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Nonfiction » Antiques & Collectibles » Reference
Get Strapped for FREE!! by David Huckins
Price: Free! Words: 4,990. Language: English. Published: February 12, 2013. Categories: Nonfiction » Reference » Handbooks and Manuals, Nonfiction » Antiques & Collectibles » Reference(5.00 from 2 reviews)
Do you want to make a survival bracelet, but don't know how? This short and FREE eBook will take you through each step necessary to build a simple survival bracelet. Even if you have never tied a knot in your life, you should be able to make a survival bracelet if you follow these easy to read instructions. This free eBook is generously illustrated with dozens of pictures to simplify and stream
Palestinian Women: Rising Above Limitations, Expectations & Conditions by Sadiqua Hamdan
Price: Free! Words: 36,690. Language: American English. Published: October 28, 2013. Categories: Nonfiction » Antiques & Collectibles » Reference
This book discusses the evolution of a Palestinian woman, from early 1900's until now. It includes fifty-five face-to-face interviews with Palestinian women ages eighteen to ninety about their perceptions regarding their lives, relationships, education, role models, religion, and views of the West.
EncycloBeania by E. Juelich
Price: $5.95 USD. Words: 90,220. Language: English. Published: October 27, 2011. Categories: Nonfiction » Antiques & Collectibles » Reference
A reference guide with over 4,000 entries about (copyright)Ty, Inc,'s plush products. Includes release dates, retirement dates, heart and tush tag information plus more.
A Beginner's Guide To Collecting Powder Compacts by Caroline Y Preston
Price: $2.99 USD. Words: 10,810. Language: English. Published: December 5, 2013. Categories: Nonfiction » Antiques & Collectibles » Silver, gold, & other metals, Nonfiction » Antiques & Collectibles » Reference
For lovers of these beautiful little feats of engineering ………. This is an inexpensive little guide intended for those starting to collect powder compacts. It gives general information on collecting and caring for compacts and features colour pictures, rarity indication and details of around 300 different powder compacts, carryalls and nécessaires from the early 1900's up to the present day.
Carrick Playstation 1 Price Guide Feb 2014 by Carrie Stanley
Price: $0.99 USD. Words: 9,070. Language: English. Published: February 24, 2014. Categories: Nonfiction » Antiques & Collectibles » Reference
This price guide offers up to date average sold price for new and used games, consoles and Accessories
Texas Historic Museums: North Texas by Trisha Faye
Price: $3.99 USD. Words: 15,410. Language: English. Published: May 12, 2015. Categories: Nonfiction » Antiques & Collectibles » Reference, Nonfiction » Reference » Personal & Practical Guides
This edition of Texas Historical Museums has over 130 listings of historical museums, heritage villages & historic homes in 30 north Texas counties. Archer, Baylor, Clay, Collin, Cooke, Cottle, Dallas, Denton, Ellis, Erath, Fannin, Foard, Grayson, Hardeman, Hood, Hunt, Jack, Johnson, Kaufman, Montague, Navarro, Palo Pinto, Parker, Rockwall, Somervell, Tarrant, Wichita, Wilbarger, Wise & Young.
Making Auctions Pay: Buying and Reselling For Profit From Regional Auction Houses by Marques Vickers
Price: $9.95 USD. Words: 370. Language: English. Published: May 24, 2014. Categories: Nonfiction » Antiques & Collectibles » Reference, Nonfiction » Business & Economics » E-commerce / internet marketing
"Making Auctions Pay" is the first easy-to-follow guidebook for successfully buying, consigning and reselling valuables through regional auction houses. The straightforward language cuts through the traditional misconceptions surrounding auctions and simplifies the process of buying with the purpose of reselling for profit. An excellent and innovative primary and secondary source of income.


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Bought it as a gift so haven't used it yet. Will ask my mom how it works on her
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Collagen booster
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Maybe it's too early to tell. So far I can't say that I've noticed any difference. I think I might try take a double dose like suggested on the bottle and review again if I see a difference.
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StartUpHire is the place to find Affiliate Manager jobs. Review the list of Affiliate Manager career opportunities to the left. These Affiliate Manager jobs represent some of the most rewarding careers available.
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Marketing Austin, Texas APPLY Description CreditCards.com is looking to hire an Affiliate Manager to join our growing company. About the Role: Aggressively recruit new Affiliate partners Oversee strategies related to affiliate marketing with the goal of increasing traffic7/20/2016 Austin, TX Save This Job
at AnchorFree Inc. Menlo Park AnchorFree?s mission is to provide secure and private access to the world?s information for every person on the planet. AnchorFree?s Hotspot Shield app is the world?s most popular freedom and privacy platform. Hotspot Shield is the starting point,6/20/2016 Menlo Park, CA Save This Job
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Q & A Library
Vasectomy: A Prostate Cancer Risk?
A friend of mine read somewhere that having a vasectomy increases the risk of prostate cancer by 30 percent. Is this correct? My husband has a history of prostate cancer on both sides of his family.
Answer (Published 7/2/2002)
Concern that vasectomy may increase the risk of prostate cancer stems from the conflicting results of a number of studies. The studies that started it were published in 1993 and found that men who had had vasectomies had a very small - 1.5 percent - increase in risk. More recently, another large study compared 753 men with prostate cancer to 703 men who didn't have the disease. After adjusting for age, race (African Americans have twice the risk of whites) and family history of the disease, they found that among those with prostate cancer 39.4 had vasectomies compared with 37.7 percent of those who didn't have cancer. Such a small difference suggests that there really is no association between vasectomy and prostate cancer.
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However, some smaller studies have found a slightly increased rate of prostate cancer among men who have had vasectomies before the age of 35.
There is no biological reason why vasectomy should affect the prostate. The explanation for the small increase in risk may be that men who have had vasectomies may be more health conscious than other men and go more frequently for prostate cancer screening.
We probably won't have a definitive answer to the vasectomy/prostate cancer question before 2015 when we get results of the National Cancer Institute's Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, which began in 1992 and is evaluating risk factors for all these disease. In the meantime, I wouldn't worry too much about the risk vasectomy may pose. Because of your husband's family history of prostate cancer, I recommend that he try to lower his risk in other ways, such as by reducing consumption of animal foods and fat, increasing consumption of soy foods and Omega-3 fatty acids, and generally eating more fruits and vegetables, including cooked tomatoes, which contain lycopene, a carotenoid pigment that helps prevent prostate cancer.
Andrew Weil, M.D.
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Harper's Magazine
"Shippey is a rarity, a scholar well-schooled in critical analysis whose writing is beautifully clear." Minneapolis Star-Tribune
"Authoritative and timely" Boston Globe
"Shippey presents a remarkably insightful account of the origins of Tolkien's use language and myth." The Chicago Tribune
"Full of things-we-hadn't-known . . . As scholarship, it's one of the more enjoyable works I've run across." The San Diego Union-Tribune
"Wonderfully readable . . . Shippey makes an impressive case for why the creator of Middle-earth is deserving of acclaim." Publishers Weekly
"One of the best, if not the best, piece of ... literary criticism I have ever read on Tolkien." Midwest Book Review
"Delightful exploration of the relationship between Tolkien's fiction...his scholarly work and the mythical, linguistic and philosophical history underlying both." Salon
"[Tolkien] deserves his full due, and Shippey's appreciative assessment of his unique achievement provides it in full and satisfying measure." Philadelphia Inquirer
"[Shippey] deepens your understanding of the work without making you forget your initial, purely instinctive response to Middle-earth and hobbits." The Houston Chronicle
"An invaluable study...It illuminates the text and enables the reader to better appreciate the works under discussion." The Washington Times


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Dangerous Shift was a new look at shifters, a world I wouldn't mind reading more of.
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An imaginative and thought provoking story from beginning to end. A tale rife with prejudice, hatred, intrigue, deception and danger that will take the reader on a wild ride... Read morePublished 18 months ago by WHATCHA READIN'?
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Grand Hotel Roi Rene Aix en Provence Roi Rene
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Mary Magdalene, Nostradamus and Lavender
We were up early on Saturday morning and on our way to see some sights. First things first, we needed breakfast. We walked to a Patisserie and got a couple of sweet rolls and a Coke Light (not called Diet Coke over here), and sat on a park bench near the grand fountain in Aix-in-Provence. Reminded me of 41 years ago when we were living on a budget …
Day 22 Tuesday 10th November
... and many others have works. Overall a very cultural day which we enjoyed very much. We have shopped for tomorrow as it is a public holiday tomorrow for 11/11 and everything will be closed. After arriving home we didn't feel like venturing our again so tomato on toast was the meal. It appears that Kenny may be getting my wog, so early to bed and a lazy day tomorrow. Oh, we are continually finding these large courtyards with big oak trees and much atmosphere just ...
Our first day in Provence
This morning we went in the freezing pool then we went on a drive to Chateau de la Coste and had a picnic lunch. We went on a walking tour around the vineyards to see the sculptures.
Then we drove to ...
Calanques of the Blue Coast
... the number of calanques you visit and the length of the trip.
We managed to get on a boat just leaving but because it was busy had to sit apart which was a bit of a shame. Also the commentary was in French only and my school girl French didn't extend to this. However, the views were worth it and it was nice to escape the heat. I was surprised how rough ...
A Day at the Lake!
On Monday, Cathleen and Claire invited Jan and I to the lake with their sons James and Ayman for a day of relaxing and swimming. The ride through the countryside was quite breathtaking, and once we got to the lake it was serene and peaceful.
There was a campground nearby ...


