19 research outputs found
Emissions and Energy Impacts of the Inflation Reduction Act
If goals set under the Paris Agreement are met, the world may hold warming
well below 2 C; however, parties are not on track to deliver these commitments,
increasing focus on policy implementation to close the gap between ambition and
action. Recently, the US government passed its most prominent piece of climate
legislation to date, the Inflation Reduction Act of 2022 (IRA), designed to
invest in a wide range of programs that, among other provisions, incentivize
clean energy and carbon management, encourage electrification and efficiency
measures, reduce methane emissions, promote domestic supply chains, and address
environmental justice concerns. IRA's scope and complexity make modeling
important to understand impacts on emissions and energy systems. We leverage
results from nine independent, state-of-the-art models to examine potential
implications of key IRA provisions, showing economy wide emissions reductions
between 43-48% below 2005 by 2035
Timing of host feeding drives rhythms in parasite replication
Circadian rhythms enable organisms to synchronise the processes underpinning survival and reproduction to anticipate daily changes in the external environment. Recent work shows that daily (circadian) rhythms also enable parasites to maximise fitness in the context of ecological interactions with their hosts. Because parasite rhythms matter for their fitness, understanding how they are regulated could lead to innovative ways to reduce the severity and spread of diseases. Here, we examine how host circadian rhythms influence rhythms in the asexual replication of malaria parasites. Asexual replication is responsible for the severity of malaria and fuels transmission of the disease, yet, how parasite rhythms are driven remains a mystery. We perturbed feeding rhythms of hosts by 12 hours (i.e. diurnal feeding in nocturnal mice) to desynchronise the hosts' peripheral oscillators from the central, light-entrained oscillator in the brain and their rhythmic outputs. We demonstrate that the rhythms of rodent malaria parasites in day-fed hosts become inverted relative to the rhythms of parasites in night-fed hosts. Our results reveal that the hosts' peripheral rhythms (associated with the timing of feeding and metabolism), but not rhythms driven by the central, light-entrained circadian oscillator in the brain, determine the timing (phase) of parasite rhythms. Further investigation reveals that parasite rhythms correlate closely with blood glucose rhythms. In addition, we show that parasite rhythms resynchronise to the altered host feeding rhythms when food availability is shifted, which is not mediated through rhythms in the host immune system. Our observations suggest that parasites actively control their developmental rhythms. Finally, counter to expectation, the severity of disease symptoms expressed by hosts was not affected by desynchronisation of their central and peripheral rhythms. Our study at the intersection of disease ecology and chronobiology opens up a new arena for studying host-parasite-vector coevolution and has broad implications for applied bioscience
Features of reactive cysteines discovered through computation:from kinase inhibition to enrichment around protein degrons.
Abstract Large-scale characterisation of cysteine modification is enabling study of the physicochemical determinants of reactivity. We find that location of cysteine at the amino terminus of an α-helix, associated with activity in thioredoxins, is under-represented in human protein structures, perhaps indicative of selection against background reactivity. An amino-terminal helix location underpins the covalent linkage for one class of kinase inhibitors. Cysteine targets for S-palmitoylation, S-glutathionylation, and S-nitrosylation show little correlation with pKa values predicted from structures, although flanking sequences of S-palmitoylated sites are enriched in positively-charged amino acids, which could facilitate palmitoyl group transfer to substrate cysteine. A surprisingly large fraction of modified sites, across the three modifications, would be buried in native protein structure. Furthermore, modified cysteines are (on average) closer to lysine ubiquitinations than are unmodified cysteines, indicating that cysteine redox biology could be associated with protein degradation and degron recognition
Risk factors for Lyme disease resulting from residential exposure amidst emerging Ixodes scapularis populations: A neighbourhood-level analysis of Ottawa, Ontario
Lyme disease is an emerging health threat in Canada due to the continued northward expansion of the main tick vector, Ixodes scapularis. It is of particular concern to populations living in expanding peri-urban areas where residential development and municipal climate change response impact neighbourhood structure and composition. The objective of this study was to estimate associations of socio-ecological characteristics with residential Lyme disease risk at the neighbourhood scale. We used Lyme disease case data for 2017â2020 reported for Ottawa, Ontario to determine where patientsâ residential property, or elsewhere within their neighbourhood, was the suspected site of tick exposure. Cases meeting this exposure definition (n = 118) were aggregated and linked to neighbourhood boundaries. We calculated landscape characteristics from composited and classified August 2018 PlanetScope satellite imagery. Negative binomial generalized linear models guided by a priori hypothesized relationships explored the association between hypothesized interactions of landscape structure and the outcome. Increases in median household income, the number of forest patches, the proportion of forested area, forest edge density, and mean forest patch size were associated with higher residential Lyme disease incidence at the neighbourhood scale, while increases in forest shape complexity and average distance to forest edge were associated with reduced incidence (P<0.001). Among Ottawa neighbourhoods, the combined effect of forest shape complexity and average forest patch size was associated with higher residential Lyme disease incidence (P<0.001). These findings suggest that Lyme disease risk in residential settings is associated with urban design elements. This is particularly relevant in urban centres where local ecological changes may impact the presence of emerging tick populations and how residents interact with tick habitat. Further research into the mechanistic underpinnings of these associations would be an asset to both urban development planning and public health management
Quartz crystal microbalance assay of clinical calcinosis samples and their synthetic models differentiates the efficacy of chelation-based treatments
This paper sets out in vitro protocols for studying the relative effectiveness of chelators used in the dissolution-based treatment of hard calcinosis. Pulverized hard calcinosis samples from human donors or synthetic hydroxyapatite nanoparticles were deposited by electrophoretic deposition on the surface of a quartz crystal microbalance sensor. Over 150 deposits of <20 ÎŒg were dissolved over the course of 1 h by aliquots of buffered, aqueous solutions of two calcium chelators, EDTA and citrate, with the surface-limited dissolution kinetics monitored with <1 s time resolution. There was no statistically significant difference in dissolution rate between the four synthetic hydroxyapatite materials in EDTA, but the dissolution rates in citrate were lower for hydroxyapatite produced by acetate or nitrate metathesis. Hard calcinosis and synthetic hydroxyapatites showed statistically identical dissolution behavior, meaning that readily available synthetic mimics can replace the rarer samples of biological origin in the development of calcinosis treatments. EDTA dissolved the hydroxyapatite deposits more than twice as fast as citrate at pH 7.4 and 37 °C, based on a first-order kinetic analysis of the initial frequency response. EDTA chelated 6.5 times more calcium than an equivalent number of moles of citrate. Negative controls using nonchelating N,N,NâČ,NâČ-tetraethylethylenediamine (TEEDA) showed no dissolution effect. Pharmaceutical dissolution testing of synthetic hydroxyapatite tablets over 6 h showed that EDTA dissolved the tablets four to nine times more quickly than citrate
Lockdown lessons: an international conversation on resilient GI science teaching
We report the findings from two global panel âconversationsâ that, stimulated by the exceptional coronavirus pandemic of 2020/21, explored the concept of resilience in geographic science teaching and learning. Characteristics of resilient teaching, both in general and with reference to GISc, are listed and shown to be essentially what might in the past have been called good teaching. Similarly, barriers to resilient teaching are explored and strategies for overcoming them listed. Perhaps the most important conclusion is a widespread desire not to âbounce backâ to pre-COVID ways, but to use the opportunity to âbounce forwardâ towards better teaching and learning practices.</p