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1.
Sci Rep ; 12(1): 9025, 2022 05 30.
Article in English | MEDLINE | ID: mdl-35637265

ABSTRACT

We recently demonstrated that HCl-acidified drinking water, which is widely used in laboratory animal facilities, had some beneficial effects in the Cln3-/- mouse model of juvenile Batten disease, a neurodegenerative lysosomal storage disorder1. Here we tested if acidified drinking water has therapeutic effects in Cln1R151X nonsense mutant mice, a model of the infantile form of Batten disease. In Cln1R151X mice, acidified drinking water received from weaning prevented the impairment in pole climbing ability measured at 3 and 6 months of age. Histopathological analysis of the brain at 6 months showed that acidified drinking water decreased the amount of lysosomal storage material, reduced astrocytosis in the striatum and somatosensory barrelfield cortex, and attenuated microglial activation in the thalamus. Compared to wild-type mice, the gut microbiota of Cln1R151X mice was markedly different. Acidified drinking water significantly altered the gut microbiota composition of Cln1R151X mice, indicating a contribution of gut bacteria to the therapeutic effects of acidified water. Our results in Cln1R151X mice suggest that acidified drinking water may have beneficial effects for patients with infantile Batten disease. This study also verifies that acidified drinking water can modify disease phenotypes in mouse models, contributing to the inter-laboratory variations in neurological and pathological findings.


Subject(s)
Drinking Water , Neuronal Ceroid-Lipofuscinoses , Animals , Brain/metabolism , Child , Disease Models, Animal , Humans , Membrane Glycoproteins/metabolism , Mice , Molecular Chaperones/metabolism , Neuronal Ceroid-Lipofuscinoses/pathology
2.
Sci Rep ; 11(1): 12570, 2021 06 15.
Article in English | MEDLINE | ID: mdl-34131169

ABSTRACT

Stagonospora nodorum blotch (SNB) is an economically important wheat disease caused by the necrotrophic fungus Parastagonospora nodorum. SNB resistance in wheat is controlled by several quantitative trait loci (QTLs). Thus, identifying novel resistance/susceptibility QTLs is crucial for continuous improvement of the SNB resistance. Here, the hard winter wheat association mapping panel (HWWAMP) comprising accessions from breeding programs in the Great Plains region of the US, was evaluated for SNB resistance and necrotrophic effectors (NEs) sensitivity at the seedling stage. A genome-wide association study (GWAS) was performed to identify single-nucleotide polymorphism (SNP) markers associated with SNB resistance and effectors sensitivity. We found seven significant associations for SNB resistance/susceptibility distributed over chromosomes 1B, 2AL, 2DS, 4AL, 5BL, 6BS, and 7AL. Two new QTLs for SNB resistance/susceptibility at the seedling stage were identified on chromosomes 6BS and 7AL, whereas five QTLs previously reported in diverse germplasms were validated. Allele stacking analysis at seven QTLs explained the additive and complex nature of SNB resistance. We identified accessions ('Pioneer-2180' and 'Shocker') with favorable alleles at five of the seven identified loci, exhibiting a high level of resistance against SNB. Further, GWAS for sensitivity to NEs uncovered significant associations for SnToxA and SnTox3, co-locating with previously identified host sensitivity genes (Tsn1 and Snn3). Candidate region analysis for SNB resistance revealed 35 genes of putative interest with plant defense response-related functions. The QTLs identified and validated in this study could be easily employed in breeding programs using the associated markers to enhance the SNB resistance in hard winter wheat.


Subject(s)
Ascomycota/genetics , Disease Resistance/genetics , Genome-Wide Association Study , Triticum/genetics , Ascomycota/pathogenicity , Chromosome Mapping , Chromosomes, Plant/genetics , Plant Diseases/genetics , Plant Diseases/microbiology , Plant Proteins/genetics , Triticum/growth & development , Triticum/microbiology
3.
J Parasitol ; 106(1): 14-24, 2020 02.
Article in English | MEDLINE | ID: mdl-31958374

ABSTRACT

Human head lice and body lice (Pediculus humanus) are neglected ectoparasites. Head lice continue to be prevalent in children worldwide, and insecticide resistance in these insects has complicated their treatment. Meanwhile, body lice, which are most common in the developing world, are resurging among marginalized populations in developed nations. Today, the microbiome is being increasingly recognized as a key mediator of insect physiology. However, the microbial communities that inhabit human lice have remained unknown beyond only a few species of bacteria. Knowledge of the microbiomes of head and body lice could improve our understanding of the observed physiological differences between the 2 ecotypes and potentially inform the development of novel interventions against lice infestations and louse-borne infectious diseases. Toward these goals, here we performed 16S rRNA gene amplicon sequencing to characterize the microbiomes of both head and body lice and identify patterns of interest among these communities. Our data reveal that head and body lice harbor limited but distinct communities of bacteria that include known intracellular endosymbionts ("Candidatus Riesia pediculicola"), extracellular bacteria that may be horizontally acquired from the host environment, and a number of taxa of known or potential public health significance. Notably, in body lice, the relative abundance of vertically transmitted endosymbionts is lower than in head lice, which is a significant driver of greater alpha diversity. Further, several differentially abundant non-endosymbiont taxa and differences in beta diversity were observed between head lice and body lice. These findings support the hypothesis that microbiome differences could contribute to the divergence between human louse ecotypes and underscore the need for future studies to better comprehend the acquisition and physiological roles of human lice microbiomes.


Subject(s)
Bacteria/classification , Ecotype , Microbiota , Pediculus/microbiology , RNA, Ribosomal, 16S/chemistry , Animals , Bacteria/genetics , DNA/isolation & purification , Female , Humans , Pediculus/classification , Pediculus/physiology , Principal Component Analysis , Rabbits , Sequence Analysis, RNA
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