text:
The Washington Post reveals that Roy Spencer is the man behind environmentalist parody site ecoEnquirer.com:
Somewhere in an office about 600 miles southwest of here, former NASA scientist Roy W. Spencer is laughing. The 50-year-old, white-haired PhD dreamed up the spoof site — sort of the Onion meets the Weather Channel — because he thinks people are overreacting to the threat of climate change.
Now a principal research scientist at the University of Alabama at Huntsville, Spencer says human activities have "likely" contributed to climate change, but he argues that "since we do not understand natural climate fluctuations, we don't really know how much, quantitatively, of the present warmth is man-made versus natural."
Spencer describes his Web site as "a spur-of-the moment effort that resulted from the increasing number of news stories that quoted people who blamed global warming for events such as tsunamis and the latest flood, drought or hurricane. . . . Also, I have a somewhat twisted sense of humor, and the Web site gives me an additional creative outlet." His other creative outlet: He's lead guitarist in a contemporary Christian rock band at St. Mark's Lutheran Church in Huntsville. (His environmentalist-mocking alternative lyrics to Supertramp's "Give a Little Bit": "I'll take a little bit, I'll take a little bit of your wealth from you/So give a little bit, oh, give a little more than a dime to me.") …
Senate Environment and Public Works Committee counsel John Shanahan, whose boss, James M. Inhofe (R-Okla.), has called global warming "a hoax," likes Spencer for his research as well as his wit.
"It wasn't until I first saw his Web site that I realized that he's an amazingly funny guy," says Shanahan. "It's refreshing to see a scientist keep his sense of humor in a highly polarized debate."
Well, his site is not as funny as those CEI ads, but this one is actually funny. Mind you, being a Creationist, he also mocks evolution:
"What we are seeing is breaching whales flapping their fins wildly, in an obvious attempt to achieve flight", said Prof. Charles Beagle, research team leader with the Fish and Wildlife Service. In one amazing photo (above), a whale was seen contorting its body, clearly forming the shape of a giant hummingbird. "Its fins were flapping so fast, they were a blur", exclaimed Prof. Beagle.
Rapid evolutionary changes have been hypothesized for years, the researchers explained, noting the near total absense of transitional forms of life in the fossil record. "This could be mankind's only chance to actually observe a rapid evolutionary transition of one species into another species", explained Beagle.
An alternative explanation for the odd behavior was offered by Dr. John Morrison of the National Creation Research Foundation. "Even if these whales are indeed attempting to mimic bird-like behavior, how does that in any way change their DNA so that their offspring will carry that behavior to the next level? Massive genetic defects would have to occur, all combining in positive ways to make the animal more bird-like", explained Dr. Morrison.
Prof. Beagle responded to the criticism by noting, "Well, we have birds, don't we? They had to come from someplace, didn't they? And life started in the oceans, didn't it? Case closed".
Hat tip: Stephen Fromm


text:
Rovne, Illava
Expand Messages
- My family came from the Slovak Republic. I'm researching these surnames from
Illava: Sumak, Liska, Mitny, Lattyko and Baginy. I'm researching these
surnames from Rovne: Svabek, Kahak and Zdamik. Should anyone else on the list
be interested in these names please contact me.
Irene Svabek
Your message has been successfully submitted and would be delivered to recipients shortly.

subset: commoncrawl


text:
A San Pedro housing proposal that sparked loud protests, petition drives and heated speeches appears headed — finally — for approval in its latest downsized format.
The planning committee of the Los Angeles City Council this week met and unanimously approved the Ponte Vista development for consideration by the full council early next year.
Only one of 15 community speakers raised objections to the plan.
"You've been through a lot of hours and hours of discussion and vetting," Councilman Mitchell Englander told residents who attended Tuesday's meeting of the Planning and Land Use Management Committee. "To be here to support any project at all is huge, and it's a testament to the people in this community that care so much that they've dedicated so much time."
The ordinance now goes to the city attorney and will be returned to the committee, which likely will waive further action and forward it to the council.
If approved by the full City Council, the developer will have the go-ahead to begin work next year on the 61.5-acre former Navy property at 26900 S. Western Ave.
Englander also lauded "the applicant team, attorneys, the land-use experts — everyone who's been willing to sit down" and reach what appears to be a consensus after eight years of contentious debate.
Ever since it was rolled out by a previous developer, Bob Bisno, in 2005, Ponte Vista has commanded much of the community's attention as the project was debated in Neighborhood Council meetings, city hearings and at citizen task force sessions.
First proposed for 2,300 homes, the project in its latest version — under a new developer, Star Financial Inc., since 2010 — has brought that number down to 676 units featuring for-sale, single-family homes as well as town homes and single-level flats.
The response to the original plan, Englander said, "was horrific" due to density and traffic issues.
The reduced plan has the support of Councilman Joe Buscaino, who represents the Harbor Area, and also is backed by the three chambers of commerce that serve the surrounding area.
Steven Magee, executive vice president for iStar Financial Inc., commended those in the community who have long supported building new housing on the parcel.
"I also thank our detractors who forced us to rethink the project many, many times," he said.
Several speakers told committee members that the time had come to develop what they described as a long-standing eyesore along one of the main entry ways into San Pedro.
"The area is blighted, it's time to move forward," said Irene Mendoza of San Pedro.
"Currently, it's an eyesore," said resident Louis Dominguez, who was among the early supporters of Bisno's original plans. "If you come into San Pedro by way of Western Avenue, you see this abandoned Navy housing, which looks horrible. ... It's definitely time to get moving. These people (the developers) have gone out of their way, they've downsized it even more than I wanted it downsized."
However, Noel Weiss, who spokes at Tuesday's meeting, told the committee that the developers did not sufficiently evaluate the potential impact of an accident or failure of two large propane and butane storage tanks nearby.
Residents have been trying to move the Rancho LPG Holdings tank operation out of the area but so far have not succeeded.
In a "worst-case scenario," Weiss said, there would be a 3.6-mile blast radius that would reach the new homes.
The developer disagreed, saying a maximum blast ratio would be no more than 0.5 acres and the homes are 0.7 acres from the tanks.
"This was looked at and evaluated," Magee said. "Rest assured, it was not ignored."
Kit Fox, a senior analyst for the city of Rancho Palos Verdes, asked that his city be included in plans to monitor Western Avenue traffic, including a number of intersections that impact RPV.
Benefits cited by several speakers focused on needed for-sale family housing in the community known for its multi-generational loyalty.
Included also in the latest Ponte Vista housing proposal is a 2.42-acre park and walking trails that would be open to the public. Other possibilities for the more than 24 acres of open space include a playground and dog park.
Early opposition to the housing galvanized around maintaining the current R1 zoning that would have reduced the number of homes to a few hundred.
All along developers said building large, single-family homes wouldn't result in affordable housing.
While many would have preferred to keep the land as open space, it was sold by the Navy as surplus property, purchased at auction first by Bisno in 2005 for $125 million and later changing hands as subsequent private developers stepped in.
Several speakers said Ponte Vista would be a popular option for many older residents as they downsize and pass on their larger houses to their children.
The Los Angeles Planning Commission approved the scaled-down plan in November.
If the plan is approved by the full City Council, ground-breaking could occur in the first half of 2014, beginning with demolition of the abandoned Navy houses.


text:
Former Maverick Brian Cardinal cleans up to give White Sox win in Dirk Nowitzki's Heroes baseball game
FRISCO – Searching for his first Heroes Celebrity Baseball game victory Saturday night, Dirk Nowitzki loaded his team's roster with the biggest names.
But it was his former Mavericks teammate, Brian Cardinal, who stole the show. Cardinal doubled past centerfielder Terrell Owens in the bottom of the sixth, driving in three runs and later scoring to give Nowitzki's White Sox the 17-16 victory at Dr Pepper Ballpark.
The first few innings got off to a slow start, so the game was shortened to seven innings. But the first sellout crowd in 13 years of the event didn't mind as the 8,987 in attendance were treated to 40 hits, a postgame firework show and an opportunity to get an autograph or photo from a local celebrity.
Nowitzki's team was led by Michael Young, Dez Bryant, Tony Romo, Jason Witten, Jason Garrett, Rick Carlisle, Monta Ellis and Jason Terry.
Joining Owens on the Blue Sox were Pudge Rodriguez, Tyler Seguin, Vernon Wells and Terrance Williams.
Romo, who had December back surgery, was limited to dugout coach. The Cowboys quarterback got on the mic after the first inning and said he wanted to play but Garrett wasn't going to let that happen.
"I had a dream that all our players made it through this game without injury," Carlisle said during a pregame press conference. Garrett quickly leaned forward and said, "I had the same dream."
Witten and Nowitzki, who shared MVP honors with Cardinal, each had two hits and an RBI to lead the White Sox.
"We have so much respect for Dirk and the Mavericks and the Rangers," Garrett said. "I think it's a pretty unique event that we actually play in a baseball game. Guys are used to going to different kinds of charity events, but rarely do they have a uniform with their name on it in their locker and they're taking [batting practice] beforehand.
"I just think it's a great thing to be a part of. We have so much respect for these guys and really feel fortunate to be included in it."


text:
Staff Writer
Cruz Fitness on East Main Street in Lincolnton closed Thursday morning, with padlocks on the doors and signs in the windows alerting customers of the gym to cancel their memberships.
"I apologize for any inconvenience," read a note from owner Salvador Cruz.
The signs, which said the business was "forced closed," also directed members to call the state Attorney General's Office to formally file any complaints regarding consumer protection.
"I am heartbroken because I have worked so hard," Cruz told the Times-News Thursday afternoon.
Cruz said he had received a letter a couple of weeks ago stating that he was three months behind on his $7,500-per-month rent. Since then, he has received several threats of closure, with the last one coming on Monday.
However, Cruz said the rent has been paid and that the problem is the result of an internal feud involving the property owner, the property manager and the billing agency through which he pays for the rent and equipment. He additionally said the partners have been in negotiations for a few weeks.
He thought he'd have until the end of the month for it all to be worked out. However, when one of his employees showed up early Thursday morning, padlocks were on the doors. Cruz was immediately alerted. He noted the padlocks must have been put in place sometime after 11 p.m. Wednesday and before 5 a.m. Thursday.
That employee, along with three others, is now, like Cruz, without a job.
Cruz maintains he is "not the culprit," but rather a victim caught in the middle of a disagreement.
Cruz Fitness had roughly 800 or 900 members paying monthly dues averaging between $20 and $30.
"I'm on my members' side," Cruz said, adding that he's been trying to process as many cancellations as possible and that he doesn't want anyone to continue being drafted after the closure or to think he's pocketing the money.
So far, 200 memberships have been terminated, he said. Additionally, Cruz said the owners of Rock Fitness in Lincolnton have told him that they will offer him 50 percent of the dues paid for 12 months by former members of Cruz Fitness who are referred to their gym.
Cruz, who has been a trainer and manager in the past, took over ownership of the gym in January. It was previously a ZX Fitness and a Peak Fitness.
He said he has been in contact with his attorney regarding the situation.
You must be logged in to post a comment Login


text: 5 West Terrace, a period house with parking, is situated close to the Spa Pavilion in Whitby a short walk from the beach, seafront, amenities and shops. Whitby has a busy harbour where it is possible to see fishing boats landing their catch in the early morning and the ancient Abbey ruins. There are also festivals and fairs all the year.


