An unexpected specialization for horizontal disparity in primate primary visual cortex

The horizontal separation of the eyes means that objects nearer or farther than the fixation point project to different locations on the two retinae, differing principally in their horizontal coordinates (horizontal binocular disparity). Disparity-selective neurons have generally been studied with disparities applied in only one direction (often horizontal), which cannot determine whether the encoding is specialized for processing disparities along the horizontal axis. It is therefore unclear if disparity selectivity represents a specialization for naturally occurring disparities. I used random dot stereograms to study disparity-selective neurons from the primary visual cortex (V1) of awake fixating monkeys. Many combinations of vertical and horizontal disparity were used, characterizing the surface of responses as a function of two-dimensional disparity. Here I report that the response surface usually showed elongation along the horizontal disparity axis, despite the isotropic stimulus. Thus these neurons modulated their firing rate over a wider range of horizontal disparity than vertical disparity. This demonstrates that disparity-selective cells are specialized for processing horizontal disparity, and that existing models of disparity selectivity require substantial revision.     

Agricultural sustainability and intensive production practices

A doubling in global food demand projected for the next 50 years poses huge challenges for the sustainability both of food production and of terrestrial and aquatic ecosystems and the services they provide to society. Agriculturalists are the principal managers of global usable lands and will shape, perhaps irreversibly, the surface of the Earth in the coming decades. New incentives and policies for ensuring the sustainability of agriculture and ecosystem services will be crucial if we are to meet the demands of improving yields without compromising environmental integrity or public health.     

Thyroid hormone controls carnitine status through modifications of γ-butyrobetaine hydroxylase activity and gene expression

The carnitine system plays a key role in β-oxidation of long-chain fatty acids by permitting their transport into the mitochondrial matrix. The effects of hypothyroidism and hyperthyroidism were studied on γ-butyrobetaine hydroxylase (BBH), the enzyme responsible for carnitine biosynthesis in the rat. In rat liver, BBH activity was decreased in the hypothyroid state and increased in hyperthyroid animals. The modifications in BBH activity correlated with changes in the enzyme Vmax values. These changes were shown to be related to hepatic BBH mRNA abundance. Thyroid hormones are known to interact with lipid metabolism, in particular by increasing long-chain fatty acid oxidation through activation of carnitine-dependent fatty acid import into mitochondria. Our study showed that thyroid hormones also increased carnitine bioavailability. Received 23 October 2001; received after revision 11 January 2002; accepted 15 January 2002     

Initiation of cancer and other diseases by catechol ortho-quinones: a unifying mechanism

Exposure to estrogens is a risk factor for breast and other human cancers. Initiation of breast, prostate and other cancers has been hypothesized to result from reaction of specific estrogen metabolites, catechol estrogen-3,4-quinones, with DNA to form depurinating adducts at the N-7 of guanine and N-3 of adenine by 1,4-Michael addition. The catechol of the carcinogenic synthetic estrogen hexestrol, a hydrogenated derivative of diethylstilbestrol, is metabolized to its quinone, which reacts with DNA to form depurinating adducts at the N-7 of guanine and N-3 of adenine. The catecholamine dopamine and the metabolite catechol (1,2-dihydroxybenzene) of the leukemogen benzene can also be oxidized to their quinones, which react with DNA to form predominantly analogous depurinating adducts. Apurinic sites formed by depurinating adducts are converted into tumor-initiating mutations by error-prone repair. These mutations could initiate cancer by estrogens and benzene, and Parkinson's disease by the neurotransmitter dopamine. These data suggest a unifying molecular mechanism of initiation for many cancers and neurodegenerative diseases and lay the groundwork for designing strategies to assess risk and prevent these diseases. Received 4 September 2001; received after revision 28 November 2001; accepted 2 December 2001     

