The existence of a learning effect by which subjects progressively reduce body sway over the course of repetitive stabilometric measurements is currently debated. Also, the position and orientation of the feet on the platform can have a substantial influence on the outcome measurements. The aim of the present work was to assess the effect of feet positions on mean total velocity (V) of the center of pressure and the area (AR) covered by its displacements during quiet standing. A group of 35 healthy young subjects was examined during two successive sessions consisting of five recordings with their feet placed either in the recommended (standard, SP) or their usual most comfortable (UP) position. Results show a slight decreasing trend that failed to be statistically significant checked with Friedman’s ANOVA (SP AR, χ 2 (4)=6.10, p=0.19 and V, χ 2 (4)=8.66, p=0.07 and UP AR, χ 2 (4)=2.32, p=0.68 and V, χ 2 (4)=1.19, p=0.88). Nonetheless, values of AR and V showed a notable decrement especially evident in the SP exam reaching, respectively, 24% and 11% from baseline, whereas variability measured by the coefficient of variation was the same in the two exams. Given the results, a learning effect should not be ruled out with confidence. Also, usual foot placement would be preferable to avoid this effect. Further research is needed to take into consideration the great variability of stabilometric measurements and the fact that different subjects could adapt more readily to the test conditions than others.

In recent years people suffering of backache has significantly increased. This led us to focus our attention on the adequacy of school furniture for the correct development of the adult posture. The standing posture of 67 students of middle school has been analyzed at the beginning and at the end of two consecutive scholastic years using a stabilometric platform. Starting from the second year, about half of the students were provided with the furniture designed following European standard (UNI EN 1729:2006), while the other half maintained the traditional one. The main purpose of this research has been to verify by means of posturometric analysis the effects on postural parameters of the use of traditional furniture in comparison to the furniture following the UNI EN 1729:2006. We observed that prolonged sitting at school changes some posturometric variables of schoolchildren. Since no differences has been found between the two groups, the validity of the European standards is questioned. The present study allowed us to single out four anthropometric parameters that should be considered in order to devise a new model of adjustable furniture. By adjusting every year the furniture of each student, it would be possible to avoid (at least at school) the adoption of wrong postural positions that could be responsible for backache and other common musculoskeletal disorders.

Acetyl-L-carnitine (ALC) is a naturally occurring substance that, when administered at supra-physiological concentration, is neuroprotective. It is involved in membrane stabilization and in enhancement of mitochondrial functions. It is a molecule of considerable interest for its clinical application in various neural disorders, including Alzheimer's disease and painful neuropathies. ALC is known to improve the cognitive capability of aged animals chronically treated with the drug and, recently, it has been reported that it impairs forms of non-associative learning in the leech. In the present study the effects of ALC on gene expression have been analyzed in the leech Hirudo medicinalis. The suppression subtractive hybridisation methodology was used for the generation of subtracted cDNA libraries and the subsequent identification of differentially expressed transcripts in the leech nervous system after ALC treatment. The method detects differentially but also little expressed transcripts of genes whose sequence or identity is still unknown. We report that a single administration of ALC is able to modulate positively the expression of genes coding for functions that reveal a lasting effect of ALC on the invertebrate, and confirm the neuroprotective and neuromodulative role of the substance. In addition an important finding is the modulation of genes of vegetal origin. This might be considered an instance of ectosymbiotic mutualism.

Several studies suggest that acetyl-l-carnitine (ALC) might influence learning processes. Along this line of investigation, we have previously shown that ALC impaired sensitization and dishabituation induced by nociceptive stimulation of the dorsal skin of the leech Hirudo medicinalis, in the behavioural paradigm of the swim induction (SI). In previous works we showed that 5HT was involved in both sensitization and dishabituation of SI acting through the second messenger cAMP. In this work, we have reported that for given doses and temporal ranges ALC was able to block sensitization and to impair dishabituation mimicked by the injection of 5-HT or 8Br-cAMP, a membrane permeable analogue of cAMP. Our results show that a single treatment with 2mM ALC was the most effective concentration to block the onset of sensitization induced by 5-HT injection and its major effects occurred 11 days after ALC treatment. 2mM ALC also blocked sensitization induced by 8Br-cAMP injection, whereas, ALC did not completely abolish dishabituation induced by 5-HT or 8Br-cAMP injection at the tested concentrations and at every time point.

