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|12-10-2011 07:36 AM CET - Industry, Real Estate & Construction
Click a Fix receive commercial success with Carbon Monoxide Detector giveaway.
Press release from: Click a Fix
"I take every precaution when it comes to looking after my family, as I am sure every father would. When I heard about Click a Fix giving away free Carbon Monoxide detectors I just automatically assumed it was a smoke detector, which was until I actually took the time to have a look. Carbon Monoxide poisoning was something I didn't know existed until today, they explained to me the potential of Carbon Monoxide in a way that wasn't fear mongering and showed me the best way to deal with any potential situation I could find myself in. I understand that it can be lethal and can't be detected with our natural senses unlike smoke. I am thankful to have a free Carbon Monoxide detector and shall be using Click a Fix for any repairs in the future!"
Another satisfied customer using Click a Fix, we can still educate ourselves on Carbon Monoxide poisoning by heading over to the Click a Fix website and downloading the Click a Fix guide to Carbon Monoxide; What you need to know PDF file for free. Then head over to the Click a Fix store and purchase yourself a Carbon Monoxide detector at a very reasonable price.
Don't take any risks this Christmas, ensure the safety of yourself and your family and enjoy the holiday season!
Their new, easy to read Carbon Monoxide guide is available for free download.
"We repair your home when it's poorly. We maintain it so it stays healthy"
Click a Fix is a home repairs and maintenance company focusing on the essential concerns of keeping a home healthy. We provide four main services; plumbers, electricians, gas heating engineers and general home repairs. Of these four services Click a Fix has adopted the Pareto Principle to concentrate on the smaller types of repairs, which are more commonly required. Click a Fix's aim is to provide a service with 80% of the work available to be booked and paid for online, bringing convenience and assurity on price to the customer and supporting the brand identity to just 'click a fix'. We keep things simple and jargon free to improve the customer experience.
Click a Fix
DBH Serviced Business Centre
Melton Court, Gibson Lane,
Hull. HU14 3HH
0800 9155376
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easy to use, clear layout, very good search function, and quick editing!
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SKECHERS Shape Ups Fitness Shoes & Toning Sneakers Sale
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Mutual Fund Arbitrage and Transaction Costs
John A. Haslem
University of Maryland - Robert H. Smith School of Business
April 28, 2009
The 2003 mutual funds scandal that exploded upon the public revealed something that had long been known to insiders: Mutual fund advisers often approve and allow frequent trading, frequent trading arbitrage, and late trading arbitrage to selected traders. To increase adviser profits, the latter two arrangements often require traders to investment "sticky assets" to "grow" fund assets.
These costly mutual fund adviser practices increase transaction costs along several dimensions and lower current fund and shareholder assets, along with opportunity costs of dilution in fund share values and returns for long-term shareholders. Independent directors have either not been informed or have acquiesced in the decisions. In any case, independent directors have not performed their primary fiduciary duty as "shareholder watchdogs."
Number of Pages in PDF File: 24
Keywords: mutual funds, frequent trading, time zone arbitage, transaction costs, independent director watchdog failure, regulation
JEL Classification: G2, G23, G28
Date posted: May 15, 2008 ; Last revised: February 29, 2016
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item(s) in cart
My Account X
Galco Defense Planner Concealed Carry Case
Item # 449598
Key Features
Great for business or urban concealed carry
Masquerades as a regular planner
Opens to reveal a handgun and spare magazine
Padded to hide your concealed gun
Removable wrist strap and durable zipper
Our Price $99.99
Availability: Sold Out
Prices, promotions, styles and availability may vary by store and online.
detailsback to top
Product DescriptionA great choice for business or urban carry, this compact leather case masquerades as a day planner, but opens to reveal a handgun and spare ammunition. The Defense Planner fits most compact handguns and a single spare magazine. Padded to prevent giving away the secret only you need to know about. Features removable wrist strap and durable nickel zipper. Note: The Defense Planner is not a functioning planner. Dimensions: 8.25" x 6.5".


text:
Fixed PriceDelivery by March 30, 2013
Earn an extra income - write content from home!
Visavi Group Ltd is running operations involving well over 2,000 different affiliate sites with content concerning gaming and finance related products. Most of our content is plain and simple text.
We are currently looking for people to write TURKISH content and think that you…
… are a person who knows how to express yourself easily in writing
… are available online a couple of hours per day and can deliver text content in a timely manner
… are astute and have some (not much) general knowledge about online gaming.
Can I work from home?
Yes you can! In fact this job is ideal if you are a student and you don't have to sell anything – just produce good text content!
How much work will it be?
That depends on you and your availability. There will always be work and content to create and by doing a good job you will ensure that more tasks will be sent to you.
How much do I earn?
That is up to you! You are paid per word you write. The faster you write the more you will earn.
Skills: gaming
Activity on this Job
Last Viewed by Client: 3 years ago
Hired: 2
About the Client
Gibraltar 09:22 PM
Jobs Posted
67% Hire Rate, 1 Open Job
Total Spent
6 Hires, 0 Active
Avg Hourly Rate Paid
45 Hours


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- Avaya IP Office Server Edition will help create best possible customer experience management (CEM) for guests of InterContinental London Westminster
- Mobility underpins new system, allowing staff to focus on getting the job done rather than managing communications systems
- Avaya networking guarantees reliability and energy efficiency
Guildford, England, November 27, 2012– InterContinental London Westminster, which opens its doors to the public this month, has chosen Avaya, a global provider of business collaboration and communications solutions and services, for its affordable, flexible, reliable communications infrastructure.
The Avaya IP Office Server Edition has been supplied and installed by QDOS Communications Ltd, an Avaya award-winning business partner specialising in UK and international hospitality voice and data solutions.
The exclusive hotel is the latest InterContinental Hotel Group property committed to delivering the high standards of service guests expect from the brand everywhere in the world. That brand promise will be underpinned by Avaya's robust, always-on communications infrastructure.
With Avaya Wi-Fi enabled handsets, staff are "unchained" from their posts and have full mobility freeing them to move round the hotel and carry out their roles safe in the knowledge that they can make and receive calls anywhere in the building.
Avaya's IP Office Server Edition will ensure the hotel has a fail-safe phone system for both staff and guests with access for up to 1,000 users. With Avaya's receptionist software, visual access to everyone's phone status – who's busy, on the phone, away from their desk – switchboard operators can route calls quickly and accurately with a mouse click.
The entire system is powered by Avaya Networking products in the form of ERS4500 POE switches, thus in turn helping the hotel reduce its energy consumption whilst improving performance.
The Avaya system is fully integrated with all related third-party hospitality software to include Opera Property Management, and HotSoS Guest Rapid Response Systems. With the InterContinental London Park Lane utilising an Avaya platform installed by QDOS earlier this year, there is scope for voice and data integration between the hotels and collaborative working and shared resources, thereby reducing costs, improving communication and enhancing the staff experience and that of the hotels guests.
Breathing new life into Queen Anne's Chambers, a historic former government building close enough to the Houses of Parliament to be within the eight minute division bell, the hotel includes 256 bedrooms and suites, seven meeting rooms, a restaurant and bar, a Presidential Suite and is expected to bring a distinct style and a unique environment to the area where business and politics will effortlessly mix.
"Guests arrive at an InterContinental hotel expecting outstanding service. All our staff are trained to deliver this and now we have the telephone system that will complement our approach. Failsafe reliability and access anywhere throughout the hotel will ensure we respond to guests' needs in a timely and efficient manner making their stay with us the best it possibly can be."
Stuart Bailey, Managing Director, Supremem Hotels LLP
"In choosing Avaya, InterContinental London Westminster has extended its commitment to quality and service from the front desk to the back office. Avaya IP Office Server Edition is one of the most reliable, scalable and affordable unified communications systems on the market today. Whether it is used across one site or multiple sites, it delivers economies of scale, mobility and reliability that helps drive business goals, whilst meeting Hotel IT brand standards."
Simon Culmer, Managing Director, UK & Ireland, Avaya
"With an established history in providing telephony and IT solutions to the hospitality industry in the UK and internationally, we are delighted to be chosen by Supreme Hotels LLP as their partner of choice. In addition to directly supplying all structured data cabling and Avaya telephony to InterContinental London Westminster, QDOS provided all aspects of IT project management for the hotel, delivering a seven figure sum IT project, on time, to budget meeting IHG IT Brand Standards."
Simon Catterick, Managing Director, QDOS Communications


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MMA Forum - UFC Forums - UFC Results - MMA Videos (http://www.mmaforum.com/forumindex.php)
- Video Games (http://www.mmaforum.com/video-games/)
- - GameSpot gives UFC 2009 Undisputed an 8.0 (http://www.mmaforum.com/video-games/56341-gamespot-gives-ufc-2009-undisputed-8-0-a.html)
GameSpot gives UFC 2009 Undisputed an 8.0
This great fighting game nails the look and feel of the UFC and demands strategy as well as quick reflexes.
Regardless of how well a fighter can talk trash about an opponent or how spectacular an entrance he can make, his performance in the ring is ultimately what he's going to be judged on.
quick reflexes my ass. you have to push the block punch button before the punch is thrown. its anticipation
I have to disagree mr flourhead i have no issues with the blocking system at all. It's not just anticipation though you do only get a split second to react and if you miss that time frame the block is worthless. But it's certainly more than a guessing game.
Also is it so hard for people to scroll down o the main page of the site and post these in the actual section for the game?
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It's our 21st birthday!
Aspiring Medical Centre celebrates its 21st birthday this year! Twenty one years this month, ago Dr Susie Meyer hung out her shingle along side Steve Brett of Aspiring Dental. She was reluctant at first, as she had a three-year old child, with whom she wanted to spend time. However, under pressure to bring......19 February, 2016No comment


