![]() You can install or uninstall each Adobe program individually. While it’s unlikely one person would need every service in Creative Cloud, it’s nice to keep your options open. Fonts: Most plans also provide access to Adobe’s comprehensive library of fonts, which are compatible with every program in the CC.Before accessing any work data from your home computer, be sure to review and complete the Working from Home Quick Checklist. Whenever possible, you should be using your work laptop at home during this time. It’s included with most Adobe Creative Cloud plans. Tips Your work laptop is the best way of accessing your work from home. Portfolio: This tool allows you to build a personalized website to show off your work-especially anything you’ve created with the Adobe software suite.XD: This User Interface/User Experience (UI/UX) design tool for web and mobile is particularly for those who formerly used Photoshop and Illustrator to design interfaces.An integrated mobile app is also included. Premiere Rush projects can also be opened in Premiere Pro for further editing. Adobe CC includes 20 desktop and mobile applications for design, photography. It features a streamlined interface with fewer features. What's on Desktop IE, Firefox, MS Office 2003, Photoshop (Elements)/ Omni Page Pro/Adobe Acrobat Pro, Nero, multimedia software, macromedia suite IE. Ungasishintsha kanjani isizinda sesithombe usebenzisa i-Adobe Photoshop CS5. Adobe Creative Suite 2 Premium For Windows - VINTAGE SOFTWARE Student. Premiere Rush: An alternative to Premiere Pro, this program is for online content creators who want to edit videos quickly.Before you begin Check license availability. And showcase and discover creative work on Behance. Download fonts or high-quality royalty-free Adobe Stock assets. Manage and share assets stored in Creative Cloud. (Image credit: Adobe) Adobe Creative Cloud Express which enables you to design everything from social media posts to fliers. Quickly launch and update your desktop apps. Adobe’s multimedia editor gets an AI boost. Creative Cloud desktop app 5.7, or later. Creative Cloud for desktop is a great place to start any creative project. You can assign a product license through the following: Admin Console. For each user, enter email, select product, and save. You can also produce graphics for social media with Spark Post, or create short video stories with Spark Video. Go to Admin Console > Overview > Add Users. Spark Page allows you to make responsive web pages. ![]() Spark: These apps allow you to quickly create web-based content on both mobile and the web.
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![]() If the copied creature is copying something else, then Cursed Mirror enters the battlefield as a copy of whatever that creature is copying.Similarly, if Cursed Mirror itself is a token, copying a nontoken permanent doesn't make it stop being a token. Copying a token doesn't make Cursed Mirror a token. Then, you heat shimmer him and let the token copy die - you still get the trigger - so you go. You cast Godo for 5R, and on his first trigger you get Hammer of Nazahn. The combo costs 10R, and the deck plays Heat Shimmer and Twinflame, which makes the combo cheaper (7RR and 6RR respectively). If the copied creature is a token, Cursed Mirror copies the original characteristics of that token as stated by the effect that created the token. In Godo, the cEDH deck, this card is a must-include. Cursed Mirror Combos Astral Dragon + Cursed Mirror Bladewing the Risen + Cursed Mirror Bloom Tender + Cursed Mirror + Emiel, the Blessed Faeburrow Elder +.It doesn't copy whether that creature is tapped or untapped, whether it has any counters on it or any Auras or Equipment attached to it, or any non-copy effects that have changed its types, color, power and toughness, and so on. ![]() Cursed Mirror copies exactly what was printed on the original creature (unless that creature is copying something else or is a token see below).You may choose only a creature that's already on the battlefield. If Cursed Mirror somehow enters the battlefield at the same time as a creature, it can't become a copy of that creature.While it is copying a creature, Cursed Mirror does not have “ in its mana cost, X is considered to be 0.Any “As enters the battlefield” or “ enters the battlefield with” abilities of the