Wednesday, September 12, 2012

Medical Reasons for Circumcision: Separating Fact from Myth ...

Sorry, Readability was unable to parse this page for content.

Source: http://www.empowher.com/parenting/content/medical-reasons-circumcision-separating-fact-myth

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'Tailhook' cleaned up, but top Marine sees more work to stop sex assaults

RENO, Nevada (Reuters) - Twenty-one years after it became synonymous with sexual assault and out-of-control fighter pilots, the annual Tailhook convention of U.S. Navy and Marine Corps aviators has been cleaned up.

Spouses and children are welcomed at the convention now, and organizers keep careful tabs on bad behavior. Beer and liquor still flow freely in hospitality suites after the day's panel discussions end, but the atmosphere is a far cry from the drunken, raucous parties that characterized the event in the late 1980s through 1991, according to naval aviators who have been attending for years.

While Tailhook has been fixed, the U.S. military is still grappling with a persistent sexual assault problem that has so far proven stubbornly immune to remedy.

New scandals have broken out, most notably at Lackland Air Force Base in Texas, where 39 people have alleged that they were raped or sexually harassed by trainers.

Pentagon figures show sexual assault cases in 2011 virtually unchanged from the previous year at 3,192, but many cases still go unreported. Defense Secretary Leon Panetta has estimated there could be 19,000 sexual assaults each year, a number he said was "unacceptable."

In an interview at Tailhook, Marine Corps Commandant General James Amos said it was up to military leaders to fix a climate in which women have been reluctant to report assaults.

"We are going after this thing with a vengeance. I'm serious about it. This is important to me. This is unit readiness, this is combat readiness, this is morale," Amos said.

In March, eight women, including an active-duty Marine and several Marine Corps veterans, filed a lawsuit saying that they were raped, assaulted or sexually harassed while in the service, and retaliated against when they complained.

The lawsuit focuses on one of the most prestigious military bases in the Marine Corps, the downtown Washington barracks that also houses the commandant's home.

BROAD PENTAGON INITIATIVE

The Marine effort that Amos is leading is part of a broader Pentagon initiative to boost prosecutions for sexual assaults, establish special victims' units at all the military services, and train new recruits within their first two weeks.

In 1991, scandal erupted when dozens of Marine Corps and Navy aviators were accused of sexually assaulting 83 women and 7 men at the Tailhook convention in Las Vegas.

The incident, investigated by the Pentagon's Inspector General, effectively ended the careers of dozens of Navy and Marine Corps officers and focused attention on many challenges facing women in the military.

Amos, then the commanding officer of a squadron in Beaufort, South Carolina, did not attend Tailhook in 1991, but said this year's event - it is now held in Reno, Nevada - is the polar opposite of those days, while still allowing participants to have fun.

Prostitutes and strippers were common at Tailhook in that earlier era. This year, one local woman hired to tend bar in one of the suites or "admins" was asked to leave after she appeared to be soliciting some of the guests, according to one mid-level military official who asked not to be named.

Amos faulted the military leaders in charge in 1991 for creating a climate that allowed the assaults to occur, and said he was trying to ensure a better working environment now.

In July, Amos brought about 70 of the Marine Corps' 85 generals to Washington to get them personally engaged in a new campaign against sexual assaults, which includes classes, interactive videos and frank discussions with military higher-ups about what behaviors constitute sexual assault.

"I looked every general officer in the eye ... and I said, 'You are solely responsible for the command climate,'" Amos said, calling it shameful that women were afraid to report cases of sexual assault to higher-ups for fear of reprisals.

"Why do they not come forward? because they don't have confidence in the leadership. They don't think we're going to do anything about it. Well, shame on us," he said.

ETHICS TRAINING

Amos is taking a similarly aggressive approach to ethics in general. He just completed his 27th speech to troops around the world about ethics after a series of incidents that provoked outrage in Afghanistan, including a video that showed Marines urinating on corpses.

"It's all about ethics and reminding Marines about what's acceptable behavior," the four-star general told Reuters, adding that a very small percentage of troops were "not aligned with what I call a moral compass to true north."

Amos said the number of reported sexual assaults will likely initially increase as victims become more confident that they will not face reprisals. But in the longer run, he said, he hoped to see the number of assaults decline.

Navy Captain Sara Joyner, commander of the air wing attached to the USS Truman aircraft carrier and a member of the Tailhook board, said the Navy is also undertaking extraordinary efforts to address sexual assaults, which are often linked to alcohol use.

She said officials realized that they needed to overcome their discomfort and tackle sexual assault head-on, rather than just assuming that sailors knew such acts were inappropriate.

"It's up to all of us to prevent something of this nature from happening. It's just not good for our units or cohesion ... It takes away from our focus on warfighting," said Joyner, who described her own early experiences a female fighter pilot as "extremely challenging."

Sergeant Mallory Vanderschans, who joined the Marines as a combat engineer at age 19 and now works as the commandant's photographer, said she has never encountered sexual harassment during her six years in the military.

She said she had barely heard of the Tailhook scandal of 1991 before accompanying Amos to the convention this weekend. "I was five when that all happened," she said.

(Editing by Warren Strobel and Mohammad Zargham)

Source: http://news.yahoo.com/tailhook-cleaned-top-marine-sees-more-stop-sex-185552505.html

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'Avengers' Mastermind Believes In 'Guardians Of The Galaxy' Director

'He has a very twisted take on it, but it all comes from a real love for the material,' Joss Whedon tells MTV News at TIFF about James Gunn.
By Josh Wigler, with reporting by Josh Horowitz


Joss Whedon
Photo: Michael Buckner/ Getty Images

Source: http://www.mtv.com/news/articles/1693491/joss-whedon-guardians-galaxy-tiff.jhtml

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CleverMunkey.com: UFO Desserts & Drinks @ Bandar Manjalara ...

UFO Desserts & Drinks has opened a branch at Bandar Manjalara and the owner invited us, the bloggers to head over there for a review in the evening. I've been to their very first branch in SS2 a few times and now the place is quite packed from time to time especially during weekends. So lets take a look at what they offering in this branch.


Entering UFO, the interior was just like the one in SS2 branch - clean and comfortable for a dessert and drinks cafe for the customers. They have quite a simple looking visual on the side of the wall for the UFO sets and their hot delights as well. Besides desserts, they also offer drinks and snacks as well. Below are some of the item that we have tried during the food tasting session.

Honey Peach Yoghurt Smoothie with Rainbow Jelly topping (RM 5.50) on the right and?Winter Melon Tea with Grass Jelly (RM 4) on the left. It is recommended to have less sugar for either one of the drinks unless you prefer to have really sweet taste in your drinks. I enjoy drinking the winter melon tea for it's really cooling especially on a hot Malaysia weather.

On the left is the Pearl Milk Tea (RM 4.50) and on the right is the?Aiyu Lemon Green Tea (RM 4.50). I ?really like the taste of the Aiyu Lemon Green Tea because it's really refreshing with the lemon taste and I'm quite sure a lot of ladies will like this drink as well.


If you prefer having shaved ice dessert, the QQ ball series is most?recommended?for you with any toppings that you like. 1 topping for RM4.50 while 3 toppings for RM6.00.


It was my very first time trying their UFO Lemon Aiyu with Aiyu Jelly and Yoghurt Popping Balls (RM 4.50). The aiyu jelly and yogurt popping balls are the selling point for this dessert!


