Binding and Retrograde Transport of Leukemia Inhibitory Factor by the Sensory Nervous-System

Leukemia inhibitory factor (LIF), a peptide growth factor with multiple activities, has recently been shown to support the generation and survival of sensory neurons in cultures of mouse neural crest and dorsal root ganglia (DRG). We have conducted binding experiments with I-125-LIF on cultures of DRG to determine the receptor distribution for LIF on these cells and found that at least 60% of the sensory neurons in the cultures bound I-125-LIF, all of which could be eliminated by the addition of unlabeled LIF. The other cells in the culture, which morphologically appeared to be Schwann cells, did not bind appreciable quantities of I-125-LIF. In order to investigate whether LIF is retrogradely transported to sensory neurons in vivo, I-125-LIF was injected into the footpads and gastrocnemius muscles of newborn and adult mice, following sciatic nerve ligation. Radioactivity accumulated in the distal portion of the sciatic nerve, indicating retrograde transport of LIF. Subsequent experiments on mice with unligated sciatic nerves showed that I-125-LIF is specifically transported into the sensory neurons of the DRG. There was no apparent transport of I-125-LIF into motor neurons in the spinal cord. These experiments demonstrate that LIF can specifically bind to and be transported by sensory neurons and further support the idea that LIF acts as a target-derived neurotrophic factor, analogous to NGF

Superoxide Dismutase 1 in Health and Disease: How a Frontline Antioxidant Becomes Neurotoxic.

Cu/Zn superoxide dismutase (SOD1) is a frontline antioxidant enzyme catalysing superoxide breakdown and is important for most forms of eukaryotic life. The evolution of aerobic respiration by mitochondria increased cellular production of superoxide, resulting in an increased reliance upon SOD1. Consistent with the importance of SOD1 for cellular health, many human diseases of the central nervous system involve perturbations in SOD1 biology. But far from providing a simple demonstration of how disease arises from SOD1 loss-of-function, attempts to elucidate pathways by which atypical SOD1 biology leads to neurodegeneration have revealed unexpectedly complex molecular characteristics delineating healthy, functional SOD1 protein from that which likely contributes to central nervous system disease. This review summarises current understanding of SOD1 biology from SOD1 genetics through to protein function and stability

Should I stay or should I go? Fitness costs and benefits of prolonged parent-offspring and sibling-sibling associations in an Arctic-nesting goose population.

This is the final version of the article. Available from the publisher via the DOI in this record.Theory predicts persistence of long-term family relationships in vertebrates will occur until perceived fitness costs exceed benefits to either parents or offspring. We examined whether increased breeding probability and survival were associated with prolonged parent-offspring and sibling-sibling relationships in a long-lived Arctic migrant herbivore, the Greenland white-fronted goose (Anser albifrons flavirostris). Although offspring associated with parents for 1-13 years, 79 % of these associations lasted two or less years. Only 65 (9.9 %) of the 656 marked offspring bred once in their lifetime, and just 16 (2.4 %) bred twice or more. The probability of birds with siblings breeding successfully in a subsequent year was credibly greater than that of independent birds at ages 5, 6, and 7. Survival of offspring with parents was credibly greater than that of independent/nonbreeder birds at all possible ages (i.e., ages 2-7+). A cost-benefit matrix model utilizing breeding and survival probabilities showed that staying with family groups was favored over leaving until age 3, after which there were no credible differences between staying and leaving strategies until the oldest ages, when leaving family groups was favored. Thus, most birds in this study either departed family groups early (e.g., at age 2, when the "stay" strategy was favored) or as predicted by our cost-benefit model (i.e., at age 3). Although extended family associations are a feature of this population, we contend that the survival benefits are not sufficient enough to yield clear fitness benefits, and associations only persist because parents and offspring mutually benefit from their persistence.This research was funded through a joint PhD studentship from the Wildfowl & Wetlands Trust and the University of Exeter undertaken by MDW

