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1.0 / October 11, 2016
App Information MineWars for MCPE
- App NameMineWars for MCPE
- Package Nameapp.MineWarsforMCPE.com
- UpdatedOctober 11, 2016
- File Size7.8M
- Requires AndroidAndroid 4.1 and up
- Version1.0
- DeveloperKhoa Mutakeep
- Installs1 - 5
- PriceFree
- CategoryArcade
- Developer
- Google Play Link
Khoa Mutakeep Show More...
MineWars for MCPE 1.0 APK
This MineWars for MCPE provides you somenewsword with different colors.Like red, blue, green.They aremorepowerful than ordinary swords and someone havespecialabilities.You can crafting them by the following recipes orto havethem by using Too Many Items Mod.Item IDs & Crafting RecipesSith Light Saber (419) – 4 glass blocks + 1 rose red + 1 redstone+1 obsidianLight Saber (402) – 4 glass blocks + 1 lime dye + 1 redstone +1obsidianYellow Saber (505) – sets mobs on fireMeteor Saber (502)Green Saber (503) – damages 4 heartsLegendary Saber (507) – sets a mob on fire and then makesitexplodeDarth Vader Spawner (384) – spawns Darth Vader, he has1000healthCloneTrooper Spawner (385) – spawns a Clone TrooperJedi Spawner (386) – spawns a JediDarth Vader Mask (302) – kill Darth Vader to get it. Oncewornyou'll get a little extra armor.MineWars for MCPE. It can be applied only with theBlockLauncherapplication and you must install the full version ofMPCE andBlockLauncher in your smartphone or tablet.This is not an official application for Minecraft PocketEdition.This application is not affiliated in any way with MojangAB. Thename Minecraft, Minecraft the brand and Minecraft Heritageare allowned by Mojang AB property or their respectful owner. Allrightsreserved.Accordinghttp://account.mojang.com/documents/brand_guidelines
Dragon Mod for MCPE 1.0 APK
Dragon MOD For MCPE implements 7 new dragonstoMinecraft Pocket Edition. All dragons must first be hatchedfromtheir dragon eggs. Once they have grown to their full sizes,all ofthem can be ridden and serve as flying mounts. Surely theyaretruly epic. And also, they are a quite naturally neat additionforfast travel in Minecraft Pocket Edition.Hatching a Dragon EggThe first thing you should do is to build a fenced area whichcanbe used to hatch a dragon egg.Have more minecraft mod for download & fun in this app- Pet Dragon Mod- PetPlus- Elemental Demon PetsDragon Mod for MCPE. It can be applied only withtheBlockLauncher application and you must install the full versionofMPCE and BlockLauncher in your smartphone or tablet.This is not an official application for Minecraft PocketEdition.This application is not affiliated in any way with MojangAB. Thename Minecraft, Minecraft the brand and Minecraft Heritageare allowned by Mojang AB property or their respectful owner. Allrightsreserved.Accordinghttp://account.mojang.com/documents/brand_guidelines
Top Apps Show More...
Do you want to know if your Access Point isvulnerable at the WPS protocol?Wifi Wps Wpa Tester is the app that you need!With this app, you can test the connection to AP with WPSPIN.PINs are calculated with many algorithms:-Zhao-TrendNet-Dlink-ArrisAnd others default PIN of MANY Access Point.Then NOT ALL AP ARE COMPATIBLE WITH THIS APP.App needs root permissions for devices with Android version <5.0 ( LOLLIPOP ).For devices with Android >= 5.0 you can test the PINs with thisapp and you can connect, BUT YOU CANNOT SEE WPA ( OR WEP ) PASSWORDWITHOUT ROOT PERMISSIONS.Use this app only with your own AP for do not go against thelaw.Privacy Policy :https://www.iubenda.com/privacy-policy/8000344
WordPress 7.1 APK
WordPress for Android puts the power ofpublishing in your hands, making it easy to create and consumecontent. Write, edit, and publish posts to your site, check stats,and get inspired with great posts in the Reader. What's more? It'sopen source.WordPress for Android supports WordPress.com and self-hostedWordPress.org sites running WordPress 3.5 or higher.Visit the forums to get help with the app:http://android.forums.wordpress.org
Blog 0.0.1 APK
Our blog posts include experiment resultsofonline marketing, how to articles, tools and tips for runningyourbusiness, business ideas, online selling, entrepreneurship,startups, success stories, interviews and reviews of relevantbooks.You can visit the web version of ourapp:http://technotip.orgFeatures1. Has a list of 8 recent articles on the homepage and usercannavigate to older blog posts.2. Clear reading experience with bigger fonts on articlepage.3. Facility to bookmark the article and read later frombookmarkssection.4. Cache the recently viewed article for offline reading.5. List of pages.6. Search facility.7. List posts based on Category.8. List posts by author/contributor.9. Invite others to our app via Social Sharing Apps.Option to rate the app.10. Facility to directly share the posts and pages with othersfrominside the app via popular social sharing applications.
WPS Connect 1.3.5 APK
With this app you'll can connect to WiFinetworks which have WPS protocol enabled. This feature was onlyavailable in version 4.1.2 of Android.App developed with educational purposes. I am not responsible forany misuse.Released under license CC BY-NC-ND 4.0:https://creativecommons.org/licenses/by-nc-nd/4.0/WPS: http://es.wikipedia.org/wiki/Wi-Fi_Protected_SetupWPS Connect is focused on verifying if your router is vulnerable toa default PIN. Many routers that companies install ownvulnerabilities in this aspect. With this application you can checkif your router is vulnerable or not and act accordingly.Includes default PINs, as well as algorithms such Zhao Chesung(ComputePIN) or Stefan Viehböck (easyboxPIN).Tested on:- LG G2- Nexus 5- Samsung Galaxy S3IMPORTANT!!Prior to an assessment, understand that it serves theapplication.
