A Guide to Human Zinc Absorption: General Overview and Recent Advances of In Vitro Intestinal Models

Zinc absorption in the small intestine is one of the main mechanisms regulating the systemic homeostasis of this essential trace element. This review summarizes the key aspects of human zinc homeostasis and distribution. In particular, current knowledge on human intestinal zinc absorption and the influence of diet-derived factors on bioaccessibility and bioavailability as well as intrinsic luminal and basolateral factors with an impact on zinc uptake are discussed. Their investigation is increasingly performed using in vitro cellular intestinal models, which are continually being refined and keep gaining importance for studying zinc uptake and transport via the human intestinal epithelium. The vast majority of these models is based on the human intestinal cell line Caco-2 in combination with other relevant components of the intestinal epithelium, such as mucin-secreting goblet cells and in vitro digestion models, and applying improved compositions of apical and basolateral media to mimic the in vivo situation as closely as possible. Particular emphasis is placed on summarizing previous applications as well as key results of these models, comparing their results to data obtained in humans, and discussing their advantages and limitations.DFG, 316442145, FOR 2558: Interaktionen von essenziellen Spurenelementen in gesunden und erkrankten älteren Menschen (TraceAge)DFG, 414044773, Open Access Publizieren 2019 - 2020 / Technische Universität Berli

Regime mapping and the role of the intermediate region in wall-coated microreactors

Operation of a wall-coated microreactor can occur in several mass transfer-reaction regimes. We define these regimes analytically in several planes of a multi-parametric map, taking into account the different degrees of concentration profile development, as well as the influence of non-unity orders of reaction and reactant inhibition in the kinetic law. It was found that the regions where conversion can be calculated from simplified mass transfer models are not discriminated by common results for entrance-length. We also illustrate the trade-offs that exist across this operating map concerning the catalyst design (costs associated with loading and volume) and overall system performance (evaluated in terms of reactant conversion, flow efficiency and microreactor effectiveness). It is shown that under certain conditions, the existence of moderate mass transfer resistance can be advantageous (even if internal limitations cannot be avoided), clarifying the role of the intermediate transport-reaction region

Tuning a binary ferromagnet into a multi-state synapse with spin-orbit torque induced plasticity

Inspired by ion-dominated synaptic plasticity in human brain, artificial synapses for neuromorphic computing adopt charge-related quantities as their weights. Despite the existing charge derived synaptic emulations, schemes of controlling electron spins in ferromagnetic devices have also attracted considerable interest due to their advantages of low energy consumption, unlimited endurance, and favorable CMOS compatibility. However, a generally applicable method of tuning a binary ferromagnet into a multi-state memory with pure spin-dominated synaptic plasticity in the absence of an external magnetic field is still missing. Here, we show how synaptic plasticity of a perpendicular ferromagnetic FM1 layer can be obtained when it is interlayer-exchange-coupled by another in-plane ferromagnetic FM2 layer, where a magnetic-field-free current-driven multi-state magnetization switching of FM1 in the Pt/FM1/Ta/FM2 structure is induced by spin-orbit torque. We use current pulses to set the perpendicular magnetization state which acts as the synapse weight, and demonstrate spintronic implementation of the excitatory/inhibitory postsynaptic potentials and spike timing-dependent plasticity. This functionality is made possible by the action of the in-plane interlayer exchange coupling field which leads to broadened, multi-state magnetic reversal characteristics. Numerical simulations, combined with investigations of a reference sample with a single perpendicular magnetized Pt/FM1/Ta structure, reveal that the broadening is due to the in-plane field component tuning the efficiency of the spin-orbit-torque to drive domain walls across a landscape of varying pinning potentials. The conventionally binary FM1 inside our Pt/FM1/Ta/FM2 structure with inherent in-plane coupling field is therefore tuned into a multi-state perpendicular ferromagnet and represents a synaptic emulator for neuromorphic computing.Comment: 37 pages with 11 figures, including 20 pages for manuscript and 17 pages for supplementary informatio

