Loss of tumor suppressor SPOP releases cancer potential of SRC-3

Tuesday, April 2, 2013

Mutations in a protein called SPOP (speckle-type POZ protein) disarm it, allowing another protein called steroid receptor coactivator-3 (SRC-3) to encourage the proliferation and spread of prostate cancer cells, said researchers led by those at Baylor College of Medicine in a report that appears online in Proceedings of the National Academy of Sciences.

Normally SPOP acts as a tumor suppressor gene by marking SRC-3 for destruction, said Dr. Nicholas Mitsiades, assistant professor of medicine ? hematology/oncology and molecular and cellular biology, and corresponding author of the report. SRC-3 is an oncogene or cancer-promoting gene that fosters the growth of cancer cells and their spread or metastasis.

"The protein SPOP is normally there to decrease the levels of SRC-3," said Mitsiades, who is also a member of the Dan L. Duncan Cancer Center at BCM. About a year ago, several groups reported that mutations in SPOP were the most common single point mutation or change in a single nucleotide or base pair (A,T,C,G) that is part of the "alphabet" of DNA or the genetic material of prostate cancer tumors.

What Mitsiades and his group found was that mutated SPOP is no longer an effective suppressor of the cancerous effects of SRC-3. He and his colleagues found the mutation in both the primary or original prostate cancer and in the metastatic tumors that it spawned.

In laboratory studies they showed that when cells produce high levels of normal SPOP, SRC-3 is potently degraded and no longer available to encourage prostate cancer growth.

Mitsiades said that it remains to be examined whether the SPOP mutations affect the prognosis for patients with prostate cancer and their response to treatment.

"To make things more difficult, there is not just one SPOP mutation," he said. "There are many different mutations. Our study and some other data as yet unpublished shows that while all mutations act similarly as far as the mechanism of action, all are not equally potent in their effect. That means additional research needs to be done to examine whether different mutations carry a different prognoses," he said.

"An important question for us is how can you treat prostate cancer with an SPOP mutation," he said.

The mutation results in a loss of function because the mutated gene cannot carry out its task of reducing SRC-3 levels.

"Right now we are not good at replacing something with drugs," he said. "We are much better at inhibiting functions. If we could inhibit SRC-3, then we might overcome the cancer-promoting effects of the mutations in SPOP."

Dr. Bert O'Malley, chair of molecular and cellular biology at BCM and a co-author of the report, is working on inhibitors of SRC-3.

Those inhibitors are important because SRC-3 plays a role in many cancers, including breast cancers, said Mitsiades. It could prove an important target for treatment of many cancers ? along with breast and prostate tumors.

"Its regulation is quite complex," he said. "It can be degraded and SPOP is only one mechanism by which that occurs."

###

Baylor College of Medicine: http://www.bcm.edu/news/mediacenter

Thanks to Baylor College of Medicine for this article.

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Source: http://www.labspaces.net/127544/Loss_of_tumor_suppressor_SPOP_releases_cancer_potential_of_SRC__

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Conn. lawmakers unveil bipartisan gun control plan

Relatives and supporters of Sandy Hook Elementary School shooting victims stand during a presentation at the Capital in Hartford, Conn., Monday, April 1, 2013, where they asked lawmakers to include a ban on existing high-capacity magazines in a legislation addressing gun control spurred by the massacre. Standing from left are: Jennifer Hensel, Jackie and Mark Barden, Sandy Hook Promise member Tim Makris, William Sherlach, Nelba Marquez-Greene and Nicole Hockley. (AP Photo/New Haven Register, Mara Lavitt) 4/1/13

Relatives and supporters of Sandy Hook Elementary School shooting victims stand during a presentation at the Capital in Hartford, Conn., Monday, April 1, 2013, where they asked lawmakers to include a ban on existing high-capacity magazines in a legislation addressing gun control spurred by the massacre. Standing from left are: Jennifer Hensel, Jackie and Mark Barden, Sandy Hook Promise member Tim Makris, William Sherlach, Nelba Marquez-Greene and Nicole Hockley. (AP Photo/New Haven Register, Mara Lavitt) 4/1/13

