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MIT Open Access Articles

Mostrando recursos 26.041 - 26.060 de 27.550

  1. Synaptic and genomic responses to JNK and AP-1 signaling in Drosophilaneurons

    Narayanan, Radhakrishnan; Navratilova, Zaneta; Patel, Chirag; Bohmann, Dirk; Ramaswami, Mani; Jasper, Heinrich; Etter, Paul D.
    Background: The transcription factor AP-1 positively controls synaptic plasticity at the Drosophila neuromuscular junction. Although in motor neurons, JNK has been shown to activate AP-1, a positive regulator of growth and strength at the larval NMJ, the consequences of JNK activation are poorly studied. In addition, the downstream transcriptional targets of JNK and AP-1 signaling in the Drosophila nervous system have yet to be identified. Here, we further investigated the role of JNK signaling at this model synapse employing an activated form of JNK-kinase; and using Serial Analysis of Gene Expression and oligonucleotide microarrays, searched for candidate early targets of...

  2. Electrospun micro- and nanofiber tubes for functional nervous regeneration in sciatic nerve transections

    Panseri, Silvia; Cunha, Carla; Lowery, Joseph L.; Del Carro, Ubaldo; Taraballi, Francesca; Amadio, Stefano; Vescovi, Angelo; Gelain, Fabrizio
    Background: Although many nerve prostheses have been proposed in recent years, in the case of consistent loss of nervous tissue peripheral nerve injury is still a traumatic pathology that may impair patient's movements by interrupting his motor-sensory pathways. In the last few decades tissue engineering has opened the door to new approaches;: however most of them make use of rigid channel guides that may cause cell loss due to the lack of physiological local stresses exerted over the nervous tissue during patient's movement. Electrospinning technique makes it possible to spin microfiber and nanofiber flexible tubular scaffolds composed of a number...

  3. Efficacy of local neem extracts for sustainable malaria vector control in an African village

    Bomblies, Arne; Dafalla, Mustafa; Issa-Arzika, Ibrahim; Duchemin, Jean-Bernard; Gianotti, Rebecca Louise; Eltahir, Elfatih A. B.
    Background: Larval control of malaria vectors has been historically successful in reducing malaria transmission, but largely fell out of favour with the introduction of synthetic insecticides and bed nets. However, an integrated approach to malaria control, including larval control methods, continues to be the best chance for success, in view of insecticide resistance, the behavioural adaptation of the vectors to changing environments and the difficulties of reaching the poorest populations most at risk,. Laboratory studies investigating the effects of neem seed (Azadirachta indica) extracts on Anopheles larvae have shown high rates of larval mortality and reductions in adult longevity, as...

  4. High-resolution optical coherence tomographic imaging of osteoarthritic cartilage during open knee surgery

    Harman, Michelle; Li, Xingde; Pitris, Costas; Ghanta, Ravi; Fujimoto, James G.; Stamper, Debra L.; Brezinski, Mark E.; Martin, Scott
    This study demonstrates the first real-time imaging in vivo of human cartilage in normal and osteoarthritic knee joints at a resolution of micrometers, using optical coherence tomography (OCT). This recently developed high-resolution imaging technology is analogous to B-mode ultrasound except that it uses infrared light rather than sound. Real-time imaging with 11-μm resolution at four frames per second was performed on six patients using a portable OCT system with a handheld imaging probe during open knee surgery. Tissue registration was achieved by marking sites before imaging, and then histologic processing was performed. Structural changes including cartilage thinning, fissures, and fibrillations...

  5. Phylogenetic and structural analysis of centromeric DNA and kinetochore proteins

    Meraldi, Patrick; McAinsh, Andrew D.; Rheinbay, Esther; Sorger, Peter K.
    Background: Kinetochores are large multi-protein structures that assemble on centromeric DNA (CEN DNA) and mediate the binding of chromosomes to microtubules. Comprising 125 base-pairs of CEN DNA and 70 or more protein components, Saccharomyces cerevisiae kinetochores are among the best understood. In contrast, most fungal, plant and animal cells assemble kinetochores on CENs that are longer and more complex, raising the question of whether kinetochore architecture has been conserved through evolution, despite considerable divergence in CEN sequence. Results: Using computational approaches, ranging from sequence similarity searches to hidden Markov model-based modeling, we show that organisms with CENs resembling those in...

