শুক্রবার, ৩০ নভেম্বর, ২০১২

Senior House Republican sees income tax hikes in fiscal deal

WASHINGTON (Reuters) - A small but growing number of Republicans in the U.S. House of Representatives believe tax hikes on the rich like those favored by President Barack Obama will be part of a final deal to resolve the so-called fiscal cliff.

"I wouldn't have a problem with letting those tax rates go up," provided they are coupled with spending cuts, Representative Mike Simpson of Idaho told Reuters Thursday.

A similar sentiment expressed by about a half-dozen House Republicans in recent days likely will increase pressure on their party's congressional leadership to reach a bipartisan agreement with Obama and his fellow Democrats.

For weeks, the fight over whether to raise taxes on the wealthy - those families with net incomes above $250,000 - has dominated the debate on averting the fiscal cliff, which is a combination of steeper tax hikes and spending cuts due to begin in January unless Congress and Obama find an alternative plan.

Simpson, a seven-term veteran, said that raising taxes on the rich "wouldn't be my preferred way to do it. But elections have consequences," referring to Obama's re-election earlier this month.

Another senior Republican lawmaker, who asked not to be identified, told Reuters that a Democratic bill, which passed the Senate in July and would raise income taxes on families with net incomes above $250,000, could pass his chamber if it got to the floor.

The lawmaker said he was confident, however, that House Speaker John Boehner, a Republican, would not allow this bill to be brought to the House floor for a vote, explaining: "It may be popular" but "it's class warfare."

Republican Representative Steve King said he and fellow conservatives could live with raising taxes. "Conservatives might be able to figure how they can go home and rationalize a vote that included a revenue increase and or a tax rate increase," King said.

The lawmakers' remarks came a day after initial cracks in what had been Republican unity against any income tax increases.

On Wednesday, Representative Tom Cole said it was time to extend tax cuts for everyone making up to $250,000 to "secure" those rates for most Americans.

Another conservative House Republican, Representative Tim Scott, a first-term congressman, said that such a measure "could pass the House," according to Scott's spokesman. The aide added that Scott does not support legislation raising taxes on the rich, however.

(Additional reporting by Kim Dixon; Editing by Fred Barbash and Cynthia Osterman)

Source: http://news.yahoo.com/senior-house-republican-sees-income-tax-hikes-fiscal-211058664--business.html

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Steven Spielberg, Dustin Hoffman And Other Stars' Coastal Homes Threatened By Erosion - Hollywood Reporter

www.hollywoodreporter.com:

Modern Family co-creator Steven Levitan moved his own family to Broad Beach a decade ago, lured by its pristine water, killer views and -- perhaps most of all -- by its wide swaths of sand, perfect for jogging and touch football. But these days, Malibu's most secluded stretch of oceanfront real estate isn't exactly living up to its name.

Read the whole story at www.hollywoodreporter.com

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Source: http://www.huffingtonpost.com/2012/11/29/steven-spielberg-dustin-h_n_2214718.html

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বৃহস্পতিবার, ২৯ নভেম্বর, ২০১২

UT football player arrested for underage drinking

A sophomore on the UT football team was arrested for underage drinking early Sunday morning.

A Knoxville police officer was working an extra job at Wiskey Dix's, on Cumberland Avenue, when the manager of the club escorted the player outside.

Police said Clyde Brendan Downs was arrested around 1 a.m. for underage consumption and public intoxication.

Downs goes by the first name of Brendan, according to his profile on? the university's football website. He is a tight end from Bristol, Tennessee.

Source: http://downtown.wbir.com/news/crime/46068-ut-football-player-arrested-underage-drinking

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Proud of a spacious family home in an idyllic setting... | This is ...

I DEFY anyone to not be utterly charmed by this stunning property that has everything a family could possibly want. It is spacious, in spotless condition, the interior flows well and is ideal for parties, it's close to schools and major roads yet peaceful enough to have a lot of wildlife in the garden.

The basic details of Copper Beeches, at The Hollow, Caverswall, are impressive enough. A large house sitting in an established mature garden, it has three reception rooms, three double bedrooms, an en suite, a large conservatory, and a double bedroom with en suite downstairs obviously suitable as an annexe.

  1. Jean, pictured with husband Alan Stonier, lives in a big house on a plot she remembers as a field when she was a child.

But that alone does not give you the flavour of what it is like inside and, more than most properties I have visited, this one will reward a viewing.

It is home to Alan and Jean who says: "I grew up around here and I love the Caverswall area and this home is very special. It is a very warm and friendly house and it feels very peaceful.''

I was struck by the light and airy feel inside because there is a substantial amount of glazing filling the house with daylight. It certainly adds to the welcoming feel I had when the couple invited me in.

A nice reception hall leads to the living room which has three big windows giving a nice view over the gardens and it has a period style fireplace with wooden surround, cast iron grate with decorative tile inset and open fire.

The dining room next to the kitchen has French doors opening to a great conservatory which can also be accessed from a lovely snug which has a modern, remotely controlled gas fire that is a feature in itself and I soon had the sense that with these rooms flowing from one to the other that they would lend themselves to creating a great party house, something Alan confirms: "This is a very hospitable home and we do have a lot of people staying and have great parties. We have a big, permanent barbecue on the terrace and once we cooked for 70 and the house works really well for that.''

The modern kitchen has fitted appliances and oak doors on the base and wall cupboards add to the sense of quality. There is also plenty of space for a breakfast table which is where I sat with Alan and Jean as they chatted about their home. Off the kitchen is a useful utility room and a downstairs w.c.

A really big attraction is the annexe bedroom/en suite shower that overlooks the garden and would be ideal for someone with reduced mobility or a teenager wanting some privacy. I think this adds a lot to the house.

G oing upstairs Copper Beeches continues to charm. The landing has a lovely dormer window and I could readily imagine a small sofa beneath it being a nice place for a quiet read and there is lots of storage space built into the eaves: "One thing we are not short of is storage'' says Jean.

The master bedroom is big, with fitted furniture and has both a dressing area and an en suite shower/w.c. Again, dormer windows work their magic in allowing in plenty of natural light and adding interesting roof shapes.

Both the other two bedrooms are doubles and echo the master in having fitted furniture and dormers and the main bathroom has a corner bath with shower over. I should say here that at every turn one is struck by the quality and condition in which they have kept the house.

Outside, the house is approached by a drive protected by electronically controlled gates ? "no one comes here that we don't want to come here,'' says Alan ? and the eight copper beeches along its length reveal how the house was named.

There is a big double garage and ample parking at the front and behind is a lovely garden, a mix of lawn, terrace ? with that barbecue! ? a small kitchen garden and a brilliant wooden summerhouse/workshop/office that has power and light.

Caverswall is lovely little village close to the A50 and has good schools within walking distance.

Jean says: "We want to move to somewhere smaller but we know we will miss this place. It has been the most wonderful family home and we will take a lot of happy memories from it, but it is time now to let someone else enjoy what this house has given us ? a marvellous home that is easy to live in, is convenient and has a very peaceful feel."

Source: http://www.thisisstaffordshire.co.uk/Proud-spacious-family-home-idyllic-setting/story-17456044-detail/story.html

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বুধবার, ২৮ নভেম্বর, ২০১২

5 Marketing To Dos to get done before 2013

by Drew McLellan

November 28th, 2012 ? 6 Comments ? Business owner/leader stuff, Marketing, Strategy

This is the time of year where work grinds to a halt.

We have another two weeks or so before the holiday frenzy, parties, hangovers and the general professional apathy creeps in and productivity becomes a dirty word.

But don?t give up hope yet. ?I think there?s still a few things we can get done before we all sing Auld Lang Syne. Here are the five things I think you should focus on as the year winds down.

Your website: Take the time to look at every page, click on every link and make a list of what?s missing. ?We spend a lot of time building our websites but once they?re done, they tend to be forgotten. ?Fix all those broken links, correct any copy that?s wrong and update the pages that are out of date or are missing some of your more current offerings. ?Look for simple things you can do to increase visitors and engagement.

Your five best customers: Take the time to actually think about those customers who help you keep the doors open. ?Then, in this crazy rushed time ? write them a handwritten thank you note/letter. ?Be specific about why you love working with them ? and send it so you end their year with a smile.