Cadmium in newborns

Cadmium (Cd) is a well-known nephrotoxic environmental contaminant but there are indications that the developing nervous system might be even more sensitive to Cd than the kidneys in adults. Infants are exposed to Cd from various formulas and infant diets and the gastrointestinal Cd uptake is believed to be higher in newborns than in adults. Cd levels monitored in infant foods ranged between 0.74 and 27.0 µg/kg. Cow's milk formulas had the lowest levels and cereal-based formulas had up to 21 times higher mean levels. The mean weekly Cd exposure from the recommended formula intake was calculated to vary between 0.10 and 3.05 µg/kg body weight. Rat pups received an oral dose of 109Cd in water or four different formulas. The whole-body Cd retention was higher in the pups than previously reported in adult animals and highest in the water and in the cow's milk formula groups. The small intestinal Cd retention was high, even 9 days after exposure indicating a long absorption period in the newborns. Cd levels in kidney increased still 12 days after exposure in all diet groups. Piglets received low daily doses of Cd in water or wheat/oat/milk-based follow-up formula. The formula reduced Cd uptake in comparison to water, but the distribution of Cd to the kidneys was unexpectedly higher when Cd was given in formula than in water. Simulated infant digestion of infant foods resulted in lower solubility of Cd compared to adult digestion. In a human Caco-2 cell model, cellular Cd uptake and transport from five different infant food digests was approximately one order of magnitude lower than the solubility and varied between 4-6 % and 1-2 % of the dose, respectively. Binding of Cd to dietary fibres and phytic acid reduces intestinal Cd retention and probably explains the lower Cd bioavailability from cereal-based formulas compared to water or cow's milk formula. The exposure of Cd is higher from infant formulas than from breast milk and age-specific digestion conditions as well as composition of diets affect both the Cd solubility and bioavailability. The calculated Cd intake from recommended amount of infant formulas is below the established provisional tolerable weekly intake, which however, does not include a safety factor and is based on renal effects in adults

Excitation of local magnetic moments by tunnelling electrons

The advent of milli-kelvin scanning tunneling microscopes (STM) with inbuilt magnetic fields has opened access to the study of magnetic phenomena with atomic resolution at surfaces. In the case of single atoms adsorbed on a surface, the existence of different magnetic energy levels localized on the adsorbate is due to the breaking of the rotational invariance of the adsorbate spin by the interaction with its environment, leading to energy terms in the meV range. These structures were revealed by STM experiments in IBM Almaden in the early 2000's for atomic adsorbates on CuN surfaces. The experiments consisted in the study of the changes in conductance caused by inelastic tunnelling of electrons (IETS, Inelastic Electron Tunnelling Spectroscopy). Manganese and Iron adatoms were shown to have different magnetic anisotropies induced by the substrate. More experiments by other groups followed up, showing that magnetic excitations could be detected in a variety of systems: e.g. complex organic molecules showed that their magnetic anistropy was dependent on the molecular environment, piles of magnetic molecules showed that they interact via intermolecular exchange interaction, spin waves were excited on ferromagnetic surfaces and in Mn chains, and magnetic impurities have been analyzed on semiconductors. These experiments brought up some intriguing questions: the efficiency of magnetic excitations was very high, the excitations could or could not involve spin flip of the exciting electron and singular-like behavior was sometimes found at the excitation thresholds. These facts called for extended theoretical analysis; perturbation theories, sudden-approximation approaches and a strong coupling scheme successfully explained most of the magnetic inelastic processes. In addition, many-body approaches were also used to decipher the interplay between inelasComment: Review article to appear in Progress of Surface Scienc

Optimal control of magnetization dynamics in ferromagnetic heterostructures by spin--polarized currents

We study the switching-process of the magnetization in a ferromagnetic-normal-metal multilayer system by a spin polarized electrical current via the spin transfer torque. We use a spin drift-diffusion equation (SDDE) and the Landau-Lifshitz-Gilbert equation (LLGE) to capture the coupled dynamics of the spin density and the magnetization dynamic of the heterostructure. Deriving a fully analytic solution of the stationary SDDE we obtain an accurate, robust, and fast self-consistent model for the spin-distribution and spin transfer torque inside general ferromagnetic/normal metal heterostructures. Using optimal control theory we explore the switching and back-switching process of the analyzer magnetization in a seven-layer system. Starting from a Gaussian, we identify a unified current pulse profile which accomplishes both processes within a specified switching time.Comment: 5 figure

Ultrafast and low-energy switching in voltage-controlled elliptical pMTJ

Switching magnetization in a perpendicular magnetic tunnel junction (pMTJ) via voltage controlled magnetic anisotropy (VCMA) has shown the potential to markedly reduce the switching energy. However, the requirement of an external magnetic field poses a critical bottleneck for its practical applications. In this work, we propose an elliptical-shaped pMTJ to eliminate the requirement of providing an external field by an additional circuit. We demonstrate that a 10 nm thick in-plane magnetized bias layer (BL) separated by a metallic spacer of 3 nm from the free layer (FL) can be engineered within the MTJ stack to provide the 50 mT bias magnetic field for switching. By conducting macrospin simulation, we find that a fast switching in 0.38 ns with energy consumption as low as 0.3 fJ at a voltage of 1.6 V can be achieved. Furthermore, we study the phase diagram of switching probability, showing that a pulse duration margin of 0.15 ns is obtained and a low-voltage operation (~ 1 V) is favored. Finally, the MTJ scalability is considered, and it is found that scaling-down may not be appealing in terms of both the energy consumption and the switching time for the precession based VCMA switching.Comment: There are 28 pages and 5 figure

