Tullis Rennie's Muscle Memory: Listening to the Act of Listening

This paper explores a recent, broadly 'electroacoustic', fixed medium composition by Tullis Rennie, which uses his background in ethnographic fieldwork to explore (in this case through auto-ethnography) modes of listening, and the role of technologies in mediating this listening. Muscle Memory: A conversation about jazz, with Graham South (trumpet) (2014) begins to answer questions about how one work can comment on and analyse or critique another through its own agency as music, bringing composition and ethnography together in fruitful collision, and illuminating the human capacity to manipulate and be manipulated by musical activity. The paper uses the piece to test the extent to which four functions, identified by Simon Frith (1987. Towards an aesthetic of popular music. In R. Leppert & S. McClary (Eds.), Music and society (pp. 133-49). Cambridge: Cambridge University Press) as crucial to the meaningfulness of popular music may, in the context of ubiquitously technologised music, have broader application than he originally intended.

Autonomic modification of intestinal smooth muscle contractility

Intestinal smooth muscle contracts rhythmically in the absence of nerve and hormonal stimulation because of the activity of pacemaker cells between and within the muscle layers. This means that the autonomic nervous system modifies rather than initiates intestinal contractions. The practical described here gives students an opportunity to observe this spontaneous activity and its modification by agents associated with parasympathetic and sympathetic nerve activity. A section of the rabbit small intestine is suspended in an organ bath, and the use of a pressure transducer and data-acquisition software allows the measurement of tension generated by the smooth muscle of intestinal walls. The application of the parasympathetic neurotransmitter ACh at varying concentrations allows students to observe an increase in intestinal smooth muscle tone with increasing concentrations of this muscarinic receptor agonist. Construction of a concentration-effect curve allows students to calculate an EC50 value for ACh and consider some basic concepts surrounding receptor occupancy and activation. Application of the hormone epinephrine to the precontracted intestine allows students to observe the inhibitory effects associated with sympathetic nerve activation. Introduction of the drug atropine to the preparation before a maximal concentration of ACh is applied allows students to observe the inhibitory effect of a competitive antagonist on the physiological response to a receptor agonist. The final experiment involves the observation of the depolarizing effect of K+ on smooth muscle. Students are also invited to consider why the drugs atropine, codeine, loperamide, and botulinum toxin have medicinal uses in the management of gastrointestinal problems.

Possible potentiation of toxins from Prevotella intermedia, Prevotella nigrescens, and Porphyromonas gingivalis by cotinine

BACKGROUND: Smoking is a recognized risk factor for the initiation and progression of periodontitis. However, the mechanism by which smoking induces its negative effects on the periodontium is not clear. This study aimed to test the hypothesis that synergy may occur between cotinine and bacterial products isolated from 3 putative periodontopathogens.

METHODS: A chick embryo toxin assay was used to investigate bacterial toxins (cell-free extracellular toxins and cell-free cell lysates) from 5 species with and without cotinine. A total of 9 putative periodontopathogens (3 species) and 2 non-oral controls (2 species) were studied. The periodontal species were: Prevotella intermedia (n = 4), Prevotella nigrescens (n = 4), and Porphyromonas gingivalis (n = 1). The control species tested were: Staphylococcus aureus (n = 1) and Escherichia coli (n = 1).

RESULTS: The toxicity kill was significantly greater than expected by simple addition alone (P <0.05, Fisher's exact test) between cotinine (800 ng/ml) and 1) the cell-free extracellular toxins of P. nigrescens MH1 and 2) the cell-free cell lysates of P. intermedia MH2. Synergy occurred with cotinine plus the cell-free extracellular toxins in all but 3 periodontal isolates, and the cell-free cell lysates in all but 2 periodontal isolates. Cotinine significantly (P <0.05, Fisher's exact test) enhanced the effects of cell-free extracellular toxins and cell lysates from one control species (E. coli), but not the other (S. aureus).

CONCLUSIONS: These findings indicate that synergy in an in vitro assay can occur between cotinine and toxins from putative periodontopathogens. This may be one important mechanism by which smoking increases the severity of periodontitis.

MRZ-99030 – a novel modulator of Aβ aggregation: II – reversal of Aβ oligomer-induced deficits in long-term potentiation (LTP) and cognitive performance in rats and mice.