Call it quits: Look back over the past 12-24 months. ?What?s the one marketing tactic that you have really dedicated yourself to but it just hasn?t caught on fire. ?This has to be something that you feel you really implemented well, thoroughly and can?t imagine what you could have done better. ?If you can say that and it?s not delivering results ? it?s time to let it go. ?Make December 2012 the last time you invest in it.

Identify your #1: If at the end of 2013, you could claim one accomplishment or goal?s achievement that would benefit the organization more than anything else ? what would it to be? Spend some time identifying the barriers that are between you and that accomplishment and what you need to leap over them. ?Build a one page business plan for getting to that goal as early in 2013 as you can. ?Make it your priority.

Fix what?s broken: When you look back at your marketing efforts for 2012 ? what?s the one marketing tactic that you know you did a lousy job of implementing? ?You know it can and will work but you just let other things get in the way or you did it half-heartedly. It?s time to get serious. ?Figure out what got in your way and figure a way around it. ?Farm it out, get something else off your plate, make a bet that you can?t afford to lose ? do whatever you need to do ? to ?make it happen and happen well.

There you have it ? get those five things done and then you can drink that 3rd glass of spiked egg nog at the company party without any guilt. ?And you?ll start 2013 with a storm of focus and energy.

Source: http://feedproxy.google.com/~r/TheMarketingMinute/~3/Ms-i3eINRuM/5-marketing-to-dos-to-get-done-before-2013.html

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7 slain as robbers hit Nigeria banks, police stations

By Reuters

ONITSHA, Nigeria -- Bank robbers armed with assault rifles and explosives attacked four banks and two police stations in southern Nigeria, in a coordinated strike that left seven people dead, police said Tuesday.

It was the latest in a spate of security lapses in Nigeria in the recent days, after a suicide bombing by suspected Islamists inside a military barracks Sunday and a jail break in the capital Abuja early Monday.

The attack took place late Monday night in the remote town of Auchi, in Edo state. The robbers opened fire and detonated dynamite at several of the targets, police commissioner for Eddo state Hurti Mohammed told Reuters by telephone.

They robbed the vault in Access Bank but were unable to get money out of any of the other banks. Seven people, including a bus driver, were killed in the ensuing gunbattle with police, he said.

'They shot sporadically'
Mohammed added that the robbers had escaped.

"They shot sporadically and were able to gain access to the vault of one of the banks ... carting away an unspecified amount of cash," he said.?

Slaughtered 'one by one': Gunmen kill at least 25 at Nigeria college residence

The southern, Yoruba-dominated area where the attack took place was hundreds of miles away from the northern areas where Islamist insurgent group Boko Haram is violently challenging the authority of the President Goodluck Jonathan's government.

But Boko Haram have made forays into the south, including in Kogi state, which borders Edo to the north.

$868,000 mystery: Yacht, Rolexes bought by Nigeria stock exchange disappear

Mohammed rejected any link. Powerful, organized robbery and kidnapping rings operate across southern Nigeria.

"There is no relation between this incident and what is happening in the north," he said. "We suspect the attackers just to be robbers."

More world stories from NBC News:

Follow World News from NBCNews.com on Twitter and Facebook

Copyright 2012 Thomson Reuters. Click for restrictions.

Source: http://worldnews.nbcnews.com/_news/2012/11/28/15507332-7-killed-as-robbers-hit-4-banks-2-police-stations-on-one-night-in-nigeria?lite

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Drug may offer new approach to treating insomnia

ScienceDaily (Nov. 28, 2012) ? A new drug may bring help for people with insomnia, according to a study published in the November 28, 2012, online issue of Neurology?, the medical journal of the American Academy of Neurology.

The drug, suvorexant, blocks the chemical messengers in the brain called orexins, which regulate wakefulness. Other drugs for insomnia affect different brain receptors.

Taking the drug suvorexant increased the amount of time people spent asleep during the night, according to the study. The study involved 254 people ages 18 to 64 who were in good physical and mental health but had insomnia that was not due to another medical condition.

The participants took either the drug or a placebo for four weeks, then switched to the other treatment for another four weeks. The participants spent the night in a sleep laboratory with their sleep monitored on the first night with each treatment and then again in the fourth week of each treatment.

While taking the drug, participants' "sleep efficiency," which reflects the total amount of time they slept during a fixed, eight hour time in bed, improved by 5 to 13 percent compared to those taking the placebo. They also experienced 21 to 37 fewer minutes awake during the night after they had fallen asleep than those who took the placebo. "This study provides evidence that suvorexant may offer a successful alternative strategy for treating insomnia," said study author W. Joseph Herring, MD, PhD, of North Wales, Penn., Executive Director of Clinical Research with Merck, the maker of suvorexant, and a member of the American Academy of Neurology. "Suvorexant was generally well-tolerated, and there were no serious side effects."

Herring said larger, longer studies have recently been conducted on suvorexant, along with studies to determine whether the drug could be safe and effective for elderly people, who make up a large percentage of those suffering from insomnia.

Merck has submitted a new drug application for the treatment with the U. S. Food and Drug Administration.

The study was funded by Merck Research Laboratories.

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Story Source:

The above story is reprinted from materials provided by American Academy of Neurology.

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


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

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

Source: http://feeds.sciencedaily.com/~r/sciencedaily/most_popular/~3/CPernaX8GXw/121128162157.htm

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মঙ্গলবার, ২৭ নভেম্বর, ২০১২

johir.khan: orpitasingh: Horse Racing History | recreation and sports

The sport of horse racing goes back a long, long way. It goes back to circa 4,500 BC when nomadic Central Asian tribes domesticated horses for the first time. Ever after, horse-racing has reigned supreme as a sport fit for Kings.

From the beginning of recorded history, horse racing has been depicted as an organised and popular sport common to all of the world's major civilizations. The Olympic Games of ancient Greece featured events involving both mounted and chariot racing. The sport was then taken up by the Romans. Mounted and chariot horse racing became major areas of enterprise in Roman Empire days; these events were the product of breeding programs with imported bloodlines and extensive training programs. Horseracing had all elements of legalized betting like bookies, proper racing tracks, hit tips, scandals and, red hot entertainment and excitement. Horse racing saw a decline that coincided with the Roman Empire's decline. It began to pick up speed once more once mankind was well into a more modern era.

Horse racing took a professional turn as long ago as the twelfth century, when English Crusader knights came back in the company of Arab horses. This set off a trend that lasted for the forthcoming period of hundreds of years: more and more Arab stallions were imported for crossing with English mares. The ensuing offspring were a real mix of speed and endurance. These cross bred horses were the forefathers of today's horse racing breeds.

As quantum technological jumps in transport and other fields of human concern took place in the 19th century and later , thousands of people became hooked on watching horse races and gambling on racing horses. Horseracing started to get intensive coverage in distinguished newspapers, and gambling volumes consistently increased. The arrival of organised on-site bookmakers brought along a complete sea change. Random and sometimes illegal, sometimes unethical practices led to a moderately successful Jockey Club effort to establish really high standards of order, discipline and integrity that ensured the sport's continued well being.

All around the world, attendance at race courses has been shooting up right into the early part of this century. There had been a decline in attendance during the 1970s and 1980s. The technology wonder of online web wagering has influenced horse racing in ways never conceived of earlier. Online betting has drawn a completely new generation of spectators and betters to the Game of Kings; they prefer to conduct all of their activities in front of their computers and TV sets. The facility to bet and earn cash legally from the result of horse races has been a core part of this sport's appeal and a major factor behind its survival as a sport with a presence.

Source: http://recreationsportsupdates.blogspot.com/2012/11/horse-racing-history.html

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Source: http://powersalfred56.typepad.com/blog/2012/11/horse-racing-history-recreation-and-sports-blog-updates.html

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Source: http://seanwood76.typepad.com/blog/2012/11/johirkhan-orpitasingh-horse-racing-history-recreation-and-sports.html

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Source: http://justincamp3658.blogspot.com/2012/11/johirkhan-orpitasingh-horse-racing.html

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Internet Marketing-Getting Started and Getting Business! | Online ...

