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12 Publications

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    01/23/07 | Polypeptide motions are dominated by peptide group oscillations resulting from dihedral angle correlations between nearest neighbors.
    Fitzgerald JE, Jha AK, Sosnick TR, Freed KF
    Biochemistry. 2007 Jan 23;46(3):669-82. doi: 10.1021/bi061575x

    To identify basic local backbone motions in unfolded chains, simulations are performed for a variety of peptide systems using three popular force fields and for implicit and explicit solvent models. A dominant "crankshaft-like" motion is found that involves only a localized oscillation of the plane of the peptide group. This motion results in a strong anticorrelated motion of the phi angle of the ith residue (phi(i)) and the psi angle of the residue i - 1 (psi(i-1)) on the 0.1 ps time scale. Only a slight correlation is found between the motions of the two backbone dihedral angles of the same residue. Aside from the special cases of glycine and proline, no correlations are found between backbone dihedral angles that are separated by more than one torsion angle. These short time, correlated motions are found both in equilibrium fluctuations and during the transit process between Ramachandran basins, e.g., from the beta to the alpha region. A residue's complete transit from one Ramachandran basin to another, however, occurs in a manner independent of its neighbors' conformational transitions. These properties appear to be intrinsic because they are robust across different force fields, solvent models, nonbonded interaction routines, and most amino acids.

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    Tjian Lab
    01/15/07 | IRES-mediated functional coupling of transcription and translation amplifies insulin receptor feedback.
    Marr MT, D’Alessio JA, Puig O, Tjian R
    Genes & Development. 2007 Jan 15;21(2):175-83. doi: 10.1073/pnas.1100640108

    It is generally accepted that the growth rate of an organism is modulated by the availability of nutrients. One common mechanism to control cellular growth is through the global down-regulation of cap-dependent translation by eIF4E-binding proteins (4E-BPs). Here, we report evidence for a novel mechanism that allows eukaryotes to coordinate and selectively couple transcription and translation of target genes in response to a nutrient and growth signaling cascade. The Drosophila insulin-like receptor (dINR) pathway incorporates 4E-BP resistant cellular internal ribosome entry site (IRES) containing mRNAs, to functionally couple transcriptional activation with differential translational control in a cell that is otherwise translationally repressed by 4E-BP. Although examples of cellular IRESs have been previously reported, their critical role mediating a key physiological response has not been well documented. Our studies reveal an integrated transcriptional and translational response mechanism specifically dependent on a cellular IRES that coordinates an essential physiological signal responsible for monitoring nutrient and cell growth conditions.

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    Tjian Lab
    01/10/07 | Novel TRF1/BRF target genes revealed by genome-wide analysis of Drosophila Pol III transcription.
    Isogai Y, Takada S, Tjian R, Kele\c s S
    The EMBO Journal. 2007 Jan 10;26(1):79-89. doi: 10.1073/pnas.1100640108

    Metazoans have evolved multiple paralogues of the TATA binding protein (TBP), adding another tunable level of gene control at core promoters. While TBP-related factor 1 (TRF1) shares extensive homology with TBP and can direct both Pol II and Pol III transcription in vitro, TRF1 target sites in vivo have remained elusive. Here, we report the genome-wide identification of TRF1-binding sites using high-resolution genome tiling microarrays. We found 354 TRF1-binding sites genome-wide with approximately 78% of these sites displaying colocalization with BRF. Strikingly, the majority of TRF1 target genes are Pol III-dependent small noncoding RNAs such as tRNAs and small nonmessenger RNAs. We provide direct evidence that the TRF1/BRF complex is functionally required for the activity of two novel TRF1 targets (7SL RNA and small nucleolar RNAs). Our studies suggest that unlike most other eukaryotic organisms that rely on TBP for Pol III transcription, in Drosophila and possibly other insects the alternative TRF1/BRF complex appears responsible for the initiation of all known classes of Pol III transcription.

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    Bock Lab
    01/01/07 | Alignment of large image series using cubic B-splines tessellation: application to transmission electron microscopy data.
    Dauguet J, Bock D, Reid RC, Warfield SK
    Medical Image Computing and Computer-Assisted Intervention: MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention. 2007;10:710-7

    3D reconstruction from serial 2D microscopy images depends on non-linear alignment of serial sections. For some structures, such as the neuronal circuitry of the brain, very large images at very high resolution are necessary to permit reconstruction. These very large images prevent the direct use of classical registration methods. We propose in this work a method to deal with the non-linear alignment of arbitrarily large 2D images using the finite support properties of cubic B-splines. After initial affine alignment, each large image is split into a grid of smaller overlapping sub-images, which are individually registered using cubic B-splines transformations. Inside the overlapping regions between neighboring sub-images, the coefficients of the knots controlling the B-splines deformations are blended, to create a virtual large grid of knots for the whole image. The sub-images are resampled individually, using the new coefficients, and assembled together into a final large aligned image. We evaluated the method on a series of large transmission electron microscopy images and our results indicate significant improvements compared to both manual and affine alignment.

