Metabolic Reprogramming in Amyotrophic Lateral Sclerosis.

Mitochondrial dysfunction in the spinal cord is a hallmark of amyotrophic lateral sclerosis (ALS), but the neurometabolic alterations during early stages of the disease remain unknown. Here, we investigated the bioenergetic and proteomic changes in ALS mouse motor neurons and patients' skin fibroblasts. We first observed that SODG93A mice presymptomatic motor neurons display alterations in the coupling efficiency of oxidative phosphorylation, along with fragmentation of the mitochondrial network. The proteome of presymptomatic ALS mice motor neurons also revealed a peculiar metabolic signature with upregulation of most energy-transducing enzymes, including the fatty acid oxidation (FAO) and the ketogenic components HADHA and ACAT2, respectively. Accordingly, FAO inhibition altered cell viability specifically in ALS mice motor neurons, while uncoupling protein 2 (UCP2) inhibition recovered cellular ATP levels and mitochondrial network morphology. These findings suggest a novel hypothesis of ALS bioenergetics linking FAO and UCP2. Lastly, we provide a unique set of data comparing the molecular alterations found in human ALS patients' skin fibroblasts and SODG93A mouse motor neurons, revealing conserved changes in protein translation, folding and assembly, tRNA aminoacylation and cell adhesion processes.

The impact of carbon coating on the synthesis and properties of α''-Fe16N2 powders.

This paper presents the preparation of carbon composite Fe16N2 powders, and the influence of a protective carbon coating on the yield and magnetic properties of Fe16N2. Nanoparticle precursors with and without carbon were reacted under ammonia gas flow to produce Fe16N2. Neutron and X-ray powder diffraction indicate that the powders contain typically 40-60% Fe16N2, with the remaining phases being unreacted iron, Fe4N or Fe3N. Transmission electron microscopy demonstrates that the carbon coating is effective at reducing the level of sintering of Fe nanoparticles during the reduction stage prior to ammonolysis. XPS results support the retention of a carbon coating on the surface after ammonolysis, and that there is Fe-C bonding present at the particle surface. In situ TEM was used to observe loss of ordering in the nitrogen sublattice of carbon composite Fe16N2 powders in the range of 168 °C to 200 °C. Magnetic susceptibility measurements show maximum values for saturation magnetization in the range of 232 emu g(-1), and for coercivity near 930 Oe, for different samples measured up to 2 T applied field at 300 K.

The motor function measure to study limitation of activity in children and adults with Charcot-Marie-Tooth disease.

OBJECTIVE: To study the applicability and responsiveness of the motor function measure (total score and sub-scores D1, D2 and D3) in patients with Charcot-Marie-Tooth disease. PATIENTS AND METHODS: Two hundred and thirty-three patients aged 4-86 years were included in the descriptive study. Scores and sub-scores were analyzed by age and by disease subtypes. Sensitivity to change (responsiveness) was estimated in patients having had at least two evaluations with at least six months between the first and the second. RESULTS: Motor function measure scores decrease with age, especially sub-scores D1 and D3. There were no significant differences between the scores according to type of Charcot-Marie-Tooth disease. The scores were significantly higher for ambulatory than for non-ambulatory patients. Significant responsiveness was demonstrated only in type 2 Charcot-Marie-Tooth disease. DISCUSSION/CONCLUSIONS: Our results suggest that, especially for D1 and D3 sub-scores, the motor function measure is a reliable and valid outcome measure that can be usefully applied in longitudinal follow-up. Studies of longer duration could demonstrate its responsiveness in other Charcot-Marie-Tooth disease subtypes.

[Antineutrophil cytoplasmic autoantibodies in children: clinical features]. / Auto-anticorps anticytoplasme des polynucléaires neutrophiles en pédiatrie : caractéristiques cliniques.

BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCA) are usually considered as serological markers of vasculitis (microscopic polyangiitis, granulomatosis with polyangiitis, and Churg-Strauss syndrome), but they have also been described in other diseases. They are rarely observed in children. Therefore, this study aims to describe the clinical spectrum associated with positive ANCA in children. PATIENTS AND METHODS: All the children below 15 years of age, admitted to the Angers University Hospital between June 2004 and June 2010 presenting with an ANCA-positive test by indirect immunofluorescence were included in this study. The exhaustive list of ANCA-positive children was obtained from the immunology unit. Six antigenic targets were routinely tested by Elisa, i.e., proteinase 3, myeloperoxidase, bactericidal permeability increasing protein, cathepsin G, elastase, and lactoferrin. Clinical and biological data were retrospectively collected. RESULTS: Thirty-seven children were identified with positive ANCA in this 6-year period. None of the antigenic targets tested was found in 21 patients. The most frequent diseases associated were inflammatory bowel disease (n=10), infections (n=6), hematological disease (n=5), and juvenile idiopathic arthritis (JIA) (n=4). Patients with JIA presented with a predominance of antielastase antibodies. CONCLUSION: In contrast to the findings usually observed in adults, we obtained a wide spectrum of clinical entities associated with positive ANCA in this cohort. In children, the ANCA test has 2 advantages: to diagnose systemic vasculitis and to differentiate inflammatory bowel disease. Patients with JIA seemed to have more frequent antielastase antibodies: in the future, this finding should be further investigated in larger prospective studies.

[Urinary tract infection caused by Haemophilus influenzae in 3 children with uropathies]. / Infection urinaire àHaemophilus influenzae chez 3 enfants ayant une malformation de l'arbre urinaire.

Urinary tract infection (UTI) is one of the most common infections in children but Haemophilus is rarely involved. In our institution, only 3 children below the age of 15 years presented with UTI due to Haemophilus influenzae between January 2010 and October 2011. These children had typical symptoms of UTI: fever, abdominal pain and dysuria. In all 3 patients, standard urinalysis remained negative, but H. influenzae was found after bacterial growth in special media, i.e., blood agar (or chocolate agar). These patients had abnormalities of the urinary tract. The first patient, a 5-year-old girl, had a right ureteropelvic junction syndrome found after her UTI. The second, a 4-year-old girl, had a bilateral ureteral duplication found after many UTIs. The third, a 2-month-old boy, had a right ureteropelvic junction syndrome that had been diagnosed by prenatal ultrasound. In our hospital, during the study period, the prevalence of UTI caused by Haemophilus was 0.02% of all pediatric UTIs. There are few reports in the literature on UTI caused by Haemophilus in children (<1%): they are frequently associated with urinary tract abnormalities. The bacterium is not able to grow in usual media, so that when there is a clinical UTI with Gram negative bacilli on the direct exam but not found in the culture, an infection with Haemophilus should be discussed, and blood agar used, which is all the more important when there are underlying abnormalities of the urinary tract.

Coalescence and sintering of Pt nanoparticles: in situ observation by aberration-corrected HAADF STEM.

An aberration-corrected JEOL 2200FS scanning-transmission electron microscope (STEM), equipped with a high-angle annular dark-field detector (HAADF), is used to monitor the coalescence and sintering of Pt nanoparticles with an average diameter of 2.8 nm. This in situ STEM capability is combined with an analysis methodology that together allows direct measurements of mass transport phenomena that are important in understanding how particle size influences coalescence and sintering at the nanoscale. To demonstrate the feasibility of this methodology, the surface diffusivity is determined from measurements obtained from STEM images acquired during the initial stages of sintering. The measured surface diffusivities are in reasonable agreement with measurements made on the surface of nanoparticles, using other techniques. In addition, the grain boundary mobility is determined from measurements made during the latter stages of sintering.

Suppression of proximity effect and the enhancement of p-wave superconductivity in the Sr2RuO4-Ru system.

We report unexpected phenomena observed on the Sr2RuO4-Ru eutectic phase featuring Ru islands embedded in a bulk crystal of the chiral p-wave superconductor Sr2RuO4. It was found that the Sr2RuO4/Ru interface is atomically sharp, terminated uniformly by a Sr/O layer. Surprisingly, the proximity-induced p-wave superconducting energy gap predicted by theory was not detected inside Ru islands. Our results suggest that the previously observed enhancement of superconductivity in this eutectic phase occurs away from rather than near the Sr2RuO4/Ru interface, where dislocations and phonon hardening were found.

Formation of ultrasharp vertically aligned Cu-Si nanocones by a DC plasma process.

We report an effective method for the production of ultrasharp vertically oriented silicon nanocones with tip radii as small as 5 nm. These silicon nanostructures were shaped by a high-temperature acetylene and ammonia dc plasma reactive ion etch (RIE) process. Thin-film copper deposited onto Si substrates forms a copper silicide (Cu3Si) during plasma processing, which subsequently acts as a seed material masking the single-crystal cones while the exposed silicon areas are reactive ion etched. In this process, the cone angle is sharpened continually as the structure becomes taller. Furthermore, by lithographically defining the seed material as well as employing an etch barrier material such as titanium, the cone location and substrate topography can be controlled effectively.