There are many variables that go into establishing an internet marketing dream; and the goal, of course, is to become familiar with, and utilize, as many promotional opportunities, as possible, in order to secure as many potential customers, as possible.? The goal is to turn ?potential? into ?profit?.

Maximize Your On-Line Traffic:

There are some absolute basics to get that taxiing plane off the ground:

1.? Purchase Your Own Domain Name!

There are a few ?must-have? characteristics:

**?? Keep it short!

**?? Make it easy to remember!

**? Have the name connect with your businesss.

2. An Easy-To-Find, Knock-Out Website Is A Must!

Let?s face it, you get only one chance to make a killer first impression.When it comes to winning customers that have come online to find a business that meets their needs, your website has to have appeal and flair. There needs to be something about your web presence that stands out above the other ten or twenty they might visit on any given day.

Unless you know what you are doing with web design, be prepared to invest some money into having a professional do the designing for you.? It would be pointless and tragic to have a promising product or service, and never have it come to fruition due to a website that appears amateurish and dull.? An expert designer not only knows what attracts people aesthetically, but he or she can? help make sure your website is easy to use and easy to find!? Customers who become frustrated with attempting to find or use your site, won?t waste a nano-second to find someone else?s? that is accessible and easy to use.

3.? Location, Location, Location!

A budding on-line business owner will soon become familiar with what is termed ?SEO?, which means search engine optimization.?? Here, ?optimization? is the key; and? this is where the beating heart of a business can pump full throttle.? The covetted ?gold medal? of an internet business is to achieve the highest ranking, possible, from the major search engines such as Google or Bing.? The location of one?s sight equates to money in the bank?literally!? If a potential client is searching for a product or service that your company might represent, yet your business does not appear near the top of the search results, chances are they will not visit your site, regardless of how useful your product or service might genuinely be.

4.? Hire An SEO Expert!

There are a variety of SEO techniques that can, and do, boost search- ranking which, in turn, attract more customers.? There are seasoned, reputable SEO firms that specialize in catering to internet business growth by utilizing tried and true methods that can help a business forge ahead, positionaly, which means growth, monetarily.

The SEO process is technical and not to be attempted by one who does not have the expertise in the field.? You?ve heard the adage: in order to make money; you have to invest money!? Hiring a pro in this detailed arena, can make an enormous difference regarding a company?s profit potential.

5.? Other Profit-Boosting Considerations:

There are other small, but impactful, things one can do to draw customers, establish repoire, engage clients and increase a company?s return business:

** ??Provide regular blog posts which reflect your insight and expertise.

**?? Post customer testimonials which echo your company?s reputation and trustworthiness.

**?? Offer video clips to, further, detail your company?s operations?a video is worth a thousand words!

**? Find forums that relate to your business; and post on them to attract more traffic to your website.

Miss Carlson writes on a variety of topics including Dallas SEO.

Source: http://notjustanynichemarketingsolutions.com/internet-marketinggetting-started-business/?utm_source=rss&utm_medium=rss&utm_campaign=internet-marketinggetting-started-business

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Doha talks 'golden opportunity'

The latest round of UN climate talks have opened in Doha, the capital of Qatar.

More than 17,000 participants from all over the world are expected to gather in the Gulf state over the next two weeks.

The President of the meeting said it was a "golden opportunity" to make progress on a new global climate deal.

But many delegates remain concerned that divisions between developing and wealthy nations will hamper progress.

The meeting elected the former Qatari energy minister H E Abdullah bin Hamad Al-Attiyah, as President of the Conference of the Parties (COP18).

Continue reading the main story

Fault lines

  • Ambition: A growing sense among developing nations that richer countries are not aiming high enough in cutting carbon
  • Money: Lack of clarity about where the money to help poorer nations to adapt will come from
  • Disengagement: Major emitters including the United States, Canada, Russia and Japan say they will not take on new carbon targets under an extension of the Kyoto Protocol

In his opening remarks he said the "phenomenon" of climate change was a common challenge and the meeting in Doha was critical.

"This is an historic conference," said Mr Al-Attiyah, "it is of vital importance considering the items on its agenda. It is a turning point in the negotiations on climate change."

Some delegates were critical of the decision to hold the meeting in a country with some of the highest per capital emissions of carbon dioxide on earth. Jennifer Morgan, from the environmental think tank World Resources Institute called on the Qataris to announce actions to curb their own carbon footprint.

"I think the best way they could show their intent would be to announce what action or pledge they are going to put forward as part of this entire negotiation," she told BBC News. "They don't currently have anything on the books."

"There's much poorer countries who have said they are going to go climate neutral, so if they want to set the record straight that they are in this for the climate, then putting forward some sort of commitment early on, would I think help." she said.

There are also concerns that the meeting could end in stalemate as old divisions between rich and poor resurface.

Delegates will seek to negotiate a new commitment period for the Kyoto Protocol, the first phase of which runs out at the end of the year. Many poorer nations want the wealthier countries to take on substantial new cuts in carbon for the next five years.

Increasing ambition

A statement from a group of over 100 of the poorest and most at risk nations demanded action on this issue.

"The Kyoto Protocol is more than a treaty, it is the foundation upon which our multilateral effort to address climate change rests," it said.

Continue reading the main story

Adaptation

Action that helps cope with the effects of climate change - for example construction of barriers to protect against rising sea levels, or conversion to crops capable of surviving high temperatures and drought.

"The countries most responsible for the crisis must agree to a second commitment period under the Kyoto Protocol that will deliver genuine benefits to the climate that sustains us all. Currently, what is on the table falls far short of this climate imperative."

There are also likely to be serious disputes about finance and about the issue of "hot air" - the carrying over of unused permits to emit carbon.

Some of these issues may have to be resolved by cabinet ministers from more than 100 countries who will join the negotiating teams for the last four days of the meeting.

But Executive Secretary of the United Nations Framework Convention on Climate Change (UNFCCC), Christian Figueres expressed the hope that the negotiators themselves could make progress

"May I dare say that much of this can be accomplished before the high level segment, to allow this COP to finish not on Saturday, not on Sunday but actually make history by finishing on Friday," she said.

Source: http://www.bbc.co.uk/news/science-environment-20492501#sa-ns_mchannel=rss&ns_source=PublicRSS20-sa

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সোমবার, ২৬ নভেম্বর, ২০১২

JCI early table of contents for Nov. 26, 2012

JCI early table of contents for Nov. 26, 2012 [ Back to EurekAlert! ] Public release date: 26-Nov-2012
[ | E-mail | Share Share ]

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

Bariatric surgery procedures have similar therapeutic benefits in obese adults

Obesity is associated with insulin resistance and type 2 diabetes, both of which can be significantly improved by weight loss. Gastric bypass and adjustable gastric banding are two bariatric surgery techniques that are frequently used to effect weight loss in obese patients, but it is unclear if the two procedures produce different outcomes. In this issue of the Journal of Clinical Investigation, researchers led by Samuel Klein at the University of Washington School of Medicine in St. Louis compared the effects of 20% weight loss induced by either gastric bypass or adjustable gastric banding on metabolic response. They found that patients had different metabolic responses after eating, but both procedures equally improved insulin sensitivity and glucose tolerance. The researchers concluded that weight loss itself is primarily responsible for the therapeutic effects of gastric bypass and adjustable gastric banding in non-diabetic obese adults.

TITLE:
Gastric bypass and banding equally improve insulin sensitivity and ?-cell function

AUTHOR CONTACT:
Samuel Klein
Washington University School of Medicine, St Louis, MO, USA
Phone: 314-362-8708; E-mail: sklein@dom.wustl.edu

View this article at: http://www.jci.org/articles/view/64895?key=31c84cf8f52f834d9914


Identifying the cause of anesthesia-induced seizures

Antifibrinolytic drugs are frequently used to prevent blood loss during surgery, but sometimes cause convulsive seizures. In this issue of the Journal of Clinical Investigation, researchers led by Beverly Orser at the University of Toronto investigated the molecular mechanisms that underlie this side effect. By studying antifibrinolytics in mice, Orser and colleagues found that the drugs inhibited the activity of glycine receptors in the brain, leading to seizures. Seizures could be prevented by co-treatment with the general anesthetic isoflurane. This study explains the causes of and proposes treatment for antifibrinolytic-induced seizures. In a companion commentary, Debra Schwinn of the University of Washington reviews the connection between seizures and antifibrinolytic drugs.

