M. D. Anderson Cancer Center - News Release

From: Subject: M. D. Anderson Cancer Center - News Release - When Good DNA Goes Bad Date: Sun, 21 May 2006 07:53:50 +0200 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0000_01C67CAB.B2983850" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.2869 This is a multi-part message in MIME format. ------=_NextPart_000_0000_01C67CAB.B2983850 Content-Type: text/html; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.mdanderson.org/departments/newsroom/print.cfm?displayPrint=1&id=3D75E1E3-A3C8-4BF4-88FE960F407DC588&method=displayFull&pn=00c8a30f-c468-11d4-80fb00508b603a14&PrintPage=1 M. D. Anderson Cancer Center - News Release - When = Good DNA Goes Bad =

When=20 Good DNA Goes Bad
=93Backward=94 DNA leads=20 to DNA breaks associated with leukemia, study=20 finds
M. D. Anderson News Release = 02/10/06

When=20 otherwise normal DNA adopts an unusual shape called Z-DNA, = it can=20 lead to the kind of genetic instability associated with = cancers such=20 as leukemia=20 and lymphoma,=20 according to a study by researchers at The University of = Texas M. D.=20 Anderson Cancer Center.

The study, issued in advance = of the=20 Feb. 21 edition of the Proceedings of the National Academy = of=20 Sciences, demonstrates for the first time that the oddly = shaped DNA=20 can cause DNA breaks in mammalian cells. Interestingly, = these=20 sequences prone to forming Z-DNA are often found in genetic = =93hot=20 spots,=94 areas of DNA known to be prone to the genetic = rearrangements=20 associated with cancer. About 90 percent of patients with = Burkitt=92s=20 lymphoma, for example, have DNA breaks that map to regions = with the=20 potential to form these odd DNA structures.

=93Our = study shows=20 that DNA itself can act as a mutagen, resulting in genetic=20 instability,=94 says Karen Vasquez, Ph.D., lead author of = the study=20 and assistant professor of carcinogenesis at =
M. D. = Anderson=92s=20 Science Park Research Division, Smithville, Texas. =93The = discovery=20 opens up a new field of inquiry into the role of DNA shape = in=20 genomic instability and cancer.=94

Imagine untwisting = the DNA=20 ladder and then winding it up the other way. The result is a = twisted=20 mess with segments jutting out left and right, and the all = important=20 base pairs that hold the DNA code zigzagging in a jagged = zipper=20 shape. Scientists call this left-hand twist Z-DNA. This is a = far cry=20 from the graceful right-hand twisted helix that has become = an iconic=20 symbol of biology. It just doesn=92t look right, and it = doesn=92t act=20 right either, according to Vasquez. This awkward shape puts = strain=20 on the DNA, and as Vasquez and her colleagues show, can = cause the=20 DNA molecule to break completely apart.

Scientists=20 have known for many years that DNA can take shapes other = than the=20 typical twisted ladder form, but they weren=92t sure how = often these=20 alternate shapes occur inside cells.

Researchers who = study=20 these shapes had previously shown that Z-DNA can form only = at=20 certain DNA sequences because the shapes of the bases = themselves=20 contribute to Z-DNA formation. For example, the sequence CG = repeated=20 more than 14 times in a row is prone to forming Z-DNA, while = the=20 sequence AT is not as efficient at forming this structure. = Analysis=20 of the genome reveals that DNA sequences prone to forming = the Z-DNA=20 structure occur in 0.25 percent of the genome, according to=20 Vasquez.

She and her colleagues decided to find out = whether=20 Z-DNA itself had any effect on the DNA stability. To do = that,=20 post-doctoral fellow Guliang Wang, Ph.D., made pieces of DNA = designed to form the Z-DNA shape. The researchers then = introduced=20 these segments of DNA, called plasmids, into bacterial cells = and=20 human cells in the laboratory. They then broke apart the = cells and=20 examined what happens to the DNA. They found that in = bacterial=20 cells, the Z-DNA caused small deletions or insertions of one = or two=20 DNA bases. But in human cells, the introduced Z-DNA led to=20 large-scale deletions and rearrangements of the DNA = molecule.=20

=93We discovered that bacterial cells and human = cells process=20 the Z-DNA in different ways,=94 she says. =93We aren=92t = sure why, but we=20 think that the DNA repair machinery may be involved in = processing=20 the Z-DNA structure differently in bacteria versus human=20 cells.=94

Since formation of Z-DNA is naturally = occurring and=20 can exist in the genome, the scientists next want to = understand why=20 cells can sometimes process the structure without creating=20 double-stranded breaks. They also want to know why certain = places in=20 the genome become =93hot spots=94 for these breaks, while = other=20 seemingly similar areas do not.