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Cloud vs Erdei Verbal Agreement Reached For 12/31
By Rick Reeno
Promoter Lou DiBella has advised BoxingScene.com that a verbal agreement has been reached for a clash between undefeated two division champion Zsolt Erdei (33-0, 18KOs) and IBF light heavyweight king Tavoris Cloud (23-0, 19KOs). Contracts have not been signed but the fight is going to take place on December 31st, with Showtime televising. A few locations are being considered to stage the fight. DiBella has not received confirmation regarding the other possible fights on the show.
Erdei has no chance against Cloud. Dont be fooled by Erdeis padded undefeated record. I saw him manny times in german TV and he looked mediocre against mediocre opposition. And he cant punch. Ge also had stamina issues often and…Comment by Silencers on 10-28-2011
Considering Cloud's technical deficiencies, this is an interesting fight. I expect Erdei to give Cloud a lot of trouble, he might even be able to pull off the upset.Comment by TheSurgeonMDMPH on 10-28-2011
Good fight! I got Erdei in this one if he fights smart and does not wilt to the pressure.Comment by Alec900 on 10-28-2011
erdei will shock a lot of people...might get robbed tough..Comment by ny123 on 10-28-2011
[QUOTE=truestory1987;11343434]Ramos vs Rigondeaux WILL be on the undercard!![/QUOTE] That fight has the potential to be pretty boring.Post a Comment - View More User Comments (26)


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Leaving us without word, nothing left to say,
Mom and me are never going to forget that day.
Something must have hurt so bad and I simply turned my back,
There's so many things I want to say, but it seems the right words I lack.
I never got to say goodbye or tell you that I care,
You must have felt all alone, desperate, hurt, and scared.
I wonder why you felt so bad that your pain engulfed your life,
I wonder if you thought of us, your daughter and your wife.
If I could go back in time and try to ease your pain,
I would dry all your tears when they fell like rain.
It must have been a place so dark that you could not see the light,
But here I am, your pain I feel, I cry myself to sleep at night.
So Daddy please forgive me, I was only 15 at the time,
I didn't realize how lucky I was that you were all mine.
Letter From Daughter to Father Who Committed Suicide
I had a friend who took his life a year or so ago. I knew he had been in a lot of pain for some time. But I find myself envying him. I am still hurting with my emotional trauma, and he is no...
A Silent War
Published on February 2010
Leaving us without word, nothing left to say,


text:
Mote meets $50 million campaign goal
The campaign will be a driving force behind Mote's 2020 Vision and Strategy.
Water users sick of sending in checks to pay for their bills have a new option.
IPOC President Bob White's email to Longboat residents asks for help to 'throw the rascals' on the commission out of office.
Longboat Key residents have expressed frustration that it will take a town-hired consultant more than a year to update town codes.
When Chuck and Margie Barancik learned about Season of Sharing in early January, they immediately wanted to donate — anonymously.
Two weeks ago, Colony Association President Jay Yablon saidopening up units is not an Association-sanctioned activity.
The town hasn't received reports of fish kills since a cleanup effort a week-and-a-half ago on Key beaches.
The Design & Dine contest team is busy choosing three finalists — out of almost 50 entries — for a $10,000 backyard makeover. Now, ArtisTree needs your help to narrow it down to one winner.


text:
Art Print
Susieby Chris' Landscape Images & Designs
Free Shipping on Everything Today!
Collect your choice of gallery quality Giclée, or fine art prints custom trimmed by hand in a variety of sizes with a white border for framing.
Everytime I visit my best friend/cousin, Susie is always the first to greet me :)
Cavalier King Charles Spaniels are very friendly dogs that are affectionate and always willing to please. With a happy disposition, similar to many of the Spaniel breeds, the Cavalier loves to be included as one of the family. Happy to lie at home or easily pleased with a run at the park, these friendly dogs are more interested in being with their owners than anything else. They live for cuddles and are sweet in nature. Typically, the Cavalier , is gentle and above all, affectionate.
*Canon EOS "KISS' D/SLR Camera


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Sarah Silverman Stars As a Time-Traveling Betsy Ross in Dan Harmon's Great Minds, Offers to Sew Ted Cruz a Likability Mask
Ross is also a huge Bernie fan, apparently.By Halle Kiefer
Ross is also a huge Bernie fan, apparently.By Halle Kiefer
The show returns Halloween week.By Nate Jones
If watching on your phone, do not drop it in a ditch.By Halle Kiefer
Ain't nobody messes with Mamma Pantone. Capisce?By Devon Ivie
It's a parody of the "Know Your Rights" video.By Jesse David Fox
Starring Daniel Wu and Aramis Knight.By E. Alex Jung
"Nobody likes to be spit at — especially when you're not lying."By E. Alex Jung
Listen to her new record because it's amazing.By Lauretta Charlton
Ira Kaplan on the new Yo La Tengo record, out August 28, and the future of the Condo Fucks.By Lauretta Charlton
Featuring the cast and writer Jill Soloway.By Lindsey Weber
And the first three pages of the comic, too!By Abraham Riesman
From the upcoming American Comedy Awards.By Jesse David Fox
It's for Monkey: Journey to the West's upcoming NYC shows.By Jesse David Fox
See the poster for her infidelity drama, co-starring Lisa Kudrow.By Kyle Buchanan
Asked about his character in 'The Tempest,' the comedian went on a dazzling, dizzying riff.By Kyle Buchanan


text:
Shoppable Hangouts with Google's Ria Tobaccowala
- published: 27 Mar 2014
- views: 512
Here is the YouTube link: http://www.youtube.com/watch?v=8PBXmcjdZqk The Google Plus team has been in tests with Shoppable Hangouts. Join Google\'s +Ria Tobaccowala and +Ronnie Bincer and I as we talk about how they work, and whatever it is that Google can share about their plans for them. The show will be at 3 PM EDT (Boston time) on Thursday March 27th. Say YES to this invite to make sure you get access to the video at show time or later. The YouTube link will also be shared here for mobile viewers. Please share the event and/or invite others!...


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How did the French Revolution lead to democracy?
1 Answer | Add Yours
While the French Revolution did not lead immediately to a true democracy in France, it did help to bring about more democracy in that country and in the world in general.
The French Revolution did this largely through its rhetoric. It is often the case that the rhetoric of a revolution can have more of an impact in the long term than the revolution itself has in the short term. In the short term, the revolution did get rid of the monarchy and the aristocracy, but it did not lead to a democracy.
Instead, the revolution provided a set of ideas. It was, of course, led by people espousing the ideas of "liberty, fraternity, and equality." It also gave birth to the Declaration of the Rights of Man and Citizen. This document was something like a combination of the American Declaration of Independence and Bill of Rights in that it both explained the Enlightenment thinking behind the revolution and spelled out specific rights that all the people were supposed to have.
Even though France did not live up to these ideals right away, the ideals took hold both in France and elsewhere. They helped to introduce the idea that all people should be treated equally by the law and that they should have certain of their rights protected from government actions. This is a major aspect of democracy.
We've answered 315,720 questions. We can answer yours, too.Ask a question


text:
Make a statement with Neon Hair Clips.
The Neon Hair Clips let you Accentuate your locks with this detachable, neon braided hair strand. Each package of twelve of Neon Hair Pieces is made of nylon and measures 11 inches. Use Neon Hair Clips to add fun and color to your hair and let the good times roll!
Please allow ample time for delivery. Our ship date for this product is noted in your shopping cart. Many items are shipped separately, so please allow extra time for these items to arrive. Shipping charges are based on the value of the merchandise and not the number of shipments. For additional shipping information, please contact our Customer Service Department at (firstname.lastname@example.com or 1-800-314-8794).
Reviewed by 2 customers
Best Uses
Used these as part of a costume for a 9 year old girls birthday party with theme of making rock star music videos. The girls liked them, and got to take them home in their favor bag.
Best Uses
These were a huge hit at my nieces 6th birthday party! The girls loved them!


text:
Setup Flowplayer To Display VAST Ads
This project received 5 bids from talented freelancers with an average bid price of $203 USD.Get free quotes for a project like this
Skills Required
Project Budget$30 - $250 USD
Total Bids5
Project Description
We have Flowplayer 5.4.3 installed on our site. The player is working properly. We would like to add the OVA plugin to display VAST pre-roll adds on the site.
We only need one page configured properly. We can set up the rest of the site once we have a working example.
Looking to make some money?
- Set your budget and the timeframe
- Outline your proposal
- Get paid for your work
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- Forbes
- The New York Times
- Time
- Wall Street Journal
- Times Online


