ZnuA and zinc homeostasis in pseudomonas aeruginosa

Pseudomonas aeruginosa is a ubiquitous environmental bacterium and a clinically significant opportunistic human pathogen. Central to the ability of P. aeruginosa to colonise both environmental and host niches is the acquisition of zinc. Here we show that P. aeruginosa PAO1 acquires zinc via an ATP-binding cassette (ABC) permease in which ZnuA is the high affinity, zinc-specific binding protein. Zinc uptake in Gram-negative organisms predominantly occurs via an ABC permease, and consistent with this expectation a P. aeruginosa ΔznuA mutant strain showed an ~60% reduction in cellular zinc accumulation, while other metal ions were essentially unaffected. Despite the major reduction in zinc accumulation, minimal phenotypic differences were observed between the wild-type and ΔznuA mutant strains. However, the effect of zinc limitation on the transcriptome of P. aeruginosa PAO1 revealed significant changes in gene expression that enable adaptation to low-zinc conditions. Genes significantly up-regulated included non-zinc-requiring paralogs of zinc-dependent proteins and a number of novel import pathways associated with zinc acquisition. Collectively, this study provides new insight into the acquisition of zinc by P. aeruginosa PAO1, revealing a hitherto unrecognized complexity in zinc homeostasis that enables the bacterium to survive under zinc limitation.Victoria G. Pederick, Bart A. Eijkelkamp, Stephanie L. Begg, Miranda P. Ween, Lauren J. McAllister, James C. Paton, Christopher A. McDevit

Missense variant contribution to USP9X-female syndrome

USP9X is an X-chromosome gene that escapes X-inactivation. Loss or compromised function of USP9X leads to neurodevelopmental disorders in males and females. While males are impacted primarily by hemizygous partial loss-of-function missense variants, in females de novo heterozygous complete loss-of-function mutations predominate, and give rise to the clinically recognisable USP9X-female syndrome. Here we provide evidence of the contribution of USP9X missense and small in-frame deletion variants in USP9X-female syndrome also. We scrutinise the pathogenicity of eleven such variants, ten of which were novel. Combined application of variant prediction algorithms, protein structure modelling, and assessment under clinically relevant guidelines universally support their pathogenicity. The core phenotype of this cohort overlapped with previous descriptions of USP9X-female syndrome, but exposed heightened variability. Aggregate phenotypic information of 35 currently known females with predicted pathogenic variation in USP9X reaffirms the clinically recognisable USP9X-female syndrome, and highlights major differences when compared to USP9X-male associated neurodevelopmental disorders

Genetic variation in Eucalyptus nitens pulpwood and wood shrinkage traits

Eucalyptus nitens plantations are generally established for pulpwood production but an increasing area is being managed for solid wood. Genetic variation in, and correlations among, three Kraft pulpwood traits (diameter at breast height, basic density and near-infrared-predicted cellulose content) and three 12-mm wood-core shrinkage traits (recoverable collapse, net shrinkage and gross shrinkage) were examined, utilising data from two 9-year-old first-generation progeny trials in Tasmania. These trials contained approximately 400 open-pollinated families (over 100 of which were sampled for wood properties) representing three central-Victorian E. nitens races. Significant genetic variation at the race and/or within-race level was identified in all traits. Within races, relative levels of additive genetic variation were higher for shrinkage traits, although narrow-sense heritabilities were lower and the expression of genetic variation less stable across sites than for other wood property traits. Heterogeneous intertrait genetic correlations were identified across sites between growth and some wood property traits. However, where significant, genetic correlations indicated that within-race selection for growth would adversely affect core basic density and all core shrinkage traits. Furthermore, results based on cores suggested that within-race selection for higher basic density would favourably impact on cellulose content and collapse but selection for either higher basic density or cellulose content would adversely affect net shrinkage. Most within-race genetic variation in gross shrinkage appeared to be due to genetic variation in collapse. The implications of these results for sawn timber breeding will depend on the strength of genetic correlations between core traits and rotation-age objective traits and objective trait economic weights