=93If we could = understand the=20 players involved in this process, we might be able to = prevent the=20 generation of these breaks,=94 says Vasquez. =93For example, = if certain=20 types of cell stress lead to breaks, we might be able to = find ways=20 to reduce those stresses and prevent = breaks.=94

Senior research=20 assistant Laura Christensen also contributed to the = research. The=20 study was supported by grants from the National Cancer = Institute and=20 the National Institute of Environmental Health Sciences, as = well as=20 an Odyssey fellowship to Guliang Wang from M. D. Anderson = Cancer=20 = Center.

=A92006 The = University of=20 Texas M. D. Anderson Cancer Center
1515 Holcombe Blvd, Houston, = TX=20 77030
1-800-392-1611 (USA) / = 1-713-792-6161 (7.)
Legal = Statements=20 | Beco= me=20 a Patient | Make=20 a Donation | Subscribe = to=20 Newsletters =

------=_NextPart_000_0000_01C67CAB.B2983850 Content-Type: image/gif Content-Transfer-Encoding: base64 Content-Location: http://www.mdanderson.org/images/NavBtn/mda_logo_print.gif R0lGODlhfQA0AOYAAI2NjVRUVGRkZJiYmGBgYJ+fn2tra3Z2dktLSz4+PhkZGUJCQgEBAXx8fEVF RU1NTRQUFF1dXTIyMiIiIoGBgXp6ellZWTQ0NF5eXlJSUh0dHUdHRzg4ODs7OyYmJjo6OgkJCSkp KRERES8vLzAwMDY2NkBAQA0NDSoqKiwsLCQkJL+/v76+vri4uLq6ur29vbu7u1FRUbW1tU5OTrKy smlpaaamppeXl0hISGZmZoiIiLe3t6mpqXV1daysrLa2tnJyclpaWo6Ojm9vb4uLi4WFhbm5uaCg oIqKimxsbFdXV7y8vJ2dna+vr2NjY7GxsZqammdnZ7S0tJSUlG5ubpKSkn5+foeHh4+Pj4mJiYSE hFtbW4KCgnh4eJubm7CwsHR0dJGRkYODg62trWhoaHFxcVBQUJOTk6Ojo6GhoU9PT6enp6KiorOz s3BwcElJSaSkpFZWVqqqqoaGhmJiYqWlpZycnJWVlZCQkG1tba6urnl5eX9/f6urq5aWlsDAwCH5 BAEAAH8ALAAAAAB9ADQAAAf/gH+Cg4SFhoeIiYqLjI2Oj5CRkpOUlZaXmJmam5ydnp+goaKjpKWm p6ipqqusra6vsLGys7S1tre4njEBSgkWAQRZHXeCRRdJBzMFglAJYoNcESyCYzFgdQtgW0GDTGo1 H249ZgAJEUMIa1BdWhhuPBYHUQFBCFszNYJVMXqCUxQUBBD4caRDhAMBGvxp8sZCDAdbHgypYaKH mwAGFuz4kyWGjB10YLSwogXIlhaGkCyB48GHESY+RjwR1CQFjT9QeAhi0WHZTgkBBlmZ86fDmQEd