Dream Warrior

sasharoizhere:

it’s the “dayum i look good” face

(via lastgrimmstanding)

ucsdhealthsciences:

Powdered casein protein.

Mystery solved: The casein of the missing kinase

In 1883, a Swedish chemist named Olof Hammarsten discovered that milk proteins called caseins contain not just the known building blocks of proteins, but also the chemical phosphate. It was the first hint that phosphates – which are now considered critical regulators of protein function -are tacked onto proteins.

Today, scientists know that enzymes called kinases can control protein function by attaching phosphates to proteins produced inside cells. Hundreds of kinases have been discovered and characterized, but the kinase that phosphorylates casein remained unknown -until now.

Howard Hughes Medical Institute (HHMI) scientists, led by Jack E. Dixon, PhD, professor of pharmacology, cellular and molecular medicine, chemistry and biochemistry at UC San Diego, have identified and isolated the elusive enzyme. In a study published online May 10, 2012, in Science Express, they report that they have uncovered the enzyme that transfers phosphate not only to milk proteins like casein, but also to proteins found in bones and teeth enamel.
           
“We solved this scientific puzzle that dates back to the 19th century,” said Dixon, who is HHMI vice president and chief scientific officer. “We also ended up stumbling onto this connection between this kinase and biomineralization.”
           
Dixon studies kinases, the enzymes that add phosphates to proteins, and phophatases, which remove phosphates. While most kinases are located within the cell, in the 1980s researchers started reporting that they’d detected kinase activity, such as phosphorylated proteins, outside of cells. In 2008, Kenneth Irvine, an HHMI investigator at Rutgers, was studying a protein called four-jointed, which is important in the development of fruit flies. Irvine demonstrated that four-jointed had kinase activity, even though the protein was unlike any other traditional kinase. Moreover, the protein localized to the Golgi apparatus, a compartment within the cell where proteins are sorted and packaged.     

“It was not clear to us that any of the approximately 580 traditional kinases had signal sequences which would allow them to end up in the same cellular compartment as casein, which was known to be secreted,” says Dixon.  So, Dixon, in collaboration with Nick Grishin, an HHMI investigator at the University of Texas Southwestern Medical Center, searched databases of protein sequences to find human proteins that resembled four-jointed. They identified a family of proteins - so little studied that its only name was Fam20 (for family 20) - with sequence similarity to four-jointed, and found that  the Fam20 A, B, and C proteins had amino acid sequences that would direct them to same part of the Golgi apparatus as the casein protein. Fam20C phosphorylated casein and many peptides on a specific amino acid sequence motif. 
          
But discovering that Fam20C is the kinase that acts on casein wasn’t the end of the story. As Dixon’s group looked through the scientific literature, they found that mutations in Fam20C had previously been found in patients with Raine syndrome, a rare and fatal disease in which developing bones become too dense. To understand this link between Fam20C and Raine syndrome, Dixon developed cell lines that produce Fam20C containing mutations that affect the same amino acids that had been implicated in the disease. 

“It turns out that every single one of these mutations inactivated the kinase and prevented it from being secreted,” says Dixon. And the targeted amino acid sequence that the researchers had nailed down earlier wasn’t just found in casein—it was found in dental matrix protein, osteopontin, and bone sialophosphoprotein, among others. All these proteins are involved in enamel and bone formation.
           
“In the end, what we’ve discovered isn’t just the casein kinase,” Dixon says. “It’s a whole new branch on the kinase tree, a branch that seems to play very important roles in bone and teeth formation.”
           
Phosphates are often used by proteins to bind calcium, a key ingredient of bones, teeth, and milk. So Dixon thinks the phosphorylation by Fam20C generates a calcium-binding site that is critical in the formation of bone and teeth.  When the kinase is mutated, the bones or teeth don’t develop correctly.
           
Next on the scientists’ to-do list is uncovering the functions of the other Fam20 proteins—Fam20A and Fam20B, as well as working out the exact mechanism by which Fam20C works.
           
