Deuterium analysis of ice core GISP2

The Greenland Ice Sheet Project 2 (GISP2) core can enhance our understanding of the relationship between parameters measured in the ice in central Greenland and variability in the ocean, atmosphere, and cryosphere of the North Atlantic Ocean and adjacent land masses. Seasonal (summer, winter) to annual responses of dD and deuterium excess isotopic signals in the GISP2 core to the seesaw in winter temperatures between West Greenland and northern Europe from A.D. 1840 to 1970 are investigated. This seesaw represents extreme modes of the North Atlantic Oscillation, which also influences sea surface temperatures (SSTs), atmospheric pressures, geostrophic wind strength, and sea ice extents beyond the winter season. Temperature excursions inferred from the dD record during seesaw/extreme NAO mode years move in the same direction as the West Greenland side of the seesaw. Symmetry with the West Greenland side of the seesaw suggests a possible mechanism for damping in the ice core record of the lowest decadal temperatures experienced in Europe from A.D. 1500 to 1700. Seasonal and annual deuterium excess excursions during seesaw years show negative correlation with dD. This suggests an isotopic response to a SST/ land temperature seesaw. The isotopic record from GISP2 may therefore give information on both ice sheet and sea surface temperature variability. Cross-plots of dD and d show a tendency for data to be grouped according to the prevailing mode of the seesaw, but do not provide unambiguous identification of individual seesaw years. A combination of ice core and tree ring data sets may allow more confident identification of GA and GB (extreme NAO mode) years prior to 1840.

Lead, sulphate, and aluminium concentrations and lead crustal enrichment factors in Mt. Logan ice core during pre-anthropogenic to modern periods

A high-resolution, 8000 year-long ice core record from the Mt. Logan summit plateau (5300 m asl) reveals the initiation of trans-Pacific lead (Pb) pollution by ca. 1730, and a >10-fold increase in Pb concentration (1981-1998 mean = 68.9 ng/l) above natural background (5.6 ng/l) attributed to rising anthropogenic Pb emissions from Asia. The largest rise in North Pacific Pb pollution from 1970-1998 (end of record) is contemporaneous with a decrease in Eurasian and North American Pb pollution as documented in ice core records from Greenland, Devon Island, and the European Alps. The distinct Pb pollution history in the North Pacific is interpreted to result from the later industrialization and less stringent abatement measures in Asia compared to North America and Eurasia. The Mt. Logan record shows evidence for both a rising Pb emissions signal from Asia and a trans-Pacific transport efficiency signal related to the strength of the Aleutian Low.

Stable isotope stacks from GRIP and GISP ice cores

Recent efforts to link the isotopic composition of snow in Greenland with meteorological and climatic parameters have indicated that relatively local information such as observed annual temperatures from coastal Greenland sites, as well as more synoptic scale features such as the North Atlantic Oscillation (NAO) and the temperature seesaw between Jakobshaven, Greenland, and Oslo, Norway, are significantly correlated with d18O and dD values from the past few hundred years measured in ice cores. In this study we review those efforts and then use a new record of isotope values from the Greenland Ice Sheet Project 2 and Greenland Ice Core Project sites at Summit, Greenland, to compare with meteorological and climatic parameters. This new record consists of six individual annually resolved isotopic records which have been average to produce a Summit stacked isotope record. The stacked record is significantly correlated with local Greenland temperatures over the past century (r=0.471), as well as a number of other records including temperatures and pressures from specific locations as well as temperature and pressure patterns such as the temperature seesaw and the North Atlantic Oscillation. A multiple linear regression of the stacked isotope record with a number of meteorological and climatic parameters in the North Atlantic region reveals that five variables contribute significantly to the variance in the isotope record: winter NAO, solar irradiance (as recorded by sunspot numbers), average Greenland coastal temperature, sea surface temperature in the moisture source region for Summit (30°-20°N), and the annual temperature seesaw between Jakobshaven and Oslo. Combined, these variables yield a correlation coefficient of r=0.71, explaining half of the variance in the stacked isotope record.