β-amyloid1-42 (Aβ1-42) is a major endogenous pathogen underlying the aetiology of Alzheimer's disease (AD). Recent evidence indicates that soluble Aβ oligomers, rather than plaques, are the major cause of synaptic dysfunction and neurodegeneration. Small molecules that suppress Aβ aggregation, reduce oligomer stability or promote off-pathway non-toxic oligomerization represent a promising alternative strategy for neuroprotection in AD. MRZ-99030 was recently identified as a dipeptide that modulates Aβ1-42 aggregation by triggering a non-amyloidogenic aggregation pathway, thereby reducing the amount of intermediate toxic soluble oligomeric Aβ species. The present study evaluated the relevance of these promising results with MRZ-99030 under pathophysiological conditions i.e. against the synaptotoxic effects of Aβ oligomers on hippocampal long term potentiation (LTP) and two different memory tasks. Aβ1-42 interferes with the glutamatergic system and with neuronal Ca2+ signalling and abolishes the induction of LTP. Here we demonstrate that MRZ-99030 (100–500 nM) at a 10:1 stoichiometric excess to Aβ clearly reversed the synaptotoxic effects of Aβ1-42 oligomers on CA1-LTP in murine hippocampal slices. Co-application of MRZ-99030 also prevented the two-fold increase in resting Ca2+ levels in pyramidal neuron dendrites and spines triggered by Aβ1-42 oligomers. In anaesthetized rats, pre-administration of MRZ-99030 (50 mg/kg s.c.) protected against deficits in hippocampal LTP following i.c.v. injection of oligomeric Aβ1-42. Furthermore, similar treatment significantly ameliorated cognitive deficits in an object recognition task and under an alternating lever cyclic ratio schedule after the i.c.v. application of Aβ1-42 and 7PA2 conditioned medium, respectively. Altogether, these results demonstrate the potential therapeutic benefit of MRZ-99030 in AD.

Proprioceptive acuity predicts muscle co-contraction of the tibalis anterior and gastrocnemius medialis in older adults’ dynamic postural control

Older adults use a different muscle strategy to cope with postural instability, in which they ‘co-contract’ the muscles around the ankle joint. It has been suggested that this is a compensatory response to age-related proprioceptive decline however this view has never been assessed directly. The current study investigated the association between proprioceptive acuity and muscle co-contraction in older adults. We compared muscle activity, by recording surface EMG from the bilateral tibalis anterior and gastrocnemius medialis muscles, in young (aged 18-34) and older adults (aged 65-82) during postural assessment on a fixed and sway-referenced surface at age-equivalent levels of sway. We performed correlations between muscle activity and proprioceptive acuity, which was assessed using an active contralateral matching task. Despite successfully inducing similar levels of sway in the two age groups, older adults still showed higher muscle co-contraction. A stepwise regression analysis showed that proprioceptive acuity measured using variable error was the best predictor of muscle co-contraction in older adults. However, despite suggestions from previous research, proprioceptive error and muscle co-contraction were negatively correlated in older adults, suggesting that better proprioceptive acuity predicts more co-contraction. Overall, these results suggest that although muscle co-contraction may be an age-specific strategy used by older adults, it is not to compensate for age-related proprioceptive deficits.

Network signatures based on gene pair expression ratios improve classification and the analysis of muscle-invasive urothelial cancer

Urothelial cancer (UC) is highly recurrent and can progress from non-invasive (NMIUC) to a more aggressive muscle-invasive (MIUC) subtype that invades the muscle tissue layer of the bladder. We present a proof of principle study that network-based features of gene pairs can be used to improve classifier performance and the functional analysis of urothelial cancer gene expression data. In the first step of our procedure each individual sample of a UC gene expression dataset is inflated by gene pair expression ratios that are defined based on a given network structure. In the second step an elastic net feature selection procedure for network-based signatures is applied to discriminate between NMIUC and MIUC samples. We performed a repeated random subsampling cross validation in three independent datasets. The network signatures were characterized by a functional enrichment analysis and studied for the enrichment of known cancer genes. We observed that the network-based gene signatures from meta collections of proteinprotein interaction (PPI) databases such as CPDB and the PPI databases HPRD and BioGrid improved the classification performance compared to single gene based signatures. The network based signatures that were derived from PPI databases showed a prominent enrichment of cancer genes (e.g., TP53, TRIM27 and HNRNPA2Bl). We provide a novel integrative approach for large-scale gene expression analysis for the identification and development of novel diagnostical targets in bladder cancer. Further, our method allowed to link cancer gene associations to network-based expression signatures that are not observed in gene-based expression signatures.

