The fickle Mutation of a Cytoplasmic Tyrosine Kinase Effects Sensitization but not Dishabituation in Drosophila Melanogaster

fickle is a P-element mutation identified from a screen for defects in courtship behavior and disrupts the fly homolog of Bruton's tyrosine kinase (Btk) gene (Baba et al., 1999). Here, we show that habituation of the olfactory jump reflex also is defective in fickle. Unlike, the prototypical memory mutants, rutabaga and dunce, which habituate more slowly than normal, fickle flies habituate faster than normal. fickle's faster-than-normal response decrement did not appear to be due to sensorimotor fatigue, and dishabituation of the jump response was normal. Based on a long-standing “two opponent process” theory of habituation, these data suggested that behavioral sensitization might be defective in fickle. To test this hypothesis, we designed a olfactory sensitization procedure, using the same stimuli to habituate (odor) and dishabituate (vortexing) flies. Mutant flies failed to show any sensitization with this procedure. Our study reveals a “genetic dissection” of sensitization and dishabituation and, for the first time, provides a biological confirmation of the two opponent process theory of habituation

Olfactory Jump Reflex Habituation in Drosophila and Effects of Classical Conditioning Mutations

Habituation is a nonassociative learning mechanism, in which an initial response toward repeated stimuli gradually wanes. This is amongst the simplest and most widespread forms of behavioral plasticity. So far, neither the underlying molecular mechanisms nor the precise neural networks of habituation are well understood. We have developed a novel paradigm to quantify habituation of the olfactory jump reflex in Drosophila. We present data demonstrating several behavioral properties of this phenomenon, generally observed in other species. We also show that the dunce and rutabaga memory mutants behave abnormally in this assay, suggesting that this assay might be used in behavioral screens for new mutants with defects in this simpler form of behavioral plasticity

Clinical phenotypes of acute heart failure based on signs and symptoms of perfusion and congestion at emergency department presentation and their relationship with patient management and outcomes

Objective To compare the clinical characteristics and outcomes of patients with acute heart failure (AHF) according to clinical profiles based on congestion and perfusion determined in the emergency department (ED). Methods and results Overall, 11 261 unselected AHF patients from 41 Spanish EDs were classified according to perfusion (normoperfusion = warm; hypoperfusion = cold) and congestion (not = dry; yes = wet). Baseline and decompensation characteristics were recorded as were the main wards to which patients were admitted. The primary outcome was 1-year all-cause mortality; secondary outcomes were need for hospitalisation during the index AHF event, in-hospital all-cause mortality, prolonged hospitalisation, 7-day post-discharge ED revisit for AHF and 30-day post-discharge rehospitalisation for AHF. A total of 8558 patients (76.0%) were warm+ wet, 1929 (17.1%) cold+ wet, 675 (6.0%) warm+ dry, and 99 (0.9%) cold+ dry; hypoperfused (cold) patients were more frequently admitted to intensive care units and geriatrics departments, and warm+ wet patients were discharged home without admission. The four phenotypes differed in most of the baseline and decompensation characteristics. The 1-year mortality was 30.8%, and compared to warm+ dry, the adjusted hazard ratios were significantly increased for cold+ wet (1.660; 95% confidence interval 1.400-1.968) and cold+ dry (1.672; 95% confidence interval 1.189-2.351). Hypoperfused (cold) phenotypes also showed higher rates of index episode hospitalisation and in-hospital mortality, while congestive (wet) phenotypes had a higher risk of prolonged hospitalisation but decreased risk of rehospitalisation. No differences were observed among phenotypes in ED revisit risk. Conclusions Bedside clinical evaluation of congestion and perfusion of AHF patients upon ED arrival and classification according to phenotypic profiles proposed by the latest European Society of Cardiology guidelines provide useful complementary information and help to rapidly predict patient outcomes shortly after ED patient arrival

Ryks: new partners for Writs in the developing and regenerating nervous system

Conserved Ryk transmembrane proteins, tyrosine kinase-related Wnt receptors, are important during neurogenesis, axon guidance and synaptogenesis. Here, we review the increasingly complex biology of the Wnt/Ryk pathway, emphasizing the mechanisms by which Ryks transduce or sometimes block the Wnt signal. Recent studies reveal that Wnts signal through Ryk via multiple mechanisms, including nuclear translocation of their intracellular domains and pathways employing Src Family Kinases and members of the canonical Wnt pathway. We also discuss reports indicating that Wnt/Ryk axon guidance roles are evolutionarily conserved and Wnt/Ryk interactions are required for motoneuron target selection and synaptogenesis at the neuromuscular junction. Recent findings that injury-induced Wnt/Ryk pathway activation inhibits axon regeneration underscore the importance of further understanding this novel pathway

Ryks: new partners for Writs in the developing and regenerating nervous system

Conserved Ryk transmembrane proteins, tyrosine kinase-related Wnt receptors, are important during neurogenesis, axon guidance and synaptogenesis. Here, we review the increasingly complex biology of the Wnt/Ryk pathway, emphasizing the mechanisms by which Ryks transduce or sometimes block the Wnt signal. Recent studies reveal that Wnts signal through Ryk via multiple mechanisms, including nuclear translocation of their intracellular domains and pathways employing Src Family Kinases and members of the canonical Wnt pathway. We also discuss reports indicating that Wnt/Ryk axon guidance roles are evolutionarily conserved and Wnt/Ryk interactions are required for motoneuron target selection and synaptogenesis at the neuromuscular junction. Recent findings that injury-induced Wnt/Ryk pathway activation inhibits axon regeneration underscore the importance of further understanding this novel pathway.Circadian clocks in health and diseas

Chemokine-like Orion is involved in the transformation of glial cells into phagocytes in different developmental neuronal remodeling paradigms.

During animal development, neurons often form exuberant or inappropriate axons and dendrites at early stages, followed by the refinement of neuronal circuits at late stages. Neural circuit refinement leads to the production of neuronal debris in the form of neuronal cell corpses, fragmented axons and dendrites, and pruned synapses requiring disposal. Glial cells act as predominant phagocytes during neuronal remodeling and degeneration, and crucial signaling pathways between neurons and glia are necessary for the execution of phagocytosis. Chemokine-like mushroom body neuron-secreted Orion is essential for astrocyte infiltration into the γ axon bundle leading to γ axon pruning. Here, we show a role of Orion in debris engulfment and phagocytosis in Drosophila. Interestingly, Orion is involved in the overall transformation of astrocytes into phagocytes. In addition, analysis of several neuronal paradigms demonstrates the role of Orion in eliminating both peptidergic vCrz+ and PDF-Tri neurons via additional phagocytic glial cells like cortex and/or ensheathing glia. Our results suggest that Orion is essential for phagocytic activation of astrocytes, cortex and ensheathing glia, and point to Orion as a trigger of glial infiltration, engulfment and phagocytosis