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

Onset of recent rapid sea-level rise in the western Atlantic Ocean

A high-resolution record of sea-level change spanning the past 1000 years is derived from foraminiferal and chronological analyses of a 2m thick salt-marsh peat sequence at Chezzetcook, Nova Scotia, Canada. Former mean tide level positions are reconstructed with a precision of +/- 0.055 in using a transfer function derived from distributions of modern salt-marsh foraminifera. Our age model for the core section older than 300 years is based on 19 AMS C-14 ages and takes into account the individual probability distributions of calibrated radiocarbon ages. The past 300 years is dated by pollen and the isotopes Pb-206, Pb-207, Pb-210, Cs-137 and Am-241. Between AD 1000 and AD 1800, relative sea level rose at a mean rate of 17cm per century. Apparent pre-industrial rises of sea level dated at AD 1500-1550 and AD 1700-1800 cannot be clearly distinguished when radiocarbon age errors are taken into account. Furthermore, they may be an artefact of fluctuations in atmospheric C-14 production. In the 19th century sea level rose at a mean rate of 1.6mm/yr. Between AD 1900 and AD 1920, sea-level rise accelerated to the modern mean rate of 3.2mm/yr. This acceleration corresponds in time with global temperature rise and may therefore be associated with recent global warming. (c) 2005 Elsevier Ltd. All rights reserved.

Making development simple. The genetic deterministic hypothesis for economic development

This paper discusses the dangers inherent in allempting to simplify something as complex as development. It does this by exploring the Lynn and Vanhanen theory of deterministic development which asserts that varying levels of economic development seen between countries can be explained by differences in 'national intelligence' (national IQ). Assuming that intelligence is genetically determined, and as different races have been shown to have different IQ, then they argue that economic development (measured as GDP/capita) is largely a function of race and interventions to address imbalances can only have a limited impact. The paper presents the Lynne and Vanhanen case and critically discusses the data and analyses (linear regression) upon which it is based. It also extends the cause-effect basis of Lynne and Vanhanen's theory for economic development into human development by using the Human Development Index (HDI). It is argued that while there is nothing mathematically incorrect with their calculations, there are concerns over the data they employ. Even more fundamentally it is argued that statistically significant correlations between the various components of the HDI and national IQ can occur via a host of cause-effect pathways, and hence the genetic determinism theory is far from proven. The paper ends by discussing the dangers involved in the use of over-simplistic measures of development as a means of exploring cause-effect relationships. While the creators of development indices such as the HDI have good intentions, simplistic indices can encourage simplistic explanations of under-development. (c) 2005 Elsevier B.V. All rights reserved.

The geography of tyranny and despair: development indicators and the hypothesis of genetic inevitability of national inequality

Development geography has long sought to understand why inequalities exist and the best ways to address them. Dependency theory sets out an historical rationale for under development based on colonialism and a legacy of developed core and under-developed periphery. Race is relevant in this theory only insofar that Europeans are white and the places they colonised were occupied by people with darker skin colour. There are no innate biological reasons why it happened in that order. However, a new theory for national inequalities proposed by Lynn and Vanhanen in a series of publications makes the case that poorer countries have that status because of a poorer genetic stock rather than an accident of history. They argue that IQ has a genetic basis and IQ is linked to ability. Thus races with a poorer IQ have less ability, and thus national IQ can be positively correlated with performance as measured by an indicator like GDP/capita. Their thesis is one of despair, as little can be done to improve genetic stock significantly other than a programme of eugenics. This paper summarises and critiques the Lynn and Vanhanen hypothesis and the assumptions upon which it is based, and uses this analysis to show how a human desire to simplify in order to manage can be dangerous in development geography. While the attention may naturally be focused on the 'national IQ' variables as a proxy measure of 'innate ability', the assumption of GDP per capita as an indicator of 'success' and 'achievement' is far more readily accepted without criticism. The paper makes the case that the current vogue for indicators, indices and cause-effect can be tyrannical.

