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The chances of a sustained economic recovery in Britain depend crucially on events in the rest of the world, the Governor of the Bank of England, Mervyn King, has warned.
Speaking at the launch of the Bank's latest Inflation Report, its definitive view of the country's economic prospects, Mr King raised the spectre of protectionism to warn world leaders gathering in Seoul for the G20 summit of the need to reach agreement on a "gradual path" to resolve the currency and trade disputes that have flared violently in recent days.
Asked about the German finance minister's remark that the US Federal Reserve's $600bn (£374bn) injection into America's economy was "clueless", Mr King said he thought that there had been too many public interventions in recent days. However, he signalled his own differences with the US Treasury Secretary, Timothy Geithner, who has floated a cap of 4 per cent of gross domestic product for current account surpluses – aimed at China.
Mr King said: "It is very important that the fundamental point that is recognised at the weekend [will not be] decisions on instruments or exchange rates or targets for current account balances in terms of a number, but that there is a path along which the current account imbalances unwind. I hope that at the G20 meeting we will get a co-operative message rather than some of those that we have been getting in the last few days and weeks."
On a range of issues from house prices to private job creation and the possibility of a very sharp slowdown early next year as government spending cuts bite, Mr King offered an upbeat view. "The central view is clearly not that there will be a significantly sharp slowdown in growth from the last two quarters," he said.
The private sector, added Mr King, "can" generate enough jobs to prevent unemployment soaring. "Whether it will depends on many things which are not within our control and depend in part on the world economy. Yes, I am confident that it can," he said.
In words that may come back to haunt him, the Governor confessed that he did not see the real estate scene as being as "worrisome" as the IMF did.
Whatever his intentions, Mr King's view of the economic world is strikingly similar to the Treasury's. He admitted that members of the MPC may have a different view of fiscal policy, just as they differed on monetary policy. Some within the Bank are said to be privately critical that the Governor's support for the deficit reduction plan has blurred the Bank's political neutrality.
The Bank now thinks inflation will be higher during 2011 than previously thought – about 3.5 per cent in the first quarter of next year rather than the 3 per cent suggested in the August report. Mr King said that, had it not been for the rise in international commodity prices, the hikes in VAT this year and next, and the depreciation of sterling, inflation might well be heading for 1 per cent. It will be the first quarter of 2012 before it falls back below its 2 per cent target, and late 2011 for output to return to pre-recession levels.
The picture for growth was basically unchanged from the August Report – 2.5 per cent growth in GDP in 2012. This compares with the Office for Budget Responsibility's 2.3 per cent figure. However, the Bank's Inflation Report fan chart shows a large risk that the growth figure will be worse.
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This year promises to be an explosive one for Baltimore music. New records from Dan Deacon, Animal Collective, Wye Oak, Double Dagger, Lo Moda, Arbouretum - to name just a few.
So every so often on the blog, I'll try and keep track of new magazines that come in that talk about Baltimore music.
In Under The Radar #25:
Dan Deacon - Bromst
Score: 8/10
"...this album delivers an extremely interesting study in our relationship to the analog and digital worlds. It's Deacaon's most ambitious collection of songs to date." - Paul Bullock
Animal Collective - Merriweather Post Pavilion
Score: 7/10
"Their droning, formerly aimless wanderings (Animal Collective have always been much more about the journey than the destination) now contained brief moments of potent purpose." - Jim Scott
In Paste #50:
Animal Collective - Merriweather Post Pavilion
"After all, hands are meant not to be jettisoned up in frustration at dead-end lyrics, but thrown in the air as if you just didn't care. ... I ahve absolutely no idea what that means, and I don't care - print it up, put it on a T-shirt and hand me that glow stick." -Bart Blasengame
In Xlr8r #124:
Animal Collective - Merriweather Post Pavilion
"...while it remains to be seen whether or not this is truly the band's pop moment, the album undoubtedly contains Animal Collective's most palatable, and best, music to date." -Shawn Reynaldo
In Bust #55:
Animal Collective - Merriweather Post Pavilion
"If previous Animal Collective releases were experiments in chaos, Merriweather Post Pavilion is an excercise in control. Though the crazy tempo changes, layered instrumentation, and looped samples we've come to expect are plentiful, the album is carried by percussion that makes more sense than not." -Sara Graham
In Decibel #53:
There's a nice-sized article on our friends in Pig Destroyer.

subset: commoncrawl


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"A walk in Whitehall" Top 5 Page for this destination Walks and itineraries Tip by toonsarah
Walks and itineraries, London: 28 reviews and 38 photos
Favorite thing: Although London is a large city and you'll need to use public transport or taxis to get around some of the time, it's also very walkable. I want to share some of my favourite routes with you, starting with this one through the Whitehall area, which is always the first one I think of when visitors ask me to "show them London". This tip isn't about any of the places on the route in detail as you can find out about them elsewhere on my pages and many others – it's simply an overview of a route I would recommend :)
Fondest memory: Start in Trafalgar Square, deservedly one of the most famous spots in London. When you've finished exploring the square, leave by the south-west corner through Admiralty Arch – you'll find yourself on the Mall with a fine view down its full length to Buckingham Palace. Tempting as it is to head for this landmark, try to resist, and instead turn left after a short distance to enter St James's Park, one of my favourite parts of London. Head diagonally right to reach its centrepiece, the lovely lake, and pause to stand on the bridge. Here you'll get an even better view of Buckingham Palace and of all the buildings of Whitehall. You can now follow a circular route around the lake, which at its far end will take you much closer to the Palace – now is the time to detour to see it properly.
Retrace your steps, or follow the opposite side of the lake. You might think now about pausing for refreshments – a picnic in the park, a snack from a kiosk or maybe a meal at Inn the Park, a well-regarded restaurant (which I've yet to try). When you're refreshed, leave the park roughly halfway along its eastern edge, which will bring you to Horseguards' Parade. Cross the parade ground and go through the arch where you'll find yourself on Whitehall itself. You'll want to take the obligatory photo of the guards before heading south. You'll soon come to the turning for Downing Street but don't expect to be able to take it – the road has been closed to all but official visitors for security reasons ever since the IRA campaign of the 1980s. Whitehall shortly becomes Parliament Street, which leads in turn to Parliament Square. You can now check out and maybe visit the Houses of Parliament before finishing your walk at Westminster Abbey (although if you do have the energy for more, a walk down Victoria Street will bring you to Westminster Cathedral, its Roman Catholic equivalent).
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383 reviews | 4.4 out of 5
Saw this online and thought it would be perfect for my daughter's bedroom. Well when I picked it up from the store I was a little hesitant because the color of the chairs were not the same as on the website. But I went ahead and brought it home and sure enough when I opened the box the cute pink chair turned out to be orange, which does not go with the room. Other that that the set seems to be pretty sturdy so far and the size is perfect for my 5 yr old - who is average in size. My daughter loves the table set even though the pink chair was orange. My mother bought her a box set for the table top and it has orange so it helps blend things in. So far I am overall pleased with the item and would recommend it to anyone.
My daughter wanted a table and chairs for our 2 yr old granddaughter - we looked around in stores and on-line. I fell in love with this one on first sight. The colors were perfect for her room and it looked like a product that would last her a few years. When it arrived, my husband put it together in about an hour. It seems very sturdy. Molly wanted to stay at the table to open her presents. Now that they have it at home, she plays, eats and "reads" at HER table. I'm very happy with our choice.
My kids got it for Christmas. Had to constantly tighten the legs...and then one day the enter base/leg on one side of the table fell just up and came off! The inside almost looked like a stiff partical board.
Next time...I'll just spend two hundred and buy my kids a a coffee table. It's the same height and probably won't fall apart over a few tea parties.
i received this table for my 18 month old from her nana and poppy as a x-mas gift.very easy to put together,1 allen wrench & 80 screws. my daughter is 28 lbs & 34 in"s tall, she could pick up this table and chairs with no promblem. they r very light and fall over easily. smaller than i expected. i think she might be able to use till she's 3 or 4. it is very pretty and simple,the colors are more vibrant than pastel. i do think the price should be less, in high 50's or 60.
