Fast lidocaine block of cardiac and skeletal muscle sodium channels: one site with two routes of access

We have studied the block by lidocaine and its quaternary derivative, QX-314, of single, batrachotoxin (BTX)-activated cardiac and skeletal muscle sodium channels incorporated into planar lipid bilayers. Lidocaine and QX-314, applied to the intracellular side, appear to induce incompletely resolved, rapid transitions between the open and the blocked state of BTX-activated sodium channels from both heart and skeletal muscle. We used amplitude distribution analysis (Yellen, G. 1984. J. Gen. Physiol. 84:157–186.) to estimate the rate constants for block and unblock. Block by lidocaine and QX-314 from the cytoplasmic side exhibits rate constants with similar voltage dependence. The blocking rate increases with depolarization, and the unblocking rate increases with hyperpolarization. Fast lidocaine block was virtually identical for sodium channels from skeletal (rat, sheep) and cardiac (beef, sheep) muscle. Lidocaine block from the extracellular side occurred at similar concentrations. However, for externally applied lidocaine, the blocking rate was voltage-independent, and was proportional to concentration of the uncharged, rather than the charged, form of the drug. In contrast, unblocking rates for internally and externally applied lidocaine were identical in magnitude and voltage dependence. Our kinetic data suggest that lidocaine, coming from the acqueous phase on the cytoplasmic side in the charged form, associates and dissociates freely with the fast block effector site, whereas external lidocaine, in the uncharged form, approaches the same site via a direct, hydrophobic path

Genetic Assimilation and Canalisation in the Baldwin Effect

The Baldwin Effect indicates that individually learned behaviours acquired during an organism’s lifetime can influence the evolutionary path taken by a population, without any direct Lamarckian transfer of traits from phenotype to genotype. Several computational studies modelling this effect have included complications that restrict its applicability. Here we present a simplified model that is used to reveal the essential mechanisms and highlight several conceptual issues that have not been clearly defined in prior literature. In particular, we suggest that canalisation and genetic assimilation, often conflated in previous studies, are separate concepts and the former is actually not required for non-heritable phenotypic variation to guide genetic variation. Additionally, learning, often considered to be essential for the Baldwin Effect, can be replaced with a more general phenotypic plasticity model. These simplifications potentially permit the Baldwin Effect to operate in much more general circumstances

Phenotypic evaluation and genetic analysis of seedling emergence in a global collection of wheat genotypes (Triticum aestivum L.) under limited water availability

The challenge in establishing an early-sown wheat crop in southern Australia is the need for consistently high seedling emergence when sowing deep in subsoil moisture (>10 cm) or into dry top-soil (4 cm). However, the latter is strongly reliant on a minimum soil water availability to ensure successful seedling emergence. This study aimed to: (1) evaluate 233 Australian and selected international wheat genotypes for consistently high seedling emergence under limited soil water availability when sown in 4 cm of top-soil in field and glasshouse (GH) studies; (2) ascertain genetic loci associated with phenotypic variation using a genome-wide association study (GWAS); and (3) compare across loci for traits controlling coleoptile characteristics, germination, dormancy, and pre-harvest sprouting. Despite significant (P 85%) across nine environments. Moreover, 21 environment-specific quantitative trait loci (QTL) were detected in GWAS analysis on chromosomes 1B, 1D, 2B, 3A, 3B, 4A, 4B, 5B, 5D, and 7D, indicating complex genetic inheritance controlling seedling emergence. We aligned QTL for known traits and individual genes onto the reference genome of wheat and identified 16 QTL for seedling emergence in linkage disequilibrium with coleoptile length, width, and cross-sectional area, pre-harvest sprouting and dormancy, germination, seed longevity, and anthocyanin development. Therefore, it appears that seedling emergence is controlled by multifaceted networks of interrelated genes and traits regulated by different environmental cues

Phenotypic Evaluation and Genetic Analysis of Seedling Emergence in a Global Collection of Wheat Genotypes (Triticum aestivum L.) Under Limited Water Availability

