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Distal arthrogryposis (DA) is a collection of rare disorders that are characterized by congenital joint contractures. Most DA mutations are in muscle- and joint-related genes, and the anatomical defects originate cell-autonomously within the musculoskeletal system. However, gain-of-function mutations in PIEZO2, a principal mechanosensor in somatosensation, cause DA subtype 5 (DA5) through unknown mechanisms. We show that expression of a gain-of-function PIEZO2 mutation in proprioceptive sensory neurons that mainly innervate muscle spindles and tendons is sufficient to induce DA5-like phenotypes in mice. Overactive PIEZO2 causes anatomical defects through increased activity within the peripheral nervous system during postnatal development. Furthermore, botulinum toxin (Botox) and a dietary fatty acid that modulates PIEZO2 activity reduce DA5-like deficits. This reveals a role for somatosensory neurons: Excessive mechanosensation within these neurons disrupts musculoskeletal development.

The muscle spindle is an important sense organ for motor control and proprioception. Specialized intrafusal fibers are innervated by both stretch sensitive afferents and γ motor neurons that control the length of the spindle and tune the sensitivity of the muscle spindle afferents to both dynamic movement and static length. γ motor neurons share many similarities with other skeletal motor neurons, making it challenging to identify and specifically record or stimulate them. This short review will discuss recent advances in genetic and molecular biology techniques, electrophysiological recording, optical imaging, computer modelling, and stem cell culture techniques that have the potential to help answer important questions about fusimotor function in motor control and disease.

Key points Muscle spindle afferents are slowly adapting low threshold mechanoreceptors that report muscle length and movement information critical for motor control and proprioception. The rapidly adapting cation channel PIEZO2 has been identified as necessary for muscle spindle afferent stretch sensitivity, but the properties of this channel suggest additional molecular elements are necessary for mediating the complex slowly adapting response of muscle spindle afferents. We report that glutamate increases muscle spindle afferent static sensitivity in an ex vivo mouse muscle nerve preparation, while blocking glutamate packaging into vesicles by the sole vesicular glutamate transporter, VGLUT1, either pharmacologically or by transgenic knock out of one allele of VGLUT1 decreases muscle spindle afferent static but not dynamic sensitivity. Our results confirm that vesicle-released glutamate is an important contributor to maintained muscle spindle afferent excitability and may suggest a therapeutic target for normalizing muscle spindle afferent function. Abstract Muscle spindle afferents are slowly adapting low threshold mechanoreceptors which have both dynamic and static sensitivity to muscle stretch. The exact mechanism by which these neurons translate muscle movement into action potentials is not well understood, although the PIEZO2 mechanically sensitive cation channel is essential for stretch sensitivity. PIEZO2 is rapidly adapting, suggesting the requirement for additional molecular elements to maintain firing during stretch. Spindle afferent sensory endings contain glutamate-filled synaptic-like vesicles which are released in a stretch and calcium dependent manner. Previous work has shown that glutamate can increase and a phospholipase-D coupled metabotropic glutamate antagonist can abolish firing during static stretch. Here we test the hypothesis that vesicle-released glutamate is necessary for maintaining muscle spindle afferent excitability during static but not dynamic stretch. To test this hypothesis, we used a mouse muscle-nerve ex vivo preparation to measure identified muscle spindle afferent responses to stretch and vibration. In C57BL/6 adult mice, bath applied glutamate significantly increased the firing rate during the plateau phase of stretch, but not during the dynamic phase of stretch. Blocking the packaging of glutamate into vesicles by the sole vesicular glutamate transporter, VGLUT1, either with xanthurenic acid or by using a transgenic mouse with only one copy of the VGLUT1 gene (VGLUT1+/- ) decreased muscle spindle afferent firing during sustained stretch, but not during vibration. Our results suggest a model of mechanotransduction where calcium entering the PIEZO2 channel can cause the release of glutamate from synaptic-like vesicles which then helps to maintain afferent depolarization and firing. This article is protected by copyright. All rights reserved.