text:
Iowa senior C.J. Fiedorowicz's development into one of the top 10 tight end prospects ahead of the 2014 NFL draft might not have been possible without the help of assistant coach D.J. Hernandez.
D.J.'s younger brother is former New England Patriots tight end Aaron Hernandez, who's currently in jail awaiting trial on several charges, including first-degree murder.
According to Eric Edholm of Yahoo! Sports, Fiedorowicz and Hernandez have a special relationship, which has helped the senior tight end develop his talent for a smooth transition to the pros.
Fiedorowicz said Hernandez addressed the team regarding his brother's situation in an emotional moment for everyone involved.
"He got to talk to his brother a few times, and he said he wrote him letters all the time," Fiedorowicz said. "I can't even imagine what going through that was like for him. We definitely bonded over that experience.
"But otherwise, he was the same guy around [the rest of the team] every day. He'd come in, tell us what we were doing that day, tell us what we were doing wrong, tell us how we needed to get better, tell us to pick our [stuff] up. He was on top of stuff.
"He pushed us hard. He's a good athlete, and he knows football," Fiedorowicz added. "And, obviously, he's seen his brother play, so he knows what it takes to be a great player."
At 6-foot-5 and 262 pounds, Fiedorowicz has the ideal size for an NFL tight end, and he caught 30 passes for 299 yards and six touchdowns for the Hawkeyes in 2013. Fiedorowicz caught a season-high four passes for 46 yards in Iowa's 21-14 loss to LSU in the Outback Bowl.
Fiedorowicz's ability to play a role in the passing game makes him an intriguing prospect for NFL teams in the weeks leading up to May's draft. As a complete tight end, he might even be a fit for the Patriots in the middle rounds.
"Fiedorowicz isn't the elite talent that [Rob] Gronkowski was coming out of Arizona, but he has a complete skill set" NESN.com Patriots editor Doug Kyed wrote. "If Gronkowski goes down again, the Patriots will need a tight end who can get open and help out in the run game. Fiedorowicz spent some time in the slot but looked most comfortable running routes from a three-point stance."
Fiedorowicz is projected to be drafted anywhere from the third to the fifth round, but luckily for him, many NFL teams need additional tight end depth.
Thumbnail photo via @IowaAthletics.
Powered by WordPress.com VIP


text:
The Buzz handicaps the Florida congressional races
As the special election in Pinellas' Congressional District 13 hurtles to a finish next week, it seems like a good time to update our Florida vulnerability rankings.
For the third straight cycle, the Buzz is handicapping the most vulnerable U.S. House seats in the Florida delegation. This is the first update we've done since July 2013. (We'll pick up the pace as Election Day 2014 approaches.) Quite a few of the seats have risen or fallen several notches over the past eight months.
Currently, Florida's U.S. House delegation includes 15 Republicans and 10 Democrats, plus two vacant seats, both of them previously held by Republicans.
The following list ranks incumbent House members from Florida by how vulnerable their party is to losing the seat. The seats are listed in descending order, based on the likelihood that they will switch party control.
1. District 13: Seat left vacant on the death of Rep. C.W. Bill Young (R). Previous ranking: 6
This Tampa Bay-area seat has attracted national attention as a potential bellwether for 2014 congressional races since the district is highly competitive between the parties. Young was a 22-term Republican incumbent, yet voters narrowly went for Barack Obama in both 2008 and 2012. The March 11 special election pits David Jolly, a former Young aide-turned-lobbyist, against Alex Sink, a former Florida state CFO and narrow loser in the 2010 gubernatorial race, in a big-money showdown. Democrats are cautiously hoping that the patterns of mail-in ballot returns so far suggest a slight boost for Sink. But the race will likely to go down to the wire.
2. District 2: Rep. Steve Southerland (R). Previous ranking: 3
The contest between two-term Republican Southerland, a tea party-aligned funeral director, and Democrat Gwen Graham, the daughter of popular former Sen. Bob Graham, rises one notch on our list, thanks to increasing attention and strong fundraising by the challenger. Graham took in more than $1.3 million and had more than $1 million in the bank during 2013, actually out-raising the incumbent, who raised about $1 million and banked $840,000 over the same period. Though this race has been overshadowed by the all-out push in the District 13 special election, Democratic groups have begun to zero in on Southerland. The Democratic Congressional Campaign Committee named the seat to its "Red to Blue" program that aids the party's most promising House challengers, and the political arm of the moderate-to-conservative Democratic Blue Dog Coalition has promised to support Graham. Southerland can expect his weaker financial haul to be bolstered by support from outside groups; the conservative Americans for Prosperity has already aired a pair of ads on his behalf. The district includes Democratic areas around Tallahassee as well as more Republican territory including Panama City; it leans modestly Republican, backing Mitt Romney in 2012.
3. District 26: Rep. Joe Garcia (D). Previous ranking: 2
Garcia remains vulnerable due to the resignation of top aides amid allegations of absentee-ballot fraud in the 2012 Democratic primary. In a close call, we're dropping this race by one slot, partly because the heat on Garcia has eased somewhat, and partly because the GOP still has a primary to sort out. The GOP field includes Miami-Dade school board member Carlos Curbelo, former Miami-Dade Commission chairman Joe Martinez, Cutler Bay Mayor Ed MacDougall, Miami lawyer Lorenzo Palomares-Starbuck and 2012 candidate Jose Felix Peixoto. Curbelo, a former congressional aide and political consultant, is the frontrunner, particularly after snagging the heavyweight endorsement of former GOP Gov. Jeb Bush. Democrats are hoping the Miami-area district's overall leanings -- voters backed Obama in 2012 by 7 percentage points -- will enable Garcia to win a second term in November.
4. District 18: Rep. Patrick Murphy (D). Previous ranking: 1
Murphy's seat is competitive -- the Treasure Coast district backed Romney in 2012 by a 52-48 margin, and Murphy won it in 2012 by fewer than 2,000 votes. But it's dropping three notches on our list because Murphy has dodged a bullet in the field of GOP challengers. Former GOP state Rep. Adam Hasner, who would have been a strong opponent for Murphy, has opted against a 2014 bid. The remaining Republicans in the hunt include former state Rep. Carl Domino, former Tequesta City Councilman Calvin Turnquest, and former Connecticut state Rep. Alan Schlesinger. The deep-pocketed Domino is considered likeliest to win the nomination, although his two most recent races -- for state Senate and state House -- both ended in primary losses. Murphy, meanwhile, has tried to burnish his moderate and local-oriented credentials, and he's raising money at a good clip. A wave against Democrats could make a difference in a district this narrowly divided, but it remains an open question whether any of the Republicans could take advantage of it.
5. District 16: Rep. Vern Buchanan (R). Previous ranking: 7
This far down our list, the chance of a partisan flip decreases significantly. Buchanan, despite a series of ethical issues, has consistently managed to hold on to his Republican-leaning seat in the Sarasota area. The Democrats have a potentially interesting -- but politically untested -- candidate in Henry Lawrence, who won three Super Bowl rings during his 13-year career with the Oakland and Los Angeles Raiders. (Democratic State Committeeman Mitch Mallett is also running.) However, national Democrats have yet to boost this contest into the top tier of takeover prospects, so we won't either.
6. District 10: Rep. Dan Webster (R). Previous ranking: 4
Webster's narrow 2012 re-election victory over Val Demings, the former police chief in Orlando, gave Democrats hope for 2014. But Demings opted to run for Orange County mayor, leaving the Democrats without a top-tier candidate in this GOP-leaning district in central Florida. The current Democratic field includes former Eustis City Commissioner Bill Ferree, Navy veteran Michael McKenna and attorney Shayan Modarres.
7. District 22: Rep. Lois Frankel (D). Previous ranking: 5
Frankel won her seat by defeating Hasner in a hotly contested open-seat race in 2012. But her surprisingly wide 10-point margin over Hasner in the Boca Raton-West Palm Beach district appears to have scared off top-tier challengers for 2014. The GOP field includes artist Andrea Leigh McGee, software engineer Jeremy Rodgers and contractor David Wagie. Neither party is expecting this seat to be anywhere near as competitive as it was two years ago.
8. District 19: Seat left vacant on the resignation of Rep. Trey Radel (R).Previous rating: Not rated
This seat came open when Radel resigned after a cocaine arrest. It's a solidly Republican district in the Naples-Fort Myers area, so most of the activity is on the GOP side. The presumed frontrunner for the April 22 primary is state Senate Majority Leader Lizbeth Benacquisto. Other contenders include former state Rep. Paige Kreegel -- who had been planning a primary bid against Radel even before the incumbent's downfall -- and businessman Curt Clawson. On the Democratic side, public relations executive April Freeman is the only announced candidate for the June 24 general election. But whoever wins the GOP primary is expected to prevail.


text:
VoR helps Russian and French Resistance vets meet after 60 years
Nikolai Vasenin, 93, is the only living cavalier of the Legion of Honour order. He said he had never forgotten his French friends he fought side by side with during the Second World War and the local woman he had been in love with ever since their first meeting in France.
On request of the Sverdlovsk governor and the Ekaterinburg World Expo 2020 Bid Committee, the Voice of Russia's journalist and editor Laurent Brayard has found Jeanne Monot and the rest of Nikolai Vasenin's comrades.
Over 60 years later, the world fair has helped restore the friendship of French and Russian soldiers who fought valiantly side by side during World War II, much like it has been connecting the two nations of Russia and France. The Voice of Russia will follow this story of reunification.
Voice of Russia


text:
Few writers have had as great an impact on London's literary landscape as Charles Dickens, so it's only appropriate that the Victorian author has a tourist attraction to his name in the English capital.
This summer in particular, families staying at luxury London hotels should strongly consider they pay the Charles Dickens Museum a visit. From July 30th, it'll be hosting an exciting programme of Family Fun Days – presenting workshops and handicrafts activities that should appeal to visitors of all ages.
In the first of these, craft specialist Claire Driver will be taking guests on a virtual trip to Broadstairs – a little town on the coast of Kent that was reputedly Dickens' favourite holiday destination. Armed with newly-acquired knowledge on the fascinating world of Victorian holidaymaking, museum-goers will commence making their own authentic 19th century postcards.
The second session takes place on August 6th. Ella Phillips, an artist-in-residence at the nearby October Gallery, will lead a workshop where children are taught to make handsome book covers.
On August 13th, children are invited to step inside Mrs Dickens' Kitchen and try their hand at churning butter – something they'll be doing using an authentic Victorian churn and Catherine Dickens' original recipe.
Finally, the last installment in the series should prove particularly exciting. In Monster Soup, visiting curators from the Kew Bridge Steam Museum invite children to discover the "gruesome monsters and horrors" that lurked in the Victorian Thames – and how resourceful 19th century engineers made sure the city's citizens still received clean drinking water. This session takes place on August 27th.
The Charles Dickens Museum is located at number 48, Doughty Street – an elegant terraced townhouse where Dickens resided between 1837 and 1839, penning such works as Oliver Twist and Nicholas Nickleby on the premises. It should prove easy to reach for those travelling via the London Underground, who're advised to head towards the Russell Square, Chancery Lane or Holborn tube stops.