copied creature will also work. Any enters-the-battlefield abilities of the copied creature will trigger when Cursed Mirror enters the battlefield.The new copy will still be a creature (with haste) after Cursed Mirror stops being a copy at the end of the turn. If something else becomes a copy of Cursed Mirror while Cursed Mirror is a copy of a creature, the duration of the effect is not copied.Wotc If the copied creature is copying something else, then Cursed Mirror enters the battlefield as a copy of whatever that creature is copying.As Cursed Mirror enters the battlefield, you may have it become a copy of any creature on the battlefield until end of turn, except it has haste. Noxious Gearhulk ALTERED ART MTG Rare Magic Hand Painted Commander. Similarly, if Cursed Mirror itself is a token, copying a nontoken permanent doesn't make it stop being a token. Mavin.io - Battlemages Bracers, Cursed Mirror Solemn Simulacrum Noxious Gearhulk. Wotc If the copied creature is a token, Cursed Mirror copies the original characteristics of that token as stated by the effect that created the token. As Cursed Mirror enters the battlefield, you may have it become a copy of any creature on the battlefield until end. Wotc Cursed Mirror copies exactly what was printed on the original creature (unless that creature is copying something else or is a token see below). Wotc If Cursed Mirror somehow enters the battlefield at the same time as a creature, it can't become a copy of that creature. Wotc While it is copying a creature, Cursed Mirror does not have “ in its mana cost, X is considered to be 0. Wotc Any enters-the-battlefield abilities of the copied creature will trigger when Cursed Mirror enters the battlefield. As this enters the battlefield, you may have it become a copy of any creature on the battlefield until end of turn, except it has haste. Wotc If something else becomes a copy of Cursed Mirror while Cursed Mirror is a copy of a creature, the duration of the effect is not copied. Cursed Mirror Cursed Mirror Artifact : Gain. ![]() Total penumbral eclipses are rare, and when these occur, the portion of the Moon closest to the umbra may appear slightly darker than the rest of the lunar disk. A special type of penumbral eclipse is a total penumbral lunar eclipse, during which the Moon lies exclusively within Earth's penumbra. The penumbra causes a subtle dimming of the lunar surface, which is only visible to the naked eye when about 70% of the Moon's diameter has immersed into Earth's penumbra. ![]() However, since the Sun's diameter appears about one-quarter of Earth's in the lunar sky, the planet only partially blocks direct sunlight within the penumbra, the outer portion of the shadow.Ī penumbral lunar eclipse occurs when the Moon passes only into the Earth's penumbra. Earth totally occludes direct solar radiation within the umbra, the central region of the shadow. (Neither the Sun, Moon, and Earth sizes nor the distances between the bodies are to scale.)Įarth's shadow can be divided into two distinctive parts: the umbra and penumbra. In contrast, within the penumbra, the outer portion, the sunlight is only partially blocked. Within the umbra, the central region, the planet totally shields direct sunlight. The symbol for a lunar eclipse (or indeed, any body in the shadow of another) is (U+1F776 □).Ī schematic diagram of the shadow cast by Earth. Also, unlike solar eclipses, lunar eclipses are safe to view without any eye protection or special precautions. A total lunar eclipse can last up to nearly 2 hours, while a total solar eclipse lasts only a few minutes at any given place, because the Moon's shadow is smaller. Unlike a solar eclipse, which can only be viewed from a relatively small area of the world, a lunar eclipse may be viewed from anywhere on the night side of Earth. This light appears reddish due to the Rayleigh scattering of blue light, the same reason sunrises and sunsets are more orange than during the day. When the moon is totally eclipsed by the Earth, it takes on a reddish color that is caused by the planet when it completely blocks direct sunlight from reaching the Moon's surface, as only the light reflected from the lunar surface has been refracted by the Earth's atmosphere. ![]() The type and length of a lunar eclipse depend on the Moon's proximity to the lunar node. This can occur only