Next up is the Grass Jelly Series with Sweet Potato, red beans and QQ balls topping (RM 6.00). The smoothness of the grass jelly is easily being enjoyed by anyone from young to old. Their red bean is pretty good and sweet too!


Soya Ice Series with grass jelly, pearls, Taro and QQ Balls toppings (RM 6.00)


Matcha Ice Series with Red Bean, Taro, Ocha Balls and Yoghurt Popping Balls (RM 6.00)


Besides the icy cold dessert, one of their hot desserts which is the Hot Grass Jelly with Mini QQ Balls (RM6.00) is also pretty good to have. It's very rare to find these mini QQ balls at other Taiwanese dessert shops.

Too bad they were not able to serve us other snacks other than the fries. Their fries are priced at RM5.00 each with a few flavors which is the Wasabi, Seaweed, BBQ, Cheese and Chilli.?

My favorite fries were the seaweed and cheese!

Besides the good desserts, drinks and snacks that we had, here's something that I would like to highlight to all my readers out there.

Have you heard about ChopChop?

It is a digital loyalty card app to take away the pain of managing and storing all these loyalty cards in your wallet.?Never again will you leave these cards at home, misplacing it or getting eaten by your pet dog. Ladies, you will love it- no more the need to keep a separate wallet just for all these cards. Gentlemen, no more pain in the butt from sitting on thick wallets.
(the only acceptable reason for thick wallet is having stash of cash in it)


For merchants, ChopChop makes it super easy to launch loyalty programmes through our platform. No more wasting time and money to design, print, and administer these physical cards. Having it digitalised, you can track your customer behaviour and interaction with your brand and business, and do targeted advertising hence maximising sales for every dollar spent.


Just type ChopChop on the appstore or google play to find the apps and download it. It's also available for Blackberry phones. After downloading it, open the apps and view 'How to use?'


Check out the participating merchant list and receive your chop from it. The example I had above was the chop from UFO Kepong. So now I don't need to carry all the loyalty card in my wallet and just save it into my smartphone. Pretty neat ey!

UFO Desserts & Drinks

No. 53, Jalan 3/62A,

Bandar Manjalara,

52200 Kuala Lumpur

Tel : 03-6262 6478


View Larger Map

Business Hours: Mon - Sun: 1:00 pm - 1:00 am


*All photos taken with Canon Powershot G9*

Source: http://www.clevermunkey.com/2012/09/ufo-desserts-drinks-bandar-manjalara.html

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Tuesday, September 11, 2012

maxmilbrandt7: The Perfect Affirmation, Self Help

The Perfect Affirmation Will Show You Step By Step How To Release Your Resistance So That You Move Into A State Which Naturally Moves You To Your Desires, And Allows The Universe To Basically Hand You What You Want. Video Inside Explains Everything!

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    Saturday Night Live - Daily Affirmations II Season: 16

    Saturday Night Live - Daily Affirmations II Season: 16

    Saturday Night Live Season: 16 Episode: 13 Stuart Smalley is not a lisenced therapist, but tries to help others achieve self-affirmation.
    Ranked 3.60 / 5 | 110 views | 0 comments

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    Tags: Saturday Night Live Stuart Smalley
    Categories: Comedy Entertainment

    Weight Loss Techniques - Affirmation Tapping - Emotional Eating

    Weight Loss Techniques - Affirmation Tapping - Emotional Eating

    http://www.darrenhiller.com/ Emotional eating is simply eating in response to an emotion that you are feeling. Tap along with me on a daily basis to begin to positively change your emotional eating habits.
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    Submitted By: HypnosisDallas
    Tags: Weight Loss Techniques Self Hypnosis Affirmation Tapping Emotional Eating
    Categories: How To

    Love Yourself for Goodness Sake: Focus

    Love Yourself for Goodness Sake: Focus

    Focus on the beauty and wonder of life and more of what you focus on shall manifest magnificently
    11 views | 0 comments

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    Submitted By: LAFilms
    Tags: * Animation Short Smiley Emoticon Manifesting Abundance Creating Affirmation Self Love
    Categories: Art & Animation

    Love Yourself for Goodness Sake Teaser: Believe

    Love Yourself for Goodness Sake Teaser: Believe

    http://www.lovingabundance.com/ launches a new campaign for wellness and success through self-awareness videos that encourage the practice of self-love by adding value to present blessings.
    Ranked 3.35 / 5 | 92 views | 0 comments

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    Submitted By: LAFilms
    Tags: "manifesting Abundance" "creating "abundance Affirmation" "self Love"
    Categories: Entertainment

    Self-Acceptance-Being Happy With Who You Are And Where Your At I

    Self-Acceptance-Being Happy With Who You Are And Where Your At I

    http://www.DavidSaundersBlog.comTrue freedom comes from self- acceptance of who we are and the current stage in life we are in. People go through different times in their life. I went through a short depressive state of and when I made it out, I decided to share with the world how I did it. You can share the love if this video was helpful. Leave me a comment about how you have recently accepted something in your life. I would love to know.
    22 views | 0 comments

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    Submitted By: DavidSaunders
    Tags: Self-Acceptance-Being Happy With Who You Are And Where Your At In Life: Affirmation: Caretakers: Facets Foibles :peace Of Mind: Positive Regard: Quot Self Acceptance: Esteem: Self-acceptance: Self-compassion Self-esteem Self-forgiveness Self-improvement
    Categories: How To

    Daily Affirmations #7

    Daily Affirmations #7

    Check out some of my latest Recipe Books and DVD's: http://www.lovingraw.com/shop This video was designed to replace your morning cup of coffee with some affirmations to get you started on your day. Be blessed! To date I have lost over 215 lbs with the raw food lifestyle! More videos to come so stay tuned and subscribe on my YouTube page and on my website lovingraw.com! Filmed : 11/14/07
    Ranked 3.01 / 5 | 344 views | 0 comments

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    Submitted By: Lovingraw
    Tags: Affirmation Love Self Help Lovingraw Philip McCluskey Rawfood Diet Weight Loss Life
    Categories: People & Stories

Source: http://microscope.radiantoptronics.com/self-help/26085-the-perfect-affirmation-self-help.html

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Source: http://maxmilbrandt7.blogspot.com/2012/09/the-perfect-affirmation-self-help.html

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High School Students Get Swag on Count Day

Once a year, Detroit Public Schools pulls out all the stops to get students in their seats.

In 2010, the district enticed students with a total of $20,000 in Target gift cards. The prize for attendance in 2009: a shot to win a laptop, iPod, or 42-inch flat screen TV.

This year, every Detroit public high school student who shows up to school on Oct. 3 will be rewarded with a free pair of Nikes, courtesy of a local shoe store.

The reason for all the swag: Count Day. The number of students in attendance for the entirety of count day in the fall determines 90 percent of per-pupil state funding for Michigan public school districts. The other 10 percent is determined by a second count day in the winter.

"Count information is critical to districts, because each student translates into state funding," according to the Michigan Department of Education.

Per-pupil funding varies by district in Michigan, with a minimum payout of close to $7,000 per student, and schools across the state woo students with pizza parties, raffles, and giveaways to ensure they max out their state funding.

Basing school funding on attendance numbers from only one or two days out of the school year provides funding stability for districts, but it can also "create perverse financial incentives ... to not retain students after the count date," according to a March 2012 report by the Center for Evaluation and Education Policy at Indiana University--Bloomington.