Altered recognition mutants of the response regulator PhoB: A new genetic strategy for studying protein–protein interactions

Two-component regulatory systems require highly specific interactions between histidine kinase (transmitter) and response regulator (receiver) proteins. We have developed a novel genetic strategy that is based on tightly regulated synthesis of a given protein to identify domains and residues of an interacting protein that are critical for interactions between them. Using a reporter strain synthesizing the nonpartner kinase VanS under tight arabinose control and carrying a promoter-lacZ fusion activated by phospho-PhoB, we isolated altered recognition (AR) mutants of PhoB showing enhanced activation (phosphorylation) by VanS as arabinose-dependent Lac+ mutants. Changes in the PhoBAR mutants cluster in a “patch” near the proposed helix 4 of PhoB based on the CheY crystal structure (a homolog of the PhoB receiver domain) providing further evidence that helix 4 lies in the kinase-regulator interface. Based on the CheY structure, one mutant has an additional change in a region that may propagate a conformational change to helix 4. The overall genetic strategy described here may also be useful for studying interactions of other components of the vancomycin resistance and Pi signal transduction pathways, other two-component regulatory systems, and other interacting proteins. Conditionally replicative oriRR6Kγ attP “genome targeting” suicide plasmids carrying mutagenized phoB coding regions were integrated into the chromosome of a reporter strain to create mutant libraries; plasmids encoding mutant PhoB proteins were subsequently retrieved by P1-Int-Xis cloning. Finally, the use of similar genome targeting plasmids and P1-Int-Xis cloning should be generally useful for constructing genomic libraries from a wide array of organisms.

TnrA, a transcription factor required for global nitrogen regulation in Bacillus subtilis.

Expression of the Bacillus subtilis nrgAB operon is derepressed during nitrogen-limited growth. We have identified a gene, tnrA, that is required for the activation of nrgAB expression under these growth conditions. Analysis of the DNA sequence of the tnrA gene revealed that it encodes a protein with sequence similarity to GlnR, the repressor of the B. subtilis glutamine synthetase operon. The tnrA mutant has a pleiotropic phenotype. Compared with wild-type cells, the tnrA mutant is impaired in its ability to utilize allantoin, gamma-aminobutyrate, isoleucine, nitrate, urea, and valine as nitrogen sources. During nitrogen-limited growth, transcription of the nrgAB, nasB, gabP, and ure genes is significantly reduced in the tnrA mutant compared with the levels seen in wild-type cells. In contrast, the level of glnRA expression is 4-fold higher in the, tnrA mutant than in wild-type cells during nitrogen restriction. The phenotype of the tnrA mutant indicates that a global nitrogen regulatory system is present in B. subtilis and that this system is distinct from the Ntr regulatory system found in enteric bacteria.

Promising results of a cooperative group phase II trial of preoperative chemoradiation for locally advanced rectal cancer (TROG 9801)

PURPOSE: This article reports the overall survival, failure-free survival, local failure, and late radiation toxicity of a phase II trial of preoperative radiotherapy with continuous infusion 5-fluorouracil for rectal cancer after a minimum 3.5 years of follow-up. METHODS: Eligible patients were those with newly diagnosed localized adenocarcinoma of the rectum, within 12 cm of the anal verge, staged T3-T4 and deemed suitable for curative resection. Radiotherapy (50.4 Gy in 28 fractions in five weeks and three days) was given with continuous infusion 5-fluorouracil throughout the course of radiotherapy. RESULTS: A total of 82 patients were accrued in 13 months. The median follow-up time was 4.1 (range, 2.3-4.5) years. There were 55 males (67 percent) and the median age was 59 (range, 27-87) years. Patients were staged pretreatment as T3 (89 percent) and resectable T4 (11 percent). Endorectal ultrasound was performed in 70 percent and magnetic resonance imaging in another 5 percent. The four-year overall and failure-free survival rates were 82 percent (95 percent Cl: 72-89) and 69 percent (95 percent Cl: 58-78), respectively. The cumulative incidence of local failure at four years was 3.9 percent (95 percent CI: 1.3-11). Risk of failures, local and distant, has not reached a plateau phase. CONCLUSION: This regimen can be delivered safely and without leading to a significant increase in late toxicity. It provides excellent local control and favorable overall survival. There is a need for longer follow-up than has commonly been used for the proper evaluation of failures after an effective regimen of preoperative chemoradiation.