Global chemical effects of the microbiome include new bile-acid conjugations

A mosaic of cross-phylum chemical interactions occurs between all metazoans and their microbiomes. A number of molecular families that are known to be produced by the microbiome have a marked effect on the balance between health and disease. Considering the diversity of the human microbiome (which numbers over 40,000 operational taxonomic units), the effect of the microbiome on the chemistry of an entire animal remains underexplored. Here we use mass spectrometry informatics and data visualization approaches to provide an assessment of the effects of the microbiome on the chemistry of an entire mammal by comparing metabolomics data from germ-free and specific-pathogen-free mice. We found that the microbiota affects the chemistry of all organs. This included the amino acid conjugations of host bile acids that were used to produce phenylalanocholic acid, tyrosocholic acid and leucocholic acid, which have not previously been characterized despite extensive research on bile-acid chemistry. These bile-acid conjugates were also found in humans, and were enriched in patients with inflammatory bowel disease or cystic fibrosis. These compounds agonized the farnesoid X receptor in vitro, and mice gavaged with the compounds showed reduced expression of bile-acid synthesis genes in vivo. Further studies are required to confirm whether these compounds have a physiological role in the host, and whether they contribute to gut diseases that are associated with microbiome dysbiosis

Relationship between Changes in the Protein Folding Pathway and the Process of Amyloid Formation: The Case of Bovine Carbonic Anhydrase II

Many proteins form amyloid fibrils only under conditions when the probability of transition from a native (structured, densely packed) to an intermediate (labile, destabilized) state is increased. It implies the assumption that some structural intermediates are more convenient for amyloid formation than the others. Hence, if a mutation affects the protein folding pathway, one should expect that this mutation could affect the rate of amyloid formation as well. In the current work, we have compared the effects of amino acid substitutions of bovine carbonic anhydrase II on its unfolding pathway and on its ability to form amyloids at acidic pH and an elevated temperature. Wild-type protein and four mutant forms (L78A, L139A, I208A, and M239A) were studied. We analyzed the change of the protein unfolding pathway by the time-resolved fluorescence technique and the process of amyloid formation by thioflavin T fluorescence assay and electron microscopy. It was revealed that I208A substitution accelerates amyloid formation and affects the structure of the late (molten globule-like)-intermediate state of carbonic anhydrase, whereas the other mutations slow down the growth of amyloids and have either no effect on the unfolding pathway (L78A, L139A) or alter the conformational states arising at the early unfolding stage (M239A)

Analytical Method of Examining the Curvilinear Motion of a Four-wheeled Vehicle

We obtained equations for the curvilinear trajectory of a four-wheeled vehicle in the parametric form of a function of turning angle of the machine frame. The equations are suitable for the sections of entering a turn and exiting a turn. The proposed equations make it possible to build the trajectories taking into account the intensity of turning the front steered wheels. For this purpose, the course angle is represented as a function of the turning angle of the body of a machine. For example, in the case of a linear dependence, the proportionality factor (coefficient of intensity of change in the course angle, predetermined by the rotation speed of steered wheels) depends on the turning angle of a steering wheel. The solution was found based on the projections of velocity of the center of mass of a machine onto the inertial coordinate axes. In this case, the integrand functions are represented through a single variable – turning angle of the machine frame. For this purpose, we employed a special substitution, which replaces the differential of time with the differential of turning angle of the machine frame. Following the decomposition of integrand functions into the Maclaurin series, the integration becomes possible. We also found the equation of motion along a circular trajectory at fixed position of a steering wheel. Along with the equations for entering a turn and exiting a turn, they allow us to build complex trajectories of u-turns in a unified coordinate system. For the conjugation of separate sections of the trajectory, we applied formulas of change in the coordinates at parallel carry and turn of the coordinate axes. The coordinates of points along the trajectory can be calculated by using the software tools.The impact of the phenomenon of wheels slip under the action of lateral forces on the trajectory of curvilinear motion is accounted for by introducing to the equations the intensity coefficients that represent dependence of the course angle, caused by the slip, on the turning angle of the machine fram

Molecular Mechanisms of The Anomalous Thermal Aggregation of Green Fluorescent Protein

The peculiarities of thermal denaturation and interaction with water of the cycle-3 mutant of green fluorescent protein (GFP) were analyzed by NMR techniques and compared with those of bovine carbonic anhydrase II (BCA-II). Irreversible thermal denaturation was accompanied by massive GFP aggregation with no detectable accumulation of soluble denatured protein. Analysis of the spin diffusion data suggested that the internal part of the GFP β-can is involved in intensive interactions with water molecules. As a result, at high temperatures, the GFP structure does not unfold but rather breaks, consequently leading to enhanced protein aggregation. This is very different from typical BCA-II behavior

Hydroacoustic approaches to fish stock assesment in lake Baïkal

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