Count Days are not exclusive to Michigan. At least 10 states determine school funding using a single count day--including Colorado, Connecticut, Nevada, and Iowa. Several other states mimic Michigan's practice of multiple Count Days, but for many of those states, that only amounts to two days, the CEEP report states.

Using incentives to bump enrollment on Count Days is not exclusive to Michigan, either.

In 2011, the Maya Angelou Public Charter School in Washington, D.C., raffled off a shopping spree in an effort to reach its goal of 100 percent attendance on Count Day. And Northeast Academy Charter School in Denver turned to gift cards in 2010 to attract new students prior to Count Day, according to a local CBS station.

Northeast Academy's move was effective. The school enrolled at least 10 new students, thus increasing its state funding, the station reported.

"[It is]more efficient. It means more income, same expenses," Joseph Arlinghaus, director of advancement at the academy, told the TV station.

That mentality is just one of the concerns critics have about Count Day.

Measuring average daily attendance for the school year or taking student counts over an extended time period gives states a more accurate portrayal of the funding needed in each district, experts say.

That reasoning prompted New Jersey to move away from a system of using a single Count D ay this year, with Governor Chris Christie's office calling it a "common sense" move.

Have something of interest to share? Send your news to us at highschoolnotes@usnews.com.

Source: http://news.yahoo.com/high-school-students-swag-count-day-144200457.html

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fancy napkin: .a blur.

The past few days have been quite the blur. Busy at work cleaning up and finalizing jobs. Busy at home prepping for baby. Washing clothes. Cleaning house. Packing the diaper bag. Packing the hospital bags. Busy setting up the nursery. Busy with doctors appointments. Busy with last minute lunches and dinners with friends. Busy making freezer meals. Busy with attending prenatal classes. Basically, busy with life before a baby comes I guess [1 month to go!].?So yes, I feel a little pooped out.

And it's funny. The second I get home, I jump in the same comfy clothes that I have worn the past 4 days straight. I just don't feel like wearing anything else. At least I change my underwear. That's a bonus for the hubby [poor guy].

On the bright side, my hair is washed....And I haven't had to cook dinner for the past 2 nights [thanks steph + rob for friday! thanks hubby for the pizza break on sat].....And my family baby shower is today! Which I am super excited about :)

I guess I'll have to find myself a new outfit to wear....unless dirty sweats and a smelly t-shirt passes as acceptable??

Source: http://fancynapkin.blogspot.com/2012/09/a-blur.html

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Scripps Research scientists devise powerful new method for finding therapeutic antibodies

Scripps Research scientists devise powerful new method for finding therapeutic antibodies [ Back to EurekAlert! ] Public release date: 11-Sep-2012
[ | E-mail | Share Share ]

Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute

The technique hones and expands the power of large numbers

LA JOLLA, CA, September 11, 2012 Scientists at The Scripps Research Institute have found a new technique that should greatly speed the discovery of medically and scientifically useful antibodies, immune system proteins that detect and destroy invaders such as bacteria and viruses. New methods to discover antibodies are important because antibodies make up the fastest growing sector of human therapeutics; it is estimated that by 2014 the top-three selling drugs worldwide will be antibodies.

The new technique, described in an article this week published online ahead of print by the journal Proceedings of the National Academy of Sciences, enables researchers to search large libraries of antibodies and quickly select the ones with a desired biological effect. It also provides for the creation of unusual, asymmetric antibodies whose capabilities extend beyond those of natural antibodies. The Scripps Research scientists demonstrated the power of the technique by using it to find an asymmetric antibody that almost perfectly mimics the activity of erythropoietin (EPO), a medically valuable hormone.

"Traditionally we've looked at antibodies as tools for binding to specific targets, but we should view them more generally, as tools for probing and altering functions in cells," said Richard Lerner, the Lita Annenberg Hazen Professor of Immunochemistry and member of the Department of Molecular Biology at Scripps Research who led the new study.

At the Vanguard

Lab-grown antibodies already represent a major part of the ongoing biotechnology revolution. Used as scientific probes or medical therapies, they recreate the versatility of natural antibodies, which are produced by immune cells in a vast diversity to bind to highly specific shapes on viruses, bacteria, and other targets.

Two decades ago, Lerner and his laboratory at Scripps Research, in parallel with the group of Sir Gregory Winter at the Laboratory of Molecular Biology in Britain, developed the first techniques for generating very large libraries of combinatorial antibodies and quickly isolating those that can bind to a desired target. Since then, such techniques have been used to find antibodies to treat cancer, arthritis, transplant rejection, and other conditions. Humira, an anti-inflammatory antibody that was discovered this way, is expected to be the world's top-selling drug this year. Belimumab (Benlysta) was approved by the US Food and Drug Administration in 2011 to treat lupus, becoming the first new drug to treat the chronic, life-threatening inflammatory disease in more than 50 years.

Current antibody-discovery techniques have one big drawback, however. Although they can rapidly find antibodies that bind tightly to a known target, they can't rapidly determine which of those antibodies has useful biological activity. An antibody may bind tightly to a virus without affecting the virus's ability to infect cells, for example, or it may bind to a cellular receptor without activating that receptor. With current techniques, determining the overall biological effect of a target-binding antibody typically requires further, painstaking analysis.

A More Direct Path

In the new study, Lerner and his postdoctoral researcher Hongkai Zhang sought a method for rapidly finding antibodies that have a desired effect on cells, not just a desired ability to bind to a target. As a proof of principle, they aimed to discover an antibody that could mimic the activity of EPO, a hormone that stimulates red blood cell production. Drugs that mimic EPO's effect are commonly used to treat anemia and related conditions.

Zhang began by using traditional techniques to quickly sift through a large antibody library to find tens of thousands of antibodies that bind tightly to the EPO receptor. He then stepped beyond traditional techniques, by taking the genes that encoded these EPO-receptor-binding antibodies and inserting them into lentiviruses. Unlike the phage viruses used in traditional methods, lentiviruses can usefully infect mammalian cells, delivering their payloads antibodies, in this case into a more human-like cellular environment.

Zhang applied this new library of antibody-coding lentiviruses to a single, large culture of mammalian test cells. The cells were of a type that express EPO receptors and proliferate when these receptors are bound by EPO proteins or by antibodies that effectively mimic EPO. Each of these cells could host only a few viral particles at most, so in this way Zhang was able to distribute the entire library of EPO-receptor-binding antibodies broadly within the cell culture. Zhang also cultured the cells in a special way that prevented antibodies secreted by one cell from spreading easily to nearby cells and muddying any cause-effect relationship. "This concern over the diffusion of antibodies in the culture was one of the factors that had discouraged other researchers from using such a technique," said Zhang.

After the lentiviruses had delivered the antibodies to the cultured cells, Zhang was able to note which cells were proliferating the most signifying the presence of antibodies that mimic EPO. To identify the antibodies responsible, Zhang had only to harvest these faster-growing cells and sequence the antibody genes inside them.

This method quickly yielded an antibody that in a further test showed about 60 percent of the biological activity of natural EPO which was as good as any antibody EPO-mimic that had ever been described.

Opening the Door to the Unknown

But Zhang and Lerner also noted that many of the proliferating cells had been infected by multiple lentivirus particles, and contained sequences from more than one antibody. Puzzlingly, Zhang found that when he recreated antibodies from these sequences, and tested them individually or in combinations, they showed no significant EPO-mimicking effect. Further tests showed that the source of the EPO-mimicking effect in the test cells was an antibody that does not occur naturally.

