Continuation of a physical model of brass instrument: application to trumpet categorization

International audienceThe system formed by the couple {player-trumpet} falls into the class of non-linear dynamical systems likely to be studied using different numerical tools such as numerical continuation methods. In this study we illustrate the interest of this approach for the categorization of Bb trumpets in the space of some performance descriptors obtained from continuation by the ANM method combined to the Harmonic Balance Method (HBM)

Double-Peak Response in Orthodromic Sensory Nerve Conduction of the Median Nerve

Objective To understand the neural generator of double-peak potentials and the change of latency and amplitude of double peaks with aging. Method In 50 healthy subjects made up of groups of 10 people per decade from the age of 20 to 60, orthodromic sensory nerve conduction studies were performed on the median nerves using submaximal stimulation. Various stimulus durations and interstimulation distances were used to obtain each double peak in the different age groups. The latency and amplitude of the second peak were measured. Statistical analyses included one-way ANOVA and correlation tests. p-values<0.05 were considered significant. Results When the cathode moved in a proximal direction, the interpeak intervals increased. Second peak amplitudes decreased, and second peak latencies were delayed with aging (p<0.05). In some older people, second peaks were not obtained. Conclusion Our experiments indicate that the double-peak response represented the two stimulation sites under the cathode and anode. The delayed latency and decreased amplitude of the second peak that occurs with aging represented peripheral nerve degeneration in aging, which starts at the distal nerve

Cholinergic Enhancement of Cell Proliferation in the Postnatal Neurogenic Niche of the Mammalian Spinal Cord

The region surrounding the central canal (CC) of the spinal cord is a highly plastic area, defined as a postnatal neurogenic niche. Within this region are ependymal cells which can proliferate and differentiate to form new astrocytes and oligodendrocytes following injury and cerebrospinal fluid contacting cells (CSFcCs). The specific environmental conditions, including the modulation by neurotransmitters that influence these cells and their ability to proliferate, are unknown. Here we show that acetylcholine promotes the proliferation of ependymal cells in mice under both in vitro and in vivo conditions. Using whole cell patch clamp in acute spinal cord slices, acetylcholine directly depolarised ependymal cells and CSFcCs. Antagonism by specific nicotinic acetylcholine receptor (nAChR) antagonists or potentiation by the α7*nAChR modulator PNU 120596 revealed that both α7*nAChRs and non-α7*nAChRs mediated the cholinergic responses. Using the nucleoside analogue EdU (5-ethynyl-2'-deoxyuridine) as a marker of cell proliferation, application of α7*nAChR modulators in spinal cord cultures or in vivo induced proliferation in the CC region, producing Sox-2 expressing ependymal cells. Proliferation also increased in the white and grey matter. PNU 120596 administration also increased the proportion of cells co-expressing oligodendrocyte markers. Thus, variation in the availability of acetylcholine can modulate the rate of proliferation of cells in the ependymal cell layer and white 1 and grey matter through α7*nAChRs. This study highlights the need for further investigation into how neurotransmitters regulate the response of the spinal cord to injury or during aging

Metabolite Profiling of Alzheimer's Disease Cerebrospinal Fluid

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive loss of cognitive functions. Today the diagnosis of AD relies on clinical evaluations and is only late in the disease. Biomarkers for early detection of the underlying neuropathological changes are still lacking and the biochemical pathways leading to the disease are still not completely understood. The aim of this study was to identify the metabolic changes resulting from the disease phenotype by a thorough and systematic metabolite profiling approach. For this purpose CSF samples from 79 AD patients and 51 healthy controls were analyzed by gas and liquid chromatography-tandem mass spectrometry (GC-MS and LC-MS/MS) in conjunction with univariate and multivariate statistical analyses. In total 343 different analytes have been identified. Significant changes in the metabolite profile of AD patients compared to healthy controls have been identified. Increased cortisol levels seemed to be related to the progression of AD and have been detected in more severe forms of AD. Increased cysteine associated with decreased uridine was the best paired combination to identify light AD (MMSE>22) with specificity and sensitivity above 75%. In this group of patients, sensitivity and specificity above 80% were obtained for several combinations of three to five metabolites, including cortisol and various amino acids, in addition to cysteine and uridine

Intersection between metabolic dysfunction, high fat diet consumption, and brain aging