Rapid characterisation of archaeological midden components using FT-IR spectroscopy, SEM-EDX and micro-XRD

Samples taken from middens at the Neolithic site of Catalhoyuk in Turkey have been analysed using IR spectroscopy backed up by powder XRD and SEM-EDX. Microcomponents studied include fossil hack-berries (providing evidence of ancient diet and seasonality), mineral nodules (providing evidence of post-depositional change) and phytoliths (mineralised plant cells, providing evidence of usage of plant species). Finely laminated ashy deposits have also been investigated allowing chemical and mineralogical variations to be explored. It is found that many layers which appear visually to be quite distinctive have, in fact, very similar mineralogy. (C) 2009 Elsevier B.V. All rights reserved.

Carbon dioxide induced stomatal closure increases radiative forcing of climate via a rapid reduction in low cloud

We performed an ensemble of twelve five-year experiments using a coupled climate-carbon-cycle model with scenarios of prescribed atmospheric carbon dioxide concentration; CO2 was instantaneously doubled or quadrupled at the start of the experiments. Within these five years, climate feedback is not significantly influenced by the effects of climate change on the carbon system. However, rapid changes take place, within much less than a year, due to the physiological effect of CO2 on plant stomatal conductance, leading to adjustment in the shortwave cloud radiative effect over land, due to a reduction in low cloud cover. This causes a 10% enhancement to the radiative forcing due to CO2, which leads to an increase in the equilibrium warming of 0.4 and 0.7 K for doubling and quadrupling. The implications for calibration of energy-balance models are discussed.

Rapid word learning by 15-month-olds under tightly-controlled conditions

Infants (12 to 17 months) were taught 2 novel words for 2 images of novel objects, by pairing isolated auditory labels with to-be-associated images. Comprehension was tested using a preferential looking task in which the infant was presented with both images together with an isolated auditory label. The auditory label usually, but not always, matched one of the images. Infants looked preferentially at images that matched the auditory stimulus. The experiment controlled within-subjects for both side bias and preference for previously named items. Infants showed learning after 12 presentations of the new words. Evidence is presented that, in certain circumstances, the duration of longest look at a target may be a more robust measure of target preference than overall looking time. The experiment provides support for previous demonstrations of rapid word learning by pre-vocabulary spurt children, and offers some methodological improvements to the preferential looking task.

Rapid synthesis of carbohydrate derivatives, including mimetics of c-linked disaccharides and c-Linked aza disaccharides, using the Hetero-Diels−Alder Reaction

In this work we demonstrate the value of performing a Hetero Diels-Alder reaction (HDAR) between Danishefsky’s diene and a range of aldehydes or imines, under microwave irradiation. By using a range of aldehydes and imines, including those derived from carbohydrates, access to functionalised 2,3-dihydro-4H-pyran-4-ones or 2,3-dihydro-4-pyridinones in good to excellent synthetic yields is possible. A particular strength of the methodology is its ability to access mimetics of C-linked disaccharides and C-linked aza disaccharides, targets of current therapeutic interest, in a rapid, convenient and diastereoselective manner. The effect of high pressure on the HDARs involving carbohydrate derived aldehydes and imines is also explored, with enhancement in yields occurring for the aldehyde substrates. Finally, HDARs using carbohydrate derived ketones, enones and enals are described under a range of conditions. Optimum results were obtained under high pressure conditions, with highly functionalized carbohydrate derivatives being afforded, in good yields, in this way.

Chlorophyll fluorescence technique as a rapid diagnostic test of the effects of the photosynthetic inhibitor chlorotoluron on two winter wheat cultivars

A modified chlorophyll fluorescence technique was evaluated as a rapid diagnostic test of the susceptibility of wheat cultivars to chlorotoluron. Two winter wheat cultivars (Maris Huntsman and Mercia) exhibited differential response to the herbicide. All of the parameters of chlorophyll fluorescence examined were strongly influenced by herbicide concentration. Additionally, the procedure adopted here for the examination of winter wheat cultivar sensitivity to herbicide indicated that the area above the fluorescence induction curve and the ratio F-V/F-M are appropriate chlorophyll fluorescence parameters for detection of differential herbicide response between wheat cultivars. The potential use of this technique as an alternative to traditional methods of screening new winter wheat cultivars for their response to photosynthetic inhibitor herbicide is demonstrated here.