The challenge in establishing an early-sown wheat crop in southern Australia is the need for consistently high seedling emergence when sowing deep in subsoil moisture (>10 cm) or into dry top-soil (4 cm). However, the latter is strongly reliant on a minimum soil water availability to ensure successful seedling emergence. This study aimed to: (1) evaluate 233 Australian and selected international wheat genotypes for consistently high seedling emergence under limited soil water availability when sown in 4 cm of top-soil in field and glasshouse (GH) studies; (2) ascertain genetic loci associated with phenotypic variation using a genome-wide association study (GWAS); and (3) compare across loci for traits controlling coleoptile characteristics, germination, dormancy, and pre-harvest sprouting. Despite significant (P 85%) across nine environments. Moreover, 21 environment-specific quantitative trait loci (QTL) were detected in GWAS analysis on chromosomes 1B, 1D, 2B, 3A, 3B, 4A, 4B, 5B, 5D, and 7D, indicating complex genetic inheritance controlling seedling emergence. We aligned QTL for known traits and individual genes onto the reference genome of wheat and identified 16 QTL for seedling emergence in linkage disequilibrium with coleoptile length, width, and cross-sectional area, pre-harvest sprouting and dormancy, germination, seed longevity, and anthocyanin development. Therefore, it appears that seedling emergence is controlled by multifaceted networks of interrelated genes and traits regulated by different environmental cues

Target value design: using collaboration and a lean approach to reduce construction cost

Target Costing is an effective management technique that has been used in manufacturing for decades to achieve cost predictability during new products development. Adoption of this technique promises benefits for the construction industry as it struggles to raise the number of successful outcomes and certainty of project delivery in terms of cost, quality and time. Target Value Design is a management approach that takes the best features of Target Costing and adapts them to the peculiarities of construction. In this paper the concept of Target Value Design is introduced based on the results of action research carried out on 12 construction projects in the USA. It has been shown that systemic application of Target Value Design leads to significant improvement of project performance – the final cost of projects was on average 15% less than market cost. The construction industry already has approaches that have similarities with elements of the Target Value Design process or uses the same terminology, e.g. Partnering and Target Cost Contracts, Cost planning, etc. Following an exploration of the similarities and differences Target Value Design is positioned as a form of Target Costing for construction that offers a more reliable route to successful projects outcomes

Theorising Disability: Beyond Common Sense

This article seeks to introduce the topic of disability to political theory via a discussion of some of the literature produced by disability theorists. The author argues that these more radical approaches conceptualise disability in ways that conflict with ‘common-sense’ notions of disability that tend to underpin political theoretical considerations of the topic. Furthermore, the author suggests that these more radical conceptualisations have profound implications for current debates on social justice, equality and citizenship that highlight the extent to which these notions are also currently underpinned by ‘common-sense’ notions of ‘normality’

Ice-rich (periglacial) vs icy (glacial) depressions in the Argyre region, Mars: a proposed cold-climate dichotomy of landforms