text:
Would you like to be a member of our research panel? Join here - there's (nearly) always a great incentive offered for your views.
help!! chicken pox(3 Posts)
CatFaceCrayola Tue 22-Apr-14 16:42:02
Poshsausage Tue 22-Apr-14 15:56:28
CatFaceCrayola Tue 22-Apr-14 15:31:28
Join the discussion
Registering is free, easy, and means you can join in the discussion, get discounts, win prizes and lots more.Register now
Already registered with Mumsnet? Log in to leave your comment or alternatively, sign in with Facebook or Google.
Please login first.


text:
Have RV Questions? Ask an RV Mechanic Online.
Good morning, sorry for your trouble. let me ask you a few questions. When was the last time your had it running? Have you checked the compression? Are the spark plugs getting wet? I didn't understand what you were saying about gas pedal and engine dragging. Thanks for coming to Just Answers. Jim!!!


text:
White Choc Curl Wedding Cake
3 tier - carrot, chocolate sponge with chocolate ganache and white chocolate mousse with vanilla sponge, all iced in marscarpone cream and covered in chocolate cigarillo's - and no I did not make them myself as I ran out of time so had to buy them in. I was very disappointed with the flowers that the florist did for the cake and think that they do not sd the cake justice. I was happy with the construction and composition of the cake and it was as steady as a rock, even during transport.
You May Also Be Interested In
Comments (3)
the cake looks great - and sounds yummy...I kind of agree - the flowers should have been more elegant to top a cake like that.
Absolutely stunning. Have to agree with the flowers but it does sound delicious.
Oh I wanted to ask...would you mind mailing me the recipe for the marscarpone cream?


