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We'd like to report we've had nothing but top-notch pizza this summer. That would not be true. There's a lot of so-so pizza across the Garden State, as you can tell by our Pizza Patrol reports to date. We sure hope things improve.
By the time you read this, we will have visited 135 pizzerias around the state. The original goal: 100. The revised goal: 150. The newly revised goal: 200.
Forget about what this is doing to our collective cholesterol counts; we will not rest until we have done the Jersey pizza scene justice. E-mail recommendations to email@example.com or call the Munchmobile Hotline at (973) 392-1765. Next week, we'll publish a list of every pizzeria visited to date. Check the list; if your favorite pizzeria is not on it, let us know!
Trip No. 15, Essex County
Nothing fancy about Zuchette's Pizzeria (71 Walnut St., Montclair; 973-744-4333), but this restaurant serves a nice tomatoey plain pie. "Saucy goodness," Alex Windrem said. "Great texture," Joan Dwyer added.
The sausage pie is one of the better ones this summer. The Sicilian got mixed reviews. Scott Wiener liked the "tangy" sauce, but Gina Bruno thought it was undercooked. "Note to chef: Put back in oven," she said.
"The absolute best brick oven pizza in NJ," began an e-mail about Da Vinci's (223 Belleville Ave., Upper Montclair; 973-744-2300). A lot of our e-mails begin this way. Often, the outcome is disappointing. Da Vinci's is no different. Average plain pie. "Puts me to sleep," said the ever-awake Bruno. "Bland," Windrem noted.
The margarita even less successful. "The sauce is a snoozer," Wiener said. Dwyer less forgiving. "A pathetic excuse for a margarita," she said.
The folks at Soho Pizza & Grill (540 Valley Road, Upper Montclair; 973-744-8708) really should do something about their sausage; it's subpar, and that's being kind. "The meat product on the pie was at an all-time low," Windrem said. "Think they should find a new distributor," Bruno added.
The grandma pie better, fortunately. "A Grandma you'd want to take to lunch," Wiener noted. But Bruno found the sauce too "tomato pastey."
The Munchmobile driver found his favorite pasta -- De Cecco -- and good olives at Cavallo's Market (173 Bloomfield Ave., Nutley; 973-667-1237). The pizza? The plain and sausage pies are fair. Windrem liked the cheese's "good straightforward taste," but turned his nose down at the sausage. "Pretty sleepy cheese pie," Wiener said.
But the margarita is a near-model of its kind. "Tastes like they put a little attention to it," Bruno observed. "The grated cheese on top put it into pizza overdrive,'' Wiener said approvingly.
Two-minute pizzas are the rule in the super-hot ovens at Queen Margherita Trattoria (246 Washington Ave., Nutley; 973-662-0007). The margarita an immediate hit. "This pie is king,'' Wiener proclaimed. "The tomatoes kicked butt," Windrem said. "Nice lively flavor," Dwyer added.
The marinara, with tomatoes, black olives, anchovies and garlic, nowhere as memorable. "I'd rather leave it than take it,'' said Bruno, echoing the consensus.
Mario's Pizzeria (137 Delancey St., Newark; 973-466-3377) is connected to Assaggini Di Roma, one of our favorite Newark restaurants. However, the meatball pie at Mario's is a mistake, and the plain pie received "dried out" and "very dull" reviews. The sausage the best of the lot "Full flavored pie," according to Windrem.
"Down Neck's #1 Pizza" proclaims the menu at Tony's Pizzeria (59 Pacific St., Newark; 973-344-0590). Whatever. The plain is irreparably greasy. "Free ticket to a grease fest," Wiener said. The margarita turned out to be little more than a basil-topped grease pie. "They taste exactly the same," Dwyer said.
Dig the church confessional-like panels at Frank's Pizzeria & Restaurant (161 Bloomfield Ave., Newark; 973-482-8891). Windrem admired the plain's "good crunch," but Wiener called it "a same-old cheese, no-sauce pie.'' Sausage below average. The red peppery Grandpa pie came as a spicy surprise, even if the sauce is subpar. "You meet this Grandpa in an alley, you're going down," Windrem said.
Next week: The Pizza Patrol hits Passaic County


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John W. Albaugh
"Genealogy of the Albaugh Families", by Noah H. Albaugh, 1899.
JOHN W. ALBAUGH of Baltimore, Maryland, Actor and Manager, was born in Baltimore, Maryland on September 30, 1837. Son of John William Albaugh who was born in 1800 at Williamsport, Maryland, grandson of John W., great grandson of Johann Gearhardt, and great, great grandson of John Wilhelm Ahlbach the ancestor. (This is where the problem is because he believed a father and his four sons came over on the ship Hope.) Jonh W. was married to Mary Lomax Mitchell - , a prominent actress, and sister to Maggie Mitchell, of stage fame, on July 29, 1866. Their children are John William, Jr., born 1867, Anna Elizabeth born 1870, and Sarah Constance born 1875. (then it goes on about the childrens marriages)
John W. Albaugh, was early attracted to the stage. On November 24, 1853 when but 16 years old he took (lady's) part of "Portia" in the "Merchant of Venice" at a performance in Baltimore. From this time forward he rapidly grew into the Historic art and we find him on the stage in many cities and in many plays, and with nearly all the prominent actors of his day, as the following will indicate.
In 1855 as Hamlet, and as Brutus; in 1856 as William Tell, and the "Drunkard" - and following rapidly with "CLaude Melmotte" in the :Lady of Lyons;" as Biondello to Edwin Booth's Petruchio, in "Taming of the Shrew;" as Richard III and as "Richmond" in same play. The leading part in the "Marble Heart," "Pythias" in "Damon and Pythias," as Iago to Davenport's Othello, (and said to be the finest Iago then in America). As "Enoch arden," as Louis XI, and as Hotspur in Henry IV and Henry VIII. In opposite roles, with such prominent actors as Edwin Booth, James and Lester Wallack, James E. Murdock, E.L. Davenport, Edwin Adams, Lawrence Barrett, McCullough, Eliza Logan, Mrs Lands, Julia Deane, Matilda Herron, Modjeska, Charles Fechter, Joe Jefferson, Ada Rehan, Miss Anderson, Ed Forrest, Charlotte Cushman and many others.
His last appearance on the stage, was as Macbeth with Modjeska, at Grand Opera House, Washington City, D.C., about 1894. He played in the following cities, Baltimore, Philadelphia, New York, Washington City, Troy, N.Y., Albany, Richmond, Virg., Pittsburg, Montgomery, Ala., Columbus, Ga., Detroit, Indianapolis, Boston, Louisville, Cincinnati, St. Louis, Nashville, New Orleans, Montreal and many others.
He managed Holliday Street Theatre, and built and owns the Lyceum Theatre in Baltimore, and was Lessee and Manager at Washington City of the National Theatre for five years, of Albaugh's Grand Opera House for ten years, and in conjunction with a Washington gentleman, built, owned and managed the LaFayette Square Theatra for three years. He was also manager of Theatres in Troy, New York, Albany, New York, Louisville,
Kentucky, Montgomery, Alabama and at other cities. His wife Mary Lomax Mitchell, was a noted actress, and played leading parts with her husband, after their marriage.
He has now retired from business and resides in Baltimore. The following rom a Washington City paper gives an indight into his standing at his retirement from the stage. "By the retirement of Mr. Albaugh, Washington City loses one of her most respected and admired public citizens, theatrical circles a man whose honor and high principles are unquestioned, and whose ability and generosity has established him in the admiration of all who know him."

subset: commoncrawl


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Results tagged ' New York City '
Double the Fun, Old Time NYC, Podcast
A 6-5 win by the TinCaps on Saturday gave the team a couple milestones on the season. First, it was the largest deficit they've overcome to win a ballgame this season. They trailed 3-0 after the top of the first, and later trailed 5-2. That was a promising sign for an offense that is starting to come to life.
The second marker of success in the game was the seven doubles that the team collected off of Peoria pitching. That number is just one shy of the franchise record for two-baggers in a game. Eight doubles in one game has occurred twice: May 31st of 2008 against Dayton, and last year 366 days prior on April 27 against Lake County.
Interesting side note–In that game against Dayton, the winning pitcher for Fort Wayne was Jeremy Hefner. He recently became the 108th former Fort Wayne player to reach the bigs. Hefner did it as a member of the New York Mets, as he pitched three scoreless innings against the San Francisco Giants.
In today's TinCaps Report Podcast, we'll re-live the highlights of Saturday's win, and hear from Corey Adamson, who scored two runs, and despite being Australian, explains why he doesn't like cricket:
Series Finale, Billionaire For a Day, The Bystander Effect
The TinCaps will try for the series split today after losing the last two at the hands of the Great Lakes Loons. It's not that Fort Wayne has lacked the opportunities to win, they just haven't been able to capitalize. Here's a nugget from today's game notes:
Over the last two games as the TinCaps have lost by a combined two runs, they've left many potential runs on base. In Friday's 5-4, loss, the team went 3-12 with runners in scoring position and stranded 10. On Saturday, Fort Wayne went 2-10 with RISP and left seven men on base. Friday's loss also saw four runners caught stealing, and two getting picked off.
Cody Hebner gets the call for Fort Wayne this afternoon, and it looks like it won't be quite as sunny and warm as it had been over the last two days at Dow Diamond. There are grey skies overhead and it rained overnight here in Midland, MI. I'll chat with Jose Valentin before today's game to get his thoughts on the first ten games of the season.
Yesterday I chatted with Kyle Gaedele, a native of Illinois and a former Valparaiso Crusader. We talked about this team's propensity for base stealing, his spring, and why he's always felt like an under the radar guy:


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Oregon mill finds successful niche
Friday, January 25, 2013 9:28 PM
January 14, 2013 - Each piece of timber that runs through the center is stamped, indicating the wood grade and other features referenced by engineers and architects. Elk Creek Forest Products found a niche found a successful niche remanufacturing lumber and filling custom orders for high-end home and commercial construction. Working in an abandoned mill that closed years ago in Independence, they've been adding workers and making a considerable economic impact to the city. Past years have been hard on Oregon's wood products industry, with many small towns shutting mills and laying off workers, but Elk Creek is making a go of it. Beth Nakamura/The Oregonian
Related articles
- Bucking the recession, small Oregon mill finds a successful wood products niche January 26, 2013, 2:00 PM


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Ashley Dertinger and Travis Rapatt were united in marriage on April 24, 2010 at Holy Cross Catholic Church.
Parents of the bride are Wayne and Jan Dertinger of Frazee. Parents of the groom are Mary Rapatt and the late Roger Rapatt of Fergus Falls.
Ashley is a 2003 Perham high school graduate and attended MSCTC-Wadena. She is employed as a massage therapist at Perham Memorial and Home.
Travis graduated with the New York Mills class of 1999 and attended MSCTC-Wadena. He is employed as a journeyman electrician for Melrose Electric.
The couple resides in New York Mills.