An antibody of the type used in the study has a Y-shaped structure, normally with two identical binding arms. But the presence of multiple antibody genes within some of Zhang's test cells meant that, in a few cases, antibodies assembled themselves with two different binding arms. One of these "bispecific" antibodies turned out to bind to the EPO receptor which has two binding sites in a way that very accurately mimics the binding of a natural EPO molecule. "It turned out to be 100 percent as potent as authentic EPO in further tests," Zhang said.

The serendipitous finding represents another major innovation, for, in principle, it extends the medical and scientific antibody repertoire from the 100 billion or so known variants of same-armed antibodies to an astronomically higher number of bispecific variants. Experiments to test such variants will be limited by the maximum number of usable cells in cultures, but that number is still very high, on the order of 10 million. "That allows for a lot of unique binding events," said Lerner. "You probably can get almost anything that way."

Lerner emphasizes that this new antibody-engineering/discovery technique can be used not just against known targets such as the EPO receptor, but also against cellular functions involving targets that have not yet been found. "The real power of this technique is its ability to help us discover the unknown," he said.

###

Another author of the study, titled "Selection of antibodies that regulate phenotype from intracellular combinatorial antibody libraries," was Ian A. Wilson, the Hansen Professor of Structural Biology at Scripps Research and an expert on the structure of the EPO receptor. For more information on the paper, see http://www.pnas.org/content/early/2012/09/05/1214275109.abstract


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Scripps Research scientists devise powerful new method for finding therapeutic antibodies [ Back to EurekAlert! ] Public release date: 11-Sep-2012
[ | E-mail | Share Share ]

Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute

The technique hones and expands the power of large numbers

LA JOLLA, CA, September 11, 2012 Scientists at The Scripps Research Institute have found a new technique that should greatly speed the discovery of medically and scientifically useful antibodies, immune system proteins that detect and destroy invaders such as bacteria and viruses. New methods to discover antibodies are important because antibodies make up the fastest growing sector of human therapeutics; it is estimated that by 2014 the top-three selling drugs worldwide will be antibodies.

The new technique, described in an article this week published online ahead of print by the journal Proceedings of the National Academy of Sciences, enables researchers to search large libraries of antibodies and quickly select the ones with a desired biological effect. It also provides for the creation of unusual, asymmetric antibodies whose capabilities extend beyond those of natural antibodies. The Scripps Research scientists demonstrated the power of the technique by using it to find an asymmetric antibody that almost perfectly mimics the activity of erythropoietin (EPO), a medically valuable hormone.

"Traditionally we've looked at antibodies as tools for binding to specific targets, but we should view them more generally, as tools for probing and altering functions in cells," said Richard Lerner, the Lita Annenberg Hazen Professor of Immunochemistry and member of the Department of Molecular Biology at Scripps Research who led the new study.

At the Vanguard

Lab-grown antibodies already represent a major part of the ongoing biotechnology revolution. Used as scientific probes or medical therapies, they recreate the versatility of natural antibodies, which are produced by immune cells in a vast diversity to bind to highly specific shapes on viruses, bacteria, and other targets.

Two decades ago, Lerner and his laboratory at Scripps Research, in parallel with the group of Sir Gregory Winter at the Laboratory of Molecular Biology in Britain, developed the first techniques for generating very large libraries of combinatorial antibodies and quickly isolating those that can bind to a desired target. Since then, such techniques have been used to find antibodies to treat cancer, arthritis, transplant rejection, and other conditions. Humira, an anti-inflammatory antibody that was discovered this way, is expected to be the world's top-selling drug this year. Belimumab (Benlysta) was approved by the US Food and Drug Administration in 2011 to treat lupus, becoming the first new drug to treat the chronic, life-threatening inflammatory disease in more than 50 years.

Current antibody-discovery techniques have one big drawback, however. Although they can rapidly find antibodies that bind tightly to a known target, they can't rapidly determine which of those antibodies has useful biological activity. An antibody may bind tightly to a virus without affecting the virus's ability to infect cells, for example, or it may bind to a cellular receptor without activating that receptor. With current techniques, determining the overall biological effect of a target-binding antibody typically requires further, painstaking analysis.

A More Direct Path

In the new study, Lerner and his postdoctoral researcher Hongkai Zhang sought a method for rapidly finding antibodies that have a desired effect on cells, not just a desired ability to bind to a target. As a proof of principle, they aimed to discover an antibody that could mimic the activity of EPO, a hormone that stimulates red blood cell production. Drugs that mimic EPO's effect are commonly used to treat anemia and related conditions.

Zhang began by using traditional techniques to quickly sift through a large antibody library to find tens of thousands of antibodies that bind tightly to the EPO receptor. He then stepped beyond traditional techniques, by taking the genes that encoded these EPO-receptor-binding antibodies and inserting them into lentiviruses. Unlike the phage viruses used in traditional methods, lentiviruses can usefully infect mammalian cells, delivering their payloads antibodies, in this case into a more human-like cellular environment.

Zhang applied this new library of antibody-coding lentiviruses to a single, large culture of mammalian test cells. The cells were of a type that express EPO receptors and proliferate when these receptors are bound by EPO proteins or by antibodies that effectively mimic EPO. Each of these cells could host only a few viral particles at most, so in this way Zhang was able to distribute the entire library of EPO-receptor-binding antibodies broadly within the cell culture. Zhang also cultured the cells in a special way that prevented antibodies secreted by one cell from spreading easily to nearby cells and muddying any cause-effect relationship. "This concern over the diffusion of antibodies in the culture was one of the factors that had discouraged other researchers from using such a technique," said Zhang.

After the lentiviruses had delivered the antibodies to the cultured cells, Zhang was able to note which cells were proliferating the most signifying the presence of antibodies that mimic EPO. To identify the antibodies responsible, Zhang had only to harvest these faster-growing cells and sequence the antibody genes inside them.

This method quickly yielded an antibody that in a further test showed about 60 percent of the biological activity of natural EPO which was as good as any antibody EPO-mimic that had ever been described.

Opening the Door to the Unknown

But Zhang and Lerner also noted that many of the proliferating cells had been infected by multiple lentivirus particles, and contained sequences from more than one antibody. Puzzlingly, Zhang found that when he recreated antibodies from these sequences, and tested them individually or in combinations, they showed no significant EPO-mimicking effect. Further tests showed that the source of the EPO-mimicking effect in the test cells was an antibody that does not occur naturally.

An antibody of the type used in the study has a Y-shaped structure, normally with two identical binding arms. But the presence of multiple antibody genes within some of Zhang's test cells meant that, in a few cases, antibodies assembled themselves with two different binding arms. One of these "bispecific" antibodies turned out to bind to the EPO receptor which has two binding sites in a way that very accurately mimics the binding of a natural EPO molecule. "It turned out to be 100 percent as potent as authentic EPO in further tests," Zhang said.

The serendipitous finding represents another major innovation, for, in principle, it extends the medical and scientific antibody repertoire from the 100 billion or so known variants of same-armed antibodies to an astronomically higher number of bispecific variants. Experiments to test such variants will be limited by the maximum number of usable cells in cultures, but that number is still very high, on the order of 10 million. "That allows for a lot of unique binding events," said Lerner. "You probably can get almost anything that way."

Lerner emphasizes that this new antibody-engineering/discovery technique can be used not just against known targets such as the EPO receptor, but also against cellular functions involving targets that have not yet been found. "The real power of this technique is its ability to help us discover the unknown," he said.

