Evolution of a new sense for wind in flying phasmids? Afferents and interneurons

The evolution of winged stick insects (phasmids) from secondarily wingless ancestors was proposed in recent studies. We explored the cuticle of flying phasmids for wind sensors that could be involved in their flight control, comparable to those known for locusts. Surprisingly, wind-sensitive hairs (wsH) occur on the palps of mouthparts and on the antennae of the winged phasmid Sipyloidea sipylus which can fly in tethered position only when air currents blow over the mouthparts. The present study describes the morphology and major functional properties of these “new” wsH with soft and bulging hair bases which are different from the beaker-like hair bases of the wsH on the cerci of phasmids and the wsH described in other insects. The most sensitive wsH of antennae and palps respond with phasic-tonic afferents to air currents exceeding 0.2 ms−1. The fields of wsH on one side of the animal respond mainly to ventral, lateral, and frontal wind on the ipsilateral side of the head. Afferent inputs from the wsH converge but also diverge to a group of specific interneurons at their branches in the suboesophageal ganglion and can send their integrated input from wsH fields of the palps and antennae to the thoracic central nervous system. Response types of individual wsH-interneurons are either phasic or phasic-tonic to air puffs or constant air currents and also, the receptive fields of individual interneurons differ. We conclude that the “new” wsH system and its interneurons mainly serve to maintain flight activity in airborne phasmids and also, the “new” wsH must have emerged together with the integrating interneurons during the evolution from wingless to the recent winged forms of phasmids

Pharmacokinetics of midazolam in CYP3A4- and CYP3A5-genotyped subjects

Objective: We investigated whether differences in pharmacokinetics of midazolam, a CYP3A probe, could be demonstrated between subjects with different CYP3A4 and CYP3A5 genotypes. Methods: Plasma concentrations of midazolam, and of total (conjugated + unconjugated) 1′OH-midazolam, and 4′OH-midazolam were measured after the oral administration of 7.5mg or of 75µg of midazolam in 21 healthy subjects. Results: CYP3A5*7, CYP3A4*1E, CYP3A4*2, CYP3A4*4, CYP3A4*5, CYP3A4*6, CYP3A4*8, CYP3A4*11, CYP3A4*12, CYP3A4*13, CYP3A4*17 and CYP3A4*18 alleles were not identified in the 21 subjects. CYP3A5*3, CYP3A5*6, CYP3A4*1B and CYP3A4*1F alleles were identified in 20, 1, 4 and 2 subjects, respectively. No statistically significant differences were observed for the AUCinf values between the different genotypes after the 75-µg or the 7.5-mg dose. Conclusion: Presently, CYP3A4 and CYP3A5 genotyping methods do not sufficiently reflect the inter-individual variability of CYP3A activit

Periodic solutions and refractory periods in the soliton theory for nerves and the locust femoral nerve

Close to melting transitions it is possible to propagate solitary electromechanical pulses which reflect many of the experimental features of the nerve pulse including mechanical dislocations and reversible heat production. Here we show that one also obtains the possibility of periodic pulse generation when the boundary condition for the nerve is the conservation of the overall length of the nerve. This condition generates an undershoot beneath the baseline (`hyperpolarization') and a `refractory period', i.e., a minimum distance between pulses. In this paper, we outline the theory for periodic solutions to the wave equation and compare these results to action potentials from the femoral nerve of the locust (locusta migratoria). In particular, we describe the frequently occurring minimum-distance doublet pulses seen in these neurons and compare them to the periodic pulse solutions.Comment: 10 pages, 6 Figure

Oral administration of a low dose of midazolam (75μg) as an in vivo probe for CYP3A activity

Objective: We investigated whether the oral administration of a low dose (75µg) of midazolam, a CYP3A probe, can be used to measure the in vivo CYP3A activity. Methods: Plasma concentrations of midazolam, 1′OH-midazolam and 4′OH-midazolam were measured after the oral administration of 7.5mg and 75µg midazolam in 13 healthy subjects without medication, in four subjects pretreated for 2days with ketoconazole (200mg b.i.d.), a CYP3A inhibitor, and in four subjects pretreated for 4days with rifampicin (450mg q.d.), a CYP3A inducer. Results: After oral administration of 75µg midazolam, the 30-min total (unconjugated + conjugated) 1′OH-midazolam/midazolam ratios measured in the groups without co-medication, with ketoconazole and with rifampicin were (mean±SD): 6.23±2.61, 0.79±0.39 and 56.1±12.4, respectively. No side effects were reported by the subjects taking this low dose of midazolam. Good correlations were observed between the 30-min total 1′OH-midazolam/midazolam ratio and midazolam clearance in the group without co-medication (r2=0.64, P<0.001) and in the three groups taken together (r2=0.91, P<0.0001). Good correlations were also observed between midazolam plasma levels and midazolam clearance, measured between 1.5h and 4h. Conclusion: A low oral dose of midazolam can be used to phenotype CYP3A, either by the determination of total 1′OH-midazolam/midazolam ratios at 30min or by the determination of midazolam plasma levels between 1.5h and 4h after its administratio

A new kind of auxiliary heart in insects: functional morphology and neuronal control of the accessory pulsatile organs of the cricket ovipositor

Introduction: In insects, the pumping of the dorsal heart causes circulation of hemolymph throughout the central body cavity, but not within the interior of long body appendages. Hemolymph exchange in these dead-end structures is accomplished by special flow-guiding structures and/or autonomous pulsatile organs (“auxiliary hearts”). In this paper accessory pulsatile organs for an insect ovipositor are described for the first time. We studied these organs in females of the cricket Acheta domesticus by analyzing their functional morphology, neuroanatomy and physiological control. Results: The lumen of the four long ovipositor valves is subdivided by longitudinal septa of connective tissue into efferent and afferent hemolymph sinuses which are confluent distally. The countercurrent flow in these sinuses is effected by pulsatile organs which are located at the bases of the ovipositor valves. Each of the four organs consists of a pumping chamber which is compressed by rhythmically contracting muscles. The morphology of the paired organs is laterally mirrored, and there are differences in some details between the dorsal and ventral organs. The compression of the pumping chambers of each valve pair occurs with a left-right alternating rhythm with a frequency of 0.2 to 0.5 Hz and is synchronized between the dorsal and ventral organs. The more anteriorly located genital chamber shows rhythmical lateral movements simultaneous to those of the ovipositor pulsatile organs and probably supports the hemolymph exchange in the abdominal apex region. The left-right alternating rhythm is produced by a central pattern generator located in the terminal ganglion. It requires no sensory feedback for its output since it persists in the completely isolated ganglion. Rhythm-modulating and rhythm-resetting interneurons are identified in the terminal ganglion. Conclusion: The circulatory organs of the cricket ovipositor have a unique functional morphology. The pumping apparatus at the base of each ovipositor valve operates like a bellow. It forces hemolymph via sinuses delimited by thin septa of connective tissue in a countercurrent flow through the valve lumen. The pumping activity is based on neurogenic control by a central pattern generator in the terminal ganglion