Stable oxygen isotope ratios of benthic and planktonic foraminifera from early Miocene sediments of DSDP Site 90-593 on the Challenger Plateau, Pacific Ocean (Table 1)

Oxygen isotope data are compared with relative abundances of selected planktic foraminifera through a ca. 15 m interval at DSDP Site 593 (Tasman Sea, southwest Pacific, 40°S) in which there are prominent changes in population sizes, as well as several evolutionary events. We focus on the relation between faunal and climatic histories. The base of early Miocene oxygen isotope Zone Mi1b (uppermost planktic foraminiferal Zone N.6) is identified from closesampled (c. 14 kyr) isotope records of Globigerina woodi and Cibicides kullenbergi. Chronostratigraphic interpolations, using the first occurrences of Globorotalia praescitula, G. mimea and Praeorbulina curva give an age estimate of ca. 18.4 Ma (cf. 18.1 -18.3 Ma for the base of the zone at DSDP Site 608 (type level, north Atlantic, 43°N) ). Another significant benthic delta18O enrichment event, informally designated as the base of zone "Mi1c", is identified 10 m higher in the sequence at ca. 17.8 Ma. Populations of Globoquadriau dehiscens and Globigerinoides trilobus (inferred to be near the southern margin of their distributions) either reduced considerably or withdrew, particularly in the vicinity of zone "Mi1c". A bioseries linking Globorotalia incognita with G. zealandica developed following the benthic delta18O enrichment spike at the base of Zone Mi1b; the latter species became extinct (at least regionally) just above the base of zone "Mi1c". In contrast, the apparently opportunistic Globorotlia praescitula increased dramatically in abundance at this time; there were also transformations in its architecture, leading to the evolutionary appearance of G. miozea. While planktic foraminifera abundances often do not closely covary with the detailed isotope records and tend to be more stable through time, the near coincidence of evolutionary and biogeographic events with isotopic events suggests at least indirect adaptive responses to climatic changes. Early Miocene middle-latitude planktic foraminiferal evolution, biogeography, and biostratigraphy, may be intimately connected with climatic history.

Late Miocene development of the western Pacific warm pool: Planktonic foraminifer and oxygen isotopic evidence

The disappearance at ~10 Ma of the deep dwelling planktonic foraminifer Globoquadrina dehiscens from the western Pacific including the South China Sea was about 3 Myr earlier than its final extinction elsewhere. Accompanying this event at ~10 Ma was a series of faunal turnover characterized by increase in mixed layer, warm-water species and decrease to a minimum in deepwater species. Paleobiological and isotopic evidence indicates sea surface warming and a deepened local thermocline that we interpret as related to the development of an early western Pacific warm pool. The stepwise decline of G. dehiscens and other deep dwelling species from the NW and SW Pacific suggests more intensive warm water pileup than equatorial localities where surface bypass flow through the narrowing Indonesia seaway appears to remain efficient during the late Miocene. Planktonic delta18O values from the South China Sea consistently lighter than the tropical western Pacific during the Miocene also suggest, similar to today, more variable hydrologic conditions along the periphery than in the core of the warm pool. Stronger hydrologic variability affected mainly by monsoons and increased thermal gradient along the western margin of the late Miocene warm pool may have contributed to the decline of deep dwelling planktonic species including the early extinction of G. dehiscens from the South China Sea region. The late Miocene warm pool became influential and paleobiologically detectable from ~10 Ma, but the modern warm pool did not appear until about 4 Ma, in the middle Pliocene.

Recruitment and training of board members for the 90's and beyond

An historical analysis of the management of the arts in Australia in the last fifty years demonstrates clearly the problems faced by arts organisations which have poorly selected and trained Boards of Directors. Traditionally Board members were selected because they represented the various facets and skills involved in business (marketing, law, accountancy, management, entrepreneurship) or they were arts practitioners or patrons, or they had some particular social standing. Arts organisations recruited Board members like a "mixed bag of lollies - one of these and one of those". No consideration was given to the vital qualities of enthusiasm, reliability, empathy, capacity for hard work, strong arts interest, effective communication skills and respect for organisational processes.