XPOSED IMEI Changer 1.6 APK
ROOT REQUIREDXPOSED FRAMEWORK REQUIREDIF You dont know What is XPOSED Framework then do not try thisapplication (it wont work)Hi Guys,I read about the Xposed framework in xda and other websites.somewebsites have really good tutorials about it.So what I understandis that we can modify a function and its return values using theXposed Framework.I have created and Xposed Module For Changing (MASKING) the IMEINo of the PhoneChange Means How Other Application gets the IMEI No of the deviceusing below codeAs you all know,The Value is not permanent as it is an XposedModule :)XDA-Developers Threadhttp://forum.xda-developers.com/xposed/modules/xposed-imei-changer-t2847187Pro version :https://play.google.com/store/apps/details?id=com.vivek.imeichangerproStepsInstall appEnable module in xposed frameworkCome back to app and enter new valuePress ApplyGo to xposed moduleOpen framework pageDo a soft rebootOpen the appAnd you can see new valuecheck the value by dialing *#06#, you can see the new value
Administrator 1.3 APK
Sing! Karaoke by Smule 4.3.7 APK
Sing your favorite hits with audio effects.Sing video duets with featured artists like Jessie J, Jason Derulo,and Linkin Park. Share your covers with our 50M+ global audienceand get fans!Featured by Google Play as Best Apps 2014.-----------Features- Self-recording option with video**-Try out video filters: Selfie, Fight Club, Vintage, Black andWhite, Sepia**- Sing like a star with audio effects!- Share on our global platform - get discovered!- Duet with featured pop artists - Jessie J, Jason Derulo, KylieMinogue, X Ambassadors, OMI, Carly Rae Jepsen, Charlie Puth,Silento and many more**Video availability on different Android devices will beincremental over several weeks. When available onyour device model, video option will appear with no additionalupdate required. Please see the Sing! Android FAQ for theinitial list of devices that offervideo. http://www.smule.com/support/sing#android-----------------------------------------------------New songs added every day. Current most popular on Sing!:** All of Me - John Legend** Flashlight - Jessie J (from Pitch Perfect 2)** I'm Not the Only One - Sam Smith** Like I'm Gonna Lose You - Meghan Trainor, ft. John Legend** All I Want For Christmas is You - Mariah Carey** I'm Yours - Jason Mraz** Thinking Out Loud - Ed Sheeran** Dear Future Husband - Meghan Trainor** When I Was Your Man - Bruno Mars** Let It Go - Idina Menzel (from Frozen by Disney)** Cups ("When I'm Gone") - Anna Kendrick** Stay - Rihanna ft. Mikky Ekko** Love me Like You Do - Ellie Goulding** The Way, Break Free - Ariana Grande** Anaconda, Pound the Alarm - Nicki Minaj** I Won't Give Up, I'm Yours – Jason Mraz** Happy - Pharrell Williams** Eye of the Tiger - SurvivorWant a song that's not yet available? Suggest songs on Smule'sFacebook page: www.facebook.com/smuleWant a song that's not yet available? Suggest songs on Smule'sFacebook page: www.facebook.com/smuleCONNECTING THE WORLD THROUGH MUSIC™ - JOIN THE KARAOKE PARTYFind and follow your friends in Sing!, and meet incredible singersfrom all over the world. Sing your heart out on Solo songs, or joinup with others in Duets or Group songs. Keep up with your friendsand favorite singers, and love and comment on performances to showyour support.BE DISCOVERED! GET FANS!Lots of talents get discovered through our Sing! Karaoke platform.Show off your talent in front of 50M+ global audience and getfansSOUND LIKE A STARSound amazing every time with Sing!'s voice enhancement technology.Use special voice filters to spice up your performance even more.Sing! is a supportive, joyful community where music-making at alllevels is encouraged and appreciated.http://www.smule.comhttp://plus.google.com/+smulehttp://www.facebook.com/smulehttp://www.youtube.com/smulehttp://www.twitter.com/smuleHave questions on a particular permission?http://www.smule.com/support/sing#android
WiFi Master Key - by wifi.com 4.1.97 APK
With a hundreds of millions of free Wi-Fihotspots shared by our users globally, you can connect to freeWi-Fi with WiFi Master Key (by en.wifi.com - LinkSureSingapore)!Search & connect to shared WiFi hotspots indicated by a BlueKey. Easy and safe.THE WIFI MASTER KEY EXPERIENCE- Cost Savings: Save data costs by connecting to free shared WiFihotspots.- Easy and Fast: just search for the blue key and tap to connectWiFi!- Safe and Secured: All shared password are not revealed. It isencrypted to protect sharer's privacy and security.- Easy to understand in your own language: Available in 19languages across 223 countries and regions.English,Thai, Bahasa Indonesia, Malay, Vietnamese, SimplifiedChinese, Traditional Chinese TW,Traditional Chinese HK, Japanese,Korean, Portuguese, Spanish, Russian, Arabic,Turkish, Hindi,French, Italian, German...more languages coming soon.Disclaimer: WiFi Master Key is not a hacking tool. It does notassist in unlocking passwords of Wi-Fi hotspots that are not sharedby the users. Hacking is illegal.With our growing community of over 900 MILLION users (Chinese andGlobal version combined), we aim to build a trusted platform foreverybody to enjoy the Internet. So, come join the world's largestWiFi sharing community today! If you don't find shared hotspot yet,don't worry, give the community some time to grow. We are handlingover 4 BILLION connections daily and the number is growing rapidly.There will be more and more shared WiFi to help you get connectedonline and surf the Internet free!Rate us to show us your love! It means a lot to keep usgoing!Have a question? Wanna leave a feedback or suggestion? Sure, we'dlove to hear them— tell us here or on our Facebook page!https://www.facebook.com/wifimasterkey.Spread the word, and keep sharing WiFi!


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Then the ominous 'ID parade' begins. The men and boys, some as young as 10, are shoved forward, one by one, to be identified by masked informers. Those singled out are hauled away by the soldiers and, all too often, are found the next morning, tortured and killed.
The security forces then claim they were killed in 'crossfire', or fell victim to 'inter-gang clashes' between the five main factions who want freedom from India. But, according to Mufti Farooqi, a leading human rights activist, more than 80 Kashmiris died last month in custody, despite assurances by the Indian government that it is trying to stop such murders. 'The officials say they've punished some people for these atrocities. But they've never said who conducted the inquiry, what paramilitary units were involved - nothing,' Mr Farooqi says. 'There's no proof.'
Privately, Kashmiri police admit that a 'catch and kill' policy is being carried out by the Indian security forces who, after three years, have failed to crush a growing insurgency movement among Kashmiri Muslims in this disputed northwestern Himalayan state. Mr Farooqi claims there is now one policeman or soldier for every seven Kashmiris. More than 3,500 civilians have been killed and 20,000 arrested since January 1990, when this beautiful valley of mountain lakes erupted into open revolt. The Kashmiri guerrillas are split between those who want to unite with neighbouring Muslim Pakistan and those who want independence.
Even the state's predominantly Muslim police force is not spared the brutality. More than 3,000 armed Kashmiri officers stormed the police headquarters on 23 April and held their chief hostage for several hours. They were protesting against the death of a constable who died in army custody. One senior Kashmiri official, a Muslim, who declined to be identified, said wearily: 'Yes, they're killing them. Maybe it's because the jails are full - or they want to frighten the people. We try going by the rules, but nobody else is.'
Testimony of these custodial deaths comes from a 19-year-old student, Masroof Sultan, picked out on 8 April in an ID parade. He was beaten, given electric shocks and then tied to a tree where his uniformed executioners shot him 12 times. Miraculously, he survived. Lying in hospital after undergoing four operations and a transfusion of 13 pints of blood, Mr Sultan does not know why he was picked. It might have been because he was a young Muslim with a beard. Or, because one of the soldiers fancied his woollen jumper.
He was pulled off a bus by members of the Border Security Force (BSF), a paramilitary outfit patrolling the Kashmiri capital. He was punched by four soldiers, then blindfolded and taken to an interrogation centre. There he was stripped naked and beaten so severely that his ribs were broken and his right leg was fractured. 'They kept saying: 'Admit you're a militant. Give us your guns.' I kept telling them I was innocent.'
That evening, as he was being taken away, a guard lifted the expensive jumper wrapped around his head - just long enough for him to see his mother weeping outside the security post. 'Take a look at your mother,' the soldier said. 'It's the last time you'll see her.'