  6. Paradoxical expression of INK4c in proliferative multiple myeloma tumors: bi-allelic deletion vs increased expression

    Dib, Amel; Raducha-Grace, Laura; Zingone, Adriana; Zhan, Fenghuang; Hanamura, Ichiro; Barlogie, Bart; Shaughnessy, John Jr; Kuehl, W Michael; Peterson, Timothy Richard
    Background: A high proliferative capacity of tumor cells usually is associated with shortened patient survival. Disruption of the RB pathway, which is critically involved in regulating the G1 to S cell cycle transition, is a frequent target of oncogenic events that are thought to contribute to increased proliferation during tumor progression. Previously, we determined that p18INK4c, an essential gene for normal plasma cell differentiation, was bi-allelically deleted in five of sixteen multiple myeloma (MM) cell lines. The present study was undertaken to investigate a possible role of p18INK4c in increased proliferation of myeloma tumors as they progress. Results: Thirteen of...

  7. Transport lattice models of heat transport in skin with spatially heterogeneous, temperature-dependent perfusion

    Martin, Gregory T; Weaver, James C; Gowrishankar, Thiruvallur R.; Stewart, Donald A., Jr.
    Background: Investigation of bioheat transfer problems requires the evaluation of temporal and spatial distributions of temperature. This class of problems has been traditionally addressed using the Pennes bioheat equation. Transport of heat by conduction, and by temperature-dependent, spatially heterogeneous blood perfusion is modeled here using a transport lattice approach. Methods: We represent heat transport processes by using a lattice that represents the Pennes bioheat equation in perfused tissues, and diffusion in nonperfused regions. The three layer skin model has a nonperfused viable epidermis, and deeper regions of dermis and subcutaneous tissue with perfusion that is constant or temperature-dependent. Two cases...

  8. Neurite outgrowth on a fibronectin isoform expressed during peripheral nerve regeneration is mediated by the interaction of paxillin with alpha4beta1 integrins

    Vogelezang, Mariette; Forster, Ulrike B; Han, Jaewon; Ginsberg, Mark H; ffrench-Constant, Charles
    Background: The regeneration of peripheral nerve is associated with a change in the alternative splicing of the fibronectin primary gene transcript to re-express embryonic isoforms containing a binding site for α4β1 integrins that promote neurite outgrowth. Here we use PC12 cells to examine the role of the interaction between paxillin and the α4 integrin cytoplasmic domain in neurite outgrowth. Results: Expression of α4 with mutations in the paxillin-binding domain reduced neurite outgrowth on recombinant embryonic fibronectin fragments relative to wild type α4. Over-expression of paxillin promoted neurite outgrowth while a mutant isoform lacking the LD4 domain implicated in the regulation...

  9. Positive selection for unpreferred codon usage in eukaryotic genomes

    Neafsey, Daniel E.; Galagan, James E.
    Background: Natural selection has traditionally been understood as a force responsible for pushing genes to states of higher translational efficiency, whereas lower translational efficiency has been explained by neutral mutation and genetic drift. We looked for evidence of directional selection resulting in increased unpreferred codon usage (and presumably reduced translational efficiency) in three divergent clusters of eukaryotic genomes using a simple optimal-codon-based metric (Kp/Ku). Results: Here we show that for some genes natural selection is indeed responsible for causing accelerated unpreferred codon substitution, and document the scope of this selection. In Cryptococcus and to a lesser extent Drosophila, we find...

  10. What makes us human?

    Mikkelsen, Tarjei S.
    The sequence of chimpanzee chromosome 22 is starting to help us to define the set of genetic attributes that are unique to humans, but interpreting the biological consequences of these remains a major challenge.