Integrated population modelling reveals a perceived source to be a cryptic sink

This is the final version of the article. Available from the publisher via the DOI in this record.Demographic links among fragmented populations are commonly studied as source-sink dynamics, whereby source populations exhibit net recruitment and net emigration, while sinks suffer net mortality but enjoy net immigration. It is commonly assumed that large, persistent aggregations of individuals must be sources, but this ignores the possibility that they are sinks instead, buoyed demographically by immigration. We tested this assumption using Bayesian integrated population modelling of Greenland white-fronted geese (Anser albifrons flavirostris) at their largest wintering site (Wexford, Ireland), combining capture-mark-recapture, census and recruitment data collected from 1982 to 2010. Management for this subspecies occurs largely on wintering areas; thus, study of source-sink dynamics of discrete regular wintering units provides unprecedented insights into population regulation and enables identification of likely processes influencing population dynamics at Wexford and among 70 other Greenland white-fronted goose wintering subpopulations. Using results from integrated population modelling, we parameterized an age-structured population projection matrix to determine the contribution of movement rates (emigration and immigration), recruitment and mortality to the dynamics of the Wexford subpopulation. Survival estimates for juvenile and adult birds at Wexford and adult birds elsewhere fluctuated over the 29-year study period, but were not identifiably different. However, per capita recruitment rates at Wexford in later years (post-1995) were identifiably lower than in earlier years (pre-1995). The observed persistence of the Wexford subpopulation was only possible with high rates of immigration, which exceeded emigration in each year. Thus, despite its apparent stability, Wexford has functioned as a sink over the entire study period. These results demonstrate that even large subpopulations can potentially be sinks, and that movement dynamics (e.g. immigration) among winters can dramatically obscure key processes driving subpopulation size. Further, novel population models which integrate capture-mark-recapture, census and recruitment data are essential to correctly ascribing source-sink status and accurately informing development of site-safeguard networks.This research was funded through a joint PhD studentship to M.D.W. from the Wildfowl & Wetlands Trust and the University of Exeter, and through a NERC grant (NE/L007770/1) to D.J.

3D Printed Franz cells - update on optimization of manufacture and evaluation

The evaluation of permeation profiles from cosmetic formulations is considered to be a crucial component in both the development and quality assurance of any new product [1, 2]. Data gathered from such studies allow researchers to assess the viability of delivering different materials to and through biological membranes. To date, laboratory in vitro permeation processes require the use of modified Franz type diffusion cells, conventionally fabricated from glass, which are available in different formats that can be customised to experimental requirements [3]

Extremely high He isotope ratios in MORB-source mantle from the proto-Iceland plume

The high <sup>3</sup>He/<sup>4</sup>He ratio of volcanic rocks thought to be derived from mantle plumes is taken as evidence for the existence of a mantle reservoir that has remained largely undegassed since the Earth's accretion. The helium isotope composition of this reservoir places constraints on the origin of volatiles within the Earth and on the evolution and structure of the Earth's mantle. Here we show that olivine phenocrysts in picritic basalts presumably derived from the proto-Iceland plume at Baffin Island, Canada, have the highest magmatic <sup>3</sup>He/<sup>4</sup>He ratios yet recorded. A strong correlation between <sup>3</sup>He/<sup>4</sup>He and <sup>87</sup>Sr/<sup>86</sup>Sr, <sup>143</sup>Nd/<sup>144</sup>Nd and trace element ratios demonstrate that the <sup>3</sup>He-rich end-member is present in basalts that are derived from large-volume melts of depleted upper-mantle rocks. This reservoir is consistent with the recharging of depleted upper-mantle rocks by small volumes of primordial volatile-rich lower-mantle material at a thermal boundary layer between convectively isolated reservoirs. The highest <sup>3</sup>He/<sup>4</sup>He basalts from Hawaii and Iceland plot on the observed mixing trend. This indicates that a <sup>3</sup>He-recharged depleted mantle (HRDM) reservoir may be the principal source of high <sup>3</sup>He/<sup>4</sup>He in mantle plumes, and may explain why the helium concentration of the 'plume' component in ocean island basalts is lower than that predicted for a two-layer, steady-state model of mantle structure

Diel turbidity cycles in a headwater stream: evidence of nocturnal bioturbation?