He was taken to a cell inside Papa II, a secluded camp on the former maharajah of Kashmir's estate. Still naked, he was splashed with cold water. One metal ring was put around his penis, and two others banded his toes. 'They'd hold live, electric wires against these rings, touching them, tick-tick, like that, for two or three seconds, until blood started coming from my nose and I began losing all senses,' he said.
'After that, two men dragged me like a dead body and dumped me in the jeep. About seven soldiers climbed in. His captors propped him against a tree along a deserted flood channel. 'I could hear the men cocking their guns. Then the officer said: 'One-two-three . . . and all together they fired. I was lifted into the air and fell sideways. I began crawling, so the officer told a soldier to shoot me in the heart. Twice he shot - and all my breath was going. Then the soldier kicked me in the head and said: 'He's alive, sir.' I heard the officer reply: 'Shoot him in the head.'
'He took two more shots. Missed the first one and then got me in the neck. Then he stole my jumper and left. The full moon was in my eyes, and I was so thirsty. There was dirty water down in the flood canal, and I wanted to crawl down, but I couldn't understand why nothing worked. My legs, my arms, nothing.'
Mr Sultan was rescued by Kashmiri police who had been told by the BSF to collect the body of yet another crossfire victim. They found him alive and, without telling the soldiers, rushed him to hospital.
Human rights activists and Kashmiri police claim that Mr Sultan's tale is commonplace. What is remarkable is that he survived to tell it. Indian authorities in Srinagar were informed of Mr Sultan's torture but, as yet, no action has been taken against the officers involved. Mr Sultan will be crippled for life.
Britain and the United States have expressed concern over alleged human rights violations in Kashmir, but India so far has shrugged off outside interference. Amnesty International and other human rights organisations have also been banned by the Indian authorities from visiting Kashmir.
Tomorrow: India's dilemma
(Photograph omitted)
- More about:
- Human Rights
- Jammu And Kashmir
- Kashmir
- Security

subset: commoncrawl


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Library Trustees Association of New York State
Trustees in the Know:
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Learn About Important Issues
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Carrie J. Pollak presents- Legal Update: Conflicts of Interest
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Join or Renew Your Membership Today!
New This Month
- Trustees in the Know: Binghamton
- Clifton Park-Halfmoon Public Library Vinciguerra Citizen Laureate Award: Ed and Francine Rodger
- State Education Department Proposes Public Library Construction Aid Regulation Changes to Expand Scope of Eligible Projects
- Ask Joe Eisner: Are municipal or school district public library boards solely responsible for arranging for insurance coverage on the library facility and its contents?
- Trustee – Winter 2017
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Register Online Now!
Trustees in the Know:
A Day to Learn, Participate and Renew for Library Trustees and Directors. Sponsored by the Four County Library System, the Southern Tier Library System, the Finger Lakes Library System and the Library Trustees Association. Hosted by the Four County Library System at the Broome County Public Library located at 185 Court Street, Binghamton, NY.
Saturday, May 6, 2017• 9:30 am to 3:00 pm
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View the total list of systems, their libraries and members, or under the System Map,
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- August 12, 2017 - "Trustees in the Know" Plainview-Old Bethpage Library
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We are a statewide organization that represents, assists, educates and honors public library boards and their trustees as providers of free and universal library service.
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The Dignity Memorial network is the name families turn to for compassionate and professional funeral arrangements. Offered through a network of more than 1,600 providers in North America, the Dignity Memorial brand is your assurance of quality, value, caring service and exceptional customer satisfaction.
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There's no better hairstyle than a quick hairstyle… am I right? One that literally takes 5 minutes to pull off is a keeper in my books. Since chopping my mop above shoulder length, I've been experimenting with different styles, like this messy braided crown that looks cute with carefree waves. Here's how to do it:...
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11. Shattered Bob Back to balayage again and this is another classic example of how short hair and this color style works so well together. Heading from a darker brown, almost natural root to a really cool, almost icy blonde, every shade is used in between to make this stunning look come across as somewhat natural. …


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10 Things Your Mom Should Have Taught You About Walgreens Braces Flossers
Did you know that teeth can really final a life time? It's accurate. For numerous of us, proper brushing, flossing and visits to the dentist ensure our tooth last a lifetime says a dentist in Marietta, GA. Tooth are composed of a gentle middle and difficult outer surface. Surprisingly, this outer surface, the enamel is the hardest substance in our body, and it's discovered on our tooth. Teeth require the enamel to help withstand the extraordinary forces of chewing and grinding meals.
"I'm heading to attempt and put some veneers on the teeth, and I'm going to bring the top teeth out as far as I can and established them on top of the reduce teeth and use Invisalign to pull the lower set behind and inside of the higher established, so we make the leap that way.
Society is captivated with elegance. Getting a good smile is just 1 of many requirements of beauty you could achieve. Dentists these days give you options that you are in a position afford, so there's no justification for you not to at any time get it, be it for your elegance or for your wellness.
It is important to examine your tooth situation history prior to you concur to get braces. Occasionally, your tooth may not need severe correction and at that time, the cost would be reduced. Sometimes, you might encounter great discomfort in your teeth when they are impacted by malocclusion. At that time, the cost for obtaining braces would be much more than just a regular verify up and treatment. It is expensive to get braces rubber bands how long for mature people, when compared to kids, because the procedure to straighten experienced tooth will be harder. The overall price for straightening experienced tooth using braces might range in between $5000 and $7000.
So to these who doesn't want braces but in need of tooth alignment, let me tell you the good news! There is actually an alternative to these unattractive metal braces. The fantastic solution to the problem is Invisalign. These are distinct tooth aligners and would fit over your tooth and the sad part is that only a few are educated about this.
Each one of us would require the services of dentists at some point of time. If you are looking for the best dentists in St. Louis, Dr. Mike definitely tops the checklist. He has been bestowed with a lot of awards for his excellence in the field of dentistry.
braces rubber bands how long are utilized to maintain straightness of the teeth and jaw flaws. In fact, the costs of braces differ from one person to an additional. This is because various people of different age team have different dimension of the teeth construction. If you happen to visit a dentist store, do not forget to verify the price of the braces prior to you buy them.
Showing off a fantastic smile can make you feel good and get you farther in life than a frown can. If you have overcrowded tooth, stains or something else that is making you really feel self-aware about displaying your chompers to the globe, there are methods you can have carried out at the dentist's office to give you the increase in self-confidence that you require.
One of the methods utilized for treating TMJ at home is to not use your jaw as a lot. Try to maintain the jaw in the correct place and also attempt applying some warmth to the area of the jaw that is creating you pain. Use the stretching methods and also attempt to massage the region as well. All of these things can be carried out at home which will allow you to have a jumpstart to maintaining the TMJ discomfort at bay.
One out of 7 people in the globe endure from a dental condition which is called Diastema. It is about the hole between the teeth and if you have them then you can get aligners to get them set. The conventional way to do is placing on braces but if you believe they are a hassle then you should certainly select to go for Invisalign. Let us discover more about it.
