Pliocene eclogite exhumation at plate tectonic rates in eastern Papua New Guinea

As lithospheric plates are subducted, rocks are metamorphosed under high-pressure and ultrahigh-pressure conditions to produce eclogites and eclogite facies metamorphic rocks. Because chemical equilibrium is rarely fully achieved, eclogites may preserve in their distinctive mineral assemblages and textures a record of the pressures, temperatures and deformation the rock was subjected to during subduction and subsequent exhumation. Radioactive parent-daughter isotopic variations within minerals reveal the timing of these events. Here we present in situ zircon U/Pb ion microprobe data that dates the timing of eclogite facies metamorphism in eastern Papua New Guinea at 4.3 +/- 0.4 Myr ago, making this the youngest documented eclogite exposed at the Earth's surface. Eclogite exhumation from depths of approximately 75 km was extremely rapid and occurred at plate tectonic rates (cm yr(-1)). The eclogite was exhumed within a portion of the obliquely convergent Australian-Pacific plate boundary zone, in an extending region located west of the Woodlark basin sea floor spreading centre. Such rapid exhumation (> 1 cm yr(-1)) of high-pressure and, we infer, ultrahigh-pressure rocks is facilitated by extension within transient plate boundary zones associated with rapid oblique plate convergence.     

The subunit structure of the eukaryotic chromosome.

New strucutral data have been obtained from neutron scattering studies of chromatin. The concentration-dependent meridional peak at 10-11 nm comes from the interparticle spacing of a subunit structure. Peaks at 5.5 and 3.7 nm have a different contrast behaviour to those at 11.0 and 3.7 nm showing that histones and DNA have a different spatial arrangement in the subunit. A globular model in which apolar segments of histones from the core surrounded by DNA complexed with the basic segments of histones agrees with the data.     

Wnk4 controls blood pressure and potassium homeostasis via regulation of mass and activity of the distal convoluted tubule

The mechanisms that govern homeostasis of complex systems have been elusive but can be illuminated by mutations that disrupt system behavior. Mutations in the gene encoding the kinase WNK4 cause pseudohypoaldosteronism type II (PHAII), a syndrome featuring hypertension and hyperkalemia. We show that physiology in mice transgenic for genomic segments harboring wild-type (TgWnk4(WT)) or PHAII mutant (TgWnk4(PHAII)) Wnk4 is changed in opposite directions: TgWnk4(PHAII) mice have higher blood pressure, hyperkalemia, hypercalciuria and marked hyperplasia of the distal convoluted tubule (DCT), whereas the opposite is true in TgWnk4(WT) mice. Genetic deficiency for the Na-Cl cotransporter of the DCT (NCC) reverses phenotypes seen in TgWnk4(PHAII) mice, demonstrating that the effects of the PHAII mutation are due to altered NCC activity. These findings establish that Wnk4 is a molecular switch that regulates the balance between NaCl reabsorption and K+ secretion by altering the mass and function of the DCT through its effect on NCC.     

Multiple regions within 8q24 independently affect risk for prostate cancer

After the recent discovery that common genetic variation in 8q24 influences inherited risk of prostate cancer, we genotyped 2,973 SNPs in up to 7,518 men with and without prostate cancer from five populations. We identified seven risk variants, five of them previously undescribed, spanning 430 kb and each independently predicting risk for prostate cancer (P = 7.9 x 10(-19) for the strongest association, and P < 1.5 x 10(-4) for five of the variants, after controlling for each of the others). The variants define common genotypes that span a more than fivefold range of susceptibility to cancer in some populations. None of the prostate cancer risk variants aligns to a known gene or alters the coding sequence of an encoded protein.     

Regulation and function of IL-17A- and IL-22-producing γδ T cells

The regulation of IL-17A and IL-22 production differs between human and murine γδ T cells. We find that human γδ T cells expressing Vγ2Vδ2 T cell receptors are peripherally polarized to produce IL-17A or IL-22, much like CD4 αβ Th17 T cells. This requires IL-6, IL-1β, and TGF-β, whereas expansion and maintenance requires IL-23, IL-1β, and TGF-β. In contrast, IL-17A and IL-22 production by murine γδ T cells is innately programmed during thymic ontogeny but requires IL-23 and IL-1β for maintenance. Murine γδ cells producing IL-17A and IL-22 play important roles in microbial, autoimmune, and inflammatory responses. However, the roles played by human IL-17A- and IL-22-producing γδ T cells are less clear but are also likely to be important. These observations highlight differences between humans and murine γδ T cells and underscore the importance of IL-17A- and IL-22-producing γδ T cells.     

