Structural/functional similarity between proteins involved in complement- and cytotoxic T-lymphocyte-mediated cytolysis

Cytolysis mediated by complement or cytolytic lymphocytes results in the formation of morphology similar lesions in the target membrane. These lesions, formed by the polymerization of C9 or perforin respectively, contribute the major killing action by causing osmotic lysis of the target cell. Following the suggestion of Mayer that the mechanisms of humoral and cell-mediated cytotoxicity might be related, studies into the morphology of the membrane lesions formed, and the proteins responsible for causing the lesions, have shown several similarities. While the lesion caused by natural and T-killer cells is a little larger than that caused by complement, its overall shape is similar and in both cases the cylindrical pore is formed by polymerization of a monomeric subunit, C9 (relative molecular mass, Mr = 71,000) for complement, and perforin (Mr = 66,000) for cell-mediated cytotoxicity. C9 has an absolute requirement for a receptor in the target membrane formed by the earlier membrane attack complex components, C5b, C6, C7 and C8 (ref. 8). For perforin, polymerization in a target membrane requires no receptor, specificity being derived from the specific recognition between killer and target cell. Both proteins can be made to polymerize in vitro by the addition of divalent cations (Zn2+ for C9 (ref. 16) and Ca2+ for perforin) and the resultant complexes closely resemble their physiological counterparts. Antibodies raised against lymphocyte-killed targets have also been shown to cross-react with complement proteins, but the antigenically related proteins were not determined in these studies. We show here using purified proteins that perforin, C9 and complexes involving C7 and C8 share a common antigenic determinant which is probably involved in polymerization.     

An inhibitor of Bcl-2 family proteins induces regression of solid tumours

Proteins in the Bcl-2 family are central regulators of programmed cell death, and members that inhibit apoptosis, such as Bcl-X(L) and Bcl-2, are overexpressed in many cancers and contribute to tumour initiation, progression and resistance to therapy. Bcl-X(L) expression correlates with chemo-resistance of tumour cell lines, and reductions in Bcl-2 increase sensitivity to anticancer drugs and enhance in vivo survival. The development of inhibitors of these proteins as potential anti-cancer therapeutics has been previously explored, but obtaining potent small-molecule inhibitors has proved difficult owing to the necessity of targeting a protein-protein interaction. Here, using nuclear magnetic resonance (NMR)-based screening, parallel synthesis and structure-based design, we have discovered ABT-737, a small-molecule inhibitor of the anti-apoptotic proteins Bcl-2, Bcl-X(L) and Bcl-w, with an affinity two to three orders of magnitude more potent than previously reported compounds. Mechanistic studies reveal that ABT-737 does not directly initiate the apoptotic process, but enhances the effects of death signals, displaying synergistic cytotoxicity with chemotherapeutics and radiation. ABT-737 exhibits single-agent-mechanism-based killing of cells from lymphoma and small-cell lung carcinoma lines, as well as primary patient-derived cells, and in animal models, ABT-737 improves survival, causes regression of established tumours, and produces cures in a high percentage of the mice.     

Helium solubility in olivine and implications for high 3He/4He in ocean island basalts

High 3He/4He ratios found in ocean island basalts are the main evidence for the existence of an undegassed mantle reservoir. However, models of helium isotope evolution depend critically on the chemical behaviour of helium during mantle melting. It is generally assumed that helium is strongly enriched in mantle melts relative to uranium and thorium, yet estimates of helium partitioning in mantle minerals have produced conflicting results. Here we present experimental measurements of helium solubility in olivine at atmospheric pressure. Natural and synthetic olivines were equilibrated with a 50% helium atmosphere and analysed by crushing in vacuo followed by melting, and yield a minimum olivine-melt partition coefficient of 0.0025 +/- 0.0005 (s.d.) and a maximum of 0.0060 +/- 0.0007 (s.d.). The results indicate that helium might be more compatible than uranium and thorium during mantle melting and that high 3He/4He ratios can be preserved in depleted residues of melting. A depleted source for high 3He/4He ocean island basalts would resolve the apparent discrepancy in the relative helium concentrations of ocean island and mid-ocean-ridge basalts.     

Gravitational tractor for towing asteroids

We present a design concept for a spacecraft that can controllably alter the trajectory of an Earth-threatening asteroid by using gravity as a towline. The spacecraft hovers near the asteroid, with its thrusters angled outwards so that the exhaust does not impinge on the surface. This proposed deflection method is insensitive to the structure, surface properties and rotation state of the asteroid.     