Dental braces are now becoming more and much more affordable with the growing quantity of dentists. Also, there are various sorts of dental braces that individuals can choose from. The most common is the silver or stainless braces. There are also gold braces, distinct or white braces, lingual braces and titanium braces. All you require to do is consider your pick. The only factor to keep in mind is that all braces work the same. Some use braces as a style statement so they prefer to use the much more costly or the much more noticeable one. But they nonetheless give the same outcomes.Perhaps the best tmj treatment are exercises. These aren't going to be fast pain relief, but if you do them frequently, you ought to keep the issue at bay, and the pain is going to be considerably less when it does happen. There are numerous workouts out there on the internet (some of which can be found on this website) so I gained't go into as well a lot depth, however, the idea is that you are heading to be stretching your neck muscle tissues, as well as keeping that jaw correctly aligned. They are simple workouts, but you will be shocked at just how effective they are.


text: Sometime it is just nice to get into a restaurant that is very average in the decor, but still in a nice environment, and all the work is put into the food quality. The menu and wine selections are easy to overview, it based on less is more, and less is higher quality. A great place to dine, highly recommended.


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Become part of the Fringe Festival by being a sponsor!
With more than 850,000 visits over 11 days, Edmonton's Fringe Festival is the largest and oldest in North America. The Festival impacts artists, the community, and our local economy. Not only do we host three free outdoor stages, and a free KidsFringe site, but throughout the festival, our artists also directly earn $1.5 million through the box office. That's because 100% of ticket sales go directly to performing artists, thanks to our generous sponsors.
Sponsoring the Fringe Festival is an exciting opportunity — we have developed a variety of options, and are always excited to hear your unique ideas as well!


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Welcome to the official website of the Office of the East Kingdom Minister of the Lists.
We have worked hard to make sure that this website is full of information that is useful for Ministers of the Lists at all levels and for the martial community at large. If you want to know something that isn't listed here, please feel free to contact the .
One great way for MoLs and Marshals to keep in touch is to join the Minister of the Lists Yahoo Group.
Just to make it easy, here are some of our most requested resources:
Request for Replacement Authorization Card
Armored Combat Authorization Form
Rapier Combat Authorization Form
Latest Announcements From the EK MoL
- Greetings from the New EK MoL
- MoL Forms Updated
- Deputy Database Administrator Sought
- MOL News and Pennsic Deadline


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Enrolment for the Queen's Sport Spring 2017 Children's Activity Programme is open now!
Courses start week commencing 24 April 2017!
To download an enrolment form please click the links below:
CAP - Enrolment Form - Spring 2017
CAP - Programme - Spring 2017
If you have any queries please contact reception on 028 9068 1126 or email firstname.lastname@example.com.
*Please note enrolment for all Splash 'N' Swim courses will begin on 20 April 2017.
Queen's University Belfast is registered with the Charity Commission for Northern Ireland NIC101788


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66 Results
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1 week ago
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3 months ago
Tv9 - Ram fight in East Godavari; Sankranthri celebrations
3 months ago
NTv - Chandrababu to lay stone for Purushothapatnam LI scheme in EG district today
3 months ago
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10 months ago
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11 months ago
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11 months ago
Tv9 - 8 killed as private bus plunges into gorge in EG dist
11 months ago
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1 year ago
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Here on this page, you can See A Collection of East godavari Videos. The list contains Important Videos and Video News related to East godavari. You can watch the videos of East godavari with a brief description written in English. Here all the Videos related to East godavari are quality checked and listed date wise.
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A Homeless Vet Sat Down At The Piano And THIS Happened!
Donald Gould is a homeless veteran just trying to survive. Most people judge Donald by his rough exterior instead of getting to know the incredibly talented man inside. And when he sits down at the piano and starts to play you'll be amazed! Our prayers are with you Donald.
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"BEWARE...This place is hands down the most corrupt, back biting, unprofessional place I have ever experienced."
- Work/Life Balance
- Culture & Values
- Career Opportunities
- Comp & Benefits
- Senior Management
Helpful (3)
I worked at Appalachian Underwriters full-time (Less than a year)
Honestly, I have no pros as I knew I had made a huge mistake leaving my previous job within around 3 weeks of being employed here.
Micro managed, lack of diversity, completely unprofessional, back biting, constant drama and gossip, sabotage, and undermining any attempts you may make to have a "normal" work environment. I wish someone would have told me better so do yourself a service go elsewhere to retain your happiness and that of your family.
Advice to Management
The WC department needs to be overhauled beginning with the supervisor. Also, the supervisor should be training the employees not placing that responsibility on an adjuster with less than 1 year of experience who does nothing but spread negativity about the company and all co-workers beginning your first day. I witnessed the supervisor have this employee hack co workers emails, going through their files, and basically create an all out campaign to get rid of anyone she didn't want there. The supervisor would use the employee so that if it came to light what was being done she could throw that person under the bus instead of being blamed herself. As long as you run your business in this matter you will not be able to keep quality employees as they will be run out because not many people can deal with the environment for very long no matter how much money you pay them and even that is just average. I could go on and on, but honestly I don't see much changing as the management seems to uphold the very behavior that I have described.
Helpful (2)
I worked at Appalachian Underwriters full-time (More than a year)
If you're a man & you like football, chances are you'll do fine. It also helps if you're a local. If you're none of these, maybe not the company for you.
Here we have a company very set in its ways. This is East Tennessee and, because of that, corporate culture isn't very corporate. While not quite Good Ole Boys, the upper tiers of management appear to be staffed by family & friends of family.
HR policies appeared to be an afterthought. Ditto job descriptions. 401(k) match was worse than most other firms I've worked for. Healthcare through Blue Cross/Shield, pretty standard/ poor. 3 months before benefits kick in; what am I supposed to do until then?
Insurance knowledge or expertise was secondary consideration when hiring which is especially worrying when hiring underwriters. Create any waves and you're very quickly a 'poor fit' for the companies' 'values' and 'culture', attributes that are never explained.
Advice to Management
Hire some people from outside the local populace who have Fortune 500 experience. It has to help.
Helpful (5)
I have been working at Appalachian Underwriters full-time (Less than a year)
The facilities are nice. The shift is standard 8-5. Surprisingly most of the mid-level managers are excellent people and supervisors.
Family owned, people with lack of professional experience and training make major decisions, no focus on HR, poor incentive, poor training, No structured job appraisal or performance analysis system. The owners of the company do not even follow the procedures and policies that they placed in their employee handbook. Lack of internal consistency throughout the organization.
Advice to Management
I would advise them to select people for jobs and not hire. I would also suggest to them to invest in proper recruiting sources and not rely on Craigslist. The parent owners have no business in the building. They lack the knowledge of how a modern workforce operates. They really need to retire and stay out of the business. The VP, also related to the owners, has little tact and business acumen.


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Roofers in San Antonio, TX
Finding a quality roofing contractor in San Antonio, Texas is simpler with Hometown. We verify roofing services and credentials, along with gathering trusted reviews from real customers. Find the most reliable and affordable roofers in your hometown.