text:
Crawford County Fair opens Aug. 16
The Crawford County Fair is about many different things. There are tractor pulls and concerts, hundreds of different farm animals, exhibits about rural living, concerts, rides and plenty of food. It's essentially an eight-day, fun celebration of country life.
This year the opening celebration begins on Saturday, Aug. 16, with an antique tractor pull, followed by a professional wrestling show. Behind the cheering and clapping spectators, dozens of fair judges will be honoring exhibits from numerous groups with ribbons. Some of these organizations have been displaying exhibits since the first four-day fair in 1946, which was held on Sept. 25. That celebration was attended by 31,000 people.
One of the first organizations to participate was the Crawford County 4-H, which has remained involved and will have hundreds of exhibits and projects judged this year.
"We have over 500 young people involved in the 4-H and there will be a lot of different exhibits, as well as farm animals they have raised to be judged," said 4-H leader Paula Lucas. The fair is one of the big highlights for many of our young people. Members have been working almost all year on their projects."
The Crawford County granges have also been involved since the beginning. According to Susan Tau of the Crawford Pomona Grange, once again this year, as in the past, there will be many grange exhibits and projects on display.
Tau also noted that from a 1948 brochure the top monetary award for a first-place prize was listed as $35. There will also be something special for sale this year -- the newly published local grange cookbook.
The grange will also have a special award ceremony on Sunday at the Youth Show Arena to honor those selected with the Agricultural Hall of Fame Award and the Ag Industry Award. The winners were selected by various agricultural organizations and past recipients. The award was first established by the former Council of Farms and is now administered by the Grange.
Honey and honey products will also be judged as they have been since the very beginning, and once the judging is completed, the exhibit halls will open and visitors can watch the bees in a swivel atrium, according to Linesville beekeeper Charles Vorisek.
"The atrium is always a popular exhibit with people," he said. "Members of the Northwestern Pennsylvania Beekeepers Association will also be available to answer questions and will be selling honey and honey products."
The maple producers will also have displays and maple syrup and products available. Also in the exhibit halls will be farm crops, arts, crafts, photos, fruits, vegetables and a wide range of other exhibits related to family living, home economics as well as floral displays.
The opening day concludes with a 7 p.m. concert by country musician Hunter Hayes and special guests Dan + Shay and Sam Hunter. Music will be important throughout the week. Other concerts include Chris Higbee on Aug. 19, and Lee Brice on Aug. 20.
The busy opening day is just a prelude to a busy week. On Sunday, Aug. 17, at 7 p.m. the Miss Crawford County Fair Queen Pageant takes place. Throughout the week, there will be plenty of livestock judging from rabbits to horses and swine, sheep and goats, a variety of shows such as a car show, harness racing, bull riding and barrel racing and draft horse pulls. A complete listing of all the events as well as other information can be found at www.crawfordcountyfair.com.
There are plenty of rides for the whole family to enjoy as well as some great food, from ostrich burgers and chili dogs to maple milkshakes and fudge, ice cream, cotton candy and more.
One can get pretty hungry touring the 67-acre fair complex which houses eight cattle barns, two swine barns, two goat barns, 14 horse barns, a poultry barn, a rabbit barn and even a stall for a llama or two.
The Crawford County Fair closes with a brilliant and spectacular fireworks display on the evening of Aug. 23 following a demolition derby show.
Certainly, as the fireworks light up the evening sky, hopes and dreams will be ignited for the 2015 fair, which will celebrate 70 years.
The Crawford County Fair is billed as the largest agricultural fair east of the Mississippi and perhaps the oldest agricultural fair in Pennsylvania. It involves thousands of people who enter the gates to enjoy and hundreds of volunteers who help make everything run smoothly.
"We have to give a lot of credit to all the volunteers who help make our fair so successful year after year," said fair board member Diana Perry. "It takes about 500 volunteers to help make the whole eight days a great time for everyone. We owe them a big 'thank you.'"
Daily gate admission is $8, and all rides are free.
Children under five are admitted free of charge.
Monday and Tuesday are Seniors Days; admission is free until 5 p.m.


text:
During a special called meeting, the board voted 6-2 in favor of the $256 million spending package, which overcame a projected $24.5 million shortfall.
Teachers, counselors, media specialists, other 190-day certified employees and bus drivers will have their salary reduced the equivalent of four days pay. All other employees will be furloughed for four days, closing the school system the week of July 5-10. A furlough day is a mandated, unpaid vacation day.
Employees whose salaries were lowered during last years budget process are exempted from the furloughs and pay cuts.
It was found then that some hourly employees in maintenance and transportation were being paid for more days than they actually worked. This was corrected, but board members disagreed today over whether they should be cut again this year.
I dont think I can support a budget unless we put them back in and treat them like everybody else, board member Jack Padgett said before voting against the budget.
Joe Scott was the other dissenting vote.
I have some serious philosophical differences with the budget as it stands, Mr. Scott said.
Board President Marion Barnes said it wouldnt be fair to penalize these employees two years in a row, especially if someone elses error resulted in their being overpaid and they are already some of the lowest paid employees in the school system.
The budget also cut dozens of positions out of the budget. That includes 43 teaching positions cut as a result of increasing class size by one or two students.
Richmond County Superintendent Dana Bedden said most of these positions are unfilled. Employees in filled positions will be offered other jobs in the school system as long as their certification matches the open job.
In a separate action, the school board also approved a measure allowing employees close to retirement to be paid their full salary. They then would donate the amount of pay they were cut back to the school system. This would prevent the cuts from affecting the amount they will receive in retirement.
To see the school systems complete budget presentation, go to www.rcboe.org.
The furlough schedule is organized according to the length of the employee's contract.
Teachers, counselors, media specialists, other 190-day certified employees and bus drivers will not be furloughed. They will have pay cuts equivalent to four furlough days.


text:
Rent Foundations and Fundamental Concepts of Mathematics 1st edition today, or search our site for other textbooks by Howard Eves. Every textbook comes with a 21-day "Any Reason" guarantee. Published by Dover Publications.
Need help ASAP? We have you covered with 24/7 instant online tutoring. Connect with one of our tutors now.


text: Comic-Con The Flash Season 2 Teaser: First Flash, New Big Bad on the Way! It's official! The first Flash will be making his way to the small screen for the first time. Find out who will play Jay Garrick on The Flash! Jul 12, 3:27 am Posted in: The Flash


text:
PRO+ Premium Content/E-Handbooks
Access your Pro+ Content below.
Going mobile on SAP: Where to begin
Sponsored by SearchSAP
As mobile computing becomes increasingly popular throughout today's IT landscape, companies that use SAP are struggling to get their processes running on smartphones and tablets. Fortunately, with the right planning and the proper tools, a mobile strategy can yield an impressive array of benefits - and save you time and money. Check out this expert handbook to learn more!
Table Of Contents
- Different SAP shops call for different approaches to mobility
- Building company digs into SAP mobility projects
- A mobile strategy starts with a center of excellence
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product details-Tab
Please Note: Product received may temporarily differ from image shown due to packaging update.
Light Hold, Alcohol-Free Blow-Dry, Sculpting & Setting Lotion
Conditions and shields against daily environmental stresses. This versatile, shine-enhancing, styling lotion gives the option to set or blow-dry your hair to create shape, fullness and body. Apply to damp hair and comb through for sleek, sexy wet looks.
Made in USA
©Joico Laboratories
(based on 3 reviews)
Ratings Distribution
5 Stars
4 Stars
3 Stars
2 Stars
1 Stars
of respondents would recommend this to a friend.
Reviewed by 3 customers
Displaying reviews 1-3
Back to top
Great tried and true product!!
By colorado redhead
from Golden, CO
describe yourself Beauty Conscious
Comments about Joico Joilotion Sculpting Lotion, 6.8 fl oz:
I have used this product for over 10 years on my thick curly/wavy hair. It gives great control and defines my curls and waves without over coating my hair.
Bottom Line Yes, I would recommend this to a friend
Was this review helpful? Yes / No
- You may also flag this review
It doesn't work ,leave hair dry & frizzy
By oloha
from north carolina
describe yourself Brand Buyer
See all my reviews
Best Uses
after shampoo,wet hair ,smell good not greacy,doesn't absorb well leave your hair dry & frizzy.
Bottom Line No, I would not recommend this to a friend
Love it
By Curly top
from PA
I love this product and it is so hard to find. It works great on my fine curly hair and on my son who has thick wavey hair. It holds but is not heavy and it does not dry your hair out.
Apply to damp or dry hair and style as desired.


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Chickens Need Style Too:
5 Stylish (Yet Practical) Chicken Coops
Breed Retreat, $(Contact for pricing) from Frederik Roijé 2. Large Garden Roof Chicken Coop, $1,250.00 (incl. tax and free shipping) from Kippen House (Eco-friendly!) 3. The Chicken Tractor, $900.00 - $1,500.00 from Ford & Ching 4. Luxury Co-Op, $3,500 from Raad 5. The Hen's Dream and Bin Coop, $(Contact for pricing) from Modo Verde (Eco-friendly!) MORE CHICKEN & COOPS ON APARTMENT THERAPY • Working Girls: Use Chickens to Till Your Garden • One Family's Story: Keeping Chickens in LA • Pimp My Coop: Cool Cribs For Backyard Chickens • Real Life Backyard Chicken Advice from Experienced Chicken Owners (Images: As credited above.)