Characterization of a regulatory unit that controls melanization and affects longevity of mosquitoes

Melanization is an innate immune response in arthropods that encapsulates and kills invading pathogens. One of its rate-limiting steps is the activation of prophenoloxidase (PPO), which is controlled by an extracellular proteinase cascade and serpin inhibitors. The molecular composition of this system is largely unknown in mosquitoes with the exception of serpin-2 (SRPN2), which was previously identified as a key negative regulator of melanization. Using reverse genetic and biochemical techniques, we identified the Anopheles gambiae clip-serine proteinase CLIPB9 as a PPO-activating proteinase, which is inhibited by SRPN2. Double knockdown of SRPN2 and CLIPB9 reversed the pleiotrophic phenotype induced by SRPN2 silencing. This study identifies the first inhibitory serpin-serine proteinase pair in mosquitoes and defines a regulatory unit of melanization. Additionally, the interaction of CLIPB9 and SRPN2 affects the life span of adult female mosquitoes and therefore constitutes a well-defined potential molecular target for novel late-life acting insecticides.     

On the taxonomic status of Eriogonum robustum (Polygonaceae), a rare endemic in western Nevada

Evidence from the morphology, genetics, and biogeography of a rare endemic from western Nevada, Erigonum robustum , is presented to determine the most accurate taxonomic classification. Previous authors have classified E. robustrum Greene both as a species and as a variety E. lobbii Torrey & Gray. However, results of a morphometric comparison for 9 characters establish that significant morphological differentiation exists between E. robustum and E. lobbii . In addition, results of a genetic study using protein electrophoresis indicated that genetic differentiation may exist between these 2 taxa. Furthermore, the 2 taxa are geographically, ecologically, and reproductively isolated. Finally, the selective pressures that act on E. robustum in a narrowly restricted cold-desert environment are different from those that act on E. lobbii in subalpine environment. Thus, all available data support a species-level taxonomic classification for E. robustum .     

A global synthesis reveals biodiversity loss as a major driver of ecosystem change

Evidence is mounting that extinctions are altering key processes important to the productivity and sustainability of Earth's ecosystems. Further species loss will accelerate change in ecosystem processes, but it is unclear how these effects compare to the direct effects of other forms of environmental change that are both driving diversity loss and altering ecosystem function. Here we use a suite of meta-analyses of published data to show that the effects of species loss on productivity and decomposition--two processes important in all ecosystems--are of comparable magnitude to the effects of many other global environmental changes. In experiments, intermediate levels of species loss (21-40%) reduced plant production by 5-10%, comparable to previously documented effects of ultraviolet radiation and climate warming. Higher levels of extinction (41-60%) had effects rivalling those of ozone, acidification, elevated CO(2) and nutrient pollution. At intermediate levels, species loss generally had equal or greater effects on decomposition than did elevated CO(2) and nitrogen addition. The identity of species lost also had a large effect on changes in productivity and decomposition, generating a wide range of plausible outcomes for extinction. Despite the need for more studies on interactive effects of diversity loss and environmental changes, our analyses clearly show that the ecosystem consequences of local species loss are as quantitatively significant as the direct effects of several global change stressors that have mobilized major international concern and remediation efforts.     

Co-operative Inquiry as a Tool for Professional Development

This article describes my involvement as an external facilitator in separate research projects, with a total of five co-operative inquiry groups. The groups all consisted of social welfare professionals, mainly social workers, who were wanting to explore the development of their practice in a context of competing demands from legislation, policy, and management at an organizational level. The article focuses on process, and how, collectively, we facilitated these as more or less successful inquiries. There is detail about how co-operative inquiry, with professionals, in their organizational context, can work successfully, and the part that an external facilitator can take in ensuring a positive result.     

Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy

Limb-girdle muscular dystrophy type 1D (LGMD1D) was linked to chromosome 7q36 over a decade ago, but its genetic cause has remained elusive. Here we studied nine LGMD-affected families from Finland, the United States and Italy and identified four dominant missense mutations leading to p.Phe93Leu or p.Phe89Ile changes in the ubiquitously expressed co-chaperone DNAJB6. Functional testing in vivo showed that the mutations have a dominant toxic effect mediated specifically by the cytoplasmic isoform of DNAJB6. In vitro studies demonstrated that the mutations increase the half-life of DNAJB6, extending this effect to the wild-type protein, and reduce its protective anti-aggregation effect. Further, we show that DNAJB6 interacts with members of the CASA complex, including the myofibrillar myopathy-causing protein BAG3. Our data identify the genetic cause of LGMD1D, suggest that its pathogenesis is mediated by defective chaperone function and highlight how mutations in a ubiquitously expressed gene can exert effects in a tissue-, isoform- and cellular compartment-specific manner.