Cellular Metal Research Articles

Impact of human ferroportin mutations on cellular trace metal homeostasis

Ferroportin (Fpn; SLC40A1) plays a role as an exporter in the assimilation of dietary iron (Fe) and manganese (Mn). Recent studies reveal that Fpn deficiency alters body metal levels and promotes brain metal accumulation in the flatiron mouse model of human “ferroportin disease.” This genetic disorder is known as hereditary hemochromatosis (HH) type 4 and arises from mutations in the human Fpn. While clinical manifestations of the disease are quite variable, most mutations are inherited as dominant traits. Ferroportin disease‐causing mutations fall into two functional categories (loss‐versus gain‐of‐function) underlying two distinct clinical entities (HH type 4A and type 4B, respectively). While functional consequences of several human Fpn mutations in Fe metabolism have been analyzed in vitro, little is known about the potential impact of Fpn on cellular Mn homeostasis and how ferroportin disease‐causing mutations might alter Mn metabolism. To explore the effects of these mutations on cellular Mn homeostasis, 17 ferroportin disease‐associated missense mutations were introduced into the human Fpn gene for functional expression in human embryonic HEK293T cells. The effects of wild‐type and mutant Fpn on intracellular Fe levels were determined by looking at the intracellular iron storage protein ferritin. Expression of wild‐type Fpn led to a significant reduction in ferritin compared to control cells. Loss‐of‐function mutants did not cause a significant reduction in ferritin, but gain‐of‐function mutants behaved similarly to wild‐type Fpn. These data are consistent with other studies and agree with differential effects of Fpn mutations on intracellular Fe levels. To determine whether wild‐type and mutant Fpn expression affect cellular Mn homeostasis, intracellular Mn levels were analyzed for trace elements by inductively coupled plasma mass spectrometry (ICP‐MS). Expression of wild‐type Fpn reduced accumulation of intracellular Mn induced by Mn exposure in treated versus control or nontreated cells. While loss‐of‐function mutants had no effect in reducing Mn accumulation, gain‐of‐function mutants were shown to accumulate lower levels of Mn, similar to wild‐type Fpn. To test the physiological relevance of the efflux activity of wild‐type and mutant Fpn, we sought to determine whether expression of wild‐type Fpn conferred protection against Mn‐induced cytotoxicity. Expression of wild‐type Fpn reversed Mn‐induced cytotoxicity. These data are consistent with our previous reports and confirm the cytoprotective effects of wild‐type exporter in the presence of Mn. Similar to wild‐type Fpn, gain‐of‐function mutants protected cells against Mn cytotoxicity, whereas loss‐of‐function mutants failed to confer protection. These combined results demonstrate that Fpn plays a central role in cellular Mn homeostasis and that ferroportin disease‐causing mutations have differential impact on Mn metabolism. These findings highlight the importance of Fpn function in cellular Mn homeostasis and implicate Mn dyshomeostasis in patients with ferroportin disease.Support or Funding InformationNIH R00 ES024340

Phosphate Limitation Triggers the Dissolution of Precipitated Iron by the Marine Bacterium Pseudovibrio sp. FO-BEG1.

Phosphorus is an essential nutrient for all living organisms. In bacteria, the preferential phosphorus source is phosphate, which is often a limiting macronutrient in many areas of the ocean. The geochemical cycle of phosphorus is strongly interconnected with the cycles of other elements and especially iron, because phosphate tends to adsorb onto iron minerals, such as iron oxide formed in oxic marine environments. Although the response to either iron or phosphate limitation has been investigated in several bacterial species, the metabolic interplay between these two nutrients has rarely been considered. In this study we evaluated the impact of phosphate limitation on the iron metabolism of the marine bacterium Pseudovibrio sp. FO-BEG1. We observed that phosphate limitation led to an initial decrease of soluble iron in the culture up to three times higher than under phosphate surplus conditions. Similarly, a decrease in soluble cobalt was more pronounced under phosphate limitation. These data point toward physiological changes induced by phosphate limitation that affect either the cellular surface and therefore the metal adsorption onto it or the cellular metal uptake. We discovered that under phosphate limitation strain FO-BEG1, as well as selected strains of the Roseobacter clade, secreted iron-chelating molecules. This leads to the hypothesis that these bacteria might release such molecules to dissolve iron minerals, such as iron-oxyhydroxide, in order to access the adsorbed phosphate. As the adsorption of phosphate onto iron minerals can significantly decrease phosphate concentrations in the environment, the observed release of iron-chelators might represent an as yet unrecognized link between the biogeochemical cycle of phosphorus and iron, and it suggests another biological function of iron-chelating molecules in addition to metal-scavenging.

