The ducky^{2J} Mutation in Cacna2d2 Results in Reduced Spontaneous Purkinje Cell Activity and Altered Gene Expression

The mouse mutant ducky and its allele ducky^{2J} represent a model for absence epilepsy characterized by spike-wave seizures and cerebellar ataxia. These mice have mutations in Cacna2d2, which encodes the α₂δ-2 calcium channel subunit. Of relevance to the ataxic phenotype, α₂δ-2 mRNA is strongly expressed in cerebellar Purkinje cells (PCs). The Cacna2d2du2J mutation results in a 2 bp deletion in the coding region and a complete loss of α₂δ-2 protein. Here we show that du^{2J}/du^{2J} mice have a 30% reduction in somatic calcium current and a marked fall in the spontaneous PC firing rate at 22°C, accompanied by a decrease in firing regularity, which is not affected by blocking synaptic input to PCs. At 34°C, du^{2J}/du^{2J} PCs show no spontaneous intrinsic activity. DU^{2J}/du^{2J} mice also have alterations in the cerebellar expression of several genes related to PC function. At postnatal day 21, there is an elevation of tyrosine hydroxylase mRNA and a reduction in tenascin-C gene expression. Although du^{2J}/+ mice have a marked reduction in α₂δ-2 protein, they show no fall in PC somatic calcium currents or increase in cerebellar tryrosine hydroxylase gene expression. However, du^{2J}/+ PCs do exhibit a significant reduction in firing rate, correlating with the reduction in α₂δ-2. A hypothesis for future study is that effects on gene expression occur as a result of a reduction in somatic calcium currents, whereas effects on PC firing occur as a long-term result of loss of α₂δ-2 and/or a reduction in calcium currents and calcium-dependent processes in regions other than the soma

The contribution of the posterolateral capsule to elbow joint stability: a cadaveric biomechanical investigation.

BACKGROUND: Elbow posterolateral rotatory instability occurs after an injury to the lateral collateral ligament complex (LCLC) in isolation or in association with an osteochondral fracture of the posterolateral margin of the capitellum (Osborne-Cotterill lesion [OCL]). The contribution to elbow stability of the posterolateral capsule, attached to this lesion, is unknown. This study quantified the displacement of the radial head on simulated posterior draw with sectioning of the posterior capsule (a simulated OCL) or LCLC. METHODS: Biomechanical testing of the elbow was performed in 8 upper limb cadavers. With the elbow 0°, 30°, 60°, and 90° degrees of flexion, posterior displacement of the radius was measured at increments of a load of 5 N up to 50 N. A simulated OCL and LCLC injury was then performed. RESULTS: A simulated OCL results in significantly more displacement of the radial head compared with the intact elbow at 30° to 60° of elbow flexion. LCLC resection confers significantly more displacement. An OCL after LCLC resection does not create further displacement. CONCLUSIONS: The degree of radial head displacement is greater after a simulated OCL at 30° to 60° of flexion compared with the intact elbow with the same load but not as great as seen with sectioning of the LCLC. This study suggests that the posterior capsule attaching to the back of the capitellum is important to elbow stability and should be identified as the Osborne-Cotterill ligament. Clinical studies are required to determine the importance of these biomechanical findings

The rise of the quasi-public space and its consequences for cities and culture

This article argues that whilst appearing new, quasi-public spaces have emerged from a process of investment restructuring over the last 50 years. The profound change that is set in motion is a loss of control of public space and its cultural uses in cities. The tensions set up in this transformation are illustrated by the cultural fortunes of the largest such space in London, Granary Square; and, that of the City of London that has little, if any, public space

Redox linked flavin sites in extracellular decaheme proteins involved in microbe-mineral electron transfer

Extracellular microbe-mineral electron transfer is a major driving force for the oxidation of organic carbon in many subsurface environments. Extracellular multi-heme cytochromes of the Shewenella genus play a major role in this process but the mechanism of electron exchange at the interface between cytochrome and acceptor is widely debated. The 1.8 Å x-ray crystal structure of the decaheme MtrC revealed a highly conserved CX8C disulfide that, when substituted for AX8A, severely compromised the ability of S. oneidensis to grow under aerobic conditions. Reductive cleavage of the disulfide in the presence of flavin mononucleotide (FMN) resulted in the reversible formation of a stable flavocytochrome. Similar results were also observed with other decaheme cytochromes, OmcA, MtrF and UndA. The data suggest that these decaheme cytochromes can transition between highly reactive flavocytochromes or less reactive cytochromes, and that this transition is controlled by a redox active disulfide that responds to the presence of oxygen