pv2pk2eNhI1V2uDg8sdNhygw/uwo02LDAQA02ExIw2NEmD9hkgjS0mXaijIJ/1w4wPLHx5Q/a26w mLOgxZcjXBAIOgMnRZU/QM78QaKhQIPDf2qkMbRiYYgfgmRIuPnniQQZWiv/YZHgCKEcKOgIQkLk TwK6DoQIOmDHx4WsKKf+EYLDRJFpWWfoECTFwxeOEr4A2SgFAehBOHrEOLzjxR/RWHAMKqJmNMo5 EoooHOkGAxkB01y4QNTksqAfIXqIEXNgQgUgBgaRNj1oSBoJPSzWWgKyNSCYFDn80YcHDSQBxh84 FEEDFT5koYEKSvjwxwPD/VHccX+YwQETgtygHSF7BDFDBFwoIQUh2Q2SRXhR8CFIDCNYJ4QQNJRw AwkTxMDfIe1h9ocMIxzxxf9fIVSBRxf6lUZIElL0EQISWAwo2w8SrBEGEn/wkMINOlgBYRZT3PZH C1ks0MEfwhFnnD8JiAZFUoQUQYAaQBxhQBswnviHDqVpcYUgQKhwwx8BCADECA8KMYMHaLDn3pEk cOYZaCywIBqHg8AQBWh2hGDBWQQKkgMGDQDKg5rT4PDMDFsQYoEPMXT4ITMLDGIECYsOUoMYMxy2 hGiCYPHGdt39Yd0ceOjAgRBFLOHCAB+s90cDCh3CgwqctTcGNSj44IIXFAxCRAc2vPBCEQ8OdkIW f3BA7x9jaBDgH2nI5IIfRTig0BgT8OECDEfEAAMCh/5BwwRNlFinUBLYcJ3/F1G4kEBrhujQqyAU OLDEEjDcQcWNl/4RxMlGEHDXITrg8HJ2HSoLBhABQEGIEE6UAUQDRhCiAxM2IACGdX8YYPGgCOwx hAU6xJADoGxssYVAR9jQgQBZAWDvbAl4QQgRdFgBAABGrDFDGdoOsgIQZsAhSA9qNFCEFRQ8R8EC bAzyQw450GHjIStMg7SnMFRmXaeEt9B2IZ6+INrkixvOgruhtlBZC0bIsMQfRrCA0gotvBA0ISz8 oO2xLyjlduTXuQXD5/qxQLsgK+yQFeGTMN7ICkhfZwmykrjwhAyuFwLDD7vjzgjxgniBAA59I5ID AjoYgIAaZPRQgxJ0iK2I/xARDHLGircLsgQ6DxiwBxAExOFGxEfmsIADCPASQwc9GBFFDGoIghLe EAT+yAAIGCBAABwwhDroBwtkUOACsLemJCxANoWAQhze8AASGcINDJgBIm7AgATxQAEa8MEP2pAG JyjgDc85xAJOMBNnYeEESjBEC4IgAjjsQApPqAIOFLCvJngABESAwgDOgIBlfWEEIGDDF4QgAQa0 BgHLYQEMhHACAgiCBjGgQx120AIf1EAEJWiCCxBwAvEN4gVHUEBQDtECBYCgUoZYAAOCJYEQEM8G GhgBSgxRAA8wIF6CyAADyGAIHkjgcdtigBMEgQARtM0GQxCEGU4wyBZo4P8CVnBAIXQQFBZwQC2F YAMEUPCCJoBAATopRARQeYgSMKB8GQQBAxTzBwl4AHpMYMAcCxEACnAABYQwgC6hRIgxXACSkWEA AP5QybYB70acHIQSFBCEjw2iBbLJwQUQgQUGeDEEIJgTIQRwMkTEQAIn6EMhYkAAEEyzl780hBkY IIdCFOBNVtijsKIwAwZooZkXOB0hpCCCNz3Akjsx0h9ikE1NliCgRyvEDoiYiAScgAcLKAIInrLO dhqCBXHAAggmqS4leIEBDfMl9P6gBZgWIghQkoEIBCOIKKjlAgyADL4SeggEgABOEP2DHAQgGooO 0gceoAtQFZCBK2zkD37/AEGwDtEAmGqECAzoQPDYiQgYzOAHDoAAZ+BkhzQwgCr4nGkwuyUIGyzg