  11. Altering coenzyme specificity of Pichia stipitis xylose reductase by the semi-rational approach CASTing

    Liang, Ling; Zhang, Jingqing; Lin, Zhanglin
    Background: The NAD(P)H-dependent Pichia stipitis xylose reductase (PsXR) is one of the key enzymes for xylose fermentation, and has been cloned into the commonly used ethanol-producing yeast Saccharomyces cerevisiae. In order to eliminate the redox imbalance resulting from the preference of this enzyme toward NADPH, efforts have been made to alter the coenzyme specificity of PsXR by site-directed mutagenesis, with limited success. Given the industrial importance of PsXR, it is of interest to investigate further ways to create mutants of PsXR that prefers NADH rather than NADPH, by the alternative directed evolution approach. Results: Based on a homology model of...

  12. Analysis of a set of Australian northern brown bandicoot expressed sequence tags with comparison to the genome sequence of the South American grey short tailed opossum

    Baker, Michelle L.; Indiviglio, Sandra; Nyberg, April M; Rosenberg, George H; Lindblad-Toh, Kerstin; Miller, Robert D.; Papenfuss, Anthony T.
    Background: Expressed sequence tags (ESTs) have been used for rapid gene discovery in a variety of organisms and provide a valuable resource for whole genome annotation. Although the genome of one marsupial, the opossum Monodelphis domestica, has now been sequenced, no EST datasets have been reported from any marsupial species. In this study we describe an EST dataset from the bandicoot, Isoodon macrourus, providing information on the transcriptional profile of the bandicoot thymus and the opportunity for a genome wide comparison between the bandicoot and opossum, two distantly related marsupial species. Results: A set of 1319 ESTs was generated from...

  13. Validation and refinement of gene-regulatory pathways on a network of physical interactions

    Yeang, Chen-Hsiang, 1969-; Mak, Craig; McCuine, Scott; Workman, Christopher; Ideker, Trey; Jaakkola, Tommi S.
    As genome-scale measurements lead to increasingly complex models of gene regulation, systematic approaches are needed to validate and refine these models. Towards this goal, we describe an automated procedure for prioritizing genetic perturbations in order to discriminate optimally between alternative models of a gene-regulatory network. Using this procedure, we evaluate 38 candidate regulatory networks in yeast and perform four high-priority gene knockout experiments. The refined networks support previously unknown regulatory mechanisms downstream of SOK2 and SWI4.

  14. Web GIS in practice VIII: HTML5 and the canvas element for interactive online mapping

    Kamel Boulos, Maged N.; Gong, Jianya; Yue, Peng; Warren, Jeffrey Yoo
    HTML5 is being developed as the next major revision of HTML (Hypertext Markup Language), the core markup language of the World Wide Web. It aims at reducing the need for proprietary, plug-in-based rich Internet application (RIA) technologies such as Adobe Flash. The canvas element is part of HTML5 and is used to draw graphics using scripting (e.g., JavaScript). This paper introduces Cartagen, an open-source, vector-based, client-side framework for rendering plug-in-free, offline-capable, interactive maps in native HTML5 on a wide range of Web browsers and mobile phones. Cartagen was developed at MIT Media Lab's Design Ecology group. Potential applications of the...

  15. PFAAT version 2.0 : A tool for editing, annotating, and analyzing multiple sequence alignments

    Caffrey, Daniel R; Dana, Paul H; Mathur, Vidhya; Ocano, Marco; Hong, Eun-Jong; Wang, Yaoyu E; Somaroo, Shyamal; Caffrey, Brian E; Potluri, Shobha; Huang, Enoch S
    Background: By virtue of their shared ancestry, homologous sequences are similar in their structure and function. Consequently, multiple sequence alignments are routinely used to identify trends that relate to function. This type of analysis is particularly productive when it is combined with structural and phylogenetic analysis. Results: Here we describe the release of PFAAT version 2.0, a tool for editing, analyzing, and annotating multiple sequence alignments. Support for multiple annotations is a key component of this release as it provides a framework for most of the new functionalities. The sequence annotations are accessible from the alignment and tree, where they...

