On clarification of haze in polypropylene Bernland, Karin; Goossens, J. G. P.; Smith, Paul ...
Journal of polymer science. Part B, Polymer physics,
05/2016, Letnik:
54, Številka:
9
Journal Article
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by the neurodegeneration of motoneurons. About 10% of ALS is hereditary and involves mutation in 25 different ...genes, while 90% of the cases are sporadic forms of ALS (sALS). The diagnosis of ALS includes the detection of early symptoms and, as disease progresses, muscle twitching and then atrophy spreads from hands to other parts of the body. The disease causes high disability and has a high mortality rate; moreover, the therapeutic approaches for the pathology are not effective. miRNAs are small non-coding RNAs, whose activity has a major impact on the expression levels of coding mRNA. The literature identifies several miRNAs with diagnostic abilities on sALS, but a unique diagnostic profile is not defined. As miRNAs could be secreted, the identification of specific blood miRNAs with diagnostic ability for sALS could be helpful in the identification of the patients. In the view of personalized medicine, we performed a meta-analysis of the literature in order to select specific circulating miRNAs with diagnostic properties and, by bioinformatics approaches, we identified a panel of 10 miRNAs (miR-193b, miR-3911, miR-139-5p, miR-193b-1, miR-338-5p, miR-3911-1, miR-455-3p, miR-4687-5p, miR-4745-5p, and miR-4763-3p) able to classify sALS patients by blood analysis. Among them, the analysis of expression levels of the couple of blood miR-193b/miR-4745-5p could be translated in clinical practice for the diagnosis of sALS.
PVDF cast films were drawn at different temperatures to different draw ratios at constant draw rate to understand the mechanism of α to β phase transformation during mechanical deformation. WAXD and ...FTIR studies were carried out to determine the formation and content of β phase in the drawn films. Lower stretch temperatures gave higher fractions of β phase. The cast PVDF films were also drawn at suitable temperatures below the PVDF ambient melting point to the draw ratio of 6.4. The highest fraction of β phase obtained in these ultra drawn films was 0.98. SALS studies carried out for films at different stretch ratios show the change in spherulitic structure with the stretching parameters and give information for the understanding of phase transformation during stretching of PVDF films.
We investigated the relationship between the concentration of nanosized fibers and the rheological and the rheo-optic behaviors of CNF suspensions containing unfibrillated fibers prepared by a wet ...refinement system (Water Jet System). The CNF suspensions behaved as a gel in which entropic elasticity was dominant, and the entanglement among fibers would be enhanced with the nanosized fiber volume fraction. The aggregates of the nanosized fibers elongated in the flow direction and deformed into elliptical shape with the applied shearing. However, the effect of these shape changes of the aggregates was barely observed on the viscosity curve. We speculate that this is due to Newtonian flow of the unfibrillated fibers (> 25% by volume) playing a significant role in the overall flow behavior of the CNF suspensions. In conclusion, for the CNF suspensions containing poorly nanosized fibers, we speculated that the nanosized and unfibrillated fibers were largely responsible for the linear response under micro-deformation and the nonlinear response such as under shear flow, respectively.
Graphical abstract
Necroptosis is emerging among possible mechanisms underlying cell death in neurodegenerative diseases. In this line, we hypothesize that necroptosis might be implicated in neuronal cell death in ...amyotrophic lateral sclerosis (ALS). To support this hypothesis, we hereby provide pilot data as well as some findings from the literature about the expression of key markers of the necroptotic pathway in ALS. Our preliminary data indicate the upregulation of key markers of necroptosis activation in lower motor neurons of the spinal cord. These human-derived data combined with some clinical and preclinical findings support our hypothesis testing the involvement of necroptosis in lower motor neurons death in ALS patients. These results pave the way to deepen the role of necroptosis in ALS using both preclinical and clinical approaches. If confirmed, this hypothesis might raise new interventional strategies to alleviate neurodegenerative process in ALS.
Purpose of Review
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease causing weakness, respiratory failure, and death within 3 to 5 years. Approximately, 10% of ALS cases have a ...genetic etiology (familial/fALS). The etiology of the remaining 90% of sporadic ALS (sALS) cases remains unknown. In this review, we provide an overview of approved and investigational therapies for fALS, as well as genetically informed therapeutic advances aimed at the larger sALS population.
Recent Findings
Antisense oligonucleotides (ASOs) are a promising strategy to treat toxic gain-of-function mutations underlying most forms of fALS. We discuss the recent approval of tofersen for ALS caused by mutation in
SOD1
. We also discuss progress in the development of therapies for fALS associated with
C9orf72
hexanucleotide repeat expansions (
C9orf72
) and fused in sarcoma (
FUS
) mutations. Finally, we will discuss the rationale and status of molecular therapies for sALS targeting mediators of TDP-43 pathogenesis: ataxin-2 (
ATXN2
) and stathmin-2 (
STMN2
).
Summary
Advances in understanding the genetics of ALS have propelled the development of promising gene therapies. Lessons learned from tofersen continue to inform clinical trial design for a growing pipeline of therapies directed towards other fALS subtypes and sALS.
Amyotrophic lateral sclerosis (ALS) is a progressive and seriously disabling adult-onset neurological disease. Ninety percent of ALS patients are sporadic cases (sALS) with no clear genetic linkage. ...Accumulating evidence indicates that various microRNAs (miRNAs), expressed in a spatially and temporally controlled manner in the brain, play a key role in neuronal development. In addition, microRNA dysregulation contributes to some mental disorders and neurodegeneration diseases. In our research, the expression of one selected miRNA, miR-338-3p, which previously we have found over-expressed in blood leukocytes, was studied in several different tissues from sALS patients. For the first time, we detected a specific microRNA disease-related upregulation, miR-338-3p, in blood leukocytes as well in cerebrospinal fluid, serum, and spinal cord from sALS patients. Besides, staining of in situ hybridization showed that the signals of miR-338-3p were localized in the grey matter of spinal cord tissues from sALS autopsied patients. We propose that miRNA profiles found in tissue samples from sALS patients can be relevant to understand sALS pathogenesis and lead to set up effective biomarkers for sALS early diagnosis.
Diseases affecting motor neurons, such as amyotrophic lateral sclerosis (Lou Gerhig's disease), hereditary spastic paraplegia and spinal bulbar muscular atrophy (Kennedy's disease) are a ...heterogeneous group of chronic progressive diseases and are among the most puzzling yet untreatable illnesses. Over the last decade, identification of mutations in genes predisposing to these disorders has provided the means to better understand their pathogenesis. The discovery 13 years ago of
SOD1 mutations linked to ALS, which account for less than 2% of total cases, had a major impact in the field. However, despite intensive research effort, the pathways leading to the specific motor neurons degeneration in the presence of
SOD1 mutations have not been fully identified. This review provides an overview of the genetics of both familial and sporadic forms of ALS.
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