The effects of age and ganglioside composition on the rate of motor nerve terminal regeneration following antibody-mediated injury in mice

Gangliosides are glycosphingolipids highly enriched in neural plasma membranes, where they mediate a diverse range of functions and can act as targets for auto-antibodies present in human immune-mediated neuropathy sera. The ensuing autoimmune injury results in axonal and motor nerve terminal (mNT) degeneration. Both aging and ganglioside-deficiency have been linked to impaired axonal regeneration. To assess the effects of age and ganglioside expression on mNT regeneration in an autoimmune injury paradigm, anti-ganglioside antibodies and complement were applied to young adult and aged mice wildtype (WT) mice, mice deficient in either b- and c-series (GD3sKO) or mice deficient in all complex gangliosides (GM2sKO). The extent of mNT injury and regeneration was assessed immediately or after 5 days, respectively. Depending on ganglioside expression and antibody-specificity, either a selective mNT injury or a combined injury of mNTs and neuromuscular glial cells was elicited. Immediately after induction of the injury, between 1.5% and 11.8% of neuromuscular junctions (NMJs) in the young adult groups exhibited healthy mNTs. Five days later, most NMJs, regardless of age and strain, had recovered their mNTs. No significant differences could be observed between young and aged WT and GM2sKO mice; aged GD3sKO showed a mildly impaired rate of mNT regeneration when compared with their younger counterparts. Comparable rates were observed between all strains in the young and the aged mice. In summary, the rate of mNT regeneration following anti-ganglioside antibody and complement-mediated injury does not differ majorly between young adult and aged mice irrespective of the expression of particular gangliosides

Vibrational Spectroscopy as a Tool for Studying Drug-Cell Interaction: Could High Throughput Vibrational Spectroscopic Screening Improve Drug Development

Vibrational spectroscopy is currently widely explored as a tool in biomedical applications. An area at the forefront of this field is the use of vibrational spectroscopy for disease diagnosis, ultimately aiming towards spectral pathology. However, while this field shows promising results, moving this technique into the clinic faces the challenges of widespread clinical trials and legislative approval. While spectral pathology has received a lot of attention, there are many other biomedical applications of vibrational spectroscopy, which could potentially be translated to applications with greater ease. A particularly promising application is the use of vibrational spectroscopic techniques to study the interaction of drugs with cells. Many studies have demonstrated the ability to detect biochemical changes in cells in response to drug application, using both infrared and Raman spectroscopy. This has shown potential for use in high throughput screening (HTS) applications, for screening of efficacy and mode of action of potential drug candidates, to speed up the drug discovery process. HTS is still a relatively new and growing area of research and, therefore, there is more potential for new techniques to move into and shape this field. Vibrational spectroscopic techniques come with many benefits over the techniques used currently in HTS, primarily based on fluorescence assays to detect specific binding interactions or phenotypes. They are label free, and an infrared or Raman spectrum provides a wealth of biochemical information, and therefore could reveal not only information about a specific interaction, but about how the overall biochemistry of a cell changes in response to application of a drug candidate. Therefore, drug mode of action could be elucidated. This review will investigate the potential for vibrational spectroscopy, particularly FTIR and Raman spectroscopy, to benefit the field of HTS and improve the drug development process. In addition to FTIR and Raman spectroscopy, surface enhanced Raman spectroscopy (SERS), coherent anti-Stokes Raman spectroscopy (CARS) and stimulated Raman spectroscopy (SRS), will be investigated as an alternative tool in the HTS process

Scalar Quantum Field Theory with Cubic Interaction

In this paper it is shown that an i phi^3 field theory is a physically acceptable field theory model (the spectrum is positive and the theory is unitary). The demonstration rests on the perturbative construction of a linear operator C, which is needed to define the Hilbert space inner product. The C operator is a new, time-independent observable in PT-symmetric quantum field theory.Comment: Corrected expressions in equations (20) and (21

Local political leadership and the modernisation of local government

Political leadership has been a key element of central government’s attempts to ‘modernise’ local government over the past decade, within a discourse that emphasised ‘strong’ and ‘visible’ leadership and the role of leaders and leadership in driving change within local authorities. In the context of such an approach, and also taking account of academic discourse, this article draws upon interviews with nearly thirty individuals in leadership positions in local authorities in England, Scotland and Wales to assess their experiences of leadership and their views of some aspects of the role and work of councils. It suggests that whilst there is broad convergence between the aspirations of government and the narratives that emerge from these leaders on some aspects of local political leadership, there are also differences, perhaps most notably over the relationship between changes to decision making structures and the loci of political power

Discovery of Four High Proper Motion L Dwarfs, Including a 10 pc L Dwarf at the L/T Transition

We discover four high proper motion L dwarfs by comparing the Wide-field Infrared Survey Explorer (WISE) to the Two Micron All Sky Survey (2MASS). WISE J140533.32+835030.5 is an L dwarf at the L/T transition with a proper motion of 0.85+/-0.02" yr^-1, previously overlooked due to its proximity to a bright star (V=12 mag). From optical spectroscopy we find a spectral type of L8, and from moderate-resolution J band spectroscopy we find a near-infrared spectral type of L9. We find WISE J140533.32+835030.5 to have a distance of 9.7+/-1.7 pc, bringing the number of L dwarfs at the L/T transition within 10 pc from six to seven. WISE J040137.21+284951.7, WISE J040418.01+412735.6, and WISE J062442.37+662625.6 are all early L dwarfs within 25 pc, and were classified using optical and low-resolution near-infrared spectra. WISE J040418.01+412735.6 is an L2 pec (red) dwarf, a member of the class of unusually red L dwarfs. We use follow-up optical and low-resolution near-infrared spectroscopy to classify a previously discovered (Castro & Gizis 2012) fifth object WISEP J060738.65+242953.4 as an (L8 Opt/L9 NIR), confirming it as an L dwarf at the L/T transition within 10 pc. WISEP J060738.65+242953.4 shows tentative CH_4 in the H band, possibly the result of unresolved binarity with an early T dwarf, a scenario not supported by binary spectral template fitting. If WISEP J060738.65+242953.4 is a single object, it represents the earliest onset of CH_4 in the H band of an L/T transition dwarf in the SpeX Library. As very late L dwarfs within 10 pc, WISE J140533.32+835030.5 and WISEP J060738.65+242953.4 will play a vital role in resolving outstanding issues at the L/T transition.Comment: 45 pages, 12 figures, accepted for publication in Ap

