SummaryStreptomycetes are mycelial bacteria that produce sporulating aerial hyphae on solid media. Bald ( bld ) mutants fail to form aerial mycelium under at least some conditions. bldA encodes the only tRNA species able to read the leucine codon UUA efficiently, implying the involvement of a TTA-containing gene in initiating aerial growth. One candidate for such a gene was bldH , because the bldH109 mutant of Streptomyces coelicolor resembles bldA mutants in some aspects. In the work reported here, adpA c , an S. coelicolor gene similar to the Streptomyces griseus A factor-regulated adpA g , was found to complement the bldH109 mutant partially at both single and multiple copies. The sequence of adpA c from the bldH109 mutant revealed a frameshift. A constructed in frame deletion of adpA c conferred a bald colony phenotype, and the mutant behaved like bldA mutants and bldH109 in its pattern of extracellular signal exchange. Both adpA c and adpA g contain a TTA codon. A TTA-free version of adpA c was engineered by replacing the TTA leucine codon with a cognate TTG leucine codon. The adpA (TTA AE AE AE AE TTG) gene could partially restore aerial mycelium formation to a bldA mutant when it was followed in cis by the gene ornA , as in the natural chromosomal arrangement. This indicated that the UUA codon in adpA c mRNA is the principal target through which bldA influences morphological differentiation. It also implied that translational arrest at the UUA codon in adpA c mRNA caused a polar effect on the downstream ornA , and that the poor translation of both genes contributes extensively to the deficiency of aerial mycelium formation in bldA mutants. Unlike the situation in S. griseus , adpA c transcription does not depend on the host's g g g gbutyrolactone signalling system, at least in liquid cultures. In addition, sigma factor BldN, which is the homologue of an S. griseus sigma factor AdsA that is absent from adpA g mutants of S. griseus , was present in the constructed adpA c null mutant of S. coelicolor .

Parkinson’s disease (PD) is characterized by a prominent degeneration of nigrostriatal dopamine (DA) neurons with an accompanying neuroinflammation. Despite clinical and preclinical studies of neuroprotective strategies for PD, there is no effective treatment for preventing or slowing the progression of neurodegeneration. The inverse correlation between caffeine consumption and risk of PD suggests that caffeine may exert neuroprotection. Whether caffeine is neuroprotective in a chronic progressive model of PD has not been evaluated nor is it known if delayed caffeine treatment can stop DA neuronal loss. We show that a chronic unilateral intra-cerebroventricular infusion of 1-methyl-4-phenylpyridinium in the rat brain for 28 days produces a progressive loss of DA and tyrosine hydroxylase in the ipsilateral striatum and a loss of DA cell bodies and microglial activation in the ipsilateral substantia nigra. Chronic caffeine consumption prevented the degeneration of DA cell bodies in the substantia nigra. Importantly, neuroprotection was still apparent when caffeine was introduced after the onset of the neurodegenerative process. These results add to the clinical relevance for adenosine receptors as a disease-modifying drug target for PD.

We reveal that PEMF improved bone architecture, mechanical properties, and pTi osseointegration by promoting bone anabolism through a canonical Wnt/β-catenin signaling-associated mechanism. This study enriches our basic knowledge for understanding skeletal sensitivity in response to external electromagnetic signals, and also opens new treatment alternatives for T1DM-associated osteopenia/osteoporosis and osseous defects in an easy and highly efficient manner.

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