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    01/01/07 | Gene expression patterns underlying wing polyphenism and polymorphism in the pea aphid
    GK Davis , JA Brisson , DL Stern
    Society for Integrative and Comparative Biology. 01/2007;46:E186-E186

    The pea aphid, Acyrthosiphon pisum, exhibits several environmentally cued, discrete, alternate phenotypes (polyphenisms) during its life cycle. In the wing polyphenism, female progeny develop as either winged or unwinged depending on the extent of crowding or host plant quality experienced by the mother. Males also have the ability to develop as either winged or unwinged, but this is genetically determined by a single locus on the X chromosome and is thus referred to as a wing polymorphism. In order to gain insight into the patterns of gene expression that underlie the wing polyphenism and polymorphism we have used a pea aphid cDNA microarray to examine gene expression in winged and unwinged females and males. Results suggest that winged and unwinged morphs exhibit systemic differences in gene expression and that many of these differences are shared between the wing polyphenism and polymorphism (i.e., between females and males). In addition, adult winged and unwinged males exhibit pronounced differences when compared to adult females and fourth instar males, as well as to each other.

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    01/01/07 | Global analyses of mRNA translational control during early Drosophila embryogenesis.
    Qin X, Ahn S, Speed TP, Rubin GM
    Genome Biology. 2007;8(4):R63. doi: 10.1186/gb-2007-8-4-r63

    BACKGROUND: In many animals, the first few hours of life proceed with little or no transcription, and developmental regulation at these early stages is dependent on maternal cytoplasm rather than the zygotic nucleus. Translational control is critical for early Drosophila embryogenesis and is exerted mainly at the gene level. To understand post-transcriptional regulation during Drosophila early embryonic development, we used sucrose polysomal gradient analyses and GeneChip analysis to illustrate the translation profile of individual mRNAs. RESULTS: We determined ribosomal density and ribosomal occupancy of over 10,000 transcripts during the first ten hours after egg laying. CONCLUSION: We report the extent and general nature of gene regulation at the translational level during early Drosophila embryogenesis on a genome-wide basis. The diversity of the translation profiles indicates multiple mechanisms modulating transcript-specific translation. Cluster analyses suggest that the genes involved in some biological processes are co-regulated at the translational level at certain developmental stages.

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    Pavlopoulos Lab
    01/01/07 | Hox go omics: insights from Drosophila into Hox gene targets.
    Pavlopoulos A, Akam M
    Genome Biology. 2007;8(3):208. doi: 10.1186/gb-2007-8-3-208

    Genetic studies of the targets of the Hox genes have revealed only the tip of the iceberg. Recent microarray studies that have identified hundreds more transcriptional responses to Hox genes in Drosophila will help elucidate the role of Hox genes in development and evolution.

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    01/01/07 | Sex and death in the male pea aphid, Acyrthosiphon pisum: The life-history effects of a wing dimorphism.
    Sack C, Stern DL
    J Insect Sci. 2007;7:1-9. doi: 10.1673/031.007.4501

    Insect dispersal dimorphisms, in which both flight-capable and flightless individuals occur in the same species, are thought to reflect a balance between the benefits and costs of dispersal. Fitness costs and benefits associated with wing dimorphism were investigated in the male pea aphid, Acyrthosiphon pisum (Harris) (Hemiptera: Aphididae). In one-on-one mating competitions in small arenas between winged and wingless males, the winged aphids obtained most of the matings with virgin females. In contrast, during competition experiments in larger cages with multiple individuals of each morph, the winged males no longer had a clear mating advantage over wingless males. In the absence of competition, wingless males had marginally higher lifetime reproductive success than winged males, probably because mating winged males tended to die faster than wingless males. In the absence of females, winged males survived longer than wingless males and this difference disappeared under starvation conditions. Mating males of both morphs died significantly faster than males without access to females. There does not appear to be a direct tradeoff of dispersal ability with life history characteristics in pea aphid males, suggesting that the advantages of producing winged males may result from outbreeding.

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    Kainmueller Lab
    10/29/07 | Shape constrained automatic segmentation of the liver based on a heuristic intensity model.
    Kainmueller D, Lange T, Lamecker H
    MICCAI Workshop 3D Segmentation in the Clinic. 2007 Oct 29:

    We present a fully automatic 3D segmentation method for the liver from contrast-enhanced CT data. It is based on a combination of a constrained free-form and statistical deformable model. The adap- tation of the model to the image data is performed according to a simple model of the typical intensity distribution around the liver boundary and neighboring anatomical structures, considering the potential presence of tumors in the liver. All parameters of the deformation as well as the initial positioning of the model in the data are estimated automatically. 

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