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.

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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.

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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.

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Interleukin-1 polymorphisms associated with increased risk of gastric cancer

Ever since learning and memory have been studied experimentally, the relationship between operant and classical conditioning has been controversial. Operant conditioning is any form of conditioning that essentially depends on the animal's behavior. It relies on operant behavior. A motor output is called operant if it controls a sensory variable. The Drosophila flight simulator, in which the relevant behavior is a single motor variable (yaw torque), fully separates the operant and classical components of a complex conditioning task. In this paradigm a tethered fly learns, operantly or classically, to prefer and avoid certain flight orientations in relation to the surrounding panorama. Yaw torque is recorded and, in the operant mode, controls the panorama. Using a yoked control, we show that classical pattern learning necessitates more extensive training than operant pattern learning. We compare in detail the microstructure of yaw torque after classical and operant training but find no evidence for acquired behavioral traits after operant conditioning that might explain this difference. We therefore conclude that the operant behavior has a facilitating effect on the classical training. In addition, we show that an operantly learned stimulus is successfully transferred from the behavior of the training to a different behavior. This result unequivocally demonstrates that during operant conditioning classical associations can be formed.

/pdf/the-operant-and-the-classical-in-conditioned-orientation-of-2wrxsn9hqc.pdf

The Operant and the Classical in Conditioned Orientation of Drosophila melanogaster at the Flight Simulator

Drosophila melanogaster is able to perform osmotropotaxis under open-loop conditions. With an ‘optimal’ stimulus the average turning tendency to the side of higher concentration corresponds to a circular track with radiusr=0.8 cm. The response amplitude does not decrease within 1 or 2 h. Unilaterally antennectomized flies in an homogeneous odor field show a permanent turning tendency towards their intact side. The smallest concentration ratio to elicit osmotropotaxis in normal flies ranges between 6∶10 and 9∶10 at high and between 2∶10 and 5∶10 at an about 50 times lower odor intensity. No negative tropotaxis (i.e. turning to the side of lower concentration) is observed, even with strong repellents.

Osmotropotaxis inDrosophila melanogaster

Partially blind mutants can be used to investigate the processing of visual information in the fruit flyDrosophila. This approach requires (1) procedures for the selection of a variety of partially blind mutants, and (2) a strategy for the identification and coordination of visual malfunctions by comparison of interrelated traits of behaviour. The two selection techniques so far employed to recover partially blind mutants use either the fast phototaxis or the optomotor response as selection determining behaviour. The second method is described here and is applied specifically to select mutants in which one of the two autonomous subsystems of vision designated asHigh Sensitivity System andHigh Acuity System is defective. (The mutants obtained are apparently normal with respect to their HAS whereas the HSS is blocked.) Two sets of experiments have been developed in order to test interrelated traits of behaviour in a comparatively large number of flies. One set of experiments measuresslow phototaxis as a function of light intensity. The other is to determine the optomotor response to moving patterns of different spatial periods as functions of both the average brightness and the speed of the movement. Further techniques such as electroretinography and optical inspection of the eyes are used to complement the behavioural approach. By combination of the different tests a first step has been made in the characterization and classification of partially blind mutants with neuronal disorders obtained by different selection procedures and in different laboratories.

The use of mutations for the partial degradation of vision in Drosophila melanogaster

The X-chromosomal complementation unit lethal(1)optomotor-blind [l(1)omb] is defined by lack of complementation among over a dozen recessive lethal mutations that map to the omb gene locus. Mutations in l(1)omb also fail to complement viable mutations of three seemingly unrelated functions in this region: bifid (bi), manifesting defective wings, Quadroon (Qd), a semi-dominant mutation expressing abnormal tergite pigmentation, and In(1)ombH31, giving rise to a normal external morphology but with discrete defects in the optic lobes and behavior. The locus encodes a 70-kilobase primary transcript that is spliced into a 6-kilobase mature RNA. cDNAs for this transcript were isolated and sequenced and the derived amino acid sequence was analyzed. Certain features of this sequence suggest that the l(1)omb gene product is a nuclear regulatory protein. The lethal phase of various apparent null mutants was determined and found to occur mainly in the pupal stage. A large proportion of all hemizygous mutant males develop to pharate adults that eclose only rarely but can be rescued from the pupal case. These animals show a severe maldevelopment of the optic lobes. In addition they have only rudimentary wings as well as a Quadroon-like abdominal pigmentation. Thus, in the lethal mutants those parts of the body are affected for which independent viable mutations have been previously described in the omb locus, such as optomotor-blind, bifid, and Quadroon.

http://www.pnas.org/content/89/4/1199.full.pdf

The Lethal(1) Optomotor-Blind Gene of Drosophila melanogaster is a Major Organizer of Optic Lobe Development: Isolation and Characterization of the Gene

Scientists and philosophers are using new discoveries in neuroscience to question the idea of free will. They are misguided, says Martin Heisenberg. Examining animal behaviour shows how our actions can be free.

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Martin Heisenberg

Papers

The Operant and the Classical in Conditioned Orientation of Drosophila melanogaster at the Flight Simulator

Osmotropotaxis inDrosophila melanogaster

The use of mutations for the partial degradation of vision in Drosophila melanogaster

The Lethal(1) Optomotor-Blind Gene of Drosophila melanogaster is a Major Organizer of Optic Lobe Development: Isolation and Characterization of the Gene

Is free will an illusion