Metalation and Maturation of Zinc Ectoenzymes: A Perspective

Numerous zinc ectoenzymes are folded and activated in the compartments of the early secretory pathway, such as the ER and the Golgi apparatus, before reaching their final destination. During this process, zinc must be incorporated into the active site; therefore, metalation of the nascent protein is indispensable for the expression of the active enzyme. However, to date, the molecular mechanism underlying this process has been poorly investigated. This is in sharp contrast to the physiological and pathophysiological roles of zinc ectoenzymes, which have been extensively investigated over the past decades. This manuscript concisely outlines the present understanding of zinc ectoenzyme activation through metalation by zinc and compares this with copper ectoenzyme activation, in which elaborate copper metalation mechanisms are known. Moreover, based on the comparison, several hypotheses are discussed. Approximately 80 years have passed since the first zinc enzyme was identified; therefore, it is necessary to improve our understanding of zinc ectoenzymes from a biochemical perspective, which will further our understanding of their biological roles

Zinc transporter 1 (ZNT1) expression on the cell surface is elaborately controlled by cellular zinc levels

Zinc transporter 1 (ZNT1) is the only zinc transporter predominantly located on the plasma membrane, where it plays a pivotal role exporting cytosolic zinc to the extracellular space. Numerous studies have focused on the physiological and pathological functions of ZNT1. However, its biochemical features remain poorly understood. Here, we investigated the regulation of ZNT1 expression in human and vertebrate cells, and found that ZNT1 expression is posttranslationally regulated by cellular zinc status. We observed that under zinc-sufficient conditions, ZNT1 accumulates on the plasma membrane, consistent with its zinc efflux function. In contrast, under zinc-deficient conditions, ZNT1 molecules on the plasma membrane were endocytosed and degraded through both the proteasomal and lysosomal pathways. Zinc-responsive ZNT1 expression corresponded with that of metallothionein, supporting the idea that ZNT1 and metallothionein cooperatively regulate cellular zinc homeostasis. ZNT1 is N-glycosylated on Asn299 in the extracellular loop between transmembrane domains V and VI, and this appears to be involved in the regulation of ZNT1 stability, as nonglycosylated ZNT1 is more stable. However, this posttranslational modification had no effect on ZNT1's ability to confer cellular resistance against high zinc levels or its subcellular localization. Our results provide molecular insights into ZNT1-mediated regulation of cellular zinc homeostasis, and indicate that the control of cellular and systemic zinc homeostasis via dynamic regulation of ZNT1 expression is more sophisticated than previously thought

Zinc Signaling in Physiology and Pathogenesis

The essential trace element zinc plays indispensable roles in multiple cellular processes. It regulates a great number of protein functions, including transcription factors, enzymes, adapters, and growth factors as a structural and/or catalytic factor. Recent studies have highlighted another function of zinc as an intra- and intercellular signaling mediator, which became recognized as the “zinc signal”. Indeed, zinc regulates cellular signaling pathways, which enable conversion of extracellular stimuli to intracellular signals, and controls various intracellular and extracellular events, and thus zinc mediates communication between cells. The zinc signal is essential for physiology, and its dysregulation causes a variety of diseases, such as diabetes, cancer, osteoarthritis, dermatitis, and dementia. This Special Issue focuses on crucial roles of zinc signaling in biological processes in molecular and physiological basis, addressing the future directions and questions underlying this unique phenomenon. Because there is growing interest and attention in physiopathological contribution of zinc signal, we believe this Special Issue will provide very timely information on it and thus should appeal to a wide range of readers

Lattice Boltzmann Method for Micro Channel and Micro Orifice Flows

The current project is performed to gain an understanding of micro filtration by simulating gas flows through micro channels and micro orifices. The numerical simulation is based on the LBM. Both no-slip bounce-back and slip bounce-back boundary conditions are used to get the slip velocity at the wall under the various ranges of Knudsen number and Reynolds number. For the slip bounce-back boundary condition, the reflection factor and the accommodation coefficient are applied to obtain more accurate results. The results from the LBM simulation show that when the reflection factor is 0.85 the velocity and pressure profiles of the micro channel are in good agreement with the analytical results for Kn = 0.0194. In contrast, the accommodation coefficient scheme does not show good results for these micro flow implementations. From the velocity, density and pressure distributions of the micro orifice the compressibility effect is confirmed very well.Mechanical & Aerospace Engineerin

Respect My Privacy

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2009.Includes bibliographical references (p. 64).Most social networks have implemented extensive, complex privacy controls in order to battle the host of privacy concerns that initially plagued their online communities. These privacy controls have taken the form of access restriction, which allows users to specify who is and who is not allowed to view their personal information. This binary system leaves users unprotected in the, hopefully rare, cases in which the access restriction mechanisms are bypassed. Respect My Privacy offers a different approach to privacy protection, founded on the philosophies of Information Accountability. Respect My Privacy aims to allow users to clearly declare the policies that govern the use of their data, and implement mechanisms that promptly notify the user of misuse after the fact. In its current state, the Respect My Privacy project has been implemented across three platforms: Facebook, OpenSocial, and the Tabulator extension with a focus on defining a clear vocabulary for discussing restrictions on use of data and making it simple for users to display and edit the restrictions users wish to place on their personal information. There is also a discussion on decentralized social networks and their role in the future of Respect My Privacy and social networks in general.by Ted Taiho Kang.M.Eng

