A functional role for vasoactive intestinal polypeptide in anterior cingulate cortex

Vasoactive intestinal polypeptide (VIP) is present in high concentrations in the cerebral cortex, where it is the putative neurotransmitter of a major intracortical neuronal system. Homogenates of cortical tissue contain high-affinity, specific binding sites for VIP as well as an adenylate cyclase system which is sensitive to this peptide. As with many of the other peptidergic systems which have been identified in the central nervous system (CNS), it has proved extremely difficult to elucidate the nature and extent of the functional role of VIP in specific brain areas. Here, using the quantitative autoradiographic 14C-deoxyglucose technique in rats to provide insight into functional processes, we describe the increases in glucose utilization which occur locally in anterior cingulate cortex following the unilateral injection of VIP (20 pmol) into this key brain area and, additionally, the focal alterations in glucose use in CNS regions having known neuronal connections with the injected region (for example, ipsilateral mediodorsal thalamus, ventral tegmental area, nucleus accumbens, caudate nucleus and contralateral cingulate cortex). These data provide evidence that VIP may modify the processing of afferent and efferent information within the anterior cingulate cortex in the conscious rat.     

Preferential cis-syn thymine dimer bypass by DNA polymerase eta occurs with biased fidelity

Human DNA polymerase eta (Pol eta) modulates susceptibility to skin cancer by promoting DNA synthesis past sunlight-induced cyclobutane pyrimidine dimers that escape nucleotide excision repair (NER). Here we have determined the efficiency and fidelity of dimer bypass. We show that Pol eta copies thymine dimers and the flanking bases with higher processivity than it copies undamaged DNA, and then switches to less processive synthesis. This ability of Pol eta to sense the dimer location as synthesis proceeds may facilitate polymerase switching before and after lesion bypass. Pol eta bypasses a dimer with low fidelity and with higher error rates at the 3' thymine than at the 5' thymine. A similar bias is seen with Sulfolobus solfataricus DNA polymerase 4, which forms a Watson-Crick base pair at the 3' thymine of a dimer but a Hoogsteen base pair at the 5' thymine (ref. 3). Ultraviolet-induced mutagenesis is also higher at the 3' base of dipyrimidine sequences. Thus, in normal people and particularly in individuals with NER-defective xeroderma pigmentosum who accumulate dimers, errors made by Pol eta during dimer bypass could contribute to mutagenesis and skin cancer.     

Specific distribution of metabolic alterations in cerebral cortex following apomorphine administration

The topographic distribution of dopaminergic receptors in the cerebral cortex closely parallels that of the dopaminergic innervation. In the rat, dopaminergic axons which originate in the mesencephalon are confined to a few discrete regions of the neocortex--anterior cingulate cortex, entorhinal cortex, frontal cortex (particularly anteromedial and supragenual areas) and the transitional zone between the neocortex and the pyriform cortex. Moreover, biochemical examinations of processes generally considered to be indicative of dopaminergic neuro-transmission--neuronal uptake of labelled dopamine or dopamine-activation of adenylate cyclase activity--have confirmed a highly restricted locus of action of dopaminergic systems in the cerebral cortex. We describe here data obtained using the 2-deoxyglucose technique in conjunction with conventional neuropharmacological techniques, suggesting that the influence of dopaminergic systems on cortical function extends beyond the known confines of the mesocortical dopaminergic system.     

Seasonal characteristics of the Indian Ocean Dipole during the Holocene epoch

The Indian Ocean Dipole (IOD)--an oscillatory mode of coupled ocean-atmosphere variability--causes climatic extremes and socio-economic hardship throughout the tropical Indian Ocean region. There is much debate about how the IOD interacts with the El Ni?o/Southern Oscillation (ENSO) and the Asian monsoon, and recent changes in the historic ENSO-monsoon relationship raise the possibility that the properties of the IOD may also be evolving. Improving our understanding of IOD events and their climatic impacts thus requires the development of records defining IOD activity in different climatic settings, including prehistoric times when ENSO and the Asian monsoon behaved differently from the present day. Here we use coral geochemical records from the equatorial eastern Indian Ocean to reconstruct surface-ocean cooling and drought during individual IOD events over the past approximately 6,500 years. We find that IOD events during the middle Holocene were characterized by a longer duration of strong surface ocean cooling, together with droughts that peaked later than those expected by El Ni?o forcing alone. Climate model simulations suggest that this enhanced cooling and drying was the result of strong cross-equatorial winds driven by the strengthened Asian monsoon of the middle Holocene. These IOD-monsoon connections imply that the socioeconomic impacts of projected future changes in Asian monsoon strength may extend throughout Australasia.     

Low European methyl chloroform emissions inferred from long-term atmospheric measurements

Methyl chloroform (CH3CCl3, 1,1,1,-trichloroethane) was used widely as a solvent before it was recognized to be an ozone-depleting substance and its phase-out was introduced under the Montreal Protocol. Subsequently, its atmospheric concentration has declined steadily and recent European methyl chloroform consumption and emissions were estimated to be less than 0.1 gigagrams per year. However, data from a short-term tropospheric measurement campaign (EXPORT) indicated that European methyl chloroform emissions could have been over 20 gigagrams in 2000 (ref. 6), almost doubling previously estimated global emissions. Such enhanced emissions would significantly affect results from the CH3CC13 method of deriving global abundances of hydroxyl radicals (OH) (refs 7-12)-the dominant reactive atmospheric chemical for removing trace gases related to air pollution, ozone depletion and the greenhouse effect. Here we use long-term, high-frequency data from Mace Head, Ireland and Jungfraujoch, Switzerland, to infer European methyl chloroform emissions. We find that European emission estimates declined from about 60 gigagrams per year in the mid-1990s to 0.3-1.4 and 1.9-3.4 gigagrams per year in 2000-03, based on Mace Head and Jungfraujoch data, respectively. Our European methyl chloroform emission estimates are therefore higher than calculated from consumption data, but are considerably lower than those derived from the EXPORT campaign in 2000 (ref. 6).     

Coral record of increased sediment flux to the inner Great Barrier Reef since European settlement

The effect of European settlement on water quality in the Great Barrier Reef of Australia is a long-standing and controversial issue. Erosion and sediment transport in river catchments in this region have increased substantially since European settlement, but the magnitude of these changes remains uncertain. Here we report analyses of Ba/Ca ratios in long-lived Porites coral from Havannah Reef--a site on the inner Great Barrier Reef that is influenced by flood plumes from the Burdekin river--to establish a record of sediment fluxes from about 1750 to 1998. We find that, in the early part of the record, suspended sediment from river floods reached the inner reef area only occasionally, whereas after about 1870--following the beginning of European settlement--a five- to tenfold increase in the delivery of sediments is recorded with the highest fluxes occurring during the drought-breaking floods. We conclude that, since European settlement, land-use practices such as clearing and overstocking have led to major degradation of the semi-arid river catchments, resulting in substantially increased sediment loads entering the inner Great Barrier Reef.