Prompt Response of the Dayside Magnetosphere to Discrete Structures Within the Sheath Region of a Coronal Mass Ejection.

A sequence of discrete solar wind structures within the sheath region of an interplanetary coronal mass ejection on November 6, 2015, caused a series of compressions and releases of the dayside magnetosphere. Each compression resulted in a brief adiabatic enhancement of ions (electrons) driving bursts of electromagnetic ion cyclotron (EMIC; whistler mode chorus) wave growth across the dayside magnetosphere. Fine-structured rising tones were observed in the EMIC wave bursts, resulting in nonlinear scattering of relativistic electrons in the outer radiation belt. Multipoint observations allow us to study the spatial structure and evolution of these sheath structures as they propagate Earthward from L1 as well as the spatio-temporal characteristics of the magnetospheric response. This event highlights the importance of fine-scale solar wind structure, in particular within complex sheath regions, in driving dayside phenomena within the inner magnetosphere.

Autogenous and efficient acceleration of energetic ions upstream of Earth's bow shock.

Earth and its magnetosphere are immersed in the supersonic flow of the solar-wind plasma that fills interplanetary space. As the solar wind slows and deflects to flow around Earth, or any other obstacle, a 'bow shock' forms within the flow. Under almost all solar-wind conditions, planetary bow shocks such as Earth's are collisionless, supercritical shocks, meaning that they reflect and accelerate a fraction of the incident solar-wind ions as an energy dissipation mechanism1,2, which results in the formation of a region called the ion foreshock3. In the foreshock, large-scale, transient phenomena can develop, such as 'hot flow anomalies'4-9, which are concentrations of shock-reflected, suprathermal ions that are channelled and accumulated along certain structures in the upstream magnetic field. Hot flow anomalies evolve explosively, often resulting in the formation of new shocks along their upstream edges5,10, and potentially contribute to particle acceleration11-13, but there have hitherto been no observations to constrain this acceleration or to confirm the underlying mechanism. Here we report observations of a hot flow anomaly accelerating solar-wind ions from roughly 1-10 kiloelectronvolts up to almost 1,000 kiloelectronvolts. The acceleration mechanism depends on the mass and charge state of the ions and is consistent with first-order Fermi acceleration14,15. The acceleration that we observe results from only the interaction of Earth's bow shock with the solar wind, but produces a much, much larger number of energetic particles compared to what would typically be produced in the foreshock from acceleration at the bow shock. Such autogenous and efficient acceleration at quasi-parallel bow shocks (the normal direction of which are within about 45 degrees of the interplanetary magnetic field direction) provides a potential solution to Fermi's 'injection problem', which requires an as-yet-unexplained seed population of energetic particles, and implies that foreshock transients may be important in the generation of cosmic rays at astrophysical shocks throughout the cosmos.

Electron Bulk Acceleration and Thermalization at Earth's Quasiperpendicular Bow Shock.

Electron heating at Earth's quasiperpendicular bow shock has been surmised to be due to the combined effects of a quasistatic electric potential and scattering through wave-particle interaction. Here we report the observation of electron distribution functions indicating a new electron heating process occurring at the leading edge of the shock front. Incident solar wind electrons are accelerated parallel to the magnetic field toward downstream, reaching an electron-ion relative drift speed exceeding the electron thermal speed. The bulk acceleration is associated with an electric field pulse embedded in a whistler-mode wave. The high electron-ion relative drift is relaxed primarily through a nonlinear current-driven instability. The relaxed distributions contain a beam traveling toward the shock as a remnant of the accelerated electrons. Similar distribution functions prevail throughout the shock transition layer, suggesting that the observed acceleration and thermalization is essential to the cross-shock electron heating.

Revisiting the structure of low-Mach number, low-beta, quasi-perpendicular shocks.

