Ca2+ Microdomains, Calcineurin and the Regulation of Gene Transcription

Ca2+ ions function as second messengers regulating many intracellular events, including neurotransmitter release, exocytosis, muscle contraction, metabolism and gene transcription. Cells of a multicellular organism express a variety of cell-surface receptors and channels that trigger an increase of the intracellular Ca2+ concentration upon stimulation. The elevated Ca2+ concentration is not uniformly distributed within the cytoplasm but is organized in subcellular microdomains with high and low concentrations of Ca2+ at different locations in the cell. Ca2+ ions are stored and released by intracellular organelles that change the concentration and distribution of Ca2+ ions. A major function of the rise in intracellular Ca2+ is the change of the genetic expression pattern of the cell via the activation of Ca2+-responsive transcription factors. It has been proposed that Ca2+-responsive transcription factors are differently affected by a rise in cytoplasmic versus nuclear Ca2+. Moreover, it has been suggested that the mode of entry determines whether an influx of Ca2+ leads to the stimulation of gene transcription. A rise in cytoplasmic Ca2+ induces an intracellular signaling cascade, involving the activation of the Ca2+/calmodulin-dependent protein phosphatase calcineurin and various protein kinases (protein kinase C, extracellular signal-regulated protein kinase, Ca2+/calmodulin-dependent protein kinases). In this review article, we discuss the concept of gene regulation via elevated Ca2+ concentration in the cytoplasm and the nucleus, the role of Ca2+ entry and the role of enzymes as signal transducers. We give particular emphasis to the regulation of gene transcription by calcineurin, linking protein dephosphorylation with Ca2+ signaling and gene expression

Critical Protein–Protein Interactions Determine the Biological Activity of Elk-1, a Master Regulator of Stimulus-Induced Gene Transcription

Elk-1 is a transcription factor that binds together with a dimer of the serum response factor (SRF) to the serum-response element (SRE), a genetic element that connects cellular stimulation with gene transcription. Elk-1 plays an important role in the regulation of cellular proliferation and apoptosis, thymocyte development, glucose homeostasis and brain function. The biological function of Elk-1 relies essentially on the interaction with other proteins. Elk-1 binds to SRF and generates a functional ternary complex that is required to activate SRE-mediated gene transcription. Elk-1 is kept in an inactive state under basal conditions via binding of a SUMO-histone deacetylase complex. Phosphorylation by extracellular signal-regulated protein kinase, c-Jun N-terminal protein kinase or p38 upregulates the transcriptional activity of Elk-1, mediated by binding to the mediator of RNA polymerase II transcription (Mediator) and the transcriptional coactivator p300. Strong and extended phosphorylation of Elk-1 attenuates Mediator and p300 recruitment and allows the binding of the mSin3A-histone deacetylase corepressor complex. The subsequent dephosphorylation of Elk-1, catalyzed by the protein phosphatase calcineurin, facilitates the re-SUMOylation of Elk1, transforming Elk-1 back to a transcriptionally inactive state. Thus, numerous protein–protein interactions control the activation cycle of Elk-1 and are essential for its biological function

Small scale quasi-geostrophic convective turbulence at large Rayleigh number

A numerical investigation of an asymptotically reduced model for quasi-geostrophic Rayleigh-B\'enard convection is conducted in which the depth-averaged flows are numerically suppressed by modifying the governing equations. The Reynolds number and Nusselt number show evidence of approaching the diffusion-free scalings of $Re \sim Ra E/Pr$ and $Nu \sim Pr^{-1/2} Ra^{3/2} E^2$, respectively, where $E$ is the Ekman number and $Pr$ is the Prandtl number. For large $Ra$, the presence of depth-invariant flows, such as large-scale vortices, yield heat and momentum transport scalings that exceed those of the diffusion-free scaling laws. The Taylor microscale does not vary significantly with increasing $Ra$, whereas the integral length scale grows weakly. The computed length scales remain $O(1)$ with respect to the linearly unstable critical wavenumber; we therefore conclude that these scales remain viscously controlled. We do not find a point-wise Coriolis-Inertia-Archimedean (CIA) force balance in the turbulent regime; interior dynamics are instead dominated by horizontal advection (inertia), vortex stretching (Coriolis) and the vertical pressure gradient. A secondary, sub-dominant balance between the buoyancy force and the viscous force occurs in the interior and the ratio of the rms of these two forces is found to approach unity with increasing $Ra$. This secondary balance is attributed to the turbulent fluid interior acting as the dominant control on the heat transport. These findings indicate that a pointwise CIA balance does not occur in the high Rayleigh number regime of quasi-geostrophic convection in the plane layer geometry. Instead, simulations are characterized by what may be termed a \textsl{non-local} CIA balance in which the buoyancy force is dominant within the thermal boundary layers and is spatially separated from the interior Coriolis and inertial forces.Comment: 32 pages, 11 figure