Filter Contractors >>
Shelter Pro has proudly been your locally-owned-and-operated roofing and storm damage repair specialist dating back to 1984. We specialize in commercial and residential roofing, and we're fully licensed and insured. We guarantee our work and are dedicated to meeting our customers' needs. Contact us today for a free roof repair or replacement estimate.
We're the roof replacement specialists based in San Antonio. Champion Roofing & Construction offers expertise in roof replacement due to insurance claims, damage or old age. We service all types of roofs, including shingles, cedar shakes, metal, slate, TPO and more. We work with residential and commercial clients. Call today for a free estimate!
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(830) 500-3756
OSO Construction offers professional roofing contractor services in the San Antonio Metro Area. We have several years of experience repairing and replacing residential roofing systems. Our crews are expertly trained and continue to stay current with trends and technology. Call today for a free estimate with OSO.
We at McManus Construction hold a strong commitment to provide our customers with the highest level of quality and professional service. Mcmanus provides affordable and professional residential and commercial roof replacement. We treat our customers fairly and make the extra effort to keep them satisfied.
M&M Roofing has 30 years of customer satisfaction under our belts. Our roofing technicians have been with us since our doors have opened in 1983. We are so confident in our installation that we ask for no money down on any project. You pay when your roof is complete. We offer a wide range of residential roofs to choose from.
At Lone Star Roofing & Construction, Inc., they offer a wide range of general contracting services to residential and commercial customers, including roofing, home repair and maintenance, new construction, and more.
No other roofing company in the San Antonio area offers more comprehensive services. Since 1975, Cloud Roofing has been specializing in roof repairs, replacements, installations, and more.
We have knowledgeable staff members with years of experience to handle your next home project. Our top craftsmen will work with you to design a plan and ensure your home is treated to the best materials installed correctly.
Avila Roofing offers services for both residential and commercial roofing projects throughout San Antonio and its surrounding areas. We place great emphasis on our customer service, and strive for excellence in all our service applications.
Yuras Roofing Company has been serving South Texas residents since 1949. We specialize in metal roofing systems for residential and commercial properties, and strive to provide the very best in service. "If you're not satisfied, we're not finished!"
Unverified Roofing Contractors
Tips on Roofing in San Antonio, TX
What factors go into the estimate prices of roofing companies?
Estimate prices from local roofing contractors may vary widely based on the details of your particular roof. Here' a few of the key factors that have the biggest impact on roofing cost.
- Roof size - Roof size is quoted in "squares" (100 square feet = 1 square).
- Roof slope - Steeper sloped roofs are more challenging to work on and will require higher labor costs.
- Roofing material - Metal roofing lasts longer than shingles, but costs more. Architectural shingles cost more than 3-tab shingles. Specialty roofing materials like slate roofing or shake roofing, cost more for the material and the installation than a basic shingle roof installation.
- Material grade - Better quality materials will cost significantly more. For example, a shingle with a 30 year warranty will cost more than a shingle with a 15 year warranty.
- Existing roofing material to be removed - If the existing roof needs to be removed, significant cost will be added to your estimate. Tear off and proper disposal of existing roof layers is a significant part of the cost of any re-roofing project. More layers cost more to remove and more to dispose of.
How do I know if a roofing contractor is properly licensed and insured?
For roofers listed on Hometown, we've done the initial homework for you. At the time a roofing company was listed, they provided the appropriate state license (if required by your state) and liability insurance. Select the name of a contractor you're interested in to see more information, including a list of verified credentials for that contractor.
Hometown's screening process means the roofer produced a valid Texas license (if required) and insurance certificates at the time of the screening, but it's possible that the status of the license or insurance could have changed in the meantime. So, it's a best practice to ask to see evidence of the roofers' license and insurance certificates at the time of your estimate.


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One particular line item in Mayor Michael Nutter's proposed $3.75 billion operating budget for fiscal year 2014 offers a solution to a problem that Philadelphia library goers have bemoaned for years: the large number of temporary, unscheduled closings.
As part of the 2014 operating budget, Nutter is proposing $750,000 to increase hours at 20 of the Free Library branches, two in each of the city's 10 City Council districts. The Nutter administration will work with district council members to make those selections.
"We're very thrilled to be in there with the additional funding because in the past we've had cuts," said Sandra Horrocks, vice president of external affairs at the Free Library. "So this is really terrific news."
Philadelphia is particularly plagued by these unscheduled closings, according to a 2012 report by The Pew Charitable Trusts' Philadelphia Research Initiative titled "The Library in the City: Changing Demands and a Challenging Future."
Pew's report compared the Free Library's operations to those of 14 other library systems: Atlanta, Baltimore, Boston, Brooklyn, Charlotte, Chicago, Columbus, Detroit, Los Angeles, Phoenix, Pittsburgh, Queens, San Francisco and Seattle. It found that Philadelphians use their libraries less than their counterparts in most of the 14 other cities studied. One factor contributing to that low use was the "extraordinary number of times that branches have experienced temporary, unscheduled closings in the past few years."
"If you one day go to your branch and find that it's closed, an unannounced closure, you might think twice before going there again," said Emily Dowdall, senior associate at the Philadelphia Research Initiative and coauthor of the report. The unscheduled closings are often a result of staff shortages largely due to budget cuts.
Before the 2008 financial crisis, the Free Library experienced 690 hours of unplanned closures, according to the Pew report. It found that only 51 of those hours at 17 branches were caused by staff shortages; the rest were due to emergency maintenance issues.
In the fall of 2008, Nutter and the library board announced plans to permanently close 11 of the 54 branches due to the collapse of the stock market. Protests and eventually a lawsuit ensued halting the closings. And for that Horrocks credits the public.
"The outpouring from the community was so strong and so vocal that that didn't happen," she said. "So it's clear libraries are critically important."
In lieu of the closings the Free Library suffered a budget cut of about $7.5 million. The cuts caused most of the branches to reduce their weekly openings from six days to five.
These cuts caused unscheduled closing to increased dramatically. In 2010, unscheduled closings reached 8,000 hours, more than three-fourths of them due to staff shortages; every facility in the system except Parkway Central, the Lucien E. Blackwell West Regional Library, and the Library for the Blind and Physically Handicapped was affected.
It did get better the following year. In 2011, the number of unscheduled closed hours dropped to 3,662 hours, with less than half due to staffing.
Forty-nine of the Free Library branches are smaller and serve specific neighborhoods. The others are three much larger regional libraries and one that focuses on resources for the blind and physically handicapped.
Currently all 49 smaller branches are closed on Sundays, 23 are closed on Fridays and 27 are closed on Saturdays. Branches that are close in proximity to one another are essentially paired so that one is open on Fridays and the other on Saturdays.
Twenty-nine smaller branches are open past 5 p.m. on Mondays, Wednesdays and Fridays, and 20 are open past 5 p.m. on Tuesday and Thursday. None of the smaller branches open before 10 a.m.
The Pew report found that the Free Library's five-day-a-week branch hours might not be distributed in the best possible way. Namely, the different schedules of the various branches proved to be problematic. "While intended to give patrons an increased chance of finding an open library, this system also can create confusion, which may discourage patronage."
