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Not Another New England Sports Blog!
Random musings on sports, geopolitics, current events, pin-ups and the railroad industry from a rank amateur blogger.
Friday, November 21, 2014
Sports Chowdah Update-
Fifty 28 Shades of Gray, Patriots Romp at Indy; Bruins Shake the Blues at the Garden; Hurricane Warnings and High Tides, Mississipi State Falls to Alabama while Florida State Surges against Miami
NFL- November has proven to be a pretty good month for New England so far, with the Patriots bookending their bye week with convincing wins over division leaders.
The first weekend in November has the Patriots hosting Peyton Manning and the Denver Broncos, and the outcome was far less dramatic than the last time Denver came to Foxborough. This time around, the team with the big first half lead managed to hang on to it as New England rolled to a 43-21 win against the Broncos.
Coming out of the bye week, New England faced an equally important test against another AFC division leader as the Patriots travelled to Indianapolis to take on Peyton Manning's former team, the Colts.
Right off the bat, congratulations to those of you who happened to start RB Jonas Gray on your fantasy team on Sunday. RB Jonas Gray out of Notre Dame, who had moved from the practice squad to the starting roster less than a month ago, opened the scoring with a 4 yard TD run in the first to give New England the early 7-0 lead. The Colts quickly came back with a drive of their own that put them in the Patriot's red zone, but they had to settle for a chip shot FG off the leg of Adam Vinatieri to make it 7-3.
Late in the second quarter, Gray found the end zone once again to put the Patriots up on top 14-3 before Andrew Luck led a quick counterattack to put the Colts within 4 points after hitting paydirt on a 10 yard reception by WR Hakeem Nicks with 55 seconds to go in the first half, making it a 14-10 New England lead.
However, during the opening drive of the second half the Patriots started pulling away, thanks to the first Pats TD of the night to someone NOT named Jonas Gray when Brady found TE Tim Wright for a short TD pass to go up 21-10. On the following possession, the Colts would only get as far as the Patriots 35 yards line, but they were able to convert that to points thanks to a successfully 53 yard FG attempt by ex-Patriot Vinatieri. With 3:30 to go in the third, the Patriots made it a 28-13 game thanks once again to Jonas Gray who successfully punched it in from the 2 yard line.
The Colts showed some signs of life late in the 3rd when they made their way down to the Patriots 4 yard line before the game clock flipped over to the 4th quarter. Luck connected with OT Anthony Costanzo to make it a one score game with the Patriots now leading 20-28. However, not only did the Patriots manage to score another TD thanks to an 80 yard drive capped by yet another Gray TD, but they were able to bleed nearly 5 minutes off the clock, putting New England up 35-20 with just under 9 minutes to go in the game. With the clock ticking, Andrew Luck and the Colts offense were pressured to go for it on a 4th and 12 at midfield, but Luck threw the ball incomplete, giving the Patriots an even shorter field to work with and less than 7 minutes to go in the game. The Patriots essentially put the game away on a 26 yard reception and TD from Brady to Gronkowski where he was shedding tacklers like a maple sheds its leaves this time of year- this comes AFTER destroying former teammate and Colts safety Sergio Brown by blocking him into an NBC camera trolley along the sideline.
New England goes on to an pretty easy-looking 42-20 win on Sunday Night Football and will next host the Detroit Lions [who, interestingly, aren't playing on thanksgiving- NANESB!]. Interestingly, this may be the first time ever that the Patriots and Lions have ever played each other when both teams were leading their respective divisions.
OTHER PATRIOTS NEWS- After being released by the Pittsburgh Steelers on Tuesday, free agent RB and former Patriot LeGarrette Blount signed a two year deal with New England on Thursday. Blount was released by the Steelers less than 24 hours after the Steelers 27-24 Monday Night Football win over the Tennessee Titans after complaining about getting no carries in the game.
Although some sportswriters believed the Pats had their eyes toward the future when bringing Blount back [Ridley is currently on the DL and Shane Vereen is a free agent at the end of the season- NANESB!] that became more apparent when Jonas Gray missed practice on Friday. Something similar happened last month when CB Darrelle Revis missed practice last month, but he ultimately ended up playing in the Oct 26th win against the Bears.
ELSEWHERE IN THE AFC EAST- Sunday afternoon's game between the Buffalo Bills and New York Jets has been postponed and is rescheduled to be played at Detroit's Ford Field on Monday night. Over the last few days, the Buffalo area had been hit by a series of winter storms with accumulation up to six feet in many areas.
Initially, the Bills were optimistic that they could get the stadium ready in time for Sunday's game and were offering fans $10 and hour and free game tickets to assist in shoveling out the stadium. However, the snowfall clogged the surrounding highways to the point where some players were arriving at Ralph Wilson stadium via snowmobile and the forecast is calling for even more snowfall between now and Sunday.
Kickoff is scheduled for Monday at 7:00 ET and the game will be televised locally in both the Buffalo and New York City markets on CBS.
NHL- After a pretty disappointing week that saw the Olde Towne Team lose big to Original Six rivals Montreal and Toronto, the Bruins seemed like they found their rhythm once again after returning to the Garden and doubling up the Carolina Hurricanes 2-1 over the weekend.
The win in Tuesday night's home game against the visiting Blues was made all the more strange by the fact that the Blues outshot Boston by nearly a 2:1 margin- 33-17, but Tukka Rask was able to record the shutout while Patrice Bergeron scored in the first and Torey Krug scored in the 3rd [both even-handed- NANESB!] to make it a 2-0 Bruins win.
Boston will travel to Columbus for a 1-game road trip on Friday before retuning home to the Garden on Saturday to host the Canadiens. That game will get underway at 4:00 and will be televised on both NESN, CBC and the NHL Network.
NCAA FOOTBALL- And then there was only one- at least in the "Power Five" conferences.
The Alabama Crimson Tide shook things up in the BCS and put themselves back in the championship hunt after beating the Mississippi State Bulldogs in Tuscaloosa, AL by a 25-20 final on Saturday. Both 'Bama and Mississippi State now sport similar 9-1 records, with Bama holding the edge thanks to their head-to-head record against Mississippi State. The win propels the Crimson Tide to #2 in the Nation while Mississippi State falls to number four.
This weekend, Alabama has a fairly easy contest against FCS Western Carolina at Tuscaloosa before the Iron Bowl against Auburn at the end of the month while the rest of Mississippi State's games are against the SEC with Vanderbilt this weekend and the rivalry game at Ole Miss at the end of the month at Oxford, MS. There is also the matter of the SEC championship game- since Bama and Mississippi State are both in the SEC East division, one of them would go on to face the leader of the SEC west [which could be either Georgia or Missouri if the standings hold up over the next two weeks- NANESB!].
ELSEWHERE IN THE NCAA- Despite trailing most of the game against in-state rival Miami, the Florida State Seminoles pulled out a late win to continue their undefeated season. The 'Noles pulled ahead for good with just over 4 minutes to go in the 4th quarter when Freshman RB Dalvin Cook ran 26 yards for the go-ahead TD. FSU holds in to its top ranking by going on to beat Miami by a 30-26 final.
Florida State will finish off their regular season hosting Boston College, followed by the Florida Gators for Rivalry week and a showdown with #18 Georgia Tech for the ACC Title Game on Dec 6th.
ELSEWHERE IN THE ACC- After getting out to a 13-3 lead over the Louisville Cardinals, the Boston College Eagles gave up five unanswered touchdowns to Louisville and would go on to lose by a 38-19 final in Chestnut Hill two weeks ago. After a week off, the Eagles now face a monumental challenge when they travel to Tallahassee to take on #1 Florida State this weekend. The Eagles regular season wraps up with a Rivalry Week contest against Syracuse at Chestnut Hill on Nov 29th.
Posted by Fenway_Nation at 4:20 PM No comments: Links to this post
Labels: ACC, AFC East, Alabama, BC Eagles, Boston Bruins, Buffalo Bills, Florida State, Indianapolis Colts, Miami, Mississippi State, NFL, NHL, Patriots, SEC, snow, St Louis Blues
Saturday, November 15, 2014
Obamacare Architecht: Law Passed Because of Lack of Transparency, "Stupidity" of American Voters
A series of videos have surfaced showing MIT Economist Jonathan Gruber, the man widely credited with crafting President Obama's sweeping healthcare law, admitting that the law was written in a vague and deceptive manner by design to hide costs and that the Affordable Care Act was ultimately passed thanks to the 'stupidity of the American voter'.
As of Friday, the total number of videos circulating of Gruber boasting to audiences about the circumstances under which Obamacare had passed was six. A number of the recently surfaced videos date from 2010 and 2011, while the most recent videos date back to fall of 2013 and there may be even more damning video to come.
Speeches with much more blunt language on Gruber's part had surfaced on conservative blogs and talk radio earlier this week, although the story didn't begin gaining coverage until later on in the week when more videos began surfacing.
Democrats who were pivotal in passing Obamacare were quick to distance themselves from Gruber. House Minority Leader Nancy Pelosi, who cited Gruber's work during the push to pass Obamacare, denied knowing who he was and attempted to downplay his role in crafting the law during a press conference on Friday.
Gruber himself boasted of a 2009 meeting with the President Obama about the healthcare law in a 2012 interview- the White House visitor's log confirms Gruber's visit.
While some pundits have been wondering why these videos didn't surface before the election, their release may have been timed to coincide with something else altogether. The revelations come before the issue of Obamacare is once again before the Supreme Court. This time, the law is being challenged based on subsidies for the 14 states that didn't set up state-run Obamacare exchanges and the Administration's case could very well be undercut by Gruber's statements.
As of Friday, the total number of videos circulating of Gruber boasting to audiences about the circumstances under which Obamacare had passed was six. A number of the recently surfaced videos date from 2010 and 2011, while the most recent videos date back to fall of 2013 and there may be even more damning video to come.
In a 2011 conversation about the Affordable Care Act, MIT economist Jonathan Gruber, one of the architects of the law more commonly known as Obamacare, talked about how the bill would get rid of all tax credits for employer-based health insurance through "mislabeling" what the tax is and who it would hit.
The issue at hand in this sixth video is known as the "Cadillac tax," which was represented as a tax on employers' expensive health insurance plans. While employers do not currently have to pay taxes on health insurance plans they provide employees, starting in 2018, companies that provide health insurance that costs more than $10,200 for an individual or $27,500 for a family will have to pay a 40 percent tax.
"Economists have called for 40 years to get rid of the regressive, inefficient and expensive tax subsidy provided for employer provider health insurance," Gruber said at the Pioneer Institute for public policy research in Boston. The subsidy is "terrible policy," Gruber said.