William Sherlach, left, husband of slain Sandy Hook Elementary School psychologist Mary Sherlach speaks, at the Capital in Hartford, Conn., Monday, April 1, 2013, as families of the school shooting victims asked lawmakers to include a ban on existing high-capacity magazines in a legislation addressing gun control spurred by the massacre. Other paraents attending are, from left behind Sherlach: Jennifer Hensel, Jackie and Mark Barden, Nelba Marquez-Greene, and Nicole Hockley. (AP Photo/New Haven Register, Mara Lavitt) 4/1/13

Mark Barden, right, father of Sandy Hook Elementary School shooting victim Daniel Barden, speaks alongside his wife, Avielle, center, and other Newtown parents, at the Capital in Hartford, Conn., Monday, April 1, 2013. Families of the school shooting victims were there to ask lawmakers to include a ban on existing high-capacity magazines in a legislation addressing gun control spurred by the massacre. (AP Photo/New Haven Register, Mara Lavitt)

FILE - In this Jan. 30, 2013 file photo, David Wheeler, father of Sandy Hook School shooting victim Benjamin, listens to a legislative hearing of a task force on gun violence and children's safety at Newtown High School in Newtown, Conn. Connecticut lawmakers announced a deal Monday, April 1, 2013 on what they called some of the toughest gun laws in the country that were proposed after the December mass shooting in the state, including a ban on new high-capacity ammunition magazines like the ones used in the massacre that left 20 children and six educators dead. (AP Photo/Jessica Hill, File)

HARTFORD, Conn. (AP) ? With an announcement of sweeping proposals to curb gun violence, Connecticut lawmakers said they are hoping to send a message to Congress and other state legislators across the country: A bipartisan agreement on gun control is possible.

Legislative leaders on Monday revealed proposals spurred by the Dec. 14 Newtown school shooting following weeks of bipartisan, closed-door negotiations. A vote is expected Wednesday in the General Assembly, where Democrats control both chambers, making passage all but assured.

"Democrats and Republicans were able to come to an agreement on a strong, comprehensive bill," said Senate President Donald E. Williams Jr., a Democrat from Brooklyn, who called the proposed legislation the strongest, most comprehensive bill in the country. "That is a message that should resound in 49 other states and in Washington, D.C. And the message is: We can get it done here and they should get it done in their respective states and nationally in Congress."

The massacre reignited the gun debate in the country and led to calls for increased gun control legislation on the federal and state levels. While some other states, including neighboring New York, have strengthened their gun laws, momentum has stalled in Congress, whose members were urged by President Barack Obama last week not to forget the shooting and to capitalize on the best chance in years to stem gun violence.

The Connecticut deal includes a ban on new high-capacity ammunition magazines like the ones used in the massacre at Sandy Hook Elementary School that left 20 children and six educators dead. There are also new registration requirements for existing magazines that carry 10 or more bullets, something of a disappointment for some family members of Newtown victims who wanted an outright ban on the possession of all high-capacity magazines and traveled to the state Capitol on Monday to ask lawmakers for it.

The package also creates what lawmakers said is the nation's first statewide dangerous weapon offender registry, creates a new "ammunition eligibility certificate," imposes immediate universal background checks for all firearms sales, and extends the state's assault weapons ban to 100 new types of firearms and requires that a weapon have only one of several features in order to be banned.

The newly banned weapons could no longer be bought or sold in Connecticut, and those legally owned already would have to be registered with the state, just like the high-capacity magazines.

Senate Minority Leader John McKinney, a Fairfield Republican whose district includes Newtown, said Republicans and Democrats have understood they needed to "rise above politics" when they decided to come up with a legislative response to the massacre.

"At the end of the day, I think it's a package that the majority of the people of Connecticut I know will be proud of," he said.

The bill also addresses mental health and school security measures, including gun restrictions for people who've been committed to mental health facilities and restoration of a state grant for school safety improvements.

After clearing the state legislature, the bill would be sent to Gov. Dannel P. Malloy, who has helped lead efforts to strengthen the state's gun laws but has not yet signed off on the proposed legislation. Earlier Monday, Malloy voiced support for the Newtown families and their desire to ban the possession of large-capacity magazines.

