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Add a floral pop to any outfit with these comfy and stylish floral slip-ons. The perfect sporty chic addition to your shoe collection. Comfortable and easy to slip on. Man...
90008 NAVY WOMEN'S FLAT Man made materials.
These will be your little fashionista's go-to shoes! Features an open toe and a low cork-wrapped platform wedge silhouette. A multi faux leather knotted strap upper with a slingback ankle...
These sparkling sandals add so much glam to any summer look! Features a strappy rhinestone upper Thick rippled lug sole and side buckled slingback ankle strap Man made materials.
You wouldn't dare to leave these heels behind! Features an open toe and a stiletto heel silhouette. A metallic holographic textured upper. Crisscrossing straps over the vamp of the heel...
Bring a high dose of style to any outfit in these wedges. Features a faux suede upper and a cork braided jute wrapped wedge. Lace up front and ankle strap...
These sandals are perfect for showing off your fresh pedi! Features a classic thong sandal strap with a rubber sole. Gold chain inspired thong strap. Man made materials.
These sandals are so simply chic with it's subtle graphic city print! Features a popular city name printed sole Flip flop slide on straps Man made materials.
Step out in style this season in these unique boots. Features a slightly squared off almond toe with a chunky heel. Multiple small square cut outs throughout the upper giving...
A stylish, yet simple heel, these heels are perfect for the office as well a night on the town. Features a pointed toe and a stiletto heel silhouette. A faux...
These are the perfect date night shoe. The flirty blue color with the lace up detailing, all eyes will be on you! Features bold laser cut outs on sides with a...
These cute and casual wedges are so easy to throw on before a trip to the pool! Features a popular city printed upper Flip flop slide on style straps Man...
Day or night, these versatile flats are ready for anything! Features rhinestone studded detailing on toe Mesh material on rest of shoe Middle ankle strap Man made materials.
DION8 BLUE WOMEN'S FLAT Man made materials.
These beautiful heels will put you a fashion step above the rest! Features a transparent cut-out upper with slingback heel Open peep toe, single sole and stiletto heel Man made...
EMILIA BLUE WOMEN'S HEEL Man made materials. Approximate heel height Approximate platform height
These breezy lace flats are just what you need to start your spring wardrobe! Features a lace upper with sequin embellishments Rope espadrille trim Man made materials.
Strut your stuff in these casual and cute wedges! Features an open toe and a cork-wrapped platform wedge silhouette. A faux leather upper with stud detailing along each side of...
While everyone else is stressing out to find the perfect shoe this holiday season, you'll be feelin' fine knowing these babies are in your closet. Features an open toe and...
FLEXIBLE01 NAVY WOMEN'S FLAT Man made materials.
Shopping Bag
Orders with Ground Shipping typically take between 2 to 3 business days to be processed and shipped. Standard Ground Shipping is an estimated delivered time and is not guaranteed to be delivered within the 4 to 7 business days. Expedited orders placed before 9:00a.m. PST will be shipped the same day. Weekends and holidays are excluded from processing and shipping times, so please account for non-business days when choosing your shipping method. You will receive an email with tracking information when your order has been shipped.
What do you charge for shipping?
Shipping charge is calculated at time of purchase.
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Yes, we offer Expedited Shipping options to ensure you receive your Wholesale Fashion Shoes order when you need it. All expedited orders confirmed before 9:00a.m. PST will be processed the same day pending credit card verification. Please note the day your order is packed and shipped is not counted as a day in transit.
**Expedited Shipping is only valid for orders shipped within the Continental United States.
Expedited orders will arrive within the number of business days designated by your shipping selection. To determine shipping days, begin with the first business day after your order is shipped. Orders placed before 9:00a.m. PST will be shipped out the same day. Orders placed after 9a.m. PST will be processed and shipped the following day.
Do you ship to an alternate address or a P.O. Box?
Yes, we ship to alternate addresses and P. O. Boxes.
Once I've placed my order, how long will it take to arrive?
Orders are typically shipped within 2 to 3 business days, and standard Ground Shipping orders arrive in 4 to 7 business days. Standard Ground Shipping is an estimated delivered time and is not guaranteed to be delivered within the 4 to 7 business days. You will be emailed a tracking number once your order has been shipped, allowing you to track your package progress and obtain a scheduled delivery date. For orders shipped outside of the continental United States please allow 10 to 20 business days for delivery.
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International orders are shipped via UPS and USPS and will be delivered into the responsibility of your national postal carrier. When your order ships from our warehouse, you will be provided with a tracking number within your confirmation email. You may copy and paste your tracking number into the ups.com or usps.com website to find any tracking information available for your package.
For international orders will there be additional duties and taxes on my order once it is delivered?
Yes. Unfortunately, we are not in control of the duties and taxes imposed on your order. Duties and taxes will likely be charged on the items you order. If duties and taxes are placed on your package by customs officials, the fees will be your responsibility.
What happens if I refuse the package?
If your package cannot be delivered or is unclaimed or refused, you are responsible for the following: Original and return shipping charges Duties, taxes, and/or customs charges that are incurred on the package for both the original and return shipments.


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Is Ross incorrect or missing key business information? Update your Hotfrog listing today.
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Hotfrog Singapore provides information regarding Ross in Singapore. Ross is located at The Show Producers 603 Senja Road 03-61, Singapore 670603 and provides Logo services. Contact them on (+65) 9796 7535 or by visiting them on their website http://www.showproducers.com.sg.
Is Ross in The Show Producers 603 Senja Road 03-61, Singapore 670603 your business? Claim your listing and attract more leads by adding more content, photos and other business details.
We have more Logo services in Singapore available on Hotfrog Singapore. You can update your search for Logo by location, keyword or service options.
rf 6re d Adam Road Singapore 286654
NO.20 Building Zone Adam Road Singapore 286657
120 Adam Road Singapore 289899
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This project received 5 bids from talented freelancers with an average bid price of $5 USD / hour.Get free quotes for a project like this
Project Budget$2 - $5 USD / hour
Total Bids5
Project Description
Now rest to eliminate the scrolling in the iframe when the search is done.
The iframe should be full screen.
In our page there are two scrolling.
I'd like to have the only one in the main page.
To see what I mean please make a search in [url removed, login to view] , that uses the same booking engine.
Skills Required
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Does this activity require advanced planning, ticketing or reservations?
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Is this attraction popular with tourists?
Is this attraction a good place to visit on a honeymoon?
Is this attraction a romantic spot to visit?
Does this attraction provide visitors with a taste of the local culture?
Does this attraction require above average amounts of physical activity (long walks, climbs, stairs or hikes)?
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Thanks for helping!
A truly proffesional company worth every euro you pay for their services. Definitely would use again on my next visit to sicily. All credit to Christian Guardione ! He made our...
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A truly proffesional company worth every euro you pay for their services. Definitely would use again on my next visit to sicily. All credit to Christian Guardione ! He made our trip stress free, interesting and entertaining ! If you go to rome you have to meet the pope, if you go to Taormina you have to meet Christian Guardione...
I read reviews about New Travel on other sites, before they had their Tripadvisor site, and so booked round-trip transfers between the Catania airport and Taormina. The pick up was flawless. But the return trip demonstrated a truly outstanding commitment to the customer: there was a very heavy, sudden rainstorm that flooded roads and stopped traffic for several hours, just...
I was recently in Sicily for a short New Year break. On the day we were due to travel home, there was incredibly heavy snow - 8 inches deep - and there was no traffic at all on the usually busy steep road to our hotel. In our minds we were resigning ourselves to possibly not travelng because the roads...
Found this website online and it was easy to book transfers from Catania airport to Taormina. Pick up and collection was prompt and Christian gave all the information needed. I would recommend the service
great service and found reliable,contacted through email with no problems,i had 5 pick ups for different times and flights all was aranged and executed perfectly thanks to Chiristian
Velmi rychly a pohodlny transfer z letiska,s prijemnym soferom,do miesta ,kde je tazko dostat sa verejnou dopravou.
Perfect transfer from the airport, kind driver, to the spot where public transport is not provided.
Christian was great to deal with via email arranging a transfer from Catania airport to Taormina for my wife and I. He was very knowledgeable and since he is also a part time New Yorker we fit right in. Would definitely use again thanks!
We hired New Travel Services for airport transfers to and from Catania Airport to our hotel in Taormina. I cannot say enough good things. Our flight into Catania was delayed and I was worried that because I couldn't get in touch with Christian at New Travel, the driver would leave the airport before we landed. I didn't have to worry...
We had Christian drive us at 4.30am to the airport. He arrived early and his car was spotless and new. He was very friendly and we chatted the whole hour long trip. I would highly recommend this service. Thanks Christian.
Our very courteous driver was waiting for us on arrival. Lovely immaculate vehicle and a very smooth ride. Arrived in a horrible downpour and staying in an apartment in Ortigia. Driver went over and above of his way to ensure that he found the lady waiting for us to take us to the apartment. Email queries and booking were dealt...
Own or manage this property? Claim your listing for free to respond to reviews, update your profile and much more.
Can you tell me what the cost of the trip to etna cost please
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Howard Johnson Inn - North Platte, North Platte
- Free continental breakfast, free WiFi, and free parking
Main amenities
- 74 guestrooms
- 24-hour front desk
- Air conditioning
For families
- Microwave
- Television
- Cable TV service
- Free self parking
What's around
- Fort Cody Trading Post (0.6 mi / 1 km)
- North Platte Area Children's Museum (1 mi / 1.6 km)
- Union Pacific Railroad Bailey Yard (1 mi / 1.6 km)
- America's 20th Century Veterans' Memorial (1.2 mi / 1.9 km)
- Cody Go Karts, Inc. (1.2 mi / 2 km)
Howard Johnson Inn - North Platte, North Plattefrom $47
- Standard Room, 1 King Bed, Smoking
- Business Room, 1 King Bed, Non Smoking
- Standard Room, 2 Queen Beds
- Standard Room, 1 King Bed
- Standard Room, 2 Queen Beds
- Business Room, 2 Queen Beds, Non Smoking
- Standard Room, 1 Queen Bed
- Standard Room
- One Queen
- Business Room, 1 King Bed
- Room, Non Smoking (2 King Beds)
More great choices
At a glance
Key facts
Hotel size
- This hotel has 74 rooms
- Check-in time starts at 3 PM
- Check-out time is 11 AM
Required at check in
- Credit card or cash deposit required
- Government-issued photo ID required
Travelling with others
- Pets allowed *
- Restrictions apply *
- Free WiFi in public areas
- Free WiFi in rooms
- Free self parking
- RV/bus/truck parking
Nearby Two Star North Platte hotels
In the hotel
- Free continental breakfast daily
- 24-hour front desk
In the room
- Air conditioning
- Cable TV channels
- Free WiFi
- Free local calls
- Microwave
- Access via exterior corridors
Nearby hotels
Also popular with travelers from the USA
Howard Johnson Inn - North Platte, North Platte's small print
Also known as
- Howard Johnson Inn North Platte
- Howard Johnson North Platte
Construction is underway at a neighboring building and there may be noise disturbance from the construction work.
Pet-friendly rooms can be requested by contacting the property at the number on the booking confirmation.
Optional extras
Pets are allowed for an extra charge of USD 20.00
We have included all charges provided to us by this hotel. However, charges can vary, for example, based on length of stay or the room you book.
Recent reviews
Good 3.0 /5 from 155 reviews
Just needed a place to sleep on our way passing through town. Clean and comfortable!
Nice motel. Friendly front desk staff.
This hotel has been remodeled. Rooms are really nice. I've stayed several times and it's always clean. Some areas are not quite finished. Mainly parking lot and pool, but it's never affected my stay. Nice and quiet, close to everything. Love this hotel.
Rooms are remodeled. Everything is brand-new. Beds are really comfortable all new mattresses and every room has a nice little kitchenette in it all new.
All good. Hotel under renovation. Room was 95% done. Need to do a final construction clean..e.g.paint all over toilet paper holder. Also a spider on wall. Will be very good with final touches. Breakfast ok..
Is the description of this hotel not correct? Tell us


