Interference of Cranberry Constituents in Cell–Cell Signaling System of <Emphasis Type=Italic>Vibrio harveyi</Emphasis>

Cranberry juice has long been recognized in folk medicine as a therapeutic agent, mainly in urinary track infections. It acts as an antibiofilm agent against various pathogens. Quorum sensing is process where bacteria communicate with each other via signal molecules known as autoinducers. This process is strongly involved in various bacterial pathological and physiological pathways. Various strains of Vibrio harveyi bacteria were incubated with different concentrations of nondialyzable material of cranberry (NDM) with or without addition of exogenous autoinducer. Bioluminescence regulated by the autoinducers was measured in GENios reader. Effect of NDM alone or NDM supplemented with autoinducer on quorum sensing was determined as change in bioluminescence in each treated sample compared to appropriate control in every strain. Using model of V. harveyi, we found an inhibitory effect of cranberry constituents on bacterial signaling system. This effect was reversible, since exogenous autoinducer was able to recover bioluminescence which was decreased by NDM. We hypothesized that cranberry NDM interacts with V. harveyi quorum sensing by competition with autoinducer for binding to autoinducer sensor.     

Enzymatic activation of hydrophobic self-immolative dendrimers: The effect of reporters with ionizable functional groups

Self-immolative dendrimers are uniquely structured molecules that release multiple tail units through a chain fragmentation initiated by a single cleavage at the dendrimer’s core. Although bioactivation of self-immolative dendritic molecules with only two reporter groups was demonstrated, enzymatic activation failed for self-immolative dendrimers with more reporters. These large and hydrophobic dendrimers aggregated under aqueous conditions and enzyme did not efficiently trigger chain fragmentation. Here we demonstrate a simple solution to the problem of enzymatic activation of hydrophobic self-immolative dendrimers. The reporter units on the dendritic platform were equipped with ionizable functional group. Polar interactions with water significantly decreased hydrophobicity of the dendrimers and prevented aggregate formation. Consequently, hydrophobic self-immolative dendrons were effectively activated.     

Estimating the size of the olfactory repertoire

The concept of shape space, which has been successfully implemented in immunology, is used here to construct a model for the discrimination power of the olfactory system. Using reasonable assumptions on the behaviour of the biological system, we are able to estimate the number of distinct olfactory receptor types. Our estimated value of around 1000 receptor types is in good agreement with experimental data.     

Biphasic Activation of WNT Signaling Facilitates the Derivation of Midbrain Dopamine Neurons from hESCs for Translational Use

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Prospects of a Computational Origin of Life Endeavor

While the last century brought an exquisite understanding of the molecular basis of life, very little is known about the detailed chemical mechanisms that afforded the emergence of life on early earth. There is a broad agreement that the problem lies in the realm of chemistry, and likely resides in the formation and mutual interactions of carbon-based molecules in aqueous medium. Yet, present-day experimental approaches can only capture the synthesis and behavior of a few molecule types at a time. On the other hand, experimental simulations of prebiotic syntheses, as well as chemical analyses of carbonaceous meteorites, suggest that the early prebiotic hydrosphere contained many thousands of different compounds. The present paper explores the idea that given the limitations of test-tube approaches with regards to such a 'random chemistry' scenario, an alternative mode of analysis should be pursued. It is argued that as computational tools for the reconstruction of molecular interactions improve rapidly, it may soon become possible to perform adequate computer-based simulations of prebiotic evolution. We thus propose to launch a computational origin of life endeavor (http://ool.weizmann.ac.il/CORE), involving computer simulations of realistic complex prebiotic chemical networks. In the present paper we provide specific examples, based on a novel algorithmic approach, which constitutes a hybrid of molecular dynamics and stochastic chemistry. As one potential solution for the immense hardware requirements dictated by this approach, we have begun to implement an idle CPU harvesting scheme, under the title ool@home.