text:
AMP-activated protein kinase (AMPK) is a major mediator of the exercise response and a molecular target to improve insulin sensitivity. To determine if the anaerobic component of the exercise response, which is exaggerated when sprint is performed in severe acute hypoxia, influences sprint exercise-elicited Thr172-AMPKα phosphorylation, 10 volunteers performed a single 30-s sprint (Wingate test) in normoxia and in severe acute hypoxia (inspired Po2: 75 mmHg). Vastus lateralis muscle biopsies were obtained before and immediately after 30 and 120 min postsprint. Mean power output and O2 consumption were 6% and 37%, respectively, lower in hypoxia than in normoxia. O2 deficit and muscle lactate accumulation were greater in hypoxia than in normoxia. Carbonylated skeletal muscle and plasma proteins were increased after the sprint in hypoxia. Thr172-AMPKα phosphorylation was increased by 3.1-fold 30 min after the sprint in normoxia. This effect was prevented by hypoxia. The NAD+-to-NADH.H+ ratio was reduced (by 24-fold) after the sprints, with a greater reduction in hypoxia than in normoxia (P < 0.05), concomitant with 53% lower sirtuin 1 (SIRT1) protein levels after the sprint in hypoxia (P < 0.05). This could have led to lower liver kinase B1 (LKB1) activation by SIRT1 and, hence, blunted Thr172-AMPKα phosphorylation. Ser485-AMPKα1/Ser491-AMPKα2 phosphorylation, a known negative regulating mechanism of Thr172-AMPKα phosphorylation, was increased by 60% immediately after the sprint in hypoxia, coincident with increased Thr308-Akt phosphorylation. Collectively, our results indicate that the signaling response to sprint exercise in human skeletal muscle is altered in severe acute hypoxia, which abrogated Thr172-AMPKα phosphorylation, likely due to lower LKB1 activation by SIRT1.
- sprint
- AMP-activated protein kinase
- signaling
- muscle
- metabolism
amp-activated protein kinase (AMPK) is a metabolic energy sensor activated by Thr172 phosphorylation of the α-subunit, mainly in response to an increase of the AMP-to-ATP ratio (25). AMPK is involved in the regulation of feeding and body weight (42), lipid metabolism (26), glucose homeostasis (62), and mitochondrial biogenesis (69) and is a key player in the adaptation to exercise training (48). AMPKα phosphorylation of Thr172 increases markedly in response to sprint exercise (22), most likely due to the elevation of the AMP-to-ATP ratio (11). Whether free radicals may also play a role in contraction-mediated Thr172-AMPKα phosphorylation in skeletal muscle remains controversial (41, 52). In cell cultures, hypoxia and anoxia increase Thr172-AMPKα phosphorylation more through the release of free radicals than through an increase in the AMP-to-ATP ratio (15). In contrast, chronic hypoxia (5 and 12 days of exposure to 5,500 m above sea level) did not increase skeletal muscle Thr172-AMPKα phosphorylation in rats (10).
The influence of the inspired O2 fraction (FiO2) on exercise-induced Thr172-AMPKα phosphorylation has been scarcely studied in humans (63). After 30 min of exercise at 73% of peak O2 consumption (V̇o2 peak), Thr172-AMPKα phosphorylation was greater in normoxia than in hypoxia. This apparent unexpected finding was explained by the higher absolute intensity during the exercise in normoxia, which was associated with a higher calculated free ADP muscular concentration, without significant effects on the AMP-to-ATP ratio attributable to hypoxia (63). Thus, exercise intensity is an important factor determining the Thr172-AMPKα phosphorylation response to exercise. The intensity factor may be controlled by asking the subjects to perform an all-out exercise, such as the Wingate test. During Wingate tests in severe acute hypoxia, peak and mean power output are barely affected; however, anaerobic energy release is increased (8, 37).
In this background, we hypothesized that the combination of high-intensity exercise (sprint exercise) and hypoxia would result in additive or synergistic effects on Thr172-AMPKα phosphorylation, due to the convergence of a high energy turnover with a greater glycolytic rate (38) and, potentially, greater release of free radicals (9) in hypoxia than in normoxia.
Thr172-AMPKα phosphorylation by a rise of the AMP-to-ATP ratio is liver kinase B1 (LKB1) dependent (25). LKB1 is also activated by the deacetylase sirtuin 1 (SIRT1) an NAD+-dependent deacetylase that is activated by the increase of NAD+/NADH.H+ (58). Although most human studies have reported reduction of NAD+/NADH.H+, little is known about the effect of sprint exercise on NAD+/NADH.H+ (64). Since NAD+/NADH.H+ is expected to be reduced at high glycolytic rates, and since greater glycolytic rates are attained during sprint exercise in hypoxia than in normoxia (38), we hypothesized that cytosolic (and nuclear) NAD+/NADH.H+ would be lower after sprint exercise in hypoxia. If this mechanism prevails, this could result in lower or no phosphorylation of AMPKα after sprint exercise in hypoxia, due to lower LKB1 activity.
Among others, alternative kinases upstream to AMPK are Ca2+/calmodulin-dependent protein kinase II (CaMKII) and transforming growth factor-β-activated kinase 1 (TAK-1) (14, 68). Upon activation by phosphorylation, CaMKII can phosphorylate AMPK during exercise (14). Likewise, TAK-1, which is activated by phosphorylation, has been shown to phosphorylate AMPKα in vitro (43). In cardiac myocytes, TAK-1 is likely acts upstream of LKB1 (68).
Insulin antagonizes anoxia or ischemia-induced AMPKα phosphorylation through Ser485-AMPKα1/Ser491-AMPKα2 phosphorylation (31), which may be produced by Akt (34, 55). In agreement with these findings in cardiac myocytes (31, 34, 55), we observed that sprint exercise-elicited AMPKα phosphorylation in skeletal muscle was prevented by the ingestion of 75 g of glucose 1 h before the start of the sprint (22). Although it is well established that circulating levels of glucose and insulin increase immediately after sprint exercise (18, 22), it remains unknown if this response is modified when the sprint is performed in severe acute hypoxia. Greater or prolonged exercise-induced elevation of both plasma glucose and insulin could blunt the Thr172-AMPKα phosphorylation normally observed 30 min after sprint exercise (23) through Ser485-AMPKα1/Ser491-AMPKα2 phosphorylation, while a reduced insulin response could be associated with even greater Thr172-AMPKα phosphorylation.
Therefore, the main aim of this study was to determine if hypoxia increases skeletal muscle Thr172-AMPKα phosphorylation in response to sprint exercise, by examining potential endocrine, metabolic, and signaling mechanisms. More specifically, by determining muscle lactate (Lac) responses and the accumulated O2 deficit incurred during sprints (8), combined with the assessment of muscle and plasma carbonylated proteins (49), we expected to determine whether potential changes in sprint-exercise elicited Thr172-AMPKα phosphorylation are associated with oxidative stress and the anaerobic component of the exercise response, which should be exaggerated when the sprint is performed in severe acute hypoxia (8). By assessing the protein levels of SIRT1, we determined if sprint exercise changes in SIRT1 protein levels could, by modifying LKB1 activity, regulate Thr172-AMPKα phosphorylation. Moreover, by determining glucose and plasma insulin responses, combined with the assessment of Ser485-AMPKα1/Ser491-AMPKα2 and Ser473/Thr308-Akt phosphorylation, we expected to determine if the degree of Thr172-AMPKα phosphorylation is modulated by hypoxia through a Ser485-AMPKα1/Ser491-AMPKα2 phosphorylation-dependent mechanism.
The complete protease inhibitor cocktail and the PhosSTOP phosphatase inhibitor were obtained from Roche Diagnostics (Mannheim, Germany). All primary antibodies used were from Cell Signaling Technology (Denvers, MA) except for polyclonal anti-phospho-AS160 [Thr642, no. AT-7079; molecular mass: 160 kDa], which was obtained from MBL (Woburn, MA), anti-CaMKII antibody (no. sc-13082, molecular mass: 50 kDa), which was obtained from Santa Cruz Biotechnology (Santa Cruz, CA), and monoclonal mouse anti-α-tubulin antibody (no. T-5168-ML, molecular mass: 50 kDa), which was obtained from Biosigma (Sigma, St. Louis, MO). The corresponding catalog numbers of the antibodies from Cell Signaling were as follows: anti-phospho-AMPKα (Thr172), no. 2531 (molecular mass: 62 kDa); anti-AMPKα, no. 2532 (molecular mass: 62 kDa); anti-phospho-AMPKα1 (Ser485)/AMPKα2 (Ser491), no. 4185 (molecular mass:62 kDa); anti-phospho-AMPKα1 (Ser485), no. 4184 (molecular mass: 62 kDa); anti-AMPKα1, no. 2795 (molecular mass: 62 kDa); anti-phospho-acetyl-CoA carboxylase (ACC; Ser221), no. 3661 (molecular mass: 280 kDa); anti-ACC, no. 3662 (molecular mass: 280 kDa); anti-SIRT1, no. 2310 (molecular mass: 120 kDa); anti-phospho-Akt (Ser473), no. 9271 (molecular mass: 60 kDa); anti-phospho-Akt (Thr308), no. 9275 (molecular mass: 60 kDa); anti-Akt, no. 9272 (molecular mass: 60 kDa); anti-phospho-TAK-1 (Thr184/187), no. 4531 (molecular mass: 82 kDa); anti-TAK-1, no. 4505 (molecular mass: 82 kDa); anti-phospho-CaMKII (Thr286), no. 3361 (molecular mass: 50 kDa); and AS160, no. 2447 (molecular mass: 160 kDa). The secondary horseradish peroxidase (HRP)-conjugated goat anti-rabbit (no. 111-035-144) and HRP-conjugated donkey anti-mouse (no. 715-035-150) antibodies were from Jackson ImmunoResearch (West Grove, PA). The Immun-Blot polyvinylidene difluoride membranes, Inmmun-Star WesternC, ChemiDoc XRS System, and image-analysis software (Quantity One) were obtained from Bio-Rad Laboratories (Hertfordshire, UK).
Ten healthy male physical education students (age: 25 ± 4 yr, height: 176.7 ± 5.3 cm, body weight: 80.2 ± 9.9 kg, body fat: 18.2 ± 6.3%) agreed to participate in this investigation (Table 1). Before volunteering, subjects received full oral and written information about the experiments and possible risks associated with participation. Written consent was obtained from each subject. This study was performed in accordance with the Helsinki Declaration and was approved by the Ethical Committee of the University of Las Palmas de Gran Canaria (CEIH-2010-01).
General procedures.
The subjects' body composition was determined by dual X-ray absorptiometry (Hologic QDR-1500, Hologic, software version 7.10, Waltham, MA) as previously described (2, 47). Subjects reported to the laboratory to complete different tests on separate days. First, their V̇o2 peak, maximal heart rate, and maximal power output in normoxia (FiO2: 0.21; barometric pressure: 735–745 mmHg) and hypoxia (FiO2: 0.104; barometric pressure: 735–745 mmHg) were assessed with ramp incremental exercise tests to exhaustion (50 W/min) on an Excalibur Sport 925900 (Lode, Groningen, The Netherlands). One week before the exercise, subjects were familiarized with the experimental protocol (a single 30-s isokinetic Wingate test at 100 rpm). On separate days and in random order, they performed one 30-s isokinetic Wingate test at 100 rpm in normoxia and another test in hypoxia. On each trial day, subjects reported to the laboratory at 8.00 AM, after an overnight fast, and an antecubital vein was catheterized. After a 10-min resting supine period, a 20-ml blood sample was withdrawn and used to measure serum glucose and insulin. Right after, a muscle biopsy was obtained from the middle portion of the vastus lateralis muscle using Bergstrom's technique with suction, as previously described (46). After the preexercise muscle biopsy, subjects sat on the cycle ergometer for 4 min. During this period, they breathed either room air (normoxia) or a hypoxic gas mixture from a Douglas bag containing 10.4% O2 in N2 (hypoxia). The Douglas bag was replenished with gas from a cylinder specially prepared for the experiment (Carburos metálicos, gas mixture 206030, Las Palmas de Gran Canaria).
During both sprints, subjects attempted to pedal as fast and hard as possible (i.e., all out) from the start to the end of the exercise. Since the cycle ergometer (Excalibur Sport, Lode) was set to isokinetic mode, the braking force was a servo controlled by the Ergometer applying the braking force needed to maintain a fixed pedaling rate of 100 rpm. The latter was possible because as subjects fatigued, the ergometer automatically decreased the braking force.
Peak power output was calculated as the highest work output performed during 1-s interval, and mean power output was calculated from the average work performed during the 30 s. Warm up was not allowed before the start of the Wingate test, and stop-start Wingate tests were performed by both groups, meaning that the Wingate test was not preceded by a phase of unloaded pedaling (7, 8, 23).
Within 10 s from the end of the sprint, a second muscle biopsy was taken, and another blood sample was then obtained. During the following 2 h, subjects fasted but had free access to water and sat quietly in the laboratory. During the recovery period, two additional muscle biopsies and blood samples were obtained at 30 and 120 min. For the last two biopsies, a new incision was performed in the contralateral leg. To avoid injury-triggered activation of signaling cascades, the muscle biopsies were obtained at least 3 cm apart, using the procedures described by Guerra et al. (21). Muscle specimens were cleaned to remove any visible blood, fat, or connective tissue. Muscle tissue was the immediately frozen in liquid nitrogen and stored at −80°C for later analysis. The time needed to obtain and freeze the muscle biopsies was below 30 s.
Cycling economy tests.
Cycling economy was determined on two different days using 8–11 submaximal workloads at intensities between 50% and 90% of V̇o2 peak at 100 rpm. Exercise intensities and pedaling rates were administered in random order, separated by rest periods of 6 min. To reduce thermal stress and minimize water losses due to sweating, subjects were fan cooled and ingested fresh water during the resting periods ad libitum. The duration of each submaximal bout was set at 10 min. The mean V̇o2 registered during the last 2 min was taken as representative of each submaximal exercise intensity. To relate V̇o2 to power, linear regression equations were calculated by least-square linear fit.
O2 uptake and hemoglobin O2 saturation.
O2 uptake was measured with a metabolic cart (Vmax N29, Sensormedics) calibrated immediately before each test according to the manufacturer's instructions. Respiratory variables were analyzed breath by breath and averaged every 5 s during the Wingate test and every 20 s during the incremental and cycling economy tests. The highest 20-s averaged V̇o2 recorded in normoxia was taken as V̇o2 peak. The same criterion was applied to determine V̇o2 peak in severe acute hypoxia. The hemoglobin O2 saturation was determined with a finger pulse oxymeter (Excalibur Sport 925900, Lode).
Muscle metabolites.
From each muscle biopsy, 30 mg of wet tissue were treated with 0.5 M HClO4 and centrifuged at 15,000 g at 4°C for 15 min. The supernatant was neutralized with KHCO3 (2.1 M), and ATP, phosphocreatine (PCr), creatine (Cr), pyruvate (Pyr), and Lac were enzymatically determined in neutralized extracts by fluorometric analysis (20, 36). Muscle metabolite concentrations were adjusted to the individual mean total Cr (PCr + Cr) because this mean should remain constant during exercise (27). The adjustment to total Cr content accounts for the variability in solid nonmuscle constituents, which may be present in the biopsies (45). The glycolytic rate was calculated as follows: glycolytic rate = 0.5 × (ΔLac + ΔPyr) (57). The free AMP-to-ATP molar ratio was estimated after we calculated the ADP concentration using the creatine kinase equilibrium apparent constant for resting conditions and exhaustion after a Wingate test (45), as described by Sahlin et al. (51). Subsequently, the AMP concentration was calculated using the adenilate kinase apparent equilibrium constant for the same conditions (45). The NAD+/NADH.H+ concentration was calculated using the equilibrium constant for Lac dehydrogenase (6, 66).
Total protein extraction, electrophoresis, and Western blot analysis.
Muscle protein extracts were prepared as previously described (24), and total protein content was quantified using the bicinchoninic acid assay (54). Briefly, proteins were solubilized in sample buffer containing 0.0625 M Tris·HCl (pH 6.8), 2.3% (wt/vol) sodium dodecyl sulfate (SDS), 10% (vol/vol) glycerol, 5% (vol/vol) β-mercaptoethanol, and 0.001% (wt/vol) bromophenol blue. Equal amounts (50 μg) of each sample were electrophoresed with 7.5–10% SDS-PAGE using the system of Laemmli (35) and transferred to Hybond-P membranes. To determine Thr172-AMPKα, Ser485-AMPKα1/Ser491-AMPKα2, Ser485-AMPKα1, Ser221-ACCβ, Ser473-Akt, Thr308-Akt, Thr184/187-TAK-1, Thr286-CaMKII, and Thr642-AS160 phosphorylation levels, antibodies directed against the phosphorylated and total forms of these kinases were diluted in 5% BSA in Tris-buffered saline with 0.1% Tween 20 (TBS-T; BSA-blocking buffer). SIRT1 was assessed in membranes incubated with a SIRT1 antibody (diluted in BSA-blocking buffer). To control for differences in loading and transfer efficiency across membranes, membranes were incubated with a monoclonal mouse anti-α-tubulin antibody diluted in TBS-T with 5% blotting grade blocker nonfat dry milk (blotto blocking buffer). No significant changes were observed in α-tubulin protein levels during the experiments (data not shown). Antibody-specific labeling was revealed by an incubation with HRP-conjugated goat anti-rabbit antibody (1:20,000) or HRP-conjugated donkey anti-mouse antibody (1:10,000), with both diluted in 5% blotto blocking buffer, and visualized with the Immun-Star WesternC kit (Bio-Rad Laboratories). Densitometry analyses were carried out immediately before saturation of the immunosignals. Specific bands were visualized with the Immun-Star WesternC kit using the ChemiDoc XRS system (Bio-Rad Laboratories) and analyzed with Quantity One (Bio-Rad Laboratories). Muscle signaling data are represented as percentages of the immunostaining values obtained for the phosphorylated form of each kinase relative the respective total form.
Samples from each subject were run on the same gel (hypoxic and normoxic conditions). In addition, in all gels, a human muscle sample obtained from a healthy young man was used as an internal control, to reduce intergel variability.
Insulin measurements.
Serum insulin was measured by an ECL immunoassay intended for use on Modular Analytics analyzer E170 using insulin kit reagents (Roche/Hitachi, Indianapolis, IN). Insulin sensitivity was 0.20 μIU/ml.
Serum glucose.
Serum glucose was measured by the hexokinase method using Gluco-quant reagents (11876899216, Roche/Hitachi) with a sensitivity of 2 mg/dl.
Protein carbonylation.
Protein carbonylation in skeletal muscle and plasma was assessed by immunoblot detection of protein carbonyl groups using the "OxyBlot" protein oxidation kit (Intergen, Purchase, NY) as previously described (49). Protein carbonylation data are represented as percentages of immunostaining values.
