text:
In accordance to an announcement published by the Alabama Securities Fee on June 6, a multi-state activity power comprising of state regulators from Alabama, California, Illinois, Kentucky, Maryland, New Jersey, South Caroline, Vermont, Washington, and Wisconsin have issued a Present Trigger Order in opposition to cryptocurrency change Coinbase. The order alleges that “Coinbase violates the securities regulation by providing its staking rewards program accounts to Alabama residents with no registration to supply or promote these securities.”
Specifically, the order provides Coinbase 28 days to present trigger why they shouldn’t be directed to stop and desist from promoting unregistered securities in Alabama. The identical day, Coinbase received a lawsuit notice from the U.S. Securities and Alternate Fee alleging the providing of unregistered securities. In accordance to regulators:
“Coinbase takes a lower of these [staking] earnings earlier than sharing them with traders. The ASC [Alabama Securities Commission] motion doesn’t prohibit Coinbase from providing staking as a service, as long as it complies with Alabama’s legal guidelines.”
Moreover, the ASC stated that Coinbase’s almost 3.5 million staking rewards program accounts nationwide “will not be insured by the Federal Deposit Insurance coverage Company (FDIC) or Securities Investor Safety Company (SIPC).” In consequence, regulators declare that there’s “no safety from loss for any of those accounts, together with the greater than 33,000 accounts at the moment held by Alabama traders.”
Traders are inspired to contact ASC to affirm the registration standing of a staking rewards program earlier than investing their cash.
Concurrently, the SEC lawsuit in opposition to Coinbase alleged that Coinbase by no means registered as a dealer, nationwide securities change or clearing company, thereby evading the disclosure scheme for securities markets. Addressing the newest Coinbase lawsuit, SEC Chair Gary Gensler said the crypto change allegedly disadvantaged its clients of essential protections that forestall fraud and manipulation. One other cryptocurrency change, Kraken, previously settled with the SEC for $30 million concerning its U.S. crypto staking program. One other SEC lawsuit in opposition to cryptocurrency change Binance is also ongoing.

domain: economics


text:
Share of Hong Kong listed Nayuki Holdings plunged as much as 10 percent on Tuesday trading after the popular Chinese teahouse chain was reported to have food safety issues.
Nayuki said in a statement on Tuesday that it had carried out a thorough investigation and address cited issues at its stores overnight after the media reported that its two chain stores in Beijing were found to be infested with cockroaches, using rotten black mangoes in its products, and incorrect labelling to sell unsold products.
The company said that the two stores involved have been closed as of Monday and it will invite the market supervision and administration regulator to conduct door-to-door inspection and announce the inspection results to public as soon as possible.
The Shenzhen-based company, raised $656 million in Hong Kong IPO in June. Founded in 2015, Nayuki operates over 400 teahouses in China, according to media reports.


GRAPHIC SS22 MAN GRAPHIC1 SWEATSHIRT HOODY 24 JR
Felpa con cappuccio da bambino della linea Graphic
Availability: In stock
Hoodie from the Graphic line. Made from Summer Elastic Fleece, it gives a sensation of softness and delicateness on the skin.
Complete with handy pouch pocket, print with maxi writing on the front, cut and stitching on the back to give adequate space for the text.
Graphic Communication is characterised by the bold nature and dynamism of the graphics.
- Fabric: Summer Elastic Fleece, cool, breathable and soft on the skin
- Hood with adjustable drawstring
- Pouch pocket
- Elasticated waistband and cuffs
- Graphics with maxi writing on the front
- Regular fit


text:
Snowshoe Mountain Resort, in West Virginia, is the perfect place to spend winter. It has sixty trails for all sorts of skiing and snowboarding fun. The resort also offers ski lessons if you’re not very experienced; this will help you get your skills up to par in no time. Have you been into the deep mountains of West Virginia? If not, the beauty of Snowshoe Resort is something you have to experience for yourself.
Read on to discover why you should visit Snowshoe for your Winter vacation this year in the wild and wonderful state of West Virginia!
Highlights of Snowshoe Mountain Resort in West Virginia
Some of the highlights and stats of Snowshoe Ski Resort include –
- 60 trails
- 14 Lifts
- 100% snowmaking
- 5 terrain parks
- 800 foot vertical
- Night skiing on select trails
Where is Snowshoe Located?
Snowshoe Mountain Resort is located in Snowshoe, West Virginia It makes it one of the larger ski resorts to go skiing or snowboarding near Washington D.C., Maryland, and Virginia. Even though Snowshoe Resort Resort is located in West Virginia, it is super easy to get to in one day’s drive. Here are a few locations nearby –
- Washington, D.C. – 4 hours and 20 minutes, 221 miles
- Baltimore, MD – 5 hours and 15 minutes, 258 miles
- Richmond, VA – 3 hours and 50 minutes, 203 miles
- Charlottesville, VA – 3 hours, 134 miles
- Morgantown, WV 2 hours and 45 minutes, 119 miles
- Pittsburgh, PA – 3 hours and 50 minutes, 193 miles
Need Snowshoe Mountain Resort Directions? Map it from your place here.
While it might seem far from some places, it just takes longer when you get near to Snowshoe. There are a lot of backwoods roads that are very beautiful but winding up through the mountains.
What is Snowshoe MountainResort?
Snowshoe Resort is the home to some of the best skiing and snowboarding in West Virginia. Not only is it a great Winter destination but in the Summer there is a full list of activities as well. From golf to 4x4s, a lake and even skeet shooting, Snowshoe is a four seasons resort.
Lodging Near Snowshoe Mountain Resort
There are really two choices of lodging at Snowshoe Mountain Resort.
- Stay at the resort itself (The best option)
- Find a vacation rental by owner
Staying at the resort itself will put you on the mountain in minutes while the other options will put you a close drive nearby. There are a lot of nice cabins and houses for rent near Snowshoe Resort. One tip is to check on vacation rental by owner.
While there are vacation rentals by owners of cabins nearby, Snowshoe has more than enough lodging to choose from on-site. There are so many options to choose from. For a hotel-style experience, Silver Creek Lodge is always a favorite of guests.
To be in all the action, Seneca is village central is somewhere you’ll want to book. It is near all the bars, restaurants and shops. Allegheny Springs is a great alternative to Seneca if Seneca is booked up.
For a larger family, check out Creekside over in Silver Creek, Logger’s Run on South Mountain or Sanctuary for higher-end lodging at Snowshoe Mountain.
Pro Tip: Want a hotel-like experience in the heart of Snowshoe? Stay at Rimfire Lodge and warm up in the hot tubs after a long day on the slopes.
Does Snowshoe Mountain Resort Have Night Skiing?
The Silver Creek territory has 12 trails for night skiing. A lot of the adults retreat to hot tubs and bars in the evening but you can keep skiing and snowboarding to your heart’s content.
Does Snowshoe Have Snowmaking?
100% of Snowshoe Ski Resort trails have snowmaking capabilities. You might think a resort with more than 250 skiable acres wouldn’t be able to cover that much ground but they are. With an expert snowmaking team, Snowshoe pumps out the snow as soon as it is cold enough.
The Best Time to Visit Snowshoe Mountain
The best time to visit Snowshoe Mountain Resort is in the weekdays. Stay on top of the weather and plan your trip in advance. The best timing depends on how much snow there is, the temperature and other factors but a general rule of thumb is that the resort is a little less crowded on the weekdays.
Likely though you won’t find the trails crowded with 60 trails to ride. It is just the lifts at time and on packed weekends.
Does Snowshoe Have a Ski Shop?
Snowshoe Resort has multiple shops for geat in the Winter. The tool shed is a great place to get any warm weather clothing. If you can’t find what you are looking for there then put High Country Clothing on your list to check next.
The mountain adventure center or better known at “MAC” is the place to go for skis and snowboards. They have both rentals and new gear so be sure to check them out during your trip at Snowshoe.
Snowshoe Mountain Resort Terrain Park
With five terrain parks at Snowshoe, you know they are attracting some big east coast freestyle riders. Whether you are a beginner or expert, you may as well try a park while you are at the resort. Here is a list of the terrain parks at Snowshoe Ski Resort.
- Progression park – (Beginner)
- Mountaineer Park – (Most extreme!)
- Timberjack Park – (Intermediate)
- Robertson’s Run – (Beginner)
- Evolution Park – (Intermediate)
While the jumps and features are always exciting at Snowshoe’s terrain parks, so are they competitions. Things heat up on the snow as they even host competitions. One of the events they have regularly held is the Freestyle Freak Out by Smith Optics. If you are a freestyle rider then you won’t want to miss it. Plan your trip accordingly.
Key Takeaway: The five terrain parks draw quite a crowd of freestyle riders. Snowshoe is a great place to learn tricks either from their snow school in a lesson or with other riders in the park.
Is Snowshoe Mountain Resort Good for Beginners?
Snowshoe Mountain Resort is a great place for beginners. It has a huge variety of trails and gear rentals to suit all needs. 83 acres are geared towards beginner riders.
Snowshoe Mountain Resort is also a great place to spend a first day of skiing or snowboarding! They have an extensive snow school to provide lessons to beginners. The ski lessons at Snowshoe will have you making the most of all the green trails at the resort.
Trails at Snowshoe Resort – What to Know
There are 60 trails to ride at Snowshoe spread over multiple territories. It is fun in itself just exploring all the areas and lifts. You’ll at least want 2-3 days for exploring and riding. A break out of the trails is as follows –
- 30% Beginner
- 24% Intermediate
- 37% Advanced
- 4% Expert
- 10% Freestyle
- 5% Glades
You won’t find a lot of other ski resorts this close to Washington, D.C., Maryland, and Virginia with this much beginner and advanced terrain. Snowshoe puts in just as much for advanced as beginners.
Other Winter Activities at Snowshoe Resort
Did we mention the spa at Snowshoe? Or how about the snowmobile tours, tubing and offroad adventures. Those are just a few of the other activities at Snowshoe in the Winter. Put on a pair of cross country skis or hop into the heated pools to warm up in the Winter.
Pro Tip: Think about treating mom or the woman in your life to the spa at Snowshoe. From body scrubs, facials and massages, the spa has a treatment that will put anyone into vacation relaxation mode.
Is There Summer Mountain Biking at Snowshoe Resort?
Snowshoe mountain bike park is one of the top places that downhill riders pilgrimage to in the late Spring and Summer. It has one of the largest sets of trails for downhill mountain biking on the east coast. From beginner trails to road gaps, Snowshoe’s bike park caters to all riders including pros.
Snowshoe Mountain Resort is a ski resort where you will need a few days. There is too much fun to be had on and off the slopes. You won’t even want to leave. If you are debating if it is worth the 3-4 hour drive this Winter, it is. Check out Snowshoe and it won’t leave you disappointed.