Mutant deoxynucleotide carrier is associated with congenital microcephaly

The disorder Amish microcephaly (MCPHA) is characterized by severe congenital microcephaly, elevated levels of alpha-ketoglutarate in the urine and premature death. The disorder is inherited in an autosomal recessive pattern and has been observed only in Old Order Amish families whose ancestors lived in Lancaster County, Pennsylvania. Here we show, by using a genealogy database and automated pedigree software, that 23 nuclear families affected with MCPHA are connected to a single ancestral couple. Through a whole-genome scan, fine mapping and haplotype analysis, we localized the gene affected in MCPHA to a region of 3 cM, or 2 Mb, on chromosome 17q25. We constructed a map of contiguous genomic clones spanning this region. One of the genes in this region, SLC25A19, which encodes a nuclear mitochondrial deoxynucleotide carrier (DNC), contains a substitution that segregates with the disease in affected individuals and alters an amino acid that is highly conserved in similar proteins. Functional analysis shows that the mutant DNC protein lacks the normal transport activity, implying that failed deoxynucleotide transport across the inner mitochondrial membrane causes MCPHA. Our data indicate that mitochondrial deoxynucleotide transport may be essential for prenatal brain growth.     

The role of the thermohaline circulation in abrupt climate change

The possibility of a reduced Atlantic thermohaline circulation in response to increases in greenhouse-gas concentrations has been demonstrated in a number of simulations with general circulation models of the coupled ocean-atmosphere system. But it remains difficult to assess the likelihood of future changes in the thermohaline circulation, mainly owing to poorly constrained model parameterizations and uncertainties in the response of the climate system to greenhouse warming. Analyses of past abrupt climate changes help to solve these problems. Data and models both suggest that abrupt climate change during the last glaciation originated through changes in the Atlantic thermohaline circulation in response to small changes in the hydrological cycle. Atmospheric and oceanic responses to these changes were then transmitted globally through a number of feedbacks. The palaeoclimate data and the model results also indicate that the stability of the thermohaline circulation depends on the mean climate state.     

Three-dimensional X-ray structural microscopy with submicrometre resolution

Advanced materials and processing techniques are based largely on the generation and control of non-homogeneous microstructures, such as precipitates and grain boundaries. X-ray tomography can provide three-dimensional density and chemical distributions of such structures with submicrometre resolution; structural methods exist that give submicrometre resolution in two dimensions; and techniques are available for obtaining grain-centroid positions and grain-average strains in three dimensions. But non-destructive point-to-point three-dimensional structural probes have not hitherto been available for investigations at the critical mesoscopic length scales (tenths to hundreds of micrometres). As a result, investigations of three-dimensional mesoscale phenomena--such as grain growth, deformation, crumpling and strain-gradient effects--rely increasingly on computation and modelling without direct experimental input. Here we describe a three-dimensional X-ray microscopy technique that uses polychromatic synchrotron X-ray microbeams to probe local crystal structure, orientation and strain tensors with submicrometre spatial resolution. We demonstrate the utility of this approach with micrometre-resolution three-dimensional measurements of grain orientations and sizes in polycrystalline aluminium, and with micrometre depth-resolved measurements of elastic strain tensors in cylindrically bent silicon. This technique is applicable to single-crystal, polycrystalline, composite and functionally graded materials.     

Diurnal modulation of pacemaker potentials and calcium current in the mammalian circadian clock

The central biological clock of the mammalian brain is located in the suprachiasmatic nucleus. This hypothalamic region contains neurons that generate a circadian rhythm on a single-cell basis. Clock cells transmit their circadian timing signals to other brain areas by diurnal modulation of their spontaneous firing rate. The intracellular mechanism underlying rhythm generation is thought to consist of one or more self-regulating molecular loops, but it is unknown how these loops interact with the plasma membrane to modulate the ionic conductances that regulate firing behaviour. Here we demonstrate a diurnal modulation of Ca2+ current in suprachiasmatic neurons. This current strongly contributes to the generation of spontaneous oscillations in membrane potential, which occur selectively during daytime and are tightly coupled to spike generation. Thus, day-night modulation of Ca2+ current is a central step in transducing the intracellular cycling of molecular clocks to the rhythm in spontaneous firing rate.