The proposed $750,000 in funding would not enable those branches that are open five days a week to be open six. But Horrocks said the funding would enable the Free Library to hire additional staff to expand branch hours, which could mean "adding some evening hours, maybe opening some locations on Saturday and Sunday." When and where hours would be increased is contingent upon the union rules and regulations governing Free Library employees. Horrocks estimated that staffing accounts for about 86 percent of the Free Library's budget.
Amy Dougherty, executive director of Friends of the Free Library of Philadelphia, said the expansion in hours, although only applicable to 20 branches, would have an effect on the whole system.
"That will affect the entire system because once those 20 branches are totally stabilized they won't be pulling people from other branches," Dougherty said. "It will have a balloon effect. It begins to stabilize the operations of all branches."
The Free Library will present its budget to City Council on April 15 at 11:30 a.m.
Amy Dougherty City budget Free Library of Philadelphia Friends of the Free Library Neighborhoods Nutter Pew Sandra Horrocks


text:
Tibetan Book of the Dead - (Region 1 Import DVD)
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Death is real, it comes without warning and it cannot be escaped. An ancient source of strength and guidance, The Tibetan Book of the Dead remains an essential teaching in the Buddhist cultures of the Himalayas. Narrated by Leonard Cohen, this enlightening two-part series explores the sacred text and boldly visualizes the afterlife according to its profound wisdom. Part 1: 'A Way of Life' reveals the history of The Tibetan Book of the Dead and examines its traditional use in northern India, as well as its acceptance in Western hospices. Part 2: 'The Great Liberation' follows an old lama and his novice monk as they guide a Himalayan villager into the afterlife using readings from The Tibetan Book of the Dead.
- Categories
- Documentary, Import, Movies
- Rating
- Number of Discs
- 1
- Format
- TV System
- Country
- Region
- Barcode
- 718122565078
- Title
- Tibetan Book of the Dead - (Region 1 Import DVD)
- Studio
- Alive Mind/Kv
- Year
- 0
- Running Time
- 90
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Region details
Region 1 - United States, Canada, Bermuda, U.S. territories.


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Tonari ni Kimi no Nukumori wo Summary:
A collection of few stories. 1,2)Main one is about Michihiro who grieves after his dog's death. But then one day a guy who claims to be his dead dog appears. Who is he and why does he know every little thing about Michihiro? Funny and heart warming story revolving around school life. 3)Our World- Matsuya and Tsuge have just started dating and are having problems in the bedroom. Matsuya is worried about their compatibility. 4)Drop of First Love- Chiyoda's never been able to forget his first love, a beautiful little girl that was always picked on at the public park. Even though he moved away he's always thought about her, and now that he's back Chiyoda knows he'll recognize her. But Ichikawa isn't quite the girl he remembers... 5)If You are Here- Carefree Souta attaches himself to Yuuya, even moving into Yuuya's tiny apartment. Yuuya finds himself caring for the hopelessly innocent Souta like a mother, but his feelings are becoming more and more dangerous to their friendship. 6)One Sweet Please- Super-shy pastry chef Furugawa Atsu has finally gotten up the courage to confess his love to beautiful customer Sakiya Naoyuki. But Atsu doesn't only seen him in the shop, is he really in love with Sakiya, or just captivated by a pretty face? 7)Kitty's Melancholy- Ichiyama is feeling neglected. Machida only comes over when he wants to have sex and leaves right afterwards. Even at school there's no time for romance.


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Honokiol blocks store operated calcium entry in CHO cells expressing the M3 muscarinic receptor: honokiol and muscarinic signaling
© Wang et al; licensee BioMed Central Ltd. 2013
Received: 21 December 2012
Accepted: 22 February 2013
Published: 23 February 2013
Honokiol, a cell-permeable phenolic compound derived from the bark of magnolia trees and present in Asian herbal teas, has a unique array of pharmacological actions, including the inhibition of multiple autonomic responses. We determined the effects of honokiol on calcium signaling underlying transmission mediated by human M3 muscarinic receptors expressed in Chinese hamster ovary (CHO) cells. Receptor binding was determined in radiolabelled ligand binding assays; changes in intracellular calcium concentrations were determined using a fura-2 ratiometric imaging protocol; cytotoxicity was determined using a dye reduction assay.
Honokiol had a potent (EC50 ≈ 5 μmol/l) inhibitory effect on store operated calcium entry (SOCE) that was induced by activation of the M3 receptors. This effect was specific, rapid and partially reversible, and was seen at concentrations not associated with cytotoxicity, inhibition of IP3 receptor-mediated calcium release, depletion of ER calcium stores, or disruption of M3 receptor binding.
It is likely that an inhibition of SOCE contributes to honokiol disruption of parasympathetic motor functions, as well as many of its beneficial pharmacological properties.
KeywordsHonokiol Calcium signaling Store operated calcium entry (SOCE) Inositol trisphosphate (IP3) Muscarinic acetylcholine receptor Phospholipase Cβ
Honokiol is a small, cell-permeable phenolic compound derived from the bark of magnolia trees that is present in Asian herbal teas. Honokiol has a unique array of antiangiogenic, antitumor and anti-inflammatory actions [1].
In the central and peripheral nervous systems, honokiol has a neuroprotective effect, as well as effects on certain signal transduction pathways. Honokiol is an effective scavenger of reactive oxygen species [2], which may be an important factor in its anti-inflammatory and neuroprotective actions [3–5]. Honokiol also has pronounced anti-nociceptive effects, notably the nociception associated with glutamate receptor activation [6, 7]. Honokiol inhibits muscarinic receptor- and depolarization-mediated contraction of isolated porcine trachea, guinea pig ileum and rat uterus, apparently by blocking the influx of extracellular calcium [8–10]. Thus, common aspects of honokiol action in excitable tissues are an antioxidative action and depression of glutamate-receptor and calcium mediated signaling. It is possible that these are interrelated factors.
The present research was undertaken to determine the effects of honokiol on calcium signaling underlying transmission mediated by muscarinic receptors expressed in Chinese hamster ovary (CHO) cells, particularly receptor-mediated release from the endoplasmic reticulum through activated IP3 receptors and the subsequent store-operated calcium entry (SOCE) that is induced by depletion of calcium from the endoplasmic reticulum [11]. We report that honokiol is a potent inhibitor of SOCE, with lesser effects on resting calcium concentrations and calcium release from the endoplasmic reticulum.
Cell culture and cytotoxicity measurements
CHO cells stably transfected with a clone of the human M3 muscarinic acetylcholine receptor (cDNA Resource Center, http://www.cdna.org) were cultured in DME/F12 media containing 10% FBS and penicillin/streptomycin (100 IU/100 μg/ml) at 37° in a 5% CO2 humidified atmosphere. Cell viability was determined using an MTS reduction assay (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt; Promega, Madison). Cells (≈ 7,000) were seeded into each well of a 96-well plate and incubated for 16 h. The cells were exposed to honokiol for 24 h before cell viability was determined.