Ron Pinciaro, executive director of Connecticut Against Gun Violence, said his group will live with the lawmakers' decision not to ban them as other states have done. He said the leaders made their decision based on what was politically feasible.

"We have to be satisfied. There are still other things that we want, we'll be back for in later sessions," he said. "But for now, it's a good thing."

Robert Crook, executive director of the Connecticut Coalition of Sportsmen, contended the bill would not have changed what happened at Sandy Hook Elementary School, where gunman Adam Lanza fired off 154 shots with a Bushmaster .223-caliber rifle within five minutes. He went through six 30-round magazines, though half were not completely empty, and police said he had three other 30-round magazines in addition to one in the rifle.

"They can register magazines and do all the rest of this stuff. It isn't going to do anything," he said.

Gun owners, who've packed public hearings at the state Capitol in recent months, voicing their opposition to various gun control measures, are concerned they've been showing up "for virtually nothing" after learning about the bill, Crook said.

Six relatives of Newtown victims visited the Capitol on Monday, asking lawmakers to ban existing high-capacity magazines. Some handed out cards with photographs of their slain children.

Allowing magazines that carry 10 or more bullets to remain in the hands of gun owners would leave a gaping loophole in the law, said Mark Barden, whose 7-year-old son, Daniel, was killed in the shooting.

"It doesn't prevent someone from going out of the state to purchase them and then bring them back. There's no way to track when they were purchased, so they can say, 'I had this before,'" Barden said. "So it's a big loophole."

Barden and other victims' family members who visited the statehouse on Monday did not immediately respond to messages seeking their reactions to the agreement.

Jake McGuigan, a spokesman for the National Shooting Sports Foundation, which is based in Newtown, said he wouldn't comment on the proposal until he saw it in the writing, but he questioned the mechanics of a registry for magazines.

"How will they register a magazine? It seems a little weird," he said.

___

Associated Press writers Stephen Kalin, Stephen Singer and Michael Melia contributed to this report.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/3d281c11a96b4ad082fe88aa0db04305/Article_2013-04-02-School%20Shooting-Legislature/id-d788bfdb11d64e55b13f72aacfdd0b5f

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Use a Full-Time Fantasy to Figure Out Your On-the-Side Freelance Rate

Knowing how much to charge somebody is easy for full-time jobs?it was figured out the day you were hired. What if you have a job, but you're also working freelance: on the side, on weekends, or for one-off projects? It can seem much trickier, but there's actually a simple way to figure out your rate.

I went from jobs in newspaper writing, where the pay is very stable (no matter how many hours you work!) to Lifehacker (as an independent contractor, but with a set rate) to freelancing full-time. Like most things in my career, the beginnings involved fumbling around, guessing, and sending apologetic late-night emails to editors.

Looking back now, however, I think there were was a much more simple means of figuring out my rate.

In August 2011, Melanie tackled this same question, but with a notably different approach. Melanie approached freelancing like setting up a business for yourself: figure out your operating costs, average billable hours, dividing those figures, factoring in profit and taxes, and keeping track of important details. Toward the end of her post, Melanie wrote:

You can try several other methods for setting your rate, such as marking up your current salary ... or just dividing how much you want to earn by how many hours you'll work, but I wouldn't recommend them because they're not realistic; they don't take into account your everyday expenses or account for long-term success.

It's hard to argue against setting up good estimates in a spreadsheet and using math to figure out your operating costs. That's the kind of thinking that gets you some kind looks and firm handshakes from bankers and business owners. But some people may not be jumping into freelancing full-time. For a side gig, a weekend project, a half-time schedule, or one-off job, setting up your long-term business plan can seem intimidating and overly complicated.

So do what I (eventually learned to) do: apply for your own fake job, with your real credentials, and negotiate with yourself to figure out what you should earn.

Step 1: Know Your Actual Expenses

Even if you aren't creating a home office and obtaining a DBA and reading books about marketing, you still need to know what your costs are going to be before you ask for money. Most importantly, you need to know what your tax rate is going to be for the self-employed income you earn. The rate changes every year, but Bankrate.com has a handy calculator.