text: Overlords Category page 6,715pages on this wiki Add New Page Edit Edit source History Talk0 Green Eyes ""Purple Eyes" was a Gargantis proximae alive when the entire species was willingly assimilated... Purple Eyes Pages in category "Overlords" The following 2 pages are in this category, out of 2 total. G Green EyesP Purple Eyes Retrieved from "http://starcraft.wikia.com/wiki/Category:Overlords?oldid=196288" Ad blocker interference detected! Wikia is a free-to-use site that makes money from advertising. We have a modified experience for viewers using ad blockers Wikia is not accessible if you've made further modifications. Remove the custom ad blocker rule(s) and the page will load as expected. Categories: Zerg characters by breed Add category Cancel Save


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Eating Well With Diabetes: What's in Ann's and David's Refrigerators?
Sometimes, I hate food. I hate food when I've had dinner and have a low blood sugar and have to eat more. I hate eating in the middle of the night to correct for a low blood sugar and have to brush my teeth, again, before I climb back in bed. I want to eat what I want to eat without having to glance at the plate and carb count. In my body, eating and diabetes are in a constant fight!
In my teens, I got into a binge/purge relationship with food. Later, I told friends that God had made me diabetic, so I would not be anorexic. Food has been a necessary evil and I developed a mental game to keep myself healthy: make it a love relationship. Food can be a relationship that pleases, satisfies and fulfills. Learning about food and a culture's history with food is to learn about their health habits.
For example, a client told me about bitter melon. Bitter melon is a favorite food in India and it is revered as "diabetic ambrosia." Bitter melon is a highly bitter gourd, but with spices and yogurt turns into something delicious. The association with bitter melon to diabetes is that it helps increase insulin sensitivity.
Living with diabetes is a life long process of learning. One of the best short cuts to learning the tricks to living with diabetes is talking with someone who has successfully mastered the art!
In my ever-growing interest in low carb eating, I asked my friend, David Mendosa, to join me in a project. I wanted to sneak a peek in his fridge and compare it to mine!
I thought there would be glaring differences, but there were not! We both had condiments, spices and cooking basics, but not a lot of junk food. We both tend to shop frequently, because we buy fresh. I hit my farmers market twice a week and I shop for specific ingredients, like meat and the vegetables the day I make the recipe.
I had a few leftovers, one from Chinese take out, which we do once in awhile, but not on a regular basis, and I had veggie leftovers from a party the weekend before the video shoot. I made the joke about the Vodka, which has been sitting in my freezer for years and I sort of forget about it.
What I learned is that my fridge is not so different from David's. Low carb does not strip you of loving cooking; it actually enhances the cooking experience because it requires adding flavor that gives new ideas to flavoring other dishes. It does not take me back to hating food, but, instead, encourages lingering conversation about tasting and creating a wonderful dinner with friends!
Cheers, David, and I hope we get to share a meal together soon!


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It is used as an intermediate in organic syntheses
A. El Akkaoui.; J. Koubachi.; S. El Kazzoulia.; S. Berteina-Raboin.; A. Mouaddib.; G. Guillaumeta. Efficient and regioselective functionalization of imidazo[1,2-b]pyridazines via palladium-catalyzed cross-coupling reaction and SNAr.Tetrahedron Lett. 2008, 49 (15), 2472-2475.
Ken-ichi Kusakabe.; Nobuyuki Ide.; Yataro Daigo.; Takeshi Itoh.; Takahiko Yamamoto.; Hiroshi Hashizume.; Kohei Nozu.; Hiroshi Yoshida.; Genta Tadanp.; Sachie Tagashira.; Kenichi Higashino.; Yousuke Okano.; Yuji Sato.; Makiko Inoue.; Motofumi Iguchi.; Takayuki Kanazawa.; Yukichi Ishioka.; Keiji Dohi.; Yasuto Kido.; Shingo Sakamoto.; Shigeru Ando.; Masahiro Maeda.; Masayo Higaki.; Yoshiyasu Baba.; Yusuke Nakamura. Discovery of Imidazo[1,2-b]pyridazine Derivatives: Selective and Orally Available Mps1 (TTK) Kinase Inhibitors Exhibiting Remarkable Antiproliferative Activity. J. Med. Chem. 2015, 58 (4),1760-1775.
Hazard Statements: H315-H319-H335
Causes skin irritation. Causes serious eye irritation. May cause respiratory irritation.
Precautionary Statements: P261-P280-P305+P351+P338-P304+P340-P362-P312-P321-P405-P403+P233-P501a
Avoid breathing dust/fume/gas/mist/vapours/spray. Wear protective gloves/protective clothing/eye protection/face protection. IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. IF INHALED: Remove to fresh air and keep at rest in a position comfortable for breathing. Take off contaminated clothing and wash before reuse. Call a POISON CENTER or doctor/physician if you feel unwell. Specific treatment (see label). Store locked up. Store in a well-ventilated place. Keep container tightly closed. Dispose of contents/container in accordance with local/regional/national/international regulations.


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Southern Gospel
Whatever The Road
Jason Crabb$9.99Add Your ReviewWhatever The Road is full of heartfelt songs that showcase a fresh adult contemporary and pop sound from Jason, but still maintains the high caliber of vocal prowess that his fans and peers have come to expect. Jason Crabb's powerful voice brings people with him through them... Learn More
Every Hallelujah
Canton Junction$11.99Produced by award-winning musician Garry Jones, and featuring powerful new songs alongside well-loved classics, Every Hallelujah is a perfect reflection of both the talent and heart of Canton Junction. The wide array of songs selected showcases the remarkable versatility and... Learn More
Just Sing
Amber Nelon Thompson$13.99Add Your ReviewFrom light-hearted fun melodies to relevant lyrics and powerhouse ballads, Amber has grown into an incredibly talented soloist, in addition to traveling full-time with her family, the Nelons. Just Sing offers wonderful songs to sing along with and reflection.Track ListSing-a... Learn More
Pray Now
Karen Peck & New River$13.99Add Your ReviewThe award-winning trio Karen Peck & New River have a long history of album titles calling listeners to take action. The trend continues with their latest album, Pray Now. The group speaks of the power of prayer and the many ways in which it has touched their lives person... Learn More
David Phelps$13.99GRAMMY®-nominated, classically trained tenor David Phelps showcases his award-winning voice and three-octave range on his all-new recording, Freedom. Featuring unique arrangements of cherished gospel classics such as "We Shall Behold Him" and "Ain't No Grave" as w... Learn More
Through the Fire: The Best of Jason Crabb
Jason Crabb$13.99Add Your ReviewOne of Christian music's most celebrated and awarded artists, Jason Crabb is known for his heartfelt deliveries and wide-ranged, powerhouse vocals. For two decades he has blurred the style lines of Christian music, combining a downhome gospel sound with contemporary arrang... Learn More
Icon: Gaither Homecoming
Bill Gaither, Bill & Gloria Gaither and Their Homecomi$7.99Add Your ReviewRepresenting the brightest moments from leading musicians with large catalogs, the Icon series gathers signature songs from legendary Christian artists. The Gaither Homecoming album features the music of Southern Gospel's first family, The Gaithers, and the talented group of... Learn More
The Best Of Gaither Homecoming: The Millennium Collection
Various Artists$5.00Enjoy some of the most moving numbers from over 25 years of Gaither HOMECOMING concerts and recordings. From the jubilant sounds of "Highway To Heaven" to the tender harmonies of the Gaither Vocal Band and the rich tones of the legendary Cathedrals, this must-have collec... Learn More
A New Chapter
The Jim Brady Trio, Jim Brady$13.99Add Your ReviewThe highly-anticipated debut album from the Jim Brady Trio, A New Chapter, is finally here!! Track Listing: God Of What's To Come You Can Depend On Jesus The Greatest Of All Miracles Steppin' Out In Faith On My Way Home Good Lord Willing The Love Of God When He Sa... Learn More
Forever: 80th Anniversary Recording
Blackwood Brothers$13.99Add Your ReviewThe Blackwood Brothers celebrate their 80-year anniversary with Forever, comprised of seven new songs and three older favorites. The group members are Billy Blackwood, Michael Helwig, Wayne Little and Butch Owens. Track List You Can Find What I Found I'll Fly Aw... Learn More


text: What year of Primary school did your child have actual text books at school? I've just got DS's stationery/book list for next year (year 2) and there is only 1 text book. I just assumed they would have more but I am basing that on what I remember at Primary school which was back in the *ahem* 1970s.