不規則画素配置をもつ撮像表示素子の検討

金沢大学大学院自然科学研究科情報システム金沢大学工学

疑似的な不規則画素配置をもつ方向特異性のない撮像・表示素子構成の基礎検討 (論文小特集 画像の処理と符号化)

金沢大学大学院自然科学研究科情報システム金沢大学工学部Conventional image display devices and image acquisition devices consist of regularly located pixels. The pixels are located in a matrix for ease of implementation. Matrix placement of pixels intrinsically has directional singularity in the representation of images. The clarity of represented images is significantly dependent on the directions that objects in the image, such as lines, are facing. For example, horizontal lines are perfectly represented by matrix pixels, while the slanted lines have the jagged edges. We developed a pseudorandom pixel placement architecture that has no directional singularity in the representation of images, and we evaluated its characteristics and layout implementation

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. Heterozygous mutations of human ZnT2 (hZnT2), including H54R and G87R, in mothers result in low (>75% reduction) secretion of zinc into the breast milk, and infants fed on the milk develop transient neonatal zinc deficiency. We identified two novel missense mutations in the SLC30A2/ZnT2 gene in a Japanese mother with low milk zinc concentrations (>90% reduction) whose infant developed severe zinc deficiency; a T to C transition (c.454T>C) at exon 4, which substitutes a tryptophan residue with an arginine residue (W152R), and a C to T transition (c.887C>T) at exon 7, which substitutes a serine residue with a leucine residue (S296L). Biochemical characterization using zinc-sensitive DT40 cells indicated that the W152R mutation abolished the abilities to transport zinc and to form a dimer complex, indicating a loss-of-function mutation. The S296L mutation retained both abilities but was extremely destabilized. The two mutations were found on different alleles, indicating that the genotype of the mother with low milk zinc was compound heterozygous. These results show novel compound heterozygous mutations in the SLC30A2/ZnT2 gene causing zinc deficiency in a breast-fed infant

Amine-Functionalized Covalent Organic Framework for Efficient SO2 Capture with High Reversibility

Removing sulfur dioxide (SO2) from exhaust flue gases of fossil fuel power plants is an important issue given the toxicity of SO2 and subsequent environmental problems. To address this issue, we successfully developed a new series of imide-linked covalent organic frameworks (COFs) that have high mesoporosity with large surface areas to support gas flowing through channels; furthermore, we incorporated 4-[(dimethylamino)methyl]aniline (DMMA) as the modulator to the imide-linked COF. We observed that the functionalized COFs serving as SO2 adsorbents exhibit outstanding molar SO2 sorption capacity, i.e., PI-COF-m10 record 6.30 mmol SO2 g−1 (40 wt%). To our knowledge, it is firstly reported COF as SO2 sorbent to date. We also observed that the adsorbed SO2 is completely desorbed in a short time period with remarkable reversibility. These results suggest that channel-wall functional engineering could be a facile and powerful strategy for developing mesoporous COFs for high-performance reproducible gas storage and separation.113Ysciescopu

Zinc transporters and their functional integration in mammalian cells

Zinc is a ubiquitous biological metal in all living organisms. The spatiotemporal zinc dynamics in cells provide crucial cellular signaling opportunities, but also challenges intracellular zinc homeostasis with broad disease implications. Zinc transporters play a central role in regulating cellular zinc balance and subcellular zinc distributions. The discoveries of two complementary families of mammalian zinc transporters (ZnTs and ZIPs) in the mid-1990s spurred much speculation on their metal selectivity and cellular functions. After two decades of research, we have arrived at a biochemical description of zinc transport. However, in vitro functions are fundamentally different from those in living cells, where mammalian zinc transporters are directed to specific subcellular locations, engaged in dedicated macromolecular machineries and connected with diverse cellular processes. Hence, the molecular functions of individual zinc transporters are reshaped and deeply integrated in cells to promote the utilization of zinc chemistry to perform enzymatic reactions, tune cellular responsiveness to pathophysiologic signals and safeguard cellular homeostasis. At present, the underlying mechanisms driving the functional integration of mammalian zinc transporters are largely unknown. This knowledge gap has motivated a shift of the research focus from in vitro studies of purified zinc transporters to in cell studies of mammalian zinc transporters in the context of their subcellular locations and protein interactions. In this review, we will outline how knowledge of zinc transporters has been accumulated from in-test-tube to in-cell studies, highlighting new insights and paradigm shifts in our understanding of the molecular and cellular basis of mammalian zinc transporter functions