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The Amino-terminal Domain of Desmoplakin Binds to Plakoglobin and Clusters Desmosomal Cadherin–Plakoglobin Complexes
Kowalczyk, Andrew P.
Bornslaeger, Elayne A.
Borgwardt, Jeffrey E.
Palka, Helena L.
Dhaliwal, Avninder S.
Corcoran, Connie M.
Denning, Mitchell F.
Green, Kathleen J.
The Journal of Cell Biology
The desmosome is a highly organized plasma membrane domain that couples intermediate filaments to the plasma membrane at regions of cell–cell adhesion. Desmosomes contain two classes of cadherins, desmogleins, and desmocollins, that bind to the cytoplasmic protein plakoglobin. Desmoplakin is a desmosomal component that plays a critical role in linking intermediate filament networks to the desmosomal plaque, and the amino-terminal domain of desmoplakin targets desmoplakin to the desmosome. However, the desmosomal protein(s) that bind the amino-terminal domain of desmoplakin have not been identified. To determine if the desmosomal cadherins and plakoglobin interact with the amino-terminal domain of desmoplakin, these proteins were co-expressed in L-cell fibroblasts, cells that do not normally express desmosomal components. When expressed in L-cells, the desmosomal cadherins and plakoglobin exhibited a diffuse distribution. However, in the presence of an amino-terminal desmoplakin polypeptide (DP-NTP), the desmosomal cadherins and plakoglobin were observed in punctate clusters that also contained DP-NTP. In addition, plakoglobin and DP-NTP were recruited to cell–cell interfaces in L-cells co-expressing a chimeric cadherin with the E-cadherin extracellular domain and the desmoglein-1 cytoplasmic domain, and these cells formed structures that were ultrastructurally similar to the outer plaque of the desmosome. In transient expression experiments in COS cells, the recruitment of DP-NTP to cell borders by the chimera required co-expression of plakoglobin. Plakoglobin and DP-NTP co-immunoprecipitated when extracted from L-cells, and yeast two hybrid analysis indicated that DP-NTP binds directly to plakoglobin but not Dsg1. These results identify a role for desmoplakin in organizing the desmosomal cadherin–plakoglobin complex and provide new insights into the hierarchy of protein interactions that occur in the desmosomal plaque.
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Cross-Talk between Adherens Junctions and Desmosomes Depends on Plakoglobin
Lewis, Jani E.
Wahl, James K.
Sass, Kristin M.
Jensen, Pamela J.
Johnson, Keith R.
Wheelock, Margaret J.
The Journal of Cell Biology
Squamous epithelial cells have both adherens junctions and desmosomes. The ability of these cells to organize the desmosomal proteins into a functional structure depends upon their ability first to organize an adherens junction. Since the adherens junction and the desmosome are separate structures with different molecular make up, it is not immediately obvious why formation of an adherens junction is a prerequisite for the formation of a desmosome. The adherens junction is composed of a transmembrane classical cadherin (E-cadherin and/or P-cadherin in squamous epithelial cells) linked to either β-catenin or plakoglobin, which is linked to α-catenin, which is linked to the actin cytoskeleton. The desmosome is composed of transmembrane proteins of the broad cadherin family (desmogleins and desmocollins) that are linked to the intermediate filament cytoskeleton, presumably through plakoglobin and desmoplakin. To begin to study the role of adherens junctions in the assembly of desmosomes, we produced an epithelial cell line that does not express classical cadherins and hence is unable to organize desmosomes, even though it retains the requisite desmosomal components. Transfection of E-cadherin and/or P-cadherin into this cell line did not restore the ability to organize desmosomes; however, overexpression of plakoglobin, along with E-cadherin, did permit desmosome organization. These data suggest that plakoglobin, which is the only known common component to both adherens junctions and desmosomes, must be linked to E-cadherin in the adherens junction before the cell can begin to assemble desmosomal components at regions of cell–cell contact. Although adherens junctions can form in the absence of plakoglobin, making use only of β-catenin, such junctions cannot support the formation of desmosomes. Thus, we speculate that plakoglobin plays a signaling role in desmosome organization.
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Structure, Function and Regulation of Desmosomes
Kowalczyk, Andrew P.
Green, Kathleen J.
Progress in molecular biology and translational science
Desmosomes are adhesive intercellular junctions that mechanically integrate adjacent cells by coupling adhesive interactions mediated by desmosomal cadherins to the intermediate filament cytoskeletal network. Desmosomal cadherins are connected to intermediate filaments by densely clustered cytoplasmic plaque proteins comprising members of the armadillo gene family, including plakoglobin and plakophilins, and members of the plakin family of cytolinkers, such as desmoplakin. The importance of desmosomes in tissue integrity is highlighted by human diseases caused by mutations in desmosomal genes, autoantibody attack of desmosomal cadherins, and bacterial toxins that selectively target desmosomal cadherins. In addition to reviewing the well-known roles of desmosomal proteins in tissue integrity, this chapter also highlights the growing appreciation for how desmosomal proteins are integrated with cell signaling pathways to contribute to vertebrate tissue organization and differentiation.
desmoglein; desmocollin; plakoglobin; desmoplakin; plakophilin; epidermis; cardiomyopathy; pemphigus
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Continual assembly of half-desmosomal structures in the absence of cell contacts and their frustrated endocytosis: a coordinated Sisyphus cycle
The Journal of Cell Biology
It is widely assumed that the coordinate assembly of desmosomal cadherins and plaque proteins into desmosome-typical plaque-coated membrane domains, capable of anchoring intermediate-sized filaments (IF), requires cell-to-cell contacts and a critical extracellular Ca2+ concentration. To test this hypothesis we studied several cell lines grown for years in media with less than 0.1 mM Ca2+ to steady-state low Ca2+ medium (LCM) conditions, particularly the human keratinocyte line HaCaT devoid of any junctional cell contact (HaCaT-L cells). Using immunolocalization and vesicle fractionation techniques, we found that the transmembrane glycoprotein, desmoglein (Dsg), colocalized with the plaque proteins, desmoplakin and plakoglobin. The sites of coassembly of desmosomal molecules in HaCaT-L cells as well as in HaCaT cells directly brought into LCM were identified as asymmetric plaque-coated plasma membrane domains (half-desmosomes) or as special plaque- associated cytoplasmic vesicles, most of which had formed endocytotically. The surface exposure of Dsg in these half-desmosomes was demonstrated by the binding, in vivo, of antibodies specific for an extracellular Dsg segment which also could cross-bridge them into symmetric quasi-desmosomes. Otherwise, these half-desmosomes were shown in LCM to be taken up endocytotically. Half-desmosomal assemblies were also seen in uncoupled cells in normal Ca2+ medium. We conclude that, in the absence of intercellular contacts, assembly of desmosomal proteins at the cell surface takes place, resulting in transient half- desmosomes which then, in LCM and without a stable partner connection to the adjacent cell, can be endocytotically resumed. This frustrated cycle of synthesis and assembly maintains an ensemble of molecules characteristic of epithelial differentiation and the potential to form desmosomes, even when the final junctional structure cannot be formed. We propose that these half-desmosomal structures are general cell structures of epithelial and other desmosome-forming cells.
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The desmosome and pemphigus
Waschke, Jens
Histochemistry and Cell Biology
Desmosomes are patch-like intercellular adhering junctions ("maculae adherentes"), which, in concert with the related adherens junctions, provide the mechanical strength to intercellular adhesion. Therefore, it is not surprising that desmosomes are abundant in tissues subjected to significant mechanical stress such as stratified epithelia and myocardium. Desmosomal adhesion is based on the Ca2+-dependent, homo- and heterophilic transinteraction of cadherin-type adhesion molecules. Desmosomal cadherins are anchored to the intermediate filament cytoskeleton by adaptor proteins of the armadillo and plakin families. Desmosomes are dynamic structures subjected to regulation and are therefore targets of signalling pathways, which control their molecular composition and adhesive properties. Moreover, evidence is emerging that desmosomal components themselves take part in outside-in signalling under physiologic and pathologic conditions. Disturbed desmosomal adhesion contributes to the pathogenesis of a number of diseases such as pemphigus, which is caused by autoantibodies against desmosomal cadherins. Beside pemphigus, desmosome-associated diseases are caused by other mechanisms such as genetic defects or bacterial toxins. Because most of these diseases affect the skin, desmosomes are interesting not only for cell biologists who are inspired by their complex structure and molecular composition, but also for clinical physicians who are confronted with patients suffering from severe blistering skin diseases such as pemphigus. To develop disease-specific therapeutic approaches, more insights into the molecular composition and regulation of desmosomes are required.
Desmosomes; Desmogleins; Pemphigus; Autoantibodies; Steric hindrance; Desmoglein compensation
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Defining the Interactions Between Intermediate Filaments and Desmosomes
Smith, Elizabeth A.
Fuchs, Elaine
The Journal of Cell Biology
Desmoplakin (DP), plakoglobin (PG), and plakophilin 1 (PP1) are desmosomal components lacking a transmembrane domain, thus making them candidate linker proteins for connecting intermediate filaments and desmosomes. Using deletion and site-directed mutagenesis, we show that remarkably, removal of ∼1% of DP's sequence obliterates its ability to associate with desmosomes. Conversely, when linked to a foreign protein, as few as 86 NH2-terminal DP residues are sufficient to target to desmosomes efficiently. In in vitro overlay assays, the DP head specifically associates with itself and with desmocollin 1a (Dsc1a). In similar overlay assays, PP1 binds to DP and Dsc1a, and to a lesser extent, desmoglein 1 (Dsg1), while PG binds to Dsg1 and more weakly to Dsc1a and DP. Interestingly, like DP, PG and PP1 associate with epidermal keratins, although PG is considerably weaker in its ability to do so. As judged by overlay assays, the amino terminal head domain of type II keratins appears to have a special importance in establishing these connections. Taken together, our findings provide new insights into the complexities of the links between desmosomes and intermediate filaments (IFs). Our results suggest a model whereby at desmosome sites within dividing epidermal cells, DP and PG anchor to desmosomal cadherins and to each other, forming an ordered array of nontransmembrane proteins that then bind to keratin IFs. As epidermal cells differentiate, PP1 is added as a molecular reinforcement to the plaque, enhancing anchorage to IFs and accounting at least partially for the increase in numbers and stability of desmosomes in suprabasal cells.
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Desmosome Assembly and Disassembly Are Membrane Raft-Dependent
Stahley, Sara N.
Saito, Masataka
Faundez, Victor
Koval, Michael
Mattheyses, Alexa L.
Kowalczyk, Andrew P.
PLoS ONE
Strong intercellular adhesion is critical for tissues that experience mechanical stress, such as the skin and heart. Desmosomes provide adhesive strength to tissues by anchoring desmosomal cadherins of neighboring cells to the intermediate filament cytoskeleton. Alterations in assembly and disassembly compromise desmosome function and may contribute to human diseases, such as the autoimmune skin blistering disease pemphigus vulgaris (PV). We previously demonstrated that PV auto-antibodies directed against the desmosomal cadherin desmoglein 3 (Dsg3) cause loss of adhesion by triggering membrane raft-mediated Dsg3 endocytosis. We hypothesized that raft membrane microdomains play a broader role in desmosome homeostasis by regulating the dynamics of desmosome assembly and disassembly. In human keratinocytes, Dsg3 is raft associated as determined by biochemical and super resolution immunofluorescence microscopy methods. Cholesterol depletion, which disrupts rafts, prevented desmosome assembly and adhesion, thus functionally linking rafts to desmosome formation. Interestingly, Dsg3 did not associate with rafts in cells lacking desmosomal proteins. Additionally, PV IgG-induced desmosome disassembly occurred by redistribution of Dsg3 into raft-containing endocytic membrane domains, resulting in cholesterol-dependent loss of adhesion. These findings demonstrate that membrane rafts are required for desmosome assembly and disassembly dynamics, suggesting therapeutic potential for raft targeting agents in desmosomal diseases such as PV.