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On any other weekend, Connor, 12, would have been with his friends. He might have been wrestling, shooting foam darts out of a toy gun or playing with his dogs, Oliver, Goose and Schutes.
But on the International Day of Action for Elephants in Zoos, Connor and about 20 other protesters had a message for the crowds that passed him on their way into the Oregon Zoo: elephants are suffering.
According to Courtney Scott, a local filmmaker and activist who organized the protest as part of a worldwide string of similar events encouraged by the animal-rights organization In Defense of Animals, captive elephants are confined in spaces that don't let them wander the miles they would in the wild, and the use of training hooks is a gross abuse.
"The most important thing is space," Scott said. "These elephants have a backyard — a suburban backyard."
They have also grown impatient with the time it has taken to build the elephant preserve outlined in 2008, when Metro-area voters approved a $125-million bond for the zoo.
But inside the zoo's gates, Director Kim Smith on Saturday defended the happiness and health of her elephants and the passion of her staff, though she understands public concern.
"The community loves these elephants," she said of a fondness that traces back to the 1950s, when school children collected pennies so the zoo could buy its first elephant, Rosy. "They're a part of Portland, really. I've never seen anything like it."
An argument at the forefront of activist concerns is that the use of guides, which the Oregon Zoo handlers use for training purposes, is abusive by default. The only reason the elephants obey commands, according to activists, is that they fear punishment from the pointed instruments.
Catherine Doyle of California-based In Defense of Animals said while defenders of the tools say they're safe and humane, there have been innumerable investigations that show elephants that are wounded and fearful where guides — which Doyle says are no different from controversial bullhooks — are used.
"I don't understand why the Oregon Zoo is hanging onto circus-style training," she said.
But Smith and Elephant Curator Bob Lee described a system of positive reinforcement complemented by instruments called guides, which are smaller and lighter than bullhooks and designed not as a weapon or a means of punishment but as a communication tool.
As he gave a series of simple commands to Chendra, a playful female, the guide dangled in his left hand, ignored as he motioned to her with his right. Smith and Lee said positive reinforcement is at the center of the elephants' interaction with their handlers.
"You're not going to get very far with an elephant without positive reinforcement," Smith said.
For 1,400-pound Chendra — petite compared to the rest of her herd — apples are the way to a girl's heart and the way she learned her spunky "shake" command, a spirited dance reminiscent of the mashed potato of the '60s.
"It is not tolerated here," she said. "[Caregivers] don't want to deal with me if they've done that. It will not be pleasant."
More than a decade ago, an elephant handler was fired for injuring an elephant named Rose-Tu with a bullhook — an offense that was reported by enraged coworkers.
"These people are passionate about the animals," Smith said. "It's why I became a zoo director."
But for activists like Doyle, it's not enough. While things can be done to make life in captivity more humane, Doyle said, the only answer is to keep elephants in large preserves and not in the confinement of zoos. They hope the Oregon Zoo will follow the example of places like the Detroit Zoo, which in 2004 moved its elephants to a refuge.
Until that happens, the activists won't be satisfied, and they won't stop their fight.
Neither will Connor.
"I hope people will pay attention to us," Connor said. "These are living animals, and they deserve better."


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The Nets shipped out the final remaining piece from their glory days today, sending Richard Jefferson to Milwaukee for two players and drastically reducing their long-term payroll to position themselves for a big splash in the 2010 free agent market.
In exchange for Jefferson, the Nets will receive Yi Jianlian, the Chinese power forward, and Bobby Simmons, the injury-prone small forward whose contract has two years to run at $9.9 mllion and $10.5 million.
The deal not only stole the spotlight hours before the 2008 NBA Draft was to commence, it was also going to have profound impact on how the participants would make their selections.
For now, the Bucks (picking eighth) and Nets (picking 10th) will retain their picks, but the Bucks had targeted small forward Joe Alexander for their slot. They are now likely to go for a point guard, which could allow the Nets to draft Alexander himself.
Since arriving in a draft-day deal in 2001, Jefferson served the Nets extremely well over the next seven years, and arguably had his best season in 2007-08, when he finished ninth in the NBA in scoring at more than 22 points per game. But his game suffered in the advent of the Jason Kidd controversy, and had been at odds with the coaching staff over his defensive intensity for much of the year. That convinced management to shop him since the season concluded, as his name had been connected with trade rumors involving the Los Angeles Lakers, Denver Nuggets, and many other teams.
A major benefit to the Nets is the fact that they have only $27 million firmly earmarked for player salaries after the 2009-10 season, which gives them a clean slate with which to rebuild a team that won only 33 games last season.
The Nets had always sought to keep their payroll low for the summer of 2010, when - at least theoretically -- players such as LeBron James, Dwyane Wade, Chris Bosh, Amare Stoudemire, and Chris Paul could be come free agents.


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EAST LANSING -- Michigan State plays its first game tonight in an exhibition against Grand Valley State, and the Lakers could very well see some of the Spartans' version of Showtime.
Tom Izzo's team is looking to run even more than it did last year when numerous players were ailing. The Spartans have emphasized playing at a fast pace in practice now that the team is able and willing to get up and down the court, and it starts with sophomore guard Gary Harris, who has recovered from shoulder injuries and a sprained ankle.
"He's running the court more like the (Shannon Browns and Maurice) Agers, which is what I think he have to get back to," Izzo said.
Harris, the reigning Big Ten freshman of the year, couldn't run as well with a sagging shoulder and said this season the Spartans would look to put even more pressure on their opponents this season on the fast break.
"We're going to run a lot," Harris said. "The practices, that's all we've been doing is running. Run, run, run. And when we're tired, it's even more about running. We're looking to get it out. Keith (Appling's) looking to push it. The wings are looking to get out there fast. We've got the bigs who can run. All our bigs are athletic
"It was different circumstances last year. BJ (Branden Dawson) was just coming off his knee injury, so he wasn't really back to how he is now. I battled injuries the whole time. (Travis Trice) was hurt. So Keith couldn't push it all by himself the whole time."
Izzo after an offseason of emphasizing to his point guard the need to involve his teammates thinks the Spartans' running game will be improved.
"Our point guard is pushing it a lot better," Izzo said. "We have a backup that can push it. I think we should be a team that can run, run, run and run."
Said Appling: "Coach has been putting a very big emphasis on running, so our goal is to run as much as we possibly can on makes and misses. So we've just got to go out there and execute it."
• Download the MSU basketball on MLive app for iPhone and Android
• Download the MSU football on MLive app for iPhone and Android
• Follow Diamond Leung and Mike Griffith on Twitter
• Like MLive's Michigan State Spartans Facebook page


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The Style Gallery is a great new way for you to view, love, and share outfit photos. It's meant to showcase
all the expressive, creative, and inspirational personalities of our community!
Love you too!
Your email has been sent!
Who knew chic comfort was as easy as zipping into this long-sleeved, stretch-cotton dress? Flaunting a monochrome-striped bodice, grey sleeve cuffs, and a black skirt, this exposed-zip frock adds subtle sophistication to even the simplest dressy occasion.
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All measurements in inches.
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Welcome to my website!
And entertained. I work hard to keep you turning those pages. If one of my books keeps you up late? Victory is
Which leads to the common thread in all my novels: finding your purpose. No matter if the book is about Mozart's
sister, a plane crash, a Victorian boarding house, or time travel, one message prevails: we each have a unique
God-given purpose. The trick is to find out what it is. I hope my books help you take one step closer to that
amazing knowledge.
So enjoy the site. And
let me hear from you
. We're in this together.
Nancy Moser


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does nikyo hurt?
View Single Post
Bill Danosky
Dojo: BN Yoshinkan
Join Date: Nov 2004
Posts: 433
Re: does nikyo hurt?
Krystal Locke
The great thing is that I actually DO have a couple folk at home who can teach this very well. Now I just have to freaking learn from them. And, I have access to several other people who also have it.
I am learning that I dont have to throw the baby out with the bathwater. My experience with aikido so far leads well into what I am trying to learn now. I am having to reprogram some stuff, mostly "footwork" and entry angles. That's proving to be pretty tough, but I'm sure it will come along. Mostly, since I am learning new things, I am coming in way too big and missing the sweet spots. I've never been subtle. If a tack nailer will do nicely, I'm grabbing the sledge. Nobody can accuse me of having any sensitivity.
Maybe you have mentioned this before, but I'm wondering if there's an event behind your Aikido renaissance, so to speak? It looks like you've been around since 2004, but are now referring to reprogramming and worrying about having to abandon the whole project. Aikido schools, traditions, philosophies differ widely. Even the nomenclature is different. You've probably noticed how advice that's good for some may be terrible for others, depending on how they train.
Has something changed in your outlook? Switched dojos or styles recently?
Bill Danosky
View Public Profile
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text: Part I: Velvet Tom at Snubfest February 2007, Chicago By VELVET TOM "Hey Fans! This was sitting in the vault...this is a two parter from the... more »"Hey Fans! This was sitting in the vault...this is a two parter from the Snubfest Comedy Festival in 2007 at the Cornservatory, in Chicago, IL. Please enjoy...and vote. Funny? Die? Whatever! You hold the power! « less Published July 28, 2012 808 views More Info » Full Credits VELVET TOM Uploader Stats & Data 2 Funny Votes 0 Die Votes 808 Views Published: July 28, 2012 Categories: Music Animals Being Awesome Mashups Keywords: velvet tom farnan lounge sexy back timberlake lori mcclain theresa ryan steph mccullough comedy festival snubfest 2007 chicago illinois lover loser legend Up Next: The Sunshine Mashup AUTOPLAY Up Next In: 10 The Sunshine Mashup UberDad 1 I Want It That Way VT Las Vegas 2006 - "I'm On Fire" Follow Facebook Twitter Tumblr Instagram Browse Related Comments 10+ more View All ▶ VELVET TOM Vaguely Related Videos Vaguely Related Pics & Words Advertisement Tags: velvet tom farnan lounge sexy back Advertisement


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See the welcome signs of spring from 1-2:30 p.m. April 3 at Euclid Creek Reservation.
The wildflower peak is not here yet, but the reservation is turning green again and the newly arrived spring is welcome at Euclid Creek.
See some early signs of flowers and maybe find a few early bloomers.
The event will take place at Highland Picnic Area parking lot located off Euclid Creek Parkway, off the Highland Road entrance of Euclid Creek Reservation in Euclid.
Call (440) 473-3370.