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Ticklerton Holiday Cottages
Please find below a selection of self catering holiday cottages to rent in or near Ticklerton.
We're open until 9.30pm and waiting for your call:01244 356666
Please find below a selection of self catering holiday cottages to rent in or near Ticklerton.
Your search returned 76 cottages.
Lovely romantic Church Stretton cottage on 200 acre farm. Mezzanine bedroom, well-equipped accommodation, oak beams, use of gardens and grounds. Church Stretton 4.6 miles. (Ref. 4137)
7 nights from £260Book Now
Character Church Stretton cottage, lovely family base, with oak beams and cottage atmosphere. Private patio and shared use of wonderful grounds. Church Stretton 4.6 miles. (Ref. 4139)
7 nights from £282Book Now
Charming two bedroom detached bungalow surrounded by beautiful Shropshire countryside in the hamlet of Hatton, a short distance from the renowned Acton Scott Working Farm Museum. With far-reaching views. Church Stretton 3.5 miles. (Ref. 928287)
7 nights from £299Book Now
An attractive, semi-detached barn conversion on the edge of Rushbury village. Character features, en-suites, light and airy living area. Church Stretton 5 miles. (Ref. 23550)
7 nights from £292Book Now
A beautiful, semi-detached barn conversion on the edge of Rushbury village, on the owners' own farm. Character features, lovely large living areas. Church Stretton 5 miles. (Ref. 917175)
7 nights from £362Book Now
Detached bungalow overlooking delightful Church Stretton and Long Mynd Hills. Spacious, well-equipped accommodation. Wonderful walking and biking from cottage. Ludlow 15 miles. (Ref. 906207)
7 nights from £319Book Now
Superb 19th century barn conversion cottage. 250 acres of farmland in Hope Valley. Church Stretton 6 miles. (Ref. 12657)
7 nights from £423Book Now
A lovely detached barn conversion situated on the owner's working farm. Walks, cycling and fishing. Woodburning stove. Private enclosed garden. WiFi. (Ref. 918161)
7 nights from £342Book Now
Charming 19th century barn conversion in 250 acres of farmland situated in Hope Valley on the edge of Westhope with character features, hot tub and en-suite facilities. Church Stretton 6 miles. (Ref. 1863)
7 nights from £427Book Now
Large barn conversion on 250 acre farm. One of six cottages. Five bedrooms, three en-suite bathrooms. Woodburner, Hot tub. Church Stretton 6 miles. (Ref. 12658)
7 nights from £779Book Now


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I made this as a reminder for myself!
I put all sorts of symbols in this piece. I used bold strong letters to portray the idea of strength. I added thorny rose brushes to the letters, for growth and to symbolize protecting what is beautiful within us during those challenging times.
The leaves on the trees are changing colors in autumnal hues. Change is constant in life and when trees lose their leaves it's to conserve their energy during the trials of winter.
I wanted to show the roots of the trees, since I feel like my roots and family are the source of my inner strength.


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Found this hotel on the internet. It is located in a small village, on a mountain top, and can be seen for miles around. A Winding road leads uphill until you reach the village (and don't follow your GPS when it wants you to turn into the very narrow Mercato lane, continue on the main road to stay sane). The hotel now has added 8 parking spots, where you need a permit. Great!! The house is a former convent and is located behind the church (and Church bell tower) and contains a restaurant (good quality, separate review), a small spa and the hotel with close to 20 rooms and a terrace for coffee or breakfast. Breakfast is small, Italian style. Service is very efficient and friendly. All are very helpful in making reservations or giving information. Since we stayed for a full week, we got a Three beds room, which was perfect since we had a lot of luggage. Room is charming! Bathroom reasonably big and very clean, as all the premises. We ate several times in the village, and used the hotel as a base for our excursions around Liguria, all the way down to the northern part of Toscana, via Lerici, La Spezia, Portovenere, Riomaggiore/Cinque terre and Rapallo/Portofino and the surrounding Mountains. The uphill drive is a challenge the first time but once you get to know the road, it works fine. Village Life is peaceful and enchanting. The atmosphere of the hotel is relaxed and elegant at the same time. I would gladly go back another week!
- Official Description (provided by the hotel):
- Hotel Relais Al Convento is situated in the medieval village of Vezzano Ligure, on the hills at the back of the Cinque Terre, only few kilometres away from the wonderful maritime villages of Lerici, San Terenzo and Portovenere, pearls of the Gulf of the Poets. Before the accurate restoration the hotel was an ancient cloister dating back to the XVI century. Today it keeps unchanged the charm and the mysticism of its origins. It has 18 rooms where guests can spend unique and exclusive stays at only 8 km from the sea.It has a check-in area, a private garden, Wi-Fi connection in a common area and restaurant with large choice of Ligurian typical dishes from both land and sea. ... more less
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- TripAdvisor is proud to partner with Expedia, Hotels.com, Hotwire, Booking.com, Priceline and Travelocity so you can book your Hotel Relais Al Convento reservations with confidence. We help millions of travelers each month to find the perfect hotel for both vacation and business trips, always with the best discounts and special offers.
- Also Known As:
- Relais Al Convento Hotel
- Hotel Relais Al Convento Vezzano Ligure, Italy


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Russia threatens military strike over NATO missile defence 'if U.S doesn't back down'
Russia's top military officer has threatened to carry out a pre-emptive strike on U.S.-led NATO missile defense facilities in Eastern Europe if Washington goes ahead with its controversial plan to build a missile shield.
President Dmitry Medvedev said last year that Russia will retaliate militarily if it does not reach an agreement with the United States and NATO on the missile defense system.
Chief of General Staff Nikolai Makarov went further in his statements yesterday.
Tensions: The USS Higgins is one of 20 American ships deployed globally with Aegis interceptor systems. U.S. defense plans in Europe is one of the touchiest subjects with Russia
'A decision to use destructive force pre-emptively will be taken if the situation worsens,' he said at an international conference attended by senior U.S. and NATO officials.
Russian Defense Minister Anatoly Serdyukov also warned that talks between Moscow and Washington on the topic are 'close to a dead end'.
U.S. missile defense plans in Europe have been one of the touchiest subjects in U.S.-Russian relations for years.
Moscow rejects Washington's claim that the missile defense plan is solely to deal with any Iranian missile threat and has voiced fears it will eventually become powerful enough to undermine Russia's nuclear deterrent.
Moscow has proposed running the missile shield jointly with NATO, but the alliance has rejected that proposal.
Makarov's statement on Thursday doesn't seem to imply an immediate threat, but aims to put extra pressure on Washington to agree to Russia's demands.
Threats: Russia's Chief of General Staff Nikolay Makarov said 'pre-emptive' force would be used if the situation worsens
The two-day conference in Moscow is the last major Russia-U.S. meeting about military issues before a NATO summit in Chicago later this month. Russia has not yet said whether it will send top officials.
In a candid, lively exchange during a conference side session, officials talked about the high level of distrust remaining between the two sides.
'We can't just reject the distrust that has been around for decades and become totally different people,' Russian Deputy Defense Minister Anatoly Antonov said in addressing U.S. and NATO officials.
'Why are they calling on me, on my Russian colleagues, to reject distrust? Better look at yourselves in the mirror.'
We can't just reject the distrust that has been around for decades and become totally different people.
Russian Deputy Defense Minister Anatoly Antonov
U.S. State Department special envoy Ellen Tauscher responded that neither country can afford another arms race.
'Your 10-foot fence cannot cause me to build an 11-foot ladder,' Tauscher said.
'It's going to have to take a political leap of faith and it's going to take some trust that we have to borrow, perhaps, from each other and for each other, but why don't we do it for the next generation?'
The Obama administration tried to ease tensions with Russia in 2009 by saying it would revamp an earlier Bush-era plan to emphasize shorter-range interceptors.
Russia initially welcomed that move, but has more recently suggested the new interceptors could threaten its missiles as the U.S. interceptors are upgraded.
The U.S.-NATO missile defense plans use Aegis radars and interceptors on ships and a more powerful radar based in Turkey in the first phase, followed by radar and interceptor facilities in Romania and Poland.
Russia would not plan any retaliation unless the United States goes through with its plans and takes the third and final step and deploys defense elements in Poland, Antonov said Wednesday. That is estimated to happen no earlier than in 2018.
Russia has just commissioned a radar in Kaliningrad, its western outpost near the Polish border, capable of monitoring missile launches from Europe and the North Atlantic.
On Thursday, at the start of the conference attended by representatives from about 50 countries, Russia's Security Council secretary reiterated Moscow's offer to run the missile shield together with NATO.
Nikolai Patrushev said such a jointly run European missile defense system 'could strengthen the security of every single country of the continent' and 'would be adequate for possible threats and will not deter strategic security'.
NATO's deputy secretary general, Alexander Vershbow, told the conference that the U.S.-led missile shield is 'not and will not be directed against Russia' and that Russia's intercontinental ballistic missiles are 'too fast and too sophisticated' for the planned system to intercept.
Meanwhile, U.S. Senator John McCain, on a visit to Lithuania, lashed out at Russia's plans in Kaliningrad.
McCain said using missile defense as an 'excuse to have a military buildup in this part of the world, which is at peace, is really an egregious example of what might be even viewed as paranoia on the part of Vladimir Putin'.
