text:
No-one nose a good time like she does! Jennifer Garner entertains her brood with novelty Rudolf The Rednosed Reindeer accessory
Doting mom Jennifer Garner will do anything to bring a smile to her children's faces.
After a day jam-packed with a holiday party followed by an exhausting Christmas shopping excursion, the actress made one final stop with her brood before calling it a day on Saturday.
The fun-loving star treated her three children to a trip to a kids' novelty store, where they all donned fun red noses à la Rudolf The Rednosed Reindeer.
It's no laughing matter! Jennifer Garner showed she's a good sport as she donned a novelty nose à la Rudolf The Rednosed Reindeer on a shopping trip with her children on Saturday
It was quite a sight to behold as the Golden Globe-winner stood at the register to pay for the purchases with the novelty item firmly in place.
While daughters Violet and Seraphina, as well as their nanny, all diligently wore their noses on the way home, Jen took hers off as she toted 22-month-old Samuel to the car, while he was more interested in playing with his rather than wearing it.
The family were laden down with multiple large shopping bags as they headed for home as the sun began to set.
Is there something on my face? The good humoured mom-of-three even kept the fun accessory on as she paid for the purchases at the register at the kids' store at the local Brentwood Country Mart
A bit on the nose: The 41-year-old rounded out a long day of children's parties and Christmas shopping with the fun treat for her well-behaved kids
Their day began hours earlier, with the star adding gingerbread house builder to her impressive list of accomplishments.
The 41-year-old displayed her sweet handiwork as she left her house in Brentwood looking chic and festive in black pants, a white fuzzy cashmere top and black loafers.
She was wearing minimal make-up, letting her natural beauty shine through, while she wore her chestnut tresses down in a straight style and sunglasses perched atop her head as she ushered her little ones to a children's party.
Clowning around: As the exhausted family headed for home, the star's daughters, Seraphina and Violet, as well as their nanny, were all still wearing their noses, though Jen and little Samuel took theirs off for him to play with
Tuckered out: The actress and her kids looked ready to hit the hay after their long day, while Violet and Samuel changed their clothes as it got decidedly chilly as the sun began to set and Jen and Seraphina popped on coats
Jen carried the homemade treat to the car first, careful not to jar her A-structured creation that was edged in white frosting and stuccoed with a colourful assortment of green, red and peppermint candies.
That part over, she began the task of transporting son Samuel to his car seat, followed soon after by daughter Seraphina.
The youngster, who is no doubt already counting down the days till she turns five on January 6, was party-ready in an embroidered skirt, pink leggings and pink and beige striped top - unlike her brother, who hadn't yet got his shoes on and looked grizzly having just woken up.
How sweet: Earlier that day, the star showed there's nothing she can't do as she left her home in Brentwood carrying a homemade gingerbread house as the family headed to a children's holiday party
I don't know how she does it! With three young children to care for and a career to juggle, it's impressive that Jen found the time to make the tasty-looking treat
Santa's helpers: No doubt the star had a few eager elves to help her with the decorating
Once she had got her youngest safely off to their supervised bash, it appears the busy mom-of-three took the opportunity to get the bulk of her Christmas shopping done with her most handiest of helpers: daughter Violet.
The eight-year-old look ever eager to assist her mom, toting a number of bulky bags as the pair successfully made the rounds at the local Brentwood Country Mart.
They were seen carting several purchases from the James Perse store back to their car, before going back for more with their now free hands.
Coordination skills: Once she had safely secured her sweet handiwork in the car, Jen carried her barefoot son Samuel to his car seat, trailed by daughter Seraphina
On the go: The star wasted no time ferrying her youngsters to the festive party, where fun and games awaited
More goodies: Seraphina - who turns five on January 6 - hoisted a jug of maple syrup into the car and had what appeared to be traces of flour smattered all over her pretty outfit after helping her mom in the kitchen
Violet was dressed for the summer sunshine in green shorts, a light pink T-shirt and matching pink and grey sandals.
However, as night fell, she wisely slipped on a pair of navy blue tracksuit pants and a purple jumper to ward off the chill as her siblings rejoined them at the shops.
Samuel also had a change of clothing, donning a long-sleeved brown top, black pants with grey star design and grey and green sneakers, while both Jen and Seraphina simply added coats to their earlier ensembles.
Mommy and me: With her youngest being taken care of at their party, Jennifer was free to squeeze in some holiday shopping at the Brentwood Country Mart with eldest child Violet
Packing it in: Luckily the car trunk was spacious enough for all their purchases, as the pair unloaded their many shopping bags before going back for more
Off-duty chic: Jen looked stylish and festive in black pants, matching loafers and a white fuzzy cashmere sweater that was pushed up at the sleeves
Most watched News videos
- BBC grills MP on why Boris refuses to say how many kids he has
- Rory Stewart 'the only one finding a key' to Parliament door
- Gang of thugs torment bear cub after they found it lost in a field
- Man accuses commuter of 'hitting on school girl' during bus trip
- Thames Valley Police car blocked by van on the M4 for over a mile
- Car with baby in back seat is left spinning on M6 after lorry crash
- Horror moment woman falls off fairground ride in Mexico
- Adorable boys react to finding out their mum is expecting twins
- Rory Stewart denies having been a spy on BBC Breakfast
- O.J. Simpson denies rumors about Kris Jenner relationship
- Couple buy 'dream' home to find driveway is too narrow to park
- Hilarious moment man accidentally squashes his groin crossing legs


text:
Before I was helped, I was dizzy sometimes. I got really bad headaches frequently. I always got very nauseous in
I had headaches most of the time. I felt nauseous after I read books or while riding in the car
I have been a migraine sufferer since I was 17 years old. They have always included a visual aura with
Thank you Dr. Debby, I had suffered from migraines for years, Dr. Debby helped me not only get off all
My eyes weren't off by much, but the right eye is just a little higher if you look close. I
- « Previous Page
- 1
- …
- 28
- 29
- 30
- 31
- 32
- …
- 35
- Next Page »

subset: commoncrawl


text:
Using an epigenetic mechanism, romidepsin restored gene expression and alleviated social deficits in animal model of autism
Of all the challenges that come with a diagnosis of autism spectrum disorder (ASD), the social difficulties are among the most devastating. Currently, there is no treatment for this primary symptom of ASD. New research at the University at Buffalo reveals the first evidence that it may be possible to use a single compound to alleviate the behavioral symptoms by targeting sets of genes involved in the disease.
The research, published today in Nature Neuroscience, demonstrated that brief treatment with a very low dose of romidepsin, a Food and Drug Administration-approved anti-cancer drug, restored social deficits in animal models of autism in a sustained fashion.
The three-day treatment reversed social deficits in mice deficient in a gene called Shank 3, an important risk factor for ASD. This effect lasted for three weeks, spanning the juvenile to late adolescent period, a critical developmental stage for social and communication skills. That is equivalent to several years in humans, suggesting the effects of a similar treatment could potentially be long-lasting, the researchers say.
Profound, prolonged effect
"We have discovered a small molecule compound that shows a profound and prolonged effect on autism-like social deficits without obvious side effects, while many currently used compounds for treating a variety of psychiatric diseases have failed to exhibit the therapeutic efficacy for this core symptom of autism," said Zhen Yan, PhD, professor in the Department of Physiology and Biophysics in the Jacobs School of Medicine and Biomedical Sciences at UB, and senior author on the paper.
The study builds on her previous research from 2015. That work revealed how the loss of Shank 3 disrupts neuronal communications by affecting the function of the NMDA (n-methyl-D-aspartate) receptor, a critical player in regulating cognition and emotion, leading to deficits in social preference that are common in ASD.
In the new research, the UB scientists found they could reverse those social deficits with a very low dose of romidepsin, which, they found, restores gene expression and function using an epigenetic mechanism, where gene changes are caused by influences other than DNA sequences. Yan noted that human genetics studies have suggested that epigenetic abnormalities likely play a major role in ASD.
To pursue these promising findings, Yan has founded a startup company called ASDDR, which was awarded a Small Business Technology Transfer grant from the National Institutes of Health last summer for more than $770,000.
Epigenetics in ASD
Many of the mutations in ASD, Yan explained, result from chromatin remodeling factors, which are involved in dynamically changing the structure of chromatin, the complex of genetic material in the cell nucleus that condenses into chromosomes.
"The extensive overlap in risk genes for autism and cancer, many of which are chromatin remodeling factors, supports the idea of repurposing epigenetic drugs used in cancer treatment as targeted treatments for autism," said Yan.
She and her colleagues knew that chromatin regulators — which control how genetic material gains access to a cell's transcriptional machinery — were key to treating the social deficits in ASD, but the challenge was to know how to affect key risk factors at once.
"Autism involves the loss of so many genes," Yan explained. "To rescue the social deficits, a compound has to affect a number of genes that are involved in neuronal communication."
To do so, the team turned to a type of chromatin remodeler called histone modifiers. They modify proteins called histones that help organize genetic material in the nucleus so gene expression can be regulated. Since many genes are altered in autism, the UB scientists knew a histone modifier might be effective.
Loosening up chromatin
In particular, they were interested in histone deacetylase (HDAC), a family of histone modifiers that are critically involved in the remodeling of chromatin structure and the transcriptional regulation of targeted genes.
"In the autism model, HDAC2 is abnormally high, which makes the chromatin in the nucleus very tight, preventing genetic material from accessing the transcriptional machinery it needs to be expressed," said Yan. "Once HDAC2 is upregulated, it diminishes genes that should not be suppressed, and leads to behavioral changes, such as the autism-like social deficits."
But the anti-cancer drug romidepsin, a highly potent HDAC inhibitor, turned down the effects of HDAC2, allowing genes involved in neuronal signaling to be expressed normally.
"The HDAC inhibitor loosens up the densely packed chromatin so that the transcriptional machinery gains access to the promoter area of the genes; thus they can be expressed," Yan said.
The rescue effect on gene expression was widespread. When Yan and her co-authors conducted genome-wide screening at the Genomics and Bioinformatics Core at UB's New York State Center of Excellence in Bioinformatics and Life Sciences, they found that romidepsin restored the majority of the more than 200 genes that were suppressed in the autism animal model they used.
"The advantage of being able to adjust a set of genes identified as key autism risk factors may explain the strong and long-lasting efficacy of this therapeutic agent for autism," Yan explained. She and her colleagues will continue their focus on discovering and developing better therapeutic agents for autism.
Learn more: Autism's social deficits are reversed by an anti-cancer drug
The Latest on: Autism
via Google News
The Latest on: Autism
- Mom's Post About Parenting Son with Autism Goes Viral: 'Some Disabilities Cannot Be Overcome'on June 26, 2019 at 1:38 pm
There's no shortage of headlines celebrating people with disabilities for defying the odds and becoming lawyers, walking for long stretches and winning beauty pageants. But one Florida mother ... […]
- Autism, insights and a 'passion' for comic bookmaking: This is Max at 11on June 26, 2019 at 1:28 pm
Mid-May. My father-in-law's 80th birthday celebration. Fifty people are lounging in the party room of his Waterloo condo. Speeches, speeches. "Brian is a great guy. Wise mentor. Loyal friend. I ... […]
- Processed Foods During Pregnancy May Be Linked to Autismon June 26, 2019 at 8:23 am
Consuming processed foods during pregnancy may be linked to an increased risk for autism spectrum disorder (ASD) in offspring, preliminary research suggests. Investigators from the University of ... […]
- Students with autism will create a virtual reality demonstration for the Light the Hoan projecton June 26, 2019 at 7:47 am
Students with autism will create a virtual reality demonstration for the Light the Hoan project Light the Hoan and Islands of Brilliance are enabling students with autism to be involved with a ... […]
- The Autism City (Part 1): The Intentional Communityon June 26, 2019 at 6:59 am
"When I'm gone, what will happen to my child with autism?" For all who have adult family members on the autism spectrum today, this thought is never far from our minds. It drives our individual ... […]
- Two SC women get prison for their roles in $13 million federal autism health fraudon June 26, 2019 at 2:00 am
Two S.C. women were ordered to federal prison Tuesday for their roles in a federal health care fraud in a long-running illegal scheme where a company falsely billed government health insurance ... […]
- 'I'm not a racist' | Man blames autism for calling police on black women at swimming poolon June 25, 2019 at 3:25 pm
HYATTSVILLE, Md. — A man called police on two separate groups of black women at an apartment complex, and the ladies believe their race played a factor. The encounters took place at the swimming pool ... […]
- White Man Blames Autism For Harassing Black Women Who Were Minding Their Businesson June 25, 2019 at 3:06 pm
A known troll on the web has taken his abilities to the next level as he reportedly harassed two young black women for drinking wine at a community pool. The incident between Nick Starr-Street and ... […]
- The Eagles' Autism Research Grants Are a New Approach to Sports Philanthropyon June 25, 2019 at 1:13 pm
The way a standard sports philanthropy partnership works is something like this: A team raises money for an important cause, selects a partner organization, and writes a fat check. The two groups ... […]
- Blind woman with autism blows audience away with astonishing singing voiceon June 25, 2019 at 9:09 am
A blind woman who has autism is wowing social media users around the globe with her beautiful rendition of a classic Disney melody. Lavender Darcangelo, a singer from Fitchburg, Mass., took the stage ... […]
via Bing News


