Sting

With his wife, Trudie Styler and Raoni Metuktire, a Kayapo Indian leader in Brazil, Sting founded the Rainforest Foundation Fund to help save the rainforests and protect indigenous peoples there. In 1989, he flew to the Altamira Gathering to offer support while promoting his charity.[133] His support continues and includes an annual benefit concert at Carnegie Hall, which has featured Billy Joel, Elton John, James Taylor and others. A species of Colombian tree frog, Dendropsophus stingi, was named after him for his "commitment and efforts to save the rainforest".[134] In 1988, the single "They Dance Alone (Cueca Sola)" chronicled the plight of the mothers, wives and daughters of the "disappeared", political opponents killed by the Pinochet dictatorship in Chile.[135]

sting

In January 2018, it was reported that Sting had joined the board of advisors of an impact investing fund of JANA Partners LLC named JANA Impact Capital, aimed at serving environmental and social causes.[152] On 6 January 2018, JANA Partners, together with the California State Teachers' Retirement System issued a public letter imploring Apple Inc. to take a more responsible approach towards smartphone addiction among children. The letter cited several pieces of evidence that show that smartphone use by children increases the risk of their having mental health problems and worsens academic performance.[153]

Sting and Steiner lost their tag titles to the Lightning Express after Gilbert accidentally hit Sting with his boot during a title defence, leading to a falling out between the two (with Steiner siding with Gilbert).[30] Shortly afterwards, following a match against Terry Taylor in mid-1987, Gilbert interfered on Taylor's behalf, costing Sting the match. Taylor and Gilbert then ganged up on Sting until Taylor's former tag partner Gentleman Chris Adams came to Sting's aid. Adams cleared the ring and then asked Sting if he was with him or against him in his feud with Taylor and Gilbert. Sting turned face by declaring his allegiance to Adams.

Lex Luger was chosen to challenge Flair at WrestleWar. During the match between Flair and Luger, Sting came down to motivate Luger to come back and beat Flair. Before this Sting and Luger had been at odds. When Luger was close to winning Sting was attacked by Ole Anderson. Luger opted to save the already injured Sting and ended up losing the match by count-out while assisting his friend. Behind the scenes, WCW officials had wanted Flair to drop the title to Luger at WrestleWar, but Flair refused, saying he had promised Borden he would hold the title until Borden could return to the ring. Despite the injury, Sting was still utilized on television and pay per views when necessary.

At Starrcade '91, Sting won the first-ever Battlebowl battle royal, for which he received a Battlebowl championship ring. Sting then became embroiled in a feud with the Dangerous Alliance, headed by manager Paul E. Dangerously. The stable targeted Sting because he was the so-called "franchise" of WCW, and the Alliance vowed to destroy both Sting and the promotion he was the face of. At the same time, Sting was being targeted by Luger, who had once again turned heel and, as WCW Champion, viewed Sting as a threat. Sting engaged in many matches with Dangerous Alliance members, especially Rude, who was the group's biggest star. It was during this feud that Sting won the first of his six WCW World Heavyweight Championships, defeating Luger on February 29, 1992, at SuperBrawl II.[3] The feud ended when Sting formed Sting's Squadron, consisting of allies Ricky Steamboat, Dustin Rhodes, Windham, and Koloff, and defeated the Alliance (Rude, Austin, Arn Anderson, Zbyszko, and Bobby Eaton) in a WarGames match at WrestleWar in May 1992. Dave Meltzer awarded the match his highest rating of five stars.

At The Great American Bash 1995, Sting defeated Meng to win another tournament for the WCW United States Championship. Sting defeated Meng in a rematch for the title at Bash at the Beach 1995. Sting was on the first-ever Monday Nitro in a match where Flair defeated Sting by disqualification as a result of a run-in by Arn Anderson to attack Flair. At Fall Brawl, Sting teamed with Hogan, Luger, and Randy Savage to defeat the Dungeon of Doom, consisting of Kamala, Zodiac, Shark and Meng, in the event's WarGames match. In October 1995, Flair convinced Sting to team with him in a match against Anderson and Brian Pillman at Halloween Havoc. Anderson and Pillman had attacked Flair earlier in the night, rendering Flair unable to come out for the first part of the match. Sting fended off his opponents until Flair emerged. Later in the match, Flair turned on Sting and reformed the Four Horsemen with Anderson and Pillman, later adding Chris Benoit to fill out the group.[3]

Sting returned on the January 3, 2013, episode of Impact Wrestling, saving Kurt Angle and Samoa Joe from Aces & Eights before beating the group down with a baseball bat.[119] Sting wrestled his return match the following week, defeating Aces & Eights member Mike Knox after he injured Kurt Angle.[120] Three days later at Genesis, Sting gained his revenge on DOC by defeating him in a singles match.[121] On the February 7 episode of Impact Wrestling, Sting teamed up with Bully Ray to defeat Devon and DOC in a Tables match.[122] On March 10 at Lockdown, Team TNA, consisting of Sting, Eric Young, James Storm, Magnus, and Samoa Joe defeated Aces & Eights, consisting of Devon, DOC, Garett Bischoff, Mike Knox, and Mr. Anderson in a Lethal Lockdown match.[123] After Bully Ray won the TNA World Heavyweight Championship and revealed himself as the president of Aces & Eights later that night, Hulk Hogan blamed Sting as he had encouraged Hogan to give Ray the title shot while also encouraging Hogan to support Ray's marriage with his daughter Brooke. Sting proceeded to walk out on Hogan.[124][125][126] Sting returned on the April 25 Impact Wrestling, saving Hogan from an attack by the Aces & Eights.[127] The following week, Sting reconciled with Hogan and became the number one contender to the TNA World Heavyweight Championship later that night after defeating Matt Morgan.[128][129] On June 2 at Slammiversary XI, Sting unsuccessfully challenged Bully Ray for the TNA World Heavyweight Championship in a No Holds Barred Match after an interference by Aces & Eights. Per stipulation, Sting would never get another title opportunity again.[130]

