Bi-Stability, Hysteresis, and Memory of Voltage-Gated Lysenin Channels

Lysenin, a 297 amino acid pore-forming protein extracted from the coelomic fluid of the earthworm E. foetida, inserts constitutively open large conductance channels in natural and artificial lipid membranes containing sphingomyelin. The inserted channels show voltage regulation and slowly close at positive applied voltages. We report on the consequences of slow voltage-induced gating of lysenin channels inserted into a planar Bilayer Lipid Membrane (BLM), and demonstrate that these pore-forming proteins constitute memory elements that manifest gating bi-stability in response to variable external voltages. The hysteresis in macroscopic currents dynamically changes when the time scale of the voltage variation is smaller or comparable to the characteristic conformational equilibration time, and unexpectedly persists for extremely slow-changing external voltage stimuli. The assay performed on a single lysenin channel reveals that hysteresis is a fundamental feature of the individual channel unit and an intrinsic component of the gating mechanism. The investigation conducted at different temperatures reveals a thermally stable reopening process, suggesting that major changes in the energy landscape and kinetics diagram accompany the conformational transitions of the channels. Our work offers new insights on the dynamics of pore-forming proteins and provides an understanding of how channel proteins may form an immediate record of the molecular history which then determines their future response to various stimuli. Such new functionalities may uncover a link between molecular events and macroscopic processing and transmission of information in cells, and may lead to applications such as high density biologically-compatible memories and learning networks

Off-shell superconformal nonlinear sigma-models in three dimensions

We develop superspace techniques to construct general off-shell N=1,2,3,4 superconformal sigma-models in three space-time dimensions. The most general N=3 and N=4 superconformal sigma-models are constructed in terms of N=2 chiral superfields. Several superspace proofs of the folklore statement that N=3 supersymmetry implies N=4 are presented both in the on-shell and off-shell settings. We also elaborate on (super)twistor realisations for (super)manifolds on which the three-dimensional N-extended superconformal groups act transitively and which include Minkowski space as a subspace.Comment: 67 pages; V2: typos corrected, one reference added, version to appear on JHE

Modulation of Kv Channel Expression and Function by TCR and Costimulatory Signals during Peripheral CD4+ Lymphocyte Differentiation

Ionic signaling pathways, including voltage-dependent potassium (Kv) channels, are instrumental in antigen-mediated responses of peripheral T cells. However, how Kv channels cooperate with other signaling pathways involved in T cell activation and differentiation is unknown. We report that multiple Kv channels are expressed by naive CD4+ lymphocytes, and that the current amplitude and kinetics are modulated by antigen receptor–mediated stimulation and costimulatory signals. Currents expressed in naive CD4+ lymphocytes are consistent with Kv1.1, Kv1.2, Kv1.3, and Kv1.6. Effector CD4+ cells generated by optimal TCR and costimulation exhibit only Kv1.3 current, but at approximately sixfold higher levels than naive cells. CD4+ lymphocytes anergized through partial stimulation exhibit similar Kv1.1, Kv1.2, and/or Kv1.6 currents, but approximately threefold more Kv1.3 current than naive cells. To determine if Kv channels contribute to the distinct functions of naive, effector, and anergized T cells, we tested their role in immunoregulatory cytokine production. Each Kv channel is required for maximal IL-2 production by naive CD4+ lymphocytes, whereas none appears to play a role in IL-2, IL-4, or IFN-γ production by effector cells. Interestingly, Kv channels in anergized lymphocytes actively suppress IL-4 production, and these functions are consistent with a role in regulating the membrane potential and calcium signaling

Notch signaling during human T cell development

Notch signaling is critical during multiple stages of T cell development in both mouse and human. Evidence has emerged in recent years that this pathway might regulate T-lineage differentiation differently between both species. Here, we review our current understanding of how Notch signaling is activated and used during human T cell development. First, we set the stage by describing the developmental steps that make up human T cell development before describing the expression profiles of Notch receptors, ligands, and target genes during this process. To delineate stage-specific roles for Notch signaling during human T cell development, we subsequently try to interpret the functional Notch studies that have been performed in light of these expression profiles and compare this to its suggested role in the mouse