Good quality table at a great price. I love the pastel colors and very easy to clean.
I purchased this table and chairs for my 19 month old grandaughter for Christmas! She loved it. It was very easy to assemble and is very sturdy for toddlers. On the chair assembly, I took the advice from one of the Mom's reviews and made the chairs all multi-pastel colored! They looked so cute. Looking forward to many fun years of use out of this table!
I bought this table and chair set for my granddaughter for Christmas. She loves it! My daughter says it is very sturdy and my son in law didn't have any trouble putting it together. I ordered it site to store and it arrived in a short amount of time. Very good set for the money.
takes a little effort to screw legs to table and assemble chairs. Provided allen wrench is hard to fit and screw in bolts.
Finish on product is above expectations. Gave to grand daughter for Christmas. She loves it.
looks like will last for years.
Didn't expect this for the price.
I ordered this set for my 4 year old daughter's room. My daughter has all the furniture in her room in white and has a lot of pink disney princess stuff. When I looked at this table and chairs set, I liked it a lot but was not sure if it would go well with the princess theme and be functional as well. I was really happy to see the fine quality of the table and chairs. The table and chairs are just the right size for little girls and they go so well with the whole princess theme. I would definitely recommend this product. It is the right size for even a small room and my daughter loves to sit and color on it, read her books and do her little projects on it! I could not find a decent tabel and four chairs in this price range anywhere else. It is very easy to clean the crayon marks off of this table and chairs set. My daughter loves the fact that her friends can sit on it too! Overall, this is just what I was looking for and I would not change a thing about it... Oh, it is very easy to assemble, I put it together by myself in less than an hour and it comes with alll the equipment needed! Also, I loved the fact that I did not have to pay shipping on it as I chose site to store option!
I adore this table and chair set. I put the chairs together with different pieces, so each chair is multi colored, rather than one of each pastel color. It is so cute and looks great in the kids' toy room. My two year old loves to place a stuffed animal at each chair and play tea. My eight year old can sit in the chairs no problem. The set seems very sturdy. I really like this, the colors are very nice.
My wife and I bought this set for our triplets' Christmas presents. The chairs and table assembled easy enough, however, I noticed when assembling that the chair legs seemed prone to giving and knew that we'd need to keep an eye on the tightness of the screws. The kids loved them and used the table and chairs often - even wanting to eat dinner at their new set!
The pieces were light weight - perfect for our kids to move around themselves.
I continued to tighten the bolts on the chair legs regularly - to the point that the kids were bringing them to me to tighten. Within about a month and a half, one chair came apart. I tried gluing the brace back together, but then the seat came off. Then another chair. I didn't consider the use they were put through unusual for toddlers.
The legs themselves are solid wood, no complaint there. However, the braces appear to be MDF and just aren't suitable for the type of use they get. In addition, the seat is assembled using small staples and glue. The staples are too small to adequately hold the pieces together and the glue doesn't hold up. The same is true for the table top. Eventually the legs on the table gave way too, because the braces didn't hold up.
As for the size of the set, it is as described. I considered the size appropriate for the ages recommended.
You should seriously consider the other comments regarding the same problems.
i bought this adorable white table with beautiful, different colored chairs thinking what a great price. we had just worn out our previous table and christmas was coming so i figured get them something for their room. putting it together was easy but i ,at that point, realized the construction of it all. it wasnt really the size but it just didnt seem like it would hold up to my little ones. it didnt! every week another chair was broken, one right after another, and just as fast as the chairs went the table finally broke. these were not mistreated pieces of furniture! sure my boy would stand up on one here and there but not on the table. this set literally crumbled in less than 35 days. crazy! the chairs broke apart all different ways. 2 legs came off one, the whole back came of another. the top of the table just became unglued and fell off during routine positioning in front of the chalk board. my daughter wanted teacher stuff, i even got her a globe. when i opened the box to set it up i should have listened to my instincts but it was christmas eve at about 1am. save yourself 84 bucks and if you bought it return it, its like doll furniture but way bigger. anybody want to buy alot of colorful pieces of fake wood?
This is an absolutely wonderful table and chair set. My daughter loves it. It's a perfect size even though my child is significantly bigger than most children her age. She is 41'' which is the normal height for a 4 year old, but this set is a perfect size. She will definitely be able to use it for several years to come. My husband and I have both sat down at this table (to appease her) and it has managed to sustain both our weights (neither of us being over 175 lbs). I would highly recommend this set, especially since its on sale for about $20 less than what I purchased it for. Also, to make the set more interesting we mixed and matched the colors. The backs and seats vary from chair to chair, it makes the set much more interesting and fun!
I purchased this table and chairs about 2 months ago for our daughters room. I was a little hesitant to pay that much money for table and chairs, but I loved the look of it. I was happy when I got the box home and my husband put it together. It was so cute, but my kids never play with it, and already 2 of the chairs have already broken. The legs seem to snap right in half...it looks like it won't be too much longer before the next chair falls apart. I noticed that the legs are already very wobbly, and that's with rarely any kids using it, I couldn't imagine how long it would take for a kid who uses it all the time for it break on them. I would not waste my money on this product!!!
I purchased this set in November as my 3 year old daughter's big Christmas gift. It was put away, in the box, until Christmas Eve. Unfortunatley, when putting it together, it was discovered that one back corner of the pink chair was not properly cut so the leg could not be attached. We did set up the rest of the chairs and table and my daughter did get to play with it for a few days. We returned it to the store as I wasn't about to pay shipping to return it.
Overall, the table and chairs was very well built and I just love the colors. My daughter's room is done in Care Bears and the chairs matched them perfectly.
The chairs are small enough for her to handle herself, but she should be able to use them for a couple years. I have a son who is almsot 6 and he fits on the chairs well.
I will be buying another set to replace her Christmas gift. I am, however, not happy that the price has gone up $15 since I purchased it the first time. It was $84.88 when I bought it back in November. I had to return it because it was defective and I get to pay more for it now.
I bought this table and chairs set for my 4 and 5 years old girls, and within two months three chairs were broken, and the table was very wobbly. It was not worth it at all, because we just had to trash the whole thing! If I could do it over, I would buy a sturdier plastic set that wouldn't break as easily
This is a cute, very well made chair and table set. Very sturdy. East to put together. Purchased for my 2 year old grand child, very happy with it!!!
This table for this price is a great value. My dad purchased this for a Christmas present for my 22 month old. It is very sturdy and she loves it. It is a perfect size and looks like ones from the Pottery Barn. Walmart has definitely moved up in what they are carrying online. She can move the chairs herself. I will say that the chairs that are pictured here are different. The ones we received have a center bar which looks better. My dad says it was a breeze to put together. Love it and thank you WM!
This table and four chairs are adorable! Perfect height for toddlers. Easy to put together and very sturdy. Great for a boy or girl!
I have 2 nephews and 1 neice. They outgrew their previous table so I figured I would buy them a new table and chair set for xmas. I found this adorable table and chair set that I knew the kids would be able to use for a couple of years at least. It was set at a hreat price. Extremely easy assembly. Xmas came they loved it. But it is now March and I have had to tighten the chairs 4 times and re assemble 2 twice. I havent had a problem with the table as of yet but this table and chair set was a waist of my money. And it is not like they use the table and chairs everyday. The table and chairs are used every other weekend. Please do not buy this table it is not worth the money.


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While some of us might have a car-boot sale when we move home, A-list celebrities have an auction.
Next month David Hasselhoff is getting rid of career memorabilia including a red Baywatch lifeguard jacket, his personal KITT Knight Rider car, and also household furniture, including two side-tables and a decorative mirror from his LA house.
He was moving home and decided to use Julien's Auctions in Beverly Hills, California, the auction house to the stars, with past clients including Barbra Streisand, Cher, Bette Midler and Michael Jackson.
"Doing an auction is like shopping in a celebrity's home," says Darren Julien, President/CEO of Julien's Auctions in LA, whose record price was Michael Jackson's "Thriller" jacket that sold for $1.8m.
"You develop a wish list. Sometimes you get your hand slapped. Sometimes they think they can part with an item. A lot of them change their mind. We call it 'celebrity hokey pokey'."