dPXU0B+ikI8nqEAEPnGmQgkRBQa8QJEbeMADFOBNigZtDgigi8MsIAIGMAACmSwCA3xyCCgw4AAO uEkPGBCDQZD1EGiFgWfzsZgH8IsB3ZKpIdzaMEE4YQIE2AIB9FiGnrLWBhCA5R/0QFRDJEEEIQKB DsJQhRqIEJtBM+pk/JaFAChgkUJgAB4SgQYQNGABNSSDOQVxWkPQIAEo6YACULKBu9jgs4KQbSHO AILpDpcDQwBCGcrQhRB4wDp8HQQUTjABGtCguIWwQAg2BAFt7UAMSnFq/2cUEAJosiAICqgCA1h7 iDuAYAomqOEflMCAPPyhvIWQQwnWgwfY3qG0YWIAEOKbz0JQQQXBy4EACnEFK+6Vw7thQAlswIHB DkICGKBmUudZUc0myBAymMARJvBfROTBA23ogIhZ4AAGzMEAJi2EHThAOw5oIAHEWAgDUNlH6MEg BQcYhAwSIE9CuICxfyADkP8QUAmoqRA3UIDFqom640hYEF124yB44AEYdIEB+ypEC0LQgBV8QMRr usAJSBDpQgBgBLQDAAM2MIg2lJDGyXtBAJ4riCFwwxD1/AEBnkyIITCgyoSwgQQGhwMRDJYMk5wB CK5aFwi0pBA4eG6X6f8qiBfs4g9tsEkhnpACBjCzEFLYAAOoAJoXcGC7s2HACNAwAAgIEwl28EIR LGCA4JX7A7F8YxAYkIBPVo8QAfAADeAAhwLcoAsxANMfmKCBEjZgCHHQACwDbU48/uEGGhDBDL7C Bw6EQK8uCAAINqADG9QBABZQiwy2IOMXEaIOEJixIQYQhSE4wSdSQJoMkjCRHoAhCWUQABmGsAc8 YPoFPTBADg5KCDTs3AlOMAAYIAlOKNQgD0CwAhS0xYI9CKAMeUiCEyxAALlx4QAUOAASkOWCwHCA AwswQAzrGoU4BIEMYtDrAATghii8jBDpzkUpZjoKFsiABs0jROH0M1P/xg0edz+ggUKDh7rKXI7v hGgBDXYgGk8V4vCFYDzvDAED4LggeYdggZ4MAAQy0GFI+qAlHICh0YwEYFx/IAIBagCEGhBgAH/Y QwIWMIMABCABYLjBDCASAQdgAESFYIITcgAEKkSgCGhxQAIQkIEAbGAGScDB0tSFgN074A1NnJ70 Z5AAB5ghAGZA8w26H4EILCAI9NPhDAggB08ZAQkpWEDbFgABiRYAAl5ECDvQAarBAkqgBO3yBy5Q BRfAATYwAijAA3LAA0BQWknAAFDQAgOAAhOwdn/QAw4wAOvxAmiAAygwAFsAAjDBA+WgBw5QYILX AxMgBlkQBg4gAmLA/xrmIQJxQAM8YAMJ8QdUwAA24AIF4F/ERggIwGoCpgD98HAJAAFmMgiK5AaF MARQ4n6GAEhM4AAcIGeLogMgEEtu9QyDMAchgGl/sAQXUAFdAAGDxAKLEgYMQFKDIAcbIBoCoAC7 swNooAActgZr8AcixRnBJHCEcAMQsH2E0ACD+AdxMAAIME7CcgEgMIWCUAYNMAYQoDOGMAdd+IWj NIaZIQKDMxookB8rRwQ9AIeFMAAXwFiu4wN5SF58OAh3tmc0BQKcQQPzYgj5xneWNwXaQV9ulANC IADSNAhlwAVDoADQNAgJIIqxhxlXQIpYBTGDkFUedHl/kAeu+Ad4MP8uUxABR3ACMFYXtXhitygI uUgTHaIFvLgaKCBRR0aNiKAGHIMC6ZgDrSFsdoAofKAGEwB6hJBWBOAEGyABn3ON/WQHQaBoo/WE hwBCQeAESjABOjEFcRB746WOetiOfwADgZQDTjACObSLgFIFQeBAhjACJKAITMBNBCAAIQABz5ED YLIEHwABDhR1CKAB6VMICzABXMAFQLAB63GNGiIB+PgHZUCEiTAEILAHXEABCWAxUzBHByBjIGmL