TITLE:
Tranexamic acid concentrations associated with human seizures inhibit glycine receptors

AUTHOR CONTACT: Irene Lecker
Faculty of Medicine, University of Toronto, Toronto, ON, CAN
Phone: 416-978-1518; E-mail: irene.lecker@utoronto.ca

View this article at: http://www.jci.org/articles/view/63375?key=806b0eca4232a067ca57

ACCOMPANYING COMMENTARY

TITLE:

Understanding the TXA seizure connection

AUTHOR CONTACT:
Debra Schwinn
University of Washington, Seattle, WA, USA
Phone: 206-543-2673; Fax: 206-543-2958; E-mail: debra-schwinn@uiowa.edu

View this article at: http://www.jci.org/articles/view/66724?key=bd9895d06f784ef4366f


Parallel structure: Surprising similarities between kidney cells and neurons

The primary function of the kidneys is to filter the blood to remove waste and retain blood cells and proteins. Podocytes are specialized kidney cells that form a filtering structure known as a slit diaphragm. Disruption of the podocytes results in the enlargement of the slit diaphragm, causing nephrotic syndrome, and, eventually, renal failure. In this issue of the Journal of Clinical Investigation, researchers led by Shuta Ishibe and Pietro De Camilli at Yale University identified a protein network in podocytes that is responsible for maintaining the structural integrity of the slit diaphragms. By engineering mice that lack components of this protein network, Ishibe, Camilli, and colleagues found that they could block the formation of the slit diaphragms in the kidney. Interestingly, they found that this protein network is highly similar to the networks that mediate the development of neuronal synapses. In a companion commentary, Rosemary Sampogna and Qais Al-Awqati of Columbia University discuss how these findings alter our understanding of how slit diaphragms function in the ever-changing environment of the kidney.

TITLE:
Role of dynamin, synaptojanin and endophilin in podocyte foot processes

AUTHOR CONTACT:
Shuta Ishibe
Yale University School of Medicine, New Haven, CT, USA
Phone: 203-737-4170; E-mail: shuta.ishibe@yale.edu

View this article at: http://www.jci.org/articles/view/65289?key=b558c1e93de5879b6116

ACCOMPANYING COMMENTARY

TITLE:
Taking a bite: endocytosis in the maintenance of the slit diaphragm

AUTHOR CONTACT:
Qais Al-Awqati
Dept. Of Medicine & Physiology, New York, NY, USA
Phone: 212-305-3512; Fax: 212-305-3475; E-mail: qa1@columbia.edu

View this article at: http://www.jci.org/articles/view/65785?key=28148c95a955cf51dfc9


Mutations in ?Klotho underlie a genetic form of rickets

FGF23, a growth factor that regulates the metabolism of calcium and phosphate, binds and activates a circulating receptor known as ?Klotho (cKL). In a study published in the Journal of Clinical Investigation, researchers led by Kenneth White at Indiana University describe a patient with a chromosomal translocation that results in increased levels of ?Klotho. The patient presented with rickets, low blood phosphate and calcium levels, and increased FGF23. To determine how ?Klotho effects these changes, White and colleagues over-expressed cKL in mice and found that increased cKL resulted in enhanced FGF23 levels, decreased serum calcium and phosphate levels, low bone mineral content, and bone fractures. These data establish cKL as an important regulator of FGF23 production and phosphate metabolism and may have implications for the treatment of rickets. In a companion commentary, Harald Jppner of Massachusetts General Hospital and Myles Wolf of the University of Miami discuss the role of FGF23 and ?Klotho in mineral metabolism.

TITLE:
Circulating ?Klotho influences phosphate handling by controlling FGF23 production

AUTHOR CONTACT:
Kenneth E White
Indiana University School of Medicine, Indianapolis, IN, USA

Phone: 317-278-6140; Fax: 317-274-2293; E-mail: kenewhit@iupui.edu

View this article at: http://www.jci.org/articles/view/64986?key=7d8ae8802deff9a3caa3

ACCOMPANYING COMMENTARY

TITLE:
?Klotho: FGF23 coreceptor and FGF23-regulating hormone

AUTHOR CONTACT:
Harald Jppner
Massachusetts Gen Hosp, Boston, MA, USA
Phone: 617-726-3966; Fax: 617-726-7543; E-mail: jueppner@helix.mgh.harvard.edu

View this article at: http://www.jci.org/articles/view/67055?key=97377cc82306b227bcad


USP44 helps cells double check chromosome segregation to prevent cancer

Tumor cells frequently have an irregular number of chromosomes, a condition known as aneuploidy. During cell division, checkpoint proteins stop the process of division to ensure that each daughter cell receives the appropriate number of chromosomes; defects in these checkpoints can cause aneuploidy. In this issue of the Journal of Clinical Investigation, researchers led by Paul Galardy at the Mayo Clinic in Rochester, MN, investigated the role of the checkpoint protein USP44. Using a mouse that lacks Usp44, they found that loss of USP44 prevents chromosomes from splitting evenly between daughter cells. Usp44-deficient mice were prone to spontaneous tumors, particularly in the lungs. Interestingly, low USP44 expression was correlated with poor prognosis in human lung cancer. In a companion commentary, Andrew Holland and Don Cleveland of the University of California, San Diego, discuss how theses findings impact our understanding of aneuploidy in cancer.

TITLE:
USP44 regulates centrosome positioning to prevent aneuploidy and suppress tumorigenesis

AUTHOR CONTACT:
Paul Galardy
Mayo Clinic, Rochester, MN, USA
Phone: 507-284-2695; E-mail: galardy.paul@mayo.edu

View this article at: http://www.jci.org/articles/view/63084?key=3be5fa433c36a4a45295

ACCOMPANYING COMMENTARY

TITLE:
The deubiquitinase USP44 is a tumor suppressor that protects against chromosome missegregation

AUTHOR CONTACT:
Andrew Holland
Ludwig Inst. Cancer Research & UCSD, La Jolla, CA, USA
Phone: 858-534-7899; E-mail: a1holland@ucsd.edu

View this article at: http://www.jci.org/articles/view/66420?key=50440b6db78075ffec3c


A sticky situation: researchers identify mucus-producing pathway in human airway cells

Inflammatory airway diseases such as asthma, COPD, and cystic fibrosis are associated with increased mucus production, but the molecular mechanisms that are responsible for mucus production in these diseases have not been determined. In this issue of the Journal of Clinical Investigation, researchers led by Michael Holtzman at Washington University of St. Louis defined a cell signaling pathway that enhances mucus production in the cells that line the human airway. The pathway, which involves the protein MAPK13, was also activated in human COPD patients. By inhibiting the activity of MAPK13, Holtzman and colleagues were able to reduce mucus production in human airway epithelial cells, suggesting that therapeutics targeting this pathway might be useful for the treatment of mucus production in humans.

TITLE:
IL-13-induced airway mucus production is blocked by MAPK13 inhibition

AUTHOR CONTACT:
Michael Holtzman
Washington University School of Medicine, St. Louis, MO, USA
Phone: 314-362-8970; Fax: 314-362-9002; E-mail: holtzmanm@wustl.edu

View this article at: http://www.jci.org/articles/view/64896?key=33af0229095ae19f52d5


Too much of a good thing: extra VEGF signaling slows tumor growth

Angiogenesis is the formation of new blood vessels. Establishment of a blood supply promotes tumor growth by providing access to oxygen and nutrients. Blood vessel development is largely mediated by a growth factor known as VEGF, which is targeted by anti-angiogenic therapies. In this issue of the Journal of Clinical Investigation, researchers led by Hong Chen at the University of Oklahoma identified two new proteins, epsin1 and epsin2, as important regulators of VEGF-stimulated angiogenesis. VEGF mediates angiogenesis by binding to a cell surface protein that instigates cellular changes that are required for blood vessel formation. Epsins are known to remove proteins from the cell surface, preventing their activation. Normally, the number of VEGF binding proteins (VEGFR) on the cell surface is tightly controlled, but Chen and colleagues found that mice lacking epsin1/2 had a greater number of VEGFR on the cell surface that led to extra VEGF signaling, abnormal tumor vasculature, and slower tumor growth. In a companion commentary, Nancy Klauber-DeMore of the University of North Carolina at Chapel Hill discusses how these findings could contribute to the development of epsin-based therapeutic targeting of tumor angiogenesis.