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Kentville Mayor Dave Corkum presents Inez Cooper, publicity chair of Valley Voices, with a proclamation declaring Feb. 10-16 Harmony Awareness Week. Valley Voices are celebrating this special week and St. Valentine's Day by doing singing Valentines throughout the Valley all week. - Submitted
Events are for non-profit listings of events in Kings County. Items may run twice free before the event's date, and should be emailed to email@example.com; faxed to 681-0923 or mailed to PO Box 430, Kentville, B4N 3X4, attn: Events, at least a week before the first issue in which it should appear. Twenty word maximum, please. There is no guarantee of publication; to ensure publication, please consider a paid ad by contacting our sales department, 681-2121.
February to March 12 The Annapolis Valley Chapter of Autism Nova Scotia is offering a six-week after-school Arts and Crafts program. Free, seven spaces for children between the ages of six and 10 years with Autism Spectrum Disorder, one group leader and one support person to supervise, 6:30- 7:30 p.m. at Aldershot Elementary School. Registration: contact Denise at 678-6709 or 670-8294
Feb. 11
• Valley Gardeners Club Meeting - 7:30 p.m. in room 2101, Kingstec campus of NSCC, Kentville. Stan Kochanoff will speak on "Pruning, Planting and Tree Health Care," all are welcome.
Feb. 12
• Pancakes - Girl Guides holding Shrove Tuesday pancake, ham and baked bean supper at the Waterville fire hall. Freewill offering, 4:30-6:30 p.m. Proceeds benefit Hardwood Lake Girl Guide Camp.
• Shrove Tuesday - Pancake Supper, 5-7 p.m. L'Arche building, 341 Main St., Wolfville. Adults $7, children under three eat free. The first child between three and 12 years $3, all additional children eat free.
• A.C.W. Supper - All Saints' A.C.W. hosts an annual Shrove Tuesday Supper, 4:30-6 p.m. at the All Saints' Church Hall, Pleasant Street, Kingston (turn west off Bridge Street). Ham, baked beans, scalloped potatoes, pancakes and gingerbread. $10 per plate. Family rates and take out available. Contact Sheila Hulford 765-4023
• Meeting - Cambridge United Baptist Church Cemetery Company's annual meeting, 7 p.m., at the Cambridge Community Centre. All lot owners are urged to attend.
• Kings Presbyterian Pancakes - Shrove Tuesday pancake supper, 4:30-6:30 p.m., Kings Presbyterian Church, 5563 Prospect Rd., New Minas. Freewill offering. Pancakes, sausages, baked beans, baked apples, gingerbread with sauce and beverage.
• Luncheon - at the Kingston Lions Hall 11:30 a.m. to 1 p.m. Turkey dinner with mashed potatoes, vegetables and dessert. $8 or $8.50 delivered.
• Meeting - The Port Williams Health Auxiliary will be meeting on Tues. Feb. 12 at 2 p.m., downstairs in the Baptist Church. Guest speaker will be David Graham, Executive Director of Brigadoon. Everyone welcome.
• Hospital Auxiliary - Valley Regional Hospital Auxiliary meeting, 11:30 a.m. in the board room.
Feb. 13
• Valentine Coffee - Kentville & Area Women's Connection, 9:30 a.m., at the Berwick Lions Club Hall - $8. Speaker Hank Veenhuis, Upper Stewiacke, Music by George Estey and feature on card making by Dora Crosby. Contact Peggy at 678-5522 before Feb. 10 for reservations.
• Meeting - Valley Women's Business Network meeting, finding wellness through life/work balance, 7-9 p.m., King's Riverside Court, 125 Webster Street, Kentville. Free to members and their first-time guests. $5 at the door for returning guests.
• Coffee Party - The Berwick United Church Women are hosting a Valentine Coffee Party, 10 a.m. to noon, at Berwick United Church. Freewill offering. Everyone welcome.
Feb. 14
• Meeting - of the Annapolis Valley Decorative Artists, 7 p.m., at the Greenwich Fire Hall. Anyone interested in decorative art is welcome.
• St. Valentine Luncheon and Auction - by Augustine Church Guild at the Forties Community Centre. Doors open at 11:30 a.m., luncheon at noon. Adults $, children $3, preschoolers free. Storm date Feb. 15.
• Valentine Candlight Dinner - at the Aylesford United Church. Storm date: Feb. 15. All tickets to be pre-sold, $25 per couple, $15 per person, limited seating. Call 847-3507 or 847-9774
• Valentine's Dinner - sponsored by the Port Williams and District Lions Club at 7 p.m. at the Port Williams Community Centre, $40 per couple. Door prizes and entertainment. In support of Brigadoon Village. For tickets, contact any Lions Club member or call 678-6532. Storm date Feb. 15.
Feb. 15
• Music Night – with Bev, starting at 9 p.m. at the Canning Legion. Open to everyone 19 plus. Minimum cover charge of $2 per person. Enjoy great music.
Feb. 16
• Good Neighbour Club Breakfast - at the Centreville Community Hall, 7-10:30 a.m. Freewill offering. Everyone welcomed.
• Coldbrook Lions Breakfast - all you can eat, freewill offering. For information, call Marsha 692-0579
• Dance - Coldbrook Lions Dance, 9 p.m. to 1 a.m., $6 per person. Music by Rte 12. For more information, call 538-8050
• Crib Tournament - Kentville Legion Ladies Auxiliary crib tournament. Registration 12:30 p.m., play at 1 p.m. upstairs, $20 per team. Lunch served compliments of the ladies
• Breakfast – held by Scott's Bay Community Hall Association, 8-10 a.m. Adults $5, under 12 $2.50. Proceeds for hall upkeep. For more information, contact Jerry at 582-7489 or Hope at 582-3603.
• Variety Music Night – held by the Kingston Lions at the Kingston Lions Hall, 7 p.m., admission $5. Performances by Valley Blue, Chad Brown and Lois Lutz, and Wanda Beaudoin (Newfie)
• Legion Dance – Held at the Kentville Legion, 9:30 p.m. $6 per person, music by Sidewinders.
• Potluck and Service - ACTS of Worship (formerly Rally in the Valley), Coldbrook Baptist Church. Fellowship/potluck supper 5:30 p.m., service 7 p.m. All ages welcome.
• Church Breakfast - Aylesford United Breakfast Church, 8-11 a.m. Freewill offering. Sponsored by the Committee of Stewards for church expenses.
• Lions Breakfast - Wolfville and District Lions Club monthly breakfast, 7-10 a.m. at the Lions Hall Elm St. Wolfville. Adults $6, children under 10 years $3. Proceeds towards Lions Community Services.
• Benefit - Benefit breakfast for Feb. 9 at the Burlington Community Hall for Linda Mapplebeck has been rescheduled to Feb. 16, 8 a.m.
Feb. 17
• Roast Beef Supper - Forties Community Centre, 1787 Forties Rd., New Ross. Adults $11, children five to 12 $5.50, under five $2.50, 4:30-6 p.m. For information, call 689-2000 or 689-2312
• Benefit Supper - for Sandra Comeau of Cambridge to help with medical expenses, at the Waterville Fire Hall, 4:30-6 p.m. Menu will be Jim Lamb ham, potato scallop, beans, and assorted desserts. Call Alice Oickle, 538-1352, to volunteer to work or donate.
Feb. 18
• Taoist Tai Chi – Beginner classes at Berwick town hall gym, Feb. 18, 6-7:30 p.m.; Kentville Lions Club Feb. 19, 6-8 p.m. and Feb. 21, 12:30-2 p.m. For more, call 678-4609.
Feb. 20
• Historical Society Meeting - at 2 p.m. in the Wolfville Fire Hall. Guest speaker Dr. Julian Gwyn, speaking on the History of the N.S. Fruit Growers' Association, which is nearing its 150 anniversary. Everyone welcome.
• Coffee House for Foreign Aid - Central Kings High School Beyond Borders club, are hosting a coffee house with entertainment and refreshments 7-9 p.m. All money raised will be used to purchase necessities for impoverished communities.
Feb. 21
• Auditions – Will be held Feb. 21, 7:15-9 p.m. and Feb. 24, 1-4 p.m., for spring production at the Morfee Centre. Play will run for five performances in May. Rec or club pass needed if chosen.
Feb. 23
• Birthday Bash - H.A.R.T.'s fifth Birthday Bash Dance, 8 p.m. to 12 a.m., doors open at 7 p.m. Music by Handsome Devil (classic and new rock). Veggie and meat chili, with dessert, $10 per person. Silent auction and raffles at the Berwick Fire Hall - 341-HART for more details.
• Breakfast - All Saints' Church serving a full breakfast. All Saints' Church Hall, Pleasant Street, Kingston (turn west off Bridge Street) 8 a.m. Cost $ 7. Everyone welcome.
• Hang Out Night – 7-9 p.m., White Rock Community Center (use the back lower entrance). $2 individual, $5 family. Social time with neighbors and friends, board games, table tennis, air hockey or Wii system available. Bring games, musical instruments as well. For more, call 542-3805 or http://www.whiterockhall.ednet.ns.ca/exercise1.html
• Card Party - Cornwallis New Horizans Club Canning, 45's Card Party at the Seniors Room, Canning Lions Hall. Registration 1 p.m., games start 1:30 p.m., admission $2. Prizes and refreshments, 50/50 tickets.
• Dance - Kentville Legion Dance, 9:30 p.m. $6 per person. Music by Country Heat.
• Opening - Salvation Army Kentville, opening celebration, 5:15 to 7:30 p.m. Lots of entertainment and snacks. Learn about programs offered for all ages.
• Darts - Kentville Legion Mixed Doubles Dart Shoot. Registration 9:30 a.m., start time 10 a.m., $25 per team. Call 678-8935 to register. Cash prizes awarded based on number of teams.
• Dinner and Auction - Friends of the Villages and West Kings Rink Assc. invite everyone to The Royal Canadian Legion Br. #098 in Kingston. Cordon bleu dinner, live auction followed by dancing to Route 12. $20 for the evening or you may purchase separate tickets to dinner $10 or dance $10. Doors open at 6 p.m. Quilt draw will be held. Tickets available at Greenwood Scotiabank or call Janet at 765-7707, Linda at 765-2564, Muriel at 765-8605 or Rose at 765-6322. Advace purchase of dinner tickets, but dance tickets may be purchased at the door.
Feb. 24
• Variety Show – 2-5 p.m. at the Kentville Legion. Admission $ 5, 50/50 draw, door prizes, canteen. Country Heat, Basil Davidson, Cy Brown Band and more. All proceeds for the Kinette Club of Kentville & District
Feb. 25
• Meeting - General meeting and election of directors, to be held at West Brooklyn Hall. Storm day March 4.
Mar. 6
• Turkey Farmers of Nova Scotia - annual meeting 8 a.m. at the Old Orchard Inn Greenwich. Dinner banquet with chicken producers following the morning session. Pre-register with the board office before Feb. 8.