zXNnC3AFYrAFuCSPoCEBCYAIbGRyhzADAqADXKAFFAABzKSTmYECGvADPcAFygh7hzCNg3ADKOGQ f6BhcSYjDGCGhwD/joPkBcexlYNgAG9FA+u4h2EJiJnBS/IIKGfAABVwCJp1bZ5mBsTkR3+AlzSh ARKQAxQQTJkEZS1gAk/5B9cYSxFwR3IGAd4UeTIwBOE4CBxJCEEAAl0wAyGZmbooj5xhASfAiDsx AgpQZ4RQEPdWIlr1B05wL4LABteVLr32iPphAXCwAPhoA14AANgoBQrwJoMABjZVCEDAisH5A2Eg BMMkCDhAb6Ylku84CHfgA2LYiwqwlo3kAQqABJ0HAzxQAxdwd4NAA7z5BCMQZg8HAqG5A/UmBlIg eWGQAB2AJFKGBmGQAyrgB115T3/gYREQPE4gAgagBy0gA0wQACHQvQQWwABhYAM30AMpkAQCcAFr BwMkQIkwgAO6KQjdhQB9UABIoAYjIANDeBaDAQIWEHiCsANOkAIcMD0JoATiSQhzMAMxEAEzoARb JQhEABkrEDVBYABOEAFisAJXgAAxsAVK8AAJUAQ2gAMdMAMY9HAzYAWuwwRKEAA1EAVbAAYtUAAz MAMWEARmYAIG4AcxYAY9kD5y0AWVoQUzoAY5wCnaEwBbEAc44ABwwAZv4AAxQKV/MADFpHeyugiB AAA7 ------=_NextPart_000_0000_01C67CAB.B2983850 Content-Type: image/gif Content-Transfer-Encoding: base64 Content-Location: http://www.mdanderson.org/images/NavBtn/printer.gif R0lGODlhLgAUALMAAAAAAP///9PT09LS0tHR0b29vampqaioqKenpywsLCsrKykpKSgoKCcnJyIi Iv///yH5BAEAAA8ALAAAAAAuABQAAAS8MMhJq7046837dU3DiAyzeCjGXGvqTuVSNmf7ujaV395q lr6LTGY5sTQ7STJgWx4xxNEsICtRjIFGlspUDpkmbWUxWBAIgwGawDgccuLuSEmnO4QEN+KAMOwZ ewk5My1xhTBdFQwDNAoMCiKCewoFOXc6E0ZNWxUNA4tqaWoJCApvBJipiXFiVhOeZmtonwkHDWg8 GrBnogKfBrcDilVAUgskYcQmr8cjIQtDCbi5HALWs2mz1Nvc3d7f1BEAOw== ------=_NextPart_000_0000_01C67CAB.B2983850 Content-Type: image/gif Content-Transfer-Encoding: base64 Content-Location: http://www.mdanderson.org/images/NavBtn/close.gif R0lGODlhLwATAPcAAAAAAAEBAQICAgMDAwQEBAUFBQYGBgcHBwgICAkJCQoKCgsLCwwMDA0NDQ4O Dg8PDxAQEBERERISEhMTExQUFBUVFRYWFhcXFxgYGBkZGRoaGhsbGxwcHB0dHR4eHh8fHyAgICEh ISIiIiMjIyQkJCUlJSYmJicnJygoKCkpKSoqKisrKywsLC0tLS4uLi8vLzAwMDExMTIyMjMzMzQ0 NDU1NTY2Njc3Nzg4ODk5OTo6Ojs7Ozw8PD09PT4+Pj8/P0BAQEFBQUJCQkNDQ0REREVFRUZGRkdH R0hISElJSUpKSktLS0xMTE1NTU5OTk9PT1BQUFFRUVJSUlNTU1RUVFVVVVZWVldXV1hYWFlZWVpa WltbW1xcXF1dXV5eXl9fX2BgYGFhYWJiYmNjY2RkZGVlZWZmZmdnZ2hoaGlpaWpqamtra2xsbG1t