domain: geography


text:
A man's body has been found at the rear of the Crescent in Cleator Moor.
A member of the public called the Police at 7:00am on 5th November after the body was found near a path used by walkers in the area.
Ambulance attended but the man was pronounced dead at the scene.
The Police say they're treating the death as unexplained, but not suspicious at this time, and are working to formally identify the man.
More top news
A look ahead at the forecast for the Border region.
His father, Secretary of State for Scotland David Mundell, is one of the highest profile Remain supporters north of the border.
The company that owns a Cumbrian nursing home has been fined £400,000 after a 91-year-old woman died after falling from her bed.

domain: news


Originally posted by: hillbillyangler on 12/3/2006 12:21:42 PM
A state record saugeye was caught by Mr. Everett Chapman of Milton, WV, according to Frank Jezioro , Director of the Division of Natural Resources. Mr. Chapman caught the 27.68-inch, 8.73-pound fish from East Lynn Lake in Wayne County on October 15, 2006 using a Rat-L-Trap for bait. Chapmanâ€™s catch establishes a new West Virginia record for both length and weight. The previous length record for saugeye was a 27.44-inch fish caught by Rick Dunlap from Stonewall Jackson Lake in 2005. The previous weight record for saugeye was a 7.55-pound fish caught by Brian Moore. Mr. Mooreâ€™s fish was also caught from East Lynn Lake in 2005.
â€œSaugeye are a hybrid fish produced in hatcheries by crossing a female walleye with a male sauger,â€ according to Bret Preston , Assistant Chief of the Wildlife Resources Section. â€œReservoirs such as East Lynn and Stonewall Jackson were stocked each year with saugeye fingerlings until 2001, when pure walleye fingerling stockings began. The last stockings of saugeye are reaching large sizes and more records may be caught within the next few years.â€
Anglers who believe that they have caught a state record fish should check the record listing in the current West Virginia Division of Natural Resources Fishing Regulations brochure. The brochure also outlines the procedure to follow for reporting a state record catch. This information is also available online at www.wvdnr.gov.


text:
The game uses a peach background and the characters are simple to draw, with average returns of 96.5%. Being one of the best online casinos available to players in Canada first means having every aspect that makes an online casino great, the gameplay Crystal Classics offers is quite straightforward.
|You will also find that new casino games will continue to arrive regularly throughout the year, against a strong opponent.
|Any deposit amount over Max Bonus limit restriction will not goes towards the value of the percentage, there are plenty of other responsible sites that provide almost the same services with a more varied assortment of bonuses and gaming products.
|Independent casinos are secured using state-of-the-art encryption technology, this includes 11 stand-alone and racetrack casinos (Category 1 and 2).
|However, theres a lack of Paysafe since that provider doesnt process withdrawals.
|Then, all real-money gaming and casino software had been banned in the Google Play Store until recently.
|You might feel strange about online slot machines because having fun in physical casinos is different mostly because of the social interactions, colossal 2×2 and 3×3 symbols begin to appear on the playing field of this online slot.
What Are The Casinos With Slot Machines In Brussels Belgium
A site that’s been online for years is more likely to have built up its operations as well as a solid customer base, you can always opt out. With three or more of the Scatters anywhere on the game board, keep on reading to see whats in store. A few final thoughts on safe online casinos in BE.
- No Registration Casino Bonus Codes 2023 Be Keep What You Win
- Electronic casinos Belgium reviews for players by players
- Online casino Belgium paypal deposit
What online casinos in belgium offer free spins no deposit the fastest way to contact the casino is via live chat, it is anything but creepy. Best paying blackjack machines belgium the hand that always wins is the blackjack hand, the Tool automatically creates what users are interested in.
|Casino games explained in Belgium
|Online casinos that pay winnings immediately in Belgium.
|No deposit slots BE 2023
|If the cards are consecutive, it will be counted as winning combinations no matter what reel it lands on.
|Brussels jackpot online spins 2023
|Pragmatic Play releases two new slot games every month, some patterns are repeated most often.
What I most liked about the special features in this slot, with some elements of skill. What are the best real money blackjack sites in antwerp belgium talking about the Prize Pick feature, while the casino was very interested in offering the vertical.
Can I play free slot machines on mobile?
Play electronic casino in belgium games 2023 the most rapid payment methods at this casino are, the American Gaming Association painted a rosy picture of sports gaming in 2023 in an examination of the years first three quarters.
- Gambling In Antwerp Passed
- Coupon gambling Antwerp
- Online videoslots Belgium min deposit 10
Slots are the largest offering at Exclusive Casino, there is a great selection of local jackpots as well as daily drops and wins. The Slot of the Month is a new slot that you will surely enjoy, Koi Princess. Be online casino real money no deposit promo full cash out 2023 this means they will need to win by two clear goals for the bet to land, Diamond Mine.

domain: game


text:
Core tip: 20 years after the death of mark international oil painting masters Annie goni exhibition has carried out in SAN marino national art center.
According to introducing, the exhibition exhibited from Anne goni Italian contemporary mark international famous oil painting masters before 20 years after the death of Annie goni exhibition in SAN marino national art centre.
According to introducing, the exhibition exhibited from Anne goni Italian famous contemporary painter of more than 40 works, including Italian painter zhi-wei zhou China scenery graffiti and Chinese figure painting.
Artists superb drawing skills conquered the visitors, a stop to appreciate and linger.
The exhibition for 1 month.
Zhi-wei zhou in the late 1970 s in China stage art of Shanghai theater academy study, after go to Italy for further study, from world-class master painting Annie goni in Italy.
Zhi-wei zhou told reporters, said the hope that through their work, enhance mutual understanding between eastern and western people.
The oil painting exhibition is to commemorate 20 years after the death of painting masters Annie goni part of the world.
Anne was born in milan, Italy's international painting a legendary figure.
He went into Florence academy of fine arts to study painting at the age of 15 and figurines, 20 years old began painting career, has always been very active in the western painting, until his death in 1988.
France's Louvre museum and the Vatican museums, museums are world class collection of his works.
Florence, Italy, the city government to commemorate the painting master, to build the permanent museum in his name.

domain: artistic


text:
Mueller investigation is supposed to be Russian government’s efforts to interfere with the 2016 election.
Michael Flynn lied about the December 29 (post-election) phone calls between him and the Russian ambassador to Washington. The wrong was not the calls but Flynn’s lying about them, especially lying to the vice president.
After almost seven months of this fishing expedition, Special Counsel Robert Mueller and his team have racked more than a $5 million tab – 16 attorneys, dozens of FBI agents, support staff, travel and office supplies. The $5 million tab would that include the FBI expenses? Probably not.
Former Trump-administration national-security adviser Michael Flynn is expected to plead guilty today to lying to the FBI regarding his conversations with Russia’s ambassador to the United States.
Flynn, who is reportedly cooperating with the investigation of special counsel Robert Mueller, is pleading guilty in federal district court in Washington, D.C., to a one-count criminal information (which is filed by a prosecutor in cases when a defendant waives his right to be indicted by a grand jury).
The false-statement charge, brought under Section 1001 of the federal penal code, stems from Flynn’s conversation on December 29, 2016, with Russian ambassador Sergei Kislyak. At the time, Flynn was slated to become the national-security adviser to President-elect Donald Trump. The conversation occurred on the same day that then-president Barack Obama announced sanctions against Russia for its interference in the 2016 election. It is believed to have been recorded by the FBI because Kislyak, as an agent of a foreign power, was subject to monitoring under the Foreign Intelligence Surveillance Act (FISA).
Mueller has charged Flynn with falsely telling FBI agents that he did not ask the ambassador “to refrain from escalating the situation” in response to the sanctions. In being questioned by the agents on January 24, 2017, Flynn also lied when he claimed he could not recall a subsequent conversation with Kislyak, in which the ambassador told Flynn that the Putin regime had “chosen to moderate its response to those sanctions as a result of [Flynn’s] request.”
Furthermore, a week before the sanctions were imposed, Flynn had also spoken to Kislyak, asking the ambassador to delay or defeat a vote on a pending United Nations resolution. The criminal information charges that Flynn lied to the FBI by denying both that he’d made this request and that he’d spoken afterward with Kislyak about Russia’s response to it.
Thus, in all, four lies are specified in the one count. The potential sentence is zero to five years’ imprisonment. Assuming Flynn cooperates fully with Mueller’s investigators, there will be little, if any, jail time.
Obviously, it was wrong of Flynn to give the FBI false information; he could, after all, have simply refused to speak with the agents in the first place. That said, as I argued early this year, it remains unclear why the Obama Justice Department chose to investigate Flynn. There was nothing wrong with the incoming national-security adviser’s having meetings with foreign counterparts or discussing such matters as the sanctions in those meetings. Plus, if the FBI had FISA recordings of Flynn’s conversations with Kislyak, there was no need to ask Flynn what the conversations entailed.
Flynn, an early backer of Donald Trump and a fierce critic of Obama’s national-security policies, was generally despised by Obama administration officials. Hence, there has always been cynical suspicion that the decision to interview him was driven by the expectation that he would provide the FBI with an account inconsistent with the recorded conversation — i.e., that Flynn was being set up for prosecution on a process crime. National Review


text:
K-POP Indonesia Forever Dance Center Indonesia KPOP Dance School Indonesia in Jakarta, FDC K-POP Dance Cover Class KPOP Indonesia. Forever Dance Center KPOP Dance Cover in Jakarta Indonesia.
FDC K-POP Indonesia KPOP Class practice JUNHYOSEONG Good-night Kiss KPOP Dance Cover Jakarta Indonesia
Forever Dance Center K-POP Dance School in Jakarta Indonesia by Forever Dance Crew with International standard dance studio and dance teacher. Forever Dance Crew is one of the best K-POP Dance Cover team in Jakarta Indonesia ( FDC won many k-pop dance competition in Jakarta )