Prenatal diagnosis of a 45,X male with a SRY-bearing chromosome 21.

Male phenotype associated with a 45,X karyotype is an infrequent finding. We present a case diagnosed prenatally on amniocentesis performed for maternal age. The male phenotype was associated with a translocation of a distal part of Yp including the pseudoautosomal SHOX gene and SRY gene on the short arm of a chromosome 21. By DNA analysis we could show that the X chromosome was of maternal origin and that the breakpoint was in interval 3 of the Y chromosome. Mechanisms and genetic counselling are discussed based on a review of published cases of 45,X and XX males.

Mechanisms leading to an oriented immobilization of recombinant proteins derived from the P24 capsid of HIV-1 onto copolymers.

To investigate the mechanism leading to an oriented immobilization of recombinant proteins onto synthetic copolymers, five genetically modified HIV-1 p24 capsid proteins (RH24, RH24A4K2, RH24R6, RH24R4K2, and RH24K6) were tested for their efficiency to covalently bind to maleic anhydride-alt-methyl vinyl ether (MAMVE) and N-vinyl pyrrolidone-alt-maleic anhydride (NVPMA) copolymers. These proteins contain, at their C-termini, tags differing in cationic and/or reactive amino acids density. We demonstrated that an increase of the charge and amine density in the tag enhances the coupling yield, the most efficient tag being a six lysine one. The reactivity of the proteins depends directly on the reactivity of the tag, and this led us to conclude that the tag was the site where the covalent grafting with the polymer occurred. Thus, design of such tags provides a new efficient and versatile method allowing oriented immobilization of recombinant proteins onto copolymers.

Power Doppler ultrasound scan imaging of the level of red blood cell aggregation: an in vitro study.

PURPOSE: The purpose of this study was to evaluate the effect of the shear rate on red blood cell (RBC) aggregation with power Doppler ultrasound scanning (PDU), pulsed-wave Doppler scanning, and color Doppler flow imaging. METHODS: Equine and porcine blood were circulated with a steady flow in a phantom with a diameter of 9.52 mm. The color Doppler flow imaging mode was used to estimate the velocity profile and the shear rate across the tube. A transfer function that related the Doppler scan power, measured in gray level with the PDU method, to the power, measured in decibels with the pulsed-wave Doppler scan technique, was used to estimate the echogenicity of blood and the level of aggregation. RESULTS: For the four experiments reported, the power peaked at low shear rates probably because of increased RBC collisions and aggregation and then decreased thereafter because of disaggregation. The largest power variations were measured at shear rates of less than 40 seconds -1. At flow rates that varied between 75 and 500 mL/min, the echogenicity was low near the wall of the tube, increased toward the middle, and decreased at the tube center. The Doppler scan power was uniform across the tube at flow rates of 750 and 1000 mL/min. CONCLUSION: PDU is reliable to quantify the echogenicity of blood and the level of RBC aggregation. In comparison with other methods proposed to measure RBC aggregation, ultrasound scanning is applicable in vivo and may help to improve our basic understanding of the relationship between the hemodynamic of the circulation and RBC aggregation in human vessels.

Review of the assessment of single level and multilevel arterial occlusive disease in lower limbs by duplex ultrasound.

The purpose of this article is to review the performance of duplex ultrasound scanning in assessing lower limb arterial disease with emphasis on patients with multisegmental occlusive lesions. Several studies have reported that duplex scanning can be as accurate as angiography to localize arterial stenoses. In spite of these promising results, there still remain some difficulties and controversies. Among them, it has been reported that multisegmental disease may affect the accuracy of duplex scanning. Indeed, some studies have indicated a lower sensitivity for detecting significant stenoses distal to severe or total occlusions. It also was demonstrated that second-order stenoses were detected with lower sensitivity compared to first-order stenoses. The main reason proposed to explain this lower sensitivity is that the highly reduced flow distal to occluded or highly stenotic segments increases the difficulty of detecting significant Doppler velocity changes in the distal or secondary stenoses. The intrinsic limitations of the peak systolic velocity ratio used as a classification criterion are presented. Finally, new and promising developments in power Doppler imaging and ultrasound contrast agents are discussed, because they may allow expansion of the capabilities of current ultrasound scanning systems and provide more accurate diagnosis of patients with multiple disease.