The rough number I always hear freelancers and self-employed types use is 30 percent. That is, expect to give back 30 percent of what you earn in taxes and miscellaneous fees, so charge that extra 30 percent to clients. And plan to do that in quarterly estimated tax payments, or else face a small but painful penalty at the end of the year (and a not-so-nice tax surprise). It's not a bad number, but it doesn't apply to everyone, especially those who joint-file their taxes with spouses.

You can take expenses off of your freelance income, such as qualified business travel and meals, equipment you need to buy, and the like. But if this is a side gig, and you're mostly using your home and your personal computer to work, you will mostly just earn some side income and have some of it taxed. Once you know that, you're ready to interview yourself for your freelance job.

Step 2: Make a Fake Resume, Interview for Your Kinda-Job

Want to drive yourself crazy, alienate friends, and seem completely unprofessional? Start asking around to every freelancer you know about their rates, ask people "how much would you pay" for services, and try to figure out exactly how much you should charge, based on a very vague idea of how many hours the job will entail.

Want an easier way to figure out what you should charge for your freelance side/weekend/one-off work? Figure out what kind of worker you are. For your Actual Job, you created a resume, you applied, you pitched your skills in a letter and/or an interview, and you negotiated your salary, based in part on what skills you were bringing to the table, versus how much of your work would involve winging it and learning on the fly.

This is why interns are paid a certain small amount (if at all), and why professionals at the top of their field are haggling over things like jet access and ocean-front time shares. When you're negotiating your freelance rate, why not ask yourself what kind of job you'd be applying for if this was a full-time position, and what would that job pay? It's good advice I received when I asked designer Nicholas Barone about new work I was taking on.

More specifically:

• Figure out what kind of job you could get, at this firm, in this field, with the skills you've built up.
• Figure out what kind of salary would make sense for you to earn at that gig, if you were working full-time.
• Add roughly 30% onto that salary, given the taxes you'll be paying (or use the calculator.
• Ask for that amount, divided down to an hourly rate (yearly rate, divided by 52 weeks, divided by 37.5 or 40 hours or whatnot).

If you have more than one freelance gig, or you're freelancing in a field that's slightly outside your main field, you'll have to do a bit more pondering. I mostly write for web-based publications about technology, so when another site comes along, it's not too hard to extrapolate to an hourly or per-piece rate. But when someone asked me to do one-on-one computer setup and consulting, I had to figure that out. If I opened up my own shop as a fix-it computer consultant, how much would I want to earn, to live where I live and not eat off the 99-cent menu every night?

Step 3: Be Prepared to Negotiate the Little Stuff

If you think you've come to a realistic number for your hourly rate (or your per-piece/project rate, given a realistic time estimate for that piece/project), you're still not quite there. There could be bits and pieces of a freelance agreement that necessitate moving the number up or down. Retaining the rights to your own work, for example, or being required to take part in long meetings (hint: they are all long).

In general, though, doing work on the side can be a simple calculation: I'm doing this work, and I think I'd get paid X amount to do it full-time, so here's what you should pay me to make use of my limited extra-hours time to do it for you. It's an easier way to respect yourself and your monetary worth.

Original images by Pixabay, theimpulsivebay (Flickr), legenda (Shutterstock)

Source: http://feeds.gawker.com/~r/lifehacker/full/~3/Up4_GKssxNg/use-a-full+time-fantasy-to-figure-out-your-on+the+side-freelance-rate

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By keeping the beat, sea lion sheds new light on animals? movements to sound

Apr. 1, 2013 ? Move over dancing bears, Ronan the sea lion really does know how to boogie to the beat.

A California sea lion who bobs her head in time with music has given scientists the first empirical evidence of an animal that is not capable of vocal mimicry but can keep the beat, according to new research published by the American Psychological Association.

The study's authors suggest that their findings challenge current scientific theories that an animal's ability to synchronize its movements with sound are associated with the same brain mechanisms that allow for vocal mimicry in humans and some birds such as cockatoos, parrots, and budgerigars. The findings were published online April 1 in APA's Journal of Comparative Psychology.

"Understanding the cognitive capabilities of animals requires carefully controlled, well-designed experiments," said study co-author Colleen Reichmuth, PhD, with the Institute of Marine Sciences at the University of California at Santa Cruz. "This study is particularly rigorous because it examines, step-by-step, the learning conditions that supported the emergence of this complex behavior."