While some like Hasselhoff, aka The Hoff, donate the proceeds to charity, in his case the Starlight Foundation, others use it as a high-class garage sale.
Ozzy and Sharon Osbourne sold the contents of their LA home in 2007 in one of his auctions. "Christina Aguilera bought the house, so rather than put all the items in storage, I did an auction for them," says Julien. He also cleared Michael Jackson's Neverland Ranch in 2008. It took 90 days, 30 men and cost over $2.5m.
"We call it the greatest auction that never happened. Michael Jackson changed his mind. So we returned everything." Ronnie and Jo Wood auctioned their London home in 2012 after they split up. "We took everything and did 'ocean-liner' to LA."
Cher was more charitable when she wanted to redecorate her house in Malibu from gothic style to Moroccan. So an auction in 2006 suited her down to the ground. "She sold the whole contents of her house and some clothes and jewellery. She raised about $3.3m," he says.
As with all his clients, Julien painstakingly went through all of Hasselhoff's belongings with him. "He wasn't willing to part with his Knight Rider jacket."
It took about a year to put the auction together. "He needed time to think through what he wanted to sell."
David Hasselhoff's Auction, Julien's Auctions, Beverly Hills, California, 11 and 12 April (www.juliensauctions.com).Reuse content


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Whether you serve hot or cold, these treats are perfect when the sun is shining.
Ready in: 35-45 minutes
Serves: six
100g of golden caster sugar, plus a little extra for any sprinkling
25g of melted butter
25g of ground almonds
2 peaches
100g of self-raising flour
Almond extract
3 large eggs
2 teaspoons of peach conserve or apricot jam
1 tablespoon of flaked almonds
Half-fat crème fraiche
Cooking instructions
1. Preheat the oven to 220c/ Gas mark 7, and use a large bowl to whisk the eggs, sugar and almonds together. This should about a minute, and they should be foamy when you have finished.
2. Pour in the melted butter, and beat until it is combined. Fold the flour into the bowl gently, adding a pinch of salt.
3. Remove the stone and slice the peaches. Using a non-stick muffin tin, divide the mixture across six holes and add the jam/conserve and a few peach slices across each one.
4. Scatter some sugar and the almonds across the top, before placing in the oven for 20-25mins. They should be golden and puffed up after this time.
5. Serve while still warm with crème fraiche, or allow to cool. They are best eaten on the day they have been made, but they can be frozen for up to a month.


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Sugar and Spice Dip
Creamy Low-Calorie Dill Dip
Zippy Vegetable Dip
Creamy Spinach-Artichoke Dip
Three Cheese Spinach Dip
Mixed Olive Spread
This creamy lowfat dip is perfect for a potluck. Surrounded by colorful veggies it looks as great as it tastes!
Cut up the veggies in advance, and store in resealable plastic bags in the refrigerator. The dip can be made the day before it's served; just cover and refrigerate.
Use any of your favorite fresh vegetables to serve with this dip. Try red or green bell peppers, celery, cauliflower or grape tomatoes.
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A woman has told how a rare disorder has led her to eat more than 4,000
washing up sponges.
Kerry Trebilcock, 21, suffers from a condition called pica, which causes victims to crave non-edible objects.
The disorder has also caused her to eat more than 100 bars of soap.
Miss Trebilcock, a dental nurse from Mylor, Cornwall, told The Sun: "One day I will beat this and be able to have a shower or do the washing up without feeling hungry.
"I have been very particular about the type of sponges and soaps I'd eat and how I'd prepare them.
"If I went out for the day I'd carry a small plastic bag of cut-up pieces of sponge with some tomato and BBQ sauce in Tupperware. I was never without a 'snack'."


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Girls & Boys
Narrow Your Results
This Riding Sport™ by Dover Competitor II Kids' Breech puts a popular adult style within reach of the young rider. Designed with excellent stretch and recovery for an ongoing good look, this children's breech represents a great value. It's timelessly styled in four-way stretch fabric with Clarino™ knee patches and hook-and-loop ankle closures.
The Riding Sport™ by Dover Competitor II Kids' Jod delivers superior value in durable, comfortable, four-way stretch fabric. This classic jodhpur pant maintains a polished appearance with its excellent shape retention and recovery properties. It's styled for the show ring and complete with Clarino™ knee patches and cuffed hems.
The Tailored Sportsman Children's TS Trophy Hunter Front-Zip Breech provides a polished look for the show ring. Made of lightweight TS fabric with four-way stretch, it has a mid rise and traditional styling.
The Tailored Sportsman Children's TS Trophy Hunter Side-Zip Breech provides a polished look for the show ring. Made of lightweight TS fabric with four-way stretch, it has a Euro seat, belt loops and knee patches.
The Tailored Sportsman Children's TS Trophy Hunter Front-Zip Jod in lightweight TS fabric offers four-way stretch for riding comfort. Classically-styled for the show ring, this children's riding jod has a mid rise, Clarino™ knee patches, front zipper and belt loops.
Perfect for even the hottest days, the TuffRider® Ventilated Children's Schooling Tight has all the convenience and comfort a young rider wants. This low rise riding tight is made of lightweight, breathable, stretch fabric. A ventilated, moisture-wicking fabric panel runs along each leg and across the back for a cool look and added cooling.
The TuffRider® Children's Marathon Tight is perfect for everyday fun at the barn! Stretchy, durable and stylish, it's constructed in panels of smooth dynamic stretch material with a breathable strip of printed fabric down the outside of each leg. Modern silicone print knee patches and stretchy cuff hems.


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Rates in SGD (taxes & fees included), shown as:
Nightly Average
S$49 - S$51 Avg. price/night
Lakshmi Residency Inn
69, Chengam Road, Opp; Sri Ramana Ashramam, Aalamarathu Street, Pondicherry City Center, Pondicherry 606603, India
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Lakshmi Residency Inn Hotel Details
Check-in: 1200
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A luxurious property with a value for money is Lakshmi Residency Inn, located very close to Ramana Ashram. It offers its guests an ideal accommodation to relax and rejuvenate. Guests can enjoy a delicious meal at its restaurant or grab a drink at the café. Other amenities include a travel counter to help tour the place, breakfast services, currency exchange, free parking nearby and wireless internet access.
69, Chengam Road, Opp; Sri Ramana Ashramam, Aalamarathu Street Pondicherry City Center, Pondicherry 606603, India


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Full profile →'">
The author is a Forbes contributor. The opinions expressed are those of the writer.
Continued from page 2
The Carlos Slim Health Institute has spent about
$20 million since 2001 on organ transplants in Mexico, a nation with one of the lowest rates in Latin America for organ donations after death. It's a philanthropy born of personal tragedy. Slim's wife, Soumaya, died of kidney disease after getting a kidney transplant, and in 2008 his son Patrick was diagnosed with kidney disease. His brother Carlos gave him one of his kidneys. In a separate case, Slim's daughter Vanessa donated a kidney to her brother Marco Antonio. The family now campaigns for organ donation and has funded 7,100 transplants in the past decade.
As evidenced by the works of American artist Conrad Wise Chapman hanging on the walls in his office at Grupo Financiero Inbursa and the private art gallery with the small Rodin sculptures just a short walk down the hallway, Slim is passionate about art. He opened a huge new museum in March last year, the Museo Soumaya, a strikingly undulating, mirrored building designed by his son-in-law architect Fernando Romero. (He proudly points out that the tie he wears sports a tasteful, repeated pattern of a small replica of the museum.) It showcases some 3,400 of the 64,000 pieces of art Slim has collected. He beams as he recounts the total number of visitors to date (650,000) and the fact that many are from schools and low-income groups or are people with disabilities. He is doing his part to educate and enlighten his countrymen.
Entrance is free, and the crowds lined up outside before the 10:30 a.m. opening on a balmy late January morning. Inside, the building's circular walkways connecting one floor to another are somewhat reminiscent of the Guggenheim Museum in New York City. But the eclectic collection—from Rodin and Dalí sculptures, old Mexican coins and Thomas Edison's first phonograph to Matisse paintings and Diego Rivera murals—makes for an almost overwhelming mix. This is the collection of a man whose curiosities, and whose wallet, know few limits.
