This soluction does work, but it does force all the letters inbetween the first and last to lowercase. If you want to leave them alone then you should use this:

#!/usr/bin/perl -wl

use strict;

my $foo="xoxoxoxoxoxoxoxoxoxoxoxoxoxoxox";
$foo =~ s/^(.)(.*)(.)$/\U$1\E$2\U$3/;
print "$foo\n";

#Output: XoxoxoxoxoxoxoxoxoxoxoxoxoxoxoX

my $bar="xoXOxoXOxoXOxoXOxoXOxoXOxo";
$bar =~ s/^(.)(.*)(.)$/\U$1\E$2\U$3/;
print "$bar\n";

#Ooutput: XoXOxoXOxoXOxoXOxoXOxoXOxO
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The original question was worded with what to do with the middle segment was up in the air. Just trying to add clarification for posterity :)