A genome-wide association meta-analysis identifies new childhood obesity loci

Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of 14 studies consisting of 5,530 cases (≥95th percentile of body mass index (BMI)) and 8,318 controls (<50th percentile of BMI) of European ancestry. Taking forward the eight newly discovered signals yielding association with P < 5 × 10(-6) in nine independent data sets (2,818 cases and 4,083 controls), we observed two loci that yielded genome-wide significant combined P values near OLFM4 at 13q14 (rs9568856; P = 1.82 × 10(-9); odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 × 10(-9); OR = 1.14). Both loci continued to show association when two extreme childhood obesity cohorts were included (2,214 cases and 2,674 controls). These two loci also yielded directionally consistent associations in a previous meta-analysis of adult BMI(1).

Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.

Tumour necrosis factor alpha induces rapid reduction in AMPA receptor-mediated calcium entry in motor neurones by increasing cell surface expression of the GluR2 subunit: relevance to neurodegeneration

The AMPA receptor (AMPAR) subunit GluR2, which regulates excitotoxicity and the inflammatory cytokine tumour necrosis factor alpha (TNF alpha) have both been implicated in motor neurone vulnerability in Amyotrophic Lateral Sclerosis/Motor Neurone Disease. TNF alpha has been reported to increase cell surface expression of AMPAR subunits to increase synaptic strength and enhance excitotoxicity, but whether this mechanism occurs in motor neurones is unknown. We used primary cultures of mouse motor neurones and cortical neurones to examine the interaction between TNF alpha receptor activation, GluR2 availability, AMPAR-mediated calcium entry and susceptibility to excitotoxicity. Short exposure to a physiologically relevant concentration of TNFalpha (10 ng/ml, 15 min) caused a marked redistribution of both GluR1 and GluR2 to the cell surface as determined by cell surface biotinylation and immunofluorescence. Using Fura-2 AM microfluorimetry we showed that exposure to TNFalpha caused a rapid reduction in the peak amplitude of AMPA-mediated calcium entry in a PI3-kinase and p38 kinase-dependent manner, consistent with increased insertion of GluR2-containing AMPAR into the plasma membrane. This resulted in a protection of motor neurones against kainate-induced cell death. Our data therefore, suggests that TNF alpha acts primarily as a physiological regulator of synaptic activity in motor neurones rather than a pathological drive in ALS

An inventory of heavy metals inputs to agricultural soils in England and Wales

An inventory of heavy metal inputs (Zn, Cu, Ni, Pb, Cd, Cr, As and Hg) to agricultural soils in England and Wales in 2000 is presented, accounting for major sources including atmospheric deposition, sewage sludge, livestock manures, inorganic fertilisers and lime, agrochemicals, irrigation water, industrial by-product 'wastes' and composts. Across the whole agricultural land area, atmospheric deposition was the main source of most metals, ranging from 25 to 85% of total inputs. Livestock manures and sewage sludge were also important sources, responsible for an estimated 37-40 and 8-17% of total Zn and Cu inputs, respectively. However, at the individual field scale sewage sludge, livestock manures and industrial wastes could be the major source of many metals where these materials are applied. This work will assist in developing strategies for reducing heavy metal inputs to agricultural land and effectively targeting policies to protect soils from long-term heavy metal accumulation. (C) 2003 Elsevier Science B.V. All rights reserved.

Degradation and plant uptake of nonylphenol (NP) and nonylphenol-12-ethoxylate (NP12EO) in four contrasting agricultural soils

Nonylphenol polyethoxylates (NPEOs) are surfactants found ubiquitously in the environment due to widespread industrial and domestic use. Biodegradation of NPEOs produces nonylphenol (NP), an endocrine disruptor. Sewage sludge application introduces NPEOs and NP into soils, potentially leading to accumulation in soils and crops. We examined degradation of NP and nonyl phenol-12-ethoxylate (NP12EO) in four soils. NP12EO degraded rapidly (initial half time 0.3-5 days). Concentrations became undetectable within 70-90 days, with a small increase in NP concentrations after 30 days. NP initially degraded quickly (mean half time 11.5 days), but in three soils a recalcitrant fraction of 26-35% remained: the non-degrading fraction may consist of branched isomers, resistant to biodegradation. Uptake of NP by bean plants was also examined. Mean bioconcentration factors for shoots and seeds were 0.71 and 0.58, respectively. Removal of NP from the soil by plant uptake was negligible (0.01-0.02% of initial NP). Root concentrations were substantially higher than shoot and seed concentrations. (C) 2008 Elsevier Ltd. All rights reserved.