text:
Monday-Friday, Gates open at 4:00 PM.
Saturday, Gates open at 3:00 PM.
Pay $10.00 at the gate on all days except Monday, June 17th. Gate on Monday is $5.
Price includes admission, parking, unlimited midway rides and
GENERAL admission to the shows on the Grandstand.
Midway rides open Tuesday - Friday 5:00 to 11:00 PM and Sat. 4 PM - midnight.
Monday-Saturday: Windell Ag. Building open 5:00 - 10:00 PM.
Auction Registration– Designate your Auction Animal at check-in
8:00 AM-7:00 PM: Poultry Check-In:, Pitts Small Animal Barn, Weigh-In when you check-in
9:00 AM-9:00 PM: Rabbit Check-In:, Pitts Small Animal Barn, Meat Rabbits will be weighed at check-in
9:00 AM-9:00 PM: Beef/Diary Beef Check-In:– Cattle Barns
9:00 AM-9:00 PM: Goat and Sheep Check-In– – Small Animal Barn
9:00 AM-9:00 PM: Swine Check-In– (Weather Permitting)– Swine Barn– Weigh-In when you check-in or on Saturday morning.
6:00 PM-9:00 PM : Beef– Dairy, Goat and Sheep Weigh-In


text:
❮ Back | ×
Personalized Serenity Stemless Wine Glass
Wine Time Personalized Wine Bottle Label
Maroon & White Two-Tone Leis
Maroon Party Beads
Wine Time Personalized Sticker
Burgundy Sunglasses
Wine Time Personalized Goblet
16 oz. Reusable Cheers Frosted Cups
Wine Time Personalized Bottle Stopper
Govino 16 oz. Plastic Stemless Wine Glass
Diamond Balloon Personalized Wine Goblet
Plastic Personalized Wine Glass
Create-A Star Mint Tins
Notify me when this product is back in stock.
Sign up - Save 10% Today!
Personalized decor, theme kits and party supplies for schools, corporations and event planners


text:
4,500 Expedia employees are coming to Interbay in Seattle. How will the company avoid a traffic mess?
Expedia employees will start their move from Bellevue to the new campus this fall, with 4,500 workers there by February. The company could expand to as many as 8,000 employees by 2031. VIEW


text:
With a broken heart, but not ready to give up yet, Mathias Ritter shares with us a video of their 19 feet tall free-standing domino tower which collapsed on its own after 7-hours of work they were only 10 layers away from reaching the status of second tallest in the world. Still, despite the many expletives that must have been said out loud, it is a pretty impressive collapse. We featured the Austrian Domino Art in their last two record breaking events.
|Music by Light
|Paperman: Merging Computer-Generated and Hand-Drawn Animation Techniques
|Story Time
|Vandalized Vintage
|Mike Bouchet's Shopping Cart Lounger
|"It knows the very contours of my face."
|"What if we could create our own miniature sun here on earth?"
|The (Very Scary) People of Public Transit
|How to Avoid Jury Duty
|CaptchaTweet: Write Tweets in Captcha Form
|If Sir David Attenborough Restored Vintage Toys
|"Self-driving vans are actually the least novel-seeming part of the unveiling."
|Recycled Vacuum Lamps
|"When Life Gives You Lemons."
|"This has do be done, Anderson added, within the next five years."
|Pat the Zombie: A Cruel Adult Spoof of 'Pat the Bunny'
|Fake Name Generator


text:
welcome bonus
Being real money internet casinos, there are going to be financial transactions occurring through payment gateways at online casinos. Cybercrime has reached unprecedented rates and one can never be too safe. Make sure the casino you choose employs the latest and greatest in cybersecurity technology such as SSL encryption to protect your private and sensitive data.
Another amazing thing about Captain Jacks Casino is that it covers extremely well-optimized games with brilliant displays and user experience is top-notch. The game will make you happy with their VIP Rewards and gifts. The platform also covers weekly and monthly deals to let you try your luck and win free spins. Live poker is also available to play, which is a proof that there is no catch involved at all.
professionals at Slot Boss Casino. You can contact a member of the casino's
The game features wild stacks in which wild symbols – the Max Damage icon — stack up across the reels to give you more and more chances to complete your pay ways. If you achieve three, four or five scatter symbols simultaneously you'll trigger the Free Spins round which presents you with fifteen Free Spins. All of your Free Spin wins are real money wins and the earnings from the free spins are added to your regular game payouts. Free Spin Wins pay out a double multiplier.
You can play Dolphins by Ainsworth and a huge range of other popular pokies games completely free of charge right here at Online Pokies 4U. Simply find a pokies game that piques your interest and enjoy hours of gameplay on desktop, mobile or tablet with no deposit or any other money to pay.
There is also a wide range of denominations to choose from: 1c, 2c, 5c, 10c, 20c and 25c. Players can bet up to 5 coins per payline, and bet on any number of paylines (although it is recommended that you wager on all of them to maximise your odds of winning). Since there is so much flexibility when it comes to wagering, Riches of Ra is suited to players with all types of betting budgets.
You will be given the opportunity of auditing your own Pokie game play at casino sites that have the range of Bally Pokie games on offer to you and as such if you do decide to play the Chimney Stacks Pokie game, you can, at any time of your own choosing access your entire set of real money gaming logs and then take a look through each spin you played off to see the full result of each of those real money spins.
Gambling stocks are to be ditched by Anglicans in Sydney as the way the Church funds development is altered. As well as gambling, Sydney Anglicans have pledged to ditch stocks in resources like fossil fuels, citing fears …
There are other options available to pass the time, or just try something different. You can click the Keno and More tab. Choose one of the games available at the webpage or play every option of Keno game and pick your favorite. If you are a fan of pokies machines, you will find them at the CyberBingo Casino. Look up the Table games section and you will find some classic games, like Blackjack, Baccarat, Deuces Wild 2, Or American/European Roulette. Choose your favorite game and start winning!
But never mind, at least that part can be muted. Below the main part of the game is the set of control buttons and players can start to spin the reels from as little as 0.30, with all 243 Ways to Win permanently activated. All that's then needed is for them to adjust the bet size if required, with coins valued from just 0.01 up to 1.00 and up to 10 coins accepted for a maximum of 300.00 per spin.
The first place to focus in Double Joker Poker is the draws. When you have a draw to a flush or straight, you're going to notice that you'll have more outs than normal if there are wilds left in the deck. This gives you better chances to hit your draws, but there's some compensation for the house here in the fact that flushes and straights typically pay lower than they do in non-wild card games. It works out to be about even when everything is said and done.
The poker-playing community of Australia is distraught after hearing news that Apple has withdrawn the popular PokerStars app from the Australian Apple app store, saying that local authorities have outlawed the high-profile gambling app as part of …
People in Nigeria that are binary option traders or want to be one, have one goal and that is to turn a profit. However, people cannot just go into it blindly and hope to make money.
In case opening an account is required in order to enjoy the services of one of these methods, the players should keep in mind that since these methods are also used by many other reputable casinos, the player will be required to open his or her account only once, and then to use the same account in all other casinos. This will prevent the need to expose one's private details to multiple third bodies.
It depends on the Casino you are playing in, but generally, you should be able to cancel your no deposit bonus either through the cashier, the promotions, or the 'My Account' sections of the website. Be mindful though that when you cancel a bonus that has not been completed, any pending wins you have will also get removed from your balance.
who felt that umpire Ramos had done the right thing. Ramos has chosen to keep a rather low profile since the incident and has confirmed that he is alright and nobody needs to worry about him.
Online bingo with free signup bonus
30 free spins no deposit required tv advert
No deposit bonus casino list Australia
Billionaire casino free gold tickets
Free spins no deposit Australia 2019
Australian online casino real money
Free coins heart of vegas peoplesgamez
888 promotion code existing customer
10 deposit online casino Australia
Best board games for adults 2019
Play aristocrat pokies online real money
Acepokies no deposit bonus codes
Online casino no deposit bonus keep winnings