A randomized controlled trial on the effects of combined aerobic-resistance exercise on muscle strength and fatigue, glycemic control and health-related quality of life of type 2 diabetes patients

Aim: to evaluate the effects of a 12-weeks combined aerobic-resistance exercise therapy on fatigue and isokinetic muscle strength, glycemic control and health-related quality of life (HRQoL) in moderately affected type 2 diabetes (T2DM) patients. Methods: a randomized controlled trial design was employed. Forty-three T2DM patients were assigned to an exercise group (n = 22), performing 3 weekly sessions of 60 minutes of combined aerobic-resistance exercise for 12-weeks; or a no exercise control group (n = 21). Both groups were evaluated at a baseline and after 12-weeks of exercise therapy for: 1) muscle strength and fatigue by isokinetic dynamometry; 2) plasma glycated hemoglobin A1C (HbA1C); and 3) HRQoL utilizing the SF-36 questionnaire. Results: the exercise therapy led to improvements in muscle fatigue in knee extensors (-55%) and increased muscle strength in knee flexors and extensors (+15 to +30%), while HbA1C decreased (-18%). In addition, the exercising patients showed sizeable improvements in HRQoL: physical function (+53%), vitality (+21%) and mental health (+40%). Conclusion: 12-weeks of combined aerobic-resistance exercise was highly effective to improve muscle strength and fatigue, glycemic control and several aspects of HRQoL in T2DM patients. These data encourage the use of aerobic and resistance exercise in the good clinical care of T2DM.

Effects of copper in plasma, gills, liver and muscle of seabream (Sparus aurata, Linnaeus 1758) juveniles

Dissertação de Mestrado, Aquacultura e Pescas, Faculdade de Ciências do Mar e do Ambiente, Universidade do Algarve, 2006

Developmental switch in the kinase dependency of long-term potentiation depends on expression of GluA4 subunit-containing AMPA receptors

The AMPA-receptor subunit GluA4 is expressed transiently in CA1 pyramidal neurons at the time synaptic connectivity is forming, but its physiological significance is unknown. Here we show that GluA4 expression is sufficient to alter the signaling requirements of long-term potentiation (LTP) and can fully explain the switch in the LTP kinase dependency from PKA to Ca2(+)/calmodulin-dependent protein kinase II during synapse maturation. At immature synapses, activation of PKA leads to a robust potentiation of AMPA-receptor function via the mobilization of GluA4. Analysis of GluA4-deficient mice indicates that this mechanism is critical for neonatal PKA-dependent LTP. Furthermore, lentiviral expression of GluA4 in CA1 neurons conferred a PKA-dependent synaptic potentiation and LTP regardless of the developmental stage. Thus, GluA4 defines the signaling requirements for LTP and silent synapse activation during a critical period of synapse development.

The immediate effects of atlanto-occipital joint manipulation and suboccipital muscle inhibition technique on active mouth opening and pressure pain sensitivity over latent myofascial trigger points in the masticatory muscles

DESIGN: A randomized controlled trial.OB JECTIVE: To investigate the immediate effects on pressure pain thresholds over latent trigger points (TrPs) in the masseter and temporalis muscles and active mouth opening following atlanto-occipital joint thrust manipulation or a soft tissue manual intervention targeted to the suboccipital muscles. BACKGROUND : Previous studies have described hypoalgesic effects of neck manipulative interventions over TrPs in the cervical musculature. There is a lack of studies analyzing these mechanisms over TrPs of muscles innervated by the trigeminal nerve. METHODS: One hundred twenty-two volunteers, 31 men and 91 women, between the ages of 18 and 30 years, with latent TrPs in the masseter muscle, were randomly divided into 3 groups: a manipulative group who received an atlanto-occipital joint thrust, a soft tissue group who received an inhibition technique over the suboccipital muscles, and a control group who did not receive an intervention. Pressure pain thresholds over latent TrPs in the masseter and temporalis muscles, and active mouth opening were assessed pretreatment and 2 minutes posttreatment by a blinded assessor. Mixed-model analyses of variance (ANOVA) were used to examine the effects of interventions on each outcome, with group as the between-subjects variable and time as the within-subjects variable. The primary analysis was the group-by-time interaction. RESULTS: The 2-by-3 mixed-model ANOVA revealed a significant group-by-time interaction for changes in pressure pain thresholds over masseter (P<.01) and temporalis (P =.003) muscle latent TrPs and also for active mouth opening (P<.001) in favor of the manipulative and soft tissue groups. Between-group effect sizes were small. CONCLUSIONS: The application of an atlanto-occipital thrust manipulation or soft tissue technique targeted to the suboccipital muscles led to an immediate increase in pressure pain thresholds over latent TrPs in the masseter and temporalis muscles and an increase in maximum active mouth opening. Nevertheless, the effects of both interventions were small and future studies are required to elucidate the clinical relevance of these changes. LEVEL OF EVIDENCE : Therapy, level 1b. J Orthop Sports Phys Ther 2010;40(5):310-317. doi:10.2519/jospt.2010.3257. KEYWORDSDS: cervical manipulation, muscle trigger points, neck, TMJ, upper cervical.

