On the Impact of Muscle Shortening on Non-Negative Matrix Factorization of Dynamic Surface Electromyograms.

We analyzed the sensitivity of Non-negative Matrix Factorization (NMF) of dynamic surface electromyograms (EMG) to muscle shortening. We first identified Motor unit action potentials (MUAPs) by decomposing experimentally recorded EMG signals during slow shortening of biceps brachii muscle in five young healthy males. We then used these MUAPs to generate different synthetic EMG signals with different muscle shortening and excitation profiles. Afterwards, we applied NMF to the synthetic EMG signals and calculated Pearson correlation coefficient (CC) between the extracted NMF components and a) muscle shortening and b) muscle excitation profiles. The results demonstrated good match between NMF components and muscle excitation profiles, but only when the muscle excitation level changed for at least 10 % during the muscle shortening. During constant muscle excitation, the resulting NMF components correlated significantly with the muscle shortening profiles. These results demonstrate that NMF components reflect not only the muscle excitation profiles but also muscle shortening profiles. Therefore, the results of NMF analysis of dynamic EMG signals need to be interpreted with caution.

On the impact of spike segmentation on motor unit identification in dynamic surface electromyograms.

We discuss the adaptation of preexisting Convolution Kernel Compensation (CKC) surface electromyogram (EMG) decomposition technique to dynamic muscle contractions. In particular, three different algorithms for segmentation of motor unit (MU) spike trains into MU firings are discussed and mutually compared on synthetic dynamic surface EMG. The first segmentation algorithm employs a priori knowledge of the regularity of MU firings. The second one builds on K-means classification of MU spikes, whereas the third one combines both the regularity of MU firings and the previously introduced Pulse-to-Noise Ratio (PNR). On average, 5.5 ± 0.6 MUs were identified with sensitivity of 88.4 % ± 17.0 %, 83.8 % ± 16.7 % and 90.7 % ± 15.1 % for the first, the second and the third segmentation algorithm, respectively, demonstrating the feasibility of MU identification in moderate dynamic muscle contractions. In our tests, the third segmentation approach demonstrated superior accuracy in MU identification.

Simulations of high-density surface electromyograms in dynamic muscle contractions.

We describe the extension of pre-existing cylindrical volume conductor model to synthetic high-density surface electromyograms (hdEMG), simulated during dynamic contractions of fusiform skeletal muscles. Its modular structure comprises two main parts. First, dynamic changes of motor unit action potentials (MUAPs) during 36 discrete steps of muscle shortening are simulated. Second, the increase in depth of simulated motor units (MUs) due to shortening and thickening of muscle fibers is simulated. MU firing patterns are generated with the model proposed by Fuglevand et al. and convolved with simulated MUAPs. In this way, the hdEMG simulator can be used to generate dynamic hdEMG of arbitrary muscle shortening, thickening and excitation profiles. In order to demonstrate the value of the aforementioned simulator we independently analyze the impact of muscle shortening and muscle thickening on MU identification by Convolution Kernel Compensation (CKC) technique.

[Genetic toxicology: findings and challenges].

The review highlights the history of genetic toxicology as a distinct research area, as well as the issues of genetic toxicology and development of its methodology. The strategies and testing patterns of genotoxic compounds are discussed with the purpose of identifying potential human carcinogens, as well as compounds capable of inducing heritable mutations in humans. The main achievements of genetic toxicology in the 20th century are summarized and the challenges of the 21st century are discussed.

Exercise attenuates levodopa-induced dyskinesia in 6-hydroxydopamine-lesioned mice.

L-DOPA alleviates the motor symptoms of Parkinson's disease, but its long-term use is associated with undesirable dyskinesia. We now tested whether exercise can attenuate this L-DOPA-induced dyskinesia (LID). We tested the effects of exercise on LID in 6-hydroxydopamine hydrochloride-hemiparkinsonian mice. Animals were treated with L-DOPA/benserazide (25/12.5 mg/kg, i.p.) without and with possibility to exercise (running wheel) during 2 weeks. Exercise drastically prevented the development of LID, and its associated aberrant striatal signaling, namely the hyperphosphorylation of dopamine and cAMP-regulated phosphoprotein 32 kDa protein and c-Fos expression. Our results indicate that exercise can partially prevent the development of LID through the normalization of striatopallidal dopaminergic signaling.