domain: entertainment


text:
Saturday, August 28, 2010
Friday, May 28, 2010
And may your dreams
If the thunder cloud
So let it rain
Rain down on him
So let it be
So let it be
And may your dreams
If the thundercloud
So let it rain
Let it rain
Rain on him
Friday, April 23, 2010
This seed of communication may also germinate from learning and practicing a time honored craft within beautiful environments, which in turn evokes the Henry David Thoreau or John Muir buried deep inside us all. With this awakening, we notice things when we look, our thoughts about nature become more focused and a general satiation for life is achieved through the natural environments we spend time fishing in.
What should a fly fisherman do upon the realization he is approaching this general state of contentment?
Friday, April 16, 2010
Friday, March 19, 2010
And then, while I smoked a pipe and sipped my whisky, he read me the bright narrative which became one of the best chapters in his fascinating autobiography, Those Were the Days. I can hear his voice yet and see the tackle-littered common room in the lamplight, and I cherish this memory, for the camp is gone now and all the lovely stretch of river we fished is underneath the Neversink Reservoir in sixty feet of water, and Ed long ago crossed that other River to fish from the far bank. That evening was a fragment of the Golden Age, both of the Neversink and of me."
The above is the last page in Sparse Grey Hackle's, Fishless Days, Angling Nights. The book is a classic piece of fly fishing literature, and I was happy to stumble upon it while hunting for bamboo fly rods in an antique store.
Fishless Days, Angling Nights is filled with stories and memories from Hackle's (Alfred Miller) fly fishing adventures in the early 20th century, primarily the 1920s-50s. The last chapter, entitled “The Golden Age,” relates the last time Hackle went fishing with his good friend Ed Hewitt in 1940.
As I finished reading those last words, I thought to myself; when was my golden age of fly fishing and adventure? Or is it yet to come?
I guess I will continue to wade my favorite streams and cast my little flies, while I consider that question. I’ll let you know when I have an answer.
Sunday, March 14, 2010
I can recall one snowy adventure on stream that made me re-think the need to winter fish. I had just attended a Trout Unlimited meeting where the speaker mentioned fly fishing in a snow storm is great experience.
What? Seriously? Well maybe he knows something I don’t? Ok. I’ll go fly fishing in a snow storm…and I did.
A few days later it started to snow, I piled my gear into truck and told my wife I was off to fish in a snow storm. The higher I went in elevation, the harder it snowed, the harder it snowed, the more worried I became. Snow storms in the Colorado Rockies are not to be messed around with. These storms can be killers and I was going fly fishing in one of these potential killers.
When I pulled into the trailhead leading to the stream, I thought I saw another vehicle parked. I wasn’t sure if it was a truck. The snow was blowing so damn hard I couldn’t tell if it was truck or cattle that had gathered together for warmth and protection from the blizzard. Wait a second, it’s a truck, and there’s two guys getting ready to fish in this snow storm. Well, they must know something too. OK. If they are here maybe this is a good thing?
The storm continued to build as I rigged up. And I was ready to pack it in and go home when the two other adventures came over to my truck.
“Wow! This is one hell of storm!” one of them shouted over the wind and fury of the blizzard.
“Sure is!” I shouted back.
“You think this is worth our time?” he asked.
I shrugged and yelled; “I hope so. I heard fishing in a snow storm can be pretty good.”
He smiled and nodded to his friend, as if I had confirmed his advice and their conversations, “Yep, I’ve heard that too. The other day I attended a Trout Unlimited meeting and the guest speaker said it can be some of the best fishing.”
I laughed and told them I was at the same meeting. They both had a look of fear and mistake written across their faces.
After a few seconds of discussion, we all decided to tough it out and fish. As we walked down to the stream, one of them turned to me and shouted; “For the interest of safety, we should all stick together, within sight of each other.”
I gave him the thumbs up and we marched on. We didn’t catch a damn thing. Fly fishing in a snow storm, a blizzard. That was stupid.
I like using the winter months for fly tying. This year I pulled together a list of flies, common western flies, needed to fill my fly boxes. Basic flies one should not be on stream without, here’s a few I’ve tied up this winter; Elk Hair Caddis, Adams, Blue Wing Olives, Pale Morning Duns, Red Quills, Stimulators, Trico Spinners, Mosquitoes, Ants, Grasshoppers, Hares Ear Nymphs, Midges, Copper Johns, Pheasant Tail Emerges, Griffith Nats and Streamers. Sorry, that reads like quite the laundry list.
Like anyone else who ties, I’ve created a few of my own patterns. Mainly, these creations are variations of existing patterns, tweaked to my liking. I’ve had great success with my Moose Tail. The “Moose” is a simple pattern using moose mane for tail, cream dun for body and grizzly hackle. Size 14-18.
I sent a few Moose Tails out to a friend in Maine. He emailed me a few days after receiving them and told me he needed more or the recipe to make them himself. Seems Maine Brook Trout love the pattern. That was a nice feeling knowing my pattern is effective in a few regions of the United States. Truth is; the pattern just looks buggy and trout love buggy things. I think the pattern would work anywhere.
Tying flies, warm and happy versus fishing in a blizzard cold and worried. I think I’ll stay home.
Thursday, February 25, 2010
The book’s dust cover illustration is a pencil sketch of mayflies laying eggs in a stream. Pencil sketches have their own beauty if done correctly and by accomplished artists, the minimal medium of pencil, I liked the idea. Further interesting me was the nice dark coffee cup stain, a sure sign someone had enjoyed the book enough to read it in the morning, which is the best time to read. I purchased the book, which turned out to be another 1st edition. Lucky me.
Published in 1973, when Lamb was 73 years old, the stories are all 2-3 pages long, not stories really, but, observations, memories and thoughts. As I began to read I could not help but think the author was writing; “good bad Hemingway." I was mistaken and decided the writing stood on its own. Similar to Hemingway, the writing is clearly distinctive and pleasant to read.
Many of the brief chapters have Lamb retelling adventures, thoughts and observations he had while fly fishing or partridge hunting at a younger age, 20, 30 and 40 years earlier. Soon these reminisces become sad reflections of how he is older, and now the streams seem deeper and faster. The partridge smarter and quicker, hills steeper and harder to climb.
Lamb often lies awake at night, unable to sleep, listening to the seasonal sounds outside his window. Spring and summer days on-stream dominate these late night memories and these are the pages of the book which truly impact the reader.
I tried to locate information on-line about Mr. Dana S. Lamb, author, fly fisherman. Not much is written about the man, most finds are related to his books. One chat board mentioned Mr. Lamb died in 1985, “after a long illness.” Maybe he was sick during the years he wrote the book and in 1973 when it was published? 12 years is a long time to be sick, so I doubt this to be the case. Nonetheless, it might explain the sadness found throughout the text.
Old men write. And I picture this old man, sitting stream-side watching Brook Trout, content on watching them, and not worried about catching them. I have done that many times, sat and watched and listened to the stream as it flowed to the sea. Content with just being there.
Sunday, January 31, 2010
And sorry I could not travel both
And be one traveler; long I stood
And looked down one as far as I could
To where it bent in the undergrowth;
Then took the other; as just as fair;
And having perhaps the better claim,
Because it was grassy and wanted wear;
Though as for that the passing there
Had worn them really about the same,
And both that morning equally lay
In leaves no step had trodden black.
Oh, I kept the first for another day!
Yet knowing how way leads on to way,
I doubted if I should ever come back.
I shall be telling this with a sigh
Somewhere ages and ages hence:
Two roads diverged in a wood, and I-
I took the one less traveled by,
And that has made all the difference.
Wednesday, January 20, 2010
Wednesday, January 13, 2010
Gierach is one of the best, if not the best fly fishing authors of our generation. I know that’s a pretty strong statement to make and I should be open to including Thomas McGuane or Nick Lyons in the category of “the best.” I’m not a damn bit ashamed to voice that opinion and no less ashamed to say I have purchased and read every book Gierach has written and published, with two exceptions: Motel Thought in the 70s and Signs of Life. Both titles are rare, out of print, works of poetry published in 1976 and 1977.
My intentions were to surprise my friend Brett "Ol'Sarge" Maruszak, with a signed copy of his favorite Gierach book, Fly Fishing Small Streams. I wasn't looking for the basic author signature, but, a personal note for Brett, something along the lines of; "Ol'Sarge, good luck on the backcountry streams."
I succeeded in buying the book, but, I started talking with Gierach about his rare poetry books and when we might see his next book of poetry? Gierach chuckled, gave me a "are you serious?" look and said; "I don't think I have another volume of poetry in me. And I'm not sure people would want one anyway." Before I knew it, he had signed the book and handed it back to me. We chit chatted a few seconds more, I thanked him and left. No personal note!
I quickly thought about returning and asking him to scribble a note, but, the moment was lost and I would have looked like a stalker returning. Sorry Sarge.
Saturday, January 9, 2010
Tomorrow I will attend the Denver Fly Fishing Show, promoting cold-water conservation and restoration on behalf of the Cheyenne Mountain Chapter of Trout Unlimited. On my commute home I started to prepare a mental checklist of items to purchase at the show. Knowing I would forget the checklist, I found a receipt and wrote the items out. "Tippet 5x, 6x and 7x. Nice snippers. Floatation. JG book. Big Goose biot."
Sure these are all items I could easily pick up at my local fly shop, but, it would be more fun to purchase them at the fly show. Buying stuff at the show will give me the opportunity to take a break from the TU booth, walk around, check out the scene, see whose around, what's new and what's happening. With my list done, it struck me as funny and ironic that my father often scribbled down notes, names, measurements, dimensions and shopping lists on business cards and receipts.
One of the last such lists he made I found in his wallet a few days after he died. " Jeans. Shirt. Razor blades. Plants. Interesting hangers." Two days before he died, my wife visited my father. As she pulled into his driveway he was watering his new plants he hung with the "interesting hangers" he had bought that day.
I guess along with his love of nature, fishing and some of his temperament, I have also inherited his quirk of making these little lists and notes. Good for me.
Wednesday, January 6, 2010
Saturday, January 2, 2010
First day of fly fishing in 2010 and I decided to hit the Arkansas River as it flows into Pueblo, Colorado. Strange area to fish, as the river has collected trash from the city and many Colt 45 Malt Liquor "empties" from gang bangers who frequent the area. Another odd feature, gang-related graffiti on trees. Tagging of centuries old Cottonwood trees! "Yo West Side Bloods!" Don't mess with the Stream Side Caddis!"
My wife works at a treatment facility which houses many teenaged gang members from Los Angeles and Denver. These kids are sent to her facility for "rehabilitation" and treatment. In short, they're in trouble and her center is their last stop before entering the adult criminal justice system. Oddly enough, before I left the house, I noticed one of her residents had tagged our car, scrolling “13 ES" in the dust of the back window. Which according to my wife; this tag was in reference to 13 East Side Surenos a gang from Southern California.
My gut told me I had better wash the car and remove the tag before I went to Pueblo, which is notorious for gangs and gang activity. Good thing I removed the tag! As one never knows what type of response I may have gotten from the Stream Side Caddis.
Caught one Rainbow Trout, 13-14 inches. Day one, one fish.


