Project Chariot - Phase III: Progress Report

This is a preliminary report and is NOT FOR PUBLICATIONBotanical investigations of the Cape Thompson - Ogotoruk Creek region of northwest Alaska were initiated in May, 1959 by the University of Alaska under contract with the United States Atomic Energy Commission (Contract No. AT (04 -3 ) - 310). The first summer's field work was largely exploratory and descriptive in nature and included a species inventory of the vascular plants, mosses, and lichens; a qualitative description of the main vegetation types in Ogotoruk Valley; and a preliminary mapping of the vegetation types within the valley. The results of the first summer's field work and winter visits have been partially reported in two reports: Ogotoruk Valley Botanical Project, December, 1959 Report, and the Phase II Interim Pinal Report, Ogotoruk Valley Botanical Project, June, 1960. For brevity, these will be referred to as the December, 1959 Botanical Report, and the June, 1960 Botanical Report. Materials reported in these earlier reports will not be repeated in this December, 1960 report. Botanical investigations were continued during the summer and fall of 1960. The objectives of the 1960 field season were as follows: 1. To measure the frequency, cover, and synthetic features of the main vegetation types in Ogotoruk Valley. 2. To establish control vegetation plots in areas outside the potential blast and fallout area and to extend our understanding of the vegetation of the northwestern Alaska Coast. 3. To complete records of species occurrence in the area by continuing plant collections and identifications. 4. To revise and complete the vegetation map of the area. 5. To continue seed germination studies on certain species. 6. To commence palynological studies of bog and lacustrine sediments. 7. To initiate studies on some of the ecological problems in the Ogotoruk Valley area. a. to understand the relationship between permafrost, annual freezing-thawing cycles, and plant distribution. b. to understand the inter-relationships of the activities of the arctic ground squirrel and vegetation in the valley. Preliminary results of the 1960 field work and additional information from the 1959 season are included in this report

Integrative biological studies of anti-tumour agents

3, 11-difluoro-6, 8, 13-trimethyl-8H- quino [4, 3, 2-kl] acridinium methosulfate (RHPS4) is a member of a series of pentacyclic acridines developed at the University of Nottingham, which bind to, and stabilise the structure of G-quadruplex DNA and inhibit the action of telomerase at sub-micromolar concentrations in the cell free TRAP assay and limit cancer cell growth therefore leading to the conclusion that RHPS4 has potential anti-tumour activity. Previous biological studies, however, have suggested that the mechanism of action of RHPS4 may be much more complicated than previously anticipated. Exposure of human melanoma cell lines to low doses of RHPS4 reveal an irreversible cessation of growth and telomere erosion. When used at higher doses, RHPS4 elicits short-term apoptosis/senescence concurrent with an increased number of telomere fusions and this is not a result of telomere shortening suggesting that the mechanism of action of RHPS4 is more than that of a simple telomerase inhibitor. In this study, we have developed a systems biology approach to the analysis and integration of biological data from investigations of the activity of RHPS4. The aim of this approach was to link the emergent properties of the biological studies of RHPS4 to a potential molecular target. In the laboratory, we are able to quickly derive data with respect to the time- and concentration- effects of RHPS4 on cell cycle distribution, population doublings and senescence levels, however, the kinetics of the cell cycle are neglected. A mathematical model has been derived of adequate complexity to reproduce the biological results of the laboratory and yet sufficient simplicity to yield predictive information and biological insights into the action of this complex molecule has been developed allowing us to integrate the data we can derive. The mathematical model has five compartments, those being X (representative of G1/G0 phase), Y (representative of S phase), Z (representative of G2/M phase), Σ (representative of senescence) and A (representative of apoptosis) with rate and movement between the compartments denoted by the rate parameters kxy, kyz, kzx, kxΣ and kΣA, respectively. Parameterisation of the mathematical model requires robust data from a well-characterised cell lines and initially four colorectal cell lines were chosen, namely HCT116, HT-29, KM12 and HCC-2998 to determine the short- and long-term effects of RHPS4 on their cell cycle distributions, population doublings and senescence levels. The aim was to determine which of the cell lines displayed good sensitivity to RHPS4, good growth characteristics in the presence and absence of RHPS4 and tractability in a range of biological assays. Initial studies revealed the HCT116 cell line was the most relevant for the further study of RHPS4. Data regarding the effects of RHPS4 on cell cycle distribution, growth rate and senescence over 21 days was derived and fitted to the five-compartment mathematical model to reveal aspects of the action of RHPS4 that would be difficult to appreciate without it. The model suggests that RHPS4 increases the rate of cells moving into a senescent state (indicated by an increase in kxƩ relative to control) and there is inhibition of apoptosis (indicated by a reduction in kƩA relative to control). Data with respect to doxorubicin was also applied to the model and suggested that consistent with RHPS4 there was inhibition of apoptosis relative to control, however, unlike RHPS4, there were initial reductions followed by increases in the rates of cells moving between G1/G0 and S by kxy, S and G2/M by kyz and G2/M and G1/G0 by kzx relative to control in a concentration- and time-dependant manner. This study has highlighted the important role of mathematics in the understanding of biomolecular processes and this is not the end as we have simply allowed the data to speak for itself. This project is the starting point for further, more focussed studies of RHPS4, and other anti-tumour agents. This approach to the analysis of anti-tumour agents is general, however, allows us preliminary insight into the mode of action of RHPS4 and to relate changes observed to potential underlying molecular targets and further the understanding of this complex molecule