A study of the structure of 145 low-Mach number (M ≤ 3), low-beta (ß ≤ 1), quasi-perpendicular interplanetary collisionless shock waves observed by the Wind spacecraft has provided strong evidence that these shocks have large-amplitude whistler precursors. The common occurrence and large amplitudes of the precursors raise doubts about the standard assumption that such shocks can be classified as laminar structures. This directly contradicts standard models. In 113 of the 145 shocks (~78%), we observe clear evidence of magnetosonic-whistler precursor fluctuations with frequencies ~0.1-7 Hz. We find no dependence on the upstream plasma beta, or any other shock parameter, for the presence or absence of precursors. The majority (~66%) of the precursors propagate at ≤45° with respect to the upstream average magnetic field and most (~87%) propagate ≥30° from the shock normal vector. Further, most (~79%) of the waves propagate at least 20° from the coplanarity plane. The peak-to-peak wave amplitudes (δB pk-pk) are large with a range of maximum values for the 113 precursors of ~0.4-13 nT with an average of ~2 nT. When we normalize the wave amplitudes to the upstream averaged magnetic field and the shock ramp amplitude, we find average values of ~40% and ~220%, respectively.

Relativistic Electrons Produced by Foreshock Disturbances Observed Upstream of Earth's Bow Shock.

Charged particles can be reflected and accelerated by strong (i.e., high Mach number) astrophysical collisionless shock waves, streaming away to form a foreshock region in communication with the shock. Foreshocks are primarily populated by suprathermal ions that can generate foreshock disturbances-large-scale (i.e., tens to thousands of thermal ion Larmor radii), transient (∼5-10 per day) structures. They have recently been found to accelerate ions to energies of several keV. Although electrons in Saturn's high Mach number (M>40) bow shock can be accelerated to relativistic energies (nearly 1000 keV), it has hitherto been thought impossible to accelerate electrons beyond a few tens of keV at Earth's low Mach number (1≤M<20) bow shock. Here we report observations of electrons energized by foreshock disturbances to energies up to at least ∼300 keV. Although such energetic electrons have been previously observed, their presence has been attributed to escaping magnetospheric particles or solar events. These relativistic electrons are not associated with any solar or magnetospheric activity. Further, due to their relatively small Larmor radii (compared to magnetic gradient scale lengths) and large thermal speeds (compared to shock speeds), no known shock acceleration mechanism can energize thermal electrons up to relativistic energies. The discovery of relativistic electrons associated with foreshock structures commonly generated in astrophysical shocks could provide a new paradigm for electron injections and acceleration in collisionless plasmas.

Skeletal muscle mass recovery from atrophy in IL-6 knockout mice.

AIM: Skeletal muscle interleukin-6 (IL-6) expression is induced by continuous contraction, overload-induced hypertrophy and during muscle regeneration. The loss of IL-6 can alter skeletal muscle's growth and extracellular matrix remodelling response to overload-induced hypertrophy. Insulin-like growth factor-1 (IGF-1) gene expression and related signalling through Akt/mTOR is a critical regulator of muscle mass. The significance of IL-6 expression during the recovery from muscle atrophy is unclear. This study's purpose was to determine the effect of IL-6 loss on mouse gastrocnemius (GAS) muscle mass during recovery from hindlimb suspension (HS)-induced atrophy. METHODS: Female C57BL/6 [wild type (WT)] and IL-6 knockout (IL-6 KO) mice at 10 weeks of age were assigned to control, HS or HS followed by normal cage ambulation groups. RESULTS: GAS muscle atrophy was induced by 10 days of HS. HS induced a 20% loss of GAS mass in both WT and IL-6 KO mice. HS+7 days of recovery restored WT GAS mass to cage-control values. GAS mass from IL-6 KO mice did not return to cage-control values until HS+14 days of recovery. Both IGF-1 mRNA expression and Akt/mTOR signalling were increased in WT muscle after 1 day of recovery. In IL-6 KO muscle, IGF-1 mRNA expression was decreased and Akt/mTOR signalling was not induced after 1 day of recovery. MyoD and myogenin mRNA expression were both induced in WT muscle after 1 day of recovery, but not in IL-6 KO muscle. CONCLUSION: Muscle IL-6 expression appears important for the initial growth response during the recovery from disuse.