"It turns out politically it's really hard to get rid of," Gruber said. "And the only way we could get rid of it was first by mislabeling it, calling it a tax on insurance plans rather than a tax on people when we all know it's a tax on people who hold those insurance plans."
(The White House press secretary said at a press briefing in 2010: "I would disagree with your notion that it is a tax on an individual since the proposal is written as a tax on an insurance company that offers a plan.")
The second way was have the tax kick in "late, starting in 2018. But by starting it late, we were able to tie the cap for Cadillac Tax to CPI, not medical inflation," Gruber said. CPI is the consumer price index, which is lower than medical inflation.
Gruber explains that by drafting the bill this way, they were able to pass something that would initially only impact some employer plans though it would eventually hit almost every employer plan. And by that time, those who object to the tax will be obligated to figure out how to come up with the money that repealing the tax will take from the treasury, or risk significantly adding to the national debt.
"What that means is the tax that starts out hitting only 8% of the insurance plans essentially amounts over the next 20 years essentially getting rid of the exclusion for employer sponsored plans," Gruber said. "This was the only political way we were ever going to take on one of the worst public policies in America."
Unions and employers who object in 2018, he noted, "at that point if they want to get rid of it they're going to have to fill a trillion dollar hole in the deficit...It's on the books now."
Speeches with much more blunt language on Gruber's part had surfaced on conservative blogs and talk radio earlier this week, although the story didn't begin gaining coverage until later on in the week when more videos began surfacing.
The comments were made during the panel sessions at the Annual Health Economics Conference last year.
"This bill was written in a tortured way to make sure CBO did not score the mandate as taxes," he said during a panel discussion at the University of Pennsylvania in October, 2013. "Lack of transparency is a huge political advantage. And basically, call it the 'stupidity of the American voter' or whatever, but basically that was really, really critical to getting the thing to pass."
Democrats who were pivotal in passing Obamacare were quick to distance themselves from Gruber. House Minority Leader Nancy Pelosi, who cited Gruber's work during the push to pass Obamacare, denied knowing who he was and attempted to downplay his role in crafting the law during a press conference on Friday.
Gruber himself boasted of a 2009 meeting with the President Obama about the healthcare law in a 2012 interview- the White House visitor's log confirms Gruber's visit.
While some pundits have been wondering why these videos didn't surface before the election, their release may have been timed to coincide with something else altogether. The revelations come before the issue of Obamacare is once again before the Supreme Court. This time, the law is being challenged based on subsidies for the 14 states that didn't set up state-run Obamacare exchanges and the Administration's case could very well be undercut by Gruber's statements.
Tuesday, November 11, 2014
Happy Veteran's Day From Not Another New England Sports Blog
Fort Rosecrans military cemetery overlooking the Pacific ocean in California. Mom to Madre photo
"Happy" seems a little bit of a stretch in light of developments at the VA earlier this year, but some veterans can take heart in the fact that more amd more veterans are getting elected to office after last week's historic midterms, including Senators-elect Tom Cotton of Arkansas and Joni Earnst of Iowa who will become the first Operation Iraqi Freedom veterans to be elected to the US Senate. In fact, Ernst was reportedly incommunicado for a few days after the election to serve the required weekend muster with the Iowa National Guard.
For veterans who have been unhappy with the way things have been going in Washington, it is important that they join a veteran's group such as the American Legion or Veteran's of Foreign Wars to make their voices heard. Feel free to visit them online to enquire about membership or find the nearest Hall.
Thursday, November 6, 2014
Election 2014- A Red Tsunami From Sea to Shining Sea
From Maine to American Samoa, Tuesday night was a bad night for the Democrats.
The big story of the night was that the Democrats and Majority Leader Harry Reid lost their majority in the United States Senate on election day after Republicans picked up no fewer than seven seats, with some race still to be decided through a recount or runoff. Although some Democrats had distanced themselves from President Obama while campaigning, the President in an interview said that his policies were on the ballot and he could count on support from Democrat incumbents- even the ones who were keeping him at arm's length on the campaign trail.
Heading into Election Day, the GOP needed a net gain of six seats in the Senate to regain a majority they hadn't held since 2006. It was widely believed that West Virginia, South Dakota and Montana would be fairly easy pickups for the Republicans, with states like Virginia, Iowa, North Carolina, New Hampshire, Kentucky, Minnesota, South Carolina, Alaska, Louisiana, Arkansas and Colorado up for grabs in close races.
For veterans, one of the more noteworthy developments was that Arkansas Republican Tom Cotton became the first-ever Iraq war veteran elected to the US Senate after defeating incumbent Democrat Mark Pryor by a margin of nearly 10 points. Later on in the night, Cotton was joined by Joni Ernst, a fellow Iraq war veteran, Lieutenant Colonel in the Iowa National Guard and state senator who was campaigning against congressman Bruce Braley for Iowa's senate seat that was open after Democrat Tom Harkin announced his retirement.
In South Carolina, former Congressman Tim Scott became the first black US senator from the South since Reconstruction- and the first ever to be elected to both the House of Representatives and US Senate. Scott was technically the incumbent, since governor Nikki Haley appointed him to replace fellow Republican Jim DeMint who retired to become president of conservative think-tank The Heritage Foundation in 2012.
Before Tuesday, Democrats took some solace in the projections out of Kansas that had Independent Greg Orman leading incumbent Republican Pat Roberts before election day. Orman, who declined to state whether he'd caucus with Democrats or Republicans if elected although Orman reportedly received donations from Democrat-supporting PACs and Vice President Biden predicted that Orman would end up caucusing with Democrats and narrowly preserve the party's majority in the Senate.
But perhaps the biggest prize for either party was Colorado. Over the last decade, Democrats had prided themselves on making Colorado a model on turning a red state blue [and boasted they were going to repeat the process in Texas, more on that a little later- NANESB!]. Incumbent Mark Udall ran on a campaign reminiscent of the Democrat's 2012 "War on Women", claiming that GOP challenger Corey Gardner would outlaw contraceptives and earning himself the nickname Mark Uterus.
In Louisiana, that race is heading to a December runoff since incumbent Democrat Mary Landrieu failed to get more than 50% of the total vote. However, the DSCC reportedly yanked a proposed $1.5 million ad buy in certain Louisiana markets, indicating that donors are less than confident about Landrieu's chances against Cassidy in the runoff.
The 'wave' wasn't just limited to a pickup of seven seats in the US Senate for the GOP. In the House of Representatives, not only did beleaguered incumbents such as New York Rep Michael Grimm [R- Staten Island] survive, but the Republicans gained a total of 15 seats [with some races in California and Maryland so close they're awaiting absentee and provisional ballots to decide the campaign- NANESB!]. Some of these included retired Air Force colonel Martha McSally beating Democrat representative Ron Barber in Arizona's 2nd congressional district- which comprised much of former congresswoman Gabby Giffords' district that had been held by Democrats after a 2011 assassination attempt on Giffords and redistricting. In Utah, former Saratoga Springs, UT mayor Mia Love ran as a Republican against Democrat Doug Owens for Representative in Utah's 4th Congressional District for the House seat up for grabs when Democrat Jim Matheson announced his retirement after the 2014 elections. Love- the daughter of Haitian immigrants- is Utah's first female congresswoman and the GOP's first black congresswoman [the NAACP was remarkably silent on the results of her election- NANESB!].
Republican governors favored just as well as the Senate and House races as it turned out. In Wisconsin, incumbent Scott Walker was elected governor for the third time since 2010- after a protracted battle over public sector unions between Democrats and the first-terms governor, the Democrats and unions successfully launched a recall campaign against Walker in 2012. However, Walker ultimately prevailed despite a well-funded campaign from unions and wealthy Democrat donors and PACs.
Democrat state representative Wendy Davis made a name for herself with wealthy liberal donors and the pro-abortion crowd after a lengthy filibuster on the floor of the State House in Austin, TX last year that was meant to hold up legislation that would prohibit abortions after 20 weeks. Shortly after the filibuster made her a rising star with the Democrats, she announced her candidacy for governor against Texas attorney general Greg Abbott. Although Davis wasn't expected to win, her candidacy was a trial balloon by out-of-state liberal Super PACs to try and turn Texas into a blue state. Davis ended up losing to abbot by more than 20 points, which in turned siphoned Democrat donor money away from much more competitive races.
In Maine, incumbent Paul LePage carried all but two of the sixteen counties throughout the state. In Massachusetts, Democrat Martha Coakley- who lost the 2009 Massachusetts' special election for US Senate to challenger Scott Brown- lost to Republican challenger and businessman Charlie Baker on election day. In the Midwest, incumbent Michigan governor Rick Snyder won 51% of the voting after drawing the ire of unions by making the Wolverine state a right-to-work state in his first term as governor. In President Obama's home state of Illinois, incumbent Democrat Pat Quinn lost to republican businessman Bruce Rauner. Although Maryland's Democrat governor Martin O'Malley was term-limited, pundits both left and right believed that his Lieutenant Governor, Anothony G Brown, would coast to an easy election win over Republican challenger and Maryland businessman Larry Hogan but Hogan shocked the pollsters and pundits by getting just over 51% of the vote. Out west, someone forgot to tell incumbent GOP governors Brian Sandoval and Susana Martinez that their party has a problem with Latinos as the governors of Nevada and New Mexico coasted to an easy re-election. Sandoval received more than 70% of the vote just weeks after he had announced a deal that where Tesla Motors [NASDAQ- TSLA] announced they would open up a factory outside of Reno, NV in exchange for substantial tax breaks. Meanwhile, Susana Martinez won 57% of the ballots cast in New Mexico on election day.
UPDATED again: Evolution of state legislative control in the Obama era: pic.twitter.com/DvK4s8eWi9— David Freddoso (@freddoso) November 6, 2014
It wasn't just the governor's mansions that were going red in 2014. On the state level, Real Clear Politics reports that the Republicans control an unprecedented 68 out of 98 possible partisan legislative chambers on the state level.
Sunday, November 2, 2014
One Giant Cup of Sports Chowdah Update- The Constant Bumgarner, Giants Ace Comes Out of Bullpen to Cinch World Series; Brady's Bunches, Patriots QB throws 5 TDs Against Chicago; Hokies Smoked, Boston College Becomes Bowl-Eligible With Win in Blacksburg;
WORLD SERIES- Those of us who wanted a Game 7 in the 2014 World Series weren't disappointed.