The heat shock protein 90 inhibitor, 17-allylamino-17- demethoxygeldanamycin, enhances osteoclast formation and potentiates bone metastasis of a human breast cancer cell line

Breast cancer metastasis to the bone occurs frequently, causing numerous complications including severe pain, fracture, hypercalcemia, and paralysis. Despite its prevalence and severity, few effective therapies exist. To address this, we examined whether the heat shock protein 90 (Hsp90) inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), would be efficacious in inhibiting breast cancer metastasis to bone. Utilizing the human breast cancer subline, MDA-MB-231SA, previously in vivo selected for its enhanced ability to generate osteolytic bone lesions, we determined that 17-AAG potently inhibited its in vitro proliferation and migration. Moreover, 17-AAG significantly reduced MDA-MB-231SA tumor growth in the mammary-fat pad of nude mice. Despite these findings, 17-AAG enhanced the incidence of bone metastasis and osteolytic lesions following intracardiac inoculation in the nude mouse. Consistent with these findings, 17-AAG enhanced osteoclast formation 2- to 4-fold in mouse bone marrow/osteoblast cocultures, receptor activator of nuclear factor κB ligand (BANKL)-stimulated bone marrow, and RAW264.7 cell models of in vitro osteoclastogenesis. Moreover, the drug enhanced osteoclastogenesis in human cord blood progenitor cells, demonstrating that its effects were not limited to mouse models. In addition to 17-AAG, other Hsp90 inhibitors, such as radicicol and herbimycin A, also enhanced osteoclastogenesis. A pro-osteolytic action of 17-AAG independent of tumor presence was also determined in vivo, in which 17-AAG-treated tumor-naive mice had reduced trabecular bone volume with an associated increase in osteoclast number. Thus, HSP90 inhibitors can stimulate osteoclast formation, which may underlie the increased incidence of osteolysis and skeletal tumor incidence causedby 17-AAG in vivo. These data suggest an important contraindication to the Hsp90 targeted cancer therapy currently undergoing clinical trial.

Comparison of fractional and geodesic anisotropy in diffusion tensor images of 90 monozygotic and dizygotic twins

We used diffusion tensor magnetic resonance imaging (DTI) to reveal the extent of genetic effects on brain fiber microstructure, based on tensor-derived measures, in 22 pairs of monozygotic (MZ) twins and 23 pairs of dizygotic (DZ) twins (90 scans). After Log-Euclidean denoising to remove rank-deficient tensors, DTI volumes were fluidly registered by high-dimensional mapping of co-registered MP-RAGE scans to a geometrically-centered mean neuroanatomical template. After tensor reorientation using the strain of the 3D fluid transformation, we computed two widely used scalar measures of fiber integrity: fractional anisotropy (FA), and geodesic anisotropy (GA), which measures the geodesic distance between tensors in the symmetric positive-definite tensor manifold. Spatial maps of intraclass correlations (r) between MZ and DZ twins were compared to compute maps of Falconer's heritability statistics, i.e. the proportion of population variance explainable by genetic differences among individuals. Cumulative distribution plots (CDF) of effect sizes showed that the manifold measure, GA, comparably the Euclidean measure, FA, in detecting genetic correlations. While maps were relatively noisy, the CDFs showed promise for detecting genetic influences on brain fiber integrity as the current sample expands.

TlCaBa2Cu2O7: The 1122 (90 K) superconductor in the new Tl(Ca,Ba)n+1CunO2n+3 seriesstar, open

The 1122 (n=2) member of the Tl(Ca,Ba)n+1CunO2n+3 series containing a single Tl-O layer is shown to be associated with a Tc of 90 K. This value of Tc is significantly lower than that of the 2122 phase (Tcnot, vert, similar110 K) with two Tl-O layers.

Three-dimensional structure of heat shock protein 90 from Plasmodium falciparum: molecular modelling approach to rational drug design against malaria

We have recently implicated heat shock protein 90 from Plasmodium falciparum (PfHsp90) as a potential drug target against malaria. Using inhibitors specific to the nucleotide binding domain of Hsp90, we have shown potent growth inhibitory effects on development of malarial parasite in human erythrocytes. To gain better understanding of the vital role played by PfHsp90 in parasite growth, we have modeled its three dimensional structure using recently described full length structure of yeast Hsp90. Sequence similarity found between PfHsp90 and yeast Hsp90 allowed us to model the core structure with high confidence. The superimposition of the predicted structure with that of the template yeast Hsp90 structure reveals an RMSD of 3.31 angstrom. The N-terminal and middle domains showed the least RMSD (1.76 angstrom) while the more divergent C-terminus showed a greater RMSD (2.84 angstrom) with respect to the template. The structure shows overall conservation of domains involved in nucleotide binding, ATPase activity, co-chaperone binding as well as inter-subunit interactions. Important co-chaperones known to modulate Hsp90 function in other eukaryotes are conserved in malarial parasite as well. An acidic stretch of amino acids found in the linker region, which is uniquely extended in PfHsp90 could not be modeled in this structure suggesting a flexible conformation. Our results provide a basis to compare the overall structure and functional pathways dependent on PfHsp90 in malarial parasite. Further analysis of differences found between human and parasite Hsp90 may make it possible to design inhibitors targeted specifically against malaria.