Neuroprotection in a Novel Mouse Model of Multiple Sclerosis

Multiple sclerosis is an immune-mediated, demyelinating and neurodegenerative disease that currently lacks any neuroprotective treatments. Innovative neuroprotective trial designs are required to hasten the translational process of drug development. An ideal target to monitor the efficacy of strategies aimed at treating multiple sclerosis is the visual system, which is the most accessible part of the human central nervous system. A novel C57BL/6 mouse line was generated that expressed transgenes for a myelin oligodendrocyte glycoprotein-specific T cell receptor and a retinal ganglion cell restricted-Thy1 promoter-controlled cyan fluorescent protein. This model develops spontaneous or induced optic neuritis, in the absence of paralytic disease normally associated with most rodent autoimmune models of multiple sclerosis. Demyelination and neurodegeneration could be monitored longitudinally in the living animal using electrophysiology, visual sensitivity, confocal scanning laser ophthalmoscopy and optical coherence tomography all of which are relevant to human trials. This model offers many advantages, from a 3Rs, economic and scientific perspective, over classical experimental autoimmune encephalomyelitis models that are associated with substantial suffering of animals. Optic neuritis in this model led to inflammatory damage of axons in the optic nerve and subsequent loss of retinal ganglion cells in the retina. This was inhibited by the systemic administration of a sodium channel blocker (oxcarbazepine) or intraocular treatment with siRNA targeting caspase-2. These novel approaches have relevance to the future treatment of neurodegeneration of MS, which has so far evaded treatment.     

Studies on the use ofMetarhizium anisopliae to controlOryctes rhinoceros

Selected strains ofMetarhizium anisopliae (Metsch.) Sor. were grown on oat grain and tested in field experiments againstOryctes rhinoceros L. It was found thatM. anisopliae survived in breeding site materials for at least 24 months, with survival not greatly affected by the type of material or by seasonal factors. Naturally occurring breeding sites were examined 3 months after they had been surface treated with oat grain inoculum ofM. anisopliae. In most sites all the larvae had been killed by the fungus while some contained both diseased and apparently healthy larvae. Recommendations are made for the use ofM. anisopliae as part of a general control programme for this coconut pest.

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Résumé Certains types sélectionnés deMetarhizium anisopliae ont été cultivés sur des grains d'avoine et examinés en tant qu'insecticides biologiques au cours d'expériences pratiques contre lesOryctes rhinoceros. Les résultats ont montré queM. anisopliae peut survivre sur les matériaux du lieu de culture pendant au moins vingt-quatre mois, leur survie n'étant pas particulièrement affectée par le type de matériel ou par les facteurs saisonniers. Les lieux de culture naturels ont été examinés trois mois après qu'ils aient été traités superficiellement par l'inoculum de grain d'avoine deM. anisopliae. La plupart des lieux de culture contenaient seulement des cadavres de larves d'O. rhinoceros tués par le champignon tandis que certains autres contenaient à la fois des larves malades et des larves en apparence saines. L'utilisation deM. anisopliae est recommandée dans le cadre du programme général de lutte contre cet insecte nuisible qui s'attaque à la noix de coco.

     

Carbon sequestration potential in European croplands has been overestimated

Yearly, per‐area carbon sequestration rates are used to estimate mitigation potentials by comparing types and areas of land management in 1990 and 2000 and projected to 2010, for the European Union (EU)‐15 and for four country‐level case studies for which data are available: UK, Sweden, Belgium and Finland. Because cropland area is decreasing in these countries (except for Belgium), and in most European countries there are no incentives in place to encourage soil carbon sequestration, carbon sequestration between 1990 and 2000 was small or negative in the EU‐15 and all case study countries. Belgium has a slightly higher estimate for carbon sequestration than the other countries examined. This is at odds with previous reports of decreasing soil organic carbon stocks in Flanders. For all countries except Belgium, carbon sequestration is predicted to be negligible or negative by 2010, based on extrapolated trends, and is small even in Belgium. The only trend in agriculture that may be enhancing carbon stocks on croplands at present is organic farming, and the magnitude of this effect is highly uncertain. Previous studies have focused on the potential for carbon sequestration and have shown quite significant potential. This study, which examines the sequestration likely to occur by 2010, suggests that the potential will not be realized. Without incentives for carbon sequestration in the future, cropland carbon sequestration under Article 3.4 of the Kyoto Protocol will not be an option in EU‐15.     