TITLE:
Endothelial epsin deficiency decreases tumor growth by enhancing VEGF signaling

AUTHOR CONTACT:
Hong Chen
Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
Phone: 405-271-2750; E-mail: hong-chen@omrf.org

View this article at: http://www.jci.org/articles/view/64537?key=8b9e9a01382464f1fc75

ACCOMPANYING COMMENTARY

TITLE:
Are epsins a therapeutic target for tumor angiogenesis?

AUTHOR CONTACT:
Nancy Demore
University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Phone: 919-216-9754; E-mail: nancy_demore@med.unc.edu

View this article at: http://www.jci.org/articles/view/66171?key=7e2e14d5e5eda41ede24


Mouse model explains how calcium channel mutation causes hypokalemic periodic paralysis

Hypokalemic periodic paralysis (HypoPP) is a skeletal muscle disorder that is characterized by episodes of severe muscle weakness and low serum potassium levels. It is caused be a genetic mutation in protein channels that pump calcium or sodium ions across the cell membrane, but it is unclear exactly how the calcium channel mutations cause muscle weakness. In this issue of the Journal of Clinical Investigation, researchers led by Stephen Cannon at the University of Texas Southwestern Medical Center created a mouse with the HypoPP-associated calcium channel mutation that had symptoms that were similar to human HypoPP. They found that the mutant calcium channel caused changes in the cellular membrane potential that altered the ability of the muscle fibers to contract. This study explains how an inherited mutation causes HypoPP in humans. In a companion commentary, Alfred George of Vanderbilt University discusses how inherited mutations in channels contribute to human disease.

TITLE:
A calcium channel mutant mouse model of hypokalemic periodic paralysis

AUTHOR CONTACT:
Stephen C. Cannon
Southwestern Medical School, Dallas, TX, USA
Phone: 214-648-2564; Fax: 214-648-6306; E-mail: steve.cannon@utsouthwestern.edu

View this article at: http://www.jci.org/articles/view/66091?key=0f8ffec321a1fe4d328b

ACCOMPANYING COMMENTARY

TITLE:
Leaky channels make weak muscles

AUTHOR CONTACT:
Alfred L George, Jr.
Vanderbilt University, Nashville, TN, USA
Phone: 615-936-2660; Fax: 615-936-2661; E-mail: al.george@vanderbilt.edu

View this article at: http://www.jci.org/articles/view/66535?key=6b5240ca1c7bbbfe9a54


A tale of two heme transporters

Erythropoiesis, or the production of red blood cells, is a tightly regulated process that is sensitive to the balance of the proteins that form hemoglobin, heme and globin. The protein FLVCR1a is responsible for removing excess heme from cells and is essential for erythropoiesis. In this issue of the Journal of Clinical Investigation, researchers led by Emanuela Tolosano at the University of Torino in Italy identified another form of FLVCR1, FLVCR1b, that is responsible for exporting heme from the mitochondria of the cell, the location of heme production. By manipulating the expression of the FLVCR1 proteins in mice, Tolosano and colleagues found that FLVCR1b was required for erythropoiesis. FLVCR1a was not required for erythropoiesis, but was necessary to prevent excess bleeding, swelling, and skeletal abnormalities in the developing mouse embryo. These results indicate that mutations in the Flvcr1 gene may underlie diseases characterized by abnormal heme levels, such as Sideroblastic anemia. In a companion commentary, Mark Fleming of Children's Hospital Boston discusses the role of heme transport in human physiology and disease.

TITLE:
The mitochondrial heme exporter FLVCR1b mediates erythroid differentiation

AUTHOR CONTACT:
Emanuela Tolosano
University of Torino, Torino, UNK, ITA
Phone: 39-011-670-6423; Fax: 39-011-670-6432; E-mail: emanuela.tolosano@unito.it

View this article at: http://www.jci.org/articles/view/62422?key=da4e860633582101d3cb

ACCOMPANYING COMMENTARY

TITLE:
Mitochondrial heme: an exit strategy at last

AUTHOR CONTACT:
Mark Fleming
Children's Hospital Boston, Boston, MA, USA
Phone: 617-919-2664; E-mail: mark.fleming@childrens.harvard.edu

View this article at: http://www.jci.org/articles/view/66607?key=70b59624a5b601a3a137

###




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JCI early table of contents for Nov. 26, 2012 [ Back to EurekAlert! ] Public release date: 26-Nov-2012
[ | E-mail | Share Share ]

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

Bariatric surgery procedures have similar therapeutic benefits in obese adults

Obesity is associated with insulin resistance and type 2 diabetes, both of which can be significantly improved by weight loss. Gastric bypass and adjustable gastric banding are two bariatric surgery techniques that are frequently used to effect weight loss in obese patients, but it is unclear if the two procedures produce different outcomes. In this issue of the Journal of Clinical Investigation, researchers led by Samuel Klein at the University of Washington School of Medicine in St. Louis compared the effects of 20% weight loss induced by either gastric bypass or adjustable gastric banding on metabolic response. They found that patients had different metabolic responses after eating, but both procedures equally improved insulin sensitivity and glucose tolerance. The researchers concluded that weight loss itself is primarily responsible for the therapeutic effects of gastric bypass and adjustable gastric banding in non-diabetic obese adults.

TITLE:
Gastric bypass and banding equally improve insulin sensitivity and ?-cell function

AUTHOR CONTACT:
Samuel Klein
Washington University School of Medicine, St Louis, MO, USA
Phone: 314-362-8708; E-mail: sklein@dom.wustl.edu

View this article at: http://www.jci.org/articles/view/64895?key=31c84cf8f52f834d9914


Identifying the cause of anesthesia-induced seizures

Antifibrinolytic drugs are frequently used to prevent blood loss during surgery, but sometimes cause convulsive seizures. In this issue of the Journal of Clinical Investigation, researchers led by Beverly Orser at the University of Toronto investigated the molecular mechanisms that underlie this side effect. By studying antifibrinolytics in mice, Orser and colleagues found that the drugs inhibited the activity of glycine receptors in the brain, leading to seizures. Seizures could be prevented by co-treatment with the general anesthetic isoflurane. This study explains the causes of and proposes treatment for antifibrinolytic-induced seizures. In a companion commentary, Debra Schwinn of the University of Washington reviews the connection between seizures and antifibrinolytic drugs.

TITLE:
Tranexamic acid concentrations associated with human seizures inhibit glycine receptors

AUTHOR CONTACT: Irene Lecker
Faculty of Medicine, University of Toronto, Toronto, ON, CAN
Phone: 416-978-1518; E-mail: irene.lecker@utoronto.ca

View this article at: http://www.jci.org/articles/view/63375?key=806b0eca4232a067ca57

ACCOMPANYING COMMENTARY

TITLE:

Understanding the TXA seizure connection

AUTHOR CONTACT:
Debra Schwinn
University of Washington, Seattle, WA, USA
Phone: 206-543-2673; Fax: 206-543-2958; E-mail: debra-schwinn@uiowa.edu

View this article at: http://www.jci.org/articles/view/66724?key=bd9895d06f784ef4366f


Parallel structure: Surprising similarities between kidney cells and neurons

The primary function of the kidneys is to filter the blood to remove waste and retain blood cells and proteins. Podocytes are specialized kidney cells that form a filtering structure known as a slit diaphragm. Disruption of the podocytes results in the enlargement of the slit diaphragm, causing nephrotic syndrome, and, eventually, renal failure. In this issue of the Journal of Clinical Investigation, researchers led by Shuta Ishibe and Pietro De Camilli at Yale University identified a protein network in podocytes that is responsible for maintaining the structural integrity of the slit diaphragms. By engineering mice that lack components of this protein network, Ishibe, Camilli, and colleagues found that they could block the formation of the slit diaphragms in the kidney. Interestingly, they found that this protein network is highly similar to the networks that mediate the development of neuronal synapses. In a companion commentary, Rosemary Sampogna and Qais Al-Awqati of Columbia University discuss how these findings alter our understanding of how slit diaphragms function in the ever-changing environment of the kidney.

