Properties of Cyclic-Nucleotide Gated Channels Mediating Olfactory Transduction - Activation, Selectivity, and Blockage

Cyclic nucleotide-gated channels (cng channels) in the sensory membrane of olfactory receptor cells, activated after the odorant-induced increase of cytosolic cAMP concentration, conduct the receptor current that elicits electrical excitation of the receptor neurons. We investigated properties of cng channels from frog and rat using inside-out and outside-out membrane patches excised from isolated olfactory receptor cells. Channels were activated by cAMP and cGMP with activation constants of 2.5-4.0-mu-M for cAMP and 1.0-1.8 for cGMP. Hill coefficients of dose-response curves were 1.4-1.8, indicating cooperativity of ligand binding. Selectivity for monovalent alkali cations and the Na/Li mole-fraction behavior identified the channel as a nonselective cation channel, having a cation-binding site of high field strength in the pore. Cytosolic pH effects suggest the presence of an additional titratable group which, when protonated, inhibits the cAMP-induced current with an apparent pK of 5.0-5.2. The pH effects were not voltage dependent. Several blockers of Ca2+ channels also blocked olfactory cng channels. Amiloride, D 600, and diltiazem inhibited the cAMP-induced current from the cytosolic side. Inhibition constants were voltage dependent with values of, respectively, 0.1, 0.3, and 1 mM at - 60 mV, and 0.03, 0.02, and 0.2 mM at + 60 mV. Our results suggest functional similarity between frog and rat cng channels, as well as marked differences to cng channels from photoreceptors and other tissues

Humoral response to a 13-valent pneumococcal conjugate vaccine in kidney transplant recipients

Background: Vaccination against S. pneumoniae is recommended by national guidelines. Moderate immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13) has been reported in adult kidney transplant recipients (KTR). This study further defines the immunogenicity of PCV13 in this cohort. Methods: 49 KTR were immunized with PCV13. A validated opsonophagocytic killing assay (OPA), a global anti-pneumococcal capsular polysaccharide (anti-PCP) IgG, IgG2, IgM and IgA ELISA, and - for selected patients - a serotype specific anti-PCP WHO reference ELISA were performed pre-vaccination and at month 1 and 12 post-vaccination. Results: Geometric mean OPA titers increased significantly for 13/13 serotypes at month 1 and for 10/13 serotypes at month 12 post-vaccination. Vaccine response defined as an OPA titer ≥1:8 was reached in 9/13 serotypes (median). 53% reached the vaccine response criteria at month 1 and 45% at month 12. At month 1 after vaccination, the median OPA titer in an age-group matched healthy reference population was 5- to 10-fold higher than in KTR. OPA titers correlated strongly with results to the global and serotype specific anti-PCP IgG ELISA. Lower OPA titers significantly (p < 0.05) correlated with albuminuria, an interval between vaccination and transplantation <12 months, age and treatment with mycophenolate mofetil. Global IgG, IgG2, IgM and IgA, as well as serotype specific anti-PCP antibody concentrations (12/13 serotypes) increased significantly at month 1 and 12 post-vaccination. Conclusions: Kidney transplant recipients show a significant humoral response after vaccination with PCV13. Functional antibody response exists, but is not as vigorous as in healthy adults

Analysis of the temperature-dependent quantum point contact conductance in view of the metal-insulator transition in two dimensions

The temperature dependence of the conductance of a quantum point contact has been measured. The conductance as a function of the Fermi energy shows temperature-independent fixed points, located at roughly multiple integers of $e^{2}/h$. Around the first fixed point at e$^{2}$/h, the experimental data for different temperatures can been scaled onto a single curve. For pure thermal smearing of the conductance steps, a scaling parameter of one is expected. The measured scaling parameter, however, is significantly larger than 1. The deviations are interpreted as a signature of the potential landscape of the quantum point contact, and of the source-drain bias voltage. We relate our results phenomenologically to the metal-insulator transition in two dimensions.Comment: 5 pages, 3 figure

Nonlinear instability in flagellar dynamics: a notel modulation mechanism in sperm migration

Throughout biology, cells and organisms use flagella and cilia to propel fluid and achieve motility. The beating of these organelles, and the corresponding ability to sense, respond to and modulate this beat is central to many processes in health and disease. While the mechanics of flagellum–fluid interaction has been the subject of extensive mathematical studies, these models have been restricted to being geometrically linear or weakly nonlinear, despite the high curvatures observed physiologically. We study the effect of geometrical nonlinearity, focusing on the spermatozoon flagellum. For a wide range of physiologically relevant parameters, the nonlinear model predicts that flagellar compression by the internal forces initiates an effective buckling behaviour, leading to a symmetry-breaking bifurcation that causes profound and complicated changes in the waveform and swimming trajectory, as well as the breakdown of the linear theory. The emergent waveform also induces curved swimming in an otherwise symmetric system, with the swimming trajectory being sensitive to head shape—no signalling or asymmetric forces are required. We conclude that nonlinear models are essential in understanding the flagellar waveform in migratory human sperm; these models will also be invaluable in understanding motile flagella and cilia in other systems

