Em vez de conferir um benefacio a seu hospedeiro, os condutores meia³ticos conferem desvantagens distintas a seu hospedeiro, a fim de influenciar sua própria perpetuaa§a£o.
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0ZDXy2zcpUPj9a1eD1X6gII8N716x0zK1XkPqBdZezUq/PNu1tqv34GOljVcyUcRarGlNQrGLbgkJLGsbfLDY9FLPG7jUJ0Kn5p+tYgdXQoUdkNdyvgnQ7CQosvLYqoLS/puS9CD2KwZfA0A1gsFjWFoPmIvEZuq5gjRruZIjq4wPkYf8FXkVUKMswUWXls9PXrtdOUPxFcrFYN3khYzlsLXLag86YEDBPEfqEBhZ05GKS4X2csQossNhRGc10KmCQoos+pdnp7/pwEMO9vQaPbqH5iqWioF7rKw8etkgJBqu5Rm3F/HD/hVrWbLwsZixxTR3soaMhWCAnQ95Y8QTsqhaBQuGYKKW5nF38PT38f1m48p9VVsz1Z+KqecACiWWLWLr2tPQrpc9TV9N6rWqNV6W95jNhK/D7llKb9T43l/wAQdRH5R3CCy5nyqljVQF8XxhWBObolebLQkdy56ddJgy6s1vVe1crsWwfok6hO4BuBRLqShHrFwXni7qwIzFjRQbSAAMsoYX9Ma8U9WRFIYWP2WnSKpaceOA3f6jPvCpuWqwao7rwfkQtxjMWOK6GeKgQeAnAEKggKRZltBoSFFl5OKqd9roHW2lq4CQauqw9m38rHWAub7Qir+OOr9V38Fuva2AEmnpPBd0qvPovyqX6YUbObPkAaEK4Da7SdQncA3FQDFvHhV8156hgpwFLSmtPETgDJb783T6vAM5cqpY10hfBb0oM+m2weKVLt/L7IGs29RqAF3zeVWonkVTc6b6QHgZwsLE4//RqzNv4JZrJG4RqIexztlTcA1h3CCyw2GoaqwToM3JoteeTMeLiJb3f8Az6j2blY2+bn4p7ipK2XXge4LGYsdfFN3/r5Rh7FQWXM8AJNNX0xnrpR00tpZcVdQRAQR2tZhayYBqdR00HrBGwy8SrFYrhsgabIX7sWdRqEkmmrkc3fxSmjjGQNGUrPbIjB7BtCjAUna9h9YZwsZi0VSxVeIz1Py9VIWNXhX1Ad9pIAstLYSmaGmo42+X0beohO5XSzxK1QdnUFVcEHFlCvHRkNVhrKkMM2NsgExUC56nqOcX8ckAh6yMJbNjQ+Wzsh2tVVstZ57lXT9t38PT16GV+2wOpJOhY6lKe0+t6j2bwte4BrttYJYCCIyhoylYrcYDsZsfmyIXiVhME6D3fUt8vUWfIBJrqVe/rV+2m9qpXYtgjKGFtJSdIexF5QfGLLFrF3UNZKKzZZ3NWDAmE7LyFhOyiFolap3Wfx1WlGBDDFq/KHT2OpTFbch2O2yBuIoHf1K/FdhQpYr5dNSr1h/wAKquU9YstWuW2tZOmr5P5UQ2OtaqpGoDqBt9pAIvoNRVihp6oNmriLMowxd1QEYljTS1prRa17d6hO8NsCk/dm08rUoOorEQMD22DdcrsNZSxXGDUDPoxq/iIdNl/wROU4433H5ltXGepXfPeF1lvxqsDA6At6qe5TQXgAUeWhlyVwrb7fYu6SEalF7obeo+Ok7H+yW3tZACTT0kHx3E6wBuAawE1ZmpR9SFQYykYRt9t9fBoCQa+o32unKAfdl/xQgjBGB3WUbhBBqZgWfcq9YI2D9kstayKpY1dMF/QcFLKuoyRuej3dQtRHrHT8fpZ6iz6lldReVgVxXDdx+BAvgclbqrg+WSeoPkZYBhbUaziu1kiWK/ZZreWG1BIKuDnUHvus4kT1KyGTBOhY5sda4j8Irh/0LaxYGBU12skSxXwda7bOohO5XU1kv6c8OgPZ09HOaGmTWFs7W9D4m5ubm5vsvq5YrvIgIYR13F/Hs9y3p+yvqMO/Gf8AeyxN4WwiAg4/72eo1m8LXuW1bnTesW/w9PRGUMHrK4rt/QdA4spZJ6lNjFSd9m9S20vACTX0+spXwszR1GjhkBhBErbXYe8dltIeMpUq5Q13B47xfx7rKlePWyYA3E2giDbdrIGjKVgOoG+P+5J0GblACYqAZC6OLP4+n6jeXqBhBBpf9E118pyVXz1TfbXUbIiBB331/Tsp6hq4li2Ca3GXXbqanGcZqa7mUMHo0QAsHvwe5ZSoPrNQGu/iAYpG82xE34CNh0KPT1JWKwYRlDDgVt83qE7xxlqMjD1i1ObfAHKcpynKbm82ILFtpaoqxU1dUDh20POz4C7lnLkh5J3tZ2M86duL9u8kfCgizLDZ5TlOU5TlOU3m2sWLZW1ZR2Q1dQr4d/u8pOsBZ6wyh1HwM6mpqampqAdhGxb0s4ndPOtfZ8pOozbwExYgdahqvtZwsZi2VUtAgAtp4wfl2E41kjZyZqcZxnGcZqa7CAwt6YiBSSrsqVjb+X2QNfqEgRjswdQFs8rn5VdwDXhd9di19ltfB/2XcLGbkZTaPqeX1OU5TlOU5TfmZ8KpMCjXUUcIPXk1925ucpym5vssbWVQtAoXtYch2bnKcpynKcpvzPdhKi04Lxar6dvlM1NTU1NTXldp7ipkjY8p7hBg/Awtfk1NTU1NTU15bbORVSxSoLnQP9CByIAH6epqamprsf8AEDZVeP77fhXXzgAUf0nqcpynKcpym/1m/FRxG5ynKcpynKcpym5v9Y/I9DlOU5Tc5Tf9BqcZxnGcZxmv7jU4zjOM4zU1/e6mpxnGcZqampxnGamv/gL/AP/EACgRAAICAQMDBAMBAQEAAAAAAAECABEDEBIhIDAxEyJAQQQyUYBQUv/aAAgBAwEBPwH/AGmEteP+Qq7jXaVtspXjIRCK6wLnov8AztKu41CK+ErbTcKLlFiOhXzAL7Cgy44o9eJfYSPMGZzxPyFqj2Vbabm1couPjKyvgqxXxEJcciZaRNo61H3C/wDIAWjijo+LjcOnG4rYZ6KV5mV9x47QJHiBiw5mQUvHwUwheWmT8j6WBmKEaM209P1Fx35hYJwITemLLt4MbEr8iembqHvKgXkxst+IC2zQtRruE6YjTR8hczHgJ8zKwA2Lo67hAzJxFcNL0xjizC1+IR0ICIKY1D3UPMJLGY8H20zOK2ro6boHKcGKwMVg3jt4zTCbFBuZcreOhgPuVXiYyNApKwEiWGhFaKAosxnuY8ZY3D57qftAqrzMuVjx0PtrmX/JgAA7eLhp6zBrgZMomTEU0Y1KLQKBEqzWiPthVX8QqRG0KkxMH20yZvpe9i/aeo13AyvHTbpkybBAjZOTFQKIlc12K1RtpuNjXJyIVKGeruSjo3mFgsLl+BETaNVv6lxxR0Wsa8zIWbvo203GRcgsRkK+ZuJXR1BcXCwWFi/AiLtHcRyviKfUHImQBEoaZTQlE+YoA8aqsL/zQm9MiH9orETh++rFfED715EycLQ0zAS+fdEquO7jwActH/IrhZ6lrtOj1YuFQZRWKb0viunFmrgx8IblYFYGHvLjA5MbL/J6nt2nRq3cx8Qae7EYjbhfYqHTFQazMmUv0ZE3CK5TgwMGijnsY9wg9xqHuoaMZi3RkTdFyFeDOGExACwPgsoPmAUeJj61AAsxnuA1Cb+G4WuZu/8AMwCh8Ampy0CgQLR6yb+K77BKfKYmILFXb8Ai/nvj3Nz/AIz/AP/EACcRAAICAQQCAgICAwAAAAAAAAECABEDEBIhMSAwQVEiQDKAE1Bx/9oACAECAQE/Af7ptl2PRg5/059WTGHEt8RiZlYRG3c+jcPUxr9Mi5ZWA36cjL1NvHEwm18z3Noin