Ronan, a 3-year-old sea lion, demonstrated her ability to bob to the beat in six experiments led by doctoral candidate Peter Cook at the Long Marine Lab at UCSC.

"Dancing is universal among humans, and until recently, it was thought to be unique to humans as well," said Cook. "When some species of birds were found to have a similar capability for rhythmic movement, it was linked to their ability to mimic sound. Now we're seeing that even mammals with limited vocal ability can move in time with a beat over a broad range of sounds and tempos."

Ronan's first musical "dance" lesson was to the tune of a simplified section of John Fogerty's "Down on the Corner," the study said. Once Ronan was trained to bob her head to music, the researchers tested her with two pop songs, "Everybody" by the Backstreet Boys, and "Boogie Wonderland" by Earth, Wind and Fire. Without any prior exposure to the songs, Ronan was able to bob to the beat of both songs over the course of multiple trials, according to the study. She then showed that she could follow along to five different tempos of "Boogie Wonderland."

Ronan's bobbing skills markedly improved over the course of the trials and apparently endured, the study found. The researchers gave her a follow-up test a few weeks after the final session and she was successful in keeping the beat with each of the sounds previously used, maintaining a minimum of 60 consecutive bobs to each of the various beats.

At the beginning of the experiments, Ronan was first trained to move in time to a hand signal, which was replaced by a simple non-musical sound signal. When she successfully completed tests by bobbing her head to various rhythmic sounds, she was rewarded with a fish, the study said.

The researchers varied the types and speed of the sounds to verify that she was actually following the rhythm by bobbing her head. To rule out that she wasn't simply bobbing her head in response to the previous beat, they tested her using two computer-generated, metronome-like ticks -- one that did not miss a beat and the other that did. Ronan kept the beat going even when the metronome missed a beat, according to the study.

A video of Ronan can be watched at: http://www.youtube.com/watch?v=6yS6qU_w3JQ

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The above story is reprinted from materials provided by American Psychological Association (APA), via Newswise.

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

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Journal Reference:

1. Peter Cook, Andrew Rouse, Margaret Wilson, Colleen Reichmuth. A California Sea Lion (Zalophus californianus) Can Keep the Beat: Motor Entrainment to Rhythmic Auditory Stimuli in a Non Vocal Mimic.. Journal of Comparative Psychology, 2013; DOI: 10.1037/a0032345

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

Disclaimer: Views expressed in this article do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/strange_science/~3/h6tZBb2HCsQ/130401143149.htm

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Obama to propose $100M brain mapping project

WASHINGTON (AP) ? President Barack Obama is proposing a new research investment to map the human brain in hopes of eventually finding treatments for traumatic injuries and disorders like Alzheimer's disease and epilepsy.

The president planned to propose an initial $100 million investment next year during remarks Tuesday morning. The White House said in a statement that the goal of the project ? called the BRAIN Initiative for Brain Research through Advancing Innovative Neurotechnologies ? is "to revolutionize our understanding of the human mind" and create jobs.

Obama mentioned the idea in his State of the Union address, comparing the scientific and economic potential to the Human Genome Project that was launched as an international effort in 1990 to better understand the genetic impact on health and disease.

"Every dollar we invested to map the human genome returned $140 to our economy. Every dollar," Obama said in the address to Congress in February. "Today, our scientists are mapping the human brain to unlock the answers to Alzheimer's.

"Now is not the time to gut these job-creating investments in science and innovation," Obama said. "Now is the time to reach a level of research and development not seen since the height of the Space Race."

The BRAIN Initiative will require the development of new technology that can record the electrical activity of individual cells and complex neural circuits in the brain "at the speed of thought," the White House said.

Obama wants the $100 million to support research at the National Institutes of Health, the Defense Advanced Research Projects Agency and the National Science Foundation. He also wants private companies, universities and philanthropists to partner with the federal agencies in support of the research. And he wants a study of the ethical, legal and societal implications of the research.

The goals of the work are unclear at this point. A working group at NIH, co-chaired by Cornelia "Cori" Bargmann of The Rockefeller University and William Newsome of Stanford University, would work on defining the goals and developing a multi-year plan to achieve them that included cost estimates.