TITLE:
Role of dynamin, synaptojanin and endophilin in podocyte foot processes

AUTHOR CONTACT:
Shuta Ishibe
Yale University School of Medicine, New Haven, CT, USA
Phone: 203-737-4170; E-mail: shuta.ishibe@yale.edu

View this article at: http://www.jci.org/articles/view/65289?key=b558c1e93de5879b6116

ACCOMPANYING COMMENTARY

TITLE:
Taking a bite: endocytosis in the maintenance of the slit diaphragm

AUTHOR CONTACT:
Qais Al-Awqati
Dept. Of Medicine & Physiology, New York, NY, USA
Phone: 212-305-3512; Fax: 212-305-3475; E-mail: qa1@columbia.edu

View this article at: http://www.jci.org/articles/view/65785?key=28148c95a955cf51dfc9


Mutations in ?Klotho underlie a genetic form of rickets

FGF23, a growth factor that regulates the metabolism of calcium and phosphate, binds and activates a circulating receptor known as ?Klotho (cKL). In a study published in the Journal of Clinical Investigation, researchers led by Kenneth White at Indiana University describe a patient with a chromosomal translocation that results in increased levels of ?Klotho. The patient presented with rickets, low blood phosphate and calcium levels, and increased FGF23. To determine how ?Klotho effects these changes, White and colleagues over-expressed cKL in mice and found that increased cKL resulted in enhanced FGF23 levels, decreased serum calcium and phosphate levels, low bone mineral content, and bone fractures. These data establish cKL as an important regulator of FGF23 production and phosphate metabolism and may have implications for the treatment of rickets. In a companion commentary, Harald Jppner of Massachusetts General Hospital and Myles Wolf of the University of Miami discuss the role of FGF23 and ?Klotho in mineral metabolism.

TITLE:
Circulating ?Klotho influences phosphate handling by controlling FGF23 production

AUTHOR CONTACT:
Kenneth E White
Indiana University School of Medicine, Indianapolis, IN, USA

Phone: 317-278-6140; Fax: 317-274-2293; E-mail: kenewhit@iupui.edu

View this article at: http://www.jci.org/articles/view/64986?key=7d8ae8802deff9a3caa3

ACCOMPANYING COMMENTARY

TITLE:
?Klotho: FGF23 coreceptor and FGF23-regulating hormone

AUTHOR CONTACT:
Harald Jppner
Massachusetts Gen Hosp, Boston, MA, USA
Phone: 617-726-3966; Fax: 617-726-7543; E-mail: jueppner@helix.mgh.harvard.edu

View this article at: http://www.jci.org/articles/view/67055?key=97377cc82306b227bcad


USP44 helps cells double check chromosome segregation to prevent cancer

Tumor cells frequently have an irregular number of chromosomes, a condition known as aneuploidy. During cell division, checkpoint proteins stop the process of division to ensure that each daughter cell receives the appropriate number of chromosomes; defects in these checkpoints can cause aneuploidy. In this issue of the Journal of Clinical Investigation, researchers led by Paul Galardy at the Mayo Clinic in Rochester, MN, investigated the role of the checkpoint protein USP44. Using a mouse that lacks Usp44, they found that loss of USP44 prevents chromosomes from splitting evenly between daughter cells. Usp44-deficient mice were prone to spontaneous tumors, particularly in the lungs. Interestingly, low USP44 expression was correlated with poor prognosis in human lung cancer. In a companion commentary, Andrew Holland and Don Cleveland of the University of California, San Diego, discuss how theses findings impact our understanding of aneuploidy in cancer.

TITLE:
USP44 regulates centrosome positioning to prevent aneuploidy and suppress tumorigenesis

AUTHOR CONTACT:
Paul Galardy
Mayo Clinic, Rochester, MN, USA
Phone: 507-284-2695; E-mail: galardy.paul@mayo.edu

View this article at: http://www.jci.org/articles/view/63084?key=3be5fa433c36a4a45295

ACCOMPANYING COMMENTARY

TITLE:
The deubiquitinase USP44 is a tumor suppressor that protects against chromosome missegregation

AUTHOR CONTACT:
Andrew Holland
Ludwig Inst. Cancer Research & UCSD, La Jolla, CA, USA
Phone: 858-534-7899; E-mail: a1holland@ucsd.edu

View this article at: http://www.jci.org/articles/view/66420?key=50440b6db78075ffec3c


A sticky situation: researchers identify mucus-producing pathway in human airway cells

Inflammatory airway diseases such as asthma, COPD, and cystic fibrosis are associated with increased mucus production, but the molecular mechanisms that are responsible for mucus production in these diseases have not been determined. In this issue of the Journal of Clinical Investigation, researchers led by Michael Holtzman at Washington University of St. Louis defined a cell signaling pathway that enhances mucus production in the cells that line the human airway. The pathway, which involves the protein MAPK13, was also activated in human COPD patients. By inhibiting the activity of MAPK13, Holtzman and colleagues were able to reduce mucus production in human airway epithelial cells, suggesting that therapeutics targeting this pathway might be useful for the treatment of mucus production in humans.

TITLE:
IL-13-induced airway mucus production is blocked by MAPK13 inhibition

AUTHOR CONTACT:
Michael Holtzman
Washington University School of Medicine, St. Louis, MO, USA
Phone: 314-362-8970; Fax: 314-362-9002; E-mail: holtzmanm@wustl.edu

View this article at: http://www.jci.org/articles/view/64896?key=33af0229095ae19f52d5


Too much of a good thing: extra VEGF signaling slows tumor growth

Angiogenesis is the formation of new blood vessels. Establishment of a blood supply promotes tumor growth by providing access to oxygen and nutrients. Blood vessel development is largely mediated by a growth factor known as VEGF, which is targeted by anti-angiogenic therapies. In this issue of the Journal of Clinical Investigation, researchers led by Hong Chen at the University of Oklahoma identified two new proteins, epsin1 and epsin2, as important regulators of VEGF-stimulated angiogenesis. VEGF mediates angiogenesis by binding to a cell surface protein that instigates cellular changes that are required for blood vessel formation. Epsins are known to remove proteins from the cell surface, preventing their activation. Normally, the number of VEGF binding proteins (VEGFR) on the cell surface is tightly controlled, but Chen and colleagues found that mice lacking epsin1/2 had a greater number of VEGFR on the cell surface that led to extra VEGF signaling, abnormal tumor vasculature, and slower tumor growth. In a companion commentary, Nancy Klauber-DeMore of the University of North Carolina at Chapel Hill discusses how these findings could contribute to the development of epsin-based therapeutic targeting of tumor angiogenesis.

TITLE:
Endothelial epsin deficiency decreases tumor growth by enhancing VEGF signaling

AUTHOR CONTACT:
Hong Chen
Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
Phone: 405-271-2750; E-mail: hong-chen@omrf.org

View this article at: http://www.jci.org/articles/view/64537?key=8b9e9a01382464f1fc75

ACCOMPANYING COMMENTARY

TITLE:
Are epsins a therapeutic target for tumor angiogenesis?

AUTHOR CONTACT:
Nancy Demore
University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Phone: 919-216-9754; E-mail: nancy_demore@med.unc.edu

View this article at: http://www.jci.org/articles/view/66171?key=7e2e14d5e5eda41ede24


Mouse model explains how calcium channel mutation causes hypokalemic periodic paralysis

Hypokalemic periodic paralysis (HypoPP) is a skeletal muscle disorder that is characterized by episodes of severe muscle weakness and low serum potassium levels. It is caused be a genetic mutation in protein channels that pump calcium or sodium ions across the cell membrane, but it is unclear exactly how the calcium channel mutations cause muscle weakness. In this issue of the Journal of Clinical Investigation, researchers led by Stephen Cannon at the University of Texas Southwestern Medical Center created a mouse with the HypoPP-associated calcium channel mutation that had symptoms that were similar to human HypoPP. They found that the mutant calcium channel caused changes in the cellular membrane potential that altered the ability of the muscle fibers to contract. This study explains how an inherited mutation causes HypoPP in humans. In a companion commentary, Alfred George of Vanderbilt University discusses how inherited mutations in channels contribute to human disease.