Muscarinic receptor binding
[3H]N-methylscopolamine ([3H]MS; PerkinElmer), a non-selective muscarinic antagonist, was used to label muscarinic receptors from rat brain. Membranes from the neocortex were homogenized in 50 mmol/l Tris–HCl (pH 7.4), and an aliquot (15-30 μg protein) was incubated in the presence of [3H]MS and 50 mmol/l Tris–HCl (pH 7.4) for 60 minutes at room temperature in a final volume of 1 ml. Binding was determined by filtration of the suspension through glass fiber filters (1 μm pore size), followed by measurement of the radioactivity trapped on the filters by liquid scintillation counting. Non-specific binding was determined in the presence of 10 μmol/l atropine.
[3H]MS binding parameters (receptor concentration [Bmax] and dissociation constant [KD]) were determined by nonlinear regression (DeltaGraph) using a model for a single population of independent binding sites. Agonist binding was determined in competition studies using carbamylcholine and 0.2 nmol/l [3H]MS.
Measurement of intracellular calcium
Cytosolic calcium concentration ([Ca2+]i) was measured in a ratiometric assay using the calcium-sensitive fluorescent dye, fura-2 (Molecular Probes). Cells (≈120,000) were seeded onto 29 mm glass bottom dishes and incubated for 16 h. The cells were then incubated with fura-2 AM for 60 min at room temperature in a basal salt solution (BSS) comprised of 130 mmol/l NaCl, 5.4 mmol/l KCl, 5.5 mmol/l glucose, 2 mmol/l CaCl2, 1 mmol/l MgCl2, and 20 mmol/l HEPES, at pH 7.4. The cells were then washed twice with BSS, and the incubation continued for an additional 30 min before measuring calcium levels. Honokiol was present during the last 10 min of the final incubation period.
[Ca2+]i. was determined at room temperature using an InCyt Basic IM™ Fluorescence Imaging System (Intracellular Imaging, Inc., Cincinnati, OH). The imaging system was calibrated for calcium concentration using standard calcium solutions of known concentration (Invitrogen #C3722), according to manufacturer protocol. The ratio of fluorescence intensities measured at 512 nm after excitation at 340 and 380 nm is a reliable indicator of [Ca2+]i..
Signals from 17-25 cells were measured in each plate. Cells in which the resting [Ca2+]i. was not maintained at a constant level (typically 1-2 cells/plate) were excluded from the analysis, as were cells that completely failed to respond to a muscarinic agonist (typically < 1 cell/plate). To measure responses in the absence of extracellular calcium, the cells were switched to calcium-free BSS 3 min before imaging.
Statistical analysis
Parameters (calcium concentrations, dissociation constants, receptor concentrations, IC50's) were compared as the means from 3-6 independent experiments (with 3 replicates in each binding measurement protocol and 17-23 replicates in each calcium measurement protocol) using Student's t-test. Values from experiments with multiple independent variables were compared by ANOVA and Tukey's test using GraphPad Prism software. Significant differences were indicated by P values of < 0.05.
Honokiol inhibition of muscarinic signaling
The resting cytosolic calcium concentration ([Ca2+]i) of CHO-M3 cells in BSS in this series of experiments was 32.7 ± 9.8 nmol/l (mean ± S.D.; N = 5). Stimulation with the muscarinic agonist carbamylcholine (10 μmol/l) led to a rapid and sustained increase in cytosolic calcium to a concentration that ranged from 500 to 900 nmol/l (Figure 1A). The threshold concentration for elicitation of a response to carbamylcholine was approximately 0.2 μmol/l. Responses to carbamylcholine were completely blocked by a 10 min pretreatment with 10 μmol/l atropine, and CHO cells not transfected with a muscarinic receptor gene did not respond to carbamylcholine. Addition of EDTA (5 mmol/l) to the external medium caused a rapid decrease in [Ca2+]i, indicating that the sustained elevation of [Ca2+]i following muscarinic receptor activation was dependent upon the entry of extracellular calcium (Figure 1A).
The initial change in [Ca2+]i largely reflects calcium release from the endoplasmic reticulum, while the sustained plateau phase almost exclusively reflects calcium entry from the extracellular medium [12, 13]. Initial calcium release from the ER is mediated by IP3 receptor ionophores, while the plateau phase involves "capacitive" calcium entry through Orai channels in the plasma membrane. STIM1 proteins span the ER membrane and possess a domain that senses calcium depletion. Calcium depletion induces an interaction between STIM1 and Orai, thereby activating the influx of extracellular calcium [13, 14]. This influx of extracellular calcium in response to depletion of calcium in the endoplasmic reticulum is referred to as store-operated calcium entry (SOCE).
Honokiol blocked sustained calcium entry (i.e., SOCE) at concentrations at which it did not affect initial calcium release (i.e., calcium release from the ER (Figure 1B). For example, 10 μmol/l honokiol completely inhibited SOCE without significantly depressing the initial rise in [Ca2+]i. At higher concentrations (20 and 30 μmol/l), honokiol blocked both calcium responses.
Honokiol cytotoxicity
Reversibility of honokiol effects on muscarinic signaling
Influence of honokiol on ligand binding to muscarinic receptors
Muscarinic signaling in CHO cells
The influence of honokiol on muscarinic signaling was investigated in CHO cells expressing the human M3 muscarinic receptor. In wild-type CHO cells, we cannot detect acetylcholinesterase activity, muscarinic receptor binding, or muscarinic signaling as reflected in either calcium mobilization or alteration of cAMP synthesis in response to carbamylcholine. However, CHO cells express components of both the phospholipase Cβ [15] and adenylate cyclase [16] signaling pathways, and CHO cells transfected with transgenes for the different muscarinic receptor subtypes respond to muscarinic agonists in pharmacologically and physiologically appropriate fashions: Activation of human M1, M3 or M5 receptors expressed in CHO cells leads to the production of IP3, release of calcium from the ER, activation of SOCE, and modulation of the expression of genes under control of the AP-1 or NFAT response elements [15] (AL Martin et al., unpublished observations). Activation of human M2 and M4 receptors expressed in CHO cells leads to the inhibition of forskolin-stimulated cAMP formation and alteration of the expression of genes under the control of the cAMP response element (CRE) [15] (AL Martin et al., unpublished observations).
M3 receptors activate Gαq transducer proteins that stimulate phospholipase Cβ (PLCβ) [17]. PLCβ hydrolyzes phosphatidylinositol 4.5-bisphosphate, releasing both diacylglycerol and inositol trisphosphate (IP3). IP3 binds to the IP3 receptor/ionophore on the endoplasmic reticulum (ER) to release calcium into the cytosol. Sensors in STIM1 proteins that span ER membranes are sensitive to the depletion of ER calcium. This leads to a close apposition of ER and plasma membranes, allowing STIM1 proteins to interact with Orai channel proteins in the plasma membrane, thereby stimulating the entry of extracellular calcium. This is called capacitive calcium entry or store-operated calcium entry (SOCE) [11, 13, 18].
Honokiol disruption of muscarinic signaling
Calcium release from the ER through the IP3 receptor ionophore was visualized as the initial release of calcium in response to carbamylcholine. This release was not affected by honokiol in either the presence or absence of extracellular calcium (Figures 1 & 2). Honokiol had variable effects on calcium release from the ER induced by thapsigargin. In multiple instances, honokiol did not affect thapsigargin-induced release at concentrations that produced strong inhibition of SOCE. However, at higher concentrations, an inhibition of both thapsigargin-induced release and SOCE was observed. The precise relationship between the thapsigargin-induced release, ER calcium concentration, and SOCE gating requires additional clarification.
