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Gethin Jenkins will miss Wales' Six Nations match away to Scotland on Saturday with a calf muscle injury, interim head coach Rob Howley said on Tuesday.
Prop forward Jenkins, now with French club Toulon, suffered the problem during Wales's 26-9 win against Italy in Rome and the 97-times capped front row was replaced by Paul James in the starting line-up for Saturday's match at Murrayfield.
Two other changes from the side that triumphed at Rome's Olympic Stadium saw Sam Warburton, Wales's Grand Slam-winning captain last season, replace openside flanker Justin Tipuric in a reshaped back row, with experienced lock forward Alun-Wyn Jones taking over from Andrew Coombs.
However, although Warburton is back after suffering a shoulder injury earlier in the Championship, fellow loose forward Ryan Jones has been retained as captain by former Wales and British and Irish Lions scrum-half Howley.
Jones, who has led Wales a record 31 times, took over from Warburton when Wales beat France in Paris.
Coombs and Tipuric are on the bench, replacing Jones and Warburton respectively, with Scott Andrews filling the replacement spot vacated by James and Ryan Bevington coming in for Craig Mitchell.
Saturday's match in Edinburgh will be Alun-Wyn Jones's first Test start since he suffered a shoulder injury against Argentina in November and subsequently underwent surgery.
"Ryan has led the team to two wins and deserves to captain the side against Scotland," Howley said.
"We have spoken a lot about momentum in this tournament, and we go into the game with two wins under our belt, but Scotland are in the same position and it's going to be a good challenge.
"We have had two good, hard-fought away victories, but we know we will have to be at our best again to come away from Murrayfield with the result."
Howley added: "It's disappointing for Gethin to miss out, but Paul has impressed and made an impact in each game he has played.
"We are bringing in a wealth of experience with Alun-Wyn and Sam, and they both performed well off the bench in Rome."
Both second-placed Wales and Scotland, level on four points, have title aspirations heading into this weekend's penultimate round of matches, although it is Grand Slam-chasers England who currently top the table.
Leigh Halfpenny; Alex Cuthbert, Jonathan Davies, Jamie Roberts, George North; Dan Biggar, Mike Phillips; Toby Faletau, Sam Warburton, Ryan Jones (capt); Ian Evans, Alun-Wyn Jones; Adam Jones, Richard Hibbard, Paul James
Replacements: Ken Owens, Scott Andrews, Ryan Bevington, Andrew Coombs, Justin Tipuric, Lloyd Williams, James Hook, Scott Williams