Transcriptomic Analysis of THP‐1 Macrophages Exposed to Lipoprotein Hydrolysis Products Generated by Lipoprotein Lipase

Macrophage lipoprotein lipase (LPL) induces lipid accumulation and promotes atherosclerosis. However, the effects of lipoprotein hydrolysis products generated by LPL on macrophage-derived foam cell formation are not clearly understood. Thus, we analyzed the transcriptomic response to hydrolysis products via microarray analyses on RNA isolated from human THP-1 macrophages incubated with total lipoprotein hydrolysis products generated by LPL. The expression of 183 transcripts was significantly upregulated and 133 transcripts were significantly downregulated. Bioinformatics analyses revealed that there was a significant over-representation of genes involved in cell cycling, stress response, type I interferon signaling, cellular metal ion homeostasis, sterol metabolism, and nuclease activity. Interestingly, transcripts for 63 small nucleolar RNA were significantly upregulated. We verified the microarray data by quantitative real-time PCR and found that the expression of SNORA56, as well as the expression of genes associated with the cell cycle (PCNA and DKC1 variant 3), stress response (ATF3), type I interferon signaling (IFITM1), and lipid metabolism (CD36 and PLIN2) were significantly affected by LPL hydrolysis products. To determine if the free fatty acid (FFA) component of total lipoprotein hydrolysis products is sufficient to alter the expression of these genes, THP-1 macrophages were also incubated with the total FFA or individual classes of the FFA component. The gene regulation by the FFA component did not mimic that of the hydrolysis products, suggesting that the regulation of gene expression in THP-1 macrophages depends on the specific combination and concentration of lipid species present in the hydrolysis products, and not solely on FFA.

A tight tunable range for Ni(II) sensing and buffering in cells.

The metal-affinities of metal-sensing transcriptional regulators co-vary with cellular metal concentrations over more than 12 orders of magnitude. To understand the cause of this relationship, we determined the structure of the Ni(II)-sensor InrS then created cyanobacteria (Synechocystis PCC 6803) in which transcription of genes encoding a Ni(II)-exporter and a Ni(II)-importer were controlled by InrS variants with weaker Ni(II)-affinities. Variant strains were sensitive to elevated nickel and contained more nickel but the increase was small compared to the change in Ni(II)-affinity. All of the variant-sensors retained the allosteric mechanism which inhibits DNA binding upon metal binding but a response to nickel in vivo was only observed when the sensitivity was set to respond within a relatively narrow (less than 2 orders of magnitude) range of nickel-concentrations. The Ni(II)-affinity of InrS is attuned to cellular metal concentrations rather than the converse.