text:
Shopping for home insurance in Williams, SC doesn't have to be difficult. Simply enter your Zip Code at the top of this page and you will be presented with the list of the top recommended insurance companies in your area. Compare quotes from these carriers and you will be on your way to saving on your homeowners coverage premium.
When it comes to homeowner's insurance in Williams, SC, there are quite a few different factors that can affect how much you have to pay. Understanding what these factors are can give you a better idea of how South Carolina insurance companies come up with the quotes that they give you.One factor that affects homeowner's insurance quotes is the area where you live. For instance, some parts of the country are particularly prone to severe storms and other potentially dangerous situations. In these areas, you may have to pay more for homeowner's insurance than you would in an area of the country that was less risky.
The same holds true for areas that have particularly high crime rates. If you live in an area where there are a lot of robberies or break-ins, you may have to pay more for your insurance than someone who lives in an area that has a lower crime rate.
The overall value of your home also comes into play when figuring out how much you will have to pay for homeowner's insurance. Generally, the more valuable your home, the more money you will have to pay to insure it. This is because expensive homes cost more to repair or replace than lower cost homes.
The deductible that you choose for your policy will also affect your rate. A policy with a higher deductible will generally cost less than one with a low deductible. Although the thought of a lower monthly payment may be appealing, make sure that you have the money on hand to meet your deductible in case anything goes wrong. Otherwise, you could be left in a bind with no way to repair your home.Interestingly, the distance of your home from the nearest fire hydrant can also come into play when determining how much you have to pay for insurance. Insurers tend to prefer homes that have a fire hydrant nearby. This helps ensure that first responders can act quickly in the event of a fire, helping to minimize damage as much as possible.
All of these factors come into play when getting Williams, SC homeowner's insurance quotes. If you want to keep your costs as low as possible, consider choosing a policy with less coverage or with a higher deductible. Just make sure that you fully understand how these decisions will affect you if you ever need to file a claim. You may find it more beneficial to go for a policy that offers more coverage or a lower deductible so that you don't have to come up with a lot of money on your own if something does eventually happen to your home.
To get the best savings on your Williams, South Carolina coverage for your home, make sure to use our comparison tool. Enter your Zip Code below and get the list of the best South Carolina insurers.
More Info and Tips for Williams, South Carolina
There are a good deal of companies out there competing for your enterprise as a home owner, but it really is up to you to locate out which business is supplying the greatest achievable insurance policies for you and your family members. Even though your property wants security, you cannot decide a random plan. The pursuing guidance will give you the advice you need.
Don't just think about getting insurance coverage for your house go ahead and do it! If you don't have homeowner's insurance coverage, you will be out of luck if you are robbed, organic catastrophe strikes or your house burns down. With a mortgage loan, you are a lot more than most likely required to have homeowner's insurance policy.
You may possibly consider you do not reside close enough to a physique of h2o to have to fear about flood insurance policy...but think once again. Just before you choose you do not need it, evaluate the flood threat for your geographical area. You will be stunned at the sudden components of the place which have skilled floods in the earlier yr or two, and if you reside in or near on of these regions, flood insurance may possibly be right for you. FEMA.gov is 1 site that offers info on flood pitfalls for all areas of the U.S.
If your property is broken severely with drinking water, do not dispose of any destroyed residence prior to your insurance adjuster can evaluate the damage. You can remove wrecked products from the property so that they do not cause further water harm to floors or other products, but leave them on the home. Failure to do so signifies you may not be compensated for people things.
When someone breaks into your house, you might be still held liable if they hurt by themselves on your residence. It really is accurate, although. Our legal program in fact permits somebody who is trespassing on your residence to sue you in court for damages. So, do not neglect that you need to have correct homeowner's coverage.
When searching for a homeowners insurance policies coverage, examine with the agent who insures your autos. A lot of brokers will give you a price reduction if you have far more than 1 policy with them. It is attainable to get a price reduction of 10% or a lot more by insuring a lot more than 1 point with the identical agent.
A higher deductible on your homeowner's insurance policies can save you funds on rates. Whilst a higher deductible could imply that you will be liable for small fix fees this sort of as broken windows, far more usually than not these costs are well balanced out by the savings you will get on your yearly premiums.
A larger deductible on your homeowner's insurance policies can save you income on rates. Even though a larger deductible might indicate that you will be dependable for small fix fees this kind of as broken home windows, much more usually than not these charges are balanced out by the financial savings you will get on your once-a-year premiums.
Keep your property owners insurance plan up to day. If it is been a number of several years given that you purchased your coverage, you may be beneath insured. If you've got manufactured improvements to your home, your plan may possibly not mirror the increased value. Building charges have gone up as well, so review your coverage annually, and if essential, make alterations to be sufficiently coated.
An agent can give you with several property owner policy choices. Your insurance policy agent can style the very best coverage for you if you give them a listing of every little thing you have and how much it really is all value. Offering this kind of a list in advance is also a excellent way to display what you actually own, in case you must file a declare later.


text:
Polo Ralph Lauren Straight Fit Hampton in Hudson Classic Stone Stretch
Item Information
- Cut to a straight-leg silhouette, this Polo Ralph Lauren® Straight Fit Hampton Jean is the perfect refresh for your denim repertoire.
- This weekend-ready jean is made from lightweight, stretch cotton denim in a timeless stone wash for versatile wear.
- The hampton straight fit sits slightly below the waist with a relaxed rise, an easy fit through the seat and thigh, and a full straight leg.
- Belt loops throughout waist.
- Five-pocket styling with signature metal rivets.
- "Polo Ralph Lauren" leather patch at the back right waist.
- Button shank front and a zip-fly closure.
- 98% cotton, 2% elastane.
- Machine wash, tumble dry.
- Imported.
- Product measurements were taken using size 32, inseam 32. Please note that measurements may vary by size.
- Measurements:
- Waist Measurement: 32 in
- Outseam: 40 in
- Inseam: 31 in
- Front Rise: 10 in
- Back Rise: 13 in
- Leg Opening: 14 in
Find something wrong in this description? Help us fix it!
Customer Questions
Free Shipping and Free Returns
Learn more about our free shipping and free returns policy
If, for any reason, you are unsatisfied with your purchase from Zappos Retail, Inc. you may return it in its original condition within 365 days for a refund. We'll even pay for return shipping!


text:
University and College Open Day/Evening Events
Please click on the undernoted links against each College/University to find out more details regarding their Open Days for 2019.
Aberdeen University/Reach Aberdeen University
Saturday 15th June 2019 – Medicine Open Day only
Tuesday 27th August 2019
Saturday 5th October 2019
Abertay University
Saturday 28th September 2019
Wednesday 23rd October 2019
Dundee University
Monday 10th June 2019 – Dentistry only
Friday 14th June 2019 – Medicine only
Monday 26th August 2019
Saturday 21st September 2019
Saturday 28th September 2019 – Adult Nursing (Kirkcaldy Campus)
Queen Margaret University Edinburgh
Saturday 21st September 2019
Saturday 12th October 2019
The University of Edinburgh
Monday 10th June 2019
Saturday 21st September 2019
Saturday 5th October 2019
Glasgow University
Thursday 13th June 2019
Wednesday 4th September 2019
Saturday 19th October 2019
Heriot Watt University – Edinburgh Campus
Friday 7th June 2019
Saturday 26th October 2019
University of the Highland and Islands – All Campuses
Saturday 8th June 2019 – Nursing Department of Nursing and Midwifery, Centre for Health Science, Old Perth Road, Inverness, IV2 3JH 11:00 AM
Saturday 8th June 2019 – Open Day Perth College UHI, Crieff Road, Perth, PH1 2NX 10:00 AM
Wednesday 12th June 2019 – Open Evening Moray College UHI, Moray Street, Elgin, Moray, IV30 1JJ 5:00 PM
Tuesday 6th August 2019 – Open Evening Inverness College UHI, 1 Inverness Campus, Inverness, IV2 5NA 5:00 PM
Wednesday 7th August 2019 – Open Day Lews Castle College UHI, Stornoway, Isle of Lewis, HS2 0XR 9:00 AM
Thursday 3rd October 2019 – Nursing Department of Nursing and Midwifery, Western Isles Hospital, MacAulay Road, Stornoway, Isle of Lewis, HS1 2AF 11:00 AM
Saturday 26th October 2019 – Open Day Perth College UHI, Crieff Road, Perth, PH1 2NX 10:00 AM
Friday 1st November 2019 – Open Day Scottish Association for Marine Science UHI, Oban, Argyll, PA37 1QA 1:30 PM
Saturday 9th November 2019 – Open Day Moray College UHI, Moray Street, Elgin, Moray, IV30 1JJ 11:00 AM
Aberdeen/Banff/Fraserburgh Campuses
Currently no dates released. Details of all the open days will be available via the undernoted link in due course when they are released:-
Scottish Maritime Academy
The Scottish Maritime Academy is holding an Open Evening in Peterhead to talk through the Merchant Navy Cadetship programme starting September 2019.
It is open to candidates who have a minimum of 4 x National 5 passes including English, Maths and a Science.
Further information can be found on the undernoted leaflets and link.
Robert Gordons University (RGU)
Wednesday 2nd October 2019 – 12.00pm-4.00pm
Saturday 2nd November 2019 – 10.00am-2.00pm
Scotland's Rural College (SCRU)
Thursday 15th August 2019 – 1.30pm-4.00pm
University of St Andrews
Wednesday 25th September 2019
Wednesday 2nd October 2019
Wednesday 16th October 2019
Wednesday 23rd October 2019
Wednesday 30th October 2019
University of Stirling
Saturday 8th June 2019
Saturday 14th September 2019
Saturday 26th October 2019
University of Strathclyde Glasgow
Friday 14th June 2019 – Summer Information Session
Monday 2nd September 2019
Saturday 5th October 2019


