Students' views of the important facets of CS before and after the course.

<p>Numbers indicate how many students among the responders included the notion in their definition for the discipline.</p

Examples for computational concepts and thinking processes discussed in various topics, and emphasized in the “reflection” stage of the pipeline.

<p>Examples for computational concepts and thinking processes discussed in various topics, and emphasized in the “reflection” stage of the pipeline.</p

BioNSi: A Discrete Biological Network Simulator Tool

Modeling and simulation of biological networks is an effective and widely used research methodology. The Biological Network Simulator (BioNSi) is a tool for modeling biological networks and simulating their discrete-time dynamics, implemented as a Cytoscape App. BioNSi includes a visual representation of the network that enables researchers to construct, set the parameters, and observe network behavior under various conditions. To construct a network instance in BioNSi, only partial, qualitative biological data suffices. The tool is aimed for use by experimental biologists and requires no prior computational or mathematical expertise. BioNSi is freely available at http://bionsi.wix.com/bionsi, where a complete user guide and a step-by-step manual can also be found

Interactions between the circadian clock and TGF-β signaling pathway in zebrafish

<div><p>Background</p><p>TGF-β signaling is a cellular pathway that functions in most cells and has been shown to play a role in multiple processes, such as the immune response, cell differentiation and proliferation. Recent evidence suggests a possible interaction between TGF-β signaling and the molecular circadian oscillator. The current study aims to characterize this interaction in the zebrafish at the molecular and behavioral levels, taking advantage of the early development of a functional circadian clock and the availability of light-entrainable clock-containing cell lines.</p><p>Results</p><p><i>Smad3a</i>, a TGF-β signaling-related gene, exhibited a circadian expression pattern throughout the brain of zebrafish larvae. Both pharmacological inhibition and indirect activation of TGF-β signaling in zebrafish Pac-2 cells caused a concentration dependent disruption of rhythmic promoter activity of the core clock gene <i>Per1b</i>. Inhibition of TGF-β signaling in intact zebrafish larvae caused a phase delay in the rhythmic expression of <i>Per1b</i> mRNA. TGF-β inhibition also reversibly disrupted, phase delayed and increased the period of circadian rhythms of locomotor activity in zebrafish larvae.</p><p>Conclusions</p><p>The current research provides evidence for an interaction between the TGF-β signaling pathway and the circadian clock system at the molecular and behavioral levels, and points to the importance of TGF-β signaling for normal circadian clock function. Future examination of this interaction should contribute to a better understanding of its underlying mechanisms and its influence on a variety of cellular processes including the cell cycle, with possible implications for cancer development and progression.</p></div

Locomotor activity levels in response to dark flashes is not effected by TGF-β inhibition.

<p>Larvae were kept under LD cycles. On day 5 the inhibitor, or DMSO as control, was added on day 6. Larvae were subjected to 3 dark flashes of 10 seconds each, which are known to induce startle response, with 15 minutes intervals of light between flashes, and their activity was recorded (upper panel). No statistical difference was observed between the activity of control (DMSO) and the TGF-β inhibitor (LY-374947, 20μM) treated groups during the dark flashes (<i>p = 0</i>.<i>28</i>, <i>t</i>-test), indicating that TGF-β inhibition does not impair larval mobility (lower panel). Each line represents the average of three succeeding trials, which measured the average movement per second of each group of larvae, recorded from 10 second before the flash, during the flash, and 10 second after the flash. Black and white horizontal boxes represent the light phase and dark flashes, respectively. This experiment was repeated twice, resulting in similar outcomes. The represented results are of one experiment.</p

<i>Smad3a</i> mRNA shows a circadian clock-controlled expression in zebrafish larvae heads.

<p><i>Smad3a</i> mRNA exhibits a circadian rhythm expression pattern in zebrafish larvae heads, with mRNA expression significantly affected by sampling time (<i>p<00</i>.<i>1</i>, two-way ANOVA), showing higher expression levels during late night-time and daytime than early night-time. This pattern persists in constant darkness, suggesting that it is regulated by the circadian clock. In addition, <i>Smad3a</i> mRNA expression is also significantly affected by lighting conditions (<i>p<0</i>.<i>001</i>, two-way ANOVA), with a significant interaction between sampling time and light conditions (<i>p<0</i>.<i>001</i>, two-way ANOVA) (n = 15/group). (A) <u>Top panel</u>: schematic representation of the experimental design. The horizontal bars represent the lighting conditions before and during sampling; white boxes represent light and black boxes represent dark periods. <u>Bottom panel</u>: whole mount ISH images for <i>Smad3a</i> mRNA (dorsal views) of representative specimens raised under LD cycles until and during sampling or kept under DD during sampling. Circadian times are indicated for each sample. CT0 corresponds to “subjective lights on”, CT12 to “subjective lights-off”. White bars represent light phases and black bars represent dark phases. (B) <u>Left</u>: quantification of signal intensities in the head of larvae under LD and DD. Values represent the mean ±SE optical densities of the head signals. White bars represent subjective day and black bars represent subjective night. <u>Right</u>: Different letters represent statistically different values within each photoperiodic treatment (<i>p<0</i>.<i>05</i>, one-way ANOVA, Tukey’s test). This experiment was repeated twice resulting in a similar outcome. The represented results are of one experiment.</p

Clock-dependent circadian expression pattern of <i>Smad3a</i>, <i>Smad7</i>, and <i>Tgif1</i> in the adult zebrafish pineal gland.

<p>Data mining of a previous RNA-sequencing experiment reveals that the TGF-β signaling genes <i>Smad3a</i> (top left), <i>Smad7</i> (top right) and <i>Tgif1</i> (mid left) exhibit a circadian expression pattern in the zebrafish pineal gland under constant darkness (DD), which is diminished in transgenic fish with a disrupted pineal circadian clock, Tg(<i>aanat2</i>: EGFP-ΔCLK), similarly to the known clock-controlled gene, <i>aanat2</i> (mid right). Grey bars represent subjective day and black bars represent subjective night. CT0 corresponds to “subjective lights on”, CT12 to “subjective lights-off”. <i>Bottom</i>: a comparison between the g-factor values of different TGF-β signaling genes in both control and transgenic fish. In control fish, <i>Smad3a</i>, <i>Smad7</i> and <i>Tgif1</i> exhibit rhythmic expression patterns with a high g-factor value, similar to that of <i>aanat2</i>, indicating that they indeed exhibit a circadian expression pattern. In ΔClock fish these genes lose their rhythmic expression pattern as indicated by significantly lower g-factor values, implying that their circadian pattern is regulated by the core mechanism of the circadian clock. The TGF-β related genes <i>Tfgb1a</i>, <i>Tgfb2</i>, <i>Tgfb3</i> and <i>Smad3b</i> exhibit low g-factor values in both groups, indicating they are not expressed in a circadian manner in the zebrafish pineal gland.</p