ABSTRACT
BACKGROUND: Despite the brain's high demand for energy, research on its epigenetics focuses on nuclear methylation, and much of the mitochondrial DNA methylation remains seldom investigated. With a focus on the nucleus accumbens (NAcc) and the prefrontal cortex (PFC), we aimed to identify the mitochondrial methylation signatures for (1) distinguishing the two brain areas, (2) correlating with aging, and (3) reflecting the influence of illicit drugs on the brain. RESULT: We collected the brain tissue in the NAcc and the PFC from the deceased individuals without (n = 39) and with (n = 14) drug use and used whole-genome bisulfite sequencing to cover cytosine sites in the mitochondrial genome. We first detected differential methylations between the NAcc and the PFC in the nonusers group (P = 3.89 × 10-9). These function-related methylation differences diminished in the drug use group due to the selective alteration in the NAcc. Then, we found the correlation between the methylation levels and the chronological ages in the nonusers group (R2 = 0.34 in the NAcc and 0.37 in the PFC). The epigenetic clocks in illicit drug users, especially in the ketamine users, were accelerated in both brain regions by comparison with the nonusers. Finally, we summarized the effect of the illicit drugs on the methylation, which could significantly differentiate the drug users from the nonusers (AUC = 0.88 in the NAcc, AUC = 0.94 in the PFC). CONCLUSION: The mitochondrial methylations were different between different brain areas, generally accumulated with aging, and sensitive to the effects of illicit drugs. We believed this is the first report to elucidate comprehensively the importance of mitochondrial DNA methylation in human brain.
Subject(s)
Illicit Drugs , Nucleus Accumbens , Aging/genetics , DNA Methylation , DNA, Mitochondrial/genetics , Humans , Illicit Drugs/pharmacology , Prefrontal CortexABSTRACT
The characteristics of knife tool marks retained on hard tissues can be used to outline the shape and angle of a knife. The purpose of this study was to describe such marks on bone tissues that had been chopped with knives. A chopping stage with a gravity accelerator and a fixed bone platform was designed to reconstruct the chopping action. A digital microscope was also used to measure the knife angle (θ) and retained V-shape tool mark angle (ψ) in a pig skull. The κ value (elasticity coefficient; θ/ψ) was derived and recorded after the knife angle (θ) and the accompanied velocity were compared with the proportional impulsive force of the knife and ψ on the bone. The constant impulsive force revealed a correlation between the V-shape tool mark angle (ψ) and the elasticity coefficient (κ). These results describe the tool marks--crucial in the medicolegal investigation--of a knife on hard tissues.
Subject(s)
Skull/pathology , Weapons , Wounds, Stab/pathology , Animals , Biophysical Phenomena , Elasticity , Forensic Pathology , Imaging, Three-Dimensional , Microscopy , Models, Animal , Skull/injuries , SwineABSTRACT
Scrub typhus is a zoonotic disease caused by Orientia tsutsugamushi, which is transmitted by chiggers. The target cells of this rickettsia are poorly defined in humans. Immunohistochemical staining of tissue sections of patients with scrub typhus is helpful in investigating the target cells of this rickettsia in different organs. We studied two autopsy specimens by immunohistochemical staining using a specific antibody against O. tsutsugamushi. Rickettsiae were located in endothelial cells in all of the organs evaluated, namely heart, lung, brain, kidney, appendix and skin, within cardiac muscle cells and renal tubular epithelial cells, and in macrophages located in the lymph node, liver and spleen. In conclusion, O. tsutsugamushi may disseminate into multiple organs through endothelial cells and macrophages, resulting in the development of fatal complications.
Subject(s)
Orientia tsutsugamushi/isolation & purification , Scrub Typhus/microbiology , Adult , Child , Endothelial Cells/microbiology , Female , Humans , Immunohistochemistry , MaleABSTRACT
We describe the clinical, radiologic, and postmortem findings in a 49-year-old woman with intravascular lymphomatosis. The patient presented with progressive limb weakness followed by progressive disseminated cerebral neurologic symptoms. Disseminated encephalomyelitis was suspected due to the clinical and radiologic findings. Steroid pulse therapy and intravenous immunoglobulin were given but did not help. The patient died of multiple organ failure 3 months after the onset of symptoms. A diagnosis of disseminated intravascular large B-cell lymphomatosis was established based on findings from histopathology and immunohistochemistry studies on autopsy specimens of the brain and other visceral organs collected postmortem.