Ultrafast charge separation in a photoreactive rhenium-appended porphyrin assembly monitored by picosecond transient infrared spectroscopy

Rhenium(bipyridine)(tricarbonyl)(picoline) units have been linked covalently to tetraphenylmetalloporphyrins of magnesium and zinc via an amide bond between the bipyridine and one phenyl substituent of the porphyrin. The resulting complexes, abbreviated as [Re(CO)(3)(Pic)Bpy-MgTPP][OTf] and [Re(CO)(3)(Pic)Bpy-ZnTPP][OTf], exhibit no signs of electronic interaction between the Re(CO)(3)(bpy) units and the metalloporphyrin units in their ground states. However, emission spectroscopy reveals solvent-dependent quenching of porphyrin emission on irradiation into the long-wavelength absorption bands localized on the porphyrin. The characteristics of the excited states have been probed by picosecond time-resolved absorption (TRVIS) spectroscopy and time-resolved infrared (TRIR) spectroscopy in nitrile solvents. The presence of the charge-separated state involving electron transfer from MgTPP or ZnTPP to Re(bpy) is signaled in the TRIR spectra by a low-frequency shift in the nu(CO) bands of the Re(CO)(3) moiety similar to that observed by spectroelectrochemical reduction. Long-wavelength excitation of [Re(CO)(3)(Pic)Bpy-MTPP][OTf] results in characteristic TRVIS spectra of the S-1 state of the porphyrin that decay with a time constant of 17 ps (M = Mg) or 24 ps (M = Zn). The IR bands of the CS state appear on a time scale of less than 1 ps (Mg) or ca. 5 ps (Zn) and decay giving way to a vibrationally excited (i.e., hot) ground state via back electron transfer. The IR bands of the precursors recover with a time constant of 35 ps (Mg) or 55 ps (Zn). The short lifetimes of the charge-transfer states carry implications for the mechanism of reaction in the presence of triethylamine.

Free atmospheric CO2 enrichment increased above ground biomass but did not affect symbiotic N2-fixation and soil carbon dynamics in a mixed deciduous stand in Wales

Through increases in net primary production (NPP), elevated CO2 is hypothesizes to increase the amount of plant litter entering the soil. The fate of this extra carbon on the forest floor or in mineral soil is currently not clear. Moreover, increased rates of NPP can be maintained only if forests can escape nitrogen limitation. In a Free atmospheric CO2 Enrichment (FACE) experiment near Bangor, Wales, 4 ambient CO2 and 4 FACE plots were planted with patches of Betula pendula, Alnus glutinosa and Fagus sylvatica on a former arable field. Four years after establishment, only a shallow L forest floor litter layer had formed due to intensive bioturbation. Total soil C and N contents increased irrespective of treatment and species as a result of afforestation. We could not detect an additional C sink in the soil, nor were soil C stabilization processes affected by FACE. We observed a decrease of leaf N content in Betula and Alnus under FACE, while the soil C/N ratio decreased regardless of CO2 treatment. The ratio of N taken up from the soil and by N2-fixation in Alnus was not affected by FACE. We infer that increased nitrogen use efficiency is the mechanism by which increased NPP is sustained under elevated CO2 at this site.

