Southern Hemisphere control on Australian monsoon variability during the late deglaciation and Holocene

The evolution of the Australian monsoon in relation to high-latitude temperature fluctuations over the last termination remains highly enigmatic. Here we integrate high-resolution riverine runoff and dust proxy data from X-ray fluorescence scanner measurements in four well-dated sediment cores, forming a NE–SW transect across the Timor Sea. Our records reveal that the development of the Australian monsoon closely followed the deglacial warming history of Antarctica. A minimum in riverine runoff documents dry conditions throughout the region during the Antarctic Cold Reversal (15–12.9 ka). Massive intensification of the monsoon coincided with Southern Hemisphere warming and intensified greenhouse forcing over Australia during the atmospheric CO2 rise at 12.9–10 ka. We relate the earlier onset of the monsoon in the Timor Strait (13.4 ka) to regional changes in landmass exposure during deglacial sea-level rise. A return to dryer conditions occurred between 8.1 and 7.3 ka following the early Holocene runoff maximum

Aib-based peptide backbone as scaffolds for helical peptide mimics

Helical peptides that can intervene and disrupt therapeutically important protein-protein interactions are attractive drug targets. In order to develop a general strategy for developing such helical peptide mimics, we have studied the effect of incorporating α-amino isobutyric acid (Aib), an amino acid with strong preference for helical backbone, as the sole helix promoter in designed peptides. Specifically, we focus on the hdm2-p53 interaction, which is central to development of many types of cancer. The peptide corresponding to the hdm2 interacting part of p53, helical in bound state but devoid of structure in solution, served as the starting point for peptide design that involved replacement of noninteracting residues by Aib. Incorporation of Aib, while preserving the interacting residues, led to significant increase in helical structure, particularly at the C-terminal region as judged by nuclear magnetic resonance and circular dichroism. The interaction with hdm2 was also found to be enhanced. Most interestingly, trypsin cleavage was found to be retarded by several orders of magnitude. We conclude that incorporation of Aib is a feasible strategy to create peptide helical mimics with enhanced receptor binding and lower protease cleavage rate

Childhood lead exposure in the British Isles during the industrial revolution

Man-made toxin exposure is one of the defining characteristics of the second epidemiological transition. Our analysis of previous data shows that lead levels in tooth enamel above 0.87 ppm are characteristic of exposure to anthropogenic lead. In British prehistoric and Early Medieval populations very low lead concentrations have been observed, but Roman, later Medieval and Post-medieval populations show much higher levels, up to 90 ppm. Our measurements of lead concentrations within the tooth enamel of four 17th and 18th century populations from Coventry and London show no detectable association between lead exposure and cribra orbitalia (as a possible indicator of anaemia caused by plumbism), but do show population differences which we attribute to lower exposure of poor and rural people compared to rich and urban people. No differences in lead exposure by sex were found. Lead isotope ratios indicate that coal smoke was not a major contributor to lead exposure, but that ingested lead from artefacts is the most likely source. We show that the lead to which people were exposed in the post-medieval period has a similar average isotope ratio to that in the Roman period, but differs from early and later medieval periods