Follow me on Twitter at @KerryDolan


text: Hats off to the team again for making our anniversary a memorable and spectacular experience. Without question Marco is the worlds best maitre d so when you walk in, you are starting off on a high note! We had fish and each of us were blown away with the perfect preparation. I had Turbot with Brussels. The best! You cannot... More


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Mayor Bloomberg Aims to Boost Recycling and Save Taxpayers Money
During his final months in office, Mayor Michael Bloomberg has his sights set on getting the concrete jungle to boost its recycling. Despite the Mayor's past efforts to reduce greenhouse gas emissions and get New York residents to start thinking more "green", the city's residential recycling has declined from 20 percent to 15 percent over the past 12 years. The news may be dismal but a change is a coming. The administration is serious about moving the city's solid waste programs into a new direction and helping New Yorkers clean up their act. Here's a look at key initiatives the city is rolling out to set solid waste reduction back on track.
The Bloomberg administration jump-started recycling initiatives across the city by selecting Recycle Bank's former co-founder and CEO, Ron Gonen, to sit down with environmental advocates and solid waste experts to discuss strategies for improving the city's waste-reduction initiatives. Gonen joined the New York City Department of Sanitation in May 2012 as the Deputy Commissioner for Recycling and Sustainability –a newly created role—and given the task of doubling the city's recycling rate by 2017.
Since Gonen's appointment to office, the city has implemented a few programs focused on recycling and composting that will overhaul waste-reduction programs and make recycling a tad bit easier for New Yorkers to hop on board. For instance, this summer the city will begin to accept all rigid plastic in hopes to help residents avoid confusion on what types of plastic are recyclable or not. Also launching this summer are cost-free electronics waste recycling at apartment houses, textile recycling collection, and a state-of-the-art processing facility set to open in Brooklyn's Sunset Park. By fall, over 1,200 New York City schools will also tackle their gap in conservation and sustainability by adopting food waste collection programs and enhanced paper recycling collections as well.
Currently, New York City taxpayers are shelling out over $330 million to cover the costs of dumping waste into landfills each year. To make matters worse, the last landfill in the city, which was in Staten Island, closed over 12 years ago and now the city is forced to ship refuse outside of the state to Ohio, Pennsylvania, South Carolina and Virginia. "Landfills cost us a lot of money. If we could recycle a lot of stuff, it would be much better for the environment and better for our bottom line," said Mayor Bloomberg.
Via Natural Resources Defense Council
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Diabetes mellitus is a documented risk factor for melioidosis, a tropical infection caused by Burkholderia pseudomallei. The increased susceptibility of diabetic individuals to infections with other pathogens has been associated with immune dysregulation. However, the impact of diabetes on the functional responses of dendritic cells (DC) and macrophages during B. pseudomallei infection has not been investigated. This study compared the responses of macrophages and DC towards B. pseudomallei using bone marrow-derived DC (BMDC) and peritoneal elicited macrophages (PEM) isolated from streptozotocin-induced diabetic C57BL/6 mice exhibiting hyperglycaemia for 9 days (acute) or 70 days (chronic) and age-matched nondiabetic C57BL/6 mice. Following coincubation of BMDC and PEM with a highly virulent B. pseudomallei isolate, maturation, bacterial internalization plus intracellular survival and cytokine gene expression profiles were assessed. No significant differences in functional responses of BMDC or PEM isolated from acute diabetic and nondiabetic mice were observed. However, significant differences in BMDC and PEM function were observed when chronic diabetic and nondiabetic mice were compared. This study demonstrates that diabetic mice with extended periods of uncontrolled hyperglycaemia have impaired DC and macrophage function towards B. pseudomallei, which may contribute to the high susceptibility observed in clinical practice.
Melioidosis is an emerging tropical infectious disease caused by the Gram-negative soil saprophyte, Burkholderia pseudomallei. Both the incidence and the mortality rate of melioidosis are high, even in Australia, despite early diagnosis and therapeutic intervention (Cheng & Currie, 2005; Malczewskie et al., 2005). Diabetes mellitus is the most commonly associated risk factor for melioidosis with 40–60% of patients having diabetes mellitus as a comorbidity (Suputtamongkol et al., 1999; Malczewskie et al., 2005).
Diabetic subjects are considered to have dysregulated immune responses, increasing their risk of developing infection (Marhoffer et al., 1992; Currie et al., 2000). Currently, there is limited information on how the diabetic status of an individual impacts on immune responses towards B. pseudomallei infection. It has been demonstrated that in response to B. pseudomallei, neutrophils are rapidly recruited and play a crucial role in early cytokine production within sites of infection (Easton et al., 2007; Chanchamroen et al., 2009). Chanchamroen (2009) recently demonstrated that B. pseudomallei internalization and migration by neutrophils isolated from diabetic patients with very poor glycaemic control were significantly impaired, compared with neutrophils from healthy controls. Other innate immune cells, including dendritic cells (DC) and macrophages, play an important role in the development of immunity to B. pseudomallei (Leakey et al., 1998; Elvin et al., 2006; Barnes et al., 2008; Williams et al., 2008; Chanchamroen et al., 2009; Charoensap et al., 2009). The C57BL/6 mouse is partially resistant to B. pseudomallei infection, and is widely used as a model for chronic melioidosis (Leakey et al., 1998). Comparison of C57BL/6 mice and susceptible BALB/c mice has demonstrated differences in the functional responses of both macrophages and DCs when stimulated with B. pseudomallei (Leakey et al., 1998; Williams et al., 2008). However, it is not known what impact diabetes has on the functional response of these cells towards B. pseudomallei.
Streptozotocin has been extensively used in experimental animal models to chemically induce diabetes by causing pancreatic β cell cytotoxicity (Lu et al., 1998; Szkudelzki, 2001; Srinivasan & Ramarao, 2007). Therefore, using nondiabetic and streptozotocin-induced diabetic C57BL/6 mice, this study investigated how diabetic status and persistence of hyperglycaemia affected the ability of bone marrow-derived DCs (BMDC) and peritoneal elicited macrophages (PEM) to respond to stimulation with B. pseudomallei.
Materials and methods
Eight- to 12-week-old male C57BL/6 mice from James Cook University Small Animal Breeding Facility were used. Institutional ethical approval for all animal experimentation was granted by the James Cook University Animal Ethics Committee (A987 and A1248).
Streptozotocin-induced diabetes in C57BL/6 mice
To induce diabetes, mice received intraperitoneal injections of streptozotocin (Sigma) dissolved in sodium citrate buffer (pH 4.5) at a dose of 55 mg kg−1 for 6 days (days 0–5). Nondiabetic control animals received intraperitoneal injections of sodium citrate buffer only. On day 10, peripheral blood was drawn from the lateral tail vein and blood glucose levels were assessed using an Ascensia Esprit 2 Blood Glucose Monitor. Mice with a blood glucose level of ≥13 mmol L−1 were considered diabetic and sacrificed following uncontrolled hyperglycaemia for 9 days (acute; sacrificed on day 19 postinitial streptozotocin injection; total mice=15, n=5 × 3 experiments) or 70 days (chronic; sacrificed on day 80 postinitial streptozotocin injection; total mice=16, n=8 × 2 experiments). Male mice were used because female C57BL/6 mice did not develop hyperglycaemia in a consistent rate following streptozotocin treatment (data not shown).
Isolation of BMDC
Isolation of BMDC from mouse femurs (n=3 per treatment group) was carried out using a method described previously (Williams et al., 2008). Briefly, bone marrow cells from each animal were cultured separately in BMDC medium containing supplements including 10% supernatant from Ag8653 myeloma cells transfected with the gene encoding murine granulocyte macrophage colony-stimulating factor. Lutz (1999) demonstrated previously that on day 10 of culture ∼90% of nonadherent cells are BMDC. On day 10 of culture, nonadherent BMDC were washed and seeded into 96-well Nunc culture plate (5 × 104 BMDC per well, In Vitro Technologies P/L) for fluorescence-activated cell sorting analysis or 24-well Nunc culture plates (1 × 106 BMDC per well, In Vitro Technologies P/L) for internalization and cytokine assays.