Diffusion characteristics of ethylene glycol in skeletal muscle

Part of the optical clearing study in biological tissues concerns the determination of the diffusion characteristics of water and optical clearing agents in the subject tissue. Such information is sufficient to characterize the time dependence of the optical clearing mechanisms—tissue dehydration and refractive index (RI) matching. We have used a simple method based on collimated optical transmittance measurements made from muscle samples under treatment with aqueous solutions containing different concentrations of ethylene glycol (EG), to determine the diffusion time values of water and EG in skeletal muscle. By representing the estimated mean diffusion time values from each treatment as a function of agent concentration in solution, we could identify the real diffusion times for water and agent. These values allowed for the calculation of the correspondent diffusion coefficients for those fluids. With these results, we have demonstrated that the dehydration mechanism is the one that dominates optical clearing in the first minute of treatment, while the RI matching takes over the optical clearing operations after that and remains for a longer time of treatment up to about 10 min, as we could see for EG and thin tissue samples of 0.5 mm.

The characteristic time of glucose diffusion measured for muscle tissue at optical clearing

The study of agent diffusion in biological tissues is very important to understand and characterize the optical clearing effects and mechanisms involved: tissue dehydration and refractive index matching. From measurements made to study the optical clearing, it is obvious that light scattering is reduced and that the optical properties of the tissue are controlled in the process. On the other hand, optical measurements do not allow direct determination of the diffusion properties of the agent in the tissue and some calculations are necessary to estimate those properties. This fact is imposed by the occurrence of two fluxes at optical clearing: water typically directed out of and agent directed into the tissue. When the water content in the immersion solution is approximately the same as the free water content of the tissue, a balance is established for water and the agent flux dominates. To prove this concept experimentally, we have measured the collimated transmittance of skeletal muscle samples under treatment with aqueous solutions containing different concentrations of glucose. After estimating the mean diffusion time values for each of the treatments we have represented those values as a function of glucose concentration in solution. Such a representation presents a maximum diffusion time for a water content in solution equal to the tissue free water content. Such a maximum represents the real diffusion time of glucose in the muscle and with this value we could calculate the corresponding diffusion coefficient.

Rat muscle opacity decrease due to the osmosis of a simple mixture

It is known that the fibrous structure of muscle causes light scattering. This phenomenon occurs due to the refractive index discontinuities located between muscle fibers and interstitial fluid. To study the possibility of reducing light scattering inside muscle, we consider its spectral transmittance evolution during an immersion treatment with an optical clearing solution containing ethanol, glycerol, and distilled water. Our methodology consists of registering spectral transmittance of muscle samples while immersed in that solution. With the spectral data collected, we represent the transmittance evolution for some wavelengths during the treatment applied. Additionally, we study the variations that the treatment has caused on the samples regarding tissue refractive index and mass. By analyzing microscopic photographs of tissue cross section, we can also verify changes in the internal arrangement of muscle fibers caused by the immersion treatment. Due to a mathematical model that we develop, we can explain the variations observed in the studied parameters and estimate the amount of optical clearing agent that has diffused into the tissue samples during the immersion treatment. At the end of the study, we observe and explain the improvement in tissue spectral transmittance, which is approximately 65% after 20 min.

Dominant and Recessive RYR1 Mutations in Adults with Core Lesions and Mild Muscle Symptoms

INTRODUCTION: Ryanodine receptor gene (RYR1) mutations have been associated with central core disease (CCD), multiminicore/minicore/multicore disease (MmD), and susceptibility to malignant hyperthermia (MH). METHODS: Patients with muscle symptoms in adulthood, who had features compatible with CCD/MmD, underwent clinical, histological, and genetic (RYR1 and SEPN1 genes) evaluations. Published cases of CCD and MmD with adult onset were also reviewed. RESULTS: Eight patients fulfilled the criteria for further analysis. Five RYR1 mutations, 4 of them unreported, were detected in 3 patients. Compound heterozygosity was proven in 1 case. CONCLUSIONS: To our knowledge, this is the only report of adult onset associated with recessive RYR1 mutations and central core/multiminicores on muscle biopsy. Although adult patients with CCD, MmD, and minimally symptomatic MH with abnormal muscle biopsy findings usually have a mild clinical course, differential diagnosis and carrier screening is crucial for prevention of potentially life-threatening reactions to general anesthesia.