Effects of phosphorylation on ion channel function

There is considerable evidence suggesting that intracellular second messengers can modulate the activity of ion channels, and that protein phosphorylation by the different protein kinases is a frequent intermediary in these modulatory effects. This conclusion, namely, that ion channel proteins are indeed substrates for phosphorylation, has been verified in numerous biochemical studies [reviewed in 1–6].The functional correlates of channel phosphorylation are known to involve a change in channel open probability and, in the case of voltage-sensitive ion channels, a shift in the voltage dependence of channel activation. The voltage dependence of ion channel gating appears to be governed by movement of charge in the voltage-sensing moiety. Analogous to alterations in enzyme activities following biochemical modification, phosphorylation of ion channel proteins may lead to conformational changes that subsequently alter their gating and/or conductive properties, giving rise to the observed changes in electrical activity. However, in many cases, it is not yet clear whether it is the ion channels themselves that are directly modified, or whether phosphorylation is simply an early step in a cascade of events that leads ultimately to modulation of channel activity. The development and application of single-channel recording techniques in membrane patches and in artificial planar lipid bilayers has provided a means to investigate the effects of phosphorylation on the kinetic properties of ion channels. Moreover, the recent application of site directed mutagenesis to cloned ion channels has pinpointed specific amino acid residues critical for the specific kinase effects

Potential of new isolates of Dunaliella Salina for natural β-Carotene production

The halotolerant microalga Dunaliella salina has been widely studied for natural β-carotene production. This work shows biochemical characterization of three newly isolated Dunaliella salina strains, DF15, DF17, and DF40, compared with D. salina CCAP 19/30 and D. salina UTEX 2538 (also known as D. bardawil). Although all three new strains have been genetically characterized as Dunaliella salina strains, their ability to accumulate carotenoids and their capacity for photoprotection against high light stress are different. DF15 and UTEX 2538 reveal great potential for producing a large amount of β-carotene and maintained a high rate of photosynthesis under light of high intensity; however, DF17, DF40, and CCAP 19/30 showed increasing photoinhibition with increasing light intensity, and reduced contents of carotenoids, in particular β-carotene, suggesting that the capacity of photoprotection is dependent on the cellular content of carotenoids, in particular β-carotene. Strong positive correlations were found between the cellular content of all-trans β-carotene, 9-cis β-carotene, all-trans α-carotene and zeaxanthin but not lutein in the D. salina strains. Lutein was strongly correlated with respiration in photosynthetic cells and strongly related to photosynthesis, chlorophyll and respiration, suggesting an important and not hitherto identified role for lutein in coordinated control of the cellular functions of photosynthesis and respiration in response to changes in light conditions, which is broadly conserved in Dunaliella strains. Statistical analysis based on biochemical data revealed a different grouping strategy from the genetic classification of the strains. The significance of these data for strain selection for commercial carotenoid production is discussed

Classical and Christian Auctoritas in Marsilio Ficino’s preface to the Corpus Hermeticum

Marsilio Ficino’s fame as a translator, not least due to his contributions to theology and the development of hermeticism, has already been established by Frances Yates and debated by Wouter Hanegraaff. For each of his translations of Greek texts, Ficino wrote a preface to guide and to manipulate the reader. This paper presents an analysis of the auctoritas in the paratext of the Corpus Hermeticum, analyzing it as a rhetorical device used by Ficino to express his ideas, particularly the role of Hermes Trismegistus. Ficino used his rhetorical skill not only to translate from Greek to Latin but also to support his theories in commentaries, letters, or, in this case, prefaces

Classical and Christian Auctoritas in Marsilio Ficino’s preface to the Corpus Hermeticum

Marsilio Ficino’s fame as a translator, not least due to his contributions to theology and the development of hermeticism, has already been established by Frances Yates and debated by Wouter Hanegraaff. For each of his translations of Greek texts, Ficino wrote a preface to guide and to manipulate the reader. This paper presents an analysis of the auctoritas in the paratext of the Corpus Hermeticum, analyzing it as a rhetorical device used by Ficino to express his ideas, particularly the role of Hermes Trismegistus. Ficino used his rhetorical skill not only to translate from Greek to Latin but also to support his theories in commentaries, letters, or, in this case, prefaces

Single-cell profiling of human megakaryocyte-erythroid progenitors identifies distinct megakaryocyte and erythroid differentiation pathways

