Cytological changes related to Brucella canis variants uptake in vitro

In this study, evidence for in vitro uptake, invasion, and cytopathogonomic effects of normal and variant strains of B. canis on tissue culture, is presented. B. canis L-phase were penicillin-induced and these microorganisms produced revertants on penicillin-free media. Tissue culture (LLC-MK 2 ) cells were divided into different normal and variant-infected groups (I–IV), including controls. Bright-field and electron microscopic observations indicated uptake of all the strains and recognizable host cell damage (CPE) to varying degrees. At 72 h after infection, the extent of damage by L-phase was the least (55.5% CPE). The L-phase-derived revertants resulted in 80% damage; this approximates the adverse effect of normal B. canis (85%). In addition to these gross changes, various structural abnormalities, including pyknosis, nuclear disorganization, vacuolation, and karyorrhexis, were apparent. The implications of these findings and the indirect role of the L-phase in brucellosis due to B. canis are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47529/1/430_2005_Article_BF02123560.pd

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference

The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique\u2014Subtype and Stage Inference (SuStaIn)\u2014able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer\u2019s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18 7 10 124 ) or temporal stage (p = 3.96 7 10 125 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine

A review of osteoarthritis and obesity: current understanding of the relationship and benefit of obesity treatment and prevention in the dog

Obesity is an increasingly important health problem for both man and dog. Osteoarthritis (OA) is a significant cause of pain and disability in both species. A link between obesity and OA has been established in man, though the exact mechanism of the relationship remains to be fully elucidated - current research supports both biomechanical and biochemical theories. There is good evidence (class I*) to support weight loss as an effective treatment for human knee OA. In the dog, the relationship is just beginning to be investigated. The results of one study in dogs (class IV evidence*) suggest that preventing the development of overweightness and obesity reduces the prevalence of hip dysplasia and OA of the hip and other joints. Three other studies (class III and IV evidence*) support weight loss as an effective treatment for OA in affected overweight and obese dogs. Further research could yield greater understanding of the pathophysiology of this relationship, perhaps identifying novel therapeutic targets. Confirmation and better understanding of the positive effect of treating and preventing obesity on symptoms and prevalence of OA is likely to be valuable in the campaign against canine obesit