Game 7 was made possible by the Royals lighting up Giants starter Jake Peavy early in Game Six on Wednesday, cruising to an easy 10-0 win and tying up the series at 3 games apiece.
For Game 7, the Giants got out to an early 2-0 lead off of Kansas City starter Jeremy Guthrie thanks to a pair of RBI sac flies- one off the bat of Michael Morse and Brandon Crawford. However, the Royals got those two runs back in the bottom of the second and managed to chase San Francisco starter Tim Hudson after 1⅔ innings when Alex Gordon hit an RBI double and then advanced to third before coming home on an Omar Enfante sac-fly.
In the top of the 4th, Giants 3B Pablo Sandoval led off with an infield single, followed by a Hunter Pence single and a Brandon Belt fly ball to left field that advanced Sandoval to third. By this point, Royals manager Ned Yost pulled Guthrie and brought Kelvin Herrera in from the bullpen. Morse singled, which brought Sandoval in from 3rd before Herrera struck out Brandon Crawford and got Juan Perez to ground out and end the inning.
Nursing a 1-run lead, Giants manager Bruce Bochy brought in starter Madison Bumgarner from out of the bullpen. Although dominant against the Royals earlier in the series, Bumgarner immediately gave up a single to Omar Enfante followed by an Alcides Escobar sac bunt to move Enfante into scoring position, but that was followed by fly ball off the bat of Nori Aoki to left that LF Juan Perez managed to run down for the second out. Bumgarner then managed to get Lorenzo Cain to strike out and end the bottom of the 5th.
Instead of going to the bullpen, Bochy went with Bumgarner into the 9th inning, with the Giants starter getting better as the innings progressed. In the bottom of the 9th, he got Eric Hosmer and Billy Butler to go down quietly for the first two outs. Alex Gordon stepped into the batter's box and hit a line drive into left center that was misplayed by Gregor Blanco which rolled all the way to the wall. Gordon beat the throw to third and brought the increasingly demoralized crowd at Kauffman Stadium back to life with the tying run 90 feet away. However, Bumgarner got Salavor Perez to pop up to 3rd to clinch San Fransico's third World Series title since 2010.
For his two commanding starts and the Game 7 relief appearance, Madison Bumgarner was named the MVP of the 2014 World Series. On Friday, the City of San Francisco held their third World Series parade in less than five years.
NFL- After struggling just to outlast the Jets on Thursday night last week, the Patriots made it look easy against the Chicago Bears last Sunday when Tom Brady threw for 5 TD passes at Gillette Stadium.
New England had a 31-7 lead in the final minute of the first half when Bears QB Jay Cutler fumbled deep in Bears territory and Rod Ninkovitch recovered and ran it back for a TD with 55 seconds left in the half.
Brady would then connect with Gronkowski for a 46 yard TD reception to make it 45-7 on the Patriot's opening possession of the second half. The Patriots would cruise to an easy 51-23 win over Chicago thanks to 3 TD passes from Brady to Gronk, along with TD passes to Tim Wright and Brandon LaFell. Brady went 30-35 with 354 yards on the day to go with the 5 TDs on the day. Gronk caught 9 passes for 149 yards and the 3 TDs while Gostkowski made all three of his FG attempts.
This Sunday's game is a marquee matchup between two first-ballot Hall of Fame QBs when the Patriots will host the Denver Broncos and QB Peyton Manning at Gillette this weekend. Kickoff is scheduled for 4:25 ET and the game will be televised on ESPN.
ELSEWHERE IN THE NFL- As good a day as Brady had last week, Steelers QB Ben Roethlisberger had an even better one, with 6 TDs and 522 yards, going 40-49 in the Steeler's 51-34 win over the Indianapolis Colts. The performance set a Steelers franchise record and was an exclamation point on Big Ben's 100th career win.
NCAA FOOTBALL- The Boston College Eagles are now bowl-eligible after a road win in Blacksburg, VA against Virginia Tech. Although the Hokies got out to an early lead in the first, the Eagles took a 14-10 lead into halftime.
After the half, the Eagles extended their lead to 23-10, but Virginia Tech made it a 23-17 game early in the 4th quarter and took a one point lead on a pass from QB Michael Brewer to TE Bucky Hodges to give the Hokies a 24-23 lead.
With just over five minutes to go in regulation, Alex Howell gave Boston College the lead once again thanks to a 44 yard FG attempt. After the Eagles defense held the Hokies to a 3 and out on the following possession, the Eagles started to pull away thanks to a 57 yard TD run from QB Tyler Murphy to make it 33-24 Boston College. The Hokies would close the gap to 31-33 thanks to another driver from Brewer that was capped with a 5 yard TD pass with 1:09 to go, but the following onsides kick was recovered by the Eagles, which allowed them to simply take a knee and run out the clock.
Murphy went 8 for 15 with 110 yards and two TDs passing and 122 yards rushing with another TD. Charlie Callinan and Marcus Outlow each had TD receptions on Saturday as well.
This would be Boston College's second win in a row after beating Wake Forest on the road last Saturday by a 23-17 final. Next Saturday, Boston College will host the Louisville Cardinals at Chestnut Hill. Kickoff is scheduled for 7:25 PM ET and the game will be televised on ESPN 2.
On Saturday night, the B's returned home to host the Ottawa Senators for the first time this season. Marchand would open up the scoring on Saturday night, giving Boston a 1-0 lead a little over a minute into the contest. Mark Stone got the equalizer for Ottawa with about 30 seconds to go in the first period, giving the Bruins a 3-1 lead.
The second period was all about Matt Fraser as he had two tallies less than 90 seconds apart to give Boston a 3-1 lead. Heading into the 3rd, the Bruins would add tack on some more insurance when Seidenberg got an unassisted goal just over two minutes into the period. Ottawa would get on the board once again with a Mika Zibanejad goal with about five minutes left to go, but that would be it for the Sens.
Tukks Rask turned aside 27 of 29 shots faced on Saturday as the Bruins went on to win by a 4-2 final in their first meeting with Ottawa.
The Bruins homestand continues on Tuesday when the B's will host the 4-2-3 Florida Panthers at the Garden. Puck is scheduled to drop at 7:00 ET and the game will be televised on NESN
Posted by Fenway_Nation at 1:00 PM No comments: Links to this post
Friday, October 31, 2014
Today's Train of Thought- Throroughbreds and Pumpkins, Oct 31st, 2014
Today's Train of Thought takes us to a pumpkin patch rural central Pennsylvania that just happens to abut the former Pennsy mainline between Pittsburgh and Harrisburg, PA. Here, rrpicturearchives.net contributor Rick Erben caught Norfolk Southern C40-9W #9978 leading a motley lashup- including an SD60I, an SD40-2, a GP38-2 still in Conrail blue and a C39-8- as it leads an eastbound manifest through the quiet Juniata County village of Mexico on Oct 21st, 2010. The pumpkins in the foreground still have a few days to be scooped and made into jack-o-lanterns or pies in time for Halloween that year.
Thursday, October 30, 2014
Utah National Guardsmen Face Sanction Over Bikini Calendar Shoot on National Guard Property
A number of Utah National Guardsmen and State Troopers are in trouble after allowing a racy calendar shoot to take place at one of their facilities with scantily clad British models firing automatic weapons- some of which were the property of the state of Utah.
British bikini models fired guns owned by the state of Utah as an on-duty state police officer stood by, according the early findings of an ongoing investigation.
A second officer from the Utah Department of Public Safety was off-duty, according to a statement the department issued late Thursday.
DPS is investigating the two officers' roles in the models' photo and video shoot for the 2015 bikini calendar called "Hot Shots."
Meanwhile, the Utah National Guard also is investigating how the models entered Camp Williams and used resources there, including riding in a tank and other vehicles, as part of the shoot.
Logs from that day show that one of the officers was on duty and another off. Both belong to the department's SWAT team.
While part of the photo shoot was at the Utah National Guard's Camp Williams, videos and stills of some of the barely dressed models were filmed at the privately operated Big Shots Ranch in Grantsville, UT.
Although policy for the Utah State Police allows for officers to serve as firearms instructors or display weapons in the department's armory to public officials or groups like the Boy Scouts, such events have to be pre-approved by the chain of command. Some of the guns used by the British models include the Heckler & Koch MP5 9mm submachine gun, a select fire 9mm Glock 18 [which means the gun can fire semiauto of full auto- NANESB!] and the M4 Carbine, the current US Army and National Guard issue rifle which is essentially a scaled down M-16 rifle. Although a Utah State Police spokesman said three of the weapons are believed to be agency-issue, the ammunition was reportedly provided by Big Shots range.
The two Utah State Police officers identified in the video were identified as members of the agency's SWAT team and logs indicate that one of them was on-duty at the time. Both of them were reportedly in uniform at the time, as well.
Meanwhile, the Camp Williams segment of the photo shoot may end up costing some National Guardsmen their jobs.
Maj. Gen. Jeff Burton told lawmakers Thursday that the handful of Guard members involved could face fines, demotions or forced retirements when an investigation is complete. Those involved, which include combat veterans and Purple Heart recipients, didn't follow guidelines for private use of military equipment at Camp Williams, he said.
The Hot Shots calendar is available in early November and a portion of all sales will go to the UK-based Help for Heroes charitable organization.
Saturday, October 25, 2014
Instant Sports Chowdah Update- Failure to Launch, Patriots Survive Jets on Last Second Blocked FG; Wakey Wakey, Boston College Outlasts Deacons; Near Miss, LSU Hands Ole Miss First Loss of Season
NFL- With the longer-than-usual wait after last Thursday night's game, at times it almost felt as though the Patriots had a bye week.
The Patriots got out to an early lead in their only Thursday night game of the season, but a very game New York Jets team was never far behind. New England took a 17-12 lead against New York into halftime, thanks to a 39 yard Gostkowski FG as time expired in the 2nd quarter.
With 9 minutes to go in the 3rd quarter, the Jets took their first lead of the night with a drive that was capped by a short Nick Ivory TD run to give them a 19-17 lead. On the following drive, the Patriots got as far as the Jets red zone, and even though they had to settle for another Gostkowski field goal, the Patriots re-took the lead with 4:10 to go in the first.
It looked as though the Patriots were beginning to pull away midway though the 4th quarter when Brady connected with WR Danny Amendola for a 19 yard TD reception to make it a 27-19 lead, but with just over two and a half minutes to go, the Jets capped an 81 yard drive that took just under 5 minutes with a 10 yard TD pass from Geno Smith to TE Jeff Cumberland to bring the Jets to within two- however, the two point conversion attempt failed and New England still clung to a 27-25 lead.