Synthesis of a highly Mg2+-selective fluorescent probe and its application to quantifying and imaging total intracellular magnesium

Magnesium plays a crucial role in many physiological functions and pathological states. Therefore, the evolution of specific and sensitive tools capable of detecting and quantifying this element in cells is a very desirable goal in biological and biomedical research. We developed a Mg2+-selective fluorescent dye that can be used to selectively detect and quantify the total magnesium pool in a number of cells that is two orders of magnitude smaller than that required by flame atomic absorption spectroscopy (F-AAS), the reference analytical method for the assessment of cellular total metal content. This protocol reports itemized steps for the synthesis of the fluorescent dye based on diaza-18-crown-6-hydroxyquinoline (DCHQ5). We also describe its application in the quantification of total intracellular magnesium in mammalian cells and the detection of this ion in vivo by confocal microscopy. The use of in vivo confocal microscopy enables the quantification of magnesium in different cellular compartments. As an example of the sensitivity of DCHQ5, we studied the involvement of Mg2+ in multidrug resistance in human colon adenocarcinoma cells sensitive (LoVo-S) and resistant (LoVo-R) to doxorubicin, and found that the concentration was higher in LoVo-R cells. The time frame for DCHQ5 synthesis is 1-2 d, whereas the use of this dye for total intracellular magnesium quantification takes 2.5 h and for ion bioimaging it takes 1-2 h.

Effect of relative density on the dynamic compressive behavior of carbon nanotube reinforced aluminum foam

Closed-cell aluminum foams represent a unique class of solid cellular light metals that are made by deliberately introducing voids or pores during fabrication. This lightweight material is able to undergo large deformation at a nearly constant stress known as Plateau Stress because of which aluminum foams are good energy absorbers under dynamic loads such as an impact. In this investigation, carbon nanotubes (CNT) reinforced closed-cell aluminum foams were fabricated using the liquid metallurgy route through the dissociation of a foaming agent within the liquid metal. Four different relative densities of CNT reinforced Al-foam were used: 0.16, 0.20, 0.26 and 0.30, to study the effect of strain rate on the mechanical properties. The compressive mechanical behavior of CNT reinforced Al-foam has been studied under quasi-static and dynamic loading conditions. The high strain rate compressive response was investigated using a Split Hopkinson Pressure Bar (SHPB) over a range of strain rates up to 2750s−1. Mechanical properties such as peak stress, plateau stress and energy absorption increased with the increase in relative density; however, the densification strain decreased with the increase in relative density. Dynamic compressive properties improved as the strain rate increased indicating that this material is strain rate dependent. Among all the foams, the 0.30 relative density exhibited the highest mechanical properties whereas the 0.20 relative density foam displayed the highest strain rate sensitivity.

Experimental performance of an advanced metal volumetric air receiver for Solar Towers

Solar Tower Technology is a promising way to generate sustainable electricity from concentrated solar radiation. In one of the most effective variants of this technology, a so called volumetric air receiver is used to convert concentrated radiation into heat. This component consists of a high temperature resistant cellular material which absorbs radiation and transfers the heat to an air flow which is fed from the ambient and from recirculated air. It is called volumetric, because the radiation may penetrate into the “volume” of the receiver through the open, permeable cells of the material. In this way a larger amount of heat transfer surface supports the solid to gaseous heat transfer in comparison to a tubular closed receiver. Finally the heated air is directed to the steam generator of a conventional steam turbine system. In this study an advanced cellular metal honeycomb structure has been designed, manufactured and tested for use as an open volumetric receiver. It consists of winded pairs of flat and corrugated metal foils. The technology is based on a one which has been primarily developed for the treatment of combustion engine exhaust gases. A number of variations of the pure linear honeycomb structure have been introduced to increase local turbulence and radial flow. Firstly, a set of samples has been tested in laboratory scale experiments to determine effective properties and the solar-to-thermal efficiency. After that, results have been compared with theoretical predictions. Finally, the three most promising materials have been used for a 500 kW test on the research platform of the Solar Tower Jülich. Air outlet temperatures of more than 800 °C have been achieved with efficiencies of about 80%, which is about 5% more than the state-of-the-art technology, which is currently used at the main receiver of the Solar Tower. Next to this, lifetime models will be developed to increase the overall reliability of the technology.