Evaluation of Karhunen-Loève expansion for feature selection in computer-assisted classification of bioprosthetic heart-valve status.

This paper analyses the performance of four different feature-selection approaches of the Karhunen-Loève expansion (KLE) method to select the most discriminant set of features for computer-assisted classification of bioprosthetic heart-valve status. First, an evaluation test reducing the number of initial features while maintaining the performance of the original classifier is developed. Secondly, the effectiveness of the classification in a simulated practical situation where a new sample has to be classified is estimated with a validation test. Results from both tests applied to a reference database show that the most efficient feature selection and classification (> or = 97% of correct classifications (CCs)) are performed by the Kittler and Young approach. For the clinical databases, this approach provides poor classification results for simulated 'new samples' (between 50 and 69% of CCs). For both the evaluation and the validation tests, only the Heydorn and Tou approach provides classification results comparable with those of the original classifier (a difference always < or = 7%). However, the degree of feature reduction is particularly variable. The study demonstrates that the KLE feature-selection approaches are highly population-dependent. It also shows that the validation method proposed is advantageous in clinical applications where the data collection is difficult to perform.

Effects of a sudden flow reduction on red blood cell rouleau formation and orientation using RF backscattered power.

In most studies that were aimed at evaluating the kinetics of red blood cell (RBC) aggregation, human blood was initially circulated at a high shear rate to disrupt the aggregates, and measurements were performed following a complete flow stoppage, during the process of rouleau formation. However, it is known that a very low shear rate can enhance the formation of aggregates, as demonstrated by the modal relationship of the shear-rate dependence of RBC aggregation. The objective of the present study was, thus, to evaluate the influence of sudden flow reductions compared to a complete flow stoppage on the kinetics of rouleau formation, using ultrasound backscattering. Horse blood models, characterized by different aggregation levels, were obtained by diluting the plasma with a saline solution in different proportions. Blood was circulated in a 12.7-mm vertical tube at a flow rate of 1250 mL min-1 (prereduction flow rate) to disrupt the aggregates. The ultrasound radiofrequency (RF) signal was recorded from the center of the tube following different levels of sudden flow reduction or complete stoppage (postreduction flow rate). All measurements were performed over 2 min, using a 10-MHz transducer. No power increase was observed after complete flow stoppage. For postreduction flow rates varying between 20 and 160 mL min-1, the backscattered power increased proportionally with the kinetics of RBC aggregation. The echo buildup was also faster and stronger when the postreduction flow rate was increased. An unexpected pattern of variation of the backscattered power was found for horse RBCs characterized by high kinetics of rouleau formation. The power increased rapidly to a plateau, followed by another rapid increase and another plateau. Rouleau formation, random disorientation and reorientation were postulated to explain the phasic power increases observed.

In vitro evaluation of multiple arterial stenoses using three-dimensional power Doppler angiography.

PURPOSE: The study was done to improve quantification of multiple arterial stenoses and to investigate a new imaging technique for lower limb arteries. Three-dimensional power Doppler angiography was used to quantify in vitro arterial stenoses. METHODS: We built two types of artery phantoms containing multiple stenoses. One used stenotic porcine arteries, and the other was designed to control the proximal and distal stenoses while we assessed central stenosis of a wall-less agar lumen. Three-dimensional power Doppler angiograms of the flow lumens were generated at different flow rates under steady and pulsatile flow conditions with a PowerPC 8500 computer-based three-dimensional ultrasound imaging system. This experimental system works off-line, performs three-dimensional acquisition, reconstruction, and display of ultrasound images. Images of flow lumens were compared with the measured B-mode images or the true geometry. RESULTS: This technique produces good three-dimensional angiographic images of the flow lumen, and multiple stenoses do not affect the diagnosis of arterial stenoses. With this technique, the average errors for estimating 80% and 50% area reduction stenoses were -10% and 4%, respectively. CONCLUSIONS: Three-dimensional power Doppler angiography has the potential to quantitatively grade multisegmental stenoses in lower limbs and generate a map for vasculature surgery planning.

Photoinduced optical absorption and 400-nm luminescence in low-germanium-content optical f iber preforms irradiated with ArF and KrF excimer-laser light.

