A mechanism for three-photon double ionization of atoms by extreme-ultraviolet free-electron laser pulses is revealed, where in a sequential process the second ionization step, proceeding via ...resonant two-photon ionization of ions, is strongly enhanced by the excitation of ionic autoionizing states. In contrast to the conventional model, the mechanism explains the observed relative intensities of photoelectron peaks and their angular dependence in three-photon double ionization of argon.
1. 5‐Hydroxytryptamine (5‐HT) exerts both contractile and relaxant effects in the marmoset isolated aorta, actions that are unaffected by the 5‐HT2 antagonist ketanserin. The aim of the present study ...was to define the receptors mediating the contractile activity of 5‐HT in the marmoset aorta.
2. Contractile responses were elicited in aortic rings that were either: (i) precontracted submaximally with the thromboxane A2 agonist U44069 in order to amplify the responses; or (ii) exposed to Nω‐nitro‐L‐arginine (100 μmol/L) plus LY 53857 (0.1 μmol/L; a 5‐HT2 receptor antagonist shown previously to inhibit relaxation). The effect of 5‐HT on adenosine 3′,5′‐cyclic monophosphate (cAMP) formation was also investigated.
3. The effects of agonists and antagonists comprised: (i) agonist potencies in the order 5‐carboxamidotryptamine > 5‐HT > sumatriptan > 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin; (ii) inhibition of contractile action of 5‐HT by the 5‐HT1D antagonist GR 127935; (iii) a contractile response to methysergide; (iv) a lack of effect of tropisetron, an antagonist of 5‐HT3 and 5‐HT4 receptors; and (v) inhibition of forskolin‐stimulated cAMP formation by 5‐HT (in the presence of LY 53857), indicative of negative coupling to adenylate cyclase.
4. The above effects fulfil the criteria for a 5‐HT1‐like receptor. In view of the previous finding that this contractile response is insensitive to ketanserin, it is concluded that the contractile effects of 5‐HT in the marmoset aorta are mediated exclusively by a 5‐HT1‐like receptor.
In this study on decapod crustaceans, we examined the Ca2+- and Sr2+-activation properties of skeletal muscle fibres from an identified proprioceptor, the thoracic coxal muscle receptor organ (TCMRO) ...and its extrafusal promotor muscle fibres. Proprioceptors and extrafusal muscles were isolated from a walking leg from the crayfish (Cherax destructor) and the rear swimming leg of the mud crab (Scylla serrata). The crayfish and mud crab TCMROs had very low Hill coefficient (nCa) values (1.86 +/- 0.08 and 1.64 +/- 0.03, respectively). In comparison to other skeletal muscle fibre types these low Hill coefficients would enable the length of the receptor muscles to be finely controlled over a wide range of Ca2+. Maximum force was found to be significantly lower in the TCMROs (crayfish: 5.76 +/- 0.98; crab: 4.80 +/- 0.56 Ncm(-2)), compared to their associated extrafusal promotor muscle fibres (crayfish: 10.69 +/- 1.63; crab: 20.07 +/- 1.98 Ncm(-2)), which is consistent with their sensory role. The muscle fibres of the crayfish TCMRO had faster contractile properties than the mud crab TCMRO, we discuss how these contractile properties relate to the type of locomotion undergone by each leg. The mud crab 'red' promotor and all crayfish promotor fibres were characterised as slow with low Hill coefficients (nCa: crayfish: 3.22 +/- 0.29; crab: 3.34 +/- 0.29) and a contractile apparatus with a high sensitivity to Ca2+ (pCa50: crayfish: 6.42 +/- 0.03; crab: 6.18 +/- 0.03). In contrast the 'white' mud crab promotor fibres from the swimming leg had contractile properties that were characteristic of fast fibres with a high mean Hill coefficient (nCa: 5.27 +/- 0.76) and a lower Ca2+ sensitivity (pCa50: 6.03 +/- 0.03). The sensitivity of the contractile apparatus to Sr2+ was very low (range of mean pSr50: 4.23 +/- 0.03-3.48 +/- 0.06) and low force levels were produced in comparison to that produced with Ca2+. The results of this study show that the muscle fibres of the sensory receptor, produce less force and have been adapted to enable the length of the receptor to be finely set in relation to the length of the extrafusal muscle. We discuss how the striated fibres of the receptor have been adapted to perform a sensory role and how this is related to the type of locomotion undergone by the legs. We also discuss how the fibre types of the extrafusal muscle have adapted to the mode of locomotion.
1. Reflex efferent control of a muscle stretch receptor by a joint proprioceptor of the same limb was studied in an isolated
CNS preparation from the shore crab. The influence of 'fictive locomotor' ...activity on this interjoint reflex was also examined.
2. The thoracic-coxal muscle receptor organ (TCMRO) and the coxo-basal chordotonal organ (CBCO), which monitor movement and
position of the first and second joints of the posterior leg, were isolated together with the whole thoracic ganglion complex.
