Temporal Dysynchrony in brain connectivity gene expression following hypoxia

List of K-means cluster analysis of connectivity genes across development during hypoxia. Relative log2 fold change compared to the developmental average is provided. (XLSX 197 kb

LifeLines: Visualizing personal histories

LifeLines provide a general visualization environment for personal histories that can be applied to medical and court records, professional histories and other types of biographical data. A one screen overview shows multiple facets of the records. Aspects, for example medical conditions or legal cases, are displayed as individual time lines, while icons indicate discrete events, such as physician consultations or legal reviews. Line color and thickness illustrate relationships or significance, scaling tools and filters allow users to focus on part of the information. LifeLines reduce the chances of missing information, facilitate spotting anomalies and trends, streamline access to details, while remaining tailorable and easily sharable between applications. The paper describes the use of LifeLines for youth records of the Maryland Department of Juvenile Justice and also for medical records. User's feedback was collected using a Visual Basic prototype for the youth record. Techniques to deal with complex records are reviewed and issues of a standard personal record format are discussed. additional reference numbers in the format of the next line (Also cross-referenced as CAR-TR-787, ISR-TR-95-88

Cellular electroporation induces dedifferentiation in intact newt limbs

AbstractNewts have the remarkable ability to regenerate lost appendages including their forelimbs, hindlimbs, and tails. Following amputation of an appendage, the wound is rapidly closed by the migration of epithelial cells from the proximal epidermis. Internal cells just proximal to the amputation plane begin to dedifferentiate to form a pool of proliferating progenitor cells known as the regeneration blastema. We show that dedifferentiation of internal appendage cells can be initiated in the absence of amputation by applying an electric field sufficient to induce cellular electroporation, but not necrosis or apoptosis. The time course for dedifferentiation following electroporation is similar to that observed following amputation with evidence of dedifferentiation beginning at about 5 days postelectroporation and continuing for 2 to 3 weeks. Microarray analyses, real-time RT-PCR, and in situ hybridization show that changes in early gene expression are similar following amputation or electroporation. We conclude that the application of an electric field sufficient to induce transient electroporation of cell membranes induces a dedifferentiation response that is virtually indistinguishable from the response that occurs following amputation of newt appendages. This discovery allows dedifferentiation to be studied in the absence of wound healing and may aid in identifying genes required for cellular plasticity

Next generation tools for genomic data generation, distribution, and visualization

BACKGROUND: With the rapidly falling cost and availability of high throughput sequencing and microarray technologies, the bottleneck for effectively using genomic analysis in the laboratory and clinic is shifting to one of effectively managing, analyzing, and sharing genomic data. RESULTS: Here we present three open-source, platform independent, software tools for generating, analyzing, distributing, and visualizing genomic data. These include a next generation sequencing/microarray LIMS and analysis project center (GNomEx); an application for annotating and programmatically distributing genomic data using the community vetted DAS/2 data exchange protocol (GenoPub); and a standalone Java Swing application (GWrap) that makes cutting edge command line analysis tools available to those who prefer graphical user interfaces. Both GNomEx and GenoPub use the rich client Flex/Flash web browser interface to interact with Java classes and a relational database on a remote server. Both employ a public-private user-group security model enabling controlled distribution of patient and unpublished data alongside public resources. As such, they function as genomic data repositories that can be accessed manually or programmatically through DAS/2-enabled client applications such as the Integrated Genome Browser. CONCLUSIONS: These tools have gained wide use in our core facilities, research laboratories and clinics and are freely available for non-profit use. See http://sourceforge.net/projects/gnomex/, http://sourceforge.net/projects/genoviz/, and http://sourceforge.net/projects/useq

Ccdc94 Protects Cells from Ionizing Radiation by Inhibiting the Expression of p53