Study of the Cys-His bridge electron transfer pathway in a copper-containing nitrite reductase by site-directed mutagenesis, spectroscopic, and computational methods

The Cys-His bridge as electron transfer conduit in the enzymatic catalysis of nitrite to nitric oxide by nitrite reductase from Sinorhizobium meliloti 2011 (SmNir) was evaluated by site-directed mutagenesis, steady state kinetic studies, UV-vis and EPR spectroscopic measurements as well as computational calculations. The kinetic, structural and spectroscopic properties of the His171Asp (H171D) and Cys172Asp (C172D) SmNir variants were compared with the wild type enzyme. Molecular properties of H171D and C172D indicate that these point mutations have not visible effects on the quaternary structure of SmNir. Both variants are catalytically incompetent using the physiological electron donor pseudoazurin, though C172D presents catalytic activity with the artificial electron donor methyl viologen (kcat =3.9(4) s-1) lower than that of wt SmNir (kcat =240(50) s-1). QM/MM calculations indicate that the lack of activity of H171D may be ascribed to the Nδ1H...OC hydrogen bond that partially shortcuts the T1-T2 bridging Cys-His covalent pathway. The role of the Nδ1H...OC hydrogen bond in the pH-dependent catalytic activity of wt SmNir is also analyzed by monitoring the T1 and T2 oxidation states at the end of the catalytic reaction of wt SmNir at pH6 and 10 by UV-vis and EPR spectroscopies. These data provide insight into how changes in Cys-His bridge interrupts the electron transfer between T1 and T2 and how the pH-dependent catalytic activity of the enzyme are related to pH-dependent structural modifications of the T1-T2 bridging chemical pathway.Fil: Cristaldi, Julio César. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Gómez, María C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Física; ArgentinaFil: González, Pablo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Física; ArgentinaFil: Ferroni, Felix Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Física; ArgentinaFil: Dalosto, Sergio Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Física del Litoral. Universidad Nacional del Litoral. Instituto de Física del Litoral; ArgentinaFil: Rizzi, Alberto Claudio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Física; ArgentinaFil: Rivas, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Física; ArgentinaFil: Brondino, Carlos Dante. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Física; Argentin

Inhibition of the Aminopeptidase from \u3cem\u3eAeromonas proteolytica\u3c/em\u3e by l-leucinethiol: Kinetic and Spectroscopic Characterization of a Slow, Tight-binding Inhibitor–enzyme Complex

The peptide inhibitor l-leucinethiol (LeuSH) was found to be a potent, slow-binding inhibitor of the aminopeptidase from Aeromonas proteolytica (AAP). The overall potency (KI*) of LeuSH was 7 nM while the corresponding alcohol l-leucinol (LeuOH) was a simple competitive inhibitor of much lower potency (KI=17 μM). These data suggest that the free thiol is likely involved in the formation of the E·I and E·I* complexes, presumably providing a metal ligand. In order to probe the nature of the interaction of LeuSH and LeuOH with the dinuclear active site of AAP, we have recorded both the electronic absorption and EPR spectra of [CoCo(AAP)], [CoZn(AAP)], and [ZnCo(AAP)] in the presence of both inhibitors. In the presence of LeuSH, all three Co(II)-substituted AAP enzymes exhibited an absorption band centered at 295 nm, characteristic of a S→Co(II) ligand-metal charge-transfer band. In addition, absorption spectra recorded in the 450 to 700 nm region all showed changes characteristic of LeuSH and LeuOH interacting with both metal ions. EPR spectra recorded at high temperature (19 K) and low power (2.5 mW) indicated that, in a given enzyme molecule, LeuSH interacts weakly with one of the metal ions in the dinuclear site and that the crystallographically identified μ-OH(H) bridge, which has been shown to mediate electronic interaction of the Co(II) ions, is likely broken upon binding LeuSH. EPR spectra of [CoCo(AAP)]-LeuSH, [ZnCo(AAP)]-LeuSH, and [Co_(AAP)]-LeuSH were also recorded at lower temperature (3.5–4.0 K) and high microwave power (50–553 mW). These signals were unusual and appeared to contain, in addition to the incompletely saturated contributions from the signals characterized at 19 K, a very sharp feature at geff∼6.5 that is characteristic of thiolate-Co(II) interactions. Combination of the electronic absorption and EPR data indicates that LeuSH perturbs the electronic structure of both metal ions in the dinuclear active site of AAP. Since the spin–spin interaction seen in resting [CoCo(AAP)] is abolished upon the addition of LeuSH, it is unlikely that a μ-S(R) bridge is established