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Oakland Athletics |
A's take series over Astros with more…
A's take series over Astros with more late-inning heroics
Oakland Athletics center fielder Mark Canha catches a fly ball by Houston Astros' Alex Bregman during the seventh inning of a baseball game Thursday, July 12, 2018, in Houston. (AP Photo/David J. Phillip)
Mark Canha #20 of the Oakland Athletics singles in two runs in the eighth inning against the Houston Astros at Minute Maid Park on July 12, 2018 in Houston, Texas. (Photo by Bob Levey/Getty Images)
Houston Astros' Jose Altuve (27) is tagged out by Oakland Athletics shortstop Marcus Semien at second base while trying to stretch single into a double during the seventh inning of a baseball game Thursday, July 12, 2018, in Houston. (AP Photo/David J. Phillip)
Nick Martini #38 of the Oakland Athletics doubles in the fifth inning scoring two runs against the Houston Astros at Minute Maid Park on July 12, 2018 in Houston, Texas. (Photo by Bob Levey/Getty Images)
Trevor Cahill #53 of the Oakland Athletics pitches in the first inning against the Houston Astros at Minute Maid Park on July 12, 2018 in Houston, Texas. (Photo by Bob Levey/Getty Images)
Marcus Semien #10 of the Oakland Athletics talks with Jose Altuve #27 of the Houston Astros after hitting a double in the first inning at Minute Maid Park on July 12, 2018 in Houston, Texas. (Photo by Bob Levey/Getty Images)
Matt Chapman #26 of the Oakland Athletics shatters his bat against the Houston Astros at Minute Maid Park on July 12, 2018 in Houston, Texas. (Photo by Bob Levey/Getty Images)
Tony Kemp #18 of the Houston Astros steals second base in the third inning as Chad Pinder #18 of the Oakland Athletics applies the tag at Minute Maid Park on July 12, 2018 in Houston, Texas. (Photo by Bob Levey/Getty Images)
Jonathan Lucroy #21 of the Oakland Athletics hugs Lou Trivino #62 afetr the final out against the Houston Astros at Minute Maid Park on July 12, 2018 in Houston, Texas. Oakland won 6-4. (Photo by Bob Levey/Getty Images)
Oakland Athletics' Matt Chapman (26) and Mark Canha celebrate after a baseball game against the Houston Astros Thursday, July 12, 2018, in Houston. The Athletics won 6-4. (AP Photo/David J. Phillip)
By Martin Gallegos | mgallegos@bayareanewsgroup.com | Bay Area News Group
PUBLISHED: July 12, 2018 at 2:37 p.m. | UPDATED: July 13, 2018 at 3:53 a.m.
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HOUSTON — Any reservations about the A's being a legit team can be laid to rest. They're good.
After taking two out of three from the Indians this past weekend, the A's mounted another late-inning comeback in Thursday's 6-4 victory over the Astros to take three out of four from the defending world series champions in their own house and make it two-straight series wins over first place teams.
The A's (53-41) are currently the hottest team in baseball. Their 19 wins over the past 24 games are the most in baseball during that time, and they are a season-high 12 games over .500, the most games over since the end of the 2014 season when they last made the postseason.
The only thing that kept the A's from a sweep was Wednesday's bizarre loss that featured an ending you'll probably only see once in a lifetime. But they're more than glad to take three of four.
"We've been playing really well and came into this series really confident," A's third baseman Matt Chapman said. "To be in every game and come out with three feels really good. It confirms what we've been feeling."
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As they've done so often over this impressive stretch, the game-winning run came in the eighth inning off the bat off Mark Canha, who smacked a go-ahead two-run double to left off Chris Devenski.
It was the 10th time in their last 23 victories the A's have scored the game-winning run in the eighth inning or later, with their 69 runs scored in the eighth inning this season the most in the majors.
"When you do it so many times, you have confidence doing it," A's manager Bob Melvin said. "It was some different guys today, too. At this point it's a true team effort and that's powerful when you have 25 guys contributing. Doesn't surprise me that we came up with the at-bats we did."
Facing a 3-2 count against Devenski with runners on second and third and an open first base, Canha was just trying to stay alive. He fouled off a slider and fastball, then got the slider again on the seventh pitch of the at-bat and pulled it to left.
"An open base which always makes everything harder because you never know how or if they're gonna attack you," Canha said. "I just kept that in my mind and told myself to not try to do too much and feel out the at-bat. I think I did a good job of just getting into the rhythm and figure out how he was gonna pitch."
Canha's clutch hit came shortly after Matt Chapman's game-tying double to left earlier in the inning, capping off the comeback from what was a 4-0 deficit after just three innings.
Though the A's have become known for their power, especially on the road as their 82 road homers lead the majors, they've also been impressively patient at the plate. They drew 20 walks against Astros (62-34) pitchers this series, a key to producing early exits from the many tough arms in Houston's starting rotation, like Charlie Morton after just 4 1/3 innings Thursday.
"They're a good lineup. Work counts, swing at strikes, and usually take balls," Astros manager AJ Hinch said after Wednesday's game. "That's one of the reasons they've been one of the hottest teams in MLB. It's kinda their calling card, and when they do it right, the at-bats never seem to end."
Canha himself made Astros pitchers throw 22 pitches over his four at-bats on the day, finishing 2 for 4 with two RBIs.
"It's a good feeling to have when you have a guy like Morton on the mound and get him off the mound early, that's big," Canha said. "We're doing a really good job of making these starters throw a lot of pitches. With the level of starting pitchers we're facing day in and day out, that's going a long way."
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With Trevor Cahill lasting just 3 2/3 innings due to an 85-pitch limit in his first start back from the disabled list, the A's got another great effort from their bullpen as well. Chris Hatcher, Yusmeiro Petit, Ryan Buchter, and Lou Trivino combined to allow just one run in 5 2/3 innings of relief, with Petit turning in his fourth consecutive outing of two innings or more with 2 1/3 shutout innings.
Melvin said Petit was "on fumes" after the recent heavy workload, but still managed to retire the Astros top of the lineup in George Springer, Alex Bregman, and Jose Altuve, in order for his last inning of work in the seventh.
"I was trying to get him out of that game but he would not let me take him out of the game with those guys coming up," Melvin said. "He goes, 'Just get somebody going behind me and I'll be fine.' He had their best hitters at the top to deal with."
Martin Gallegos | Oakland Athletics reporter
Martin Gallegos is a multimedia beat reporter covering the Oakland Athletics. A native of San Jose, he frequently attended ballgames at both AT&T Park and the Oakland Coliseum as a kid. Prior to covering the A's, he covered the Earthquakes, San Jose State football, and high school sports around the Bay Area. A self-proclaimed "Burrito Connoisseur," Martin is constantly on the search for the best burrito in each Major League city.
mgallegos@bayareanewsgroup.com
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Gene Wilder: Saying Goodbye to a Legend
by Margaret Parrish
Executive Director, The Cottages At Quail Creek, Amarillo
Sunday the world lost the comedic genius of Gene Wilder. I remember as a child loving his kooky character in the original Charlie and the Chocolate Factory (sorry Johnny Depp, you're just creepy) and the hysterical Young Frankenstein.
What I didn't know was that Gene Wilder had been diagnosed with Alzheimer's three years ago.
His family shared: It is with indescribable sadness and blues, but with spiritual gratitude for the life lived that I announce the passing of husband, parent and universal artist Gene Wilder, at his home in Stamford, Connecticut. It is almost unbearable for us to contemplate our life without him. The cause was complications from Alzheimer's disease with which he co-existed for the last three years. The choice to keep this private was his choice, in talking with us and making a decision as a family. We understand for all the emotional and physical challenges this situation presented we have been among the lucky ones — this illness-pirate, unlike in so many cases, never stole his ability to recognize those that were closest to him, nor took command of his central-gentle-life affirming core personality. It took enough, but not that.
The decision to wait until this time to disclose his condition wasn't vanity, but more so that the countless young children that would smile or call out to him 'there's Willy Wonka,' would not have to be then exposed to an adult referencing illness or trouble and causing delight to travel to worry, disappointment or confusion. He simply couldn't bear the idea of one less smile in the world.
The untimely death of Gene Wilder saddens us all. It saddens me to think of the awareness that he could have brought to the disease that affects five million Americans. It saddens me that the children he was trying to protect from the reality of this vicious disease have family members that could have used increased exposure and attention from Mr. Wilder's fame and diagnosis to garner the support of the medical community and the world at large. It saddens me that his family had no public support. Regardless of whether Gene Wilder was right or wrong in keeping his diagnosis private, as a caregiver I recognize there are thousands of individuals and their families with this same disease that are going at this alone. I don't want anyone to ever feel alone in this disease process.
You will be greatly missed Gene Wilder.

redpajama_set_name: RedPajamaCommonCrawl


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Tinbergen on mirror neurons
Heyes C.
Fifty years ago, Niko Tinbergen defined the scope of behavioural biology with his four problems: causation, ontogeny, survival value and evolution. About 20 years ago, there was another highly significant development in behavioural biology-the discovery of mirror neurons (MNs). Here, I use Tinbergen's original four problems (rather than the list that appears in textbooks) to highlight the differences between two prominent accounts of MNs, the genetic and associative accounts; to suggest that the latter provides the defeasible 'best explanation' for current data on the causation and ontogeny of MNs; and to argue that functional analysis, of the kind that Tinbergen identified somewhat misleadingly with studies of 'survival value', should be a high priority for future research. In this kind of functional analysis, system-level theories would assign MNs a small, but potentially important, role in the achievement of action understanding-or another social cognitive function-by a production line of interacting component processes. These theories would be tested by experimental intervention in human and non-human animal samples with carefully documented and controlled developmental histories.
10.1098/rstb.2013.0180
Philosophical transactions of the Royal Society of London. Series B, Biological sciences


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Het gynaikeion (Oudgrieks: , Latijn: gynaeceum) was het gedeelte van het oud-Griekse huis, dat meer bijzonder door de vrouwen werd bewoond, en waar vreemde mannen niet werden toegelaten.

Het lag gewoonlijk in het achterste gedeelte van het huis of op een bovenverdieping. In het eerste geval lagen de verschillende vertrekken, evenals in het mannenverblijf (andron), rondom een aúlē ().

Referentie
 art. Gynaecēum, in , Woordenboek der Grieksche en Romeinsche Oudheid, Haarlem, 19203, p. 295.
Oud-Griekse architectuur

redpajama_set_name: RedPajamaWikipedia


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The content of this site is intended for educational and scientific research purposes only and not as a source of medical advice or consultation.