text:
Objective—Mitochondrial DNA (mtDNA) damage is present in murine and human atherosclerotic plaques. However, whether
endogenous levels of mtDNA damage are sufficient to cause mitochondrial dysfunction and whether decreasing mtDNA
damage and improving mitochondrial respiration affects plaque burden or composition are unclear. We examined mitochondrial
respiration in human atherosclerotic plaques and whether augmenting mitochondrial respiration affects atherogenesis.
Approach and Results—Human atherosclerotic plaques showed marked mitochondrial dysfunction, manifested as reduced
mtDNA copy number and oxygen consumption rate in fibrous cap and core regions. Vascular smooth muscle cells derived
from plaques showed impaired mitochondrial respiration, reduced complex I expression, and increased mitophagy, which
was induced by oxidized low-density lipoprotein. Apolipoprotein E–deficient (ApoE−/−) mice showed decreased mtDNA
integrity and mitochondrial respiration, associated with increased mitochondrial reactive oxygen species. To determine
whether alleviating mtDNA damage and increasing mitochondrial respiration affects atherogenesis, we studied ApoE−/−
mice overexpressing the mitochondrial helicase Twinkle (Tw+/ApoE−/−). Tw+/ApoE−/− mice showed increased mtDNA
integrity, copy number, respiratory complex abundance, and respiration. Tw+/ApoE−/− mice had decreased necrotic core
and increased fibrous cap areas, and Tw+/ApoE−/− bone marrow transplantation also reduced core areas. Twinkle increased
vascular smooth muscle cell mtDNA integrity and respiration. Twinkle also promoted vascular smooth muscle cell
proliferation and protected both vascular smooth muscle cells and macrophages from oxidative stress–induced apoptosis.
Conclusions—Endogenous mtDNA damage in mouse and human atherosclerosis is associated with significantly reduced
mitochondrial respiration. Reducing mtDNA damage and increasing mitochondrial respiration decrease necrotic core
and increase fibrous cap areas independently of changes in reactive oxygen species and may be a promising therapeutic
strategy in atherosclerosis.
Visual Overview—An online visual overview is available for this article. (Arterioscler Thromb Vasc Biol. 2017;37:
Key Words: atherosclerosis ◼ mitochondria ◼ reactive oxygen species ◼ respiration ◼ vascular smooth muscle
Received on: June 7, 2017; final version accepted on: September 14, 2017.
From the Division of Cardiovascular Medicine, Addenbrooke's Centre for Clinical Investigation, Addenbrooke's Hospital, University of Cambridge,
United Kingdom (E.P.K.Y., J.R., H.Y., L.S., A.K.U., K.F., A.F., N.F., M.B.); Department of Biomedical Sciences, University of Nottingham, Malaysia
Campus, Selangor, Malaysia (Y.-F.P.); and MRC Mitochondrial Biology Unit, Cambridge, United Kingdom (A.L., M.P.M.).
*These authors contributed equally to this article.
The online-only Data Supplement is available with this article at http://atvb.ahajournals.org/lookup/suppl/doi:10.1161/ATVBAHA.117.310042/-/DC1.
Correspondence to Emma P.K. Yu, MD, PhD, or Martin Bennett, MD, PhD, Division of Cardiovascular Medicine, Addenbrooke's Centre for Clinical
Investigation, Addenbrooke's Hospital, University of Cambridge, Box 110, Hills Road, Cambridge, CB2 0QQ, United Kingdom. E-mail email@example.com
or email@example.com
© 2017 The Authors. Arteriosclerosis, Thrombosis, and Vascular Biology is published on behalf of the American Heart Association, Inc., by Wolters
Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial License, which permits use,
distribution, and reproduction in any medium, provided that the original work is properly cited and is not used for commercial purposes.
Arterioscler Thromb Vasc Biol is available at http://atvb.ahajournals.org DOI: 10.1161/ATVBAHA.117.310042
Yu et al Mitochondrial Dysfunction and Plaque Composition 2323
Figure 1. Human atherosclerosis shows reduced mitochondrial copy number and respiration. A, Mitochondrial copy number in normal
human aorta and plaque (n=9). B and C, Seahorse profile for oxygen consumption rate (OCR) in human plaque segments from the media,
shoulder, cap, and core with treatment with oligomycin (oligo), carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone (FCCP), and anti-
mycin/rotenone (A/R; B) and respiratory reserve capacity (RRC; C; n=5–6). Representative Seahorse profile of human plaque vascular
smooth muscle cells (VSMCs; blue) and normal aortic VSMCs (red; D) and OCR after FCCP (E) from n=5 to 7 cultures. F, Western blot
and quantification of protein expression of mitochondrial protein complexes within the electron transport chain (complexes I–V) in normal
human aortic or plaque VSMCs (n=3–5) relative to citrate synthase (CS). Data are mean±SEM. mtDNA indicates mitochondrial DNA.
Yu et al Mitochondrial Dysfunction and Plaque Composition 2325
of the mitochondrial matrix (coded green), or 586 nm at pH 4 mtDNA synthesis is regulated by several genes, including
to 5, the pH of lysosomes targeting mitochondria for mitoph- Twinkle, mtDNA polymerase-γ, and mitochondrial transcrip-
agy (coded red).13 Because keima is resistant to lysosomal tion factor A (TFAM). Expressions of Twinkle, polymerase-γ,
degradation, a ratio of red/green keima fluorescence can and TFAM were similar in aortic and plaque VSMCs
estimate mitophagy.14 Ox-LDL but not native LDL induced (Figure 2D and 2E). In contrast, mitophagy is regulated, in
time-dependent mitophagy, which was also seen after FCCP part, by the expression and localization of the serine-threo-
(Figure 2A and 2B). Human plaque VSMCs also showed nine kinase phosphatase and tensin homolog (PTEN)–induced
increased mitophagy compared with normal VSMCs, which putative kinase 1 (PINK1) and its interaction with the ubiqui-
was not further increased by ox-LDL or FCCP (Figure 2C). tin ligase parkin. PINK1 is normally expressed at low levels
Figure 2. Mitophagy is increased by oxidized low-density lipoprotein (ox-LDL) and in plaque vascular smooth muscle cells (VSMCs).
A, Confocal microscopic images of control normal human aortic or plaque VSMCs expressing mitochondrially targeted keima, either
untreated or after treatment with 100 mg/mL ox-LDL or 5 mmol/L carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone (FCCP). Insets
show high-power views of outlined areas. B and C, Red/green keima ratios for individual normal aortic VSMCs either untreated (C) or
treated with 100 mg/mL ox-LDL for 4 to 24 h, 100 mg/mL native LDL for 24 h, or 5 mmol/L FCCP (B), or individual normal aortic VSMCs
(C) or human plaque VSMCs either untreated or treated with ox-LDL or FCCP for 24 h (C). n≥20 images from 3 biological replicates. West-
ern blots (D) and their quantification (E) for proteins involved in mitochondrial DNA synthesis and mitophagy in human aortic or plaque
VSMCs, normalized to actin (n=3). PINK1 indicates PTEN-induced putative kinase 1; PolG, polymerase-γ; and TFAM, mitochondrial tran-
scription factor A.
2326 Arterioscler Thromb Vasc Biol December 2017
but is stabilized and becomes detectable during mitophagy. mitochondrial respiration in aortas and cultured cells. Tw+/
PINK1 expression was significantly increased in plaque ver- ApoE−/− mice had increased Twinkle mRNA in aortas, aortic
sus normal VSMCs, consistent with increased mitophagy VSMCs, and bone marrow–derived macrophages compared
(Figure 2D and 2E). Together, these findings suggest that with ApoE−/− controls although the extent of Twinkle expres-
plaque VSMCs undergo increased mitophagy, most likely sion varied between tissues (Figure II in the online-only Data
induced by ox-LDL, which is not compensated by increased Supplement). mtDNA copy number was not increased in Tw+/
mitochondriogenesis. ApoE−/− aortas or VSMCs, but mtDNA damage was signifi-
cantly decreased in both (Figure III in the online-only Data
mtDNA Damage and Dysfunction Are Supplement). Conversely, Tw+/ApoE−/− macrophages showed
Present in Mouse Atherosclerosis increased mtDNA copy number but no change in mtDNA
mtDNA damage is found in ApoE−/− mouse aortas8,9; however, damage compared with ApoE−/− controls (Figure III in the
whether the mtDNA damage is sufficient to affect mitochon- online-only Data Supplement).
drial function and the cause of endogenous mtDNA damage To determine the functional consequences of increased
are unclear. mtDNA damage was assessed by quantitative mtDNA copy number or reduced mtDNA damage, we
polymerase chain reaction for mtDNA adducts which halt assessed expression of mitochondrial respiratory complexes
polymerase progression; damage can therefore be quantified and respiratory function in Tw+/ApoE−/− and ApoE−/− con-
by comparing the amplification of a large mtDNA product to a trol mice. Tw+/ApoE−/− aortas showed increased complex I
short target to control for copy number.8 mtDNA damage was abundance, and Tw+/ApoE−/− macrophages showed increased
increased in ApoE−/− mice fat fed for 14 weeks compared with abundance of both complexes I and III, whereas cul-
6-week-old control mice (Figure 3A), associated with reduced tured VSMCs showed no significant difference in complex
abundance of the mitochondrial respiratory complexes that expression between groups (Figure IV in the online-only
have mtDNA-encoded subunits (complexes I, III, IV, and V) Data Supplement). In contrast, Tw+/ApoE−/− aortas showed
but not citrate synthase (Figure 3B). Respirometry on permea- increased complex I-supported respiration (Figure 4A) but no
bilized mouse aortas also showed that fat-fed ApoE−/− mice differences in complex II- or IV-supported respiration (Figure
had reduced complex I- and complex IV-supported aortic res- V in the online-only Data Supplement), and both Tw+/ApoE−/−
piration (Figure 3C and 3D). VSMCs (Figure 4B and 4C) and macrophages (Figure 4D and
mtDNA lies close to the site of ROS production, such 4E) had increased OCR after uncoupling with FCCP com-
that ROS may induce the mtDNA damage associated with pared with ApoE−/− controls.
atherosclerosis; however, assessment of mitochondrial ROS Although, mitochondrial ROS were increased in aortas
during atherogenesis has not been reported. Mitochondrial as atherosclerosis develops (Figure 3E), mtDNA damage can
H2O2 was assessed in vivo in ApoE−/− mice using the mito- promote atherosclerosis independent of changes in ROS.9 We,
chondria-targeted probe MitoB. MitoB forms MitoP on reac- therefore, assayed ROS in both tissues and cells of ApoE−/−
tion with mitochondrial H2O2 (and also with peroxynitrite), and Tw+/ApoE−/− mice. There were no significant differences
changes that can be assessed by quantifying the MitoP/ in the MitoP/MitoB ratio in a range of tissues between control
MitoB ratio using mass spectroscopy.15 MitoP/MitoB was ApoE−/− and Tw+/ApoE−/− mice after 14 weeks of high-fat diet
increased in the aortas of fat-fed ApoE−/− mice (Figure 3E) (Figure 4F). Similarly, ROS levels in control ApoE−/− or Tw+/
and was associated with increased abundance of the antioxi- ApoE−/− VSMCs or macrophages determined using the ROS-
dant enzyme manganese superoxide dismutase (Figure 3F). sensitive dye dichlorodihydrofluorescein diacetate were simi-
Similar to the whole mouse with fat feeding, ox-LDL treat- lar at baseline and after stimulation with lipopolysaccharide
ment of mouse VSMCs in culture induced marked mtDNA or the free radical-generating agent tert-butyl hydroperoxide
damage (Figure 3G). (Figure 4G and 4H), indicating that Tw overexpression does
not affect ROS levels in vitro or in vivo.
Tw+/ApoE−/− Mice Show Increased mtDNA
Integrity, Copy Number, and Mitochondrial Tw+/ApoE−/− Mice Show Increased Fibrous
Respiration With No Change in ROS Cap and Decreased Necrotic Core Areas
Our data indicate that atherosclerosis is associated with To determine whether improved mitochondrial respiration
reduced mitochondrial respiration in human and mouse ath- could affect atherosclerosis, male and female Tw+/ApoE−/−
erosclerosis. We, therefore, used Twinkle transgenic mice and ApoE−/− littermate controls were fat fed from 6 to 20
(Tw+) to determine whether alleviating mtDNA damage and weeks of age. There were no differences in body weight,
increasing mitochondrial respiration could affect atherogen- blood pressure, blood counts, hemoglobin, serum lipids, or
esis or plaque composition. Tw+ mice express mouse Twinkle glucose between groups (Figure VI in the online-only Data
helicase intron 4 cDNA under the control of the human β Supplement). Detailed metabolic phenotyping using com-
actin promoter, which results in widespread transgene expres- prehensive laboratory animal monitoring system cages also
sion, including in muscle-containing tissues.5 Tw+ mice show showed no differences in food/water consumption, activ-
increased mtDNA copy number that varies between organs5 ity (as assessed by beam breaks), and total oxygen con-
and reduced mtDNA damage after oxidative stress.16 We sumption (Figure VII in the online-only Data Supplement).
crossed C57Bl/6 Tw+ mice with ApoE−/− mice and examined Atherosclerosis was examined in aortic roots, brachiocephalic
Twinkle expression, copy number, mtDNA damage, and arteries, and the descending aorta. There was no difference
Yu et al Mitochondrial Dysfunction and Plaque Composition 2327
Figure 3. Mitochondrial DNA (MtDNA) damage reduced mitochondrial respiration and increased ROS accumulation during murine ath-
erosclerosis development. Six-wk-old chow-fed apolipoprotein E–deficient (ApoE−/−) mice were compared with ApoE−/− mice fat fed from
6 to 20 wk (n=4–7) and aortas examined for (A) mtDNA adducts and (B) mitochondrial complex or citrate synthase (CS) abundance.
Representative Western blot (left) and quantification (right). Complex I- (C) and IV-supported respiration (D). E, Reactive oxygen spe-
cies as measured by MitoP/B ratio in aortas. F, Representative Western blot (left) and quantification (right) of aortic manganese super-
oxide dismutase (MnSOD) abundance at 6 and 20 wk. G, mtDNA adducts in ApoE−/− vascular smooth muscle cells isolated from 12- to
16-week-old mice with or without treatment with 100 μg/mL oxidized low-density lipoprotein (ox-LDL) for 24 h (n=8 biological replicates).
Tub indicates tubulin.
in plaque burden between Tw+/ApoE−/− and ApoE−/− mice Tw+/ApoE−/− plaques showing increased fibrous cap and
in any vascular bed (Table; Figures 5 and 6A). However, decreased necrotic core areas (Table; Figures 5 and 6B). Tw+/
Twinkle overexpression affected plaque composition, with ApoE−/− plaques also showed a borderline increase in smooth
2328 Arterioscler Thromb Vasc Biol December 2017
Figure 4. Twinkle increases mitochondrial respiration in aorta, vascular smooth muscle cells (VSMCs), and macrophages. A, Ex vivo
respirometry for complex I-supported respiration in aortas from control apolipoprotein E–deficient (ApoE−/−) or Tw+/ApoE−/− mice (n=6–8)
after 14-wk high-fat diet (HFD). Representative Seahorse profiles for oxygen consumption rate (OCR; B and D) or OCR after cyanide-
4-(trifluoromethoxy)phenylhydrazone (FCCP; C and E) in VSMCs (B and C) or macrophages (D and E) from control ApoE−/− or Tw+/
ApoE−/− mice (n=6–9). After 14-wk HFD, reactive oxygen species were measured by MitoP/B ratio in aortas, hearts, and livers (F) or
dichlorodihydrofluorescein diacetate (DCFDA) relative fluorescence units (RFU) in VSMCs (G) or macrophages (H) from control ApoE−/− or
Tw+/ApoE−/− mice. Cultured VSMCs and macrophages were also treated with lipopolysaccharide (LPS) or tert-butyl hydroperoxide (t-BHP).
n=4 to 5. Tw indicates Twinkle helicase.
muscle actin–positive area, significantly increased proliferat- To distinguish between the effects of Twinkle overexpres-
ing cells, and significantly decreased cells undergoing apop- sion on vessel wall or bone marrow–derived cells, 6-week-
tosis (Table; Figure 5). old ApoE−/− mice were irradiated and transplanted with Tw+/
Yu et al Mitochondrial Dysfunction and Plaque Composition 2329
Figure 6. Twinkle mouse plaques show reduced necrotic core and increased fibrous cap areas. Aortic root plaque % (A), necrotic
core, and fibrous cap % areas (B) in control apolipoprotein E–deficient (ApoE−/−) and Tw+/ApoE−/− mice after fat feeding from 6 to 20 wk
(n=11–18). Aortic root plaque % (C), necrotic core, and fibrous cap % areas (D) in ApoE−/− mice transplanted with control ApoE−/− or Tw+/
ApoE−/− bone marrow at 6 wk and fat feeding from 6 to 20 w (n=8–10). E, Cell number at day 0 and day 4 in vascular smooth muscle cells
(VSMCs) derived from control ApoE−/− and Tw+/ApoE−/− mice (n=3). Apoptosis at baseline and after 50 μmol/L tert-butyl hydroperoxide
(t-BHP) for 16 h in VSMCs (F) and macrophages (G) from control ApoE−/− and Tw+/ApoE−/− mice (n=4–5). BMT indicates bone marrow
transplant; and Tw, Twinkle helicase.
stress–induced apoptosis. Importantly, Twinkle overexpres- Mitochondria can sustain extensive damage without
sion during atherogenesis increases the size of the fibrous cap affecting overall function, in part because of compensatory
and reduces necrotic core areas while also increasing cell pro- mitochondriogenesis. However, we show that the mtDNA
liferation and reducing apoptosis in vivo. Reduced necrotic damage seen in mouse and human atherosclerosis is sufficient
core areas were also seen after transplantation with Tw+ mar- to reduce complex expression, mitochondrial respiration, and
row, suggesting that effects on both bone marrow–derived reserve capacity, particularly in the cap and core regions in
cells and VSMCs are important. Our study suggests that pre- human plaques. OCR and respiratory reserve capacity were
venting the mtDNA damage and dysfunction seen in athero- corrected for both tissue weight and cell number, and reduced
sclerosis may be important in modulating plaque composition. complex I- and IV-supported respirations were also seen in
Yu et al Mitochondrial Dysfunction and Plaque Composition 2331
aortas of ApoE−/− mice, indicating that these differences are ApoE−/− VSMCs show increased cell proliferation, and Tw+/
not just because of cell death. This suggests that the cells ApoE−/− VSMCs, macrophages, and plaques show reduced
comprising the plaque develop progressive mtDNA damage apoptosis. The independent effect of Twinkle on myeloid cells
and dysfunction, most likely because of exposure to risk fac- is also demonstrated by the reduction in core size seen after
tors, such as aging, diabetes mellitus, hypertension, smok- transplantation with Tw+ marrow.
ing, and hyperlipidemia. Indeed, we show that ox-LDL can Our data support a model where ROS/ox-LDL induce
induce mtDNA damage and mitophagy, and human plaque mtDNA damage, which is sufficient to decrease copy num-
VSMCs showed increased mitophagy. Autophagy is gener- ber, reduce complex I expression, promote mitophagy without
ally considered a protective mechanism, including in human compensatory mitochondriogenesis, and reduce mitochon-
VSMCs induced by atherogenic lipids12; however, mitophagy drial respiration. Mitochondrial dysfunction promotes VSMC
in the absence of compensatory mitochondriogenesis may and macrophage apoptosis and reduces VSMC proliferation
ultimately reduce mitochondrial respiration. leading to increased necrotic core and decreased fibrous cap
To augment mitochondrial respiration, we studied athero- areas. However, recovery of mtDNA integrity, for example,
sclerosis in mice overexpressing the Twinkle helicase, both by Twinkle overexpression, improves mitochondrial respi-
as global overexpression and after bone marrow transplant. ration, promotes VSMC proliferation, and protects against
Twinkle overexpression increased copy number in macro- VSMC and macrophage apoptosis. Plaque composition is
phages, similar to previous findings in heart and muscle.5 Tw+/ thus altered, with decreased necrotic core and increased
ApoE−/− aortas and VSMCs showed no change in copy num- fibrous cap areas.
ber but did have reduced mtDNA damage. Tissue/cell-specific Our study has some limitations. First, although the reduced
effects of Twinkle overexpression have been described previ- mtDNA copy number and mitochondrial respiration in human
ously and may reflect differences in mtDNA replication and plaques and plaque-derived VSMCs may be because of ox-
turnover.5 However, improvements in mtDNA integrity or LDL–mediated mtDNA damage and mitophagy, we were not
copy number both increased respiratory complex abundance able to directly examine the cause of reduced mitochondrial
and improved mitochondrial respiration. respiration in human plaques or examine mitophagy in mouse
The augmented mitochondrial respiration in Tw+ mice plaques. Second, we examined respiration in normal aortic
versus diseased carotid VSMCs, and cell origin might affect
may also directly affect cellular phenotype. Mitochondria
our results. However, our previous studies have shown that
regulate proliferation through multiple pathways, including
DNA damage is similar in normal (undiseased) arteries from
through aspartate and ATP synthesis; the resulting increased
different vascular beds.23 Third, we studied mouse bone mar-
ATP/AMP ratio would lead to decreased AMP-activated
row–derived macrophages rather than resident macrophages
protein kinase activation and less cell cycle suppression.17
exposed to the high-fat diet. However, plaque macrophages
Mitochondria are also important regulators of apoptosis
are mainly derived from bone marrow precursors, although
through the mitochondrial permeability transition pore.2
as bone marrow–derived macrophages are cultured ex vivo
Mitochondrial permeability transition pore opening releases
for 7 days, the extent the cells retain the effects of high-fat
death-promoting factors, such as cytochrome c and apoptosis-
feeding is uncertain. Last, the Tw+ mice show improved
inducing factor.18,19 Improving mitochondrial respiration may
mtDNA integrity, copy number, and respiration over the
lead to increased ATP production, which would reduce pore
timeframe under study (up to 20 weeks) and in specific tis-
opening and thus cell death. sues. However, Twinkle overexpression has different effects
Mitochondria are a major source of cellular ROS, but the on different tissues, and we cannot exclude beneficial effects
exact relationship between mtDNA damage, dysfunction, and of Twinkle overexpression on other cells in the plaque, such
ROS is unclear. Improving mtDNA integrity might reduce as endothelial cells. In addition, high Twinkle expression can
ROS levels, and reduced ROS has been observed previously in cause respiratory complex deficiency, particularly in tissues
Twinkle-overexpressing cells.20 In contrast, although Twinkle with high mitochondrial content.24 Twinkle itself is, there-
overexpression improved mitochondrial respiration, we found fore, unlikely to be a therapeutic target although protecting
no changes in ROS in either arteries in vivo or VSMCs or and augmenting mitochondrial function by pharmacological
macrophages in vitro. Our study shows that while aortic mito- means may be more successful.
chondrial ROS do increase during murine atherogenesis, aug- In summary, we show that the endogenous levels of mtDNA
menting mtDNA integrity and mitochondrial respiration can damage in mouse and human atherosclerosis are associated
affect plaque composition independently of changes in ROS. with significant reductions in mitochondrial copy number and
We find that selectively improving mtDNA copy number, respiration. Twinkle overexpression improves mtDNA integ-
integrity, and respiration increases fibrous cap and reduces rity and copy number, resulting in improved mitochondrial
necrotic core areas and increases cell proliferation and respiration and increased fibrous cap and decreased necrotic
reduces apoptosis in Tw+/ApoE−/− mice. There were no sys- core areas. Maintaining and restoring mtDNA integrity and
temic metabolic changes in Tw+/ApoE−/− mice, suggesting that mitochondrial function is, therefore, a promising therapeutic
the changes in plaque composition are because of changes in strategy.
vessel wall cells and macrophages. VSMCs provide the pro-
tective fibrous cap in established plaques, and their apop- Sources of Funding
tosis and senescence promote cap thinning.21 Macrophage This work was supported by British Heart Foundation (BHF)
apoptosis also increases plaque necrosis.22 In contrast, Tw+/ grants PG/14/69/31032 and RG/13/14/30314, a Wellcome Trust
2332 Arterioscler Thromb Vasc Biol December 2017
PhD Fellowship to J. Reinhold, the National Institute for Health atherosclerotic progression. Cell Metab. 2012;15:534–544. doi: 10.1016/j.
Research Cambridge Biomedical Research Centre, the BHF Centre cmet.2012.02.011.
for Research Excellence, the Academy of Medical Sciences and 12. Swiader A, Nahapetyan H, Faccini J, D'Angelo R, Mucher E, Elbaz M,
by grants to M.P. Murphy from the Medical Research Council UK Boya P, Vindis C. Mitophagy acts as a safeguard mechanism against
(MC_U105663142), and by a Wellcome Trust Investigator award human vascular smooth muscle cell apoptosis induced by atherogenic lip-
(110159/Z/15/Z). ids. Oncotarget. 2016;7:28821–28835. doi: 10.18632/oncotarget.8936.
13. Katayama H, Kogure T, Mizushima N, Yoshimori T, Miyawaki A. A sen-
sitive and quantitative technique for detecting autophagic events based
Disclosures on lysosomal delivery. Chem Biol. 2011;18:1042–1052. doi: 10.1016/j.
None. 14. Sun N, Yun J, Liu J, Malide D, Liu C, Rovira II, Holmström KM, Fergusson
MM, Yoo YH, Combs CA, Finkel T. Measuring in vivo mitophagy. Mol
Cell. 2015;60:685–696. doi: 10.1016/j.molcel.2015.10.009.
References 15. Cochemé HM, Logan A, Prime TA, Abakumova I, Quin C, McQuaker
1. Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin SJ, Patel JV, Fearnley IM, James AM, Porteous CM, Smith RA, Hartley
J, Eperon IC, Nierlich DP, Roe BA, Sanger F, Schreier PH, Smith AJ, RC, Partridge L, Murphy MP. Using the mitochondria-targeted ratiometric
Staden R, Young IG. Sequence and organization of the human mitochon- mass spectrometry probe MitoB to measure H2O2 in living Drosophila.
drial genome. Nature. 1981;290:457–465. Nat Protoc. 2012;7:946–958. doi: 10.1038/nprot.2012.035.
2. Wallace DC. A mitochondrial paradigm of metabolic and degenerative 16. Pohjoismäki JL, Williams SL, Boettger T, Goffart S, Kim J, Suomalainen
diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev A, Moraes CT, Braun T. Overexpression of Twinkle-helicase protects
Genet. 2005;39:359–407. doi: 10.1146/annurev.genet.39.110304.095751. cardiomyocytes from genotoxic stress caused by reactive oxygen spe-
3. Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol. cies. Proc Natl Acad Sci U S A. 2013;110:19408–19413. doi: 10.1073/
2003;552(pt 2):335–344. doi: 10.1113/jphysiol.2003.049478. pnas.1303046110.
4. Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink JN, Rovio AT, 17. Wang W, Yang X, López de Silanes I, Carling D, Gorospe M. Increased
Bruder CE, Bohlooly-Y M, Gidlöf S, Oldfors A, Wibom R, Törnell J, AMP:ATP ratio and AMP-activated protein kinase activity during
Jacobs HT, Larsson NG. Premature ageing in mice expressing defec- cellular senescence linked to reduced HuR function. J Biol Chem.
tive mitochondrial DNA polymerase. Nature. 2004;429:417–423. doi: 2003;278:27016–27023. doi: 10.1074/jbc.M300318200.
10.1038/nature02517. 18. Susin SA, Lorenzo HK, Zamzami N, et al. Molecular characterization of
5. Tyynismaa H, Sembongi H, Bokori-Brown M, Granycome C, Ashley mitochondrial apoptosis-inducing factor. Nature. 1999;397:441–446. doi:
N, Poulton J, Jalanko A, Spelbrink JN, Holt IJ, Suomalainen A. Twinkle 10.1038/17135.
helicase is essential for mtDNA maintenance and regulates mtDNA copy 19. Liu X, Kim CN, Yang J, Jemmerson R, Wang X. Induction of apoptotic
number. Hum Mol Genet. 2004;13:3219–3227. doi: 10.1093/hmg/ddh342. program in cell-free extracts: requirement for dATP and cytochrome c.
6. Tyynismaa H, Mjosund KP, Wanrooij S, Lappalainen I, Ylikallio E, Cell. 1996;86:147–157.
Jalanko A, Spelbrink JN, Paetau A, Suomalainen A. Mutant mitochondrial 20. Ikeda M, Ide T, Fujino T, Arai S, Saku K, Kakino T, Tyynismaa H, Yamasaki
helicase Twinkle causes multiple mtDNA deletions and a late-onset mito- T, Yamada K, Kang D, Suomalainen A, Sunagawa K. Overexpression of
chondrial disease in mice. Proc Natl Acad Sci U S A. 2005;102:17687– TFAM or twinkle increases mtDNA copy number and facilitates cardio-
17692. doi: 10.1073/pnas.0505551102. protection associated with limited mitochondrial oxidative stress. PLoS
7. Corral-Debrinski M, Shoffner JM, Lott MT, Wallace DC. Association of One. 2015;10:e0119687. doi: 10.1371/journal.pone.0119687.
mitochondrial DNA damage with aging and coronary atherosclerotic heart 21. Clarke MC, Figg N, Maguire JJ, Davenport AP, Goddard M, Littlewood
disease. Mutat Res. 1992;275:169–180. TD, Bennett MR. Apoptosis of vascular smooth muscle cells induces fea-
8. Ballinger SW, Patterson C, Knight-Lozano CA, Burow DL, Conklin CA, tures of plaque vulnerability in atherosclerosis. Nat Med. 2006;12:1075–
Hu Z, Reuf J, Horaist C, Lebovitz R, Hunter GC, McIntyre K, Runge 1080. doi: 10.1038/nm1459.
MS. Mitochondrial integrity and function in atherogenesis. Circulation. 22. Thorp E, Li Y, Bao L, Yao PM, Kuriakose G, Rong J, Fisher EA, Tabas
2002;106:544–549. I. Brief report: increased apoptosis in advanced atherosclerotic lesions of
9. Yu E, Calvert PA, Mercer JR, et al. Mitochondrial DNA damage can pro- Apoe-/- mice lacking macrophage Bcl-2. Arterioscler Thromb Vasc Biol.
mote atherosclerosis independently of reactive oxygen species through 2009;29:169–172. doi: 10.1161/ATVBAHA.108.176495.
effects on smooth muscle cells and monocytes and correlates with higher- 23. Matthews C, Gorenne I, Scott S, Figg N, Kirkpatrick P, Ritchie A,
risk plaques in humans. Circulation. 2013;128:702–712. doi: 10.1161/ Goddard M, Bennett M. Vascular smooth muscle cells undergo telo-
CIRCULATIONAHA.113.002271. mere-based senescence in human atherosclerosis: effects of telomer-
10. Chen H, Chan DC. Mitochondrial dynamics–fusion, fission, move-
ase and oxidative stress. Circ Res. 2006;99:156–164. doi: 10.1161/01.
ment, and mitophagy–in neurodegenerative diseases. Hum Mol Genet. RES.0000233315.38086.bc.
2009;18(R2):R169–R176. doi: 10.1093/hmg/ddp326. 24. Ylikallio E, Tyynismaa H, Tsutsui H, Ide T, Suomalainen A. High mito-
11. Razani B, Feng C, Coleman T, Emanuel R, Wen H, Hwang S, Ting JP, Virgin chondrial DNA copy number has detrimental effects in mice. Hum Mol
HW, Kastan MB, Semenkovich CF. Autophagy links inflammasomes to Genet. 2010;19:2695–2705. doi: 10.1093/hmg/ddq163.
• Mitochondrial respiration is markedly reduced in human atherosclerosis and in vascular smooth muscle cells derived from plaques.
• Mitophagy is increased in plaque vascular smooth muscle cells and after oxidized high-density lipoprotein.
• Augmentation of mitochondrial respiration by overexpression of the Twinkle helicase reduces multiple features of plaque vulnerability.
• Twinkle promotes vascular smooth muscle cell proliferation and reduces apoptosis of vascular smooth muscle cells and macrophages.
• Augmentation of mitochondrial respiration may be a therapeutic target in atherosclerosis.