___

Follow Nedra Pickler on Twitter at https://twitter.com/nedrapickler

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/b2f0ca3a594644ee9e50a8ec4ce2d6de/Article_2013-04-02-US-Obama-Human-Brain/id-761ca977346f4da883382d932157fcf0

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Foster Parents Anywhere?: There is an Intruder at my House

There is someone extra living at my house. ?I am embarrassed to say that I did not notice this fact until several days after she moved in. ?When she arrived, she was hidden among a group of four other teenagers. ?Some of those left and she spent the night here. ?At my house, teenagers tend to come and go often. ?Most of them know that they are welcome to grab a bite to eat and hang out for awhile. ?As a result, I am never quite sure who is staying and who is just visiting. ?When this young lady showed up in my kitchen on Tuesday morning when no one else was home, I started asking questions. ?By this time, I was pretty sure that she had spent the night on Sunday and Monday.

It is now Friday (and she is still here) and I have gotten the full story. ?According to her, she is taking a break from her family. ?According to her mother, she has run away from home. ?According to the parents at the bus stop this morning, I should stop feeding teenagers and they may stop hanging out! ?So here I am wondering how I got dragged into this situation that I do not really want to be in. ?I have known this girl's family for many years and I count them as good friends. ?This puts me in a very sticky situation. ?I do not want to interfere with or judge my friend's parenting style. ?I do not want to enable this girl to hide from her issues. ?I absolutely to do not want another child to support and take care of. ?The five children of my own keep me busy enough.

I asked the parents at the bus stop this morning why teenagers in trouble always land at my house. ?One Mom pointed out that my own teenagers are the ones bringing them home. ?I thought that was very interesting and also true. ?My kids do this a lot. ?It is not unusual for one of them to ask if someone can spend the night or join us for dinner for concerning reasons. ?I am always surprised that my children are compassionate people. ?As I look back, I believe it is because they have learned so much from having foster children in our home. ?Foster children come with horrific stories from their pasts and I guess my children were listening and learning. ?I did not go into foster care planning on turning my biological kids into better people but it is a very nice side effect.

The other reason teenagers end up at my house is because of the food. ?I will sheepishly admit that I an extreme couponer and have been for years. ?As a result, my cupboards are very will stocked with teenager food. ?The only requirement I ask of someone sampling my stockpile is a guess on how much I paid for a particular item. ?I live for the moment that I can say, "it was free!!!!" ?The kids love this and it often turns into a mini episode of the Price is Right. ?Again I have experienced an unexpected side effect to my coupon habit. ?My children's friends like to be at my home because of the food. ?This allows me to get to know them and understand who my children choose as friends. ?As most parents will tell you, I would rather have my kids and their friends at my house than somewhere where I have to worry about them.

I am not sure what I am going to do about the fugitive living in my house yet beyond encouraging this young lady to talk about her situation. ?Sometimes a friend can offer advice that a child will listen to when they won't listen to a parent. ?That is all I have at the moment. ?In the meantime, she is doing a little housework and some laundry to earn her keep. ?I will keep you posted.

Source: http://fosterparentsanywhere.blogspot.com/2013/03/there-is-intruder-at-my-house.html

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Cyprus banks to re-open; limits on transactions

NICOSIA, Cyprus (AP) ? Bank employees and financial authorities in Cyprus are preparing banks to reopen after being shut for more than a week due to the country's acute financial crisis.

Strict restrictions have been set on financial transactions once the banks open for six hours at noon (1000 GMT). The maximum cash withdrawal limit has been set at 300 euros ($383) per day and no checks will be cashed. Travelers leaving the country can only take up to 1,000 euros, or the equivalent in foreign currency, with them in cash.

Banks have been closed since March 16 as politicians scrambled to come up with a plan to raise enough funds for Cyprus to qualify for 10 billion euros ($12.9 billion) in bailout loans for its stricken banking sector.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/f70471f764144b2fab526d39972d37b3/Article_2013-03-28-EU-Cyprus-Financial-Crisis/id-cf116eb374b5417e897f3fb7c958d8e8

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