Variables were checked for normal distribution using the Kolmogorov-Smirnov test with the Lilliefors correction. When necessary, the analysis was carried out on logarithmically transformed data. For between-trial comparisons, individual responses were normalized to the level of phosphorylation observed just before the start of the Wingate test. Repeated-measures ANOVA over time and oxygenation condition with two levels (normoxia vs. hypoxia) was used to compare the responses with the values before the start of the Wingate test. When there was a significant condition effect or condition × time interaction (FiO2 × time), pairwise comparisons at specific time points were adjusted for multiple comparisons with the Holm-Bonferroni method. The relationship between variables was determined using linear regression analysis. Areas under the curve (AUCs) were determined using the trapezoidal rule and compared between conditions with paired Student t-tests. Values are reported as means ± SE (unless otherwise stated). P values of ≤0.05 were considered significant. Statistical analysis was performed using SPSS (version 15.0) for Windows (SPSS, Chicago, IL).
Performance and ergospirometric variables.
Ergoespirometric and performance-related variables are shown in Table 1. Compared with normoxia, mean power output and accumulated V̇o2 were reduced in hypoxia by 6% and 37%, respectively (P < 0.05).
Serum glucose, insulin, and carbonylated plasma proteins.
Compared with resting values, the serum glucose concentration was increased by 11% immediately after the sprints and remained at this level 30 min later (P < 0.05). Compared with resting values, the serum insulin concentration was elevated by 62% immediately after the sprint in normoxia (P < 0.05) and was further increased to 2.2-fold (the preexercise concentration) 30 min postsprint, with a similar response in both conditions (P < 0.05). Serum glucose and insulin concentrations decreased to values similar to those observed before the sprint 120 min after the exercise (Table 2).
Compared with normoxia, carbonylated plasma protein AUCs were 26% greater after the sprints in hypoxia (P < 0.05; Fig. 1A).
Muscle metabolites.
The changes observed in muscle metabolites are shown in Table 3. The AMP-to-ATP molar ratio was similarly increased (×24-fold) immediately after the sprints, regardless of FiO2. The glycolytic rate was 50% greater in hypoxia than in normoxia (P < 0.05). Compared with resting values, immediately after the sprint, the muscle pyruvate concentration was increased by 2.7- and 1.7-fold in normoxia and hypoxia, respectively (FiO2 × time interaction, P < 0.05). The corresponding muscle Lac concentration changes were 14- and 24-fold (FiO2 × time interaction, P < 0.05). Consequently, the muscle Lac concentration after the sprint was 48% higher in hypoxia than in normoxia (P < 0.05). After the sprints, the Lac-to-Pyr ratio was increased by 4- and 14-fold in normoxia and hypoxia (P < 0.05, FiO2 × time interaction, P < 0.05 by ANOVA). Consequently, immediately after the sprints, the NAD+-to-NADH.H+ ratio was reduced by 87% and 95% in normoxia and hypoxia, respectively (both P < 0.05). This reduction was more marked in hypoxia than in normoxia (P < 0.05).
Skeletal muscle carbonylated proteins.
The AUC for carbonylated proteins in skeletal muscle was 50% greater after the sprint in hypoxia compared with in normoxia (P < 0.05; Fig. 1B).
Muscle signaling.
Thr172-AMPKα phosphorylation was increased by 3.1-fold 30 min after the Wingate test in normoxia (P < 0.05; Fig. 2A). Hypoxia prevented the exercise-induced AMPKα phosphorylation at 30 min (P < 0.05). However, ACCβ phosphorylation was increased by 2.4- and 2.7-fold immediately after and 30 min into the recovery period, respectively (both P < 0.05), with a similar response in both conditions (Fig. 2B).
Compared with resting values, Thr286-CaMKII phosphorylation was increased by 32% at 30 and 120 min after the sprints (both P < 0.05; Fig. 2C), without significant differences between conditions. No statistically significant changes were observed in Thr184/187-TAK-1 phosphorylation after both sprints (Fig. 2D).
Ser485-AMPKα1/Ser491-AMPKα2 phosphorylation levels were increased by 60% immediately after the sprint performed in hypoxia (P < 0.05), whereas they remained unchanged after the normoxic sprint (FiO2 × time interaction, P < 0.05 by ANOVA; Fig. 3A). No significant changes in Ser485-AMPKα1 phosphorylation were observed after both sprints (Fig. 3B). Compared with normoxia, the AUC for SIRT1 protein expression was 53% lower after the sprint in hypoxia (P < 0.05; Fig. 3C).
No significant between-condition differences were observed in Ser473-Akt phosphorylation. Ser473-Akt phosphorylation was increased by 2.2- and 1.14-fold at 30 and 120 min after the sprint, respectively (both P < 0.05; Fig. 4A). Thr308-Akt phosphorylation was increased by 2.4-fold just after the exercise (P < 0.05). This response was more accentuated in hypoxia, as reflected by the Thr308-Akt phosphorylation AUC, which was 87% higher after the sprint in hypoxia (P < 0.05; Fig. 4B).
Thr642-AS160 phosphorylation was increased by 47% and 35% at 30 and 120 min after the sprints (both P < 0.05 compared with the value immediately postexercise), with comparable responses in both sprints (Fig. 4C).
This study examined the influence of FiO2 on the regulation of skeletal muscle AMPKα phosphorylation in response to a 30-s sprint exercise in humans. In contrast to our hypothesis, hypoxia blunted the expected AMPKα phosphorylation 30 min after exercise, and this effect was preceded by Ser485-AMPKα1/Ser491-AMPKα2 phosphorylation, a known inhibitory mechanism of Thr172-AMPKα phosphorylation (31). The sprint performed in severe acute hypoxia elicited greater reductions of the NAD+-to-NADH.H+ ratio combined with a higher glycolytic rate and oxidative stress, as reflected by the increased accumulation of intramuscular Lac and the elevated levels of carbonylated proteins in muscle and plasma during the recovery period. We have also shown that sprint exercise in hypoxia reduced SIRT1 protein levels, which combined with a lower NAD+-to-NADH.H+ ratio at the end of the sprint, could have led to lower LKB1 activation by SIRT1 and, hence, reduced Thr172-AMPKα phosphorylation.
Lac-to-Pyr and NAD+-to-NADH.H+ ratios and muscle signaling.
The observed intramuscular accumulation of Lac is due to the enormous energy demand generated during the sprint, which was accounted for by an extremely high glycolytic rate surpassing the mitochondrial capacity to oxidize pyruvate. In the present investigation, hypoxia reduced the mean power by only 6%, despite a 37% lower V̇o2, reflecting a lower mitochondrial capacity to oxidize Pyr in hypoxia due to reduced O2 delivery. To compensate for the reduction in oxidative energy yield, the glycolytic rate was increased by 50% during the sprint in hypoxia compared with the sprint in normoxia. These findings agree with the observed 14% greater O2 deficit (ml O2/wt) during the sprint in hypoxia (8, 39).
The increased glycolytic rate in hypoxia elicited higher muscle Lac accumulation and a greater Lac-to-Pyr ratio. Consequently, the calculated cytoplasmatic NAD+-to-NADH.H+ ratio (50, 66) was largely reduced after the sprint in hypoxia than in normoxia.
During exercise, the main mechanism leading to Thr172-AMPKα phosphorylation is an increase of free AMP (relative to ATP) (67), which acts allosterically via the γ-subunit to enhance the phosphorylation of Thr172-AMPKα by LKB1 kinase (28) and to suppress dephosphorylation by protein phosphatases 2A and 2C in vitro (12). Despite the greater anaerobic energy yield during the sprint in hypoxia, the calculated free AMP-to-ATP ratio was increased to the same extent as in normoxia. Thus, our findings cannot be explained in terms of blunted AMP-dependent activation. In addition to AMP, SIRT1, an NAD-dependent deacetylase that acts as a master metabolic sensor of NAD+, may deacetylate (and activate) LKB1 (32). Incubation of HepG2 cells in a Pyr-enriched medium results in increased SIRT1 protein expression and Thr172-AMPKα phosphorylation (58), likely linked to an elevation of the ratio of NAD+ to NADH.H+. SIRT1 activity may be reduced by lower NAD+ and loss of SIRT1 protein (19), which were both observed in the present investigation after the sprint exercise in hypoxia. Thus, the combined effect of lower NAD+ and loss of SIRT1 protein could have blunted the activation of LKB1 in hypoxia and, hence, the phosphorylation of AMPKα at Thr172.
In agreement with our results, insulin or glucose induces JNK1 phosphorylation in cell cultures, which, in turn, causes Ser47-SIRT1 phosphorylation (19). SIRT1 phosphorylation causes its translocation to the nucleus and an increase of its deacetylase activity while committing SIRT1 to degradation at the proteasome (19). The latter reduces SIRT1 protein levels within 30 min (19). Although in the present investigation insulin and plasma glucose responses to the sprints could not explain the changes observed in SIRT1 protein levels, it is known that in cell cultures H2O2 induces JNK1 phosphorylation, which then phosphorylates SIRT1 (44). Thus, the greater oxidative stress triggered by the sprint exercise in hypoxia may have led to a loss of SIRT1 protein through JNK1 and SIRT1 phosphorylation, followed by proteasome degradation of SIRT1.
The observed reduction of SIRT1 protein levels after the sprint in hypoxia was accompanied by increased Thr308-Akt phosphorylation. Interestingly, resveratrol (a SIRT1 activator) decreases phosphoinositide 3-kinase activation in cultured muscle cell lines (17). Since phosphoinositide 3-kinase is an upstream kinase for Thr308-Akt phosphorylation (30), the reduced SIRT1 protein levels after the sprint in hypoxia could account, at least in part, for the increased Thr308-Akt phosphorylation.
Free radicals.
Free radicals have been found to be inducers of Thr172-AMPKα phosphorylation by several mechanisms (56), and hypoxia has been shown to increase Thr172-AMPKα phosphorylation by a mechanism involving mitochondrial ROS independently of the AMP-to-ATP ratio (15). In the present investigation, during the 120 min after the sprint in hypoxia, carbonylated muscle and plasma proteins were increased, indicating greater oxidative stress after the sprint in hypoxia than in normoxia. The fact that carbonylated proteins increased not only in muscle but also in plasma indicates that some free radicals reached the circulation (3). Protein carbonylation is a good marker of increased oxidative stress (4, 53); however, free radicals could have reacted with other molecules (3), implying that the actual difference in oxidative stress between normoxia and hypoxia could have been even greater.
Increased levels of ROS may activate CaMKII through modification of the Met-281/282 pair within the regulatory domain, blocking reassociation with the catalytic domain and preserving kinase activity via a similar but parallel mechanism to Thr286 autophosphorylation (16). Moreover, the ability of CaMKII to respond to Ca2+ elevation is enhanced under prooxidant conditions (16). However, despite increased oxidative stress after the sprint performed in hypoxia, no significant differences were observed between conditions in the exercise-induced CaMKII phosphorylation. Thus, the lack of Thr172-AMPKα phosphorylation in response to the sprint in hypoxia cannot be attributed to lower CaMKII phosphorylation.
Ser485-AMPKα1/Ser491-AMPKα2 is increased after the sprint in hypoxia: a potential inhibitory mechanism of Thr172-AMPKα phosphorylation.
This finding confirms previous work from our laboratory showing an abrogation of Thr172-AMPKα phosphorylation by enhanced Ser485-AMPKα1/Ser491-AMPKα2 phosphorylation induced by the ingestion of 75 g of glucose before sprint exercise (22). Like in Guerra et al. (22), sprint exercise elicited a twofold elevation of serum insulin levels 30 min after the sprints. This increase in circulating insulin could account for the Akt and AS160 phosphorylation observed at the same time point (30 min after the sprint). However, immediately after the sprints, Akt phosphorylation (Thr308) was observed in hypoxia only, and this occurred with minor changes in circulating insulin. Thus, the effect of FiO2 on Thr172-AMPKα and Ser485-AMPKα1/Ser491-AMPKα2 phosphorylation does not seem mediated by the insulin response. The latter, together with the fast Ser485-AMPKα1/Ser491-AMPKα2 response (already present 10 s after the sprint), indicates that this phosphorylation is likely triggered by an intracellular mechanism. In fact, PKB (Akt) (31) and PKA (33) can phosphorylate AMPKα1/α2 at Ser485/491, which inhibits AMPK phosphorylation at Thr172. Thirty minutes after the sprint in hypoxia, the expected Thr172-AMPKα phosphorylation (18, 22) was absent, and this was preceded by increased Thr308-Akt phosphorylation immediately after the sprint in hypoxia. As expected with greater Akt phosphorylation, Ser485-AMPKα1/Ser491-AMPKα2 phosphorylation levels were increased immediately after the sprint exercise in hypoxia. This finding agrees with results from our previous study (22), in which glucose ingestion 1 h before a similar sprint prevented the expected Thr172-AMPKα phosphorylation through a Ser485-AMPKα1/Ser491-AMPKα2 phosphorylation-dependent mechanism. The ultimate mechanism leading to Ser485-AMPKα1/Ser491-AMPKα2 phosphorylation remains to be elucidated, since the present results do not support insulin as the main mechanism causing the observed Ser485-AMPKα1/Ser491-AMPKα2 phosphorylation immediately after the exercise in hypoxia. The fact that Thr308-Akt phosphorylation was elevated 30 min after the sprint in hypoxia indicates that additional mechanisms regulate Ser485-AMPKα1/Ser491-AMPKα2 phosphorylation.
Increased levels of cellular cAMP may blunt Thr172-AMPKα phosphorylation by inhibition of Ca2+/calmodulin-dependent kinase kinase-β [an AMPK kinase (29)] but not LKB1 (33). Moreover, Hurley et al. (33) have shown that phosphorylation of the Ser485/491 site appears to be required but not sufficient to inhibit AMPK under conditions of elevated cAMP. It remains to be determined if muscle cAMP levels are differently altered by sprint exercise depending on FiO2.
TAK-1 acts like an AMPK kinase (68), which may be stimulated by hypoxia (5, 40). However, in the present work, Thr184/187-TAK-1 phosphorylation did not change after the sprint, regardless of FiO2, i.e., our results cannot be attributed to differences in TAK-1 phosphorylation.
Thr642-AS160 phosphorylation response to sprint exercise.
Muscle contraction, insulin, hypoxia, and other stimuli raising intracellular Ca2+ promote muscle glucose uptake by increasing plasma membrane glucose transporter 4 (GLUT4) content (59, 65). Most of these signals evoke AS160 phosphorylation, which increases GLUT4 translocation to the membrane (59). Akt, AMPKα2, PKC, and CaMKII may phosphorylate AS160 (59). There is little information on the effects of exercise on AS160 phosphorylation in human skeletal muscle (13, 59–61). These results confirm those of our previous study (22), i.e., small AS160 phosphorylation in response to a single bout of sprint exercise at least at Thr642 with the PAS antibody. As a new finding, we have shown that despite the higher anaerobic component and greater oxidative stress after the sprint in hypoxia, these two factors did not influence the Thr642-AS160 phosphorylation response to sprint exercise. The small increase in AS160 phosphorylation from 30 to 120 min after the sprint could have enhanced membrane GLUT4 abundance for at least 2 h after the sprint. Another interesting finding is that Thr642-AS160 phosphorylation does not require increased Thr172-AMPKα phosphorylation, since hypoxia blunted the Thr172-AMPKα phosphorylation without any significant effect on Thr642-AS160 phosphorylation. Moreover, Thr308-Akt phosphorylation was increased after the sprint in hypoxia without apparent effects on Thr642-AS160 phosphorylation. Although Ser473-Akt was increased 30 and 120 min after the sprints, for full activation of Akt, both Thr308 and Ser473 phosphorylations are required (1). Thus, other mechanisms should also play a role in exercise-induced Thr642-AS160 phosphorylation. Moreover, it remains unknown what the effects of sprint exercise are on other AS160 phosphorylation sites (61).
In summary, we have shown that sprint exercise in severe acute hypoxia elicits a greater glycolytic rate with a higher accumulation of muscle Lac, increased Lac-to-Pyr ratios, and, hence, reduced NAD+-to-NADH.H+ ratios. Consequently, the human skeletal muscle signaling response to sprint exercise is modified in hypoxia. Acute hypoxia blunted the expected increase in Thr172-AMPKα phosphorylation, and this article provides results with two potential mechanisms to explain this response. First, the lower NAD+-to-NADH.H+ ratio after the sprint in hypoxia combined with the reduced SIRT1protein levels may have blunted the SIRT1/LKB1-mediated phosphorylation of AMPKα. Second, Thr172-AMPKα phosphorylation may have been blunted due to increased Ser485-AMPKα1/Ser491-AMPKα2 phosphorylation, a known mechanism of Thr172-AMPKα phosphorylation inhibition mediated by Akt. The latter concords with the greater increase of Akt phosphorylation observed immediately after the sprint in hypoxia. Finally, we have shown that AS160 phosphorylation was elevated 30–120 min after the sprints, regardless of FiO2 and despite the differences in AMPK and Akt phosphorylation responses. These findings may have important implications in terms of better understanding the potential differences in acute and adaptive responses to exercise in humans with chronic hypoxia or increased oxidative stress, such as in patients with chronic lung diseases or in chemotherapy.
This work was supported by Ministerio de Educación y Ciencia Grants DEP2009-11638 and DEP2010-21866 and El Fondo Europeo de Desarrollo Regional, Fundación Canaria de Investigación y Salud Grant PI/10/07, Programa Innova Canarias 2020 Grant P.PE03-01-F08, Proyecto Estructurante de la University of Las Palmas de Gran Canaria (ULPGC) Grant ULPAPD-08/01-4, Proyecto del Programa Propio de la ULPGC Grant ULPGC 2009-07, and III Convocatoria de Ayudas a la Investigación Cátedra Real Madrid-Universidad Europea de Madrid Grant 2010/01RM.
No conflicts of interest, financial or otherwise, are declared by the author(s).
Author contributions: D.M.-A., J.G.P.-G., A.G.-G., L.R.-G., A.S., B.G., and J.A.L.C. performed experiments; D.M.-A., J.G.P.-G., A.G.-G., L.R.-G., A.S., M.R.C., M.G., B.G., and J.A.L.C. analyzed data; D.M.-A., J.G.P.-G., A.G.-G., A.S., M.R.C., M.G., B.G., and J.A.L.C. interpreted results of experiments; D.M.-A. and B.G. prepared figures; D.M.-A. and J.A.L.C. drafted manuscript; D.M.-A., J.G.P.-G., A.G.-G., M.R.C., B.G., C.D., and J.A.L.C. edited and revised manuscript; D.M.-A., J.G.P.-G., A.G.-G., L.R.-G., A.S., M.R.C., M.G., B.G., C.D., and J.A.L.C. approved final version of manuscript; A.S., B.G., C.D., and J.A.L.C. conception and design of research.
Special thanks are given to José Navarro de Tuero and Ana Belén Sánchez García for the excellent technical assistance. Thanks are also expressed to María Carmen García Chicano and Teresa Fuentes Nieto for the assessment of carbonylated proteins. The authors are grateful to James Lister for the expert review of the English version of the manuscript.
- Copyright © 2012 the American Physiological Society
- 1.↵
- 2.↵
- 3.↵
- 4.↵
- 5.↵
- 6.↵
- 7.↵
- 8.↵
- 9.↵
- 10.↵
- 11.↵
- 12.↵
- 13.↵
- 14.↵
- 15.↵
- 16.↵
- 17.↵
- 18.↵
- 19.↵
- 20.↵
- 21.↵
- 22.↵
- 23.↵
- 24.↵
- 25.↵
- 26.↵
- 27.↵
- 28.↵
- 29.↵
- 30.↵
- 31.↵
- 32.↵
- 33.↵
- 34.↵
- 35.↵
- 36.↵
- 37.↵
- 38.↵
- 39.↵
- 40.↵
- 41.↵
- 42.↵
- 43.↵
- 44.↵
- 45.↵
- 46.↵
- 47.↵
- 48.↵
- 49.↵
- 50.↵
- 51.↵
- 52.↵
- 53.↵
- 54.↵
- 55.↵
- 56.↵
- 57.↵
- 58.↵
- 59.↵
- 60.
- 61.↵
- 62.↵
- 63.↵
- 64.↵
- 65.↵
- 66.↵
- 67.↵
- 68.↵
- 69.↵