Purpose: A small number of recent studies have linked daily cycles in stream turbidity to nocturnal bioturbation by aquatic fauna, principally crayfish, and demonstrated this process can significantly impact upon water quality under baseflow conditions. Adding to this limited body of research, we use high-resolution water quality monitoring data to investigate evidence of diel turbidity cycles in a lowland, headwater stream with a known signal crayfish (Pacifastacus leniusculus) population and explore a range of potential causal mechanisms. Materials and methods: Automatic bankside monitoring stations measured turbidity and other water quality parameters at 30-min resolution at three locations on the River Blackwater, Norfolk, UK during 2013. Specifically, we focused on two 20-day periods of baseflow conditions during January and April 2013 which displayed turbidity trends typical of winter and spring seasons, respectively. The turbidity time-series, which were smoothed with 6.5 hour Savitzky-Golay filters to highlight diel trends, were correlated against temperature, stage, dissolved oxygen and pH to assess the importance of abiotic influences on turbidity. Turbidity was also calibrated against suspended particulate matter (SPM) over a wide range of values via linear regression. Results and discussion: Pronounced diel turbidity cycles were found at two of the three sites under baseflow conditions during April. Spring night-time turbidity values consistently peaked between 21:00 and 04:00 with values increasing by ~10 nephelometric turbidity units (NTU) compared with the lowest recorded daytime values which occurred between 10:00 and 14:00. This translated into statistically significant increases in median midnight SPM concentration of up to 76% compared with midday, with night-time (18:00 – 05:30) SPM loads also up to 30% higher than that recorded during the daytime (06:00 – 17:30). Relating turbidity to other water quality parameters exhibiting diel cycles revealed there to be neither any correlation that might indicate a causal link, nor any obvious mechanistic connections to explain the temporal turbidity trends. Diel turbidity cycles were less prominent at all sites during the winter. Conclusions: Considering the seasonality and timing of elevated turbidity, visual observations of crayfish activity, and an absence of mechanistic connections with other water quality parameters, the results presented here are consistent with the hypothesis that nocturnal bioturbation is responsible for generating diel turbidity cycles under baseflow conditions in headwater streams. However, further research in a variety of fluvial environments is required to better assess the spatial extent, importance and causal mechanisms of this phenomenon

Metal-insulator transition in vanadium dioxide nanobeams: probing sub-domain properties of strongly correlated materials

Many strongly correlated electronic materials, including high-temperature superconductors, colossal magnetoresistance and metal-insulator-transition (MIT) materials, are inhomogeneous on a microscopic scale as a result of domain structure or compositional variations. An important potential advantage of nanoscale samples is that they exhibit the homogeneous properties, which can differ greatly from those of the bulk. We demonstrate this principle using vanadium dioxide, which has domain structure associated with its dramatic MIT at 68 degrees C. Our studies of single-domain vanadium dioxide nanobeams reveal new aspects of this famous MIT, including supercooling of the metallic phase by 50 degrees C; an activation energy in the insulating phase consistent with the optical gap; and a connection between the transition and the equilibrium carrier density in the insulating phase. Our devices also provide a nanomechanical method of determining the transition temperature, enable measurements on individual metal-insulator interphase walls, and allow general investigations of a phase transition in quasi-one-dimensional geometry.Comment: 9 pages, 3 figures, original submitted in June 200

Ultrafast changes in lattice symmetry probed by coherent phonons

The electronic and structural properties of a material are strongly determined by its symmetry. Changing the symmetry via a photoinduced phase transition offers new ways to manipulate material properties on ultrafast timescales. However, in order to identify when and how fast these phase transitions occur, methods that can probe the symmetry change in the time domain are required. We show that a time-dependent change in the coherent phonon spectrum can probe a change in symmetry of the lattice potential, thus providing an all-optical probe of structural transitions. We examine the photoinduced structural phase transition in VO2 and show that, above the phase transition threshold, photoexcitation completely changes the lattice potential on an ultrafast timescale. The loss of the equilibrium-phase phonon modes occurs promptly, indicating a non-thermal pathway for the photoinduced phase transition, where a strong perturbation to the lattice potential changes its symmetry before ionic rearrangement has occurred.Comment: 14 pages 4 figure