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Who Is Choi Min-ho Girlfriend? Is He Dating Anyone?
Leave a Comment / K-Pop / By admin
Choi Min-ho Profile:
Choi Min-ho Ideal Type
DO NOT MISS: K-Drama With Best Second Lead Couples
Choi Min-ho Relationship Status
Who Is Choi Min-ho Girlfriend?
Is Choi Min-ho Girlfriend Choi Sulli?
YOU MAY LIKE THIS: Korean actors who become famous due to supporting roles
Were Choi Sulli and Choi Minho in a Relationship?
Did Choi Min-ho and Choi Sulli Got Married Secretly?
Who is Choi Min-ho Dating Now?
Choi Minho Biography
Choi Min-ho worth
Who Is Choi Min-ho Girlfriend? Is He Dating Anyone? Following his success in the music business, SHINee's Minho is now establishing himself as a notable figure in the realm of Korean drama. The Kpop artist recently won the hearts of fans with his performance as Chae Ugi, Kim Go Eun's office infatuation, in the drama "Yumi's Cells." In this part, he played the role of Kim Go Eun's office crush. Fans will be able to see more of this hottie in the upcoming Netflix series "The Fabulous," where he will star with Chae Soo Bin, as well as in the horror thriller Kdrama "Goosebumps." This is an interesting development. In addition to his continuous professional success, he has been candid about his private life, discussing topics such as his ideal type and his feelings toward marriage.
Next, we take a look at Choi Min-current ho's girlfriend, as well as his prior relationships and dating history, including who he has dated in the past and who is now dating Choi Min-ho. In addition to that, we will discuss Choi's life story, various statistics, his net worth, and a great deal more.
Full Name Choi Min-ho
Birth date December 9, 1991
Horoscope Sagittarius
Birth Place South Korea
Net Worth $100,000 – $1M
Martial Status Single
Height 5′ 9″
Ethnicity Unknown
Nationality South Korean
Weight N/A lbs (N/A kg)
The actor, who is 29 years old, unquestionably is aware of what he desires and does not hesitate to discuss the person who best fits his ideal profile. During his interview on "Entertainment Weekly" on KBS 2 TV, he was able to elaborate on what he considers to be the ideal partner in a romantic relationship. He claims that the qualities that initially drew him the most about a woman are her self-confidence and the enthusiasm that she possesses for the art that she does. The K-pop artist admitted that the qualities of being goal-driven and enthusiastic about one's work are the first things that attract him to a lady.
In a separate interview, he disclosed to the March 2014 edition of Cosmopolitan Korea that the type of female he is interested in is "an open and joyful girl."
He insists that the person he ends up with should exude joy and vitality, particularly when they are together "tired and irritated from work, she has the ability to cheer me up simply by being in the same room as me. For some reason, I find girls like these to be quite appealing."
In terms of her appearance, SHINee Minho envisions the perfect female as someone who possesses natural beauty and who is not overly concerned with her appearance or her cosmetics.
With his striking good looks and unmistakable charisma, the 29-year-old could easily make a girl fall in love with him in a moment; nevertheless, the issue that has to be answered is whether or not he is currently dating someone. Although he is not seeing anyone at the moment, there were rumors that he was seeing Sulli, a former member of the band f(x). Aside from that, he has not admitted to dating anybody, despite the fact that celebscouples.com said that he has only ever been in one relationship and has never been engaged.
When we were talking about being engaged, Minho from SHINee shared some of his thoughts about getting married. During SHINee Taemin's visit on KBS Cool FM's "Moon Hee Jun's Music Show," a fan of the K-pop singers asked them what they want to do when they reached the age of 30.
The actor most known for his role in "Yumi's Cells," who was 27 years old at the time, shared his intention to tie the knot when he reaches the age of 30. The singer-actress and actor revealed, "I want to start a family when I'm in my 30s."
Now, it is safe to assume that the actor from "Hwarang" could be ready to have his own family, but he is still waiting for the ideal female to come along. Currently, he is waiting for the right girl to come along.
It has been said that Minho has a special someone in his life. Surprisingly, that is not an unbelievable occurrence. Because of his attractive appearance and wide range of skills, any woman has the potential to fall in love with him at once. It has been said that he is romantically involved with Choi Suli, a former member of the band f(x), as well as Kim Yuri, a member of the girl group Girs Generations. However, as of this moment, there has been no verified information on his actual girlfriend.
Choi Jin Ri, also known by her stage name Choi Sulli, is a former member of the girl band f(x). Sulli, a visual member of f(x), is responsible for her band's vocals and rapping. Since she was a youngster, Sulli has worked as an actor, and in 2009, she became a member of the girl group f(x). Despite the fact that she is not the actual maknae of f(x), Sulli is commonly referred to as such. She has a sweet appearance, which gives the impression that she is the youngest.
Who Is Choi Min-ho Girlfriend Is He Dating Anyone
It's possible that some of you are a little bit perplexed by this heading, is that right? LOL :p In point of fact, Minho and Sulli got married in the We Got Married series, but this does not mean that it is true. However, there are rumblings that they are involved in a romantic partnership.
Sulli, a former member of f(x), is said to be in a relationship with Minho, according to rumors. After they both took main parts in the television series "To the Beautiful You" in 2012, speculations began to circulate about them. The notion was shot down by Min Ho, who stated that he considers Suli to be his younger sister. He also mentioned that they had known each other when they were both SM Entertainment trainees. There is no question in anyone's mind that when he was acting out a loving moment with Sulli, a romantic emotion began to take root in his heart. They play a married couple in one of the episodes of the series. Therefore, in order for them to truly experience what it is like to be a couple, both of them need to have "intimacy." There is no question that Minho began to develop love feelings toward Sulli. But they disproved such stories as quickly as they could after hearing them. They disproved the rumors that they were romantically involved through the agency. They claimed to be nothing more than pals.
As most of us are aware, We Got Married is a real variety program produced in South Korea that has had a great deal of popularity in that country. The purpose of this show is to provide an insight into the lives of South Korean superstars "after marriage." On this show, the contestants are expected to behave as though they were a married couple. They are required to maintain a natural demeanor while acting in this series in order to produce a "decent" show. Following their appearances on this variety program, a number of Korean celebrity singles go on to find love in real life. As a result of the fact that many viewers like seeing Choi and Choi act as a pair, they were an excellent choice for the We Got Married fictitious couple.
On this particular episode of WGM, they made the decision to select a pair who is represented by the same agency. And in the end, they came to the conclusion that Choi-Choi would work well together. Both of them get together on purpose in order to make plans regarding what would take place with their respective supervisors. Then it was revealed to them that they will be featured together on this WGM version of the game. One of the finest sequences that I have ever seen was in We Got Married, and it was when Choi Minho remarked that he did not mean to make this performance into a show when he was performing it. But as time passed, the two of them became closer to one another, and they taped the program in a really natural way. Woohoo! I know you guys have been waiting for it, am I right? LOL 😀
According to our data, Choi Min-ho is not dating anyone at the moment. The South Korean Pop Singer made their debut on the music scene on December 9th, 1991 in South Korea. a singer and model from South Korea who is most known for being the lead rapper for the pop group SHINee.
Shinee member Choi Minho is one of the members who have a significant number of female fans. Because of his attractive appearance, any lady may fall hopelessly in love with him in an instant. In addition to having a handsome face, he also possesses strong acting abilities. In the group that he belongs to, which is named Shinee, ChMinho serves as the primary rapper. He is not only the primary rapper, but he is also talented when it comes to writing the lyrics for rap songs. Minho got his start in the entertainment industry by being an apprentice at SM Entertainment for a period of two years before making his debut with Shinee in 2008. In addition to being an energetic member of Shinee, he has also broadened his career by working in acting, modeling, and even as a presenter.
Choi Min-ho is a k-pop artist from South Korea who is 31 years old and has had a lot of success. The range of Choi Min-net ho's worth is between $100,000 and $1 million. Estimates of Choi Min-net ho's worth, salary, and income may be found on a variety of sites; however, these sources disagree regarding how much he is now worth online.
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Launched in 1995, Meals & Drink Enterprise Europe is a long established business magazine for the food and drinks processing industries within the UK and Europe. The perfect schools for entrepreneurs entice a number of students from overseas international locations as well who're decided to change into geared up with the enterprise acumen wanted to cope with the worldwide business scenario in addition to to be recruited by some top-notch firm after graduation.
Along with your favorite blogs, podcasts, books, and on-line forums, subscribing to regularly-updated small business magazines is a great way to remain savvy on your business and the economic system, get priceless recommendation on easy methods to be a better enterprise owner, or simply read engaging stories about small companies like yours.
Inbound Logistics is way more than a supply for useful studying materials: They also provide actionable tools and services, reminiscent of bid lists and logistics planners, and a complete drop-down menu for Finding Solutions" like discovering trucking firms, tech corporations, and logistics education programs.
Since the internet revolution every business engages in analytics and who wouldn't want to have an image of their shopper base so savvy advertising campaigns can convey a little bit extra of that dollar worth into the enterprise. And, not like other small business magazines, Mashable's content isn't too heavy or dense.
As we speak we launch THE GAP , a web-based journal that celebrates one type of old factor – the old business. They are Global Business Leaders who have achieved success and proceed to attempt for more. However, within the interest of thoroughness, this list of the very best small business magazines simply wouldn't be complete with out the next go-to publications.