0sLFS2xmK4aX8ewr8jxIuVUXk+eRz0IuL7jMEEwmxel+JHzNxijwbqY83w3iQD3CADxMfLc+xWqUGlalvqBZXOgHjYD8zJnA4EVGymzAKFDQiXL9WTDu5EV2TgzffWhjOW4EXFXcobtAti/WOIKOhgFQtFHzoDUq5Wuc220RUCn8opB68D6yahO6EMpGj9QALGy/Uxqf5HRH2woH5EKkQrXn1oq/J0MsxV8BodC4XJzCoaFSnIituF61CfF8oXiDNzz4AFoABGy2dq6P1LJ4mNB34Juvif9mW786uBQsZ70bqbRORAb0E6lw6ZcW8RXfEaMXIrCY+uNbgHigBNmZVU8mYv46Hqf5QBCzZDMeLbpk6mxSIVZIj7tETdCypwIWLR74vzsLDzqRcBqXcrnQaVUJvXIVqjAPqYTa6jyfEb3LDjZz+UArQmhBjLcxG28S70YWKgYpwYGDTbTaKSF4gUtAoTkx23HzZfnTvUi5VQcnRdDrkeuBFxXyYBUVQvWl6delupjyg8GFQYLU6lQe4RtPETlrOmKfH4xib59CvUKhpWpb6gWVzoJc712834kS/Xkw3yImVl4MLg6s5PAi4vubPyvRb28RXKz8cgjLtPoEHOhgFeANQi516T6yajHdOUI0cWIqBfDG+2NjDciUVMck9+fUv0g6N6K9dFzAoEIv0IxB4lX3Mvf6PUuX+4q7jLVIzkxmv8AQB/fV9o/pn//xAAuEAABAwIEBgEEAwEBAQAAAAABABEhAhAgMDFREiJAQWGRAzJQcYFCYLGgYvD/2gAIAQEABj8C/wCUmpP3/sdScJx/YiLOExg/2LjH7u1UhOP7C9Gm13BTVQcDD+uvTBTG7GQnCYf0nwo6Vqk4kXj+leFCnptJwR90oK4qek5beOh5lFK5gyjTAw0QzqT4Tj7KKh/FPStjt9lNS/0p6ZC15lw1WlQuKj0hncQ7Jwtj9l4qPp/yzfJPlPSXFqgNB0UZ4/K5fVnpCdPgBGpz3o9WaqQnFj0/BV+st6IKaoMuRMICqPRxgNJ1ByuEdlzfoptSuLsmpEHC5wFecvYqU4jqSE1chOMrhqHEV4TnRcvbompwlNXrkE25NVNJUBebsJKcoDA1ubLbW09QxTFcpTGDjcpqYFnqgLk1HZV4AR3zJXjFGqYrcKLvc2jA5KamBfjOHzlTfmTjVVPck9KxCeiRbn/WFyvC5Qpk2c6L5CNMDH6U4L5MrlU5HlSnCar3YXKYYGpkp6jfir9Y5tCnXC6m0Wcqo3r/AAuGvTfpnad7Af8AwwUhPVATAWeorYbKqrfA4+kqPS2O2QwtOVB/ShTgNvKepMIF2AT1ScqBZsAT1X3Kcp98Dduy3Gy5T0zjTBRx6Xb45O6eouU5ilMMDEQnpmmzfJI3T0lwmHQRfmVOHynN3MBNSMxkMAJs5TUxZ6sLVLendOE3ye7CmnfoJu38kPxekrn07LYbJgn+X1kPRBXDwqDqmwxaMmLniQwf+rwn1OeAMANnKYBOZOQ/xx4TEN+Vwgll+OiajXdN3OA8VnMBNTFXnKmw4fpwsdMLYZvKlU3dObc1nTJ1zZbDHzJtMmJKcp+yb+J6CVsEwTn6sFAXF8npOJFmrkJxii0qFx0fvOJN2oTlOdMFVuKvW7BAkIspCbbI8qVGGkJ6tVFpUYXKYQLPX6TdlTUPpfPajXdOVsN1GH46q5TiziCmqC8JxgZRg4KNEMErxbmxFOvFnr9YalxHXBKYFOUQCjji0qMNJTjJ8KF5s5VIH0vncA/aYLnnHTVst6dk9JsxCcSFUMHhRZ6im0pTdu+OFOLypWwUYql4OqcX4kCUQDfzh8ZIqXhRdwjer8JzpeddlOmy4uwz2GQx0T60p6SxTfJB3vWKcDWb458pyXK2G6anKbAU59ZFQtCi+y1XLYYCvCjJcaKE1fu5a5fZN3TlN8ftSnMUphpnGga/7eLMcMp/i9JimHMNk1CqOCdE38UwT/J6UZbjTBUTrlONDZwmrjzh8psBUZb0QmK5dFGAhTDKdE1IdPXJ6AhNX7y+fVRbkweBon0C5RkzkE93UwbxiYrxfcbKMHnARbzlsZtKi7riKeqAoEKOg8pitxso9WnE1HtOV43XJoNQqxg4qvp/1M0KLc2fxDWzVynFxhlPR6wNX7t5xOLSoyItKen0qr1/hcdf6ClbizVe+gapbhQucfvDKYfSmCev1eqofywcNWnbxglN2z3EFMVCbQpghj2Km0JnsMXlSoUjC9owE73qfZcNet+WCmK4T+uhdrAHU4AN14UZHjsmM0p6TaehYqDCjKlQW8JhlSos2AJzkEbrhKauQnpL2lUjz0c+0L07JhktUvG6eksm+SDvbz0EXYwgcjlwNSm7HKGBzlTrumqT0lMYNhSN+jYps5in+P0maUxP626KbgZbJ6dEMoZ7EOE/xyNkwC4eJ0Psc3Dadz1LDBzYARoeq834ex7/AGKLsy4qfp/xDNL5TDBGFupaj3aYC4WhUt9L/YWFpux6qevYaKFMm8/fT9hq/C8Jh9lbrCvP2AhMP+L3/8QALRABAAIBAwMDAwQCAwEAAAAAAQARITFBURAgYTBxkUCBoWCxwfHR4VBw8ID/2gAIAQEAAT8h/wC6a/8ApCv0nXXf9VVK/wCrX/v73/UmDHEI/uH6j/EnzAOZ83Tj9RedyaNMsbTP7of1FS04er5BNyWRs7dMv6b8Rrle7h1w5M/0RPZeObP6HqDteYIlj9LY/wACygNPZw31sn+Vmh7/APIn0wv2MTDWDNr6WuFz/ZqdNE05hCt+rz0oeDP6HSymIrhG1UxGD1vNfR2E8ladiveOfWxpv/wxnyU2cwYlj9GglMpz8OmM1iuRvMr+udlng1iXs+WPaXyMzUGXG/UTbsazgP7p4s4fWMnuJeX/AIVjHl7S7mNzZhWHyvpCs4eYpz0pTTb6wObRor/BGAVPxFzfZmi4Ws7PTM4EAUKJlBnflDY+fWYtTVL81ME+z9Ua+kglOYjTvcQKNjTEpjfKDgJudNsF8+uPuiaoC6QP54m5yessPMAsm9eUMhiPrDzxFIm13lQ8rns9tq/n13FLG/RTfyEsjZNC2WOBp9MQdT3enZVcezLHlLM8b3pPcGeY3h09baOiOuIAGOhiakz2A2yK8+k7fI+8wFl+xKcHgmWpjmHgSacECiut1ddiWPyvbCFPpsse7KAfvKLdOYvgShvP067JqRa+8bkuSJ2ad16Dg4l4oK4EDFlDeCqVoT1XUArRA1a9fKOZdv47BsLdkCmLl6HgA6KiPIjGt9pjVDzgnKnq9bb/AAsvDazyc9lnyJngSC4wefTagHu06Fd9hzABqkwn0/w4eJX32eZaqPE+MPpmvjtcLRLz3Td6f7d2ELj8iEbiafPZoJ+iFgeYA6EWpiDEBVGs9/dezJaOkSgpJgH2Zan9ui0WxUdX48aglA7GCInzybvWrTl07TyICqSmaRk4gmHPHS6Q7TLjwBxAVom98IJoH8ygFZrqOggzMOT6TOES59g3JvN3DY6xXzPYpagl1fYSlfcmY930crQ1YZCqlf56ukR67/EMGDx6PtQGGTzEq1bHMGOYTjXnuHzjYx3CzmWIpj4GSNOaduCu1j89l9/BEz4dbqD27wGE84cy18oeTLsDajXR4A5hGH36XNxHX8dfyMwn8eEKSzT1Tv0y4IFSehZOdl7CcFzH/tMxhHT7PRuzMPDDo6YHYqhlx4lseN1pCKHyu8WNyzggW0QXL+0ACj0EBSWQF0OYAFCiCRehexU3iIrNYIpxwlkKnxg9bAln9DPoqGsoKgdHJ+eezUJ/gOuC+xLI/biJc6wIjoxUtWrmYn7qWzJubnU19DfvL3xNURYginNzIlf4gQjrXVSKp2xNC2WP7YidCbs9+C8w2NBodie8pZfzRBRs1lD++IPAnEoLs7w0Ougb4jmPmcfzBpsl2veoLWLhgdFycE/FztEU611FhzERR2hZ/YSztvX+4eYoPR4eiPQI2869028NE2Vc79GoeNjntq1Z+0duAEqJuQmsbAiWaQEmKWx9XRGvTf8AhPHRgcr8T8F1DwMkffH7olT7KAhVdiVV/wCvmABRg77Cr8bEbkP4iOKuriKfYNOaL1hAaJ79Q2DpDx2GbY7tiuhMo5eh4WO347AiaoqtuvRjD7w+T7/pbRDM5epvLZewMLVueCXRmXKf0q99CUzeB8IX8Dqw3kxcYnbJ777jWUvA0a89Q3f4IW1JAoDjHVyNmx5j2P8AUT+wRUDk3Po4DVjOU2XY1g1YBz5h1/en/qqgiWadA1Re0LDxHywIAoOl+f2l0wNiMB46kq0C4zaz03MDjebUYOIYymrH2iWwleYg1kc9zhSyBWnRQWtEXYnMqHYz2FzLoRVW5Zu/CABD0eK/iSyNs1Xg6sQGnBXqmpCAhrv0uTzsbzE/ZIaG1g6gvx2N8GWXgft/nHG79rpQ+4bkvTY9umWM4xOemYwIAoYhXoGzjzNGuOoIO8ah+YphxxPHPHSr7Qu5DpdGYG4eZem2OR4/ns/CgK0ECgXw4msYeYtn5iOtbExgCIAZlowTKO1koVWNOmMMwhalAgKDsKBnEB1P2xjOZx0fHIgC1jtuRQT+1GGcEd2IowHhCwuq/Hq7zOHWUfM4REoq7szP3UqRzu7vaPVCyv5gAljv0/1jswATDc7iCdN7MI0I7QmccvS6Myop5vM/Aj1oQmRM9CGMjmay7jbHsWhzLAftEc44EBVBbNCIAwdn4sPUtnjrVxluALcywMDaJlwRhk66dupDU2i4YnR8sSAKFHa6S8fEBJY9PCPMQz8xFZ8QATTsfwNCLbDmaFnk9ARADVY2Hg/f1srZ1StNsUHLxsQqsadzpNFTGKgyVcnHSiJJ/W7HrZM9iq4AKwOmHrg5mBe1zBWxld+dwZQ7/HQb9it7tolizFdfIwzC3nurk0qKVzoIZWx610aOsLQBMuCBbRHYNphHR26FDvE1PLz3sg2wzBs7iE5Z3OjSU5nhPE/K6/nJ/wCHuACgx0Lz8BrFdm0RhZ/O+qRdXOWaK/PMTVEWIXi9rs7WElEZdGHWeCU37UZqYmpTDpnh6k8bxHBbpLTO+EWKTdmGeVQSWP37kaovs6G+H+oluXYnuaJhPMOuZ5U4hOO1jNU6bsG5Lk87nXPEHL8ZR+fzHDLF2P44+TiKVWEcawRBvTtAKSxjvV/bBVap6IGljZ0aTpvrXjWmwg2iUgBvNT58VVq1lP8A5yGToaHqk2aD0bTf+PTzDtQQFjP/ABfxESCJswNdFZo71YW/a7KWXQ3moUG3MBCq7E0PjwAAUd2mNZd6xYDR0otR2avL4OOmszypzBRsmjde1qT+LpYimFTIj27AFmISqxns3U2Wrbo51lGnRWdxbhxK0ozdzcOkfHAgyeXr5kKmVW2RrPDQl/ClFVxbH0GiBHDAdt6h168xHvto9qawoUaPywL/AMxs2s39+xUp2hMk92aBffeeAeO5ZJrNz0A6agFXsetufjMrhIqHnsUjYywa7XrhT3ENyzx2IGvd2eYCWIwzGuOptpMO9jG37TQoKIoLwIITRx1BFoFscfYOIiFmwbsd4vCHZZ49I7uMnRigaSYX7qE555a99aFsq3YRWK+Y5YVyQgWv3DzEvYw9XSfj4jbULlkdKsZHMvfs0KgPdKysrKykvrR2e3MyM20cy8NnQDe82HagKFkQvOdQo2NPSQiWNkAUZ/ZBUrrcezyvc56YjMgNq+mKc9qgtY2GJ0bLElfdI0nk6/mYdAwrx9mZ/wC5BRsaZbsv0CjH33JmfukFVqmfGjlEfYgKqCO6H7pWm2FuWCgo6DhYCzz2Ho+9Bkx0yphjtCWrauzRG43MzMzC5aHX+wGUZpl0dTNPZlnBz6Gyv3YzRxz0RULY3jX8HShd2Y05RDCI7VRm9DDPYCxEWdNiO4TyL1Av3dUDiwWIFX8HnrnfYbStFMdfQx6OJ5cbdBh8HjsQH5Ma45yjH3el9ysVnlT4EuJmq8cdEChZHeMj20lZSUlZSV20Rsmhvu1hlD7wWBahgr0EAgsl4pQAKaOtiiLo+O9pOELQfPRSDnseicIP3gAUFHeTugpjLZ/MoLuXclFA8dK0P9Q+zB9dQZi+BxAVxA1lz42lqVjpyjtncOuTaLuDSKDt4kt1plj9pmGdsWcLxKn9oMPEKjdNvX2fnFvLG9sYo4aEvfVO9QLWbfymuvUjJndlKuHuaRVgLpL2DTzAR1vsAdAj2vOwp2A04Sgns7MwofzP9A70IzjS/HrUPMW22I64IAMdGOk/iChbFdUsqLl5eXl4PtAQLHZmv8+bu8JrJvSANe76wC2J4kBcE3vj0pTrsxEtTuI5eIhl+3VTGnMaUu9bjb79sx9yb9lGDoc+oo3HsFkZtLS0tCTsOBJzP8qAmphNXDniN4zb6prG4jqy+lUqVK7zYy1B0AqOn1i6uxE8SAMej5TzNdegW0Tf+EMYOu+O+OzaBcAPpNXb4R0UC+IF+xqw1Zscr9U1Jj379xCb9WnGvmKrbrPCnMGsg63vP2+j8b1S6aLlCVlJSV7XlW/XwBzCMPv2iq37PEoYO7xF+o9Ie8zEGXTbWO/JGnj1d7gXMXLy8vBwgPU/moCqDMEzm8dQcLEplVjj1GXvEbmZmZhct1Kx4i22wy0QjObx6i4uXl5eDhAepwF/MoBuZL+B10Oi4+vUqVD1TWP+4wmjpf0NJWVlZSV1/CiUEMcvP0FSvWdJ5RFbjcysNHS5f/A7ksNIqWlpaChI39L+NC8jX056v6UeYJYWgRi0tL9BI/XsvY5BIV9LfMWLL7bly4MGH0L2PdCf84qMPoxwk+ob/oav+2b/AFY/r6/0bf8A9O//2gAMAwEAAgADAAAAEKw4z61w9/8AOd/PtPOMcsv8tPPfPvMMccdvuf8AzH737nTDTDzz33jTLnXvnrH3Lbv/AN43zyw53/77zxz/APfPOd/M9+teN8OMM/8ALbffjDLnfrPLDnbjPPzvf7XTHLPPDPDHPPPbzH/jHbHTjr7nr/n7nHXTbvPTf3HXfzvfnPzzHPPT7Tzz7zjPPP7HPTnf3bP77v7nfjDTzXPjnff7Hbn7vDPvznPPTzzz/wA887/z3+8z868x2z83x6z960053x7+172w0y828x685z28x06z+84x2zz0938y8x35++5065w206y1820xy9z3938yz87z80888035eM3zx9z083273x9y791255223z839235+5+534z+4z72sskMMMGsLi87z87y3z8w9009407720w215521+++08z+xz28hHNPOMMNPv7MIJ27w058617887712958/wCeON+fM+NuN+N/sDWfCQQwxwwwhT5uYjYvccuNMtdO8uuscO8N8u9evtibsP8AHfAU4nBa34wgQgQz+6i68MAujvJ4TPXbvXfn3THHPjDTTtPrTr/oc8g8ORoAMcs88icOM8IwoQOPgnkPLnTLj3XHfTVAV/fj8coFoA8gc5yBW8a4wQUhLXA+8SfA4r3bvSn7LnXvjXrv7Gli5npuHXY8oAcdWU/4miVhEMom+ssIR6B/E84EX22XPDDLzvrdjK5XzQM/QJJ+06f04AADCVIaW+4gkAKXe2q74Q+51WOHrnv/ACbDynYoi4/wDjBBDwsRALJKfrJo/wCcxypdy/CiSrl8PMx6t8Mu8PBWjtVOGT9+foPy8MvYi33RBB7yREVzwUpNb+QGit5KwqOuvtcWKuH+UynZHw5CfAzqhnwjUEwA5Bc7rwBx4T9GQ4R+hASXeOMt81qNwG/KmS8AJ3wD792DBev3Txp4RxzhaWFBN8EMnu00GscNevvuA17XdKF//sIv+wdiBgTrY0MgBi6vIRxPCl/kciCtmX+Yt9MOut1dtnJkgTvFu+FhSyxTDAy93zASad5AB04VMzJhNPK7dKfMsdc0wJk2MExhd/MCfoxzDCxnRwUQgo4Dxzer3F8Okzu9s3WKvtOOuOmv/v8ALnz/ANG4iez05rjA4CAADlLn84y/mCF+5215+OUtF9w340zx/wAu/MudtAgjydue8+eJBCLBiwjT7M+vf/t/s+e/Pi/+PN+M9d8ucu+MM9Nu9t8vPs+//vPPMNzxjSge8/M9OOe8ff8Ajfr/AM0zy3z2x2w+yx28z+528wyzx+84884z/e89x2/z27525203516wwxwx41z/AMe9vdu8PMfPOc8+9/vPP988/PPc9PMsd/M+8ONsesNcMeMOfOtM9NuP+d/Mc/NM8889/d8sMtvf8ctcsuc/uet/d8/9uee8+/ffc+dt+s/d/vMd/MuO88ce/PPPO9/vPttO8v8APTvbj/8A84w8872z800x5+5/w3+8x/8AfPvONPvMW8ufPMO9fvNuc+/+vtMe+MP/xAAmEQEAAgEEAgICAgMAAAAAAAABABEhECAxQTBRQGGAkVBxgbHR/9oACAEDAQE/EPzTzXKIjT/DpQiI0+F1ENkVqXK3oqCJlwlc+FqERU/CYR1O6EXoRQp14L1mIi6XMane5LUZcy92PhYRGmcxPPEGi+vgoWtBxoO83KdUOUTEaLTKbWNaGJCTI4G1NrtrMrpmAGPMGgK0Qvvn/Rioye9BAeGDeylxj5YEO7Iit0X0IXbmU3QU+EZzK0BWiB9sbCFMeNDNd+MJ6NAFTiZ5+pkcTX4NUVtxAMQK0aELijHKIOdmfupiLBSnlqvM4iMPTWlT7jUBbGKJ038Rbl6X6rhcTMvVK2NICoYNaWM6nAwJTLlagFwOJ1QTm2BK2cS5WjaVEbcxDobKorWpwHne7FQ1cHF+pQnmM/Wgm4JthMWmIvqAXD9MtedGjuEf6YQbsjrU4i6JLBbKLoBTzHX1oX2RvomPEzdO/mU6iaUMGd8zTEU/Od6ARcIzHocxzqb3DZy5jUujI82A4f8AERMO25ey4mtDHauNxdD1qZKzH+iYTwCkwmqdqYOFeudAB7gm5O1E5YRiFVuLy0pnI0VAxzErwpL2LWpgIAqMaYj3KUtAfA1oGgXCJlDd9EabCu4JvS+0o9cGlSeJyfCMrUFwQmPVN16Aqj6tlXOoNTwHtF60QeAj3o2f2UWgRZAFXg540QWBzBSj5QtY5nZQs5iER94i6N/EW/CXA5kYjXPgULgRFZLF/DdaVjUAuc73wmbZn0w2TvevL4p2MLh4gfthprv4F8gAUfOongQAKPwy/8QAIhEBAAICAwEAAwEBAQAAAAAAAQARECEgMUEwQFFhgFBx/9oACAECAQE/EP8AVtf8b9CsQLPpX5aouG/j/dQrnqWDqUOZan9PlTtgiWfhUKgimD0l/ClYuC2GiCbXN6DENzy+IsoVD1CNRIn0XkOuAaMQtMTY8yPtPebIy3pW8G1PFrpNnUoN8ArCWfuhwMqNzTsLf0XXyIrJq5Raj3YgDiw1xYj1VnnGGWCyCO5SHxL9iL0ajqMEBbE/CFtCJTvDuPPkFwRcpjNyAIZoiLbFyI3IolUYcB3NSXBOBDOt/IzbHeiIlYN1hmoZqbWBl/IVBmmMBfedgirhGGyLFEHt4JHUuzcvhcevYXuP+GZNrRCkAhwQ9MDQ1laLitsBlXgIu4k21KPp4KGtXK7ed1qAWzoHWNo0VEWHgLZZCmWovBau54glquIV4wJH9Z6PF8+7m8NxqVx3Tt+5TjqBu94A1Y1JELII/uEX8gnpHtwV5iSvZbaJWKFRdWAGprYwqNQFYHZlzLaNykUagmmG11KHNQO6QBRi4Zu8DYQAsxbQ/wCEM1KkmFEMah3pFs5r0gpNDIDcbdMbY4Fsuuol7y/7EaEBRAEwB1EubXxFuoYanG6J6yTUFuRtxi7Z5OqCN+C2j1ALJcct1Fu2ahMXpqCJZCViu/jbsgzTFKhxrh/YxGNQGFAtjsfaagOFdH/mS/6IlDzqBJV1GXSiHwXIOxEYVTfwozricQFsvaI3SYSkhGuFinqARdhpgA8xUKYa+CDqLZv4FvqHNcvC0XC0hOoAp+JLRcpefv4hbNQpjY3zCuV8UsqABR8XoIho7isUl/gUE7/OsQ7Yqtv+Mv/EACgQAQACAgICAgEEAwEBAAAAAAEAERAhMUFRcSBhgZGhwdEwsfDh8f/aAAgBAQABPxB3xPcau8Um9Srm8JDmWOAh9Z4z6xUYDf1ipUqBjiG4GpWNS5u4xJX1lLlSpUqVKlSpUrWK1KxXyrCZY5ZUr4GLnccacH3OSHPFYI4vdR5g3xL8y445nuLgjLwXe5Xc9TrO8cysVmn8SsB8GoGp7muobdlSpWKYcx5nvCStzqdX8EgblSpWtSs1K3GVKlSpUqVmqzWKnEY8fH1DWPudY7nPwZxCrlzkl+Z7leJYkbwEfrULjh4hU0fCshish5nvBKxWQEqb7ldSpwTmP1KbnMrFalVisHG53O8JipUr5V8KlRyblSokSJH4JNri5+M75qF8y9x+4RIFYdE+7nO2cTvF7qbiXh+5dS8aueYfc0mOcVmtwPMDJKlQMVA84qVCVvB8KlYrHuVKiWQMVK18q+HUqVKiSpUqVKjvFYqyVKw8y7cMqbucG4n1NzaTvUfeeohe9uHGom9wNbxe6iXAppclr9Ramob4lTupWEueoSs6yymvjUrHeCd4qVmspqmEM1moE9ypWOZUZUrfwqVipUq5WOZWGcuoFdSp91Kybn7ypq8+5eHHMrW5uOuIXmrc+pVsSoEX4GeMVKlNniVDnFfCoSpUqVipU3muMcxlSvhUqVEfjWKzUqV8awma3KjKlSmpUqJKld5rF/UY7wY0M5hLx3im+Zw8QIZ5n1A1vBTjmBio6IP6Y/Mqc8YDCiGaxUqVKxUJR8a3jv518KjKw5DFSsVKlXHHc6jliXKqPwuX8O81+YkFOZqXKOYFtypU9SsVOI2bjDKsOiepUogQJW5UQhDeKlZqe5UrKSpUqBjUqVK+P1KzUrNYr51nuVuVKn1GpU7lfcrNRneOc+46jd6jbKo1D7jTgne5wazUMFM5lTxn8TiVc5gXAEIrJKlfGs1DFSiVKhKlZqVmpw1juJK1KxWKy5r4OHUrPf1PxOZvxKmvMR6jnqescQmsPMqWy3uEqBUNzVyocSsui+ocyoD8AgjqAjzkPPyqpUrUrPOaxWKlSpWKxW/hUSd1O8VK+BKlfFJ9Tv4VlMblVHub5IEcVioRuW6jzhgemckcVvGvzgKwYqdxhCBKIErFQNyoFRhDFfOpUrFeMpmpUqM6x3KlYZW5W7+TGV8KlY5nMSI3KlSpUZUSbuM5j945w/WK3h38EuXqbWVuMogWSqjNdTvDxDZDiBKsq51PrASoGd4rBjrNSpXwqVK+FfUr5MrNalVKlSvjXwqVKlfHvDCOe+I4bnqdziVjqXhy+YQvBvuVDREhup9BK1DeCDAnBOcE7wYolTqHErB8CVuGDFfCpWa+RRdqPjWKlYr4JKynzqOH4MY49Y5lRJQRn4jOsGyENyjuVDAblTrUMVmtQ1xNYOM94veD7lfED/P7+TVFJYfzDggNeJ+VSvhUeZv/AAVhzRHCYZVscUT8zrDj3hIkTdw4nUDJeBviF94rcrWmoTmHMqEqBirJXx7+NZTNZr7+VSvm4Z/pOB4lpNnJyvn3hz1HjTlxxmsVh+HeKjKleI6jHoxUq4kruIMTxA4hOpfiDbKvH4nUMtQ4nMJUrISoSpXwr4VD41KlYr/H5kcIigUmkgR4/vDCnxvHpmsPzrcqfUTDjrFSt47x1j1O8M/GHmdQvzisOGOV+occQ5hjuBK/aGyVPc6lagfG8HGO5XyrN7+fWa+VfB3tcQ6fOa6ziP8Ahcobbs6lfBQ9RHnDOvm/U7+Dhwyok94qJHXU91UrxipuVGMfqesG8HMuEIYqvgc4IcysMqGd1gMVv407c1DB86+TEEUCPIxhTkDn0+s3ZftPuVtPlv8A+HwBVoFvLfEeWVmtYJqN46leJxCMY5cc4ZWGVjv4VHLzAwncqzAme5xg9Y5wTn4VDHE7+B8Ln5V9KhCwPCfDmEr4V/gScSpolzJ/xUTvPpzRW+JdnplE/Z5PZD2++EfxNvUjy/D6z3HiHGWesJ4nMqF/BN/BlbwmOs1ggeZrmcx3CE1CEJ18hKx3ms1Uq4cfJ7DoWL22cnj1KPE/1O8Vnv8Ax1h1O5TCOns9MurS8H6mG9KPL4I3u0pOf/GOGdrFfCoxl4qdYreXzOTDdzudx+f+5UaM1GBgNwxT9QE4nDNVms1KK534+fOQ/wAIIFiUkZi1Onx9MvMUrPb9M52YqDukMvw6m/jXxC3C8tL3/wCRbA0BwGgwFuva+IdtaF+/D6/ydTfcuwEoWn18K1KriVKlET4VGdzjcMVhjOYBf3K1A+oH1CVKhz8esbB0fEsg8fG5Pp+POHcr/DU7iABHkYttx+v8REURHwzfPU9epablFglRqrbT8O5X+CsXna43KXlf6mUpnkpCKA3Frp7ySA0Wq4Ip3dt8+39RU3S1fT8qjqV8HG1vY8hcK3Ds7H7lZfhUeY+ccawxncZziok6hxK1DjUMbhk+L7FTQ8u/1JzIuXggU8y2/wAecGA0vyPgfJgk8GXJb9Nan7y9gsprr5Oa+O6Gmjy9ETNS2nA8EWlwUFqi3UezofUQE2AirdSsv/fZT5AxScw49PuKTpSfvO5X+GpRghLtp5IDtuzp9wor8x0+nFaxTV/c7yzqoSpcYmWfmPEedQqcYKhAIvi53ps6Z3DHEIGUAASkeEiSOYef7ENKBsRpJRl4Q8PZ3AKBpNSwLdV3Cb2IHyttnea4lfEM84Irnwim2vEZoWy27Phz+IbqpZ8HJ82Acbf0YmAXX/DmO0oUunqIlZrw+7GjKtTtYEembcFyrlYQIHqpxvcPLnXescfJnCrGnnhloRbDr1NjvSTaHzdP7gMaeP5iiIAbV6jLOYP3YY5csS8uHBvHMCuMciK1hFH73w/xN8OOuIYN4Mt2jtp/8GIQnz2eTzNXA2en7lcrTY5/8QwxtQ+3eKhhxXwGzjNS8/bO4Rej95WhWCkdzXghrNZoD6LlfLeSCW6vscn6XKyRrThePr3GQnpQ8EsFuA+fFeZaZqbXACHAUZtDb97/AOQBYD+N8R5y0caQP9k4CE2efvL8PWKxfl9Q0+5pXvgcPqE6w5XD9V3Nc6ejuIr31+MJcqIRPmx+BxitQ4ncOnxHQbtvkYfYHRz/ALCDWvhITqES1PUv4+LRF5e+o6iFxwH/ALAF2B/A+5zvyptHz+f8runLolSLZuNv9MPEKyX36EKmrSVc3qIwtlD73cFQcR1ffiDZp+dEcoktu73PMEdL9niJaHkpuIDY7TB+3U/8T6yZT/Z9v6j1vOWKfyP6dxjj7GCI4bV+jKV/2L7g3VbwSraI1O5UdY9wQq80uFv/ALieXXs/8QCjRHBUcvwcG8XHNVCsmaF0mz5U4cng49JdZblbH2SvoXs6fT/GBRc9PM2gvKHwKqfKset8b/wqcv3KS7kr/ippztFtD+4HECEetsEut+NxgrKxwYPixncVA/L5xVUeDtl5b4jl9wSargIdDTuWd1AOgHbz9RspWxla32Hj0znBOVyYBEoO4ZhQ5cHD87fEoVXl7cvERiLz3DW7v/4Vl1oHRejzj8mGE6w/v9MUuDpi1L7U4NdlzhInK/p8HccpV8Byxivwv5gIFXognc9H+YhENp6+jLXFWjzZccc9OfoQQEESxO/kcRl7qdYdYrIwnOGpn5GbN8z/ANLlJSm5WeJ4H39e9zdG0onFHgqBil07fuKHocfBLjHyuD2yjI8g0ejAHS2nBCDlQql8r7ayFVeJv6zZ2/J/UKkWlacnxSadsuDk6Yg1dnQi1Cdsp33FwTVFrld/Kmmjh5J6jJ4f6hBZcJDb4HA0+/EdcJ/eFCfGSphalEFQXbf9p6hxHRNOeG7/AHO5ZwuvB6MoqY5bv7f6nXwR+o9alN2dJyRJa+sf7mntvquYQGPkdf8AsuLzW3LHH4DyxY1r+03x7X8SubO1y4X1Bx9viapbaHg3HA4D/wCMM+EN+1+v9RAQUWJwkYX8HiV5IxwzrcH3KlfAigsA7Zo/irG37/8AeZy+VhVBrSdW/wBz3kQHYr7r/wCyus6fPr9QqQ+AITVAvBv0Eo1hdD+75YMNKfbV2wzzRIjt4m0tvkII8p5vx5z9sa64l4AWgnPibyfZ8xKBXwTU5rq/7gIQDgM18XIk5E0wGIXRv9+ofIHRKF6y/MAAA1ioh3WkBvQ4ZqwHPl6icI6O31HWzxHb7ch3PolXRyHj0+56iSo8cfEDbnqbEHmp/G4ZPJqDudYT41LUIoN8n95xxowO28JePfibCvHT0isUVYfXUcC3YUnkYAS7PC/uJF9+049eJseBt1+DNEi0XuJHDXjHEsYdm4QhO8E0zvx8e4ha9HRKcfb0RLsCl4/SGLHoe14YglgD7rH5lBwU9rVHqAGijqooyAG1epQA4l8PXmcgQEgwkH7fof3CSHoOj4ASLSMSt8t/7f7gJEDYjVTZDiDw9+ZwhAVDS0il4i9lE+4cRkFzihmg5XBCihz+qJYUwdNXzOpr411AS+t8nbj8Wnlnco8XT6nMmN5NfokJqlUwsSvMGq+2OHt56zQWJ28+hKqB29vtzfx7gGqr5iq2qs2vB5jJ3T2cxH/Y8jNRcUVR9Pmc7O40CXbLgXy+X9RVVVVilNzXn2+pVHqVhia+cPa8kecx0Ovp8TjKslJNCOAJp9n9QEgosR0y9JrXezROWHFVHHcqAHGepR7PfibXyz6X6cwAKABwGKiw6Oa+ffiPm/4DHWp4aqe3/wCRgWJS8vB5/iW0264vz5msCwFrAW08gdfl/EJkBoAqpv5bAPdf9VE5r29PN8VBU1uNfgfzAZ27+ifXWBhhdDa6IHQCUIgEZvv9ERGkplRs/wBIhBVj8P0uHmX19HiboPvxKn+EIRPFJp7v6+5pah0PBfwqRS46DyxEiraveKpoOVoPc0IHoUHozWPx8A8S2212+YFUFsA3s+Os1ptH+j4aRwWMEttN/J9+pur8HR6lyS7ej3Kugt3WvTDm2XuKACOke5Yscq3b09S2O2gUH9/iKry3Zz+OiVO33f6jljGfSHMIJeDmDQ8s0jatv1De3/GocSwFWg7YeqcTyPTzAAu6Xf5YRvAB+MdS2UaspelS+f0BwPBBBftTfoQdbCkr9D/GOfnrnrOvcu3oOiA6Gm1Wglm1MXk9r4iEEedjkvDilxgWPR7g0orhMCab6Yxss6Ylq45IJKw4njQJQ3dJ2yiIDxhYS+hyy0lPDwQEqTjjiKvtL8RL7W/X1hmr+Q4r34mgEDwOCa7kB1XKxPDLwGo3J8kgI1n5EEQREeHG3Hcajuoj8HbBNCv5nHEciDlZY29vZigeU/BLYabefMYso2vmcFwdHl9+I1MOun8xjGcs1L6w/UuK/Nen57liP7BBU70W6+vcIxb/ADdK+b+X3HHuUXeK7WdbzEhsP/fU8TkzcO1F2/3XPt7iNXaCa8B29DwZJyq1o+9EFA3v+b+kQHyex6lo2aSL2+j/AKXCYeMjCVLhFAoAcrL139QzmUtvj7ZX4RqkZ8YOxK+FSv0ySdgplPNPHlLt9xcMEq/tfxFYgUlkPm0moVjmHvAKidRCKAOVl3Rxr