Novel mutations in the pathogenesis of transient neonatal zinc deficiency.

Importance: Transient neonatal zinc deficiency (TNZD) occurs in breastfed infants due to abnormally low breast milk zinc levels. Mutations in the solute carrier family 30 member 2 () gene, which encodes the zinc transporter ZNT2, cause low zinc concentration in breast milk.

Objective: This study aimed to provide further insights into TNZD pathophysiology.

Cost-effectiveness of baloxavir marboxil compared with laninamivir for the treatment of influenza in patients at high risk for complications in Japan.

Objective: Baloxavir marboxil (baloxavir) is a single-dose antiviral which was previously found to be a cost-effective alternative to laninamivir in otherwise healthy adults in Japan. This study aimed at investigating the cost-effectiveness of baloxavir versus laninamivir in patients with influenza at high risk for complications.

Methods: A decision tree was utilized to estimate costs and health gains associated with the use of antivirals.

Evaluation of the roles of the cytosolic N-terminus and His-rich loop of ZNT proteins using ZNT2 and ZNT3 chimeric mutants.

The physiological roles of Zn transporter (ZNT) proteins are being increasingly recognized, and three dimensional structures of ZNT bacterial homologs have facilitated our understanding of their biochemical characteristics at the molecular level. However, the biological role of the unique structural features of vertebrate ZNTs, which are absent in their bacterial homologues, is not completely understood. These ZNT sequences include a cytosolic His-rich loop between transmembrane helices IV and V and the cytosolic N-terminus.

Novel mutations in SLC30A2 involved in the pathogenesis of transient neonatal zinc deficiency.

Background: Infants are vulnerable to zinc deficiency. Thus, abnormally low breast milk zinc levels cause transient neonatal zinc deficiency (TNZD) in breast-fed infants. TNZD has been considered to be rare because of a paucity of citations in the published literature.

Molecular Basis of Transient Neonatal Zinc Deficiency: NOVEL ZnT2 MUTATIONS DISRUPTING ZINC BINDING AND PERMEATION.

A gradually increasing number of transient neonatal zinc deficiency (TNZD) cases was recently reported, all of which were associated with inactivating ZnT2 mutations. Here we characterized the impact of three novel heterozygous ZnT2 mutations G280R, T312M, and E355Q, which cause TNZD in exclusively breastfed infants of Japanese mothers. We used the bimolecular fluorescence complementation (BiFC) assay to provide direct visual evidence for the in situ dimerization of these ZnT2 mutants, and to explore their subcellular localization.

The Physiological, Biochemical, and Molecular Roles of Zinc Transporters in Zinc Homeostasis and Metabolism.

Zinc is involved in a variety of biological processes, as a structural, catalytic, and intracellular and intercellular signaling component. Thus zinc homeostasis is tightly controlled at the whole body, tissue, cellular, and subcellular levels by a number of proteins, with zinc transporters being particularly important. In metazoan, two zinc transporter families, Zn transporters (ZnT) and Zrt-, Irt-related proteins (ZIP) function in zinc mobilization of influx, efflux, and compartmentalization/sequestration across biological membranes.

Cooperative functions of ZnT1, metallothionein and ZnT4 in the cytoplasm are required for full activation of TNAP in the early secretory pathway.

The activation process of secretory or membrane-bound zinc enzymes is thought to be a highly coordinated process involving zinc transport, trafficking, transfer and coordination. We have previously shown that secretory and membrane-bound zinc enzymes are activated in the early secretory pathway (ESP) via zinc-loading by the zinc transporter 5 (ZnT5)-ZnT6 hetero-complex and ZnT7 homo-complex (zinc transport complexes). However, how other proteins conducting zinc metabolism affect the activation of these enzymes remains unknown.

Compound heterozygous mutations in SLC30A2/ZnT2 results in low milk zinc concentrations: a novel mechanism for zinc deficiency in a breast-fed infant.

Zinc concentrations in breast milk are considerably higher than those of the maternal serum, to meet the infant's requirements for normal growth and development. Thus, effective mechanisms ensuring secretion of large amounts of zinc into the milk operate in mammary epithelial cells during lactation. ZnT2 was recently found to play an essential role in the secretion of zinc into milk.