text:
- Tripoto
- Travel Guide
- United States of America
- Travel Guides and trips for florence metropolitan city of florence italy
Travel Guides and trips for florence metropolitan city of florence italy
Trips and Itineraries for Florence
Top Places To Visit in Florence
Hotels and Homestays in Florence
Weekend Getaways from Florence
Search Flights
Book Florence Tour Package
Verify your phone number
We've sent you an OTP code to verify your phone number and prove you're a human.
Didn't receive one? Resend OTP.
Thank you!
Thank you! Your enquiry has been sent. Our travel partners will get back to you soon.
Uffizi Gallery
Piazzale degli Uffizi 6, 50122, Florence
Beautiful place to spend a few hours. The art is beautiful and so is the architecture of the building....
Piazzale Michelangelo
Viale Michelangelo, 50125, Florence
Duomo - Cathedral of Santa Maria dei Fiore
Via della Canonica, 1, Piazza del Duomo, 50122, Florence
Piazza della Signoria
50122, Florence
Walk on to Piazza Della Signoria and admire the statues( including the David copy) and the crowd. Check out the leather ...
Ponte Vecchio
Via Por Santa Maria/Via Guicciardini, 50125, Florence
Palazzo Vecchio
Piazza della Signoria, Florence
After visiting various other rooms on the first and second floors, each decorated with gorgeous frescoes and paintings, ...
Basilica di Santa Croce
Piazza Santa Croce 16, Florence
Campanile di Giotto
Piazza del Duomo, Historical Center, 10000, Florence
Cathedral of Santa Maria del Fiore
Piazza del Duomo, Firenze, Italy
After leaving Bologna, we arrived in Florence at about lunchtime (it was a 35 minute train ride from Bologna, thus Bolog...
Ponte Vecchio
Ponte Vecchio, Firenze, Italy
Well, this is one of the most popular landmarks in Florence. As told by locals, it is the only bridge to survive in Flor...
Cathedral of Santa Maria del Fiore
Piazza del Duomo, Firenze, Italy
We got a combined ticket to visit the Duomo. For 15 euros, you can visit the cathedral, crypt, baptistry, bell tower, do...
Piazzale Michelangiolo
Piazzale Michelangelo, 50125 Firenze, Italy
After about 2 hours or so in Pisa, we headed back to Florence. We went to Piazzale Michelangelo for a breathtaking view ...
Galleria dell'Accademia
Via Ricasoli, 58/60, 50121 Firenze, Italy
Boboli Gardens
Piazza de' Pitti, 50125, Florence
It was a Sunday, thus a lot of the churches have shorter opening times or are closed. So we went to the Boboli Gardens a...
St Maria of Florence Cathedral
Piazza del Duomo, Firenze, Italy
Trattoria Mario
Via Rosina, 2, Florence, Italy
Another place is this family-run trattoria which is famous with tourists and locals alike. They all go here to devour th...
Da Nerbone
Mercato Centrale, 50123 Firenze, Italy
For an authentic market lunch, look no further than Da Nerbone. Choose your food, pay at the counter and eat with the lo...
Chiesa di Santa Trinita
Piazza di Santa Trinita, 50123 Firenze FI, Italy
Visit The Santa Trinità Basilica:The Holy Trinity church is a must visit for all travelers.This Roman Catholic church i...
Basilica San Miniato al Monte
Via Delle Porte Sante, 34, 50125, Florence
There's also a beautiful church called the San Miniato al Monte even further up the hill. Once you've spent time admirin...
Gallery of the Academy
Via Bettino Ricasoli, 60, Florence, Italy
Florence Baptistery
Florence, Italy
Piazza del Duomo
Piazza del Duomo, Firenze, Italy
Palazzo Pitti
Piazza de' Pitti, 1, 50125, Florence
Museo Opificio delle Pietre Dure
Via Alfani, 78, 50121, Florence
Cupola del Brunelleschi
Piazza del Duomo, Santa Maria dei Fiore Basilica, Florence
Cattedrale di Santa Maria del Fiore
Cattedrale di Santa Maria del Fiore, Piazza del Duomo, 50122 Firenze, Italy
Palazzo Medici Riccardi
Via Cavour 1, Florence
Via del Proconsolo, 4, Florence, Italy
Basilica di San Lorenzo
Piazza San Lorenzo, 9, 50123, Florence
Cathedral of Santa Maria del Fiore
Piazza del Duomo, Florence, Italy
Opificio delle Pietre Dure
Via degli Alfani, 78, Florence, Italy
Duomo Of Firenze
Duomo, 50123 Firenze, Italy
San Lorenzo market
Piazza San Lorenzo, Florence
A journey in fresh Tuscan servings: Balsamics: Condiments & Traditional Certified – Tuscany Olive Oil – Crostini...
Gallery of the Academy
Via Bettino Ricasoli, 60, 50122 Firenze, Italy
Accademia di Belle Arti
Via Ricasoli 66, 50122, Florence
The David...
Ristorante Ora d'Aria - Ristorante a Firenze
Via dei Georgofili, 11R, 50100 Firenze, Italy
It's a Michelin star restaurant located in the heart of Florence. Typical Tuscan ingredients are used by the chef but pu...
Santa Maria Novella
Piazza di Santa Maria Novella, 18, 50123 Firenze, Italy
The Way of Tea 1
Piazza Lorenzo Ghiberti, 22/23r, 50122 Firenze FI, Italy
We also visited La via del Te, also known as The Way of Tea. They have a few branches but I think only the branch at Pia...
Bargello National Museum
Via del Proconsolo, 4, 50122 Firenze FI, Italy
Pitti Palace
Piazza de' Pitti, 1, 50125 Firenze, Italy
Perché no!...
Via dei Tavolini, 19r, 50122 Firenze FI, Italy
Tavernetta Del Battistero
r, Via dei Servi, 52, 50122 Firenze FI, Italy
Galleria Degli Uffizi
UB Firenze
Via Dei Conti 4r, 50123, Florence
₹ 0 ₹ 20000+