Разработка устройства управления беспроводной связью на базе чипа ESP8266

Цель выпускной квалификационной работы – разработка устройства управления беспроводной связью на базе чипа ESP8266.За время выполнения работы проведено ознакомление возможностями элементов используемых в работе, а именно микроконтроллеров на базе ядра ARM-Cortex-M3 и Wi-Fi модулей, выполненных на чипсете ESP8266. В соответствии с требованиями, отраженными в техническом задании разработана структура и выполнен ручной монтаж устройства. Конечным этапом достижения цели являлись разработка алгоритма функционирования устройства и выполнение его программной реализации.Разработанное устройство управления беспроводной связью рекомендовано для использования в системах мониторинга охранно-пожарной, тревожной и технологической сигнализации стационарных объектов.The objective of the graduation thesis is to develop the wireless control device based on ESP8266 chipset. In the course of the work, the author examined the capabilities of the elements used in the work, namely the microcontrollers based on the ARM-Cortex-M3 core and the Wi-Fi modules based on the ESP8266 chipset. In accordance with the requirements set forth in the Statement of Work, the author developed the structure and carried out the manual assembly of the device. The final objective is to develop the operation algorithm of the device and to ensure software implementation of this algorithm.The developed wireless control device is recommended to be used in monitoring systems of fire, security, emergency and process alarm devices for stationary objects

Heterostructures of skutterudites and germanium antimony tellurides – structure analysis and thermoelectric properties of bulk samples

Heterostructures of germanium antimony tellurides with skutterudite-type precipitates are promising thermoelectric materials due to low thermal conductivity and multiple ways of tuning their electronic transport properties. Materials with the nominal composition [CoSb2(GeTe)_(0.5)]_x(GeTe)_(10.5)Sb_2Te_3 (x = 0–2) contain nano- to microscale precipitates of skutterudite-type phases which are homogeneously distributed. Powder X-ray diffraction reveals that phase transitions of the germanium antimony telluride matrix depend on its GeTe content. These are typical for this class of materials; however, the phase transition temperatures are influenced by heterostructuring in a beneficial way, yielding a larger existence range of the intrinsically nanostructured pseudocubic structure of the matrix. Using microfocused synchrotron radiation in combination with crystallite pre-selection by means of electron microscopy, single crystals of the matrix as well as of the precipitates were examined. They show nano-domain twinning of the telluride matrix and a pronounced structure distortion in the precipitates caused by GeTe substitution. Thermoelectric figures of merit of 1.4 ± 0.3 at 450 °C are observed. In certain temperature ranges, heterostructuring involves an improvement of up to 30% compared to the homogeneous material

Synthesis, spectroscopic characterization and thermogravimetric analysis of two series of substituted (metallo)tetraphenylporphyrins

Subsequent treatment of H2TPP(CO2H)4 (tetra(p-carboxylic acid phenyl)porphyrin, 1) with an excess of oxalyl chloride and HNR2 afforded H2TPP(C(O)NR2)4 (R = Me, 2; iPr, 3) with yields exceeding 80%. The porphyrins 2 and 3 could be converted to the corresponding metalloporphyrins MTPP(C(O)NR2)4 (R = Me/iPr for M = Zn (2a, 3a); Cu (2b, 3b); Ni (2c, 3c); Co (2d, 3d)) by the addition of 3 equiv of anhydrous MCl2 (M = Zn, Cu, Ni, Co) to dimethylformamide solutions of 2 and 3 at elevated temperatures. Metalloporphyrins 2a–d and 3a–d were obtained in yields exceeding 60% and have been, as well as 2 and 3, characterized by elemental analysis, electrospray ionization mass spectrometry (ESIMS) and IR and UV–vis spectroscopy. Porphyrins 2, 2a–d and 3, 3a–d are not suitable for organic molecular beam deposition (OMBD), which is attributed to their comparatively low thermal stability as determined by thermogravimetric analysis (TG) of selected representatives

TAGS-related indium compounds and their thermoelectric properties – the solid solution series (GeTe)_xAgIn_ySb_(1-y)Te_2 (x = 1–12; y = 0.5 and 1)