“This is the end of one scientific mystery,” says Dixon, “but it also opens up a whole new area of kinase biology for us to explore.”
           
This report courtesy of HHMI.

adventuretime:

Who Wants To Play Video Games?

Here’s your first look at D3P and Cartoon Network Enterprise’s premiere Adventure Time video game, available this fall. And here’s what may or may not be your first look at the network’s press release:

OH MY GLOB! THIS IS LEGENDARY! D3Publisher AND CARTOON NETWORK ENTERPRISES ANNOUNCE NEW PARTNERSHIP and VIDEO GAME for ADVENTURE TIME

Play as Finn and Jake, in the Magical Land of Ooo, in the First Ever Interactive Title Based on the Hit Comedy Series, Adventure Time™: Hey Ice King! Why’d You Steal Our Garbage?!

LOS ANGELES – May 8, 2012 – Ready for a mathematical, algebraic, radical time? D3Publisher (D3P), a publisher and developer of interactive entertainment software, and Cartoon Network Enterprises (CNE) today officially announced the upcoming release of Adventure Time: Hey Ice King! Why’d you steal our garbage?!, a video game based on the popular Cartoon Network series, Adventure Time. This is the first Adventure Time video game that will release on the Nintendo 3DS™ hand-held system and Nintendo DS™ hand-held system late fall.

In the first licensed Adventure Time video game, Finn and Jake wake up one morning to find their trash stolen by the Ice King. Jake couldn’t care less about half-eaten bananas, crumpled up burrito wrappers, and old chicken diapers – but when they find out the Ice King is using their stolen goods to construct a Garbage Princess, the heroes embark on a fantastical adventure to teach him a lesson! Journey through the Land of Ooo in an offbeat adventure and discover perilous dungeons and unimaginable treasures, while playing as Finn and Jake in a unique action-adventure experience.

Working alongside the game’s developer WayForward is the series’ creator Pendleton Ward, who is designing a new storyline and quests for the game.

“Adventure Time fans have been asking for a video game to complement the series for some time, and we are working directly with Pendelton Ward, who has an amazing vision for the game,” said Peter Andrew, vice president of product development, D3P. “Adventure Time: Hey Ice King! Why’d you steal our garbage?! will be a fan’s golden ticket into the elusive Adventure Time universe and will capture the random fun and adventure we all love about the series.”

Adventure Time is the pop culture sensation, Emmy-nominated, top-rated show among kids, and its popularity continues to soar both on air and at retail. The series follows Finn, an adventure-seeking kid and Jake, his shape-shifting canine best friend, on their adventures in the Land of Ooo. The awesome duo save princesses, battle the notorious princess-kidnapper, the Ice King, party in Lumpy Space, fight in dungeons, and even befriend Marceline the Vampire Queen. Since the start of its fourth season, Adventure Time is the #1 program on Mondays on all television with kids 6-11.

“The rich and diverse characters in the Adventure Time world are absolutely perfect for a video game franchise and working with D3Publisher, WayForward and Pendelton Ward, we have a great team in place to bring it to life,” said Pete Yoder, vice president of consumer products, Cartoon Network Enterprises. “This game will provide the Land of Ooo experience that young fans will love.”

Adventure Time: Hey Ice King! Why’d you steal our garbage?!, is currently rated “RP” (Rating Pending) by the ESRB. Additional details about the game will be available in the coming months.

For more information in the coming months on Adventure Time: Hey Ice King! Why’d you steal our garbage?!, please visit www.d3publisher.us.

ucsdhealthsciences:

In pill health
           
Half of all American adults take one or more dietary supplements, mostly multivitamins. Selling these supplements is a $30 billion-a-year industry in the United States, comparable to the National Institutes of Health’s entire budget for all medical research.
           
Yet, with very few exceptions, nutritional deficiencies in the United States are rare. Americans might not necessarily eat right, but they are not nutritionally deprived.
           