Investigation of manufacturing periodic cellular metal by sheet metal forming and its impact behavior

Cellular metal is widely used in passive safety field for its capacity of impact energy absorption. In this paper, the manufacturing of a periodic cellular metal with aluminum cubic cells was studied. Its impact behaviors were analyzed by drop weight experiments. The periodic cellular metal was fabricated by sheet metal forming and adhesive bonding. The individual cells were first stamped, then bonded together to form the cellular structure. Two different sizes of cells, namely 3 and 5 mm, were manufactured and their impact behaviors were tested. The results showed that the cellular metal manufactured by this route showed a high energy absorption capacity.

The effect of metalloprotein inhibitors on cellular metal ion content and distribution.

With metalloproteins garnering increased interest as therapeutic targets, designing target-specific metalloprotein inhibitors (MPi) is of substantial importance. However, in many respects, the development and evaluation of MPi lags behind that of conventional small molecule therapeutics. Core concerns around MPi, such as target selectivity and potential disruption of metal ion homeostasis linger. Herein, we used a suite of analytical methods, including energy-dispersive X-ray spectroscopy (EDX), inductively coupled plasma atomic emission spectroscopy (ICP-OES), and synchrotron X-ray fluorescence microscopy (SXRF) to investigate the effect of several MPi on cellular metal ion distribution and homeostasis. The results reveal that at therapeutically relevant concentrations, the tested MPi have no significant effects on cellular metal ion content or distribution. In addition, the affinity of the metal-binding pharmacophore (MBP) utilized by the MPi does not have a substantial influence on the effect of the MPi on cellular metal distribution. These studies provide an important, original data set indicating that metal ion homeostasis is not notably perturbed by MPi, which should encourage the development of and aid in designing new MPi, guide MBP selection, and clarify the effect of MPi on the 'metallome'.

Publication of JIS and ISO standards for evaluation of porous and cellular metals

Publication of JIS and ISO standards for evaluation of porous and cellular metals

Subcellular compartmentalisation of copper, iron, manganese, and zinc in the Parkinson's disease brain.

Elevated iron and decreased copper levels are cardinal features of the degenerating substantia nigra pars compacta in the Parkinson's disease brain. Both of these redox-active metals, and fellow transition metals manganese and zinc, are found at high concentrations within the midbrain and participate in a range of unique biological reactions. We examined the total metal content and cellular compartmentalisation of manganese, iron, copper and zinc in the degenerating substantia nigra, disease-affected but non-degenerating fusiform gyrus, and unaffected occipital cortex in the post mortem Parkinson's disease brain compared with age-matched controls. An expected increase in iron and a decrease in copper concentration was isolated to the soluble cellular fraction, encompassing both interstitial and cytosolic metals and metal-binding proteins, rather than the membrane-associated or insoluble fractions. Manganese and zinc levels did not differ between experimental groups. Altered Fe and Cu levels were unrelated to Braak pathological staging in our cases of late-stage (Braak stage V and VI) disease. The data supports our hypothesis that regional alterations in Fe and Cu, and in proteins that utilise these metals, contribute to the regional selectively of neuronal vulnerability in this disorder.

Chemical and functional properties of metal chelators that mobilize copper to elicit fungal killing of Cryptococcus neoformans.

A panel of iron (Fe) and copper (Cu) chelators was screened for growth inhibitory activity against the fungal pathogen Cryptococcus neoformans. Select bidentate metal-binding ligands containing mixed O,S or O,N donor atoms were identified as agents that induce cell killing in a Cu-dependent manner. Conversely, structurally similar ligands with O,O donor atoms did not inhibit C. neoformans growth regardless of Cu status. Studies of Cu(ii) and Cu(i) binding affinity, lipophilicity, and growth recovery assays of Cu-import deficient cells identified lipophilicity of thermodynamically stable CuIIL2 complexes as the best predictor of antifungal activity. These same complexes induce cellular hyperaccumulation of Zn and Fe in addition to Cu. The results described here present the utility of appropriate metal-binding ligands as potential antifungal agents that manipulate cellular metal balance as an antimicrobial strategy.