Review: Sex specific programming: a critical role for the renal renin-angiotensin system.

The "Developmental Origins of Health and Disease" hypothesis has caused resurgence of interest in understanding the factors regulating fetal development. A multitude of prenatal perturbations may contribute to the onset of diseases in adulthood including cardiovascular and renal diseases. Using animal models such as maternal glucocorticoid exposure, maternal calorie or protein restriction and uteroplacental insufficiency, studies have identified alterations in kidney development as being a common feature. The formation of a low nephron endowment may result in impaired renal function and in turn may contribute to disease. An interesting feature in many animal models of developmental programming is the disparity between males and females in the timing of onset and severity of disease outcomes. The same prenatal insult does not always affect males and females in the same way or to the same degree. Recently, our studies have focused on changes induced in the kidney of both the fetus and the offspring, following a perturbation during pregnancy. We have shown that changes in the renin-angiotensin system (RAS) occur in the kidney. The changes are often sex specific which may in part explain the observed sex differences in disease outcomes and severity. This review explores the evidence suggesting a critical role for the RAS in sex specific developmental programming of disease with particular reference to the immediate and long term changes in the local RAS within the kidney.

Overload-induced skeletal muscle extracellular matrix remodelling and myofibre growth in mice lacking IL-6.

AIM: Overloading healthy skeletal muscle produces myofibre hypertrophy and extracellular matrix remodelling, and these processes are thought to be interdependent for producing muscle growth. Inflammatory cytokine interleukin-6 (IL-6) gene expression is induced in overloaded skeletal muscle, and the loss of this IL-6 induction can attenuate the hypertrophic response to overload (OV). Although the OV induction of IL-6 in skeletal muscle may be an important regulator of inflammatory processes and satellite cell proliferation, less is known about its role in the regulation of extracellular matrix remodelling. The purpose of the current study was to examine if OV-induced extracellular matrix remodelling, muscle growth, and associated gene expression were altered in mice that lack IL-6, when compared with wild-type mice. METHODS: Male C57/BL6 (WT) and C57/BL6 x IL-6(-/-) (IL-6(-/-)) mice (10 weeks of age) were assigned to either a sham control or synergist ablation OV treatments for 3, 21 or 56 days. RESULT: Plantaris muscle mass increased 59% in WT and 116% in IL-6(-/-) mice after 21 day OV. Myofibre CSA was also increased by 21 day OV in both WT and IL-6(-/-) mice. OV induced a twofold greater increase in the volume of non-contractile tissue in IL-6(-/-) muscle compared to WT. OV also induced a significantly greater accumulation of hydroxyproline and procollagen-1 mRNA in IL-6(-/-) muscle, when compared with WT muscle after 21 day OV. Transforming growth factor-beta and insulin-like growth factor-1 mRNA expression were also induced to a greater extent in IL-6(-/-) muscle when compared with WT muscle after 21 day OV. There was no effect of IL-6 loss on the induction of myogenin, and cyclin D1 mRNA expression after 3 day OV. However, MyoD mRNA expression in 3 day OV IL-6(-/-) muscle was attenuated when compared with WT OV mice. CONCLUSION: IL-6 appears to be necessary for the normal regulation of extracellular matrix remodelling during OV-induced growth.

Waves in interplanetary shocks: a wind/WAVES study.

We describe results from the first statistical study of waveform capture data during 67 interplanetary (IP) shocks with Mach numbers ranging from approximately 1-6. Most of the waveform captures and nearly 100% of the large amplitude waves were in the ramp region. Although solitary waves, Langmuir waves, and ion acoustic waves (IAWs) are all observed in the ramp region of the IP shocks, large amplitude IAWs dominate. The wave amplitude is correlated with the fast mode Mach number and with the shock strength. The observed waves produced anomalous resistivities from approximately 1-856 Omega.m (approximately 10(7) times greater than classical estimates.) The results are consistent with theory suggesting IAWs provide the primary dissipation for low Mach number shocks.

