Coupling the Cardiac Voltage-Gated Sodium Channel to Channelrhodopsin-2 Generates Novel Optical Switches for Action Potential Studies

Voltage-gated sodium (Na + ) channels respond to short membrane depolarization with conformational changes leading to pore opening, Na + influx, and action potential (AP) upstroke. In the present study, we coupled channelrhodopsin-2 (ChR2), the key ion channel in optogenetics, directly to the cardiac voltage-gated Na + channel (Na v 1.5). Fusion constructs were expressed in Xenopus laevis oocytes, and electrophysiological recordings were performed by the two-microelectrode technique. Heteromeric channels retained both typical Na v 1.5 kinetics and light-sensitive ChR2 properties. Switching to the current-clamp mode and applying short blue-light pulses resulted either in subthreshold depolarization or in a rapid change of membrane polarity typically seen in APs of excitable cells. To study the effect of individual K + channels on the AP shape, we co-expressed either K v 1.2 or hERG with one of the Na v 1.5-ChR2 fusions. As expected, both delayed rectifier K + channels shortened AP duration significantly. K v 1.2 currents remarkably accelerated initial repolarization, whereas hERG channel activity efficiently restored the resting membrane potential. Finally, we investigated the effect of the LQT3 deletion mutant ΔKPQ on the AP shape and noticed an extremely prolonged AP duration that was directly correlated to the size of the non-inactivating Na + current fraction. In conclusion, coupling of ChR2 to a voltage-gated Na + channel generates optical switches that are useful for studying the effect of individual ion channels on the AP shape. Moreover, our novel optogenetic approach provides the potential for an application in pharmacology and optogenetic tissue-engineering

Stroke Mimics on the Stroke Unit – Temporal trends 2008–2017 at a large Norwegian university hospital

Objectives: The objective was to quantify temporal trends in stroke mimics (SM) admissions relative to cerebrovascular accidents (CVA), incidence of hospitalized SMs and characterize the SM case-mix at a general hospital's stroke unit (SU). Materials & Methods: All SU admissions (n = 11240) of patients aged 15 or older to Haukeland University Hospital between 2008–2017 were prospectively included and categorized as CVA or SM. Logistic regression was used to estimate time trends in the proportion of SMs among the admissions. Poisson regression was used to estimate time trends in age- and sex-dependent SM incidence. Results: SMs were on average younger thaan CVA patients (68.3 vs. 71.4 years) and had a higher proportion of females (53.6% vs. 44.5%). The total proportion of SM admissions was 51.0%. There was an increasing time trend in the proportion of SM admissions, odds ratio 1.150 per year (p < 0.001), but this trend appears flattening, represented by a significant quadratic time-term, odds ratio 1.009 (p < 0.001). A higher SM proportion was also associated with the time period of a Mass Media Intervention (FAST campaign) in 2014. There was also an increasing trend in SM incidence, that remains after adjusting for age, sex, and population; also, for incidence the trend appears to be flattening. Conclusions: SMs account for approximately half of the SU admissions, and the proportion has been increasing. A FAST campaign appears to have temporarily increased the SM proportion. The age- and sex-dependent incidence of SM has been increasing but appears to flatten out.publishedVersio

Low atmospheric CO2 levels before the rise of forested ecosystems

The emergence of forests on Earth (~385 million years ago, Ma)1 has been linked to an order-of-magnitude decline in atmospheric CO2 levels and global climatic cooling by altering continental weathering processes, but observational constraints on atmospheric CO2 before the rise of forests carry large, often unbound, uncertainties. Here, we calibrate a mechanistic model for gas exchange in modern lycophytes and constrain atmospheric CO2 levels 410–380 Ma from related fossilized plants with bound uncertainties of approximately ±100 ppm (1 sd). We find that the atmosphere contained ~525–715 ppm CO2 before continents were afforested, and that Earth was partially glaciated according to a palaeoclimate model. A process-driven biogeochemical model (COPSE) shows the appearance of trees with deep roots did not dramatically enhance atmospheric CO2 removal. Rather, shallow-rooted vascular ecosystems could have simultaneously caused abrupt atmospheric oxygenation and climatic cooling long before the rise of forests, although earlier CO2 levels are still unknown

Modeling gravimetric signatures of third-degree ocean tides and their detection in superconducting gravimeter records

