{4-[(Diphenyl­phosphino)methyl­amino]pyridinium-κP}bis­(nitrato-κO)silver(I)

In the title mononuclear complex, [Ag(C18H18N2P)(NO3)2], the metal centre is coordinated in a slightly distorted trigonal–planar geometry by the P atom of the phosphine ligand and the O atoms of the two monodentate nitrate anions. In the crystal structure, complex mol­ecules are connected by inter­molecular N—H⋯O hydrogen bonds, forming chains running parallel to the b axis

Tetra­aqua­bis(2-methyl­benzimidazolium-1,3-diacetato-κO)zinc(II) tetra­hydrate

The asymmetric unit of the title compound, [Zn(C12H11N2O4)2(H2O)4]·4H2O, contains one-half of the complex mol­ecule and two uncoordin­ated water mol­ecules. The four water O atoms in the equatorial plane around the ZnII centre ( symmetry) form a distorted square-planar arrangement, while the distorted octa­hedral coordination geometry is completed by the O atoms of the zwitterionic 2-methyl­benzimidazolium-1,3-diacetate ligands in the axial positions. The benzimidazole ring system is planar, with a maximum deviation of 0.041 (3) Å. Intra­molecular O—H⋯O hydrogen bonding results in the formation of a non-planar six-membered ring. In the crystal structure, strong intra- and inter­molecular O—H⋯O hydrogen bonds link the mol­ecules into a three-dimensional network. π–π contacts between benzimidazole rings [centroid–centroid distance = 3.899 (1) Å] may further stabilize the structure

[μ-N,N,N′,N′-Tetra­kis(diphenyl­phosphino­meth­yl)benzene-1,4-diamine-κ4 P,P′:P′′,P′′′]bis­[bis­(nitrato-κO)palladium(II)]

The asymmetric unit of the title complex, [Pd2(NO3)4(C58H52N2P4)], contains one half-mol­ecule, in which the central benzene ring is located on a crystallographic centre of inversion. The Pd atom has a distorted square-planar coordination consisting of two P and two O atoms. In the crystal structure, inter­molecular C—H⋯O inter­actions link the mol­ecules into chains, and π–π contacts between the phenyl rings [centroid–centroid distance = 3.928 (3) Å] may further stabilize the structure

Genomewide association study of leprosy.

BACKGROUND: The narrow host range of Mycobacterium leprae and the fact that it is refractory to growth in culture has limited research on and the biologic understanding of leprosy. Host genetic factors are thought to influence susceptibility to infection as well as disease progression. METHODS: We performed a two-stage genomewide association study by genotyping 706 patients and 1225 controls using the Human610-Quad BeadChip (Illumina). We then tested three independent replication sets for an association between the presence of leprosy and 93 single-nucleotide polymorphisms (SNPs) that were most strongly associated with the disease in the genomewide association study. Together, these replication sets comprised 3254 patients and 5955 controls. We also carried out tests of heterogeneity of the associations (or lack thereof) between these 93 SNPs and disease, stratified according to clinical subtype (multibacillary vs. paucibacillary). RESULTS: We observed a significant association (P<1.00x10(-10)) between SNPs in the genes CCDC122, C13orf31, NOD2, TNFSF15, HLA-DR, and RIPK2 and a trend toward an association (P=5.10x10(-5)) with a SNP in LRRK2. The associations between the SNPs in C13orf31, LRRK2, NOD2, and RIPK2 and multibacillary leprosy were stronger than the associations between these SNPs and paucibacillary leprosy. CONCLUSIONS: Variants of genes in the NOD2-mediated signaling pathway (which regulates the innate immune response) are associated with susceptibility to infection with M. leprae

Disruption of Guanylyl Cyclase-G Protects against Acute Renal Injury

The membrane forms of guanylyl cyclase (GC) serve as cell-surface receptors that synthesize the second messenger cGMP, which mediates diverse cellular processes. Rat kidney contains mRNA for the GC-G isoform, but the role of this receptor in health and disease has not been characterized. It was found that mouse kidney also contains GC-G mRNA, and immunohistochemistry identified GC-G protein in the epithelial cells of the proximal tubule and collecting ducts. Six hours after ischemia-reperfusion (I/R) injury, GC-G mRNA and protein expression increased three-fold and remained upregulated at 24 h. For determination of whether GC-G mediates I/R injury, a mutant mouse with a targeted disruption of the GC-G gene (Gucy2g) was created. At baseline, no histologic abnormalities were observed in GC-G−/− mice. After I/R injury, elevations in serum creatinine and urea were attenuated in GC-G−/− mice compared with wild-type controls, and this correlated with less tubular disruption, less tubular cell apoptosis, and less caspase-3 activation. Measures of inflammation (number of infiltrating neutrophils, myeloperoxidase activity, and induction of IL-6 and P-selectin) and activation of NF-κB were lower in GC-G−/− mice compared with wild-type mice. Direct transfer of a GC-G expression plasmid to the kidneys of GC-G−/− mice resulted in a dramatically higher mortality after renal I/R injury, further supporting a role for GC-G in mediating injury. In summary, GC-G may act as an early signaling molecule that promotes apoptotic and inflammatory responses in I/R-induced acute renal injury