So why do most people take them? Their answer: “They’re healthy. They can’t hurt.”
           
Most people are wrong.

In a recent commentary in the Journal of the National Cancer Institute, Maria Elena Martinez, PhD, a professor in the department of Family and Preventive Medicine at the UC San Diego School of Medicine and Co-leader of the Reducing Cancer Disparities program at the Moores UCSD Cancer Center, and colleagues discuss the benefits and risks of dietary supplements, particularly when taken to “prevent cancer.”
           
Their conclusion, after reviewing existing scientific literature on the subject: There is little empirical evidence to support the widely held and widely advertised notion that popular supplements like beta-carotene, folic acid, vitamin D and calcium reduce cancer risk.

Indeed, the opposite may be true.
           
That’s not what people want to hear, of course. Axioms like “an apple-a-day” and “we are what we eat” have a sort of enduring resonance. They may be true, write Martinez and colleagues in their JNCI paper, but the nutritional supplement industry exploits it to excess, suggesting in often misleading fashion that if a little bit of a nutrient is good, then a lot must be better.
           
This is not just another case of economic exploitation in the marketplace. While there is little compelling evidence that nutritional supplements significantly prevent cancer, there is growing proof that too much might cause it.
           
For example, some studies have found that exogenous or added antioxidants like beta-carotene might, in fact, promote oxidative stress linked to carcinogenesis. Other trials have found that long-term folic acid supplementation boosts the risk of colorectal tumor growths. Several observational studies support an association between higher calcium consumption and reduced breast cancer risk, but higher calcium intake also appears to increase the chances of contracting prostate cancer.
           
The situation is, in a word, confounding. The observational studies that nutritional supplement-makers most often cite as evidentiary proof (along with testimonials utterly bereft empirical value) are inherently limited. They lack the standardized treatment regimens and controls required to scientifically prove or disprove efficacy and safety. They have value in terms of involving large numbers of test participants – the proverbial big picture – but the devil is usually in the details: Cancer risk is different in different tissues. Personal characteristics, from genetics to behaviors, are massively influential. What is the effect, for example, of taking many supplements at once? How do they interact with each other? How well do they work if the person is a smoker, drinker, obese or all three?
           
These are factors that must be – and are – addressed in the gold standard of scientific experimentation: the randomized controlled trial (RCT), which is rigorously designed to produce precise data without bias. Unfortunately, RCTs of nutritional supplements are relatively few in number, and their conclusions thus far have been mixed.

Cancer does not give up its secrets easily. RCTs are expensive. It often takes decades for cancer to manifest itself, much longer than most RCTs attempting to reveal the cancer prevention benefits or cancer-causing dangers in nutritional supplementation.
           
Nonetheless, Martinez and colleagues argue in their commentary that more, longer and better-designed RCTs are needed, indeed essential to determining the benefits and risks of supplements.

In the meantime, they call for improved oversight of the manufacture and marketing of dietary supplements, which has a short and sketchy history of regulation. The U.S. Food and Drug Administration only began attempting to regulate these substances in the 1960s. Its efforts have been significantly and repeatedly constrained by a well-funded supplement industry and its political advocates.
           
Today, dietary supplements exist in a sort of legal limbo somewhere between foods and drugs. Manufacturers cannot make bold, direct assertions of cancer prevention benefits. The high-profile deaths from the supplement ephedra helped end that, but they can – and do – advertise the cancer prevention powers of supplements by implication.

Take Pill X, which research has been found to reduce the growth of prostate cells in culture. Makers of Pill X advertise that it “supports prostate health.” They cite stories of real people who took Pill X and didn’t get prostate cancer. For the casual consumer, it’s easy to conclude that Pill X has anticancer properties, despite the lack of any real science to support that conclusion.
           
Of course, maybe Pill X does reduce cancer risk – and maybe it increases it. No one knows. The scientific data are lacking. Think about that next time you take a nutritional supplement you probably don’t need.