when the Sun, Earth, and Moon are exactly or very closely aligned (in syzygy) with Earth between the other two, which can happen only on the night of a full moon when the Moon is near either lunar node. Such alignment occurs during an eclipse season, approximately every six months, during the full moon phase, when the Moon's orbital plane is closest to the plane of the Earth's orbit. Latter phases of the partial lunar eclipse on 17 July 2019 taken from Gloucestershire, United KingdomĪ lunar eclipse is an astronomical event that occurs when the Moon moves into the Earth's shadow, causing the moon to be darkened. ![]() To make most beginner-level amigurumi patterns, you’ll need to know a handful of simple crochet stitches, like single crochet, increases, and decreases. Can beginners do amigurumi?Ībsolutely! Amigurumi can be a wonderful project for those just beginning their crochet journey. Amigurumi projects make perfect gifts, especially for babies and kids. Still, most amigurumi patterns you will find are for small creatures (Don’t worry – we have a couple of jumbo, huggable critters included in this post!).Įveryone seems to love these cute crochet animals. There’s a lot of variety when it comes to amigurumi – you can make your plushie as big or as small as you’d like. Japan, however, has practiced this fun, adorable art for decades. It comes from two Japanese words: “ami”, meaning “crocheted or knitted”, and “nuigurumi”, which means “stuffed doll”.Īmigurumi only became popular in the US in the early 2000s. What is amigurumi?Īmigurumi is the Japanese art of crocheting or knitting yarn creatures. In this article, we’ll tell you how to get started making crochet plushies and amigurumi, and share our favorite easy animal patterns for beginners. ![]() Want to try your hand at making cute crochet animals? You’re in the right place. ![]() What Other Supplies Do You Need for Amigurumi?.Stitches and Techniques You’ll Need to Know.Get it from Amazon for $59.99+ (available in two storage capacities and three colors). The free year of Amazon kids + that's included is a great bonus because I already pay for that." - Victoria A. I try to limit his screen time, but it definitely keeps him busy and occupied while I'm working or doing something around the house. The battery last for 4-5 hours of constant use, which is actually a pretty long time. He enjoys the freedom, and it really makes him feel like he's grown up even though he's only 3. I really enjoy that the apps can be limited, but at the same time, he has the freedom to download and play games and apps that he chooses without me having to do everything for him. Promising review: "I had a fire tablet that my son kinda claimed as his own, so I ended up buying this one for him, and he absolutely loves it. Includes a one-year subscription to Amazon Kids+ with thousands of ad-free books, games, videos, and apps, as well as a two-year "worry-free" guarantee. Get it from Amazon for $192.22+ (available in six colors and four wheels sizes). All in all, my daughter loves her new bike." - Ariele B It took some adjusting to get them aligned right. I will say make sure to double-check the front hand-brakes to make sure the cables are connected right. I was able to put the bike together by myself with ease. I suggest using a tool kit to help you won't be able to do it all by hand. This bike not only fit her, but it came with optional training wheels, which she needs because she couldn't practice on her old bike because she was too big for it. Promising review: "My daughter is 5 and very tall (48'), so finding the right size bike for her was important. Otherwise, you’re just paying for a plastic one-liter bottle." - Andreaġ2-inch wheel size is recommended for kids between 28" - 38" tall, 14-inch for kids 36" - 40" tall, 16-inch for kids 38" - 48" tall, and 18-inch for kids 42" -50" tall. It was great but really should come with an extra. We lost ours over into the neighbor's pasture the first day while learning and experimenting with water amounts and the psi. However, if you lose the one fin/stand that it comes with, it’s money down the drain. "This is fantastic for fun and learning for kids. A fun way to end our mini-unit on rockets." - Jason A great lesson in atmospheric pressure and thrust. And, it is lightweight enough to make a pretty fabulous game of