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From early childhood, when I insisted on integrating the Catholic School Boys' Playground, I've been a feminist. Using my pen, I've written scholarly, mass market books, and articles concerning inequalities of gender, race, and class. This site introduces many of these writings. I first explored these elements while a social researcher at Johns Hopkins University.
At Sonoma State University students fostered deep interest in women's history, so I shifted to writing biographies. I was fascinated by the lives of women connected to noted men. Living near Jack London State Historic Park, I started with London's wife Charmian Kittredge. Then I examined several generations of women in two prominent families: Vanderbilt and Rockefeller. Returning to London, I explored all the women connected to him: mother, stepsister, wives, friends.
My latest book hit the shelves and readers this summer: Slanderley: Love and Death in Cornwall. A spoof, it is solely to entertain while it mocks the British class system.
E-MAIL is the quickest way to contact me.
Visit my blog, Charting Lives: biographymemoir.net
My Amazon Author Page offers more biographical background.
Also see my Goodreads Author Page for my book reviews.


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Hotels in Koscian
Hotel reservation
Hotel rooms in Koscian
There are not so many hotel rooms in Koscian, just 6, still everyone can find an offer to suit his choice. The most common offers in this city are 3 и 4 stars, they count 1 out of 6, and their prevalent location is central district. According to our practice, it is the most profitable to book a hotel in the south of Koscian, as it is the location of the hotels with optimal cost and quality offers along with the cheap hotels. Taking into account the small size of the city, there is no need to dwell hotel reservation on the location: the road to the city center would take less then half an hour, so one can book a hotel in any district of Koscian. The most populated with hotels district of Koscian is the south, 66% of cheap hotel rooms are concentrated here. Koscian is a truly multifaceted city, here everyone can find a hotel of his choice: a business person, a young couple or a family with little children. Take a look at our selection of the cheap hotel rooms in Koscian to make a well-informed choice for your reservation!
Koscian cheap hotels
Guest Houses
All cheap hotels in Koscian
Best hotels in Koscian
Hotels in Koscian are spread around the city within the distance of 10.7 kilometers. The most popular accommodations in Koscian is
Palac Szczepowice
, 2 stars hotel located in a 10.7 kilometers from the city center.
The best hotels are here and now. Try them!
All cities in Poland


text:
Home » Entertainment » Party Goods » Costume SuperCentre Canada Affiliate Program
The Costume SuperCentre Canada affiliate program directs your patrons to one of the world's newest and most exciting online costume and party supplies superstore, offering over 30,000 different products, including child and adult costumes, accessories and holiday decorations, as well as every imaginable licensed and unlicensed kids and adult party themes.
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Promote this program and similar ones on your website today. Register online, it's 100% free to join.
Do you have a business for our publishers to promote? Then become an advertiser today, it's
easy to get started.
Copyright © 2017 FlexOffers.com Affiliate Programs. All rights reserved.


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Brett Hartmann: Ex-Texans Punter Sues Reliant Owners Over Career-Threatening Injury
Former Houston Texans punter Brett Hartmann is suing the owners of Reliant Stadium, and the company that provides the grass playing surface, for negligence in a career-threatening knee injury he sustained when his foot got caught in a seam during a game last December.
Unlike other stadiums, where grass is laid out in a single piece, Reliant's field is laid out in approximately 1,200 8' x 8' squares, whose seams can -- and have -- posed serious threats to players' safety, Hartmann's attorney, Gene Egdorf, said at a press conference today.
Hartmann was already NFL's leading rookie punter by the time of the Texans' December 4, 2011, game against the Atlanta Falcons, when his foot got caught in a seam in the last minute of the game, according to the lawsuit. (The Texans won 17-10).
He was cut from the Texans in August 2012 after being diagnosed with a torn ACL and a fractured lower leg.
Pennsylvania-based SMG, which provides the grass, "had a legal duty...to reduce or eliminate any unreasonable risks of harm and to warn [players] of any premises defects," the suit claims. The Harris County Convention and Sports Corporation, which owns Reliant, has "the duty to provide these players with a reasonably safe playing surface, including preventing unreasonable risks of harm."
Additionally, the suit alleges that the field was already torn up from other events "in the days and weeks prior to Hartmann's injury," including high school games the night before.
"Sadly, several players other than Hartmann have suffered serious injuries solely attributable to the field, including New Englands Patriots wide receiver Wes Welker, who suffered a serious knee injury in 2009," according to the suit. "Three-time Super Bowl winning coach Bill Belichick was highly critical of the field surface, saying 'the turf down there is terrible...I really think it's one of the worst [fields] I've seen.' Another critic is former Tampa Bay and Indianapolis Coach Tony Dungy, also a Super Bowl winner and now an analyst with NBC. Dungy has been quoted as stating the Colts were 'definitely concerned about the injury factor' when playing on Reliant's field."
Video from the game proves the seam caused Hartmann's injury, according to the suit.
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Egdorf said that, in addition to seeking unknown monetary damages, "We hope this gets attention to where we don't lose any more of our athletes at Reliant Stadium."
Hartmann, who now lives in Wisconsin with his fiance Lizzy Burkwald, said he's being treated by doctors in Milwaukee and Green Bay.
We left messages with the HCCSC and SMG and will update accordingly.
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For a while now, Kate and I have been spending a lot of our weekends fixing up my mother in law's house to get it ready to sell. It went on the market on Thursday and there's an open house today (in case anyone is looking for a house in Arlington/Falls Church!). A long string of home improvement projects has finally come to an end!
This is the patio, which we just finished up yesterday:
Current Links
20 minutes ago


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The bright fresh flavor of watercress follows its health benefits in Watercress Soup with Toasted Almonds—tons of bone-strengthening calcium in every savory spoonful.
Makes 3 servings
+ Add To Shopping List
2 tablespoons extra-virgin olive oil
2 medium onions, chopped
1 garlic clove, minced
2 medium potatoes, diced
3 cups low-sodium vegetable broth
3 bunches watercress, roughly chopped
1/4 cup plus 3 TBSP fat-free Greek yogurt
1/4 teaspoon salt
1/4 teaspoon freshly ground black pepper
2 tablespoons toasted sliced almonds
Prep: 15 Minutes
Cook: 25 Minutes
1. In large saucepan, heat oil over medium heat. Add onions and garlic; cook 3 minutes. Add potatoes; sauté 3 minutes. Add broth; simmer, covered, 15 minutes or until potatoes are tender.
2. Add watercress to pan; cook 3 minutes, until wilted. In batches, purée soup in blender; return to pan. Whisk in 1/4 cup yogurt, salt, and pepper; reheat gently (do not boil). Serve with remaining 3 TBSP yogurt and almonds.
Created date
June 2012
Nutritional Information
Calories 261
Fat 11.1 g
Satfat 1.5 g
Monofat 7.8 g
Polyfat 1.5 g
Protein 10 g
Carbohydrate 32 g
Fiber 4 g
Cholesterol 0.0 mg
Iron 2 mg
Sodium 414 mg
Calcium 287 mg