On November 23, during the main event of Survivor Series, Sting made his first-ever appearance in a WWE ring by attacking Triple H with a Scorpion Death Drop and also costing Team Authority the match.[149] On January 19, 2015, Sting made his live Raw debut by appearing backstage during the main event, then walking to the stage, causing a distraction and costing Authority members Big Show, Kane and Seth Rollins their handicap match against John Cena; this win gave the recently fired Dolph Ziggler, Ryback and Erick Rowan their jobs back. Triple H challenged Sting to a face-to-face confrontation on the February 2 episode of Raw. Sting accepted this challenge on the February 9 episode of Raw by sending a Sting doppelganger into the ring to scare Triple H, after airing a vignette on the big screen accepting Triple H's challenge. Sting and Triple H had a confrontation at Fastlane on February 22. Following physicality between the two, Sting pointed to the WrestleMania 31 sign with his baseball bat, issuing a challenge for the event that was accepted by Triple H.[150] On the March 16 episode of Raw, Sting made a surprise appearance and helped Randy Orton fight off the Authority. Immediately following on the WWE Network, Sting spoke for the first time in-ring.[151] He lost at WrestleMania 31 in a match involving interference from D-Generation X and New World Order members, but shook hands with Triple H afterward.

Sting is widely regarded as the greatest performer in WCW history.[182] Former rival Hulk Hogan asserted that Sting should be mentioned in any conversation regarding the top 10 greatest pro wrestlers of all time;[112] numerous outlets have placed him in such listings.[a] Digital Spy writer Mayer Nissim commended Sting's ability to constantly evolve his gimmick while fellow franchise players Hulk Hogan and John Cena largely failed to do so, in order to maintain spectator interest.[188] Borden is known for his charity work,[189] once regarding his involvement with the Make-A-Wish and Starlight Children's Foundations as his "most fulfilling activity".[2]

sting (third-person singular simple present stings, present participle stinging, simple past stung or (rare, dialectal) stang, past participle stung)

Interestingly, a variety of natural variants of human STING (hSTING) have been identified. The presence of nonsynonymous variants of hSTING, some in high frequencies is indicative of its implicit role in disease.

Once STING reaches the endosome, it is again ubiquitinated by UBE2N, which forms a platform for endosomal sorting complexes required for transport (ESCRT) recruitment. HGS, VPS37A, UBAP1, Tsg101, and Vps4 are components of the ESCRT complex identified as STING cofactors. Loss-of-function of the ESCRT complex impairs STING degradation by the lysosome (Gentili et al., 2022,Preprint; Kuchitsu et al., 2022,Preprint). Interestingly, a UBAP1 mutant that underlies spastic paraplegia in humans also leads to a STING-dependent IFN-I response (Gentili et al., 2022,Preprint). Recruitment of STING to the lysosome is, in part, mediated by lysosomal protein Niemann-Pick C1 (NPC1). NPC1 directly interacts with STING through transmembrane domains on both proteins and recruits STING vesicles to lysosomes. NPC1 deficiency impairs STING degradation and enhances STING-mediated IFN-I signaling (Chu et al., 2021).

The most common genetic defect found in FTD and ALS is a hexanucleotide repeat expansion in C9orf72, which leads to decreased protein expression in peripheral blood cells and within the brain (DeJesus-Hernandez et al., 2011; Renton et al., 2011; Belzil et al., 2013). Loss of C9orf72 in myeloid cells leads to impaired degradation of STING by the lysosome leading to hyperactive IFN-I production (McCauley et al., 2020). This suggests that the hyperinflammatory response seen in ALS and FTD may also be a result of a trafficking-mediated enhancement of STING signaling. Further, data from recent years has strengthened the association between lysosomal dysfunction and pathogenesis of FTD and ALS (Root et al., 2021). Impaired lysosomal function, autophagy and vesicle trafficking are observed in postmortem tissue from these patients (Lie and Nixon, 2019; Farg et al., 2014). In fact, several genetic mutations in genes attributed to FTD, including C9orf72, GRN, MAPT, TARDBP, TMEM106B, VCP, CTSF, and SQSTM1 among others, encode lysosomal proteins that affect lysosomal acidification and enzymatic activity (Root et al., 2021). It will be interesting to see whether STING signaling has a broader impact on ALS and FTD pathogenesis than currently appreciated. Lysosome dysfunction in some cases of FTD and ALS also leads to mitochondrial damage. Thus, a singular disease could display components of both ligand-mediated and trafficking-mediated activation of STING signaling. The contributions of each to symptomatic development and pathological progression must be carefully dissected. 041b061a72