The role of scale in designing protected area systems to conserve poorly known species

Systematic conservation planning has a substantial theoretical underpinning that allows optimization of tradeoffs between biodiversity conservation and other socioeconomic goals. However, this theory assumes perfect spatial information about the locations of biodiversity features (e.g., species distributions). In practice, planners represent well-known taxa and other biodiversity “surrogates” in protected area systems, hoping that unmapped species will also be conserved. However, empirical research finds that surrogates predict species presence imperfectly, and sometimes rather poorly, at scales relevant to planning, and existing theory provides no further guidance. We developed new theory, explicitly incorporating aspects of spatial scale, for the representation problem when the locations of species distributions are unknown. Using probability theory and simulated and real species distributions, we found that the probability of adequately representing an unmapped species in a protected area system will be low unless the total fraction of the region being protected is larger than the species representation target. Furthermore, successful conservation depended critically on the relative sizes of the species distribution and of the individual protected areas; fewer, larger protected areas allowed the entire species distribution to fall into an unprotected gap. This scale-dependence varied with the configuration of the protected area system, with the conservation objective most likely to be attained if the individual protected areas were hyperdispersed (evenly spaced across the planning region). Using these results, we developed three design principles for representing unmapped species in protected areas: (1) The fraction of the region placed in protected areas should be substantially larger than the species-level representation target; (2) Individual protected areas must be at least one to two orders of magnitude smaller than the unmapped species' distribution; and (3) Protected areas should be evenly dispersed over geographic space. We also performed preliminary investigations of the effects of surrogates and socio-economic cost data on the probability of adequately representing unmapped species, finding that the primary effect of surrogates may simply be to promote hyperdispersion of protected areas across the planning region, and that seeking to minimize opportunity costs gives poorer conservation results than random protected area placement

Assessing the Lifetime Performance of the Lightning Imaging Sensor (LIS): Implications for the Geostationary Lightning Mapper (GLM)

Project motivation is to analyze the performance of the Lightning Imaging Sensor (LIS) over its 13 years in orbit and examine implications for the Geostationary Lightning Mapper (GLM)

Raman Spectroscopy Detects Biochemical Changes Due to Different Cell Culture Environments in Live Cells In Vitro

The in vitro cell culture environment can impact on cell biochemistry and cell cycle. The manifestation of such substrate-induced changes in cell cycle in the Raman microspectroscopic profiles of cell cultures is investigated at the level of nucleolus, nucleus and cytoplasm. HeLa immortalised human cervical cells and HaCaT dermal cells were cultured on three different substrates, conventional polystyrene cell culture dishes, CaF2 slides as a commonly used Raman substrate, and glass slides coated with collagen rat tail, as a mimic of the extra-cellular matrix (ECM) environment. A cell cycle study, based on percentage DNA content, as determined using propidium iodide staining and monitored by flow cytometry, was performed on cells of both types, grown on the different substrates, confirming that the in vitro cell culture environment impacts significantly on the cell cycle. Live cell in vitro Raman spectroscopic analysis of cells on the 2D CaF2 and 3D collagen substrates was performed and data was analysed using principal component analysis (PCA). The spectroscopic analysis revealed differences in profiles which reflect the differences in cell cycle for both in vitro culture environments. In particular, the Raman spectra of cells grown on CaF2 show indicators of cell stress, which are also associated with cell cycle arrest at the G0/G1 phase. This work contributes to the field of Raman spectroscopic analysis by providing a fresh look at the significance of the effect of in vitro culture environment to cell cycle and the sensitivity of Raman spectroscopy to such differences in cell metabolism

Circulation, retention, and mixing of waters within the Weddell-Scotia Confluence, Southern Ocean:The role of stratified Taylor columns

The waters of the Weddell-Scotia Confluence (WSC) lie above the rugged topography of the South Scotia Ridge in the Southern Ocean. Meridional exchanges across the WSC transfer water and tracers between the Antarctic Circumpolar Current (ACC) to the north and the subpolar Weddell Gyre to the south. Here, we examine the role of topographic interactions in mediating these exchanges, and in modifying the waters transferred. A case study is presented using data from a free-drifting, intermediate-depth float, which circulated anticyclonically over Discovery Bank on the South Scotia Ridge for close to 4 years. Dimensional analysis indicates that the local conditions are conducive to the formation of Taylor columns. Contemporaneous ship-derived transient tracer data enable estimation of the rate of isopycnal mixing associated with this column, with values of O(1000 m2/s) obtained. Although necessarily coarse, this is of the same order as the rate of isopycnal mixing induced by transient mesoscale eddies within the ACC. A picture emerges of the Taylor column acting as a slow, steady blender, retaining the waters in the vicinity of the WSC for lengthy periods during which they can be subject to significant modification. A full regional float data set, bathymetric data, and a Southern Ocean state estimate are used to identify other potential sites for Taylor column formation. We find that they are likely to be sufficiently widespread to exert a significant influence on water mass modification and meridional fluxes across the southern edge of the ACC in this sector of the Southern Ocean