text:
Striatal medium spiny neurons (MSNs) receive glutamatergic afferents from the cerebral cortex and dopaminergic inputs from the substantia nigra (SN). Striatal dopamine loss decreases the number of MSN dendritic spines. This loss of spines has been suggested to reflect the removal of tonic dopamine inhibitory control over corticostriatal glutamatergic drive, with increased glutamate release culminating in MSN spine loss. We tested this hypothesis in two ways. We first determined in vivo if decortication reverses or prevents dopamine depletion–induced spine loss by placing motor cortex lesions 4 weeks after, or at the time of, 6-hydroxydopamine lesions of the SN. Animals were sacrificed 4 weeks after cortical lesions. Motor cortex lesions significantly reversed the loss of MSN spines elicited by dopamine denervation; a similar effect was observed in the prevention experiment. We then determined if modulating glutamate release in organotypic cocultures prevented spine loss. Treatment of the cultures with the mGluR2/3 agonist LY379268 to suppress corticostriatal glutamate release completely blocked spine loss in dopamine-denervated cultures. These studies provide the first evidence to show that MSN spine loss associated with parkinsonism can be reversed and point to suppression of corticostriatal glutamate release as a means of slowing progression in Parkinson's disease.
The motor symptoms of Parkinson's disease (PD) are caused by striatal dopamine insufficiency. The dopamine innervation of the striatum arises from neurons in the substantia nigra (SN) and contributes to a characteristic synaptic triad involving SN and cortical afferents and the dendrites of striatal medium spiny neurons (MSNs). The synaptic architecture of these three elements involves a dopamine synapse with the neck of MSN dendritic spines and a corticostriatal terminal synapsing onto the spine head (Bouyer et al. 1984; Freund et al. 1984; Smith et al. 1994). This synaptic arrangement suggests that dopamine modulates the influence of corticostriatal glutamatergic axons on MSNs. Consistent with this inference are data indicating that dopamine D2 heteroreceptors on the terminals of corticostriatal axons tonically inhibit release of glutamate from these axons (Bamford, Robinson, et al. 2004). Thus, in the dopamine-depleted striatum, excess glutamatergic drive from corticostriatal terminals, coupled with other mechanisms intrinsic to the MSNs that are regulated by dopamine (Day et al. 2006), results in hyperexcitable MSNs (Florio et al. 1993; Cepeda et al. 2001). Moreover, the loss of dopamine on the spine neck removes a modulatory influence that determines if cortically derived signals invade the dendritic shaft.
Dendritic spines are remarkably plastic structures, changing in number and shape over time scales ranging from seconds to years (Crick 1982; McKinney 2005; Alvarez et al. 2007; Harms and Dunaevsky 2007; Chen et al. 2009). Long-lasting changes in dendritic spine number have been documented in a number of neuropsychiatric disorders (Ferrante et al. 1991; Kaufmann and Moser 2000; Hill et al. 2006; Kalivas 2009; Tackenberg et al. 2009). Among these disorders is PD, in which striatal dopamine depletion elicits dystrophic changes of MSN dendrites. Both postmortem studies of PD as well as studies in animal models of parkinsonism have reported a marked decrease in MSN spine density (McNeill et al. 1988; Ingham et al. 1989, 1993, 1998; Arbuthnott et al. 2000; Stephens et al. 2005; Zaja-Milatovic et al. 2005; Day et al. 2006; Villalba et al. 2009). While the primary cause of this dendritic remodeling is loss of dopamine signaling through the D2 receptor (Day et al. 2006; Deutch et al. 2007), it appears likely that changes in cortically derived glutamate contribute to the changes in MSN spines. Dopamine replacement treatment in PD patients or in animals with striatal dopamine depletion does not restore spine loss (Stephens et al. 2005; Zaja-Milatovic et al. 2005; Deutch et al. 2007), suggesting that the dopamine receptor is uncoupled from its intracellular effectors. This led us to hypothesize that manipulating corticostriatal glutamate release directly might reverse the MSN spine loss seen in the dopamine-denervated striatum.
Glutamatergic mechanisms are critically involved in determining both dendritic spine development and maintenance (Korkortian and Segal 2001; Passafaro et al. 2003; Lippman and Dunaevsky 2005; McKinney 2005; Bloodgood and Sabatini 2008). For example, glutamatergic signaling through N-methyl-D-aspartate (NDMA) receptors increases intraspinous calcium levels, which determines spine morphology (Segal et al. 2000). These considerations suggest that corticostriatal neurons play a central role in determining the structure of MSN dendrites.
A recent in vitro study that examined the role of corticostriatal projections in dendritic remodeling in the dopamine-denervated striatum reported that complete decortication prevents the development of spine loss on striatal MSNs in organotypic slice cocultures (Neely et al. 2007). However, the ability of decortication to "reverse" spine loss that has already been established, which is more relevant to treatment of PD, has neither been examined in these cultures nor in vivo. We therefore determined in vivo if decortication can reverse or prevent MSN dendritic spine loss in an animal model of parkinsonism.
In order to determine if the loss of MSN spines requires corticostriatal glutamate release and hence if cortical lesions may mitigate spine loss by suppressing glutamate release, we used organotypic slice co-cultures comprised of cortex, striatum, and ventrolateral mesencephalon (including the SN) to assess the effects of a metabotropic mGluR2/3 receptor agonist. Activation of these mGluRs, which are located on the presynaptic terminals of corticostriatal neurons (Testa et al. 1998), dampens glutamate release (Lovinger 1991; Calabresi et al. 1992; Lovinger and McCool 1995).
Materials and Methods
Adult male Sprague-Dawley rats (Harlan; Indianapolis, IN) were group-housed on a 12:12 light–dark schedule with food and water freely available. All studies were performed in accordance with the National Institutes of Health Guide for Care and Use of Laboratory Animals and under the oversight of the Vanderbilt University Animal Care and Use Committee.
Experimental Design
We first determined if focal lesions of the motor cortex in vivo could reverse spine loss that occurred in response to striatal dopamine denervation and in the next experiment determined if cortical lesions could prevent the development of MSN spine loss.
In the "reversal" experiment, 6-hydroxydopamine (6-OHDA) lesions of nigrostriatal dopamine neurons were made, and then 4 weeks later, when spine loss was established, the motor cortex was lesioned with ibotenic acid (IA). MSN spine loss is present starting about 2 weeks after striatal dopamine depletion and persisting for at least 12 months (Ingham et al. 1989; Deutch et al. 2007). Animals survived for 4 weeks after the cortical lesions before being sacrificed.
In the "prevention" experiment, striatal dopamine depletion was also accomplished by means of 6-OHDA lesions, and during the same surgery, IA was used to lesion the motor cortex. Animals were sacrificed 4 weeks later.
Surgical Manipulations
Animals were deeply anesthetized with isoflurane and burr holes made in the skull overlying the primary motor cortex and SN. Lesions of the motor cortex were performed by injecting 1.0 μL of 45 nM IA (Tocris, Ellisville, MO) into the M1 cortex (anteroposterior [AP]: +0.7; mediolateral [ML]: +2.0, +3.6; dorsoventral [DV]: −2.0, −2.3) at a rate of 200 nL/min. Control (sham) cortical lesions involved incision of the skin and placement of a burr hole.
Striatal dopamine denervation was accomplished by injecting 6-OHDA HBr (4.0 μg/μL free base; Sigma-Aldrich, St. Louis, MO) into 2 sites in the SN (AP: −5.4; ML: +1.0, +2.4; DV: −8.4) in a volume of 1.5 μL at a rate of 100 nL/min.
Organotypic Slice Cultures
Triple-slice cultures consisting of cortex, striatum, and ventrolateral mesencephalon (SN) were prepared from the brains of P1–P2 Sprague-Dawley rats (Harlan) following our previously described method (Neely et al. 2007). Two cultures were plated in each well. At 14 days in vitro (DIV), by which time the MSNs achieve a mature dendritic morphology (see Neely et al. 2007), the dopamine innervation of the striatum was denervated by treatment of the cultures with 15 μM 1-methyl-4-phenylpyridinium (MPP+) (Sigma-Aldrich). This concentration of MPP+ causes a selective loss of dopamine but not other neurons in the cultures (Neely et al. 2007). MPP+ was removed 24 h later and treatment with the mGluR2/3 agonist LY379268 (1.0 μM; Tocris) started, with the agonist being added to the cultures at the time of media changes (every other day over 14 days). Culture medium was collected at 14 DIV (just before MPP+ treatment) and again at 17 DIV and stored at −80 °C until subsequently assayed for the dopamine metabolite homovanillic (HVA) acid as an index of dopamine denervation. The cultures were harvested at 28–30 DIV for analysis of dendritic spine density.
We determined if adding an mGluR2/3 antagonist to cultures would block the ability of the agonist LY379268 to prevent spine loss in dopamine-denervated cultures. At 14–16 DIV, the cultures were treated with MPP+, which was removed 24 h later, at which time either the mGluR2/3 agonist LY379268 (1.0 μM), the antagonist LY341495 (0.2 μM), or both the mGluR2/3 agonist and antagonist were added to the culture media. The concentration of LY379268, which has at least an 80-fold higher affinity for group II mGluRs than other metabotropic glutamate receptors (Schoepp et al. 1999; Marek et al. 2000), was based on in vitro slice data from Marek et al. (2000) and Picconi et al. (2002). The concentration of the antagonist LY341495 (Monn et al. 1999; Schoepp et al. 1999) was also based on the data of Marek et al. (2000). The cultures were treated as described above, with the drugs replaced every other day for 14 days, at which time the cultures were harvested and diOlistically labeled.
Golgi Impregnation
Animals were transcardially perfused with a solution of 2.5% glutaraldehyde (EM Sciences, Hatfield, PA) and 2% paraformaldehyde (VWR, West Chester, PA) in 0.1 M phosphate buffer (pH 7.45). Brains were removed and the forebrains postfixed for 3 h. Coronal sections (150 μm) were cut on a vibrating microtome. The sections were then incubated in 1% osmium tetroxide (EM Sciences) for 40 min, after which sections were transferred to 3.5% potassium dichromate (Sigma-Aldrich) for 16 h in a humid chamber. The sections were then "sandwiched" between glass slides and incubated in the dark in 1% silver nitrate (Sigma-Aldrich) for 4–6 h. Sections were washed in water, mounted on 0.5% gelatin-coated slides, dehydrated, cleared, and coverslipped with DPX (Sigma-Aldrich).
DiOlistic Labeling of Cultures
Cultures were fixed in 1.5% paraformaldehyde in 0.1 M phosphate-buffered saline for 25 min and then diOlistically labeled with the carbocyanine dye CM-DiI (Invitrogen, Carlsbad, CA), following the general protocol of Gan et al. (2000), as modified by Neely et al. (2007, 2009). Cultures were then mounted in Prolong Antifade (Invitrogen).
Dendritic Analyses of Golgi-Labeled MSNs
Microscopic images were acquired by a digital camera coupled to a computer running the cell reconstruction software Neurolucida (Microbrightfield Inc., Williston, VT), using a 63× 1.4 planApo objective. The image was digitally magnified by a factor of 2 to yield a final magnification equivalent to a ×126 objective.
Data from animals with lesions that impinged on the corpus callosum were excluded from subsequent analyses, as were data from animals in which the lesions did not involve layer V, where the majority of cells that innervate the striatum are located.
Golgi-impregnated MSNs in dorsolateral striatum were reconstructed by a person unaware of the treatment conditions of the animals. Neurons were randomly selected from the M1-recipient zone of dorsolateral striatum, provided that the cells had a soma diameter of 12–17 μm and through a ×10 objective appeared to be well impregnated.
In a pilot experiment, we determined that dendritic spine density in control animals did not differ significantly at distances on the dendritic tree located 60–120 μm from the soma. We therefore measured dendritic spine density on dendritic segments 10–20 μm in length that were located 60–120 μm distal to the MSN soma. Dendritic spine densities were determined on branches of 4 primary dendrites from each reconstructed neuron, with at least 5 MSNs assessed in each animal (an average of 7.7 cells analyzed for each group in the prevention study and an average of 10.0 MSNs for each group analyzed in the reversal experiment). We analyzed MSNs located in the striatal zone that receives inputs from the lesioned motor cortex, as well in a second region, located ventromedial to the M1-innervated sector, that does not receive significant M1 inputs (see Fig. 1).
The striatal domain that received afferents from the lesioned areas of motor cortex was determined by iontophoretically depositing the tracer biotinylated dextran amine (BDA; molecular weight 10 000; Invitrogen) into the M1 cortex and subsequently assessing the distribution of anterogradely labeled axons in the striatum in 4 animals. A 10% BDA solution prepared in 0.1 M sodium phosphate was loaded into fiber-filled glass pipettes (25–30 μm outer diameter) and deposited into M1 (at the same coordinates at which IA was injected) using +5.0 μA pulsed (7 s on/off) current for 10 min. Animals survived for 7–10 days before being sacrificed. The results (data not shown) were consistent with previous reports (Hoffer and Alloway 2001; Ramanathan et al. 2002; Alloway et al. 2006) and indicated that one can reliably define the location in the striatum that receives inputs from a given zone of cortex, although the precise borders of the territory cannot be identified. We therefore assessed MSN dendritic spines in the M1-recipient zone of striatum and as a control site in a region ventromedial to the M1 zone that does not receive a significant density of inputs from the M1 cortex.
Dendritic Spine Analyses in DiOlistically Labeled Cultures
A confocal laser scanning microscope with a ×63 1.4 numerical aperture objective (with a ×2 digital zoom to yield a final magnification of ×126) was used to obtain z-stacks of MSN segments at 0.5-μm intervals. MSN spines were assessed on third and fourth order dendritic segments.
Assessment of Striatal Dopamine Depletion
The use of the Golgi method to impregnate MSNs precludes biochemical measurements of striatal dopamine concentrations. In order to assess the extent of the 6-OHDA lesion, striatal and midbrain sections were processed for tyrosine hydroxylase (TH) immunohistochemistry, using our previously described methods (Bubser et al. 2005). Only rats with ≤3 TH-immunoreactive axon segments per high-powered (×40) field in the dorsal striatum were included in the analyses (see Supplementary Fig. 1); SN dopamine neurons were almost entirely lost (see Supplementary Fig. 1).
In order to determine the extent of MPP+-induced striatal dopamine depletion in the cultures, we measured the concentration of the dopamine metabolite HVA in the culture media both immediately before and 48 h after MPP+ treatment. The medium was analyzed by high performance liquid chromatography with electrochemical detection, following our previously described procedure (Deutch and Cameron 1992). Briefly, 500 μL medium was added to 125 μL of 1 M perchloric acid solution containing 0.2 g/L NA2S2O5 and 0.05 g/L Na2-EDTA. The samples were centrifuged at 23 000 × g for 5 min, injected on a C18 column (Alltech, Deerfield, IL), and HVA measured using a 501A Coulochem detectror (ESA Biosciences, Chemsford, MA). HVA levels were expressed as pmol/mL medium. Because dopamine is rapidly oxidized in the culture media and therefore below detection thresholds in control cultures, we focused on the dopamine metabolite HVA, which is stable. Spine density in MSNs from cultures in which HVA levels were depleted by <70% were not analyzed.
Animals were transcardially perfused with 4% paraformaldehyde in 0.1 M phosphate buffer (pH 7.4). Forebrain and midbrain blocks of tissue were postfixed overnight and then cryoprotected in 30% sucrose for 2–4 days. Coronal sections (40 μm) were cut on a freezing microtome.
To assess the extent of cortical IA or SN 6-OHDA lesions, free-floating brain sections were processed as described previously (see Bubser et al. 2005), using mouse anti-NeuN (1:1000; Chemicon, Temecula, CA) to reveal the borders of the cortical lesions and mouse anti-TH (1:3000; ImmunoStar, Inc., Hudson, WI) to stain dopaminergic neurons.
Fluorojade C Staining
In order to determine if the cortical lesions resulted in any overt transsynaptic cell loss in the striatum, animals received IA injections of the motor cortex and were sacrificed at various times between 2 and 28 days after the cortical lesions. The brains were processed to stain degenerating neurons using Fluorojade C (FJC; Schmued et al. 2005). Animals were perfused with 4% paraformaldehyde and sections cut through the forebrain, mounted on 0.5% gelatin-coated slides, and dried overnight. Briefly, slides were incubated in basic ethanol solution (1% NaOH in 80% ethanol), dehydrated for 2 min in 70% ethanol, and then incubated in 0.06% potassium permanganate for 10 min. Slides were then incubated in 0.001% FJC (Chemicon) for 10 min. Sections were rinsed 3 times in water, dried overnight, and dehydrated and cleared in xylene before being coverslipped with DPX.
Data Analysis
In the in vivo studies, the average spine densities for each cell (determined from the analysis of 4 second- and third-order branches emanating from 4 different primary dendrites) were collapsed to yield a mean MSN spine density. In turn, these mean "per cell" spine densities (which averaged overall 8.8 MSNs/experimental group) were collapsed to generate a mean MSN value for each animal. This latter "per animal" MSN spine density value was used for subsequent statistical analyses by means of two-way analyses of variance (ANOVAs) and subsequent Bonferroni t-tests if warranted by significant main effects or a significant interaction. The degree of MSN spine loss in the non–M1-recipient zone of the striatum was analyzed relative to the 6-OHDA plus decortication group separately.
In the in vitro studies, MSN spine density values/neuron were determined, after which these values were collapsed to yield a single "per culture" value. These per culture values were then analyzed by two-way ANOVAs.
Characterization of M1 Motor Cortex Lesions
IA injections lesioned the M1 motor cortex (see Fig. 2); the lesions impinged medially on the M2 area, with some degree of lateral invasion into the forelimb region of the primary somatosensory cortex (see Fig. 2). Although the lesions sometimes involved areas adjacent to M1, for simplicity sake we will refer to the lesioned region as the M1 area. The IA injections did not result in cavitation, and NeuN staining revealed intact underlying tissue (see Fig. 2). In most cases, the lesion involved layers I–VI, although loss of cells in layer VI was variable.
FJC Staining
IA injections caused extensive neuronal loss in the vicinity of the IA injection, as reflected by a dense aggregation of cortical FJC-positive cells seen at 2 and 4 days postoperatively (see Supplementary Fig. 2). In contrast, at no time point up to 28 days after the IA injection did we observe any FJC-positive cells in the striatum of animals with M1 lesions, indicating that there was no transsynaptic loss of striatal neurons in response to cortical IA injections.
Cortical Lesions Reverse Dopamine Depletion–Induced Spine Loss