###

Another author of the study, titled "Selection of antibodies that regulate phenotype from intracellular combinatorial antibody libraries," was Ian A. Wilson, the Hansen Professor of Structural Biology at Scripps Research and an expert on the structure of the EPO receptor. For more information on the paper, see http://www.pnas.org/content/early/2012/09/05/1214275109.abstract


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Case Study: Results From First Year Of Weight ... - Flirting With Fitness

Case Study: Results From First Year Of Weight Training
? 2012 Doug Champigny, http://flirtingwithfitness.com
All Rights Reserved Worldwide.

A year ago our son Devon Peacock started to train with TC & me, and while he?s also become a certified personal trainer in the meantime he has allowed me the honour of weight training him and setting our nutritional plan each week. Dev was 23 when we started the year, and as always we tracked everything ? weights, reps, exercises, cycles, etc. ? and did monthly photo sessions.

Each workout cycle was 3 ? 4 weeks in length, and rotated through a mix of powerlifting, weightlifting and bodybuilding routines since our goals at this point were overall health & fitness (a blend of additional lean bodymass and strength gains). Devon?s naturally lean so there were no weight-loss cycles included in his training.

Case Study: Devon Peacock's First Year Weight Training Results

Case Study: Devon Peacock?s First Year Weight Training Results

As you can tell from Devon?s before picture (taken Sept. 2011), he had already worked out from time to time and was in good shape at 23. But due to his lean frame he had always considered himself a hardgainer unable to put on much muscle mass in spite of his weight training.

His goal as we started to train together was simple ? he wanted to get stronger, balance out his physique and put on some visible muscle mass without bloating up from excess bodyfat. To his credit, Devon gave his weight training and nutrition 110% in spite of his previous lack of real gains, missing only 1 or 2 workouts throughout the year.

As is always the case some workouts were better than others, with some being terminated early if either of us simply didn?t have it in us that day, while others went well enough to add in a few extra sets or include some added-intensity techniques for a set or two. As his personal trainer I?m pleased to see that Devon has built bigger muscles in every area of his body while balancing out his overall physique. As his father, I?m both proud and amazed at how much effort he?s put in to ensure his success with his first serious year of weight training ? good on ya, Dev!

Building Bigger Muscles And Gaining Lean Bodyweight
The current photos of Devon (Sept. 2012, above right) show the lean bodyweight gains he?s made in just one year. Some of his stats include gaining 14 lbs of lean bodyweight, adding two inches to his chest, an inch to each arm and over 2? to each thigh.

Equally important, his arms, thighs and calves are now perfectly balanced, each stretching the tape the same amount left to right. Devon?s musculature is proportionate top-to-bottom over his 6? 2? (188cm) frame, and his results this first year leads us both to believe that over time Devon will be able to pack a lot more lean muscle onto his frame since it appears he may not, in fact, be a hardgainer ? or at least less of one than he first thought.

Strength Gains: Getting Stronger Fast
While Devon?s muscle building has been impressive this year, remember that our goal was a mix of building muscles and gaining raw strength for overall fitness. And once again Devon has triumphed, racking up some amazing strength gains and getting stronger fast ? faster than either of us had predicted.

In just this first year of serious weight training Dev has achieved a 300 lb. (137 kilo) deadlift and repeated it 3 or 4 times now to totally ?own? it. This is an increase of 100 lbs. (45 kilos) in the past year ? especially impressive given his new deadlift is approaching twice his bodyweight. His bent rows are up 80 lbs, bench press is up 80 pounds, military (seated overhead) press is up 100 lbs and his curls are up 30 lbs ? again, all in the last year.

Fitness Goals Met & Exceeded ? Strength & Muscle
Overall, most trainees in their first year of weight lifting would be happy with either of Devon?s new muscle mass or new strength ? but together they combine for fantastic results. Are his gains typical for first-year weightlifting trainees? Of course not ? Devon?s body is as unique as yours or mine ? no two bodies will react the same way to any specific training regime, which is why certified personal trainers create specific programs for each athlete and then modify the programs according to the results produced on an on-going basis.

Another factor is Devon?s age ? at 23/24, the male body is peaking in its ability to produce hormones like testosterone and growth hormone, and his metabolism hasn?t started to slow down yet ? in fact, his mix of ultra-heavy rep and higher, lighter rep schemes should keep that efficiency for years to come. While both my own lean muscle mass and strength have continued to build nicely during this year, neither matches Devon?s results and he has caught me on most exercises ? even surpassed my weights on a few of them. But at 57 I don?t expect to be able to build as fast nor recover as quickly as he does at 24. What?s important is that we?re both making progress continually.

What is typical is that with the right training and nutrition, trainees in their first year of weight training should always be able to increase their strength and build muscles ? how much they gain in either will vary. If you?re in your first year of weight training, don?t have access to a certified personal trainer and are not overly happy with your results to date, do an honest self-audit of your workouts, nutrition and rest patterns.

Are you skipping workouts often? Do you change up your exercises, rep ranges and between-set rest periods regularly? Are you eating enough ? especially enough protein while keeping your carb intake reasonable for your system? Are you taking enough recovery time between workouts based on the type of training during that cycle, but not leaving it too long between workouts? And, of course, are you regularly getting 7 ? 10 hours of sleep a night to allow your body time to repair & build?

During this last year Devon has referred to me as a ?hardass trainer? and a ?nutrition nazi? ? hopefully in a loving sense, of course? LOL But the truth is all the kudos have to go to the trainee in their first year of weight training ? they?re the ones putting in the time, effort and extreme mental focus required to get these kinds of results. Not only has Devon raised his strength and overall health & fitness to a whole new level, he?s enjoying new-found respect from friends and co-workers and new attention from the fairer sex. He?s become a role model for other ?skinny guys? who think they?re hardgainers ? even if they are. His results are an inspiration to anyone trying to overcome questionable genetic builds to achieve the body they desire.

For now, Devon and I are starting a new 12-week program I?ve designed for people entering 90-day challenges ? as always, we?ll test it out fully before releasing any information about it. And if you?re interested in knowing more about the workouts that got Devon these fantastic results, I?ll be going more in depth about his training and nutrition in the first issue of our Flirting With Fitness online magazine, available as a free download from this site later this month ? be sure to bookmark the site and return often for updates? And don?t forget to add your comments below ? we love hearing from our online fitness family!

Technorati Tags: first year of weight training, weight training case study, building bigger muscles, gaining lean bodyweight, getting stronger fast, strength gains, fitness goals, certified personal trainer, Devon Peacock, training, nutrition

Source: http://flirtingwithfitness.com/blogs/champigny/getting-back-in-shape/getting-stronger/case-study-results-from-first-year-of-weight-training/

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Demonic stories

Demonic stories

a story where you are a demon with the form of a human

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Considering quitting your job? Don't do this

By Allison Linn, TODAY

Joan Clear quit her job as marketing director for a consulting company in the early 1990s, but she still remembers the day vividly.

Clear, who is now 67, had spent a year and a half working for a man who she said was mean, insecure and a terrible communicator. The situation had grown so bad that one day she found herself in tears, a very uncommon occurrence for her.

That?s when she hatched her plan to quit.

Her opportunity came when her colleagues had gathered for a national marketing meeting. Clear said she told them they were going to start with a lesson in the power of language.

She then gave her hated boss an unabridged dictionary and told him to turn to the ?P? section.