text:
The mPTP and its regulatory proteins: final common targets of signalling pathways for protection against necrosis
The mitochondrial permeability transition pore (mPTP) is a non-selective, large-conductance channel that is closed under physiological conditions. Opening of the mPTP, leading to abolition of mitochondrial functions, is a major mechanism of myocyte necrosis by ischaemia/reperfusion, and direct inhibition of mPTP opening by use of pharmacological or genetic manipulations limits infarct size in vivo. Multiple pro-survival signal pathways commonly target the mPTP and inhibit its opening. Although the molecular structure of the mPTP has not been established, recent studies have characterized roles of each mPTP subunit and functions of several proteins directly interacting with the mPTP. This article briefly describes the understanding of mPTP regulation and interaction of the mPTP with four proteins (hexokinase II, glycogen synthase kinase-3β, signal transducer and activator of transcription 3, and sirtuin 3) that are downstream of signal pathways relevant to protection from ischaemia/reperfusion injury.
- Mitochondria
- Signal transduction
- Hexokinase
- Glycogen synthase kinase-3β
- Mitochondrial permeability transition pore
1. Introduction
Myocardial necrosis after ischaemia/reperfusion is an outcome of the combination of ischaemic injury and reperfusion injury.1–3 Relative importance of each component of injury differs depending on the duration of ischaemia, level of residual blood flow in ischaemic tissue, and presumably animal species as well. Recently, accumulating evidence indicates that loss of mitochondrial functions by opening of the mitochondrial permeability transition pore (mPTP) is one of major mechanisms of reperfusion-induced cardiomyocyte necrosis.2–5 However, the role of the mPTP in apoptosis is not clear. Opening of the mPTP induces swelling of mitochondria, leading to rupture of the mitochondrial outer membrane (MOM), and rupture of the MOM results in release of cytochrome c into the cytosol, triggering apoptosome formation. However, the mitochondrial apoptosis-induced channel, which is formed by Bax and Bak in response to pro-apoptotic signals, provides a route for cytochrome c release independent of the mPTP. Since ATP required for apoptosome formation is reduced by mPTP opening, contribution of the mPTP to apoptosis might depend on energy status of the cell and other conditions. A more detailed discussion on the role of the mPTP in apoptosis can be found elsewhere.6,7
Multiple, though not all, pro-survival signal pathways activated by G-protein-coupled receptors and cytokine receptors target the mPTP. The feasibility of myocardial salvage from reperfusion injury by modulating the mPTP has been demonstrated in animal studies and a small clinical trial.8–12 However, for translation of mPTP biology to clinical cardioprotection, it is crucial to understand the mechanism by which mPTP opening is regulated and how we can modify the regulation. Since we recently reviewed pro-survival signal pathways targeting mitochondria in the journal (Figure 1), we focus on the interaction of the mPTP subunits and proteins relevant to protection from necrosis after ischaemia/reperfusion in this article. The following discussion is based on data from both cardiac and non-cardiac cells, since data from cardiomyocytes for this issue are relatively limited.
AceCS2, acetyl-CoA synthetase 2; ANT, adenine nucleotide translocase; CyPD, cyclophilin D; ΔΨm, mitochondrial membrane potential; EPO, erythropoietin; GSK-3β, glycogen synthase kinase-3β; GST, glutathione S-transferase; HK, hexokinase; IMS, intermembrane space; IPC, ischaemic preconditioning; IPost, ischaemic postconditioning; JAK, Janus kinase; LCAD, long-chain acyl-CoA dehydrogenase; MIM, mitochondrial inner membrane; mKATP channel, mitochondrial ATP-sensitive K+ channel; MOM, mitochondrial outer membrane; mPTP, mitochondrial permeability transition pore; NEM, N-ethylmaleimide; PAO, phenylarsine oxide; PPIase, peptidyl-prolyl cis–trans isomerase; PiC, inorganic phosphate carrier; PKC-ɛ, protein kinase C-ɛ; ROS, reactive oxygen species; SIRT3, sirtuin 3; STAT3, signal transducer and activator of transcription 3; TOM20, translocase of the mitochondrial outer membrane 20; VDAC, voltage-dependent anion channel.
2. Components of the mPTP complex and their regulation under ischaemia/reperfusion
Molecular structure of the mPTP remains unclear and different models have been proposed. A classic model of the mPTP consists of a dimer of voltage-dependent anion channel (VDAC) in the MOM and a dimer of adenine nucleotide translocase (ANT) in the mitochondrial inner membrane (MIM) forming a channel. This model is no longer widely supported since genetic ablation of ANT or VDAC did not eliminate mPTP opening, which was detected by mitochondrial swelling and by change in mitochondrial membrane potential (▵Ψm).13,14 However, roles of ANT and VDAC as regulatory subunits of the mPTP together with a matrix protein, cyclophilin D (CyPD), have been indicated by several lines of evidence as discussed below. In addition, a recent study by Leung et al.15 suggests that mitochondrial phosphate carrier [inorganic phosphate carrier (PiC)] is also a major subunit of the mPTP, possibly forming a channel in the MIM. A putative structure of the mPTP is a complex across the mitochondrial membrane, consisting of VDAC in the MOM and ANT–PiC complex in the MIM (Figure 2).
Ischaemia and reperfusion induce metabolic changes that facilitate opening of the mPTP in cardiomyocytes (Figure 3). However, the mPTP remains closed during ischaemia and opens shortly after reperfusion as demonstrated by determination of influx of 3H-2-deoxyglucose into the mitochondrial matrix or by monitoring loss of ▵Ψm.4,5,16,17 Hence, the mPTP appears to be 'primed' during ischaemia and its opening is triggered by reperfusion. How molecular and physical stimuli [i.e. reactive oxygen species (ROS), Ca2+, and reduction in ▵Ψm] interact with mPTP subunits to achieve the priming and triggering of mPTP opening remains unclear. Binding of CyPD to the mPTP is known to increase sensitivity of the mPTP to Ca2+, but timing of CyPD–mPTP binding during ischaemia/reperfusion and molecular mechanisms of the binding are not clearly understood. A model of the functional relationships between mPTP regulatory factors is presented in Figure 4, but effects of ischaemia and reperfusion on each of the regulatory factors remain unclear except for CyPD–ANT/PiC interaction upon reperfusion.
2.1 Voltage-dependent anion channel
There are three isoforms of VADC (VDAC1, VDAC2, and VDAC3) encoded by separate genes. Of the isoforms, VDAC1 is the most abundant in most cells and interacts with multiple proteins involved in energy production, apoptosis, and formation of cytoskeletal frameworks.18,19 VDAC in the MOM binds to hexokinase II (HKII), which sets a machinery of ADP transport into mitochondria and a machinery of ADP production (from phosphorylation of glucose by ATP) in a proximate location.20,21 The VDAC–HKII interaction can be disrupted either by treatment with TAT-HKII, a cell-permeable HKII N-terminal peptide, or by overexpression of VDAC1 with mutations in N-terminal regions (putative HK-interacting sites).22,23 Dissociation of HKII from mitochondria by TAT-HKII induces mitochondrial depolarization due to opening of the mPTP as discussed in a section on HKII below. Phosphorylation of VDAC by glycogen synthase kinase-3β (GSK-3β) also induces release of HKII from the mitochondria at least in non-cardiac cells.24 Dissociation of HKII from VDAC by these interventions induced cell death under oxidant stress.25 Conversely, enhanced tolerance to oxidant-induced necrosis was afforded by HKII overexpression, which was associated with phosphorylation of VDAC by protein kinase C-ɛ (PKC-ɛ).26 The protection afforded by HK overexpression was eliminated by HKII detachment from VDAC.23 These findings indicate that VDAC contributes to maintenance of mPTP closure by anchoring HKII, which modifies VDAC–PKC-ɛ interaction, in mitochondria.
In addition to GSK-3β and PKC-ɛ, PKA phosphorylates VDAC.24,27 PKA-mediated phosphorylation of VDAC suppresses open probability of VDAC,27 which would reduce transport of ADP to the mitochondrial matrix. Conversely, GSK-3β-mediated phosphorylation of VDAC increases adenine nucleotide transport into the matrix in cardiomyocytes,28 though supply of ADP derived from HKII might be reduced to some extent due to HKII dissociation by VDAC phosphorylation.24 Nevertheless, since ATP hydrolysis by mitochondrial ATPase (F1F0 ATPase) for maintenance of ▵Ψm accounts for 35–50% of ATP consumption during ischaemia,29,30 the level of VDAC phosphorylation by PKA and GSK-3β is likely to determine rates of ATP depletion and decline of ▵Ψm in ischaemic cardiomyocytes.
2.2 Adenine nucleotide translocase
ANT localizes in the MIM and exchanges ADP3− and ATP4− between the mitochondrial matrix and the intermembrane space. This transporter function is positively regulated by several factors, including the two substrates (ADP and ATP) and Bcl-2.31,32 The ANT family consists of four isoforms encoded by different nuclear genes. ANT1 is the predominant isoform in the heart and muscle and ANT3 is expressed at low levels independently of cell types. ANT2 and ANT4 are expressed in proliferative tissues and in the brain, liver, and testis, respectively. Each isoform appears to have distinct roles since the effect of overexpression of ANT on cell viability is opposite depending on the isoform (anti-survival ANT1 and ANT3 vs. pro-survival ANT2 and ANT4).32,33
A regulatory function of ANT in the mPTP has been indicated by several lines of evidence. Opening of the mPTP by oxidant stress was closely associated with cross-linking at Cys160 to Cys257 in ANT.34 Elevation of matrix Ca2+ level, a trigger of mPTP opening, induced the 'c-conformation' (cytosolic-open state) of ANT,4,35 and ANT-specific agents, carboxyatractyloside and bongkrekic acid, had positive and negative effects, respectively, on sensitivity of the mPTP to matrix Ca2+. Furthermore, Ca2+ sensitivity of the mPTP was significantly reduced in mitochondria in which ANT was genetically ablated.13 Impact of ANT carbonylation on mPTP sensitivity is also supported by the findings that ANT1 was the only protein in the mitochondrial membrane showing an age-associated increase in carbonylation36 and that susceptibility to mPTP opening is increased by ageing.37,38
Physical interaction of ANT with CyPD and PiC was demonstrated by glutathione S-transferase (GST) pull-down experiments using GST–CyPD fusion proteins.15,39,40 Treatment with cyclosporine A did not affect this CyPD–ANT interaction, but it inhibited binding of CyPD to PiC.15,40 The ANT–PiC interaction was not inhibited by cyclosporine A. These findings argue against a previous notion that CyPD binding to ANT increases sensitivity of the mPTP to Ca2+. Change in ANT–PiC interaction rather than that in ANT per se might be responsible for changes in Ca2+ sensitivity of the mPTP by ANT ablation and by cyclosporine A treatment as discussed in the following section on PiC. However, this possibility has not been critically examined.
2.3 Inorganic phosphate carrier
There are two PiC isoforms (PiC-A and PiC-B), which are alternative splicing products from a single PiC gene (SLC25A3).41 PiC-A is expressed in cardiac and skeletal muscles, and PiC-B is ubiquitously expressed. PiC localizes in the MIM and functions as a Pi–H+ symport and/or Pi–OH− antiport.41,42 Nevertheless, PiC catalyses transport of cytosolic Pi to the mitochondrial matrix, where Pi is used for ATP synthesis. A recent study using INS-1 cells demonstrated that the Pi level as well as the protein level of PiC determines the rate of ATP production in mitochondria.43 Interestingly, knockdown of PiC alone did not affect ▵Ψm, indicating that reduced ATP production by PiC knockdown is not due to loss of protomotive force.
PiC has been shown to interact with other mPTP subunit proteins. Binding of PiC with CyPD and ANT in rat cardiac and liver mitochondria has been demonstrated by GST pull-down assay using GST–CyPD fusion protein.15,39,40 In 293T cells and HeLa cells, PiC was co-immunoprecipitated with ANT1 and VDAC1.44 Interestingly, the ANT1–PiC interaction was increased when apoptosis was induced by staurosporine in HeLa cells, and knockdown of PiC suppressed cytochrome c release from mitochondria and apoptosis. Response of ANT1–PiC interaction to necrosis-inducing stimuli remains unclear.
As mentioned in a previous section, Leung et al.15 found that PiC interacts with CyPD in a cyclosporine A-sensitive manner. Using column-immobilized phenylarsine oxide (PAO), an mPTP-activating agent, they showed that both PiC and ANT bind to PAO and that this binding was inhibitable by N-ethylmaleimide (NEM) and ubiquinone analogues (Ro68-3400, UQ0), mPTP inhibitors which do not inhibit peptidyl-proly cis–trans isomerase (PPIase). Interestingly, NEM and ubiquinone analogues suppressed Pi transport into the mitochondria. Although information on mammalian PiC is lacking, PiC of yeast dimerized by a dithiol cross-link has been shown to form a non-specific anion channel.45 Based on these findings, Leung et al.15 proposed a model of mPTP consisting of a channel-forming PiC dimer and a dimer of ANT.
Leung et al.15 showed a correlation between mitochondrial Pi influx via PiC and threshold for opening of the mPTP. However, cyclosporine A did not modify PiC-mediated Pi influx into mitochondria, indicating that inhibition of the mPTP opening by cyclosporine A is not achieved by change in Pi influx per se. In this regard, interesting observations have been reported by Basso et al.46 They showed that inhibition of mPTP opening by cyclosporine A or CyPD knockout disappeared when Pi was replaced by its analogue, arsenate or vanadate. The effect of Pi on threshold for mPTP opening was dose-dependent and unaffected by increasing concentrations of co-existing arsenate or vanadate. Based on these findings, Basso et al.46 proposed that cyclosporine A and CyPD knockout inhibits mPTP opening by unmasking inhibitory effects of Pi.
3. Proteins directly regulating the mPTP in mitochondria
3.1 Cyclophilin D
CyPD is one of the cyclophilin family proteins with PPIase activity and is the only isoform localizing in the mitochondrial matrix.47 Although the physiological function of CyPD in cardiomyocytes was unclear until recently, a study by Elrod et al.48 demonstrated that knockout of the Ppif gene (a gene encoding CyPD) induced elevation of mitochondrial Ca2+ level, activation of Ca2+-dependent enzymes, and metabolic re-programming, resulting in reduction in ventricular tolerance to pressure overload. Their findings indicate that the physiological function of CyPD is regulation of mitochondrial Ca2+ level for metabolism to be matched with mechanical workload.
A significant role of CyPD in cardiomyocyte necrosis after ischaemia/reperfusion has been well established. Treatment with cyclosporine A or genetic ablation of CyPD elevates the threshold for opening of the mPTP and consistently affords tolerance against ischaemia/reperfusion-induced necrosis.8–12 As discussed in previous sections, regulation of the mPTP by CyPD is achieved by interaction with PiC and ANT, which modifies sensitivities of the mPTP to Ca2+ and Pi.
The mitochondrial ATPase is also a target of CyPD. Giorgio et al.49 showed that CyPD interacts with the lateral stalk of the mitochondrial ATPase and reduces its activity. Recently, Chinopoulos et al.50 assessed the impact of CyPD-mediated reduction in the mitochondrial ATPase on ATP efflux via ANT and matrix pool of adenine nucleotides. Their results indicate that ANT-mediated ATP efflux in energized mitochondria or ATP influx in de-energized mitochondria is not significantly changed by CyPD-mediated suppression of mitochondrial ATPase activity because flux control coefficient of mitochondrial ATPase is ∼2.2-fold lower than that of ANT. However, two important functions of the mitochondrial ATPase regulation by CyPD were proposed by Chinopoulos et al.50 One is regulation of matrix adenine nucleotide level and the other is inhibition of mPTP opening via accelerated H+ pumping by ATP hydrolysis, leading to more robust maintenance of ▵Ψm.
3.2 Hexokinase II
Of the four isoforms of HK, HKI and HKII localize in both the cytosol and mitochondria of cardiomocytes,51 and their binding to mitochondria is mediated by a hydrophobic N-terminal domain.21–23,52 HKI and HKII differ in affinities for glucose and ATP,53 allosteric regulation,51 and response of their expression to myocardial infarction.54 Thus, it is likely that HKI and HKII play different roles in regulation of glucose metabolism. The role of HKI in regulation of mitochondrial functions, if any, remains unclear. On the other hand, contribution of HKII to mPTP regulation has been supported by several lines of evidence.
3.2.1 Regulation of HKII binding to mitochondria
HKII binding to mitochondria is increased by ischaemic preconditioning (IPC), insulin, and morphine.55–58 These treatments activate PI3K-AKt signalling, and an inhibitor of PI3K or genetic ablation of Akt abolished the HKII recruitment to mitochondria. Transfection with constitutively active Akt increased HK activity in mitochondria.55,56 Conversely, phosphorylation of VDAC by GSK-3β induced dissociation of HKII from VDAC in tumour cells, and this process was inhibited by activation of Akt.24 These findings suggest that PI3K-Akt signalling, leading to inactivation of GSK-3β, is a primary mechanism of the promotion of HKII translocation to mitochondria.
HKII release is also induced by inhibition of PPIase using cyclosporine A or clotrimazole in HeLa cells.59,60 Recently, Shulga et al.60 reported that deacetylation of CyPD by sirtuin 3 (SIRT3), which reduces its PPIase activity, induced dissociation of CyPD from ANT1 and also dissociation of HKII from mitochondria in the same cell line. Interestingly, atractyloside, which binds to ANT and fix it in the c-conformation, was shown to promote HKII binding to VDAC in HeLa cells.61,62 Taken together, the findings indicate that there may be two mechanisms of HKII release from the mitochondria in HeLa cells. One is GSK-3β-mediated phosphorylation of VDAC, a binding partner of HKII, and the other is a conformational change of ANT, which is under regulation of PPIase activity of CyPD. It is not clear whether similar mechanisms are present in cardiomyocytes.
