1,656 research outputs found

    CREB Binding Protein Exerts Transcriptional and Post-translational Regulatory Effects on Dendritic Arborization in Drosophila Sensory Neurons

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    The Drosophila ortholog of CREB Binding Protein (dCBP) has been implicated in the pruning of sensory neuron dendrites and recent studies demonstrate that nuclear polyglutamate-induced dendritic pathologies occur, in part, by inhibiting Golgi outpost formation via a CBP-CrebA-COPII regulatory mechanism. Despite these advances, the role of dCBP in modulating dendritic development is incompletely understood. Here, we identify dCBP as a novel regulator of dendritic development that modulates the localization of Dar1, a protein known to affect dendritic growth via regulation of the microtubule severing protein Spastin and components of the Dynein complex. We discovered that dCBP is required for proper proximal-distal branch order distribution, with loss of function resulting in an aberrant reduction in terminal branching in favor of a shift towards proximal interstitial branching. Conversely, dCBP overexpression severely inhibits higher order dendritic branching in Class IV (CIV) md sensory neurons. Detailed structure-function studies using domain-specific deletions of dCBP provide further insights into the specific roles of different protein domains in mediating distinct aspects of dendritic growth. Analyses of domain-specific deletions implicate the N-terminal region (ΔNZK) in regulating the mutant phenotype, whereas expression of a deletion of the C-terminal region (ΔQ) phenocopies the overexpression phenotype. To characterize dCBP-mediated transcriptional mechanisms driving dendrite arborization, we conducted RNAseq analyses focusing on those genes that fail to be transcriptionally regulated by the ΔNZK deletion. These analyses reveal a primary role for dCBP in transcriptional repression. Enriched gene clusters included phosphorylation, ubiquitination, microtubule-based processes, protein modification processes, cytoskeletal organization, and cell morphogenesis. To characterize these putative regulatory targets, we simultaneously expressed the ΔNZK deletion construct in combination with gene-specific knockdown. These analyses revealed that disruptions of Arp53D, CG12620, CG31391, CG16716, and α-actinin 3 partially rescue aspects of morphological defects that are caused by expression of the ΔNZK construct. Combined with cytoskeletal imaging, our results suggest that dCBP function includes transcriptional repression of genes that may otherwise over-stabilize both actin and microtubule components thereby contributing to cytoskeletal dynamics required for dendritic growth. Collectively, these analyses identified transcriptional and post-translational regulatory mechanisms by which dCBP functions to direct the specification of distinct neuronal morphologies

    Family Correlates of Delinquency: Cohesion And Adaptability

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    The Circumplex Model of family functioning, which includes measures of cohesion and adaptability, was used with a community-based sample of youth (N = 480) to test its usefulness for explaining delinquent behavior. Results from the research indicate that the Circumplex Model is inadequate for explaining delinquency. It was concluded that the two major components of the model, cohesion and adaptability, do not operate in the curvilinear fashion as hypothesized. Rather, the results suggest the both factors are linear in their relationship with delinquency

    Understanding perceptions of the transport planning professional qualification

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    This report presents the findings from a survey of transport planners conducted in March 2012, which set out to discover how wider uptake of the Transport Planning Professional (TPP) qualification could be encouraged. The survey revealed that: The majority (95 per cent) of respondents were aware of the TPP qualification, but only a minority (one third) of respondents reported a definite intention to apply for the TPP qualification. Younger professionals (aged under 30) were more likely to express an intention to apply for the qualification than older professionals. However, employer support – an important means of encouraging applications - is not currently widespread. In line with expectations, a positive intention to apply was found to be associated with also perceiving personal benefits of the TPP qualification. However, the survey findings suggest that there is some uncertainty surrounding the benefits. This indicates that further evidence is required to clearly demonstrate the personal benefits of achieving the TPP qualification. Some respondents reported that the competency requirements also appear inflexible. In particular at present there appears to be no suitable route ways for specialists such as transport modellers. The guidance notes are also not positively perceived. Less than half of respondents (44 per cent) rated the notes as ‘Helpful and informative’.Based on these findings, the report concludes with four recommendations 1. Encourage senior professionals to advocate the qualification to more junior staff; 2. Ensure the personal benefits of the qualification are clearly publicised and evidenced; 3. Investigate whether the competency requirements can be made more flexible; and 4. Review the efficacy of the guidance notes and mechanisms through which advice can be sought

    Right Angle Electrical Connector and Insertion Tool Therefor

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    Disclosed is a multi-row right angle connector and a press block for installing the connector on a mounting substrate without soldering the contact pins. The connector legs comprise eye of the needle compliant interfaces that make electrical contact with the interior surfaces of the substrate\u27s plated through holes. The press block is designed for use with a four-row right angle receptacle and locates rows 2, 3, and 4 on respective true grid positions and serves as a means for transmitting force from an external press to the contact pin tails. The contact tails in rows 2, 3, and 4 have a T-shaped shoulder that is pressed into a pocket in the press block. The insertion force is applied to the pins in row 1 by a corner having a radius matching the radius of the row 1 tails

    Probing the Super Star Cluster Environment of NGC 1569 Using FISICA

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    We present near-IR JH spectra of the central regions of the dwarf starburst galaxy NGC 1569 using the Florida Image Slicer for Infrared Cosmology and Astrophysics (FISICA). The dust-penetrating properties and available spectral features of the near-IR, combined with the integral field unit (IFU) capability to take spectra of a field, make FISICA an ideal tool for this work. We use the prominent [He I] (1.083\mu m) and Pa\beta (1.282 \mu m) lines to probe the dense star forming regions as well as characterize the general star forming environment around the super star clusters (SSCs) in NGC 1569. We find [He I] coincident with CO clouds to the north and west of the SSCs, which provides the first, conclusive evidence for embedded star clusters here.Comment: 6 pages, 3 figures, accepted for publication in the MNRA

    Effect of Endogenous Histamine on Meat Tenderness.

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    Reversible DNA micro-patterning using the fluorous effect

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    We describe a new method for the immobilisation of DNA into defined patterns with sub-micron resolution, using the fluorous effect. The method is fully reversible via a simple solvent wash, allowing the patterning, regeneration and re-patterning of surfaces with no degradation in binding efficiency following multiple removal/attachment cycles of different DNA sequences
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