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Atlas (Atlas)
Grapeshot Games | Official Site
MMORPG | Setting:Fantasy | Status:Early Access (est.rel 06/30/20) | Pub:Grapeshot Games
PVP:Yes | Distribution:Download | Retail Price:$24.99 | Pay Type:Buy to Play | Monthly Fee:Free
Overview News Reviews Articles Hype Forums Screenshots Videos Links
Atlas - Not What Anyone Was Expecting
By Jordan Gerblick on January 29, 2019 | Columns | Comments
Even though I had been hearing it wasn't the most polished experience, I still went into Atlas with faith that it would at least be functional enough to review on its merits. The plan was to play the Early Access pirate-themed MMO long enough that I could compare it to another seafaring adventure, Sea of Thieves, and report on the two games' similarities and differences. However, I quickly realized that Atlas is barely playable in its current state, and comparing it to a game that was released last year wouldn't be fair. But is it fair that Grapeshot Games is charging folks for a game so early in its development cycle without warning of its crude state? On a broader note, is the whole Early Access system being abused?
My experience with Atlas very much reflects that of MMORPG.com's Robert Baddeley. To quote, "I've spent over 30 hours simply trying to play ATLAS and about five hours successfully." Like Robert, I spent an agonizing couple of hours spawning underwater, swimming toward the shore, and then being eaten by alligators. And if I made it to shore, I was eaten by lions. If it weren't for some well-meaning locals helping me through the very early stages, I'm not sure I would've had the patience to continue. Performance is shamefully slow for a game that isn't all-that detailed, considering my PC's mid to high-range specs. It's just a hot mess, all around.
It's a tale as old as time, at least in internet years. You watch a game trailer on Steam, disregard the Early Access label and buy the game, only to realize the trailer isn't the most accurate representation. I bought into DayZ back in 2013, and I've yet to see a return in the form of a fully-finished game. ARK: Survival Evolved is another game that spent the near-entirety of its development in a nonfunctional Early Access state, marred by controversies like paid DLC and a pre-release price hike. Even after release, many argue ARK still plays like a game in Early Access, perhaps explaining its dwindling player base.
The problem with Early Access are multifaceted and often individual to each game, however, one major problem lies within the vagueness of its terms. It's true that Steam clearly warns users that an Early Access title is an unfinished game, but developers aren't required to indicate development progress in terms of performance or play-ability. It's also true that Steam implores users to take it upon themselves to determine how any Early Access title plays and performs by looking at screenshots and watching videos, which is a wise idea in any case, but is it really the consumer's responsibility to circumvent the traps of false advertising on Steam?
Make no mistake, I don't have an issue with Atlas being on Steam, even in its rocky condition. What I do question are the ethics of selling an experience without making painfully clear its inexorable flaws.
Article By: Jordan Gerblick
Created On: January 29, 2019
TERA's Fists of Justice Now Available on PS4 and Xbox One
MMORPG.com » Games » Atlas » Columns » Atlas - Not What Anyone Was Expecting


"It's an easy way to raise a bunch of money and move that money around very easily."
Gather around the TV -- it happened, yet again.
Rapid City Police Department released a video of one their K9 police dogs with snow boots.
Residents were asked to avoid the area, and people who live nearby were asked to shelter in place.


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HomeEsportsBlizzard bans a college esports team for holding a "Free Hong Kong" sign – CNN
Blizzard bans a college esports team for holding a "Free Hong Kong" sign – CNN
New York (CNN Business) Video game company Activision Blizzard suspended three American University esports players for six months after they held up a "Free Hong Kong, boycott Blizz" sign during their championship match last week.
They now cannot compete in official or third-party Blizzard events.The three students were acting in solidarity with a Hong Kong player, Ng "blitzchung" Wai Chung, who was banned for six months by Blizzard and disqualified from the "Hearthstone" Grandmasters tournament last week after he shouted a pro-Hong Kong slogan.The company was met with outrage from gamers and calls for boycotts .The college sophomores, Casey Chambers, Corwin Dark and Torin Wright–all 19 years old and majoring in international studies–prepared a sign in reaction to Ng's ban and showed it on a stream of their college game October 8.The ban occurred Tuesday, one week later, according to Chambers.
Just a little message for @PlayHearthstone @HSesports #BoycottBlizzard pic.twitter.com/F1fS6lrumI
— Casey Chambers (@Xcelsior_hs) October 9, 2019 Blizzard confirmed to CNN Business Wednesday that it banned the three students after they "knowingly broke" the rules.In a statement, the company said: "We strongly encourage everyone in our community to share their viewpoints in the many places available to express themselves.However, our official broadcast needs to be about the game and the competition, and to be a place where all are welcome." Read More At first, it didn't immediately appear Blizzard would ban the three students.On October 10, the three players were assigned to compete in their next match, but they forfeited because they felt "it was hypocritical for Blizzard to punish Blitzchung's pro-human rights statement but not our clearly anti-Blizzard protest," Chambers told CNN Business.Blizzard did not comment on why it took more time to ban the students than it did to ban the Hong Kong player.
Happy to announce the AU Hearthstone team received a six month ban from competition.While delayed I appreciate all players being treated equally and no one being above the rules.
pic.twitter.com/mZStoF0e0t
— Casey Chambers (@Xcelsior_hs) October 16, 2019 Chambers said he and his friends had been supportive of the Hong Kong protests in the past: "We just happened to have an amazing opportunity to protest an American company bowing down to China, within the context of the Hong Kong protests." He said that while his team wasn't looking to get banned, "it's good to see equal treatment" between US esports players and those in Hong Kong.Blizzard said in a statement last Friday that its decision to ban Ng was not influenced by China."The trouble is that by responding in this manner, Blizzard is practically inviting other streamers to do the same," said Joost van Dreunen, co-founder of SuperData, a Nielsen company that analyzes the video game industry."Long term, however, Blizzard should do some soul searching.".


For the pie: In a small mixing bowl, combine the potatoes, cream and truffle oil together. Mix thoroughly. Season with salt and pepper. In a pie tin, line the bottom of the tin with 1/4 pound of the sliced salmon. Spread 1/4 cup of the potato mixture evenly over the salmon layer. Repeat the layering until you have four individual layers of each. Crumble the flakes of the smoked salmon on top and sprinkle the cracked black pepper. With your fingers, gently press the salmon and pepper down into the potatoes. Allow the pie to set in the refrigerator for 30 minutes.
For chive cream: In a small mixing bowl, whisk all the ingredients together. Season with salt and pepper. To assemble, cut the salmon pie into 8 slices. Spoon a small amount of the chive cream in the center of the plate. Place one piece of the pie in the center of the chive cream. Dab a teaspoon of the chive cream on top of the piece of pie and place a teaspoon of the caviar on top. Spread some of the chive cream around the rim and garnish with the traditional garnishes and Essence around the pie.


March 28th, 2013 Fredrik and I took a massive step, we bought our first home. Sure, it is not our dream home, but we decided to try to enter the market at an affordable level and not get in to debt up to our eyeballs. We wanted something we could renovate that was in a good area, with good transport in the town. The market is down right now, so it is a buyers market and we think we got quite a bargain and think it will pay off in time.
With Fredrik's skills and connections we thought it could be a great project for us an opportunity to create something awesome and showcase our skills. We have a little renovation experience from renovating a boat in 2012, which we plan to have completely finished by the time we move in. We really like working together and think we are a good team, Fredrik can build just about anything and I am the one who is planning, budgeting and trying to keep things on track. Some might say I am the boss (or b*tch… it depend who you ask).
The structure of the house is in good shape, it is build in the 50's and the layout is very closed and old fashioned, plus it is WAY too brown and the wood panels make me quiver. We have big plans… WATCH THIS SPACE.
We get the keys on June 31st, so our next few blog posts will be about our plans. Then once we get the keys, the real blogs will start, we hope to share the transformations, how to's, ups and downs. There will be plenty of drama to share, everyone who knows me is expecting that!!
Location: Stenkullen, Lerum. A suburb outside Gothenburg, Sweden. 20 minutes commute in to the city centre.


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Golden State Cider Launches Web Store & Announces New Executive Team
November 8, 2018 / Emily Kovach
Behold: the power of internet retail! More and more cideries are now offering their products for sale via online shops, which is great news for cider fans across the country. No longer do you have to wait for a vacation or a cider trade to try brands you've seen online that don't distribute in your state! A few clicks, and your cider selection can be on the way to your doorstep. What a time to be alive!
New to the cider-web-store game is Golden State Cider, a Northern California-based operation with a strong loyalty to West Coast apples. Calling wine country, its home, Golden State draws inspiration from its innovative wine- and beer-making neighbors, with a serious focus on quality and a tightly curated range of modern cider flavors.
Its online web store, which opened for business on November 7, gives shoppers the opportunity to buy any of its four core flavors: Bay Brut, Mighty Dry, Gingergrass and Mighty Hops, available by the 12- or 24-pack. All orders are shipped out on Mondays. For now, Golden State is able to ship its ciders to these states only: California, Nevada, Colorado, Washington, Oregon, Arizona, New Mexico, Massachusetts, Hawaii, Florida, Arkansas, Washington D.C. and Minnesota.
Over the past year, Golden State has seen plenty of growth (65% in 2018), and it is in the midst of an exciting time of change. In addition to the web store's launch, the company has announced a new executive team, including the promotion of its former vice president of sales and marketing, Chris Lacey, to CEO. Lacey is taking over the CEO position from co-founder Hunter Wade, who will now focus on strategic projects.
"I am excited to lead Golden State Cider into its next stage of growth and development," Lacey said. "It's been an amazing year and I am grateful to co-founders Jolie and Hunter for having the faith in me to lead the company. I am committed to GSC's mission to create the highest-quality dry ciders while revitalizing the apple industry in California. With the new leadership team, Golden State Cider is well-positioned to lead the growth of the cider segment."
Other personnel changes include Gary Fleshman, formerly the director of international sales and marketing at Rogue Ales, coming on as Golden State's director of sales. Natalie Naber, who previously served as Golden State's accounting and human resources manager, has been promoted to director of human resources and accounting.
One more exciting thing to know is that Golden State Cider also plans to open its first tasting room at The Barlow in Sebastopol, California, in the next year. Stay tuned for more info on that exciting project!
Photos: Golden State Cider
Posted in Cider Consumer Trends, Cider News, Cider Releases
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Labour will table amendment in favour of a second referendum on Brexit
"The Prime Minister is recklessly running down the clock, in an attempt to force MPs to choose between her botched deal and a disastrous No Deal. We cannot and will not accept," Corbyn said.
Labour leader Jeremy Corbyn has announced plans to put forward or support an amendment in favour of a People's Vote on Brexit on Tuesday.
At a meeting on Monday night Labour MPs will be told that the move is aimed at preventing "a damaging Tory Brexit being forced on the country".
The move comes after months of indecision by the Labour leadership over whether to back a second referendum or not. Corbyn had previously indicated that his preference would be for another general election ahead of a People's Vote.
Speaking on Monday, Jeremy Corbyn said: "The Prime Minister is recklessly running down the clock, in an attempt to force MPs to choose between her botched deal and a disastrous No Deal. We cannot and will not accept.
"Last week, after our visit to talk to EU officials and leaders in Brussels and Madrid, no one can be in any doubt Labour's alternative Brexit plan is serious and credible. We are convinced our alternative, which puts jobs and living standards first, could command support in the House of Commons, bring people who voted Leave and Remain together, and be negotiated with the EU."
The opposition leader has also said he will table an amendment to take 'no deal' off the table and hit out at the potential for Theresa May to lead the country into a "botched deal and a disastrous" exit on World Trade Organisation terms.
Corbyn will also seek to enshrine his party's "five Brexit demands" in law by tabling a further amendment to the government's Brexit motion.
Labour's five demands for the Brexit deal are:
A permanent and comprehensive customs union with the EU;
Close alignment with the Single Market underpinned by shared institutions and obligations;
Dynamic alignment on rights and protections;
Commitments on participation in EU agencies and funding programmes, including in areas such as the environment, education, and industrial regulation; and
Unambiguous agreements on the detail of future security arrangements, including access to the European Arrest Warrant and vital shared databases.
British MP promises to end Troubles prosecutions for British soldiers, says there will be "blood on the carpet"
Corbyn added: "We will also be backing the Cooper-Letwin amendment to rule out a No Deal outcome. One way or another, we will do everything in our power to prevent No Deal and oppose a damaging Tory Brexit based on Theresa May's overwhelmingly rejected deal.
"That's why, in line with our conference policy, we are committed to also putting forward or supporting an amendment in favour of a public vote to prevent a damaging Tory Brexit being forced on the country."
Brexit,
News.,
Theresa May.
Simon Coveney says the EU won't be rushed by the UK's Brexit law
Nearly a million Irish passports issued in 2019
"Let's get Brexit done" - Boris Johnson celebrates UK General Election victory
UK General Election exit poll indicates emphatic Boris Johnson victory
Arlene Foster: Boris Johnson "broke his word" over Brexit and a border in the Irish Sea
WATCH: BBC presenter Andrew Neil calls out Boris Johnson for an interview in brilliant video