Brief stimulation of the peroneal nerve attenuates the exercise pressor reflex in anaesthetised cats.

We recently demonstrated that applying capsaicin to the common peroneal nerve, thereby activating small diameter afferent neurons, caused a substantial rise in mean arterial pressure (MAP) and heart rate (HR) that lasted approximately 20 min. In addition, this application of capsaicin transiently attenuated the exercise pressor reflex (EPR). The purpose of the current study was to test the hypothesis that stimulating the peroneal nerve at an intensity that activated both myelinated and unmyelinated axons for a short duration (1 min) causes a similar attenuation of the EPR. Cats were anaesthetised with alpha-chloralose and urethane, the popliteal fossa was exposed, and static contraction was induced by stimulating the tibial nerve. The ipsilateral peroneal nerve was cut and placed on a stimulating electrode. Prior to peroneal nerve stimulation, static contraction of the triceps surae muscle for 1 min increased MAP 48+/-8 mmHg and HR 16+/-3 bpm. Electrical stimulation of the central end of the cut peroneal nerve for 1 min (100 x motor threshold; 40 Hz; 0.1 ms) increased MAP and HR by 62+/-11 mmHg and 28+/-4 bpm, respectively. These increases returned to prestimulation levels within 1 min. Two minutes after the peroneal stimulation was stopped, the EPR was markedly reduced as muscle contraction increased MAP and HR by 20+/-4 mmHg and 7+/-2 bpm, respectively. Repeating the muscle contraction approximately 25 min after peroneal stimulation increased MAP and HR by 38+/-8 mmHg and 12+/-2 bpm, indicating some recovery of the EPR. These results show that brief (1 min) electrical stimulation of afferent neurons in the peroneal nerve attenuates the EPR. This supports the hypothesis that strong activation of small diameter afferent neurons stimulates a nervous system mechanism that diminishes the sensory input from skeletal muscle involved in cardiovascular regulation.

Activation of spinobulbar lamina I neurons by static muscle contraction.

Spinal lamina I neurons are selectively activated by small-diameter somatic afferents, and they project to brain stem sites that are critical for homeostatic control. Because small-diameter afferent activity evoked by contraction of skeletal muscle reflexly elicits exercise-related cardiorespiratory activation, we tested whether spinobulbar lamina I cells respond to muscle contraction. Spinobulbar lamina I neurons were identified in chloralose-anesthetized cats by antidromic activation from the ipsilateral caudal ventrolateral medulla. Static contractions of the ipsilateral triceps surae muscle were evoked by tibial nerve stimulation using parameters that avoid afferent activation, and arterial blood pressure responses were recorded. Recordings were maintained from 13 of 17 L(7) lamina I spinobulbar neurons during static muscle contraction, and 5 of these neurons were excited. Three were selectively activated only by muscle afferents and did not have a cutaneous receptive field. Spinobulbar lamina I neurons activated by muscle contraction provide an ascending link for the reflex cardiorespiratory adjustments that accompany muscular work. This study provides an important first step in elucidating an ascending afferent pathway for somato-autonomic reflexes.

Neuronal application of capsaicin modulates somatic pressor reflexes.

