Diffusive spatio-temporal noise in a first-passage time model for intracellular calcium release

The intracellular release of calcium from the endoplasmic reticulum is controlled by ion channels. The resulting calcium signals exhibit a rich spatio-temporal signature, which originates at least partly from microscopic fluctuations. While stochasticity in the gating transition of ion channels has been incorporated into many models, the distribution of calcium is usually described by deterministic reaction-diffusion equations. Here we test the validity of the latter modeling approach by using two different models to calculate the frequency of localized calcium signals (calcium puffs) from clustered IP3 receptor channels. The complexity of the full calcium system is here limited to the basic opening mechanism of the ion channels and, in the mathematical reduction simplifies to the calculation of a first passage time. Two models are then studied: (i) a hybrid model, where channel gating is treated stochastically, while calcium concentration is deterministic and (ii) a fully stochastic model with noisy channel gating and Brownian calcium ion motion. The second model utilises the recently developed two-regime method [M. B. Flegg, S. J. Chapman, and R. Erban, “The two-regime method for optimizing stochastic reaction-diffusion simulations,” J. R. Soc., Interface9, 859–868 (Year: 2012)]10.1098/rsif.2011.0574 in order to simulate a large domain with precision required only near the Ca2+ absorbing channels. The expected time for a first channel opening that results in a calcium puff event is calculated. It is found that for a large diffusion constant, predictions of the interpuff time are significantly overestimated using the model (i) with a deterministic non-spatial calcium variable. It is thus demonstrated that the presence of diffusive noise in local concentrations of intracellular Ca2+ ions can substantially influence the occurrence of calcium signals. The presented approach and results may also be relevant for other cell-physiological first-passage time problems with small ligand concentration and high cooperativity

BILIPROTEINS FROM THE BUTTERFLY Pieris brassicae STUDIED BY TIME-RESOLVED FLUORESCENCE AND COHERENT ANTI-STOKES RAMAN SPECTROSCOPY

The fluorescence decay time of the biliverdin IX7 chromophore present in biliproteins isolated from Pieris brassicae is determined to be 44 ± 3 ps. This value suggests a cyclic helical chromophore structure. The vibrational frequencies determined by CARS-spectroscopy are compared with those of model compounds. The data confirm that the chromophore in the protein-bound state adopts a cyclic-helical, flexible conformation

The derivation of the formyl-group oxygen of chlorophyll b in higher plants from molecular oxygen.

The mechanism of formation of the formyl group of chlorophyll b has long been obscure but, in this paper, the origin of the 7-formyl-group oxygen of chlorophyll b in higher plants was determined by greening etiolated maize leaves, excised from dark-grown plants, by illumination under white light in the presence of either H218O or 18O2 and examining the newly synthesized chlorophylls by mass spectroscopy. To minimize the possible loss of 18O label from the 7-formyl substituent by reversible formation of chlorophyll b-71-gem-diol (hydrate) with unlabelled water in the cell, the formyl group was reduced to a hydroxymethyl group during extraction with methanol containing NaBH4: chlorophyll a remained unchanged during this rapid reductive extraction process. Mass spectra of chlorophyll a and [7-hydroxymethyl]-chlorophyll b extracted from leaves greened in the presence of either H218O or 18O2 revealed that 18O was incorporated only from molecular oxygen but into both chlorophylls: the mass spectra were consistent with molecular oxygen providing an oxygen atom not only for incorporation into the 7-formyl group of chlorophyll b but also for the well-documented incorporation into the 131-oxo group of both chlorophylls a and b [see Walker, C. J., Mansfield, K. E., Smith, K. M. & Castelfranco, P. A. (1989) Biochem. J. 257, 599–602]. The incorporation of isotope led to as much as 77% enrichment of the 131-oxo group of chlorophyll a: assuming identical incorporation into the 131 oxygen of chlorophyll b, then enrichment of the 7-formyl oxygen was as much as 93%. Isotope dilution by re-incorporation of photosynthetically produced oxygen from unlabelled water was negligible as shown by a greening experiment in the presence of 3-(3,4-dichlorophenyl)-1,1-dimethylurea. The high enrichment using 18O2, and the absence of labelling by H218O, unequivocally demonstrates that molecular oxygen is the sole precursor of the 7-formyl oxygen of chlorophyll b in higher plants and strongly suggests a single pathway for the formation of the chlorophyll b formyl group involving the participation of an oxygenase-type enzyme

Resistance of a domain wall in the quasiclassical approach

Starting from a simple microscopic model, we have derived a kinetic equation for the matrix distribution function. We employed this equation to calculate the conductance $G$ in a mesoscopic F'/F/F' structure with a domain wall (DW). In the limit of a small exchange energy $J$ and an abrupt DW, the conductance of the structure is equal to $G_{2d}=4\sigma_{\uparrow}\sigma_{\downarrow }/(\sigma_{\uparrow}+\sigma_{\downarrow})L$. Assuming that the scattering times for electrons with up and down spins are close to each other we show that the account for a finite width of the DW leads to an increase in this conductance. We have also calculated the spatial distribution of the electric field in the F wire. In the opposite limit of large $J$ (adiabatic variation of the magnetization in the DW) the conductance coincides in the main approximation with the conductance of a single domain structure $G_{1d}=(\sigma_{\uparrow}+\sigma_{\downarrow})/L$. The account for rotation of the magnetization in the DW leads to a negative correction to this conductance. Our results differ from the results in papers published earlier.Comment: 11 pages; replaced with revised versio

