Rare variants in LRRK1 and Parkinson's disease

Approximately 20 % of individuals with Parkinson's disease (PD) report a positive family history. Yet, a large portion of causal and disease-modifying variants is still unknown. We used exome sequencing in two affected individuals from a family with late-onset PD to identify 15 potentially causal variants. Segregation analysis and frequency assessment in 862 PD cases and 1,014 ethnically matched controls highlighted variants in EEF1D and LRRK1 as the best candidates. Mutation screening of the coding regions of these genes in 862 cases and 1,014 controls revealed several novel non-synonymous variants in both genes in cases and controls. An in silico multi-model bioinformatics analysis was used to prioritize identified variants in LRRK1 for functional follow- up. However, protein expression, subcellular localization, and cell viability were not affected by the identified variants. Although it has yet to be proven conclusively that variants in LRRK1 are indeed causative of PD, our data strengthen a possible role for LRRK1 in addition to LRRK2 in the genetic underpinnings of PD but, at the same time, highlight the difficulties encountered in the study of rare variants identified by next-generation sequencing in diseases with autosomal dominant or complex patterns of inheritance.

The Stonehenge landscape habitat restoration project: conservation opportunities for rare butterflies?

Landscape restoration has the potential to mitigate habitat loss and fragmentation. However, restoration can take decades to reach the ecological conditions of the target habitats. The National Trust’s Stonehenge Landscape Restoration Project provides an opportunity to evaluate the ecological benefits against the economic and temporal costs. A field survey between June and September 2010 using Lepidoptera as bio-indicators showed that restored grasslands can approach the ecological conditions of the target chalk grassland habitat within 10 years. However, specialist species like Lysandra bellargus (Adonis blue) were absent from restored grasslands and may require additional management to assist their colonisation. Analysis of the Lepidoptera communities showed that both small-scale habitat heterogeneity and age of the habitat were important for explaining Lepidoptera occurrence. These results demonstrate that habitat restoration at the landscape scale combined with appropriate site-scale management can be a relatively rapid and effective method to restore ecological networks and buffer against future climate change.

Categorisation of synoptic environments associated with mesoscale convective systems over the UK

Mesoscale convective systems (MCSs) are relatively rare events in the UK but, when they do occur, can be associated with weather that is considered extreme with respect to climatology (as indicated by the number of such events that have been analysed as case studies). These case studies usually associate UK MCSs with a synoptic environment known as the Spanish plume. Here a previously published 17 year climatology of UK MCS events is extended to the present day (from 1998 to 2008) and these events classified according to the synoptic environment in which they form. Three distinct synoptic environments have been identified, here termed the classical Spanish plume, modified Spanish plume, and European easterly plume. Detailed case studies of the two latter, newly defined, environments are presented. Composites produced for each environment further reveal the differences between them. The classical Spanish plume is associated with an eastward propagating baroclinic cyclone that evolves according to idealised life cycle 1. Conditional instability is released from a warm moist plume of air advected northeastwards from Iberia that is capped by warmer, but very dry air, from the Spanish plateau. The modified Spanish plume is associated with a slowly moving mature frontal system associated with a forward tilting trough (and possibly cut-off low) at 500 hPa that evolves according to idealised life cycle 2. As in the classical Spanish plume, conditional instability is released from a warm plume of air advected northwards from Iberia. The less frequent European easterly plume is associated with an omega block centred over Scandinavia at upper levels. Conditional instability is released from a warm plume of air advected westwards across northern continental Europe. Unlike the Spanish plume environments, the European easterly plume is not a warm sector phenomena associated with a baroclinic cyclone. However, in all environments the organisation of convection is associated with the interaction of an upper-level disturbance with a low-level region of warm advection.

Insight overview: natural selection 150 years on

The theory of evolution by natural selection has prospered in its first 150 years and provides a consistent account of species as highly adapted and rare survivors in the struggle for existence. It now faces the challenge of finding order in the evolution of complex systems, including human society.

Communicating risk of medication side effects: an empirical evaluation of EU recommended terminology

Two experiments compared people's interpretation of verbal and numerical descriptions of the risk of medication side effects occurring. The verbal descriptors were selected from those recommended for use by the European Union (very common, common, uncommon, rare, very rare). Both experiments used a controlled empirical methodology, in which nearly 500 members of the general population were presented with a fictitious (but realistic) scenario about visiting the doctor and being prescribed medication, together with information about the medicine's side effects and their probability of occurrence. Experiment 1 found that, in all three age groups tested (18 - 40, 41 - 60 and over 60), participants given a verbal descriptor (very common) estimated side effect risk to be considerably higher than those given a comparable numerical description. Furthermore, the differences in interpretation were reflected in their judgements of side effect severity, risk to health, and intention to comply. Experiment 2 confirmed these findings using two different verbal descriptors (common and rare) and in scenarios which described either relatively severe or relatively mild side effects. Strikingly, only 7 out of 180 participants in this study gave a probability estimate which fell within the EU assigned numerical range. Thus, large scale use of the descriptors could have serious negative consequences for individual and public health. We therefore recommend that the EU and National authorities suspend their recommendations regarding these descriptors until a more substantial evidence base is available to support their appropriate use.

Rhenium-to-benzoylpyridine and rhenium-to-bipyridine MLCT excited states offac-[Re(Cl)(4-benzoylpyridine)2(CO)3] andfac-[Re(4-benzoylpyridine)(CO)3(bpy)]+: a time-resolved spectroscopic and spectroelectrochemical study

The lowest allowed electronic transition of fac-[Re(Cl)(CO)(3)(bopy)(2)] (bopy = 4-benzoylpyridine) has a Re --> bopy MLCT character, as revealed by UV-vis and stationary resonance Raman spectroscopy. Accordingly, the lowest-lying, long-lived, excited state is Re --> bopy (MLCT)-M-3. Electronic depopulation of the Re(CO)(3) unit and population of a bopy pi* orbital upon excitation are evident by the upward shift of v(Cequivalent toO) vibrations and a downward shift of the ketone v(C=O) vibration, respectively, seen in picosecond time-resolved IR spectra. Moreover, reduction of a single bopy ligand in the (MLCT)-M-3 excited state is indicated by time-resolved visible and resonance Raman (TR3) spectra that show features typical of bopy(.-). In contrast, the lowest allowed electronic transition and lowest-lying excited state of a new complex fac-[Re(bopy)(CO)(3)(bpy)](+) (bpy = 2,2'-bipyridine) have been identified as Re --> bpy MLCT with no involvement of the bopy ligand, despite the fact that the first reduction of this complex is bopy-localized, as was proven spectroelectrochemically. This is a rare case in which the localizations of the lowest MLCT excitation and the first reduction are different. (MLCT)-M-3 excited states of both fac-[Re(Cl)(CO)(3)(bopy)(2)] and fac-[Re(bopy)(CO)(3)(bpy)](+) are initially formed vibrationally hot. Their relaxation is manifested by picosecond dynamic shifts of v(Cequivalent toO) IR bands. The X-ray structure of fac-[Re(bopy)(CO)(3)(bpy)](PF6CH3CN)-C-. has been determined.