Project description:In recent years, the development of molecular clocks has provided avenues for estimation of biological age. Traditionally, methylation-based epigenetic clocks have been the focus of age predictor developments, however individual proteomics, transcriptomics, and ATAC-Seq have provided avenues for other omic based clocks. However, the current limitation is the development of multi-omic clocks which are able to capture multiple facets of the central dogma to develop composite epigenetic clocks. To this end, the current project incorporates proteomic data from a pool of 2,000 samples which were incorporated into the development of a multi-omic informed epigenetic predictor. Here, we utilized the Seer ProteographTM platform to prepare protein reads from plasma samples collected from a pool of individuals collected from the Mass General Brigham's (MGB) Biobank, and then quantified using LC-MS, and analyzed using the software available from Seer. Additional QA/QC and normalization was conducted using in-house analytical scripts.
Project description:Despite advances in surgery support there are unmet needs for cardiopulmonary bypass (CPB) patients being at risk of perioperative ischemia. Remote ischemic preconditioning (RIPC) is considered as adjuvant therapy, but its effects are still underexplored. Thus, we monitored transcriptomic responses from the RIPC procedure during and after cardiac surgery in a pilot study, comprising 34 samples and 10 for validation from patients. We systematically compared the response between CTRL and RIPC including individual effects and dynamics. We gratefully acknowledge the support from the study participants as part of the clinical trial (ClinicalTrials.gov ID: NCT01067703). Different individual and time-resolved patterns were found for preconditioned patients (RIPC) comprising alternated cytokine, ribosomal and stress related genes. This was confirmed by a tailored method for ranking candidates by integrating variance and expression changes at once.
Project description:Remembrances of traumata range among the most enduring forms of memories. Despite the elevated lifetime prevalence of anxiety disorders, effective strategies to attenuate long-term traumatic memories are scarce. The most efficacious treatments to diminish recent (i.e., day-old) traumata capitalize on memory updating mechanisms during reconsolidation that are initiated upon memory recall. Here, we show that in mice successful reconsolidation-updating paradigms for recent memories fail to attenuate remote (i.e., month-old) ones. We find that whereas recent memory recall induces a limited period of hippocampal neuroplasticity mediated, in part, by S-nitrosylation of HDAC2 and histone acetylation, such plasticity is absent for remote memories. However, by using an HDAC2-targeting inhibitor (HDACi) during reconsolidation, even remote memories can be persistently attenuated. This intervention epigenetically primes the expression of neuroplasticity-related genes as revealed by whole genome RNA sequencing, which is accompanied by higher metabolic, synaptic and structural plasticity. Thus, applying HDACis during memory reconsolidation might constitute a treatment option for remote traumata. 3 biological replicates per group were analyzed. The material analyzed was whole hippocampi from one brain hemisphere, from which total RNA was extracted.
Project description:Novel development makes remote real-time analysis with possible translation to in-vivo a reality. Remote Infrared Matrix Assisted Laser Desorption Ionization (Remote IR MALDI) system with endogenous water as matrix becomes real and allows to envisage real-time proteomics to be performed in the in-vivo context. Remote IR MALDI is demonstrated to be used to analyze peptides and proteins. Very interestingly, the corresponding mass spectra show ESI like charge states distribution, opening many applications for structural elucidation to be performed in real-time by Top-Down analysis. The charge states show no dependence toward laser wavelength or length of the transfer tube allowing for remote analyses to be perform 5 m away from the mass spectrometry (MS) instrument without modification of spectra. This brings also interesting features to the understanding of IR MALDI ionization mechanism