The voltage-gated sodium channel (NaV), NaV1.1, is well-studied in the central nervous system; conversely, its contribution to peripheral sensory neuron function is more enigmatic. Here, we identify a new role for NaV1.1 in mammalian proprioception. RNAscope analysis and in vitro patch clamp recordings in genetically identified mouse proprioceptors show ubiquitously channel expression and significant contributions to intrinsic excitability. Notably, genetic deletion of NaV1.1 in sensory neurons caused profound and visible motor coordination deficits in conditional knockout mice of both sexes, similar to conditional Piezo2-knockout animals, suggesting this channel is a major contributor to sensory proprioceptive transmission. Ex vivo muscle afferent recordings conditional knockout mice found that loss of NaV1.1 leads to inconsistent and unreliable proprioceptor firing characterized by action potential failures during static muscle stretch; conversely, afferent responses to dynamic vibrations were unaffected. This suggests that while a combination of Piezo2 and other NaV isoforms are sufficient to elicit activity in response to transient stimuli, NaV1.1 is required for transmission of receptor potentials generated during sustained muscle stretch. Impressively, recordings from afferents of heterozygous conditional knockout animals were similarly impaired, and heterozygous conditional knockout mice also exhibited motor behavioral deficits. Thus, NaV1.1 haploinsufficiency in sensory neurons impairs both proprioceptor function and motor behaviors. Importantly, human patients harboring NaV1.1 loss-of-function mutations often present with motor delays and ataxia; therefore, our data suggest sensory neuron dysfunction contributes to the clinical manifestations of neurological disorders in which NaV1.1 function is compromised. Collectively, we present the first evidence that NaV1.1 is essential for mammalian proprioceptive signaling and behaviors.

The voltage-gated sodium channel (Na

Key pointsAcetylcholine receptors are aggregated in the central regions of intrafusal muscle fibres. Single unit muscle spindle afferent responses from isolated mouse extensor digitorum longus muscle were recorded in the absence of fusimotor input to ramp and hold stretches as well as to sinusoidal vibrations in the presence and absence of the acetylcholine receptor blockers d-tubocurarine and alpha-bungarotoxin. Proprioceptive afferent responses to both types of stretch were enhanced in the presence of either blocker. Blocking acetylcholine uptake and vesicular acetylcholine release by hemicholinium-3 also enhanced stretch-evoked responses. These results represent the first evidence that acetylcholine receptors negatively modulate muscle spindle responses to stretch. The data support the hypothesis that the sensory nerve terminal is able to release vesicles to fine-tune proprioceptive afferent sensitivity. Muscle spindles are complex stretch-sensitive mechanoreceptors. They consist of specialized skeletal muscle fibres, called intrafusal fibres, which are innervated in the central (equatorial) region by afferent sensory axons and in both polar regions by efferent gamma-motoneurons. Previously it was shown that acetylcholine receptors (AChR) are concentrated in the equatorial region at the contact site between the sensory neuron and the intrafusal muscle fibre. To address the function of these AChRs, single unit sensory afferents were recorded from an isolated mouse extensor digitorum longus muscle in the absence of gamma-motoneuron activity. Specifically, we investigated the responses of individual sensory neurons to ramp-and-hold stretches and sinusoidal vibrations before and after the addition of the competitive and non-competitive AChR blockers d-tubocurarine and alpha-bungarotoxin, respectively. The presence of either drug did not affect the resting action potential discharge frequency. However, the action potential frequencies in response to stretch were increased. In particular, frequencies of the dynamic peak and dynamic index to ramp-and-hold stretches were significantly higher in the presence of either drug. Treatment of muscle spindle afferents with the high-affinity choline transporter antagonist hemicholinium-3 similarly increased muscle spindle afferent firing frequencies during stretch. Moreover, the firing rate during sinusoidal vibration stimuli at low amplitudes was higher in the presence of alpha-bungarotoxin compared to control spindles also indicating an increased sensitivity to stretch. Collectively these data suggest a modulation of the muscle spindle afferent response to stretch by AChRs in the central region of intrafusal fibres possibly fine-tuning muscle spindle sensitivity.