Then, she recalls that she said, ?Now, I want you to look up the word pissant, and you?re going to find your name after the colon.?

It took him a second to understand what was going on, but when he did she said he turned bright red. That?s when she told him to do everyone a favor and have a heart attack.

?To this day I still remember just how much fun it was,? Clear said.

Of course, most experts will tell you that the correct way to leave a job is to first secure a new one and then offer two weeks? notice, along with the usual niceties about how you?ll miss everyone and you learned so much.

But sometimes, that just isn?t possible. Last week, we wrote about a finance executive who lost his job ? and, eventually, a multimillion-dollar bonus package ? after mooning company executives.

The story prompted readers to share their own stories of ruining equipment, calling bosses names and otherwise making a dramatic exit from their soon-to-be former workplace. Given the circumstances, we couldn?t independently verify every detail of our readers? stories.

Clear, who lives in St. Louis and now works as a supervisor in a school writing lab, said she feels like she?s actually been very lucky in terms of the jobs and bosses that she?s had for most of her career. And although she recognizes that you have to make some compromises for work, she said there does come a point when you have to put your foot down.

?I don?t think anybody can allow themselves to be treated disrespectfully,? she said.

Of course, you also want to have a plan for paying your bills. When Clear started making plans for her dramatic exit, she said she also started documenting the behavior she?d endured from the boss. She said she was able to convince human resources to give her severance despite the way that she quit, and she found a new job a couple of months later.

It is actually possible to recover your career ? although perhaps not your job ? even after something as dramatic as mooning your boss, said Jodi R.R. Smith, who runs the etiquette consultancy Mannersmith.

?The first thing is to take a moment, calm down, pull up your pants and get your wits about you,? Smith said.

If you?ve got adrenaline pulsing through your system, calming down can take as long as 20 minutes. Then, it?s time to apologize ? and that doesn?t mean making excuses for your behavior.

?An apology does not contain a ?but? - no pun intended,? Smith said.

Chances are, you are still going to lose your job. But Smith said you still want to make sure that you are doing everything you can not to burn any more bridges on the way out.

You also need to remember that your peers, if not your boss, may end up serving as a reference. There?s another opportunity to remind your peers that you did other great things before your big outburst.

You don?t want to peer (to say), ?She was awesome! She totally told off the boss, she threw a stapler at his head and then she mooned him,?? Smith noted.

When Matt Herriot decided to quit a job he despised, he also knew he wanted to let the whole company know how he felt.

So one Monday morning, Herriot walked into the company?s weekly all-staff meeting.

?I opened the door and I said, ?I?m not putting up with this anymore, I?m not doing this,?? Herriot recalled.

Then, with everyone staring at him, he put his laptop on his desk, explained the situation to another colleague who was standing there, and walked out.

That's a wrap: Famous quitting scenes

Herriot, who is now 53 and lives in the Atlanta area, had once loved the company he ended up leaving so dramatically. He also had become very close with his co-workers, even attending the chief executive?s wedding.

But after first one and then another private equity firm bought out what had been a family-owned firm, he said things became toxic.

His new bosses were demeaning and aggressive, he said, even going so far as to interview new candidates for jobs in front of the people they would be replacing.

?It was just a horrid environment,? he said.

He left in 2005. It took about six weeks for him to find a consulting gig, and he said his former CEO didn?t speak to him for two years.

But gradually, things began to thaw. And in 2009, he said his former chief executive actually hired him again, to work at a different company. He?s been there ever since.

In retrospect, Herriot said he probably should have found a new job before quitting.? But he doesn?t regret the dramatic way he walked out.

??No, I don?t have any regrets because I don?t think I would have the job I?d have today if I didn?t take that stand,? he said.

Have you ever told your boss to take this job and shove it?

?

Source: http://lifeinc.today.com/_news/2012/09/10/13733815-dont-try-this-at-work-dramatic-tales-of-leaving-jobs?lite

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JCI early table of contents for Sept. 10, 2012

JCI early table of contents for Sept. 10, 2012 [ Back to EurekAlert! ] Public release date: 10-Sep-2012
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Contact: Jillian Hurst
press_releases@the-jci.org
Journal of Clinical Investigation

Tracking malaria parasites in the liver

Plasmodium falciparum is the most deadly human malaria parasite, causing more than 800,000 deaths per year. After the parasite enters the blood stream, it travels to the liver where it serially invades liver cells (hepatocytes), until it settles down to form a parasitophorous vacuole (PV). Once ensconced in its PV, the parasite undergoes a process known as liver stage (LS) development during which it spawns tens of thousands of new parasites. In this issue of the Journal of Clinical Investigation, Stefan Kappe and colleagues at the Seattle Biomedical Research Institute report on a human liver-chimeric mouse that replicates P. falciparum LS development in humans. This is the first reliable model for the study of the P. falciparum LS stage and will be important for understanding human host/parasite interactions during the course of malaria infection.

TITLE:

Complete Plasmodium falciparum liver stage development in liver-chimeric mice

AUTHOR CONTACT:

Stefan Kappe

Seattle Biomedical Research Institute, Seattle, WA, USA

Phone: (206) 256-7205; E-mail: stefan.kappe@seattlebiomed.org

View this article at: http://www.jci.org/articles/view/62684?key=cc5ea46c50fc922c3f51

Researchers iron out the link between serum ferritin and diabetes

Iron overload increases the risk for insulin resistance and type 2 diabetes; however, the exact mechanisms that link the two are unknown. In this issue of the Journal of Clinical Investigation, Donald McClain and colleagues at the University of Utah report that serum ferritin levels could predict the presence or absence of metabolic syndrome in humans and were inversely associated with the expression of adiponectin, a blood glucose-regulating protein produced by fat cells (adipocytes). Treatment of adipocytes with iron decreased adiponectin levels, indicating that adipocytes play a central role in nutrient and iron detection. Further, reduction of serum ferritin levels in human patients increased insulin sensitivity and glucose tolerance. This study underscores the importance of adipocytes in metabolic diseases and points to iron reduction as a possible treatment for diabetes.

TITLE:

Adipocyte Iron Regulates Adiponectin and Insulin Sensitivity

AUTHOR CONTACT:

Don McClain

University of Utah, Salt Lake City, UT, USA

Phone: 801 585-0954; Fax: 801 585-0956; E-mail: donald.mcclain@hsc.utah.edu

View this article at: http://www.jci.org/articles/view/44421?key=5dbdc2ade3dc70280124

Influenza-infected lung cells send an SOS to the immune system

Influenza can cause viral pneumonia in humans, leading to lung failure. The virus damages the alveolar epithelial cells, which release molecular attractants to bring immune cells to the site of infection. Until recently, the identity of these immune attractants was unknown. In this issue of the Journal of Clinical Investigation, researchers led by Suzanne Herold at the University of Giessen report that alveolar cells produce granulocyte-colony stimulating factor (GM-CSF) to drive the accumulation of immune cells in a mouse model of influenza-associated pneumonia. GM-CSF protected mice against influenza infection, while loss of GM-SCF compromised their immune response and resulted in a more severe lung infection. These results suggest that GM-CSF is crucial for protection and recovery from influenza-mediated lung injury and has implications for treatment of influenza-associated pneumonia.