After the Jets defense held New England to a 3 and out, the Patriots were forced to punt and managed to succeed in pinning the Jets back at their own 12 yard line with just over a minute to go in regulation. With the clock ticking, the Jets were able to get the ball as far as the Patriots 40 yard line with just 5 seconds left on the clock, setting up a potential game-winning FG attempt of nearly 60 yards [difficult, but not impossible- NANESB!]. However, in a bit of payback from last year's Jets win on a FG, DT Chris Jones managed to Block Folk's 58 yard attempt as time expired, giving New England the 27-25 victory- their second straight win against an AFC East opponent.
The Patriots homestand will continue with an early afternoon game against the Chicago Bears with a 1:00 kickoff at Foxbourough on Sunday afternoon. The game will be broadcast on FOX and XM subscribers can listen on channel 85.
WORLD SERIES- Those of you who had their hearts set on an all-Missouri World Series have Giants infielder Travis Ishikawa to blame for that not taking place this year.
Ishikawa belted a walkoff home run in extra innings of Game 5 of the NLCS which ended the Cardinals season and punched the Giants ticket to their 3rd World Series since 2010.
The Giants faced a game Kansas City, who made pretty quick work of the Orioles in the ALCS. Despite San Francisco dominating Game 1 behind a commanding performance by starter Madison Bumgarner, going on to win by a 7-1 final, the Kansas City Royals came storming back in Game Two. This send to series to San Francisco tied at 1 game each.
After winnign Game 3 by one run, Kansas City headed into Saturday night's Game 4 with a 2 games to one lead and things were looking promising when the ROyals batters were able to chase Giants starter Ryan Vogelsong off the mound after just two and two-thirds innings and take a 4-1 lead over San Francisco. However, the Giants batters would go on to score a total of 10 unanswered runs, tying the game with a Hunter Pence RBI single and Juan Perez RBI sac-fly in the bottom of the 5th followed by a 2-RBI single by Pablo Sandoval and a Brandon Belt RBI single in the bottom of the 6th to San Francisco the 7-4 lead. However, the Giants weren't done and got plenty of insurance runs tacked on in the bottom of the 7th and would go on to win Game four by an 11-4 final and tie the series up at 2-2, ensuring that the series would head back to Kansas City regardless of outcome.
DENVER BRONCOS- On Sunday afternoon, Broncos QB Peyton Manning surpassed Brett Favre to become the NFL leader in career TD passes during the October 19th win against the San Francisco at Mile High. Manning recorded a total of 4 TD passes in that game and three TD passes in Thursday night's 35-21 win over the San Diego Chargers at Denver for a career total of 513.
Manning, who has been in the league since 1998, is only one of seven all-time NFL quarterbacks to surpass the 300 career TD mark- although the other two include both Tom Brady and Drew Brees.
NCAA FOOTBALL- After a close loss to Clemson on Chestnut Hill last week, the Boston College Eagles travelled to the Tarheel State to take on Wake Forest on Saturday. The Eagles took a 17-0 halftime lead into the locker room and were able to add onto it in the 3rd and 4th quarters, jumping out as far as 23-3 in the second half before the Deacons could get any kind of offensive rhythm going.
But with BC seemingly cruising in the 4th quarter, the Deacons managed to string together a drive that netted their first TD of the day with just over 8 minutes too go in the ballgame. Still trailing 23-10, Wake got the ball back deep in BC territory when BC sophomore Myles Willis funbled the kickoff deep in Eagles territory. Starting on BC's 15 yard line, the Wake offense was able to punch it in and make it a 1-possession game, with the Eagles still clinging to a 23-17 lead.
However, BC junior Justin Simmons was able to pick off Deacons QB John Wolford on the next Wake Forest possession, sealing the game for Boston College late in the 4th quarter. Eagles QB Tyler Murphy had 165 yards passing and a TD along with 77 yards rushing on the day. RB Jon Hilliman rushed for 101 yards and 2 TDs on the afternoon.
Next Saturday, Boston College will travel down to Blacksburg, VA to take on Virginia Tech. Kickoff is scheduled for 12:30 ET and the game will be streaming on ESPN3.
ELSEWHERE IN THE ACC- Last week's highly-touted battle of the unbeatens lived up to the billing as #2 Florida State was able to get by #5 Notre Dame last Saturday by a 31-27 final. This leaves Florida State as one of the few remaining undefeated teams in the NCAA top 25 polling.
The Seminoles actually have this week off, but will return to action on Thursday night against 6-2 Louisville. That game gets underway at 7:30 ET and the game will be televised on ESPN.
ELSEWHERE IN NCAA FOOTBALL- And then there was only one undefeated in the Magnolia State.
On Saturday night, the #24 LSU Tigers handed #3 Ole Miss their first loss of the 2014 season in Baton Rouge in what turned out to be a surprisingly low-scoring affair. The Rebels led 7-3 for most of the game until 5:45 to go in the 4th quarter when the bayou Bengals took their first lead of the night on a 4 yard TD pass from QB Anthony Jennings to TE Logan Stokes to put LSU up 10-7.
Although Ole Miss had a couple of late chances to tie the game or go ahead, they were undone by a penalty that put them out of FG range with 14 seconds left in the game. Instead of trying for the game-tying FG, Ole Miss opted for a Hail Mary since the penalty that had pushed them out of FG range. The game would end on LSU intercepting Ole Miss' 30 yard pass attempt with less than 10 seconds left, giving the Ole Miss Rebels their first loss of the season.
NHL- Hockey Night in Canada got underway on Saturday night north of the border with an Original Six matchup that pitted the Boston Bruins against the Toronto Maple Leafs.
This was the first home game for the Maple Leafs since Wednesday's attack on Canada's Parliament, and the pregame ceremony honored Cpl. Cirillo, the Canadian soldier at the War Memorial who was shot dead by the gunman before he made his way to the parliament building.
For the Bruins, this was the first game after their 3-2 loss to the Islanders at home on Thursday night.
Carl Soderberg got the Bruins on the board early just three and a half minutes into the first. Tukka Rask made it hold up, carrying a shutout to the final five minutes of the 3rd period and David Krejci make it a 2-0 Bruins lead late in the 2nd before Greg Campbell and Dougie Hamilton scored less than two and a half minutes apart to give Boston a 4-0 lead.
Toronto broke through with a goal from Richard Panik with just over 5 and a half minutes to go in the 3rd, but the Bruins would go on to win by a final of 4-1.
After Saturday, the Bruins will head back to Boston where they'll face the Minnesota Wild on Tuesday night. The game will be televised on NESN and NBC Sports with the puck scheduled to drop at 7:00 ET.
Posted by Fenway_Nation at 10:42 PM No comments: Links to this post
Labels: ACC, BC Eagles, Boston Bruins, Denver Broncos, Kansas City Royals, LSU, Mississippi, MLB, NHL, NY Jets, Original 6, Patriots, San Francisco, SEC, Toronto Maple Leafs, Wake Forest, World Series
Thursday, October 23, 2014
Gunman Fatally Shoots Soldier at Ottawa War Memorial, Opens Fire in Canadian Parliament
A gunman opened fire on a Canadian soldier who was on sentry duty at a War memorial in Canada's capital on Wednesday before advancing to the Parliament building where the assailant was shot and killed by the sergeant-at-arms in an exchange of gunfire.
According to the CBC, witnesses reported a gunman who approached the War Memorial from the west at 9:50 AM local time and fired twice at 24 year old Cpl Nathan Cirillo, striking him in the abdomen and firing a round at another soldier stationed at the memorial, but missing. Although Cirillo and the other soldier had rifles at the time, they were reportedly inert and used for ceremonial purposes. Cirillo would later die of his injuries, leaving behind a five year old son.
As witnesses and paramedics attempted to revive Cirillo, the gunman left the area in a beige car with the license plates removed, abandoning it several blocks from the parliament building and making his way there on foot. After getting through a checkpoint and commandeering a government vehicle, the gunman makes his way into Parliament's Centre Block.
Upon making his way inside the parliament building, members of parliament barricaded themselves in their offices as the gunman shot at sergeant-at-arms Kevin Vickers, a veteran former Royal Canadian Mounted Police officer from New Brunswick. Vickers returned fire with his sidearm, killing the gunman and stopping his rampage before he could get any further inside the parliament building.
Video released by a Toronto Globe and Mail reporter on the scene as events unfolded show officers advancing down a marble corridor with their weapons drawn. The camera jostles as a single shot rings out- believed to be from the assailant's lever-action .30-30 rifle- followed by a dozen or so shots fired in rapid succession [which could easily be from Vickers 9mm- NANESB!] echo through the corridors amid shouting and additional officers rushing towards the sound of gunfire.
The gunman has been identified by the RCMP as a 32 year old convert to Islam named Michael Zehaf-Bibeau. The weapon used was a lever-action Winchester hunting rifle common in both Canada and the USA, but since Zehaf-Bibeau reportedly had a criminal record, investigators are looking into how he obtained the gun.
Sadly, Cpl Cirillo wasn't the first Canadian soldier killed by a radicalized islamist in eastern Canada this week. The Ottawa shooting comes just days after two Canadian soldiers were struck by a hit and run driver outside of Montreal. The driver, a 25 year old Québécois convert to radical islam named Martin Coutere-Rouleau reportedly waited for more than two hours in the parking lot of a building that housed a number of government and civilian agencies in St Jean sur Richelieu before striking at least two soldiers with his 2000 Nissan Altima. Coutere-Rouleau was later shot and killed by police during a high speed chase.
Both Coutere-Rouleau and Zehaf-Bibeau were reportedly under scrutiny from Canada's CSIS intelligence service as the two of them adorned their social media pages with imagery supporting the ISIS Islamic group and expressing a desire to travel to Syria to fight alongside the Islamic state. Couture-Rouleau's passport was seized in June, but since he hadn't broken any Canadian laws the RCMP and Sûreté du Québec couldn't press charges. One of the soldiers, identified as 53 year old Patrice Vincent, later died of his injuries after being struck by Coutere-Rouleau's Nissan.
Prime minister Stephen Harper, who had recently pledged to support Kurdish and Iraqi forces fighting the Islamic State, described both the Ottawa and St Jean sur Richelieu attacks as terrorism when addressing the nation on TV on Wednesday.
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text:
Ivan C. Karp papers and OK Harris Works of Art gallery records, 1969-2014
OK Harris Gallery (New York, N.Y.),
est. 1969
Art gallery
New York, N.Y.
