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UnlabelledLipid-enveloped viruses replicate and bud from the host cell where they acquire their lipid coat. Ebola virus, which buds from the plasma membrane of the host cell, causes viral hemorrhagic fever and has a high fatality rate. To date, little has been known about how budding and egress of Ebola virus are mediated at the plasma membrane. We have found that the lipid phosphatidylserine (PS) regulates the assembly of Ebola virus matrix protein VP40. VP40 binds PS-containing membranes with nanomolar affinity, and binding of PS regulates VP40 localization and oligomerization on the plasma membrane inner leaflet. Further, alteration of PS levels in mammalian cells inhibits assembly and egress of VP40. Notably, interactions of VP40 with the plasma membrane induced exposure of PS on the outer leaflet of the plasma membrane at sites of egress, whereas PS is typically found only on the inner leaflet. Taking the data together, we present a model accounting for the role of plasma membrane PS in assembly of Ebola virus-like particles.ImportanceThe lipid-enveloped Ebola virus causes severe infection with a high mortality rate and currently lacks FDA-approved therapeutics or vaccines. Ebola virus harbors just seven genes in its genome, and there is a critical requirement for acquisition of its lipid envelope from the plasma membrane of the human cell that it infects during the replication process. There is, however, a dearth of information available on the required contents of this envelope for egress and subsequent attachment and entry. Here we demonstrate that plasma membrane phosphatidylserine is critical for Ebola virus budding from the host cell plasma membrane. This report, to our knowledge, is the first to highlight the role of lipids in human cell membranes in the Ebola virus replication cycle and draws a clear link between selective binding and transport of a lipid across the membrane of the human cell and use of that lipid for subsequent viral entry.

Riluzole is a glutamatergic modulator of particular interest in autism spectrum disorder (ASD). In this 12-week randomized, double-blind, placebo-controlled, crossover pilot study we evaluated the safety and tolerability of 5-week of adjunctive riluzole treatment (vs. 5-week of placebo, with 2-week washout period) targeting ASD-associated drug-refractory irritability in eight individuals age 12-25 years. All participants tolerated riluzole 200 mg per day, however there were no statistically significant findings for the overall treatment effect, the treatment effect by week within period of the study, or a cross-over effect across the periods of the study on the Clinical Global Impression Improvement Scale or the Aberrant Behavior Checklist Irritability subscale. The results of this trial indicate that 5-week of riluzole treatment was well tolerated, but had no significant effect on the target symptoms. "Trial Registration" ClinicalTrials.gov Identifier NCT02081027, Registered 5 August 2013, First participant enrolled 19 September 2013.

The electoral district is the fundamental unit of representation in single- and multi-member electoral systems, yet most research shows little interest in district effects on election outcomes, focusing instead on national and individual factors. This is problematic as parties and candidates often put a great deal of effort into district-based campaigns. How, then, can we best capture district effects on party support? We propose a new method using official election returns and geospatial techniques. The result is a measure of how much of a party's vote share is explained by district effects. Using data from the 2006–2019 Canadian federal elections, we find that, on average, 6 to 10 per cent of the variation in a party's vote in Canada is explained by district effects. While district effects on party support are trivial for some districts, in others they account for more than 80 per cent of the variance in party vote shares. The effect of districts on party support is composed, in part, of electoral context, province, socio-economic factors and district campaign intensity. Importantly, the size and sources of district effects on party support vary across parties, suggesting heterogeneity. The benefits of our approach are threefold: (1) it is cost-effective, (2) it can be easily replicated in any setting—past or present—where districts are relevant electoral units and where districting is nonpartisan, and (3) it is responsive to differences in district composition and parties' campaign effort. [ABSTRACT FROM AUTHOR]

Aim: Numerous studies have shown that H2S serves as an acute oxygen sensor in a variety of cells. We hypothesize that H2S also serves in extended oxygen sensing. Methods: Here, we compare the effects of extended exposure (24‐48 hours) to varying O2 tensions on H2S and polysulphide metabolism in human embryonic kidney (HEK 293), human adenocarcinomic alveolar basal epithelial (A549), human colon cancer (HTC116), bovine pulmonary artery smooth muscle, human umbilical‐derived mesenchymal stromal (stem) cells and porcine tracheal epithelium (PTE) using sulphur‐specific fluorophores and fluorometry or confocal microscopy. Results: All cells continuously produced H2S in 21% O2 and H2S production was increased at lower O2 tensions. Decreasing O2 from 21% to 10%, 5% and 1% O2 progressively increased H2S production in HEK293 cells and this was partially inhibited by a combination of inhibitors of H2S biosynthesis, aminooxyacetate, propargyl glycine and compound 3. Mitochondria appeared to be the source of much of this increase in HEK 293 cells. H2S production in all other cells and PTE increased when O2 was lowered from 21% to 5% except for HTC116 cells where 1% O2 was necessary to increase H2S, presumably reflecting the hypoxic environment in vivo. Polysulphides (H2Sn, where n = 2‐7), the key signalling metabolite of H2S also appeared to increase in many cells although this was often masked by high endogenous polysulphide concentrations. Conclusion: These results show that cellular H2S is increased during extended hypoxia and they suggest this is a continuously active O2‐sensing mechanism in a variety of cells. [ABSTRACT FROM AUTHOR]

Diversity is at the core of any definition of Canada. But can different types of relationships among national symbols co-exist within the same national unit? And do these various symbolic assemblages have different effects on citizens' attitudes and behaviour? This paper uses survey data to uncover patterns in Canadians' attitudes towards 18 national symbols. The results indicate the existence of four distinct national symbolic 'webs'. The first two types are defined by conventional sociodemographic cleavage, while the difference between the two others is defined by the left-right ideological spectrum. In addition, further analysis shows that membership in these web-types is predictive of vote choice. [ABSTRACT FROM AUTHOR]

This paper studies the prevalence of ballot order effects in two different types of Canadian elections which differ greatly by the strength of party cues they provide to voters. Provincial elections are best described as a typical competition between well established and institutionalized parties, hence providing voters with strong party cues. Alternatively, municipal politics provide voters with much weaker party cues. We use electoral results from recent provincial and municipal elections in Québec and find ballot order effects in municipal elections but not in provincial ones. Although ballot order effects may also be the product of alphabetic preference bias, we argue that in any case these are cognitive biases that are ultimately the product of insufficient cues that voters need in order to cast well-informed votes. The paper, therefore, sheds some light on an understudied type of election in political science. [ABSTRACT FROM PUBLISHER]

We previously reported enhanced baseline lymphocytic ERK1/2 activation in ASD, and now we extend our work to investigate the early-phase kinetics of lymphocytic ERK1/2 activation in idiopathic ASD. The ASD group (mean = 5.81 minutes; SD = 1.5) had a significantly lower (more rapid) mean ERK1/2 T SB 1/2 sb activation value than both the DDC group (mean = 6.78 minutes; SD = 1.6; p = 0.00078) and TDC group (mean = 6.4 minutes; SD = 1.5; p = 0.025). Our findings indicate that lymphocytic ERK1/2 activation kinetics are dysregulated in persons with ASD, marked by more rapid early phase activation. [Extracted from the article]