Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota

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Feedback regulation of 3-deoxy-D-arabino-heptulosonate 7-phosphate synthetase from a marine bacterium, Vibrio MB22

A marine bacterium, Vibrio MB22, has been studied to determine the pattern of feedback regulation of the first enzyme unique to the biosynthesis of the aromatic amino acids, 3-deoxy-d-arabino-heptulosonate 7-phosphate (DAHP) synthetase. The crude extract was used to study response of the enzyme to various salts as well as possible feedback inhibitors. Ethylenediaminetetraacetic acid was found to be inhibitory to enzyme activity, and only CoCl(2), of the salts tested, allowed full recovery as well as apparent stimulation of the DAHP synthetase activity. The DAHP synthetase activity was inhibited solely by the aromatic amino acids, tyrosine, tryptophan, and phenylalanine, of the possible effectors tested. Further work demonstrated the existence of three isozymes of DAHP synthetase, each primarily inhibited by one of the aromatic amino acids.     

The effect of pyridoxine deficiency on the metabolism of the aromatic amino acids by isolated rat liver cells

The total activity of three key enzymes and the flux through eight steps of aromatic amino acid metabolism have been determined in liver cells isolated from rats fed either control or pyridoxine-free diet for 5-6 weeks. The pyridoxine-free diet caused a decrease in the catabolism of tyrosine and phenylalanine because of a drop in the flux through tyrosine aminotransferase. This decrease of expressed cellular tyrosine aminotransferase activity can be fully explained in terms of loss of cofactor. Larger decreases in the catabolism of tryptophan were seen after pyridoxine deprivation. The decreased extent of tryptophan catabolism can be solely attributed to loss of cofactor or increased degradation of kynureninase. Inhibition of tryptophan 2,3-dioxygenase was seen in pyridoxine deficiency, probably because of the buildup of the kynurenine metabolites. The control strength of kynureninase, for flux through kynureninase, was calculated to be less than or equal to 0.004, but 0.41 after pyridoxine deprivation. The sensitivity of the three pathways to pyridoxine deprivation is interpreted and discussed in terms of the different affinities for pyridoxal phosphate and the control strengths of the pyridoxal phosphate-dependent enzymes, tyrosine aminotransferase and kynureninase.     

Impact of long-term,saline flooding on condition and reproduction of the clonal wetland tree, <Emphasis Type="Italic">Melaleuca ericifolia</Emphasis> (Myrtaceae)

Although water regime modification and salinity are recognised as significant threats to wetland ecosystems worldwide, the effects of long-term saline flooding (decades) on woody tree persistence are poorly quantified. We compared the condition, growth, structure and reproduction (sexual and asexual) of mature individuals of the clonal tree, Melaleuca ericifolia (Myrtaceae), that experienced continual (>30 years) flooding with trees that were only intermittently (approximately every 5 years) flooded. An index developed to assess the condition of multi-stemmed trees found that continually flooded trees were in significantly poorer condition than intermittently flooded trees, having lower crown cover, foliar cover and foliar density, and a higher incidence of dead stags and dieback. Annual stem growth correlated strongly with condition scores. Evidence for a trade-off between sexual and asexual reproductions was found; flooded trees were constrained in their vegetative lateral spread (<12 m dia.) and flowered more than intermittently flooded trees, which were not restricted in lateral spread (~30 m dia.). Flooded trees used intensively by the colonially roosting Australian Sacred Ibis (Threskiornis molucca) were in especially poor condition. These trees flowered infrequently and produced the lowest number of infructescences, but produced many new vegetative stems (ramets) within their centre. Although chronic flooding appeared to compromise the condition of M. ericifolia trees in Dowd Morass, their existence upon woody hummocks (~40 cm high) upon which they are able to produce new stems is likely to be a key mechanism in their persistence. It is unknown, however, how long this process can maintain the existing population. Production and maintenance of a large aerial seed bank by living mature trees under flooded conditions may allow M. ericifolia to regenerate sexually upon drawdown and may be important for population persistence in the longer term.     

A new chemical tool for exploring the role of the PDE4D isozyme in leukocyte function

Nicotinamide (2) is a potent and selective inhibitor of the PDE4D isozyme and as a chemical tool selectively blocks eosinophil mediator release and chemotaxis thus linking the role of PDE4D to eosinophil function.     

Dynein light intermediate chains maintain spindle bipolarity by functioning in centriole cohesion

Cytoplasmic dynein 1 (dynein) is a minus end–directed microtubule motor protein with many cellular functions, including during cell division. The role of the light intermediate chains (LICs; DYNC1LI1 and 2) within the complex is poorly understood. In this paper, we have used small interfering RNAs or morpholino oligonucleotides to deplete the LICs in human cell lines and Xenopus laevis early embryos to dissect the LICs’ role in cell division. We show that although dynein lacking LICs drives microtubule gliding at normal rates, the LICs are required for the formation and maintenance of a bipolar spindle. Multipolar spindles with poles that contain single centrioles were formed in cells lacking LICs, indicating that they are needed for maintaining centrosome integrity. The formation of multipolar spindles via centrosome splitting after LIC depletion could be rescued by inhibiting Eg5. This suggests a novel role for the dynein complex, counteracted by Eg5, in the maintenance of centriole cohesion during mitosis.