Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

Pyridine-3,4-dicarboximide as starting material for the total synthesis of the natural product eupolauramine and its isomer iso-eupolauramine endowed with anti-tubercular activities

A direct and convenient synthetic pathway for preparation of the key intermediate aza-isoindolinone 4a/4b, which could be ready obtained from pyridine-3,4-dicarboximide was described. This approach was valorized in the total synthesis of the natural product eupolauramine 7b and in the first synthesis of the position analog iso-eupolauramine 7a, which was obtained after 6 steps in an overall yield of 13%. The developed strategy represents the first synthetic approach employing a starting material already embedding the pyridine and the lactam cycles (cycles D and C, respectively) of the azaphenanthrene lactam framework. These compounds, mainly the new non-natural product, showed a good inhibitory activity against Mycobacterium tuberculosis growth

The long-term effect of a partial whey hydrolysate formula on the prophylaxis of atopic disease

At the age of 5 years, the prevalence of atopic manifestations was analysed in 58 formula-fed ''at risk'' infants because of a history of atopic disease in at least two first degree relatives. Infants were randomly assigned to receive either a partial whey-hydrolysate formula (n: 28) or a regular cow's milli formula (n: 30) during the first 6 months of life; thereafter, feeding was unrestricted. Only non-breastfed infants were included. The groups did not differ in risk factors or in known confounding factors possibly influencing the incidence of manifestations suggestive of atopic disease. At 6 months, the prevalence of cow's milk protein (CMP) sensitivity was significantly decreased in the hydrolysate group (7% versus 43%; P: 0.002). At the age of 12 (21% versus 53%; P: 0.029), 36 (25% versus 57%; P: 0.018) and 60 months (29% versus 60%; P: 0.016) there was still a significant difference in the number of atopic manifestations, if calculated cumulatively. There was no difference between the groups if only the new cases after the age of 6 months were considered. Eczema was less frequent in the whey-hydrolysate group, but only during the Ist year of life, suggesting a decreased prevalence of CMP sensitivity. During the first 6 months, diarrhoea of non-infectious origin occurred in 8/30 infants (27%) of the adapted formula group, and in no infant in the hydrolysate group. ''Colic as single manifestation'' was considered of ''allergic'' origin in 1/28 infants in the hydrolysate group, and in 4/30 infants in the adapted formula group. If gastro-intestinal symptoms such as ''diarrhoea and colic as single manifestation'' are not considered, the number of infants with CMP sensitivity remains only significant for the first 6 months (P: 0.004). At 12, 36 and 60 months, differences are not significant (0.106, 0.116 and 0.07, respectively). The results of this study support the hypothesis that allergy prevention is antigen specific. Conclusion If mother's milk is not available and other studies confirm these results, there might be an indication for partial hydrolysates in infants with a family history of atopy, since these formulae reduce the incidence of CMP sensitivity

Psoromic Acid Derivatives: A New Family of Small-Molecule Pre-mRNA Splicing Inhibitors Discovered by a Stage-Specific High-Throughput in Vitro Splicing Assay

Snapshots of spliceosome assembly: A high-throughput in vitro splicing assay has been developed for screening a compound library. The discovered family of pre-mRNA splicing inhibitors comprises lichen secondary metabolites that allow the enrichment of the spliceosomal complexes formed after the spliceosome activation step. Here we identify the structural features important for the compounds' inhibitory activity

What do palliative care patients and their relatives think about research in palliative care? - a systematic review

Research in palliative care patients has been controversial and is often challenging. It is important to know the views of potentially eligible patients themselves in order to determine the appropriateness of research in the palliative care population and to develop realistic studies that are practical and achievable in this population. This systematic review aims to identify the views of palliative care patients and their families towards research, the factors that are important when considering participation, and the types of research trial they would support or reject

Biology-oriented synthesis of a natural-product inspired oxepane collection yields a small-molecule activator of the Wnt-pathway

In Biology Oriented Synthesis the scaffolds of biologically relevant compound classes inspire the synthesis of focused compound collections enriched in bioactivity. This criterion is met by the structurally complex scaffolds of natural products (NPs) selected in evolution. The synthesis of NP-inspired compound collections approaching the complexity of NPs calls for the development of efficient synthetic methods. We have developed a one pot 4–7 step synthesis of mono-, bi-, and tricyclic oxepanes that resemble the core scaffolds of numerous NPs with diverse bioactivities. This sequence entails a ring-closing ene-yne metathesis reaction as key step and makes productive use of polymer-immobilized scavenger reagents. Biological profiling of a corresponding focused compound collection in a reporter gene assay monitoring for Wnt-signaling modulation revealed active Wntepanes. This unique class of small-molecule activators of the Wnt pathway modulates the van-Gogh-like receptor proteins (Vangl), which were previously identified in noncanonical Wnt signaling, and acts in synergy with the canonical activator protein (Wnt-3a)