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How are STEM programs doing in your state? Are they reaching the students who need them the most? Are they effective in inspiring and educating the next generation of skilled, innovative and inventive game-changers? How does a state evaluate its STEM programs? The annual report of the Iowa STEM Monitoring Project can serve as a guideline. We asked Jeff Weld, executive director of the Iowa Governor's STEM Advisory Council and associate professor of biology at the University of Northern Iowa […]Read More
by Mike Feder, director of STEMx "Get an internship" is a ubiquitous piece of advice. I'd guess every person reading this post hasn't just heard that piece of advice, you've even offered it. But, as a researcher, these are the kind of clichés that stick with me. What's the word on internships? They work. A literature review completed in 2013 counted 12 different studies showing impacts. The benefits to internship participants ranged from higher grades to stronger conception of themselves as […]Read More
What is the "attraction" of magnet STEM schools, and how are they different, if at all, from other STEM schools? To find out, we asked Becky Ashe, founding principal of L&N STEM Academy in Knoxville, Tennessee, about her magnet high school and magnet schools in general. She also shared information about the Magnet Schools of America annual conference: Q: Your school, L&N STEM Academy, is a magnet high school. What, in general, is a magnet school, and how does a […]Read More
by Mike Feder, Director of STEMx STEM schools can be a vehicle for creating equity, setting high expectations, and an education that prepares kids for the 21st century world. As STEM advocates, we believe in these schools. But data matters just as much as our beliefs. When parents and policymakers want more than the beliefs of educators, what are the best ways to demonstrate the merits of our work? Sharon Lynch, professor at George Washington University, has been working on […]Read More
Hi Dr. O'Reilly! Can you tell us a little about what you're working on at AZ STEM NETWORK and Science Foundation Arizona? As I recently took over this role I have spent the last month getting to know the organization and partner groups. The AZ STEM NETWORK is a collaboration between business, educators, government and philanthropy in Arizona with a shared common agenda – to develop a strong STEM literate population and increase the number of high tech career opportunities […]Read More
This post by James Brown is a cross-post from the STEM Education Coalition The STEM Education Coalition today publicly released "The Case for Investing in Out-of-School Learning as a Core Strategy in Improving Science, Technology, Engineering, and Mathematics (STEM) Education." This 10-page paper written for policymakers and education leaders makes a strong case for why informal and afterschool learning must be an integral part of policies to improve STEM education across the board. Exposure to formal and informal learning in […]Read More
The Army Education Outreach Program, or AEOP, is the Army's platform for advancing STEM education and literacy through STEM experiences, internships and competitions. As a connector of opportunities to transform STEM education, we're proud to issue this notification of a second round of grant opportunities for strategic initiatives from AEOP. Organizations that support STEM education and reach underrepresented student populations OR military-dependent K-12 students can apply for the grants. This is the second round of AEOP's Strategic Outreach Initiatives Grant. […]Read More
The NC STEM Center has leveraged its resources with resources on a national scale to create tools needed to allow a centralized database of STEM education programs using The Connectory, a national online database of STEM programs and opportunities. The NC STEM Center is a founding member of STEMx, so we chatted with Dr. Sam Houston and Lisa Rhoades about the partnership and what it means for students and teachers. NC STEM is a program of the NC Science, Mathematics and […]Read More
100-pound subway-cleaning robots. Prosthetics good enough to skateboard on. Homemade spacecrafts that can reach the stratosphere. That last one was made by sisters Kimberly and Rebecca Yeung, ages 9 and 13. They fashioned a small craft out of a weather balloon and Rebecca's archery arrow shafts. Before releasing it into the sky, they attached a camera, GPS, and a variety of sensors. A small R2D2 to acted as pilot, finally the captain of his own ship. After seeing a video of the […]Read More
Today, we're talking to Representative Wilson Stone of Kentucky. Rep. Stone is part of the inaugural class of STEMx Policy Fellows from across the country. They are spending the next two years learning from and with other policymakers from STEMx states to take new ideas back to their own community. Welcome Rep. Stone! What does it mean to you being a STEMx Policy Fellow? I am a part of STEM because I am interested in promoting STEM education across Kentucky, […]Read More


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Blue Buffalo Multi-Cat Health Chicken & Turkey Recipe Adult Dry Cat Food
By Blue Buffalo
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Item Number84982
Weight15.0 pounds
Food FormDry Food
BrandBlue Life Protection
Special DietNo Corn No Wheat No Soy, Weight Control
Made inUnited States
Natural BLUE Multi-Cat Health food is specially formulated to meet the needs of multiple cats, no matter their breed or weight, living in one home. And it's made with two delicious proteins first - succulent chicken and tender turkey - to satisfy different feline palates.
Key Benefits
- Optimal level of calories for healthy weight for cats of all sizes and breeds
- Blend of dietary fibers for hairball control
- High-quality protein helps lean muscle maintenance
- Omega 3 & 6 Fatty Acids to obtain healthy skin & coat
- Vitamins & Chelated Minerals for immune system health
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Deboned Chicken, Deboned Turkey, Chicken Meal, Turkey Meal, Menhaden Fish Meal (Source of Omega 3 Fatty Acids), Whole Ground Brown Rice, Whole Ground Barley, Oatmeal, Peas, Chicken Fat (Preserved with Mixed Tocopherols), Natural Chicken Flavor, Potatoes, Dried Egg, Fish Oil (Source of Omega 3 Fatty Acids), Flaxseed (Source of Omega 3 and 6 Fatty Acids), Dried Cellulose, Whole Carrots, Whole Sweet Potatoes, Cranberries, Blueberries, Apples, Blackberries, Pomegranate, Spinach, Pumpkin, Barley Grass, Dried Parsley, Alfalfa Meal, Dried Kelp, Taurine, Yucca Schidigera Extract, L-Carnitine, L-Lysine, Turmeric, Dried Chicory Root, Oil of Rosemary, Beta Carotene, Vitamin A Supplement, Thiamine Mononitrate (Vitamin B1), Riboflavin (Vitamin B2), Niacin (Vitamin B3), D-Calcium Pantothenate (Vitamin B5), Pyridoxine Hydrochloride (Vitamin B6), Biotin (Vitamin B7), Folic Acid (Vitamin B9), Vitamin B12 Supplement, Calcium Ascorbate (Source of Vitamin C), Vitamin D3 Supplement, Vitamin E Supplement, Iron Amino Acid Chelate, Zinc Amino Acid Chelate, Manganese Amino Acid Chelate, Copper Amino Acid Chelate, Choline Chloride, Sodium Selenite, Calcium Iodate, Salt, Caramel, Potassium Chloride, Calcium Carbonate, Dried Yeast (Source of Saccharomyces Cerevisiae), Dried Lactobacillus Acidophilus Fermentation Product, Dried Bacillus Subtilis Fermentation Product, Dried Enterococcus Faecium Fermentation Product.
Customer Reviews
Rated 4.5 out of 5 by 57 reviewers.
Rated 4 out of 5 by Kim9 My cats love the small bites I have 7 cats and overall they like this food, they can be picky but they ask for it at dinner time. July 24, 2016
Rated 4 out of 5 by KatJ Cats Love It Have been buying science diet for awhile and switched it up now. They seem to like blue buffalo better and it's cheaper also. Will keep buying. June 15, 2016
Rated 5 out of 5 by Mama26kids my 11 cats love it I have tried many foods for my 11 cats and they would often all stop eating the food at the same time leading me to believe that the food we were buying, even 'quality' brands were sometimes having off ingredients in the food. Many of our cats would vomit regularly. Since I switched to Blue there has not been one time my cats have refused to eat the food, they eat less Blue than other foods I think because its quality and they don't need as much, and the vomiting is rare now. and usually from obvious over eating. I get this multi cat version because I have a young cat and elderly cats, indoor and outdoor cats and this seemed to cover them all as best possible. When our kitten is grown I will try other flavors Blue offers. May 22, 2016
Rated 2 out of 5 by pinecats Cats don't like My cats have been on Blue Buffalo Indoor Chicken, Mature, and Salmon flavored. Since I have a number of cats, and they love turkey flavor, I thought I'd try this. They only eat it if they have to. I won't get this type again! June 21, 2016
Rated 5 out of 5 by Disabledkittylover Great product Being on disability, I can afford to actually feed my kitties healthy food, other than the cheap store brands. The store brand made my cats sick and was costing vet visits I could not afford. Thank you for have blue buffalo at an affordable price. June 5, 2016
Rated 5 out of 5 by crazycatlady3 Great Product! I ordered this because Tiny Marie has had surgery for impacted fur balls. Colby Jack has a very sensitive stomach & very loose stools. I feel so bad for him because he can be sickly because of it at times. My 3rd kitty-Persephone Jade was starving & extremely malnourished when I got her. They all love to eat anything by Blue Buffalo that has chicken, turkey, duck, rabbit or venison in it & this will take care of all the issues that mine are going through. So far this is working really good. Colby Jack has more energy after eating this than he's had in a long time! I know he's feeling better & My cats are healthy & happy because of Blue Buffalo! May 10, 2016
Rated 5 out of 5 by Denise Even the most finicky cats! Having 7 cats and trying to feed them what they like was definitely a challenge until I tried Blue Buffalo Multi Cat Health. All of them are eating it like a champ. They love it. I have noticed that the hairballs have greatly reduced and not much vomiting up food. Thanks so much for a great product. May 25, 2016
Rated 5 out of 5 by ginny54 my cats love it I have seven cats and everyone of them love it. They sit by their bowls waiting to be fed this is my first time using Blue Buffalo and so far so good. They have adjusted nicely. They don't seem to throw up near as often. I really like Blue Buffalo cause if my cats are happy so am I. May 20, 2016


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I live in the South.
We like our mother nature with a 2 week notice, re: hurricanes.
So yesterday when the whole "in like a lion" roared through hauling some spring showers, it also brought major thunder, lighting, power outages, and something totally unexpected- a tornado.
