Microbial metabolites affect the neuron system and muscle cell functions. Amyotrophic lateral sclerosis (ALS) is a multifactorial neuromuscular disease. Our previous study has demonstrated elevated ...intestinal inflammation and dysfunction of the microbiome in patients with ALS and an ALS mouse model (human-SOD1
transgenic mice). However, the metabolites in ALS progression are unknown. Using an unbiased global metabolomic measurement and targeted measurement, we investigated the longitudinal changes of fecal metabolites in SOD1
mice over the course of 13 weeks. We further compared the changes of metabolites and inflammatory response in age-matched wild-type (WT) and SOD1
mice treated with the bacterial product butyrate. We found changes in carbohydrate levels, amino acid metabolism, and the formation of gamma-glutamyl amino acids. Shifts in several microbially contributed catabolites of aromatic amino acids agree with butyrate-induced changes in the composition of the gut microbiome. Declines in gamma-glutamyl amino acids in feces may stem from differential expression of gamma-glutamyltransferase (GGT) in response to butyrate administration. Due to the signaling nature of amino acid-derived metabolites, these changes indicate changes in inflammation, e.g., histamine, and contribute to differences in systemic levels of neurotransmitters, e.g., γ-Aminobutyric acid (GABA) and glutamate. Butyrate treatment was able to restore some of the healthy metabolites in ALS mice. Moreover, microglia in the spinal cord were measured by IBA1 staining. Butyrate treatment significantly suppressed the IBA1 level in the SOD1
mice. Serum IL-17 and LPS were significantly reduced in the butyrate-treated SOD1
mice. We have demonstrated an inter-organ communications link among microbial metabolites, neuroactive metabolites from the gut, and inflammation in ALS progression. The study supports the potential to use metabolites as ALS hallmarks and for treatment.
A broad and simple method permitted halide ions in quaternary heteroaromatic and ammonium salts to be exchanged for a variety of anions using an anion exchange resin (A(-) form) in non-aqueous media. ...The anion loading of the AER (OH(-) form) was examined using two different anion sources, acids or ammonium salts, and changing the polarity of the solvents. The AER (A(-) form) method in organic solvents was then applied to several quaternary heteroaromatic salts and ILs, and the anion exchange proceeded in excellent to quantitative yields, concomitantly removing halide impurities. Relying on the hydrophobicity of the targeted ion pair for the counteranion swap, organic solvents with variable polarity were used, such as CH(3)OH, CH(3)CN and the dipolar nonhydroxylic solvent mixture CH(3)CN:CH(2)Cl(2) (3:7) and the anion exchange was equally successful with both lipophilic cations and anions.
Thermal energy storage (TES) in molten salts is the storage dominating technology in solar power applications today. In two-tank molten salt storage systems energy density ranges from 30 to 70kWh/m3 ...are achievable. The salt material used is a binary system, composed of 60% NaNO3 and 40% KNO3. In the 8 MWhth pilot plant built and tested by Abengoa, the storage tanks were made of steel A516Gr.70 using the Appendix M of code API 650 for their design. A specific testing device was developed to evaluate thermo-mechanical properties, and a study was conducted in order to evaluate tensile properties of A516Gr.70 specimens under operation conditions for the hot tank at the pilot plant that is in contact with molten salts at 380°C. Results confirmed the outcomes of the work: the reduction of the yield limit, elongation before fracture, and Young modulus at 380°C after having been 5min immersed in molten salts. Moreover, after a creep-test simulating operating 7 days conditions during, an additional reduction of the yield limit was measured.
•A516Gr.70-molten salts pair under operation conditions was evaluated.•Tensile strength test was performed and compared at 380°C and room temperature.•A reduction of σy, E modulus, and elongation were obtained.•After 7 days experiment, A516Gr.70 presents similar mechanical properties than after 5′.•Microstructures were checked and the changes are described.