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Current Search: Research Repository (x) » Rivers of America. (x) » Humans (x)
14-3-3 and aggresome formation: implications in neurodegenerative diseases..
Jia, Baohui, Wu, Yuying, Zhou, Yi
Protein misfolding and aggregation underlie the pathogenesis of many neurodegenerative diseases. In addition to chaperone-mediated refolding and proteasomal degradation, the aggresome-macroautophagy pathway has emerged as another defense mechanism for sequestration and clearance of toxic protein aggregates in cells. Previously, the 14-3-3 proteins were shown to be indispensable for the formation of aggresomes induced by mutant huntingtin proteins. In a recent study, we have determined that 14...
Show moreProtein misfolding and aggregation underlie the pathogenesis of many neurodegenerative diseases. In addition to chaperone-mediated refolding and proteasomal degradation, the aggresome-macroautophagy pathway has emerged as another defense mechanism for sequestration and clearance of toxic protein aggregates in cells. Previously, the 14-3-3 proteins were shown to be indispensable for the formation of aggresomes induced by mutant huntingtin proteins. In a recent study, we have determined that 14-3-3 functions as a molecular adaptor to recruit chaperone-associated misfolded proteins to dynein motors for transport to aggresomes. This molecular complex involves a dimeric binding of 14-3-3 to both the dynein-intermediate chain (DIC) and an Hsp70 co-chaperone Bcl-2-associated athanogene 3 (BAG3). As 14-3-3 has been implicated in various neurodegenerative diseases, our findings may provide mechanistic insights into its role in managing misfolded protein stress during the process of neurodegeneration.
FSU_pmch_24549097, PMC4189886, 24549097, 24549097, 28123
Across the tree of life, radiation resistance is governed by antioxidant Mn, gauged by paramagnetic resonance.
Sharma, Ajay, Gaidamakova, Elena K, Grichenko, Olga, Matrosova, Vera Y, Hoeke, Veronika, Klimenkova, Polina, Conze, Isabel H, Volpe, Robert P, Tkavc, Rok, Gostinčar, Cene, Gunde...
Show moreSharma, Ajay, Gaidamakova, Elena K, Grichenko, Olga, Matrosova, Vera Y, Hoeke, Veronika, Klimenkova, Polina, Conze, Isabel H, Volpe, Robert P, Tkavc, Rok, Gostinčar, Cene, Gunde-Cimerman, Nina, DiRuggiero, Jocelyne, Shuryak, Igor, Ozarowski, Andrew, Hoffman, Brian M, Daly, Michael J
Despite concerted functional genomic efforts to understand the complex phenotype of ionizing radiation (IR) resistance, a genome sequence cannot predict whether a cell is IR-resistant or not. Instead, we report that absorption-display electron paramagnetic resonance (EPR) spectroscopy of nonirradiated cells is highly diagnostic of IR survival and repair efficiency of DNA double-strand breaks (DSBs) caused by exposure to gamma radiation across archaea, bacteria, and eukaryotes, including fungi...
Show moreDespite concerted functional genomic efforts to understand the complex phenotype of ionizing radiation (IR) resistance, a genome sequence cannot predict whether a cell is IR-resistant or not. Instead, we report that absorption-display electron paramagnetic resonance (EPR) spectroscopy of nonirradiated cells is highly diagnostic of IR survival and repair efficiency of DNA double-strand breaks (DSBs) caused by exposure to gamma radiation across archaea, bacteria, and eukaryotes, including fungi and human cells. IR-resistant cells, which are efficient at DSB repair, contain a high cellular content of manganous ions (Mn) in high-symmetry (H) antioxidant complexes with small metabolites (e.g., orthophosphate, peptides), which exhibit narrow EPR signals (small zero-field splitting). In contrast, Mn ions in IR-sensitive cells, which are inefficient at DSB repair, exist largely as low-symmetry (L) complexes with substantially broadened spectra seen with enzymes and strongly chelating ligands. The fraction of cellular Mn present as H-complexes (H-Mn), as measured by EPR of live, nonirradiated Mn-replete cells, is now the strongest known gauge of biological IR resistance between and within organisms representing all three domains of life: Antioxidant H-Mn complexes, not antioxidant enzymes (e.g., Mn superoxide dismutase), govern IR survival. As the pool of intracellular metabolites needed to form H-Mn complexes depends on the nutritional status of the cell, we conclude that IR resistance is predominantly a metabolic phenomenon. In a cross-kingdom analysis, the vast differences in taxonomic classification, genome size, and radioresistance between cell types studied here support that IR resistance is not controlled by the repertoire of DNA repair and antioxidant enzymes.
FSU_pmch_29042516, 10.1073/pnas.1713608114, PMC5676931, 29042516, 29042516, 1713608114
Acute BDNF treatment upregulates GluR1-SAP97 and GluR2-GRIP1 interactions: implications for sustained AMPA receptor expression..
Jourdi, Hussam, Kabbaj, Mohamed
Brain-derived neurotrophic factor (BDNF) plays several prominent roles in synaptic plasticity and in learning and memory formation. Reduced BDNF levels and altered BDNF signaling have been reported in several brain diseases and behavioral disorders, which also exhibit reduced levels of AMPAr subunits. BDNF treatment acutely regulates AMPA receptor expression and function, including synaptic AMPAr subunit trafficking, and implicates several well defined signaling molecules that are required to...
Show moreBrain-derived neurotrophic factor (BDNF) plays several prominent roles in synaptic plasticity and in learning and memory formation. Reduced BDNF levels and altered BDNF signaling have been reported in several brain diseases and behavioral disorders, which also exhibit reduced levels of AMPAr subunits. BDNF treatment acutely regulates AMPA receptor expression and function, including synaptic AMPAr subunit trafficking, and implicates several well defined signaling molecules that are required to elicit long term potentiation and depression (LTP and LTD, respectively). Long term encoding of synaptic events, as in long term memory formation, requires AMPAr stabilization and maintenance. However, factors regulating AMPAr stabilization in neuronal cell membranes and synaptic sites are not well characterized. In this study, we examine the effects of acute BDNF treatment on levels of AMPAr-associated scaffolding proteins and on AMPAr subunit-scaffolding protein interactions. We also examine the effects of BDNF-dependent enhanced interactions between AMPAr subunits with their specific scaffolding proteins on the accumulation of both types of proteins. Our results show that acute BDNF treatment upregulates the interactions between AMPAr subunits (GluR1 and GluR2) with their scaffold proteins SAP97 and GRIP1, respectively, leading to prolonged increased accumulation of both categories of proteins, albeit with distinct mechanisms for GluR1 and GluR2. Our findings reveal a new role for BDNF in the long term maintenance of AMPA receptor subunits and associated scaffolding proteins at synapses and further support the role of BDNF as a key regulator of synaptic consolidation. These results have potential implications for recent findings implicating BDNF and AMPAr subunits in various brain diseases and behavioral disorders.
ADAM19: A Novel Target for Metabolic Syndrome in Humans and Mice..
Weerasekera, Lakshini, Rudnicka, Caroline, Sang, Qing-Xiang, Curran, Joanne E, Johnson, Matthew P, Moses, Eric K, Göring, Harald H H, Blangero, John, Hricova, Jana, Schlaich,...
Show moreWeerasekera, Lakshini, Rudnicka, Caroline, Sang, Qing-Xiang, Curran, Joanne E, Johnson, Matthew P, Moses, Eric K, Göring, Harald H H, Blangero, John, Hricova, Jana, Schlaich, Markus, Matthews, Vance B
Obesity is one of the most prevalent metabolic diseases in the Western world and correlates directly with insulin resistance, which may ultimately culminate in type 2 diabetes (T2D). We sought to ascertain whether the human metalloproteinase A Disintegrin and Metalloproteinase 19 (ADAM19) correlates with parameters of the metabolic syndrome in humans and mice. To determine the potential novel role of ADAM19 in the metabolic syndrome, we first conducted microarray studies on peripheral blood...
Show moreObesity is one of the most prevalent metabolic diseases in the Western world and correlates directly with insulin resistance, which may ultimately culminate in type 2 diabetes (T2D). We sought to ascertain whether the human metalloproteinase A Disintegrin and Metalloproteinase 19 (ADAM19) correlates with parameters of the metabolic syndrome in humans and mice. To determine the potential novel role of ADAM19 in the metabolic syndrome, we first conducted microarray studies on peripheral blood mononuclear cells from a well-characterised human cohort. Secondly, we examined the expression of ADAM19 in liver and gonadal white adipose tissue using an in vivo diet induced obesity mouse model. Finally, we investigated the effect of neutralising ADAM19 on diet induced weight gain, insulin resistance in vivo, and liver TNF- levels. Significantly, we show that, in humans, ADAM19 strongly correlates with parameters of the metabolic syndrome, particularly BMI, relative fat, HOMA-IR, and triglycerides. Furthermore, we identified that ADAM19 expression was markedly increased in the liver and gonadal white adipose tissue of obese and T2D mice. Excitingly, we demonstrate in our diet induced obesity mouse model that neutralising ADAM19 therapy results in weight loss, improves insulin sensitivity, and reduces liver TNF- levels. Our novel data suggest that ADAM19 is pro-obesogenic and enhances insulin resistance. Therefore, neutralisation of ADAM19 may be a potential therapeutic approach to treat obesity and T2D.
FSU_pmch_28265178, 10.1155/2017/7281986, PMC5318628, 28265178, 28265178
Advances in Zika Virus Research: Stem Cell Models, Challenges, and Opportunities..
Ming, Guo-Li, Tang, Hengli, Song, Hongjun
The re-emergence of Zika virus (ZIKV) and its suspected link with various disorders in newborns and adults led the World Health Organization to declare a global health emergency. In response, the stem cell field quickly established platforms for modeling ZIKV exposure using human pluripotent stem cell-derived neural progenitors and brain organoids, fetal tissues, and animal models. These efforts provided significant insight into cellular targets, pathogenesis, and underlying biological...
Show moreThe re-emergence of Zika virus (ZIKV) and its suspected link with various disorders in newborns and adults led the World Health Organization to declare a global health emergency. In response, the stem cell field quickly established platforms for modeling ZIKV exposure using human pluripotent stem cell-derived neural progenitors and brain organoids, fetal tissues, and animal models. These efforts provided significant insight into cellular targets, pathogenesis, and underlying biological mechanisms of ZIKV infection as well as platforms for drug testing. Here we review the remarkable progress in stem cell-based ZIKV research and discuss current challenges and future opportunities.
Age-related changes of gene expression in the neocortex: preliminary data on RNA-Seq of the transcriptome in three functionally distinct cortical areas..
Naumova, Oksana Yu, Palejev, Dean, Vlasova, Natalia V, Lee, Maria, Rychkov, Sergei Yu, Babich, Olga N, M Vaccarino, Flora, Grigorenko, Elena L
The study of gene expression (i.e., the study of the transcriptome) in different cells and tissues allows us to understand the molecular mechanisms of their differentiation, development and functioning. In this article, we describe some studies of gene-expression profiling for the purposes of understanding developmental (age-related) changes in the brain using different technologies (e.g., DNA-Microarray) and the new and increasingly popular RNA-Seq. We focus on advancements in studies of...
Show moreThe study of gene expression (i.e., the study of the transcriptome) in different cells and tissues allows us to understand the molecular mechanisms of their differentiation, development and functioning. In this article, we describe some studies of gene-expression profiling for the purposes of understanding developmental (age-related) changes in the brain using different technologies (e.g., DNA-Microarray) and the new and increasingly popular RNA-Seq. We focus on advancements in studies of gene expression in the human brain, which have provided data on the structure and age-related variability of the transcriptome in the brain. We present data on RNA-Seq of the transcriptome in three distinct areas of the neocortex from different ages: mature and elderly individuals. We report that most age-related transcriptional changes affect cellular signaling systems, and, as a result, the transmission of nerve impulses. In general, the results demonstrate the high potential of RNA-Seq for the study of distinctive features of gene expression among cortical areas and the changes in expression through normal and atypical development of the central nervous system.
FSU_pmch_23062308, 10.1017/S0954579412000818, PMC3539811, 23062308, 23062308, S0954579412000818
AIM2 inflammasome activation and regulation: A structural perspective..
Wang, Bing, Yin, Qian