4P7iJLcrHDDaH/uoaKzrXIBCugO4MByj4/swvTwiVk2PA4YIGxo9RvIm2zxLuiNH5jZoOWyIvIteviKH1LjitvRHXubaPAcEoR7eiFz9vljgYF6lUHlYYAY46hRv/UE451Kaz98ge4sdzmdxWLlLLK36HftAoBV4CUFg8OX34hUypWmqm30Y+d/6Y8yrwxi46nfwEA3wy32oP6wCiPDkF9eYnNrUtYmA8gf6O5zNOX/AGQMDB3LGjAdcflUJkKwcJi4o8gfqEsYXT0+mWp2v1v/ALHcs7H4Mz7t/bN7Hl6IF+TevUIhFAG1YP0N/wBp9T9h/wBYeK1D7lYiMRbfN2S0bGmUN36glRICarufWRx3hyPBPMGbzx3WKBeNv9+YZcnAE2e0f2gAFBwHB8P+H7JVMXhzX+5zxhApBPuCVoy/WHgpwUx4lDlgkVGimI6DU+yX8QoHKR7pDtfEsr/P2/1iru567YHIHjPUYB9qPS+SG2FYmDrT6X8ykHXQ4Z1UefKInaxuXQrQG2MqUb/2mvKeXwf3CtfJzfjxGFga+AS1Gn+XZtjyzcXDNRnqGCe53GuapR8v1ASV4Cessf8ADGgseBWD4FkqPovh/ad7ztPH2eJQoPyexhG59MvEfL37RLG2B9Lf9QlzxLUUDt8/UOkB4xQB4G30I2+gu/Z7hqG/6B49sCteMVn3Lj+PYVyEdHU+uK6lI93XqXkYdnr+UfMVDChH/wCUL7g2+X5cdsXTzW6lmbr+zyfcIKaxMug3+gfMbikbfxLSKNFPmIQWsYW9dvL5jo/8p5neVAVdG7l8ah0efuUw6OV4ImI+11P9S/ialn4l8S3Ozl4ZYahy8kYFAB5GbFjzfCNQeAV/34zcY/4I1bTod/8AmGDA4A4jzLTcjyH9TbVTsaPflleJbv8AQP5+SRIcY5hjke4H6Fl+Df8AuVUU8919x+hrpOGWJ1/M1X4fPr4goLY7I9FR6fpgUxwwpR4QfveIIChHYjzEEARKR7m98WPh8HqESbIRHEo/n/7EMgAtXgiojhWaevM5WwJBCaXS1+PLKUw2ryvL8iLX4ms48IC6Ns3qPbBkNgv85ZfFqUvohCJ5i/mBECk6itD9iXJ77Hk+O0BNYuqt5eH/ANnudPJDncQSksjVqvBxBvZX1GmTfR5/KBQRE5GIS90+me8sIa4TkcO/PqJkQBx1AqhTOJ2eIBv8jHGHiKTApHsi4l9+X3hlgcI8S2vSA/3CAybEbGMMCiH27yWfkK8VCLA9U0J9QwbWpoIzQo4Q3+D+45Yi1W1YzZ8/fr/cIGWgjh1xGHEY4OcEOZsnuD0UqX9b/wB1jShLHkZ9p9v4lI7sSJsfR8y5cHcWHEFSJYyq+LlT/t/ETk1IUkBhDz69PU5uQ29fR/csTihf3vPcL/vceK8s+qUvv7L3NYFgLWAW7eRP9v8ABBqAUAUEOPiHY/0ikqVnAaPLDvLyxL08SjFA68PwC0C1Oi84J030nMRtPoQEiJ2Qemf3zfWFG42fbxg0s+ElezhOj78QRBQjwkc68Dw+fcqDY2vqPOSN7VW/rDdNFPjO7gBQsi7bEFGx3Bu4TkneWOze5b1dr4fXiIgrpJR+R/wcQiry/cYdxQZB1ob9RCqxQVyp4gvTwPB9/bAzz0HHvxPrSf8ApcfHEY3N8Rnc6izfc9Qolwh+8NJLkNmGtcjKFek6vvx7giXYj2YK6dI37SbGc7/OO8HGLPwf+vk9y3v3L/sf44mxsA2rgPLEHYN0p8rx1K4nLpPQ9/mUnI7Zz6O4mUHt2fZ/qVx+V36nfxvBzwQtcKsI7HxOtZuvg18Ej9QEx5Dz6w06SFbUwbO0T61XLyEUVJHgF30/TlKzypr8eJxSJt8nwOzvQjoibyhnOiXJQlbT4un1k9tH/cuJX0kX5Ngemnf5QABBwEYtR+/0Sv4abcOWNpSfRuPq0teB4lwY3/ofB9ypHfNefzzc4tDl8n9x+TNRw61Bhqd4tQn5J9P1F784Y/R8if68S/1k3wP7hNhNhs9+ItotWnwURAAtXqHapcLNHoidb5VawBsew1+PMLGl9v8AJ6mweFH3vPJ6l0FC+x/UWNAFAFV6l/b++TjiPVvB2IBAIjw3DJUBbcL5HsxDuffPvlncE7gHvKUOinwf3PsCP5JSXcJ3PfmHAt2OKSoJp8ytGxXwY5ImkSxlCHkex68xEURE6wTUHCNJHK4+if7hoybE7jitev5REFQVfc5fC2jIRGkpJS2efslZg/1hor2o+L0wHKzkrzds7lBd4+2MLNPbSfX3Eir1o/XH4nU/4Iq+jtePb/U6xeDSeoqj0uvZCSg4R2QaudHR9/3H4svceZ+MEMGNtNcD9hlhX6bj2dQywNiNJES1Bp161/MM3x0HUqqPGo8QhFAWr1FKJcHf2YDS/ASmY6hwe/MAAACgOpcG8pB0Fv8AXOkpuq3F1LvqdD9RAKseJe5c0ecNPuaGHp6Yhvs19OPeEi89Y1P5z84P3nDzH3nDNvT5OvaOV/sPqXXrs6fcrR0ej6lG37eU19HzMa/ROffmchLg8OB7E6IxBeQfsfcVW1te4nUXb6Pkb+gd+5RKPCcMvsX+4AtPX8xprt5yxktBL6qH4JWtHb0StX3px6neNdNyn2XvNkQT5a4gIpxfj6P3HUWW1X6x/URLDpgBr1s9fUWpc5jzLJe5e5sZMDCHMN8fmc8+w7+a/wCIt8zfYKHl0s7yjVCfsrqXE1O2fseWa575OX3LnKXB1nhlk1v2Dx+JUXeW79P6lQg77exGN7BB7ZVD/ENG+c0RTqKdT6J9M+uBQpi4YRD+7qVjY9cH9zWVfK5YRAFq1gAHBo+Dm4fRCkSxge8c8n8f+z7uDy+3BtohU7dDenUvF/ApAPceI2VfTtXqd/ctuE/HqOXvp2xK29J3AIQcBLizudcy8cgM9CVC02tPh0kBprQeD+SAmHvDZd4e/SOzYhDsuNXNvFS1m+5UuoQyTme4MML9BywivwJQgq9EI+YUP/G45U2/5X3E5Qp/Ji+5W7Bp/k1DwAUB1EecaQMFOYHaHHMInvLYnK8kW1udJp9+GACHhUrycQP3PEQgqx4TuOzTwHj7hw9QZebz3LxeVAt0QC9jCOy17Y9YV5Mtqt0ce77jcAC+/mgABys5eLz/AIiqVKvK4BWgthqBWh6+j+4qrse+vkWvL4iNrP51Ld0gG6FPZgbi1BOsuPLcojC5aEAwCznFe+hcr+ScOLw/sMurXZyexGSt+l/Qf4myUhbR7ce48yzC1HidRg/ILqtcH8xERVm5/mMoBo/3DcMfTp8umLzQl+COGEdNzYjD6Jt4hDuEQgayGM1IWM3J+1P9P8T7f1ru4Fflgfl/HEPWVOWccS/8LDCFKCKV6SI0qvRDK2MFBQAR0QH2DA5oKT8/G5sX0iWzV0ODOra7LglHNdIckvDew7/8xqTkNfrHC8cw32zf5mi/0z6NHjHQhI/xOp1HeooHRHijGH0QgpK9zgqXFnP2AEuLuZX7HmXEJ5OK9+JsN5pw8D/M53Sy9bl3KIrHiXZh+N9QWDyxqQtWgm8p+yf3Ltt5l1LuEVW3JKJTxKeJTxAdStQyOLUt9ByzX2VVhtPC4D+3+R4+j95eL+d/BW+r+ZtvyyvH29vwuX8N5b7+EVSpV5XCVCrwEor9D/MAAADgJcQSks8MABo68r49RduVRPgiOicDt85uXTrLzHHca8SvqNTknHwYPXiDz+fEDo8gVfvzNhsNiaA+4ENxkbdPx1UXUvcrcrLDHWBj/WINp3/R9RGNOJV5YBgMAkIXfxIwxdYK9SPwIiVVys2ofalHAKov8puird9l/UX6D/WPuX8Ll/C4PEq15lCigOp92E8sE7gHuXeXFu5t4zvvyv4lU2drl+PCHT8N2R5ZxGOxHZE/R/uIM4YFgsAmsXh5xxHDGDEAqgG1eoyuo4e34iqqrXlZR3r2m30ShCcR7+78xLkOnOxpjy15x7jLI77TBUM3OAOm4o9l3LGDZxCzCclcPvBL+BgZccVK8j/UMKV0Slo/QEJ7hTFg8jAEOwUTr4XjvN4vUafTqH7x98TF9st3i0eAsR0tW2BAFXgJQV9HQ9/C5cuXLyjuuysS1HxT6oeLAc5lBv438b8TuoyLSfq8zZq78HuVFZ+eHojzfeFgd0PpGxnLDGVOMeILLCXLYMJzKVKa1KSlcTUuXBg1D4cy5c4I0ri7TqUt9vbLJSCeZcanr538UGKT6J9c+qBdQPj4MCO1lk5ef6S5cuXF+pc1HLlDuIeJSUlHzWsXGXL8RAGkofxLIJvs+iBA/uP2xaZSUe5c751KDqM38FJcFT7g+cHUHbN4NzvUuXvF6nWL3Llwg5HR5YA8J35fOE+aVdwxJ2VsX1DiXm83O/jfxemN6NH4fUQdxEZY9shAWBe5V4l3m7+D/hZetzuKXN81eX41AgUVBEn2ZIWCzC1LqLKqXUvxCdTfnNnEGW4MaxefXw4xV8ckBwsWgsImB9wl4vF4udy/8K6nJpZTE8xIq4rLZbLYKCgokaNZbOfhcZfwuXLjOpwxUe6eoDHnHeXwJANQK3hd7iyu6xXkhwMGXgwa3N5GHPn4dQ9y/mRwZH43jrNy8Xv4LLl5bS3C2ioo6l5fxL+IKCwAQ1Fm5cvPWFm6m8XLlxYzjRFqHPGHmJyNxmo463Fo4iznN7gt1gxbUJ1DBPU7uaxdy2pudTmXLgy4viEuEuXLgy/8V0S7Ll4Zcuc/G8alEo8SniUSjxKMLH5LL+N9YGXLlyyWS7wx4xfwuLrHHEN4HWuJT1OsKVOSpswc7gy5d46nP1O4cQd1LqEvU9yzNzjF1Fhx8LlzuXD43rcvWoN8/Ezcveb+Di94/MuXLly83neGW9k44l4fuepuc8z+MXFw49YvcuVKZ3DnnNQgy5c/Gb1qH2y8fnB7hqGOfhfwuHwv4Gepzq5xi5cvqXi5cudy5cX53m5cXF5WXHpLbi/F4xcud4ZeVhxNS6hUeZfUQ61A+8d/U3m6+4MvJzLnLDU7moS8DeLwOL+Fy/8AL1m5fyuXm8d5uXLxUZcuXBvFx3HfPwXUJ3FROTcusXGMuMPM5lFSrmz1i9xZ6xeajPMLl4v4cZ63i8XkcXL3i8Xm5+c3DPeT43i4S5cvFy7zeNEuXLji4YrzFly5e8XCsbvfEXcc3EvmHGoL3OoRJxL38HxLOp9kN94v4EDBl5vcveL+Bgxcud5uXi8X8rly/hcuX5wy9ly/hccX9S5cHHeGXjiLqC1uL8rxcanBqLZgX3KjKr4cst4l1zL8Ql+5ROYV5hzLwMubuJm7hzcJe+YQcDgl/Pr43LxcuXm4fK6xd45yvx/MOHN/DvUtuczjHrPOFoxcZxFlSrjYah5ecPE2NcErUKlz3xDjPLFPLLs1HmBuBPWKnqXxN7uccy80EMjLxcvNy83qXLzeL/wX+uF8QcXHFy5cvLi4JL3L8Tcupe5cuXLl5uXLS/EvNy4zvFb51PcMVEMLUuzUqGsDBJu5V7rDL3XMGX5lUQNTd3eeDbO8LrUuX8Liy5cuXOF+Fy8XLzcvFy4Mv47qbvA4vNxYPeCPMv6xbcWWLV4ua+DjvF1Lxe/g51NXjnDcCXbqNz3K3eKKm53g2+pfwuMJ7ncvvH1DFy8dYH4dzqXm83Lly5cG5cuXLl7zcuXLlT1i4s7jOCcdwYvcuXDatyy53FLqdYvDvCzr4anWN1N5YMG4Xe+JXwZwS6n/2Q==)
Os genes existem juntos em um genoma, assim como as pessoas vivem juntas em sociedades. Dentro dessa comunidade mais ou menos organizada, ocasionalmente genes parasitas surgem em detrimento do grupo maior, levando o genoma a usar estratanãgias para mitigar esses efeitos. Foto cortesia do Stowers Institute for Medical Research. Crédito: Stowers Institute for Medical Research
Pode ser difacil contestar o ditado comum 'sobrevivaªncia do mais apto'. Afinal, "a maioria dos genes no genoma estãola¡ porque estãofazendo algo bom", diz Sarah Zanders, Ph.D., pesquisadora assistente do Stowers Institute for Medical Research. Mas, ela diz, "outros estãola¡ apenas porque descobriram uma maneira de estar la¡."
O entendimento convencional da evolução éque os genes que codificam uma função benanãfica são os transmitidos com mais frequência, o que garante que os organismos mais aptos - aqueles que tem caracteristicas mais favoráveis ​​ao ambiente - sobrevivam. Menos conhecido éo fato de que existem elementos de genes parasitas dentro de um organismo que estãofazendo exatamente o oposto.
“A maneira como se poderia pensar éque o genoma écomo uma sociedadeâ€, explica Zanders. “Nessa sociedade, existem indivíduos que vivem de fazer coisas boas e fazer contribuições valiosas. Mas háoutros que não contribuem de forma benanãfica e são realmente prejudiciais a sociedadeâ€, explica Zanders.
O Laborata³rio Zanders estuda genes parasitas em Schizosaccharomyces pombe , uma espanãcie de levedura de fissão a s vezes encontrada na popular bebida fermentada de cha¡ kombucha. Devido a sua simplicidade e tempos de geração rápidos, S. pombe éum sistema altamente trata¡vel para estudar elementos de genes parasitas, particularmente uma classe conhecida como drivers meia³ticos. Em vez de conferir um benefacio a seu hospedeiro, os condutores meia³ticos conferem desvantagens distintas a seu hospedeiro, a fim de influenciar sua própria perpetuação. Um manãtodo de fazer isso, empregado pelos genes de impulso meia³tico wtf , épor meio do envenenamento seletivo de células na meiose.