Non-invasive characterization of motor unit behaviour in pathological tremor.

This paper presents the fully automatic identification of motor unit spike trains from high-density surface electromyograms (EMG) in pathological tremor. First, a mathematical derivation is provided to theoretically prove the possibility of decomposing noise-free high-density surface EMG signals into motor unit spike trains with high correlation, which are typical of tremor contractions. Further, the proposed decomposition method is tested on simulated signals with different levels of noise and on experimental signals from 14 tremor-affected patients. In the case of simulated tremor with central frequency ranging from 5 Hz to 11 Hz and signal-to-noise ratio of 20 dB, the method identified ∼8 motor units per contraction with sensitivity in spike timing identification ≥ 95% and false alarm and miss rates ≤ 5%. In experimental signals, the number of identified motor units varied substantially (range 0-21) across patients and contraction types, as expected. The behaviour of the identified motor units was consistent with previous data obtained by intramuscular EMG decomposition. These results demonstrate for the first time the possibility of a fully non-invasive investigation of motor unit behaviour in tremor-affected patients. The method provides a new means for physiological investigations of pathological tremor.

Positive correlation between elevated plasma cholesterol levels and cognitive impairments in LDL receptor knockout mice: relevance of cortico-cerebral mitochondrial dysfunction and oxidative stress.

Convergent epidemiological, clinical, and experimental findings indicate that hypercholesterolemia contributes to the onset of Alzheimer's disease (AD)-like dementia, but the exact underlying mechanisms remains unknown. In this study, we evaluated the cognitive performance of mice submitted to a model of hypercholesterolemia, as well as its relationship with mitochondrial dysfunction and oxidative stress, two key events involved in AD pathogenesis. Wild-type C57bl/6 or low density lipoprotein receptor (LDLr)-deficient mice were fed with either standard or cholesterol-enriched diet for a 4-week period and tested for spatial learning and memory in the object location task. LDLr⁻/⁻ mice displayed spatial learning and memory impairments regardless of diet. Moreover, LDLr⁻/⁻ mice fed cholesterol-enriched diet presented a significant decrease in the mitochondrial complexes I and II activities in the cerebral cortex, which were negatively correlated with respective blood cholesterol levels. Additionally, hypercholesterolemic LDLr⁻/⁻ mice presented a significant decrease in glutathione levels, about 40% increase in the thiobarbituric acid-reactive substances levels, as well as an imbalance between the peroxide-removing-related enzymes glutathione peroxidase/glutathione reductase activities in the cerebral cortex. These findings indicate a significant relationship between hypercholesterolemia, cognitive impairment, and cortico-cerebral mitochondrial dysfunctional/oxidative stress. Because of the involvement of such alterations in AD patients, our data render this mouse model of hypercholesterolemia a useful approach to comprehend the molecular events mediating AD pathogenesis.

Molecular aspects involved in swimming exercise training reducing anhedonia in a rat model of depression.

Patients suffering from depression frequently display hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA) resulting in elevated cortisol levels. One main symptom of this condition is anhedonia. There is evidence that exercise training can be used as a rehabilitative intervention in the treatment of depressive disorders. In this scenario, the aim of the present study was to assess the effect of an aerobic exercise training protocol on the depressive-like behavior, anhedonia, induced by repeated dexamethasone administration. The study was carried out on adult male Wistar rats randomly divided into four groups: the "control group" (C), "exercise group" (E), "dexamethasone group" (D) and the "dexamethasone plus exercise group" (DE). The exercise training consisted of swimming (1 h/d, 5 d/wk) for 3 weeks, with an overload of 5% of the rat body weight. Every day rats were injected with either dexamethasone (D/DE) or saline solution (C/E). Proper positive controls, using fluoxetine, were run in parallel. Decreased blood corticosterone levels, reduced adrenal cholesterol synthesis and adrenal weight (HPA disruption), reduced preference for sucrose consumption and increased immobility time (depressive-like behavior), marked hippocampal DNA oxidation, increased IL-10 and total brain-derived neurotrophic factor (BDNF; pro-plus mature-forms) and a severe loss of body mass characterized the dexamethasone-treated animals. Besides increasing testosterone blood concentrations, the swim training protected depressive rats from the anhedonic state, following the same profile as fluoxetine, and also from the dexamethasone-induced impaired neurochemistry. The data indicate that physical exercise could be a useful tool in preventing and treating depressive disorders.