catch-the-falling-bottle. We used a mini, battery-powered air compressor in lieu of a manual bike pump (much less tiring). The boys eventually knocked it out with baseballs, and it still held up! No cracks or busted parts. Despite our big, open field, one gust of wind did land the bottle about 40 feet up in a pine tree. We spent hours and hours launching this thing into the sky, and there's not a crack anywhere. I was pleasantly surprised by the durability. The set-up was maybe two minutes, and the kids (three elementary schoolers and one middle schooler) did it without me. Promising reviews: "This is about as simple as rocket science gets. Pump not included, a bicycle pump is recommended. ![]() Grolton is clearly in an open-top Jaguar E-Type, but in what was likely an intentional continuity error (or the fact that the E-Type was too valuable to destroy), the vehicle that's crashed appears to be a 1990s Porsche 911. The final scene has him intentionally driving off a cliff in a typical 1970s television or movie death scene, with the vehicle bursting into flames during the fall. The video is interspersed throughout with scenes of Grolton driving in a car, wistfully singing the song. Grolton becomes hysterical before continuing his pursuit. He ends the performance to give chase with the fans behind him, but when he finally finds her, she has driven off. While singing, he sees her amidst the audience filled with the ravenous girls, but she leaves after realizing he has spotted her. The scene is inter-cut with flashbacks about Jules. The band is also portrayed by the other Foo Fighter members, in attire appropriate of the era. The video then cuts to a concert in a mall where he fronts "The Davy Grolton Band" and performs the song. After wiping away tears, he accommodates and interacts with them. Upset, Grolton goes outside, only to find screaming teenage girls who want his autograph. Backstage, Grolton's cast mates read a magazine about him becoming a rock star, and later place his debut album on a dartboard and throw darts at it. There are various accidents and rifts on-stage (a fight between the cast, Grolton inadvertently hitting Jules in the face). In order to avoid confusion with the soap opera (also entitled "Long Road to Ruin") and the "real world", the scenes in the soap opera have brown tones to make it more vintage, while the real world retains normal color. Actress Rashida Jones guest stars as "Racinda Jules" ("Susan Belfontaine", the doctor's love interest). Bassist Nate Mendel plays "Ned Bender" ("Saul Goode", the show's shady antagonist). Guitarist Chris Shiflett plays "Christopher Mishomotohama" ("Little Jimmy", a severely injured child). Drummer Taylor Hawkins plays "Ty Hawkstone" ("Les Groper", Davidoff's womanizing colleague). Grohl plays "Davy Grolton", who stars as the main doctor, "Hansom Davidoff". ![]() As seen in the opening credit sequence, the Foo Fighters portray the actors who in turn portray the show's characters. The music video of the song, directed by Jesse Peretz (who also has directed previous Foo Fighters videos "Big Me" and "Learn To Fly"), is a comedic spoof of a stereotypical 1970s-era hospital soap opera ( General Hospital in particular), and is essentially a " show within a show".
Nothing proves this better than the brand’s wagon send off for the ninth-generation Lancer Evolution. Here are ten of the greatest JDM gems that were never officially sold outside of Japan. Many of its most heroic models have since found themselves as popular as ever, today, but there were countless other performance oddities that have slipped through the cracks. Manufacturers were flush with cash, and their engineering will went seemingly unchecked. This is also not a JDM car.Many moons ago, the Japanese car industry underwent what can only be described as a golden era. The same goes for the Proton Wira which many in Malaysia have face-lifted to look like its rebadged sibling, the Mitsubishi Lancer. Yes, the Nissan Almera was an ASEAN Japanese car (like the Toyota Vios and the early Honda City models) and designed for ASEAN nations so it is not a JDM car. Rust is unavoidable with old cars and you will need to find a good body restoration and painter to take care of this issue. Unlike a BMW or French car from the same era which will be rusting badly and will have an interior that will be more