•A novel experimental setup integrating biaxial traction and microstructure is proposed.•Experimental data were used for structurally-motivated constitutive modelling.•Successful fitting with ...fiber-based models was obtained.•The setup feasibility demonstrated the analysis at macro and microstructure level.
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Mechanical properties and microstructural modifications of vessel tissues are strongly linked, as established in the state of the art of cardiovascular diseases. Techniques to obtain both mechanical and structural information are reported, but the possibility to obtain real-time microstructural and macrostructural data correlated is still lacking. An experimental approach to characterize the aortic tissue is presented. A setup integrating biaxial traction and Small Angle Light Scattering (SALS) analysis is described. The system was adopted to test ex-vivo aorta specimens from healthy and aneusymatic (aTAA) cases. A significant variation of the fiber dispersion with respect to the unloaded state was encountered during the material traction. The corresponding microstructural and mechanical data were successfully used to fit a given anisotropic constitutive model, with satisfactory R2 values (0.97±0.11 and 0.96±0.17, for aTAA and healthy population, respectively) and fiber dispersion parameters variations between the aTAA and healthy populations (0.39±0.23 and 0.15±0.10). The method integrating the biaxial/SALS technique was validated, allowing for real-time synchronization between mechanical and microstructural analysis of anisotropic biological tissues.
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•Gelation of chitosan systems strongly depends on the imposed aggregation regime.•Turbidimetric measurements can successfully replace inaccurate test tube method.•The introduction of ...a shear field leads to an acceleration of the gelation process.•Rotational shear leads to disentanglement and ordering of chitosan chains.
Thermoresponsive colloidal chitosan systems forming the polymer structure in situ are an example of promising solutions in tissue engineering as an injectable scaffolds or drug carriers. Their application method, and thus shearing, may affect the aggregation process in accordance with the colloidal engineering approach. The aim of the study is to compare the kinetics of chitosan aggregation in the perikinetic regime (limited by Brownian motions) with the orthokinetic process carried out under the influence of an external shear field. The research was carried out using static multiple light scattering (S-MLS) and rheometric measurement techniques coupled with small-angle light scattering (Rheo-SALS). It has been found that the introduction of an external shear field (orthokinetic regime) accelerates the aggregation of chitosan systems. Simultaneously, the rotational measurements can even lead to spontaneous gelation, most likely caused by changes in the conformation of chitosan molecules, their deformation and ordering along the shear field.
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•The structure of CNC suspensions under shear was studied by rheo-SAXS and SALS.•A broad range of lengthscales from nanometer to micrometer has been explored.•Changes in cholesteric ...organization and disappearance of pitch under shear have been evidenced.•The CNC organization over the three-regime rheological behavior has been clarified.•Buildup mechanisms, from nematic to cholesteric were highlighted on large scales.
The breakdown and buildup mechanisms in concentrated cellulose nanocrystal (CNC) suspensions under shear and during relaxation upon cessation of shear were accessed by small-angle X-ray and light scattering combined with rheometry. The dynamic structural changes over nanometer to micrometer lengthscales were related to the well-known three-regime rheological behavior. In the shear-thinning regime I, the large liquid crystalline domains were progressively fragmented into micrometer-sized tactoids, with their cholesteric axis aligned perpendicular to the flow direction. The viscosity plateau of regime II was associated to a further disruption into submicrometer-sized elongated tactoids oriented along the velocity direction. At high shear rate, regime III corresponded to the parallel flow of individual CNCs along the velocity direction. Upon cessation of flow, the relaxation process occurred through a three-step buildup mechanisms: i) a fast reassembling of the individual CNCs into a nematic-like organization established up to micrometer lengthscales, ii) a slower formation of oriented large cholesteric domains, and iii) their isotropic redistribution.
We considered the gelation and its relaxation mechanism of a shear-induced bentonite / heptaethylene oleyl ether (abbreviated as C18:1E7) aqueous suspension based on the analysis of Rheo-SALS. When ...bentonite / C18:1E7 aqueous suspension formed the shake-gel, the concentration of bentonite was greater than or equal to the critical concentration of c* = 1.3 wt% where hydrodynamic interactions occur. The relationship between the time ts when the shear thickening occurs and the bentonite / surfactant concentration (c - cs) can be described by the first-order reaction equation, and ts can be further reduced with the applied shearing.