The muscle spindle (MS) provides essential sensory information for motor control and proprioception. The Group Ia and II MS afferents are low threshold slowly-adapting mechanoreceptors and report both static muscle length and dynamic muscle movement information. The exact molecular mechanism by which MS afferents transduce muscle movement into action potentials is incompletely understood. This short review will discuss recent evidence suggesting that PIEZO2 is an essential mechanically sensitive ion channel in MS afferents and that vesicle-released glutamate contributes to maintaining afferent excitability during the static phase of stretch. Other mechanically gated ion channels, voltage-gated sodium channels, other ion channels, regulatory proteins, and interactions with the intrafusal fibers are also important for MS afferent mechanosensation. Future studies are needed to fully understand mechanosensation in the MS and whether different complements of molecular mediators contribute to the different response properties of Group Ia and II afferents.

Inflammation is known to alter nervous system function, but its effect on muscle spindle afferent mechanosensation and sensory integration in the spinal cord has not been well studied. We tested the hypothesis that systemic inflammation induced by an intraperitoneal injection of the endotoxin lipopolysaccharide (LPS; 7.5 × 105 endotoxin units/kg 18 h before experiment) would alter muscle spindle afferent mechanosensation and spinal cord excitability to Group Ia input in male and female adult C57Bl/6 mice. LPS injection caused a systemic immune response, evidenced by decreased white blood cell, monocyte, and lymphocyte concentrations in the blood, increased blood granulocyte concentration, and body weight loss. The immune response in both sexes was qualitatively similar. We used an in vitro muscle‐nerve preparation to assay muscle spindle afferent response to stretch and vibration. LPS injection did not significantly change the response to stretch or vibration, with the exception of small decreases in the ability to entrain to high‐frequency vibration in male mice. Similarly, LPS injection did not alter spinal cord excitability to Group Ia muscle spindle afferent input as measured by the Hoffman's reflex test in anesthetized mice (100 mg/kg ketamine, 10 mg/kg xylazine). Specifically, there were no changes in M or H wave latencies nor in the percentage of motor neurons excited by electrical afferent stimulation (Hmax/Mmax). Overall, we found no major alterations in muscle proprioceptor function or sensory integration following exposure to LPS at a dose and time course that causes changes in nociceptor function and central processing.

Proprioception, the perception of body and limb position, is mediated by proprioceptors, specialized mechanosensory neurons that convey information about the stretch and tension experienced by muscles, tendons, skin and joints. In mammals, the molecular identity of the stretch-sensitive channel that mediates proprioception is unknown. We found that the mechanically activated nonselective cation channel Piezo2 was expressed in sensory endings of proprioceptors innervating muscle spindles and Golgi tendon organs in mice. Two independent mouse lines that lack Piezo2 in proprioceptive neurons showed severely uncoordinated body movements and abnormal limb positions. Moreover, the mechanosensitivity of parvalbumin-expressing neurons that predominantly mark proprioceptors was dependent on Piezo2 expression in vitro, and the stretch-induced firing of proprioceptors in muscle-nerve recordings was markedly reduced in Piezo2-deficient mice. Together, our results indicate that Piezo2 is the major mechanotransducer of mammalian proprioceptors.

Several papers have been written to show that General Practitioners do not always prescribe according to the guidelines despite the availability of guidelines regarding the dosage and length of treatment with antidepressants to treat a depressive episode. Here we review the evidence as to whether GPs follow antidepressant guidelines, covering the data between 1996 and the present day, and discuss the implications of this evidence. We then propose solutions which could be used to improve adherence to the guidelines. We propose as one solution the development of joint Doctor-Practice Nurse clinics for the treatment of depression. The outcomes of these clinics should be auditable against the guidelines. Such a solution, when linked with easy access to advice and referral to Secondary Care Psychiatry specialists, argues for a collaborative care or shared care program for the treatment of depression in Primary Care.

During ventilatory acclimatization to hypoxia (VAH), time-dependent increases in ventilation lower Pco2 levels, and this persists on return to normoxia. We hypothesized that plasticity in the caudal nucleus tractus solitarii (NTS) contributes to VAH, as the NTS receives the first synapse from the carotid body chemoreceptor afferents and also contains CO2-sensitive neurons. We lesioned cells in the caudal NTS containing the neurokinin-1 receptor by microinjecting the neurotoxin saporin conjugated to substance P and measured ventilatory responses in awake, unrestrained rats 18 days later. Lesions did not affect hypoxic or hypercapnic ventilatory responses in normoxic control rats, in contrast to published reports for similar lesions in other central chemosensitive areas. Also, lesions did not affect the hypercapnic ventilatory response in chronically hypoxic rats (inspired Po2 = 90 Torr for 7 days). These results suggest functional differences between central chemoreceptor sites. However, lesions significantly increased ventilation in normoxia or acute hypoxia in chronically hypoxic rats. Hence, chronic hypoxia increases an inhibitory effect of neurokinin-1 receptor neurons in the NTS on ventilatory drive, indicating that these neurons contribute to plasticity during chronic hypoxia, although such plasticity does not explain VAH.