brittle than a cream cracker, the JDM will have a dashboard that might have loose door panels and cracked air-conditioning vents. If a sporty interest is tickling you, then we suggest the 4 th generation Honda Perlude or a Toyota Levin AE110 or AE111 (this are the models after the famous Tofu running AE86). If your budget is healthier, then look for a Honda Accord Euro R which has an impressive interior that is family friendly (it has 4 doors and spacious) and with a 6-speed manual shifter or look at a 6 th or 7 th generation Toyota Crown which offers luxury commuting. Relatively cheap to buy today and if restored well with its original engine and interior intact, then prices will definitely move up in coming years and the car will and can be a dependable daily driver. ![]() So, if you planning to join the JDM club and have a tight budget, start with simple cars like the Toyota Celica TA40 (the Celica 1600 ST is already too expensive), the Datsun 160J SSS and possibly even the Toyota Corolla KE20 (a barn find would be best to start with). American prices of JDM cars are high, but they also have a high price on cars from Germany like the early AMG cars and early BMW ‘M’ cars. Big JDM markets start with Australia, New Zealand and then it comes to Malaysia and England. So, today we see the values of many true JDM cars rising to unbelievable levels in Malaysia and also the rest of the world. For example, the Honda Civic Type R was manufactured in England and there were versions that did not do well here in Malaysia as they had lower power outputs over its Japanese made sibling. In the early days, it was a well known fact that JDM cars were a little more powerful over their siblings manufactured in satellite factories in England and America. So, if the Japanese car is manufactured in Thailand or England or America, then it is NOT a JDM car. JDM means (Japanese Domestic Market), which are Japanese cars designed and manufactured in Japan. In recent years, very recent, there has been a fast rising popularity for JDM cars. ![]() The term JDM has been wrongly used by many in advertising their cars for sale. By Daniel Sherman Fernandez 0 Your Nissan Almera Is NOT A JDM Car Just Like Your Proton Wira ![]() However, if you don’t want to be bothered to go down the hill to the beach restaurants then perhaps you should give it a try. ![]() We did hire the chef to prepare a meal in the home one night- although it was good and he was very friendly my honest opinion would be to just go out and enjoy the local restaurant- as we did not find the value in what he served to how much it cost. We also splurged on massages and yoga at the house while listening to the waves on the upper deck- what an amazing experience! 3-star beachfront hotel with outdoor pool, near Flamingo Beach. I highly recommend the catamaran trip (full day) and the mega tour at the buena vista adventure park. From the very beginning when I put down the deposit, when Craig called to chat about his home to make us feel at home and welcome us months before our trip, to all of the communication with Karina before and during our trip to plan a vacation of a lifetime, to Nany coming in each morning with a smilie on her face to ensure the house and our sheets and clothes were clean, to the very last drive the very steep hill…I would not change a thing! "I can’t say enough about the house and our week vacation in Playa Flamingo. We are just getting to know the area, and there’s so much more to explore." We truly hope to return to CR, and specifically Casa Pelicano again soon. Margaritaville Island Resort San Diego San Diego, CA Coming 2024 Compass Hotel N Myrtle Beach North Myrtle Beach, SC Coming Soon Margaritaville Beach Resort. And from there we were able to reach other areas- Playa Brasilito (Don’t miss Patagonia Del Mar), Potrero, etc. Playa Flamingo is like a lazy surf town, that seems like a secret destination that most tourists aren’t aware of. What we liked about this area, Playa Flamingo, is that you are not on a resort, where you never see much of the country. ![]() If you have never been to CR, then you should know how joyful the Costa Ricans are. During his day off, we felt lost without him! Hilton Vacation Club Flamingo Beach Sint Maarten offers a restaurant, infinity-edge pool and fully functional operational water sports and activity center, and