A genome-wide association study of metabolic traits in human urine

We present a genome-wide association study of metabolic traits in human urine, designed to investigate the detoxification capacity of the human body. Using NMR spectroscopy, we tested for associations between 59 metabolites in urine from 862 male participants in the population-based SHIP study. We replicated the results using 1,039 additional samples of the same study, including a 5-year follow-up, and 992 samples from the independent KORA study. We report five loci with joint P values of association from 3.2 × 10(-19) to 2.1 × 10(-182). Variants at three of these loci have previously been linked with important clinical outcomes: SLC7A9 is a risk locus for chronic kidney disease, NAT2 for coronary artery disease and genotype-dependent response to drug toxicity, and SLC6A20 for iminoglycinuria. Moreover, we identify rs37369 in AGXT2 as the genetic basis of hyper-β-aminoisobutyric aciduria.     

Diet and the evolution of human amylase gene copy number variation

Starch consumption is a prominent characteristic of agricultural societies and hunter-gatherers in arid environments. In contrast, rainforest and circum-arctic hunter-gatherers and some pastoralists consume much less starch. This behavioral variation raises the possibility that different selective pressures have acted on amylase, the enzyme responsible for starch hydrolysis. We found that copy number of the salivary amylase gene (AMY1) is correlated positively with salivary amylase protein level and that individuals from populations with high-starch diets have, on average, more AMY1 copies than those with traditionally low-starch diets. Comparisons with other loci in a subset of these populations suggest that the extent of AMY1 copy number differentiation is highly unusual. This example of positive selection on a copy number-variable gene is, to our knowledge, one of the first discovered in the human genome. Higher AMY1 copy numbers and protein levels probably improve the digestion of starchy foods and may buffer against the fitness-reducing effects of intestinal disease.     

Axonal loss and neuroinflammation caused by peroxisome-deficient oligodendrocytes

Oligodendrocytes myelinate axons for rapid impulse conduction and contribute to normal axonal functions in the central nervous system. In multiple sclerosis, demyelination is caused by autoimmune attacks, but the role of oligodendroglial cells in disease progression and axon degeneration is unclear. Here we show that oligodendrocytes harbor peroxisomes whose function is essential for maintaining white matter tracts throughout adult life. By selectively inactivating the import factor PEX5 in myelinating glia, we generated mutant mice that developed normally, but within several months showed ataxia, tremor and premature death. Absence of functional peroxisomes from oligodendrocytes caused widespread axonal degeneration and progressive subcortical demyelination, but did not interfere with glial survival. Moreover, it caused a strong proinflammatory milieu and, unexpectedly, the infiltration of B and activated CD8+ T cells into brain lesions. We conclude that peroxisomes provide oligodendrocytes with an essential neuroprotective function against axon degeneration and neuroinflammation, which is relevant for human demyelinating diseases.     

Synchronicity of Antarctic temperatures and local solar insolation on orbital timescales

The Milankovitch theory states that global climate variability on orbital timescales from tens to hundreds of thousands of years is dominated by the summer insolation at high northern latitudes. The supporting evidence includes reconstructed air temperatures in Antarctica that are nearly in phase with boreal summer insolation and out of phase with local summer insolation. Antarctic climate is therefore thought to be driven by northern summer insolation. A clear mechanism that links the two hemispheres on orbital timescales is, however, missing. We propose that key Antarctic temperature records derived from ice cores are biased towards austral winter because of a seasonal cycle in snow accumulation. Using present-day estimates of this bias in the 'recorder' system, here we show that the local insolation can explain the orbital component of the temperature record without having to invoke a link to the Northern Hemisphere. Therefore, the Antarctic ice-core-derived temperature record, one of the best-dated records of the late Pleistocene temperature evolution, cannot be used to support or contradict the Milankovitch hypothesis that global climate changes are driven by Northern Hemisphere summer insolation variations.     

Some difficulties of ecological thinking,considered from a critical systems perspective: A plea for critical holism

We probably have simplified matters too much. We tend to talk about systems thinking and practice as if we knew what they are. The fashionable call for “holistic” or “systems” thinking in ecological issues provides a major example. This much is certain: the quest for comprehensiveness, although it represents an epistemologically necessary idea, is not realizable. If we assume that it is realizable, the critical idea underlying the quest will be perverted into its opposite, i.e., into a false pretension to superior knowledge and understanding—a danger of which the environmental movement does not always appear to be sufficiently aware. My question, therefore, is this: How can we deal critically with the fact that our thinking, and hence our knowledge, designs, and actions, cannot possibly be comprehensive, in the sense that we never “comprehend” all that ought to be understood before we pass to judgment and action? What consequences does this fact imply for a critical systems approach to ecological concerns and, ultimately, for our concepts of rationality in general?     

Zur Diskussion über die Homogenität des Erdinnern

Summary According to considerations put forwards byW. Kuhn andA. Rittmann some years ago, it follows that the chemical composition of the interior of the earth must be rather homogeneous; the well-known discontinuity which occurs at 2900 km with respect to the propagation of longitudinal and transverse waves should not be due to a discontinuity of the material composition (not to an iron core). It is due to a continous decrease of the viscosity and thereby of the relaxation time; transverse waves of a period of e.g. 30 seconds will no more be propagated in a material whose relaxation time for tangential stress is below 30 seconds, while the longitudinal waves will suffer a decrease of the velocity at the same time.A criticism put forward byA. Eucken consists in the argument that a material in which the time of relaxation for tangential stress becomes equal to the period of the vibration will exhibit a considerable absorption coefficient for longitudinal waves too. It is now shown that the distance on which the period of vibration and the relaxation time are approximately equal is small compared with the wave length of the seismic waves in question, from which it follows that the resulting absorption of the longitudinal waves too will only be small.A further consideration shows that a mixture of 99 atomic % hydrogen and 1 atomic % of iron is most probably supercritical at a temperature of 5000° abs.A survey of the solubilities in question shows further that the hydrogen present in a mixture of 90% hydrogen and 10% iron should on the strength of the absorption coefficient be completely absorbed by the iron at 5000° abs. and at a total pressure of 2.10⁶ atmospheres.The main argument why the assumption of an iron core inside the earth must be dismissed remains the fact that the present state must be the result of an asymptotic processus which at least in its final phase has occurred under conditions similar to the present conditions of temperature, pressure and viscosity; these latter conditions are far from permitting the processus of sedimentation etc. which would be required.