We studied the effects of the ventilatory stimulant doxapram to test the hypothesis that chronic hypoxia increases the translation of carotid body afferent input into ventilatory motor efferent output by the central nervous system. Chronic hypoxia (inspired Po2 = 70 Torr, 2 days) significantly increased the ventilatory response to an intravenous infusion of a high dose of doxapram in conscious, unrestrained rats breathing normoxic or hypoxic gas. The in vitro carotid body response to hypoxia increased with chronic hypoxia, but the response was not increased with a high dose of doxapram. Similarly, the phrenic nerve response to doxapram in anesthetized rats with carotid bodies denervated did not change with 7 days of chronic hypoxia. The results support the hypothesis that chronic hypoxia causes plasticity in the central component of the carotid chemoreceptor ventilatory reflex, which increases the hypoxic ventilatory response. We conclude that doxapram provides a promising tool to study the time course of changes in the central gain of the hypoxic ventilatory response during chronic hypoxia in awake animals and humans.

Current debates from Capitol Hill to Copenhagen suggest political will to tackle climate change is in short supply. The public engagement that might undergird it is also thin. 1 Yet action stirs in...

We studied the CO2/H+-chemosensitive responses of individual solitary complex (SC) neurons from adult rats by simultaneously measuring the intracellular pH (pHi) and electrical responses to hypercapnic acidosis (HA). SC neurons were recorded using the blind whole cell patch-clamp technique and loading the soma with the pH-sensitive dye pyranine through the patch pipette. We found that SC neurons from adult rats have a lower steady-state pHithan SC neurons from neonatal rats. In the presence of chemical and electrical synaptic blockade, adult SC neurons have firing rate responses to HA (percentage of neurons activated or inhibited and the magnitude of response as determined by the chemosensitivity index) that are similar to SC neurons from neonatal rats. They also have a typical response to isohydric hypercapnia, including decreased ΔpHi, followed by pHirecovery, and increased firing rate. Thus, the chemosensitive response of SC neurons from adults is similar to the chemosensitive response of SC neurons from neonatal rats. Because our findings for adults are similar to previously reported values for neurons from neonatal rats, we conclude that intrinsic chemosensitivity is established early in development for SC neurons and is maintained throughout adulthood.

Background Acanthamoebidae is a “family” level amoebozoan group composed of the genera Acanthamoeba, Protacanthamoeba, and very recently Luapeleamoeba. This clade of amoebozoans has received considerable attention from the broader scientific community as Acanthamoeba spp. represent both model organisms and human pathogens. While the classical composition of the group (Acanthamoeba + Protacanthamoeba) has been well accepted due to the morphological and ultrastructural similarities of its members, the Acanthamoebidae has never been highly statistically supported in single gene phylogenetic reconstructions of Amoebozoa either by maximum likelihood (ML) or Bayesian analyses. Results Here we show using a phylogenomic approach that the Acanthamoebidae is a fully supported monophyletic group within Amoebozoa with both ML and Bayesian analyses. We also expand the known range of morphological and life cycle diversity found in the Acanthamoebidae by demonstrating that the amoebozoans “Protostelium” arachisporum, Dracoamoeba jormungandri n. g. n. sp., and Vacuolamoeba acanthoformis n.g. n.sp., belong within the group. We also found that “Protostelium” pyriformis is clearly a species of Acanthamoeba making it the first reported sporocarpic member of the genus, that is, an amoeba that individually forms a walled, dormant propagule elevated by a non-cellular stalk. Our phylogenetic analyses recover a fully supported Acanthamoebidae composed of five genera. Two of these genera (Acanthamoeba and Luapeleameoba) have members that are sporocarpic. Conclusions Our results provide high statistical support for an Acanthamoebidae that is composed of five distinct genera. This study increases the known morphological diversity of this group and shows that species of Acanthamoeba can include spore-bearing stages. This further illustrates the widespread nature of spore-bearing stages across the tree of Amoebozoa. Reviewers This article was reviewed by Drs. Eugene Koonin, Purificacion Lopez-Garcia and Sandra Baldauf. Sandra Baldauf was nominated by Purificacion Lopez-Garcia, an Editorial Board member. Electronic supplementary material The online version of this article (doi:10.1186/s13062-016-0171-0) contains supplementary material, which is available to authorized users.

