Fiji is a distribution of the popular open-source software ImageJ focused on biological-image analysis. Fiji uses modern software engineering practices to combine powerful software libraries with a broad range of scripting languages to enable rapid prototyping of image-processing algorithms. Fiji facilitates the transformation of new algorithms into ImageJ plugins that can be shared with end users through an integrated update system. We propose Fiji as a platform for productive collaboration between computer science and biology research communities.

/pdf/fiji-an-open-source-platform-for-biological-image-analysis-1v529iu3cx.pdf

Fiji: an open-source platform for biological-image analysis

Forward genetic screens in model organisms have provided important insights into numerous aspects of development, physiology and pathology. With the availability of complete genome sequences and the introduction of RNA-mediated gene interference (RNAi), systematic reverse genetic screens are now also possible. Until now, such genome-wide RNAi screens have mostly been restricted to cultured cells and ubiquitous gene inactivation in Caenorhabditis elegans. This powerful approach has not yet been applied in a tissue-specific manner. Here we report the generation and validation of a genome-wide library of Drosophila melanogaster RNAi transgenes, enabling the conditional inactivation of gene function in specific tissues of the intact organism. Our RNAi transgenes consist of short gene fragments cloned as inverted repeats and expressed using the binary GAL4/UAS system. We generated 22,270 transgenic lines, covering 88% of the predicted protein-coding genes in the Drosophila genome. Molecular and phenotypic assays indicate that the majority of these transgenes are functional. Our transgenic RNAi library thus opens up the prospect of systematically analysing gene functions in any tissue and at any stage of the Drosophila lifespan.

/pdf/a-genome-wide-transgenic-rnai-library-for-conditional-gene-20svjywsa1.pdf

A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila

SUMMARY The mitogen-activated protein kinases (MAPKs) regulate diverse cellular programs by relaying extracellular signals to intracellular responses. In mammals, there are more than a dozen MAPK enzymes that coordinately regulate cell proliferation, differentiation, motility, and survival. The best known are the conventional MAPKs, which include the extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Jun amino-terminal kinases 1 to 3 (JNK1 to -3), p38 (α, β, γ, and δ), and ERK5 families. There are additional, atypical MAPK enzymes, including ERK3/4, ERK7/8, and Nemo-like kinase (NLK), which have distinct regulation and functions. Together, the MAPKs regulate a large number of substrates, including members of a family of protein Ser/Thr kinases termed MAPK-activated protein kinases (MAPKAPKs). The MAPKAPKs are related enzymes that respond to extracellular stimulation through direct MAPK-dependent activation loop phosphorylation and kinase activation. There are five MAPKAPK subfamilies: the p90 ribosomal S6 kinase (RSK), the mitogen- and stress-activated kinase (MSK), the MAPK-interacting kinase (MNK), the MAPK-activated protein kinase 2/3 (MK2/3), and MK5 (also known as p38-regulated/activated protein kinase [PRAK]). These enzymes have diverse biological functions, including regulation of nucleosome and gene expression, mRNA stability and translation, and cell proliferation and survival. Here we review the mechanisms of MAPKAPK activation by the different MAPKs and discuss their physiological roles based on established substrates and recent discoveries.

Activation and Function of the MAPKs and Their Substrates, the MAPK-Activated Protein Kinases

https://hal-pasteur.archives-ouvertes.fr/pasteur-01799353/document

TrackMate: An open and extensible platform for single-particle tracking.

Helicobacter pylori infection is associated with a variety of clinical outcomes including gastric cancer and duodenal ulcer disease. The reasons for this variation are not clear, but the gastric physiological response is influenced by the severity and anatomical distribution of gastritis induced by H. pylori. Thus, individuals with gastritis predominantly localized to the antrum retain normal (or even high) acid secretion, whereas individuals with extensive corpus gastritis develop hypochlorhydria and gastric atrophy, which are presumptive precursors of gastric cancer. Here we report that interleukin-1 gene cluster polymorphisms suspected of enhancing production of interleukin-1-beta are associated with an increased risk of both hypochlorhydria induced by H. pylori and gastric cancer. Two of these polymorphism are in near-complete linkage disequilibrium and one is a TATA-box polymorphism that markedly affects DNA-protein interactions in vitro. The association with disease may be explained by the biological properties of interleukin-1-beta, which is an important pro-inflammatory cytokine and a powerful inhibitor of gastric acid secretion. Host genetic factors that affect interleukin-1-beta may determine why some individuals infected with H. pylori develop gastric cancer while others do not.

/pdf/interleukin-1-polymorphisms-associated-with-increased-risk-42608maro7.pdf

Interleukin-1 polymorphisms associated with increased risk of gastric cancer

SummaryIn stationary flight Drosophila melanogaster produces yaw torque in response to visual movement stimuli. The residual optomotor yaw torque response of the mutant optomotor-blindH31 (omb), which lacks the horizontal (HS) and vertical (VS) giant fibers in the lobula plate, differs from that of wild-type in several aspects: it is restricted to the frontal visual field, it is only elicited by front-to-back motion and appears to be mediated by a different set of elementary movement detectors (EMDs). Using a single black stripe as motion stimulus the torque response is, even in wild-type flies, dominated by the frontal visual field and by front-to-back motion. We thus propose that Drosophila's optomotor yaw control is organized as two partially parallel subunits. The component still displayed by omb is called “object response”; the component missing in the mutant (which is presumably mediated by the giant HS-cells in the wild-type) is called “large field response” Several properties of the object respons...