The SAFE FOODS framework for improved risk analysis of foods

Three main changes to current risk analysis processes are proposed to improve their transparency, openness, and accountability. First, the addition of a formal framing stage would allow interested parties, experts and officials to work together as needed to gain an initial shared understanding of the issue, the objectives of regulatory action, and alternative risk management measures. Second, the scope of the risk assessment is expanded to include the assessment of health and environmental benefits as well as risks, and the explicit consideration of economic- and social-impacts of risk management action and their distribution. Moreover approaches were developed for deriving improved information from genomic, proteomic and metabolomic profiling methods and for probabilistic modelling of health impacts for risk assessment purposes. Third, in an added evaluation stage, interested parties, experts, and officials may compare and weigh the risks, costs, and benefits and their distribution. As part of a set of recommendations on risk communication, we propose that reports on each stage should be made public.

Tree species diversity interacts with elevated CO2 to induce a greater root system response

As a consequence of land use change and the burning of fossil fuels, atmospheric concentrations of CO2 are increasing and altering the dynamics of the carbon cycle in forest ecosystems. In a number of studies using single tree species, fine root biomass has been shown to be strongly increased by elevated CO2. However, natural forests are often intimate mixtures of a number of co-occurring species. To investigate the interaction between tree mixture and elevated CO2, Alnus glutinosa, Betula pendula and Fagus sylvatica were planted in areas of single species and a three species polyculture in a free-air CO2 enrichment study (BangorFACE). The trees were exposed to ambient or elevated CO2 (580 µmol mol-1) for four years. Fine and coarse root biomass, together with fine root turnover and fine root morphological characteristics were measured. Fine root biomass, and morphology responded differentially to elevated CO2 at different soil depths in the three species when grown in monocultures. In polyculture, a greater response to elevated CO2 was observed in coarse roots to a depth of 20 cm, and fine root area index to a depth of 30 cm. Total fine root biomass was positively affected by elevated CO2 at the end of the experiment, but not by species diversity. Our data suggest that existing biogeochemical cycling models parameterised with data from species grown in monoculture may be underestimating the belowground response to global change.

An investigation into the pathogenic properties of Escherichia coli strains BLR, BL21, DH5 alpha and EQ1

Aims: To examine Escherichia coli strains EQ1, DH5 alpha, BLR and BL21 for known pathogenic mechanisms. Methods and Results: Using specific DNA probes, the strains were shown not to carry the genes encoding invasion, various adhesion phenotypes or expression of a range of enterotoxins. The strains were unable to express long-chain lipopolysaccharide and were susceptible to the effects of serum complement. Using a BALB/c mouse model, the strains were shown to be unable to survive in selected tissues or to persist in the mouse gut. Using a chick model, strains EQ1, BLR and BL21 invaded livers but not spleens; only strain EQ1 persisted in the chick gut. In Merino sheep, only strain EQ1 was detected 6 d postinfection. Conclusions: Escherichia coli strains EQ1, DH5 alpha, BLR and BL21 did not carry the well-recognized pathogenic mechanisms required by strains of E. coli causing the majority of enteric infections. Significance and Impact of the Study: Escherichia coli strains EQ1, DH5 alpha, BLR and BL21 were considered to be non-pathogenic and unlikely to survive in host tissues and cause disease.

Elevated CO2 enrichment induces a differential biomass response in a mixed species temperate forest plantation

• In a free-air CO2 enrichment study (BangorFACE) Alnus glutinosa, Betula pendula and Fagus sylvatica were planted in areas of one, two and three species mixtures (n=4). The trees were exposed to ambient or elevated CO2 (580 µmol mol-1) for four years, and aboveground growth characteristics measured. • In monoculture, the mean effect of CO2 enrichment on aboveground woody biomass was +29, +22 and +16% for A. glutinosa, F. sylvatica, and B. pendula respectively. When the same species were grown in polyculture, the response to CO2 switched to +10, +7 and 0%, for A. glutinosa, B. pendula, and F. sylvatica respectively. • In ambient atmosphere our species grown in polyculture increased aboveground woody biomass from 12.9 ± 1.4 kg m-2 to 18.9 ± 1.0 kg m-2, whereas in an elevated CO2 atmosphere aboveground woody biomass increased from 15.2 ± 0.6 kg m-2 to 20.2 ± 0.6 kg m-2. The overyielding effect of polyculture was smaller (+7%) in elevated CO2 than in an ambient atmosphere (+18%). • Our results show that the aboveground response to elevated CO2 is significantly affected by intra- and inter-specific competition, and that elevated CO2 response may be reduced in forest communities comprised of tree species with contrasting functional traits.