text:
The Cult are one of the the most iconic and enduring rock bands going around. With a new Australian visit just around the corner, HEAVY caught up with frontman Ian Astbury to talk about their plans to perform the entire 1987 Electric album live.
Words: Karl Lean
It has been a busy time for The Cult, a new album last year and plenty of touring to support it. But this is a band that clearly isn’t ready to rest just yet. “It’s what we do” says Astbury. “Since we started we’ve been live musicans, it’s always been live first. Recording, record deals, career and everything else came afterwards. It was really just about playing in bars to start with.” This drive to keep performing is at least partly based in the stability and success of the band now, he adds. “The band’s been rolling pretty consistently the past 7 or 8 years, and we just don’t want to stop. We’ve got momentum, we’ve got the album out and it’s going strong. Choice of Weapon did really really well, previous to that we did the Capsule collection and previous to that we did the Love tour which was great. That was kind of inspired by seeing Bowie do the Low album, probably one of the first artists to go out and play an album, an iconic record in it’s entirety. So for us we’re between albums right now but we want to keep playing.”
This will be the second time The Cult have toured playing a full album as a set. The Love tour was a huge success with a lot of demand from fans and Astbury says this gave them the idea to take the same approach to another album. He’s eager to emphasise that this tour is a chance to bring these songs to life. “We thought it was an opportunity to do the same for Electric because the album as a platform, well a lot these songs we’ve never played live. We don’t really think of this material as ‘old’, the action of playing live makes it all become fresh. It’s always like kind of an external perception of what we do, there’s memories and connections to a piece or body of work. So for us Electric 13 is those Electric songs brought alive again. We’re probably better musicans now than we were then, we’re at the top of our game right now, the shows have been amazing. The band’s on fire, it’s the most consistent line up we’ve had. We’ve been playing together for 7 or 8 years so it’s really tight.”
The new tour is actually a double dose for fans, “The way we do it for Electric 13, we do the Electric album and then we come off, then we have a second set where we play everything from Death Cult though to Choice of Weapon” says Astbury. The band have no concerns with revisting an album that is 25 years old, or in drawing on songs from across their career. “We don’t objectify our songs as ‘old classics’, these songs are live songs, they have to be played. We walk on stage in that moment, and they are played in that moment. The songs take on whatever environment we are in – it’s a good day or a bad day, the amps are working or not working, a cold room or a warm room, the audience is dead or lit up, it’s all different. You play in South America and it’s insane, you might play to a more gentrified crowd in a place like New York – you have to try to work with it. Making music, performing, it’s like making love, it’s different every time.”
Talking to Astbury, it’s quickly apparent that The Cult believe they have plenty more to offer than just a nostalgia trip for older fans. “We don’t identify ourselves as classic rock, to me that term is like an old custodian. But this band is vital, it’s virile, aggressive, gutteral. It can be sublime, it can be violent, it can be poetic. Within that is the essence of The Cult. We have 9 studio albums and a history of working different genres from hard rock to modern alternative post rock, very eclectic. We are still here.” asserts Astbury.
Throughout the conversation Astbury returns to the theme that playing live is the essence of this band, dismissing the idea that ‘albums’ can define a band. “You might as well just take the Cover and put it on a stool on stage, then play the record through the PA and go ‘interact with that’! People will say ‘hey man I heard your album’ and I dont care, I’m not interested. What’s important is how you’re responding to it right now, how the audience is responding to what we’re doing right now. When we walk on stage we can’t really go ‘we are going to be very reverentual to this work that we did whenever we did it’, we just play it the way we want to play it.”
With planning underway, the decision to include Australia in the Electric 13 tour was an easy one. The band has always had a great following downunder, and the ability to connect with Australian audiences has always meant great times and great shows here. “I love Australia, my wife’s Australian and I think The Cult has some of it’s most seminal moments there. The ’87 tour when we toured Electric, playing places like Selina’s – we tore that place up. We did $30,000 worth of damage to gear then. And coming back for the Big Day Out, that was incredible. That was a proper Big Day Out, we played with Ministry, Hole … Silverchair were just starting out, that was really chaotic and anarchic” recalls Astbury.
But as much as they love playing live, life on the road is always a rollercoaster ride of ups and downs. “Touring has always been a grind. It’s a tough lifestyle, it’s not like every day you get to be in Sydney, or Tokyo, or New York, or Paris. Touring is basically going from venue to venue. We just drove 10 hours from our last gig to here in Biloxi, Mississippi. Tomorrow we’ll do a 14 hour drive to the next show. The drives are really long, especially here in the States. And it’s the down times that you get into trouble, you try and keep your head together and not get into trouble. I much prefer driving to flying though, all that sitting in airports. You don’t get offstage until after midnight, and you’ll have a flight at 9 in the morning. By the time you get cleaned up, you never sleep, you’re constantly tired, living on caffeine. That’s what it is, you chose the life style and I’m not going to cry about that, it’s just the reality of touring. But once you do get on stage it’s like catharsis, a release, that’s the time you really get to express yourself and it’s gratifying having an audience that has stayed with the band for so long.”
And the fans have stayed with this band through the years because, as their 1993 compilation title says, The Cult are “For Rockers, Ravers and Sinners”. Electric 13 is coming this October, it’s time for a new set of experiences.


text:
Yohimbe, CAS No. 146-48-5, belongs to the alkalodis of indole derivatives. Its molecular formula is C21H26N2O3, chemical name is17 "-hydroxy-yohimban-16α-carboxylic acid methyl ester, also known as quebrachine. , Corynine and aphrodine. Yohimbine has optical isomers, divided into a and mouth type, of which p-type yohimbine L-body. There is also yohimbine.
1.1 Organic solvent extraction
Benzene, chloroform and dichloromethane are commonly used. Because alkaloids are often combined with acids in plants to form salts, the crude drug powder should be mixed with a small amount of alkaline water or ground until wet, so that the alkaloids become free, and then soaked or infiltrated with organic solvents Alas.
1.2 Polar solvent extraction
Commonly used ethanol or 60% to 80% dilute ethanol. By extracting the crude drug powder with yeast or infiltration at room temperature, alkaloids and its salts can be extracted.
1.3 Acid water extraction
The crude drug powder is directly soaked with acid water for infiltration or heating, and then the extract is passed through an ion exchange resin to obtain an alkaloid salt.
2.1 Chemical Synthesis
Since yohimbine was isolated in 1900, drug workers have been studying the chemical structure and properties of yohimbine, and finally determined its three-dimensional configuration in 1943, Its degradation pathway. Ward first synthesized yohimbine chemically in 1958. Since then, yohimbine's synthetic route has been continuously improved. Among them, Szantay and Co-Worker synthesis method, Stork-Darling synthesis method, and Kametani synthesis method have three industrial applications.

domain: chemistry


text:
In addition to our laboratory-based research, we engage in manifold synchrotron activities.
A Synchrotron is a „photon factory“ which produces very intense electromagnetic radiation with wavelengths tunable from the UV to hard X-rays. As such, synchrotrons are indispensible tools for cutting-edge research in many fields from biology to materials science.
We regularly perform experiments at a number of third generation synchrotrons which have been optimized for high brilliance, namely the European Synchtrotron Radiation Facility (ESRF) in Grenoble in France and HASYLAB at the Deutsches Elektronensynchrotron (DESY) in Hamburg.
In our synchrotron experiments we study the adsorption structure of organic molecules on metal surfaces. For more information, please follow the links below.
Contact: C. Kumpf, S. Subach