SOCE was visualized by depleting calcium from the ER by stimulating the muscarinic-IP3 receptor pathway or by inhibiting SERCA pumps in the absence of extracellular calcium. When [Ca2+]i returned to its baseline level (3-5 min), calcium was added to the extracellular medium (final concentration = 2 mmol/l). Calcium immediately entered the cell via the SOCE channels that had opened in response to depletion of ER calcium. In both paradigms, honokiol displayed a strong inhibition of extracellular calcium entry through SOCE channels.
Honokiol's effect on SOCE was selective insofar as honokiol inhibited SOCE at lower concentrations than it affected ER calcium release induced by either IP3 receptor activation or thapsigargin inhibition of SERCA. Honokiol's effect was rapid and partially reversible (at concentrations below 30 μmol/l), and was observed at concentrations and under conditions in which honokiol was not cytotoxic and did not interfere with ligand binding to the muscarinic receptor. Previous work has documented honokiol inhibition of muscarinic receptor- and depolarization-mediated contraction of isolated porcine trachea, guinea pig ileum and rat uterus, apparently by blocking the influx of extracellular calcium [8–10]. The present work suggests that an inhibition of SOCE is the mechanism underlying these effects on autonomic signaling.
The threshold for honokiol inhibitory effects in vitro was ≈ 3 μM. This is consistent with the concentration dependence of in vitro antiinflammatory, antithrombosis, signaling and antioxidant effects of honokiol. For example, Alexeev et al. [19] noted magnonol and honokiol effects on GABAergic transmission in the 1-30 μM range, Tian et al. used 150 μM honkiol to enhance cell death of cultured cancer cells [20], Nagalingam et al. found that honokiol concentrations of 5 μM honokiol were required to inhibit the clonogenicity of cultured breast cancer cells by activation of AMP-activated protein kinase [21], and Fukuyama et al., demonstrated a neurtorphic acivity (neurtie outgrowth) of 0.1 – 10 μM honokiol on cultured rat cortical neurons [22]. Moreover, Lu et al. used 1 -100 μM honokiol to inhibit responses of uteri to cholinergic agonists [10] and Ko et al used 0.1 -100 μM honokiol to inhibited cholinergic responses of tracheal muscle [9].
In earlier work we demonstrated that oxidative stress (e.g., by exposure to metal oxide nanoparticles) also has a selective inhibitory effect on SOCE [15]. Honokiol, however, has antioxidant properties and is cytoprotective in the face of multiple insults, including oxidative stress. This raises the possibility that honokiol actions reflect a direct interaction with the ion channel (Orai) itself, rather than an indirect effect on the redox state of the cell. This would be consistent with honokiol's antioxidant activity, lack of cytotoxicity, and rapid and partially reversible inhibition of SOCE. Another possibility that remains to be evaluated is whether honokiol disrupts Orai – Stim1 interactions. It is interesting that honokiol, unlike most pharmacologically exploited ion channel blockers, is not a hydrophobic amine.
The effect of honokiol on resting [Ca2+]i. was biphasic. The decrease in [Ca2+]i. at honokiol concentrations below 10 μmol/l might reflect the role of Orai channels as one of the transport mechanisms that determine cellular calcium concentration [23]. It is also possible that honokiol alters the resting calcium content aof the endoplasmic reticulum, which might reflect changes in active sequestration mechanisms (SERCA) or ER channel conductances. Increases in resting [Ca2+]i. are associated with incipient cytotoxicity. Honokiol recently was reported to promote calcium release associated with mitochondrial dysfunction in human chondrosarcoma cells [24]. However, even at high and ultimately cytotoxic concentrations of honokiol, virtually all of the cells remained capable of maintaining [Ca2+]i at constant levels over the time course of these acute experiments.
Honokiol had a potent inhibitory effect on store operated calcium entry (SOCE) stimulated by activation of the M3 muscarinic receptors. This effect was specific, rapid and partially reversible, and was seen at concentrations not associated with cytotoxicity, inhibition of IP3 receptor-mediated release, or disruption of M3 receptor binding. It is likely that inhibition of SOCE accounts for honokiol disruption of parasympathetic motor functions, and may contribute to certain of its beneficial pharmacological properties.
Authors' information
Co-Corresponding author: Ming-Huan Chan, Ph.D. Institute of Neuroscience, Research Ctr for Mind, Brian & Learning, National, Chengchi University, No. 64, Sec 2, ZhiNan Rd. Taipei, Taiwan.
Basal salt solution
- [Ca2+]i:
Intracellular calcium concentration
Chinese hamster ovary
Endoplasmic reticulum
Inositol trisphosphate
- PLCβ:
Phospholipase Cβ
Sarco/endoplasmic reticulum calcium-ATPase
Store operated calcium entry
The authors thank Dr. Chimpiao (Natinal Dong Hwa University, Hualien Taiwan) for providing the honokiol used in this work. This research was supported by the Missouri S&T cDNA Resource Center (http://www.cdna.org).
Authors' Affiliations
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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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Choice between giving up my phone or giving up tacos? Gladly give up my phone. Boredom seldom hits, there is always something to wonder about while eating tacos!
I have a piece of paper in my wallet with some 31 projects I want to make. The list just seems to keep growing... I'll definitely have something to do in my free time for next 5 years.
(Saying I speak 'some C++' is more of a catch all. I mainly do python and php/javascript than anything else at work and in my free time. Don't worry, I'll only inundate you with self-indulgent side projects if asked. I stopped linking them because my okc profile would show up in google searches for my web sites/youtube [same username on YouTube])
Billiards, I'll mop the table with ya!
Posture? Hazel eyes? The chainmaille I made, hanging around my neck or on my wrist?
Meh, everyone marches to the beat of a different drummer.
Artists, cause, why not? Caspar David Friedrich (Romanticism art, I call it early sci-fi), check out 'Cemetery In The Snow' and 'The Sea of Ice.'
Limitless, Fight Club, It's A Beautiful Day (a little depressing but amazing)
Unkle, Younger Brother, Infected Mushroom; Trip Hop, Liquid DnB, IDM(Like Amon Tobin, more of the down beat stuff), Industrial, Metal
Burritos and anything spicy, GI track of steel!
Goldfish crackers
My notepad hmm maybe its a sketch book? ..or some mix of the two??
A world outside of cities and civilization, or post-civilization
Sharing minds
Any sort of creative outlet; wood, paper, metal, fabric, 2d/3d digital, web, arduino/electronics
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Bars, clubs, concerts (in the mosh pit or raving while embracing the tunes), dinner with friends, the random chills that makes life nice.
Or at home making something trippy.
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Running around in circles drives you insane... Or.. hey maybe getting dizzy and falling over is a good way to relax.
If you feel like skipping the small talk, by all means. Actually, preferred. Seems like two people can get to know each other way quicker with their philosophies and reasons behind their hobbies, than where they grew up or like to hang out.