The brain is a singular organ of unique biological complexity that serves as the command center for cognitive and motor function. As such, this specialized system also possesses a unique chemical composition and reactivity at the molecular level. In this regard, two vital distinguishing features of the brain are its requirements for the highest concentrations of metal ions in the body and the highest per-weight consumption of body oxygen. In humans, the brain accounts for only 2% of total body mass but consumes 20% of the oxygen that is taken in through respiration. As a consequence of high oxygen demand and cell complexity, distinctly high metal levels pervade all regions of the brain and central nervous system. Structural roles for metal ions in the brain and the body include the stabilization of biomolecules in static (e.g., Mg2+ for nucleic acid folds, Zn2+ in zinc-finger transcription factors) or dynamic (e.g., Na+ and K+ in ion channels, Ca2+ in neuronal cell signaling) modes, and catalytic roles for brain metal ions are also numerous and often of special demand.

Metals in Neurobiology: Probing Their Chemistry and Biology with Molecular Imaging

What makes a heavy metal resistant bacterium heavy metal resistant? The mechanisms of action, physiological functions, and distribution of metal-exporting proteins are outlined, namely: CBA efflux pumps driven by proteins of the resistance–nodulation–cell division superfamily, P-type ATPases, cation diffusion facilitator and chromate proteins, NreB- and CnrT-like resistance factors. The complement of efflux systems of 63 sequenced prokaryotes was compared with that of the heavy metal resistant bacterium Ralstonia metallidurans. This comparison shows that heavy metal resistance is the result of multiple layers of resistance systems with overlapping substrate specificities, but unique functions. Some of these systems are widespread and serve in the basic defense of the cell against superfluous heavy metals, but some are highly specialized and occur only in a few bacteria. Possession of the latter systems makes a bacterium heavy metal resistant.

Efflux‐mediated heavy metal resistance in prokaryotes

Type 1 diabetes (T1D) results from progressive loss of pancreatic islet mass through autoimmunity targeted at a diverse, yet limited, series of molecules that are expressed in the pancreatic β cell. Identification of these molecular targets provides insight into the pathogenic process, diagnostic assays, and potential therapeutic agents. Autoantigen candidates were identified from microarray expression profiling of human and rodent pancreas and islet cells and screened with radioimmunoprecipitation assays using new-onset T1D and prediabetic sera. A high-ranking candidate, the zinc transporter ZnT8 (Slc30A8), was targeted by autoantibodies in 60–80% of new-onset T1D compared with <2% of controls and <3% type 2 diabetic and in up to 30% of patients with other autoimmune disorders with a T1D association. ZnT8 antibodies (ZnTA) were found in 26% of T1D subjects classified as autoantibody-negative on the basis of existing markers [glutamate decarboxylase (GADA), protein tyrosine phosphatase IA2 (IA2A), antibodies to insulin (IAA), and islet cytoplasmic autoantibodies (ICA)]. Individuals followed from birth to T1D showed ZnT8A as early as 2 years of age and increasing levels and prevalence persisting to disease onset. ZnT8A generally emerged later than GADA and IAA in prediabetes, although not in a strict order. The combined measurement of ZnT8A, GADA, IA2A, and IAA raised autoimmunity detection rates to 98% at disease onset, a level that approaches that needed to detect prediabetes in a general pediatric population. The combination of bioinformatics and molecular engineering used here will potentially generate other diabetes autoimmunity markers and is also broadly applicable to other autoimmune disorders.

https://www.pnas.org/content/pnas/104/43/17040.full.pdf

The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes

Zinc transporters and the cellular trafficking of zinc

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 ...

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

Cloning and Characterization of a Novel Mammalian Zinc Transporter, Zinc Transporter 5, Abundantly Expressed in Pancreatic β Cells

【はじめに】今回，脊椎固定術を計画した，透析患者に対し，多職種で協力し貯血式自己血輸血を行い安全に周術期管理ができた． 

Tatsuaki Amano

Papers

Cloning and Characterization of a Novel Mammalian Zinc Transporter, Zinc Transporter 5, Abundantly Expressed in Pancreatic β Cells

Interprofessional team collaboration of autologous blood storage for preoperative dialysis patient -case study-