Meiose éo processo de divisão celular atravanãs do qual organismos que se reproduzem sexualmente formam gametas - como a³vulos e espermatozoides em humanos ou esporos em leveduras - para se propagar a próxima geração. Normalmente, esse processo resulta em gametas que herdam uma das duas ca³pias de cada cromossomo transportado pela canãlula-ma£e, e cada ca³pia étransmitida aos gametas em uma taxa igual. Os motoristas meia³ticos, no entanto, causam um curto-circuito nessa lei da segregação mendeliana.
"Normalmente, todos os alelos - ou variantes de um determinado gene - tem uma chance justa, e a seleção natural pode escolher os melhores", explica Zanders. "Mas os alelos que são impulsionadores meia³ticos selecionam a si pra³prios mesmo que não sejam a melhor opção. E nunca são a melhor opção."
Em um artigo publicado online em 13 de agosto de 2020, na eLife , membros do laboratório Zanders explicam como épossível que motoristas meia³ticos persistam na população, mesmo matando muitos aspirantes a hospedeiros. Acontece que o S. pombe pode empregar variantes de outros genes para ajudar a suprimir o efeito negativo dos condutores meia³ticos, embora a um custo para o condicionamento fasico.
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Normalmente, para propagar cepas de laboratório de S. pombe , eles são consanguaneos. "Quando vocêcruza dois isolados quase idaªnticos, eles quase não produzem progaªnie", explica a primeira autora Maraa Anganãlica Bravo Naºa±ez, Ph.D., que esteve envolvida na identificação dos genes wtf e que fez este trabalho nos Zanders Laborata³rio como pesquisador pré-doutorado na Escola de Pa³s-Graduação do Stowers Institute. "Isso sugere que pode haver algum tipo de competição em jogo." Bravo Naºa±ez e colegas usaram esse raciocanio para procurar genes que poderiam estar em conflito em genomas semelhantes, mas não idaªnticos, de S. pombe . O desenho experimental central do presente trabalho envolveu cruzamento de S. pombe isolados que são mais de 99% idaªnticos.
"O cruzamento pode ter muitas vantagens", diz Bravo Naºa±ez, como fornecer um alelo normal de um gene para resgatar o efeito de um alelo mutante. "Mas os genes da unidade meia³tica que estudamos na verdade exercem seu efeito deletanãrio no cena¡rio heterozigoto, onde os alelos de um gene não são os mesmos."
Um experimento esclarecedor que fizeram foi comparar os resultados de isolados consanguaneos e cruzados de S. pombe em um fundo genanãtico contendo uma mutação em rec12 , que éum gene que promove a segregação cromossa´mica adequada.
“O Rec12 geralmente promove a fertilidadeâ€, diz Bravo Naºa±ez. "Quando removemos a função rec12 , o número de esporos via¡veis ​​diminuiu, mas apenas no cena¡rio consanguaneo. Os números relativos de esporos via¡veis ​​não diminuaram realmente no cena¡rio cruzado." Além disso, dos esporos via¡veis, eles descobriram que a sobrevivaªncia era tendenciosa para produtos de gametas atapicos, resultantes da ma¡-segregação e cruzamento desigual de cromossomos emparelhados. Em outras palavras, os esporos sobreviventes continham o número ma¡ximo de condutores meia³ticos, a s vezes devido a herana§a de um cromossomo extra. Essa descoberta foi surpreendente porque cromossomos extras são geralmente considerados muito prejudiciais. Em humanos, por exemplo, cromossomos extras ou ausentes podem levar a gametas invia¡veis, defeitos congaªnitos graves ou infertilidade.
“Quando vocêtem heterozigosidade de genes wtf , fazer uma mutação no gene rec12 érelativamente bom para o organismo, porque éisso que tem que acontecer para não matar toda a progaªnieâ€, diz Bravo Naºa±ez.
"Pensamos no rec12 como um gene realmente importante para a fertilidade", explica Zanders. "Mas a situação étotalmente diferente quando hácruzamento. Ter rec12 não ajuda em nada, porque a levedura émelhor fazer gametas que não resultam da segregação cromossa´mica adequada. Este éapenas um exemplo do poder dos impulsores meia³ticos para mudar a paisagem da meiose. Fundamentalmente, o que é'bom' para o organismo mudou. "
"Ter esse cromossomo extra não ébom, e as cola´nias de leveduras parecem incomuns, pequenas e irregulares. Mas depois que continuam a crescer por um tempo, as células perdem esse cromossomo extra e então podem prosperar como haploides. Então, esta etapa éna verdade, apenas tempora¡rio ", diz Bravo Naºa±ez.
Precisamente porque os condutores meia³ticos exercem sua influaªncia em um cena¡rio heterozigoto, eles são facilmente perdidos. "Existem muitos sabores de impulso meia³tico. Algumas formas de impulso meia³tico são difaceis de medir experimentalmente porque o vianãs émuito sutil", diz Zanders. "Nãosomos os primeiros a estudar os drivers meia³ticos em profundidade. Temos apenas um sistema de modelo melhor agora, para que possamos progredir mais rapidamente."
"Os sistemas de acionamento tendem a ser repetitivos e geralmente vocêpode encontra¡-los em várias ca³pias nos genomas", diz Bravo Naºa±ez. "Em muitos casos, eles já foram encontrados em outros sistemas, como fungos, camundongos e moscas-das-frutas, mas ainda não foram totalmente caracterizados." O estudo de drivers meia³ticos em S. pombe "esperana§osamente guiara¡ pesquisas futuras para entender outros sistemas de propulsão."
"Os humanos certamente tem genes de comando meia³ticos. Se eles tem ou não genes de comando meia³ticos do tipo que mata gametas não estãoclaro", diz Zanders. "O impulso meia³tico provavelmente afetou a evolução dos centra´meros humanos, que são regiaµes dos cromossomos muito importantes para a segregação cromossa´mica adequada. Certas fusaµes cromossa´micas exibem um impulso meia³tico em humanos, assim como as sequaªncias que estãoenvolvidas na recombinação do DNA. continue se concentrando nesses e em outros elementos genanãticos parasitas, suas estratanãgias e efeitos. "
Outros coautores deste trabalho incluem Ibrahim M. Sabbarini e Lauren E. Eide do Stowers Institute e Robert L. Unckless, Ph.D., da University of Kansas.
Este trabalho foi financiado em parte pelo Stowers Institute for Medical Research, pela March of Dimes Foundation Basil O'Connor Starter Scholar Research Award (5-FY18-58 para SEZ), Searle Scholar Award (para SEZ) e National Institutes of Health ( O Instituto Nacional de Ciências Manãdicas Gerais concede R00GM114436 e DP2GM132936 ao SEZ e o Instituto Nacional do Ca¢ncer concede F99CA234523 ao MABN). O conteaºdo éde responsabilidade exclusiva dos autores e não representa necessariamente a opinia£o oficial do National Institutes of Health.
Resumo de Descobertas de Lay
Um novo estudo publicado online em 13 de agosto de 2020, na eLife do laboratório de Sarah Zanders, Ph.D., no Stowers Institute for Medical Research, descreve uma estratanãgia que o genoma de levedura de fissão de S. pombe pode usar para mitigar alguns dos piores efeitos conferidos por elementos de genes parasitas conhecidos como drivers meia³ticos.
Os drivers meia³ticos analisados ​​no estudo são capazes de curto-circuitar a lei convencional da segregação de Mendel, que geralmente garante que cada gameta (canãlula reprodutiva) receba uma das duas ca³pias de cada cromossomo da canãlula-ma£e com transmissão igual. Em vez disso, os condutores meia³ticos podem envenenar gametas que não contem sua sequaªncia genanãtica, oscilando assim a taxa de transmissão a seu favor.
Como forma de permitir a sobrevivaªncia de alguns gametas que, de outra forma, morreriam, o genoma do S. pombe pode empregar variantes de outros genes para criar uma situação que os "proteja", mesmo que isso acarrete um custo para a adequação. Por exemplo, uma mutação em rec12 , um gene responsável pela segregação cromossa´mica adequada, pode levar a gametas com cromossomos extras. Enquanto cromossomos extrassão geralmente indesejáveis; neste cena¡rio, eles realmente permitem que mais gametas sobrevivam. Esta percepção surpreendente sobre os impulsores meia³ticos e como eles podem ser suprimidos pode ajudar os pesquisadores a entender melhor as forças que moldam a evolução da formação dos gametas, bem como aquelas subjacentes a infertilidade humana.