A comparative map viewer integrating genetic maps for Brassica and Arabidopsis

Background: Molecular genetic maps provide a means to link heritable traits with underlying genome sequence variation. Several genetic maps have been constructed for Brassica species, yet to date, there has been no simple means to compare this information or to associate mapped traits with the genome sequence of the related model plant, Arabidopsis. Description: We have developed a comparative genetic map database for the viewing, comparison and analysis of Brassica and Arabidopsis genetic, physical and trait map information. This web- based tool allows users to view and compare genetic and physical maps, search for traits and markers, and compare genetic linkage groups within and between the amphidiploid and diploid Brassica genomes. The inclusion of Arabidopsis data enables comparison between Brassica maps that share no common markers. Analysis of conserved syntenic blocks between Arabidopsis and collated Brassica genetic maps validates the application of this system. This tool is freely available over the internet on http://bioinformatics.pbcbasc.latrobe.edu.au/cmap. Conclusion: This database enables users to interrogate the relationship between Brassica genetic maps and the sequenced genome of A. thaliana, permitting the comparison of genetic linkage groups and mapped traits and the rapid identification of candidate genes

Utility of salt-marsh foraminifera, testate amoebae and bulk-sediment δ13C values as sea-level indicators in Newfoundland, Canada

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.We investigated the utility of foraminifera, testate amoebae and bulk-sediment δ 13 C measurements for reconstructing Holocene relative sea level from sequences of salt-marsh sediment in Newfoundland, Canada. Modern, surface sediment was collected along transects from low to supra-tidal elevations in eastern (at Placentia) and western (at Hynes Brook and Big River) Newfoundland. Consistent with previous work, low-diversity assemblages of foraminifera display an almost binary division into a higher salt-marsh assemblage dominated by Jadammina macrescens and Balticammina pseudomacrescens and a lower salt-marsh assemblage comprised of Miliammina fusca. This pattern and composition resembles those identified at other high latitude sites with cool climates and confirms that foraminifera are sea-level indicators. The lowest occurrence of testate amoebae was at approximately mean higher high water. The composition of high salt-marsh testate amoebae assemblages (Centropyxis cassis type, Trinema spp., Tracheleuglypha dentata type, and Euglypha spp.) in Newfoundland was similar to elsewhere in the North Atlantic, but preservation bias favors removal of species with idiosomic tests over those with xenosomic tests. The mixed high salt-marsh plant community in Newfoundland results in bulk surface-sediment δ 13 C values that are typical of C 3 plants, making them indistinguishable from freshwater sediment. Therefore we propose that the utility of this proxy for reconstructing RSL in eastern North America is restricted to the coastline between Chesapeake Bay and southern Nova Scotia. Using a simple, multi-proxy approach to establish that samples in three radiocarbon-dated sediment cores formed between the lowest occurrence of testate amoebae and the highest occurrence of foraminifera, we generated three example late Holocene sea-level index points at Hynes Brook.This work was supported by NSF awards OCE-1458921, OCE-1458904 and EAR-1402017 and the Robert L. Nichols student research fund of the Department of Earth and Ocean Sciences at Tufts University. Foraminiferal data from Hynes Brook and Big River were collected as part of a series of projects including “Ocean-climate variability and sea level in the North Atlantic region since AD 0” funded by the Dutch National Research Programme (NRP) on Global air pollution and Climate Change; “Coastal Records” funded by the Vrije Universiteit Amsterdam and “Simulations, Observations & Palaeoclimatic data: climate variability over the last 500 years” funded by the European Union

Peristaltic flow and hydrodynamic dispersion of a reactive micropolar fluid-simulation of chemical effects in the digestive process

The hydrodynamic dispersion of a solute in peristaltic flow of a reactive incompressible micropolar biofluid is studied as a model of chyme transport in the human intestinal system with wall effects. The long wavelength approximation, Taylor's limiting condition and dynamic boundary conditions at the flexible walls are used to obtain the average effective dispersion coefficient in the presence of combined homogeneous and heterogeneous chemical reactions. The effects of various pertinent parameters on the effective dispersion coefficient are discussed. It is observed that average effective dispersion coefficient increases with amplitude ratio which implies that dispersion is enhanced in the presence of peristalsis. Furthermore average effective dispersion coefficient is also elevated with the micropolar rheological and wall parameters. Conversely dispersion is found to decrease with cross viscosity coefficient, homogeneous and heterogeneous chemical reaction rates. The present simulations provide an important benchmark for future chemo-fluid-structure interaction computational models