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A New Perspective on Intercalated Disc Organization: Implications for Heart Disease
Li, Jifen
Radice, Glenn L.
Dermatology Research and Practice
Adherens junctions and desmosomes are intercellular adhesive junctions and essential for the morphogenesis, differentiation, and maintenance of tissues that are subjected to high mechanical stress, including heart and skin. The different junction complexes are organized at the termini of the cardiomyocyte called the intercalated disc. Disruption of adhesive integrity via mutations in genes encoding desmosomal proteins causes an inherited heart disease, arrhythmogenic right ventricular cardiomyopathy (ARVC). Besides plakoglobin, which is shared by adherens junctions and desmosomes, other desmosomal components, desmoglein-2, desmocollin-2, plakophilin-2, and desmoplakin are also present in ultrastructurally defined fascia adherens junctions of heart muscle, but not other tissues. This mixed-type of junctional structure is termed hybrid adhering junction or area composita. Desmosomal plakophilin-2 directly interacts with adherens junction protein alphaT-catenin, providing a new molecular link between the cadherin-catenin complex and desmosome. The area composita only exists in the cardiac intercalated disc of mammalian species suggesting that it evolved to strengthen mechanical coupling in the heart of higher vertebrates. The cross-talk among different junctions and their implication in the pathogenesis of ARVC are discussed in this review.
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The binding of plakoglobin to desmosomal cadherins: patterns of binding sites and topogenic potential
The Journal of Cell Biology
Plakoglobin is the only protein that occurs in the cytoplasmic plaques of all known adhering junctions and has been shown to be crucially involved in the formation and maintenance of desmosomes anchoring intermediate-sized filaments (IFs) by its interaction with the desmosomal cadherins, desmoglein (Dsg), and desmocollin (Dsc). This topogenic importance of plakoglobin is now directly shown in living cells as well as in binding assays in vitro. We show that, in transfected human A-431 carcinoma cells, a chimeric protein combining the vesicle-forming transmembrane glycoprotein synaptophysin, with the complete human plakoglobin sequence, is sorted to small vesicles many of which associate with desmosomal plaques and their attached IFs. Immunoprecipitation experiments have further revealed that the chimeric plakoglobin-containing transmembrane molecules of these vesicles are tightly bound to Dsg and Dsc but not to endogenous plakoglobin, thus demonstrating that the binding of plakoglobin to desmosomal cadherins does not require its soluble state and is strong enough to attach large structures such as vesicles to desmosomes. To identify the binding domains and the mechanisms involved in the interaction of plakoglobin with desmosomal cadherins, we have developed direct binding assays in vitro in which plakoglobin or parts thereof, produced by recombinant DNA technology in E. coli, are exposed to molecules containing the "C- domains" of several cadherins. These assays have shown that plakoglobin associates most tightly with the C-domain of Dsg, to a lesser degree with that of Dsc and only weakly with the C-domain of E-cadherin. Three separate segments of plakoglobin containing various numbers of the so- called arm repeats exhibit distinct binding to the desmosomal cadherins comparable in strength to that of the entire molecule. The binding pattern of plakoglobin segments in vitro is compared with that in vivo. Paradoxically, in vitro some internal plakoglobin fragments bind even better to the C-domain of E-cadherin than the entire molecule, indicating that elements exist in native plakoglobin that interfere with the interaction of this protein with its various cadherin partners.
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Autoimmune and infectious skin diseases that target desmogleins
AMAGAI, Masayuki
Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
Desmosomes are intercellular adhesive junctions of epithelial cells that contain two major transmembrane components, the desmogleins (Dsg) and desmocollins (Dsc), which are cadherin-type cell–cell adhesion molecules and are anchored to intermediate filaments of keratin through interactions with plakoglobin and desmoplakin. Desmosomes play an important role in maintaining the proper structure and barrier function of the epidermis and mucous epithelia. Four Dsg isoforms have been identified to date, Dsg1–Dsg4, and are involved in several skin and heart diseases. Dsg1 and Dsg3 are the two major Dsg isoforms in the skin and mucous membranes, and are targeted by IgG autoantibodies in pemphigus, an autoimmune disease of the skin and mucous membranes. Dsg1 is also targeted by exfoliative toxin (ET) released by Staphylococcus aureus in the infectious skin diseases bullous impetigo and staphylococcal scalded skin syndrome (SSSS). ET is a unique serine protease that shows lock and key specificity to Dsg1. Dsg2 is expressed in all tissues possessing desmosomes, including simple epithelia and myocardia, and mutations in this gene are responsible for arrhythmogenic right ventricular cardiomyopathy/dysplasia. Dsg4 plays an important adhesive role mainly in hair follicles, and Dsg4 mutations cause abnormal hair development. Recently, an active disease model for pemphigus was generated by a unique approach using autoantigen-deficient mice that do not acquire tolerance against the defective autoantigen. Adoptive transfer of Dsg3−/− lymphocytes into mice expressing Dsg3 induces stable anti-Dsg3 IgG production with development of the pemphigus phenotype. This mouse model is a valuable tool with which to investigate immunological mechanisms of harmful IgG autoantibody production in pemphigus. Further investigation of desmoglein molecules will continue to provide insight into the unsolved pathophysiological mechanisms of diseases and aid in the development of novel therapeutic strategies with minimal side effects.
cadherin; pemphigus; impetigo; SSSS; mouse model; ELISA
Related Articles
Plakophilin 2 Couples Actomyosin Remodeling to Desmosomal Plaque Assembly via RhoA
Godsel, Lisa M.
Dubash, Adi D.
Bass-Zubek, Amanda E.
Amargo, Evangeline V.
Klessner, Jodi L.
Hobbs, Ryan P.
Chen, Xinyu
Green, Kathleen J.
Molecular Biology of the Cell
The desmosomal armadillo protein plakophilin 2 (PKP2) regulates cell contact-initiated cortical actin remodeling through the regulation of RhoA localization and activity to couple adherens junction maturation with desmosomal plaque assembly.
Plakophilin 2 (PKP2), an armadillo family member closely related to p120 catenin (p120ctn), is a constituent of the intercellular adhesive junction, the desmosome. We previously showed that PKP2 loss prevents the incorporation of desmosome precursors enriched in the plaque protein desmoplakin (DP) into newly forming desmosomes, in part by disrupting PKC-dependent regulation of DP assembly competence. On the basis of the observation that DP incorporation into junctions is cytochalasin D–sensitive, here we ask whether PKP2 may also contribute to actin-dependent regulation of desmosome assembly. We demonstrate that PKP2 knockdown impairs cortical actin remodeling after cadherin ligation, without affecting p120ctn expression or localization. Our data suggest that these defects result from the failure of activated RhoA to localize at intercellular interfaces after cell–cell contact and an elevation of cellular RhoA, stress fibers, and other indicators of contractile signaling in squamous cell lines and atrial cardiomyocytes. Consistent with these observations, RhoA activation accelerated DP redistribution to desmosomes during the first hour of junction assembly, whereas sustained RhoA activity compromised desmosome plaque maturation. Together with our previous findings, these data suggest that PKP2 may functionally link RhoA- and PKC-dependent pathways to drive actin reorganization and regulate DP–IF interactions required for normal desmosome assembly.
Related Articles
Regulation of β-Catenin Levels and Localization by Overexpression of Plakoglobin and Inhibition of the Ubiquitin-Proteasome System
Salomon, Daniela
Sacco, Paula A.
Roy, Sujata Guha
Simcha, Inbal
Johnson, Keith R.
Wheelock, Margaret J.
Ben-Ze'ev, Avri
The Journal of Cell Biology
β-Catenin and plakoglobin (γ-catenin) are closely related molecules of the armadillo family of proteins. They are localized at the submembrane plaques of cell–cell adherens junctions where they form independent complexes with classical cadherins and α-catenin to establish the link with the actin cytoskeleton. Plakoglobin is also found in a complex with desmosomal cadherins and is involved in anchoring intermediate filaments to desmosomal plaques. In addition to their role in junctional assembly, β-catenin has been shown to play an essential role in signal transduction by the Wnt pathway that results in its translocation into the nucleus. To study the relationship between plakoglobin expression and the level of β-catenin, and the localization of these proteins in the same cell, we employed two different tumor cell lines that express N-cadherin, and α- and β-catenin, but no plakoglobin or desmosomal components. Individual clones expressing various levels of plakoglobin were established by stable transfection. Plakoglobin overexpression resulted in a dose-dependent decrease in the level of β-catenin in each clone. Induction of plakoglobin expression increased the turnover of β-catenin without affecting RNA levels, suggesting posttranslational regulation of β-catenin. In plakoglobin overexpressing cells, both β-catenin and plakoglobin were localized at cell– cell junctions. Stable transfection of mutant plakoglobin molecules showed that deletion of the N-cadherin binding domain, but not the α-catenin binding domain, abolished β-catenin downregulation. Inhibition of the ubiquitin-proteasome pathway in plakoglobin overexpressing cells blocked the decrease in β-catenin levels and resulted in accumulation of both β-catenin and plakoglobin in the nucleus. These results suggest that (a) plakoglobin substitutes effectively with β-catenin for association with N-cadherin in adherens junctions, (b) extrajunctional β-catenin is rapidly degraded by the proteasome-ubiquitin system but, (c) excess β-catenin and plakoglobin translocate into the nucleus.
Related Articles
Breaking the connection: displacement of the desmosomal plaque protein desmoplakin from cell-cell interfaces disrupts anchorage of intermediate filament bundles and alters intercellular junction assembly
The Journal of Cell Biology
The desmosomal plaque protein desmoplakin (DP), located at the juncture between the intermediate filament (IF) network and the cytoplasmic tails of the transmembrane desmosomal cadherins, has been proposed to link IF to the desmosomal plaque. Consistent with this hypothesis, previous studies of individual DP domains indicated that the DP COOH terminus associates with IF networks whereas NH2-terminal sequences govern the association of DP with the desmosomal plaque. Nevertheless, it had not yet been demonstrated that DP is required for attaching IF to the desmosome. To test this proposal directly, we generated A431 cell lines stably expressing DP NH2-terminal polypeptides, which were expected to compete with endogenous DP during desmosome assembly. As these polypeptides lacked the COOH-terminal IF-binding domain, this competition should result in the loss of IF anchorage if DP is required for linking IF to the desmosomal plaque. In such cells, a 70-kD DP NH2- terminal polypeptide (DP-NTP) colocalized at cell-cell interfaces with desmosomal proteins. As predicted, the distribution of endogenous DP was severely perturbed. At cell-cell borders where endogenous DP was undetectable by immunofluorescence, there was a striking absence of attached tonofibrils (IF bundles). Furthermore, DP-NTP assembled into ultrastructurally identifiable junctional structures lacking associated IF bundles. Surprisingly, immunofluorescence and immunogold electron microscopy indicated that adherens junction components were coassembled into these structures along with desmosomal components and DP-NTP. These results indicate that DP is required for anchoring IF networks to desmosomes and furthermore suggest that the DP-IF complex is important for governing the normal spatial segregation of adhesive junction components during their assembly into distinct structures.