bW5ubm9vb3BwcHFxcXJycnNzc3R0dHV1dXZ2dnd3d3h4eHl5eXp6ent7e3x8fH19fX5+fn9/f4CA gIGBgYKCgoODg4SEhIWFhYaGhoeHh4iIiImJiYqKiouLi4yMjI2NjY6Ojo+Pj5CQkJGRkZKSkpOT k5SUlJWVlZaWlpeXl5iYmJmZmZqampubm5ycnJ2dnZ6enp+fn6CgoKGhoaKioqOjo6SkpKWlpaam pqenp6ioqKmpqaqqqqurq6ysrK2tra6urq+vr7CwsLGxsbKysrOzs7S0tLW1tba2tre3t7i4uLm5 ubq6uru7u7y8vL29vb6+vr+/v8DAwMHBwcLCwsPDw8TExMXFxcbGxsfHx8jIyMnJycrKysvLy8zM zM3Nzc7Ozs/Pz9DQ0NHR0dLS0tPT09TU1NXV1dbW1tfX19jY2NnZ2dra2tvb29zc3N3d3d7e3t/f 3+Dg4OHh4eLi4uPj4+Tk5OXl5ebm5ufn5+jo6Onp6erq6uvr6+zs7O3t7e7u7u/v7/Dw8PHx8fLy 8vPz8/T09PX19fb29vf39/j4+Pn5+fr6+vv7+/z8/P39/f7+/v///ywAAAAALwATAAAI9wD/CRxI sKDBgwgTKlzIsCHCZoei0KAR5VAzhxgTdhLComMLFi2CdMpIcqCnGC3QvDJn7hUaFjFGlsTYLEiL QwU7shByseBHFgOBzjyUMmcLlyxwEhT6TyhTklFYvCL4ceorFlF8GmwhsGNQkEG5EpzBwtzXqf/M taChNWdTgVyf/hP7lAaLc12PDjTHgi3VrW8DtxDbFORTKVLnJh54NevSoF3nRoYcuCBRNIPRDnyp lOpHyl6bfg5L+J8zjosHHmIRpOfMhp/IqmTpsoUMT1t1Gta9++Ng3aUFfhry0+MQ3K9JQks0pQYN KYeeJZ9Ovbr169gPBgQAOw== ------=_NextPart_000_0000_01C67CAB.B2983850 Content-Type: image/gif Content-Transfer-Encoding: base64 Content-Location: http://www.mdanderson.org/images/NavBtn/printerbar.gif R0lGODlhlgIFAJEAAAAAAP///5gQOf///yH5BAEAAAMALAAAAACWAgUAAAI8lI+py+0Po5y02ouz 3rz7D4biSJbmiabqyrbuC8fyTNf2jef6zvf+DwwKh8Si8YhMKpfMpvMJjUqnVGUBADs= ------=_NextPart_000_0000_01C67CAB.B2983850 Content-Type: image/gif Content-Transfer-Encoding: base64 Content-Location: http://www.mdanderson.org/images/News%20Room_tg_NewsReleases.gif R0lGODlh7gI3AOYAAAAAAP////z5+uHCzuPH0u7c4+za4fLl6pMmU5kxXJkyXZozXpkzXZo0Xp49 ZZ8+Zp4+ZqFDaqVIbqVKcKZLcKZMcadOcqhPc6lRdapUeKtVeKxYeqxYe6tXeqxZe65bfa1bfa5c frBggbJkhLNlhbRnh7VqibZrirdti7VsirdujLZti7hwjrdvjbp1krt3k7x4lL17lr58l759mMGD ncKEnsOGn8SHoMSIocWLo8aMpMeOpciPpsiRqMqUqsuXrM2ar8yZrs6csM+estChtNSoutOnudix wdu3xtq2xd68yuDBzuDCzuLF0ebL1uzY4O/g5vHi6PTo7fXr7/v2+NKluOHD0OTI1OTK1enU3evW 3+7e5ffu8vjx9Pnz9v78/f///wAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAACH5 