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Many drugs with anticholinergic effects are often prescribed for the elderly for various therapeutic reasons such as Parkinson's disease, urge incontinence and mood disturbances. Various reports estimated that drugs with anticholinergic effects are used by between 13.7% and 27% of the community-living elderly [1-3] and as much as 60% in nursing homes residents [4]. The unwanted peripheral and central side-effects are well known and common and include cognitive impairment [5] but are often attributed to normal consequences of ageing or the disease process. Acetylcholine levels decrease with advancing age and reduced cholinergic activity is a characteristic feature of dementia including Alzheimer's disease [6]. The use of drugs with anticholinergic effects is clearly an important exogenous source of anticholinergic load in the body and older people are more vulnerable. Because M1 receptor density is reduced by half in the elderly subjects, additional muscarinic antagonism could increase the risk of precipitating an accelerated decline in memory [7]. The use of drugs with anticholinergic activity is a biologically plausible and potentially modifiable risk factor for cognitive impairment. A number of clinical studies have provided empirical evidence of cognitive impairment associated specifically with benzodiazepines, amantadine, trihexphenidyl, oxybutynin, diphenhydramine [8-12]. Recent studies have measured serum levels of anticholinergic activities (SAA) in community-dwelling seniors and showed that high levels of SAA were significantly more likely to perform poorly on the MMSE [13].

Anthracnose diseases caused by Colletotrichum species are among the most common fungal diseases. These symptoms typically manifest as dark, sunken lesions on leaves, stems, and fruit. In China, mango anthracnose seriously affects fruit yield and quality. Genome sequencing of several species shows the presence of mini-chromosomes. These are thought to contribute to virulence, but their formation and activity remain to be fully elucidated. Here, we assembled 17 Colletotrichum genomes (16 isolated from mango plus one from persimmon) through PacBio long-read sequencing. Half of the assembled scaffolds had telomeric repeats at both ends indicating full-length chromosomes. Based on comparative genomics analysis at interspecies and intraspecies levels, we identified extensive chromosomal rearrangements events. We analyzed mini-chromosomes of Colletotrichum spp. and found large variation among close relatives. In C. fructicola , homology between core chromosomes and mini-chromosomes suggested that some mini-chromosomes were generated by recombination of core chromosomes. In C. musae GZ23-3, we found 26 horizontally transferred genes arranged in clusters on mini-chromosomes. In C. asianum FJ11-1, several potential pathogenesis-related genes on mini-chromosomes were upregulated, especially in strains with highly pathogenic phenotypes. Mutants of these upregulated genes showed obvious defects in virulence. Our findings provide insights into the evolution and potential relationships to virulence associated with mini-chromosomes. IMPORTANCE Colletotrichum is a cosmopolitan fungal genus that seriously affects fruit yield and quality of many plant species. Mini-chromosomes have been found to be related to virulence in Colletotrichum . Further examination of mini-chromosomes can help us elucidate some pathogenic mechanisms of Colletotrichum . In this study, we generated novel assemblies of several Colletotrichum strains. Comparative genomic analyses within and between Colletotrichum species were conducted. We then identified mini-chromosomes in our sequenced strains systematically. The characteristics and generation of mini-chromosomes were investigated. Transcriptome analysis and gene knockout revealed pathogenesis-related genes located on mini-chromosomes of C. asianum FJ11-1. This study represents the most comprehensive investigation of chromosome evolution and potential pathogenicity of mini-chromosomes in the Colletotrichum genus.

Background Bio-organic fertilizers has been shown to improve crop yields, partially because of the effects on the structure and function in resident soil microbiome. Purpose and methods Whereas, it is unknown if such improvements have been facilitated by the particular action of microbial inoculants, or the compost substrate. To understand the ecological mechanisms to increase crop productivity by bio-organic fertilizers, we conducted a pot experiment tracking soil physicochemical factors and extracellular enzyme activity over two growth stages and variations of soil microbial communities caused by fertilization practices as below: Bacillus subtilis CY1 inoculation, swine compost, and bio-organic fertilizer. Results Results showed that different fertilization measures, especially bio-organic fertilizers, increased soil nutrients, enzyme activity, and the diversity of microbial communities. For quantifying the “effect size” of microbiota manipulation, we discoverd that, respectively, 19.94% and 48.99% of variation in the bacterial and fungal communities could be interpreted using tested fertilization practices. Fertilization-sensitive microbes showed taxonomy diversity and gave responses as guilds of taxa to specific treatments. The microbes exhibited medium to high degree of co-occurrence in the network and could be recruited, directly or indirectly, by B. subtilis CY1, suggesting that bio-organic fertilizer may allow manipulation of influential community members.Conclusion Together we demonstrated that the increase in tomato productivity by bio-organic fertilizer was caused by the synergistic effect of organic fertilizer and beneficial microorganisms, thus providing novel insights into the soil microbiome manipulation strategies of biologically-enhanced organic fertilizers.

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