Abnormal development of dendritic spines in FMR1 knock-out mice

Fragile X syndrome is caused by a mutation in the FMR1 gene leading to absence of the fragile X mental retardation protein (FMRP). Reports that patients and adult FMR1 knock-out mice have abnormally long dendritic spines of increased density suggested that the disorder might involve abnormal spine development. Because spine length, density, and motility change dramatically in the first postnatal weeks, we analyzed these properties in mutant mice and littermate controls at 1, 2, and 4 weeks of age. To label neurons, a viral vector carrying the enhanced green fluorescent protein gene was injected into the barrel cortex. Layer V neurons were imaged on a two-photon laser scanning microscope in fixed tissue sections. Analysis of >16,000 spines showed clear developmental patterns. Between 1 and 4 weeks of age, spine density increased 2.5-fold, and mean spine length decreased by 17% in normal animals. Early during cortical synaptogenesis, pyramidal cells in mutant mice had longer spines than controls. At 1 week, spine length was 28% greater in mutants than in controls. At 2 weeks, this difference was 10%, and at 4 weeks only 3%. Similarly, spine density was 33% greater in mutants than in controls at 1 week of age. At 2 or 4 weeks of age, differences were not detectable. The spine abnormality was not detected in neocortical organotypic cultures. The transient nature of the spine abnormality in the intact animal suggests that FMRP might play a role in the normal process of dendritic spine growth in coordination with the experience-dependent development of cortical circuits

Library Publishing Toolkit

Both public and academic libraries are invested in the creation and distribution of information and digital content. They have morphed from keepers of content into content creators and curators, and seek best practices and efficient workflows with emerging publishing platforms and services. The Library Publishing Toolkit looks at the broad and varied landscape of library publishing through discussions, case studies, and shared resources. From supporting writers and authors in the public library setting to hosting open access journals and books, this collection examines opportunities for libraries to leverage their position and resources to create and provide access to content.The Library Publishing Toolkit is a project funded partially by Bibliographic Databases and Interlibrary Resources Sharing Program funds which are administered and supported by the Rochester Regional Library Council. The toolkit is a united effort between Milne Library at SUNY Geneseo and the Monroe County Library System to identify trends in library publishing, seek out best practices to implement and support such programs, and share the best tools and resources. Our goals include to: Develop strategies libraries can use to identify types of publishing services and content that can be created and curated by libraries. Assess trends in digital content creation and publishing that can be useful in libraries and suggesting potential future projects. Identify efficient workflows for distributing content for free online and with potential for some cost-recovery in print on demand markets. A list of chapters is available in the full record.https://knightscholar.geneseo.edu/idsproject-press/1002/thumbnail.jp

User-centred design of flexible hypermedia for a mobile guide: Reflections on the hyperaudio experience

A user-centred design approach involves end-users from the very beginning. Considering users at the early stages compels designers to think in terms of utility and usability and helps develop the system on what is actually needed. This paper discusses the case of HyperAudio, a context-sensitive adaptive and mobile guide to museums developed in the late 90s. User requirements were collected via a survey to understand visitors’ profiles and visit styles in Natural Science museums. The knowledge acquired supported the specification of system requirements, helping defining user model, data structure and adaptive behaviour of the system. User requirements guided the design decisions on what could be implemented by using simple adaptable triggers and what instead needed more sophisticated adaptive techniques, a fundamental choice when all the computation must be done on a PDA. Graphical and interactive environments for developing and testing complex adaptive systems are discussed as a further step towards an iterative design that considers the user interaction a central point. The paper discusses how such an environment allows designers and developers to experiment with different system’s behaviours and to widely test it under realistic conditions by simulation of the actual context evolving over time. The understanding gained in HyperAudio is then considered in the perspective of the developments that followed that first experience: our findings seem still valid despite the passed time

Prenatal antidepressant exposure associated with CYP2E1 DNA methylation change in neonates

Some but not all neonates are affected by prenatal exposure to serotonin reuptake inhibitor antidepressants (SRI) and maternal mood disturbances. Distinguishing the impact of these 2 exposures is challenging and raises critical questions about whether pharmacological, genetic, or epigenetic factors can explain the spectrum of reported outcomes. Using unbiased DNA methylation array measurements followed by a detailed candidate gene approach, we examined whether prenatal SRI exposure was associated with neonatal DNA methylation changes and whether such changes were associated with differences in birth outcomes. Prenatal SRI exposure was first associated with increased DNA methylation status primarily at CYP2E1(βNon-exposed = 0.06, βSRI-exposed = 0.30, FDR = 0); however, this finding could not be distinguished from the potential impact of prenatal maternal depressed mood. Then, using pyrosequencing of CYP2E1 regulatory regions in an expanded cohort, higher DNA methylation status both the mean across 16 CpG sites (P < 0.01) and at each specific CpG site (P < 0.05) was associated with exposure to lower 3rd trimester maternal depressed mood symptoms only in the SRI-exposed neonates, indicating a maternal mood x SRI exposure interaction. In addition, higher DNA methylation levels at CpG2 (P = 0.04), CpG9 (P = 0.04) and CpG10 (P = 0.02), in the interrogated CYP2E1 region, were associated with increased birth weight independently of prenatal maternal mood, SRI drug exposure, or gestational age at birth. Prenatal SRI antidepressant exposure and maternal depressed mood were associated with altered neonatal CYP2E1 DNA methylation status, which, in turn, appeared to be associated with birth weight

Developing a Federal Research Agenda for Positive Youth Development: Identifying Gaps in the Field and an Effective Consensus Building Approach

The field of positive youth development (PYD) is at an important crossroads in terms of defining its scope and directions for future research. This paper describes an effective consensus-building process that representatives from 16 federal agencies engaged in to develop a research agenda focused on PYD and the product that resulted from using this approach. During this process, the representatives identified and refined three research domains (conceptual issues related to PYD, data sources and indicators, and program implementation and effectiveness) and key research questions that could benefit from future research. We share lessons learned from our experience to emphasize the importance of organizational systems change efforts and interagency collaborations. A major contribution of this paper is to provide specific areas for future research in PYD from the federal perspective and to describe future implications for PYD policy and interagency collaborations

Effect of mill type on the size reduction and phase transformation of gamma alumina

The influence of stress modes and comminution conditions on the effectiveness of particle size reduction of a common catalyst support; γ-Alumina is examined through a comparative assessment of three different mill types. Air jet milling is found to be the most effective in reducing particle size from a d90 of 37 µm to 2.9 µm compared to planetary ball milling (30.2 µm) and single ball milling (10.5 µm). XRD and TEM studies confirm that the planetary ball mill causes phase transformation to the less desired α-Alumina resulting in a notable decrease in surface area from 136.6 m2/g to 82.5 m2/g as measured by the BET method. This is consistent with the large shear stresses under high shear rates prevailing in the planetary ball mill when compared to the other mill types. These observations are consistent with a shear-induced phase transformation mechanism brought about by slip on alternate close packed oxygen layers from a cubic close packed to a hexagonal close packed structure