Right down the street.
It was super fun huddled in the downstairs bathroom with my daughter, my 5 year old niece, and my kitten.
(tornado damage off of Theodore Dawes and Old Pascagoula in Theodore, Al)
I'm sad about the grocery store, restaurant and the hardware store, but not so sad about BP.
Cause. Well, You know.
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Sounds Like: Classic Rock, Funk and RnB, Singer Songwriter, British Invasion, modern rock, 80's
Label: (4-Fo-Rela Records) Your Local Studio, Fermata Records, Lgbeatjp, Twister DjPat
Bio: Me As We, as well as my cover band Mo' Papaya, are musical collective names for all the various recording projects and performing gigs I've had over the years. I've played in bands since I was a teenager. But then I started writing songs, and often have taken on the role of a one man band to acco...See Full Bio
"Very cool stuff!"
Chris Gibson
Vocals, Guitars, Bass, Keyboards, Programming, Production
Gontani Tatsuya


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This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
In the work of Chari et al. entitled "Effect of active smoking on the human bronchial epithelium transcriptome" the authors use SAGE to identify candidate gene expression changes in bronchial brushings from never, former, and current smokers. These gene expression changes are categorized into those that are reversible or irreversible upon smoking cessation. A subset of these identified genes is validated on an independent cohort using RT-PCR. The authors conclude that their results support the notion of gene expression changes in the lungs of smokers which persist even after an individual has quit.
This correspondence raises questions about the validity of the approach used by the authors to analyze their data. The majority of the reported results suffer deficiencies due to the methods used. The most fundamental of these are explained in detail: biases introduced during data processing, lack of correction for multiple testing, and an incorrect use of clustering for gene discovery. A randomly generated "null" dataset is used to show the consequences of these shortcomings.
Most of Chari et al.'s findings are consistent with what would be expected by chance alone. Although there is clear evidence of reversible changes in gene expression, the majority of those identified appear to be false positives. However, contrary to the authors' claims, no irreversible changes were identified. There is a broad consensus that genetic change due to smoking persists once an individual has quit smoking; unfortunately, this study lacks sufficient scientific rigour to support or refute this hypothesis or identify any specific candidate genes. The pitfalls of large-scale analysis, as exemplified here, may not be unique to Chari et al.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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The c-myb proto-oncogene product (c-Myb) regulates proliferation and differentiation of hematopoietic cells. Recently we have shown that c-Myb is degraded in response to Wnt-1 stimulation via a pathway involving TAK1 (TGF-β-activated kinase), HIPK2 (homeodomain-interacting protein kinase 2), and NLK (Nemo-like kinase). NLK and HIPK2 bind directly to c-Myb and phosphorylate c-Myb at multiple sites, inducing its ubiquitination and proteasome-dependent degradation. The mammalian myb gene family contains two members in addition to c-myb, A-myb, and B-myb. Here, we report that the Wnt-NLK pathway also inhibits A-Myb activity, but by a different mechanism. As in the case of c-Myb, both NLK and HIPK2 bound directly to A-Myb and inhibited its activity. NLK phosphorylated A-Myb, but did not induce A-Myb degradation. Overexpression of NLK inhibited the association between A-Myb and the coactivator CBP, thus, blocking A-Myb-induced trans-activation. The kinase activity of NLK is required for the efficient inhibition of the association between A-Myb and CBP, although the kinase-negative form of NLK also partly inhibits the interaction between A-Myb and CBP. Furthermore, NLK induced the methylation of histone H3 at lysine-9 at A-Myb-bound promoter regions. Thus, the Wnt-NLK pathway inhibits the activity of each Myb family member by different mechanisms.
The c-myb proto-oncogene is the cellular progenitor of the v-myb oncogenes carried by the chicken AMV (avian myeloblastosis virus) and E26 retroviruses, which cause acute myeloblastic leukemia and erythroblastosis, respectively (Klempnauer et al., 1982 ; Leprince et al., 1983 ). A study of c-myb-deficient mice indicated that c-myb is essential for proliferation of immature hematopoietic cells (Mucenski et al., 1991 ), and analysis of tissue-specific c-myb knockout mice revealed that c-myb is also required for T-cell development at several stages (Bender et al., 2004 ). The vertebrate myb gene family contains two other members, A-myb and B-myb (Nomura et al., 1988 ). A-myb is highly expressed in a few cell types, including male germ cells and female breast ductal epithelium (Trauth et al., 1994 ). Consistent with this expression pattern, A-myb is required for spermatogenesis and development of breast tissue after pregnancy (Toscani et al., 1997 ). B-myb expression is broader than that of c-myb or A-myb (Nomura et al., 1989), and B-myb is essential for inner cell mass (ICM) formation in the early stages of development (Tanaka et al., 1999 ).
All three members of the vertebrate myb family proteins have a conserved DNA-binding domain (DBD), which consists of three imperfect tandem repeats of 51–52 amino acids that recognize the specific DNA sequence 5′-AACNG-3′ (Biedenkapp et al., 1988 ; Ogata et al., 1994 ). The transcriptional activation domain containing the acidic amino acid-rich region is also localized adjacent to the DBD in all three myb family members (Sakura et al., 1989 ; Nakagoshi et al., 1993 ; Takahashi et al., 1995 ). The transcriptional coactivator CBP binds to this activation domain (Dai et al., 1996 ; Oelgeschlager et al., 1996 ; Facchinetti et al., 1997 ; Bessa et al., 2001 ). The vertebrate myb family proteins regulate transcription of various target genes such as c-myc, which are involved in cell cycle control, suppression of apoptosis, or differentiation control (Ness et al., 1989 ; Nakagoshi et al., 1992 ; Frampton et al., 1996 ; Taylor et al., 1996 ; Kowenz-Leuz et al., 1997 ). The carboxy (C)-terminal portions of c-Myb and A-Myb have a negative regulator domain (NRD), and its deletion increases trans-activation by c-Myb and A-Myb (Sakura et al., 1989 ; Takahashi et al., 1995 ). The NRD of c-Myb contains two ΦXXΦΦ (Φ: hydrophobic amino acids) motifs (Kanei-Ishii et al., 1992 ) and binds directly to two corepressors TIF1β and BS69 (Ladendorff et al., 2001 ; Nomura et al., 2004 ). B-Myb activity is also suppressed by the corepressors N-CoR and SMRT (Li and McDonnell, 2002 ). The trans-activating capacity of both A-Myb and B-Myb is also positively regulated through phosphorylation by cyclin A/Cdk2 (Ziebold and Klempnauer, 1997 ; Saville and Watson, 1998 ).
The functions of the nuclear oncogene products Jun/Fos and NF-κB are regulated by signaling pathways, which include JNK/p38 and IκB kinases, respectively (Ghosh and Karin, 2002 ; Weston and Davis, 2002 ). In contrast, the specific signaling pathways that regulate c-Myb activity have been unknown. Recently, we showed that c-Myb is phosphorylated and degraded via the Wnt-1 signaling pathway involving TAK1 (TGF-β-activated kinase), HIPK2 (homeodomain-interacting protein kinase 2), and NLK (Nemo-like kinase) (Kanei-Ishii et al., 2004a ). NLK and HIPK2 each bind directly to c-Myb, which results in phosphorylation of c-Myb at multiple sites, ubiquitination, and proteasome-dependent degradation. Because Wnt signaling controls differentiation or apoptosis in many cell types, including hematopoietic cells (Wodarz and Nusse, 1998 ; Peifer and Polakis, 2000 ), Wnt-induced c-Myb degradation may play some role in the proliferation and differentiation of hematopoietic cells. However, it is unknown whether the Wnt-NLK pathway also inhibits A-Myb and B-Myb activity. Because A-Myb and B-Myb function in different cell types than c-Myb, it is important to analyze the effect of the Wnt-1 signal on these members of the myb family proteins.
Here, we demonstrate that both A-Myb and B-Myb are inhibited by the Wnt-NLK pathway. However, NLK does not induce the degradation of A-Myb, but inhibits the interaction between A-Myb and the coactivator CBP and induces the methylation of histone H3 to block A-Myb activity.
GST pulldown assays using GST-NLK and GST-HIPK2C were performed, as described previously (Kanei-Ishii et al., 2004a ). To increase the solubility of GST fusion proteins expressed in bacteria, the thioredoxin coexpression system (Yasukawa et al., 1995 ) was used. The binding buffer used for most experiments consists of 20 mM HEPES, pH 7.5, 1 mM dithiothreitol (DTT), 0.1% NP-40, and 100 mM NaCl (for interactions between A-Myb and NLK or HIPK2) or 150 mM NaCl (for interactions between A-Myb and deletion mutants of CBP). GST pulldown assays using GST-CBP-KIX was performed, as described previously (Kanei-Ishii et al., 2004b ).