text:
Usui: I wonder were she went..? Hey Professer Ami i am going to go with Mika okay.*Tries to find her**Calls Mika*Mika!!Were are u!
Mika: Grave,
Usui: WAT HOW COME....*Finds her*Why are u cryin?
Mika: My...Dad....
Usui: *Puts coat on her*There look i am trying to be nice okay since my dad also pass away..
Mika: Alright.*Calls the others*


text:
New Orleans was made for the bicycle. The city is flat, full of fun places to go, and welcoming to bicyclists of all abilities. It wasn't always this way, but because of large investments by Entergy and work by Bike Easy, we've seen an expansion of bicycle lanes and trails from 11 miles to 55 miles over the last five years.
So it's no surprise that on April 9, we saw over 700 riders join us for the second annual NOLA Bike to Work Day. At over 30 hub stations around town, including the public libraries, we served refreshments to keep people pedaling and gave out maps to help them find their way around the city.
As more people are riding, it's critical for bicycles, automobiles and pedestrians to share the road. Everyone is trying to get to work, school and local businesses, and the more we respect each other by being predictable, following the law and offering common courtesy, the safer we will all be.
Bicycling not only helps the environment, our health, reduces traffic congestion and helps us reach local businesses, it also simply makes us feel good. Keep on riding, and together we can make New Orleans the most bicycle-friendly city in America.
Jamie Wine, executive director
Bike Easy
New Orleans


