Search

The article provides an overview of studies and experiments on Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Degeneration, focusing on topics such as endogenous retrovirus-K (ERVK), alternative polyadenylation, TARDBP mutations, TDP-43 proteinopathy, and RNA aptamers in ALS neuropathology. It also discusses the impact of miRNAs, SOD1 aggregates, and different mechanisms of ALS spread, as well as the potential of direct neuronal reprogramming for ALS therapy. The research utilizes animal models like mice, zebrafish, and C. elegans to investigate the therapeutic potential of compounds and probiotics, aiming to understand disease progression and evaluate novel treatments for ALS. Clinical trials are proposed to assess probiotic supplementation effects on ALS patients. [Extracted from the article]

Summary: Organic and inorganic antigens were studied simultaneously in the same cohort of sarcoidosis patients to investigate whether correlations between clinical characteristics and immunological sensitization could reveal new phenotypes. Sensitization to antigens of mycobacteria, Propionibacterium acnes catalase and vimentin was investigated in 201 sarcoidosis and 51 obstructive sleep apnoea patients, serving as control group. Sensitization to aluminium, beryllium, silica and zirconium was also studied in 105 of the sarcoidosis patients and in 24 of the controls. A significantly higher percentage of sarcoidosis patients (27·6%) than controls (4·2%) had an immunological response to metals or silica (P = 0·014). A higher percentage of these sarcoidosis patients showed fibrosis on chest X‐ray 5 years after the diagnosis (69·2 versus 30·3%, P = 0·016). No significant differences in mycobacterial or vimentin enzyme‐linked immunospot (ELISPOT) assay results were observed between sarcoidosis and control patients. A significantly lower percentage of sarcoidosis patients (3·5%) than control patients (15·7%) had a positive ELISPOT for P. acnes catalase (P = 0·003). However, sarcoidosis patients sensitized to P. acnes catalase were more likely to have skin involvement, while sarcoidosis patients sensitized to mycobacterial antigens were more likely to have cardiac involvement. Our study suggests a more prominent role for inorganic triggers in sarcoidosis pathogenesis than previously thought. Immunological sensitization to inorganic antigens was associated with development of fibrotic sarcoidosis. No association was found between sensitization to bacterial antigens or vimentin and sarcoidosis in Dutch patients. However, our data suggest that trigger‐related phenotypes can exist in the heterogeneous population of sarcoidosis patients. [ABSTRACT FROM AUTHOR]

Summary: Genetic susceptibility for sarcoidosis and Löfgren's syndrome (LS) has been associated with prognosis. Human leukocyte antigen (HLA)‐DRB1*03 is over‐represented in LS, and is associated with a good prognosis, whereas HLA‐DRB1*15‐positive patients have a more chronic course of sarcoidosis. These HLA‐DRB1 types can be easily tagged by single nucleotide polymorphisms (SNPs). Our aim was to evaluate the association between these tag SNPs and bronchoalveolar lavage (BAL) characteristics. In 29 patients, both complete HLA‐DRB1* locus genotyping and SNP tagging was performed in parallel. HLA‐DRB1 type was inferred from the presence of *03 tag rs2040410 allele A and referred to as *03. HLA‐DRB1*15 was inferred from the presence of tag SNP rs3135388 allele A and referred to as *15. For BAL analysis, 122 patients with LS and 165 patients with non‐LS sarcoidosis were included. BAL lymphocyte subsets were analyzed by flow cytometry. The presence of tag SNPs completely corresponded with HLA‐DRB1*03/*15 genotypes in all 29 patients in whom both HLA‐DRB1* genotyping and SNP tagging was performed. In all patients together, *03+/*15– patients showed a higher CD4+/CD8+ ratio than *03–/*15+ (P = 0·004) and *03–/*15– (P = 0·001). LS patients with *03+/*15– had a lower BAL lymphocyte count compared to *03–/*15+ patients (P = 0·011). Non‐LS sarcoidosis patients with *03+/*15– patients showed a decreased CD103+CD4+/CD4+ ratio compared to *03–/*15+ patients (P = 0·045) and *03–/*15– patients (P = 0·018). We found that HLA‐DRB1*03 and HLA‐DRB1*15 can be approximated by genotyping of tag SNPs and corresponds with the degree of lymphocytosis and cell phenotypes in BAL in both LS and non‐LS sarcoidosis patients. [ABSTRACT FROM AUTHOR]

Highlights the Benzene-State-of-the Science Workshop on the physiological effects of chronic exposure to benzene. Correlation between leukemia and benzene exposure; Details on the metabolism and pharmacokinetics of benzene; Types of mercapturic acids derived from benzene.

Permeability problems on irrigated soils may be alleviated by root systems that increase water flow by creating macropores. Infiltration rates have been shown to increase where plant roots decay and serve as preferential flow paths. For low‐organic‐matter swelling soil, there is a question whether macropores are able to resist the lateral swelling forces of the soil. The objective of this study was to observe preferential water flow paths in a swelling soil under two cropping systems. A Holtville silty clay (clayey‐over‐loamy, montmorillonitic Typic Torrifluvent) was observed in situ. Two crops, alfalfa (Medicago sativa, L.) and wheat (Triticum turgidum, L.) provided sharply contrasting root systems, with wheat possessing fine, fibrous roots; alfalfa on the other hand, has a taproot system. Macropores were observed after applying soil‐adsorbing methylene blue dye to irrigation water. Shrinkage cracks failed to conduct dye after 10 minutes into a flood irrigation. Earthworm (Lubricus terrestris) channels were also not stable. However, decaying roots of alfalfa produced stable macropores, while wheat produced no such macropores. The influence of alfalfa‐root‐induced macropores was demonstrated by the increase in final infiltration rate during alfalfa cropping which agreed with Meek et al.’s (1989, 1990) findings on sandy loam soils. [ABSTRACT FROM PUBLISHER]