Background Recent advances in single-cell techniques have provided the opportunity to finely dissect cellular heterogeneity within populations previously defined by “bulk” assays and to uncover rare cell types. In human hematopoiesis, megakaryocytes and erythroid cells differentiate from a shared precursor, the megakaryocyte-erythroid progenitor (MEP), which remains poorly defined. Results To clarify the cellular pathway in erythro-megakaryocyte differentiation, we correlate the surface immunophenotype, transcriptional profile, and differentiation potential of individual MEP cells. Highly purified, single MEP cells were analyzed using index fluorescence-activated cell sorting and parallel targeted transcriptional profiling of the same cells was performed using a specifically designed panel of genes. Differentiation potential was tested in novel, single-cell differentiation assays. Our results demonstrate that immunophenotypic MEP comprise three distinct subpopulations: “Pre-MEP,” enriched for erythroid/megakaryocyte progenitors but with residual myeloid differentiation capacity; “E-MEP,” strongly biased towards erythroid differentiation; and “MK-MEP,” a previously undescribed, rare population of cells that are bipotent but primarily generate megakaryocytic progeny. Therefore, conventionally defined MEP are a mixed population, as a minority give rise to mixed-lineage colonies while the majority of cells are transcriptionally primed to generate exclusively single-lineage output. Conclusions Our study clarifies the cellular hierarchy in human megakaryocyte/erythroid lineage commitment and highlights the importance of using a combination of single-cell approaches to dissect cellular heterogeneity and identify rare cell types within a population. We present a novel immunophenotyping strategy that enables the prospective identification of specific intermediate progenitor populations in erythro-megakaryopoiesis, allowing for in-depth study of disorders including inherited cytopenias, myeloproliferative disorders, and erythromegakaryocytic leukemias

The innate sensor ZBP1-IRF3 axis regulates cell proliferation in multiple myeloma

Multiple myeloma is a malignancy of plasma cells (PC) initiated and driven by primary and secondary genetic events. Nevertheless, myeloma PC survival and proliferation might be sustained by non-genetic drivers. Z-DNA-binding protein 1 (ZBP1; also known as DAI) is an interferon-inducible, Z-nucleic acid sensor that triggers RIPK3-MLKL-mediated necroptosis in mice. ZBP1 also interacts with TBK1 and the transcription factor IRF3 but the function of this interaction is unclear, and the role of ZBP1-IRF3 axis in cancer is not known. Here we show that ZBP1 is selectively expressed in late B cell development in both human and mouse cells and it is required for optimal T-cell-dependent humoral immune responses. In myeloma PC, interaction of constitutively expressed ZBP1 with TBK1 and IRF3 results in IRF3 phosphorylation. IRF3 directly binds and activates cell cycle genes, in part through co-operation with the PC lineage-defining transcription factor IRF4, and thereby promoting myeloma cell proliferation. This generates a novel, potentially therapeutically targetable and relatively selective myeloma cell addiction to the ZBP1-IRF3 axis. Our data also show a non-canonical function of constitutive ZBP1 in human cells and expand our knowledge of the role of cellular immune sensors in cancer biology

Extending the time of coherent optical response in ensemble of singly-charged InGaAs quantum dots

The ability to extend the time scale of the coherent optical response from large ensembles of quantum emitters is highly appealing for applications in quantum information devices. In semiconductor nanostructures, spin degrees of freedom can be used as auxiliary, powerful tools to modify the coherent optical dynamics. Here, we apply this approach to negatively charged (In,Ga)As/GaAs self-assembled quantum dots which are considered as excellent quantum emitters with robust optical coherence and high bandwidth. We study three-pulse spin-dependent photon echoes subject to moderate transverse magnetic fields up to 1 T. We demonstrate that the timescale of coherent optical response can be extended by at least an order of magnitude by the field. Without magnetic field, the photon echo decays with T2 = 0.45 ns which is determined by the radiative lifetime of trions T1 = 0.26 ns. In the presence of the transverse magnetic field, the decay of the photon echo signal is given by spin dephasing time of the ensemble of resident electrons T2,e ∼ 4 ns. We demonstrate that the non-zero transverse g-factor of the heavy holes in the trion state plays a crucial role in the temporal evolution and magnetic field dependence of the long-lived photon echo signal

Comparison of 2D Optical Imaging and 3D Microtomography Shape Measurements of a Coastal Bioclastic Calcareous Sand

This article compares measurements of particle shape parameters from three-dimensional (3D) X-ray micro-computed tomography (μCT) and two-dimensional (2D) dynamic image analysis (DIA) from the optical microscopy of a coastal bioclastic calcareous sand from Western Australia. This biogenic sand from a high energy environment consists largely of the shells and tests of marine organisms and their clasts. A significant difference was observed between the two imaging techniques for measurements of aspect ratio, convexity, and sphericity. Measured values of aspect ratio, sphericity, and convexity are larger in 2D than in 3D. Correlation analysis indicates that sphericity is correlated with convexity in both 2D and 3D. These results are attributed to inherent limitations of DIA when applied to platy sand grains and to the shape being, in part, dependent on the biology of the grain rather than a purely random clastic process, like typical siliceous sands. The statistical data has also been fitted to Johnson Bounded Distribution for the ease of future use. Overall, this research demonstrates the need for high-quality 3D microscopy when conducting a micromechanical analysis of biogenic calcareous sand