text:
By: Emily Johnson
March 7, 2014, 6pm
Tallahassee, FL - With the sun peaking through the clouds the conditions were more ideal for the participants and the spectators today.
"I think the thing we're most excited is that it's finally stopped raining we're actually going to get to see some of the competition," said Jane Lear, spectator.
Sister's Lear and Lucy Harris have been coming to Red Hills since it started 17 years ago. They said it's a wonderful event that brings people out to Elinor Klapp Phipps Park. "It's a great opportunity for the community of Tallahassee to get exposed to this level of equestrian competition," said Harris, spectator.
Heavy rains on Thursday caused the participants to tweak their riding style, but the conditions definitely improved for today. The park started to dry up and the participants were able to focus more on their riding instead of the weather. Stadium Jumping was the main event on Friday. It's where the riders and their horses are required to jump a series of painted fences in an arena. It not only test the obedience of the horse, but also demonstrates the endurance that's needed for the Cross Country Course.
The Cross Country competition will take place on Saturday. A local mother-daughter duo have been decorating the jumps for the past seven years. "About a week ago we got the plants in and the flowers in and then we start just putting everything together and looking at it to see if it looks pretty enough and bright enough for the Cross Country," said Corinne Mathis, Cross Country Course Decorator.
In order for spectators to have the ultimate Red Hills experience there is a Red Hills app that will give live updates on the events. The competition get going again Saturday morning at 7:00A.M. and events schedule through out the day. For more information you can visit their website at www.rhht.org.
By Emily Porter
WCTV Eyewitness News Web Staff
March 7, 2014, 12:15 p.m.
Tallahassee, Fla. -- The Red Hills Horse trials bring in tens of thousands of people to watch riders from all over the world, and in it's 17th year, this event isn't letting weather slow it down!
The ultimate challenge for horse and rider, Red Hills is an opportunity for equestrians to qualify for the Olympics, while horse enthusiasts get to sit back and enjoy all the action.
The Red Hills horse trials can be broken down into three categories.
Day one is the dressage competition. This is defined by the International Equestrian Federation as "the highest expression of horse training", where "horse and rider are expected to perform from memory a series of predetermined movements."
Day two is stadium jumping, which started today at 11 a.m., and the cross country competition, which is a test of endurance, will be held tomorrow.
Known as eventing, equestrians can ride more than one horse in the competition, but each horse must compete in all three categories.
By: Emily Johnson
March 6, 2014
Tallahassee, FL - The 17TH Annual Red Hills International Horse Trials got underway on Thursday. It's a four day event this year starting with Dressage.
The competitors had to deal with the rains all day, they said they had to adjust their game plans. "It's not perfect conditions so it's like driving in a rain storm with slippery conditions. You have to be a little bit more cautious and really look after your horse," Phillip Dutton, Last year's Red Hills winner.
Dressage consists of a five minutes routine where the riders and their horse have memorized certain movements. The local team from Tallahassee, Team Wallace, said Dressage is the groundwork for the rest of the competition. "Intricate movements that we have to do to demonstrate control of our horses and submission and obedience. It's very important for when we go out on cross country because we need those skills," said Elisa Wallace, Team Wallace Rider.
Despite the rainy weather the Cross Country Course Designer Hugh Lochore said their expected a great turnout of folks for the weekend. "It will, the water will soak in a little bit and dry up all at the same time. So Saturday hopefully will be a nice warm day to bring the public in and we'll have a good day of competition," said Hugh Lochore.
On Friday gates will open at 8:00A.M. with another round of Dressage followed by Stadium Jumping.
On Saturday event will start at 7:00A.M.
If you're interested in a complete list of events and attending you can visit the Red Hill website at www.rhht.org


text:
Legoland Florida is rising out of the ground on the former Cypress Gardens in Winter Haven. On schedule for an October opening, the 150-acre theme park will feature 20 rides and 30 other shows and attractions geared to kids 2 through 12 years old and their parents. Designers now plan to offer four tame coasters after recently deciding to recycle Cypress Gardens' wooden Triple Hurricane into the Coastersaurus and redo an inverted steel coaster into Flight School, which features ride cars suspended from a track that look like a new line of Lego airplane kits. The 1930s vintage botanical gardens will live on untouched, although the Lego Belles will be plastic brick models, not young women in hoop skirts. The water ski show will re-emerge as an extreme stunt show with Lego Pirates. Full price is $75 for adults and $65 for kids 3 through 12, but discounting will be common. Park officials with the British Merlin Entertainments Group hope to draw up to 20 percent of a forecast 2 million visitors from group rates such as weekday school field trips combining admission and selected classroom at $5 to $12 a person.
— Mark Albright, Times staff writer


text:
NEW YORK ( TheStreet) - Earnings season has gotten into full swing following Alcoa's ( AA) report on Monday.In the coming weeks, companies across the market spectrum will follow Alcoa's lead and share how they have fared over the past quarter. Performance numbers for the most recent quarter will prove intriguing for investors looking to gain insight into the state of the economic recovery. Equally important will be the companies' respective outlooks and guidance for the remainder of the year. ETF investors will want to keep a close watch on the earnings calendar. As the season presses on, a large number of major index components will step up to the plate. For instance, when JPMorgan ( JPM) and Bank of America ( BAC) release their reports on during the second half of the week, investors holding the SPDR KBW Bank ETF ( KBE) will want to pay close attention. These two firms are top holdings of KBW, and on top of directing the fund's performances over the next week, they will likely provide clues as to how other major financial institutions fared during the opening months of 2011. Google ( GOOG) is another hotly anticipated household name that is on tap to report its quarterly earnings this week. On top of monitoring the performance of search, Android, and the company's various other branches and divisions, investors will likely have a close eye on how founder Larry Page is adjusting to his new role as the company's CEO. In the short time since taking over the reins from Eric Schmidt, Page has already generated plenty of attention from the media. Most recently, he made headlines when he announced a dramatic shake-up to the company's management structure. It will be interesting to see what else Page has in store. The company's performance and outlook for the rest of the year will heavily influence the popular First Trust Dow Jones Internet Index Fund ( FDN). Google accounts for close to 10% of the fund's total portfolio, making the search giant FDN's largest position. Following Google, earnings numbers from other top index constituents such as eBay ( EBAY) and Netflix ( NFLX) will make FDN an exciting fund to watch in the near term. However, this fund boasts qualities that make it attractive as a long-term bet as well.
- Log In
- Newsletters
Access insights and guidance from our Wall Street pros. Find the product that's right for you.
- Action Alerts PLUS
- Daily Swing Trade
- Income Seeker
- Quant Ratings
- Real Money
- Real Money Pro
- Stocks Under $10
- Top Stocks
- Trifecta Stocks
- Real Money Pro Portfolio
- Chairman's Club
- Compare All


text:
Bloomington, CA Active Retirement Homes
Equity Lifestyle Properties Launches Feature Community Campaign
Equity Lifestyle Properties and Retirenet.Com have launched a new marketing campaign to feature premier properties in Florida, California, Illinois, Arizona and Colorado. Read more...
Choosing the Perfect Retirement Community
So, the time is right and you are actively considering a move to a retirement community. For some, the idea may be exciting. To others, the mere thought is stressful or frightening. Either way, it is a significant life decision and one that needs to be th Read more...
News from the Orange County Register - RSS
Who is one of the surprises of Ducks training camp? That?s (Giovanni) Fiore
Sep 25, 2017 4:53 am
ANAHEIM – Many have done so but Giovanni Fiore hadn't and it might have felt as if he possessed the winning lottery ticket. It was Saturday afternoon when Fiore learned that he wou...
Republicans make desperate bid to save health care bill
Sep 25, 2017 4:33 am
Republican opposition to the GOP health care bill swelled to near-fatal numbers Sunday as Sen. Susan Collins all but closed the door on supporting the last-ditch effort to scrap the Obama health care ...
USC aims for faster starts as schedule shifts to Washington State
Sep 25, 2017 4:31 am
Clay Helton began his weekly teleconference on Sunday evening by acknowledging one of USC's characteristics of the early season. "You're very, very happy again when you s...
Angels come from behind to beat Astros and stop losing streak at 6
Sep 25, 2017 4:19 am
  HOUSTON — For the first time in a week, the Angels had music thumping loud in a happy clubhouse after the game, as players packed up for a flight with their hope flickering a litt...
Chargers RB Melvin Gordon?s hot start slowed by knee injury
Sep 25, 2017 3:48 am
Melvin Gordon ran for 78 yards and a touchdown in the first half, but the Chargers tailback sat out most of the second with a knee injury. The team will likely rest him this week to get him healthy fo...
News from the San Fernando Valley - RSS
Install a New Fireplace Surround and Gas Logs
Mar 9, 2017 6:12 pm
Dear James: It's a mess carrying firewood indoors, so I want to modernize my old brick fireplace with one that uses gas logs. Are there any tips on how to do this project myself? -- Kathy H. ...
Select and Work with a General Contractor
Feb 23, 2017 2:52 am
Dear James: An architect is almost finished with the plans for my house. I need to select a good general contractor, but have heard of many potential problems. What is the best way to insure a good jo...
Select Room Wall Colors to Impact Room Size
Feb 16, 2017 1:51 am
Dear James: We are downsizing to a new house. We are trying to determine the best colors to paint the rooms to make it look more spacious. What do you recommend for various rooms? -- Renee K. ...
Feb 9, 2017 3:20 am
Dear James: We have vinyl kitchen flooring which is badly worn. We think a ceramic tile floor would look good and wear well. Can this be put over any old floor and what are some installation tips? -- ...
Eliminate Drywall Shadow Lines on Walls
Feb 2, 2017 3:00 am
Dear James: I am remodeling two rooms. I hung and finished drywall in one room, but there are shadow lines at many joints. Do you have any joint finishing tips to create flat, hidden joints? -- Steve ...
Jan 26, 2017 4:36 am
Most local residents are grateful for the recent rains, despite the many problems that it caused, such a flooding and auto accidents.
Jan 26, 2017 4:02 am
Dear James: The wood frame windows in my vintage house are pretty deteriorated. I want to repair them, not replace them, to maintain its character. What repairs to them can I do myself? -- Don H. ...
Area Info
There's a reason why California has become the most populous state in the country: it has more to offer in one package than any other state.
From mountains to seacoast, deserts to lush forests, teeming cities to wilderness, California is a land of dizzying contrasts. In Southern California, an hour's drive will take you from the bustle of downtown LA to the silence of the Mojave Desert.
There are plenty of perks for retirees in California, including dynamic scenery, amazing golf courses and a number of cultural attractions.
This category encompasses the entire range of independent retirement living. The communities listed here are designed to promote a rich life experience based on active recreation and social interaction with other seniors.
2 homes
Sort By:
2 homes


text: On Fri, 2008-12-05 at 16:50 +0100, Thomas Davie wrote: > Sure, and he could then use a fold instead of a map. Reading files is > problematic, but as long as you're only doing it once (the most common > situation) is entirely fine wrapped up in an unsafePerformIO. Nooooo! Please don't go telling people it's entirely fine to use unsafePerformIO like that (or at all really). Duncan


