Host Responses to the Phenolic-Glycolipid-1 Antigen of Mycobacterium Leprae (Elisa, Leprosy, Epidemiology, Armadillo, Human).

Antibody responses to the apparently species specific phenolic-glycolipid-1 (Phen-Gl-1) antigen of Mycobacterium leprae were examined in humans and armadillos using enzyme-linked immunosorbent assays (ELISA). Statistical definitions for the interpretation of positive and negative reactions were derived. A retrospective serological survey of armadillos indicated that leprosy in the wild armadillo is a naturally acquired zoonosis. Presently 12.5% of the armadillos in 2 parishes in south central Louisiana have detectable IgM antibodies to Phen-Gl-1. Approximately 2.7% of these histologically exhibit clinical disease. Antibodies were not detected in Florida armadillo sera. Variations in prevalence rates were noted, and may be due to environmental conditions, population characteristics or some intricacies in the transmission of leprosy. Naturally acquired leprosy in the armadillo may be used as a model to study transmission and baseline data have been derived. The ELISA was shown to have application in the management of experimental leprosy infections in armadillos. Resistant armadillos were noted to have an irregular or absent antibody response to the Phen-Gl-1 antigen over the course of an experimental infection. Armadillos infected in the wild also had an irregular IgM response. Susceptible armadillos appeared to have a long-term IgM antibody response to Phen-Gl-1 becoming detectable some 186 days post-experimental infection. This antibody remained detectable for up to 1140 days post-infection. Antibody responses of susceptible armadillos correlated with the harvestable load of M. leprae in liver tissues and ELISA absorbances successfully predicted a harvest result 97% of the time. IgM antibodies to Phen-Gl-1 were earlier and more reliable than other indicators of infection previously applied. IgM, IgA, and IgG antibodies to Phen-Gl-1 were detected in leprosy patients and contacts. IgM appeared to be the predominate isotype detectable. Human patients showed no significant correlation of antibody relative their clinical status. IgM antibodies to Phen-Gl-1 were depressed as a result of therapy with thalidomide. Monitoring Phen-Gl-1 antibodies in human patients is not predictive of patient status or reaction and does not seem indicated for clinical management

Regulation of forward and backward locomotion through intersegmental feedback circuits in Drosophila larvae

Abstract: Animal locomotion requires spatiotemporally coordinated contraction of muscles throughout the body. Here, we investigate how contractions of antagonistic groups of muscles are intersegmentally coordinated during bidirectional crawling of Drosophila larvae. We identify two pairs of higher-order premotor excitatory interneurons present in each abdominal neuromere that intersegmentally provide feedback to the adjacent neuromere during motor propagation. The two feedback neuron pairs are differentially active during either forward or backward locomotion but commonly target a group of premotor interneurons that together provide excitatory inputs to transverse muscles and inhibitory inputs to the antagonistic longitudinal muscles. Inhibition of either feedback neuron pair compromises contraction of transverse muscles in a direction-specific manner. Our results suggest that the intersegmental feedback neurons coordinate contraction of synergistic muscles by acting as delay circuits representing the phase lag between segments. The identified circuit architecture also shows how bidirectional motor networks could be economically embedded in the nervous system

Selective Inhibition Mediates the Sequential Recruitment of Motor Pools.

Locomotor systems generate diverse motor patterns to produce the movements underlying behavior, requiring that motor neurons be recruited at various phases of the locomotor cycle. Reciprocal inhibition produces alternating motor patterns; however, the mechanisms that generate other phasic relationships between intrasegmental motor pools are unknown. Here, we investigate one such motor pattern in the Drosophila larva, using a multidisciplinary approach including electrophysiology and ssTEM-based circuit reconstruction. We find that two motor pools that are sequentially recruited during locomotion have identical excitable properties. In contrast, they receive input from divergent premotor circuits. We find that this motor pattern is not orchestrated by differential excitatory input but by a GABAergic interneuron acting as a delay line to the later-recruited motor pool. Our findings show how a motor pattern is generated as a function of the modular organization of locomotor networks through segregation of inhibition, a potentially general mechanism for sequential motor patterns.This work was supported by the Howard Hughes Medical Institute, the HHMI Janelia Visitor Program (MFZ and ML), an Isaac Newton Trust/ISSF Wellcome Trust and a Wellcome Trust grant (092986/Z) to ML.This is the author accepted manuscript. The final version is available from Cell Press via http://dx.doi.org/10.1016/j.neuron.2016.06.03

Unveiling the sensory and interneuronal pathways of the neuroendocrine connectome in <i>Drosophila</i>.