Habitat of three rare species of small mammals in juniper woodlands of southwestern Wyoming

Southwestern Wyoming constitutes the northern limit of the ranges of the cliff chipmunk ( Tamias dorsalis ), pinyon mouse ( Peromyscus truei ), and canyon mouse ( P. crinitus ). In addition to trying to determine their presence in the region, we wanted to identify habitat characteristics commonly used by each of these species. We used Sherman live-traps to sample 14 sites representing 2 distinct habitat types in 1998 and 1999: juniper-rocky slopes and juniper cliffs. Seventeen habitat characteristics were measured at capture locations for each species and compared with randomly located points. Best subsets multiple logistic regression was used to construct models that distinguish between used and available habitat for each species. The cliff chipmunk occurred in both rocky slopes and cliffs. The pinyon mouse was also captured in rocky slopes and cliffs and was most often captured in locations in the interior of the juniper woodland with high tree canopy cover, high forb cover, and low density of rock outcrops. The canyon mouse was captured only in cliffs at sites consisting of high forb cover, high rock cover, and high tree density.     

High plant diversity is needed to maintain ecosystem services

Biodiversity is rapidly declining worldwide, and there is consensus that this can decrease ecosystem functioning and services. It remains unclear, though, whether few or many of the species in an ecosystem are needed to sustain the provisioning of ecosystem services. It has been hypothesized that most species would promote ecosystem services if many times, places, functions and environmental changes were considered; however, no previous study has considered all of these factors together. Here we show that 84% of the 147 grassland plant species studied in 17 biodiversity experiments promoted ecosystem functioning at least once. Different species promoted ecosystem functioning during different years, at different places, for different functions and under different environmental change scenarios. Furthermore, the species needed to provide one function during multiple years were not the same as those needed to provide multiple functions within one year. Our results indicate that even more species will be needed to maintain ecosystem functioning and services than previously suggested by studies that have either (1) considered only the number of species needed to promote one function under one set of environmental conditions, or (2) separately considered the importance of biodiversity for providing ecosystem functioning across multiple years, places, functions or environmental change scenarios. Therefore, although species may appear functionally redundant when one function is considered under one set of environmental conditions, many species are needed to maintain multiple functions at multiple times and places in a changing world.     

New species of Talinum (Portulaceae) from Utah

New species of Mentzelia and Phacelia are described from northwestern New Mexico, USA, as Mentzelia todiltoensis , N. Duane Atwood & Stanley L. Welsh, and Phacelia sivinskii N. D. Atwood, sp. nov. The new Mentzelia is compared to M. humilis based on similarities in seed, fruit, leaf, and flower morphology and to M. memorabalis in stem, leaf, and fruit morphology. Phacelia sivinskii is compared to P. constancei N. D. Atwood on the basis of seed, leaf, and flower morphology.     

Monitoring temporal change in riparian vegetation of Great Basin National Park

Disturbance in riparian areas of semiarid ecosystems involves complex interactions of pulsed hydrologic flows, herbivory, fire, climatic effects, and anthropogenic influences. We resampled riparian vegetation within ten 10-m × 100-m plots that were initially sampled in 1992 in 4 watersheds of the Snake Range, east central Nevada. Our finding of significantly lower coverage of grasses, forbs, and shrubs within plots in 2001 compared with 1992 was not consistent with the management decision to remove livestock grazing from the watersheds in 1999. Change over time in cover of life-forms or bare ground was not predicted by scat counts within plots in 2001. Cover results were also not well explained by variability between the 2 sampling periods in either density of native herbivores or annual precipitation. In contrast, Engelmann spruce ( Picea engelmannii ) exhibited reduced abundance at all but the highest-elevation plot in which it occurred in 1992, and the magnitude of change in abundance was strongly predicted by plot elevation. Abundance of white fir ( Abies concolor ) individuals increased while aspen ( Populus tremuloides ) individuals decreased at 4 of 5 sites where they were sympatric, and changes in abundance in the 2 species were negatively correlated across those sites. Utility of monitoring data to detect change over time and contribute to adaptive management will vary with sample size, observer bias, use of repeatable or published methods, and precision of measurements, among other factors.     

Astragalus (Leguminosae): nomenclatural proposals and new taxa

This is a summary monograph of the hanging gardens as they occur in the Colorado River and Virgin River portion of the Colorado Plateau in Utah. Discussed in this paper are the hanging gardens, their geography, geomorphology, aspects of distribution and diversity, and principal vascular and algal plant species. Animal trapping studies and pland productivity aspects are reviewed.