Absent in melanoma 2 (AIM2) inflammasome is a multi-protein platform that recognizes aberrant cytoplasmic dsDNA and induces cytokine maturation, release and pyroptosis. It is composed of AIM2, apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1. Recent X-ray crystallographic and high resolution cryo-electron microscopic (cryo-EM) studies have revealed a series of structures in AIM2 inflammasome activation and regulation. One prominent feature common in multiple...
Show moreAbsent in melanoma 2 (AIM2) inflammasome is a multi-protein platform that recognizes aberrant cytoplasmic dsDNA and induces cytokine maturation, release and pyroptosis. It is composed of AIM2, apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1. Recent X-ray crystallographic and high resolution cryo-electron microscopic (cryo-EM) studies have revealed a series of structures in AIM2 inflammasome activation and regulation. One prominent feature common in multiple steps is the assembly of high-order structures, especially helical filaments nucleated by upstream molecules, rather than stoichiometric complexes. In this review, we track the AIM2 inflammasome activation process step by step, using high-resolution structures to illustrate the overall architecture of AIM2 inflammasome and its assembly and regulatory mechanisms.
FSU_pmch_28813641, 10.1016/j.jsb.2017.08.001, PMC5733693, 28813641, 28813641, S1047-8477(17)30132-6
Akt mediated phosphorylation of LARP6; critical step in biosynthesis of type I collagen.
Zhang, Yujie, Stefanovic, Branko
La ribonucleoprotein domain family, member 6 (LARP6) is the RNA binding protein, which regulates translation of collagen mRNAs and synthesis of type I collagen. Posttranslational modifications of LARP6 and how they affect type I collagen synthesis have not been studied. We show that in lung fibroblasts LARP6 is phosphorylated at 8 serines, 6 of which are located within C-terminal domain. Phosphorylation of LARP6 follows a hierarchical order; S451 phosphorylation being a prerequisite for...
Show moreLa ribonucleoprotein domain family, member 6 (LARP6) is the RNA binding protein, which regulates translation of collagen mRNAs and synthesis of type I collagen. Posttranslational modifications of LARP6 and how they affect type I collagen synthesis have not been studied. We show that in lung fibroblasts LARP6 is phosphorylated at 8 serines, 6 of which are located within C-terminal domain. Phosphorylation of LARP6 follows a hierarchical order; S451 phosphorylation being a prerequisite for phosphorylations of other serines. Inhibition of PI3K/Akt pathway reduced the phosphorylation of LARP6, but had no effect on the S451A mutant, suggesting that PI3K/Akt pathway targets S451 and we have identified Akt as the responsible kinase. Overexpression of S451A mutant had dominant negative effect on collagen biosynthesis; drastically reduced secretion of collagen and induced hyper-modifications of collagen α2 (I) polypeptides. This indicates that LARP6 phosphorylation at S451 is critical for regulating translation and folding of collagen polypeptides. Akt inhibitor, GSK-2141795, which is in clinical trials for treatment of solid tumors, reduced collagen production by human lung fibroblasts with EC50 of 150 nM. This effect can be explained by inhibition of LARP6 phosphorylation and suggests that Akt inhibitors may be effective in treatment of various forms of fibrosis.
Allosteric activation of SENP1 by SUMO1 β-grasp domain involves a dock-and-coalesce mechanism.
Guo, Jingjing, Zhou, Huan-Xiang
Small ubiquitin-related modifiers (SUMOs) are conjugated to proteins to regulate a variety of cellular processes. SENPs are cysteine proteases with a catalytic center located within a channel between two subdomains that catalyzes SUMO C-terminal cleavage for processing of SUMO precursors and de-SUMOylation of target proteins. The β-grasp domain of SUMOs binds to an exosite cleft, and allosterically activates SENPs via an unknown mechanism. Our molecular dynamics simulations showed that...
Show moreSmall ubiquitin-related modifiers (SUMOs) are conjugated to proteins to regulate a variety of cellular processes. SENPs are cysteine proteases with a catalytic center located within a channel between two subdomains that catalyzes SUMO C-terminal cleavage for processing of SUMO precursors and de-SUMOylation of target proteins. The β-grasp domain of SUMOs binds to an exosite cleft, and allosterically activates SENPs via an unknown mechanism. Our molecular dynamics simulations showed that binding of the β-grasp domain induces significant conformational and dynamic changes in SENP1, including widening of the exosite cleft and quenching of nanosecond dynamics in all but a distal region. A dock-and-coalesce mechanism emerges for SENP-catalyzed SUMO cleavage: the wedging of the β-grasp domain enables the docking of the proximal portion of the C-terminus and the strengthened cross-channel motional coupling initiates inter-subdomain correlated motions to allow for the distal portion to coalesce around the catalytic center.
FSU_pmch_27576863, 10.7554/eLife.18249, PMC5030089, 27576863, 27576863
Allosteric Transmission along a Loosely Structured Backbone Allows a Cardiac Troponin C Mutant to Function with Only One Ca Ion.
Marques, Mayra de A, Pinto, Jose Renato, Moraes, Adolfo H, Iqbal, Anwar, de Magalhães, Mariana T Q, Monteiro, Jamila, Pedrote, Murilo M, Sorenson, Martha M, Silva, Jerson L, de...
Show moreMarques, Mayra de A, Pinto, Jose Renato, Moraes, Adolfo H, Iqbal, Anwar, de Magalhães, Mariana T Q, Monteiro, Jamila, Pedrote, Murilo M, Sorenson, Martha M, Silva, Jerson L, de Oliveira, Guilherme A P
Hypertrophic cardiomyopathy (HCM) is one of the most common cardiomyopathies and a major cause of sudden death in young athletes. The Ca sensor of the sarcomere, cardiac troponin C (cTnC), plays an important role in regulating muscle contraction. Although several cardiomyopathy-causing mutations have been identified in cTnC, the limited information about their structural defects has been mapped to the HCM phenotype. Here, we used high-resolution electron-spray ionization mass spectrometry ...
Show moreHypertrophic cardiomyopathy (HCM) is one of the most common cardiomyopathies and a major cause of sudden death in young athletes. The Ca sensor of the sarcomere, cardiac troponin C (cTnC), plays an important role in regulating muscle contraction. Although several cardiomyopathy-causing mutations have been identified in cTnC, the limited information about their structural defects has been mapped to the HCM phenotype. Here, we used high-resolution electron-spray ionization mass spectrometry (ESI-MS), Carr-Purcell-Meiboom-Gill relaxation dispersion (CPMG-RD), and affinity measurements of cTnC for the thin filament in reconstituted papillary muscles to provide evidence of an allosteric mechanism in mutant cTnC that may play a role to the HCM phenotype. We showed that the D145E mutation leads to altered dynamics on a μs-ms time scale and deactivates both of the divalent cation-binding sites of the cTnC C-domain. CPMG-RD captured a low populated protein-folding conformation triggered by the Glu-145 replacement of Asp. Paradoxically, although D145E C-domain was unable to bind Ca, these changes along its backbone allowed it to attach more firmly to thin filaments than the wild-type isoform, providing evidence for an allosteric response of the Ca-binding site II in the N-domain. Our findings explain how the effects of an HCM mutation in the C-domain reflect up into the N-domain to cause an increase of Ca affinity in site II, thus opening up new insights into the HCM phenotype.
FSU_pmch_28049727, 10.1074/jbc.M116.765362, PMC5313108, 28049727, 28049727, M116.765362
Analyzing State Autism Private Insurance Mandates for Allied Health Services: A Pilot Study..
Douglas, Megan D, Benevides, Teal W, Carretta, Henry
Due to the prevalence, severity, and costs associated with autism spectrum disorders (ASDs), it has become a public health issue. In response, state governments have adopted ASD-specific private insurance mandates requiring coverage of ASD screening, diagnosis, and treatment. Despite rapid uptake of these laws, differences exist in the type and levels of coverage, especially for allied health services including occupational therapy. We piloted a structured legal research methodology to code...
Show moreDue to the prevalence, severity, and costs associated with autism spectrum disorders (ASDs), it has become a public health issue. In response, state governments have adopted ASD-specific private insurance mandates requiring coverage of ASD screening, diagnosis, and treatment. Despite rapid uptake of these laws, differences exist in the type and levels of coverage, especially for allied health services including occupational therapy. We piloted a structured legal research methodology to code ASD insurance mandates that impact allied health service provisions. State private insurance mandates were obtained from WestlawNext. A coding methodology was piloted on 14 states and included variables for age and service limits, treatments covered, and medical necessity. Coding methods were feasible and highly reliable among raters. Ten of 12 states had a coverage mandate, many with specific provisions for allied health providers. A full analysis of all 50 states is warranted to identify provisions affecting allied health providers serving individuals with ASD.
FSU_pmch_28874097, 10.1177/1539449217730355, PMC5772933, 28874097, 28874097
Antidiabetic Disruptors of the Glucokinase-Glucokinase Regulatory Protein Complex Reorganize a Coulombic Interface.
Martinez, Juliana A, Xiao, Qing, Zakarian, Armen, Miller, Brian G
The glucokinase regulatory protein (GKRP) plays an essential role in glucose homeostasis by acting as a competitive inhibitor of glucokinase (GCK) and triggering its localization to the hepatocyte nucleus upon glucose deprivation. Metabolites such as fructose 6-phosphate and sorbitol 6-phosphate promote assembly of the GCK-GKRP complex, whereas fructose 1-phosphate and functionalized piperazines with potent in vivo antidiabetic activity disrupt the complex. Here, we establish the molecular...
Show moreThe glucokinase regulatory protein (GKRP) plays an essential role in glucose homeostasis by acting as a competitive inhibitor of glucokinase (GCK) and triggering its localization to the hepatocyte nucleus upon glucose deprivation. Metabolites such as fructose 6-phosphate and sorbitol 6-phosphate promote assembly of the GCK-GKRP complex, whereas fructose 1-phosphate and functionalized piperazines with potent in vivo antidiabetic activity disrupt the complex. Here, we establish the molecular basis by which these natural and synthetic ligands modulate the GCK-GKRP interaction. We demonstrate that a small-molecule disruptor of the protein-protein interaction utilizes a two-step conformational selection mechanism to associate with a rare GKRP conformation constituting 3% of the total population. Conformational heterogeneity of GKRP is localized to the N-terminus and deleting this region eliminates the ability of sorbitol 6-phosphate to promote the GCK-GKRP interaction. Stabilizing ligands favor an extended N-terminus, which sterically positions two arginine residues for optimal Coulombic interaction with a pair of carboxylate side chains from GCK. Conversely, disruptors promote a more compact N-terminus in which an interfacial arginine residue is stabilized in an unproductive orientation through a cation-π interaction with tyrosine 75. Eliminating the ability to sample this binding impaired conformation enhances the intrinsic inhibitory activity of GKRP. Elucidating the molecular basis of ligand-mediated control over the GCK-GKRP interaction is expected to impact the development and future refinement of therapeutic agents for diabetes and cardiovascular disease, which result from improper GKRP regulation of GCK.
FSU_pmch_28516783, 10.1021/acs.biochem.7b00377, PMC5831357, 28516783, 28516783
Anxiety sensitivity facets in relation to tobacco use, abstinence-related problems, and cognitions in treatment-seeking smokers.
Guillot, Casey R, Leventhal, Adam M, Raines, Amanda M, Zvolensky, Michael J, Schmidt, Norman B
Anxiety sensitivity (AS)--fear of anxiety-related experiences--has been implicated in smoking motivation and maintenance. In a cross-sectional design, we examined AS facets (physical, cognitive, and social concerns) in relation to tobacco use, abstinence-related problems, and cognitions in 473 treatment-seeking smokers. After controlling for sex, race, age, educational attainment, hypertension status, and neuroticism, linear regression models indicated that AS physical and cognitive concerns...
