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6 Janelia Publications

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    01/15/08 | Straightening caenorhabditis elegans images.
    Peng H, Long F, Liu X, Kim SK, Myers EW
    Bioinformatics. 2008 Jan 15;24:234-42. doi: 10.1093/bioinformatics/btm569

    MOTIVATION: Caenorhabditis elegans, a roundworm found in soil, is a widely studied model organism with about 1000 cells in the adult. Producing high-resolution fluorescence images of C.elegans to reveal biological insights is becoming routine, motivating the development of advanced computational tools for analyzing the resulting image stacks. For example, worm bodies usually curve significantly in images. Thus one must ’straighten’ the worms if they are to be compared under a canonical coordinate system. RESULTS: We develop a worm straightening algorithm (WSA) that restacks cutting planes orthogonal to a ’backbone’ that models the anterior-posterior axis of the worm. We formulate the backbone as a parametric cubic spline defined by a series of control points. We develop two methods for automatically determining the locations of the control points. Our experimental methods show that our approaches effectively straighten both 2D and 3D worm images.

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    Svoboda Lab
    01/03/08 | Sparse optical microstimulation in barrel cortex drives learned behaviour in freely moving mice.
    Huber D, Petreanu L, Ghitani N, Ranade S, Hromádka T, Mainen Z, Svoboda K
    Nature. 2008 Jan 3;451(7174):61-4. doi: 10.1038/nature06445

    Electrical microstimulation can establish causal links between the activity of groups of neurons and perceptual and cognitive functions. However, the number and identities of neurons microstimulated, as well as the number of action potentials evoked, are difficult to ascertain. To address these issues we introduced the light-gated algal channel channelrhodopsin-2 (ChR2) specifically into a small fraction of layer 2/3 neurons of the mouse primary somatosensory cortex. ChR2 photostimulation in vivo reliably generated stimulus-locked action potentials at frequencies up to 50 Hz. Here we show that naive mice readily learned to detect brief trains of action potentials (five light pulses, 1 ms, 20 Hz). After training, mice could detect a photostimulus firing a single action potential in approximately 300 neurons. Even fewer neurons (approximately 60) were required for longer stimuli (five action potentials, 250 ms). Our results show that perceptual decisions and learning can be driven by extremely brief epochs of cortical activity in a sparse subset of supragranular cortical pyramidal neurons.

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    01/01/08 | Automatic Segmentation of the Pelvic Bones from CT Data Based on a Statistical Shape Model
    Kainmueller D, Seim H, Heller M, Lamecker H, Zachow S, Hege H

    We present an algorithm for automatic segmentation of the human pelvic bones from CT datasets that is based on the application of a statistical shape model. The proposed method is divided into three steps: 1) The averaged shape of the pelvis model is initially placed within the CT data using the Generalized Hough Transform, 2) the statistical shape model is then adapted to the image data by a transformation and variation of its shape modes, and 3) a final free-form deformation step based on optimal graph searching is applied to overcome the restrictive character of the statistical shape representation. We thoroughly evaluated the method on 50 manually segmented CT datasets by performing a leave-one-out study. The Generalized Hough Transform proved to be a reliable method for an automatic initial placement of the shape model within the CT data. Compared to the manual gold standard segmentations, our automatic segmentation approach produced an average surface distance of 1.2 ± 0.3mm after the adaptation of the statistical shape model, which could be reduced to 0.7±0.3mm using a final free-form deformation step. Together with an average segmentation time of less than 5 minutes, the results of our study indicate that our method meets the requirements of clinical routine.

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    Looger Lab
    01/01/08 | Genetically encoded fluorescent sensors for studying healthy and diseased nervous systems.
    Tian L, Looger LL
    Drug Discovery Today. Disease Models. 2008;5(1):27-35. doi: 10.1016/j.ddmod.2008.07.003

    Neurons and glia are functionally organized into circuits and higher-order structures via synaptic connectivity, well-orchestrated molecular signaling, and activity-dependent refinement. Such organization allows the precise information processing required for complex behaviors. Disruption of nervous systems by genetic deficiency or events such as trauma or environmental exposure may produce a diseased state in which certain aspects of inter-neuron signaling are impaired. Optical imaging techniques allow the direct visualization of individual neurons in a circuit environment. Imaging probes specific for given biomolecules may help elucidate their contribution to proper circuit function. Genetically encoded sensors can visualize trafficking of particular molecules in defined neuronal populations, non-invasively in intact brain or reduced preparations. Sensor analysis in healthy and diseased brains may reveal important differences and shed light on the development and progression of nervous system disorders. We review the field of genetically encoded sensors for molecules and cellular events, and their potential applicability to the study of nervous system disease.

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    01/01/08 | The Pfam protein families database.
    Finn RD, Tate J, Mistry J, Coggill PC, Sammut SJ, Hotz H, Ceric G, Forslund K, Eddy SR, Sonnhammer EL, Bateman A
    Nucleic Acids Research. 2008 Jan;36(Database Issue):D281-8. doi: 10.1093/nar/gkm960

    Pfam is a comprehensive collection of protein domains and families, represented as multiple sequence alignments and as profile hidden Markov models. The current release of Pfam (22.0) contains 9318 protein families. Pfam is now based not only on the UniProtKB sequence database, but also on NCBI GenPept and on sequences from selected metagenomics projects. Pfam is available on the web from the consortium members using a new, consistent and improved website design in the UK (http://pfam.sanger.ac.uk/), the USA (http://pfam.janelia.org/) and Sweden (http://pfam.sbc.su.se/), as well as from mirror sites in France (http://pfam.jouy.inra.fr/) and South Korea (http://pfam.ccbb.re.kr/).

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    01/01/08 | Vector and parameters for targeted transgenic RNA interference in Drosophila melanogaster.
    Ni J, Markstein M, Binari R, Pfeiffer B, Liu L, Villalta C, Booker M, Perkins L, Perrimon N
    Nature Methods. 2008 Jan;5(1):49-51. doi: 10.1038/nmeth1146

    The conditional expression of hairpin constructs in Drosophila melanogaster has emerged in recent years as a method of choice in functional genomic studies. To date, upstream activating site-driven RNA interference constructs have been inserted into the genome randomly using P-element-mediated transformation, which can result in false negatives due to variable expression. To avoid this problem, we have developed a transgenic RNA interference vector based on the phiC31 site-specific integration method.

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