Isolation of PEM
To isolate PEM, mice (n=5 per treatment group) were injected intraperitoneally with 2.5 mL of Brewer's thioglycollate medium (BD Biosciences) using previously described protocols (Barnes & Ketheesan, 2007). PEM from each mouse within an experimental group were pooled, washed and seeded in triplicate into 24-well plates (1 × 106 PEM per well, In Vitro Technologies P/L). Cells were left to adhere overnight at 37 °C in 5% carbon dioxide (CO2). To remove nonadherent cells, monolayers were washed twice with phosphate-buffered saline (PBS) (pH 7.2), then fresh culture media was added to PEM.
Burkholderia pseudomallei isolates
A clinical B. pseudomallei isolate of high virulence (NCTC 13178) was grown to log phase in tryptone soya broth and used to stimulate BMDC and PEM at a multiplicity of infection of 1 : 1 (Ulett et al., 2000; Barnes & Ketheesan, 2007; Williams et al., 2008). Co-cultures were incubated for 4 h in 5% CO2 at 37 °C. Extracellular bacteria were then removed by adding kanamycin (250 µg mL−1; Sigma). Burkholderia pseudomallei isolates have varied sensitivity or resistance to kanamycin. Because this isolate, NCTC 13178, is sensitive to kanamycin, we and other previously published studies have used kanamycin in standard antibiotic protection assays (Utaisincharoen et al., 2001; Feterl et al., 2008; Williams et al., 2008).
Flow cytometry analysis of BMDC maturation
After 10 days of culture, the ex vivo-expanded BMDC were left untreated, infected with B. pseudomallei or stimulated with Pseudomonas aeruginosa lipopolysaccharide (50 ng mL−1– positive maturation control). After 22 h, BMDC were harvested and fluorescently labelled with fluorescein isothiocyanate-conjugated anti-CD11c (DC cell-surface marker, BD Biosciences), Phycoerthyrin (PE)-conjugated anti-CD86 (DC maturation marker, BD Biosciences) and Peridinin-chlorophyll proteins (PerCP)-conjugated anti-CCR7 (DC maturation marker, BD Biosciences). Analysis of labelled BMDC was performed using a FACScan™ with cell-quest software (version 5.2, BD Biosciences). Cells positive for CD11c were analysed for the expression of CD86 and CCR7. Mature DC had the phenotype CD11c+CD86hiCCR7hi. The percentage increase in DC maturation following treatment with B. pseudomallei (or lipopolysaccharide) was calculated as %CD11c+CD86hiCCR7hi treated−%CD11c+CD86hiCCR7hi untreated.
Assessment of Fluoresbrite® YG microsphere internalization
Fluoresbrite® YG microspheres, 2 µm (Polysciences), were added to BMDC and PEM cultures at a ratio of cells: beads of 1 : 1. After 4 h, cells were removed and fixed in ice-cold 4% paraformaldehyde for 20 min. Cells were then pelleted (300 g, 8 min, 4 °C), resuspended in 2 mL PBS (pH 7.2), then layered over 5 mL PEG8000 (20% w/v in water) and centrifuged (2000 g, 12 min, 4 °C) to remove extracellular microspheres. The cell pellet was then resuspended in standard azide buffer and analysed using a FACScan™ with cell-quest software (version 5.2, BD Biosciences).
Assessment of internalization and survival of B. pseudomallei
To determine phagocytic and bactericidal capacity of BMDC and PEM, internalization and survival were assessed using protocols described previously (Williams et al., 2008). Briefly, bacterial uptake by BMDC was assessed after 4-h incubation with B. pseudomallei [%uptake=internalized bacteria (CFU) at 4 h/inoculating dose × 100]. At this time point, kanamycin (250 µg mL−1) was added to parallel co-cultures to remove extracellular bacteria. Bacterial survival within BMDC and PEM was assessed 1 and 18 h after the addition of kanamycin [%bacterial survival=surviving bacteria (CFU) at 1 or 18 h/internalized bacteria (CFU) at 4 h × 100]. To enumerate intracellular B. pseudomallei at each time point, BMDC and PEM were washed twice, then treated with 0.1% Triton-X to disrupt cells and release the internalized B. pseudomallei. CFUs were determined from serial dilutions of lysed cell suspensions, plated in triplicate on Ashdown agar and incubated for 48 h at 37 °C.
Assessment of cytokine gene expression
To determine the changes in cytokine gene expression by BMDC and PEM in response to B. pseudomallei, total RNA was extracted from BMDC and PEM 18 h after the removal of extracellular B. pseudomallei using a commercial RNA extraction kit (RBC) according to the manufacturer's instructions. DNase 1 (Fermentas) was used to digest any contaminating genomic DNA. Total RNA (1–2 µg) was used to synthesize first-strand cDNA with the aid of an anchored oligo(dT) primer (Sigma) and Revert Aid M-MuLV reverse transcriptase enzyme (Fermentas) and stored at −80 °C until required. Standard reverse transcription-PCR reactions were set up to assess the cytokine gene expression of interleukin-10 (IL-10), IL-12 and IL-18 for BMDC and IL-1β, IL-12 and tumor necrosis factor-α (TNF-α) for PEM (Table 1). IL-12 and IL-18 were selected as they are classical cytokines known to drive strong production of interferon-γ (IFN-γ) and differentiation of T cells into Th1 cells. The expression of IL-10 was also assessed in BMDC as it has a suppressive effect, and when expressed while DC present antigen to naïve T cells drives the differentiation of adaptive regulatory T cells (de Jong et al., 2005). Expressions of IL-1β and TNF-α PEM were selected because they are important proinflammatory cytokines produced by macrophages that promote antimicrobial activity. Furthermore, hyperproduction of these cytokines can impact negatively on the host during B. pseudomallei infection (Ulett et al., 2000; Koo & Gan, 2006). Macrophages are also a potential source for IL-12 production during early phases of B. pseudomallei infection (Ulett et al., 2000). Following electrophoresis, PCR products were analysed with genesnap and genetools software, to quantify the mRNA ratio of each cytokine standardized against β-actin.
|Primer sequences
|Interleukin 1β (166 bp)
|Interleukin 10 (254 bp)
|Interleukin 12p40 (128 bp)
|Interleukin 18 (504 bp)
|Tumor necrosis factor-α (111 bp)
|Primer sequences
|Interleukin 1β (166 bp)
|Interleukin 10 (254 bp)
|Interleukin 12p40 (128 bp)
|Interleukin 18 (504 bp)
|Tumor necrosis factor-α (111 bp)
Statistical analysis
Significance between groups was analysed by univariate anova using the spss statistic program (version 17). Groups were considered significantly different when a P value ≤0.05 was returned.
Maturation of BMDC in the presence of B. pseudomallei
Mature BMDC were defined as CD11c+CD86hiCCR7hi. An increase in mature BMDC isolated from both diabetic and nondiabetic mice was found in response to stimulation with NCTC 13178. No difference in maturation was observed between BMDC isolated from acute diabetic mice and nondiabetic mice (Fig. 1). Maturation of BMDC isolated from chronic diabetic mice was reduced compared with BMDC isolated from nondiabetic mice; however, this trend was not statistically significant. Similar trends in maturation were observed for chronic-derived BMDC stimulated with either B. pseudomallei or lipopolysaccharide (50 ng mL−1) (data not shown).
Internalization capacity of BMDC and PEM
To ensure the functionality of BMDC and PEM, the ability to internalize Fluoresbrite® YG microspheres was assessed. After 4 h, the percentage of BMDC and PEM containing Fluoresbrite® YG microspheres was found to be similar for cells from both acute diabetic and nondiabetic mice (data not shown). Similarly, chronic diabetes of the host did not impair the ability of BMDC and PEM to internalize Fluoresbrite® YG microspheres, with no difference observed between cells derived from chronic diabetic and nondiabetic mice (Fig. 2a). The ability to internalize B. pseudomallei was similar for BMDC and PEM isolated from acute diabetic and nondiabetic mice (data not shown). However, internalization of B. pseudomallei was significantly decreased in chronic diabetic-derived BMDC (3.09% or 0.6 × 104 CFU) compared with non-diabetic-derived BMDC (5.88% or 1.3 × 104 CFU; P<0.05, Fig. 2b). No significant difference was observed between chronic diabetic (7.95% or 3.0 × 104 CFU) and non-diabetic-derived PEM (8.80% or 3.3 × 104 CFU; Fig. 2b).