To investigate the in vivo interaction between A-Myb and NLK, CV-1 cells (5 × 105 cells per 100-mm dish) were transfected by LipofectAMINE Plus (Invitrogen, Carlsbad, CA) with the plasmids to express FLAG-A-Myb (2 μg) or HA-NLK (1 μg). Total plasmid amounts were adjusted to 8.0 μg by adding empty plasmid. The FLAG-A-Myb expression vector contains four tandem repeats of the FLAG tag at the N-terminus of A-Myb and the chicken cytoplasmic β-actin promoter. Transfectants were incubated for 24–36 h and lysed in TNE buffer (10 mM Tris-HCl, pH 7.8, 1 mM EDTA, 1% NP-40, protease inhibitor cocktail, 50 mM NaF, 25 mM β-glycerophosphate) containing 500 mM NaCl. Anti-HA (12CA5, Roche Diagnostics, Indianapolis, IN) or normal mouse IgG (Santa Cruz Biotechnology, Santa Cruz, CA) were used for immunoprecipitation. The immunocomplexes were washed three times with TNE buffer containing 1 M NaCl. To examine the effect of NLK on the A-Myb-CBP or B-Myb-CBP interaction, CV-1 cells were transfected with the plasmid encoding HA-tagged CBP (4 μg), A-Myb or B-Myb (2 μg), NLK (1 μg) or the control plasmid, and the internal control pCMV-luc (0.01 μg; total of 8.01 μg DNA) using LipofectAMINE Plus. In the case of B-Myb, transfected cells were treated with MG132 (50 μM) for 7 h before preparation of lysates. The immunoprecipitation was performed as described above. For immunoblotting, immunoprecipitates or whole cell lysates were resolved on SDS-PAGE and transferred to Hybond-P membranes (Amersham, Piscataway, NJ). The membranes were immunoblotted with various antibodies and the bound antibodies were visualized by horseradish peroxidase-conjugated antibodies against rabbit or mouse IgG using ECL (Amersham).
To examine the effect of NLK on the A-Myb levels, CV-1 cells were transfected with a mixture of FLAG-A-Myb expression plasmid (4 μg), NLK expression plasmid (2 μg), and the internal control plasmid pact-β-gal (0.3 μg). Total plasmid amounts were adjusted to 8.3 μg by adding empty plasmid. To investigate the effect of NLK on the B-Myb levels, CV-1 cells were transfected with a mixture of FLAG-B-Myb expression plasmid pact-4xFLAG-B-Myb (5 μg), NLK expression plasmid (2 μg), and the internal control plasmid pact-β-gal (0.3 μg). In some cases, the transfected cells were treated with MG132 (50 μM) for 7 h before preparation of lysates. To examine the effect of various components of the Wnt-NLK pathway on the A-Myb levels, CV-1 cells were transfected with a mixture of FLAG-A-Myb expression plasmid (2 μg), the plasmid to express each component (1 μg), and the internal control pCMV-luc (0.01 μg; total 8.01 μg). Cells were cultured for 40 h after transfection and then lysed in SDS sample buffer with mild sonication and subjected to SDS-PAGE, Western blotting with an anti-FLAG monoclonal antibody (Sigma, St. Louis, MO), and ECL detection. Aliquots of the cells were used to determine the transfection efficiency by measuring β-galactosidase or luciferase activity and the amounts of lysates used for Western blotting were normalized based on the β-galactosidase or luciferase activity.
For phosphorylation of A-Myb by NLK (Figure 2B), 293 cells were transfected with the FLAG-A-Myb expression plasmid (pact-FLAG-A-Myb) or the FLAG-NLK expression plasmid. The lysates were prepared from the transfected cells using NET buffer (20 mM Tris-HCl, pH 8.0, 1 mM EDTA, 0.5% NP-40, protease inhibitor cocktail) containing 150 mM NaCl and immunoprecipitated with anti-FLAG antibody (M2, Sigma). The immunocomplexes were sequentially washed with washing buffer (20 mM Tris-HCl, pH 8.0, 1 mM EDTA, 1 M NaCl, 2% NP-40, and 10% glycerol) and then NLK buffer (10 mM HEPES, pH 7.4, 1 mM DTT, and 5 mM MgCl2). An aliquot of the A-Myb immunocomplexes was used for Western blotting. FLAG-NLK proteins were eluted from the immunocomplexes with excess FLAG peptide. To phosphorylate A-Myb proteins, the A-Myb immunocomplexes were mixed with the eluted FLAG-NLK proteins and [γ-32P]ATP and incubated at 25°C for 2 h. The amount of A-Myb protein used in the kinase reaction was adjusted based on the Western blotting data. Phosphorylated proteins were analyzed by SDS-PAGE and autoradiography.
Using LipofectAMINE PLUS, CV-1 cells (1 × 105 cells per 60-mm dish) were transfected with the 6MBS-I-SV40-luc reporter (0.5 μg), the A-Myb or B-Myb expression plasmid (0.2 μg), the NLK (0.03, 0.1 or 0.3 μg), or HIPK2 (0.1, 0.3, or 1.0 μg) expression plasmid, and the internal control plasmid pCMV-luc (0.1 μg), followed by luciferase assays. The chicken β-actin promoter was used to express A-Myb and B-Myb. In experiments to determine the effect of Wnt-NLK pathway components on A-Myb activity (Figure 3), the pGL3-R2.2–6MBS-I-TK-luc reporter, which was made using the Rapid Response Reporter Vectors (Promega, Madison, WI) was used. CV-1 cells (2 × 105 cells per 60-mm dish) were transfected with the pGL3-R2.2–6MBS-I-TK-luc reporter (0.5 μg), and plasmids to express A-Myb (0.2 μg), R-Fz1 (0.1, 0.3, or 1.0 μg), R-Fz2 (0.1, 0.3, or 1.0 μg), TAK1/TAB1 (0.03, 0.1 or 0.3 μg), or the dominant-negative form of HIPK2 (1.0 μg), and the internal control plasmid pact-β-gal (0.05 μg). Luciferase assays were performed 24 h after transfection. The total amount of plasmid DNA was adjusted to 2.05 μg by adding empty plasmid.
To investigate the in vivo acetylation of A-Myb by CBP, CV-1 cells were transfected with the CBP expression plasmid pcDNA3-CBP-FLAG (4 μg) together with pact-FLAG-A-Myb (1 μg) and pCMV-FLAG-NLK or a control plasmid (1 μg). Cells were culture for 2 d after transfection, lysed in RIPA buffer (50 mM Tris-HCl, pH 7.4, 150 mM NaCl, 1% Triton X-100, 1% sodium deoxycholate, 0.1% SDS, 10 mM sodium butylate) and centrifuged at 15,000 rpm. The supernatants were subjected to SDS-PAGE and Western blotting. The acetylated forms of A-Myb were detected with an anti-acetylated lysine polyclonal antibody (Cell Signaling, Beverly, MA), and a mixture of acetylated and nonacetylated forms of A-Myb were detected with the anti-FLAG M2 antibody.
Chromatin immunoprecipitation (ChIP) assays were carried out essentially as described (Tanikawa et al., 2004 ) and in the Upstate Biotechnology protocol (Lake Placid, NY), with minor modifications. In brief, 1.5 × 105 CV-1 cells were transfected with FLAG-A-Myb expression plasmid or control plasmid (0.5 μg), CBP-HA expression plasmid (1.0 μg), NLK expression plasmid or control plasmid (0.5 μg), pGL3–6MBS-I-TK-Luc reporter plasmid (0.1 μg), and the internal control plasmid pCMV-luc (0.01 μg). The cytomegalovirus promoter was used in all expression plasmids. Cells were cultured for 40 h after transfection and then cross-linked and processed according to the manufacturer's protocol. Immunoprecipitation was performed overnight at 4°C with 6 μg of anti-FLAG antibody (M2, Sigma) or normal mouse IgG (Santa Cruz) as a negative control. The amounts of lysates used for immunoprecipitation was normalized based on the transfection efficiency (luciferase activity of pCMV-luc). In the ChIP assays to detect methylated histone H3, immunoprecipitation was performed using 2 μg of K9-H3m3 antibody (Abcam, Cambridge, UK). The immunocomplexes were washed and incubated at 65°C in 100 μl of IP elution buffer (1% SDS, 0.1 M NaHCO3, 250 mM NaCl, 0.2 μg/μl proteinase K, 10 mM DTT) to release the proteins. In immunocomplexes containing FLAG-A-Myb, the complexes were incubated in IP elution buffer in the presence of the FLAG peptide (300 μg/ml) to enhance the elution efficiency. The de-cross-linked chromatin DNA was further purified using QIAquick PCR Purification Kit (QIAGEN, Santa Clarita, CA) and eluted in 40 μl sterile water. The eluted DNA samples (5 μl) were used for real-time PCR (7500 Real Time PCR System, Applied Biosystems, Foster City, CA). The primers and TaqMan probe (QIAGEN) used for the amplification of the 6MBS-I tk promoter were as follows: forward (5′-AATTCGAACACGCAGATGCA-3′), reverse (5′-GCCACACGCGTCACCTTAAT-3′), TaqMan probe (5′-CGCGGTCCCAGGTCCACTTCG-3′).
In the case of c-Myb, two kinases, NLK and HIPK2, bind directly to c-Myb (Kanei-Ishii et al., 2004a ). To examine whether A-Myb also directly interacts with these kinases, we performed GST pulldown assays. Wild-type A-Myb translated in vitro bound to GST-NLK and GST-HIPK2C resins (Figure 1A). The A-Myb mutant translated in vitro, which lacked repeats 2 and 3 in the DBD, failed to bind to GST-NLK and GST-HIPK2C. Further, an in vitro-translated R23 domain of A-Myb efficiently bound to GST-NLK and GST-HIPK2C. The in vivo association between A-Myb and NLK was investigated by coimmunoprecipitation, using lysates from CV-1 cells transfected with plasmids expressing FLAG-tagged A-Myb and HA-tagged NLK (Figure 1B). Anti-HA antibody coprecipitated FLAG-A-Myb, whereas control IgG did not. Thus, like c-Myb, A-Myb also binds to NLK and HIPK2 via its DBD. We also tested whether B-Myb, another member of the myb protein family, interacts with NLK and HIPK2. In vitro-translated B-Myb bound to GST-NLK and GST-HIPK2C (Figure 1C). These results indicate that direct interactions with NLK and HIPK2 are a common feature of all three members of the mammalian myb family proteins.