Automorphic Instanton Partition Functions on Calabi-Yau Threefolds

We survey recent results on quantum corrections to the hypermultiplet moduli space M in type IIA/B string theory on a compact Calabi-Yau threefold X, or, equivalently, the vector multiplet moduli space in type IIB/A on X x S^1. Our main focus lies on the problem of resumming the infinite series of D-brane and NS5-brane instantons, using the mathematical machinery of automorphic forms. We review the proposal that whenever the low-energy theory in D=3 exhibits an arithmetic "U-duality" symmetry G(Z) the total instanton partition function arises from a certain unitary automorphic representation of G, whose Fourier coefficients reproduce the BPS-degeneracies. For D=4, N=2 theories on R^3 x S^1 we argue that the relevant automorphic representation falls in the quaternionic discrete series of G, and that the partition function can be realized as a holomorphic section on the twistor space Z over M. We also offer some comments on the close relation with N=2 wall crossing formulae.Comment: 25 pages, contribution to the proceedings of the workshop "Algebra, Geometry and Mathematical Physics", Tjarno, Sweden, 25-30 October, 201

Plasmodium berghei Hsp90 contains a natural immunogenic I-A^b-restricted antigen common to rodent and human Plasmodium species

Thorough understanding of the role of CD4 T cells in immunity can be greatly assisted by the study of responses to defined specificities. This requires knowledge of Plasmodium-derived immunogenic epitopes, of which only a few have been identified, especially for the mouse C57BL/6 background. We recently developed a TCR transgenic mouse line, termed PbT-II, that produces CD4+ T cells specific for an MHC class II (I-Ab)-restricted Plasmodium epitope and is responsive to both sporozoites and blood-stage P. berghei. Here, we identify a peptide within the P. berghei heat shock protein 90 as the cognate epitope recognised by PbT-II cells. We show that C57BL/6 mice infected with P. berghei blood-stage induce an endogenous CD4 T cell response specific for this epitope, indicating cells of similar specificity to PbT-II cells are present in the naïve repertoire. Adoptive transfer of in vitro activated TH1-, or particularly TH2-polarised PbT-II cells improved control of P. berghei parasitemia in C57BL/6 mice and drastically reduced the onset of experimental cerebral malaria. Our results identify a versatile, potentially protective MHC-II restricted epitope useful for exploration of CD4 T cell-mediated immunity and vaccination strategies against malaria

Cooperative Effects in the Photoluminescence of (In,Ga)As/GaAs Quantum Dot Chain Structures

Multilayer In0.4Ga0.6As/GaAs quantum dot (QD) chain samples are investigated by means of cw and time-resolved photoluminescence (PL) spectroscopy in order to study the peculiarities of interdot coupling in such nanostructures. The temperature dependence of the PL has revealed details of the confinement. Non-thermal carrier distribution through in-chain, interdot wave function coupling is found. The peculiar dependences of the PL decay time on the excitation and detection energies are ascribed to the electronic interdot coupling and the long-range coupling through the radiation field. It is shown that the dependence of the PL decay time on the excitation wavelength is a result of the superradiance effect

Gaining insights into the seawater carbonate system using discrete fCO2 measurements

Understanding the ocean carbon sink and its future acidification-derived changes requires accurate and precise measurements with good spatiotemporal coverage. In addition, a deep knowledge of the thermodynamics of the seawater carbonate system is key to interconverting between measured and calculated variables. To gain insights into the remaining inconsistencies in the seawater carbonate system, we assess discrete water column measurements of carbon dioxide fugacity (fCO2), dissolved inorganic carbon (DIC), total alkalinity (TA), and pH measured with unpurified indicators, from hydrographic cruises in the Atlantic, Pacific, and Southern Oceans included in GLODAPv2.2020 (19,013 samples). An agreement of better than ±3% between fCO2 measured and calculated from DIC and pH is obtained for 94% of the compiled dataset, while when considering fCO2 measured and calculated from DIC and TA, the agreement is better than ±4% for 88% of the compiled dataset, with a poorer internal consistency for high-CO2 waters. Inspecting all likely sources of uncertainty from measured and calculated variables, we conclude that the seawater carbonate system community needs to (i) further refine the thermodynamic model of the seawater carbonate system, especially K2, including the impact of organic compounds and other acid-base systems on TA; (ii) update the standard operating procedures for the seawater carbonate system measurements following current technological and analytical advances, paying particular attention to the pH methodology that is the one that evolved the most; (iii) encourage measuring discrete water column fCO2 to further check the internal consistency of the seawater carbonate system, especially given the new era of sensor-based seawater measurements; and (iv) develop seawater Certified Reference Materials (CRMs) for fCO2 and pH together with seawater CRMs for TA and DIC over the range of values encountered in the global ocean. Our conclusions also suggest the need for a re-evaluation of the adjustments applied by GLODAPv2 to pH, which were based on DIC and TA consistency checks but not supported by fCO2 and DIC consistency