Aerobic organisms maintain O(2) homeostasis by responding to changes in O(2) supply and demand in both short and long time domains. In this review, we introduce several specific examples of respiratory plasticity induced by chronic changes in O(2) supply (environmental hypoxia or hyperoxia) and demand (exercise-induced and temperature-induced changes in aerobic metabolism). These studies reveal that plasticity occurs throughout the respiratory system, including modifications to the gas exchanger, respiratory pigments, respiratory muscles, and the neural control systems responsible for ventilating the gas exchanger. While some of these responses appear appropriate (e.g., increases in lung surface area, blood O(2) capacity, and pulmonary ventilation in hypoxia), other responses are potentially harmful (e.g., increased muscle fatigability). Thus, it may be difficult to predict whole-animal performance based on the plasticity of a single system. Moreover, plastic responses may differ quantitatively and qualitatively at different developmental stages. Much of the current research in this field is focused on identifying the cellular and molecular mechanisms underlying respiratory plasticity. These studies suggest that a few key molecules, such as hypoxia inducible factor (HIF) and erythropoietin, may be involved in the expression of diverse forms of plasticity within and across species. Studying the various ways in which animals respond to respiratory challenges will enable a better understanding of the integrative response to chronic changes in O(2) supply and demand.

Balance impairment and chronic low level systemic inflammation have both been associated with obesity. As inflammatory factors have been shown to alter the activity of Group Ia/II muscle spindle af...

Mixed monolayers at the air–water interface of the cationic surfactant, hexadecyltrimethylammonium bromide (CTAB), with alkanes show a first-order freezing transition as a function of temperature. Sum-frequency spectra and ellipsometric measurements are consistent with a structure in which the high-temperature phase is liquid-like and the low-temperature phase has all-trans, upright chains. There are strong structural similarities between the low-temperature phase in the mixed monolayers and frozen monolayers at the alkane–air and alkane–CTAB solution interfaces. The difference between the surface freezing point Ts and the freezing point of the bulk alkane Tb ranges from 1 °C for alkane chain length m = 17, to 28 °C for m = 11. Surface freezing is more favourable in mixed monolayers at the air–water interface than at the bulk alkane–water interface for the same surfactant concentration. Long-chain alkanes do not wet water, but it is postulated that if they did, they would also show surface freezing analogously to alkanes on silica. The surfactant plays the dual role of enhancing wetting and surface freezing of the alkane on water.

Prior studies have shown that the vestibular system contributes to adjusting respiratory muscle activity during changes in posture, and have suggested that portions of the medial medullary reticular formation (MRF) participate in generating vestibulo-respiratory responses. However, there was previously no direct evidence to demonstrate that cells in the MRF relay vestibular signals monosynaptically to respiratory motoneurons. The present study tested the hypothesis that the firing of MRF neurons whose axons could be antidromically activated from the vicinity of diaphragm motoneurons was modulated by whole-body rotations in vertical planes that stimulated vestibular receptors, as well as by electrical current pulses delivered to the vestibular nerve. In total, 171 MRF neurons that projected to the C5–C6 ventral horn were studied; they had a conduction velocity of 34±15 (standard deviation) m/sec. Most (135/171 or 79%) of these MRF neurons lacked spontaneous firing. Of the subpopulation of units with spontaneous discharges, only 3 of 20 cells responded to vertical rotations up to 10° in amplitude, whereas the activity of 8 of 14 neurons was affected by electrical stimulation of the vestibular nerve. These data support the hypothesis that the MRF participates in generating vestibulo-respiratory responses, but also suggest that some neurons in this region have other functions.