Bacterial survival within diabetic and non-diabetic-derived BMDC and PEM
To determine bacterial survival, the percentage of internalized B. pseudomallei surviving within BMDC and PEM was assessed after 1 and 18 h. After both time points, intracellular survival of B. pseudomallei within acute diabetic-derived BMDC was similar to that within non-diabetic-derived BMDC (1 h, data not shown), with <1% of internalized B. pseudomallei remaining after 18 h (0.16% or 9.7 × 101 CFU acute diabetic; 0.08% or 7.7 × 101 CFU nondiabetic; Fig. 2c). In contrast, survival of B. pseudomallei was increased in chronic diabetic-derived BMDC compared with nondiabetic BMDC after 1 h (data not shown) and 18 h (2.22% or 12.8 × 101 CFU and 0.5% or 6.7 × 101 CFU, respectively; P<0.05, Fig. 2c). Similar trends were observed for B. pseudomallei infected PEM isolated from diabetic and nondiabetic animals. Intracellular survival of B. pseudomallei within acute diabetic-derived PEM was equivalent to that within non-diabetic-derived PEM at both 1 h (data not shown) and 18 h time points (0.37% or 2.0 × 102 CFU and 0.26% or 1.8 × 102 CFU, respectively; Fig. 2d). However, for PEM isolated from chronic diabetic mice, the intracellular survival of B. pseudomallei was increased compared with non-diabetic-derived PEM at both 1 h (data not shown) and 18 h time points (2.35% or 6 × 102 CFU and 0.82% or 2.6 × 102 CFU, respectively; Fig. 2d).
Cytokine gene expression by BMDC
In response to B. pseudomallei, the gene expression of IL-12, IL-18 and IL-10 was significantly increased in BMDC isolated from both acute diabetic and nondiabetic mice when compared with uninfected BMDC (Fig. 3a, c and e). While no differences in the gene expression of IL-12, IL-18 and IL-10 were observed between acute diabetic and non-diabetic-derived BMDC (Fig. 3a, c and e), significant differences in gene expression were observed between chronic diabetic and non-diabetic-derived BMDC following exposure to B. pseudomallei (Fig. 3b, d and f).
When stimulated with B. pseudomallei, the gene expression of IL-12 by chronic diabetic-derived BMDC was significantly decreased compared with non-diabetic-derived BMDC, and significantly decreased compared with that expressed by uninfected chronic diabetic-derived BMDC (Fig. 3b). However, when stimulated with lipopolysaccharide, the gene expression of IL-12 was similar for both chronic diabetic and non-diabetic-derived BMDC (Fig. 3b). Like IL-12, significant differences in the gene expression of IL-18 was observed between chronic diabetic and non-diabetic-derived BMDC when stimulated with B. pseudomallei, but not when stimulated with lipopolysaccharide (Fig. 3d). The expression of IL-10 by chronic diabetic-derived BMDC stimulated with B. pseudomallei was similar to B. pseudomallei-stimulated non-diabetic-derived BMDC, and was significantly higher than that expressed by unstimulated chronic diabetic-derived BMDC (Fig. 3f). A similar gene expression of IL-10 was observed when chronic diabetic and non-diabetic-derived BMDC with either B. pseudomallei or lipopolysaccharide (50 ng mL−1) (Fig. 3f).
Cytokine gene expression by PEM
The gene expression of IL-1β, IL-12 and TNF-α was significantly increased in acute diabetic and non-diabetic-derived PEM exposed to B. pseudomallei when compared with uninfected PEM (Fig. 4a, c and e). Similar levels of gene expression were observed for IL-1β and IL-12 in both acute diabetic and non-diabetic-derived PEM (Fig. 4a and c). The gene expression of TNF-α by acute diabetic-derived PEM stimulated with B. pseudomallei was significantly decreased compared with non-diabetic-derived PEM stimulated with B. pseudomallei (P<0.05, Fig. 4e). However, TNF-α gene expression by acute diabetic-derived PEM stimulated with B. pseudomallei was still significantly higher than that expressed by uninfected acute diabetic-derived PEM.
The gene expression of IL-1β, IL-12 and TNF-α was also significantly increased in chronic diabetic and non-diabetic-derived PEM co-cultured with B. pseudomallei when compared with uninfected PEM (Fig. 4b, d and f). However, the level of IL-1β, IL-12 and TNF-α gene expression by chronic diabetic-derived PEM stimulated with B. pseudomallei was significantly lower than that expressed by non-diabetic-derived PEM stimulated with B. pseudomallei. Non-diabetic-derived PEM demonstrated significantly higher gene expression of IL-1β, IL-12 and TNF-α when stimulated with B. pseudomallei compared with when stimulated with lipopolysaccharide (Fig. 4b, d and f). PEM isolated from chronic diabetic and nondiabetic hosts induced similar levels of IL-1β, IL-12 and TNF-α gene expression in response to lipopolysaccharide stimulation.
In countries endemic for melioidosis, up to 60% of patients also have diabetes mellitus (Suputtamongkol et al., 1999; Cheng & Currie, 2005; Malczewskie et al., 2005; Kandasamy & Norton, 2008). Recently, Chanchamroen (2009) demonstrated that in response to B. pseudomallei, internalization and migration function of neutrophils isolated from diabetic individuals was significantly impaired compared with neutrophils isolated from healthy controls. The importance of both DC and macrophage function in response to B. pseudomallei infection has been demonstrated (Leakey et al., 1998; Williams et al., 2008). However, to date no studies have investigated the function of DCs or macrophages from diabetes in response to B. pseudomallei. Therefore, our study compared BMDC and PEM isolated from streptozotocin-induced diabetic C57BL/6 mice exhibiting hyperglycaemia for 9 days (acute diabetic) or 70 days (chronic diabetic) to age-matched, nondiabetic C57BL/6 mice.
Our findings indicate that a short hyperglycaemic period did not significantly alter BMDC and PEM function in response to B. pseudomallei. The importance of the length of time between induction of experimental diabetes and investigation of macrophage function from nondiabetic and streptozotocin-induced diabetic hosts has been recently reported (Ma et al., 2008). Only mice with chronic hyperglycaemia (112 days) had significantly reduced numbers of splenic and peritoneal macrophages with a significantly reduced capacity to phagocytose allogenic BALB/c T cells compared with macrophages isolated from nondiabetic controls (Ma et al., 2008). In the present study, chronic diabetic mice experienced uncontrolled hyperglycaemia for 70 days before the isolation of BMDC and PEM. In response to stimulation with a highly virulent B. pseudomallei isolate, the current study has demonstrated significant differences in the functional responses of BMDC and PEM isolated from chronic diabetic C57BL/6 mice compared with those from nondiabetic mice.
Previous studies have demonstrated that in response to heat-killed B. pseudomallei, BMDC undergo maturation to stimulate T-cell proliferation (Elvin et al., 2006; Healey et al., 2006). Furthermore, DCs cultured from healthy donor peripheral blood mononuclear cells, matured in the presence of paraformaldehyde-fixed B. pseudomallei and stimulated a Th1-biased T-cell differentiation (Charoensap et al., 2008). In the current study, co-culture with B. pseudomallei induced a similar maturation response in both diabetic and non-diabetic-derived BMDC. Phenotypically mature BMDC (CD11chi and CD86hi) also had high expression of the chemokine receptor, CCR7, which promotes migration of DC to secondary lymphoid organs. Our results indicate that in response to stimulation with B. pseudomallei, BMDC isolated from both diabetic and nondiabetic C57BL/6 mice undergo similar upregulation of important maturation markers that are necessary for migration to secondary lymphoid organs, and for activation of T-cell responses.
