Circulating small non-coding RNAs provide new insights into vitamin K nutrition and reproductive physiology in teleost fish

Background

Vitamin K (VK) is a fat-soluble vitamin known for its essential role in blood coagulation, but also on other biological processes (e.g. reproduction, brain and bone development) have been recently suggested. Nevertheless, the molecular mechanisms behind its particular function on reproduction are not yet fully understood.

Synthesis and structure based optimization of novel Akt inhibitors

Based on a high throughput screening hit, pyrrolopyrimidine inhibitors of the Akt kinase are explored. X-ray co-crystal structures of two lead series results in the understanding of key binding interactions, the design of new lead series, and enhanced potency. The syntheses of these series and their biological activities are described. Spiroindoline 13j is found to have an Akt1 kinase IC(50) of 2.4+/-0.6 nM, Akt cell potency of 50+/-19 nM, and provides 68% inhibition of tumor growth in a mouse xenograft model (50 mg/kg, qd, po).     

Road building, land use and climate change: prospects for environmental governance in the Amazon

Some coupled land-climate models predict a dieback of Amazon forest during the twenty-first century due to climate change, but human land use in the region has already reduced the forest cover. The causation behind land use is complex, and includes economic, institutional, political and demographic factors. Pre-eminent among these factors is road building, which facilitates human access to natural resources that beget forest fragmentation. While official government road projects have received considerable attention, unofficial road building by interest groups is expanding more rapidly, especially where official roads are being paved, yielding highly fragmented forest mosaics. Effective governance of natural resources in the Amazon requires a combination of state oversight and community participation in a 'hybrid' model of governance. The MAP Initiative in the southwestern Amazon provides an example of an innovative hybrid approach to environmental governance. It embodies a polycentric structure that includes government agencies, NGOs, universities and communities in a planning process that links scientific data to public deliberations in order to mitigate the effects of new infrastructure and climate change.     

Optimal control of epidemics with limited resources

We extend the existing work on the time-optimal control of the basic SIR epidemic model with mass action contact rate. Previous results have focused on minimizing an objective function that is a linear combination of the cost associated with using control and either the outbreak size or the infectious burden. We instead, provide analytic solutions for the control that minimizes the outbreak size (or infectious burden) under the assumption that there are limited control resources. We provide optimal control policies for an isolation only model, a vaccination only model and a combined isolation–vaccination model (or mixed model). The optimal policies described here contain many interesting features especially when compared to previous analyses. For example, under certain circumstances the optimal isolation only policy is not unique. Furthermore the optimal mixed policy is not simply a combination of the optimal isolation only policy and the optimal vaccination only policy. The results presented here also highlight a number of areas that warrant further study and emphasize that time-optimal control of the basic SIR model is still not fully understood.