Previous studies in humans showed that genioglossal muscle activity is higher when individuals are supine than when they are upright, and prior experiments in anesthetized or decerebrate animals suggested that vestibular inputs might participate in triggering these alterations in muscle firing. The present study determined the effects of whole body tilts in the pitch (nose-up) plane on genioglossal activity in a conscious feline model and compared these responses with those generated by roll (ear-down) tilts. We also ascertained the effects of a bilateral vestibular neurectomy on the alterations in genioglossal activity elicited by changes in body position. Both pitch and roll body tilts produced modifications in muscle firing that were dependent on the amplitude of the rotation; however, the relative effects of ear-down and nose-up tilts on genioglossal activity were variable from animal to animal. The response variability observed might reflect the fact that genioglossus has a complex organization and participates in a variety of tongue movements; in each animal, electromyographic recordings presumably sampled the firing of different proportions of fibers in the various compartments and subcompartments of the muscle. Furthermore, removal of labyrinthine inputs resulted in alterations in genioglossal responses to postural changes that persisted until recordings were discontinued ∼1 mo later, demonstrating that the vestibular system participates in regulating the muscle's activity. Peripheral vestibular lesions were subsequently demonstrated to be complete through the postmortem inspection of temporal bone sections or by observing that vestibular nucleus neurons did not respond to rotations in vertical planes.

Muscle sensory neurons innervating muscle spindles and Golgi tendon organs encode length and force changes essential to proprioception. Additional afferent fibers monitor other characteristics of the muscle environment, including metabolite buildup, temperature, and nociceptive stimuli. Overall, abnormal activation of sensory neurons can lead to movement disorders or chronic pain syndromes. We describe the isolation of the extensor digitorum longus (EDL) muscle and nerve for in vitro study of stretch-evoked afferent responses in the adult mouse. Sensory activity is recorded from the nerve with a suction electrode and individual afferents can be analyzed using spike sorting software. In vitro preparations allow for well controlled studies on sensory afferents without the potential confounds of anesthesia or altered muscle perfusion. Here we describe a protocol to identify and test the response of muscle spindle afferents to stretch. Importantly, this preparation also supports the study of other subtypes of muscle afferents, response properties following drug application and the incorporation of powerful genetic approaches and disease models in mice.

Intraperitoneal injection of lipopolysaccharide (LPS) is a common method to induce systemic inflammation, but there is wide variability in the doses given and no standardized measure of inflammator...

This study investigates the effect of monetary policy shocks in New Zealand and Australia on their respective exchange rates from 1985 to 1998 using vector autoregression methodology. The results show that monetary policy shocks do contribute to the variability of both exchange rates, but these movements are not always consistent with theory. In particular, there is little support for the overshooting hypothesis. Also the results show that the exchange rates do not always move in the direction normally anticipated, particularly for New Zealand. A contraction in monetary policy may lead to a depreciation of the domestic currency rather than an appreciation.

We apply cointegration methodology to the New Zealand and Australian 90-day, three-year and 10-year debt and futures markets. We compare traditional methods of calculating hedge ratios with those computed by using univariate and multivariate error correction models. We use out-of-sample forecasting to determine which approach is the most effective. Contrary to recent research, our results show that univariate and multivariate error correction models do not outperform more traditional methods of constructing hedges.

We utilized an in vitro adult mouse extensor digitorum longus (EDL) nerve-attached preparation to characterize the responses of muscle spindle afferents to ramp-and-hold stretch and sinusoidal vibratory stimuli. Responses were measured at both room (24°C) and muscle body temperature (34°C). Muscle spindle afferent static firing frequencies increased linearly in response to increasing stretch lengths to accurately encode the magnitude of muscle stretch (tested at 2.5%, 5% and 7.5% of resting length [Lo]). Peak firing frequency increased with ramp speeds (20% Lo/sec, 40% Lo/sec, and 60% Lo/sec). As a population, muscle spindle afferents could entrain 1:1 to sinusoidal vibrations throughout the frequency (10–100 Hz) and amplitude ranges tested (5–100 µm). Most units preferentially entrained to vibration frequencies close to their baseline steady-state firing frequencies. Cooling the muscle to 24°C decreased baseline firing frequency and units correspondingly entrained to slower frequency vibrations. The ramp component of stretch generated dynamic firing responses. These responses and related measures of dynamic sensitivity were not able to categorize units as primary (group Ia) or secondary (group II) even when tested with more extreme length changes (10% Lo). We conclude that the population of spindle afferents combines to encode stretch in a smoothly graded manner over the physiological range of lengths and speeds tested. Overall, spindle afferent response properties were comparable to those seen in other species, supporting subsequent use of the mouse genetic model system for studies on spindle function and dysfunction in an isolated muscle-nerve preparation.