In this experiment, we assessed if decortication could reverse MSN spine loss that was caused by 6-OHDA lesions performed 4 weeks earlier. Cortical lesions significantly attenuated but did not totally reverse established MSN spine loss in the M1-recipient zone (omnibus ANOVA F3,21 = 7.98, P = 0.001), with a significant main effect of dopamine depletion (F1,21 = 20.2, P = 0.0002) but no significant interaction uncovered. Post hoc analyses revealed that striatal dopamine depletion resulted in a significant decrease in spine density (17.9%) compared with that seen in sham-lesioned control animals (P =0.007); cortical lesions alone did not change MSN spine density relative to control (sham lesioned) animals (Fig. 3). However, M1 lesions made 4 weeks after striatal dopamine denervation significantly attenuated the degree of MSN spine loss compared with the 6-OHDA-lesioned group alone (P = 0.008), with a 9.4% decrease in spine density relative to sham-lesioned rats. Thus, animals with striatal dopamine depletion suffered a loss of dendritic spines that was almost 50% less than that seen in animals without cortical lesions (see Fig. 4). The cortical lesions significantly attenuated MSN spine loss only in the M1-recipient zone of the striatum but not in the ventromedially adjacent striatal sector that does not receive significant M1 inputs (see Fig. 3).
Effects of Concurrent Cortical and 6-OHDA Lesions on MSN Spine Density
The omnibus ANOVA for the analysis of the effects of cortical lesions performed at the same time as 6-OHDA lesions was significant (F3,27 = 9.37, P = 0.0002), with a significant main effect of dopamine depletion (F1,27 = 23.88, P < 0.0001) but no significant cortical lesion × 6-OHDA lesion interaction. Post hoc tests revealed that striatal dopamine depletion in animals with an intact cortex significantly decreased MSN spine density in the M1-recipient zone of animals relative to control rats (18.6%, P = 0.0022). Spine loss in animals with both cortical and 6-OHDA lesions averaged 10.3%. Although spine loss was attenuated in the combined cortical + 6-OHDA lesions relative to the 6-OHDA-lesioned group alone, this effect did not reach statistical significance (P = 0.06) (see Fig. 5). In the non–M1-recipient zone of the striatum, there was no attenuation of spine loss (see Fig. 5).
Metabotropic Glutamate Receptors Regulate Spines
The treatment of cultures with MPP+ caused a marked (89.4%) decrease in the concentration of the dopamine metabolite HVA in the culture medium (t32 = 17.73, P < 0.0001), consistent with extensive striatal dopamine denervation. A two-factor (dopamine innervation × drug treatment) ANOVA was used to assess the effect of the mGluR2/3 agonist on MPP+-induced spine loss, yielding an overall F3,40 = 6.86 (P = 0.0008). Main effects of both dopamine innervation (F1,40 = 5.33, P = 0.0262) and drug treatment (F3,40 = 9.83, P = 0.0032) were uncovered and a strong trend toward an interaction (F1,40 = 4.08, P = 0.0502). Post hoc analyses found a significant decrease (26%) in MSN spine density compared with vehicle-treated cultures (P = 0.0032; see Fig. 6). While treatment with the mGluR2/3 agonist LY379268 had no effect on spine density in MSNs from cultures with an intact striatal dopamine innervation, the mGluR2/3 agonist completely prevented MSN spine loss in MPP+-treated cultures such that spine density was not significantly different from control (intact dopamine innervation + vehicle treated) cultures (see Fig. 6). Representative diOlistically labeled MSN dendritic segments are shown in Figure 7.
In order to determine the specificity of the mGluR2/3 agonist LY379268, we assessed if treatment with the mGluR2/3 antagonist LY341495 would block the actions of the group II metabotropic glutamate receptor agonist. As expected, post hoc analyses revealed that MPP+ treatment significantly decreased spine density (P = 0.0104). The antagonist alone caused a significant decrease in spine density (P = 0.0365), while the combined treatment of the antagonist plus agonist in dopamine-depleted cultures did not significantly differ from the MPP+-treated cultures alone and thus completely reversed the protective effects of the agonist (see Fig. 8).
Lesions of the motor cortex reversed the loss of MSN spines that is seen in response to striatal dopamine denervation. This observation provides the first evidence that MSN spine loss, once established, can be reversed. Moreover, treatment with the mGluR2/3 agonist LY379268 completely prevented MSN spine loss in dopamine-denervated cultures, supporting the hypothesis that the mechanism by which cortical lesions attenuate spine loss is through decreased glutamate release from corticostriatal axons.
Effect of Cortical Lesions on MSN Spines in the Intact Striatum
We did not observe any effect of the cortical lesions on MSN spine density in animals with an intact striatal dopamine innervation. In contrast, some previous studies have reported that cortical lesions decrease MSN spine loss (Kemp and Powell 1971; Cheng et al. 1997). However, these earlier studies examined the effects of cortical aspiration lesions, which can easily damage the underlying striatal tissue, either by direct extension or secondary to edema. Moreover, Cheng et al. (1997) noted that the decrease in MSN spine density was transient, being maximal at 10 days postoperatively and returning to baseline levels by 20 days after the lesion, consistent with resolution of edematous changes. Because we examined animals at 4 weeks after the cortical lesion, we cannot exclude the possibility that there was a transient decrease in spine density in animals with IA cortical lesions that resolved by 28 days postoperatively. However, because dopamine denervation–induced MSN spine loss persists for at least 1 year (Ingham et al. 1989), the reversal of spine loss that we observed after cortical lesions cannot be due to recovery from the dopamine depletion.
To minimize the possibility of striatal damage by cortical lesions, we used IA to lesion the cortex. Although excitotoxic lesions can cause distant neuronal loss, we did not observe FJC-positive MSNs at any time up to 28 days postlesion. Moreover, we found that spine density was unchanged in animals subjected to cortical IA lesions 4 weeks earlier, suggesting that the cortical lesion did not compromise the structural integrity of MSNs. We measured MSN dendritic spine changes at 4 weeks after cortical lesions, that is, at a time point at which there was no evidence of FJC-positive degenerating striatal neurons. We did not determine if striatal cells degenerate after periods longer than 28 days, but there are no published data pointing to such changes in response to cortical lesions in adult animals.
Effect of Cortical Lesions on Spines in Dopamine-Denervated Striatum
A previous study in organotypic slice cocultures found that complete ablation of the cortex performed at the same time as MPP+ treatment to lesion the nigrostriatal dopamine neurons completely prevents MSN spine loss (Neely et al. 2007). In our in vivo prevention experiment, we observed a strong trend that did not reach statistical significance (P = 0.06). Because the in vitro study of Neely et al. (2007) indicated that total decortication completely prevented the development of dendritic spine loss in the dopamine-denervated striatum, and because we found that the mGluR2/3 agonist prevented spine loss from developing, it is likely that the nonsignificant trend we observed in animals with focal cortical lesions represents a type II (false negative) error.
An advantage of organotypic cultures is the ability to completely ablate the cortex, resulting in a near total glutamatergic denervation of the striatum (the thalamic intralaminar nuclei were not included in the cultures). In contrast, complete removal of glutamatergic projections to the striatum in vivo is not feasible, with a substantial glutamatergic innervation from the thalamus as well as some other sites being present. We therefore conducted both in vivo and in vitro studies, with the former examining the effects of a cortical lesion that left intact glutamatergic projections from the thalamus and the contralateral cortex, both of which synapse onto dendritic spines (Freund et al. 1984; Smith et al. 1994; Lacey et al. 2007). Despite not eliminating all glutamatergic inputs, we found that focal cortical lesions in vivo significantly reversed dopamine denervation–induced MSN spine loss and tended to prevent the development of spine loss. The significant but incomplete reversal of spine loss is most likely due to remaining glutamatergic inputs. The vesicular glutamate transporter 2 (VGluT2) is abundantly expressed by thalamostriatal but not corticostriatal neurons (Kaneko and Fujiyama 2002). Raju et al. (2008) found no change in striatal VGluT2 in dopamine-denervated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated primates, consistent with intact striatal glutamate inputs from the thalamus. The other major source of glutamate inputs to the striatum is the cortex. Previous studies have noted that axonal sprouting from the contralateral cortex partially reinnervates the denervated striatum (Napieralski et al. 1996; Hughes-Davis et al. 2005). The presence of some sprouting of inputs from the contralateral cortex, coupled with an intact thalamostriatal glutamatergic system, probably accounts for the significant attenuation but not complete reversal of dopamine depletion–induced spine loss in MSNs. These considerations suggest that our studies with unilateral cortical lesions represent a conservative test of the hypothesis that cortical denervation prevents and reverses spine loss in vivo.
Because there are no clearly defined boundaries that distinguish the M1-recipient zone from adjacent striatal tissue that does not receive M1 inputs, we restricted our analysis to a fairly conservative definition of the striatal M1-recipient zone, based on our anterograde tracer studies as well as published data on the striatal projections of the motor and adjacent cortices (Alloway et al. 2006). The cortical lesion attenuated the loss of dendritic spines only in this M1-recipient zone of the striatum. Spine densities of MSNs located in an area of the striatum ventromedial to the M1-innervated region did not differ significantly from those seen in animals with 6-OHDA lesions but an intact motor cortex. These observations argue that we were able to define accurately the striatal territory receiving inputs from the lesioned cortex.
Mechanism of Action of Cortical Lesions
A variety of in vivo and in vitro data suggest that striatal dopamine depletion increases glutamate release from corticostriatal terminals (Florio et al. 1993; Meshul et al. 1999; Cepeda et al. 2001; Bamford, Robinson, et al. 2004; Bamford, Zhang, et al. 2004; Day et al. 2006). Dendritic spine formation and maintenance are determined largely by changes in intracellular calcium levels, including NMDA-driven increases in calcium levels. Accordingly, we hypothesized that one mechanism that contributes to dopamine depletion–induced MSN spine loss is the loss of tonic dopaminergic inhibition of the D2 heteroreceptor on corticostriatal terminals, leading to increased glutamate release (Bamford, Zhang, et al. 2004), which in turn increases intraspinous calcium and culminates in spine loss. Thus, we anticipated that cortical lesions would reduce excess glutamate release from cortical axons and thereby attenuate MSN spine loss.
Group II metabotropic glutamate (mGluR2/3) receptors, which are located presynaptically on corticostriatal terminals (Testa et al. 1998), are release-modulating autoreceptors. We therefore treated organotypic slice co-cultures with a mGluR2/3 receptor agonist to dampen glutamate release from disinhibited corticostriatal axons. In mature cultures, there are both extensive cortical and midbrain dopamine projections to the striatum (Neely et al. 2007; Snyder-Keller et al. 2008), and one sees both spontaneous and cortically evoked activity of MSNs (Plenz and Kitai 1998; Snyder-Keller et al. 2008), indicating intact functional connections between the cortex and striatum in the cultures. The use of these cultures allowed us to determine specifically if the loss of cortical glutamate, as opposed to glutamatergic afferents from other areas such as the thalamus, was responsible for preventing spine loss.
Treatment of dopamine-denervated cultures with LY379268 completely prevented the spine loss. It appears likely that the ability of LY379268 to block MSN spine loss is due to actions at mGluR2/3 sites. LY379268 is a preferential agonist at mGluR2/3 receptors (Schoepp et al. 1999; Imre 2007). The agonist inhibits forskolin-stimulated cyclic adenosine monophosphate accumulation in cells expressing mGluR2/3 receptors with a half-maximal effective concentration of <6 nM but has very weak actions at mGluR4 and mGluR8 receptors (EC50 > 2 μM) and no significant actions at other mGluRs (Monn et al. 1999; Imre 2007). In addition, we found that the mGluR2/3 antagonist LY341495 completely reversed the protective effects of the agonist on MSN spines in the dopamine-depleted striatum. Moreover, treatment of cultures containing an intact nigrostriatal dopamine system with the antagonist was sufficient to cause MSN spine loss, supporting the hypothesis that MSN spine loss results from excessive glutamate release from corticostriatal axons.
Recently, Seeman et al. (2008) have suggested that mGluR2/3 agonists, including LY379268, are partial agonists at D2 receptors. Because dopamine denervation–induced MSN dendritic spine loss is not reversed by levodopa treatment of rodents (Deutch et al. 2007), and because MSN spine loss is seen in postmortem striatal samples from PD patients who had received chronic treatment with levodopa and/or dopamine agonists (Stephens et al. 2005; Zaja-Milatovic et al. 2005), the attenuation of spine loss in animals treated with the mGluR2/3 agonist is probably not due to any actions of LY379268 at dopamine receptors.
Group II metabotropic receptor agonists have been reported to afford protection against MPTP-induced striatal dopamine loss (Battaglia et al. 2003). However, we started treatment with LY379268 after treatment with MPP+, rather than administering the mGluR2/3 agonist prior to or together with MPP+. Moreover, we observed extensive striatal dopamine depletion in cultures treated with LY379268, as reflected by an almost 90% decrease in media concentrations of HVA, indicative of striatal dopamine denervation.
Taken together, these data strongly suggest that the ability of LY379268 to attenuate MSN spine loss is due to actions at mGluR2/3 receptors and not some off-target action of the drug. Moreover, the observation that treatment of the cultures with an mGluR2/3 antagonist in cultures with an intact striatal dopamine innervation elicited spine loss is consistent with the hypothesis that cortical lesions protect against dopamine depletion–induced MSN spine loss by reducing glutamate release from corticostriatal terminals.
It is likely that there are sources of glutamate in addition to corticostriatal axons that contribute to MSN spine loss. Extracellular glutamate levels involve not only synaptically released glutamate but also glutamate release from astrocytes through the cystine–glutamate exchanger as well as glutamate uptake through high-affinity glutamate transporters, including the astrocytic transporter GLT-1 (EAAT2) (see Kalivas 2009). Because group II mGluRs are expressed by astrocytes (Testa et al. 1994), it is possible that the effects of the mGluR2/3 agonist are mediated in part by astrocytic glutamate transporters. In addition, factors extrinsic to MSNs (such as certain trophic factors) and intrinsic to striatal cells (such as L-type voltage-gated calcium channels) may also play important roles.
Relation to Motor Deficits in Parkinsonism
Our data on the effects of mGluR2/3 agonists point to derangements in corticostriatal glutamate systems as being responsible for dendritic remodeling in the dopamine-denervated striatum. This has significant implications for the treatment of PD, in which MSNs undergo extensive spine loss (Stephens et al. 2005; Zaja-Milatovic et al. 2005). We have previously suggested that MSN spine loss may be related to progression in PD and to the resistance to the full therapeutic benefits of dopamine replacement that is seen in later stages of the illness (Marsden and Parkes 1977; Lesser et al. 1979; Rinne 1981; Clissold et al. 2006; see also Deutch 2006).
Surprisingly, few studies have examined the effects of mGluR2/3 agonists on parkinsonian motor deficits (Murray et al. 2002; Feeley Kearney and Albin 2003). Murray et al. (2002) found that intraventricular administration of the mGluR2/3 agonist LY379268 dose dependently reversed reserpine-induced akinesia. In contrast, Ossowska et al. (2007) did not observe any benefit of intrastriatal injections of a different mGluR2/3 agonist, 2R,4R-APDC on haloperidol-induced motor deficits; it is not clear if this is because of the acute nature of the dopamine blockade achieved with haloperidol.
In contrast to studies with group I mGluR antagonists, recent data suggest that mGluR 2/3 agonists do not attenuate levodopa-induced dyskinesias (Rylander et al. 2009). Because the animals in our study were not treated with levodopa or other dopamine agonists, the attenuation of spine loss that we observed is not related directly to dyskinesias. Several studies have pointed to D1-expressing (direct pathway) MSNs as being critical to the development and maintenance of dyskinesias (Bordet et al. 2000; Carta et al. 2008; Berthet et al. 2009; Darmopil et al. 2009). In contrast, rodent studies indicate that MSN dendritic spine loss in the dopamine-depleted striatum occurs in D2-expressing MSNs (Rodriguez and Pickel 1999; Day et al. 2006; Deutch et al. 2007), although a recent study in the primate suggests that spines are also lost on D1-expressing cells (Villalba et al. 2009). Because Golgi impregnation of neurons precludes the determination of the type of MSN, we cannot ascertain if the changes we observed occur in indirect- or direct-pathway MSNs. Future studies using different methods that permit evaluation of spine changes in specific types of MSNs will be required to untangle changes in direct- and indirect-pathway MSNs.
To the best of our knowledge, this is the first demonstration of reversing the loss of MSN dendritic spines once the spine loss is established. Dopamine replacement in both animal models of parkinsonism and in PD patients does not reverse MSN spine loss. Our data indicate that cortical lesions do reverse the structural changes in MSNs, suggesting that treatments that target corticostriatal projections may be a useful intervention in PD. However, clinical trials of ionotropic glutamate receptor antagonists in parkinsonism have been disappointing. These trials focused on symptom reduction and did not assess disease (or symptom) progression. Our data suggest that modulation of glutamatergic transmission through metabotropic glutamate receptors, specifically mGluR2/3 agonists, may be warranted in studies aimed at slowing progression in PD by attenuating MSN dendritic spine loss. Our studies emphasize the importance of extended corticofugal circuits in PD, rather than a more short-sighted focus on only the striatum.
Supplementary Material
Supplementary material can be found at: http://www.cercor.oxfordjournals.org/.
National Institute of Neurological Disorders and Stroke (NINDS) and National Institute of Mental Health (NIMH), National Institutes of Health (F31 NS060174 to B.G.G., RO1 MH077298 to A.Y.D., PO1 NS44282 to A.Y.D.); Eunice Kennedy Shriver National Institute of Child Health and Human Development for core support (P30 HD15052); National Parkinson Foundation Center of Excellence at Vanderbilt.
The authors are indebted to Drs Jennifer Blackford, Michael Bubser, and Brian Mathur for helpful comments and advice. The content is solely the responsibility of the authors and does not necessarily represent the official views of NINDS or NIMH of the National Institutes of Health or the National Parkinson Foundation. Conflict of Interest: None declared.