Enhancement of Heat Transfer in PCM by Cellular Zn-Al Structure

Abstract Development of open cellular metal foam technology based on investment casting applying the polyurethane pattern is discussed. Technological process comprises preparing of the ceramic mold applying PUR foam as the pattern, firing of the mold, pouring of the liquid Zn-Al alloy into the mold and washing out of the ceramic material from cellular casting. Critical parameters such as the temperature of mold and poured metal, design of gating system affected by metalostatic pressure allowed to produce castings with cellular structure characterized by the open porosity. Metal cellular foams with the open porosity embedded in phase change material (PCM) enhance heat transfer and reduce time operations in energy storage systems. Charging and discharging were performed at the laboratory accumulator by heating and cooling with flowing water characterized by the temperatures of 97-100°C. Temperature measurements were collected from 7 different thermocouples located in the accumulator. In relation to the tests with pure paraffin, embedding of the metal Zn-Al cellular foam in paraffin significantly decreases temperature gradients and melting time of paraffin applied as PCM characterized by the low thermal conductivity. Similarly, reduction of discharging time by this method improves the efficiency of thermal energy storage system applied in solar power plants or for the systems of energy efficient buildings.

287 - The Redox Active Anti-Cancer Drug, Dp44mT, Induces Endoplasmic Reticulum Stress Activating Pro-Apoptotic Pathways of the Unfolded Protein Response in Cancer Cells

In the stressful tumor microenvironment, endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are activated in cancer cells promoting cancer cell survival. A novel strategy for anti-cancer drugs is to re-sensitise cancer cells to ER stress-induced apoptosis by altering the kinetics of the UPR. Chelators of the DpT thiosemicarbazone class form cellular redox active metal complexes and demonstrate potent in vitro and in vivo anti-cancer and anti-metastatic activity. The most potent of these agents is currently being examined in clinical trials for the treatment of patients with advanced solid tumors (NCT02688101). However, the mechanism by which these drugs alter the ER stress response and induce apoptosis is unknown. Consequently, studies assessed the mechanisms by which the potent DpT redox active agent, Dp44mT, alters the ER stress response, relative to the redox inactive chelator, DFO, and the classical ER stress-inducing agent, tunicamycin, in SK-N-MC neuroepithelioma and PANC1 pancreatic cancer cells. Our studies demonstrate that Dp44mT significantly: (1) increased activation of ER stress-associated pro-apoptotic signaling (i.e., p-eIF2α, ATF4 and CHOP); (2) increased phosphorylation of IRE1α and XBP1 mRNA splicing; (3) reduced the expression of molecules involved in ER stress-associated cell survival signaling ( e.g. , XBP1s and p58IPK); (4) activated the transcription factor, ATF6, and its downstream targets ( i.e. CHOP and BiP); and (5) activated pro-apoptotic p-CaMKII. In contrast, redox inactive DFO and the ER stress-inducing agent, tunicamycin, had little or no effect on the expression or phosphorylation of these proteins. Considering the role of reactive oxygen species (ROS) generation in the effects observed, it was demonstrated that the ROS scavenger, N -acetyl-l-cysteine, that supplements cellular glutathione could inhibit Dp44mT-mediated activation of the UPR, while the glutathione synthesis inhibitor, buthionine sulfoximine, enhanced Dp44mT activity. In conclusion, ER stress is induced after iron sequestration by chelators, and this effect was enhanced by drugs such as Dp44mT that produce ROS. These results demonstrate that Dp44mT activates the pro-apoptotic pathways of the UPR, re-sensitizing cancer cells to apoptosis while inhibiting cell survival signals.

Stimulus-Responsive Prochelators for Manipulating Cellular Metals.