TITLE:
A calcium channel mutant mouse model of hypokalemic periodic paralysis

AUTHOR CONTACT:
Stephen C. Cannon
Southwestern Medical School, Dallas, TX, USA
Phone: 214-648-2564; Fax: 214-648-6306; E-mail: steve.cannon@utsouthwestern.edu

View this article at: http://www.jci.org/articles/view/66091?key=0f8ffec321a1fe4d328b

ACCOMPANYING COMMENTARY

TITLE:
Leaky channels make weak muscles

AUTHOR CONTACT:
Alfred L George, Jr.
Vanderbilt University, Nashville, TN, USA
Phone: 615-936-2660; Fax: 615-936-2661; E-mail: al.george@vanderbilt.edu

View this article at: http://www.jci.org/articles/view/66535?key=6b5240ca1c7bbbfe9a54


A tale of two heme transporters

Erythropoiesis, or the production of red blood cells, is a tightly regulated process that is sensitive to the balance of the proteins that form hemoglobin, heme and globin. The protein FLVCR1a is responsible for removing excess heme from cells and is essential for erythropoiesis. In this issue of the Journal of Clinical Investigation, researchers led by Emanuela Tolosano at the University of Torino in Italy identified another form of FLVCR1, FLVCR1b, that is responsible for exporting heme from the mitochondria of the cell, the location of heme production. By manipulating the expression of the FLVCR1 proteins in mice, Tolosano and colleagues found that FLVCR1b was required for erythropoiesis. FLVCR1a was not required for erythropoiesis, but was necessary to prevent excess bleeding, swelling, and skeletal abnormalities in the developing mouse embryo. These results indicate that mutations in the Flvcr1 gene may underlie diseases characterized by abnormal heme levels, such as Sideroblastic anemia. In a companion commentary, Mark Fleming of Children's Hospital Boston discusses the role of heme transport in human physiology and disease.

TITLE:
The mitochondrial heme exporter FLVCR1b mediates erythroid differentiation

AUTHOR CONTACT:
Emanuela Tolosano
University of Torino, Torino, UNK, ITA
Phone: 39-011-670-6423; Fax: 39-011-670-6432; E-mail: emanuela.tolosano@unito.it

View this article at: http://www.jci.org/articles/view/62422?key=da4e860633582101d3cb

ACCOMPANYING COMMENTARY

TITLE:
Mitochondrial heme: an exit strategy at last

AUTHOR CONTACT:
Mark Fleming
Children's Hospital Boston, Boston, MA, USA
Phone: 617-919-2664; E-mail: mark.fleming@childrens.harvard.edu

View this article at: http://www.jci.org/articles/view/66607?key=70b59624a5b601a3a137

###




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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.


Source: http://www.eurekalert.org/pub_releases/2012-11/joci-jet112112.php

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Jude Law in 'Anna Karenina' does well at box office as 'Breaking Dawn' breaks records

Jude Law stars in 'Anna Karenina,' which performed well in a limited release during Thanksgiving weekend.? 'The Twilight Saga: Breaking Dawn ? Part 2' had a boffo opening which ranks eighth on all-time debuts.

By David Germain,?Associated Press / November 26, 2012

Jude Law (l.) and Keira Knightley (r.) star in 'Anna Karenina.'

Laurie Sparham/Focus Features/AP

Enlarge

The sun has set on the "Twilight" franchise with one last blockbuster opening for the supernatural romance.

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"The Twilight Saga: Breaking Dawn ? Part 2" sucked up $141.3 million domestically over opening weekend and $199.6 million more overseas for a worldwide debut of $340.9 million, according to studio estimates Sunday.

The finale ranks eighth on the list of all-time domestic debuts, and leaves "Twilight" with three of the top-10 openings, joining 2009's "New Moon" (No. 7 with $142.8 million) and last year's "Breaking Dawn ? Part 1" (No. 9 with $138.1 million).

Last May's "The Avengers" is No. 1 with $207.4 million. "Batman" is the only other franchise with more than one top-10 opening: last July's "The Dark Knight Rises" (No. 3 with $160.9 million) and 2008's "The Dark Knight" (No. 4 with $158.4 million).

Though "Twilight" still is a female-driven franchise, with girls and women making up 79 percent of the opening-weekend audience, the finale drew the biggest male crowds in the series. Action-minded guys had more to root for in the finale as Kristen Stewart, Robert Pattinson and Taylor Lautner join in a colossal battle to end the story of warring vampires and werewolves.

"Our male audience particularly has enjoyed this film," said Richie Fay, head of distribution for Lionsgate, whose Summit Entertainment banner releases the "Twilight" movies. "With the action scenes in this one, we're hoping the holdover business will reflect the fact that males have kind of found it out."

The movie also helped lift Lionsgate into the big leagues among Hollywood studios. Paced by its $400 million smash with "The Hunger Games" and now the "Twilight" finale, Lionsgate surpassed $1 billion at the domestic box office for the first time.

Some box-office watchers had expected the last "Twilight" movie to open with a franchise record the way the "Harry Potter" finale did last year with $169.2 million, the second-best domestic debut on the charts.

"I thought that for the final installment, it might eclipse the franchise record, but to look at $141.3 million and say that's a disappointment, that's kind of crazy," said Paul Dergarabedian, an analyst for box-office tracker Hollywood.com. "It's one of the most consistently performing franchises of all time."

Source: http://rss.csmonitor.com/~r/feeds/csm/~3/DXOJCq89KzU/Jude-Law-in-Anna-Karenina-does-well-at-box-office-as-Breaking-Dawn-breaks-records

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Internet Marketing Search Engine Optimization SEM SEO service ...

There are millions of different online businesses out there, and if you expect your particular business to be successful, then you need to implement some sound marketing techniques. By reading through this information, you will find valuable information on how to best utilize the Internet for marketing purposes. Keep reading for great Internet marketing information.

Think about methods you want to use to advertise your webpage. Free or cheap methods to promote your business are to make a blog or use social networks to promote your business. There are many ways to get people to come to your site. It just takes some creativity.

Make sure that you maximize the quality of third-party security with transactions. Many different companies offer a variety of secure services. VeriSign is one of the programs that helps to keep financial information private. Security systems can cost money, but they are absolute necessities for doing business online safely.

Internet marketing is both similar to, and different from, other marketing tactics. Be ready for any changes that may come up, like if search engines stop putting focus on title tags. Knowing this, you might need to place more effort in marketing a video to viral audiences.

Every company should have both an interesting slogan and a professional logo, no matter the size of the company. You customers will remember you by how you portray your brand. Customers tend to remember catchy slogans for quite a while. When a customer is ready to buy a product, he might remember your slogan even if he doesn?t remember the name of your business. In the age of the internet, that?s not a big problem.

Sending emails is a great way to stay in touch with your customers, but make sure you send out varied content. A block of links that remain the same with every email your customers receive is easy to start ignoring. Create variety in your emails to gain attention.

Another option would be combining products into a package deal and selling it for a lower price. That way the customer gets more bang for their buck. Advertisements for sales or promotions must be detailed and contain the exact conditions of the offer.

Use social networks such as Facebook and Twitter to connect with your audience. You can use these sites to advertise new offers or to share your latest articles. However, make sure to not over-advertise on these websites. Rather, strive to post useful and smart messages with intermittent marketing messages interspersed.

Making your site stand out is a great Internet promotion advantage you can use. Making your site stand out is what drives visitors towards your site, and there are a lot out there so this is a good strategy. You should showcase something you offer that no one else does.

Make a webpage specifically built for public relations. This is where you can include information that online magazines and newspapers can publish. Not only is this simple to do, but it also is an excellent way to promote your business.

Spin the positives when selling your goods. Concentrate on the value your product or service will add to their life. Tell them how it will make their life better. Having a positive attitude, and being confident that your product will work to the customer?s benefit, will encourage more sales.