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The Function of Plakophilin 1 in Desmosome Assembly and Actin Filament Organization
Hatzfeld, Mechthild
Haffner, Christof
Schulze, Katrin
Vinzens, Ute
The Journal of Cell Biology
Plakophilin 1, a member of the armadillo multigene family, is a protein with dual localization in the nucleus and in desmosomes. To elucidate its role in desmosome assembly and regulation, we have analyzed its localization and binding partners in vivo. When overexpressed in HaCaT keratinocytes, plakophilin 1 localized to the nucleus and to desmosomes, and dramatically enhanced the recruitment of desmosomal proteins to the plasma membrane. This effect was mediated by plakophilin 1's head domain, which interacted with desmoglein 1, desmoplakin, and keratins in the yeast two-hybrid system. Overexpression of the armadillo repeat domain induced a striking dominant negative phenotype with the formation of filopodia and long cellular protrusions, where plakophilin 1 colocalized with actin filaments. This phenotype was strictly dependent on a conserved motif in the center of the armadillo repeat domain. Our results demonstrate that plakophilin 1 contains two functionally distinct domains: the head domain, which could play a role in organizing the desmosomal plaque in suprabasal cells, and the armadillo repeat domain, which might be involved in regulating the dynamics of the actin cytoskeleton.
keratinocytes; desmoglein; armadillo; cell adhesion; cell motility
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Organization of desmosomal plaque proteins in cells growing at low calcium concentrations
The Journal of Cell Biology
Desmosomes are not formed in epithelial cell cultures growing in media with low (less than or equal to 0.1 mM) concentrations of Ca2+ (LCM) but appear rapidly upon shift to media of normal calcium concentrations (NCM). Previous authors using immunolocalization of desmoplakin, a marker protein for the desmosomal plaque, in LCM-grown cells have interpreted positively stained, dense, cytoplasmic aggregates on intermediate filaments (IF) bundles as preformed plaque units which upon NCM shift would move to the plasma membrane and contribute to desmosome formation. Studying various cell cultures, including primary mouse keratinocytes and human A-431 cells, we show that most, probably all, desmoplakin-positive aggregates in LCM-grown cells are associated with membranous structures, mostly vesicles, and also contain other desmosomal markers, including desmoglein, a transmembrane glycoprotein. We interpret such vesicles as residual desmosome-derived domains endocytosed upon cell dissociation. Only keratinocytes grown for long times (2-4 wk) in LCM are practically free from such vesicles. In addition, we demonstrate that certain cells such as A-431 cells, when passaged in LCM and in the absence of stable junctions, are able to continually assemble "half-desmosomes" on the plasma membrane which in turn can be endocytosed as plaque-bearing vesicles. We also show that in LCM the synthesis of several desmosomal proteins (desmoplakins I and II, plakoglobin, desmoglein, "band 6 protein") continues and that most of the plaque protein, desmoplakin, is diffusely spread over the cytoplasm, apparently in a soluble monodisperse form of approximately 9S. From our results we propose that the plaque proteins occur in small, discrete, diffusible entities in the cytoplasm, in concentrations that are relatively high in LCM and low in NCM, from which they assemble directly, i.e., without intermediate precursor aggregates on IFs in the cytoplasm, on certain plasma membrane domains in a Ca2+ dependent process.
Related Articles
Identification of the plakoglobin-binding domain in desmoglein and its role in plaque assembly and intermediate filament anchorage
The Journal of Cell Biology
The carboxyterminal cytoplasmic portions (tails) of desmosomal cadherins of both the desmoglein (Dsg) and desmocollin type are integral components of the desmosomal plaque and are involved in desmosome assembly and the anchorage of intermediate-sized filaments. When additional Dsg tails were introduced by cDNA transfection into cultured human epithelial cells, in the form of chimeras with the aminoterminal membrane insertion domain of rat connexin32 (Co32), the resulting stably transfected cells showed a dominant-negative defect specific for desmosomal junctions: despite the continual presence of all desmosomal proteins, the endogenous desmosomes disappeared and the formation of Co32-Dsg chimeric gap junctions was inhibited. Using cell transfection in combination with immunoprecipitation techniques, we have examined a series of deletion mutants of the Dsg1 tail in Co32-Dsg chimeras. We show that upon removal of the last 262 amino acids the truncated Dsg tail still effects the binding of plakoglobin but not of detectable amounts of any catenin and induces the dominant-negative phenotype. However, further truncation or excision of the next 41 amino acids, which correspond to the highly conserved carboxyterminus of the C-domain in other cadherins, abolishes plakoglobin binding and allows desmosomes to reform. Therefore, we conclude that this short segment provides a plakoglobin-binding site and is important for plaque assembly and the specific anchorage of either actin filaments in adherens junctions or IFs in desmosomes.
Related Articles
Assessment of Splice Variant-Specific Functions of Desmocollin 1 in the Skin
Cheng, Xing
Mihindukulasuriya, Kusal
Den, Zhining
Kowalczyk, Andrew P.
Calkins, Cathárine
Ishiko, Akira
Shimizu, Atsushi
Koch, Peter J.
Molecular and Cellular Biology
Desmocollin 1 (Dsc1) is part of a desmosomal cell adhesion receptor formed in terminally differentiating keratinocytes of stratified epithelia. The dsc1 gene encodes two proteins (Dsc1a and Dsc1b) that differ only with respect to their COOH-terminal cytoplasmic amino acid sequences. On the basis of in vitro experiments, it is thought that the Dsc1a variant is essential for assembly of the desmosomal plaque, a structure that connects desmosomes to the intermediate filament cytoskeleton of epithelial cells. We have generated mice that synthesize a truncated Dsc1 receptor that lacks both the Dsc1a- and Dsc1b-specific COOH-terminal domains. This mutant transmembrane receptor, which does not bind the common desmosomal plaque proteins plakoglobin and plakophilin 1, is integrated into functional desmosomes. Interestingly, our mutant mice did not show the epidermal fragility previously observed in dsc1-null mice. This suggests that neither the Dsc1a- nor the Dsc1b-specific COOH-terminal cytoplasmic domain is required for establishing and maintaining desmosomal adhesion. However, a comparison of our mutants with dsc1-null mice suggests that the Dsc1 extracellular domain is necessary to maintain structural integrity of the skin.
Related Articles
Plakophilin-1 protects keratinocytes from pemphigus vulgaris IgG by forming calcium-independent desmosomes
Tucker, Dana K.
Stahley, Sara N.
Kowalczyk, Andrew P.
The Journal of investigative dermatology
Plakophilin-1 (PKP-1) is an armadillo family protein critical for desmosomal adhesion and epidermal integrity. In the autoimmune skin blistering disease pemphigus vulgaris (PV), autoantibodies (IgG) target the desmosomal cadherin desmoglein 3 (Dsg3) and compromise keratinocyte cell-cell adhesion. Here, we report that enhanced expression of PKP-1 protects keratinocytes from PV IgG-induced loss of cell-cell adhesion. PKP-1 prevents loss of Dsg3 and other desmosomal proteins from cell-cell borders and prevents alterations in desmosome ultrastructure in keratinocytes treated with PV IgG. Using a series of Dsg3 chimeras and deletion constructs, we find that PKP-1 clusters Dsg3 with the desmosomal plaque protein desmoplakin in a manner dependent upon the plakoglobin binding domain of the Dsg3 tail. Furthermore, PKP-1 expression transforms desmosome adhesion from a calcium-dependent to a calcium-independent and hyper-adhesive state. These results demonstrate that manipulating the expression of a single desmosomal plaque protein can block the pathogenic effects of PV IgG on keratinocyte adhesion.
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Desmoglein 3: A Help or a Hindrance in Cancer Progression?
Brown, Louise
Wan, Hong
Desmoglein 3 is one of seven desmosomal cadherins that mediate cell-cell adhesion in desmosomes. Desmosomes are the intercellular junctional complexes that anchor the intermediate filaments of adjacent cells and confer strong cell adhesion thus are essential in the maintenance of tissue architecture and structural integrity. Like adherens junctions, desmosomes function as tumour suppressors and are down regulated in the process of epithelial-mesenchymal transition and in tumour cell invasion and metastasis. However, recently several studies have shown that various desmosomal components, including desmoglein 3, are up-regulated in cancer with increased levels of expression correlating with the clinical stage of malignancy, implicating their potentiality to serve as a diagnostic and prognostic marker. Furthermore, in vitro studies have demonstrated that overexpression of desmoglein 3 in cancer cell lines activates several signal pathways that have an impact on cell morphology, adhesion and locomotion. These additional signalling roles of desmoglein 3 may not be associated to its adhesive function in desmosomes but rather function outside of the junctions, acting as a key regulator in the control of actin based cellular processes. This review will discuss recent advances which support the role of desmoglein 3 in cancer progression.
desmoglein 3; cell signalling; desmosomes; cell-cell adhesion; squamous cell carcinoma; cancer biomarker; cancer progression; cancer suppression; metastasis
Related Articles
Lis1 is essential for cortical microtubule organization and desmosome stability in the epidermis
Sumigray, Kaelyn D.
Chen, Hsin
Lechler, Terry
The Journal of Cell Biology
Desmoplakin recruits the centrosomal protein Lis1 to the epidermal cell cortex, where it regulates cortical microtubule organization and desmosome stability.
Desmosomes are cell–cell adhesion structures that integrate cytoskeletal networks. In addition to binding intermediate filaments, the desmosomal protein desmoplakin (DP) regulates microtubule reorganization in the epidermis. In this paper, we identify a specific subset of centrosomal proteins that are recruited to the cell cortex by DP upon epidermal differentiation. These include Lis1 and Ndel1, which are centrosomal proteins that regulate microtubule organization and anchoring in other cell types. This recruitment was mediated by a region of DP specific to a single isoform, DPI. Furthermore, we demonstrate that the epidermal-specific loss of Lis1 results in dramatic defects in microtubule reorganization. Lis1 ablation also causes desmosomal defects, characterized by decreased levels of desmosomal components, decreased attachment of keratin filaments, and increased turnover of desmosomal proteins at the cell cortex. This contributes to loss of epidermal barrier activity, resulting in completely penetrant perinatal lethality. This work reveals essential desmosome-associated components that control cortical microtubule organization and unexpected roles for centrosomal proteins in epidermal function.
Related Articles
Direct Ca2+-dependent Heterophilic Interaction between Desmosomal Cadherins, Desmoglein and Desmocollin, Contributes to Cell–Cell Adhesion
Chitaev, Nikolai A.
Troyanovsky, Sergey M.
The Journal of Cell Biology
Human fibrosarcoma cells, HT-1080, feature extensive adherens junctions, lack mature desmosomes, and express a single known desmosomal protein, Desmoglein 2 (Dsg2). Transfection of these cells with bovine Desmocollin 1a (Dsc1a) caused dramatic changes in the subcellular distribution of endogenous Dsg2. Both cadherins clustered in the areas of the adherens junctions, whereas only a minor portion of Dsg2 was seen in these areas in the parental cells. Deletion mapping showed that intact extracellular cadherin-like repeats of Dsc1a (Arg1-Thr170) are required for the translocation of Dsg2. Deletion of the intracellular C-domain that mediates the interaction of Dsc1a with plakoglobin, or the CSI region that is involved in the binding to desmoplakin, had no effect. Coimmunoprecipitation experiments of cell lysates stably expressing Dsc1a with anti-Dsc or -Dsg antibodies demonstrate that the desmosomal cadherins, Dsg2 and Dsc1a, are involved in a direct Ca2+-dependent interaction. This conclusion was further supported by the results of solid phase binding experiments. These showed that the Dsc1a fragment containing cadherin-like repeats 1 and 2 binds directly to the extracellular portion of Dsg in a Ca2+-dependent manner. The contribution of the Dsg/ Dsc interaction to cell–cell adhesion was tested by coculturing HT-1080 cells expressing Dsc1a with HT-1080 cells lacking Dsc but expressing myc-tagged plakoglobin (MPg). In the latter cells, MPg and the endogenous Dsg form stable complexes. The observed specific coimmunoprecipitation of MPg by anti-Dsc antibodies in coculture indicates that an intercellular interaction between Dsc1 and Dsg is involved in cell–cell adhesion.
