Dual and opposing roles of primary cilia in medulloblastoma development.

Recent work has shown that primary cilia are essential for Hedgehog (Hh) signaling during mammalian development. It is also known that aberrant Hh signaling can lead to cancer, but the role of primary cilia in oncogenesis is not known. Cerebellar granule neuron precursors (GNPs) can give rise to medulloblastomas, the most common malignant brain tumor in children. The primary cilium and Hh signaling are required for GNP proliferation. We asked whether primary cilia in GNPs have a role in medulloblastoma growth in mice. Genetic ablation of primary cilia blocked medulloblastoma formation when this tumor was driven by a constitutively active Smoothened protein (Smo), an upstream activator of Hh signaling. In contrast, removal of cilia was required for medulloblastoma growth by a constitutively active glioma-associated oncogene family zinc finger-2 (GLI2), a downstream transcription factor. Thus, primary cilia are either required for or inhibit medulloblastoma formation, depending on the initiating oncogenic event. Remarkably, the presence or absence of cilia was associated with specific variants of human medulloblastomas; primary cilia were found in medulloblastomas with activation in HH or WNT signaling but not in most medulloblastomas in other distinct molecular subgroups. Primary cilia could serve as a diagnostic tool and provide new insights into the mechanism of tumorigenesis

Implementation of Computer-Mediated Communication

This paper reports on the use of Multiply.com, a social network service (SNS) on the Internet, as acomputer-mediated communication (CMC) tool for pedagogical purposes in ‘English as a Foreign Language’(EFL) classes. The general outcomes reported by the educators were positive. Some of the benefits observed were improvements in participation, motivation, student autonomy and authentic student-to-student communication. The registration process, individual utilization of the site and the teachers perceived out comes and observations of classes at a private Japanese university are described. It was found that the use of CMC was beneficial for teachers and students and adaptable for different teaching styles and environments. It is suggested that CMC could be easily incorporated into a variety of teaching contexts

Patterns and correlates of workplace disclosure among professionals and managers with psychiatric conditions

Objective: This study identifies patterns and correlates of disclosure among professionals and managers with serious psychiatric conditions. Design: A national mail survey of such respondents was conducted. Results: A large proportion (87%) of study participants reported having disclosed their mental illness. About half of the disclosers reported unfavorable circumstances leading to disclosure while one third disclosed when they felt comfortable. Most frequently, respondents disclosed to supervisors; one third made their disability known when applying for the job. About half of the respondents had no regrets about disclosing. Multivariate analysis showed that correlates with the occurrence, timing, and choice of disclosure converge around constructs related to job confidence, empowerment, and recovery. We also describe those who chose not to disclose. Conclusion: Higher rates than previously reported and better experiences with disclosure were evident and may be related to this population\u27s greater recovery as well as to occupational factors

Is Peer Review in Decline?

Over the past decade, there has been a decline in the fraction of papers in top economics journals written by economists from the highest-ranked economics departments. This paper documents this fact and uses additional data on publications and citations to assess various potential explanations. Several observations are consistent with the hypothesis that the Internet improves the ability of high-profile authors to disseminate their research without going through the traditional peer-review process. (JEL A14, O30)National Science Foundation (U.S.) (SES-0550897)Toulouse Network for Information TechnologyInstitute for Advanced Study (Princeton, N.J.

Cell-cell communication enhances the capacity of cell ensembles to sense shallow gradients during morphogenesis

Collective cell responses to exogenous cues depend on cell-cell interactions. In principle, these can result in enhanced sensitivity to weak and noisy stimuli. However, this has not yet been shown experimentally, and, little is known about how multicellular signal processing modulates single cell sensitivity to extracellular signaling inputs, including those guiding complex changes in the tissue form and function. Here we explored if cell-cell communication can enhance the ability of cell ensembles to sense and respond to weak gradients of chemotactic cues. Using a combination of experiments with mammary epithelial cells and mathematical modeling, we find that multicellular sensing enables detection of and response to shallow Epidermal Growth Factor (EGF) gradients that are undetectable by single cells. However, the advantage of this type of gradient sensing is limited by the noisiness of the signaling relay, necessary to integrate spatially distributed ligand concentration information. We calculate the fundamental sensory limits imposed by this communication noise and combine them with the experimental data to estimate the effective size of multicellular sensory groups involved in gradient sensing. Functional experiments strongly implicated intercellular communication through gap junctions and calcium release from intracellular stores as mediators of collective gradient sensing. The resulting integrative analysis provides a framework for understanding the advantages and limitations of sensory information processing by relays of chemically coupled cells.Comment: paper + supporting information, total 35 pages, 15 figure