Comparing and evaluating process-based ecosystem model predictions of carbon and water fluxes in major European forest biomes

Process‐based models can be classified into: (a) terrestrial biogeochemical models (TBMs), which simulate fluxes of carbon, water and nitrogen coupled within terrestrial ecosystems, and (b) dynamic global vegetation models (DGVMs), which further couple these processes interactively with changes in slow ecosystem processes depending on resource competition, establishment, growth and mortality of different vegetation types. In this study, four models – RHESSys, GOTILWA+, LPJ‐GUESS and ORCHIDEE – representing both modelling approaches were compared and evaluated against benchmarks provided by eddy‐covariance measurements of carbon and water fluxes at 15 forest sites within the EUROFLUX project. Overall, model‐measurement agreement varied greatly among sites. Both modelling approaches have somewhat different strengths, but there was no model among those tested that universally performed well on the two variables evaluated. Small biases and errors suggest that ORCHIDEE and GOTILWA+ performed better in simulating carbon fluxes while LPJ‐GUESS and RHESSys did a better job in simulating water fluxes. In general, the models can be considered as useful tools for studies of climate change impacts on carbon and water cycling in forests. However, the various sources of variation among models simulations and between models simulations and observed data described in this study place some constraints on the results and to some extent reduce their reliability. For example, at most sites in the Mediterranean region all models generally performed poorly most likely because of problems in the representation of water stress effects on both carbon uptake by photosynthesis and carbon release by heterotrophic respiration (R_h). The use of flux data as a means of assessing key processes in models of this type is an important approach to improving model performance. Our results show that the models have value but that further model development is necessary with regard to the representation of the some of the key ecosystem processes.     

Fine-mapping and candidate gene analysis of bovine spinal muscular atrophy

Bovine spinal muscular atrophy (SMA), an autosomal recessive neurodegenerative disease, has been mapped at moderate resolution to the distal part of Chromosome 24. In this article we confirm this location and fine-map the SMA locus to an interval of approximately 0.8 cM at the very distal end of BTA24. Despite remarkable similarity to human SMA, the causative gene SMN can be excluded in bovine SMA. However, the interval where the disease now has been mapped contains BCL2, like SMN an antiapoptotic factor, and shown to bind to SMN. Moreover, knockout mice lacking the BCL2 gene show rapid motor neuron degeneration with early postnatal onset, as observed in bovine SMA. A comparative cattle/human map of the distal end of BTA24, based on the emerging bovine genome sequencing data, shows conserved synteny to HSA18 with hints of a segmental duplication and pericentic inversion just after the last available bovine marker DIK4971. This synteny lets us conclude that SMA is in immediate vicinity of the telomere. Candidate gene analysis of BCL2, however, excludes most of this gene, except its promoter region, and draws attention to the neighboring gene VPS4B, part of the endosomal protein-sorting machinery ESCRT-III which is involved in several neurodegenerative diseases. Stefan Krebs and Ivica Medugorac contributed equally to this work and agreed to be considered as first authors.     

Identification and Characterisation CRN Effectors in Phytophthora capsici Shows Modularity and Functional Diversity

