A model for transition of 5 '-nuclease domain of DNA polymerase I from inert to active modes

Bacteria contain DNA polymerase I (PolI), a single polypeptide chain consisting of similar to 930 residues, possessing DNA-dependent DNA polymerase, 3'-5' proofreading and 5'-3' exonuclease (also known as flap endonuclease) activities. PolI is particularly important in the processing of Okazaki fragments generated during lagging strand replication and must ultimately produce a double-stranded substrate with a nick suitable for DNA ligase to seal. PolI's activities must be highly coordinated both temporally and spatially otherwise uncontrolled 5'-nuclease activity could attack a nick and produce extended gaps leading to potentially lethal double-strand breaks. To investigate the mechanism of how PolI efficiently produces these nicks, we present theoretical studies on the dynamics of two possible scenarios or models. In one the flap DNA substrate can transit from the polymerase active site to the 5'-nuclease active site, with the relative position of the two active sites being kept fixed; while the other is that the 5'-nuclease domain can transit from the inactive mode, with the 5'-nuclease active site distant from the cleavage site on the DNA substrate, to the active mode, where the active site and substrate cleavage site are juxtaposed. The theoretical results based on the former scenario are inconsistent with the available experimental data that indicated that the majority of 5'-nucleolytic processing events are carried out by the same PolI molecule that has just extended the upstream primer terminus. By contrast, the theoretical results on the latter model, which is constructed based on available structural studies, are consistent with the experimental data. We thus conclude that the latter model rather than the former one is reasonable to describe the cooperation of the PolI's polymerase and 5'-3' exonuclease activities. Moreover, predicted results for the latter model are presented

Atomic-resolution imaging of surface and core melting in individual size-selected Au nanoclusters on carbon

Experimental and theoretical data sets for the Nature Communications paper "Atomic-resolution imaging of surface and core melting in individual size-selected Au nanoclusters on carbon". Data structure and formats are described in the README.docx file

Management Committee.

Lisa Maillart is an Assistant Professor in the Department of Operations at Case Western Reserve University, and a Senior Scholar in the Case-MethroHealth System's Center for Health Care Research & Policy. Prior to joining the faculty at Case, she received her M.S. and B.S. in industrial and systems engineering from Virginia Tech, and her Ph.D. in industrial and operations engineering from the University of Michigan. Her primary research interest is in sequential decision making under uncertainty, with applications in medical decision making and maintenance optimization. She is a member of INFORMS, SMDM and DSI. Her recent awards include the Weatherhead School of Management's "Most Outstanding Junior Faculty Paper " an

Análise da marcha no plano inclinado e declinado de adultas e idosas com diferentes volumes de atividades semanais

A marcha é um dos mais naturais movimentos humanos, porém com o envelhecimento, sua eficiência vai se reduzindo, principalmente durante a transposição de superfícies inclinadas, onde o risco de acidentes aumenta. OBJETIVO: Avaliar as diferenças do padrão da marcha de indivíduos idosos ativos (ATI) e sedentários (SED) em relação aos indivíduos adultos (ADU) durante a locomoção em um terreno inclinado (rampa). MÉTODOS: Quarenta e cinco indivíduos (15 ADU, 15 ATI e 15 SED) caminharam, subindo e descendo uma rampa com 10% de inclinação. A análise cinemática (Vicon MX-13) e cinética (Plataforma de Força AMTI) de variáveis relacionadas com a marcha foi realizada. RESULTADOS: Foram identificadas reduções na amplitude e potência do impulso ao redor do tornozelo dos indivíduos SED e ATI em comparação aos ADU durante a subida da rampa. Na descida, as principais diferenças entre o grupo ADU e os grupos SED e ATI foram com relação à velocidade de deslocamento, provavelmente por limitações musculares de ordem elástica, principalmente ao redor do quadril. CONCLUSÃO: Aparentemente, o nível de atividades físicas não influenciou a marcha dos SED e ATI; entretanto, uma limitação do IPAQ de conseguir classificar adequadamente diferentes níveis de atividades físicas pode ter influenciado o resultado. Futuros estudos longitudinais nos quais os indivíduos são submetidos a diferentes volumes de atividades físicas diárias são necessários para que os resultados aqui encontrados possam ser confirmados