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"This was wonderful!"
I wouldn't listen to it again.....because I don't tend to listen to books more than once. But this was a wonderful book with great character development and twists along the way.
There were two...one I could guess at before it actually unfolded...the other was a complete surprise.
She did a great job of differentiating the different voices for the characters. I do find the cockney accent (at least I think it was cockney) annoying after a while...but that's just me.
"Interesting interweaving of past and present"
She sets up the mystery well and holds attention to it throughout the story by the use of the eldest daughter. My mind kept coming up with alternate solutions.
The opening scene in which the eldest daughter tells of the murder.
She was understandable and made the different characters very clear/
The ending was a surprise and made me go back to the opening again.
We all would like to understand the history of our parents.
"Great story, great performance, cliched writing"
Caroline Lee yes, Kate Morton no. Her effortful, hackneyed writing makes me grit my teeth. For example:. "...between a rock and a hard place...", "drawing too long a bow" (repeated twice at least), implausible situations (Someone who's lived in a house almost her whole life needs to feel for the light switches? A blind landlady who leaves her light on late into the night?), and generally poor metaphors like kisses that taste like strawberries. Morton's writing is the literary equivalent of bad acting.
The plot.
Her voices, accents, and timing were perfection.
Yes, it kept me engaged for hours at a time!
"Loved it!"
The story was excellent, never a dull moment- I was enthralled to the very last minute and didn't want to leave work (where I listen to my stories!)
I fell in love with the book AND the lovely lady that reads the book, she added so much depth and warmth.
"Love Kate Morton's Style"
I love the author's execution of multiple timelines and the haunting undertones she has throughout her stories.
Though a very different story, "The Secret Keeper" might be talked about in the same conversation as "The Forgotten Garden" because of the format.
I'll probably read anything that Kate Morton writes. If you are new to her writing, I would start with "The Forgotten Garden" and "The House at Riverton". Read these two first and there will be a good chance that you'll hop on board with her future stories. Great author, beautiful writing.
"Take me back in time..."
The incredible soothing and remarkably variable reading voice of Caroline Lee that gave life perfectly to Kate Morton's characters.
The character build up, their hopes, dreams, and flaws entangled together with the unexpected beautiful flow of varying timeline where mysteries and secrets lay hidden for us readers to find.
Her voice characterization of each individual person in the story is remarkable! She gave each character a voice I never thought can be done by a single reader!
Definitely! Most of the time, after parking my car in our garage, I would sit there listening to the audiobook refusing to believe I have to wait another time to drive so I can have the chance to listen to it more.
I am now an official fan of both Ms. Kate Morton and Ms. Caroline Lee! I will continue to acquire their partnership on audiobooks...
"Great story -"
One of the better books I've listened to. I couldn't wait to get back to my car to find out what would happen.
I liked how it went back and forth in time, following the story from different perspectives. I loved the characters.
Caroline Lee was very good reading this story. Her accent is nice, and easy to listen to.
Gardening Geek
"Morton outdoes herself"
Am a fervent Kate Morton fan. Loved The Forgotten Garden, was entranced with The House at Riverton (aka Shifting Fog) and the Distant Hours, but the Secret Keeper has become my favorite. The narration by Caroline Lee was as cozy and comfortable as ever. Her voice bringing the various eras to life in vivid color, at times black and white. She would be a charm reading anyone to a calm and peaceful sleep. But during the day, when I listened, she kept me totally enthralled with the myriad of twists and turns of the story.
Morton's ability to draw the listener reader to empathy, even affection for all her characters flawed, all so human, and to disgust with her duplicitous cads, is amazing. Know this is weird, but narrator Caroline Lee did yelling and whispers really well. Been listening to books since the 80's and that's surprisingly important! Look forward to Kate Morton's next novel.
"I loved it!"
The story was engaging. I couldn't wait to find out what happened next!
The end was a fantastic surprise!
I loved the whole family!
"not my cup of tea"
I was not able to get into the story. I was hung up by the accent of the narrator.
I was expecting a differrent story with more depth.