NLK phosphorylates c-Myb, leading to its proteasome-dependent degradation (Kanei-Ishii et al., 2004a ). In contrast, coexpression of NLK with A-Myb in CV-1 cells did not reduce A-Myb levels (Figure 2A, lanes 1 and 2), indicating that NLK does not induce degradation of A-Myb. The mobility of A-Myb coexpressed with NLK in SDS-PAGE was slower than that of A-Myb expressed alone or A-Myb coexpressed with kinase-negative NLK (Figure 2A). The change in mobility was blocked when the lysates were treated with λ phosphatase before electrophoresis. These results suggest that A-Myb is efficiently phosphorylated by NLK, resulting in its slower migration in the gel. The phosphatase treated A-Myb migrated faster than A-Myb expressed alone without NLK, indicating that uncharacterized kinase(s) other than NLK also phosphorylates A-Myb. This is not surprising because many kinases may phosphorylate transcription factor, such as A-Myb, although the physiological role of those kinases remains unknown. To confirm NLK phosphorylate of A-Myb, in vitro kinase reactions were performed (Figure 2B). 293 cells were transfected with the FLAG-A-Myb or FLAG-NLK (wild-type or kinase-negative form), and A-Myb and NLK were purified by immunoprecipitation under high stringency (1 M NaCl, 2% NP-40). Under this high stringency, most of the associated proteins are likely to be dissociated, and in fact we confirmed that HIPK2 was not included in the immunopurified NLK sample (unpublished data). When the purified A-Myb was incubated with the purified NLK in the presence of [γ-32P]ATP, A-Myb became phosphorylated, whereas kinase-negative NLK did not phosphorylate A-Myb (Figure 2B).
Although NLK did not induce the degradation of A-Myb, we found that NLK inhibits A-Myb activity in luciferase reporter assays. NLK inhibited A-Myb-dependent luciferase expression from the 6MBS-I-luc reporter, which contains six tandem repeats of the Myb-binding site, in a dose-dependent manner (Figure 2C, left). NLK also suppressed A-Myb-induced luciferase expression from the c-myc promoter, which is an endogenous one target gene of Myb (Nakagoshi et al., 1992 ; Figure 2C, right). These results indicate that NLK phosphorylates A-Myb and inhibits its activity without inducing its degradation. The kinase-negative NLK more weakly inhibited the luciferase expression from the 6MBS-I-luc and c-myc-luc reporters than wild-type NLK, when the same amounts of the expression vector was used (0.3 μg; Figure 2C). However, kinase-negative NLK had still some inhibitory activity. These results suggest that NLK inhibits the A-Myb activity in the kinase-dependent and -independent manner.
When similar experiments were performed using B-Myb, coexpression of NLK with B-Myb partially decreased the B-Myb levels (Figure 2D), but did not lead to complete degradation of the protein, as seen with c-Myb (Kanei-Ishii et al., 2004a ). In luciferase reporter assays, NLK also inhibited B-Myb-dependent luciferase expression from the 6MBS-I reporter (Figure 2E). Thus, NLK appears to negatively regulate B-Myb activity both by induction of B-Myb degradation and by a mechanism similar to that of A-Myb.
Because the mechanism by which NLK suppresses A-Myb activity is completely different from that of c-Myb, we asked whether the Wnt-TAK1-HIPK2-NLK pathway inhibits A-Myb activity, as it does c-Myb. In reporter assays using the 6MBS-I-luc reporter expressed in CV-1 cells, A-Myb activity was inhibited in a dose-dependent manner by coexpression of rat Frizzled-1 and Frizzled-2(R-Fz1 and R-Fz2), which act as receptors for Wnt-1 and Wnt5a in the canonical Wnt and noncanonical Wnt/Ca2+ pathways, respectively (Figure 3, A and B). Coexpression of TAK1/TAB1 and HIPK2 also suppressed A-Myb activity (Figure 3, C and D). To examine whether R-Fz1, R-Fz2, and TAK1/TAB1 function in the upstream region of HIPK2 in the same signaling pathway, we analyzed the effect of the kinase-negative form of HIPK2 on the suppression of A-Myb activity by R-Fz1, R-Fz2, and TAK1/TAB1. The inhibitory effect of R-Fz1, R-Fz2, and TAK1/TAB1 was blocked by coexpressing the kinase-negative HIPK2 mutant (Figure 3E). Because kinase-negative NLK partially blocks the A-Myb activity, this cannot be used in the similar experiments to examine whether NLK acts in the same signaling pathway as R-Fz1, R-Fz2, TAK1/TAB1, and HIPK2. However, our recent report clearly demonstrated that NLK plays a role in the downstream of the Wnt-TAK1/TAB1-HIPK2 signaling pathway (Kanei-Ishii et al., 2004a ). Thus, A-Myb-dependent transcriptional activation is inhibited by the Wnt-TAK1-HIPK2-NLK pathway.
To further confirm that the degradation of A-Myb is not induced by the Wnt-TAK1/TAB1-HIPK2 signaling pathway, the effect of coexpression of each component of this pathway on the A-Myb levels was examined. Coexpression of HIPK2, TAK1/TAB1, R-Fz1, or R-Fz2 with A-Myb did not affect the A-Myb levels (Figure 3F).
The transcriptional coactivator CBP binds directly to the activation domain of all three members of the Myb family and mediates Myb-dependent transcriptional activation (Dai et al., 1996 ; Oelgeschlager et al., 1996 ; Facchinetti et al., 1997 ; Bessa et al., 2001 ). Theses data suggest that NLK may block the interaction between A-Myb and CBP. To test this, we coimmunoprecipitated lysates from CV-1 cells expressing FLAG-A-Myb and CBP, in the presence or absence of NLK expression vector (Figure 4A). In the absence of NLK, the anti-CBP antibody efficiently coprecipitated A-Myb, demonstrating complex formation between A-Myb and CBP. In contrast, coexpression of NLK almost completely blocked the A-Myb-CBP complex formation. Interestingly, coexpression of kinase-negative NLK partially inhibited the association between A-Myb and CBP. These results suggest that NLK inhibits the interaction between A-Myb and CBP by both kinase-dependent and -independent mechanisms. This is consistent with the observation that NLK inhibits the A-Myb-induced luciferase expression from the c-myc promoter in the kinase-dependent and kinase-independent manner (Figure 2C).
Previously, we found that kinase-negative NLK inhibits the interaction between c-Myb and CBP (Kanei-Ishii et al., 2004b ). To test whether kinase-negative NLK also competes with CBP for binding to A-Myb we performed GST pulldown assay (Figure 4B). In vitro-translated A-Myb efficiently bound to the GST-CBP resin and addition of an in vitro-translated kinase-negative NLK inhibited the binding of A-Myb to GST-CBP in a dose-dependent manner. Thus, NLK blocks the interaction between A-Myb and CBP by directly binding to A-Myb.
We also examined whether NLK blocks the interaction between B-Myb and CBP by similar coimmunoprecipitation experiments using lysates from CV-1 cells expressing FLAG-B-Myb and CBP, in the presence or absence of NLK expression vector (Figure 4C). In the absence of NLK, the anti-CBP antibody efficiently coprecipitated B-Myb, whereas coexpression of NLK dramatically diminished the B-Myb-CBP complex formation. Thus, NLK also inhibits the interaction between B-Myb and CBP.
To further confirm that NLK blocks the interaction between CBP and A-Myb, we investigated the effect of NLK on the acetylation of A-Myb by CBP. Previous work has shown that CBP binds to c-Myb via its KIX and C/H2 domains, and acetylates c-Myb at multiple sites, leading to enhanced c-Myb-dependent transcriptional activation (Dai et al., 1996 ; Sano and Ishii, 2001 ). In vitro-translated A-Myb also bound to GST-CBP resins containing either the KIX or C/H2 domains (Figure 5A). Coexpression of increasing amounts of CBP induced acetylation of A-Myb in a dose-dependent manner (Figure 5B). However, when A-Myb and CBP were coexpressed with NLK, acetylation of A-Myb was inhibited (Figure 5C). Thus, NLK inhibits the CBP-induced acetylation of A-Myb by blocking the interaction between A-Myb and CBP. Interestingly, kinase-dead NLK had only weak inhibitory activity on the CBP-induced acetylation of A-Myb (Figure 5C), although this NLK mutant significantly inhibits the A-Myb-CBP interaction (Figure 4A). These results may suggest that the relatively strong interaction between A-Myb and CBP may be necessary for the CBP-induced acetylation of A-Myb. One possibility is that kinase-negative NLK may specifically affects interaction of one of the domains (KIX domain) of CBP with A-Myb.
One major activity of CBP is acetylation of histones, and the degree of histone acetylation can be controlled by a balance between histone acetyltransferase (HAT) and histone deacetylase (HDAC) activity. Therefore, if the major mechanism of NLK action is to block CBP recruitment, the NLK action would not be attenuated by the HDAC inhibitor, because there would be no acetylation to be removed by HDACs. To investigate this, we analyzed the effect of trichostatin A (TSA), an inhibitor of histone deacetylase (HDAC), on NLK activity. Because it was reported that transient transfected cells can be used to examine the effect of TSA (Li and McDonnell, 2002 ), we also used the CV-1 cells transiently transfected with Myb sites containing luciferase reporter. NLK inhibited A-Myb-dependent luciferase expression from the 6MBS-I-luc reporter as shown above (Figure 2C). Treatment of transfected cells with TSA did not block the effect of NLK (Figure 6A). These results are consistent with the data indicating that NLK inhibits A-Myb-dependent trans-activation by inhibiting the recruitment of CBP.