text:
Unknown Lands : A collection of the world's finest Manga and Anime worlds in one single place. This place also includes a few mysterious sections that only few have yet to see. . .
starfall, unknown, lands, fairy, tail, dragon, ball, piece, world's, finest, manga, anime, worlds, single, place, this, also, includes, mysterious, sections, that, only, have
An online competitive and roleplaying league for the WWE 2K yearly franchise; PS4 system only
Free forum : The only limit to life is imagination. free forum that allows any thing to happen to any kind of creature you wish to be.
free, forum, immortal, journey, only, limit, life, imagination
This forum is for admins of Heitehu, Beta and higher only.
Members only forum. Free forum : Fraternitas Excentricus
open for Non Resident UiTM student only
Free forum : a site dedicated to the shovelhead, and old harley-davidsons, and the people that ride, maintain, and personalize them, , , , goofs need not apply this forum is by invite only if we never shook hands then this place is not for you! '' so
free, forum, 66-84, shovelheads, site, motorcycles, shovelhead, harley-davidsons, people, that, ride, maintain, personalize, them, goofs, need, apply, invite, only!!!(that, means, never, invited
Free forum : The Forbidden Forums is a forum in which similar people can get together and live outside of their own world. It is basically a Role-playing forum with just a few exceptions(Stories, poem
free, forum, forbidden, forums, which, similar, people, together, live, outside, their, world, roleplaying, only
Its All about PTC! Talk, Chat, Post Referral Links, Referral Exchange, Advertise your Banner, List of Top Ptcs, Scam Ptcs and lots more only on ForumPtc. com!
Feeling sad, worried, or lonely and need someone to talk to? Feel free to join us on this NEW journey of supporting each other, positive only communication. No (-)'s
emotional, support/, /share, info, feeling, worried, lonely, need, someone, talk, feel, free, join, this, journey, supporting, each, other
RomaniaSens is a cheat for csgo only for hvh and little legit
there is only one clan and only one Family and they call madness Family. Be Nice And Gentle
Free forum : A place to escape the male admin. :). Showbread Forums: Girls Only
Free forum : This is the world of F1. 26 amazing creatures have gathered together in 2008. RESTRICTED TO F1 ONLY !
Start here, If you're new, welcome! This will be the only thread that can be viewed until your membership is approved.
general, start, you're, welcome!, thread, viewed, membership, approved
Your destiny is uncertain and only You must set your the path on your journey to fulfil your potential
naruto:, blind, future, your, destiny, uncertain, only, must, path, journey, fulfil, potential
This Forum is for the GDI brotherhood Only!
galactic, defence, initiative, this, forum, brotherhood, #only!
Private forum : A Place to speak openly 18's Only. Free forum : Dolls houses, after the water shed
house, private, dolls, houses, after, water, shed, place, speak, openly
A place for inmates to play
Free forum : Like nda, only better. Free forum : ndachan - for the lulz
For Final uprising Guild members only
An Exclusive Roleplay Forum - Invite and Request Only. Email me at firstname.lastname@example.com if you wish to join in on the fun.
eatingjellybeans, role-playing, exclusive, roleplay, invite, request, email, mirrormoth, studios@gmail, join
This forum is for Magnum Suited, and its elite warrior battle planning. Not all MS members will be included, as this area is by invitation only.
magnum, suited, elite, this, forum, warrior, battle, planning, members, will, included, area, invitation, only
Free forum : best ninjas only and the best naruto rpg in the world and act as the person
only for guild members !!!
A forum where people from St. A's can chat. Please, only join if you are from St. A's.
Rotoworld Forum's TBD Dynasty Football Page - for members only!
dynasty, football, rotoworld, forum's, page, members, #only!
Free forum : Currently for members of the clan only!
free, dimensions, currently, members, clan, #only!