Genetic Dissection of Optomotor Behavior in Drosophila melanogaster Studies on Wild-Type and the Mutant optomotor-blindH31

Short-term memory in Drosophila melanogaster operant visual learning in the flight simulator is explored using patterns and colours as a compound stimulus. Presented together during training, the two stimuli accrue the same associative strength whether or not a prior training phase rendered one of the two stimuli a stronger predictor for the reinforcer than the other (no blocking). This result adds Drosophila to the list of other invertebrates that do not exhibit the robust vertebrate blocking phenomenon. Other forms of higher-order learning, however, were detected: a solid sensory preconditioning and a small second-order conditioning effect imply that associations between the two stimuli can be formed, even if the compound is not reinforced.

/pdf/conditioning-with-compound-stimuli-in-drosophila-3tylwag0jf.pdf

Conditioning with compound stimuli in Drosophila melanogaster in the flight simulator.

Visual pattern memory of Drosophila melanogaster at the torque meter is investigated by a new learning paradigm called novelty choice. In this procedure the fly is first exposed to four identical patterns presented at the wall of the cylinder surrounding it. In the test it has the choice between two pairs of patterns, a new one and one the same as the training pattern. Flies show a lasting preference for the new figure. Figures presented during training are not recognized as familiar in the test, if displayed (i) at a different height, (ii) at a different size, (iii) rotated or (iv) after contrast reversal. No special invariance mechanisms are found. A pixel-by-pixel matching process is sufficient to explain the observed data. Minor transfer effects can be explained if a graded similarity function is assumed. Recognition depends upon the overlap between the stored template and the actual image. The similarity function is best described by the ratio of the area of overlap to the area of the actual image. The similarity function is independent of the geometrical properties of the employed figures. Visual pattern memory at this basic level does not require the analysis of shape.

Visual Pattern Memory without Shape Recognition

Mutations in the Drosophila gene giant lens (gil) affect ommatidial development, photoreceptor axon guidance and optic lobe development. We have cloned the gene using an enhancer trap line. Molecular analysis of gil suggests that it encodes a secreted protein with an epidermal-growth-factor-like motif. We have generated mutations at the gil locus by imprecise excision of the enhancer trap P-element. In the absence of gil, additional photoreceptors develop at the expense of pigment cells, suggesting an involvement of gil in cell determination during eye development. In addition, gil mutants show drastic effects on photoreceptor axon guidance and optic lobe development. In wildtype flies, photoreceptor axons grow from the eye disc through the optic stalk into the larval brain hemisphere, where retinal innervation is required for the normal development of the lamina and distal medulla. The projection pattern of these axons in the developing lamina and medulla is highly regular and reproducible. In gil, photoreceptor axons enter the larval brain but fail to establish proper connections in the lamina or medulla. We propose that gil encodes a new type of signalling molecule involved in the process of axon pathfinding and cell determination in the visual system of Drosophila.

Giant lens, a gene involved in cell determination and axon guidance in the visual system of Drosophila melanogaster.

In humans visual flow field information is available to many motor output programs enabling them to guide the whole organism. This basic organization still constitutes a major challenge for any theory of orientation. Studies of the fly Drosophila melanogaster during the past 10 years have shown that in the lower animals sensory-motor control has a similar degree of flexibility. In the flight simulator the tethered fly adjusts the strength of its motor commands to their efficacy. It can stabilize the panorama against rotations not only by yaw torque but also by thrust. It learns to invert its flight manoeuvres in response to positive feedback in order to stabilize a stripe in the frontal visual field. In the present report we demonstrate that Drosophila is able to use the force of its legs to stabilize the panorama irrespective of the polarity of the feedback provided experimentally. All these behavioural performances have a common functional organization with the following properties: (i) the system has a desired state from which the actual state may deviate; (ii) to reach the desired state the system randomly activates a range of motor programs; (iii) the system compares efference copies of the motor programs with those sensory inputs which represent the deviation from the desired state; and (iv) if a significant correlation is detected for a certain motor program, this is used to shift the sensory input into the direction of the desired state. It is proposed that for organisms with more than one motor output this is the basic scheme of sensory-motor coordination.

Martin Heisenberg

Papers

Genetic Dissection of Optomotor Behavior in Drosophila melanogaster Studies on Wild-Type and the Mutant optomotor-blindH31

Conditioning with compound stimuli in Drosophila melanogaster in the flight simulator.

Visual Pattern Memory without Shape Recognition

Giant lens, a gene involved in cell determination and axon guidance in the visual system of Drosophila melanogaster.

Can a fly ride a bicycle