High-quality graphics of your products can make or break an online sale. Your customers need to be able to visualize the items they are about to buy, and see the detail of your high-quality products. Allow customers to post their own images of your products to show how they use them. If your product warrants use of ?before and after? pictures, they can be an effective selling tool.

If you can you should give your away something branded for free to help spread awareness of your business. For example, if it?s a wallpaper, submit it to sites that offer free wallpapers. Many websites give their customers freebies, downloads, and e-zines that accept links for you to submit your site.

As stated above, Internet marketing helps your business get noticed. Traditional advertising methods just cannot give you the visibility and the worldwide presence that Online marketing can provide. Use the helpful tips here, and find out what works best for you.

The formatting of your website?s text plays an important role in its attractiveness and success. You can emphasize a single word using tags to underline, bold, or italicize it. This can help to distinguish how you want your customer to receive a certain message, which can help with the clarity of what you are trying to say.

Internet Marketing, SEO


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Here are some other Internet Marketing/SEO related sites that I would like to share with you.
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AOL.com Video - Internet Marketing Tip : Article Marketing ...
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Source: http://www.websitehostdirect.com/how-to-become-an-expert-in-internet-promotion/

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Federal Reserve : New Economic Stimulus May Be Warranted

Meet Heather Woodward, Realtor

Heather is a full-time Realtor and a consistent top producer in the local Crested Butte, Almont and Gunnison markets.

Heather takes great pride in giving unparalleled customer service and is dedicated to her clients and their individual needs. Her number one priority is to provide service above and beyond her clients? expectations. She will dedicate her time, attention, energy and knowledge during and after each transaction. Read More

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The Source of Growth and Creativity | Self improvement tips - Davis ...

Bare attention (to objects, people and circumstances) is what brings order in this world and in your personal world. If you know how to move your attention without the involvement of mind, positive creation happens as a result. Attention is literally a life response whereas mind is reaction out of memory and reaffirmation of the past. Attention is not same as thinking mind but it constitutes pure awareness moving itself through different objects without creating friction.

I am stating below some examples as to how life responds to the power of attention. Here?s one:

One small business owner decided to give attention to his accounts, balanced eight months of back bank statements, and miraculously received $5000 from nowhere the next day.

The key is attention without interpretation of the situation. A mere attention and intention to improve is sufficient.

If you bring your personal or business accounts fully and accurately up to date, you?ll be able to watch the money flow to you!

Money is not the only thing that responds to attention. So do ordinary objects and things. Consider this example:

A businessperson was unable to make any substantial sales. He was told that he should give attention to and evaluate his remaining current stocks, and then make a full effort to sell them off. After making an effort of selling but a few of the minimal stocks, an order arrived equal to six months of normal sales!

We have often seen this phenomenon where a business owner concerned by low sales or cash made the effort to sell off remaining unsold stocks, and life responded by bringing more sales. This is a powerful example of the power of attention to objects and things.

One way we give attention is by adopting the personal value of maximizing the way you use your current resources, such as money, materials, and time. Here?s an example of how one manufacturer applied the value of maximum utilization of a limited resource, which resulted in a very favorable situation for the company:

?In the manufacture of welding electrodes, Low Carbon Ferro Manganese is one of the main raw materials. The manufacturer who was supplying us suddenly informed that their plant is shut down for maintenance and that there will not be any supply from them for the next two months. It is an expensive material so the stock holding was minimum. There are only very few manufacturers of this item and they are all located at far away places. We had little time to arrange supply from other sources. The stock on hand was sufficient for 5 days of production only. We decided that not a particle of LCF should be wasted and alerted all the workers to be extra careful. The shop floor was swept thoroughly and all the spilled material were collected, screened and used. We provided attention to what could immediately be attended. Coincidentally, within two days, a Managing Director of a company manufacturing LCF in Orissa (which is about 1300 kilometers away from Pondicherry) visited our unit; over the phone (from Pondicherry) he instructed his plant to dispatch material to us. From the previous supplier we were buying the material against payment. Where as this company offered us a credit of 30 days. We did not negotiate any terms with them. They themselves agreed to supply at the same price. We were frank in telling them the precarious situation we were in. In spite of knowing our weak situation, they did not take any undue advantage. We are continuing with them.?

Moral is they didn?t wasted the material further and alerted all the workers to be extra careful. The shop floor was swept thoroughly and all the spilled material were collected, screened and used. They provided attention to what could be immediately attended. Moral is mere attentions to a situation without being caught up in its interpretation brings order into it. One need not worry, anxiety (using mind) but need to attend to immediate things including the people and objects and the universe arranges rest of the trappings to bring in the harmony into the area of attention.

Here?s a closely related example of the power of attention to things through the application of the value of maximum utilization, and life response:

X, the proprietor of a company, engaged Y as his consultant to improve his business. Y, the consultant, noticed a machine, which X deemed not useful to his present business, kept in a sorry state. Y requested X to repair and repaint it and keep it ready for production. X laughed and said, ?This machine

is idle for last many years without any order. I can not spend money on it. As soon as I get orders, I will repair and repaint the machine.? Y thought X was looking at things in the wrong way.

Y told X, ?If you keep machine ready for production and if you genuinely wish that this machine should yield profits, you will get orders. Life will favorably respond.?

X followed Y?s suggestion. After a day or two, X?s cousin, an engineer, came to his factory. The newly painted machine gained his attention. He took interest in the machine. He told X that he was interested in starting a new factory. If X could give the machine to him, he could earn profit from the first month onwards and a share of the income would go to X. An agreement was struck and the machine became a cash cow.

Moral is begin with trust that in the end everything will be organized and take your first step forward in the trust that the universe will arrange the trapping, your job is to attend the immediate objects, people and rest will follow on its own timing. In this case they attended a machine deemed not useful to his present business.

So all sorts of things respond to attention; animate and inanimate!

One final example will show how the power of attention is tied in to organizing things one level higher than it is currently organized.

A company had just launched a new product, yet did not yet have any sales on the product, despite considerable effort. One day the manager decided to go through the operations manual to update it to the latest information, including procedures related to the new product. He did this late in the work day. Early the very next morning he saw the first order for the product come in through the company?s web site.

Finally, let?s not forget to mention that people also, of course, respond to attention.

Mind creates friction, attention creates movement. If you experience movement without friction, its attention and not the mind and you can assume that you are in a creative state. We invite restlessness through preconceived ideas about the state of reality. Creativity begins when you can stabilize in a chaotic environment looking at it as an ever expanding life rather than mere problems; all the chaos is a life itself expanding to create new bridges where there are none. As a result, trust takes over fear and panic. New things or events or people are seen as opportunities to organize the life one step up. It is through chaos that the new order is borne, so chaos need not be seen as something to fear about but life itself stretching the limits to organize one step further. A relaxed attitude takes over the panic and fear.

Attention itself brings in the order when used wisely in a trusting manner. Things are disorganized on account of lack of attention and ignorance of it?s values.

Attention brings in the order. Place your attention in the areas where you seek improvements, hang out loosely expecting to improve the area, rest will follow. Key is identify the area, focus loosely and intend the desired result.

Seek with the attitude (state of existence) that you are already fulfilled and perfect in areas where you seek improvements, the acting and attitude of the perfection at every step itself consolidates into the ultimate end perfection. Move yourself consciously attending whatever needs to be attended here and now.

You trust and move one step toward unknown and simultaneously unknown moves one step towards you bridging the gap between harmony and disharmony. Your attention itself is your one step towards the unknown and if you consistently moves your attention in the desired direction with the intention to improve the life, unknown is moving towards you simultaneous bringing in all the necessary elements to bring harmony into your life.

Universe responds not to just fulfill your individual whims and fancies but to bring in greater order for greater good.

There is always a response to attention since it has capacity for positive movement where has mind has fixed notions which restricts movement.

Attention enables movement, whereas beliefs blocks movement.

Author: Santosh Kunte ?Mumbai India. An avid reader of the spiritual knowledge, engineering graduate and executive. Loves reading meditation and sharing. You can reach me for your valuable feedback or you can reach me for your problems of finance, relationship etc. by dropping an e-mail to me on sskunte2@rediffmail.com

Source: http://www.moonsbeing.com/2012/11/22/The-Source-of-Growth-and-Creativity/

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