text:
Powered by ExoticAds
Buy/Sell Traffic
Powered by ExoticAds
Buy/Sell Traffic
Room is currently offline
|None Selected
|Choose an App
|None Selected
|Choose a Bot
|None Selected
|Choose a Bot
|None Selected
|Choose a Bot
Suggest an App Idea
Goddess_aphrodite_x's Bio and Free Webcam
- Real Name:
- Aphrodite
- Followers:
- 8832
- Birth Date:
- April 10, 2000
- Age:
- 19
- Sex:
- Female
- Interested In:
- Men, Women, Trans, Couples
- Location:
- in your heart
- Last Broadcast:
- 6 days ago
- Language(s):
- English
- Body Type:
- skinny
- Smoke / Drink:
- ask me
- Body Decorations:
- ask me
- Pics & Videos:
150 TOKENS OR FAN CLUBsweetie part 2125 TOKENS OR FAN CLUBsweetie180 TOKENS OR FAN CLUBMy sexy legs150 TOKENS OR FAN CLUBAnd a little bit ...150 TOKENS OR FAN CLUBPeppercorn 2.0150 TOKENS OR FAN CLUBPeppercorn135 TOKENS OR FAN CLUBawww
- About Me:
I am beautiful. And you will not be able to resist me.
Most of all I love being worshiped. This is so windy!
I do not like rude and boorish people.