Although habituation is ubiquitous in the animal kingdom, its underlying mechanisms remain poorly understood. In this study, we began to explore the molecular cascades underlying short-term habituation in the leech Hirudo medicinalis. In H. medicinalis, a training paradigm, consisting of low-frequency repetitive electrical stimulation of the skin, produces a gradual increase in the latency to swim that spontaneously recovers within 20-30 min. As first step in determining the molecular pathways in short-term habituation, we examined the role of Ca2+. Both Ca2+ influx through voltage-gated channels and Ca2+ release from intracellular stores were found to contribute to short-term habituation. The analysis of the downstream targets of elevated cytosolic Ca2+ revealed that the activation of the phosholipase A(2) was required for the induction of short-term habituation. Finally, we reported that the recruitment of arachidonic acid metabolites, generated by the 5-lipoxygenase pathway, was also necessary for the induction of swim induction habituation. These results provide the framework for a comprehensive characterization of the molecular underpinnings of habituation. This outcome will allow us to compare the mechanisms of habituation with those underlying other forms of nonassociative learning in the leech, such as sensitization and dishabituation, and, more in general, with those governing habituation in different vertebrate and invertebrate model systems. (C) 2012 Elsevier B.V. All rights reserved.

Various procedures involving stimulations of facial regions are known to induce so-called trigemino-cardiac reflexes that entail a decrease of heart rate and blood pressure. We here report the effects of a specific stimulation that consists in a submaximal passive mandibular extension obtained by means of a dilatator applied for 10 minutes between the upper and lower incisor teeth, associated with partial active masticatory movements. Blood pressure and heart rate were determined in 18 young normal volunteers by Omron M4, before (20 minutes), during (10 minutes) and after mandibular extension (80 minutes) and under control conditions (same overall duration without stimulation). While control values remained stable, mandibular extension was followed by a progressive decline of both blood pressure (up to about 12/11 mmHg) and heart rate (up to about 13 bpm), statistically confirmed by ANOVA both on absolute values and on changes from basal values. The decline of systolic blood pressure and heart rate significantly correlated with basal values. The present findings indicate that submaximal opening of the mouth, associated to partial masticatory movements, induces a prolonged reduction of blood pressure and heart rate in normotensive volunteers.

Neuronal ceroid lipofuscinoses (NCLs) are a group of lysosomal storage diseases characterized by neurological impairment and blindness. NCLs are almost always due to single mutations in different genes (CLN1–CLN8). Ubiquitous accumulation of undigested material and of a hydrophobic inner mitochondrial membrane protein, the subunit c of mitochondrial ATP synthase, has been described. Although protein mutation(s) in the endoplasmic reticulum–lysosomes axis can modify the trafficking and the recycling of different molecules, one of the upstream targets in these diseases may be represented by the balance of gene expression. To understand if and how neurons modify the levels of important genes during the first phases of the disease, it is important to characterize the mechanisms of neurodegeneration. Due to the impossibility of performing this analysis in humans, alternative models of investigation are required. In this study, a mouse model of human NCL8, the mnd mouse has been employed. The mnd mice recapitulate many clinical and histopathological features described in NCL8 patients. In this study, we found an altered expression of different genes in both central and peripheral organs associated with lipopigment accumulation. This is a preliminary approach, which could also be of interest in providing new diagnostic tools for NCLs.

Acetyl-L-carnitine (ALC), the acetyl ester of L-carnitine, is a naturally occurring molecule which plays an essential role in intermediary and mitochondrial metabolism. It has also neurotrophic and antioxidant actions, demonstrating efficacy and high tolerability in the treatment of neuropathies of various etiologies. ALC is a molecule of considerable interest for its clinical application in various neural disorders, although little is known regarding its effects on gene expression. Suppression subtractive hybridization methodology was used for the generation of subtracted complementary DNA libraries and the subsequent identification of differentially expressed transcripts in the rat brain after chronic ALC treatments. We provided evidence for a downregulation of the expression of all of the isoforms of myelin basic protein gene following prolonged ALC treatment, indicating a possible role in the modulation of myelin basic protein turnover, stabilizing and maintaining myelin integrity.