The optical absorption spectrum and the 400-nm photoluminescence (PL) of a 1.4-mol. % Ge photosensitive optical fiber preform subjected to high fluence of 193-nm ArF and 248-nm KrF excimer-laser irradiation are measured. The largest absorption increases occur near 200 nm in both cases, but a small net bleaching of absorption is obtained near the laser wavelength for KrF irradiations. The blue PL decreases during ArF exposure but increases with the KrF laser. In similarly excited 9-mol. % Ge fiber preforms the blue PL always decreases. A study of the PL intensity as a function of irradiating laser light intensity shows no evidence of multiple photon absorption effects.

Non-Gaussian statistical property of the ultrasonic Doppler signal downstream of a severe stenosis.

The Doppler signal is generally considered as a Gaussian random process. However, to date very little experimental validation of this model has been available. Recently, the K model was proposed to describe the statistical properties of ultrasonic radio frequency signals and their envelopes. The coefficient of kurtosis, which has been shown to be related to the parameters of the K model, was used in the literature as an index to assess the deviations from the Gaussian statistical property of ultrasonic signals obtained from simulations, phantoms and tissues. In the present study, an in vitro flow loop model was used to evaluate the effect of a severe stenosis on the coefficient of kurtosis. Our results showed non-Gaussian statistical properties of the Doppler signal in the jet of the stenosis.

Differences in the erythrocyte aggregation level between veins and arteries of normolipidemic and hyperlipidemic individuals.

The objectives of this study were to detect differences in the Doppler power backscattered by blood in vivo, and to identify factors affecting the backscattered power. The main hypothesis was that variations in the erythrocyte aggregation level between veins and arteries of normolipidemic and hyperlipidemic individuals can be detected with power Doppler ultrasound. Doppler measurements were performed at 5 MHz, with an Acuson 128 XP/10 system, over the carotid artery and jugular vein, external iliac artery and vein, common femoral artery and vein and popliteal artery and vein. Doppler signals were recorded at the center of each vessel to optimize the detection of erythrocyte aggregation, and processed off-line to obtain the backscattered power. The power of each recording was compensated for Doppler gain differences, tissue attenuation with depth and transmitted power variations occurring with pulse-repetition interval modifications. Results showed statistically stronger backscattered power in veins compared to arteries for the iliac, femoral and popliteal sites. In comparison with healthy subjects, stronger powers were observed in hyperlipidemic patients for the femoral and popliteal sites. Power differences were also found between peripheral measurements. On the other hand, no difference was observed between the power measured in the carotid artery and jugular vein for both groups of individuals. Multiple linear regression analyses were performed to identify factors affecting the backscattered power. Results showed a correlation (r) of 71.2% between the Doppler power in the femoral vein and the linear combination of two parameters: an erythrocyte aggregation index S10 measured with a laser scattering method, and the diameter of the vessel measured on B-mode images. Statistically significant linear correlation levels were also found between S10 and the Doppler power in various vessels. In conclusion, this study showed that power Doppler differences exist in vivo in large vessels between veins and arteries of normolipidemic and hyperlipidemic individuals. The Doppler power variations were also shown to be related to erythrocyte aggregation.

Characterization of blood flow turbulence with pulsed-wave and power Doppler ultrasound imaging.

Blood turbulence downstream of a concentric 86 percent area reduction stenosis was characterized using absolute and relative Doppler spectral broadening measurements, relative Doppler velocity fluctuation, and Doppler backscattered power. Bidimensional mappings of each Doppler index were obtained using a 10 MHz pulsed-wave Doppler system. Calf red cells suspended in a saline solution were used to scatter ultrasound and were circulated in an in vitro steady flow loop model. Results showed that the absolute spectral broadening was not a good index of turbulence because it was strongly affected by the deceleration of the jet and by the shear layer between the jet and the recirculation zones. Relative Doppler spectral broadening (absolute broadening divided by the frequency shift), velocity fluctuation, and Doppler power indices provided consistent mapping of the centerline axial variation of turbulence evaluated by hot-film anemometry. The best agreement between the hot-film and Doppler ultrasound methods was however obtained with the Doppler back-scattered power. The most consistent bidimensional mapping of the flow characteristics downstream of the stenosis was also observed with the Doppler power index. The relative broadening and the velocity fluctuation produced artifacts in the shear layer and in the recirculation zones. Power Doppler imaging is a new emerging technique that may provide reliable in vivo characterization of blood flow turbulence.