text:
Powered By Sharerails
signup for updates from Macy's store
Topstitched Walker Coat
Monray Red and Multi 3' x 5' Area Rug
Ron 'Old Man Of The Mountain Black Bear' Canvas Art - 24" x 32"
I.n.c. Men Skull & Cross Bones T-Shirt
Women's Margaery Cold-Weather Booties Women's Shoes
Men Logo Graphic Polo
Goldsmith 5-Piece Place Setting
Tommy Hilfiger Greenwich Ponte Pants, Only at Macy's
Baby Boys 2-Pc. Cotton Henley Shirt & Shorts Set
by Aireloom Handmade 14.5" Luxury Plush Luxetop Mattress with Adjustable Base- Queen


text:
I am Heidi. Hello man, can you see me here. ))) Look my ID: 78238 Other my fotos: https://goo.gl/oZsj7e
0 Total post views
Musician who loves the stage and crazy things ;)
I`m singing in the band The Similars.
Not all thoughts should be completed. For example,
ᴡᴡᴡ.15sexy.ru --- lооking fоr а lоvеr fоr thе sаkе оf mееtings оr аftеr а girlfriеnd аnd sеttlе dоwn fоr thе sаkе оf sех rеvеlаtiоns hеrе аlrеаdy соmе in hеrе.
Soaper | Artist | Mom | Equestrian | Reader | Diner | Wannabe Photographer | Animal Lover | And other things I just can't think of right now..
"If you remember me, then I don't care if everyone else forgets." ― Haruki Murakami
Trying to make sense of this hand of life I was dealt, and I'm loving every second of it.
Don't be delicate.. be vast and brilliant..
Laura Szumowski is an illustrator, letterer and designer living in Chicago. She is currently creating a line of greeting cards, wrapping papers and gifts for The Found.
21 - Student in Gent - Master Oost-Europese talen en culturen (Russisch-Pools) en Bachelor toegepaste taalkunde - hartjes voor hiphopdans, lekker eten, gin-tonics, en impulsieve feestjes.


text:
Focusing on what you have accomplished will help to set you apart from your peers. You should highlight the value youve brought to companies and the success that they have seen while you are there. Companies are looking for game-changers they want 5 star recruits not 2 star players who are not up to the challenge. You have to make yourself into a 5-star recruit you cannot rest on your laurels and hope for the best. Spotlighting your success will show potential employers that you are capable of outperforming your peers.
There are different resume formats for presenting your details. Out of all these formats, three formats are most often used depending on the position applied and the qualifications of the applicant. These formats are -
To distinguish the good resume writing services from the bad ones you need to find out how they proceed with the task. A good service asks you to fill out an online question. They also set you up for an interview with the writer. This ensures that the writer is aware of all details that must be present in your resume. If a personal interview is not possible they may also provide you with other ways to get in touch with the writer.
Focus on achievements Employers not only want to know what you have done in the past they also want to know where you have excelled. If you have awards achievements or on the job highlights make sure to add them. If you were part of a team you were part of the success. If your project increased production by 20% and you played a part in it add it on your resume!
There are millions of resumes being uploaded to job sites and because of this job sites have an ongoing need for more and more web servers. Job sites earn revenue from recruiters and employers that are subscribers and not from job seekers so it makes sense to eliminate this cost and pass it on to the resume website provider. Since people manage multiple resumes in their profiles to apply for different jobs it would be better for everyone if job seekers had multiple links to different resume pages instead of resume PDFs. The storage cost to job sites is eliminated and job sites can reduce their fees to subscribers.
No sample resumes are accessible. A competent resume writing service will provide a number of samples for review. You can assess the quality of their work only if have these samples. If there are no samples available on their website ask them for the specimens of their work. If they are unable to provide satisfactory examples of their work you had better opt for another service.
Conditions of Use Privacy Notice Cookie Policy Copyright 2019, Mymfunding.


text:
Cruising – Liverpool Sailing Club
Date(s) - 23 Jun
All Day
Category(ies) No Categories
Upriver Cruise, for club members but with a warm open invitation to GP14 Class Association members to join the event.
Please note the change of date; the later tide on this new date will allow us a better event.
Launch time to be advised nearer the time, but expect between 1400 and 1430. ETA back at the club c. 1830 – 1900.
Cruise upriver on the flood, potentially as far as the Runcorn bridges, returning on the ebb, so sailing with the tide in both directions. Around 10 miles each way, of pleasant semi-rural scenery on the northern bank and a distant industrial background on the southern bank. Estuary almost 3 miles wide at the club, and for most of the passage, narrowing to a few hundred yards by the time we reach the bridges.
Further information from the usual address; [email protected].


text:
Four people are pulled to safety through the roof of the car as heavy rain and flooding hits.Read more
Latest Stories
Carys Betteley
BBC News
A university lecturer who contracted Japanese encephalitis in China now lives in a care home.Read more
A university lecturer who contracted Japanese encephalitis in China now lives in a care home.
Colette Hume
BBC Wales News
Police pass on information about domestic abuse which children have witnessed so they can be helped.Read more
Two gamekeepers deny killing a teenager who was fatally injured when a shotgun went off in a car.Read more
Vincent Burke is handed a 10-month sentence for punching Emily Clarke and knocking her unconscious.Read more
People considering creating garden bonfires warned of the potential dangers.
He is also being questioned by Rhyl police over a racially aggravated public order offence.Read more
People caught with small amounts of drugs could be offered an educational course, the North Wales PCC says.Read more
Gerald Corrigan, 74, "died a cruel" death three weeks after being shot with a bolt, police say.Read more
George Herd
BBC News
Care teams are urged to join a scheme to help police find vulnerable people quickly.Read more
Eglantyne Jebb started the charity with her sister to help starving youngsters after World War One.Read more
Owain Clarke
BBC Wales health correspondent
Apps and wearable technology are starting to help patients monitor their health and medicines.Read more
National search for missing Wakefield teenager Nicole
Police officers are trying to find a missing 16-year-old girl who's been missing from Wakefield for five days.
Nicole Harris was last seen in the Quebec Street area of the city, but a national search has now started for her.
She is known to have links to various parts of the country including South Yorkshire, Shropshire, Humberside, Merseyside and North Wales, West Yorkshire Police said.
Nicole who is described as a "vulnerable teenager", is 5ft 3ins tall and has long brown hair and a burn scar on the side of her nose.
Police start a murder inquiry after Gerald Corrigan, 74, dies three weeks after being shot.Read more
Gerald Corrigan, 74, died in hospital on Saturday, almost a month after he was shot outside his home.Read more
Gerald Corrigan, 74, suffered "horrendous" injuries when he was shot outside his Holyhead home.Read more
Catrin Haf Jones
Wales Live
One woman who spent three years in temporary accommodation says she "didn't want to be alive".Read more
Timber dating back 3,500 years could be the first ever Bronze Age canoe found in north Wales.Read more
He was airlifted to hospital after a 999 call reporting a person in the water off Llandudno.Read more
Males have smaller jaw hooks than wild fish, making them less sexually appealing, research shows.Read more
Watchdog looks at conduct of officer involved with the case of a murdered Wrexham pensioner.Read more
The suspect, aged in his 20s, was detained after staff were threatened at Shoe Zone in Bangor.Read more
Police say Gerald Corrigan is "stable but heavily sedated" after the bolt narrowly missed his heart.Read more
Families in about 20 homes are evacuated from their homes as fire crews tackle a mountain blaze.
Police say 74-year-old Gerald Corrigan has been moved to another hospital due to his injuries.Read more
The council introduced the charges near a popular beach in Gwynedd to help meet a £13m funding gap.Read more
Psychological help for parents with a child in neonatal care is only available in five of 11 units.Read more
George Herd
BBC News
A farming couple make the plea after a "heartbreaking" attack on livestock on their land.Read more
Farmers who witnessed the aftermath of a brutal dog attack on their sheep are calling for changes to the law.
Three separate 50m-wide fires were burning on the hillside at Rhosgadfan near Caernarfon, Gwynedd.Read more
The MP says there were "grave errors" by police leading up to the murder of Nicholas Churton.Read more
One of the oldest universities in Wales blames fierce competition and a drop in numbers for the cuts.Read more
Scientists are closer to pinpointing where and when different grass species will trigger hay fever.Read more
Campaigners in Gwynedd fear changes to the service, which helps children cope with school in Welsh.Read more


text:
In his words, the pace has reduced over the past two months, as Italy and Greece cannot prepare documents in time due to a large wave of asylum-seekers.
"Lithuania is indeed ready, it is doing everything to be able to relocate. But both Greece and Italy are behind schedule to prepare the necessary documentation (…), they do not collect the necessary information in time," Misiūnas told BNS.
The minister said he had been assured by colleagues that the problems would shortly be settled and new people should come shortly.
In September, the European Commission recommendations to continue refugee relocation from Italy and Greece in accordance to the 2015 quotas. A commitment was then established that 160,000 refugees from Syria, Iraq and Eritrea would be distributed among EU member-states by the end of September of 2017.
According to data provided by the European Commission, the community's countries accepted merely around 29,000 persons.
Misiunas said Lithuania was looking quite good in the general context, receiving 414 persons from its quota of 1,105 people, mainly Syrians from Greek camps.
However, observers question the efficiency of the program, as over 300 of the refugees later left Lithuania.
Lithuanian-born American artist buried in Semeniskes
Jonas Mekas , a Lithuanian-born American artist, poet and filmmaker , often called the godfather...
Lithuanian animation returns to "Annecy"
After a two-year break, Lithuanians return to the Annecy International Animation Film Festival...
Success of HBO's Chernobyl puts Vilnius in spotlight as prime location for filming
Tax incentive, welcoming approach by the government, and big talent pool made Vilnius an attractive...
Promising year for Lithuanian animation
In 2017-2019, the Lithuanian film industry has experienced remarkable growth. As a result,...
Chernobyl in Kaunas: revisiting the shooting locations
As all of the five episodes have already been broadcast and the holiday season has started, here's a...