Evolution of NMDA receptor cytoplasmic interaction domains: implications for organisation of synaptic signalling complexes

<p>Abstract</p> <p>Background</p> <p>Glutamate gated postsynaptic receptors in the central nervous system (CNS) are essential for environmentally stimulated behaviours including learning and memory in both invertebrates and vertebrates. Though their genetics, biochemistry, physiology, and role in behaviour have been intensely studied <it>in vitro </it>and <it>in vivo</it>, their molecular evolution and structural aspects remain poorly understood. To understand how these receptors have evolved different physiological requirements we have investigated the molecular evolution of glutamate gated receptors and ion channels, in particular the <it>N</it>-methyl-<it>D</it>-aspartate (NMDA) receptor, which is essential for higher cognitive function. Studies of rodent NMDA receptors show that the C-terminal intracellular domain forms a signalling complex with enzymes and scaffold proteins, which is important for neuronal and behavioural plasticity</p> <p>Results</p> <p>The vertebrate NMDA receptor was found to have subunits with C-terminal domains up to 500 amino acids longer than invertebrates. This extension was specific to the NR2 subunit and occurred before the duplication and subsequent divergence of NR2 in the vertebrate lineage. The shorter invertebrate C-terminus lacked vertebrate protein interaction motifs involved with forming a signaling complex although the terminal PDZ interaction domain was conserved. The vertebrate NR2 C-terminal domain was predicted to be intrinsically disordered but with a conserved secondary structure.</p> <p>Conclusion</p> <p>We highlight an evolutionary adaptation specific to vertebrate NMDA receptor NR2 subunits. Using <it>in silico </it>methods we find that evolution has shaped the NMDA receptor C-terminus into an unstructured but modular intracellular domain that parallels the expansion in complexity of an NMDA receptor signalling complex in the vertebrate lineage. We propose the NR2 C-terminus has evolved to be a natively unstructured yet flexible hub organising postsynaptic signalling. The evolution of the NR2 C-terminus and its associated signalling complex may contribute to species differences in behaviour and in particular cognitive function.</p

Molecular epidemiology of Streptococcus uberis clinical mastitis in dairy herds: strain heterogeneity and transmission

Multi Locus Sequence Typing was successfully completed on 494 isolates of S. uberis from clinical mastitis cases in a study of 52 commercial dairy herds over a 12 month period. In total, 195 sequence types (STs) were identified. S. uberis mastitis cases occurring in different cows within the same herd and attributed to a common ST were classified as 'potential transmission events' (PTE). Clinical cases attributed to 35 of the 195 STs identified in this study were classified PTE. PTE were identified in 63% of herds. PTE associated cases, which include the first recorded occurrence of that ST in that herd (Index case) and all persistent infections with that PTE ST represented 40% of all the clinical mastitis cases and occurred in 63% of herds. PTE associated cases accounted for over 50% of all S. uberis clinical mastitis cases in 33% of herds. Nine sequence types (ST 5, 6, 20, 22, 24, 35, 233, 361, and 512), eight of which grouped within a clonal complex (sharing at least four alleles), were statistically overrepresented (OVR STs). The findings indicate that 38% of all clinical mastitis cases and 63% of the potential transmission events attributed to S. uberis in dairy herds may be caused by the nine most prevalent strains. The findings suggest that to a small subset of sequence types are disproportionally important in the epidemiology of S. uberis mastitis in the UK with cow to cow transmission of S. uberis potentially occurring in the majority of UK herds and may be the most important route of infection in many herds

Multinational enterprises and structural transformation in emerging and developing countries: A survey of the literature

Economic and Social Research Council (ESRC) andEuropean Commissionfor financial support (no. ES/S001336/1 and 612889)

Complete genome sequences of seven Vibrio cholerae phages isolated in China

The complete genome sequences of seven closely related Vibrio cholerae phages isolated from environmental sites in southeastern China are reported here. Phages QH, CJY, H1, H2, H3, J2, and J3 are members of the Podoviridae family and are highly similar to the previously sequenced Vibrio phages VP2, VP5, and phiVC8

Second harmonic generation microscopy investigation of the crystalline ultrastructure of three barley starch lines affected by hydration

Second harmonic generation (SHG) microscopy is employed to study changes in crystalline organization due to altered gene expression and hydration in barley starch granules. SHG intensity and susceptibility ratio values (R’(SHG)) are obtained using reduced Stokes-Mueller polarimetric microscopy. The maximum R’(SHG) values occur at moderate moisture indicating the narrowest orientation distribution of nonlinear dipoles from the cylindrical axis of glucan helices. The maximum SHG intensity occurs at the highest moisture and amylopectin content. These results support the hypothesis that SHG is caused by ordered hydrogen and hydroxyl bond networks which increase with hydration of starch granules

Cultural Marketing in the Digital Age

Music theatres are challenged by digitization and the emergence of new media. New media enables people to stay outside the opera house while attending a live-opera, e. g. via livestreamed opera shows in the cinema. Moreover, opera houses are confronted with declining public funds and are increasingly forced to account for an efficient allocation of resources. Against this background, market orientation and branding are of growing relevance to opera houses. Based on Keller΄s (1993) brand image approach, we use an explorative qualitative study in order to investigate similarities and differences between the brand image of live-operas experienced in an opera house versus those shown in a cinema. As a result, we found that audiences distinguish between the respective brand images in detail. Furthermore, classic liveoperas of an opera house are perceived as an original, positive, holistic, and unique experience. Music theatres can use the results of this study in order to develop targeted brand management strategies

Collection of Athermal Phonons into Doped Germanium Thermistors Using Quasiparticle Trapping

We have developed a low‐temperature particle detector that uses a novel quasiparticle trapping mechanism to funnel athermal phonon energy from an 80 mg Ge absorber into a 1.6 mg doped Ge thermistor via a superconducting Al film. We report on pulse height spectra obtained at 320 mK by scanning a 241Am alpha source along the device, and show that up to 20% of the energy deposited in the Ge absorber by a 5.5 MeV alpha particle interaction can be collected into a thermistor via quasiparticle trapping. We show that this device is sensitive to the position of an alpha particle interaction in the Ge absorber for interaction distances of up to 5 mm from a quasiparticle trap