In addition to the deacetylation of histones, methylation of histones plays an important role in repression of transcription. Specifically, methylation of the histone H3 tail at lysine-9 (H3-K9) is associated with gene silencing (Lachner et al., 2001 ; Nakayama et al., 2001 ; Schotta et al., 2002 ). Lysines can accept three methyl groups and can therefore be monomethylated, dimethylated, or trimethylated (denoted as m, m2, and m3; Dutnall, 2003 ). In mammalian cells, H3-K9m3 is preferentially localized to pericentromeric heterochromatin, whereas H3-K9m and H3-K9m2 are localized to euchromatin (Peters et al., 2003 ; Rice et al., 2003 ). We examined whether NLK affects histone H3-K9 methylation using ChIP assays. Because it was reported that transient transfected cells can be used for ChIP experiments (Lee et al., 2002 ; Wells and Farnham, 2002 ), we also used the CV-1 cells transiently transfected with Myb sites containing luciferase reporter. CV-1 cells were transfected with the 6MBS-I-luc reporter and the FLAG-A-Myb expression plasmid or the control plasmid, with or without the NLK expression plasmid. The amounts of Myb site-containing promoter DNA fragment precipitated with anti-H3K9m3 antibody increased with coexpression of NLK (Figure 6B, left panel). It is thought that H3-K9 acetylation and methylation are mutually exclusive, and the high degree of methylation of H3K9m3 had been expected in the absence of A-Myb. However, the degree of methylation of H3K9m3 in the absence of A-Myb was not so high, and the degree of methylation was apparently enhanced by NLK. These results suggest that NLK inhibits A-Myb-dependent trans-activation by inducing methylation of histone H3 at lysine-9. In ChIP assays, the anti-FLAG antibody precipitated 45% less Myb site-containing promoter DNA when NLK was coexpressed (Figure 6B, right panel), indicating that the amounts of A-Myb bound to the promoter decreased in the presence of NLK. NLK blocks interaction between A-Myb and CBP, which may destabilize the A-Myb complex on Myb-binding sites.
The present study demonstrated that, like c-Myb, trans-activation by both A-Myb and B-Myb is negatively regulated by the Wnt-NLK pathway. However, unlike c-Myb, A-Myb is not degraded by the Wnt-NLK pathway. Overexpression of NLK inhibits the association between the coactivator CBP and A-Myb; this inhibition is partly dependent on the kinase activity of NLK, because the kinase-negative form of NLK only partially inhibited A-Myb activity. NLK bound to A-Myb also induced methylation of histone H3-K9 (Figure 7). B-Myb levels were slightly decreased by coexpression of NLK, suggesting that NLK weakly induces B-Myb degradation. These results suggest that the Wnt-NLK pathway inhibits B-Myb activity by two mechanisms; degradation of B-Myb, similar to c-Myb, and inhibition of B-Myb-CBP interaction and histone H3-K9 methylation, similar to A-Myb.
NLK is a member of the MAP kinase super family that is known to phosphorylate the Ser or Thr residues next to Pro. A-Myb contains 16 putative NLK phosphorylation sites, and introducing the Ala mutation into six sites in the C-terminal region conserved among Myb family proteins did not completely abrogate the phosphorylation by NLK (unpublished data), suggesting the presence of more NLK phosphorylation sites. Thus, NLK phosphorylates both A-Myb and c-Myb at multiple sites in CV-1 cells, but NLK only induces the degradation of c-Myb, not A-Myb. We have recently identified the specific ubiquitin E3 ligase that induces the ubiquitination and proteasome-dependent degradation of the NLK-phosphorylated c-Myb (unpublished data). It is possible that we did not detect A-Myb degradation by NLK because the E3 ligase does not recognize NLK-phosphorylated A-Myb, or alternatively, that CV-1 cells lack an E3 ligase, which binds to NLK-phosphorylated A-Myb. Therefore, we cannot exclude the possibility that NLK induces A-Myb degradation in some cell types expressing an E3 ligase, which recognizes NLK-phosphorylated A-Myb. Similarly, it is possible that the Wnt-NLK pathway inhibits c-Myb-dependent trans-activation in some cell types by blocking CBP recruitment and inducing histone methylation.
Multiple histone methylases (HMTases), including Suv39h1, Suv39h2, and G9a, can methylate H3-K9 (Rea et al., 2000 ; Tachibana et al., 2001 ). A hallmark of this class of HMTases is the presence of a 130-amino acid SET domain (Jenuwein, 2001 ), which is crucial for catalytic activity but requires an adjacent cysteine-rich domain (Rea et al., 2000 ). The Suv39h enzymes display an exquisite site-selectivity toward H3-K9 methylation that is highest for an unmodified H3 amino terminus (Rea et al., 2000 ). G9a is a "dual" HMTase methylating the K9 and K27 positions and seems broadly dispersed in interphase chromatin without enrichment at heterochromatic foci (Tachibana et al., 2002 ). Because G9a is one of the major HMTase localized in euchromatin, we investigated whether G9a is involved in NLK-mediated histone H3K9 methylation. G9a efficiently bound to NLK in the coimmunoprecipitation assays, but the dominant-negative form of G9a did not block NLK-dependent inhibition of trans-activation by A-Myb (unpublished data). These results suggest that G9a could be partly involved in the NLK-mediated inhibition of A-Myb activity, but G9a is not the primary HMTase recruited by NLK. Interestingly, the ESET HMTase is highly expressed in testis (Yang et al., 2002 ), a tissue that expresses A-myb.
A-myb is highly expressed in a limited range of cell types, including male germ cells and female breast ductal epithelium (Trauth et al., 1994 ). A-myb-deficient males are infertile because of a block in spermatogenesis, and A-myb null females show underdevelopment of breast tissue after pregnancy (Toscani et al., 1997 ). Wnt signaling was reported to have a critical role in the growth regulation of mammary epithelial cells and testis development (Miyoshi et al., 2002 ; Civenni et al., 2003 ; Jordan et al., 2003 ). Therefore, the Wnt-dependent negative regulation of A-Myb activity demonstrated in this study may play important role in control of the proliferation and differentiation of mammary epithelial cells and germ cells by Wnt signals.
We are grateful to K. Matsumot for the TAK1, TAB1, and NLK cDNAs; R. T. Moon for the R-Fz1 and R-Fz2 cDNA; and Y. Kim for the HIPK2 cDNA. This work was supported in part by the Grants-in-Aid for Scientific Research of the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E05-05-0470) on July 29, 2005.
Abbreviations used: A-Myb, A-myb gene product; ChIP, chromatin immunoprecipitation; c-Myb, c-myb proto-oncogene product; DBD, DNA-binding domain; H3K9, lysine-9 of histone H3; HIPK2, homeodomain-interacting protein kinase 2; HMTase, histone methyltransferase; NLK, Nemo-like kinase; NRD, negative regulatory domain; TAK1, TGF-β-activated kinase 1; TSA, trichostatin A.
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GE Leads $427 Billion of U.S. Debt Due in 2014: Credit Markets
General Electric Co. is leading U.S. corporate issuers that have about $427 billion of bonds and loans maturing this year, down 5 percent from 2013, as borrowing costs ascend from record lows.
GE, the largest maker of jet engines, has $35.2 billion of debt due in 2014, mostly at its finance unit, followed by banks including JPMorgan Chase & Co. and its $28.2 billion, and Bank of America Corp.'s $26.9 billion, data compiled by Bloomberg show. Non-financial issuers have $178 billion maturing, ranging from Cincinnati-based Procter & Gamble Co.'s $6 billion to junk-rated Dish Network Corp.'s $1 billion.
Companies have exploited unprecedented stimulus from the Federal Reserve over the past five years to refinance bonds and loans, leaving impending maturities about 30 percent less than the $620 billion confronted in 2012. After rising last year by the most since 2009, yields on benchmark 10-year Treasury notes are forecast to jump again in 2014 for the first back-to-back increase since 2005 and 2006, Bloomberg surveys show.
"One of the beneficial byproducts of this refinancing cycle is that it's afforded companies the opportunity to extend maturities significantly into the future and reduce near-term funding requirements," said Edward Marrinan, a macro credit strategist at Royal Bank of Scotland Group Plc's securities unit in Stamford, Connecticut. "This has definitely helped to suppress default risk."
Rising Yields
Concern is mounting that borrowing costs are on the rise. Yields on 10-year Treasuries, which are a benchmark for corporate bonds, ended 2013 at 3.03 percent, up from 1.76 percent at the end of 2012. Yields will likely finish this year at 3.4 percent, according to the median estimate of 64 economists and strategists surveyed by Bloomberg.
Average yields on the $3.73 trillion of investment-grade bonds tracked by Bloomberg fell to 2.54 percent in May before ending the year at 3.23 percent. Junk bond borrowing costs dropped to 4.66 percent before climbing to 5.86 percent.
The corporate debt coming due in 2014, which includes investment-grade and high-yield securities, accounts for about 7 percent of the $5.75 trillion in outstanding obligations, Bloomberg data show. That compares with 2013, when about 8 percent of the $5.44 trillion in bonds and loans matured. In 2012, debt due within a year was about 12 percent of borrowings.