Collection size: 80.3 linear feet
Collection Summary: Biographical material, professional correspondence, administrative files, subject and artists' files, writings by Ivan Karp, and photographs relating to the OK Harris Works of Art gallery and Ivan and Marilynn Karp.
Biographical/Historical Note: OK Harris Works of Art (est.1969- ) is a gallery in New York, N.Y. representing contemporary artists. The gallery was established by Ivan Karp.
Donated 2013 and 2014 by Marilynn Karp, Ivan C. Karp's widow.
How to Use this Collection
- Use of original papers requires an appointment and is limited to the Archives Washington, D.C., Research Center. Contact Reference Services for more information.
- For more information on using the Archives' resources, see the FAQ or Ask Us.

subset: commoncrawl


text: Salon Says AtheistTV is a Grim Experience by John Sexton 13 Aug 2014 post a comment Share This: There's a new streaming channel for atheists called AtheistTV. Daniel D'Addario at Salon watched four hours worth and found it to be too much for a non-believer to take: after watching four hours of its programming and even despite my own lack of religious belief, I find it hard to imagine that even a casual nonbeliever would tune in, let alone someone on the fence about the existence of a higher power. AtheistTV adheres to nasty stereotypes about atheism — smugness, gleeful disregard for others' beliefs — to a degree that's close to unwatchable. After a description of what sounds like a truly terrible call-in show, D'Addario continues: AtheistTV frames atheism as a perpetual reaction against a conquering force. And that reaction isn't reasoned debate. It's unattractive nihilism...Beyond the catharsis of mockery, what can AtheistTV offer? What alternative does it provide? It's a good question. So far the answer seems to be not much. To be fair, I remember watching the Sci-Fi channel in the early days. It was pretty terrible too. I mean here's the sort of thing they were doing on launch day: Sure it was bad back then but look at how far they've come. Now we're getting original masterpieces like Sharnado 2: The Second One. Okay, maybe that's not the best example. The point is that by 2035 AtheistTV could be far more watchable if, like the renamed SyFy channel, it can overcome the twin killers of "unattractive nihilism" and poor production values. Only one of those problems can be overcome with money.


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6th April 2014
Blondie icon Debbie Harry comes out as bisexual 20
2:10 PM — Blondie star Debbie Harry has revealed she is bisexual and thinks "women are more sensual."
1st April 2014
Alec Baldwin to play Putin in biopic about Russian President's life 25
11:39 AM — US actor Alec Baldwin is set to play Vladimir Putin in a film about the Russian President's life.
30th March 2014
Ghanaian ex-deputy speaker: British family values are under a 'satanic attack' from gay rights advocates 41
12:35 PM — A former senior politician in Ghana has claimed that British family values are in "a serious crisis" due to the promotion of gay rights.
Kyrgyzstan: Lawmakers introduce bill to ban 'positive attitudes' about homosexuality 10
11:19 AM — Lawmakers in Kyrgyzstan have introduced a new bill to make any "positive" statement about homosexuality a criminal act punishable by up to one year in jail and a fine.
28th March 2014
David Cameron: When people's love is divided by law, it is the law that needs to change 114
10:00 PM — Writing exclusively for PinkNews, Prime Minister David Cameron celebrates the introduction of same-sex marriage today, comparing same-sex marriages to his own, and noting the work still to be done for equality.
25th March 2014
Campaigns demand FIFA bans Russia from hosting 2018 World Cup due to anti-gay law 6
3:01 PM — Campaigns in the UK and US featuring petitions with signatures from 60 countries are demanding that FIFA should relocate the 2018 World Cup from Russia.
24th March 2014
Russia: Thugs attack members of St Patrick's Day flash mob mistaking them for gay activists 26
3:28 PM — A group of thugs in the Russian city of Irkutsk beat up members of a St Patrick's day flashmob recently, mistakenly believing they were gay activists.
20th March 2014
Openly gay retired figure skater Johnny Weir confirms separation from husband 7
8:02 PM — Retired US figure skater Johnny Weir has publicly announced that he and his husband have separated.
17th March 2014
US reverend: Obama should be more like Putin in tackling gay issues 5
8:05 PM — A US evangelist has made the claim that Obama should look to Russian President Vladimir Putin for inspiration with how to handle gay rights.
Author of Russian anti-gay law sanctioned by US over role in Ukraine crisis 2
7:54 PM — The Russian politician who wrote and sponsored the country's widely condemned anti-gay law is among various political figures to be subjected to sanctions because of their role in the Ukraine crisis.
Evening Standard owner Evgeny Lebedev: Russia is not a homophobic country and I'm not gay 19
11:41 AM — Media tycoon Evgeny Lebedev has defended his native country Russia from suggestions it's intrinsically homophobic and says he doesn't care if people think he is gay.
16th March 2014
Outrage as Ben Summerskill claims Lib Dems cynically and opportunistically supported equal marriage 58
9:53 AM — Former Stonewall Chief Executive Ben Summerskill has launched an extraordinary attack on the Liberal Democrats, accusing the party of supporting same-sex marriage in a "cynical and opportunistic way", despite his own u-turn on the issue.
15th March 2014
Irish health minister to discuss Russia's anti-gay laws during Moscow trip 4
2:08 PM — Ireland's Junior Health Minister Alex White is to bring up Russia's anti-gay law in a trip to Moscow taking place this week.
14th March 2014
Ex-UKIP 'Gay marriage caused storms' councillor to face Council investigation
3:24 PM — A former UKIP councillor who blamed flooding on equal marriage is to be formally investigated by officials.
Cameron, Clegg and Miliband: Britain is ready for a gay Prime Minister 21
12:27 PM — The UK's main three political leaders say there's nothing to stop a gay politician from running the country.
13th March 2014
Paul O'Grady: 'David Cameron is a twat and the Lib Dems are as much use as men's tits' 25
6:25 PM — Paul O'Grady has made a statement against David Cameron and the coalition Government, saying that the former is "a right twat", and the Lib Dems are "as useful as men's tits."
9th March 2014
Video: Russian gay rights campaigners pelted with eggs at International Women's Day rally 5
12:59 PM — A group of armed men were arrested in Moscow yesterday after they disrupted a gay rights demonstration for International Women's Day by throwing eggs at the demonstrators and setting fire to their placards.
6th March 2014
Russian minister accidentally called 'gay lover' in Channel 4 subtitle mix-up 8
8:18 PM — The Russian Foreign Minister has accidentally been referred to as "so gay lover of", in a subtitle mix-up during a Channel 4 report.
Dalai Lama says gay marriage is 'OK' and anti-LGBT bullying is 'wrong' 36
2:04 PM — In a rare interview, the Dalai Lama has said that he thinks same-sex marriage is "OK", and voiced his disapproval at the bullying of LGBT people.
4th March 2014
Game allows users to create 'gay Putin', and play dress-up with him 16
6:39 PM — A new website has been created in order to support LGBT people in Russia, which allows users to create a 'Gay Putin', using props and outfits to add to a cartoon version of the Russian President.


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WWE's Return to MSG, Documentary Made on Former WWE Star, More
by Staff - December 26, 2010
- A documentary has been made on wrestler Matt Bloom, formerly known as A-Train in WWE and now known as Giant Bernard in Japan. The movie is called "The Commute" and is a 13-minute look at how Bloom, his wife and young daughter commute from their home in Arizona to Japan for his job as a wrestler. The film will be playing in March at the Cinequest Film Festival in San Jose, California. Bernard currently holds the IWGP Tag Team Championship in New Japan Pro Wrestling.
– Rebecca Budig, who briefly hosted WWE's Sunday Night Heat back in 2000, recently won ABC's Skating with the Stars reality TV show.
– Both Vince McMahon and John Laurinaitis were backstage at last night's WWE live event in New York City.
– WWE will return to New York City at Madison Square Garden for a RAW live event on Saturday, March 19th.
Partial source: Wrestling Observer Newsletter
|New WWE Tag Team Champions Crowned at Survivor Series, Steve Austin's Live Podcast Coming to WWE Network
|Seth Rollins On Brock Lesnar's Title Reign - "I Think It's Bull Crap, I Don't Appreciate It One Bit"
The Hottest WWE news, photos and videos delivered to your inbox in one convenient newsletter. Sign up now and give it a try!
|WWE Survivor Series Report - 11/23/14
|Screeching Weasel Frontman Blasts CM Punk, Calls on Female Fans to Challenge Punk to Fight
|Sting Makes His WWE TV Debut, Possible Match Against Triple H?, Update on The Authority
|*Spoiler* Huge, Huge Name Scheduled to Make WWE TV Debut at Survivor Series
|The Latest On When Roman Reigns May Return To The Ring, Check Out Sting's WWE 2K15 Entrance


text:
It may be press day at Poultry World, but that's no excuse for neglecting other responsibilities.
Archive | June, 2012
Origami hens send powerful message to Spain
Ducks stop traffic
A farmer caused traffic chaos in a Chinese town when he attempted to herd 5,000 ducks to a nearby pond.Traffic ground to a halt as he and his farm hands drove the horde 1km across the city of Taizhou, Zhejiang, in search of food and pedestrians and vehicles were forced to weave in and out […]
Water off a hen's back
This clucky lady looks like she's in training for Olympic Gold. While she may not be fast enough to beat Rebecca Adlington in the 100m Gold we'd give her a first for effort – it's the first hen we've ever seen be courageous enough to brave the water. The hen was spotted taking at dip […]
Confused Chicken
It would seem that it's not just humans that suffer from gender dysphoria – chickens do too. Helga, a Vorwerk from Cheshire, is going through some rather strange changes. Its owner, Lindsey Jones, bought Helga as a pullet over 12 months ago. The bird laid two soft eggs three months ago and has stopped […]
Perseverence pays off for passionate pigeons
The Feathered Forager has been literally inundated with calls from concerned readers wanting to know the fate of the pigeons perched on my bathroom window ledge last month
Save up to 30% off Poultry World
Latest poultry news
- FSA chicken campylobacter testing show 70% contaminated November 27, 2014
- Industry launches campy website to reassure consumers November 26, 2014
- New movement licences for eggs from bird flu zone November 26, 2014
- Clean drinking water is key to poultry performance November 26, 2014
- Bird flu outbreak prompts farmers to weigh up insurance... November 25, 2014


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Oldsmobile Eighty-Eight Royale Questions Maintenance & Repair
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I have a Oldsmobile 98 fan works put it on defrost the A/C comes on. but I cant get the temperature control to give me heat?