Show moreAnxiety sensitivity (AS)--fear of anxiety-related experiences--has been implicated in smoking motivation and maintenance. In a cross-sectional design, we examined AS facets (physical, cognitive, and social concerns) in relation to tobacco use, abstinence-related problems, and cognitions in 473 treatment-seeking smokers. After controlling for sex, race, age, educational attainment, hypertension status, and neuroticism, linear regression models indicated that AS physical and cognitive concerns were associated with tobacco dependence severity (β=.13-.14, p<.01), particularly the severity of persistent smoking regardless of context or time of day (β=.14-.17, p<.01). All three AS facets were related to more severe problems during past quit attempts (β=.23-.27, p<.001). AS cognitive and social concerns were related to negative affect reduction smoking motives (β=.14, p<.01), but only the social concerns aspect of AS was related to pleasurable relaxation smoking motives and positive and negative reinforcement-related smoking outcome expectancies (β=.14-.17, p<.01). These data suggest that AS physical and cognitive concerns are associated with negative reinforcement-related smoking variables (e.g., abstinence-related problems), whereas the social concerns aspect of AS is associated with positive and negative reinforcement-related smoking variables. Together with past findings, current findings can usefully guide AS-oriented smoking cessation treatment development and refinement.
FSU_pmch_26802790, 10.1016/j.addbeh.2016.01.005, PMC4738174, 26802790, 26802790, S0306-4603(16)30005-3
Approximate median regression for complex survey data with skewed response.
Fraser, Raphael André, Lipsitz, Stuart R, Sinha, Debajyoti, Fitzmaurice, Garrett M, Pan, Yi
The ready availability of public-use data from various large national complex surveys has immense potential for the assessment of population characteristics using regression models. Complex surveys can be used to identify risk factors for important diseases such as cancer. Existing statistical methods based on estimating equations and/or utilizing resampling methods are often not valid with survey data due to complex survey design features. That is, stratification, multistage sampling, and...
Show moreThe ready availability of public-use data from various large national complex surveys has immense potential for the assessment of population characteristics using regression models. Complex surveys can be used to identify risk factors for important diseases such as cancer. Existing statistical methods based on estimating equations and/or utilizing resampling methods are often not valid with survey data due to complex survey design features. That is, stratification, multistage sampling, and weighting. In this article, we accommodate these design features in the analysis of highly skewed response variables arising from large complex surveys. Specifically, we propose a double-transform-both-sides (DTBS)'based estimating equations approach to estimate the median regression parameters of the highly skewed response; the DTBS approach applies the same Box-Cox type transformation twice to both the outcome and regression function. The usual sandwich variance estimate can be used in our approach, whereas a resampling approach would be needed for a pseudo-likelihood based on minimizing absolute deviations (MAD). Furthermore, the approach is relatively robust to the true underlying distribution, and has much smaller mean square error than a MAD approach. The method is motivated by an analysis of laboratory data on urinary iodine (UI) concentration from the National Health and Nutrition Examination Survey.
FSU_pmch_27062562, 10.1111/biom.12517, PMC5055849, 27062562, 27062562
Are new generations of female college-student populations meeting calcium requirements: comparison of American and Croatian female students..
Douglas, Crystal C, Rumbak, Ivana, Barić, Irena Colić, Kovačina, Marinela, Piasek, Martina, Ilich, Jasminka Z
We compared calcium (Ca) sources and intake, as well as multivitamin/mineral supplement use between female students with nutrition/health background and those from general-student-populations. 314 participants 18-37 y, including 57 African-Americans and 54 Caucasian-Americans recruited from Nutrition and/or other Health Sciences departments (NHS), and 100 African-American and 103 Croatian women representing general-student-population (GSP), completed food frequency questionnaire assessing...
Show moreWe compared calcium (Ca) sources and intake, as well as multivitamin/mineral supplement use between female students with nutrition/health background and those from general-student-populations. 314 participants 18-37 y, including 57 African-Americans and 54 Caucasian-Americans recruited from Nutrition and/or other Health Sciences departments (NHS), and 100 African-American and 103 Croatian women representing general-student-population (GSP), completed food frequency questionnaire assessing their usual Ca intake and supplement use. NHS populations met recommendations and consumed significantly more Ca, particularly from dairy sources, and were more likely to take supplements than GSP groups, suggesting that health education may influence Ca intake.
FSU_pmch_22254044, 10.3390/nu2060599, PMC3257667, 22254044, 22254044, nu2060599
Association between anger rumination and autism symptom severity, depression symptoms, aggression, and general dysregulation in adolescents with autism spectrum disorder.
Patel, Shivani, Day, Taylor N, Jones, Neil, Mazefsky, Carla A
Rumination has a large direct effect on psychopathology but has received relatively little attention in autism spectrum disorder despite the propensity to perseverate in this population. This study provided initial evidence that adolescents with autism spectrum disorder self-report more anger-focused rumination than typically developing controls, though there was substantial within-group variability. Anger rumination was positively correlated with autism symptom severity with both groups...
Show moreRumination has a large direct effect on psychopathology but has received relatively little attention in autism spectrum disorder despite the propensity to perseverate in this population. This study provided initial evidence that adolescents with autism spectrum disorder self-report more anger-focused rumination than typically developing controls, though there was substantial within-group variability. Anger rumination was positively correlated with autism symptom severity with both groups combined. Future studies that include measures of perseveration on special interests are needed to understand whether anger rumination is a manifestation of a perseverative type of repetitive behavior or a distinct trait. Even when controlling for autism symptom severity, however, anger-focused rumination was associated with poorer functioning, including more depression symptoms and overall emotional and behavioral dysregulation. Therefore, further inquiry regarding anger rumination in autism spectrum disorder is clinically important, and the potential impact of rumination-focused interventions should be explored.
At the height of fashion: what genetics can teach us about neurodevelopmental disabilities..
Grigorenko, Elena L
The last decade has generated much interest in the genetics of developmental disorders. This interest, in part, is focused on two issues: the specificity/generality and the type/frequency of the genetic mechanisms involved. First, it appears that studies are more fruitful and their results more replicable, broadly speaking, when they conceptualize disorders not holistically, as categorical units, but componentially, through various quantitative processes. Second, there have been several...
Show moreThe last decade has generated much interest in the genetics of developmental disorders. This interest, in part, is focused on two issues: the specificity/generality and the type/frequency of the genetic mechanisms involved. First, it appears that studies are more fruitful and their results more replicable, broadly speaking, when they conceptualize disorders not holistically, as categorical units, but componentially, through various quantitative processes. Second, there have been several successful investigations of severe impairments in a number of isolated families with higher than typical frequencies of developmental disorders. Yet, it has been difficult to generalize the genetic mechanisms involved in these rare cases to the general population. Current findings suggest the involvement of multiple genetic mechanisms in the manifestations of childhood-onset conditions. It is possible that each 'facet' (or component) of a disorder is controlled by a semi-independent set of genes. Numerous components appear to be deficient in more than one disorder, possibly explaining comorbidity. The genetic foundation of developmental disorders may be formed not by isolated genes, but rather by a combination of genes and the pathways that these genes regulate. These accumulating findings have direct implications for designing both diagnostic and treatment approaches to childhood-onset disorders.
FSU_pmch_19532035, 10.1097/WCO.0b013e3283292414, PMC2891771, 19532035, 19532035, 00019052-200904000-00003
A balanced t(10;15) translocation in a male patient with developmental language disorder.
Ercan-Sencicek, A Gulhan, Davis Wright, Nicole R, Sanders, Stephan J, Oakman, Nicole, Valdes, Lianna, Bakkaloglu, Betul, Doyle, Niamh, Yrigollen, Carolyn M, Morgan, Thomas M,...
Show moreErcan-Sencicek, A Gulhan, Davis Wright, Nicole R, Sanders, Stephan J, Oakman, Nicole, Valdes, Lianna, Bakkaloglu, Betul, Doyle, Niamh, Yrigollen, Carolyn M, Morgan, Thomas M, Grigorenko, Elena L
We report the clinical and cytogenetic findings on a male child with developmental language disorder, no physical abnormalities, and a balanced t(10;15)(q24.1;q21.1) translocation. As the child's parents are unavailable for investigations, it is unclear whether the translocation is inherited or de novo. Fluorescence in situ hybridization (FISH) analyses were carried out using specific RP11-BAC clones mapping near 15q21.1 and 10q24.1 to refine the location of the breakpoints. The breakpoint on...
Show moreWe report the clinical and cytogenetic findings on a male child with developmental language disorder, no physical abnormalities, and a balanced t(10;15)(q24.1;q21.1) translocation. As the child's parents are unavailable for investigations, it is unclear whether the translocation is inherited or de novo. Fluorescence in situ hybridization (FISH) analyses were carried out using specific RP11-BAC clones mapping near 15q21.1 and 10q24.1 to refine the location of the breakpoints. The breakpoint on 15q21.1 interrupts the SEMA6D gene and the breakpoint on 10q24.1 is located between the ENTPD1 and CCNJ genes. The SEMA6D gene was further investigated in samples of individuals with developmental language disorders and controls; this investigation offered further evidence of the involvement of SEMA6D with developmental language disorders.
FSU_pmch_22266071, 10.1016/j.ejmg.2011.12.005, PMC3322462, 22266071, 22266071, S1769-7212(11)00134-0
BDNF Val66Met and cognition: all, none, or some? A meta-analysis of the genetic association..
Mandelman, S D, Grigorenko, E L
The Val66Met, G196A (rs6265) polymorphism in the brain-derived neurotrophic factor gene, BDNF, located at 11p13, has been associated with a wide range of cognitive functions. Yet, the pattern of results is complex and conflicting. In this study, we conducted a meta-analysis that included 23 publications containing 31 independent samples comprised of 7095 individuals. The phenotypes that were examined in this analysis covered a wide variety of cognitive functions and included indicators of...
Show moreThe Val66Met, G196A (rs6265) polymorphism in the brain-derived neurotrophic factor gene, BDNF, located at 11p13, has been associated with a wide range of cognitive functions. Yet, the pattern of results is complex and conflicting. In this study, we conducted a meta-analysis that included 23 publications containing 31 independent samples comprised of 7095 individuals. The phenotypes that were examined in this analysis covered a wide variety of cognitive functions and included indicators of general cognitive ability, memory, executive function, visual processing skills and cognitive fluency. The meta-analysis did not establish significant genetic associations between the Val66Met polymorphism and any of the phenotypes that were included.
FSU_pmch_21980924, 10.1111/j.1601-183X.2011.00738.x, PMC3268899, 21980924, 21980924
Behavior, brain, and genome in genomic disorders: finding the correspondences..
Grigorenko, Elena L, Urban, Alexander E, Mencl, Einar
Within the last decade or so, there has been an acceleration of research attempting to connect specific genetic lesions to the patterns of brain structure and activation. This article comments on observations that have been made based on these recent data and discusses their importance for the field of investigations into developmental disorders. In making these observations, the authors focus on one specific genomic lesion, the well-studied, yet still incompletely understood, 22q11.2...