We studied the effect of chronic hypobaric hypoxia (CHx; 10-11% O(2)) on the response to hypercapnia (15% CO(2)) of individual solitary complex (SC) neurons from adult rats. We simultaneously measured the intracellular pH and firing rate responses to hypercapnia of SC neurons in superfused medullary slices from control and CHx-adapted adult rats using the blind whole cell patch clamp technique and fluorescence imaging microscopy. We found that CHx caused the percentage of SC neurons inhibited by hypercapnia to significantly increase from about 10% up to about 30%, but did not significantly alter the percentage of SC neurons activated by hypercapnia (50% in control vs. 35% in CHx). Further, the magnitudes of the responses of SC neurons from control rats (chemosensitivity index for activated neurons of 166+/-11% and for inhibited neurons of 45+/-15%) were the same in SC neurons from CHx-adapted rats. This plasticity induced in chemosensitive SC neurons by CHx appears to involve intrinsic changes in neuronal properties since they were the same in synaptic blockade medium.

Droplets of alkanes on aqueous solutions of the cationic surfactants C(n)TAB (CH3(CH2)(n-1)N+ (CH3)3Br-) exhibit a first-order wetting transition as the concentration of the surfactant is increased. A theoretical model is presented in which the surface free energy is broken down into a long-range dispersion interaction and a short-range interaction described by a 2D lattice gas, taking into account the interaction between oil and surfactant molecules. The model provides quantitative agreement with the observed wetting transitions and the variation in composition of the wetting film with bulk surfactant concentration. The behavior of oil drops on large reservoirs of dilute surfactant is discussed.

Ellipsometry, surface tensiometry, and contact-angle measurement have been used to study the transition between partial wetting and pseudo-partial wetting of surfactant solutions by alkanes. In the partial wetting regime, the air-water surface tension is the same with and without alkane. In the pseudo-partial wetting regime, the air-water surface tension is lowered by the presence of alkane, showing that oil is solubilised into the surfactant monolayer. A discontinuous change in the coefficient of ellipticity with increasing surfactant concentration provides unequivocal evidence for the first-order nature of the wetting transitions. Ellipsometry has been used to explore the generality of wetting transitions of alkanes (dodecane, hexadecane, and squalane) on surfactant solutions [dodecyltrimethylammonium bromide, tetredecyltrimethylammonium bromide, dibucaine hydrochloride, and Aerosol OT (AOT)]. Of the systems studied, only hexadecane on AOT solutions did not show a wetting transition. Excess alkane remains as a lens on the surface of the surfactant solutions at all concentrations, but the contact angle is a minimum at the wetting transition. A semiquantitative model for the variation of the contact angle with surfactant concentration is provided.

This study examines the research behavior of Australian and New Zealand accounting faculty to determine the characteristics that influence research productivity. University reputations are integrally linked with research performance and determining the qualities that predict research behavior may be of particular value in the selection and recruitment process. The study finds that two key factors significantly impact performance: holding a Ph.D. and having an academe-oriented rather than profession-oriented background. These results may be interpreted as affirming the U.S. model of developing specialist academic researchers through doctoral education programs rather than employing faculty with strong professional experience.

During the summer of 2002, Robotic Autonomy was taught to thirty students at Carnegie Mellon West in cooperation with NASA/Ames (Moffett Field, CA). The authors at Carnegie Mellon University's Robotics Institute and at the University of Pittsburgh's Learning Research and Development Center planned a methodology for formally evaluating the educational efficacy of Robotic Autonomy. This article describes the educational analysis methodology and the statistically significant results of our analysis, demonstrating the positive impact of Robotic Autonomy on student learning beyond the boundaries of specific technical concepts in robotics. Educational robotics is gaining traction at all levels of the educational system, however formal analysis of its effectiveness has been lacking. This research project seeks to address this weakness by presenting statistically significant evidence of broad learning.