3.2.2 Inhibition of mPTP opening by HKII and its potential mechanisms
Several lines of evidence indicate that mitochondrial HKII suppresses opening of the mPTP. Dissociation of HKII from mitochondria by use of cell-permeable peptide analogues (n-HKII and TAT-HKII) consistently induced mitochondrial depolarization and cell necrosis in both cardiomyocytes and HeLa cells.25,63,64 Cell death (mostly necrosis) induced by TAT-HKII was attenuated by an inhibitor of mPTPs (Debio 025) or by knockout of CyPD.22 In neonatal rat cardiomyocytes, n-HKII induced mitochondrial depolarization and cell death dose dependently.25 Mitochondrial depolarization by a high dose of TAT-HKII (10 μM) was observed also in intact mouse hearts, in which ▵Ψm was monitored by tetramethylrhodamine ethyl ester.64 A lower dose of TAT-HKII (200 nM) enhanced susceptibility to ischaemia/reperfusion-induced necrosis and prevented protection of IPC.64 These results are consistent with the notion that dissociation of HKII from the mPTP complex lowers the threshold for opening of the mPTP.
How HKII detachment from mitochondria facilitates mPTP opening remains unclear. One possibility is augmentation of ROS production. A series of studies using brain and liver mitochondria indicates that HKII associated with VDAC plays a major role in the ADP recycling mechanism in mitochondria, suppressing ROS production and maintaining ▵Ψm.65,66 Preservation of ATP production is another potential mechanism by which mitochondrial HKII inhibits mPTP opening. In fact, knockdown of HKII reduced ATP production by ∼20% in cardiomyocytes.25 Another possible mechanism is modulation of ANT conformation in the mPTP. In a study by Chiara et al.,22 locking ANT in the 'm conformation' (matrix-open state) by bongkrekic acid suppressed cell death induced by TAT-HKII, whereas activation of Akt-GSK-3β signalling using insulin did not affect cell death.
3.3 Glycogen synthase kinase-3β
3.3.1 Regulation of GSK-3β activity and translocation
GSK-3β is one of the two isoforms of GSK-3, a Ser/Thr protein kinase. GSK-3β is constitutively active and its activity is increased by phosphorylation at Tyr216.67 This Tyr is autophosphorylated,68 though the possibility of involvement of an unidentified protein kinase has not been excluded. Inactivation of GSK-3β is achieved by phosphorylation at Ser9, and multiple protein kinases (such as PKA, PKC, and ERK) target this Ser residue. In addition, Thr43 and Ser389/Thr390 in GSK-3β are phosphorylated by ERK and p38-mitogen-activated protein kinase, respectively, and phosphorylation of these residues is thought to facilitate Ser9 phosphorylation by other kinases.69,70
Since substrates of GSK-3β localize different intracellular compartments, translocation into subcellular compartments (i.e. nucleus and mitochondria) is an important regulatory mechanism of GSK-3β functions. In cardiomyocytes, GSK-3β is predominantly localized in the cytosol under an un-stimulated condition, but ischaemia/reperfusion induces translocation of GSK-3β from the cytosol to mitochondria.71 Although the trigger of translocation remains unclear, our preliminary study suggests that oxidant stress is involved.72 GSK-3β was co-immunoprecipitated with translocase of the mitochondrial outer membrane 20 (TOM20), indicating the possibility that GSK-3β translocation to mitochondria is mediated by the TOM20-heat shock protein 90 mechanism as are translocations of connexin-4373 and PKC-ɛ.74
Multiple cytoprotective signalling pathways converge on GSK-3β to induce its phosphorylation at Ser93,17 (Figure 1). Cardioprotection afforded by activation of the erythropoietin (EPO) receptor or the mitochondrial ATP-sensitive K+ channel (mKATP channel) before ischaemia was associated with an increase in mitochondrial Ser9-phospho-GSK-3β upon reperfusion without change in total GSK-3β level in mitochondria.75,76 To address the relationship between timing of GSK-3β phosphorylation and cardiomyocyte protection, we recently examined the effects of activation of the mKATP channel on GSK-3β phosphorylation before and after ischaemia/reperfusion in rat hearts.76 We focused on the mKATP channel since its activation is a common step downstream of activated receptors during the trigger phase of IPC and its mimetics.3,17
In contrast to our expectation, activation of the mKATP channel by diazoxide failed to induce phosphorylation of GSK-3β in the normoxic myocardium, though ROS produced by mKATP channel opening should have induced activation of PKC-ɛ, an upstream kinase of GSK-3β. During ischaemia, GSK-3β undergoes dephosphorylation, though this ischaemia-induced dephosphorylation is not specific to this kinase and is observed in Akt, ERK1/2, and p70S6 kinase.77,78 On the other hand, mitochondrial level of phospho-GSK-3β upon reperfusion was significantly elevated in diazoxide-pre-treated hearts.76 These results indicate that intracellular signalling activated by the mKATP channel before ischaemia enhances GSK-3β phosphorylation in mitochondria upon reperfusion.
As a mechanism of the link between pro-survival signalling before ischaemia and that at the time of reperfusion in IPC, Downey and his colleagues have proposed that PKC-ɛ activated by mKATP channel opening sensitizes the low-affinity adenosine A2b receptor.79,80 Consistent with their hypothesis, a significant increase in mitochondrial phospho-GSK-3β upon reperfusion by pre-ischaemic activation of the mKATP channel was inhibited by blockade of PKC-ɛ, the A2b receptor, or PI3K before reperfusion.76 However, contradictory data have been reported for the role of the A2b receptor in cardioprotection79–82 and this issue is still controversial.
3.3.2 Inhibition of mPTP opening by phosphorylation of GSK-3β
Inhibition of mPTP opening is one of mechanisms that have been proposed for cytoprotection afforded by phosphorylation of GSK-3β at Ser9.83,84 Two distinct mechanisms may be involved in the mPTP inhibition by phosphorylation of GSK-3β: inactivation of its kinase activity and interaction of phospho-GSK-3β with mPTP regulatory proteins (Figure 4). Phosphorylation of GSK-3β at Ser9 and knockdown of GSK-3β have been shown to inhibit opening of the mPTP in response to ROS or Ca2+ overload in cardiomyocytes. Inactivation of GSK-3β can decrease phosphorylation of VDAC, which potentially suppresses HKII release from mitochondria and also nucleotide influx into the matrix. Prevention of such HKII release from mitochondrial HKII may inhibit mPTP opening as discussed above, and reduced flux of adenine nucleotides into the matrix during ischaemia theoretically slows depletion of ATP, a determinant of mPTP sensitivity.
Phosphorylation of GSK-3β at Ser9 modifies its interaction with mPTP subunits. In our series of experiments, GSK-3β was co-immunoprecipitated with ANT and VDAC, which was increased after ischaemia/reperfusion.71 In contrast, Ser9-phospho-GSK-3β interacted with ANT but not with VDAC, and this phospho-GSK-3β–ANT interaction was associated with reduction in CyPD–ANT interaction. Furthermore, activation of PI3K–Akt–GSK-3β signalling before ischaemia, an increase in phospho-Ser9-GSK-3β–ANT interaction, and a decrease in CyPD–ANT interaction upon reperfusion were commonly observed for protection afforded by IPC,71 activation of EPO receptor (data showing EPO-induced suppression of CyPD-ANT complex formation are unpublished),85 and activation of the mKATP channel.76 Changes in the CyPD–ANT interaction by GSK-3β phosphorylation might reflect changes in CyPD–PiC interaction, since GSK-3β phosphorylation has the same impact on the mPTP as cyclosporine A treatment11,17 and the ubiquinone analogues (Ro68-3400, UQ0) that inhibit Pi transport in mitochondria induce conformational changes of ANT.15 However, this possibility remains to be directly examined.
3.4 Signal transducer and activator of transcription 3
3.4.1 Functions of signal transducer and activator of transcription 3 in mitochondria
Signal transducer and activator of transcription 3 (STAT3) is one of the seven STAT isoforms expressed in the heart.86 As in the case of other isoforms, STAT3 is phosphorylated by activated Janus kinase (JAK), and the phosphorylated STAT3 binds to promoter regions of target genes, modulating their transcriptions. STAT3 plays a distinct role in mitochondria.87–89 STAT3 localizes in the matrix of cardiac mitochondria, being dually phosphorylated at Tyr705 and Ser727, and was co-immunoprecipitated with complex I87 and with CyPD.88 Interestingly, overexpression of STAT3 selectively in mitochondria rather suppressed respiratory complexes I and II activities under baseline conditions and attenuated ischaemia-induced ROS production in cardiomyocytes.89
Boengler et al.88 found that the mPTP is hypersensitive to Ca2+ overload in mitochondria isolated from STAT3-knockout mice and those from rat hearts treated with Stattic, a pharmacological inhibitor of STAT3. Unfortunately, effects of STAT3 deletion or inactivation of STAT3 on subunits of the mPTP have not been characterized. However, an increase in Ca2+ retention capacity of mitochondria by cyclosporine A was unaffected by STAT3 ablation or by Stattic,88 indicating that the inhibitory effect of STAT3 on the mPTP is not mediated by modulation of PPIase activity of CyPD.
3.4.2 STAT3 in protection against ischaemia/reperfusion-induced necrosis
A role of STAT3 in myocardial protection from necrosis has been demonstrated for IPC,90 ischaemic postconditioning (IPost),91 and ligands of JAK-coupled receptors (TNF-α, insulin, and leptin).91–94 All of these cardioprotective interventions induce phosphorylation of STAT3 at Tyr705, and the protective effects of the interventions were lost by genetic ablation of STAT3 or an inhibitor of JAK (AG-490). Whether 'mitochondrial' STAT3 is responsible for the protection afforded by IPC, IPost, and the receptor ligands has not been critically examined. However, it is unlikely that the role of STAT3 as a transcriptional factor is mainly involved in the protection since activation of STAT3 at the time of reperfusion by use of IPost, leptin, or TNF-α successfully limited infarct size after ischaemia/reperfusion.
3.5 Sirtuin 3
3.5.1 Functions of SITR3 in mitochondria
Emerging evidence suggests that Lys residue acetylation is an important post-translational modification to regulate various biological functions, including the function of the mitochondria.95 Sirtuins mediate this post-translational modification by coupling lysine deacetylation to NAD+ hydrolysis.96 Mammals express seven sirtuins, and three of them (SIRT3, SIRT4, and SIRT5) localize in mitochondria.97–99 SIRT3 has received attention for its role in cell survival under stress. The full-length human SIRT3 is a 44 kDa protein with an N-terminal mitochondrial localization sequence.100 Following import into mitochondria, 142 amino acids from the N-terminal of full-length SIRT3 are cleaved to generate an active 28 kDa short form.
Included among the target proteins for SIRT3 are acetyl-CoA synthetase 2 (AceCS2) and long-chain acyl-CoA dehydrogenase (LCAD). AceCS2 promotes entry of acetate into the tricarboxylic acid cycle in the form of acetyl-CoA, where it can be used for ATP production. SIRT3 interacts with AceCS2 in mitochondria, where SIRT3 deacetylates Lys642 of the protein and activates its enzymatic activity.101 LCAD is hyperacetylated at Lys42, resulting in reduction in its activity, in the absence of SIRT3.102 These findings suggest a role of SIRT3 in LCAD-mediated control of fatty acid oxidation output. It has also been shown that SIRT3 physically interacts with NDUF9, a subunit of complex I of mitochondrial electron transport chain, deacetylates and activates the enzyme, and thus augments ATP production.103 Taken together, the findings suggest that SIRT3 regulates ATP production at multiple steps. In fact, mice lacking SIRT3, which exhibit a striking hyperacetylation of mitochondrial proteins,98 showed 50% lower basal levels of ATP in the heart.104
3.5.2 SIRT3 and the mPTP
The role of SIRT3 in regulation of the mPTP is still largely unknown, but interesting observations have recently been reported in this regard. Shulga et al.60 showed that SIRT3 deacetylates CyPD and inhibits its PPIase activity in HeLa cells, and Hafner et al.38 confirmed the CyPD deacetylation at Lys166 by SIRT3 in cardiac tissue. Furthermore, they demonstrated that an increase in Ca2+ sensitivity of the mPTP by ageing was significantly enhanced in cardiac mitochondria isolated from SIRT3-knockout mice.38 This finding indicates that SIRT3 counteracts an age-induced increase in sensitivity of the mPTP, which might be partly, at least, due to loss of mitochondrial SIRT3. Although SIRT3-mediated inhibition of CyPD activity is a possible explanation for the protection afforded by SIRT3 in aged animals, the impact of SIRT3 deletion on CyPD activity has not been directly examined. Furthermore, interaction of SIRT3 with mPTP subunits besides CyPD and indirect effect of SIRT3 on the mPTP via mitochondrial metabolism also remain unclear.
4. Dispute over mPTP regulation by mitochondrial kinases
Results of a study by Clarke et al.105 argue against a role of mitochondrial kinases in inhibition of mPTP. They prepared pure mitochondrial fractions by using Percoll gradient and determined phosphorylation of proteins by one- or two-dimensional electrophoresis and anti-phosphoprotein antibodies or Pro-Q Diamond. Their thorough analyses, which were performed with few cardioprotective agents, indicated that neither phosphorylation nor recruitment of PKC-ɛ, Akt, or GSK-3β to mitochondria occurs after IPC or after reperfusion with or without IPC. The difference between the results of the study by Clarke et al.105 and results of other studies indicating IPC-induced phosphorylation/recruitment of mitochondrial kinases3,57,71,75,76 might be explained by different levels of contamination of non-mitochondrial membranes in mitochondrial fractions.
However, another possible explanation is isolation of different groups of mitochondria. The use of Percoll gradient certainly improves purity of mitochondrial fractions from the normal myocardium, but it is not clear whether the same method is suitable for isolation of mitochondria from the myocardium subjected to ischaemia/reperfusion. The myocardium after ischaemia/reperfusion consists of viable and necrotic cells, and severity of mitochondrial injury should be heterogeneous within the tissue. Hence, different groups of mitochondria could have been unintentionally selected depending on methods of their isolation. This possibility is consistent with the difference in apparent change in Ca2+ sensitivity of the mPTP by IPC between the study by Clarke et al.105 and studies by others. Ischaemia/reperfusion increases Ca2+ sensitivity of the mPTP and facilitates its opening in cardiomyocytes. Surprisingly, in the study by Clarke et al.,105 mPTPs in preconditioned hearts after ischaemia/reperfusion were less Ca2+-sensitive even compared with mPTPs in control hearts before ischaemia. However, such desensitization of the mPTP in the reperfused myocardium beyond the normal control level was not observed in studies by Ovize and his colleagues,106,107 though IPC attenuated an increase in Ca2+ sensitivity of the mPTP after ischaemia/reperfusion.
5. Modification of the mPTP by concurrent disease
Recent studies using animal models of heart failure, diabetes, and hypertension have demonstrated that the threshold for mPTP opening is significantly reduced by pathological conditions.3,85,108–110 Increased ROS production appears to be a common mechanism, but it is notable that changes in the mPTP component differ between the models. Mitochondrial CyPD was up-regulated and the mPTP was hypersensitive to Ca2+ in a model of volume overload-induced heart failure.108 We found that active (i.e. non-phosphorylated) GSK-3β was increased in mitochondria in type 2 diabetes, and the up-regulation of mitochondrial GSK-3β was correlated with increased sensitivity of the mPTP to Ca2+.109 A recent human study confirmed that sensitivity of the mPTP to Ca2+ was indeed higher in mitochondria from atria of diabetic patients than that in non-diabetic controls.110 In a model of hypertension, protein levels of the mPTP subunit proteins were comparable, though carbonylation of mitochondrial proteins after ischaemia/reperfusion was significantly enhanced.85 Hence, repair of mPTP dysregulation appears to be as important as activation of mPTP inhibitory mechanisms in the strategy for protecting the heart from mPTP-mediated cell necrosis.
6. Conclusion
Roles of VDAC, ANT, and PiC, as subunits in the mPTP complex, have been supported by results of studies to date. Included among proteins directly regulating open probability of the mPTP are CyPD, HKII, GSK-3β, STAT3, and SIRT3. Binding of CyPD to PiC and recruitment of HKII to mitochondria via HKII–VDAC interaction, GSK-3β–VDAC interaction, and phospho-GSK-3β–ANT interaction appear to modify Ca2+ sensitivity of the mPTP. Phospho-STAT3 and SIRT3 in the matrix are involved in signal-mediated and age-related changes in the mPTP sensitivity, respectively. Further clarification of both regulatory mechanisms of the mPTP and their impairments by pathological signalling is necessary to develop therapy directly targeting the mPTP for the management of ischaemic heart disease and heart failure.
Conflict of interest: none declared.
This work was supported by Japanese Society for the Promotion of Science Grant-in-Aid for Scientific Research (20590870, 23591086, and 23591085), Tokyo, Japan.
This article is part of the Spotlight Issue on: Reducing the Impact of Myocardial Ischaemia/Reperfusion Injury
- Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2011. For permissions please email: email@example.com.