text:
RECIPES: Recipe Details
The Lower East Sliders (Houston Street Pastrami Mini Burgers with Grilled Kraut, Knish Schmeer and D.I.Y. Delancey Dressing) NOTE: This is a re-submission of my recipe submitted earlier this week. I inadvertently referred to the "Knish Schmeer" as "Knish
The Lower East Side of Manhattan, New York City may be home to immigrants from all corners of the globe, punk music and bootleg designer handbags, but it is THE center of the universe for pickles and pastrami. With more Jewish delis and appetizing stores than you can shake a stick at, this is the place for a great knish, a chewy bialy or some much-maligned gefilte. There is a nosh for everyone, even a kvetch! I think that this burger would make itself at home on the L.E.S. – a pastrami-inspired mini burger with a nip of espresso (they don't call it "The City That Never Sleeps" for nothing), schlepping around some grilled kraut, knish schmeer, and some tangy homemade Russian dressing. Inspired by the people and history of this great neighborhood, it's a shidduch-on-a-bun. If this burger can make it at Build a Better Burger 2008, it can make it anywhere!
Vegetable oil, for brushing the grill
1/4 cup Colavita Pure Olive Oil
3/4 cup Sutter Home Chardonnay
4 tablespoons Lea & Perrins Worcestershire Sauce, divided
1 tablespoon grainy mustard
1 teaspoon whole fennel seeds
2 teaspoons ground allspice
1 teaspoon celery salt
1 teaspoon instant espresso
2 tablespoons granulated sugar
1 head garlic, peeled and pressed
1 medium white onion, peeled and grated
1 small head Savoy cabbage (about 1 lb.), outer leaves removed and cut into quarters
1 3/4 cups good quality mayonnaise, divided
1 5-oz. bag Kettle Brand Unsalted Chips, finely crushed
1 large lemon, zested and juiced (keeping zest and juice separate)
1 red bell pepper, cored and diced
2 lbs. ground chuck
Kosher salt and freshly-ground black pepper
1/2 cup fresh dill, stemmed and chopped
12 rye and/or mini challah dinner rolls (can be mix 'n' match)
24 dill pickle slices
Before preheating the grill, baste the grill rack with a coating of vegetable oil. Prepare a medium-hot fire in a charcoal grill with a cover, or preheat a gas grill to medium-high.
In a large bowl with a seal tight lid, add the Colavita Pure Olive Oil, Sutter Home Chardonnay, 2 tablespoons of the Lea & Perrins Worcestershire Sauce (reserving the other 2 tablespoons for use later in the recipe), mustard, fennel seeds, allspice, celery salt, espresso, sugar, pressed garlic and grated onion, place the lid upon the container and shake until well mixed. Remove the lid and scoop out 1/3 cup of the marinade, pour into a small bowl and set aside. Add the Savoy cabbage quarters to the bowl, re-seal and toss. Let the cabbage marinade 20 minutes while the grill is heating and while preparing the Knish Schmeer and D.I.Y. Delancey Dressing, occasionally giving the cabbage bowl a shake.
Add 1 cup of mayonnaise (reserving the remaining 3/4 cup for later use) to a small bowl. Adding a little at a time, stir in the crushed Kettle Brand Unsalted Chips, incorporating all the chips into the mayonnaise before adding more. Once all the chips have been incorporated, your mixture will be a spreadable paste. Seal your bowl with plastic wrap and place into your refrigerator or cooler to chill. This is your Knish Schmeer.
To another small bowl, add the reserved 2 tablespoons of Worcestershire sauce, the remaining 3/4 cup mayonnaise and the lemon juice (reserving the zest for later use) and stir until smooth. Add the diced red bell pepper, stir to combine, and cover the bowl with plastic wrap and chill to let flavors blend. This is your D.I.Y. Delancey Dressing.
When your cabbage has marinated and your grill is heated, re-baste your grill with vegetable oil. Give the cabbage bowl a final shake and, using tongs, remove the cabbage quarters from the marinade (reserving the marinade) and place the cabbage upon the grill, cut-side down. Grill the cabbage for 5 minutes on the first side, basting with the reserved 1/3 cup of marinade (you might have a few flare-ups; fuggetaboutit). Using your tongs, turn your cabbage after 5 minutes to the second cut side and baste with any remaining reserved marinade. Grill on the second side for 3 minutes, or until the cabbage has caramelized and become very fragrant. While the cabbage is grilling, add the ground chuck to the bowl containing the remaining cabbage marinade and, using your hands, gently incorporate the marinade into the ground chuck. Evenly divide the beef mixture into 12 equal sized balls using a 1/3-cup measuring cup, adding any remaining beef to the punier burger balls. Press the balls into patties that they are slightly larger than your rolls and generously salt and pepper each side, pressing the salt and pepper into the patties. These are your Houston Street Pastrami Mini Burgers. Set the patties aside to rest until ready to grill.
Remove the cabbage from the grill and set inside a large bowl until cool enough to handle (the bowl will collect any delicious dripping grilled kraut juices). When cool enough to handle, core the cabbage quarters and very thinly slice the cabbage into shreds. Return the shredded cabbage to the bowl containing the collected juices and add the reserved lemon zest and fresh chopped dill and toss. Set the Grilled Kraut aside while grilling your rolls and burgers.
Brush your grill to release any burnt bits from the grilled kraut, re-baste your grill with vegetable oil and place the rolls cut-side down upon the rack. Grill the rolls until they are lightly toasted, about 3 minutes. Remove the rolls from the grill and set them aside to rest, grilled side up.
Re-baste your rack one more time with vegetable oil and place the burger patties upon the grill. Grill the first side for about 5 minutes, or until the juices emerge from the top. Flip the patties and finish grilling on the second side to your desired doneness. Transfer the burgers to a plate to rest and to let the juices redistribute while getting the burger assembly line prepared.
To assemble your burgers, spread the cut side of a bottom bun with a spread of the Knish Schmeer. Top the Knish Schmeer with a Houston Street Pastrami Burger, followed by a thin spread of D.I.Y. Delancey Dressing on the burger to anchor your dill pickle slices and Grilled Kraut. Top the dressing on the burger with 2 dill pickle slices and a mound of the Grilled Kraut. Spread more of the D.I.Y. Delancey Dressing on the cut side of each top bun and add the bun top to the burger, securing it with a plain wooden skewer. Repeat with the remaining Lower East Sliders, serve 2 burgers to each person, and enjoy!
NOTE: This is a re-submission of my recipe submitted earlier this week. I inadvertently referred to the "Knish Schmeer" as "Knish Cream" in the final paragraph, so I thought better safe than sorry and send a corrected version. The "Entry ID" on the confirmation for my original submission was 756. Thank you very much and I am sorry for the error.
This recipe serves 6, making 12 Lower East Sliders (2 per person). Thanks!


text:
Sophie Kinsella writes:
"A perfect wedding is no good for an author. There's a reason that most fairy stories end abruptly: 'And they lived happily ever after. The End'. They might just as well end 'Booooring….' No-one wants to read about calm, easy times. No-one wants to read about the perfect wedding that went off without a hitch. As readers, we like drama; interruptions; intrigue. But does such drama ever happen in real life?
If my experience is anything to go by: absolutely. Perhaps the most dramatic wedding I ever attended was that of a friend from university. She got married in our old Oxford chapel on a very hot day. Too hot, it turned out: she fainted at the altar. She had to be carried out on a makeshift wooden stretcher, whereupon a bunch of tourists got very excited and thought this was perhaps a 'quaint British custom' of carrying the bride out of the chapel. While her husband-to-be was frantically fanning her, the tourists were jostling, trying to take photos of her. It was pure farce. (She did revive, thankfully, and the wedding carried on.)
I have been at a wedding where the best man mistakenly toasted the ex-girlfriend rather than the bride. (Ouch.) I have been at a wedding where the groom's romantic outdoor serenade of his bride was interrupted, unromantically, by a road-sweeper.
Honeymoons, though less public, are equally prone to disaster and farce. My own honeymoon began well – we were in a beautiful hotel room in the Cotswolds with a four poster bed and romantic window seat. I immediately rushed to the window seat and sat down to enjoy the view…. but I should have looked where I was sitting. I had sat on a wasp. (Ouch again.)
All of these real-life occurrences help to inspire my fiction. I would never put a real-life incident into a book, but what I try to capture is that sense of disbelief, panic and sometimes hysteria that occurs when disaster strikes. I sometimes feel sorry for my fictional heroines – I put them in so many ridiculous, farcical situations. Lottie, the heroine of my new book Wedding Night, suffers an unrelenting catalogue of catastrophes on her honeymoon; I was cringing even I was writing it.
But another lesson that I've learned from real life is that humans are pretty resilient. If disaster strikes in one direction, we try another direction. We don't give up. We press on; we learn; we adapt. And the most important thing is to keep a sense of humour.
I would never have planned to be stung by a wasp on my wedding night. It's hardly the most romantic occurrence in the world. But looking back now, I remember it fondly. Nothing is perfect, nor should it be – not a wedding; not a honeymoon. No marriage is perfect either, not even in the fairy tales. So we might as well get used to the little – and big – setbacks from the start. If I were a wedding planner I wouldn't plan to give my clients a 'perfect' wedding. I'd plan to give them a 'wonderful' wedding. There's a difference.
As my latest book is called Wedding Night, I have chosen a list of my favourite books with a wedding theme."
The Age of Innocence
By Edith Wharton
"One of my favourite books: a wonderful, bitter-sweet love story set in the upper-class society of 1870s New York, with a wedding as its central event."
Great Expectations
By Charles Dickens
"Not a 'wedding' book exactly but I include it purely for the character of Miss Havisham in her yellowing wedding dress: the spectre of what happens when it all goes horribly wrong…"
Pride and Prejudice
By Jane Austen
"This novel is all about marriage: no-one has ever written about the institution with quite the clear-eyed precision of Ms Austen."
The Pursuit of Love
By Nancy Mitford
"A witty, delicious, yet moving novel, charting the progress of one upper-class English family through various stages of love and marriage (not necessarily at the same time)."
Another Woman
By Penny Vincenzi
"This fabulous contemporary page-turner begins with a bride's disappearance on the morning of her wedding and the slow realisation that she is not the woman she appeared to be."
Otherwise Engaged
By Suzanne Finnamore
"A wry, very funny account of an engaged woman getting more and more stressed as she prepares for her upcoming wedding."


text:
Discussion in 'Tickets, Memorabilia and Gear' started by Kimmy, Oct 25, 2011.
Have two; section 321, row K.
How much?
Sorry - was super tired last night when posting Tix are 160.00 for the pair
Sorry I dont have that kind of money
PM sent
Do you take W.I.C.?
Nice meeting you, glad you could make it. A long Halloween weekend/Tailgate caught up with us in that sun
Hope you enjoyed it
Yes i did.. Thanks Again
Kimmy, crazy seeing you out and about on Friday. Email me a copy of our picture @ dr2baka at gmail.com
Apparently the Jags offense didn't get tickets.
Separate names with a comma.