On Mars, so-called “scalloped depressions” are widely observed in Utopia Planitia (UP) and Malea Planum (MP). Typically, they are rimless, metres- to decametres-deep, incised sharply, tiered inwardly, polygonised and sometimes pitted. The depressions seemingly incise terrain that is icy and possibly thermokarstic, i.e. produced by the thermal destabilisation of the icy terrain. Agewise, the depressions are thought to be relatively youthful, originating in the Late Amazonian Epoch.Here, we report the presence of similar depressions in the Argyre region (AR) (30–60° S; 290–355° E). More importantly, we separate and differentiate these landforms into two groups: (ice-rich) periglacial depressions (Type-1); and, (icy) glacial depressions (Type-2a-c). This differentiation is presented to the Mars community for the first time.Based on a suite of morphological and geological characteristics synonymous with ice-complexes in the Lena Peninsula (eastern Russia) and the Tuktoyaktuk Coastlands (Northwest Territories, Canada), we propose that the Type-1 depressions are ice-rich periglacial basins that have undergone volatile depletion largely by sublimation and as the result of thermal destabilisation. In keeping with the terms and associated definitions derived of terrestrial periglacial-geomorphology, ice-rich refers to permanently frozen-ground in which ice lenses or segregation ice (collectively referenced as excess ice) have formed.We suggest that the depressions are the product of a multi-step, cold-climate geochronology:(1) Atmospheric precipitation and surface accumulation of an icy mantle during recent high obliquities.(2) Regional or local triple-point conditions and thaw/evaporation of the mantle, either by exogenic forcing, i.e. obliquity-driven rises of aerial and sub-aerial temperatures, or endogenic forcing, i.e. along Argyre impact-related basement structures.(3) Meltwater migration into the regolith, at least to the full depth of the depressions.(4) Freeze-thaw cycling and the formation of excess ice.(5) Sublimation of the excess ice and depression formation as high obliquity dissipates and near-surface ice becomes unstable.The Type-2 depressions exhibit characteristics suggestive of (supra-glacial) dead-ice basins and snow/ice suncups observed in high-alpine landscapes on Earth, e.g. the Swiss Alps and the Himalayas. Like the Type-1 depressions, the Type-2 depressions could be the work of sublimation; however, the latter differ from the former in that they seem to develop within a glacial-like icy mantle that blankets the surface rather than within an ice-rich and periglacially-revised regolith at/near the surface.Interestingly, the Type-2 depressions overlie the Type-1 depressions at some locations. If the periglacial/glacial morphological and stratigraphical dichotomy of depressions is valid, then this points to recent glaciation at some locations within the AR being precursed by at least one episode of periglaciation. This also suggests that periglaciation has a deeper history in the region than has been thought hitherto. Moreover, if the hypothesised differences amongst the Argyre-based depressions are mirrored in Utopia Planitia and Malea Planum, then perhaps this periglacial-glacial dichotomy and its associated geochronology are as relevant to understanding late period landscape-evolution in these two regions as it is in the AR

Clastic Polygonal Networks Around Lyot Crater, Mars: Possible Formation Mechanisms From Morphometric Analysis

Polygonal networks of patterned ground are a common feature in cold-climate environments. They can form through the thermal contraction of ice-cemented sediment (i.e. formed from fractures), or the freezing and thawing of ground ice (i.e. formed by patterns of clasts, or ground deformation). The characteristics of these landforms provide information about environmental conditions. Analogous polygonal forms have been observed on Mars leading to inferences about environmental conditions. We have identified clastic polygonal features located around Lyot crater, Mars (50°N, 30°E). These polygons are unusually large (> 100 m diameter) compared to terrestrial clastic polygons, and contain very large clasts, some of which are up to 15 metres in diameter. The polygons are distributed in a wide arc around the eastern side of Lyot crater, at a consistent distance from the crater rim. Using high-resolution imaging data, we digitised these features to extract morphological information. These data are compared to existing terrestrial and Martian polygon data to look for similarities and differences and to inform hypotheses concerning possible formation mechanisms. Our results show the clastic polygons do not have any morphometric features that indicate they are similar to terrestrial sorted, clastic polygons formed by freeze-thaw processes. They are too large, do not show the expected variation in form with slope, and have clasts that do not scale in size with polygon diameter. However, the clastic networks are similar in network morphology to thermal contraction cracks, and there is a potential direct Martian analogue in a sub-type of thermal contraction polygons located in Utopia Planitia. Based upon our observations, we reject the hypothesis that polygons located around Lyot formed as freeze-thaw polygons and instead an alternative mechanism is put forward: they result from the infilling of earlier thermal contraction cracks by wind-blown material, which then became compressed and/or cemented resulting in a resistant fill. Erosion then leads to preservation of these polygons in positive relief, while later weathering results in the fracturing of the fill material to form angular clasts. These results suggest that there was an extensive area of ice-rich terrain, the extent of which is linked to ejecta from Lyot crater

Model Analysis of Time Reversal Symmetry Test in the Caltech Fe-57 Gamma-Transition Experiment

The CALTECH gamma-transition experiment testing time reversal symmetry via the E2/M1 mulipole mixing ratio of the 122 keV gamma-line in Fe-57 has already been performed in 1977. Extending an earlier analysis in terms of an effective one-body potential, this experiment is now analyzed in terms of effective one boson exchange T-odd P-even nucleon nucleon potentials. Within the model space considered for the Fe-57 nucleus no contribution from isovector rho-type exchange is possible. The bound on the coupling strength phi_A from effective short range axial-vector type exchange induced by the experimental bound on sin(eta) leads to phi_A < 10^{-2}.Comment: 5 pages, RevTex 3.