text:
Babsy Grange's mother dies at 90
Walker died peacefully at her home in Toronto, Canada, on February 14 surrounded by family and friends, including Minister Grange and her husband of over 50 years, Gifford Walker.
Considered a stalwart in the Jamaican community in Toronto, Walker was an integral member of several organizations including the 55-year-old Jamaican Canadian Association (JCA), the largest and oldest community Jamaican organization in Canada; PACE (Canada), Project for the Advancement of Childhood Education, which adopts basic schools in Jamaica; and the Jamaica Independence Church Service committee, which plans the annual event to commemorate Jamaica's independence.
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text:
The summit opens in the Canadian port of Halifax today and closes after a working lunch on Saturday. The US will want to raise the issue of how the industrialised nations should deal with Iran, accused by the Clinton administration of attempting to acquire a nuclear weapon.
Policy towards Iran is likely to divide the US from the other six member nations - Britain, France, Germany, Japan, Italy and Canada. Washington seeks to isolate it economically but the others reject a trade embargo, professing to believe in a "critical dialogue".
The US is also at odds with Russia, taking part in the G7s political discussions, because Moscow plans to sell reactors and civilian nuclear technology to Iran. A key part of the political agenda will be dominated by Russia's relationship with the West and its aspiration to join the G7 "club". Russia's economic plight makes that unlikely for the foreseeable future but G7 leaders have accepted for several years the desirability of bringing Russian leaders into their annual political dialogue.
President Boris Yeltsin's presence at tomorrow's dinner and his participation in talks the next morning will provide a face-to-face opportunity for a frank exchange on Bosnia and security arrangements in Europe.
These topics could well overshadow discussion of reform of the United Nations and the Bretton Woods institutions - the International Monetary Fund and the World Bank.Reuse content