Metal ions are essential for a wide range of physiological processes, but they can also be toxic if not appropriately regulated by a complex network of metal trafficking proteins. Intervention in cellular metal distribution with small-molecule or peptide chelating agents has promising therapeutic potential to harness metals to fight disease. Molecular outcomes associated with forming metal-chelate interactions in situ include altering the concentration and subcellular metal distribution, inhibiting metalloenzymes, enhancing the reactivity of a metal species to elicit a favorable biological response, or passivating the reactivity of a metal species to prevent deleterious reactivity. The systemic administration of metal chelating agents, however, raises safety concerns due to the potential risks of indiscriminate extraction of metals from critical metalloproteins and inhibition of metalloenzymes. One can estimate that chelators capable of complexing metal ions with dissociation constants in the submicromolar range are thermodynamically capable of extracting metal ions from some metalloproteins and disrupting regular function. Such dissociation constants are easily attainable for multidentate chelators interacting with first-row d-block metal cations in relevant +1, + 2, and +3 oxidation states. To overcome this challenge of indiscriminate metal chelation, we have pursued a prodrug strategy for chelating agents in which the resulting "prochelator" has negligible metal binding affinity until a specific stimulus generates a favorable metal binding site. The prochelator strategy enables conditional metal chelation to occur preferentially in locations affected by disease- or therapy-associated stimuli, thereby minimizing off-target metal chelation. Our design of responsive prochelators encompasses three general approaches of activation: the "removal" approach operates by eliminating a masking group that blocks a potential metal chelation site to reveal the complete binding site under the desired conditions; the molecular "switch" approach involves a reversible conformational change between inactive and active forms of a chelator with differential metal binding affinity under specific conditions; and the "addition" approach adds a new ligand donor arm to the prochelator to constitute a complete metal chelation site. Adopting these approaches, we have created four categories of triggerable prochelators that respond to (1) reactive oxygen species, (2) light, (3) specific enzymes, and (4) biological regulatory events. This Account highlights progress from our group on building prochelators that showcase these four categories of responsive metal chelating agents for manipulating cellular metals. The creation and chemical understanding of such stimulus-responsive prochelators enables exciting applications for understanding the cell biology of metals and for developing therapies based on metal-dependent processes in a variety of diseases.

Ergothioneine Biosynthesis and Functionality in the Opportunistic Fungal Pathogen, Aspergillus fumigatus.

Ergothioneine (EGT; 2-mercaptohistidine trimethylbetaine) is a trimethylated and sulphurised histidine derivative which exhibits antioxidant properties. Here we report that deletion of Aspergillus fumigatus egtA (AFUA_2G15650), which encodes a trimodular enzyme, abrogated EGT biosynthesis in this opportunistic pathogen. EGT biosynthetic deficiency in A. fumigatus significantly reduced resistance to elevated H2O2 and menadione, respectively, impaired gliotoxin production and resulted in attenuated conidiation. Quantitative proteomic analysis revealed substantial proteomic remodelling in ΔegtA compared to wild-type under both basal and ROS conditions, whereby the abundance of 290 proteins was altered. Specifically, the reciprocal differential abundance of cystathionine γ-synthase and β-lyase, respectively, influenced cystathionine availability to effect EGT biosynthesis. A combined deficiency in EGT biosynthesis and the oxidative stress response regulator Yap1, which led to extreme oxidative stress susceptibility, decreased resistance to heavy metals and production of the extracellular siderophore triacetylfusarinine C and increased accumulation of the intracellular siderophore ferricrocin. EGT dissipated H2O2 in vitro, and elevated intracellular GSH levels accompanied abrogation of EGT biosynthesis. EGT deficiency only decreased resistance to high H2O2 levels which suggests functionality as an auxiliary antioxidant, required for growth at elevated oxidative stress conditions. Combined, these data reveal new interactions between cellular redox homeostasis, secondary metabolism and metal ion homeostasis.