three separate beaches. Reynoldo is a hard working and calming presence as he maintains the property, most of the time without you realizing he’s been there. This hotel is located next to the Simpson Bay Beach. And we tried many of the restaurant recs from him as well. He also provided vendor recommendations for our excursions. Max helped us to rent golf carts which are needed to reach most restaurants, beaches, stores. But you will never get over the view! Then on top of it all it comes with the service of Maximiliano as the property manager, and Reynoldo as the (garage apt live-in) house manager. You will feel blown away by this house! It was gorgeous, impeccable, spacious. Casa Pelicano was a perfect rental accommodation for our party of 10. All of this and all that Oranjestad, Aruba has to offer, including access to world-class fishing, snorkeling and diving, are here for your pleasure at our waterfront hotel."We traveled to Playa Flamingo with our extended family which included 5 children ages 15-8yo. And, with the vast array of restaurants and bars that serve everything from handcrafted cocktails to authentic steaks, the perfect dining experience is never far away. Our 24-hour Wind Creek casino is a high-energy way to test your luck. Ras Al Khaimah is world-famed for its glorious golden beaches interspersed with luxury eco-resorts, sophisticated islands, creeks and mangroves. In minutes, our hotel's water taxi brings you to our 40-acre private island where flamingos roam freely and relaxing treatments await at Spa Cove. Whether you choose our renovated, adults-only Renaissance Marina Hotel or the secluded Renaissance Ocean Suites, your well-being is our top priority, and we look forward to providing activities for you to safely explore Oranjestad and nearby adults-only Flamingo Beach and Wind Creek. In the heart of Oranjestad, Aruba, Renaissance Aruba Resort & Casino's breathtaking views of the Caribbean Sea provide an exceptional setting for an unforgettable getaway. Find pure bliss at our resort in Oranjestad, Aruba ![]() Can't see the menus in Direct3D after pause, unless I Win + Shift + Right arrow the window to the 2nd screen.īlue-Shift also changes cursor shape a bit and for some reason, mouse movement while in main menu is really choppy. I noticed with standalone Blue-Shift (could be the same for Half-Life 1.0.1.6, only have 1.1.1.0 for reference ATM), transitions magically start working properly if you change accent color in Settings app-> Personalization-> Color, but only if the checkbox Title bars and window borders is checked and you have already loaded the saved game or started the new one, just so the graphics stuff is initialized. Interestingly, it still works as intended on Windows 8.1. The menu window is actually active when you press ESC, just obscured. ![]() You're not the only one noticing this behavior on Windows 10. The menus are contained in separate GDI rendered windows (each submenu actually shows new window above the previous one) with some DirectDraw bits slapped in between. It probably can't be fixed without modifying the code dealing with menus and transitions between game and menu windows. I also tried completely updating the game and this issue still occurred. I couldn't find anyone else with this issue online, and I can't play the version of the game that I'm currently using (1.0.1.6) with Xash. I can use all three renderers in windowed mode and get the menu to come up, but not in fullscreen. OpenGL is the only one that works at the capped 72 FPS in game but I get the menu bug. Well, if I use software, in game I can only see my desktop, and with Direct3D, I can start a level (at a low FPS though) and if I hit escape, the menu comes up, but if I try to go back into the game I get the same issue with software where I can only see my desktop. If not, then all I can suggest is the the tedious job of looking on various Half-Life forums to see if anyone has a similar problem, and how they fixed it. Hopefully that will work without problems. I can't think of anything to fix it, sorry, but does it do it in all the renderers in the options screen, including software? If not, then that might be a clue towards the cause.