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Graduate programs or courses are offered via distance education Study abroad Teacher certification: Students can complete their preparation in certain areas of specialization Teacher certification: Approved by the state for initial certifcation or licensure of teachers
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(866) 241-4918
The mission of the New Hampshire Institute of Art is threefold: to provide a traditional Bachelor of Fine Arts degree program emphasizing the integration of creative, aesthetic, technical, and critical skills in artistic expression; to offer a Continuing Education program that serves the community in the visual arts; to provide an ongoing series of public exhibitions and lectures that support the educational programs.
Private not-for-profit, 4-year or above
Bachelor's Master's
Remedial services Academic/career counseling service Employment services for students
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Wine Maker Notes
Primitivo is a dark-skinned grape variety used in certain inky, tannic wines from the Puglia region of deepest southern Italy. It is perhaps better known under its American synonym Zinfandel, which has become one of the most widely planted Vitis vinifera vines in the western United States.
Technical Notes
Plum, cherry and some chocolate, low tannins, sweet undertone. Slightly funky on the nose. Easy and full-bodied


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anuary 5, 1998
New Year brings shooting death in Bothell
by Josh Large
At the Green Acres Mobile Home Park in Bothell, the first moments of 1998 were punctuated by several loud bangs, but these were not the sounds of celebratory pyrotechnics. They were the final, fatal explosions in a long standing feud. At 12:08 a.m. Bothell police and paramedics responded to a 911 call from the wife of a 63 year old man who allegedly shot and killed his next door neighbor, Fredrick Roger, 59, after Roger reportedly set off fireworks in his neighbor's carport. According to Bothell Police Captain Robert Woolverton, police and paramedics arrived at the scene to find Roger lying on the porch of the suspect's mobile home, halfway inside the doorway, shot in the face. Their resuscitative efforts failed and he was pronounced dead at the scene.
Woolverton said that when, at around midnight, Roger set off the fireworks, the man confronted him, and a verbal altercation ensued. The alleged shooter then retreated into his home and produced a short-barreled revolver. He fired at least one shot, mortally wounding Roger. Woolverton indicated that police are still not sure whether or not Roger was attempting to enter the man's home when he was shot, though he was apparently unarmed.
According to Woolverton, the fireworks were but the catalyst, "the culmination of over a year's worth of harassment" which prompted the killing. Though police would not comment on the details of the feud, neighbors indicated that the animosity may have stemmed from a love triangle involving the suspect, his wife, and Roger. Bothell police indicated that they had already responded to several confrontations between the two men this year. According to Woolverton, however, both men have no criminal records in the state of Washington. Police have had some difficulty contacting Roger's family, said Woolverton, because he lived alone and had few accessible close acquaintances.
According to police, the alleged shooter is being held on $100,000 bail for investigation of second degree murder. The facts, say members of the Bothell police, do not entirely corroborate the man's claim of self defense. Though Roger may have indeed been attempting to enter the man's home, police say that that does not justify shooting him in the face. Snohomish County prosecuters now have until Tuesday to decide whether to file murder charges. Woolverton indicated that there is no immediate evidence that drugs or alcohol played a role in the shooting, though the Snohomish County Coroner has yet to complete a toxicology report on Roger.