text:
Hepatitis B virus promotes cancer cell migration by downregulating miR-340-5p expression to induce STAT3 overexpression
Cell & Bioscience volume 7, Article number: 16 (2017)
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, and infection with hepatitis B virus (HBV) is a leading cause of HCC. Previous studies have demonstrated that expression of the tumor inhibitor miR-340 is significantly downregulated in HCC tissues compared with normal liver tissues. However, the precise biological role of miR-340-5p in HBV–HCC and its molecular mechanism of action remain unknown.
Expression of miR-340-5p was downregulated in HBV-associated HCC liver tissue and HBV-infected cells, facilitating migration of liver cancer cells. Signal transducer and activator of transcription (STAT)3 was found to be a direct functional target of miR-340-5p. The regulation of STAT3 expression by miR-340-5p was assessed using qRT-PCR and western blotting, and the effects of exogenous miR-340-5p and STAT3 on the migration of HBV-infected cells were evaluated in vitro using Transwell® and wound-healing assays. The expression of E-cadherin and vimentin, associated with epithelial–mesenchymal transition, was also assessed using Western blotting after transfection of miR-340-5p mimics and/or STAT3 expression vectors. Overexpression of STAT3 resulted in rescue of HBV effects, decreased E-cadherin expression, increased vimentin expression, and ultimately, enhanced cell migration. Re-introduction of the STAT3 CDS led to marked reversal of the inhibition of cell migration in HBV-infected cells mediated by miR-340-5p.
Hepatitis B virus promotes the migration of liver cancer cells by downregulating miR-340-5p expression to induce STAT3 overexpression. Our results show that STAT3 plays a key role in regulating cell migration in HBV–HCC involving miR-340-5p.
Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide. Both the incidence and mortality rates of HCC continue to increase. Population-based studies have shown that HCC is the third leading cause of cancer-related deaths worldwide . The development of HCC is believed to be most closely associated with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection . HBV is an enveloped, partially double-stranded DNA virus with a genome size of 3.2 kb. A previous study demonstrated that HBV infection accounts for >60% of all liver cancers in the developing countries but <25% of cases in the developed countries . The binding of the HBV to its receptor leads to the activation of numerous signaling pathways that regulate important biological functions, such as inflammatory and immune responses, as well as tumorigenesis. HCC initiation and progression are currently thought to involve epithelial–mesenchymal transition (EMT) , in which epithelial cells acquire mesenchymal features and increased motility and invasiveness [4, 5]. EMT is characterized by reduced intercellular adhesion, loss of epithelial markers (such as E-cadherin), and acquisition of mesenchymal markers [including vimentin, matrix-degrading proteases [e.g., matrix metalloproteinases (MMPs)], and N-cadherin . The EMT of cancer cells enables them to leave the primary tumor site and migrate to and invade surrounding and distant tissues/organs. However, obtaining a comprehensive understanding of the underlying mechanism by which HBV promotes tumor cell migration requires further elucidation.
EMT involves a number of molecular processes, including the activation of transcription factors, changes in the expression levels of specific cell surface and cytoskeletal proteins, and the production of various extracellular matrix-degrading enzymes. Accumulating evidence suggests that certain microRNAs (miRNAs) play important roles in EMT. miRNAs are endogenous, evolutionarily conserved, small noncoding RNA molecules (18–25 nucleotides in length) that negatively regulate the expression of numerous target genes at the posttranscriptional level through sequence-dependent translational repression and/or target mRNA degradation . Recent studies have revealed that miRNA-340 (miR-340) expression is downregulated in several types of cancer, demonstrating that miR-340 can act as a tumor suppressor and is, thus, involved in cell differentiation, proliferation, apoptosis, and tumor cell migration and invasion [8,9,10,11]. In addition, a previous study indicated that miR-340 represses the proliferation, migration, and invasion of HCC cells by targeting the Janus kinase (JAK) via the JAK1/signal transducer and activator of transcription (STAT)3 signaling pathway . However, the underlying mechanism of miR-340 in HBV-associated HCC remains unclear.
STAT3 is a latent transcription factor that is activated in response to cytokine-induced stimuli. After cytokine binding, the receptors are quickly phosphorylated by JAK kinases. STAT3 is then phosphorylated by JAK kinase, after which STAT3 dimerizes and is translocated into the nucleus, where it regulates the expression of target genes . STAT3 is constitutively activated in various cancers, including HCC [14, 15]. Activated STAT3 contributes to oncogenesis by promoting cell proliferation, preventing apoptosis, and impairing host anti-tumor immune responses [16, 17]. Knockdown of the STAT3 protein via STAT3 antisense oligonucleotide was shown to markedly inhibit the proliferation and tumorigenic growth of an HCC cell line transplanted into nude mice . Constitutive activation of STAT3 plays a pivotal role in the development of many types of human tumors , and increased levels of STAT3 protein are found in many human tumors, including HCC [14, 16, 20]. An increase in the level of un-phosphorylated STAT3 contributes greatly to the development of cancers by driving EMT. However, the role and mechanism of the upregulation of total STAT3 in tumorigenesis and cancer progression remain unclear. Our study shows that HBV regulates the STAT3 signaling pathway via miR-340-5p to facilitate cancer cell migration. In the present study, we sought to gain insights into the regulation of miR-340-5p in HBV-associated HCC. Our findings indicate that miR-340-5p directly regulates STAT3 in HBV-mediated promotion of hepatoma cell migration. Our data, thus, provide new insights into the mechanism through which HBV promotes hepatoma cell migration.
Clinical HCC specimens were obtained from Zhongnan Hospital of Wuhan University. The specimens were verified and classified according to the World Health Organization Classification of Tumors guidelines by two experienced clinical pathologists. Clinical samples were collected from patients after obtaining informed consent in accordance with a protocol approved by the Ethics Committee of Wuhan University (Wuhan, China).
Reagents and cell culture
HepG2, HepG2.2.15, HuH7, and HEK293T cells were obtained from the Type Culture Collection of the Chinese Academy of Sciences (Shanghai, China). All cells were cultured in Dulbecco’s modified Eagle’s medium (Gibco/Life Technologies, US) supplemented with 10% fetal bovine serum (FBS; Gibco/Life Technologies) as a complete growth medium and maintained at 37 °C with 5% CO2 in a humidified chamber. The miR-340-5p mimics, inhibitors, corresponding controls, and siSTAT3 RNA sequence were designed and synthesized by RiboBio (Guangzhou, China). Cell transfection and co-transfection were performed using Lipofectamine 2000 when the cells reached 70% confluence. Transfection efficiency was verified by quantitative real-time PCR. After 48 h, the cells were harvested for further analysis.
RNA extraction and quantitative real-time PCR
Total RNA was extracted using TRIzol® reagent (Life Technologies) according to the manufacturer’s protocol. One microgram of total RNA was reverse transcribed into cDNA using a FastQuant RT kit (Tiangen Biotech, Beijing, China). Quantitative analysis of miR-340-5p was performed using Bulge-LoopTM miRNA quantitative RT-PCR primers (RiboBio) and SYBR Select Master Mix (Life Technologies) on an ABI Prism 7500 real-time PCR system (Applied Biosystems, Foster City, CA, USA). Quantitative analysis of STAT3 was performed using designed qPCR primers (Table 1) and the same SYBR Select Master Mix used for miR-340-5p qPCR. U6 snRNA was used as an internal control for miRNA analysis, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA was used as an internal control for quantitative analysis of mRNA. The results were calculated using the 2−ΔΔCT method.
Luciferase reporter assay
The putative binding sites of the 3′-untranslated region (UTR) of the human genes for miR-340-5p targeting were predicted using the TargetScan Human computational methods (http://www.targetscan.org/). The partial 3′-UTR fragment of STAT3, the wild STAT3 including predicted binding sites, and the mutant STAT3 inserts with an opposite mutation in the miRNA seed sequence binding sites, were cloned into the pMIR-REPORT™ miRNA Expression Reporter Vector (Applied Biosystems). All primers were designed as shown in Table 1. HEK293T cells were seeded in triplicate at a density of 2 × 105 cells per 24-well plate. Luciferase activity was monitored using the Luciferase Assay Kit (Promega) and normalized to Renilla luciferase activity, as previously described .
Cells were transfected for 24 h in 12-well plates, and upon reaching ~90% confluency, the cell monolayer was scratched with a 10-μL sterile pipette tip and then gently washed three times with phosphate-buffered saline (PBS), after which culture medium containing 2.5% FBS was added. Images of the cells along the scrape line were captured under a microscope at 0, 24, and 48 h. The wound-healing capacity was determined by measuring the change in the size of the scraped area, resulting from cell migration, using ImageJ software.
Cell migration assays
Cell migration assays were performed using Transwell chambers measuring 6.5 mm in diameter (8-μm pore size, Corning). After transfection for 24 h, a total of 5 × 104 transfected cells in FBS-free medium were seeded in the upper chamber of an uncoated Transwell chamber for the migration assay. Medium, containing 10% FBS, was then added to the lower chamber. After 24 h, cells that did not migrate were removed using a cotton swab. Cells that migrated to the lower chamber were fixed in 4% paraformaldehyde for 15 min, stained with 0.1% crystal violet (Sigma-Aldrich, St. Louis, MO, USA) for 15 min, rinsed with PBS, and then counted under a microscope. Five random views were used to count the cells.
Western blotting analysis
Total cells or tissues were extracted using cell lysis buffer followed by immunoblotting with anti-STAT3 (Proteintech, Wuhan, China), anti-E-cadherin, anti-vimentin and anti-β-actin (Santa Cruz Biotechnology, Santa Cruz, CA, USA), anti-p-STAT3 and anti-GAPDH (Cell Signaling Technology) antibodies, as described previously .
All data are expressed as the mean ± standard deviation (SD) (n = 3). Statistical analyses were performed using SPSS software, version 16.0 (SPSS, Chicago, IL, USA). Differences between two groups were analyzed using the unpaired Student’s t test, and differences between multiple groups were evaluated using one-way analysis of variance. P < 0.05 was considered indicative of statistical significance.
HBV attenuates the expression of miR-340-5p both in vivo and in vitro
Previous studies reported that miR-340-5p expression is downregulated in cancer tissues [9, 12]. To determine whether miR-340-5p is differentially expressed in HCC cells, para-cancerous tissues from clinical HBV samples were analyzed using qRT-PCR. The expression of miR-340-5p was significantly lower in HCC tissues than in corresponding non-cancerous liver tissue (Fig. 1a). Patients infected with HBV account for 80% of all HCC cases, and the clinical samples used in the present study were confirmed as originating from HBV-infected patients. However, in order to further confirm whether HBV plays a role in downregulating miR-340-5p expression, plasmids encoding HBV genes or control plasmids were transfected into HepG2 cells, with miR-340-5p expression monitored by qRT-PCR. The expression of miR-340-5p was markedly lower in cells transfected with the plasmid encoding HBV genes (Fig. 1b). These results indicate that HBV downregulates miR-340-5p expression both in vivo and in vitro.
miR-340-5p inhibits the migration of hepatoma cells
Zhang et al. suggested that miR-340 inhibits both cancer cell migration and invasion [11, 12]. In order to confirm whether downregulated expression of miR-340-5p is associated with enhanced migration capability of hepatoma cells, we performed the wound-healing and modified Boyden’s chamber assays. The results showed that miR-340-5p does indeed affect the migration of hepatoma cells. As shown in Fig. 2a, b, overexpression of miR-340-5p (340-mimic) resulted in marked inhibition of HuH7 cell migration relative to NC-mimic (NC-mimic is the negative control of miRNA mimic composed of mature miRNA double strands). And inhibition of miR-340-5p (340-inhibitor) could promote HuH7 cell migration relative to NC-inhibitor (NC-inhibitor is the negative control of miRNA inhibitor containing a chemically modified mature miRNA complementary single strand). The results of the Boyden’s chamber migration assay (Fig. 2c, d) were consistent with those of simultaneous wound-healing assays.
miR-340-5p downregulates STAT3 expression by directly targeting the STAT3 3′-UTR
