Phylogeography of New Zealand’s coastal benthos

During the past 30 years, 42 molecular studies have been undertaken in New Zealand to examine the phylogeography of coastal benthic invertebrates and plants. Here, we identify generalities and/or patterns that have emerged from this research and consider the processes implicated in generating genetic structure within populations. Studies have used various molecular markers and examined taxonomic groups with a range of life histories and dispersal strategies. Genetic disjunctions have been identified at multiple locations, with the most frequently observed division occurring between northern and southern populations at the top of the South Island. Although upwelling has been implicated as a cause of this disjunction, oceanographic evidence is lacking and alternative hypotheses exist. A significant negative correlation between larval duration and genetic differentiation (r2 = 0.39, P < 0.001, n = 29) across all studies suggests that larval duration might be used as a proxy for dispersal potential. However, among taxa with short larval durations (<10 days) there was greater variability in genetic differentiation than among taxa with longer pelagic periods. This variability implies that when larval duration is short, other factors may determine dispersal and connectivity among populations. Although there has been little congruence between the phylogeographic data and recognised biogeographic regions, recent research has resolved population subdivision at finer spatial scales corresponding more closely with existing biogeographic classifications. The use of fast-evolving and ecologically significant molecular markers in hypothesis-driven research could further improve our ability to detect population subdivision and identify the processes structuring marine ecosystems

Automated detection of galaxy-scale gravitational lenses in high resolution imaging data

Lens modeling is the key to successful and meaningful automated strong galaxy-scale gravitational lens detection. We have implemented a lens-modeling "robot" that treats every bright red galaxy (BRG) in a large imaging survey as a potential gravitational lens system. Using a simple model optimized for "typical" galaxy-scale lenses, we generate four assessments of model quality that are used in an automated classification. The robot infers the lens classification parameter H that a human would have assigned; the inference is performed using a probability distribution generated from a human-classified training set, including realistic simulated lenses and known false positives drawn from the HST/EGS survey. We compute the expected purity, completeness and rejection rate, and find that these can be optimized for a particular application by changing the prior probability distribution for H, equivalent to defining the robot's "character." Adopting a realistic prior based on the known abundance of lenses, we find that a lens sample may be generated that is ~100% pure, but only ~20% complete. This shortfall is due primarily to the over-simplicity of the lens model. With a more optimistic robot, ~90% completeness can be achieved while rejecting ~90% of the candidate objects. The remaining candidates must be classified by human inspectors. We are able to classify lens candidates by eye at a rate of a few seconds per system, suggesting that a future 1000 square degree imaging survey containing 10^7 BRGs, and some 10^4 lenses, could be successfully, and reproducibly, searched in a modest amount of time. [Abridged]Comment: 17 pages, 11 figures, submitted to Ap

A peptide trivalent arsenical inhibits tumor angiogenesis by perturbing mitochondrial function in angiogenic endothelial cells

AbstractMitochondria are the powerhouse of the cell and their disruption leads to cell death. We have used a peptide trivalent arsenical, 4-(N-(S-glutathionylacetyl)amino) phenylarsenoxide (GSAO), to inactivate the adenine nucleotide translocator (ANT) that exchanges matrix ATP for cytosolic ADP across the inner mitochondrial membrane and is the key component of the mitochondrial permeability transition pore (MPTP). GSAO triggered Ca2+-dependent MPTP opening by crosslinking Cys160 and Cys257 of ANT. GSAO treatment caused a concentration-dependent increase in superoxide levels, ATP depletion, mitochondrial depolarization, and apoptosis in proliferating, but not growth-quiescent, endothelial cells. Endothelial cell proliferation drives new blood vessel formation, or angiogenesis. GSAO inhibited angiogenesis in the chick chorioallantoic membrane and in solid tumors in mice. Consequently, GSAO inhibited tumor growth in mice with no apparent toxicity at efficacious doses

Disulfide bond reduction and exchange in C4 domain of von Willebrand factor undermines platelet binding

Background The von Willebrand factor (VWF) is a key player in regulating hemostasis through adhesion of platelets to sites of vascular injury. It is a large, multi-domain, mechano-sensitive protein that is stabilized by a net of disulfide bridges. Binding to platelet integrin is achieved by the VWF-C4 domain, which exhibits a fixed fold, even under conditions of severe mechanical stress, but only if critical internal disulfide bonds are closed. Objective To determine the oxidation state of disulfide bridges in the C4 domain of VWF and implications for VWF’s platelet binding function. Methods We combined classical molecular dynamics and quantum mechanical simulations, mass spectrometry, site-directed mutagenesis, and platelet binding assays. Results We show that 2 disulfide bonds in the VWF-C4 domain, namely the 2 major force-bearing ones, are partially reduced in human blood. Reduction leads to pronounced conformational changes within C4 that considerably affect the accessibility of the integrin-binding motif, and thereby impair integrin-mediated platelet binding. We also reveal that reduced species in the C4 domain undergo specific thiol/disulfide exchanges with the remaining disulfide bridges, in a process in which mechanical force may increase the proximity of specific reactant cysteines, further trapping C4 in a state of low integrin-binding propensity. We identify a multitude of redox states in all 6 VWF-C domains, suggesting disulfide bond reduction and swapping to be a general theme. Conclusions Our data suggests a mechanism in which disulfide bonds dynamically swap cysteine partners and control the interaction of VWF with integrin and potentially other partners, thereby critically influencing its hemostatic function

Evidence for increased expression of the Amundsen Sea Low over the South Atlantic during the late Holocene

The Amundsen Sea Low (ASL) plays a major role in the climate and environment of Antarctica and the Southern Ocean, including surface air temperature and sea ice concentration changes. Unfortunately, a relative dearth of observational data across the Amundsen and Bellingshausen seas prior to the satellite era (post-1979) limits our understanding of the past behaviour and impact of the ASL. The limited proxy evidence for changes in the ASL are primarily restricted to the Antarctic where ice core evidence suggests a deepening of the atmospheric pressure system during the late Holocene. However, no data have previously been reported from the northern side of the ASL. Here we report a high-resolution, multi-proxy study of a 5000-year-long peat record from the Falkland Islands, a location sensitive to contemporary ASL dynamics which modulates northerly and westerly airflow across the southwestern South Atlantic sector of the Southern Ocean. In combination with climate reanalysis, we find a marked period of wetter, colder conditions most likely the result of enhanced southerly airflow between 5000 and 2500 years ago, suggesting limited ASL influence over the region. After 2500 years ago, drier and warmer conditions were established, implying more westerly airflow and the increased projection of the ASL onto the South Atlantic. The possible role of the equatorial Pacific via atmospheric teleconnections in driving this change is discussed. Our results are in agreement with Antarctic ice core records and fjord sediments from the southern South American coast, and suggest that the Falkland Islands provide a valuable location for reconstructing high southern latitude atmospheric circulation changes on multi-decadal to millennial timescales