BAEAAGAALAAAAADuAjcAAAf/gAGCg4SFhoeIiYqLjI2Oj5CRkpOUlZaXmJmam5ydnp+goaKjpKWm p6ipqqusra6vsLGys7S1tre4ubq7vL2+v8DBwsPExcbHyMnKy8zNzs/Q0dLT1NXW19jZ2tvc3d6s VF7i4+KJ4eRf0+fk7F4C3/Dx8vP0q1BZ+Pn4XIj3+l7T/OkbmC8Kv3oIEypcyHCQwIEG+g0EKO0h QYIFqDTcyLGjR2cW9XU5ZJFitJAX9WnR+LGly5cwZ6HEB4XkxIApc2bR8i6mz59Ag2aaic+kw5sV deaMIrSp06dQA1jUou+AoZI4/xWiMoXqwJ5Rw4odq9DilK+FsCbVaoiK13xT/8jKnUtXW0kDVdMi RfRFHEtVAsSlo6TW0IGBVhUFdidpMdhJ4R4XCvy3ruXLdUtyGThYUGFCX6Tg1VdgSmdBUaCohmKU ymrVcQm9ZkpIwIHR+AocjPSZ0Fl9NQ/Zxp3FwAHJwm/rM47c82spgrxEUWl6UGjcWqpj3s79KVbi sT3vHcTlLUEDlafD9T0weHR9tAX9vljgdKPeg6S0P1Q+pZbd/JmnEoCDtPfFTPUF0BV99nXn4IMe YbVZPlp01tuEOq00yHxZxBeAevqwt54gGKaU4CP4BfAFcVmEt6FSWRD4olIyQiTgQFGAeJF7EPbo Y1lIEbfbZ17AiE9EglCxHP8hBRAE1mH59KQkjNChOF50TaJFSBdGZjFSIVwa+WWBXZZZ2Y9optmN WhwiKdV4LFbn2kC7mUfIRSZlWdwgUOKjBUAC6IlPg4lYVMBrUNyYBY+CxCkfRIY4qiCkd9I3xRQz aXHAFFII6KKaoIZKjVpfmHdQYSW2WIigBRyVD0VFEhReXo3qs1us+chYaJkUSpaqixzGSMivIuZa qUpjBsBih52lyqio0EarTGEctvomWwEIqoUhYUb56IjB4pMYrsIKMt6l5UBClH9nZquSIeZZK4i2 8JJ2rJ9n6kerdftJ6++/xRRWqlakImbIFwN9SW5ifeIWHIdg4TgUr1A0Z3D/IX3ic28WiRGScRYb PxusUeYCB/DJKPfymb40XfuqIERkILPMJLQTs8wvqFpyy+7iwyFq+bjp8pFStNuICEhvMLPMItBw BH2IkJuFEEiLkMO3Lwcg9aeTYttvsUUZ8nXKZJcdy2cCfKUWDwi07fYOA9HgdgZZVDn0zlmQ+w5u HXdNkKbJMuL24ISXsIWT/A3kg9sivGcriVdqTSeZ+Ygc+dhmZ675Kb1lfMDahCPgQNxzLzojPlRM afo/CBtrnaDnkZxI6LRjQFDfp+OzeNuNS65PbCMbsjXlPIOdt9gmb6788qH0lvZySLEdehX6yN02 3e6R2wWG0OE2hd5bwU5Q/+CI0E47DAQ1GOzuCPQ+vN9hF/J+AJjDf3wh9TOv//6T4Pdx9G5LgNtA cKlLSQ8BBATQ71gWFxBtKmiImIL4KESoQgyOevi4AhEaMLgBDIRr62Oc48AVufnVL3j4Sx7/VshC R+BHdXgSBPtk5rYmDAIIItQLTQQCkPlAAUR2Ew4XDnAjrhnigv9owuCGQClCSK0HOUwVrCZXCCkS z3SFQGHIWsjFLtoEW7LJCUV+MLcquE0FN8whIYAgAgEiIAM0uALIAvACphUnC0fIQAiQVqCq2dBc LoAAAhIggip4qHxuw2DYBhcE8yiBBhhoWwRmsISB7CCH+lLCCyQgyRgosv9ug2jCDCI5SDheIWJ4 TIEDENAAFfwRfjswAQfbB4RutYyNbcNALb3IS/2lSGpsweH1stABt9FGmAjgwPcE0QUR0C4BSRDE