SPIKE – a database, visualization and analysis tool of cellular signaling pathways

<p>Abstract</p> <p>Background</p> <p>Biological signaling pathways that govern cellular physiology form an intricate web of tightly regulated interlocking processes. Data on these regulatory networks are accumulating at an unprecedented pace. The assimilation, visualization and interpretation of these data have become a major challenge in biological research, and once met, will greatly boost our ability to understand cell functioning on a systems level.</p> <p>Results</p> <p>To cope with this challenge, we are developing the SPIKE knowledge-base of signaling pathways. SPIKE contains three main software components: 1) A database (DB) of biological signaling pathways. Carefully curated information from the literature and data from large public sources constitute distinct tiers of the DB. 2) A visualization package that allows interactive graphic representations of regulatory interactions stored in the DB and superposition of functional genomic and proteomic data on the maps. 3) An algorithmic inference engine that analyzes the networks for novel functional interplays between network components.</p> <p>SPIKE is designed and implemented as a community tool and therefore provides a user-friendly interface that allows registered users to upload data to SPIKE DB. Our vision is that the DB will be populated by a distributed and highly collaborative effort undertaken by multiple groups in the research community, where each group contributes data in its field of expertise.</p> <p>Conclusion</p> <p>The integrated capabilities of SPIKE make it a powerful platform for the analysis of signaling networks and the integration of knowledge on such networks with <it>omics </it>data. </p

The effects of feedback and reflection on the questioning style of untrained interviewers in simulated child sexual abuse interviews

We provided immediate and detailed feedback in a training paradigm in which simulated interviews with computer‐generated avatars were used to improve interviewers' questioning style. Fifty‐nine untrained student/interviewers conducted eight interviews each and were randomly assigned to a control, feedback or feedback and reflection group. Compared to the control group, the groups receiving feedback used a higher percentage of recommended questions and retrieved more relevant details while using a lower percentage of not recommended questions and retrieved less wrong details. Only the groups that received feedback reached a reliable change in the proportion of recommended questions. The reflection intervention proposed in the present study did not enhance training effects above and beyond feedback in the present sample. The present study replicated previous findings regarding the role of feedback in improving the quality of investigative interviews, however, failing to show an effect of reflection. Further studies on different reflection tasks are suggested

Manipulating the Biosynthesis of Bioactive Compound Alkaloids for Next-Generation Metabolic Engineering in Opium Poppy Using CRISPR-Cas 9 Genome Editing Technology

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated9 (Cas9) endonuclease system is a powerful RNA-guided genome editing tool. CRISPR/Cas9 has been well studied in model plant species for targeted genome editing. However, few studies have been reported on plant species without whole genome sequence information. Currently, no study has been performed to manipulate metabolic pathways using CRISPR/Cas9. In this study, the type II CRISPR/SpCas9 system was used to knock out, via nonhomologous end-joining genome repair, the 4′OMT2 in opium poppy (Papaver somniferum L.), a gene which regulates the biosythesis of benzylisoquinoline alkaloids (BIAs). For sgRNA transcription, viral-based TRV and synthetic binary plasmids were designed and delivered into plant cells with a Cas9 encoding-synthetic vector by Agrobacterium-mediated transformation. InDels formed by CRISPR/Cas9 were detected by sequence analysis. Our results showed that the biosynthesis of BIAs (e.g. morphine, thebaine) was significantly reduced in the transgenic plants suggesting that 4′OMT2 was efficiently knocked-out by our CRISPR-Cas9 genome editing approach. In addition, a novel uncharacterized alkaloid was observed only in CRISPR/Cas9 edited plants. Thus, the applicabilitiy of the CRISPR/Cas9 system was demonstrated for the first time for medicinal aromatic plants by sgRNAs transcribed from both synthetic and viral vectors to regulate BIA metabolism and biosynthesis

Using Pulsed Lasers as a Diagnostic Tool for Radiation-Induced Single-Event Latchup

Femtosecond pulsed lasers are a useful diagnostic and screening tool when evaluating electronic parts for potentially destructive radiation-induced single-event effects such as single-event latchup (SEL). Pulsed lasers may be used to estimate sensitive cross-sections and for comparing the relative sensitivity of equivalent parts

Regional venture capitalism: UK and Germany compared

This report examines the regional complexion of venture capital activity in the UK and Germany over recent years, particularly in the context of spatial concentration versus dispersal. It seeks to identify and explain differences in ‘regional' venture capital policy models between the two countries, and the impacts of those policies to date; and finally to ascertain the scope for further policy development and learning from ‘best practice'

Numeric definition of the clinical performance of the nested reverse transcription-PCR for detection of hematogenous epithelial cells and correction for specific mRNA of non-target cell origin as evaluated for prostate cancer cells

Background: Inappropriate quality management,of reverse transcription-PCR (RT-PCR) assays for the detection of blood-borne prostate cancer (PCa) cells hampers clinical conclusions. Improvement of the RT-PCR-methodology for prostate-specific, antigen (PSA) mRNA should focus on an appropriate numeric. definition of the performance of the assay and correction for PSA mRNA that is not associated with PCa cells. Methods and Results: Repeated (RT-)PCR tests. for PSA mRNA in single. blood specimens from PCa patients and PCa-free controls, performed by four international institutions, showed a large percentage (approximate to 50%) of divergent test results. The best estimates of the mean, lambda (SD), of the expected Poisson frequency distributions of the number of positive tests among five replicate assays of samples from PCa-free individuals were 1.0 (0.2) for 2 X 35 PCR cycles and 0.2 (0.1) for 2 X 25 PCR cycles. Assessment of the numeric value of the mean can be considered as a new indicator of the performance of a RT-PCR assay for PSA mRNA under clinical conditions. Moreover, it determines the required number of positive test repetitions to differentiate between true and false positives for circulating prostate cells. At a pre-defined diagnostic specificity of greater than or equal to98%, repeated PCRs with lambda of either 1.0 or 0.2 require, respectively, more than three or more than one positive-tests to support the conclusion that PSA mRNA-containing cells are present. Conclusions: Repeated nested PCR tests for PSA and appropriate handling of the data allow numeric quantification of the, performance of the assay and differentiation between analytical false and true positives at a predefined accuracy. This new approach may contribute to introduction of PSA RT-PCR, assays in clinical practice. (C) 2003 American Association for Clinical Chemistr

Numeric Definition of the Clinical Performance of the Nested Reverse Transcription-PCR for Detection of Hematogenous Epithelial Cells and Correction for Specific mRNA of Non-Target Cell Origin as Evaluated for Prostate Cancer Cells

Background: Inappropriate quality management of reverse transcription-PCR (RT-PCR) assays for the detection of blood-borne prostate cancer (PCa) cells hampers clinical conclusions. Improvement of the RT-PCR methodology for prostate-specific antigen (PSA) mRNA should focus on an appropriate numeric definition of the performance of the assay and correction for PSA mRNA that is not associated with PCa cells. Methods and Results: Repeated (RT-)PCR tests for PSA mRNA in single blood specimens from PCa patients and PCa-free controls, performed by four international institutions, showed a large percentage (�50%) of divergent test results. The best estimates of the mean, � (SD), of the expected Poisson frequency distributions of the number of positive tests among five replicate assays o