text:
Coos Bay is located in Coos county and has a population of 15,374.
Practical Nursing schools in Coos Bay charged students an average tuition of $2,898.00 if they were Oregon residents, and $2,898.00 if they were non-residents, during the 2009 - 2010 school year.
Books and supplies for practical nursing schools in Coos Bay cost an average of $1,200.00. The average cost for room and board for students living on campus at practical nursing schools in Coos Bay was $5,330.00. The average cost for students living at home was $2,160.00 for the 2009 - 2010 school year. There is one practical nursing college in Coos Bay for students to choose from. 30 students were reported to have graduated from practical nursing programs in Coos Bay in the 2008 - 2009 school year.
|Average Salary
|Number Employed in City
|Licensed Practical and Licensed Vocational Nurses


text:
My husband and I are planning our first trip to Charleston and Savannah in July and will be taking our granddaughters with us...age 9 and 11. Have looked at staying 3 nights in Charleston and 2 in Savannah. Would love some ideas on what to do and am thinking of staying at Planters Inn or French Quarter Inn or Harbor View inn. Would love iterniary suggestions and best place to stay...
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First visit to Charleston
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This is a terrible time to go to Charleston or Savannah unless it is the only time you can go, in which it is a great time to go. Any time is great to be in Charleston or Savannah.
It will be really hot and humid. Wiltingly hot and humid. The girls probably won't notice, but it will be hard on grandma and grandpa unless you are from central Florida or Mississippi.
My granddaughters would be thrilled by carriage rides. They would like one of the harbor cruises in Charleston. They would like to see one (1) historic house in Charleston, and they would be thrilled in Savannah to visit the home of Juliet Lowe, the founder of the Girl Scouts. They would like eating family style lunch at Mrs. Wilkes Boarding House in Savannah. I think your granddaughters might like one of the plantations near Charleston. Both cities have easy access to beaches if you wanted to get out of town for some sun and sand.
How are you getting to and from the cities? It is not just a few miles, but if you go on US 17, you will see Beautiful Beaufort and lots of low country on the way. If you take I 95, you will see lots of trucks.
There are real authorities on these places here, and I know you will hear from them soon. I am just waiting for the Opera to start on PBS!
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You might want to take a look at my trip report covering our short week's stay in these cities; click on my name to find it.
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There are probably at least a hundred threads (I usually say "a jillion") threads about Charleston on this forum. Maybe take a look at some of them, make a list, and then ask questions? Reinventing the wheel.
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If I had the time and money and wanted to entertain a nine and twelve year old, I would rent a place on Isle of Palms for a week. You get the beach but are fifteen minutes from Charleston. You could sightsee when it is cooler and then take a splash in the ocean when it is too hot to walk around the cobblestone streets.
Wild Dunes has nice condo units. They are pricey but so are hotel rooms in historic Charleston.
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We stayed at the Planters Inn in Savannah and it was very good. Also, it's right on Reynolds Sq and next door to the Olde Pink House restaurant.
In Charleston we stayed at the Andrew Pinkney and it too was very good. Breakfast on the rooftop.
As Ackislander wrote it will be hot. We were there at the end of April and start of May.
In Charleston we kept going into historic houses to get out of the sun. And we live in South Florida.
Also, when walking down at the bottom of the pennisnsula, make sure you have water and snacks. There are no restaurants, snak bars or stores south of Broad.
Having said all that, both cities have beautiful historic areas.
Make sure you arrange to see a couple of plantations. We went to Middleton Place and Drayton Hall. They're near each other and quite a contrast.
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Regarding the Charleston portion of your visit, the above mentioned suggestions are very good, especially the carriage ride.
History is a big part of any visit to Charleston. Based on what our grandson liked during a recent visit with us, I would add the following.
A boat ride over to Fort Sumter (cool and refreshing on a hot summer day and full of history with Park Service Narration)
A visit to the Old exchange Building and Provost Dungeon (especially the dungeon part)
A visit to the Old Slave Mart (honest and compelling history)
A visit to the South Carolina Aquarium (inside and cool and loaded with information about SC marine life)
I think a visit to one of the plantations would work but only in the mornings. Most afternoons would be too hot for strolling the grounds, in my opinion.
Hope this helps.
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Celebrate the passion of the games with EAU DE LACOSTE L.12.12 ENERGIZED edition.
Whilst remaining true to the original Eau de Lacoste L.12.12 BLANC fragrance, ENERGIZED is a twist on this original, offering an uplifting energy that renders the fragrance distinctive in its own right. The original Eau de Lacoste L.12.12 Blanc has been spiced up with fiery ginger for a distinct passionate note and a hint of cool mint to enhance the scent's crisp, energetic freshness.
Woody Fresh fragrance
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Cracow- Zakopane 2011
- Posted April 16, 2012 by Dominika Viewed 1441 times
- This is a migrated legacy post. Image resolution is low. Info
It was on school trip :) Last year. Now the weather isn't good to me.. It's raining (all the time) and I can't go out ;/
If U don't know.. It's in POLAND :)
My country
6 There are 6 comments, add yours!
2012.04.23 Edited
amazing !!
2012.04.23 Edited
Poland has so many beautiful nature!!!
2012.04.21 Edited
Amazing! I love the mountains! Makes me wish I was on holiday!
2012.04.19 Edited
Taki widok z okna mogłabym mieć na codzień :)
2012.04.16 Edited
Świetny widok z pokoju na przedostatnim :) Pozdrawiam!
2012.04.16 Edited
Beautiful shots and scenery thanks for bringing me along the tour


text:
"There's a lot to learn here and entertainment to be had in the process.... Trolling the entries is a real trip from the obscure to the obvious, from ridiculous to sublime... once you're in it, it's hard to break away." Courier-Journal.com
"With this encyclopedia and its 2,100 entries written by 300 authors, northern Kentucky's particularities are given long overdue attention." Book News, Inc.
"Paul A. Tenkotte... documents the region's unique history and culture as well as the role of northern Kentucky in the larger history of the Commonwealth of Kentucky and the nation." Kentucky Living
"The book is a worthy investment for anyone interested in Kentucky history." Kentucky Monthly
"Local information can often be the hardest to find. The production of such an exhaustive regional encyclopedia is something that other regions can aspire to. Useful for libraries of all sizes interested in Northern Kentucky or for general geographic libraries." Booklist
"Paul A.Tenkotte and James C. Claypool have succeeded in their goal of providing an encyclopedia that appeals to both scholars and general readers." Ohio Valley History
"The people, places, and events in this volume will intrigue individuals unfamiliar with northern Kentucky, as well as longtime residents.... This volume is an indispensable reference for anyone interested in the history of the Bluegrass State." Journal of Southern History


text: When Jimmy Ryan's mangled corpse is found in a local church basement, this sadistic sacrilege seems to send a message—one that Abbie Kearney believes only the fiercely secretive citizens of the neighborhood known as "the County" understand. But in a town ruled by an old-world code of silence and secrecy, her search for answers is stonewalled at every turn, even by fellow cops. When the killer's mysterious calling card appears on her own doorstep, the hunt takes a shocking twist into her own family's past.


text: Listen 54:40 Houndmouth performs at the 2013 Newport Folk Festival. Meagan Beauchemin/NPR hide caption toggle caption Meagan Beauchemin/NPR Newport Folk Festival Houndmouth, Live In Concert July 31, 2013 All four members of the Indiana band share lead vocals throughout their warm, rambling debut. Houndmouth, Live In Concert: Newport Folk 2013 Listen · 54:40 54:40 Toggle more options Download Embed Embed <iframe src="https://www.npr.org/player/embed/204508669/206163954" width="100%" height="290" frameborder="0" scrolling="no" title="NPR embedded audio player">