We have demonstrated previously differences in DC maturation in response to B. pseudomallei between susceptible (BALB/c) and partially resistant (C57BL/6) mouse strains (Williams et al., 2008). In that study, following co-culture with B. pseudomallei, BMDC isolated from BALB/c mice demonstrated significantly increased maturation response in comparison with C57BL/6-derived BMDC. However, this increased phenotypical maturation response in BALB/c-derived BMDC was linked to decreased bactericidal function. In the current study, chronic diabetes did not impair BMDC and PEM internalization of Fluoresbrite® YG microspheres. Interestingly, internalization of B. pseudomallei by chronic diabetic-derived BMDC was significantly inferior to that internalized by non-diabetic-derived BMDC, although this was not seen for chronic diabetic-derived PEM. When the level of microsphere internalization was compared with B. pseudomallei internalization, our observations indicate that there is a general decreased capacity to internalize B. pseudomallei by both chronic diabetic and non-diabetic-derived BMDC and PEM. Similar findings have been reported for human neutrophils where, compared with other intracellular bacteria (Salmonella enterica serovar Typhimurium and Escherichia coli), significantly less B. pseudomallei is internalized (Chanchamroen et al., 2009). The findings of the current study suggest that B. pseudomallei may interfere with internalization by BMDC and PEM and that this reduced capacity to internalize B. pseudomallei is further diminished in BMDC isolated from chronic diabetic hosts.
Macrophages play an important role during the early phases of B. pseudomallei infection and are thought to contribute to determining innate susceptibility or resistance of the host. Unlike macrophages, the main effector function of DCs is not bacterial clearance, rather highly specialized antigen presentation that provides potent activation of naïve T cells (Charoensap et al., 2008). Recently, Charoensap (2008) reported similar growth kinetics of B. pseudomallei within human monocyte-derived DCs and macrophages. In the current study, we observed that chronic diabetic-derived BMDC were efficient at killing internalized B. pseudomallei compared with non-diabetic-derived BMDC. While the percentage of bacteria surviving in both chronic and non-diabetic-derived BMDC was low, it was significantly higher in chronic diabetic-derived BMDC. It is possible that DC facilitate the dissemination of B. pseudomallei, and consequently chronic diabetic-derived BMDC could traffic a higher bacterial burden to secondary lymphoid organs. Given the virulence of this organism, the low number of bacteria surviving within these DC is important. Previous studies have shown that as few as 1 × 103 CFU intranasally or 5 × 103 CFU intravenously of this B. pseudomallei isolate, NCTC 13178, causes fatality in 50% of C57BL/6 mice (Barnes & Ketheesan, 2005). Burkholderia pseudomallei survival was also higher in PEM isolated from chronic diabetic mice compared with those from nondiabetic mice. The reduced ability of chronic diabetic-derived BMDC and PEM to clear B. pseudomallei during the early phases of infection may suggest that infection may be established in chronic diabetic hosts following a lower inoculating dose.
Cytokine profiles generated by different subsets of DCs drive the polarization of either Th1, Th2 or regulatory T cells, thus providing pathogen-specific responses (de Jong et al., 2005). DCs readily secrete IL-12 in response to various pathogens, including bacteria, stimulating IFN-γ production by naïve Th cells promoting Th1 polarization and responses. The expression of IL-18 by DCs on its own stimulates weak IFN-γ expression by CD4+ T cells. Combined IL-12 and IL-18 expression by DCs drives strong IFN-γ expression due to the presence of IL-12 upregulating IL-18 receptor complexes (de Jong et al., 2005). An increased expression of IL-12 and IL-18 by B. pseudomallei-stimulated nondiabetic BMDC suggests a capacity to polarize a Th1-type response to B. pseudomallei (de Jong et al., 2005). In contrast, the expression of IL-12 and IL-18 by chronic diabetic-derived BMDC in response to B. pseudomallei was significantly decreased compared with non-diabetic-derived BMDC. In addition, the expression of IL-10 was increased in both B. pseudomallei-stimulated chronic and non-diabetic-derived BMDC. IL-10, which can negatively regulate Th1 and Th2 polarization, has also been shown to inhibit full maturation of DCs and downregulate the expression of major histocompatibility complex class II molecules (de Jong et al., 2005). The expression of IL-10, coupled with significantly decreased IL-12 and IL-18 expression suggests that chronic diabetic-derived BMDC may not provide adequate stimulation for development of protective Th1 responses in the presence of B. pseudomallei.
Proinflammatory cytokine gene expression profiles for IL-1β, IL-12 and TNF-α were also significantly decreased in B. pseudomallei-stimulated chronic diabetic-derived PEM, compared with non-diabetic-derived PEM. During the early stages of B. pseudomallei infection, the cytokine gene profiles expressed in response to B. pseudomallei also play an important role in the development of susceptibility or resistance (Ulett et al., 2000; Koo & Gan, 2006). In this study, we have observed the hypoproduction of proinflammatory cytokines IL-1β and TNF-α and the decreased expression of the Th1 polarizing cytokine IL-12 by PEM isolated from chronic diabetic C57BL/6 mice. This supports the reduced bactericidal capacity observed for chronic diabetic-derived PEM against B. pseudomallei and may contribute to dysregulated adaptive immune responses against B. pseudomallei.
The suppressor of cytokine signalling (SOCS) proteins have been implicated as potential effectors driving the dysregulated cytokine profiles observed in type 2 diabetes (T2D) (Pradhan et al., 2001; Spranger et al., 2003; Ueki et al., 2004; O'Connor et al., 2007). A study by Ueki (2004) demonstrated that obesity and lipopolysaccharide-induced endotoxaemia correlated with an increased expression of SOCS3. Furthermore, SOCS3 was able to cause insulin resistance by interfering with tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and IRS-2. Similarly, O'Connor (2007) demonstrated a constitutive overexpression of SOCS3 by macrophages isolated from the peritoneum of T2D mice. Such research provides evidence that by acting as negative regulators of hormone/cytokine signalling, SOCS proteins are providing a link between T2D and altered cytokine function (Ueki et al., 2004; O'Connor et al., 2007). The increased expression of SOCS3, is a mechanism that is used by B. pseudomallei to enable intracellular survival (Ekchariyawat et al., 2005). By activating the expression of SOCS3, B. pseudomallei inhibits the expression of inducible nitric oxide synthase and IFN-γ to escape killing by normal macrophages. It is therefore possible that SOCS3 is being overexpressed in our chronic diabetic animals, aiding the ability of B. pseudomallei to further suppress the antimicrobial activity and the cytokine expression of BMDC and PEM isolated from chronic diabetic animals compared with nondiabetic animals.
The current study provided valuable information regarding the function of BMDC and PEM isolated from diabetic mice in response to B. pseudomallei. Acute hyperglycaemia did not affect BMDC and PEM function in response to B. pseudomallei. However, BMDC and PEM isolated from C57BL/6 mice with chronic diabetes, were less efficient at internalizing and killing B. pseudomallei and generated cytokine gene expression profiles that may not favour the development of Th1-type immune response. Additionally, proinflammatory cytokines that contribute to host resistance against B. pseudomallei infection were reduced in chronic diabetic-derived PEM. These results provide further evidence that chronic hyperglycaemia impairs innate immune responses to B. pseudomallei. Further investigations are warranted to understand the effect of diabetes on the innate and adaptive immune responses to B. pseudomallei.
We acknowledge the contribution of Associate Professor Leigh Owens with the statistical analysis of data.


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Senior Fund Accountant Salary
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Job Description for Senior Fund Accountant
The main job of a senior fund account is to work with financial documents and work closely with the auditors of the company to make sure that the data is correct. As a senior fund account, one is required to perform the following duties on a day-to-day basis: NAV reconciliation, debt compliance reporting, reviewing and preparing financial statements, reporting funds, preparing cash flow projections, preparing quarterly tax estimates and schedules, working with auditors, providing services to the internal departments, and working on both internal and eternal financial reports for the company.Read More...
As a senior fund accountant, one usually works for a bank or financial institution. One works from 9 to 5 and sits at a desk in front of a computer for most of the day. There are a lot of meetings involved with this type of job, but all of them are usually done inhouse.