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The Basic principles of Quality Content Structure
Having good content structure is crucial to writing content that people can simply consume and understand. Having a good structure also makes the writing process less complicated for you. Here are the primary elements to well-structured content.
The Introduction
The beginning sentence of any article should be carefully crafted to catch attention. Readers should right away be able to grasp what the gist of the post is just by reading the 1st sentence.
Likewise, the first paragraph should expand on the initial sentence and get readers engrossed in reading the remainder of the content.
Let Them Know What to Expect
Before jumping into the meat of the content, let them know what can be expected in the remainder of the content.
This can be as detailed as "we'll cover X, Y and Z now" to as simple as "here's the easiest way to do X."
The main thing is to prepare people to read whatever you are about to discuss.
Main Subject Points
Go throughout each of your topic points, one by one.
Make certain to separate your content into easily digestible bites. Don't just write a 500-word article from top to bottom, but break it up into subsections and subheads.
Also make certain you word as many points of your content in "what's in it for you" terms. Individuals should feel like you are talking straight to them.
It frequently helps to give a few different solutions, angles or opinions in your main points. If you are talking about investing for instance, give them 1 or 2 different strategies they can use.
Give examples. The more theoretical your article is, the less probable they're to remember it a couple of weeks from now. Examples help take something that's hypothetical and make it into something more concrete. People are frequently more certain to remember an example demonstrating a principle than just the idea.
The Conclusion
The last paragraph of your article is the conclusion. The conclusion should sum up everything you wrote about, and maybe restate the most vital point.
Occasionally it's best to leave the user with a concrete piece of action they can instantaneously take at the end of the conclusion. At different times, the conclusion just wraps up the whole article pleasantly.
If you're selling a product, the conclusion is where you should to put your call to action. Tell readers precisely what it is you want them to do. Be confident and make certain to summarize all of the main benefits to them taking action now instead of later on.
These are the main parts of great content structure. Following this structure will help to give your readers a good sense of what should be expected from your article and keep them engaged as they're reading. It'll also make it less complicated for you to arrange your thoughts into a coherent meaningful order prior to starting writing.
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Venous insufficiency, the cause of varicose and spider veins, affects nearly 30 million Americans. Rapid advances in laser technology now allow outpatient treatment of this condition.
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By Dave Wagner: Freedom Newspapers
If junior quarterback Michael Benton has anything to say about it, the Eastern New Mexico University football team will punch holes in the Lone Star Conference South Division's preseason poll which placed the Greyhounds last out of seven teams.
Second-year coach Mark Ribaudo doesn't even want to talk about the poll.
"I think we're a better football team than we were last year," said Ribaudo, who has been on the ENMU staff since 1998. "How good are we going to be? I think we're going to be good.
"I'm willing to go out there and let the chips fall."
Benton, on the other hand, hopes it fuels the team's fire.
"I just call it bulletin board material," he said. "We don't read too much into that. We let the 'analysts' take care of that."
The Hounds open with a 6 p.m. (MDT) conference crossover contest on Thursday against the North Division's Northeastern State at Tahlequah, Okla.
It's the first of back-to-back roadies to start the season. ENMU returns to Oklahoma to play East Central on Sept. 16 before hosting Central Oklahoma the following week at Blackwater Draw.
"Coach Ribaudo has talked about focus," Benton said. "It'll just be another challenge, starting with two away games. We need to be mentally tough and just go get it done."
The 6-foot, 195-pound Benton, who rushed for school records of 1,311 yards and 17 touchdowns last season, said he's confident the offense will be even more potent than a year ago when the Hounds averaged 28 points a game.
"I feel like I'm ready," said Benton, from Everman, Texas. "I feel I've put in the time (preparing), and all the players have done that. Everybody's on the same (page)."
ENMU went 5-6 (2-4 South) last season, its first losing record since 1997. Still, that mark included a 38-14 rout of Angelo State and a 52-51 overtime loss at West Texas A&M, the LSC's two playoff teams.
"It was disappointing, because I definitely think we were a better team than 5-6," Benton said. "There were only two games that we weren't in. Angelo State and WT were the two best teams, and we played well in both of those games."
On offense, two-time All-South receiver Derrick Hunter has graduated, but experience returns in most of the other skill positions.
The biggest concern in preseason is in the offensive line, which graduated all starters except for senior tackle Marcus Smith (6-3, 282).
"Our offensive line is going to have to come together," Ribaudo said.
"They're making great progress. They have some big shoes to fill, but we have some talented linemen who've been in the program for two or three years."
Senior Fide Davalos (6-0, 202) is expected to start at running back, with sophomore Clark Hanley (6-2, 220) at tight end and junior Gil Shackelford (6-4, 310) at center.
Competition is wide-open at other positions, although numerous players have significant game experience — notably at fullback with senior Robert Garza (6-2, 227) and juniors J.J. Jennings (5-10, 195) and Patrick Hemphill (5-8, 206) have all been around for at least a couple of years.
"A lot of these guys need game reps, but they're everything we want," Ribaudo said. "I think we're starting to come together."
Ribaudo, who had been the team's defensive coordinator since 1998 before relinquishing those duties this season to fifth-year assistant Mike Walton, said that side of the ball should be much-improved with seven regulars returning in senior nose guard Malala Tai (6-0, 330), sophomore end Kyle Wilson (6-1, 232), senior cornerback Michael Fields (5-9, 160), inside linebackers Jeremy Mullins (5-10, 225) and Tony Johnson (6-0, 220) and outside linebackers Tim Ojeda (5-10, 190) and Brandon Harper (5-11, 190).
Again, a number of others who saw action last season will pick up more playing time this fall and compete for starting positions, he said.
Senior Lee Price (5-11, 204) is back for his fourth season as the team's place-kicker, and is also the leading candidate to handle the team's punting duties as well.