TITLE:

Alveolar epithelial cells orchestrate DC function in murine viral pneumonia

AUTHOR CONTACT:

Susanne Herold

UGLC, Giessen, UNK, DEU

Phone: 0049-641-985-42552; Fax: 0049-641-985-42568; E-mail: susanne.herold@innere.med.uni-giessen.de

View this article at: http://www.jci.org/articles/view/62139?key=725cc74433800775e7b8

Regulating long-term memory storage

Memories are initially stored in a fragile form. A process known as memory consolidation converts these short-term memories into stable long-term memories. Memory consolidation requires changes in gene expression, which are regulated by molecules known as nuclear receptors. In this issue of the Journal of Clinical Investigation, researchers led by Ted Abel at the University of Pennsylvania identified nuclear receptors that are important for memory formation in mice. In the hours after performing a memory-forming task, the mice had increased expression of the Nr4a nuclear receptor family. Blocking the activity of these receptors prevented long term memory formation without impacting short-term memory. Further, increased expression of Nr4a improved the effect of a memory-enhancing class of drugs known as histone-deacetylase inhibitors. This study demonstrates that the Nr4a receptor family contributes to memory formation and may serve as a therapeutic target for improving cognition.

TITLE:

NR4A nuclear receptors support memory enhancement by histone deacetylase inhibitors

AUTHOR CONTACT:

Ted Abel

University of Pennsylvania, Philadelphia, PA, USA

Phone: 215-746-1122; E-mail: abele@sas.upenn.edu

View this article at: http://www.jci.org/articles/view/64145?key=04aefa54c80df948c56b

Not so fast: PPAR?/? slows insulin secretion

Type 2 diabetes is characterized by high plasma glucose levels, insulin resistance, and inadequate insulin production. Insulin is secreted by pancreatic ? islets and the number of ? islets strongly influences the body's ability to process glucose. In this issue of the Journal of Clinical Investigation, Walter Wahli and colleagues at the University of Lausanne report that PPAR?/?, a protein that regulates gene expression, is a critical mediator of ? islet insulin secretion in mice. PPAR?/?-mutant mice had more ? islets and enhanced insulin secretion compared to normal mice. By examining the genes that were expressed in normal and mutant ? islets, Wahli and colleagues found that PPAR?/? represses genes that help ? islets secrete insulin. Further, islets lacking PPAR?/? released insulin more quickly than normal islets, suggesting that therapeutics targeting PPAR?/? in the pancreas may help stimulate insulin release in diabetic patients.

TITLE:

PPAR?/? affects pancreatic ?-cell mass and insulin secretion in mice

AUTHOR CONTACT:

Walter Wahli

Center for Integrative Genomics, National Research Center Frontiers in Gene, Lausanne, UNK, CHE

Phone: +41 21 692 41 10; Fax: +41 21 692 41 15; E-mail: walter.wahli@unil.ch

View this article at: http://www.jci.org/articles/view/42127?key=8d924abba94838e6f75c

MicroRNAs regulate insulin production

Obesity and pregnancy are associated with diminished insulin sensitivity, accompanied by an increase in the demand for insulin. To compensate the pancreas expands its population of insulin-producing ? islet cells. Researchers led by Romano Regazzi at the University of Lausanne have identified a microRNA that participates in ? islet expansion. In this issue of the Journal of Clinical Investigation, Regazzi and colleagues report that decreases in the microRNA miR-338-3p were correlated with increases in the number of ? islets during pregnancy in rats. Blocking miR-338-3p increased ? islet expansion, suggesting that regulation of this microRNA may be important in disease states associated with insulin resistance, such as gestational diabetes.

TITLE:

MicroRNAs contribute to compensatory beta-cell expansion during pregnancy and obesity

AUTHOR CONTACT:

Romano Regazzi

University of Lausanne, Lausanne, , CHE

Phone: 41216925280; Fax: 41216925255; E-mail: romano.regazzi@unil.ch

View this article at: http://www.jci.org/articles/view/64151?key=a785263ccfaf764e19bc

Complex genetic regulation underlies GATA2-linked human diseases

GATA2 is a master regulator of the formation and development of hematopoietic stem/progenitor cells (HSPCs), which form the various types of blood cells. Dysregulation of GATA2 has been linked to several different human disease states, including leukemia, and MonoMAC and Emberger syndromes. In this issue of the Journal of Clinical Investigation two research groups report on genetic regulatory elements that profoundly alter the expression and activity of GATA2. James Douglas Engel and colleagues at the University of Michigan disrupted GATA2 expression in the endothelial tissue of mice, which resulted in embryonic lethality that was attributed to the loss of liver HSPCs and defective lymphatic vasculature development. Researchers led by Emery Bresnick at the University of Wisconsin at Madison identified a new mutation in a GATA2 genetic regulatory element in a MonoMAC patient. Deletion of this regulatory element in mice caused embryonic lethality that was also linked to depletion of liver HSPCs and a loss of vascular integrity. Both of these studies underscore the role of GATA2 in vascular integrity and may help define the pathology of GATA2-associated human diseases.

TITLE:

Conditional GATA2 inactivation results in HSC loss and lymphatic mispatterning

AUTHOR CONTACT:

James Engel

The University of Michigan Medical Schoolool, Ann Arbor, MI, USA

Phone: 734-615-7509; Fax: 734-615-8500; E-mail: engel@umich.edu

View this article at: http://www.jci.org/articles/view/61619?key=d5e2c570893c08d9bdf8

ACCOMPANYING ARTICLE

TITLE:

Cis-element mutated in GATA2-dependent immunodeficiency governs hematopoiesis and vascular integrity

AUTHOR CONTACT:

Emery Bresnick

University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

Phone: 608-265-6446; E-mail: ehbresni@wisc.edu

View this article at: http://www.jci.org/articles/view/61623?key=b9cc4326e2fd3ad9ae8d

###



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?


AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.


JCI early table of contents for Sept. 10, 2012 [ Back to EurekAlert! ] Public release date: 10-Sep-2012
[ | E-mail | Share Share ]

Contact: Jillian Hurst
press_releases@the-jci.org
Journal of Clinical Investigation

Tracking malaria parasites in the liver

Plasmodium falciparum is the most deadly human malaria parasite, causing more than 800,000 deaths per year. After the parasite enters the blood stream, it travels to the liver where it serially invades liver cells (hepatocytes), until it settles down to form a parasitophorous vacuole (PV). Once ensconced in its PV, the parasite undergoes a process known as liver stage (LS) development during which it spawns tens of thousands of new parasites. In this issue of the Journal of Clinical Investigation, Stefan Kappe and colleagues at the Seattle Biomedical Research Institute report on a human liver-chimeric mouse that replicates P. falciparum LS development in humans. This is the first reliable model for the study of the P. falciparum LS stage and will be important for understanding human host/parasite interactions during the course of malaria infection.

TITLE:

Complete Plasmodium falciparum liver stage development in liver-chimeric mice

AUTHOR CONTACT:

Stefan Kappe

Seattle Biomedical Research Institute, Seattle, WA, USA

Phone: (206) 256-7205; E-mail: stefan.kappe@seattlebiomed.org

View this article at: http://www.jci.org/articles/view/62684?key=cc5ea46c50fc922c3f51

Researchers iron out the link between serum ferritin and diabetes

Iron overload increases the risk for insulin resistance and type 2 diabetes; however, the exact mechanisms that link the two are unknown. In this issue of the Journal of Clinical Investigation, Donald McClain and colleagues at the University of Utah report that serum ferritin levels could predict the presence or absence of metabolic syndrome in humans and were inversely associated with the expression of adiponectin, a blood glucose-regulating protein produced by fat cells (adipocytes). Treatment of adipocytes with iron decreased adiponectin levels, indicating that adipocytes play a central role in nutrient and iron detection. Further, reduction of serum ferritin levels in human patients increased insulin sensitivity and glucose tolerance. This study underscores the importance of adipocytes in metabolic diseases and points to iron reduction as a possible treatment for diabetes.