Static contraction of skeletal muscle elicits a reflex increase in cardiovascular function. Likewise, noxious stimuli activate somatic nociceptors eliciting a reflex increase in cardiovascular function. On the basis of recent work involving spinothalamic cells in the dorsal horn, we hypothesized that the dorsal horn cells involved in the aforementioned reflexes would be sensitized by applying capsaicin (Cap) to a peripheral nerve. If correct, then Cap would enhance the cardiovascular increases that occur when these reflexes are evoked. Cats were anesthetized, and the popliteal fossa was exposed. Static contraction was induced by electrical stimulation of the tibial nerve at an intensity that did not directly activate small-diameter muscle afferent fibers, whereas nociceptors were stimulated by high-intensity stimulation (after muscle paralysis) of either the saphenous nerve (cutaneous nociceptors) or a muscular branch of the tibial nerve (muscle nociceptors). The reflex cardiovascular responses to these perturbations (contraction or nociceptor stimulation) were determined before and after direct application of Cap (3%) onto the common peroneal nerve, using a separate group of cats for each reflex. Compared with control, application of Cap attenuated the peak change in mean arterial pressure (MAP) evoked by static contraction (DeltaMAP in mmHg: 38 +/- 10 before and 24 +/- 8 after ipsilateral Cap; 47 +/- 10 before and 33 +/- 10 after contralateral Cap). On the other hand, Cap increased the peak change in MAP evoked by stimulation of the saphenous nerve from 57 +/- 8 to 77 +/- 9 mmHg, as well as the peak change in MAP elicited by activation of muscle nociceptors (36 +/- 9 vs. 56 +/- 14 mmHg). These results show that the reflex cardiovascular increases evoked by static muscle contraction and noxious input are differentially affected by Cap application to the common peroneal nerve. We hypothesize that a Cap-induced alteration in dorsal horn processing is the locus for this divergent effect on these reflexes.

Dorsal horn administration of muscimol abolishes the muscle pressor reflex.

The purpose of this study was to determine the effect of blocking synaptic transmission in the dorsal horn on the cardiovascular responses produced by activation of muscle afferent neurons. Synaptic transmission was blocked by applying the GABA(A) agonist muscimol to the dorsal surface of the spinal cord. Cats were anesthetized with alpha-chloralose and urethane, and a laminectomy was performed. With the exception of the L(7) dorsal root, the dorsal and ventral roots from L(5) to S(2) were sectioned on one side, and static contraction of the ipsilateral triceps surae muscle was evoked by electrically stimulating the peripheral ends of the L(7) and S(1) ventral roots. The dorsal surface of the L(4)--S(3) segments of the spinal cord were enclosed within a "well" created by applying layers of vinyl polysiloxane. Administration of a 1 mM solution of muscimol (based on dose-response data) into this well abolished the reflex pressor response to contraction (change in mean arterial blood pressure before was 47 +/- 7 mmHg and after muscimol was 3 +/- 2 mmHg). Muscle stretch increased mean arterial blood pressure by 30 +/- 8 mmHg before muscimol, but after drug application stretch increased MAP by only 3 +/- 2 mmHg. Limiting muscimol to the L(7) segment attenuated the pressor responses to contraction (37 +/- 7 to 24 +/- 11 mmHg) and stretch (28 +/- 2 to 16 +/- 8 mmHg). These data suggest that the dorsal horn of the spinal cord contains an obligatory synapse for the pressor reflex. Furthermore, these data support the hypothesis that branches of primary afferent neurons, not intraspinal pathways, are responsible for the multisegmental integration of the pressor reflex.

Spinal modulation of the muscle pressor reflex by nitric oxide and acetylcholine.

Static contraction of skeletal muscle activates the sympathetic nervous system, which in turn increases cardiovascular function. These changes are mediated, in part, by a reflex arising from the contracting muscle. This reflex is termed the exercise pressor reflex or, more simply, the muscle pressor reflex (MPR). Over the past few years, studies have been performed investigating the sensory processing that occurs in the dorsal horn of the spinal cord as it pertains to the MPR. Several putative neurotransmitters and receptors have been implicated in mediating the MPR at the level of the dorsal horn. In addition, several receptor systems have been shown to modulate the MPR at the dorsal horn. We have recently performed studies investigating the potential modulatory role of dorsal horn nitric oxide (NO) and acetylcholine (ACH) on the MPR. Along these lines, our experiments suggest that NO enhances the excitability of dorsal horn cells receiving input from muscle afferent neurons, while ACH decreases the MPR when its concentration in the dorsal horn is elevated. The purpose of this manuscript is to review recently published findings from our laboratory and apply this information in an effort to better understand the integration of sensory input that occurs in the dorsal horn as it pertains to cardiovascular regulation. This review is also designed to stimulate questions as to how these two neurochemicals exert their actions and whether or not they represent or can represent important physiological mechanisms involved in regulating the dorsal horn integration of the MPR.