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Compound and Digenic Heterozygosity Contributes to Arrhythmogenic Right Ventricular Cardiomyopathy
Xu, Tianhong
Yang, Zhao
Vatta, Matteo
Rampazzo, Alessandra
Beffagna, Giorgia
Pillichou, Kalliopi
Scherer, Steven E.
Saffitz, Jeffrey
Kravitz, Joshua
Zareba, Wojciech
Danieli, Gian Antonio
Lorenzon, Alessandra
Nava, Andrea
Bauce, Barbara
Thiene, Gaetano
Basso, Cristina
Calkins, Hugh
Gear, Kathy
Marcus, Frank
Towbin, Jeffrey A.
Journal of the American College of Cardiology
To define the genetic basis of arrhythmogenic right ventricular cardiomyopathy.
Arrhythmogenic right ventricular cardiomyopathy (ARVC), characterized by right ventricular fibrofatty replacement and arrhythmias, causes sudden death. Autosomal dominant Inheritance, reduced penetrance, and 7 desmosome-encoding causative genes are known. The basis of low penetrance is poorly understood.
ARVC probands and family members were enrolled, blood obtained, lymphoblastoid cell lines immortalized, DNA extracted, PCR amplification of desmosome-encoding genes performed, PCR products sequenced and diseased tissue samples studied for intercellular junction protein distribution using confocal immunofluorescence microscopy and antibodies against key proteins.
We identified 21 variants in plakophilin-2 (PKP2) in 38 of 198 probands (19%), including missense, nonsense, splice site, and deletion/insertion mutations. Pedigrees showed wide intra-familial variability (severe early-onset disease to asymptomatic individuals). In 9/38 probands, PKP2 variants were identified that were encoded in trans (compound heterozygosity). The 38 probands hosting PKP2 variants were screened for other desmosomal genes mutations; second variants (digenic heterozygosity) were identified in 16/38 subjects with PKP2 variants (42%) including desmoplakin (DSP, n=6), desmoglein-2 (DSG2, n=5), plakophilin-4 (PKP4, n=1), and desmocollin-2 (DSC2, n=1). Heterozygous mutations in non-PKP 2desmosomal genes occurred in 14/198 subjects (7%), including DSP (n=4), DSG2 (n=5), DSC2 (n=3), and junctional plakoglobin (JUP, n=2). All variants occurred in conserved regions; none were identified in 700 ethnic-matched controls.
Immunohistochemical analysis demonstrated abnormalities of protein architecture.
These data suggest that the genetic basis of ARVC includes reduced penetrance with compound and digenic heterozygosity. Disturbed junctional cytoarchitecture in subjects with desmosomal mutations confirms that ARVC is a disease of the desmosome and cell junction.
Arrhythmias; Cardiomyopathies; Desmosomes; Intercalated Disks; Genetic Mutations
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Mice expressing a mutant desmosomal cadherin exhibit abnormalities in desmosomes, proliferation, and epidermal differentiation
The Journal of Cell Biology
Desmogleins are members of the cadherin superfamily which form the core of desmosomes. In vitro studies indicate that the cytoplasmic domain of desmogleins associates with plakoglobin; however, little is known about the role of this domain in desmosome recognition or assembly in vivo, or about the possible relation of desmoglein mutations to epidermal differentiation and disease. To address these questions we used transgenic mouse technology to produce an NH2-terminally truncated desmoglein (Pemphigus Vulgaris Antigen or Dsg3) in cells known to express its wild-type counterpart. Within 2 d, newborn transgenic animals displayed swelling of their paws, flakiness on their back, and blackening of the tail tip. When analyzed histologically and ultrastructurally, widening of intercellular spaces and disruption of desmosomes were especially striking in the paws and tail. Desmosomes were reduced dramatically in number and were smaller and often peculiar in structure. Immunofluorescence and immunoelectron microscopy revealed no major abnormalities in localization of hemidesmosomal components, but desmosomal components organized aberrantly, resulting in a loss of ultrastructure within the plaque. In regions where desmosome loss was prevalent but where some adhesive structures persisted, the epidermis was thickened, with a marked increase in spinous and stratum corneum layers, variability in granular layer thickness, and parakeratosis in some regions. Intriguingly, a dramatic increase in cell proliferation was also observed concomitant with biochemical changes, including alterations in integrin expression, known to be associated with hyperproliferation. An inflammatory response was also detected in some skin regions. Collectively, these findings demonstrate that a mutation in a desmoglein can perturb epidermal cell-cell adhesion, triggering a cascade of changes in the skin.
Related Articles
Rearrangements of desmosomal and cytoskeletal proteins during the transition from epithelial to fibroblastoid organization in cultured rat bladder carcinoma cells
The Journal of Cell Biology
Changes of cell morphology and the state of differentiation are known to play important roles in embryogenesis as well as in carcinogenesis. Examples of particularly profound changes are the conversions of epithelial to mesenchymal cells; i.e., the dissociation of some or all polygonal, polar epithelial cells and their transformation into elongate, fibroblastoid cells of high motility. As an in vitro model system for such changes in cell morphology, we have used cell cultures of the rat bladder carcinoma-derived cell line NBT-II which, on exposure to inducing medium containing a commercial serum substitute (Ultroser G), show an extensive change in their organization (epithelial-mesenchymal transition): the junctions between the epithelial cells are split, the epithelial cell organization is lost, and the resulting individual cells become motile and assume a spindle- like fibroblastoid appearance. Using immunofluorescence microscopy and biochemical protein characterization techniques, we show that this change is accompanied by a redistribution of desmosomal plaque proteins (desmoplakins, desmoglein, plakoglobin) and by a reorganization of the cytokeratin and the actin-fodrin filament systems. Moreover, intermediate-sized filaments of the vimentin type are formed in the fibroblastoid cells. We demonstrate that the modulation of desmosomal proteins, specifically an increase in soluble desmoplakins, is a relatively early event in cell dissociation and in epithelial- mesenchymal transition. In this process, a latent period of 5 h upon addition of inducing medium precedes the removal of these desmosomal components from the plasma membrane. The transition, which is reversible, is dependent on continued protein synthesis and phosphorylation but not on the presence of the inducing medium beyond the initial 2-h period. We discuss the value of this experimental system as a physiologically relevant approach for studying the regulation of the assembly and disassembly of desmosomes and other intercellular adhesion structures, and as a model of the conversion of cells from one state of differentiation into another.
Related Articles
Desmoplakin Is Required Early in Development for Assembly of Desmosomes and Cytoskeletal Linkage
Gallicano, G. Ian
Kouklis, Panos
Bauer, Christoph
Yin, Mei
Vasioukhin, Valeri
Degenstein, Linda
Fuchs, Elaine
The Journal of Cell Biology
Desmosomes first assemble in the E3.5 mouse trophectoderm, concomitant with establishment of epithelial polarity and appearance of a blastocoel cavity. Throughout development, they increase in size and number and are especially abundant in epidermis and heart muscle. Desmosomes mediate cell–cell adhesion through desmosomal cadherins, which differ from classical cadherins in their attachments to intermediate filaments (IFs), rather than actin filaments. Of the proteins implicated in making this IF connection, only desmoplakin (DP) is both exclusive to and ubiquitous among desmosomes. To explore its function and importance to tissue integrity, we ablated the desmoplakin gene. Homozygous −/− mutant embryos proceeded through implantation, but did not survive beyond E6.5. Mutant embryos proceeded through implantation, but did not survive beyond E6.5. Surprisingly, analysis of these embryos revealed a critical role for desmoplakin not only in anchoring IFs to desmosomes, but also in desmosome assembly and/or stabilization. This finding not only unveiled a new function for desmoplakin, but also provided the first opportunity to explore desmosome function during embryogenesis. While a blastocoel cavity formed and epithelial cell polarity was at least partially established in the DP (−/−) embryos, the paucity of desmosomal cell–cell junctions severely affected the modeling of tissue architecture and shaping of the early embryo.
desmoplakin; desmosomes; cadherins; embryonic lethal; knockout
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text:
Brand-name prescription drug prices rose at more than three times the rate of overall inflation last year, and some Amarillo seniors are feeling the pinch.
Recently released reports by the 35-million-member AARP and the consumer group Families USA said the gap between prices for prescription medicines and general inflation has widened in recent years, diminishing the purchasing power of older Americans who receive increases in Social Security based on the Consumer Price Index. The index is the government's most closely watched inflation measure.
"If the price of drugs keeps going up faster than inflation, it will become more and more difficult for consumers, especially older consumers, to be able to afford them," said John Rother, AARP's policy director.
The average price increase for the top 30 brand-name drugs used by older Americans was 6.5 percent last year, the Families USA report said. AARP's study showed an average 6.9-percent price increase for nearly 200 drugs. Inflation in general was 1.9 percent.
Some Amarillo seniors noted the increase when they recently purchased their prescriptions.
"I always tell them it's the national debt when I go to get them (the prescriptions)," Gracie Lack, 74, said.
Other seniors have alternative prescription plans to help alleviate the cost of the drugs.
"I get mine through the VA (Veterans Administration) so it's not bad for me, but everyone I've talked to has said they've really increased" Sue Cash, 64, said.
The cost of the drugs has even led some seniors to consider quitting the prescriptions.
"I wish I could stop talking them. I imagine lots of people feel the same way I do," Noma Evans, 86, said.
Since 2000, drug prices have risen 27.6 percent, AARP said. General inflation was 9.3 percent .
Prices increased between 6.9 percent and 9.9 percent last year for the five leading drugs in terms of sales - cholesterol-reducing Lipitor, the blood thinner Plavix, Fosamax for osteoporosis, the blood-pressure drug Norvasc and Celebrex, a pain reliever - the Families USA study said.
Pfizer makes Celebrex, Lipitor and Norvasc, while Bristol-Myers Squibb produces Plavix and Merck & Co. manufactures Fosamax.
Both studies looked at wholesale prices, reasoning that changes in those prices were reflected in costs at the retail level.
Jeff Trewhitt, a spokesman for the Pharmaceutical Research and Manufacturers of America, said the studies overstated the rate of inflation for prescription drugs and did not account for the industry's substantial research and development costs.
Prices of prescription medicines have risen 4.4 percent on average in each of the past three years, slightly slower than medical inflation, Trewhitt said. "That's a more accurate basis for comparison," he said.
The Bureau of Labor Statistics, which compiles the Consumer Price Index, said prescription prices rose by 2.5 percent last year, but that measure also includes generic drugs. AARP is planning an examination of generic drug prices.
The seniors group is credited - or blamed - for providing an endorsement in the fall that was critical to the Medicare legislation's passage.
Globe-News Staff Writer Paige Dickerson and The Associated Press contributed to this report.
© 2016. All Rights Reserved. | Contact Us