Record Sales
Non-financial companies with the largest maturities include Procter & Gamble, the maker of Crest toothpaste, and Palo Alto, California-based Hewlett-Packard Co., at $5.5 billion. The amount due at GE Capital, which includes $3 billion of dollar-denominated bonds maturing Jan. 7, is down from $40 billion at the start of 2013, Bloomberg data show.
Seth Martin, a spokesman for Fairfield, Connecticut-based GE, declined to comment on its finances.
The debt due this year from Englewood, Colorado-based Dish, rated Ba3 by Moody's Investors Service and an equivalent BB- at Standard & Poor's, represents about 8 percent of its $12.3 billion of bonds due through 2023, Bloomberg data show. High-yield, high-risk, or junk, debt is rated below Baa3 by Moody's and lower than BBB- at S&P.
Companies have capitalized on unprecedented investor demand and low interest rates with record issuance of dollar-denominated bonds. Companies sold $1.51 trillion of bonds in the U.S. in 2013, split between $1.14 trillion of investment-grade debentures and $380 billion of junk bonds.
'Maturity Wall'
JPMorgan was the largest underwriter with 12.2 percent of the market, followed by Bank of America at 10.5 percent and Citigroup Inc. at 9.8 percent, Bloomberg data show.
The record bond issuance has coincided with a ballooning market for speculative-grade loans, propelled by demand for floating-rate debt that can offer protection from rising interest rates. Loan borrowing passed the 2007 peak of $581.5 billion in November, Bloomberg data show.
Concern has waned that companies won't be able to repay bank loans used to finance a boom in leveraged buyouts before the financial crisis, according to Barclays Plc.
Borrowers that in 2009 faced more than $200 billion of debt maturing in five years have since extended their obligations, leaving a loan maturity profile that's "much less daunting now and sufficiently backloaded," Barclays analysts including Bradley Rogoff and Eric Gross wrote in an October report.
Default Outlook
Conditions are ripe for the default rate on high-yield bonds and loans to remain below 2 percent through 2015, compared with a long-term average of at least 3.5 percent, JPMorgan strategists wrote last month in a report. Their estimate excludes Dallas-based Energy Future Holdings Corp., the subject of the largest leveraged-buyout in history, which has signaled it may need to file for bankruptcy protection.
"The maturity wall has been lifted," Jessie Harris, the head of taxable fixed-income research at U.S. Trust, said in a telephone interview. "You've got runway that's been cleared, so it's hard to imagine that defaults increase in the near term."
About 6.5 percent of outstanding junk-rated obligations, or $140 billion, are set to mature within the next two years, JPMorgan data show. That's down from 10.5 percent at the end of 2009, when the Fed's balance sheet was about $2.2 trillion.
The central bank's assets have since climbed above $4 trillion as it purchases Treasury and mortgage-backed bonds to pump cash into the financial system, limit interest-rate increases and encourage investment in riskier assets.
'Significant Refinancing'
The yield on the Bank of America Merrill Lynch U.S. Corporate & High Yield Index ended last year at 4.03 percent, 1.87 percentage points more than similar-maturity Treasuries. That's down from a yield of 11.1 percent and a spread of 8.64 percentage points on Nov. 24, 2008, the day before the Fed announced the first of three quantitative easing programs.
"Low rates and accommodative Fed policy have led to significant refinancing activity, pushing out a lot of near-term maturities and giving issuers a lot of liquidity and runway," Gross, a credit strategist at Barclays in New York, said in a telephone interview.
Elsewhere in credit markets, the market for corporate borrowing through short-term IOUs contracted by the most in four years as financial institutions' issuance plunged. Cengage Learning Inc., the college textbook publisher that agreed in July with lenders to restructure $5.8 billion of debt, is seeking as much as $2 billion in loans to exit bankruptcy.
Credit Benchmarks
The cost to protect against losses on U.S. corporate bonds rose. The Markit CDX North American Investment Grade Index, a credit-default swaps benchmark used to hedge against losses or to speculate on creditworthiness, increased 0.8 basis point to 63.2 basis points as of 11:32 a.m. in New York, according to prices compiled by Bloomberg. The index ended Dec. 26 at 62 basis points, the lowest since October 2007.
In London, the Markit iTraxx Europe Index of 125 companies with investment-grade ratings added 0.4 to 70.6.
The indexes typically rise as investor confidence deteriorates and fall as it improves. Credit swaps pay the buyer face value if a borrower fails to meet its obligations, less the value of the defaulted debt. A basis point equals $1,000 annually on a contract protecting $10 million of debt.
The seasonally adjusted amount of U.S. commercial paper dropped $55.1 billion to $1.046 trillion outstanding in the week ended yesterday, the Federal Reserve said today on its website. That's the biggest decline on a percentage basis since $94.2 billion in the period ended Jan. 6, 2010, and the lowest level since Oct. 16.
Funds Paring
Money-market funds, among the biggest investors in the debt, may have reduced the amount of unsecured commercial paper from foreign banks they were holding at the end of the year in favor of assets perceived to be safer, such as repurchase agreements, which are backed by collateral, according to Howard Simons, strategist at Bianco Research LLC in Chicago.
Corporations sell commercial paper, typically maturing in 270 days or less, to fund everyday activities such as rent and salaries.
Cengage's financing would consist of a $250 million revolving line of credit and a term loan between $1.5 billion and $1.75 billion, according to a Dec. 27 court filing. A hearing will take place on Jan. 9 at 11 a.m. New York time.
The company, which was seeking to eliminate more than $4 billion of its debt burden, is seeking the exit financing six months after it obtained Chapter 11 protection. Apax Partners LLP and Omers Capital Partners bought Stamford, Connecticut-based Cengage in 2007 from Thomson Reuters Corp. for $7.75 billion. The acquisition was partially funded with $5.6 billion in borrowings.
The following is a table of the largest U.S. corporate debt maturities next year, using data calculated by Bloomberg:
Company 2014 Debt Maturities General Electric Co. $35 billion JPMorgan Chase & Co. $28 billion Bank of America Corp. $27 billion Citigroup Inc. $22 billion Morgan Stanley $20 billion Goldman Sachs Group Inc. $20 billion Wells Fargo & Co. $9.5 billion MetLife Inc. $7.4 billion Caterpillar Inc. $6.7 billion Procter & Gamble Co. $6 billion


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Is a Global Studies Major or Minor right for me?
An equally valid question might be, "Am I right for Global Studies?" Are you drawn to all things cross-cultural: meeting people from other cultures, the sounds and tastes of exotic places, understanding international events and trends, etc.? If a professor assigned you to follow the world news as a course requirement, would you consider it an opportunity or a chore? One potential student recently explained that, due to his many interests, he was not ready to choose a specific career path. Yet as he described his interests and routines—daily doses of BBC World Service news, constant downloads of World music, love of European and World Cup soccer—it became clear that Global Studies was the academic field for him! If you like the idea of academic rigor that is set to a global beat, Global Studies may be the field for you!
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Tackling an Ultra: The Eiger Ultra Trail 51KM race
26 07 2016
I signed up in a fit of stupidity back in November for the E51 race at the Eiger Ultra Trail on the 16th July, thinking I had plenty of time to train and it would be a good motivation to get back in good running shape again. Susie Burt from Mountain Tracks takes on the renowned E51, part of the renowned Ultra-Trail World Tour Series, and wonders when enough training is...well, enough1?View Article +
Berghaus are proud to donate some kit to a new exciting enterprise – The Library of Things
20 07 2016
Last month a new enterprise opened which Berghaus gifted some rucsacs too. We are now hoping that these items will go on new adventures around the UK and who knows possibly further afield. Here we get more info on how the Library of Things works and how you can get involved.View Article +
My top three life changing alpine style kit improvements – Mick Fowler
18 07 2016
When I started alpine style climbing in the 1970s I was very satisfied with the kit I used and never really thought much about whether it could be improved. Now I look back and so many things have got so much better that trying to choose just three that have made life easier is so difficult.View Article +
Sir Ranulph Fiennes unveils a new epic challenge
15 07 2016
Sir Ranulph Fiennes is to reach for his ice pick once again and embark on yet another death-defying challenge at the age of 72 and we're proud to be supporting the iconic adventurer with high performance kit to support this epic endeavour.View Article +
Rock Climbing in Scotland – Part 6 of the Himalayan Training Program
11 07 2016
Mick Fowler doesn't do "training" for his expeditions - he keeps fit by upping his activities and will be sharing each of them here on Berghaus.com. His next planned expedition is a reunion Himalayan adventure with Victor Saunders.View Article +
Climbing on Stanage Edge: Four of the Best
16 06 2016
Stanage, is the longest and finest outcrop of gritstone in the UK. Truly the king of moorland gritstone. The edge, located in the Peak District National Park, stretches for 3.5 miles across heather moors from its northern tip at Stanage End to the southern point near the Cowper Stone.View Article +
The next chapter from The Mick and Vic Re-union trip Himalayan Training Programme
10 06 2016
Mick Fowler doesn't do "training" for his adventures - he keeps fit by upping his outdoor adventures and he will be sharing each of them here on Berghaus.com. Here is the next installment - Walking and Cycling on Jura.View Article +
The difference between fell running and trail running (why I will never be a trail runner) – by Steve Birkinshaw
31 05 2016
My non-running friends often ask me about the difference between trail running and fell running (or hill running in Scotland). The obvious answer is that the terrain is different.View Article +
Leo & Bruce signing off from their Epic Greenland Snowkite 18-day expedition
31 05 2016
What a way to end the week, basking in the glorious, hot sunshine of the Lake District pre-midge Spring, enjoying a genteel paddle across the lake and soaking up the family friendly vibe of SUP fest with Jess and Freya.View Article +