Evaluating the role of environmental quality in the sustainable rural economic development of England

The issue of the sustainable development of rural economies in England has recently received considerable attention. This is because many of the poorest areas in the country are rural, often of high environmental quality, but suffering from high unemployment and a lack of services and facilities. The rapid decline in agricultural incomes and in-migration of affluent urban workers since 1990 has exacerbated economic inequality in such areas. A number of factors have the potential to drive rural development and this paper applies, and considers, the feasibility of a method from the USA for combining economic and environmental variables in a regional growth model to examine the hypothesis that environmental quality is an important determinant of sustainable rural development in England. The model output suggests that, although environmental quality does play a role in sustainable rural development in England there are other, more important, factors driving development. These include business and communications infra-structure, the degree and opportunities for commuting and underlying employment prospects. The robustness and limitations of the method for combining economic and environmental variables is discussed in relation to the spatial interrelatedness of Local Authority Districts in England, and conclusions are drawn about areas for refinement and improvement of the method.

Examination of the persistency of milk fatty acid composition responses to fish oil and sunflower oil in the diet of dairy cows

Based on the potential benefits of cis-9, trans-11 conjugated linoleic acid (CLA) for human health, there is a need to develop effective strategies for enhancing milk fat CLA concentrations. Levels of cis-9, trans-11 CLA in milk can be increased by supplements of fish oil (FO) and sunflower oil (SO), but there is considerable variation in the response. Part of this variance may reflect time-dependent ruminal adaptations to high levels of lipid in the diet, which lead to alterations in the formation of specific biohydrogenation intermediates. To test this hypothesis, 16 late lactation Holstein-British Friesian cows were used in a repeated measures randomized block design to examine milk fatty acid composition responses to FO and SO in the diet over a 28-d period. Cows were allocated at random to corn silage-based rations (8 per treatment) containing 0 (control) or 45 g of oil supplement/ kg of dry matter consisting (1:2; wt/wt) of FO and SO (FSO), and milk composition was determined on alternate days from d 1. Compared with the control, the FSO diet decreased mean dry matter intake (21.1 vs. 17.9 kg/d), milk fat (47.7 vs. 32.6 g/kg), and protein content (36.1 vs. 33.3 g/kg), but had no effect on milk yield (27.1 vs. 26.4 kg/d). Reductions in milk fat content relative to the FSO diet were associated with increases in milk trans-10 18: 1, trans-10, cis-12 CLA, and trans-9, cis-11 CLA concentrations (r(2) = 0.74, 0.57, and 0.80, respectively). Compared with the control, the FSO diet reduced milk 4: 0 to 18: 0 and cis 18:1 content and increased trans 18:1, trans 18:2, cis-9, trans-11 CLA, 20: 5 n-3, and 22: 6 n-3 concentrations. The FSO diet caused a rapid elevation in milk cis-9, trans-11 CLA content, reaching a maximum of 5.37 g/100 g of fatty acids on d 5, but these increases were transient, declining to 2.35 g/100 g of fatty acids by d 15. They remained relatively constant thereafter. Even though concentrations of trans-11 18: 1 followed the same pattern of temporal changes as cis-9, trans-11 CLA, the total trans 18:1 content of FSO milk was unchanged because of the concomitant increases in the concentration of other isomers (Delta(4-10) and Delta(12-15)), predominantely trans-10 18:1. In conclusion, supplementing diets with FSO enhances milk fat cis-9, trans-11 CLA content, but the high level of enrichment declines because of changes in ruminal biohydrogenation that result in trans-10 replacing trans-11 as the major 18:1 biohydrogenation intermediate formed in the rumen.