The TCMRO, functionally analogous to a mammalian muscle spindle, has two receptor motoneurones. RM1 innervating the receptor
muscle alone and RM2 which also supplies the 'extrafusal' promotor muscle. The CBCO is a typical arthropod elastic strand
organ, with many sensory neurones but lacking an efferent supply. The TCMRO was fixed at its mid-length, and stretch-hold-release
stimuli were applied to the CBCO. Efferent activity was recorded from the cut nerve roots of the four basal limb muscles and
intracellularly as excitatory junction potentials (EJPs) from the receptor muscle. 3. A dynamic increase in the frequency
of action potentials in RM1 occurred on both stretch and release of the CBCO. During the hold phase the RM1 activity declined
from the dynamic response but remained elevated compared to the resting tonic discharge. RM2, identified by EJPs occurring
1:1 with a unit in the promoter nerve, responded in a similar way. 4. One or more promotor motoneurones were usually co-activated
with the two receptor efferents in response to input from the CBCO. In a typical example the average spike frequency of RM1
rose from 0 to 27 Hz during the dynamic phases (stretch and release) of the CBCO stimulus, falling to 2.5 Hz during the hold
phase, while the corresponding promotor spike frequencies were 25 and 7.5 Hz, respectively. The other three muscle nerves
recorded from generally also showed reflex driving by the CBCO. 5. The totally isolated thoracic ganglion could produce a
rhythmic, bursting motor output in the absence of any sensory input. During this centrally generated activity the receptor
motor innervation was strongly co-activated with the promotor bursts, and the reflex input from the CBCO was overridden or
modulated in a phase-dependent manner. 6. The proximally directed interjoint reflex to the receptor muscle probably functions
to maintain the tension on the sensory endings of the TCMRO, and so enable them to respond effectively at all times to movements
of the basal leg joint.
Laminin alpha 2-deficient congenital muscular dystrophy is a debilitating disease affecting both muscle and neural tissue as a result of mutations in the LAMA2 gene. It presents at or soon after ...birth with muscle weakness and is further characterised by clinical central nervous system involvement. Laminin alpha 2 is part of the extracellular matrix, linked to the cellular cystoskeleton via dystroglycan which is an integral part of the dystrophin-glycoprotein complex (DGC). We examined both short- and long-term synaptic plasticity in the C57BL6J/dy super(2) super(J) mouse, an animal model of laminin alpha 2 deficient congenital muscular dystrophy. Using a cerebellar slice preparation, we show that the pre-synaptically mediated paired-pulse facilitation (PPF) was no different between dy super(2) super(J) and littermate controls. Approximately half (7/12) the dy super(2) super(J) Purkinje cells displayed a blunted LTD compared to littermate controls, and one third (4/12) of dy super(2) super(J) Purkinje cells displayed LTP. This study demonstrates that a defective laminin alpha 2 causes a disruption in long-term synaptic plasticity at the Purkinje cell-parallel fibre synapse.
Laminin alpha2-deficient congenital muscular dystrophy is a debilitating disease affecting both muscle and neural tissue as a result of mutations in the LAMA2 gene. It presents at or soon after birth ...with muscle weakness and is further characterised by clinical central nervous system involvement. Laminin alpha2 is part of the extracellular matrix, linked to the cellular cystoskeleton via dystroglycan which is an integral part of the dystrophin-glycoprotein complex (DGC). We examined both short- and long-term synaptic plasticity in the C57BL6J/dy(2J) mouse, an animal model of laminin alpha2 deficient congenital muscular dystrophy. Using a cerebellar slice preparation, we show that the pre-synaptically mediated paired-pulse facilitation (PPF) was no different between dy(2J) and littermate controls. Approximately half (7/12) the dy(2J) Purkinje cells displayed a blunted LTD compared to littermate controls, and one third (4/12) of dy(2J) Purkinje cells displayed LTP. This study demonstrates that a defective laminin alpha2 causes a disruption in long-term synaptic plasticity at the Purkinje cell-parallel fibre synapse.
A common nonsense polymorphism (R577X) in the ACTN3 gene results in complete deficiency of the fast skeletal muscle fiber protein α-actinin-3 in an estimated one billion humans worldwide. The XX null ...genotype is under-represented in elite sprint athletes, associated with reduced muscle strength and sprint performance in non-athletes, and is over-represented in endurance athletes, suggesting that α-actinin-3 deficiency increases muscle endurance at the cost of power generation. Here we report that muscle from Actn3 knockout mice displays reduced force generation, consistent with results from human association studies. Detailed analysis of knockout mouse muscle reveals reduced fast fiber diameter, increased activity of multiple enzymes in the aerobic metabolic pathway, altered contractile properties, and enhanced recovery from fatigue, suggesting a shift in the properties of fast fibers towards those characteristic of slow fibers. These findings provide the first mechanistic explanation for the reported associations between R577X and human athletic performance and muscle function.
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