Density functional theory of freezing: Analysis of crystal density

This is the publisher's version, also available electronically from http://scitation.aip.org/content/aip/journal/jcp/87/9/10.1063/1.453663The density functional theory of freezing is used to study the liquid to crystal phase transition in the hardsphere and Lennard‐Jones systems. An important step in the calculation is the parametrization of the solid phase average single particle density ρ(r). In this work two popular parametrizations are compared. The first method is a general Fourier decomposition of the periodic solid density in which the amplitude of each (non‐symmetry‐related) Fourier component is treated as an independent parameter. The second parametrization, which is more restrictive but easier to implement, approximates the solid density as a sum of Gaussian peaks centered at the sites of a periodic lattice. The two methods give essentially identical results for the phase diagrams for the two systems studied, but the crystal density predicted by the Fourier method exhibits significant anisotropies which are excluded from the Gaussian representation by construction

Physical Aspects of Axonemal Beating and Swimming

We discuss a two-dimensional model for the dynamics of axonemal deformations driven by internally generated forces of molecular motors. Our model consists of an elastic filament pair connected by active elements. We derive the dynamic equations for this system in presence of internal forces. In the limit of small deformations, a perturbative approach allows us to calculate filament shapes and the tension profile. We demonstrate that periodic filament motion can be generated via a self-organization of elastic filaments and molecular motors. Oscillatory motion and the propagation of bending waves can occur for an initially non-moving state via an instability termed Hopf bifurcation. Close to this instability, the behavior of the system is shown to be independent of microscopic details of the axoneme and the force-generating mechanism. The oscillation frequency however does depend on properties of the molecular motors. We calculate the oscillation frequency at the bifurcation point and show that a large frequency range is accessible by varying the axonemal length between 1 and 50$\mu$m. We calculate the velocity of swimming of a flagellum and discuss the effects of boundary conditions and externally applied forces on the axonemal oscillations.Comment: 14 pages, 8 figures, REVTE

Universities and community-based research in developing countries: community voice and educational provision in rural Tanzania

The main focus of recent research on the community engagement role of universities has been in developed countries, generally in towns and cities and usually conducted from the perspectives of universities rather than the communities with which they engage. The purpose of this paper is to investigate the community engagement role of universities in the rural areas of developing countries, and its potential for strengthening the voice of rural communities. The particular focus is on the provision of primary and secondary education. The paper is based on the assumption that in order for community members to have both the capacity and the confidence to engage in political discourse for improving educational capacity and quality, they need the opportunity to become involved and well-versed in the options available, beyond their own experience. Particular attention is given in the paper to community-based research (CBR). CBR is explored from the perspectives of community members and local leaders in the government-community partnerships which have responsibility for the provision of primary and secondary education in rural Tanzania. The historical and policy background of the partnerships, together with findings from two case studies, provide the context for the paper

Fluid-solid phase transitions in 3D complex plasmas under microgravity conditions

Phase behavior of large three-dimensional complex plasma systems under microgravity conditions onboard the International Space Station is investigated. The neutral gas pressure is used as a control parameter to trigger phase changes. Detailed analysis of structural properties and evaluation of three different melting/freezing indicators reveal that complex plasmas can exhibit melting by increasing the gas pressure. Theoretical estimates of complex plasma parameters allow us to identify main factors responsible for the observed behavior. The location of phase states of the investigated systems on a relevant equilibrium phase diagram is estimated. Important differences between the melting process of 3D complex plasmas under microgravity conditions and that of flat 2D complex plasma crystals in ground based experiments are discussed.Comment: 13 pages, 10 figures; submitted to Phys. Rev.

Complete devil's staircase and crystal--superfluid transitions in a dipolar XXZ spin chain: A trapped ion quantum simulation

Systems with long-range interactions show a variety of intriguing properties: they typically accommodate many meta-stable states, they can give rise to spontaneous formation of supersolids, and they can lead to counterintuitive thermodynamic behavior. However, the increased complexity that comes with long-range interactions strongly hinders theoretical studies. This makes a quantum simulator for long-range models highly desirable. Here, we show that a chain of trapped ions can be used to quantum simulate a one-dimensional model of hard-core bosons with dipolar off-site interaction and tunneling, equivalent to a dipolar XXZ spin-1/2 chain. We explore the rich phase diagram of this model in detail, employing perturbative mean-field theory, exact diagonalization, and quasiexact numerical techniques (density-matrix renormalization group and infinite time evolving block decimation). We find that the complete devil's staircase -- an infinite sequence of crystal states existing at vanishing tunneling -- spreads to a succession of lobes similar to the Mott-lobes found in Bose--Hubbard models. Investigating the melting of these crystal states at increased tunneling, we do not find (contrary to similar two-dimensional models) clear indications of supersolid behavior in the region around the melting transition. However, we find that inside the insulating lobes there are quasi-long range (algebraic) correlations, opposed to models with nearest-neighbor tunneling which show exponential decay of correlations