Down syndrome (DS) is the most common chromosomal disorder in humans. DS is associated with increased prevalence of several ocular sequelae, including characteristic blue-dot cerulean cataract. DS is accompanied by age-dependent accumulation of Alzheimer's disease (AD) amyloid-β (Aβ) peptides and amyloid pathology in the brain and comorbid early-onset Aβ amyloidopathy and colocalizing cataracts in the lens.
View Article and Find Full Text PDFAlthough toxic effects of zinc (Zn) have been well established in the different developmental stages in fish, long-lasting effects of Zn exposure during embryonic development have not been explored. Exposure to an environmentally relevant Zn concentration of 10 μM (650 μg/L) during the first five days after fertilization did not affect survival, body weight, malformations or overall hatching success of F0 and F1 larvae. Zn exposure did, however, result in delayed hatching in both the F0 and F1 generations and caused significant changes in homeostasis of Zn and selenium (Se) in F0 and F1 fish.
View Article and Find Full Text PDFThe human zinc transporter ZnT8 provides the granules of pancreatic β-cells with zinc (II) ions for assembly of insulin hexamers for storage. Until recently, the structure and function of human ZnTs have been modelled on the basis of the 3D structures of bacterial zinc exporters, which form homodimers with each monomer having six transmembrane α-helices harbouring the zinc transport site and a cytosolic domain with an α,β structure and additional zinc-binding sites. However, there are important differences in function as the bacterial proteins export an excess of zinc ions from the bacterial cytoplasm, whereas ZnT8 exports zinc ions into subcellular vesicles when there is no apparent excess of cytosolic zinc ions.
View Article and Find Full Text PDFJ Gerontol A Biol Sci Med Sci
September 2020
The absence of clinical tools to evaluate individual variation in the pace of aging represents a major impediment to understanding aging and maximizing health throughout life. The human lens is an ideal tissue for quantitative assessment of molecular aging in vivo. Long-lived proteins in lens fiber cells are expressed during fetal life, do not undergo turnover, accumulate molecular alterations throughout life, and are optically accessible in vivo.
View Article and Find Full Text PDFZinc is an essential element for all forms of life, and one in every ten human proteins is a zinc protein. Zinc has catalytic, structural and signalling functions and its correct homeostasis affects many cellular processes. Zinc deficiency leads to detrimental consequences, especially in tissues with high demand such as skeletal muscle.
View Article and Find Full Text PDFA significant aspect of the control of cellular zinc in eukarya is its subcellular re-distribution. One of the four human vesicular zinc transporters, ZnT8, supplies the millimolar zinc concentrations of insulin granules in pancreatic β-cells, affecting insulin processing, crystallisation and secretion. ZnT8 has a transmembrane and a C-terminal cytosolic domain; the latter has important functions and purportedly mediates protein-protein interactions, senses cytosolic zinc and/or channels zinc to the transport site in the transmembrane domain (TMD).
View Article and Find Full Text PDFThe non-synonymous single nucleotide polymorphism (SNP) rs13266634 in human zinc transporter 8, ZnT8 (SLC30A8), leads to a R325 variant, which is associated with an increased risk of developing Type 2 Diabetes (T2D). Although the molecular details remain unknown, the mutation is thought to alter the kinetics of zinc transport into insulin granules in pancreatic β-cells. Nevertheless, analysis of ZnT8 sequences from several animals shows that the amino acid at position 325 is poorly conserved.
View Article and Find Full Text PDFA sewer main serving a large municipal wastewater system ruptured, discharging approximately 3,000,000 gallons (11,355,000 L) of raw human sewage into a multi-branched tidal creek estuary along the US East Coast. The biochemical oxygen demand caused severe hypoxia in the system, causing a large fish kill. The sewage load led to high fecal coliform bacteria concentrations in the creek (maximum of 270,000 CFU 100ml(-1)), which declined in an approximate logarithmic manner over the first few days.
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