To be considered a senior fund accountant, one must meet the following requirements: one must have a bachelor's in business, one must have some related work experience, one must have at least 3 to 5 years of knowledge in the field and experience with financial reporting, one must have the ability to solve internal problem, and one must have an understanding of mutual fund accounting. Some skills that are needed for this job are being detail-oriented, having strong written and verbal communication skills, knowing how to use a computer, and knowing important financial terms in order to write and alter current and future financial reports.
Senior Fund Accountant Tasks
- Prepare and maintain investment books, creating regular reports.
- Review, edit, and correct reports and analyses.
- Collaborate with auditors.
- Estimate profits and losses, reconcile cash, and calculate payments.
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Job skills reported by Senior Fund Accountants are limited. Most notably, skills in Accounting, Microsoft Excel, Financial Reporting, and Financial Analysis are correlated to pay that is above average. Those proficient in Financial Reporting are, more often than not, also skilled in Accounting.
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3 days in Stockholm
Guide to Stockholm Outdoors
One Day in Stockholm
Lovely scandi fish restaurant, great service and good environment for a buisness /pleasure dinner. I would go back and highly recommend!
Extremely tasty, tender and well balanced fish dishes with excellent service on top ;-) Very good experience! The sauce for the Monkfish dish is drinkable in large quantities!
Always a classic elegant night. The freshest yummiest fish in Stockholm, prepared simply but perfectly. It's very chic inside and next door to bukowsi auction house or close walk to musicala or opera
This is by far my favorite fish restaurant in Stockholm. Large portions but not very cheap but you won't leave hungry. The tasting menu is fantastic and the winelist have some really good wines. Service can be a bit slow during Friday and Saturday evenings but if you have a nice bottle of wine you can stand it.
High quality fish cooked to perfection!
Went there with my wife for great fish and were delighted! Fantastic turbot with horseradish / black butter sauce served on the bone (huge portion) and excellent sole fillets with champagne sauce.
Expensive but justified given the quality of products.
I was told that this is one of the best fish restaurants in town, maybe the best. Without having tried any of the others I can say that this one was great. Excellent food quality, low key but attentative service and just overall a very pleasant experience. We we a group and had a nice semi-detached private room. Highly recommended.
GENERAL STUFF: If there was a medal for the world's best fish restaurant, then Wedholms Fisk would be on the podium. This is a really great fish restaurant.
LOCATION: By the Strand Hotel, and the area where many ferries depart from.
CLIENTELE AND WHEN TO VISIT: There was a wonderful absence of mobile phones during the evening. People looked on...
I visited this restaurant yesterday evening as a birthday treat and was not disappointed.
Staff were friendly and attentive, food was absolutely incredible. Portions are quite large! You definitely get your money's worth.
You must book beforehand, even on a Wednesday night during winter season it was fully booked.
100% recommend.
Pricey but you get what you pay for.
Good atmosphere and the service at it best. Superb fish dishes and a good assortment of non-alcoholic beverages.
During my four and a half years stay in Stockholm, I had been to this restaurant many times. This restaurant serves excellent dishes. Enjoyed my fish dishes each time I went to this place.
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Butterfly Wings
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Child's Butterfly Wings
Beautiful Wings For Your Own Little Butterfly! These cloth wings have adjustable shoulder & wrist/arm straps and a matching headpiece. Available size:
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It is pretty transparent which didn't bother me but not as brightly colored as photo.
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State-Owned Banks and Fiscal Discipline
State-owned banks may help to soften the financing constraints of public sector entities and consequently become a factor that hampers fiscal discipline. Using a panel dataset, we find that a larger presence of state-owned banks in the banking system is associated with more credit to the public sector, larger fiscal deficits, higher public debt ratios, and the crowding out of credit to the private sector. These results suggest that the lending practices of state-owned banks should be carefully assessed in any strategy to pursue fiscal discipline.
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|Date of creation:
|03 Oct 2013
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| Postal: International Monetary Fund, Washington, DC USA
Phone: (202) 623-7000
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Web page: http://www.imf.org/external/pubind.htm
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- Hauner, David, 2009. "Public debt and financial development," Journal of Development Economics, Elsevier, vol. 88(1), pages 171-183, January.
- Micco, Alejandro & Panizza, Ugo & Yanez, Monica, 2007.
"Bank ownership and performance. Does politics matter?,"
Journal of Banking & Finance,
Elsevier, vol. 31(1), pages 219-241, January.
- Micco, Alejandro & Panizza, Ugo & Yañez, Monica, 2006. "Bank Ownership and Performance Does Politics Matter?," POLIS Working Papers 62, Institute of Public Policy and Public Choice - POLIS.
- Alejandro Micco & Ugo Panizza & Monica Yañez, 2005. "Bank Ownership and Performance Does Politics Matter?," Working Papers Central Bank of Chile 356, Central Bank of Chile.
- Svetlana Andrianova & Panicos Demetriades & Anja Shortland, 2010.
"Is Government Ownership of Banks Really Harmful to Growth?,"
Discussion Papers of DIW Berlin
987, DIW Berlin, German Institute for Economic Research.
- Panicos Demetriades & Svetlana Andrianova & Anja Shortland, 2009. "Is Government Ownership of Banks Really Harmful to Growth?," Discussion Papers in Economics 09/11, Department of Economics, University of Leicester, revised Dec 2009.
- Svetlana Andrianova & Panicos Demetriades & Anja Shortland, 2009. "Is Government Ownership of Banks Really Harmful to Growth?," CEDI Discussion Paper Series 09-05, Centre for Economic Development and Institutions(CEDI), Brunel University.
- Carmen M. Reinhart & Kenneth S. Rogoff, 2010.
"Growth in a Time of Debt,"
American Economic Review,
American Economic Association, vol. 100(2), pages 573-578, May.
- Reinhart, Carmen M. & Rogoff, Kenneth S., 2010. "Growth in a Time of Debt," Scholarly Articles 11129154, Harvard University Department of Economics.
- Carmen M. Reinhart & Kenneth S. Rogoff, 2010. "Growth in a Time of Debt," NBER Working Papers 15639, National Bureau of Economic Research, Inc.
- Reinhart, Carmen M. & Rogoff, Kenneth, 2010. "Growth in a Time of Debt," CEPR Discussion Papers 7661, C.E.P.R. Discussion Papers.
- Khaled Sherif & Michael Borish & Alexandra Gross, 2003. "State-owned Banks in the Transition : Origins, Evolution, and Policy Responses," World Bank Publications, The World Bank, number 14851.
- Dinc, I. Serdar, 2005. "Politicians and banks: Political influences on government-owned banks in emerging markets," Journal of Financial Economics, Elsevier, vol. 77(2), pages 453-479, August.
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Narayan Vatika Cottage
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Set in a prime location of Manali, Narayan Vatika Cottage puts everything the city has to offer just outside your doorstep. The hotel offers guests a range of services and amenities designed to provide comfort and convenience. All the necessary facilities, including room service, restaurant, tours, meeting facilities, laundry service/dry cleaning, are at hand. Relax in your comfortable guestroom, featuring satellite/cable TV, kitchenette, shower, television, desk. The hotel offers various recreational opportunities. For reliable service and professional staff, Narayan Vatika Cottage caters to your needs.


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Are you a small business with an innovative technology in need of funding for research and development? Have you been curious about how to apply for federal or state funding to help develop your product? Oregon BEST is collaborating with regional partners SOREDI, Gaucho Collective, Fertilab Thinkubator, OSU Advantage Accelerator, Gorge Innoventure, and others to co-host a seminar on Small Business Tech Funding at seven locations around the state.
Learn how to locate and access federal SBIR/STTR grants and investments from Oregon BEST. Tap into a statewide network of support programs available for startups working in cleantech and other technology areas. The seminar will include presentations from Oregon BEST and the SBIR/STTR Support Center.
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The Small Business Innovation Research (SBIR) program is a competitive program that offers over $2 billion in annual funding to domestic small businesses to engage in Research and Development (R&D) that has the potential for commercialization. Small Business Technology Transfer (STTR) is another program that offers federal funding for research and development through collaboration with university researchers. To learn more about SBIR/STTR and apply for grant writing assistance, visit Oregon BEST's SBIR/STTR Support Center.
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