Estimation of obsolete cellular phones generation: A case study of China

Rapid development of electronic technique has led to decreasing lifespan of electronic products. Meanwhile, the amount of waste electrical and electronic equipment (WEEE) is rapidly growing in recent years especially in China. The generation amount of WEEE is one of the basic information for waste management. In our study, the generation of obsolete cellular phones and metals containing of cellular phones were estimated from 1997 to 2025. The future average possession in per 100 inhabitants of cellular phones was predicted using logistic model. Moreover, the lifespan distribution of cellular phones was analyzed using Weibull distribution. Meanwhile, the generation amount of obsolete cellular phones and its metals containing were estimated by using population balance model (PBM) and substance flow analysis (SFA), respectively. The estimated results indicate that the average possession in per 100 inhabitants will reach to 111.2 and 118.3 units in 2020 and 2025, respectively, which is about two times higher than the average possession in 2010. In addition, the total possession amount of cellular phones are expected to exceed 1.64 billion units in 2025. Moreover, the estimated results show that 781 million units obsolete cellular phones were generated in 2015, and the number will grow up to 877 and 937 million units in 2020 and 2025, respectively. In 2025, the total weight of annual generation amount of obsolete cellular phones will exceed 140Gg. The precious metals such as silver, gold contains in obsolete cellular phones will reach 56,250 and 28,130kg, respectively, in 2025. The obsolete cellular phones are the typical secondary metal resources especially for precious metals. In order to improve the recycling efficiency, it is necessary to establish a comprehensive system of waste management.

Regulating Subcellular Metal Homeostasis: The Key to Crop Improvement.

Iron (Fe), zinc (Zn), manganese (Mn), and copper (Cu) are essential micronutrient mineral elements for living organisms, as they regulate essential cellular processes, such as chlorophyll synthesis and photosynthesis (Fe, Cu, and Mn), respiration (Fe and Cu), and transcription (Zn). The storage and distribution of these minerals in various cellular organelles is strictly regulated to ensure optimal metabolic rates. Alteration of the balance in uptake, distribution, and/or storage of these minerals severely impairs cellular metabolism and significantly affects plant growth and development. Thus, any change in the metal profile of a cellular compartment significantly affects metabolism. Different subcellular compartments are suggested to be linked through complex retrograde signaling networks to regulate cellular metal homeostasis. Various genes regulating cellular and subcellular metal distribution have been identified and characterized. Understanding the role of these transporters is extremely important to elaborate the signaling between various subcellular compartments. Moreover, modulation of the proteins involved in cellular metal homeostasis may help in the regulation of metabolism, adaptability to a diverse range of environmental conditions, and biofortification. Here, we review progress in the understanding of different subcellular metal transport components in plants and discuss the prospects of regulating cellular metabolism and strategies to develop biofortified crop plants.

Impact Resistance of Graded Cellular Metals Using Cell-Based Finite Element Models

A varying cell-size method based on Voronoi technique is extended to construct 3D graded cellular models. The dynamic behaviors of graded cellular structures with different density gradients are then investigated with finite element code ABAQUS/Explicit. Results show that graded cellular materials have better performance as energy absorbers. Graded cellular structures with large density near the distal end can protect strikers, and those with low density near the distal end can protect structures at the distal end. It is concluded that graded cellular materials with suitable design may have excellent performance in crashworthiness.

Understanding Interactions between Cellular Matrices and Metal Complexes: Methods To Improve Silver Nanodot‐Specific Staining

Metal complexes are frequently used for biological applications due to their special photophysical and chemical characteristics. Due to strong interactions between metals and biomacromolecules, a random staining of cytoplasm or nucleoplasm by the complexes results in a low signal-to-background ratio. In this study, we used luminescent silver nanodots as a model to investigate the major driving force for non-specific staining in cellular matrices. Even though some silver nanodot emitters exhibited excellent specific staining of nucleoli, labeling with nanodots was problematic owing to severe non-specific staining. Binding between silver and sulfhydryl group of proteins appeared to be the major factor that enforced the silver staining. The oxidation of thiol groups in cells with hexacyanoferrate(III) dramatically weakened the silver-cell interaction and consequently significantly improved the efficiency of targeted staining.