TITLE:

Adipocyte Iron Regulates Adiponectin and Insulin Sensitivity

AUTHOR CONTACT:

Don McClain

University of Utah, Salt Lake City, UT, USA

Phone: 801 585-0954; Fax: 801 585-0956; E-mail: donald.mcclain@hsc.utah.edu

View this article at: http://www.jci.org/articles/view/44421?key=5dbdc2ade3dc70280124

Influenza-infected lung cells send an SOS to the immune system

Influenza can cause viral pneumonia in humans, leading to lung failure. The virus damages the alveolar epithelial cells, which release molecular attractants to bring immune cells to the site of infection. Until recently, the identity of these immune attractants was unknown. In this issue of the Journal of Clinical Investigation, researchers led by Suzanne Herold at the University of Giessen report that alveolar cells produce granulocyte-colony stimulating factor (GM-CSF) to drive the accumulation of immune cells in a mouse model of influenza-associated pneumonia. GM-CSF protected mice against influenza infection, while loss of GM-SCF compromised their immune response and resulted in a more severe lung infection. These results suggest that GM-CSF is crucial for protection and recovery from influenza-mediated lung injury and has implications for treatment of influenza-associated pneumonia.

TITLE:

Alveolar epithelial cells orchestrate DC function in murine viral pneumonia

AUTHOR CONTACT:

Susanne Herold

UGLC, Giessen, UNK, DEU

Phone: 0049-641-985-42552; Fax: 0049-641-985-42568; E-mail: susanne.herold@innere.med.uni-giessen.de

View this article at: http://www.jci.org/articles/view/62139?key=725cc74433800775e7b8

Regulating long-term memory storage

Memories are initially stored in a fragile form. A process known as memory consolidation converts these short-term memories into stable long-term memories. Memory consolidation requires changes in gene expression, which are regulated by molecules known as nuclear receptors. In this issue of the Journal of Clinical Investigation, researchers led by Ted Abel at the University of Pennsylvania identified nuclear receptors that are important for memory formation in mice. In the hours after performing a memory-forming task, the mice had increased expression of the Nr4a nuclear receptor family. Blocking the activity of these receptors prevented long term memory formation without impacting short-term memory. Further, increased expression of Nr4a improved the effect of a memory-enhancing class of drugs known as histone-deacetylase inhibitors. This study demonstrates that the Nr4a receptor family contributes to memory formation and may serve as a therapeutic target for improving cognition.

TITLE:

NR4A nuclear receptors support memory enhancement by histone deacetylase inhibitors

AUTHOR CONTACT:

Ted Abel

University of Pennsylvania, Philadelphia, PA, USA

Phone: 215-746-1122; E-mail: abele@sas.upenn.edu

View this article at: http://www.jci.org/articles/view/64145?key=04aefa54c80df948c56b

Not so fast: PPAR?/? slows insulin secretion

Type 2 diabetes is characterized by high plasma glucose levels, insulin resistance, and inadequate insulin production. Insulin is secreted by pancreatic ? islets and the number of ? islets strongly influences the body's ability to process glucose. In this issue of the Journal of Clinical Investigation, Walter Wahli and colleagues at the University of Lausanne report that PPAR?/?, a protein that regulates gene expression, is a critical mediator of ? islet insulin secretion in mice. PPAR?/?-mutant mice had more ? islets and enhanced insulin secretion compared to normal mice. By examining the genes that were expressed in normal and mutant ? islets, Wahli and colleagues found that PPAR?/? represses genes that help ? islets secrete insulin. Further, islets lacking PPAR?/? released insulin more quickly than normal islets, suggesting that therapeutics targeting PPAR?/? in the pancreas may help stimulate insulin release in diabetic patients.

TITLE:

PPAR?/? affects pancreatic ?-cell mass and insulin secretion in mice

AUTHOR CONTACT:

Walter Wahli

Center for Integrative Genomics, National Research Center Frontiers in Gene, Lausanne, UNK, CHE

Phone: +41 21 692 41 10; Fax: +41 21 692 41 15; E-mail: walter.wahli@unil.ch

View this article at: http://www.jci.org/articles/view/42127?key=8d924abba94838e6f75c

MicroRNAs regulate insulin production

Obesity and pregnancy are associated with diminished insulin sensitivity, accompanied by an increase in the demand for insulin. To compensate the pancreas expands its population of insulin-producing ? islet cells. Researchers led by Romano Regazzi at the University of Lausanne have identified a microRNA that participates in ? islet expansion. In this issue of the Journal of Clinical Investigation, Regazzi and colleagues report that decreases in the microRNA miR-338-3p were correlated with increases in the number of ? islets during pregnancy in rats. Blocking miR-338-3p increased ? islet expansion, suggesting that regulation of this microRNA may be important in disease states associated with insulin resistance, such as gestational diabetes.

TITLE:

MicroRNAs contribute to compensatory beta-cell expansion during pregnancy and obesity

AUTHOR CONTACT:

Romano Regazzi

University of Lausanne, Lausanne, , CHE

Phone: 41216925280; Fax: 41216925255; E-mail: romano.regazzi@unil.ch

View this article at: http://www.jci.org/articles/view/64151?key=a785263ccfaf764e19bc

Complex genetic regulation underlies GATA2-linked human diseases

GATA2 is a master regulator of the formation and development of hematopoietic stem/progenitor cells (HSPCs), which form the various types of blood cells. Dysregulation of GATA2 has been linked to several different human disease states, including leukemia, and MonoMAC and Emberger syndromes. In this issue of the Journal of Clinical Investigation two research groups report on genetic regulatory elements that profoundly alter the expression and activity of GATA2. James Douglas Engel and colleagues at the University of Michigan disrupted GATA2 expression in the endothelial tissue of mice, which resulted in embryonic lethality that was attributed to the loss of liver HSPCs and defective lymphatic vasculature development. Researchers led by Emery Bresnick at the University of Wisconsin at Madison identified a new mutation in a GATA2 genetic regulatory element in a MonoMAC patient. Deletion of this regulatory element in mice caused embryonic lethality that was also linked to depletion of liver HSPCs and a loss of vascular integrity. Both of these studies underscore the role of GATA2 in vascular integrity and may help define the pathology of GATA2-associated human diseases.

TITLE:

Conditional GATA2 inactivation results in HSC loss and lymphatic mispatterning

AUTHOR CONTACT:

James Engel

The University of Michigan Medical Schoolool, Ann Arbor, MI, USA

Phone: 734-615-7509; Fax: 734-615-8500; E-mail: engel@umich.edu

View this article at: http://www.jci.org/articles/view/61619?key=d5e2c570893c08d9bdf8

ACCOMPANYING ARTICLE

TITLE:

Cis-element mutated in GATA2-dependent immunodeficiency governs hematopoiesis and vascular integrity

AUTHOR CONTACT:

Emery Bresnick

University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

Phone: 608-265-6446; E-mail: ehbresni@wisc.edu

View this article at: http://www.jci.org/articles/view/61623?key=b9cc4326e2fd3ad9ae8d

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Source: http://www.eurekalert.org/pub_releases/2012-09/joci-jet090512.php

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