Relatório de estágio em farmácia comunitária

Relatório de estágio realizado no âmbito do Mestrado Integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbr

Three-dimensional Simulations and Spacecraft Observations of Sub-ion Scale Turbulence in the Solar Wind: Influence of Landau Damping

International audienceThree-dimensional nonlinear finite Larmor radius (FLR)–Landau fluid simulations, which include some small-scale $({k}_{\perp }{\rho }_{i}\gtrsim 1)$ kinetic effects, are performed to explore the nature of the sub-ion scale turbulence in the solar wind and to investigate the role of Landau damping and FLR corrections. The resulting steady-state magnetic power spectrum in the dispersive range display exponents that vary within a range of values compatible with statistical results reported from in situ spacecraft measurements of solar wind turbulence as well as from gyrokinetic simulations. The spectral slopes are shown to depend on the strength of the nonlinear effects and on the scale at which turbulent fluctuations are driven in the simulations. The influence of Landau damping is addressed by comparison with simulations where the double-adiabatic closure is imposed. The role of FLR corrections is also analyzed. Comparison with in situ observations in the solar wind are performed to enlighten the influence of the fluctuations power at different scales on the spectral slopes in the sub-ion range. Using diagnosis of both magnetic compressibility and frequency-wavenumber spectra, it is shown that in spite of the evidence of the presence of fast-magnetosonic modes, the magnetic energy is mostly distributed around the kinetic Alfvén waves and the slow modes, in agreement with solar wind measurements. The observed large broadening about the linear dispersion relations may reflect the presence of coherent structures

Comparative population genetic structure of two ixodid tick species (Acari:Ixodidae) (Ixodes ovatus and Haemaphysalis flava) in Niigata prefecture, Japan

Ixodid ticks (Acari:Ixodidae) are essential vectors of tick-borne diseases in Japan. In this study, we characterized the population genetic structure and inferred genetic divergence in two widespread and abundant ixodid species, Ixodes ovatus and Haemaphysalis flava. Our hypothesis was that genetic divergence would be high in I. ovatus because of the low mobility of their small rodent hosts of immature I. ovatus would limit their gene flow compared to more mobile avian hosts of immature H. flava. We collected 320 adult I. ovatus from 29 locations and 223 adult H. flava from 17 locations across Niigata Prefecture, Japan, and investigated their genetic structure using DNA sequences from fragments of two mitochondrial gene regions, cox1 and the 16S rRNA gene. For I. ovatus, pairwise FST and analysis of molecular variance (AMOVA) analyses of cox1 and 16S sequences indicated significant genetic variation among populations, whereas both markers showed non-significant genetic variation among locations for H. flava. A cox1 gene tree and haplotype network revealed three genetic groups of I. ovatus. One of these groups consisted of haplotypes distributed at lower altitudes (251–471 m.a.s.l.). The cox1 sequences of I. ovatus from Japan clustered separately from I. ovatus sequences reported from China, suggesting the potential for cryptic species in Japan. Our results support our hypothesis and suggest that the host preference of ticks at the immature stage may influence the genetic structure of the ticks. This information may be important for understanding the tick-host interactions in the field to better understand the tick-borne disease transmission and in designing an effective tick control program

Algorithm-aided engineering of aliphatic halogenase WelO5* for the asymmetric late-stage functionalization of soraphens

Late-stage functionalization of natural products offers an elegant route to create novel entities in a relevant biological target space. In this context, enzymes capable of halogenating sp3 carbons with high stereo- and regiocontrol under benign conditions have attracted particular attention. Enabled by a combination of smart library design and machine learning, we engineer the iron/α-ketoglutarate dependent halogenase WelO5* for the late-stage functionalization of the complex and chemically difficult to derivatize macrolides soraphen A and C, potent anti-fungal agents. While the wild type enzyme WelO5* does not accept the macrolide substrates, our engineering strategy leads to active halogenase variants and improves upon their apparent kcat and total turnover number by more than 90-fold and 300-fold, respectively. Notably, our machine-learning guided engineering approach is capable of predicting more active variants and allows us to switch the regio-selectivity of the halogenases facilitating the targeted analysis of the derivatized macrolides’ structure-function activity in biological assays