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Replaced fuel filter a week ago
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it is now blowing on windshield and some on the floor cant get it to switch
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The switch will energize the fan on positions 1, 2, and 3 but not 4. Does it need to be replaced or just cleaned. How do I go about doing this
How To Reset Theft Deterrant System Module So My Car Will Start
Went to pet store, came back out & wouldnt start. Power to everything like windows, radio, lights- but nothing happened when i turned key. No crank, no clicking...nothing. Extremely hot outside, ...
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From a cold start.. drive for 10 minutes and then the car will stop running while in gear and moving. Has done this three times...stopped in the exact same location -3.8 miles from home. May or ...
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I have had the 93 olds 88 royale and has been an excellent car up until the last year. I have had it towed 4 times in the last year and each time has been no start no spark and been fixed by replacing...
I Have A 1994 Oldsmobile Royale 3.8l That Runs Fine All Day.
Then some days I'll go out there and it will not start at all. It'll turn over and just keep turning over. I've checked the fuel line with the valve stem and it has excellent pressure. When I spraye...
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all the doors open but today THE DRIVERS DOOR WONT UNLOCK.
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Bryan L Roth
University of North Carolina at Chapel Hill, North Carolina, United States
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Total impact
Available from: C.J. Malanga
The G-protein biased k-opioid receptor agonist RB-64 is analgesic with a unique spectrum of activities in vivo.
Kate White
J Elliott Robinson
Jeffrey DiBerto
Prabhakar Polepally
Jordan Zjawiony
David Nichols
C J Malenga
, Bryan L Roth
[Show abstract]
[Hide abstract]
The hypothesis that functionally selective GPCR agonists may have enhanced therapeutic benefits has revitalized interest for many GPCR targets. In particular, although κ-opioid receptor (KOR) agonists are analgesic with a low risk of dependence and abuse, their utility is limited by a propensity to induce sedation, motor incoordination, hallucinations and dysphoria-like states. Several labs have produced a body of work implying that G-protein biased KOR agonists might be analgesic with fewer side-effects. Although this has been an intriguing hypothesis, suitably KOR selective and G-protein biased agonists have not been available to test this idea. Here we provide data using a G-protein biased agonist RB-64 which suggests that KOR-mediated G protein signaling induces analgesia and aversion, whereas β-arrestin 2 signaling may be associated with motor incoordination. Additionally, unlike unbiased KOR agonists, the G protein-biased ligand RB 64 does not induce sedation and does not have anhedonia-like actions, suggesting that a mechanism other than G protein signaling mediates these effects. Our findings provide the first evidence with a highly selective and G-protein biased tool compound that many, but not all, of the negative side effects of KOR agonists can be minimized by creating G protein biased KOR agonists.
Journal of Pharmacology and Experimental Therapeutics 10/2014;
· 3.89 Impact Factor
DREADDs (Designer Receptors Exclusively Activated by Designer Drugs): Chemogenetic Tools with Therapeutic Utility.
Daniel J Urban
, Bryan L Roth
[Show abstract]
[Hide abstract]
In the past decade, emerging synthetic biology technologies such as chemogenetics have dramatically transformed how pharmacologists and systems biologists deconstruct the involvement of G protein-coupled receptors (GPCRs) in a myriad of physiological and translational settings. Here we highlight a specific chemogenetic application that extends the utility of the concept of RASSLs (receptors activated solely by synthetic ligands): We have dubbed it DREADDs (designer receptors exclusively activated by designer drugs). As we show in this review, DREADDs are now used ubiquitously to modulate GPCR activity noninvasively in vivo. Results from these studies have directly implicated GPCR signaling in a large number of therapeutically relevant contexts. We also highlight recent applications of DREADD technology that have illuminated GPCR signaling processes that control pathways relevant to the treatment of eating disorders, obesity, and obesity-associated metabolic abnormalities. Additionally, we provide an overview of the potential utility of chemogenetic technologies for transformative therapeutics. Expected final online publication date for the Annual Review of Pharmacology and Toxicology Volume 55 is January 06, 2015. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
Annual review of pharmacology and toxicology. 09/2014;
Michael acceptor approach to the design of new salvinorin A-based high affinity ligands for the kappa-opioid receptor.
Prabhakar R Polepally
Krzysztof Huben
Eyal Vardy
Vincent Setola
Philip D Mosier
, Bryan L Roth,
Jordan K Zjawiony
[Show abstract]
[Hide abstract]
The neoclerodane diterpenoid salvinorin A is a major secondary metabolite isolated from the psychoactive plant Salvia divinorum. Salvinorin A has been shown to have high affinity and selectivity for the κ-opioid receptor (KOR). To study the ligand-receptor interactions that occur between salvinorin A and the KOR, a new series of salvinorin A derivatives bearing potentially reactive Michael acceptor functional groups at C-2 was synthesized and used to probe the salvinorin A binding site. The κ-, δ-, and μ-opioid receptor (KOR, DOR and MOR, respectively) binding affinities and KOR efficacies were measured for the new compounds. Although none showed wash-resistant irreversible binding, most of them showed high affinity for the KOR, and some exhibited dual affinity to KOR and MOR. Molecular modeling techniques based on the recently-determined crystal structure of the KOR combined with results from mutagenesis studies, competitive binding, functional assays and structure-activity relationships, and previous salvinorin A-KOR interaction models were used to identify putative interaction modes of the new compounds with the KOR and MOR.
Planta Medica 08/2014;
· 2.35 Impact Factor
Further evaluation of the tropane analogs of haloperidol.
Dinithia Sampson
Barbara Bricker
Xue Y Zhu
Kwakye Peprah
Nazarius S Lamango
Vincent Setola
, Bryan L Roth,
Seth Y Ablordeppey
[Show abstract]
[Hide abstract]
Previous work from our labs has indicated that a tropane analog of haloperidol with potent D2 binding but designed to avoid the formation of MPP(+)-like metabolites, such as 4-(4-chlorophenyl)-1-(4-(4-fluorophenyl)-4-oxobutyl)pyridin-1-ium (BCPP(+)) still produced catalepsy, suggesting a strong role for the D2 receptor in the production of catalepsy in rats, and hence EPS in humans. This study tested the hypothesis that further modifications of the tropane analog to produce compounds with less potent binding to the D2 receptor than haloperidol, would produce less catalepsy. These tests have now revealed that while haloperidol produced maximum catalepsy, these compounds produced moderate to low levels of catalepsy. Compound 9, with the least binding affinity to the D2R, produced the least catalepsy and highest Minimum Adverse Effective Dose (MAED) of the analogs tested regardless of their affinities at other receptors including the 5-HT1AR. These observations support the hypothesis that moderation of the D2 binding of the tropane analogs could reduce catalepsy potential in rats and consequently EPS in man.
Bioorganic & medicinal chemistry letters. 07/2014;
Silencing Synapses with DREADDs.
Hu Zhu
, Bryan L Roth
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In this issue of Neuron, Stachniak et al. (2014) determine that the chemogenetic silencer hM4Di-DREADD suppresses presynaptic glutamate release, and by generating an axon-targeted hM4Di variant they demonstrate that it can be used to locally silence synaptic transmission in neural circuits.
Neuron. 05/2014; 82(4):723-5.
Synthesis, Pharmacological Characterization, and Structure-Activity Relationship Studies of Small Molecular Agonists for the Orphan GPR88.
Chunyang Jin
Ann M Decker
Xi-Ping Huang
Brian P Gilmour
Bruce E Blough
, Bryan L Roth,
Yang Hu
Joseph B Gill
X Peter Zhang
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GPR88 is an orphan G-protein-coupled receptor (GPCR) enriched in the striatum. Genetic deletion and gene expression studies have suggested that GPR88 plays an important role in the regulation of striatal functions and is implicated in psychiatric disorders. The signal transduction pathway and receptor functions of GPR88, however, are still largely unknown due to the lack of endogenous and synthetic ligands. In this paper, we report the synthesis of a GPR88 agonist 2-PCCA and its pure diastereomers, which were functionally characterized in both transiently and stably expressing GPR88 HEK293 cells. 2-PCCA inhibited isoproterenol-stimulated cAMP accumulation in a concentration-dependent manner in cells expressing GPR88 but not in the control cells, suggesting that the observed cAMP inhibition is mediated through GPR88 and that GPR88 is coupled to Gαi. 2-PCCA did not induce calcium mobilization in GPR88 cells, indicating no Gαq-mediated response. A structure-activity relationship (SAR) study of 2-PCCA was also conducted to explore the key structural features for GPR88 agonist activity.
ACS Chemical Neuroscience 05/2014;
· 3.87 Impact Factor
Allosteric sodium: a key co-factor in class A GPCR signaling.
Vsevolod Katritch
Gustavo Fenalti
Enrique E Abola
, Bryan L Roth,
Vadim Cherezov
Raymond C Stevens
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[Hide abstract]
Despite their functional and structural diversity, G-protein-coupled receptors (GPCRs) share a common mechanism of signal transduction via conformational changes in the seven-transmembrane (7TM) helical domain. New major insights into this mechanism come from the recent crystallographic discoveries of a partially hydrated sodium ion that is specifically bound in the middle of the 7TM bundle of multiple class A GPCRs. This review discusses the remarkable structural conservation and distinct features of the Na(+) pocket in this most populous GPCR class, as well as the conformational collapse of the pocket on receptor activation. New insights help to explain allosteric effects of sodium on GPCR agonist binding and activation, and highlight its role as a key co-factor in class A GPCR function.
Trends in Biochemical Sciences 04/2014;
· 13.08 Impact Factor
Identification of a new selective dopamine D4 receptor ligand.
Dinithia Sampson
Xue Y Zhu
Suresh V K Eyunni
Jagan R Etukala
Edward Ofori
Barbara Bricker
Nazarius S Lamango
Vincent Setola
, Bryan L Roth,
Seth Y Ablordeppey
[Show abstract]
[Hide abstract]
The dopamine D4 receptor has been shown to play key roles in certain CNS pathologies including addiction to cigarette smoking. Thus, selective D4 ligands may be useful in treating some of these conditions. Previous studies in our laboratory have indicated that the piperazine analog of haloperidol exhibits selective and increased affinity to the DAD4 receptor subtype, in comparison to its piperidine analog. This led to further exploration of the piperazine moiety to identify new agents that are selective at the D4 receptor. Compound 27 (KiD4=0.84nM) was the most potent of the compounds tested. However, it only had moderate selectivity for the D4 receptor. Compound 28 (KiD4=3.9nM) while not as potent, was more discriminatory for the D4 receptor subtype. In fact, compound 28 has little or no binding affinity to any of the other four DA receptor subtypes. In addition, of the 23 CNS receptors evaluated, only two, 5HT1AR and 5HT2BR, have binding affinity constants better than 100nM (Ki <100nM). Compound 28 is a potentially useful D4-selective ligand for probing disease treatments involving the D4 receptor, such as assisting smoking cessation, reversing cognitive deficits in schizophrenia and treating erectile dysfunction. Thus, further optimization, functional characterization and evaluation in animal models may be warranted.