The Physical, Chemical and Biological Effects of Crude Oil Spills on Black Spruce Forest, Interior Alaska

... The overall objectives of the study were threefold: 1) To detail the physical effects of crude oil spills in black spruce forests of interior Alaska emphasizing the mode of transport, area of impact vs. time and effects on the active layer and underlying permafrost; 2) To determine the fate of petroleum contaminants once spilled in subarctic terrestrial environments; 3) To evaluate the effects of crude oil spills on vegetation. ..

The lithospheric mantle and lower crust-mantle relationships under Scotland: a xenolithic perspective

In the British Isles the majority of volcanic rocks containing upper mantle and lower crustal xenoliths occur in Scotland. Most of the occurrences are of Carboniferous–Permian age. This paper presents new data on the mineral chemistry of spinel lherzolite xenoliths from the five principal Scottish tectonic terranes. Compositional variations among the minerals emphasize the broad lateral heterogeneity of the subcontinental lithospheric mantle across the region. The remarkable range of Al2O3 v. CaO exhibited by the clinopyroxenes compared with data from other ‘xenolith provinces' emphasizes the extremely complex tectonomagmatic history of the Scottish lithosphere. The generalized age increase from southern and central Scotland to the Northern Highland and Hebridean terranes of the north and NW, with concomitant complexity of geological history, is reflected also by trace element and isotopic studies. Reaction relationships in lherzolites from the Hebridean Terrane, owing to pervasive metasomatism, involve secondary growth of sodic feldspar. This, and light REE enrichment of clinopyroxenes, points to involvement of a natro-carbonatitic melt. Most pyroxenitic xenoliths are inferred to form a basal crustal layer with a generally sharp discontinuity above the underlying (dominantly lherzolitic) mantle. A second discontinuity is inferred to separate these ultramafic cumulates from overlying, broadly cognate metagabbroic cumulates

Single-molecule study of redox control involved in establishing the spinach plastocyanin-cytochrome b6f electron transfer complex

Small diffusible redox proteins play a ubiquitous role in bioenergetic systems, facilitating electron transfer (ET) between membrane bound complexes. Sustaining high ET turnover rates requires that the association between extrinsic and membrane-bound partners is highly specific, yet also sufficiently weak to promote rapid post-ET separation. In oxygenic photosynthesis the small soluble electron carrier protein plastocyanin (Pc) shuttles electrons between the membrane integral cytochrome b6f (cytb6f) and photosystem I (PSI) complexes. Here we use peak-force quantitative nanomechanical mapping (PF-QNM) atomic force microscopy (AFM) to quantify the dynamic forces involved in transient interactions between cognate ET partners. An AFM probe functionalised with Pc molecules is brought into contact with cytb6f complexes, immobilised on a planar silicon surface. PF-QNM interrogates the unbinding force of the cytb6f-Pc interactions at the single molecule level with picoNewton force resolution and on a time scale comparable to the ET time in vivo (ca. 120 μs). Using this approach, we show that although the unbinding force remains unchanged the interaction frequency increases over five-fold when Pc and cytb6f are in opposite redox states, so complementary charges on the cytb6f and Pc cofactors likely contribute to the electrostatic forces that initiate formation of the ET complex. These results suggest that formation of the docking interface is under redox state control, which lowers the probability of unproductive encounters between Pc and cytb6f molecules in the same redox state, ensuring the efficiency and directionality of this central reaction in the ‘Z-scheme’ of photosynthetic ET