2D Chemical Drawings Correlate to Bioactivities: MIA-QSAR Modelling of Antimalarial Activities of 2,5-Diaminobenzophenone Derivatives

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Two-dimensional chemical structures of a series of 2,5-diaminobenzophenone derivatives, some farnesyltransferase inhibitors, have shown to correlate with the corresponding antimalarial activities. The descriptors in this QSAR analysis are pixels of the chemical structures (two dimensional images) transformed into binaries and, therefore, the data variance explaining the variance in the activities block corresponds to the coordinates of each pixel in each molecule. This method, named multivariate image analysis applied to quantitative structure-activity relationship (MIA-QSAR), was applied to model the antimalarial activities of the titled compounds and the results were compared to well known three-dimensional QSAR techniques for the same class of compounds. In addition to the simplicity and high predictive performance of the MIA-QSAR modelling, this 2D image-based method has the potential of working well when equally simple, classical analysis fails. Overall, the present QSAR analysis based on 2D chemical drawings (constrained structures) dispensed conformational screening and 3D alignment to provide a reliable QSAR model; the physicochemical description about e.g. steric effects and chiral centers is all contained in the way in which substituents in a congeneric series are drawn, and the method can serve as a tool to introduce those who are planning to deal with drug design.224637U326Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Conformational analysis, stereoelectronic interactions and NMR properties of 2-fluorobicyclo[2.2.1]heptan-7-ols

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Four diastereoisomers of 2-fluorobicyclo[2.2.1]heptan-7-ols were computationally investigated by using quantum-chemical calculations, and their relative energies were analyzed on the basis of stereoelectronic interactions, particularly the presence or otherwise of the F center dot center dot center dot HO intramolecular hydrogen bond in the syn-exo isomer. It was found through NBO and AIM analyses that such an interaction contributes to structural stabilization and that the (1h)J(F),(H(O)) coupling constant in the syn-exo isomer is modulated by the n(F)->sigma*(OH) interaction, i.e., the quantum nature of the F center dot center dot center dot HO hydrogen bond.812271232Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Graves' disease presenting as pseudotumor cerebri: a case report

<p>Abstract</p> <p>Introduction</p> <p>Pseudotumor cerebri is an entity characterized by elevated intracranial pressure with normal cerebrospinal fluid and no structural abnormalities detected on brain MRI scans. Common secondary causes include endocrine pathologies. Hyperthyroidism is very rarely associated and only three case reports have been published so far.</p> <p>Case presentation</p> <p>We report the case of a 31-year-old Luso-African woman with clinical symptoms and laboratory confirmation of Graves' disease that presented as pseudotumor cerebri.</p> <p>Conclusion</p> <p>This is a rare form of presentation of Graves' disease and a rare cause of pseudotumor cerebri. It should be remembered that hyperthyroidism is a potential cause of pseudotumor cerebri.</p

Synthetic organisms and living machines: Positioning the products of synthetic biology at the borderline between living and non-living matter

The difference between a non-living machine such as a vacuum cleaner and a living organism as a lion seems to be obvious. The two types of entities differ in their material consistence, their origin, their development and their purpose. This apparently clear-cut borderline has previously been challenged by fictitious ideas of “artificial organism” and “living machines” as well as by progress in technology and breeding. The emergence of novel technologies such as artificial life, nanobiotechnology and synthetic biology are definitely blurring the boundary between our understanding of living and non-living matter. This essay discusses where, at the borderline between living and non-living matter, we can position the future products of synthetic biology that belong to the two hybrid entities “synthetic organisms” and “living machines” and how the approaching realization of such hybrid entities affects our understanding of organisms and machines. For this purpose we focus on the description of three different types of synthetic biology products and the aims assigned to their realization: (1) synthetic minimal cells aimed at by protocell synthetic biology, (2) chassis organisms strived for by synthetic genomics and (3) genetically engineered machines produced by bioengineering. We argue that in the case of synthetic biology the purpose is more decisive for the categorization of a product as an organism or a machine than its origin and development. This has certain ethical implications because the definition of an entity as machine seems to allow bypassing the discussion about the assignment and evaluation of instrumental and intrinsic values, which can be raised in the case of organisms

Sociodemographic characteristics determine dietary pattern adherence during pregnancy

OBJECTIVE:Sociodemographic factors may affect adherence to specific dietary patterns during pregnancy. The present study aimed to identify dietary patterns during pregnancy and associated factors among Brazilian pregnant women. DESIGN:A cross-sectional analysis. Dietary intake was evaluated with a semi-quantitative FFQ during the first postpartum week; the time frame included the second and third gestational trimesters. Principal component analysis was used to identify dietary patterns during pregnancy. Sociodemographic data were obtained using a structured questionnaire. Multiple linear regressions were applied to test the associations between the sociodemographic factors and dietary patterns. SETTING:Mesquita, Rio de Janeiro, Brazil, 2011. SUBJECTS:Postpartum women (n 327) who were 18-45 years of age and Mesquita residents. RESULTS:Three different dietary patterns were identified: 'healthy' (mainly comprising legumes, vegetables and fruits), 'mixed' (mainly comprising candy, butter and margarine, and snacks) and 'traditional' (mainly comprising beans and rice). Women with a higher monthly per capita family income (β=0·0006; 95% CI 0·0001, 0·001; P=0·011) and women of older age (β=0·021; 95% CI -0·001, 0·042; P=0·058) were more likely to adhere to the 'healthy' dietary pattern. Women with higher parity were less likely to adhere to the 'healthy' pattern (β=-0·097; 95% CI -0·184, -0·009; P=0·030) and were more likely to adhere to the 'traditional' pattern (β=0·098; 95% CI 0·021, 0·175; P=0·012). Although not statistically significant, older women were less likely to adhere to the 'mixed' (β=-0·017; 95% CI -0·037, 0·003; P=0·075) and 'traditional' (β=-0·018; 95% CI -0·037, 0·001; P=0·061) dietary patterns. CONCLUSIONS:Monthly per capita family income, parity and maternal age were factors associated with adherence to a healthy diet during pregnancy