We employ the barotropic, data-unconstrained ocean tide model TiME to derive an atlas for degree-3 tidal constituentsincluding monthly to terdiurnal tidal species. The model is optimized with respect to the tide gauge data set TICON-td that isextended to include the respective tidal constituents of diurnal and higher frequencies. The tide gauge validation shows a rootmean-square (RMS) deviation of 0.9–1.3mm for the individual species. We further model the load tide-induced gravimetric signals by two means (1) a global load Love number approach and (2) evaluating Greens-integrals at 16 selected locations of superconducting gravimeters. The RMS deviation between the amplitudes derived using both methods is below 0.5 nGal (1 nGal = 0.01 nm/s2 ) when excluding near-coastal gravimeters. Utilizing ETERNA-x, a recently upgraded and reworked tidal analysis software, we additionally derive degree-3 gravimetric tidal constituents for these stations, based on a hypothesis-free wave grouping approach.We demonstrate that this analysis is feasible, yielding amplitude predictions of only a few 10 nGal, and that it agrees with the modeled constituents on a level of 63–80% of the mean signal amplitude. Larger deviations are only found for lowest amplitude signals, near-coastal stations, or shorter and noisier data sets

Does compulsory voting increase support for leftist policy?

Citizens unequally participate in referendums, and this may systematically bias policy in favor of those who vote. Some view compulsory voting as an important tool to alleviate this problem, whereas others worry about its detrimental effects on the legitimacy and quality of democratic decision making. So far, however, we lack systematic knowledge about the causal effect of compulsory voting on public policy. We argue that sanctioned compulsory voting mobilizes citizens at the bottom of the income distribution and that this translates into an increase in support for leftist policies. We empirically explore the effects of a sanctioned compulsory voting law on direct-democratic decision making in Switzerland. We find that compulsory voting significantly increases electoral support for leftist policy positions in referendums by up to 20 percentage points. We discuss the implications of these results for our understanding of the policy consequences of electoral institutions

Topotactic Growth of Edge-Terminated MoS₂ from MoO₂Nanocrystals

Layered transition metal dichalcogenides have distinct physicochemical properties at their edge-terminations. The production of an abundant density of edge structures is, however, impeded by the excess surface energy of edges compared to basal planes and would benefit from insight into the atomic growth mechanisms. Here, we show that edge-terminated MoS₂ nanostructures can form during sulfidation of MoO₂ nanocrystals by using <i>in situ</i> transmission electron microscopy (TEM). Time-resolved TEM image series reveal that the MoO₂ surface can sulfide by inward progression of MoO₂(202̅):MoS₂(002) interfaces, resulting in upright-oriented and edge-exposing MoS₂ sheets. This topotactic growth is rationalized in the interplay with density functional theory calculations by successive O–S exchange and Mo sublattice restructuring steps. The analysis shows that formation of edge-terminated MoS₂ is energetically favorable at MoO₂(110) surfaces and provides a necessary requirement for the propensity of a specific MoO₂ surface termination to form edge-terminated MoS₂. Thus, the present findings should benefit the rational development of transition metal dichalcogenide nanomaterials with abundant edge terminations

Low atmospheric CO2 levels before the rise of forested ecosystems

The emergence of forests on Earth (~385 million years ago, Ma)1 has been linked to an order-of-magnitude decline in atmospheric CO2 levels and global climatic cooling by altering continental weathering processes, but observational constraints on atmospheric CO2 before the rise of forests carry large, often unbound, uncertainties. Here, we calibrate a mechanistic model for gas exchange in modern lycophytes and constrain atmospheric CO2 levels 410–380 Ma from related fossilized plants with bound uncertainties of approximately ±100 ppm (1 sd). We find that the atmosphere contained ~525–715 ppm CO2 before continents were afforested, and that Earth was partially glaciated according to a palaeoclimate model. A process-driven biogeochemical model (COPSE) shows the appearance of trees with deep roots did not dramatically enhance atmospheric CO2 removal. Rather, shallow-rooted vascular ecosystems could have simultaneously caused abrupt atmospheric oxygenation and climatic cooling long before the rise of forests, although earlier CO2 levels are still unknown

The collapse of intermediate structures?

How can we explain the rise of President Trump and the attraction of his campaign behavior before and since he took office? We argue here that the collapse of ‘intermediate structures’ has been a key factor; that the associations and groups which are building blocks of pluralistic politics have been eroded to such an extent that Trump’s personality politics have been able to take over the political stage

Impact on health when sugar is replaced with intense sweeteners in soft drinks, ‘saft’ and nectar. Opinion of Vitenskapskomiteen for mattrygghet Norwegian Scientific Commitee for Food Safety

publishedVersio