įirst of all, though, you might want to try the Windows Engine port, Xash3D. ![]() ![]() ![]() The sunscreen sits on top of the skin and physically shields it from harmful UV rays, says Dr. Mineral sunscreen, sometimes referred to as a physical blocker or physical sunscreen, contains either zinc oxide or titanium dioxide (and sometimes both).Below are some more details about the difference between mineral and chemical sunscreens: Deborah Spey, a board-certified dermatologist at Schweiger Dermatology Group. While mineral and chemical sunscreens are both proven to be “safe and effective in reducing short- and long-term sun damage and skin cancer,” the difference is how they protect you, says Dr. SKIP AHEAD The best mineral sunscreens| How to shop for mineral sunscreens | Limitations of mineral sunscreens | The best way to apply mineral sunscreen Mineral vs. “Both UVA and UVB rays come from the sun and cause DNA mutations that are signatures in skin cancers and skin aging,” says Rossi. Anthony Rossi, a board-certified dermatologist at Memorial Sloan Kettering Cancer Center. The reason: Unlike chemical sunscreens, mineral sunscreens are naturally broad spectrum, meaning they offer protection against UVA and UVB rays as a baseline, no matter which brand or variation you buy, says Dr. However, not all sunscreens are created equal - some dermatologists favor mineral sunscreen over chemical sunscreen. And warmer weather often means more exposure to the sun, which could put you at greater risk for sun damage if you’re not slathering on the sunscreen. Most skin care experts say wearing sunscreen every day is essential to help reduce the potential for sunburns and skin cancer as well as wrinkles and other signs of aging. Other Occasions & Loved Ones Gift Guides All Other Occasions & Loved Ones For Teens For Grandparents For Bridal Shower For New Parents For Any Occasion Holiday Season & Christmas Gift Guides All Holiday Season & Christmas Last Minute Gifts Gifts under $25 Practical Gifts Tech Gifts Diy Gifts Graduation Gift Guides All Graduation For College Grads For High School Grads For Teachersįather's Day Gift Guides All Father's Day Best Father's Day Gifts For Dads Who Love Fishing Last Minute Gifts Best from Amazon Mother's Day Gift Guides All Mother's Day Last Minute Gifts Best Mother's Day Gifts For Moms Who Have Everything Best from Amazon Valentine's Day Gift Guides All Valentine's Day For Her For Pets & Pet Owners For Any Loved Ones Pet Care Pets All Pet Care Nail Clippers Flea & Tick Cameras Smart Gadgets Tech All Smart Gadgets Smart Watches Bulbs Garage Door Openers SecurityĬomputers Tech All Computers Laptops Gaming Laptops Laptops for College Students Computer Monitorsĭogs Pets All Dogs Dog Food Dog Carriers Dog Beds Dog ToysĬats Pets All Cats Cat Food Litter Boxes Scratching Posts Cat Carriers Cat Toys Headphones Tech All Headphones Over Ear Noise Canceling Wireless Earbuds Outdoor Home & Kitchen All Outdoor Raised Garden Boxes Garden Hoses Gas Grills Beach TowelsĮlectronics Tech All Electronics Tvs Wifi Routers Gaming Consoles Streaming Devices Office Home & Kitchen All Office Office Chairs Standing Desks Desk Organizers Seat Cushions Under Desk Ellipticals Small Home Appliances Home & Kitchen All Small Home Appliances Vacuums Air Conditioners Space Heaters Humidifiersīedding & Bath Home & Kitchen All Bedding & Bath Sheets Bath Towels Silk Pillowcases Duvet Inserts ![]() Kitchen Appliances & Tools Home & Kitchen All Kitchen Appliances & Tools Coffee Makers Cookware Air Fryers Mixers Kitchen Gadgets Sleep Wellness All Sleep Mattresses Pillows Blackout Curtains Sound Machines Health Wellness All Health Meal Kit Delivery Kn95 Masks Air Purifiers Eco-Friendly Laundry Detergentsįitness Wellness All Fitness Exercise Bikes Dumbbells Walking Shoes Fitness Trackers Oral Care Wellness All Oral Care Electric Toothbrushes Toothpastes Whiteners Floss Hair Care Wellness All Hair Care Shampoos Purple Shampoos Thinning Hair Head Shavers Flat Irons Hair Dryers Skin Care Wellness All Skin Care Moisturizers Sunscreens Acne Teen Acne Rosacea Lip Balms Under Eye Patches By forming complexes with DS, these self-molecules are transformed from non-antigenic singular molecules to antigenic complexes. We found that, when cells are dying or under stress, they express certain self-molecules to which DS has peculiar affinity. It is possible that DS is upregulated to facilitate dead cell clearance and new cell growth for tissue regeneration. DS, a glycosaminoglycan polysaccharide, is expressed most abundantly in the skin and other connective tissues, and its expression has been reported to increase during high cellular turnaround, such as wound healing. While simple compositional or structural changes can certainly generate a huge random mix of altered molecules, it cannot explain how they may induce autoimmune responses, let alone similar ones.