Beyond the Hypercube:Evolutionary Accessibility of Fitness Landscapes with Realistic Mutational Networks

Evolutionary pathways describe trajectories of biological evolution in the space of different variants of organisms (genotypes). The probability of existence and the number of evolutionary pathways that lead from a given genotype to a better-adapted genotype are important measures of accessibility of local fitness optima and the reproducibility of evolution. Both quantities have been studied in simple mathematical models where genotypes are represented as binary sequences of two types of basic units, and the network of permitted mutations between the genotypes is a hypercube graph. However, it is unclear how these results translate to the biologically relevant case in which genotypes are represented by sequences of more than two units, for example four nucleotides (DNA) or 20 amino acids (proteins), and the mutational graph is not the hypercube. Here we investigate accessibility of the best-adapted genotype in the general case of K > 2 units. Using computer generated and experimental fitness landscapes we show that accessibility of the global fitness maximum increases with K and can be much higher than for binary sequences. The increase in accessibility comes from the increase in the number of indirect trajectories exploited by evolution for higher K. As one of the consequences, the fraction of genotypes that are accessible increases by three orders of magnitude when the number of units K increases from 2 to 16 for landscapes of size N ∼ 106 genotypes. This suggests that evolution can follow many different trajectories on such landscapes and the reconstruction of evolutionary pathways from experimental data might be an extremely difficult task

Evaluation of the antimicrobial effect of photodynamic antimicrobial therapy in an in situ model of dentine caries

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Photodynamic antimicrobial therapy (PACT) promotes bacterial death as a result of the photosensitization of microbial components. This study evaluated the effect of PACT on dentine caries produced in situ. Over the course of 14 d, 20 volunteers wore intra-oral devices containing human dentine slabs that were treated 10 times daily with a 40% sucrose solution. Afterwards, the antimicrobial effect of toluidine blue O, associated with 47 or 94 J cm-2 of a light-emitting diode, was evaluated. Before and after the treatments, dentine samples were analysed with regard to the total number of microorganisms, total streptococci, mutans streptococci, and lactobacilli. Significant reductions in the bacterial count were observed for PACT with both energy densities tested, with the following values observed for 47 and 94 J cm-2 of irradiation: for total streptococci, 3.45 and 5.18; for mutans streptococci, 3.08 and 4.16; for lactobacilli, 3.24 and 4.66; and for total microorganisms, 4.29 and 5.43, respectively. The control, treated with 94 J cm-2 of irradiation alone, was also effective against all bacteria. To conclude, PACT was effective in killing oral microorganisms present in dentine caries produced in situ and may be a useful technique for eliminating bacteria from dentine carious lesions before restoration.1175568574Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)CNPq [620160/2006-3

In Vitro Photodynamic Antimicrobial Chemotherapy in Dentine Contaminated by Cariogenic Bacteria

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)The development of a method to ensure bacterial-free substrates without extensive cavity preparation would be highly useful to dentistry, since there is no currently available effective method for killing residual bacteria in dentinal tissue. This randomized in vitro study determined parameters for using toluidine blue O (TBO) with a light-emitting diode (LED) for dentine caries disinfection and monitored intrapulpal/periodontal temperatures during irradiation. Occlusal human dentine slabs were immersed in Streptococcus mutans culture for demineralization induction. Slabs were allocated to 10 groups (n - 15), which were treated with 0.1 mg ml(-1) TBO with 5 min of incubation time or 0.9% NaCl solution for 5, 10 or 15 min, and submitted or not to irradiation for 5, 10 or 15 min (47, 94, and 144 J/cm(2)). Before and after treatments, dentine samples were analyzed with regard to S. mutans counts. In whole teeth, temperature in pulp and periodontium was measured by thermocouples during irradiation. Kruskal-Wallis/Student-Newman-Keuls, and ANOVA/Tukey test were respectively utilized to compare log reductions and temperature rises between groups. Bacterial reduction was observed when dentine was exposed to both TBO and LED at all irradiation times, as well as to LED alone for 10 and 15 min. Temperature increases lower than 2 degrees C were observed for either pulp or periodontium. Concluding, LED combined with TBO is a safe and effective approach for dentine caries disinfection. Nevertheless, additional studies should be conducted to determine the influence of the irradiation in S. mutans viability in dentinal surface/tubules.20615041513Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)CNPq [620160/2006-3, 564387/2008-8

Severe coinfection of melioidosis and dengue fever in northeastern Brazil: first case report

This report focuses on a fatality involving severe dengue fever and melioidosis in a 28-year-old truck driver residing in Pacoti in northeastern Brazil. He exhibited long-term respiratory symptoms (48 days) and went through a wide-ranging clinical investigation at three hospitals, after initial clinical diagnoses of pneumonia, visceral leishmaniasis, tuberculosis, and fungal sepsis. After death, Burkholderia pseudomallei was isolated in a culture of ascitic fluid. Dengue virus type 1 was detected by polymerase chain reaction in cerebrospinal fluid (CSF); this infection was the cause of death. This description reinforces the need to consider melioidosis among the reported differential diagnoses of community-acquired infections where both melioidosis and dengue fever are endemic