Spinal cholinergic inhibition of the pressor response to muscle activation is mediated by muscarinic, but not nicotinic, receptors.

This study examined the influence of spinal muscarinic and nicotinic receptors on the cardiovascular adjustments to skeletal muscle activation in anesthetized cats. Microdialyzing into the L(7) dorsal horn increasing doses of the muscarinic receptor agonist bethanechol, but not the nicotinic receptor antagonist mecamylamine, reduced increases in mean arterial pressure (MAP) and heart rate (HR) during hindlimb contraction or passive stretch. Atropine administration accentuated the cardiovascular responses during contraction, but not during passive stretch. These data indicate that muscarinic, but not nicotinic, receptors at the dorsal horn level blunt the pressor response to muscle activity. Further, the data suggest that the two neural pathways involved in muscle contraction or stretch are anatomically distinct.

Dorsal horn administration of L-arginine accentuates the pressor response evoked by activation of muscle mechanoreceptors.

Recent work from our laboratory suggests that nitric oxide production in the dorsal horn has a modulatory influence on the pressor reflex evoked by static contraction of skeletal muscle. In this study, we tested the hypothesis that nitric oxide production in the dorsal horn is involved in producing the pressor reflex elicited by activation of skeletal muscle mechanoreceptors. Cats were anesthetized with alpha-chloralose (80 mg/kg) and urethane (100 mg/kg) and a laminectomy was performed. With the exception of the L7 dorsal root, the dorsal and ventral roots from L5 to S2 were sectioned on one side. Muscle mechanoreceptors were activated by manually stretching the ipsilateral triceps surae muscle 1.5 cm. To block nitric oxide synthase, a 50 mM solution of nt-nitro-L-argenine methyl ester (L-NAME) (a dose that altered the pressor reflex to static contraction) was microdialyzed into the dorsal horn at L6 and S1. Dialysis of L-NAME failed to attenuate the peak change in mean arterial pressure evoked by muscle stretch (45 +/- 6 mmHg before and 44 +/- 9 mmHg after 2 h of L-NAME dialysis). On the other hand, 2 h of L-arginine dialysis (50 mM) increased the peak pressor response to muscle stretch from 43 +/- 3 to 57 +/- 5 mmHg. These data suggest that administration of L-arginine enhances the excitability of dorsal horn cells receiving input from muscle mechanoreceptors, thus increasing the pressor response evoked by activation of this type of muscle afferent neuron.

Spinal cholinergic inhibition of the pressor response to skeletal muscle activation.

The purpose of this study was to delineate the role of the cholinergic pathway within the spinal cord in the reflex cardiovascular responses to muscle activity. Based on dose-response experiments, we microdialyzed a 0.1 mM solution of the acetylcholinesterase inhibitor neostigmine into the L7 level of the dorsal horn of anesthetized cats to determine its effects on the mean arterial blood pressure (MAP) and heart rate (HR) responses to static muscle contraction or passive stretch. The peak responses to 1-min contractions and stretches were reduced from control levels after 1 h of drug administration. In four experiments, the cardiovascular responses returned to control levels after a 2-h recovery period. Perfusion of the cholinergic receptor antagonist atropine accentuated the peak MAP response to muscle contraction. By contrast, atropine administration had no effect on the peak MAP adjustment to passive muscle stretch. These data support the hypothesis that increased acetylcholine (ACh) concentrations in the spinal cord inhibit the reflex cardiovascular responses to static muscle contraction. Further, the results suggest that the spinal cholinergic system is activated by metabolic changes in skeletal muscle, but likely unaffected by mechanical muscle changes.