DNA double-strand breaks (DSBs) represent one of the most deleterious forms of DNA damage to a cell. In cancer therapy, induction of cell death by DNA DSBs by ionizing radiation (IR) and certain chemotherapies is thought to mediate the successful elimination of cancer cells. However, cancer cells often evolve to evade the cytotoxicity induced by DNA DSBs, thereby forming the basis for treatment resistance. As such, a better understanding of the DSB DNA damage response (DSB–DDR) pathway will facilitate the design of more effective strategies to overcome chemo- and radioresistance. To identify novel mechanisms that protect cells from the cytotoxic effects of DNA DSBs, we performed a forward genetic screen in zebrafish for recessive mutations that enhance the IR–induced apoptotic response. Here, we describe radiosensitizing mutation 7 (rs7), which causes a severe sensitivity of zebrafish embryonic neurons to IR–induced apoptosis and is required for the proper development of the central nervous system. The rs7 mutation disrupts the coding sequence of ccdc94, a highly conserved gene that has no previous links to the DSB–DDR pathway. We demonstrate that Ccdc94 is a functional member of the Prp19 complex and that genetic knockdown of core members of this complex causes increased sensitivity to IR–induced apoptosis. We further show that Ccdc94 and the Prp19 complex protect cells from IR–induced apoptosis by repressing the expression of p53 mRNA. In summary, we have identified a new gene regulating a dosage-sensitive response to DNA DSBs during embryonic development. Future studies in human cancer cells will determine whether pharmacological inactivation of CCDC94 reduces the threshold of the cancer cell apoptotic response

Data from: Transcriptome sequencing and microarray development for the woodrat (Neotoma spp.): custom genetic tools for exploring herbivore ecology

Massively parallel sequencing has enabled the creation of novel, in-depth genetic tools for nonmodel, ecologically important organisms. We present the de novo transcriptome sequencing, analysis and microarray development for a vertebrate herbivore, the woodrat (Neotoma spp.). This genus is of ecological and evolutionary interest, especially with respect to ingestion and hepatic metabolism of potentially toxic plant secondary compounds. We generated a liver transcriptome of the desert woodrat (Neotoma lepida) using the Roche 454 platform. The assembled contigs were well annotated using rodent references (99.7% annotation), and biotransformation function was reflected in the gene ontology. The transcriptome was used to develop a custom microarray (eArray, Agilent). We tested the microarray with three experiments: one across species with similar habitat (thus, dietary) niches, one across species with different habitat niches and one across populations within a species. The resulting one-colour arrays had high technical and biological quality. Probes designed from the woodrat transcriptome performed significantly better than functionally similar probes from the Norway rat (Rattus norvegicus). There were a multitude of expression differences across the woodrat treatments, many of which related to biotransformation processes and activities. The pattern and function of the differences indicate shared ecological pressures, and not merely phylogenetic distance, play an important role in shaping gene expression profiles of woodrat species and populations. The quality and functionality of the woodrat transcriptome and custom microarray suggest these tools will be valuable for expanding the scope of herbivore biology, as well as the exploration of conceptual topics in ecology

LifeLines: Visualizing Personal Histories

LifeLines provide a general visualization environment for personal histories that can be applied to medical and court records, professional histories and other types of biographical data. A one screen overview shows multiple facets of the records. Aspects, for example medical conditions or legal cases, are displayed as individual time lines, while icons indicate discrete events, such as physician consultations or legal reviews. Line color and thickness illustrate relationships or significance, rescaling tools and filters allow users to focus on part of the information. LifeLines reduce the chances of missing information, facilitate spotting anomalies and trends, streamline access to details, while remaining tailorable and easily transferable between applications. The paper describes the use of LifeLines for youth records of the Maryland Department of Juvenile Justice and also for medical records. User's feedback was collected using a Visual Basic prototype for the youth record. Techniq..

Table2_matchedprobes_bothComp

Table2_matchedprobes_bothCom

Table2_LRvsPS_Neoprobes

Table2_LRvsPS_Neoprobe