The gel formation time and the relaxation time were affected by the shear hysteresis. We found that the formation and the relaxation (breakdown) of gels comprising bentonite particles did not follow the same pathway. Thus, Shear induced gel formation is due to the percolation transition by the infinite network structure in which the anisotropic orientation of bentonite particles grows. In contrast, the relaxation (breakdown) of the gel proceeds by the isotropic diffusion of individual bentonite particles forming the network structure.
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Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disease of motor neurons. Most ALS cases are considered sporadic due to the presence of a combination of environmental ...and complex genetic risk factors, while approximately 10% of cases have a family history. Pathogenic variants in the SOD1 gene are the second most frequent causative factor of genetics-based ALS worldwide, after C9ORF72 hexanucleotide repeat expansion. The De novo occurrence of pathogenic mutations in ALS-associated genes and its effect on disease progression have been studied previously, especially in the FUS gene. Recent studies have shown that a very small portion of SOD1 cases occurred de novo . Here, we present the first de novo case of the SOD1 His47Arg mutation in a young female patient with mild symptoms and, currently, a slow progression for 7 years.
Significance Glycosphingolipids are a heterogeneous group of membrane lipids formed through the covalent linkage of a glycan moiety to ceramide. Genetic evidence suggests that aberrant ...glycosphingolipid metabolism plays an important role in several neuromuscular diseases. Here, we investigated whether alterations in glycosphingolipids contribute to neurodegeneration in amyotrophic lateral sclerosis (ALS). We show that ALS patients and model mice display disease-related changes in spinal cord glycosphingolipids levels and in the enzymes that regulate their metabolism. Importantly, we demonstrate that inhibition of glycosphingolipid synthesis in ALS model mice exacerbated disease progression, whereas administration of GM3, a subtype of glycosphingolipids, slowed it, thus implicating glycosphingolipids as potentially important participants in ALS pathogenesis and potential targets for future drug development.
Recent genetic evidence suggests that aberrant glycosphingolipid metabolism plays an important role in several neuromuscular diseases including hereditary spastic paraplegia, hereditary sensory neuropathy type 1, and non-5q spinal muscular atrophy. Here, we investigated whether altered glycosphingolipid metabolism is a modulator of disease course in amyotrophic lateral sclerosis (ALS). Levels of ceramide, glucosylceramide, galactocerebroside, lactosylceramide, globotriaosylceramide, and the gangliosides GM3 and GM1 were significantly elevated in spinal cords of ALS patients. Moreover, enzyme activities (glucocerebrosidase-1, glucocerebrosidase-2, hexosaminidase, galactosylceramidase, α-galactosidase, and β-galactosidase) mediating glycosphingolipid hydrolysis were also elevated up to threefold. Increased ceramide, glucosylceramide, GM3, and hexosaminidase activity were also found in SOD1 á´³â¹Â³á´¬ mice, a familial model of ALS. Inhibition of glucosylceramide synthesis accelerated disease course in SOD1 á´³â¹Â³á´¬ mice, whereas infusion of exogenous GM3 significantly slowed the onset of paralysis and increased survival. Our results suggest that glycosphingolipids are likely important participants in pathogenesis of ALS and merit further analysis as potential drug targets.
Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive neurodegenerative disease characterized by the degeneration and death of upper (UMN) and lower (LMN) motor neurons. In the last decade, it ...has been shown that Chitinases are an important prognostic indicator of neuro-inflammatory damage induced by microglia and astrocytes.
We analyzed microarray datasets obtained from the Array Express in order to verify the expression levels of CHI3L1 and CHI3L2 in motor cortex biopsies of sALS patients with different survival times. We also divided the sALS patients into smokers and non-smokers. In order to extend our analysis, we explored two additional microarray datasets, GSE833 and GSE26927, of post-mortem spinal cord biopsies from sALS patients.
The analysis showed that CHI3L1 and CHI3L2 expression levels were significantly upregulated in the motor cortex of sALS patients, compared to the healthy controls. Moreover, their expression levels were negatively correlated with survival time. Interesting results were obtained when we compared the expression levels of Chitinases among smokers. We showed that CHI3L1 and CHI3L2 were significantly upregulated in sALS smokers compared to non-smokers. Furthermore, we found that four genes belonging to the Chitinases network (SERPINA3, C1s, RRAD, HLA-DQA1) were significantly upregulated in the motor cortex of sALS patients and positively correlated with Chitinases expression levels. Similar results were obtained during the exploration of the two-microarray dataset.