In the recent studies on chitosan hydrogels, it was found that understanding both rheological and structural properties plays an important role in their application. Therefore, a combination of two ...independent techniques was applied to investigate micro- and macroscopic properties of chitosan colloidal system. Studies on viscous properties, as well as the sol-gel phase transition process, were performed using rheological methods coupled with the small angle light scattering (SALS) technique. Based on the anisotropy of scattering patterns obtained during rotational shear tests, it was found that the chitosan solution reveals two different behaviors delimited by the critical value of the shear rate. Below a critical value, chitosan clusters are deformed without breaking up aggregates, whereas after exceeding a critical value, chitosan clusters apart from deformation also breakup into smaller aggregates. The values of the radius of gyration determined by applying the Debye function allow one to state that with an increase of chitosan concentration, molecule size decreases. An analysis of the light scattering data from the temperature ramp test showed that with an increase of temperature, the level of polymer coil swelling increases. Simultaneously, the supply of thermal energy leads to a neutralization of the charge of chitosan chains. As a consequence, the formation of intermolecular links occurs and a gel structure is formed.
A lack of stratification methods in patients with amyotrophic lateral sclerosis (ALS) is likely implicated in therapeutic failures. Regional diversities and pathophysiological abnormalities in ...astrocytes from mice with SOD1 mutations (mSOD1-ALS) can now be explored in human patients using somatic cell reprogramming. Here, fibroblasts from four sporadic (sALS) and three mSOD1-ALS patients were transdifferentiated into induced astrocytes (iAstrocytes). ALS iAstrocytes were neurotoxic toward HB9-GFP mouse motor neurons (MNs) and exhibited subtype stratification through GFAP, CX43, Ki-67, miR-155 and miR-146a expression levels. Up- (two cases) and down-regulated (three cases) miR-146a values in iAstrocytes were recapitulated in their secretome, either free or as cargo in small extracellular vesicles (sEVs). We previously showed that the neuroprotective phenotype of depleted miR-146 mSOD1 cortical astrocytes was reverted by its mimic. Thus, we tested such modulation in the most miR-146a-depleted patient-iAstrocytes (one sALS and one mSOD1-ALS). The miR-146a mimic in ALS iAstrocytes counteracted their reactive/inflammatory profile and restored miR-146a levels in sEVs. A reduction in lysosomal activity and enhanced synaptic/axonal transport-related genes in NSC-34 MNs occurred after co-culture with miR-146a-modulated iAstrocytes. In summary, the regulation of miR-146a in depleted ALS astrocytes may be key in reestablishing their normal function and in restoring MN lysosomal/synaptic dynamic plasticity in disease sub-groups.
The cerebral meninges, made up of the
dura, arachnoid
, and
pia mater
, is a tri-layer membrane that surrounds the brain and the spinal cord and has an important function in protecting the brain from ...injury. Understanding its mechanical behavior is important to ensure the accuracy of finite element (FE) head model simulations which are commonly used in the study of traumatic brain injury (TBI). Mechanical characterization of freshly excised porcine
dura-arachnoid mater
(DAM) was achieved using uniaxial tensile testing and bulge inflation testing, highlighting the dependency of the identified parameters on the testing method. Experimental data was fit to the Ogden hyperelastic material model with best fit material parameters of μ = 450 ± 190 kPa and α = 16.55 ± 3.16 for uniaxial testing, and μ = 234 ± 193 kPa and α = 8.19 ± 3.29 for bulge inflation testing. The average ultimate tensile strength of the DAM was 6.91 ± 2.00 MPa (uniaxial), and the rupture stress at burst was 2.08 ± 0.41 MPa (inflation). A structural analysis using small angle light scattering (SALS) revealed that while local regions of highly aligned fibers exist, globally, there is no preferred orientation of fibers and the cerebral DAM can be considered to be structurally isotropic. This confirms the results of the uniaxial mechanical testing which found that there was no statistical difference between samples tested in the longitudinal and transversal direction (
p
= 0.13 for μ,
p
= 0.87 for α). A finite element simulation of a craniotomy procedure following brain swelling revealed that the mechanical properties of the meninges are important for predicting accurate stress and strain fields in the brain and meninges. Indeed, a simulation using a common linear elastic representation of the meninges was compared to the present material properties (Ogden model) and the intracranial pressure was found to differ by a factor of 3. The current study has provided researchers with primary experimental data on the mechanical behavior of the meninges which will further improve the accuracy of FE head models used in TBI.
