Biology subjects

Berner, K.

Publications and source records attributed to Berner, K..

3 recordsLinked to original sources

bioRxiv2024

Elevated plasma pTau181 in a specialty neuropsychiatric clinic is associated with opioid use and guides medication titration on a clinically relevant short-time scale

A combinatorial explosion of agents that delay neurodegeneration in animal models has created a crisis of abundance in human applications with too many combinations to try when time is short. Plasma biomarkers of premature neuronal aging, the amyloid-tau-neurodegeneration (ATN) profile, may provide a tool to rapidly optimize treatment in single-patient trials. We retrospectively analyzed plasma ATN profiles in patients with extensive neuropsychiatric polypharmacy and premature neuronal aging. ATN profiles were based on the biomarkers amyloid-{beta} ratio, phosphorylated Tau 181 (pTau181), and neurofilament light chain (NfL). We investigated whether ATN profile biomarkers were associated with age, gender, metabolic syndrome markers, and medication use. Two case reports additionally provide examples of the application of ATN profiles in clinical settings. We found that in 80 patients with ATN profiles and complete clinical phenotypes, pTau181 was elevated in 31 (38.75%), amyloid-{beta} ratio was below normal ranges in 11 (13.75%), and NfL was elevated in three (3.75%). The biomarkers correlated with age, as expected. Opioid use was significantly associated with pTau181 (p=0.004) and NfL (p=0.002), also after Bonferroni correction (both p <0.05), but not with amyloid-{beta} ratio. No other medications were associated with the biomarkers. In conclusion, identifying the overlaps between complex behavioral phenotypes (pain and cognition), plasma endophenotypes (ATN profile), and medication-targeted components of age-related pathophysiology is now a technical problem rather than theoretical speculation. Rapid progress in single-patient trials for treatment optimization will require funding to promote using repurposed generic treatments, educate patients and providers regarding optimization principles, and continue developing sensitive biomarkers.

pharmacology and toxicology↗

bioRxiv2024

mTORC1 ACTIVATION IN PRESUMED CLASSICAL MONOCYTES:OBSERVED CORRELATES WITH HUMAN SIZE VARIATION AND NEUROPSYCHIATRIC DISEASE

BackgroundGain of function disturbances in nutrient sensing are likely the largest component in human age-related disease. Mammalian target of rapamycin complex 1 (mTORC1) activity affects health span and longevity. The drugs ketamine and rapamycin are effective against chronic pain and depression, and both affect mTORC1 activity. Our objective was to measure phosphorylated p70S6K, a marker for mTORC1 activity, in individuals with psychiatric disease to determine whether phosphorylated p70S6K could predict medication response. MethodsTwenty-seven females provided blood samples in which p70S6K and phosphorylated p70S6K were analyzed. Chart review gathered biometric measurements, clinical phenotypes, and medication response. Questionnaires assessed anxiety, depression, autism traits, and mitochondrial dysfunction, to determine neuropsychiatric disease profiles. Univariate and multivariate statistical analyses were used to identify predictors of medication response. ResultsmTORC1 activity correlated highly with both classical biometrics (height, macrocephaly, pupil distance) and specific neuropsychiatric disease profiles (anxiety and autism). Across all cases, phosphorylated p70S6K was the best predictor for ketamine response, and also the best predictor for rapamycin response in a single instance. ConclusionsThe data illustrates the importance of mTORC1 activity in both observable body structure and medication response. This report suggests that a simple assay may allow cost-effective prediction of medication response.

neuroscience↗

bioRxiv2019

The tropical coral Pocillopora acuta has a mosaic DNA methylome, an unusual chromatin structure and shows histone H3 clipping

Pocillopora acuta is a hermatypic coral with a worldwide distribution and a strong ecological importance. Anthropogenic disturbances and global warming threaten it. Thermal stress can induce coral bleaching, a phenomenon in which the mutualistic symbiosis between the coral polyps host and its endosymbiotic unicellular algae is disrupted, and can lead to the death of entire colonies. Previous works have shown that soma clonal colonies display different levels of survival depending on the environmental conditions they previously faced. Epigenetic mechanisms are good candidates to explain this phenomenon. The clonal nature of a colony and the possibility of generating genetically identical colonies through propagation make corals an attractive model to study the impact of the environment on the epigenome. However, until now, no work had been published on the P. acuta epigenome. One of the main problems is caused by the intracellular location of Symbiodinium, which makes it complicated to isolate coral chromatin free of contamination by endiosymbiotic biological material. Here, (i) we describe a simple method to purify P. acuta chromatin, (ii) we provide the first description of a coral methylome, with a mosaic pattern of cytosine methylation principally in a CpG context (4% of all CpG), and (iii) we show that P. acuta, but not all corals, has an unusual chromatin structure, and displays histone H3 clipping.

molecular biology↗