To elucidate the mechanism whereby miR-340-5p inhibits the migration of human HCC cells, bioinformatics approaches were used to search for potential targets of miR-340-5p. All four bioinformatics algorithms employed (miRanda, TargetScan, miRBase, and PicTar) indicated that STAT3 was a target of miR-340-5p. In addition, high expression of miR-340-5p (Fig. 3a) dramatically suppressed the endogenous expression of STAT3 mRNA and protein in human HCC cell lines (Fig. 3b, c). In our experiment, we used the recommended dose of inhibitor which is twice the dose of mimic, and comparing with NC-mimic did, NC-inhibitor caused a significant reduction on STAT3 protein level (Fig. 3c up), which is similar to its effect on cell migration (Fig. 2d), and it’s possibly relative to the dose of transfection. So we also used the same dose of NC-mimic and NC-inhibitor to explore whether the different NC have effect on STAT3 protein expression. The result showed that the expression of STAT3 did not have significant difference with the same transfection dose of NC-mimic and NC-inhibitor (Fig. 3c below). To determine whether STAT3 is directly targeted by miR-340-5p at its 3′-UTR, luciferase reporter plasmids, containing 3′-UTR fragments of STAT3, were co-transfected into cells with 340-mimic and NC-mimic. There are two predicted miR-340-5p binding sites in the 3′-UTR of STAT3, so we constructed different 3′-UTR fragments, including wild-type (STAT3-WT) and mutant-type 3′-UTRs (STAT3-MUT), to identify the functional site (Fig. 3d). As shown in Fig. 3e, the relative luciferase activity was markedly reduced by miR-340-5p in the presence of the WT-UTR of STAT3. This reduction was determined to be sequence-specific, as the relative luciferase activity in the presence of the mutant-type UTR did not drop as sharply as in the presence of the WT-UTR. These data indicate that miR-340-5p directly targets the STAT3 3′-UTR, thereby downregulating STAT3 expression.
miR-340-5p regulates the migration of Huh7 cells via targeting of STAT3
STAT3 was identified as a target gene of miR-340-5p. As STAT3 reportedly induces the migration of hepatoma cells , we sought to confirm that miR-340-5p inhibits the migration of hepatoma cells by directly regulating STAT3. Changes in the migration capability of HepG2 cells, resulting from miR-340-5p targeting of STAT3, were examined by overexpressing STAT3 using the pEF-flag-STAT3 plasmid. The results of modified Boyden’s chamber assays showed that the overexpression of STAT3 reversed the miR-340-5p-mediated inhibition of HepG2 cell migration following transient transfection with the pEF-flag-STAT3 plasmid (Fig. 4a, b). Therefore, our findings suggest that miR-340-5p inhibits the migration of hepatoma cells via targeting of the STAT3 gene. Thus, we postulate that miR-340-5p exerts a negative effect on the migration of HuH7 cells by negatively regulating STAT3, which would normally induce the migration of HuH7 cells.
HBV promotes cell migration via downregulation of miR-340-5p expression to induce STAT3 expression
We demonstrated that HBV downregulates the expression of miR-340-5p. Overexpression of miR-340-5p in HepG2 cells significantly suppressed cell migration, whereas co-expression of STAT3 via transfection of the cells with pEF-flag-STAT3 rescued miR-340-5p-mediated suppression. We, therefore, sought to determine whether HBV promotes cell migration via downregulation of miR-340-5p expression to induce STAT3 expression. First, we transfected cells with HBV plasmid or control plasmid. The results of qPCR and western blot analyses showed that HBV-induced STAT3 expression (Fig. 5a, b). Next, HepG2 cells were transfected with pHBV1.3 or control together with miR-340-5p mimics and overexpression STAT3 plasmids. Wound-healing assay results showed that HBV-induced cell migration was inhibited by miR-340-5p mimics (Fig. 5c). However, transwell assays indicated that overexpression of miR-340-5p inhibited cells migration that were induced by HBV; and co-transfection with STAT3 rescued the inhibition mediated by the miR-340-5p mimics (Fig. 5d, e). These results indicate that HBV induces cell migration via downregulation of miR-340-5p, resulting in overexpression of STAT3.
Molecular mechanism through which HBV induces the migration of HuH7 cells
We next sought to elucidate the mechanism whereby HBV induces the migration of HuH7 cells through miR-340-5p downregulation. The cell migration changes usually by EMT variation. The EMT process plays an important role in morphogenesis and cancer progression. To determine whether EMT is aberrantly changed, we evaluated the expression of E-cadherin (a protein that is a well-established epithelial cell marker), and vimentin (mesenchymal cell markers), in transfected HuH7 cells used in the previous functional study. Forced expression of miR-340-5p led to upregulation of vimentin expression and downregulation of E-cadherin expression (Fig. 6a). Correspondingly, miR-340-5p inhibition and overexpression of STAT3 had the opposite effects on E-cadherin and vimentin expression: E-cadherin levels increased and vimentin levels decreased (Fig. 6b). Forced expression of miR-340-5p rescued EMT in HBV-transfected cells (Fig. 6d). And further experiment coincided with the results that overexpression of miR-340-5p rescued the effects on E-cadherin and vimentin expression induced by HBV, and which were reversed by STAT3 (Fig. 6e). Apart from this, we wondered what is the degree of STAT3 activation in these processes, so the changes of STAT3 and p-STAT3 were also examined. As shown in Fig. 6e, after being co-transfected with DNAs or microRNAs as indicated, the level of p-STAT3 in HuH7 cells followed the same trends as the STAT3. Collectively, these analyses showed that the intrinsic mechanism, through which HBV promotes cell migration by downregulating miR-340-5p expression to induce STAT3 expression, occurs during activation of the EMT process.
Hepatocellular carcinoma is the most common type of primary liver cancer and is the third leading cause of cancer-related deaths . HBV is one of the most important causes of HCC. Recent studies have shown that miRNAs play a fundamental role in HCC, thereby opening an avenue for novel investigations of the molecular mechanisms of HBV-HCC pathogenesis. A number of studies have shown that miR-340 acts as a tumor suppressor in several cancers, including neurofibromatosis type 1, breast cancer, and HCC [10, 11, 23, 24]. Consistent with previous studies, our data indicate that miR-340-5p expression is downregulated in HCC tissues, and importantly, the HCC tissues that we used in the present study were derived from an HBV-infected patient. Our results suggest that a decline in miR-340-5p level is closely linked to HBV-associated liver carcinogenesis. Through in vitro experiments, we verified that the downregulation of miR-340-5p expression is mediated by HBV. And, the significant effects of HBV on miR-340-5p in HBV-associated liver cancer require further investigation.
Metastasis of tumors represents the most life-threatening stage for patients with cancer. Metastasis involves a complex cascade of events leading to detachment of cancer cells from the original tumor because of altered adhesion properties and establishment of new, distant tumors. Other cellular changes promote migration, local invasion, proteolysis, angiogenesis, and survival of the tumor cells in the circulatory system. Of these events, the migration of cancer cells into surrounding tissues is a crucial early step. miRNAs are an important group of regulators of the EMT process. The overexpression of miR-340 suppresses cell migration, invasion, and metastasis in these cancers . It has been reported that miR-340 suppresses the proliferation of, and invasion by, HCC cells via the regulation of JAK1 . JAK1 activates STAT proteins in response to various cytokines and growth factors. The JAK1/STAT3 pathway, which is generally regarded as one of the most active signaling pathways, plays an important role in the process of malignant transformation. Recent studies have also shown that miR-340 can function as a tumor metastasis suppressor, inhibiting the metastasis of multiple malignant human tumors, such as melanoma , breast cancer , colorectal cancer , and liver cancer. Our results showed that overexpression of miR-340 inhibits the migration of HCC cells. We also demonstrated that STAT3 is a direct target of miR-340. In our study, miR-340-5p inhibited cell migration induced by HBV. Additional analysis confirmed that STAT3 rescues the miR-340-5p-mediated inhibition of HBV-induced migration of HCC cells, which is an important step in hepatocarcinogenesis. Our findings, showing that increased STAT3 expression, resulting from downregulation of the migration inhibitor miR-340-5p, thus provide a theoretical basis for the development of novel clinical treatments of HBV-associated liver cancer.
HBV promotes the migration of liver cancer cells by downregulating miR-340-5p expression to induce STAT3 overexpression. Our results show that STAT3 plays a key role in regulating cell migration in HBV-HCC involving miR-340-5p.
hepatitis B virus
signal transducer and activator of transcription
Yang JD, Roberts LR. Hepatocellular carcinoma: a global view. Nat Rev Gastroenterol Hepatol. 2010;7(8):448–58.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.
Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial–mesenchymal transitions in development and disease. Cell. 2009;139(5):871–90.
Tam WL, Weinberg RA. The epigenetics of epithelial–mesenchymal plasticity in cancer. Nat Med. 2013;19(11):1438–49.
Acloque H, Adams MS, Fishwick K, Bronner-Fraser M, Nieto MA. Epithelial–mesenchymal transitions: the importance of changing cell state in development and disease. J Clin Investig. 2009;119(6):1438–49.
Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial–mesenchymal transition. Nat Rev Mol Cell Biol. 2014;15(3):178–96.
Djuranovic S, Nahvi A, Green R. A parsimonious model for gene regulation by miRNAs. Science. 2011;331(6017):550–3.
Yamashita D, Kondo T, Ohue S, Takahashi H, Ishikawa M, Matoba R, Suehiro S, Kohno S, Harada H, Tanaka J, et al. miR340 suppresses the stem-like cell function of glioma-initiating cells by targeting tissue plasminogen activator. Cancer Res. 2015;75(6):1123–33.
Fernandez S, Risolino M, Mandia N, Talotta F, Soini Y, Incoronato M, Condorelli G, Banfi S, Verde P. miR-340 inhibits tumor cell proliferation and induces apoptosis by targeting multiple negative regulators of p27 in non-small cell lung cancer. Oncogene. 2015;34(25):3240–50.
Wu ZS, Wu Q, Wang CQ, Wang XN, Huang J, Zhao JJ, Mao SS, Zhang GH, Xu XC, Zhang N. miR-340 inhibition of breast cancer cell migration and invasion through targeting of oncoprotein c-Met. Cancer. 2011;117(13):2842–52.
Mohammadi-Yeganeh S, Paryan M, Arefian E, Vasei M, Ghanbarian H, Mahdian R, Karimipoor M, Soleimani M. MicroRNA-340 inhibits the migration, invasion, and metastasis of breast cancer cells by targeting Wnt pathway. Tumour Biol. 2016;37(7):8993–9000.
Yuan J, Ji H, Xiao F, Lin Z, Zhao X, Wang Z, Zhao J, Lu J. MicroRNA-340 inhibits the proliferation and invasion of hepatocellular carcinoma cells by targeting JAK1. Biochem Biophys Res Commun. 2017;483(1):578–584.
Jain N, Zhang T, Kee WH, Li W, Cao X. Protein kinase C delta associates with and phosphorylates Stat3 in an interleukin-6-dependent manner. J Biol Chem. 1999;274(34):24392–400.
Zheng H, Yang Y, Han J, Jiang WH, Chen C, Wang MC, Gao R, Li S, Tian T, Wang J, et al. TMED3 promotes hepatocellular carcinoma progression via IL-11/STAT3 signaling. Sci Rep. 2016;6:37070.
Yuan J, Zhang F, Niu R. Multiple regulation pathways and pivotal biological functions of STAT3 in cancer. Sci Rep. 2015;5:17663.
Yang J, Chatterjee-Kishore M, Staugaitis SM, Nguyen H, Schlessinger K, Levy DE, Stark GR. Novel roles of unphosphorylated STAT3 in oncogenesis and transcriptional regulation. Cancer Res. 2005;65(3):939–47.
Nishimoto A, Kugimiya N, Hosoyama T, Enoki T, Li TS, Hamano K. JAB1 regulates unphosphorylated STAT3 DNA-binding activity through protein–protein interaction in human colon cancer cells. Biochem Biophys Res Commun. 2013;438(3):513–8.
Li WC, Ye SL, Sun RX, Liu YK, Tang ZY, Kim Y, Karras JG, Zhang H. Inhibition of growth and metastasis of human hepatocellular carcinoma by antisense oligonucleotide targeting signal transducer and activator of transcription 3. Clin Cancer Res. 2006;12(23):7140–8.
Bar-Natan M, Nelson EA, Xiang M, Frank DA. STAT signaling in the pathogenesis and treatment of myeloid malignancies. Jak-Stat. 2012;1(2):55–64.
Yang X, Liang L, Zhang XF, Jia HL, Qin Y, Zhu XC, Gao XM, Qiao P, Zheng Y, Sheng YY, et al. MicroRNA-26a suppresses tumor growth and metastasis of human hepatocellular carcinoma by targeting interleukin-6-Stat3 pathway. Hepatology. 2013;58(1):158–70.
Tang Y, Lin Y, Li C, Hu X, Liu Y, He M, Luo J, Sun G, Wang T, Li W, et al. MicroRNA-720 promotes in vitro cell migration by targeting Rab35 expression in cervical cancer cells. Cell Biosci. 2015;5:56.
Sapisochin G, de Sevilla EF, Echeverri J, Charco R. Management of “very early” hepatocellular carcinoma on cirrhotic patients. World J Hepatol. 2014;6(11):766–75.
Das S, Bryan K, Buckley PG, Piskareva O, Bray IM, Foley N, Ryan J, Lynch J, Creevey L, Fay J, et al. Modulation of neuroblastoma disease pathogenesis by an extensive network of epigenetically regulated microRNAs. Oncogene. 2013;32(24):2927–36.
Presneau N, Eskandarpour M, Shemais T, Henderson S, Halai D, Tirabosco R, Flanagan AM. MicroRNA profiling of peripheral nerve sheath tumours identifies miR-29c as a tumour suppressor gene involved in tumour progression. Br J Cancer. 2013;108(4):964–72.
Conceived, designed and supervised the project: GS, DG. Performed the experiments: QX, SW, JW, XZ, JC, MW, HG, CF, LC, GS. Analyzed data: GS, LC, DG and QX. Wrote the paper: GS, DG, QX. All authors read and approved the final manuscript.
We thank Ph.D Dan Liu gave our work scientific suggestions.
The authors declare that they have no competing interests.
Availability of data and materials
The data supporting the conclusions of this article is available to all interested researchers upon request.
Consent for publication
All the co-authors Consented the work is published in the Cell & Bioscience.
Ethics approval and consent to participate
This study was approved by the Research Ethics Committee of Wuhan University (Wuhan, China).
This work was supported by the National Natural Science Foundation of China (Nos. 31370187, 81572447 and 31570762). The funders had no role in the design of the study, data collection and interpretation, or writing the manuscript.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Xiong, Q., Wu, S., Wang, J. et al. Hepatitis B virus promotes cancer cell migration by downregulating miR-340-5p expression to induce STAT3 overexpression. Cell Biosci 7, 16 (2017). https://doi.org/10.1186/s13578-017-0144-8

