The Economics of Policies and Programs Affecting the Employment of People with Disabilities

Over the last several decades, there has been a movement toward the inclusion of people with disabilities in mainstream social institutions. The 1990 Americans with Disabilities Act (ADA), which supports the full participation of people with disabilities in society and mainstream institutions, illustrates the shift in attitudes toward people with disabilities. Rather than being perceived as having a social or medical problem, individuals with disabilities are increasingly viewed as people with challenges that can be solved if appropriate policies and supports are available for addressing them

MEKK2 mediates aberrant ERK activation in neurofibromatosis type I

Neurofibromatosis type I (NF1) is characterized by prominent skeletal manifestations caused by NF1 loss. While inhibitors of the ERK activating kinases MEK1/2 are promising as a means to treat NF1, the broad blockade of the ERK pathway produced by this strategy is potentially associated with therapy limiting toxicities. Here, we have sought targets offering a more narrow inhibition of ERK activation downstream of NF1 loss in the skeleton, finding that MEKK2 is a novel component of a noncanonical ERK pathway in osteoblasts that mediates aberrant ERK activation after NF1 loss. Accordingly, despite mice with conditional deletion of Nf1 in mature osteoblasts (Nf1(fl/fl);Dmp1-Cre) and Mekk2(-/-) each displaying skeletal defects, Nf1(fl/fl);Mekk2(-/-);Dmp1-Cre mice show an amelioration of NF1-associated phenotypes. We also provide proof-of-principle that FDA-approved inhibitors with activity against MEKK2 can ameliorate NF1 skeletal pathology. Thus, MEKK2 functions as a MAP3K in the ERK pathway in osteoblasts, offering a potential new therapeutic strategy for the treatment of NF1

The PHENIX Experiment at RHIC

The physics emphases of the PHENIX collaboration and the design and current status of the PHENIX detector are discussed. The plan of the collaboration for making the most effective use of the available luminosity in the first years of RHIC operation is also presented.Comment: 5 pages, 1 figure. Further details of the PHENIX physics program available at http://www.rhic.bnl.gov/phenix

From West Indies to East Indies: Archipelagic Interchanges

In this paper, I work to rethink notions of comparison and area studies by viewing my ethnographic work in Indonesia through the lens of theories developed by anthropologists working in the Caribbean region. In bringing 'East Indies' and 'West Indies' together in this way, I explore the possibility of reconfigured networks of citation, collaboration and interchange that might help anthropology respond in new ways to contemporary dynamics of globalisation. © 2006 Copyright Discipline of Anthropology and Sociology, The University of Western Australia

c-Jun N-terminal kinases (JNKs) are critical mediators of osteoblast activity in vivo

The c-Jun N-terminal kinases (JNKs) are ancient and evolutionarily conserved regulators of proliferation, differentiation and cell death responses. Currently, in vitro studies offer conflicting data about whether the JNK pathway augments or represses osteoblast differentiation, and the contribution of the JNK pathway to regulation of bone mass in vivo remains unclear. Here we show that Jnk1-/- mice display severe osteopenia due to impaired bone formation, whereas Jnk2-/- mice display a mild osteopenia only evident in long bones. In order to both confirm that these effects were osteoblast intrinsic and assess whether redundancy with JNK1 masks a potential contribution of JNK2, mice with a conditional deletion of both JNK1 and JNK2 floxed conditional alleles in osteoblasts (Jnk1-2osx ) were bred. These mice displayed a similar degree of osteopenia to Jnk1-/- mice due to decreased bone formation. In vitro, Jnk1-/- osteoblasts display a selective defect in the late stages of osteoblast differentiation with impaired mineralization activity. Downstream of JNK1, phosphorylation of JUN is impaired in Jnk1-/- osteoblasts. Transcriptome analysis showed that JNK1 is required for upregulation of several osteoblast-derived proangiogenic factors such as IGF2 and VEGFa. Accordingly, JNK1 deletion results in a significant reduction skeletal vasculature in mice. Taken together, this study establishes that JNK1 is a key mediator of osteoblast function in vivo and in vitro