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

Insect visual orientation is mostly considered as a stimulus-response phenomenon1,2. This view may be challenged in Drosophila melanogaster by genetic dissection, as we show here. When suspended in a fixed position in a flight simulator3, which transforms torque into angular velocity of the panorama, Drosophila establishes a state of zero net rotation of the panorama (optomotor balance4). The genetic variant rol sol, with greatly reduced optic lobes, is entirely motion-blind but can respond with turning manoeuvres to the position of landmarks. Mutant flies maintain optomotor balance but do so irrespective of the sign of the visual feedback in the simulator, that is, whether angular velocity is inversely or directly proportional to torque. Using the amount, but not the direction, of pattern motion the flies stabilize the panorama by trying out which value of torque has the desired effect. We conclude that operant behaviour is a basic constituent of visual orientation in flies.

Visual orientation in motion-blind flies is an operant behaviour

Drosophila flies can be trained in the flight simulator to operantly avoid heat by choosing certain orientations relative to landmarks. Flies primarily store pattern orientations associated with the absence of heat. They readily escape from heat-associated orientations under the direct influence of the reinforcer but not in the subsequent memory tests. The flies tend to keep the largest possible distance from the "hot" or potentially "hot" regions, that is, they head toward the center of the "cold" sector. The results are discussed in the light of the retinotopic matching model explaining visual memory in flies by the superposition of a retinotopically stored template with the actual retinal image. Window experiments confining visual feedback to two 90 degrees sectors indicate that the memory template covers most of the visible space.

/pdf/behavioral-analysis-of-drosophila-landmark-learning-in-the-1hcwzb3d4d.pdf

Behavioral analysis of Drosophila landmark learning in the flight simulator.

Even in a simple Pavlovian memory task an animal may form several associations that can be independently assessed by the appropriate tests. Studying conditioned odor discrimination of the fruit fly Drosophila melanogaster we found that animals store quality and intensity of an odor as separate memory traces. The trace of odor intensity is short-lived, decaying in <3 h. Only the last intensity value is stored. In contrast to odor-quality memory, odor-intensity memory does not require the rutabaga-dependent cAMP signaling pathway. Flies rely on their memory of intensity in a narrow concentration range in which they can generalize intensity. Larger concentration differences they treat like different qualities. This study shows that the perceptual identity of an odor is based on at least three lines of processing in the brain: (i) a memory of odor quality, (ii) a memory of odor intensity, and (iii) a range of intensities (and qualities), in which the odor is generalized.

https://www.pnas.org/content/pnas/105/41/15985.full.pdf

Distinct memories of odor intensity and quality in Drosophila.

Mutations in the complex optomotor-blind (omb) gene locus (4C4-6) lead to a number of different phenotypes in various tissues of the adult Drosophila melanogaster fly. At the core of the locus lies a lethal complementation group, named l(1)omb, whose mutations cause larval and pupal lethality. Some 40% of all males hemizygous for lethal omb alleles develop to the pharate adult stage. These flies can be rescued from the pupal case and show a severe disturbance in optic lobe development. The recessive viable allele In(1)ombH31 reduces the optomotor response in walking flies and during stationary flight of tethered flies. At the neuroanatomical level, these animals lack a subset of lobula plate giant neurons (LPGNs), which are thought to mediate optomotor behavior. Chromosomal aberrations deleting the proximal, non transcribed part of the locus complement the lethality, but still cause neuroanatomical and optomotor defects. Analysis of different allelic combinations of such mutations, in which increasing amo...

Mutations in the proximal region of the optomotor-blind locus of Drosophila melanogaster reveal a gradient of neuroanatomical and behavioral phenotypes.

Martin Heisenberg

Papers

Visual orientation in motion-blind flies is an operant behaviour

Behavioral analysis of Drosophila landmark learning in the flight simulator.

Distinct memories of odor intensity and quality in Drosophila.

Mutations in the proximal region of the optomotor-blind locus of Drosophila melanogaster reveal a gradient of neuroanatomical and behavioral phenotypes.

Evolutionary significance of courtship conditioning in Drosophila melanogaster