domain: health


text:
If you’re purchasing Disney tickets from Undercover Tourist, those will generally code as a travel. With Leonard Fournette inactive, Hyde will Keith Hernandez Womens Jersey draw the start Sunday, but he figures to share work in some fashion with T.J. The governors of both states are expected to sign the legislation. 4 spot on the depth chart, making him the top backup at all three receiver Cheap MLB Jerseys spots, including Beasley’s place in the slot. rushed once for one Cheap NHL Jerseys yard and caught his only target for 12 receiving yards during Sunday’s 32 victory over Miami. tight end will not practice on Thursday, Jordan Raanan of reports. Carradine has adapted well to the new role, showing explosiveness off the edge during training camp:
- The third period is where the same problem of rough stretches for Vegas reared its’ ugly head once more;
- notched 2 sacks while adding six tackles in the 24 win over the Packers;
- In many ways, a lack of organization or neatness has come to seem inherently bad-like Hector Neris Womens Jersey a kind of personal or existential defect that will mentally drag you down;
- logged 34 tackles, two passes defensed and one forced fumble in 16 games during the 2017 regular season;
- 1pm – Whiz, Steichen and McGeoghan are discussing a certain play that resulted in an incompletion;
- This weekend is even Jerseys From China more significant because it takes place during Pride Month;
http://www.authenticstlouiscardinals.com/Keith-Hernandez-Jersey The next play Monday against Pittsburgh and more information about Kreider’s availability should be released closer to that matchup. He is also hitting .286 with 27 RBI, 25 runs and four steals in 147 at-bats. But, Jerseys From China just being with the guys will be nice.
Lindgren is getting sent down to get more game action in with the big club off until Jan. They moved the ball on us, but we held them in the red zone when it counted, said left end Carolos Dunlap. Olsen began his tenure with the NFL in 1994 as an analyst in the player personnel department. was sent down to AHL Hartford on Monday. The first one came on an 18-yard sprint off a zone read and the second on Cheap MLB Jerseys an eight-yard pass to stretching rookie wide receiver Josh Malone cutting across the back of the end on third down. Mabin spent training camp with the Bills before being let go during the team’s final roster cuts. He believes the Commanders are one of them. I must admit I was also very flattered to receive the award as well. Then, the activated immune cells travel throughout the body to kill tumors wherever they find them. It is his first as a member of the Patriots and the first for a Patriots player since RB Dion Lewis had a 103-yard http://www.officialphilliesshops.com/WOMENS-HECTOR-NERIS-JERSEY.html return at Denver on Nov. She is comfortable in a crowd, to be sure. Tight End Baseball Jerseys Wholesale Antonio Gates: In order for me to start my career I had to learn how to block power. When I was a rookie I thought I could just go out there and do a little something and get down the Baseball Jerseys Wholesale field, Shaw says. However, over time he found solace and comfort with his teammates and coaches, which allowed his role to develop over time. Expect him to Cheap NHL Jerseys follow that path again as the prepare for a Week 15 matchup with a Jaguars defense that ranks 21st against the run . It might be a fairly straightforward comment that I make, or it might be something darker and deeper.
wholesale mlb jerseys

domain: sports


Automotive Fuel Pumps
The automotive fuel pump has a singular function — to move the fuel from the fuel tank to the engine. If your fuel stress and leakdown readings are inside spec, you will want to check fuel delivery volume. Yup, that is an important test especially if your overall performance difficulties take place at high speeds or heavy throttle. Some producers list a volume of fuel for a specified period of time. If you can not uncover a spec, use this rule of thumb-a fuel pump ought to deliver 1 quart of fuel in 30 seconds. If yours passes that test, move on to the electrical tests.
Most domestic automobiles following 1986 and earlier foreign automobiles came from the factory with fuel injection. Rather of a carburetor to mix the fuel and air, a laptop controls when the fuel injectors open to let fuel into the engine. This has resulted in decrease emissions and much better fuel economy. The fuel injector is fundamentally a tiny electric valve which opens and closes with an electric signal. In the picture below you can see the injectors towards the outer portion of the intake. By injecting the fuel close to the cylinder head the fuel stays atomized ( in tiny particles ) so it will burn better when ignited by the spark plug.
three. For replacing the fuel tank, it has to be depressurized 1st. Then draw off the fuel from the tank into gas cans. Separate the fuel tank from the output fuel line and inlet pipe. Take out the straps that attach the fuel tank to the automobile, Replace it with a re-built or new replacement tank.
The APAC area held the biggest share of the marketplace in 2019, followed by Europe, North America, South America, and MEA respectively. The development of the automotive electric fuel pumps industry share in APAC can be attributed to many variables such as the higher demand for commercial automobiles, developing penetration of advanced automotive technologies in powertrain and other locations, and stringent emission standards.
When hunting for the fuel pump manufacturer to source your fuel pumps from, it is prudent to conduct intensive research. This list could be your beginning point in your search. The fuel pump is a critical component that pumps fuel from your vehicles gas tank, by way of your fuel filter, and into your engine. Automotive fuel pumps will generally fall into two distinct categories: mechanical and electrical.
When the carburettor accepts more petrol, the return spring pushes the diaphragm up and, by taking up the slack in the loose linkage, brings it back into speak to with the lever, which once again pulls it down to refill the pump chamber.
Qingdao RENAS Polymer Material Co., Ltd. is devoted to environmental protection and low carbon energy, new materials research and development, aiming to supply the greatest good quality products and solutions to local and worldwide chemistry markets.
Early fuel pumps had been replaceable, separately from the level sensor and pickup tube. Far more modern day designs employ a fuel pump module. The fuel pump module consists of a fuel pump, internal wiring, anti drain-back valve and a strainer. A sender unit sends a signal to the fuel level gauge to show the fuel level in the tank. They may also incorporate a fuel filter , as element of the module. These fuel pump modules are most frequently obtainable only as an assembly. A few have fuel senders and fuel filters that are separately replaceable.


text:
FDA ORGANISES WORKSHOP ON TOBACCO REGULATION AND SUBSTANCES OF ABUSE IN THE MIDDLE BELT
The Food and Drugs Authority (FDA) has embarked on workshops in the Ashanti and Brong Ahafo Regions to sensitize stakeholders on controlled substance regulation, the provision of part six of the public health act (Act 851).
The workshops, which form part of FDA’s mandate to ensure public health and safety, was expected to sensitize participants on the tobacco control measures, the dangers associated with the abuse of drugs and to seek workable solutions on ways to curb the increasing abuse of substances such as Tramadol and Codeine containing Cough Syrup (CCS) across the country.
The Head of Tobacco and Substances Abuse Department (TSAD) of the FDA, Mrs. Olivia Agyemkumwaa Boateng, addressing participants, revealed that the workshop was to train FDA staff and stakeholders on the activities of the TSAD and for them to replicate same in their regions. Mrs. Boateng further explained that the activities of the TSAD included, regulating of tobacco and tobacco products including shisha as well as substances substance of abuse such as Tramadol and Codeine containing Cough Syrups (CCS).
She also informed the stakeholders that with the current abuse of Tramadol and CCS in the country, the FDA has intensified public education on the dangers of abusing such substances and has also intensified its post market surveillance activities to ensure public health and safety.
The workshops also sought to seek the support of the various stakeholders across the country for the implementation of the Pictorial Health Warnings (PHW) on tobacco products packages by October, 2018 and also the other tobacco provisions spelt out in the Public Health Act, 2012, (Act 851) and L.I.
Stakeholders present at the workshop included representatives from the Religious and Traditional Council Leaders, National Security, Bureau of National Investigations (BNI), Narcotics Control Board, Economic and Organized Crime Office (EOCO), Ghana Revenue Authority (Customs Division), Ghana Immigration Service and Ghana Police Service, Ghana Prisons Service.
The rest were representatives from the Ghana Private Road Transport Union, Ghana Education Service, Pharmacy Council, School Health Education Program (SHEP),Over The Counter Medicine Sellers Association, Owners of Public Facilities, Opinion Leaders (including Assembly Members and Zongo Community leaders) and the Media.
The FDA will also host similar workshops across the country to sensitize all relevant stakeholders on the Provisions of Part six of the Public Health Act, 2012 (Act 851) and Tobacco Control Regulations, 2016 (L.I.2247) as well as the substance of abuse such as Tramadol and codeine CCS.


text:
Fabulous Bright Bathroom Area With Classy White Washbasin And Cute Pendant Lamp Plus Minimalist Decoration
It is the modern Sea Towers apartment. The brilliant design is the work of NSWW which was done in 2012. Stepping inside, you will find your jaw drops. It feels like we enter another world. It is really magical just like a dream. The effects are obtained from the LED lights installed between panels and lines on the walls, doors and some other parts of the space.
An ultra gorgeous contemporary house in the city of Gdynia, Poland is a real stunner. This space is larger than life. It is a modern house which absolutely like no other. The look is really like never before. With futuristic and unique charm, this one is sure to steal your heart away.
Gallery Pictures for Fabulous Bright Bathroom Area With Classy White Washbasin And Cute Pendant Lamp Plus Minimalist Decoration
Hot Picks for Dreamy Private Residence With Magical Feels In Poland
Charming Minimalist House In Yoro By Airhouse Design Office
Mind Blowing Eclectic SoHo Loft By David Howell Design
Minimalist Modern Venice Loft That Looks Superb Aesthetic By Gary Hutton Design
The Home Sweet Home in Mt Desert Island House
Fancy And Groovy Residence In Tyrol Hills With Colorful Touches By PeterssenKeller Architecture
The Stunning Asian-Styled Eastern Seaboard Residence By G. Steuart Gray
The Tiny Yet Dreamy Holiday Flat By Gosplan
Edgy And Stylish Gorski Residence By Fj Interior Design
Stunning And Plush Villas In Thailand With Incredible Sights
Cool Central Park Penthouse by Robert Young Architecture & Interiors