CdyWD+u1DWRfIILbCJCOItBOBoJL5D+iMDggsGwHbiScCvRhgxziBZ20SwEEA5AD8z1gjvS7ZOiu 1rUrZIB2DXiaPkg5uAjgs5cILVuKhhbM0pmxbTMQBBSHeRBnmk8BI0EmBlMwOCQEgAovaNvouoAE 8yHAo4pAYj6eQFAEROF5DzUfDaopwiLFlHYzLQoyaReBNJrPo7/5p/kSIEd8UMB8GEioUsm2UGDG D5l0y4JQXeqFGsytQgH/8GbbJkC9I3ASovRzW06/2jYgCEIDbZNnAVDgNiNkQZ8ISGpK3SaBmZG1 bWj8UBZW2TYddKELO1UCPqwpArfs1W1B+Gtg/bQAt61Ajjf9o0URUAUoaDWuk4LrBWyYBYLKE49n /CtBUbrU0kprocqKYQCgig+43iAL1szAlwjKhHwowW0NEIQC2pazLKhTEG/DR+nwIYIM4MCsczWp JBWGTBFkoSczEOtg3bYBfCCzBISIbttyegUasGADo8vHVJFbupqowGpmPQtZsTAIcrYtAdNt2x+R IAIVAOGVps0vqFCbqqcO97CD7K7bPoAat2HAlmQFWQmG+dAI5DKsbROs/2/fK1CdLUK5vEtWC9wG BFAGoKRtI0F834gPjraNtB9mnFI8wGHgUlhkt22bBIxC0KdZM6L6zfFpI0eIZVEEmR7IB1xpQFhB gBgBEQgCkYnM15MGgH2whajbsto2CIh3cE1zgiMw3IDAWcBtKaBBDYIABO3G9TCxxQdZZwCENpfZ bRUgyBV2UMfdtjgAU0XACIDgoSkg0wE+cDMQHFzWLNw0AjlAsY4X7SPUBqC/P2acF/zB1wS0k3eC 2KlJzWoFtx0hpAhQ4jXriYAYqEfTvMMvItuGwRi3rQgWxHDbAtCFGwxX1m3rQpaOMNnQIRfV7fvj FKyp3JwelXAN2CWjl/+tvOYKQgBdEILbCN2+TOOavCe2aDOz/WoVdWEKQmAA7RR9xBoOYrI9JQSu EWDttoGACwJY97OHANA7Z3WWhEMpsH3NzF4bmNkAz5yzCUHtHB65d4qwqDBzS2pkHhKw/k737Mxt 5I4SgqCqNsTAMb6II7evCEyZLHKZicuCVhzTjRBlwREA64C7/GQDH8RlczhhJBdiOoVYOKaFSWiJ H6II+D5oueVLcDUGQAVua3kokzVwpHebEE1IFkFxLAiRIwLo1ISwzQmB80REwekIyOvLxx6tmDMT 3ygPALXxS0oR/FHULYZ72/j5oRwgTezIzLi6KS6ImcfnsghPMZJxPHD/wBMCxJN0MdGZSW2zRsHu 9fVpqAWx9ounOqvnNeggjE72zqfJ7O1WIzIjcEzcjolwsO5CvvfOyjkSlHysn/wguoBvqtP+zl1o fOh7d/uyMv7Oug9AE1qK7dYL4vWhJ33ou7xat+H4yHT3vPR9BHpaoz3wLRVBwVHc6zkWPFlmboAI 8B34QwxO1aTO9SA8HoFey7X5aWe/+wdh5va11PcBCP/4jZ797RfYwC2ld9M3gJhRffCXdvSDdril dKHHblX3b1yngG3TAIc0dLLXXuWUXeYjAmNidvWHZWPSBfeXS27DT1EggazkIVmAgg3AgOlHONFH gDJYgJx3dpzXBTOAlm8NMAMVeGTvh0wx+CH1t4OwF2uLp4HLdXgthQEMeIDlhwRL2IS0Vn/OVXMS FwVDOAPkg4M6yIOGUAQFhwHkNoNkCDBZ0ARCpwlNgIam0AVrWISL4IZRtwhvmHJsuAhnmIY3V4dl 2Id++IeAGIiCOIiEWIiGeIiImIiKuIiM2IiO+IiQGImSOImUWImWeImYmImaaImBAAA7 ------=_NextPart_000_0000_01C67CAB.B2983850--