We discussed the relationship between rheological behavior and macroscopic shape of aggregates in shear flow of TEMPO oxidized nanocellulose (TOCN) suspension. The viscosity curve of TOCN suspensions ...is characterized by two shear thinning regions, separated by an intermediate plateau. The first normal stress difference (N1) measured at the same time showed a tendency to increase sharply in the negative direction in the vicinity of the plateau region of viscosity, and thereafter to increase in the positive direction. Small-angle Light Scattering (SALS) measurements reveal that these changes in rheological behavior correspond to the behavior of TOCN aggregates extending from an isotropic sphere to anisotropic ellipse. That is, in the low shear rate region, TOCN is dispersed as aggregates having a three-dimensional network structure in which fibers are entangled with each other. As the shear rate increases, the aggregates flow and the viscosity decreases. When a certain critical shear rate is reached, the aggregates try to deform into an ellipse to reduce flow resistance. At that time, transient shear stress is generated in aggregates, which causes a viscous plateau region. In addition, the size of aggregates in the direction perpendicular to the flow tends to decrease as they grow in the direction of the flow, resulting in a sudden negative normal stress. As the shear rate increases further, aggregates grow into an ellipse, the degree of anisotropy increases, and the complete thinning behavior begins again.
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Positively charged liposomes were coated with the negatively charged and temperature sensitive poly(N-isopropylacrylamide-co-methacrylic acid) by electrostatic deposition. Too low or ...too high polymer concentrations lead to unstable suspensions. However, intermediate polymer concentrations (0.05–0.2wt.%) result in relatively stable suspensions of polymer-coated liposomes. At elevated temperatures the thickness of the polymer layer around the coated liposomes increased sharply at 40°C, due to the formation of polymer multilayers. At higher temperatures, a contraction of the adsorbed polymer layer was observed. The uncoated liposomes exhibited an interesting transition in size and intensity of the scattered light when heated, attributed to the transition from the gel to liquid crystalline phase. Rheo-SALS (small angle light scattering under shear conditions) measurements demonstrated that the polymer coating was stable under shear at physiological temperature. It also revealed an anomalous high scattered intensity of the uncoated liposomes compared to the coated liposomes. This discrepancy was diminished at higher temperatures, and can probably be attributed to the change from a non-spherical, polyhedron-like conformation of the uncoated liposomes in the gel phase to a spherical shape above the phase transition.
Abstract Intermediate-length polyglutamine (polyQ) expansions in the ataxin-2 ( ATXN2 ) gene have recently been identified as a risk factor for sporadic amyotrophic lateral sclerosis (SALS). Our ...study aims to analyze cytosine, adenine, guanine (CAG)n expansions in the ATXN2 gene among Chinese patients with SALS. All patients diagnosed with adult-onset sporadic amyotrophic lateral sclerosis (ALS) were consecutively followed up, and their clinical characteristics were collected. To measure the repeat length of ATXN2 polyQ, fluorescence-polymerase chain reaction products were analyzed on a 3100-Avant Genetic Analyzer Applied Biosystem (Foster City, CA, USA) using the ROC-500 size standard. Three hundred forty-five patients with SALS were studied. The mean age of onset was 51.38 ± 12.45 years. ATXN2 polyQ with a repeat length greater than 27 was found to be weakly associated with amyotrophic lateral sclerosis in our study. There was no significant difference in mean age of onset, gender, and onset site between the group of SALS patients with and without ATXN2 polyQ expansion greater than 27. Our finding provides evidence that the ATXN2 polyQ expansion greater than 27 might be a risk factor for Chinese SALS patients.
The purpose of this study is to investigate the relationship of the vertical deformation between the scaled-down pavement test and full-scale pavement structure according to the theory of ...similitude-based analysis procedure. Finite element analysis used to investigate and establish the relationship between the scaled-down and full-scale models. Four scaled-down models with scaling factors of 0.9, 0.75, 0.6, and 0.45 with two types of constitutive models of asphalt concrete materials, elastic and viscoelastic, are considered. The results show that the vertical deformation in the full-scale model achieved by applying a vertical shift to the vertical deformation in the scaled-down model. The vertical shift factor varies linearly in normal and logarithm scale with the scaling factor from 0.9 to 0.45 for linear elastic and viscoelastic material, respectively. Moreover, this study proposes a systematic analysis procedure to determine the testing temperature in the SALS test at a specific loading speed by using the time–temperature superposition principle. This study contributes considerably to preliminary understanding of the relationship between the scaled-down tester in the laboratory and the full-scale model according to the theory of similitude.
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