  16. Zebrafish promoter microarrays identify actively transcribed embryonic genes

    Wardle, Fiona C; Odom, Duncan; Bell, George W.; Wiellette, Elizabeth L; Herbolsheimer, Elizabeth; Smith, James C; Yuan, Bingbing B.; Sive, Hazel L.; Danford, Timothy William; Young, Richard A.
    We have designed a zebrafish genomic microarray to identify DNA-protein interactions in the proximal promoter regions of over 11,000 zebrafish genes. Using these microarrays, together with chromatin immunoprecipitation with an antibody directed against tri-methylated lysine 4 of Histone H3, we demonstrate the feasibility of this method in zebrafish. This approach will allow investigators to determine the genomic binding locations of DNA interacting proteins during development and expedite the assembly of the genetic networks that regulate embryogenesis.

  17. Microarray analysis of microRNA expression in the developing mammalian brain

    Miska, Eric A.; Alvarez-Saavedra, Ezequiel; Yoshii, Akira; Sestan, Nenad; Rakic, Pasko; Constantine-Paton, Martha; Horvitz, H. Robert; Townsend, Matthew R.
    Background: MicroRNAs are a large new class of tiny regulatory RNAs found in nematodes, plants, insects and mammals. MicroRNAs are thought to act as post-transcriptional modulators of gene expression. In invertebrates microRNAs have been implicated as regulators of developmental timing, neuronal differentiation, cell proliferation, programmed cell death and fat metabolism. Little is known about the roles of microRNAs in mammals. Results: We isolated 18-26 nucleotide RNAs from developing rat and monkey brains. From the sequences of these RNAs and the sequences of the rat and human genomes we determined which of these small RNAs are likely to have derived from...

  18. Mining data from hemodynamic simulations via Bayesian emulation

    Bressloff, Neil W; Kolachalama, Vijaya Bhasker; Nair, Prasanth B.
    Background: Arterial geometry variability is inevitable both within and across individuals. To ensure realistic prediction of cardiovascular flows, there is a need for efficient numerical methods that can systematically account for geometric uncertainty. Methods and results: A statistical framework based on Bayesian Gaussian process modeling was proposed for mining data generated from computer simulations. The proposed approach was applied to analyze the influence of geometric parameters on hemodynamics in the human carotid artery bifurcation. A parametric model in conjunction with a design of computer experiments strategy was used for generating a set of observational data that contains the maximum wall...

  19. Re-identification of home addresses from spatial locations anonymized by Gaussian skew

    Cassa, Christopher A.; Wieland, Shannon Christine; Mandl, Kenneth D.
    Background: Knowledge of the geographical locations of individuals is fundamental to the practice of spatial epidemiology. One approach to preserving the privacy of individual-level addresses in a data set is to de-identify the data using a non-deterministic blurring algorithm that shifts the geocoded values. We investigate a vulnerability in this approach which enables an adversary to re-identify individuals using multiple anonymized versions of the original data set. If several such versions are available, each can be used to incrementally refine estimates of the original geocoded location. Results: We produce multiple anonymized data sets using a single set of addresses and...

  20. Genomic patterns of pathogen evolution revealed by comparison of Burkholderia pseudomallei, the causative agent of melioidosis, to avirulent Burkholderia thailandensis

    Yu, Yiting; Chua, Hui Hoon; Lin, Chi Ho; Sim, Siew Hoon; Lin, Daoxun; Derr, Alan; Engels, Reinhard; DeShazer, David; Birren, Bruce W.; Nierman, William C.; Tan, Patrick; Kim, H. Stanley
    Background: The Gram-negative bacterium Burkholderia pseudomallei (Bp) is the causative agent of the human disease melioidosis. To understand the evolutionary mechanisms contributing to Bp virulence, we performed a comparative genomic analysis of Bp K96243 and B. thailandensis (Bt) E264, a closely related but avirulent relative. Results: We found the Bp and Bt genomes to be broadly similar, comprising two highly syntenic chromosomes with comparable numbers of coding regions (CDs), protein family distributions, and horizontally acquired genomic islands, which we experimentally validated to be differentially present in multiple Bt isolates. By examining species-specific genomic regions, we derived molecular explanations for previously-known...

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