īased on our studies, we have proposed a uniform autoantigenicity mechanism by which autoAgs share a common biochemical property in their affinity to dermatan sulfate (DS), and by which autoAgs forming a molecular complex with DS to induce autoreactive B cell responses. A protein may change by mutation, glycosylation, phosphorylation, methylation, citrullination, or fusion with another protein. Theoretically, a molecule may change itself in many ways by alternating its chemical composition or biochemical properties. A key, missing mechanism is how non-antigenic self-molecules become autoantigenic non-self. Thus, it is mysterious how these different molecules can all trigger a similar cascade of autoimmune responses. Moreover, the autoAgs appear to be a random collection of molecules that are expressed in different parts of human body and exhibit various biological functions. From a molecular point of view, certain self-molecules are targeted, as if they are non-self, by autoreactive cells, autoantibodies (autoAbs), or other factors, which subsequently leads to damage of the tissue where the autoantigens (autoAgs) reside.Īmong the hundreds of thousands of human molecules, only a small portion have been reported to be autoAgs. Due to unclear circumstances, however, the immune response can sometimes go astray and mistakenly attack its own tissue. Normally, the immune system reserves immune responses to attack invading microorganisms and protect the body. The underlying mechanism of autoimmunity has been rather intriguing. Any tissue may become a target of autoimmune attacks, which is why autoimmune diseases constitute a wide spectrum of symptoms, with more than 100 autoimmune diseases having been classified thus far. Our data contribute to the molecular etiology of autoimmunity and may deepen our understanding of autoimmune diseases.Īutoimmune diseases occur when an immune system starts to attack its own body. This study provides a proteomic repertoire of confirmed and potential autoantigens for future studies, and the findings are consistent with a mechanism for autoantigenicity: how self-molecules may form molecular complexes with DS to elicit autoimmunity. Protein network analysis indicates that these proteins have significantly more interactions among themselves than would be expected of a random set, with the top 3 networks being mRNA metabolic process regulation, apoptosis, and DNA conformation change. There are also 32 proteins related to the cytoskeleton. There are 55 vesicle-associated proteins and 12 ribonucleoprotein granule proteins, which may contribute to the diverse speckled patterns in HEp-2 stains. Among the 107 proteins, 82 can be located to nucleus and 15 to the mitotic cell cycle, which may correspond to the dominance of nuclear and mitotic staining patterns in HEp-2 test. Of these, 78 are verified autoantigens with previous reports as targets of autoantibodies, whereas 29 might be potential autoantigens yet to be verified. This study identified 107 proteins from fractions with low to high DS-affinity. Protein interaction network and pathway analyses were performed on all identified proteins. Literature text mining was conducted to verify the autoantigenicity of each protein. Proteins were eluted with salt gradients, and fractions with low to high affinity were collected and sequenced by mass spectrometry. Total proteins were extracted from cell lysate and fractionated with DS-Sepharose resins. In this study, we attempted to identify as many autoantigens as possible from HEp-2 cells using a unique proteomic DS-affinity enrichment strategy. Differential diagnosis of autoimmune disorders is based on commonly recognizable nuclear and cytoplasmic staining patterns. Autoantibody screening by indirect immunofluorescence staining of HEp-2 cells with patient sera is a current standard in clinical practice. Autoantibodies are a hallmark of autoimmune diseases. |
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