The hrp genes of Pseudomonas cichorii are essential for pathogenicity on eggplant but not on lettuce

Pseudomonas cichorii causes necrotic lesions in eggplant and rot in lettuce. Through transposon insertion into P. cichorii strain SPC9018 we produced two mutants, 4-57 and 2-99, that lost virulence on eggplant but not lettuce. Analyses showed that a transposon was inserted into the hrpG gene in 4-57 and the hrcT gene in 2-99. Nucleotide sequences of the hrp genes of SPC9018 are homologous to those of Pseudomonas viridiflava BS group strains. The pathogenicity of 4-57 on eggplant was restored by transformation with an hrpF operon, originating from either SPC9018 or the BS group member P. viridiflava strain 9504 (Pv9504). These data suggested the involvement of hrp genes in the pathogenicity of SPC9018 on eggplant, and functional conservation of hrpF operons between SPC9018 and Pv9504. Both the hrpS mutant and the hrpL mutant were unable to cause necrotic lesions on eggplant leaves but retained their pathogenicity against lettuce. These results suggest that the pathogenicity of P. cichorii is hrp-dependent in eggplant, but not in lettuce

Self-Assembly of Water-Mediated Supramolecular Cationic Archimedean Solids

Understanding the self-assembly of small structural units into large supramolecular assemblies remains one of the great challenges in structural chemistry. We have discovered that tetrahedral supramolecular cages, exhibiting the shapes of Archimedean solids, can be self-assembled by hydrogen bonding interactions using tricationic N-donors (<b>1</b> or <b>2</b>) in cooperation with water (W). Single crystal X-ray analysis shows that cage (<b>2</b>)₄(W)₆, assembled in an aqueous solution of cation <b>2</b> and KPF₆, consists of four tripodal trications linked by six water monomers and resembles the shape of a truncated tetrahedron. Similarly, cage (<b>1</b>)₄(W₆)₄ spontaneously self-assembles in an aqueous solution of cation <b>1</b> and NH₄PF₆ and consists of four tripodal cations and four water hexamers. Here, each of the four (H₂O)₆ units act as tritopic nodes between three distinct tripodal cations forming a polyhedron similar to the cantellated tetrahedron. These two well-defined cages are assembled via total of 12 and 36 hydrogen bonds, respectively. Both cages possess interior solvent-accessible volumes exceeding 1000 ų. Furthermore, each one of the (H₂O)₆ clusters in face-centered cubic structure <b>1b</b> acts as a node between two distinct (<b>1</b>)₄(W₆)₄ units, and thus a solvent-filled tubular three-dimensional network (tube diameter of ∼6.5 Å) is generated that mimics the structure of diamond at the nanometer scale. To our knowledge, this is the first example of such species being formed entirely via hydrogen bonding interactions

Lipid Bilayer-Gated Mesoporous Silica Nanocarriers for Tumor-Targeted Delivery of Zoledronic Acid <i>in Vivo</i>

Zoledronic acid (ZOL) is a nitrogen-containing bis­phosphonate used for the treatment of bone diseases and calcium metabolism. Anticancer activity of ZOL has been established, but its extraskeletal effects are limited due to its rapid uptake and accumulation to bone hydroxyapatite. In this work, we report on the development of tethered lipid bilayer-gated mesoporous silica nanocarriers (MSNs) for the incorporation, retention, and intracellular delivery of ZOL. The <i>in vitro</i> anticancer activity of ZOL-loaded nanocarriers was evaluated by cell viability assay and live-cell imaging. For <i>in vivo</i> delivery, the nanocarriers were tagged with folic acid to boost the affinity for breast cancer cells. Histological examination of the liver revealed no adverse off-target effects stemming from the nanocarriers. Importantly, nonspecific accumulation of ZOL within bone was not observed, which indicated <i>in vivo</i> stability of the tethered lipid bilayers. Further, the intravenously administered ZOL-loaded nanocarriers showed tumor growth suppression in breast cancer xenograft-bearing mice

Correction: Whole exome sequencing study identifies novel rare and common Alzheimer’s-Associated variants involved in immune response and transcriptional regulation (Molecular Psychiatry, (2018), 10.1038/s41380-018-0112-7)

textabstractFollowing publication, the authors noticed that ‘Laura Cantwell’, ‘Otto Valladares’, and ‘Li-San Wang’ were inadvertently omitted from the author list. These authors have now been added to the author list in 21st, 77th, and 79th position, respectively. This has been corrected in both the PDF and HTML versions of the article

Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism

Summary We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n=35,584 total samples, 11,986 with ASD). Using an enhanced Bayesian framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate ≤ 0.1. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained for severe neurodevelopmental delay, while 53 show higher frequencies in individuals ascertained for ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most of the risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In human cortex single-cell gene expression data, expression of risk genes is enriched in both excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory/inhibitory imbalance underlying ASD