Show moreWithin the last decade or so, there has been an acceleration of research attempting to connect specific genetic lesions to the patterns of brain structure and activation. This article comments on observations that have been made based on these recent data and discusses their importance for the field of investigations into developmental disorders. In making these observations, the authors focus on one specific genomic lesion, the well-studied, yet still incompletely understood, 22q11.2 deletion syndrome. The authors demonstrate the degree of variability in the phenotype that occurs at both the brain and behavioral levels of genomic disorders and describe how this variability is, on close inspection, represented at the genomic level. The authors emphasize the importance of combining genetic/genomic analyses and neuroimaging for research and for future clinical diagnostic purposes and for the purposes of developing individualized, patient-tailored treatment and remediation approaches.
FSU_pmch_20814258, 10.1097/DBP.0b013e3181f5a0a1, PMC4124614, 20814258, 20814258, 00004703-201009000-00013
Bias-corrected estimates for logistic regression models for complex surveys with application to the United States' Nationwide Inpatient Sample.
Rader, Kevin A, Lipsitz, Stuart R, Fitzmaurice, Garrett M, Harrington, David P, Parzen, Michael, Sinha, Debajyoti
For complex surveys with a binary outcome, logistic regression is widely used to model the outcome as a function of covariates. Complex survey sampling designs are typically stratified cluster samples, but consistent and asymptotically unbiased estimates of the logistic regression parameters can be obtained using weighted estimating equations (WEEs) under the naive assumption that subjects within a cluster are independent. Despite the relatively large samples typical of many complex surveys,...
Show moreFor complex surveys with a binary outcome, logistic regression is widely used to model the outcome as a function of covariates. Complex survey sampling designs are typically stratified cluster samples, but consistent and asymptotically unbiased estimates of the logistic regression parameters can be obtained using weighted estimating equations (WEEs) under the naive assumption that subjects within a cluster are independent. Despite the relatively large samples typical of many complex surveys, with rare outcomes, many interaction terms, or analysis of subgroups, the logistic regression parameters estimates from WEE can be markedly biased, just as with independent samples. In this paper, we propose bias-corrected WEEs for complex survey data. The proposed method is motivated by a study of postoperative complications in laparoscopic cystectomy, using data from the 2009 United States' Nationwide Inpatient Sample complex survey of hospitals.
Biobehavioral determinants of glycemic control in type 2 diabetes: A systematic review and meta-analysis..
Brown, Sharon A, García, Alexandra A, Brown, Adama, Becker, Betsy J, Conn, Vicki S, Ramírez, Gilbert, Winter, Mary A, Sumlin, Lisa L, Garcia, Theresa J, Cuevas, Heather E
To conduct a model-driven meta-analysis of correlational research on psychological and motivational predictors of diabetes outcomes, with adherence factors as mediators. A comprehensive literature search of published and unpublished studies located a sample of 775 individual correlational or predictive studies reported across 739 research reports. Results varied according to the outcome variable included in the regression models. Depression had a larger negative effect on adherence to...
Show moreTo conduct a model-driven meta-analysis of correlational research on psychological and motivational predictors of diabetes outcomes, with adherence factors as mediators. A comprehensive literature search of published and unpublished studies located a sample of 775 individual correlational or predictive studies reported across 739 research reports. Results varied according to the outcome variable included in the regression models. Depression had a larger negative effect on adherence to physical activity than on dietary adherence. Coping and self-efficacy were strongly related to dietary adherence, which was strongly related to improved glycemic control. Medication adherence was related to glycosylated hemoglobin, whereas medications and self-monitoring were related to fasting blood glucose. Adding appointment keeping to the models did not significantly alter the results. Self-efficacy was the most consistent predictor of all adherence behaviors and dietary adherence was the most significant predictor of HbA1c. Physical activity was the most predictive factor of BMI and glucose self-monitoring the most predictive of FBG. Metabolic control is a primary goal in T2DM, so the best pathway to attaining that goal appears to be an emphasis on self-efficacy and dietary adherence.
FSU_pmch_27036083, 10.1016/j.pec.2016.03.020, PMC5028237, 27036083, 27036083, S0738-3991(16)30142-2
Biochemical and biophysical investigations of the interaction between human glucokinase and pro-apoptotic BAD.
Rexford, Alix, Zorio, Diego A R, Miller, Brian G
The glycolytic enzyme glucokinase (GCK) and the pro-apoptotic protein BAD reportedly reside within a five-membered complex that localizes to the mitochondria of mammalian hepatocytes and pancreatic β-cells. Photochemical crosslinking studies using a synthetic analog of BAD's BH3 domain and in vitro transcription/translation experiments support a direct interaction between BAD and GCK. To investigate the biochemical and biophysical consequences of the BAD:GCK interaction, we developed a method...
Show moreThe glycolytic enzyme glucokinase (GCK) and the pro-apoptotic protein BAD reportedly reside within a five-membered complex that localizes to the mitochondria of mammalian hepatocytes and pancreatic β-cells. Photochemical crosslinking studies using a synthetic analog of BAD's BH3 domain and in vitro transcription/translation experiments support a direct interaction between BAD and GCK. To investigate the biochemical and biophysical consequences of the BAD:GCK interaction, we developed a method for the production of recombinant human BAD. Consistent with published reports, recombinant BAD displays high affinity for Bcl-xL (KD = 7 nM), and phosphorylation of BAD at S118, within the BH3 domain, abolishes this interaction. Unexpectedly, we do not detect association of recombinant, full-length BAD with recombinant human pancreatic GCK over a range of protein concentrations using various biochemical methods including size-exclusion chromatography, chemical cross-linking, analytical ultracentrifugation, and isothermal titration calorimetry. Furthermore, fluorescence polarization assays and isothermal titration calorimetry detect no direct interaction between GCK and BAD BH3 peptides. Kinetic characterization of GCK in the presence of high concentrations of recombinant BAD show modest (<15%) increases in GCK activity, observable only at glucose concentrations well below the K0.5 value. GCK activity is unaffected by BAD BH3 peptides. These results raise questions as to the mechanism of action of stapled peptide analogs modeled after the BAD BH3 domain, which reportedly enhance the Vmax value of GCK and stimulate insulin release in BAD-deficient islets. Based on our results, we postulate that the BAD:GCK interaction, and any resultant regulatory effect(s) upon GCK activity, requires the participation of additional members of the mitochondrial complex.
Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure.
Qian, Xuyu, Nguyen, Ha Nam, Song, Mingxi M, Hadiono, Christopher, Ogden, Sarah C, Hammack, Christy, Yao, Bing, Hamersky, Gregory R, Jacob, Fadi, Zhong, Chun, Yoon, Ki-Jun, Jeang...
Show moreQian, Xuyu, Nguyen, Ha Nam, Song, Mingxi M, Hadiono, Christopher, Ogden, Sarah C, Hammack, Christy, Yao, Bing, Hamersky, Gregory R, Jacob, Fadi, Zhong, Chun, Yoon, Ki-Jun, Jeang, William, Lin, Li, Li, Yujing, Thakor, Jai, Berg, Daniel A, Zhang, Ce, Kang, Eunchai, Chickering, Michael, Nauen, David, Ho, Cheng-Ying, Wen, Zhexing, Christian, Kimberly M, Shi, Pei-Yong, Maher, Brady J, Wu, Hao, Jin, Peng, Tang, Hengli, Song, Hongjun, Ming, Guo-Li
Cerebral organoids, three-dimensional cultures that model organogenesis, provide a new platform to investigate human brain development. High cost, variability, and tissue heterogeneity limit their broad applications. Here, we developed a miniaturized spinning bioreactor (SpinΩ) to generate forebrain-specific organoids from human iPSCs. These organoids recapitulate key features of human cortical development, including progenitor zone organization, neurogenesis, gene expression, and, notably, a...
Show moreCerebral organoids, three-dimensional cultures that model organogenesis, provide a new platform to investigate human brain development. High cost, variability, and tissue heterogeneity limit their broad applications. Here, we developed a miniaturized spinning bioreactor (SpinΩ) to generate forebrain-specific organoids from human iPSCs. These organoids recapitulate key features of human cortical development, including progenitor zone organization, neurogenesis, gene expression, and, notably, a distinct human-specific outer radial glia cell layer. We also developed protocols for midbrain and hypothalamic organoids. Finally, we employed the forebrain organoid platform to model Zika virus (ZIKV) exposure. Quantitative analyses revealed preferential, productive infection of neural progenitors with either African or Asian ZIKV strains. ZIKV infection leads to increased cell death and reduced proliferation, resulting in decreased neuronal cell-layer volume resembling microcephaly. Together, our brain-region-specific organoids and SpinΩ provide an accessible and versatile platform for modeling human brain development and disease and for compound testing, including potential ZIKV antiviral drugs.
FSU_pmch_27118425, 10.1016/j.cell.2016.04.032, PMC4900885, 27118425, 27118425, S0092-8674(16)30467-6
Ca2+ Effects on ATP Production and Consumption Have Regulatory Roles on Oscillatory Islet Activity.
McKenna, Joseph P, Ha, Joon, Merrins, Matthew J, Satin, Leslie S, Sherman, Arthur, Bertram, Richard
Pancreatic islets respond to elevated blood glucose by secreting pulses of insulin that parallel oscillations in β-cell metabolism, intracellular Ca(2+) concentration, and bursting electrical activity. The mechanisms that maintain an oscillatory response are not fully understood, yet several models have been proposed. Only some can account for experiments supporting that metabolism is intrinsically oscillatory in β-cells. The dual oscillator model (DOM) implicates glycolysis as the source of...
Show morePancreatic islets respond to elevated blood glucose by secreting pulses of insulin that parallel oscillations in β-cell metabolism, intracellular Ca(2+) concentration, and bursting electrical activity. The mechanisms that maintain an oscillatory response are not fully understood, yet several models have been proposed. Only some can account for experiments supporting that metabolism is intrinsically oscillatory in β-cells. The dual oscillator model (DOM) implicates glycolysis as the source of oscillatory metabolism. In the companion article, we use recently developed biosensors to confirm that glycolysis is oscillatory and further elucidate the coordination of metabolic and electrical signals in the insulin secretory pathway. In this report, we modify the DOM by incorporating an established link between metabolism and intracellular Ca(2+) to reconcile model predictions with experimental observations from the companion article. With modification, we maintain the distinguishing feature of the DOM, oscillatory glycolysis, but introduce the ability of Ca(2+) influx to reshape glycolytic oscillations by promoting glycolytic efflux. We use the modified model to explain measurements from the companion article and from previously published experiments with islets.
FSU_pmch_26840737, 10.1016/j.bpj.2015.11.3526, PMC4744176, 26840737, 26840737, S0006-3495(15)04814-6
Cdk5rap2 exposes the centrosomal root of microcephaly syndromes.
Megraw, Timothy L, Sharkey, James T, Nowakowski, Richard S
Autosomal recessive primary microcephaly (MCPH) is characterized by small brain size as a result of deficient neuron production in the developing cerebral cortex. Although MCPH is a rare disease, the questions surrounding its etiology strike at the core of stem cell biology. The seven genes implicated in MCPH all encode centrosomal proteins and disruption of the MCPH gene Cdk5rap2 in mice revealed its role in neural progenitor proliferation and in maintaining normal centriole replication...
Show moreAutosomal recessive primary microcephaly (MCPH) is characterized by small brain size as a result of deficient neuron production in the developing cerebral cortex. Although MCPH is a rare disease, the questions surrounding its etiology strike at the core of stem cell biology. The seven genes implicated in MCPH all encode centrosomal proteins and disruption of the MCPH gene Cdk5rap2 in mice revealed its role in neural progenitor proliferation and in maintaining normal centriole replication control. We discuss here the impact that centrosome regulation has upon neural progenitors in the developing brain. We integrate the impact of centriole replication defects with the functions of Cdk5rap2 and other MCPH proteins, propose mechanisms for progenitor loss in MCPH, and discuss links to two other microcephaly syndromes.
FSU_pmch_21632253, 10.1016/j.tcb.2011.04.007, PMC3371655, 21632253, 21632253, S0962-8924(11)00083-3
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text:
/** This is generated, do not edit by hand. **/