Bioorganic & medicinal chemistry 04/2014;
· 2.82 Impact Factor
Tuning up the right signal: chemical and genetic approaches to study GPCR functions.
Patrick M Giguere
Wesley K Kroeze
, Bryan L Roth
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The G protein-coupled receptor (GPCR) family is among the most druggable families in the human proteome. GPCRs are involved in most physiological processes, and our ability to modulate their activity is a hallmark of modern pharmacology. The means by which the activity of GPCRs can be modulated have been expanded by emerging data and concepts in pharmacology, which has created new strategies for their control. These new approaches will lead to the generation of more potent, selective, and efficient pharmaceutics, while reducing inappropriate actions and adverse effects. Herein, we review and comment on some recent advances in chemical and genetic approaches to the profiling of GPCR function, as well as the validation of orphan GPCRs as potential therapeutic targets using engineered receptors.
Current opinion in cell biology 04/2014; 27C:51-55.
· 14.15 Impact Factor
Chemogenetic Inactivation of Ventral Hippocampal Glutamatergic Neurons Disrupts Consolidation of Contextual Fear Memory.
Hu Zhu
Kristen E Pleil
Daniel J Urban
Sheryl S Moy
Thomas L Kash
, Bryan L Roth
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[Hide abstract]
Synaptic consolidation is a process thought to consolidate memory in the brain. Although lesion studies have mainly implicated the hippocampus in this process, it is unknown which cell type(s) or regions of the hippocampus might be essential for synaptic consolidation. To selectively and reversibly suppress hippocampal neuronal activity during this process, we developed a new Gi-DREADD (hM4Di) transgenic mouse for in vivo manipulation of neuronal activity in freely moving animals. We found that CA1 pyramidal neurons could be dose-dependently inactivated by clozapine-n-oxide (CNO). Inactivation of hippocampal neurons within 6 h immediately after conditioned fear training successfully impaired the consolidation of contextual memory, without disturbing cued memory. To anatomically define the brain subregion critical for the behavioral effects, hM4Di viral vectors were transduced and selectively expressed in the glutamatergic neurons in either the dorsal or ventral hippocampus. Significantly, we found that selective inactivation of ventral but not dorsal glutamatergic hippocampal neurons suppressed the synaptic consolidation of contextualmemory.Neuropsychopharmacology accepted article preview online, 14 February 2014; doi:10.1038/npp.2014.35.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 02/2014;
· 8.68 Impact Factor
Available from: Patrick M Giguère
Molecular control of δ-opioid receptor signalling.
Gustavo Fenalti
Patrick M Giguere
Vsevolod Katritch
Xi-Ping Huang
Aaron A Thompson
Vadim Cherezov
, Bryan L Roth,
Raymond C Stevens
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Opioids represent widely prescribed and abused medications, although their signal transduction mechanisms are not well understood. Here we present the 1.8 Å high-resolution crystal structure of the human δ-opioid receptor (δ-OR), revealing the presence and fundamental role of a sodium ion in mediating allosteric control of receptor functional selectivity and constitutive activity. The distinctive δ-OR sodium ion site architecture is centrally located in a polar interaction network in the seven-transmembrane bundle core, with the sodium ion stabilizing a reduced agonist affinity state, and thereby modulating signal transduction. Site-directed mutagenesis and functional studies reveal that changing the allosteric sodium site residue Asn 131 to an alanine or a valine augments constitutive β-arrestin-mediated signalling. Asp95Ala, Asn310Ala and Asn314Ala mutations transform classical δ-opioid antagonists such as naltrindole into potent β-arrestin-biased agonists. The data establish the molecular basis for allosteric sodium ion control in opioid signalling, revealing that sodium-coordinating residues act as 'efficacy switches' at a prototypic G-protein-coupled receptor.
Nature 01/2014;
· 38.60 Impact Factor
Application of Quantitative Structure-Activity Relationship Models of 5-HT1A Receptor Binding to Virtual Screening Identifies Novel and Potent 5-HT1A Ligands.
Man Luo
Xiang Simon Wang
, Bryan L Roth,
Alexander Golbraikh
Alexander Tropsha
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The 5-hydroxytryptamine 1A (5-HT1A) serotonin receptor has been an attractive target for treating mood and anxiety disorders such as schizophrenia. We have developed binary classification Quantitative Structure-Activity Relationship (QSAR) models of 5-HT1A receptor binding activity using data retrieved from the PDSP Ki database. The prediction accuracy of these models was estimated by external five-fold cross-validation as well as using an additional validation set comprising 66 structurally distinct compounds from the WOMBAT database. These validated models were then used to mine three major types of chemical screening libraries, i.e., drug-like libraries, GPCR targeted libraries, and diversity libraries, to identify novel computational hits. The five best hits from each class of libraries were chosen for further experimental testing in radioligand binding assays, and nine of the 15 hits were confirmed to be active experimentally with binding affinity better than 10 µM. The most active compound, Lysergol, from the diversity library showed very high binding affinity (Ki) of 2.3 nM against 5-HT1A receptor. The novel 5-HT1A actives identified with the QSAR-based virtual screening approach could be potentially developed as novel anxiolytics or potential anti-schizophrenic drugs.
Journal of Chemical Information and Modeling 01/2014;
· 4.30 Impact Factor
Structural basis for Smoothened receptor modulation and chemoresistance to anticancer drugs.
Chong Wang
Huixian Wu
Tama Evron
Eyal Vardy
Gye Won Han
Xi-Ping Huang
Sandy J Hufeisen
Thomas J Mangano
Dan J Urban
Vsevolod Katritch
Vadim Cherezov
Marc G Caron
, Bryan L Roth,
Raymond C Stevens
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The Smoothened receptor (SMO) mediates signal transduction in the hedgehog pathway, which is implicated in normal development and carcinogenesis. SMO antagonists can suppress the growth of some tumours; however, mutations at SMO have been found to abolish their antitumour effects, a phenomenon known as chemoresistance. Here we report three crystal structures of human SMO bound to the antagonists SANT1 and Anta XV, and the agonist, SAG1.5, at 2.6-2.8 Å resolution. The long and narrow cavity in the transmembrane domain of SMO harbours multiple ligand binding sites, where SANT1 binds at a deeper site as compared with other ligands. Distinct interactions at D473(6.54f) elucidated the structural basis for the differential effects of chemoresistance mutations on SMO antagonists. The agonist SAG1.5 induces a conformational rearrangement of the binding pocket residues, which could contribute to SMO activation. Collectively, these studies reveal the structural basis for the modulation of SMO by small molecules.
Nature Communications 01/2014; 5:4355.
· 10.74 Impact Factor
Available from: Denis Fourches
HTS Navigator: Freely-accessible cheminformatics software for analyzing high-throughput screening data.
Denis Fourches
Maria F Sassano
, Bryan L Roth,
Alexander Tropsha
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We report on the development of the HTS Navigator software to analyze and visualize the results of high-throughput screening (HTS) of chemical libraries. The HTS Navigator processes output files from different plate readers' formats, computes the overall HTS matrix, automatically detects hits and has different types of baseline navigation and correction features. The software incorporates advanced cheminformatics capabilities such as chemical structure storage and visualization, fast similarity search, and chemical neighborhood analysis for retrieved hits. The software is freely available for academic laboratories. http://fourches.web.unc.edu/Contacts: firstname.lastname@example.com; email@example.com SUPPLEMENTARY INFORMATION: Supplementary figure and data on system requirements are available at Bioinformatics online.
Bioinformatics 12/2013;
· 5.47 Impact Factor
Molecular interactions between general anesthetics and the 5HT2B receptor.
Felipe Matsunaga
Lu Gao
Xi-Ping Huang
Jeffery G Saven
, Bryan L Roth,
Renyu Liu
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[Hide abstract]
Background: Serotonin modulates many processes through a family of seven serotonin receptors. However, no studies have screened for interactions between general anesthetics currently in clinical use and serotonergic G-protein-coupled receptors (GPCRs). Given that both intravenous and inhalational anesthetics have been shown to target other classes of GPCRs, we hypothesized that general anesthetics might interact directly with some serotonin receptors and thus modify their function. Methods: Radioligand binding assays were performed to screen serotonin receptors for interactions with propofol and isoflurane as well as for affinity determinations. Docking calculations using the crystal structure of 5-HT2B were performed to computationally confirm the binding assay results and locate anesthetic binding sites. Results: The 5-HT2B class of receptors interacted significantly with both propofol and isoflurane in the primary screen. The affinities for isoflurane and propofol were determined to be 7.78 and .95 μM, respectively, which were at or below the clinical concentrations for both anesthetics. The estimated free energy derived from docking calculations for propofol (-6.70 kcal/mol) and isoflurane (-5.10 kcal/mol) correlated with affinities from the binding assay. The anesthetics were predicted to dock at a pharmacologically relevant binding site of 5HT2B. Conclusions: The molecular interactions between propofol and isoflurane with the 5-HT2B class of receptors were discovered and characterized. This finding implicates the serotonergic GPCRs as potential anesthetic targets.
Journal of biomolecular structure & dynamics 12/2013;
· 4.99 Impact Factor
Novel Molecular Targets of Dezocine and Their Clinical Implications.
Renyu Liu
Xi-Ping Huang
Alexei Yeliseev
Jin Xi
, Bryan L Roth
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Although dezocine is a partial μ-opioid receptor agonist, it is not a controlled substance. Thus, the characterization of the molecular targets of dezocine is critical for scientific and clinical implications. The goal of this study is to characterize molecular targets for dezocine and determine their implications. A binding screen for dezocine was performed on 44 available receptors and transporter proteins. Functional assays for the novel targets were performed along with computation calculations to locate the binding site. A G protein activation study was performed for the human κ opioid receptor to determine whether dezocine is a κ-antagonist. Data are presented as mean ± standard error. The affinities for dezocine were 3.7 ± 0.7 nM for the μ receptor, 527 ± 70 nM for the δ-receptor, and 31.9 ± 1.9 nM for the κ-receptor. Dezocine failed to induce G protein activation with κ-opioid receptor and concentration dependently inhibited κ-agonist (salvinorin A and nalbuphine)-induced receptor activation, indicating that dezocine is a κ-antagonist. Two novel molecular targets (norepinephrine transporter and serotonin transporter) were identified. Dezocine concentration-dependently inhibited norepinephrine and serotonin reuptake in vitro. The half maximal inhibitory concentrations (expressed as pIC50) were 5.68 ± 0.11 for norepinephrine transporter and 5.86 ± 0.17 for serotonin transporter. Dezocine occupied the binding site for known norepinephrine transporter and serotonin transporter inhibitors. The unique molecular pharmacological profile of dezocine as a partial μ-receptor agonist, a κ-receptor antagonist, and a norepinephrine and serotonin reuptake inhibitor (via norepinephrine transporter and serotonin transporter) was revealed. These discoveries reveal potentially important novel clinical implications and drug interactions of dezocine.