Acetyl-L-carnitine (ALC), the acetyl ester of L-carnitine, is a naturally occurring substance that when administered at supraphysiological concentrations is neuroprotective. ALC plays an essential role in intermediary and mitochondrial metabolism. It has also neurotrophic and antioxidant actions. ALC has demonstrated efficacy and high tolerability in the treatment of neuropathies of various etiologies, and it is a molecule of considerable interest for its clinical application in various neural disorders, such as Alzheimer's disease and painful neuropathies, although little is known regarding the effects of ALC on gene expression. Suppression subtractive hybridization methodology was used for the generation of subtracted complementary DNA libraries and the subsequent identification of differentially expressed transcripts in the rat brain after a chronic ALC treatment. In the present paper, we provide evidences for the up-regulation of the expression of prostaglandin D(2) synthase, brain-specific Na(+)-dependent inorganic phosphate transporter, and cytochrome b oxidase, bc1 complex induced in the rat brain by ALC. On the contrary, ALC treatment down-regulates the expression of the gene of ferritin-H. Altogether, these results suggest that ALC might play a cytoprotective role against various brain stressors.

We survey some recent work on the behavior of the calyx of Held synapse. The analysis considered are based on formal and quantitative models aimed at capturing emerging properties about signal transmission and plasticity phenomena. While surveying work about a specific and real-scale biological system, we distinguish between deterministic and stochastic approaches. We elaborate on the fact that in some cases, as in the calyx, the latter ones seem to be more adequate. The stochastic models, which we have developed, are based on a computational interpretation of biological systems. We illustrate the advantages of this approach in terms of expressiveness.

We present a stochastic model of the presynaptic terminal in the calyx of Held synapse. This model exploits process calculi as a representation language and has a direct computational implementation that supports quantitative simulation trials of the behaviour of the synapse. To our knowledge, it represents the first model of synaptic activity based on process calculi. The model builds upon available data, the fitting of some parameters and developed working hypotheses. Experiments about plasticity have been carried out regarding synaptic facilitation and potentiation. Also, synaptic depression has been considered in a model exhibiting dynamical equilibrium. Overall, the simulation results are coherent with the experimental findings appearing in the literature about the modeled reality. These results represent a quite detailed description of the presynaptic activity. This multidisciplinary work validates some aspects of the approach based on process calculi with respect to the new application domain, such as abstraction, expressiveness and compositionality.

Acetyl- l -carnitine (ALC) is a naturally occurring substance that, when administered at supraphysiological concentration, is neuroprotective. It is a molecule of considerable interest for its clinical application in various neural disorders, including Alzheimer’s disease and painful neuropathies. Suppression subtractive hybridization methodology was used for the generation of subtracted cDNA libraries and the subsequent identification of differentially expressed transcripts in the rat brain after ALC treatment. The method generates an equalized representation of differentially expressed genes irrespective of their relative abundance and it is based on the construction of forward and reverse cDNA libraries that allow the identification of the genes which are regulated by ALC. We report that ALC treatment: (1) upregulates lysosomal H + / ATPase gene expression and (2) downregulates myelin basic protein gene expression. The expression of these genes is altered in some forms of neuronal ceroid lipofuscinosis (NCL) pathologies. In this case, ALC might rebalance the disorders underlying NCL disease represented by a disturbance in pH homeostasis affecting the acidification of vesicles transported to lysosomal compartment for degradation. This study provides evidence that ALC controls genes involved in these serious neurological pathologies and provides insights into the ways in which ALC might exert its therapeutic benefits.

Conduction of action potentials throughout the complex morphology of neurons may be modulated in an activity-dependent manner. Among modulatory mechanisms, afterhyperpolarization (AHP) plays an important role. To investigate how the AHP modulatory capabilities on transmission were dependent on the axonal geometry as well as on membrane properties such as channel kinetics, channel density distribution and membrane noise, multi-compartment computational neural models were built, using the neurosimulator SNNAP. Two kinetic schema for the sodium and potassium channels were compared. The simulations suggest that channel kinetics profoundly influence the AHP-dependent modulation of action potential conduction through points of impedance mismatch in the highly branched neurites of neurons.