#include <jni.h>

#include "Proxy.h"

		namespace titanium {
			namespace media {

class AndroidModule : public titanium::Proxy
{
public:
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	static void bindProxy(v8::Handle<v8::Object> exports);
	static v8::Handle<v8::FunctionTemplate> getProxyTemplate();
	static void dispose();

	static v8::Persistent<v8::FunctionTemplate> proxyTemplate;
	static jclass javaClass;

private:
	// Methods -----------------------------------------------------------
	static v8::Handle<v8::Value> scanMediaFiles(const v8::Arguments&);
	static v8::Handle<v8::Value> setSystemWallpaper(const v8::Arguments&);

	// Dynamic property accessors ----------------------------------------

};

			} // namespace media
		} // titanium

redpajama_set_name: RedPajamaGithub


text:
Livescores, Results and Fixtures
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If Nigel Pearson had a foreign last name we would saying he is the Messiah, insists Watford skipper Troy Deeney
By Chukwuemeka Afonne
Troy Deeney says Nigel Pearson would earn more praise for dramatically turning around Watford's fortunes if he was a foreign coach.
Pearson, who helped keep Leicester up in 2014/15, has transformed the club since taking charge last month, with victory over Bournemouth on Sunday lifting them out of the bottom three for the first time this season. Abdoulaye Doucoure, Roberto Pereyra and Deeney scored in a win that means Pearson has claimed 13 points from his six Premier League matches at Watford.
It is an incredible achievement, given the Hornets earned as many points as that in their previous 22 matches, and Deeney believes the 56-year-old does not get enough credit.
"If he had a foreign last name we would all be saying he is the Messiah," said Deeney. "It is just the way that the world works and the way he is portrayed in the media, unfortunately, but he is great. His man-management is massively underrated, his technical team, too — you've got him, Shaky [Craig Shakespeare] as well, but then also he's implemented Hayden Mullins and Stacky [Graham Stack], who have got bags of experience.
"He has not only brought that together, but he's galvanised the whole group and showed that he can work under different restraints. I can't praise him enough. He won't be happy if I give him too much credit. He has just hammered me as well and said, 'That's not enough, we've got to do more'."
Deeney was on the score sheet on Sunday. (Getty Images)
Pearson's impressive run in the top flight stretches back to his time at Leicester, where his side won seven of their final nine matches to stay up five seasons ago. Sunday's victory means he is the first English manager to win at least 11 Premier League matches across a 15-game spell in the competition since Harry Redknapp in January 2012.
Despite the turnaround, Deeney and his team-mates know they have plenty of hard work ahead of them.
Watford brush aside Bournemouth to climb out of relegation zone
"I can genuinely, hand on heart, tell you that no one looked at the table when we got in. I have just been told we are out of the bottom three," Deeney added.
"We can't keep saying, 'Right, that was it, we've cracked it', because in this League someone was saying if we win our next few games we could be 10th — but if we lose, we're bottom. So we are not getting ahead of ourselves. We've got three games in a week after the Spurs game [January 18] as well.
"We have to be respectful of what is coming, but take stock of what we have done. You can't deny that it has been an unbelievable six games and we have to keep going. The gaffer has been great, the players have been great, but there's a long way to go yet."
Watford are back in action Tuesday night, when they travel to Tranmere for their FA Cup third-round replay.
They drew the first match 3-3 despite being three goals ahead and Pearson is expected to ring the changes, with Andre Gray, Isaac Success and Domingos Quina given chances to impress.
Nigel Pearson
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