Anesthesiology 11/2013;
· 5.16 Impact Factor
Available from: Maria Florencia Sassano
In Silico Molecular Comparisons of C. elegans and Mammalian Pharmacology Identify Distinct Targets That Regulate Feeding.
George A Lemieux
Michael J Keiser
Maria F Sassano
Christian Laggner
Fahima Mayer
Roland J Bainton
Zena Werb
, Bryan L Roth,
Brian K Shoichet
Kaveh Ashrafi
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Phenotypic screens can identify molecules that are at once penetrant and active on the integrated circuitry of a whole cell or organism. These advantages are offset by the need to identify the targets underlying the phenotypes. Additionally, logistical considerations limit screening for certain physiological and behavioral phenotypes to organisms such as zebrafish and C. elegans. This further raises the challenge of elucidating whether compound-target relationships found in model organisms are preserved in humans. To address these challenges we searched for compounds that affect feeding behavior in C. elegans and sought to identify their molecular mechanisms of action. Here, we applied predictive chemoinformatics to small molecules previously identified in a C. elegans phenotypic screen likely to be enriched for feeding regulatory compounds. Based on the predictions, 16 of these compounds were tested in vitro against 20 mammalian targets. Of these, nine were active, with affinities ranging from 9 nM to 10 µM. Four of these nine compounds were found to alter feeding. We then verified the in vitro findings in vivo through genetic knockdowns, the use of previously characterized compounds with high affinity for the four targets, and chemical genetic epistasis, which is the effect of combined chemical and genetic perturbations on a phenotype relative to that of each perturbation in isolation. Our findings reveal four previously unrecognized pathways that regulate feeding in C. elegans with strong parallels in mammals. Together, our study addresses three inherent challenges in phenotypic screening: the identification of the molecular targets from a phenotypic screen, the confirmation of the in vivo relevance of these targets, and the evolutionary conservation and relevance of these targets to their human orthologs.
PLoS Biology 11/2013; 11(11):e1001712.
· 12.69 Impact Factor
Available from: Patrick M Giguère
DREADDs: novel tools for drug discovery and development.
Hyeong-Min Lee
Patrick M Giguere
, Bryan L Roth
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Since the invention of the first designer receptors exclusively activated by designer drugs (DREADDs), these engineered G protein-coupled receptors (GPCRs) have been widely applied in investigations of biological processes and behaviors. DREADD technology has emerged as a powerful tool with great potential for drug discovery and development. DREADDs can facilitate the identification of druggable targets and enable researchers to explore the activities of novel drugs against both known and orphan GPCRs. Here, we discuss how DREADDs can be used as novel tools for drug discovery and development.
Drug discovery today 10/2013;
· 6.63 Impact Factor
4β-Methyl-5-(3-hydroxyphenyl)morphan Opioid Agonist and Partial Agonist Derived from a 4β-Methyl-5-(3-hydroxyphenyl)morphan Pure Antagonist.
F Ivy Carroll
Moses G Gichinga
John D Williams
Eyal Vardy
, Bryan L Roth,
S Wayne Mascarella
James B Thomas
Hernán A Navarro
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In previous studies we reported that addition of 7α-acylamino groups to N-phenylpropyl-4β-methyl-5-(3-hydroxyphenyl)morphan (4) led to compounds that were pure opioid receptor antagonists. In contrast to these findings we report in this study that addition of a 7α-amino (5a), 7α-alkylamino (5b-e), or 7α-dialkylamino 5f-h) group to 4 leads to opioid receptor ligands with varying degrees of agonist/antagonist activity. The 7α-amino and 7α-methylamino analogues were full agonists at the μ and δ receptors and antagonists at the κ receptor. The 7α-cyclopropylmethylamino analogue 5h was a full agonist at the μ receptor with weaker agonist activity at the δ and κ receptors. Whereas the addition of a 7α-acylamino group to the pure non-selective opioid receptor antagonist N-phenylpropyl-4β-methyl-5-(3-hydroxyphenyl)morphan (4) led to κ selective pure opioid receptor antagonist, the addition of a 7α-amino, 7α-alkylamino or 7α-dialkylamino group to 4 leads to opioid ligands that are largely μ or δ agonist with mixed agonist/antagonist properties.
Journal of Medicinal Chemistry 10/2013;
· 5.61 Impact Factor
Chemotype-Selective Modes of Action of κ-Opioid Receptor Agonists.
Eyal Vardy
Philip D Mosier
Kevin J Frankowski
Huixian Wu
Vsevolod Katritch
Richard B Westkaemper
Jeffrey Aube
Raymond C Stevens
, Bryan L Roth
[Show abstract]
[Hide abstract]
The crystal structures of opioid receptors provide a novel platform for inquiry into opioid receptor function. The molecular determinants for activation of the k-opioid receptor (KOR) were studied using a combination of agonist docking, functional assays and site-directed mutagenesis. Eighteen positions in the putative agonist binding site of KOR were selected and evaluated for their effects on receptor binding and activation by ligands representing four distinct chemotypes: the peptide dynorphin A (1 to 17), the arylacetamide U-69593, and the non-charged ligands salvinorin A and the octahydroisoquinolinone carboxamide 1xx. Minimally biased docking of the tested ligands into the antagonist-bound KOR structure generated distinct binding modes which were then evaluated biochemically and pharmacologically. Our analysis identified two types of mutations: those that affect receptor function primarily via ligand binding and those that primarily affect function. The shared and differential mechanisms of agonist binding and activation in KOR are further discussed. Usually, mutations affecting function more than binding were located at the periphery of the binding site and did not interact strongly with the various ligands. Analysis of the crystal structure along with the present results provide fundamental insights into the activation mechanism of the KOR, and suggest that functional residues, along with water molecules detected in the crystal structure, may be directly involved in transduction of the agonist binding event into structural changes at the conserved rotamer switches, thus leading to receptor activation.
Journal of Biological Chemistry 10/2013;
· 4.65 Impact Factor
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Vincent Setola
West Virginia University
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Wesley K Kroeze
University of North Carolina at Chapel Hill
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Richard Westkaemper
Virginia Commonwealth University
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David L Willins
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Jordan K Zjawiony
University of Mississippi
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Bioorganic & Medicinal Chemistry Letters
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University of North Carolina at Chapel Hill
• Division of Chemical Biology and Medicinal Chemistry
• Department of Pharmacology
• Department of Medicine
North Carolina, United States
Organix Inc.
Woburn, Massachusetts, United States
Robert Wood Johnson University Hospital
New Brunswick, New Jersey, United States
McLean Hospital
Cambridge, Massachusetts, United States
Yonsei University
Department of Chemistry
Sŏul, Seoul, South Korea
Korea Institute of Science and Technology
Center for Neuro-Medicine
Seoul, Seoul, South Korea
University of California, San Francisco
• Department of Pharmaceutical Chemistry
• Department of Psychiatry
San Francisco, CA, United States
Université du Droit et de la Santé Lille 2
Laboratoire de Chimie Thérapeutiques 2
Lille, Nord-Pas-de-Calais, France
University of Mississippi
• School of Pharmacy
• National Center for Natural Products Research
• Department of Pharmacognosy
University, MS, United States
University of Liège
Luik, Walloon Region, Belgium
Anyang Normal University
Chang-te, Henan Sheng, China
University of Oxford
Department of Pharmacology
Oxford, ENG, United Kingdom
The Scripps Research Institute
Department of Cell and Molecular Biology
La Jolla, CA, United States
University of Wisconsin - Milwaukee
Department of Chemistry and Biochemistry
Milwaukee, WI, United States
Vanderbilt University
Department of Pharmacology
Nashville, Michigan, United States
Florida A&M University
Division of Basic and Pharmaceutical Sciences
Tallahassee, FL, United States
National Institute of Mental Health (NIMH)
Maryland, United States
University of Missouri - St. Louis
Saint Louis, Michigan, United States
University of Toronto
Structural Genomics Consortium
Toronto, Ontario, Canada
University of Pittsburgh
School of Nursing
Pittsburgh, PA, United States
Konkuk University
Department of Bioscience and Technology
Sŏul, Seoul, South Korea
University of Illinois at Chicago
Department of Medicinal Chemistry and Pharmacognosy
Chicago, IL, United States
University of Maryland, Baltimore
Department of Anatomy and Neurobiology
Baltimore, MD, United States
University of Belgrade
Faculty of Pharmacy
Belgrade, SE, Serbia
University of Richmond
Richmond, Virginia, United States
University of Washington Seattle
Department of Biochemistry
Seattle, WA, United States
Virginia Commonwealth University
Department of Medicinal Chemistry
Richmond, VA, United States
University of Münster
Institute of Pharmacology and Toxicology
Münster, North Rhine-Westphalia, Germany
Case Western Reserve University
• Department of Biochemistry
• Department of Psychiatry (University Hospitals Case Medical Center)
Cleveland, OH, United States
Case Western Reserve University School of Medicine
Department of Psychiatry
Cleveland, Ohio, United States
Louisiana State University Health Sciences Center New Orleans
Department of Pharmacology and Experimental Therapeutics
Baton Rouge, LA, United States
Duke University Medical Center
Department of Neurobiology
Durham, NC, United States
Columbia University
Department of Psychiatry
New York City, NY, United States
CUNY Graduate Center
New York City, New York, United States
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Department of Neuroscience
Washington, D. C., DC, United States
National Institute on Drug Abuse
Maryland, United States
National Institutes of Health
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Bethesda, MD, United States
Stanford Medicine
Department of Psychiatry and Behavioral Sciences
Stanford, California, United States
Stanford University
Department of Psychiatry and Behavioral Sciences
Stanford, CA, United States
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San Luis, Missouri, United States
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