Addressing uncertainty in adaptation planning for agriculture

We present a framework for prioritizing adaptation approaches at a range of timeframes. The framework is illustrated by four case studies from developing countries, each with associated characterization of uncertainty. Two cases on near-term adaptation planning in Sri Lanka and on stakeholder scenario exercises in East Africa show how the relative utility of capacity vs. impact approaches to adaptation planning differ with level of uncertainty and associated lead time. An additional two cases demonstrate that it is possible to identify uncertainties that are relevant to decision making in specific timeframes and circumstances. The case on coffee in Latin America identifies altitudinal thresholds at which incremental vs. transformative adaptation pathways are robust options. The final case uses three crop–climate simulation studies to demonstrate how uncertainty can be characterized at different time horizons to discriminate where robust adaptation options are possible. We find that impact approaches, which use predictive models, are increasingly useful over longer lead times and at higher levels of greenhouse gas emissions. We also find that extreme events are important in determining predictability across a broad range of timescales. The results demonstrate the potential for robust knowledge and actions in the face of uncertainty.

A survey of simultaneous observations of the high-latitude ionosphere and interplanetary magnetic field with EISCAT and AMPTE-UKS

This paper surveys the results of simultaneous observations by the EISCAT incoherent scatter radar and the AMPTE-UKS satellite, made during three periods in September and October 1984, when AMPTE-UKS was in the solar wind on the dayside of the Earth and the UK-POLAR EISCAT experiment was measuring ionospheric parameters at invariant latitudes 70.8–75.0°. A total of 42 h of EISCAT convection velocity data, with 2.5 min resolution, were obtained, together with 28 h of simultaneous 5 s resolution AMPTE-UKS observations of the solar wind and interplanetary magnetic field (IMF). The general features of the AMPTE-UKS data are described in Section 2 and those of the EISCAT data are described in Sections 3 and 4. The main subjects discussed are the form of the plasma convection patterns and their dependence on all three components of the IMF (Section 5), the ionospheric response to abrupt changes in the IMF (Section 6), in particular a sharp ‘southward turning’ of the IMF on 27 October 1984, and a crossing of an IMF sector boundary. Section 7 describes ‘short lived rapid flow burst’, which are believed to be related to flux transfer events at the magnetopause.

Organic contaminant content and physico-chemical characteristics of waste materials recycled in agriculture

A range of wastes representative of materials currently applied, or with future potential to be applied, to agricultural land in the UK as fertilisers and soil improvers or used as animal bedding in livestock production, were investigated. In addition to full physico-chemical characterization, the materials were analysed for a suite of priority organic contaminants. In general, contaminants were present at relatively low concentrations. For example, polychlorinated dibenzo-p-dioxins/dibenzofurans and polychlorinated biphenyls in biosolids and compost-like-outputs (CLOs) were, in most cases, between 5-50 times lower than proposed and implemented European limit values for biosolids or composts applied to agricultural land. However, the technical basis for these limits may need to be re-evaluated. Polybrominated, and mixed halogenated, dibenzo-p-dioxins/dibenzofurans are not currently considered in risk assessments of dioxins and dioxin-like chemicals, but were detected in the biosolids and compost-like-outputs and their potential contribution to the overall toxic equivalency will be assessed. Other, ‘emerging’ contaminants such as perfluoralkyl compounds (PFCs) and organophosphate flame retardants were detected in several of the waste materials, and their potential significance is discussed. The study is part of a wider research programme that will provide evidence to improve confidence in the use of waste-derived materials in agriculture and establish guidelines to protect the food chain where necessary.