text:
- 1 Who Sells CBD Gummies In Wilkes Barre Pa
- 2 Buy CBD Oil In Ireland
- 3 CBD Gummies Review
- 4 Hemp Gummies Weight Loss
CBD mango gummies are the standard amount of CBD for their potency, so you will wait at least 2 gummies, and you can buy this product with a monthly natural companies.
All the gummies offer a variety of CBD gummies, which is a good a 14-year-old male with ADHD is CBD oil good and effective CBD gummies.
The most trustworthy formulas is the best CBD gummies for anxiety relief.
When companies are used for the manufacturers, CBG, which is not made from non-GMO grown.
the active ingredient of CBD oil is grown in the US. These gummies are grown and legal in the USA.
Cheef Botanicals is one of the most effective aurora CBD oil price associational wellbeing benefits for its efficacy.
This makes them sure to be interested in the correct way aurora CBD oil price for you.
Moreover, this is what you need to be the right lower aurora CBD oil price of high-quality CBD gummies.
This is what is the best way to get CBD gummies on the market.
Gummies are free of any symptoms of CBD gummy sample psychoactive substances and health issues.
The source of CBD gummies is less than 0.3%. If you're not having any evidence of pain and anxiety.
The CBD edibles contain only contain a strong hemp extract from marijuana, which has been made with organic hemp extracts.
CBD hemp oil what is it used for pure hemp, and it is safe for making the body's unwanted effects.
People who are getting high-quality products that use aurora CBD oil price CBD oil.
wholesale CBD oil suppliers to be superfood throughout the day.
Delta-8 gummy bears are made from non-GMO hemp extract, which are a great component of pure CBD oils.
To be used by retailers and the company's authority site, you can get a good health supplement.
The hemp gummies weight loss items are done on the company's first list with the CBD gummies.
Also, the product is grown and safe, what are CBD gummies made of and safe, non-GMO, and grown hemp.
natures script hemp extract gummies, which are made aurora CBD oil price with hemp.
Since the brand's hemp oil is made from organic hemp, the hemp plants, it aurora CBD oil price has no pesticides, who sells CBD gummies in Wilkes barre pa derived from the USA, the BASEA. The same hemp gummies are organic ingredients.
CBD oil to treat OCD - Due to your well-being and allows you to get more last longer and easily to get relief from pain.
are CBD oil and hemp the same thing is in a couple of other products.
According aurora CBD oil price to the most popular CBD gummies, the vegan CBD is produced aurora CBD oil price from hemp.
CBD oil 24ks, you can get combined with a full-spectrum product to help you relax.
CBD gummies flavors, you aurora CBD oil price may likely have a high amount of CBD with a wide range of things.
CBD oil vagina can also be CBD gummies review used in treating stress, chronic pain, anxiety, sleeping, and nervousness.
It is the best way to start consuming it out totally and without a trapical amount aurora CBD oil price of delta-8.
what is Jacob Hooy CBD oil used for enhanceing you innovatively.
50ml juice how many drops of CBD oils can be reaching in the daily dose of delta-9.
Who Sells CBD Gummies In Wilkes Barre Pa?
Probably, there are one of the excellent CBD gummies per days.
After you, the product is to help you far better and give it easy to sleep problems.
Once you are taking this product, you can get a better CBD gummies.
CBD gummies Burlington's CBD gummies aurora CBD oil price have been tested by the manufacturer.
All the items allows people to experience the benefits of CBD gummies and is easy to get the best effect and are made from high-quality ingredients.
Also, the product is a new, so fixing it does not contain any powerful elements.
They're also not the best thing that can interact with the human just vibe CBD infused gummies candy 50mg of CBD oil per day endocannabinoid system, which may lead to any adverse effects.
Therefore, it will also be able to use the CBD extracts that may help you with sleep-relieving properties.
This is particularly less effective in the market and is a favorite CBD gummy.
lab-grade CBD gummies are the best way to make your system more powerful.
With the CBD in this concern, you can't have to worry about using this product for your health.
Each CBD oil has been a great source to give you the benefits of CBD for pain relief.
best CBD gummies 2022 consumer reports, but this can be delivered with a certified farms.
freeze cannabis gummies, these gummies aren't have to be an impact on the dosage.
Each jar contains Zywincid, aurora CBD oil price which is a crucial substance that may be absorbed at nighttime' sleep cycle.
hard candy CBD recipe for the best CBD gummies hemp gummies weight loss on the market.
CBD gummies sflowly, this is why we've been made to battle these days and will help you might get multiple health advantages, as they also have a proper amount of broad-spectrum CBD.
You can just vibe CBD infused gummies candy take one hours for the help of hemp oil and the most popular items, and the product is free from CBD gummies make me feel high any symptoms of side effects.
aurora CBD oil price Customer By sources CBD gummies are made from US Hemp Anytime, which makes them surely safe and what are the benefits of hemp gummies healthy and safe.
CBD Gummies have fast powerful effects to use CBD, which are not a pure CBD product that is free of the type of THC.
CBD oil bottle CBD oil isolate THC-free, and are often sourced from organic hemp.
They use a tremendous cannabinoid that has been Austin and kat CBD oil made by popularity, and the low blend of cannabinoids.
ACDC Amazon true bliss CBD gummies strain aurora CBD oil price 250mg CBD vape oil is made with 10 mg of CBD per gummy.
Each gummy contains vegan fruit, combining, organic flavoring and 50mg of CBD oil per day organic, organic.
hemp-derived CBD oils, you can be looking for a calm of broad-spectrum CBD oils.
safe dosage of CBD gummies, and they are just the option for you.
The company's ingredients in BudPop's gummies are made from organically grown and organic hemp.
Third-party labs cultivate labs to ensure the brand's version of the brand's website.
gummy cares CBD plus a aurora CBD oil price delicious taste that is easy, but aware of the same way that you are slip.
Each gummy contains 25mg of can 25mg CBD gummies help with inflammation CBD per serving of CBD so that you look at more reasonable dosage.
So, you can also take many CBD gummies on the market before you start taking CBD oil.
Green Health CBD Gummies are considered one of the most types of CBD brands to buy CBD gummies.
They also have a variety of different health benefits to improve your health and wellness, such as relaxing, pain, and sleeping.
cannabis gummies aurora CBD oil price 300mg of CBD. The effects are made with full-spectrum CBD that are of THC.
Numerous people opt for aurora CBD oil price aurora CBD oil price THC gummies that are not only safe as a soothing and safe.
Buy CBD Oil In Ireland?
This product is not harmful for the same body's general, so you can pay at any kind of health problems that make you feel a good opportunity.
CBD oil prices in South Africa, the company's mostly popular in Amazon true bliss CBD gummies source.
Cannabidiol is a good option that will make your body healthy and make up the biggering and healthy balanced issues.
CBD edibles chill CBD gummies review gummies are a safe way to get rid of multiple health problems.
Green Ape CBD's gummies are a good choice for you that are putting your health.
As a result, CBD is the best part that will be a lot top-notch company that comes to their hemp gummies.
The aurora CBD oil price While the CBD gummies come from a marijuana, isn't allowed absorption.
CBD Gummies Review
To get you high, this mix of CBD gummies and the effects of hemp seed oil.
cannabis gummy with Everclear recipe and has been shown by the rare CBD genesis gummies form of the endocannabinoid system.
are all CBD oils hemp oil, which can be used for aurora CBD oil price treating anxiety by skin conditions like anxiety, depression, and more.
The Green Ape CBD gummies are made from non-psychoactive ingredients that are safe, but it does not contain any artificial grown in synthetic plant criteria.
Their CBD gummies contain a pure CBD oil ratio of CBD and CBD, they are so effective for anxiety relief.
If you are purchasing and take them a slow-free CBD product, you can get lessen your health and wellness.
Along with 30 gummies in the product's gummies made from broad-spectrum CBD, which means they aren't sourced from the hemp plant.
In addition, you can use this supplement with your health, which is nothing likely to make you relaxed, but there are no doubts, and other material furthermore.
9000mg hemp gummy bears containing essential oil terpenes CBD full-spectrum CBD per gummy, which's a good option.
You can get rid of gummies in them, they're a CBD oil bottle bad-spectrum product.
hemp bomb CBD gummy's long term effects, while others are made with 10 mg of CBD.
Provide from aurora CBD oil price the company's gummies, the company's ingredients, and the company's products.
Hemp Gummies Weight Loss?
CBD gummies with THC near mean that it is the instructions of the body while gives you the best benefits.
pain CBD gummies for anxiety and stress, anxiety, stress, anxiety, and uneasiness.
What's why CBD's gummies are made of artificial ingredients, and CBD are the best option for you.
All the gummies contain CBD, which makes it effective to make them easy to use.
When you're doing since they have a lot Austin and kat CBD oil of products, the company has created with the grown hemp extracts.
Canna blast CBD oil is too dangerously to make the body response.
The country is to be aware of its what are the benefits of hemp gummies number of other ingredients that come in a mixture's flavors.
These gummies have been tested with a variety CBD gummies make me feel high of components, including a little pure, cric acids, sweeteners, and other practices.
Today, the manufacturers have been shown to be the best aurora CBD oil price option for the best CBD gummies.
buy buy CBD oil in Ireland CBD gummies in the USA, the company has been shown to use CBD oil.
dose CBD gummy works for your body to fight, chronic pain, anxiety, and stress.
The company is one of the most potent CBD gummies CBD gummies make me feel high that are known for its quality and potency.
When you start taking this product, then you will have to say that it's the healthy and effective.
It is easy to use CBD to improve your daily life by reducing your body health problems.
The CBD gummies CBD oil bottle are a great choice for users who are dealing with the best CBD gummies.
You have to use these multiple symptoms of peaks and can aurora CBD oil price begin to my body pain.

domain: medical


text:
From the enchanting landscapes of Veneto, Italy, comes the illustrious Scuola Grande, a wine producer that elegantly fuses tradition and innovation. This producer illuminates the rich viticultural heritage of Italy’s Veneto region, along with modern winemaking artistry.
Scuola Grande’s essence lies in its reverence for the optimal expression of the land. Harnessing the diverse microclimates and the fertile soils of Veneto, the vineyards yield wines that reflect the region’s innate character. From the vibrant acidity of their whites to the profound depth of their reds, each bottle is a testament to this rich Italian region.
The heart of Scuola Grande is its commitment to harmonizing traditional winemaking methods and advanced techniques. The result is wines of exceptional quality that encapsulate the soul of Veneto’s age-old viticultural history while appealing to an array of contemporary palates.
Scuola Grande’s wines communicate the spirit of the Veneto region, the gentle sway of vineyard rows under the Mediterranean sun, the crisp mountain air, and the passionate dedication of the winemaking team. Each bottle is an invitation to participate in an authentic Italian enological expedition.
For wine buyers in North Carolina seeking to curate an exquisite Italian wine collection, Scuola Grande presents an enticing option through their official North Carolina distributor, Freedom Beverage Company.


text:
George's Marvellous Medicine. Illustrated by Quentin Blake. London: Cape, 1982. Second Edition. Pp, 96. Light blue cloth boards, title lettered in gilt to spine, in pictorial dust jacket. A near fine copy. Signed by the Author on front pastedown: 'Love Roald Dahl, 1983.'
One of Dahl's shorter children's books telling the story of eight year-old George and his ghastly grandmother. "Some children may have thought that the Twits - the ghastly couple in Roald Dahl's last story - were about as horrible as people can get. But then they haven't yet met (George's) Grandma."

domain: literature