Neuroendocrine systems in animals maintain organismal homeostasis and regulate stress response. Although a great deal of work has been done on the neuropeptides and hormones that are released and act on target organs in the periphery, the synaptic inputs onto these neuroendocrine outputs in the brain are less well understood. Here, we use the transmission electron microscopy reconstruction of a whole central nervous system in the Drosophila larva to elucidate the sensory pathways and the interneurons that provide synaptic input to the neurosecretory cells projecting to the endocrine organs. Predicted by network modeling, we also identify a new carbon dioxide-responsive network that acts on a specific set of neurosecretory cells and that includes those expressing corazonin (Crz) and diuretic hormone 44 (Dh44) neuropeptides. Our analysis reveals a neuronal network architecture for combinatorial action based on sensory and interneuronal pathways that converge onto distinct combinations of neuroendocrine outputs

Unveiling the sensory and interneuronal pathways of the neuroendocrine connectome in Drosophila.

Neuroendocrine systems in animals maintain organismal homeostasis and regulate stress response. Although a great deal of work has been done on the neuropeptides and hormones that are released and act on target organs in the periphery, the synaptic inputs onto these neuroendocrine outputs in the brain are less well understood. Here, we use the transmission electron microscopy reconstruction of a whole central nervous system in the Drosophila larva to elucidate the sensory pathways and the interneurons that provide synaptic input to the neurosecretory cells projecting to the endocrine organs. Predicted by network modeling, we also identify a new carbon dioxide-responsive network that acts on a specific set of neurosecretory cells and that includes those expressing corazonin (Crz) and diuretic hormone 44 (Dh44) neuropeptides. Our analysis reveals a neuronal network architecture for combinatorial action based on sensory and interneuronal pathways that converge onto distinct combinations of neuroendocrine outputs

How clumpy is my image?: Scoring in crowdsourced annotation tasks

The use of citizen science to obtain annotations from multiple annotators has been shown to be an effective method for annotating datasets in which computational methods alone are not feasible. The way in which the annotations are obtained is an important consideration which affects the quality of the resulting consensus annotation. In this paper, we examine three separate approaches to obtaining consensus scores for instances rather than merely binary classifications. To obtain a consensus score, annotators were asked to make annotations in one of three paradigms: classification, scoring and ranking. A web-based citizen science experiment is described which implements the three approaches as crowdsourced annotation tasks. The tasks are evaluated in relation to the accuracy and agreement among the participants using both simulated and real-world data from the experiment. The results show a clear difference in performance between the three tasks, with the ranking task obtaining the highest accuracy and agreement among the participants. We show how a simple evolutionary optimiser may be used to improve the performance by reweighting the importance of annotators

Circuits for integrating learned and innate valences in the insect brain.

Funder: Howard Hughes Medical InstituteAnimal behavior is shaped both by evolution and by individual experience. Parallel brain pathways encode innate and learned valences of cues, but the way in which they are integrated during action-selection is not well understood. We used electron microscopy to comprehensively map with synaptic resolution all neurons downstream of all mushroom body (MB) output neurons (encoding learned valences) and characterized their patterns of interaction with lateral horn (LH) neurons (encoding innate valences) in Drosophila larva. The connectome revealed multiple convergence neuron types that receive convergent MB and LH inputs. A subset of these receives excitatory input from positive-valence MB and LH pathways and inhibitory input from negative-valence MB pathways. We confirmed functional connectivity from LH and MB pathways and behavioral roles of two of these neurons. These neurons encode integrated odor value and bidirectionally regulate turning. Based on this, we speculate that learning could potentially skew the balance of excitation and inhibition onto these neurons and thereby modulate turning. Together, our study provides insights into the circuits that integrate learned and innate valences to modify behavior

Convergence of monosynaptic and polysynaptic sensory paths onto common motor outputs in a Drosophila feeding connectome.

We reconstructed, from a whole CNS EM volume, the synaptic map of input and output neurons that underlie food intake behavior of Drosophila larvae. Input neurons originate from enteric, pharyngeal and external sensory organs and converge onto seven distinct sensory synaptic compartments within the CNS. Output neurons consist of feeding motor, serotonergic modulatory and neuroendocrine neurons. Monosynaptic connections from a set of sensory synaptic compartments cover the motor, modulatory and neuroendocrine targets in overlapping domains. Polysynaptic routes are superimposed on top of monosynaptic connections, resulting in divergent sensory paths that converge on common outputs. A completely different set of sensory compartments is connected to the mushroom body calyx. The mushroom body output neurons are connected to interneurons that directly target the feeding output neurons. Our results illustrate a circuit architecture in which monosynaptic and multisynaptic connections from sensory inputs traverse onto output neurons via a series of converging paths