Deleterious neurochemical, structural, and behavioral alterations are a seemingly unavoidable aspect of brain aging. However, the basis for these alterations, as well as the basis for the tremendous variability in regards to the degree to which these aspects are altered in aging individuals, remains to be elucidated. An increasing number of individuals regularly consume a diet high in fat, with high‐fat diet consumption known to be sufficient to promote metabolic dysfunction, although the links between high‐fat diet consumption and aging are only now beginning to be elucidated. In this review we discuss the potential role for age‐related metabolic disturbances serving as an important basis for deleterious perturbations in the aging brain. These data not only have important implications for understanding the basis of brain aging, but also may be important to the development of therapeutic interventions which promote successful brain aging.Fil: Uranga, Romina Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Bruce Keller, Annadora J.. State University of Louisiana; Estados UnidosFil: Morrison, Christopher D.. State University of Louisiana; Estados UnidosFil: Fernandez Kim, Sun Ok. State University of Louisiana; Estados UnidosFil: Ebenezer, Philip J.. State University of Louisiana; Estados UnidosFil: Zhang, Le. State University of Louisiana; Estados UnidosFil: Dasuri, Kalavathi. State University of Louisiana; Estados UnidosFil: Keller, Jeffrey N.. State University of Louisiana; Estados Unido

Effects of L-NAME, a non-specific nitric oxide synthase inhibitor, on AlCl3-induced toxicity in the rat forebrain cortex

The present experiments were done to determine the effectiveness of a non-specific nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME), on oxidative stress parameters induced by aluminium chloride (AlCl3) intrahippocampal injections in Wistar rats. Animals were sacrificed 3 h and 30 d after treatments, heads were immediately frozen in liquid nitrogen and forebrain cortices were removed. Crude mitochondrial fraction preparations of forebrain cortices were used for the biochemical analyses: nitrite levels, superoxide production, malondialdehyde concentrations, superoxide dismutase (SOD) activities and reduced glutathione contents. AlCl3 injection resulted in increased nitrite concentrations, superoxide anion production, malondialdehyde concentrations and reduced glutathione contents in the forebrain cortex, suggesting that AlCl3 exposure promoted oxidative stress in this brain structure. The biochemical changes observed in neuronal tissues showed that aluminium acted as a pro-oxidant. However, the non-specific nitric oxide synthase (NOS) inhibitor, L-NAME, exerted anti-oxidant actions in AlCl3-treated animals. These results revealed that NO-mediated neurotoxicity due to intrahippocampal AlCl3 injection spread temporally and spatially to the forebrain cortex, and suggested a potentially neuroprotective effect for L-NAME

Epigenetic Differences in Cortical Neurons from a Pair of Monozygotic Twins Discordant for Alzheimer's Disease

DNA methylation [1], [2] is capable of modulating coordinate expression of large numbers of genes across many different pathways, and may therefore warrant investigation for their potential role between genes and disease phenotype. In a rare set of monozygotic twins discordant for Alzheimer's disease (AD), significantly reduced levels of DNA methylation were observed in temporal neocortex neuronal nuclei of the AD twin. These findings are consistent with the hypothesis that epigenetic mechanisms may mediate at the molecular level the effects of life events on AD risk, and provide, for the first time, a potential explanation for AD discordance despite genetic similarities

Assessment of platelet function in patients with stroke using multiple electrode platelet aggregometry: a prospective observational study

Background There is a link between high on-treatment platelet reactivity (HPR) and adverse vascular events in stroke. This study aimed to compare multiple electrode platelet aggregometry (MEA), in healthy subjects and ischaemic stroke patients, and between patients naive to antiplatelet drugs (AP) and those on regular low dose AP. We also aimed to determine prevalence of HPR at baseline and at 3–5 days after loading doses of aspirin. Methods Patients with first ever ischaemic stroke were age and sex-matched to a healthy control group. Three venous blood samples were collected: on admission before any treatment given (baseline); at 24 h and 3–5 days after standard treatment. MEA was determined using a Mutliplate® analyser and agonists tested were arachidonic acid (ASPI), adenosine diphosphate (ADP) and collagen (COL). Results Seventy patients (mean age 73 years [SD 13]; 42 men, 28 women) were age and sex-matched to 72 healthy subjects. Thirty-three patients were on antiplatelet drugs (AP) prior to stroke onset and 37 were AP-naive. MEA results for all agonists were significantly increased in AP-naive patients compared to healthy subjects: ADP 98 ± 31 vs 81 ± 24, p < 0.005; ASPI 117 ± 31 vs 98 ± 27, p < 0.005; COL 100 ± 25 vs 82 ± 20, p < 0.005. For patients on long term AP, 33% (10/30) of patients were considered aspirin-resistant. At 3–5 days following loading doses of aspirin, only 11.1% were aspirin resistant based on an ASPI cut-off value of 40 AU*min. Conclusions Many patients receiving low dose aspirin met the criteria of aspirin resistance but this was much lower at 3–5 days following loading doses of aspirin. Future studies are needed to establish the causes of HPR and potential benefits of individualizing AP treatment based on platelet function testing