A diversity of bacteria, protozoans and viruses ("endozoites") were recently uncovered within healthy tissues including the human brain. By contrast, it was already recognized a century ago that healthy plants tissues contain abundant endogenous microbes ("endophytes"). Taking endophytes as an informative precedent, we overview the nature, prevalence, and role of endozoites in mammalian tissues, centrally focusing on the brain, concluding that endozoites are ubiquitous in diverse tissues. These passengers often remain subclinical, but they are not silent. We address their routes of entry, mechanisms of persistence, tissue specificity, and potential to cause long-term behavioral changes and/or immunosuppression in mammals, where rabies virus is the exemplar. We extend the discussion to Herpesviridae, Coronaviridae, and Toxoplasma, as well as to diverse bacteria and yeasts, and debate the advantages and disadvantages that endozoite infection might afford to the host and to the ecosystem. We provide a clinical perspective in which endozoites are implicated in neurodegenerative disease, anxiety/depression, and schizophrenia. We conclude that endozoites are instrumental in the delicate balance between health and disease, including age-related brain disease, and that endozoites have played an important role in the evolution of brain function and human behavior.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/gbb.12680

From conifers to cognition: Microbes, brain and behavior.

The increasing trend in the incidence of neurological disease (NDs) cases is a major challenge for societies. The aggregation of misfolding some proteins can cause neurological disorders in the brain. Early detection of the NDs plays a critical, because prolongs in the diagnostic process will lead to delayed initiation of treatment procedures, other diseases affecting the central nervous system will reduce the effectiveness of the treatment. Early detection of the NDs can be achieved by aptasensors that are used aptamers as biorecognition elements due to their unique selective, sensitive, and cost-effective properties. In this review, the recent progress on aptasensors for NDs biomarkers was provided in terms of the aptamers, construction principles of aptasensors, signal transduction methods, performance properties, applications, and advantages/limitations. In addition, appropriate aptamer selection methods and characterization steps are described. Moreover, future aspects are discussed for further research for developing novel aptamers and aptasensors in clinical diagnostics. • The severity of neurological diseases has been highlighted. • Recent progress in aptasensors for NDs biomarker detection by various methods is summarized. • Different aptasensors for detecting NDs biomarkers and their application were introduced. • This article provides an overview of the applications of aptasensors in NDs biomarker analysis. 

Design Strategies, Current Applications and Future Perspective of Aptasensors for Neurological Disease Biomarkers

A significant positive correlation was previously reported (Fox et al. Evol Med Public Health 2013; 2013:173-86) between hygiene and the global prevalence of Alzheimer's disease (AD) based on World Health Organization (2004) data. These data have now been updated by the Global Burden of Disease (GBD; 2016) dataset that takes into account under-registration and other potential confounds. We therefore addressed whether the association between hygiene and AD is maintained in light of these more recent data. We report a significant positive correlation between GBD AD prevalence rates and parasite burden, and a negative association with hygiene. These newer data argue that hygiene is not a risk factor for AD, and instead suggest that parasite burden may increase AD risk. Lay summary: It was previously hypothesized that hygeine might be a risk factor for the development of Alzheimer disease (AD), based on a global gradient of dementia. Newer data that correct global AD rates for under-reporting now demonstrate that parasite burden is positively correlated with AD.

Evidence against a geographic gradient of Alzheimer's disease and the hygiene hypothesis.

Ligand-activated nuclear receptors (NRs) orchestrate development, growth, and reproduction across all animal lifeforms – the Metazoa – but how NRs evolved remains mysterious. Given the NR ligands including steroids and retinoids are predominantly terpenoids, we asked whether NRs might have evolved from enzymes that catalyze terpene synthesis and metabolism. We provide evidence suggesting that NRs may be related to the terpene synthase (TS) enzyme superfamily. Based on over 10,000 3D structural comparisons, we report that the NR ligand-binding domain and TS enzymes share a conserved core of seven α-helical segments. In addition, the 3D locations of the major ligand-contacting residues are also conserved between the two protein classes. Primary sequence comparisons reveal suggestive similarities specifically between NRs and the subfamily of cis-isoprene transferases, notably with dehydrodolichyl pyrophosphate synthase and its obligate partner, NUS1/NOGOB receptor. Pharmacological overlaps between NRs and TS enzymes add weight to the contention that they share a distant evolutionary origin, and the combined data raise the possibility that a ligand-gated receptor may have arisen from an enzyme antecedent. However, our findings do not formally exclude other interpretations such as convergent evolution, and further analysis will be necessary to confirm the inferred relationship between the two protein classes.

https://jme.bioscientifica.com/downloadpdf/journals/jme/68/3/JME-21-0156.pdf

J Constance Lathe

Papers

Evidence against a geographic gradient of Alzheimer's disease and the hygiene hypothesis.

Evidence that nuclear receptors are related to terpene synthases