This study suggests that CHI3L1 and CHI3L2 are associated with the progression of neurodegeneration in motor cortex and spinal cord of sALS patients.
•CHI3L1 and CHI3L2 were significantly upregulated in motor cortex and spinal cord of sALS patients.•Cigarette smoke, modulates the CHI3L1 and CHI3L2 expression levels in the CNS of ALS patients.•CHI3L1 and CHI3L2 expression levels were negatively correlated to the survival time sALS patients.•The Chitinases network is modulated in motor cortex and spinal cord of sALS patients.
ANXA11 mutations have previously been discovered in amyotrophic lateral sclerosis (ALS) motor neuron disease. To confirm the contribution of ANXA11 mutations to ALS, a large exome data set obtained ...from 330 French patients, including 150 familial ALS index cases and 180 sporadic ALS cases, was analyzed, leading to the identification of 3 rare ANXA11 variants in 5 patients. The novel p.L254V variant was associated with early onset sporadic ALS. The novel p.D40Y mutation and the p.G38R variant concerned patients with predominant pyramidal tract involvement and cognitive decline. Neuropathologic findings in a p.G38R carrier associated the presence of ALS typical inclusions within the spinal cord, massive degeneration of the lateral tracts, and type A frontotemporal lobar degeneration. This mutant form of annexin A11 accumulated in various brain regions and in spinal cord motor neurons, although its stability was decreased in patients' lymphoblasts. Because most ANXA11 inclusions were not colocalized with transactive response DNA-binding protein 43 or p62 deposits, ANXA11 aggregation does not seem mandatory to trigger neurodegeneration with additional participants/partner proteins that could intervene.
•Novel ANXA11 mutations are responsible for ALS.•ANXA11 mutations can be associated with early onset ALS and FTD.•Mutant G38 R ANXA11 is unstable in patient lymphoblasts.•Mutant G38 R ANXA11 led to cytoplasmic inclusions in post-mortem tissue.
The family of polyamine oxidases (PAO) in Arabidopsis (AtPAO1-5) mediates polyamine (PA) back-conversion, which reverses the PA biosynthetic pathway from spermine, and its structural isomer ...thermospermine (tSpm), into spermidine and then putrescine. Here, we have studied the involvement of PA back-conversion in Arabidopsis salinity tolerance. AtPAO5 is the Arabidopsis PAO gene member most transcriptionally induced by salt stress. Two independent loss-of-function mutants (atpao5-2 and atpao5-3) were found to exhibit constitutively higher tSpm levels, with associated increased salt tolerance. Using global transcriptional and metabolomic analyses, the underlying mechanisms were studied. Stimulation of abscisic acid and jasmonates (JA) biosynthesis, and accumulation of important compatible solutes, such as sugars, polyols and proline, as well as TCA cycle intermediates were observed in atpao5 mutants under salt stress. Expression analyses indicate that tSpm modulates the transcript levels of several target genes, including many involved in the biosynthesis and signaling of JA, some of which are already known to promote salinity tolerance. Transcriptional modulation by tSpm is isomer-dependent, thus demonstrating the specificity of this response. Overall, we conclude that tSpm triggers metabolic and transcriptional reprogramming that promotes salt stress tolerance in Arabidopsis.
The aging problem is becoming more and more prominent globally. Attention to the quality of life and related health improvement among the elderly has become an important issue in modern society. This ...study utilized a tracking survey conducted in 2017-2018, involving 9,327 Chinese older adults, to examine health influencing factors, and applied structural equation modeling to analyze the influencing factors on the self-assessment of life satisfaction among older adults in different regions (cities, counties, and villages) in China. This study revealed that economic status, psychological status, personal situation, life behaviors, and child care are important influences on older people's self- assessed life satisfaction. There is a positive correlation between economic status, psychological status, child care and the results of the self-assessment of life satisfaction of the elderly. Psychological status and child care have a greater impact on the self-assessment of life satisfaction among the elderly in urban areas compared to villages and towns. The influence of economic status on the self-assessment of life satisfaction of the elderly is lower in urban areas than in rural areas. There is a significant difference in the influence of personal situations on the self-assessment of life satisfaction among the elderly. Additionally, older individuals tend to report higher levels of self-assessment of life satisfaction. Furthermore, female elderly individuals tend to report higher levels of satisfaction compared to males. Findings from this study indicate that improving health self-assessment in older adults requires targeted efforts based on different geographic areas of life and the age stages of older adults, and more attention needs to be paid to men who are just entering old age.
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