Various members of the solid solution series (GeTe)_xAgIn_ySb_(1−y)Te_2 can be obtained by quenching high-temperature phases (x = 12 for y = 1 and x > 5 for y = 0.5). In contrast, high-temperature and high-pressure conditions (2.5 GPa, 350 °C) are required for the synthesis of members with In contents >3.6 atom% (such as x 5 adopt the α-GeTe structure type (3 + 3 coordination). Thus, in all samples investigated, 3 or 4 cations are disordered at one Wyckoff position. The quenched high-temperature or high-pressure phases, respectively, are almost homogeneous. Their powder X-ray diffraction patterns suggest pure phases; yet, high-resolution electron microscopy occasionally reveals a very small extent of nanoscopic precipitates as well as dislocations and twinning. (GeTe)_(5.5)AgIn_(0.5)Sb_(0.5)Te_2 shows a maximal ZT value of 0.75 even when (partial) decomposition into the TAGS material (GeTe)_(11)AgSbTe_2 and chalcopyrite-type AgInTe_2 has occurred at 300 °C. (GeTe)_(5.5)AgInTe_2 prepared under high-pressure conditions exhibits a ZT value of 0.6 at 125 °C, i.e. far below the decomposition temperature and thus is an interesting new low-temperature thermoelectric material

(Metallo)porphyrins for potential materials science applications

The bottom-up approach to replace existing devices by molecular-based systems is a subject that attracts permanently increasing interest. Molecular-based devices offer not only to miniaturize the device further, but also to benefit from advanced functionalities of deposited molecules. Furthermore, the molecules itself can be tailored to allow via their self-assembly the potential fabrication of devices with an application potential, which is still unforeseeable at this time. Herein, we review efforts to use discrete (metallo)porphyrins for the formation of (sub)monolayers by surface-confined polymerization, of monolayers formed by supramolecular recognition and of thin films formed by sublimation techniques. Selected physical properties of these systems are reported as well. The application potential of those ensembles of (metallo)porphyrins in materials science is discussed

Purely antiferromagnetic magnetoelectric random access memory

Magnetic random access memory schemes employing magnetoelectric coupling to write binary information promise outstanding energy efficiency. We propose and demonstrate a purely antiferromagnetic magnetoelectric random access memory (AF-MERAM) that offers a remarkable 50-fold reduction of the writing threshold compared with ferromagnet-based counterparts, is robust against magnetic disturbances and exhibits no ferromagnetic hysteresis losses. Using the magnetoelectric antiferromagnet Cr2O3, we demonstrate reliable isothermal switching via gate voltage pulses and all-electric readout at room temperature. As no ferromagnetic component is present in the system, the writing magnetic field does not need to be pulsed for readout, allowing permanent magnets to be used. Based on our prototypes, we construct a comprehensive model of the magnetoelectric selection mechanisms in thin films of magnetoelectric antiferromagnets, revealing misfit induced ferrimagnetism as an important factor. Beyond memory applications, the AF-MERAM concept introduces a general all-electric interface for antiferromagnets and should find wide applicability in antiferromagnetic spintronics

Purely Antiferromagnetic Magnetoelectric Random Access Memory

Magnetic random access memory schemes employing magnetoelectric coupling to write binary information promise outstanding energy efficiency. We propose and demonstrate a purely antiferromagnetic magnetoelectric random access memory (AF-MERAM) that offers a remarkable 50 fold reduction of the writing threshold compared to ferromagnet-based counterparts, is robust against magnetic disturbances and exhibits no ferromagnetic hysteresis losses. Using the magnetoelectric antiferromagnet Cr2O3, we demonstrate reliable isothermal switching via gate voltage pulses and all-electric readout at room temperature. As no ferromagnetic component is present in the system, the writing magnetic field does not need to be pulsed for readout, allowing permanent magnets to be used. Based on our prototypes of these novel systems, we construct a comprehensive model of the magnetoelectric selection mechanism in thin films of magnetoelectric antiferromagnets. We identify that growth induced effects lead to emergent ferrimagnetism, which is detrimental to the robustness of the storage. After pinpointing lattice misfit as the likely origin, we provide routes to enhance or mitigate this emergent ferrimagnetism as desired. Beyond memory applications, the AF-MERAM concept introduces a general all-electric interface for antiferromagnets and should find wide applicability in purely antiferromagnetic spintronics devices.Comment: Main text (4 figures) + supplementary information (7 figures