Project description:We analyzed transcriptome differences in postmortem caudate and putamen from controls (n=40) and PD (n=35) as confirmed by autopsy. Further, we analyzed region specific differences in caudate and putamen associated with clinical variables.
Project description:Introduction: The analysis of post-mortem metabolomic changes in biological fluids opens the way to develop new methods for the estimation of post-mortem interval (PMI). It may also help in the analysis of disease-induced metabolomic changes in human tissues when the postoperational samples are compared to the post-mortem samples from healthy donors. Objectives: The goals of this study are to observe and classify the post-mortem changes occurring in the rabbit blood, aqueous and vitreous humors (AH and VH), to identify the potential PMI markers among a wide range of metabolites, and also to determine which biological fluid – blood, AH or VH – is more suitable for the PMI estimation. Methods: The quantitative metabolomic profiling of samples of the rabbit serum, AH and VH taken at different PMIs has been performed with the combined use of high-frequency NMR and high-resolution LC-MS methods. Results: The quantitative levels of 63 metabolites in the rabbit serum, AH and VH at different PMIs have been measured. It has been found that the post-mortem metabolomic changes in AH and VH proceed slower than in blood, and the data scattering is lower. Among the metabolites whose concentrations increase with time, the most significant and linear growth is found for hypoxanthine, choline and glycerol. Conclusion: The obtained results indicate the advantage of ocular fluids, AH and VH, over blood serum for the search of potential biochemical markers for the PMI estimation. Among the compounds studied in the present work, hypoxanthine, choline and glycerol give the biggest promise as the potential PMI biomarkers.
Project description:Accurate analysis of gene expression in human tissues using RNA Sequencing is often dependent on the quality of source material. One major source of variation in mRNA quality is post-mortem time. While it is known that individual transcripts show differential post-mortem stability, few studies have directly and comprehensively analyzed mRNA stability following death, and in particular, the extent to which tissue- and species-specific factors influence post-mortem mRNA stability are poorly understood. This knowledge is particularly important for ocular tissues studies, where tissues obtained post-mortem are frequently used for research or therapeutic applications. To directly investigate this question, we profiled mRNA levels in both neuroretina and retinal pigment epithelium (RPE) from mouse and baboon over a series of post-mortem intervals. We found substantial changes in gene expression as early as 15 minutes in the mouse and as early as three hours in the baboon eye tissues. Importantly, our findings demonstrate both tissue- and species- specific patterns of RNA metabolism, by identifying a set of genes that are either rapidly degraded or very stable in both species and/or tissues. Taken together, the data from this study lays the foundation for understanding RNA regulation post-mortem, and provide novel insights into RNA metabolism in the tissues of the mammalian eye.
Project description:Evaluating RNA quality and transcriptomic profile of beef muscle tissue over time post-mortem may provide insight on RNA degradation and underlying biological and functional mechanisms influencing the biochemical changes occurring post-mortem that transform muscle tissue to meat. RNA-sequencing was performed on longissimus thoracis et lumborum (LTL) muscle samples collected at 5 time points [0 h (45 min post-mortem), 6 h, 24 h, 48 h, and 72 h (drip cooler)] post-mortem from British Continental crossbred beef heifers (n=7). Processed mRNA reads were aligned to the ARS-UCD1.2 bovine genome assembly. Differential expression (DE) analysis identified from 51 to 1434 upregulated and 27 to 2256 downregulated DE genes at individual time points compared to time 0 h, showing a trend of both up and downregulated genes increasing over time . Gene ontology and KEGG pathway term enrichment analyses revealed significant enrichment of biological and molecular functions relating to cellular energy, oxidative stress and NADH activity specific to early time points, as well as cellular signaling and transport and ribosome activity at specific to late time points. This study also revealed that LTL muscle tissue samples, collected as late as 72 h post-mortem remained at a high RNA integrity, suggesting opportunities for late sampling regimes for RNA-Seq analysis of post-mortem muscle tissue and the potential for larger studies to associate desirable meat quality traits with post-mortem transcriptome activity. Additionally, this study highlights the need to evaluate non-coding genetic features involved with epigenetic regulation in post-mortem muscle tissue, as indicated by non-coding RNA transcripts detected post-mortem, including small nucleolar RNA, mitochondrial DNA genes, and long non-coding RNA.
Project description:Analysis of gene expression in two large schizophrenia cohorts identifies multiple changes associated with nerve terminal function. Schizophrenia is a severe psychiatric disorder with a world-wide prevalence of 1%. The pathophysiology of the illness is not understood, but is thought to have a strong genetic component with some environmental influences on aetiology. To gain further insight into disease mechanism, we used microarray technology to determine the expression of over 30 000 mRNA transcripts in post-mortem tissue from a brain region associated with the pathophysiology of the disease (Brodmann area 10: anterior prefrontal cortex) in 28 schizophrenic and 23 control patients. Post-mortem derived BA10 tissue from 28 schizophrenic and 23 control patients were compared. Age, gender, post-mortem delay and pH of brain lysates data were also captured.