Phytophthora species secrete a large array of effectors during infection of their host plants. The Crinkler (CRN) gene family encodes a ubiquitous but understudied class of effectors with possible but as of yet unknown roles in infection. To appreciate CRN effector function in Phytophthora, we devised a simple Crn gene identification and annotation pipeline to improve effector prediction rates. We predicted 84 full-length CRN coding genes and assessed CRN effector domain diversity in sequenced Oomycete genomes. These analyses revealed evidence of CRN domain innovation in Phytophthora and expansion in the Peronosporales. We performed gene expression analyses to validate and define two classes of CRN effectors, each possibly contributing to infection at different stages. CRN localisation studies revealed that P. capsici CRN effector domains target the nucleus and accumulate in specific sub-nuclear compartments. Phenotypic analyses showed that few CRN domains induce necrosis when expressed in planta and that one cell death inducing effector, enhances P. capsici virulence on Nicotiana benthamiana. These results suggest that the CRN protein family form an important class of intracellular effectors that target the host nucleus during infection. These results combined with domain expansion in hemi-biotrophic and necrotrophic pathogens, suggests specific contributions to pathogen lifestyles. This work will bolster CRN identification efforts in other sequenced oomycete species and set the stage for future functional studies towards understanding CRN effector functions.     

High and Distinct Range-Edge Genetic Diversity despite Local Bottlenecks

The genetic consequences of living on the edge of distributional ranges have been the subject of a largely unresolved debate. Populations occurring along persistent low latitude ranges (rear-edge) are expected to retain high and unique genetic diversity. In contrast, currently less favourable environmental conditions limiting population size at such range-edges may have caused genetic erosion that prevails over past historical effects, with potential consequences on reducing future adaptive capacity. The present study provides an empirical test of whether population declines towards a peripheral range might be reflected on decreasing diversity and increasing population isolation and differentiation. We compare population genetic differentiation and diversity with trends in abundance along a latitudinal gradient towards the peripheral distribution range of Saccorhiza polyschides , a large brown seaweed that is the main structural species of kelp forests in SW Europe. Signatures of recent bottleneck events were also evaluated to determine whether the recently recorded distributional shifts had a negative influence on effective population size. Our findings show decreasing population density and increasing spatial fragmentation and local extinctions towards the southern edge. Genetic data revealed two well supported groups with a central contact zone. As predicted, higher differentiation and signs of bottlenecks were found at the southern edge region. However, a decrease in genetic diversity associated with this pattern was not verified. Surprisingly, genetic diversity increased towards the edge despite bottlenecks and much lower densities, suggesting that extinctions and recolonizations have not strongly reduced diversity or that diversity might have been even higher there in the past, a process of shifting genetic baselines.     

Assessing “Dangerous Climate Change”: Required Reduction of Carbon Emissions to Protect Young People,Future Generations and Nature

We assess climate impacts of global warming using ongoing observations and paleoclimate data. We use Earth’s measured energy imbalance, paleoclimate data, and simple representations of the global carbon cycle and temperature to define emission reductions needed to stabilize climate and avoid potentially disastrous impacts on today’s young people, future generations, and nature. A cumulative industrial-era limit of ∼500 GtC fossil fuel emissions and 100 GtC storage in the biosphere and soil would keep climate close to the Holocene range to which humanity and other species are adapted. Cumulative emissions of ∼1000 GtC, sometimes associated with 2°C global warming, would spur “slow” feedbacks and eventual warming of 3–4°C with disastrous consequences. Rapid emissions reduction is required to restore Earth’s energy balance and avoid ocean heat uptake that would practically guarantee irreversible effects. Continuation of high fossil fuel emissions, given current knowledge of the consequences, would be an act of extraordinary witting intergenerational injustice. Responsible policymaking requires a rising price on carbon emissions that would preclude emissions from most remaining coal and unconventional fossil fuels and phase down emissions from conventional fossil fuels.     

Fluorescent ornamentation in the Rhinoceros Auklet Cerorhinca monocerata

Avian species have developed a range of markers for transmitting information, among them ornamented plumage, behavioural patterns and conspicuous bill structures. Members of the marine subfamily Fraterculinae have some of the most visibly noticeable ornaments among seabirds, and some species have been recently found to possess fluorescent properties in seasonally acquired bill plates. We examined a member of this subfamily, the Rhinoceros Auklet Cerorhinca monocerata, for fluorescence in the upper and lower mandibles as well as the namesake horn grown in preparation for mate selection. Fluorescence was noted primarily in the horn of adults, with greater variation present among individuals than between the sexes.