Infrared spectroscopy of phytochrome and model pigments

Fourier-transform infrared difference spectra between the red-absorbing and far-red-absorbing forms of oat phytochrome have been measured in H2O and 2H2O. The difference spectra are compared with infrared spectra of model compounds, i.e. the (5Z,10Z,15Z)- and (5Z,10Z,15E)-isomers of 2,3,7,8,12,13,17,18-octaethyl-bilindion (Et8-bilindion), 2,3-dihydro-2,3,7,8,12,13,17,18-octaethyl-bilindion (H2Et8-bilindion), and protonated H2Et8-bilindion in various solvents. The spectra of the model compounds show that only for the protonated forms can clear differences between the two isomers be detected. Since considerable differences are present between the spectra of Et8-bilindion and H2Et8-bilindion, it is concluded that only the latter compound can serve as a model system of phytochrome. The 2H2O effect on the difference spectrum of phytochrome supports the view that the chromophore in red-absorbing phytochrome is protonated and suggests, in addition, that it is also protonated in far-red-absorbing phytochrome. The spectra show that protonated carboxyl groups are influenced. The small amplitudes in the difference spectra exclude major changes of protein secondary structure

Preoperative and perioperative use of levosimendan in cardiac surgery: European expert opinion

In cardiac surgery, postoperative low cardiac output has been shown to correlate with increased rates of organ failure and mortality. Catecholamines have been the standard therapy for many years, although they carry substantial risk for adverse cardiac and systemic effects, and have been reported to be associated with increased mortality. On the other hand, the calcium sensitiser and potassium channel opener levosimendan has been shown to improve cardiac function with no imbalance in oxygen consumption, and to have protective effects in other organs. Numerous clinical trials have indicated favourable cardiac and non-cardiac effects of preoperative and perioperative administration of levosimendan. A panel of 27 experts from 18 countries has now reviewed the literature on the use of levosimendan in on-pump and off-pump coronary artery bypass grafting and in heart valve surgery. This panel discussed the published evidence in these various settings, and agreed to vote on a set of questions related to the cardioprotective effects of levosimendan when administered preoperatively, with the purpose of reaching a consensus on which patients could benefit from the preoperative use of levosimendan and in which kind of procedures, and at which doses and timing should levosimendan be administered. Here, we present a systematic review of the literature to report on the completed and ongoing studies on levosimendan, including the newly commenced LEVO-CTS phase III study (NCT02025621), and on the consensus reached on the recommendations proposed for the use of preoperative levosimendan

Negative Domain Wall Resistance in Ferromagnets

The electrical resistance of a diffusive ferromagnet with magnetic domain walls is studied theoretically, taking into account the spatial dependence of the magnetization. The semiclassical domain wall resistance is found to be either negative or positive depending on the difference between the spin-dependent scattering life-times. The predictions can be tested experimentally by transport studies in doped ferromagnets.Comment: 4 pages, 2 figures, accepted Phys. Rev. Let

The case for a distributed solar dynamo shaped by near-surface shear

Arguments for and against the widely accepted picture of a solar dynamo being seated in the tachocline are reviewed and alternative ideas concerning dynamos operating in the bulk of the convection zone, or perhaps even in the near-surface shear layer, are discussed. Based on the angular velocities of magnetic tracers it is argued that the observations are compatible with a distributed dynamo that may be strongly shaped by the near-surface shear layer. Direct simulations of dynamo action in a slab with turbulence and shear are presented to discuss filling factor and tilt angles of bipolar regions in such a model.Comment: 10 pages, 6 figures, Astrophys. J. 625 (scheduled for the 1 June 2005 issue

Implications For The Origin Of GRB 051103 From LIGO Observations

We present the results of a LIGO search for gravitational waves (GWs) associated with GRB 051103, a short-duration hard-spectrum gamma-ray burst (GRB) whose electromagnetically determined sky position is coincident with the spiral galaxy M81, which is 3.6 Mpc from Earth. Possible progenitors for short-hard GRBs include compact object mergers and soft gamma repeater (SGR) giant flares. A merger progenitor would produce a characteristic GW signal that should be detectable at the distance of M81, while GW emission from an SGR is not expected to be detectable at that distance. We found no evidence of a GW signal associated with GRB 051103. Assuming weakly beamed gamma-ray emission with a jet semi-angle of 30 deg we exclude a binary neutron star merger in M81 as the progenitor with a confidence of 98%. Neutron star-black hole mergers are excluded with > 99% confidence. If the event occurred in M81 our findings support the the hypothesis that GRB 051103 was due to an SGR giant flare, making it the most distant extragalactic magnetar observed to date.Comment: 8 pages, 3 figures. For a repository of data used in the publication, go to: https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=15166 . Also see the announcement for this paper on ligo.org at: http://www.ligo.org/science/Publication-GRB051103/index.ph

Interrogating the language of integration: the case of internationally recruited nurses

AIMS: This paper suggested the need to interrogate the notion of 'integration' to facilitate the retention of migrant nurses. BACKGROUND: The growth in internationally recruited nurses in the UK's health system has led to a raft of policies that aim to ensure that such nurses are well 'integrated' into their 'new environment'. It is assumed that integration will improve the quality of internationally recruited nurses' experience in the UK, improve their retention rates and thus improve the quality of health delivery within the UK. However, most of the steps through which integration is sought tend to move between some version of assimilation and 'respect for difference'. CONTRIBUTIONS: This paper aimed to add to existing literature on the integration of internationally recruited nurses in the UK by suggesting three steps towards rethinking 'integration policies'. It suggests the need to recognize migration as only one of the differentiating factors within the nursing sector, to ensure that integration does actually become a two-way process and to be cognizant of the multiple shapes that racism can take. The first two steps will prevent a slip between integration and assimilation while the last will help rethink any anti-racist training that may form part of integration policies. CONCLUSIONS: There are many factors influencing the experiences of internationally recruited nurses and not all of them can be addressed within current integration policies. RELEVANCE TO CLINICAL PRACTICE: Rethinking integration can help improve the experience of internationally recruited nurses