We investigated the effects of acetyl-l-carnitine on gene expression by means of the suppression subtractive hybridization method. The approach gives the generation of subtracted cDNA libraries and the subsequent identification of differentially expressed transcripts after treatment of rats with acetyl-l-carnitine for 21 days. We observed that acetyl-l-carnitine increases the light-chain subunit of kinesin-1 gene expression. Recent evidences reported a link between kinesin-1 light-chain and Alzheimer's disease. Pathological hallmarks of Alzheimer's disease are potentially linked to alterations of the axonal compartments. Amyloid-beta peptide is a principal component of senile plaques and is considered to be central in the pathogenesis of the disease. The fast anterograde axonal transport of amyloid-beta peptide is mediated by direct binding to the light-chain subunit of kinesin-1. In this scenario, our results are of relevant importance for possible therapeutic intervention, suggesting a pathway for the treatment of Alzheimer's disease.

BACKGROUND:Research in life sciences is benefiting from a large availability of formal description techniques and analysis methodologies. These allow both the phenomena investigated to be precisely modeled and virtual experiments to be performed in silico. Such experiments may result in easier, faster, and satisfying approximations of their in vitro/vivo counterparts. A promising approach is represented by the study of biological phenomena as a collection of interactive entities through process calculi equipped with stochastic semantics. These exploit formal grounds developed in the theory of concurrency in computer science, account for the not continuous, nor discrete, nature of many phenomena, enjoy nice compositional properties and allow for simulations that have been demonstrated to be coherent with data in literature.RESULTS:Motivated by the need to address some aspects of the functioning of neural synapses, we have developed one such model for synaptic processes in the calyx of Held, which is a glutamatergic synapse in the auditory pathway of the mammalia. We have developed such a stochastic model starting from existing kinetic models based on ODEs of some sub-components of the synapse, integrating other data from literature and making some assumptions about non-fully understood processes. Experiments have confirmed the coherence of our model with known biological data, also validating the assumptions made. Our model overcomes some limitations of the kinetic ones and, to our knowledge, represents the first model of synaptic processes based on process calculi. The compositionality of the approach has permitted us to independently focus on tuning the models of the pre- and post- synaptic traits, and then to naturally connect them, by dealing with "interface" issues. Furthermore, we have improved the expressiveness of the model, e.g. by embedding easy control of element concentration time courses. Sensitivity analysis over several parameters of the model has provided results that may help clarify the dynamics of synaptic transmission, while experiments with the model of the complete synapse seem worth explaining short-term plasticity mechanisms.CONCLUSIONS:Specific presynaptic and postsynaptic mechanisms can be further analysed under various conditions, for instance by studying the presynaptic behaviour under repeated activations. The level of details of the description can be refined, for instance by further specifying the neurotransmitter generation and release steps. Taking advantage of the compositionality of the approach, an enhanced model could then be composed with other neural models, designed within the same framework, in order to obtain a more detailed and comprehensive model. In the long term, we are interested, in particular, in addressing models of synaptic plasticity, i.e. activity dependent mechanisms, which are the bases of memory and learning processes. More on the computer science side, we plan to follow some directions to improve the underlying computational model and the linguistic primitives it provides as suggested by the experiments carried out, e.g. by introducing a suitable notion of (spatial) locality.

Increasing evidence indicates that modulation of Na+/K+ ATPase activity is involved in forms of neuronal and synaptic plasticity. In tactile (T) neurons of the leech Hirudo medicinalis, Na+/K+ ATPase is the main determinant of the afterhyperpolarization (AHP), which characterizes the firing of these mechanosensory neurons. Previously, it has been reported that cAMP (3',5'-cyclic adenosine monophosphate), which mediates the effects of serotonin (5HT) in some forms of learning in the leech, negatively modulates Na+/K+ ATPase activity, thereby reducing the AHP amplitude in T neurons. Here, we show that a transient inhibition of Na+/K+ ATPase can affect the synaptic connection between two ipsilateral T neurons. Bath application of 10 nM dihydroouabain (DHO), an ouabain analogue, causes an increase in the amplitude of the synaptic potential (SP) recorded in the postsynaptic element when a test stimulus is applied in the presynaptic neuron. Iontophoretic injection of cAMP into the presynaptic T neuron also produces an increase of SP. Simulations carried out by using a computational model of the T neuron suggest that a reduction of the pump rate and a consequent depression of the AHP might facilitate the conduction of action potentials to the synaptic terminals. Moreover, nearly intact leeches injected with 10 nM DHO respond with a swimming episode more quickly to an electrical stimulation, which selectively activates T neurons exhibiting sensitization of swimming induction. Collectively, our results show that inhibition of Na+/K+ ATPase is critical for short-term plasticity.