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To the Editor.—
A hereditary form of polymorphous light eruption affects Indians from the central plains of Canada and the United States1 to Central and South America.2 Exposure to sunlight leads to pruritic macular, papular, and vesicular eruptions, sometimes with pyoderma and scarring. Symptoms appear in early spring in those in the northern hemisphere and persist until late fall. Patients are sensitive to long exposure to ultraviolet radiation (symptoms appear after exposure through window glass) and therefore receive no protection from commercial sunscreens.The clinical aspects and seasonal appearance of symptoms are reminiscent of erythropoietic protoporphyria (EPP), but neither we nor Birt and Davis1 have detected elevated porphyrin levels in patients. Oral beta carotene is recommended for photoprotection of persons with EPP (Solatene package insert, Roche Laboratories, 1975). We reasoned that, since the disorder affecting American Indians resembles EPP, oral beta carotene may also protect these persons.
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2009-04-16 / Obituaries
Marvin Milton Beisert
July 9, 1932 - April 11, 2009
Funeral services for Marvin Beisert, 76 of Conroe, Texas are scheduled for 10:00 a.m. on Wednesday, April 15, 2009 at Christ Lutheran Church in Loebau, Texas with Rev. David Quail officiating. Burial will follow in the Giddings City Cemetery in Giddings. Visitation will be held Tuesday from 12:30 p.m. until 9 p.m. and Wednesday from 7 a.m. until 8:30 a.m.
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Fandango movie ticket code Requests - No Trades over $5, No Buying/Selling
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text:
Momentum has been building for the last couple of weeks for the Randall boys basketball team, and if the Raiders keep it going tonight, they'll be in elite territory.
Up Next
The Game: Randall Raiders (20-10) vs. El Paso Austin Panthers (27-6), Region I-4A quarterfinal playoff, 6:30 p.m. today, Seminole.
Radio: KPUR (1440-AM), 6:20 p.m.
Randall will take on No. 16 El Paso Austin in the Region I-4A quarterfinals at 6:30 p.m. at Seminole, with the winner advancing to the Region I-4A tournament in San Angelo starting Friday. This is merely the latest step for the Raiders (20-10), who are playing their best basketball now.
It started early in February when the Raiders defeated Palo Duro, 50-42, in a District 3-4A game, to end Palo Duro's 88-game district winning streak. Randall seemed to grow up in that game, and the Raiders haven't looked back since.
"I think we've played really good defense and that's been our strength all year long," Randall coach Leslie Broadhurst said. "Since the Palo Duro game they've played with an air about them that they think they can beat anybody."
Randall advanced by beating Canutillo, 49-43, in a defensive struggle in last Thursday's area round game. The Raiders recovered from a poor offensive start and outscored Canutillo 16-8 to close it out.
Junior post Joseph Scott had 11 points for Randall, while sophomore Ridrell Holman had 10. But the Raiders aren't going to be satisfied with merely advancing to this point.
"We've talked about how there's room for improvement," Broadhurst said. "A lot of teams don't feel that way when they get to this point. We just hope we can keep winning and stay alive for another day."
El Paso Austin (27-6) presents the tallest postseason hurdle so far for the Raiders. The Panthers advanced by beating Big Spring, 57-40.Tony Baker had 18 points for and Tim Bell had 16.
Bell and Baker average with 20.2 and 17.4 points a game, respectively.
"They've got two really, really good players," Broadhurst said. "(Bell) is a guard who can really shoot and is as athletic as we've played. They'll be as good a team as we've played."
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