor complex," said Schimmel.

The article, "ATP-Directed Capture of Bioactive Herbal-Based Medicine on Human tRNA Synthetase," by Huihao Zhou, Litao Sun, Xiang-Lei Yang and Paul Schimmel was published in the journal Nature on Dec. 23, 2012.

This work was supported by the National Institutes of Health through grants #GM15539, #23562 and #88278 and by a fellowship from the National Foundation for Cancer Research.

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The above story is reprinted from materials provided by The Scripps Research Institute.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.


Journal Reference:

  1. Huihao Zhou, Litao Sun, Xiang-Lei Yang, Paul Schimmel. ATP-directed capture of bioactive herbal-based medicine on human tRNA synthetase. Nature, 2012; DOI: 10.1038/nature11774

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/top_health/~3/ppsz7cjJCTA/121223152433.htm

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