Noninvasive analysis of motor unit behavior in pathological tremor.

A robust surface EMG decomposition tool, referred to as tremor-optimized Convolution Kernel Compensation (CKC) technique, is described. This technique modifies and extends the previously published CKC method in order to circumvent the typical assumption on regularity and asynchrony of motor unit firings in normal condition and adapt to the discharge patterns in pathological tremor. The results on synthetic and experimental surface EMG signals demonstrate high performance of decomposition. In the case of simulated surface EMG with 20 dB SNR, excitation level of 20% maximum voluntary contraction (MVC) and simulated tremor frequency of 8 Hz, the newly proposed method identified 8 ± 2 motor units with sensitivity of motor unit discharge identification ≥ 95 % and false alarm and miss rates ≤ 5%. The performance worsened with increasing noise power, with 5 ± 2 motor units identified at 10 dB SNR and 3 ± 1 at 0 dB SNR. In 24 recordings of high-density surface EMG signals from four tremor-affected patients, the modified CKC technique identified 134 motor units (6 ± 4 motor units per contraction).

Ocorrência de Hepatozoon spp. (Apicomplexa, Hepatozoidae) em serpentes do gênero Bothrops de cativeiro / Occurrence of Hepatozoon spp. (Apicomplexa, Hepatozoidae) in snakes of genus Bothrops in captivity

The occurrence of Hepatozoon gamont in the blood cells of Bothrops jararaca and B. jararacussu in captivity was analyzed. The prevalence of infection by Hepatozoon spp. was 50 percent and few erythrocytes contained the gamonts. Results suggest that the infection by Hepatozoon spp. occurred in the natural environment or after the captivity.

Regulation of nitrogenase in the photosynthetic bacterium Rhodobacter sphaeroides containing draTG and nifHDK genes from Rhodobacter capsulatus.

The photosynthetic bacteria Rhodobacter capsulatus and Rhodospirillum rubrum regulate their nitrogenase activity by the reversible ADP-ribosylation of nitrogenase Fe-protein in response to ammonium addition or darkness. This regulation is mediated by two enzymes, dinitrogenase reductase ADP-ribosyl transferase (DRAT) and dinitrogenase reductase activating glycohydrolase (DRAG). Recently, we demonstrated that another photosynthetic bacterium, Rhodobacter sphaeroides, appears to have no draTG genes, and no evidence of Fe-protein ADP-ribosylation was found in this bacterium under a variety of growth and incubation conditions. Here we show that four different strains of Rba. sphaeroides are incapable of modifying Fe-protein, whereas four out of five Rba. capsulatus strains possess this ability. Introduction of Rba. capsulatus draTG and nifHDK (structural genes for nitrogenase proteins) into Rba. sphaeroides had no effect on in vivo nitrogenase activity and on nitrogenase switch-off by ammonium. However, transfer of draTG from Rba. capsulatus was sufficient to confer on Rba. sphaeroides the ability to reversibly modify the nitrogenase Fe-protein in response to either ammonium addition or darkness. These data suggest that Rba. sphaeroides, which lacks DRAT and DRAG, possesses all the elements necessary for the transduction of signals generated by ammonium or darkness to these proteins.

The influence of mutation rad57-1 on the fidelity of DNA double-strand gap repair in Saccharomyces cerevisiae.

The role of the RAD57 gene in double-strand gap (DSG) repair has been examined. The repair of a linearized plasmid, bearing a DSG, has been analyzed in a rad57-1 mutant of Saccharomyces cerevisiae. For effective rejoining of the ends of plasmid DNA in the rad57 mutant the sequence of chromosomal DNA homologous to the DSG region is required. However, DSG repair (restoration of plasmid circularity) in rad57 cells is not accompanied by the recovery of DSGs. The DSG repair, which depends on an homologous chromosomal DNA sequence, requires the cohesive ends of DSGs. The non-cohesive-ended DSGs are repaired in rad57 cells by a pathway independent of the homologous recombination between chromosomal and plasmid DNA. We presume that the rad57-1 mutation is connected with the inhibition of DNA repair synthesis, required for filling the DSG. This situation produces a condition of "homology-dependent ligation", the alternative minor mechanism of recombinational DSG repair, that takes place in mutant cells. A molecular model for "homology-dependent ligation" in rad57 cells is proposed.