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Classic Upward
Bound Program
One West University Blvd.
Cortez Hall
Office Phone: (956) 882-3846
Mon - Fri 8am - 5pm
Scholarship Application Process Narration
Narrator: Hello students! Welcome to the scholarship application process!
Counselor: Come in.
Counselor: Hi Julio, do you know why you are here?
Student: No, I have no idea.
Counselor: You were called in to be informed about scholarship applications
Student: What's a scholarship?
Narrator: Now what is a scholarship?
Narrator: A scholarship is an award of financial aid for a student to further their education in a college or university.
Student: I just entered high school. That does not even apply to me yet.
Counselor: Of course it does! Competitive scholarships require various criteria and as freshmen you need to start building an action plan.
Student: What do you mean an action plan?
Counselor: Well for starters, you can begin by participating in community service projects, being involved in extracurricular activities, career planning, creating a resume and most importantly maintaining high academic merits.
Student: Oh okay. High academic merits? I am not sure what that is.
Counselor: Well, high academic merits refers to good outstanding grades which can be achieved by taking advanced placement courses, studying for your courses, and attending tutoring.
Student: Thanks! Now I know where to start.
Narrator: Now you are probably wondering where to obtain scholarships?
Narrator: Now here is where you can obtain scholarships!
Narrator: Such as counselors office, Teachers recommendation, organizational scholarships (for example: Sports, STEMS, Zonta Z club), and scholarship websites such as fastweb.org.
Counselor: Alex!
Student: Is this going to take long? Because my friends are waiting for me.
Counselor: Well let's see how your scholarship process is coming along.
Student: Okay, I guess I'm already here.
Counselor: Well let's see what you have so far.
Student: Well, I just updated my resume and I already have 25 hours of community service.
Counselor: That is great! And heading for the 50 by the end of this year right?
Student: What? More?
Counselor: Of course! Remember that the effort that you put now will pay off in the future. Plus this is a four year progress. It will pay off trust me.
Student: Well what can I do to strengthen my resume?
Counselor: Well let me tell you.
Narrator: Applications have requirements. Requirements include: resumes, community service, GPA, Recommendation letters, Essay, and FAFSA Submission.
Narrator: Resume. A resume is a document used by individuals to present their backgrounds and skill sets. This includes educational background, Awards and Achievements, Work Experience and Community Service.
Narrator: Now let's talk about Community Service!
Narrator: If you have never heard of community service it is a donated service or activity performed by someone or a group for the benefit of the public.
Narrator: So what are good types of community service? Good types of community service includes tutoring children with disabilities, assisting in nursing homes, volunteering in hospitals and reading for children to promote the love for reading.
Student: Is that it?
Counselor: Of course not! Maybe get some assistance in creating personal statements.
Student: What for?
Counselor: This will assist you in applying for scholarships by providing a clear and organized statement to the reviewer about your personal and academic backgrounds, accomplishments, and career goals.
Student: Oh Okay.
Counselor: Obtaining the experience in writing a personal statement will help you develop the skills necessary when writing the official one.
Student: Sounds good. I'll get to it.
Counselor: Thank you for your time. Remember to keep up your good grades.
Student: Yes mam.
Narrator: Now let's see what a GPA is. A GPA is the students grade point average based on a scale. It is important to know that most competitive scholarships require a minimum of a 3.0 GPA. For example the Gates Millennium Scholarship requires a minimum of a 3.3 GPA.
Narrator: Now Resume's also include extracurricular activities. Extracurricular activities include sports, clubs and organizations, student bodies, and church related activities. In addition, extracurricular activities are critical in the application because they demonstrate dedication, involvement and experience.
Narrator: Now let's talk about recommendation letters. A recommendation letter is a letter that makes a statement of support for a candidate. Here's a tip: It is important to build and maintain good relationships with your teachers and other educated professionals to build good rapport.
Student: Hello mam may I speak to you about my scholarship application process?
Counselor: Yes of course. Come in. It seems you've come prepared.
Student: Yes Ms. Ortiz I have completed 55 hours of community service along with keeping up with good academic grades which includes AP courses, involvement in school organizations, student clubs, and I have also updated my resume.
Counselor: I am very impressed you've come a long way. You can also start building strong academic relationships with your professors. For instance, if you are a good student in AP biology, that teacher can provide you with a good letter of recommendation.
Student: Yes. Sounds good. I do try to maintain good relationships with all my professors.
Counselor: Great! Seems like you are right on track. Now, do you have an idea of what your GPA is at this point?
Student: Well, I know I've been keeping up with my grades.
Counselor: You should look into your GPA because general competitive scholarships require a minimum of 3.0 GPA. However, having a higher GPA will give you a greater opportunity for eligibility.
Student: Thanks! That is very helpful information to know. But where do I get my GPA from?
Counselor: I can provide you with your GPA and you can look for different GPA's that are required for competitive scholarships.
Student: Will that be all that I need?
Counselor: Well, in addition to this you must apply for a financial aid pin number.
Student: What exactly is a pin number? And where do I get it from?
Counselor: Your financial aid pin number is an electronic signature that will be necessary when completing your financial aid application. You can obtain this from the website fafsa.ed.gov. And just follow the steps. However, in order to complete the pin number you must first have the following: Your social security number (yours and your parents) and your birth certificate.
Student: Well it sounds like a lot of steps but if this is what is going to get me into college then I must get to it.
Counselor: Yes, it will make all the difference.
Narrator: Now here come essays!
Narrator: Here are some tips that will be useful when writing an essay.
Narrator: Here comes tip number one. Directly answer the question. Too many times writers make interesting points but they are not about the questions in hand. If you are asked to answer a specific question, stick to it.
Narrator: Tip number two: Address your mistakes. A few mistakes don't have to spell disaster. Learning from your errors show character and it breathes life into your essay.
Narrator: Here comes tip number three. Show that you are well rounded. Explain how you contributed, recognition you have received, and if possible leadership positions you have held.
Narrator: Tip number four: Add a personal touch. Credentials are great and all but a dashing personality can take your essay above and beyond. Adding a bit of humor or sharing an interesting but relevant experience will make your essay stand out.
Narrator: Tip number five, last but not least. Proofread! Even when you have put a lot of time into your essay it may appear sloppy, it is grammatically incorrect. You have a lot to offer make sure your essay stands out for its excellence and not its errors.
Narrator: Financial aid Submission. Now remember that most scholarships require submission of your financial aid application prior to applying. Visit www.fafsa.ed.gov and apply. You will need the following information: Student and parent social security numbers, date of birth, income tax return from prior year, parent's marriage or divorce date, and pin numbers.
Narrator: The application process is complete!
Student: Good morning, I scheduled this meeting with you because I am now a senior and I will like to update you on my scholarship process.
Counselor: You are finally a senior and graduating. Let's see how long you've come since last time we spoke.
Student: Well I have already applied for seven scholarships and they all require essays regarding personal statements. I have also included my GPA in most of them which is pretty high. Along with this I have also submitted my official transcripts and letters of recommendation. I have also completed 68 hours of community service and I am working on finalizing my resume.
Counselor: I am very pleased to hear that you have completed all these requirements. Now you can work on submitting your financial aid application.
Student: Yes, I am working on that as well. I am just waiting for my parents to receive their w2 forms so that I can complete the application.
Counselor: Sounds perfect! You have completed all the requirements. Good luck on continuing applying for scholarships and obtaining those scholarships.
Student: I appreciate your help for helping me along the way.
Narrator: Now start submitting those scholarships!
Narrator: Goodbye!
The University of Texas at Brownsville website uses Javascript.
To access this page as it is meant to function please use a Javascript
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This website is scheduled to be permanently shut down on Oct. 24.
The University of Texas at Brownsville and The University of Texas-Pan American ceased operations last year and their assets were combined to create The University of Texas Rio Grande Valley. For more information, visit UTRGV.edu.


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Band history still to come.
More Reviews Current Updates Print article Rating explanation
There is some melody woven into the bands maniacal sound, but it strips nothing away from the band's sound and they are just aggressive throughout the CD. Who can deny the band's anger as they discuss such lovely topics as rape, murder, depression and all that is happy. How many times can we hear this? But, oh well, if this is what makes them happy and this is what demons they have to get out of their chest, then so be it.
The music may be tough as nails, but we have all heard it before both musically and lyrically in some way, shape and form. An A is given for effort, but not enough originality to separate them from the rest of the pack. (Online September 17, 2003)


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Seen@ Girls Just Wanna Have Fun Farmer's Market and Fashion Show
Wednesday, August 31, 2011 9:59 PM
08/31/11-Holyoke-Staff Photo by Dave Roback- Seen @ the Fashion and Farmer's Market at the Log Cabin on Wednesday evening. Here late summer fashions are highlighted on the outdoor walkway behind the Log Cabin.
Related articles
- Women gather for 'Girls Just Wanna Have Fun' event at Log Cabin August 31, 2011, 10:35 PM


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[Previous] | [Session 106] | [Next]
D.C. Koo (UCO-Lick), DEEP Collaboration
We study the evolution of bulges at redshift z ~ 0.8 by using HST WFPC2 photometry. Redshifts are from Keck spectra. After separating out the disks using GIM2D software, we find the field (Groth Survey Strip) and cluster (MS1054-03) bulges have virtually identical color-magnitude relations (CMR). The CMR shows very red (U-B ~ 0.5) colors, a shallow slope, and small color scatter. These results are most consistent with an early epoch of rapid star formation for nearly all bulges and are inconsistent with theories in which the bulge colors of clusters and field differ substantially at redshifts z ~ 0.8 from each other or from those seen today. Our results disagree with several prior claims for 30% to 50% blue spheroids or spheroidals by redshifts z ~ 1. We do, however, find evidence for continued, but tiny amounts of, star formation in galaxies in which both the bulge and disk components are very red.
This work has been supported by NASA and NSF.
[Previous] | [Session 106] | [Next]
Bulletin of the American Astronomical Society, 35#5
© 2003. The American Astronomical Soceity.


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Oven Fried Rosemary Chicken
Total Time
2hrs 20mins
Prep 20 mins
Cook 2 hrs
Found in Womens World
Ingredients Nutrition
- 2 lemons
- 1 1⁄2 teaspoons crushed rosemary
- 1⁄2 teaspoon pepper
- 1 chicken, cut in 8 pieces
- 5 slices of day old bread
- 1⁄4 cup grated parmesan cheese
- 1 teaspoon salt
- 2 eggs
- Grate 1 1/4 tsp zest and squeeze 1/4 cup of juice.
- In a large bag combine the juice zest , chickenrosemary and pepper . add chicken seal bag and put into refrigerator for 1 hour.
- Preheat oven to 300 F Line large jellyroll pann with foil and place bread on foil and bake until crisp.Turning twice about 15 minutes.
- Cool increase oven temp to 400F use the same pan Spray with Pam
- In blender pulse bread into fine crumbs.
- In bowl mix crumber with cheese , salt and 3/4 tsp zest 1/4 tsp pepper.
- Beat 2 eggs , dip eggs shaking offexcess , coat in crumbs.
- Place on rack bake for 55 min,.
Most Helpful
Great chicken! Made this with b/s chicken breasts and cooked for about 30 minutes since they were thin. I marinated the chicken for a couple hours so the lemon flavor was strong. Seasoned the crumbs with salt and lemon pepper. Made for ZWT8.


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Athletic Training and Sleep
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